Patent Publication Number: US-2007104616-A1

Title: Fluid handling cassette system for body fluid analyzer

Description:
PRIORITY CLAIM  
      This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 60/837,745, filed Aug. 15, 2006, titled FLUID HANDLING CASSETTE SYSTEM FOR BODY FLUID ANALYZER; and of U.S. Provisional Application No. 60/724,199, filed Oct. 6, 2005, titled INTENSIVE CARE UNIT BLOOD ANALYSIS SYSTEM AND METHOD. The entire disclosure of each of the above-listed provisional applications is hereby incorporated by reference herein and made a part of this specification. 
    
    
     BACKGROUND  
      1. Field  
      Certain embodiments disclosed herein relate to methods and apparatus for determining the concentration of an analyte in a sample, such as an analyte in a sample of bodily fluid, as well as methods and apparatus which can be used to support the making of such determinations.  
      2. Description of the Related Art  
      It is a common practice to measure the levels of certain analytes, such as glucose, in a bodily fluid, such as blood. Often this is done in a hospital or clinical setting when there is a risk that the levels of certain analytes may move outside a desired range, which in turn can jeopardize the health of a patient. Certain currently known systems for analyte monitoring in a hospital or clinical setting suffer from various drawbacks.  
     SUMMARY  
      One disclosed embodiment is a fluid handling system for use in bodily fluid analysis. The system comprises a first fluid handling module configured to interface with a main instrument. The first fluid handling module has a first fluid handling network and the first fluid handling network includes an infusate passage and an infusion fluid pressure member suitable for moving fluid within the infusate passage. The fluid handling system also has a second fluid handling module separate from the first module which is configured to interface with the main instrument. The second fluid handling module has a second fluid handling network and at least one sample analysis cell which is accessible via the second fluid handling network. The first and second modules are configured to interconnect and provide fluid communication between the first and second fluid handling network and the sample cells.  
      One disclosed embodiment is a body fluid analysis system comprising a body fluid analysis instrument and a first fluid handling module comprising a first housing and a first fluid handling network, the first fluid handling module being removably connected to the instrument such that the first housing engages the instrument. The system also has a second fluid handling module comprising a second housing separate from the first housing, and a sample analysis cell. The second fluid handling module is removably connected to the instrument such that the second housing engages the instrument. The first and second fluid handling modules are connected to each other and the first and second fluid handling modules are in fluid communication with each other.  
      One disclosed embodiment is a method of using a bodily fluid analysis system having a main instrument and first and second replaceable fluid handling modules removably connected to the main instrument. The analysis system has a pump at least partially formed by the first fluid handling module, and a sample analysis chamber in the second fluid handling module. The method comprises replacing the first fluid handling module at a first replacement frequency and replacing the second fluid handling module at a second replacement frequency wherein the first replacement frequency differs from the second replacement frequency.  
      One disclosed embodiment is a method of handling a bodily fluid. The method comprises drawing a volume of the bodily fluid from a patient into a fluid handling network and retaining a sample of the drawn volume in the fluid handling network. The retained sample comprises less than half of the drawn volume. The method also includes returning the balance of the drawn volume to the patient in less than five minutes after the drawing was commenced and analyzing at least a portion of the sample.  
      One disclosed embodiment is a method of handling a bodily fluid. The method comprises drawing a volume of the bodily fluid from a patient into a fluid handling network and retaining a sample of the drawn volume in the fluid handling network. The retained sample comprises less than half of the drawn volume. The method also includes returning the balance of the drawn volume to the patient and analyzing at least a portion of the sample wherein the analyzing takes at least 10 seconds to complete.  
      One disclosed embodiment is a bodily fluid analyzer comprising a fluid handling network configured for fluid communication with a bodily fluid within a patient and an analyte detection system configured to examine a sample of bodily fluid in the fluid handling network. The analyzer further comprises a processor and stored program instructions executable by the processor so that the analyzer is operable to draw a volume of the bodily fluid into the fluid handling network and retain a sample of the drawn volume in the fluid handling network. The retained sample comprises less than half of the drawn volume. The analyzer is also operable to return the balance of the drawn volume to the patient in less than five minutes after the drawing was commenced and to analyze at least a portion of the sample.  
      One disclosed embodiment is a bodily fluid analyzer comprising a fluid handling network configured for fluid communication with a bodily fluid within a patient and an analyte detection system configured to examine a sample of bodily fluid in the fluid handling network. The analyzer further comprises a processor and stored program instructions executable by the processor so that the analyzer is operable to draw a volume of the bodily fluid from a patient into a fluid handling network and retain a sample of the drawn volume in the fluid handling network. The retained sample comprises less than half of the drawn volume. The analyze is also operable to return the balance of the drawn volume to the patient and to analyze at least a portion of the sample wherein the analyzing takes at least 10 seconds to complete. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a schematic of a fluid handling system in accordance with one embodiment;  
       FIG. 1A  is a schematic of a fluid handling system, wherein a fluid handling and analysis apparatus of the fluid handling system is shown in a cutaway view;  
       FIG. 1B  is a cross-sectional view of a bundle of the fluid handling system of  FIG. 1A  taken along the line  1 B- 1 B;  
       FIG. 2  is a schematic of an embodiment of a sampling apparatus;  
       FIG. 3  is a schematic showing details of an embodiment of a sampling apparatus;  
       FIG. 4  is a schematic of an embodiment of a sampling unit;  
       FIG. 5  is a schematic of an embodiment of a sampling apparatus;  
       FIG. 6A  is a schematic of an embodiment of gas injector manifold;  
       FIG. 6B  is a schematic of an embodiment of gas injector manifold;  
       FIGS. 7A-7J  are schematics illustrating methods of using the infusion and blood analysis system, where  FIG. 7A  shows one embodiment of a method of infusing a patient, and  FIGS. 7B-7J  illustrate steps in a method of sampling from a patient, where  FIG. 7B  shows fluid being cleared from a portion of the first and second passageways;  FIG. 7C  shows a sample being drawn into the first passageway;  FIG. 7D  shows a sample being drawn into second passageway;  FIG. 7E  shows air being injected into the sample;  FIG. 7F  shows bubbles being cleared from the second passageway;  FIGS. 7H and 7I  show the sample being pushed part way into the second passageway followed by fluid and more bubbles; and  FIG. 7J  shows the sample being pushed to analyzer;  
       FIG. 8  is a perspective front view of an embodiment of a sampling apparatus;  
       FIG. 9  is a schematic front view of one embodiment of a sampling apparatus cassette;  
       FIG. 10  is a schematic front view of one embodiment of a sampling apparatus instrument;  
       FIG. 11  is an illustration of one embodiment of an arterial patient connection of the present invention;  
       FIG. 12  is an illustration of one embodiment of a venous patient connection;  
       FIGS. 13A, 13B , and  13 C are various views of one embodiment of a pinch valve, where  FIG. 13A  is a front view,  FIG. 13B  is a sectional view, and  FIG. 13C  is a sectional view showing one valve in a closed position;  
       FIGS. 14A and 14B  are various views of one embodiment of a pinch valve, where  FIG. 14A  is a front view and  FIG. 14B  is a sectional view showing one valve in a closed position;  
       FIG. 15  is a side view of one embodiment of a separator;  
       FIG. 16  is an exploded perspective view of the separator of  FIG. 15 ;  
       FIG. 17  is one embodiment of a fluid analysis apparatus;  
       FIG. 18  is a top view of a cuvette for use in the apparatus of  FIG. 17 ;  
       FIG. 19  is a side view of the cuvette of  FIG. 18 ;  
       FIG. 20  is an exploded perspective view of the cuvette of  FIG. 18 ;  
       FIG. 21  is a schematic of an embodiment of a sample preparation unit;  
       FIG. 22A  is a perspective view of another embodiment of a fluid handling and analysis apparatus having a main instrument and removable cassette;  
       FIG. 22B  is a partial cutaway, side elevational view of the fluid handling and analysis apparatus with the cassette spaced from the main instrument;  
       FIG. 22C  is a cross-sectional view of the fluid handling and analysis apparatus of  FIG. 22A  wherein the cassette is installed onto the main instrument;  
       FIG. 23A  is a cross-sectional view of the cassette of the fluid handling and analysis apparatus of  FIG. 22A  taken along the line  23 A- 23 A;  
       FIG. 23B  is a cross-sectional view of the cassette of  FIG. 23A  taken along the line  23 B- 23 B of  FIG. 23A ;  
       FIG. 23C  is a cross-sectional view of the fluid handling and analysis apparatus having a fluid handling network, wherein a rotor of the cassette is in a generally vertical orientation;  
       FIG. 23D  is a cross-sectional view of the fluid handling and analysis apparatus, wherein the rotor of the cassette is in a generally horizontal orientation;  
       FIG. 23E  is a front elevational view of the main instrument of the fluid handling and analysis apparatus of  FIG. 23C ;  
       FIG. 24A  is a cross-sectional view of the fluid handling and analysis apparatus having a fluid handling network in accordance with another embodiment;  
       FIG. 24B  is a front elevational view of the main instrument of the fluid handling and analysis apparatus of  FIG. 24A ;  
       FIG. 25A  is a front elevational view of a rotor having a sample element for holding sample fluid;  
       FIG. 25B  is a rear elevational view of the rotor of  FIG. 25A ;  
       FIG. 25C  is a front elevational view of the rotor of  FIG. 25A  with the sample element filled with a sample fluid;  
       FIG. 25D  is a front elevational view of the rotor of  FIG. 25C  after the sample fluid has been separated;  
       FIG. 25E  is a cross-sectional view of the rotor taken along the line  25 E- 25 E of  FIG. 25A ;  
       FIG. 25F  is an enlarged sectional view of the rotor of  FIG. 25E ;  
       FIG. 26A  is an exploded perspective view of a sample element for use with a rotor of a fluid handling and analysis apparatus;  
       FIG. 26B  is a perspective view of an assembled sample element;  
       FIG. 27A  is a front elevational view of a fluid interface for use with a cassette;  
       FIG. 27B  is a top elevational view of the fluid interface of  FIG. 27A ;  
       FIG. 27C  is an enlarged side view of a fluid interface engaging a rotor;  
       FIG. 28  is a cross-sectional view of the main instrument of the fluid handling and analysis apparatus of  FIG. 22A  taken along the line  28 - 28 ;  
       FIG. 29  is a graph illustrating the absorption spectra of various components that may be present in a blood sample;  
       FIG. 30  is a graph illustrating the change in the absorption spectra of blood having the indicated additional components of  FIG. 29  relative to a Sample Population blood and glucose concentration, where the contribution due to water has been numerically subtracted from the spectra;  
       FIG. 31  is an embodiment of an analysis method for determining the concentration of an analyte in the presence of possible interferents;  
       FIG. 32  is one embodiment of a method for identifying interferents in a sample for use with the embodiment of  FIG. 31 ;  
       FIG. 33A  is a graph illustrating one embodiment of the method of  FIG. 32 , and  FIG. 33B  is a graph further illustrating the method of  FIG. 32 ;  
       FIG. 34  is a one embodiment of a method for generating a model for identifying possible interferents in a sample for use with an embodiment of  FIG. 31 ;  
       FIG. 35  is a schematic of one embodiment of a method for generating randomly-scaled interferent spectra;  
       FIG. 36  is one embodiment of a distribution of interferent concentrations for use with the embodiment of  FIG. 35 ;  
       FIG. 37  is a schematic of one embodiment of a method for generating combination interferent spectra;  
       FIG. 38  is a schematic of one embodiment of a method for generating an interferent-enhanced spectral database;  
       FIG. 39  is a graph illustrating the effect of interferents on the error of glucose estimation;  
       FIGS. 40A, 40B ,  40 C, and  40 D each have a graph showing a comparison of the absorption spectrum of glucose with different interferents taken using two different techniques: a Fourier Transform Infrared (FTIR) spectrometer having an interpolated resolution of 1 cm −1  (solid lines with triangles); and by 25 finite-bandwidth IR filters having a Gaussian profile and full-width half-maximum (FWHM) bandwidth of 28 cm −1  corresponding to a bandwidth that varies from 140 nm at 7.08 μm, up to 279 nm at 10 μm (dashed lines with circles). The Figures show a comparison of glucose with mannitol ( FIG. 40A ), dextran ( FIG. 40B ), n-acetyl L cysteine ( FIG. 40C ), and procainamide ( FIG. 40D ), at a concentration level of 1 mg/dL and path length of 1 μm;  
       FIG. 41  shows a graph of the blood plasma spectra for 6 blood sample taken from three donors in arbitrary units for a wavelength range from 7 μm to 10 μm, where the symbols on the curves indicate the central wavelengths of the 25 filters;  
       FIGS. 42A, 42B ,  42 C, and  42 D contain spectra of the Sample Population of 6 samples having random amounts of mannitol ( FIG. 42A ), dextran ( FIG. 42B ), n-acetyl L cysteine ( FIG. 42C ), and procainamide ( FIG. 42D ), at a concentration levels of 1 mg/dL and path lengths of 1 μm;  
       FIGS. 43A-43D  are graphs comparing calibration vectors obtained by training in the presence of an interferent, to the calibration vector obtained by training on clean plasma spectra for mannitol ( FIG. 43A ), dextran ( FIG. 43B ), n-acetyl L cysteine ( FIG. 43C ), and procainamide ( FIG. 43D ) for water-free spectra;  
       FIG. 44  is a schematic illustration of another embodiment of the analyte detection system;  
       FIG. 45  is a plan view of one embodiment of a filter wheel suitable for use in the analyte detection system depicted in  FIG. 44 ;  
       FIG. 46  is a partial sectional view of another embodiment of an analyte detection system;  
       FIG. 47  is a detailed sectional view of a sample detector of the analyte detection system illustrated in  FIG. 46 ;  
       FIG. 48  is a detailed sectional view of a reference detector of the analyte detection system illustrated in  FIG. 46 ;  
       FIG. 49  is perspective view of an embodiment anti-clotting device showing an ultrasonic generator adjacent to a centrifuge;  
       FIG. 50  is a schematic showing details of an alternative embodiment of a sampling apparatus;  
       FIG. 51  is a schematic showing details of another alternative embodiment of a sampling apparatus;  
       FIG. 52  is a schematic view of one embodiment of a multiple fluid handling cassette system; and  
       FIG. 53  is a detailed schematic view of the cassette system of  FIG. 52 .  
       FIG. 54  is detailed schematic view of another embodiment of the cassette system of  FIG. 52 . 
    
    
      Reference symbols are used in the Figures to indicate certain components, aspects or features shown therein, with reference symbols common to more than one Figure indicating like components, aspects or features shown therein.  
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
      Although certain preferred embodiments and examples are disclosed below, it will be understood by those skilled in the art that the inventive subject matter extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the inventions, and to obvious modifications and equivalents thereof. Thus it is intended that the scope of the inventions herein disclosed should not be limited by the particular disclosed embodiments described below. Thus, for example, in any method or process disclosed herein, the acts or operations making up the method/process may be performed in any suitable sequence, and are not necessarily limited to any particular disclosed sequence. For purposes of contrasting various embodiments with the prior art, certain aspects and advantages of these embodiments are described where appropriate herein. Of course, it is to be understood that not necessarily all such aspects or advantages may be achieved in accordance with any particular embodiment. Thus, for example, it should be recognized that the various embodiments may be carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other aspects or advantages as may be taught or suggested herein. While the systems and methods discussed herein can be used for invasive techniques, the systems and methods can also be used for non-invasive techniques or other suitable techniques, and can be used in hospitals, healthcare facilities, ICUs, or residences.  
      Overview of Embodiments of Fluid Handling Systems  
      Disclosed herein are fluid handling systems and various methods of analyzing sample fluids.  FIG. 1  illustrates an embodiment of a fluid handling system  10  which can determine the concentration of one or more substances in a sample fluid, such as a whole blood sample from a patient P. The fluid handling system  10  can also deliver an infusion fluid  14  to the patient P.  
      The fluid handling system  10  is located bedside and generally comprises a container  15  holding the infusion fluid  14  and a sampling system  100  which is in communication with both the container  15  and the patient P. A tube  13  extends from the container  15  to the sampling system  100 . A tube  12  extends from the sampling system  100  to the patient P. In some embodiments, one or more components of the fluid handling system  10  can be located at another facility, room, or other suitable remote location. One or more components of the fluid handling system  10  can communicate with one or more other components of the fluid handling system  10  (or with other devices) by any suitable communication means, such as communication interfaces including, but not limited to, optical interfaces, electrical interfaces, and wireless interfaces. These interfaces can be part of a local network, internet, wireless network, or other suitable networks.  
      The Infusion fluid  14  can comprise water, saline, dextrose, lactated Ringer&#39;s solution, drugs, insulin, mixtures thereof, or other suitable substances. The illustrated sampling system  100  allows the infusion fluid to pass to the patient P and/or uses the infusion fluid in the analysis. In some embodiments, the fluid handling system  10  may not employ infusion fluid. The fluid handling system  10  may thus draw samples without delivering any fluid to the patient P.  
      The sampling system  100  can be removably or permanently coupled to the tube  13  and tube  12  via connectors  110 ,  120 . The patient connector  110  can selectively control the flow of fluid through a bundle  130 , which includes a patient connection passageway  112  and a sampling passageway  113 , as shown in  FIG. 1B . The sampling system  100  can also draw one or more samples from the patient P by any suitable means. The sampling system  100  can perform one or more analyses on the sample, and then returns the sample to the patient or a waste container. In some embodiments, the sampling system  100  is a modular unit that can be removed and replaced as desired. The sampling system  100  can include, but is not limited to, fluid handling and analysis apparatuses, connectors, passageways, catheters, tubing, fluid control elements, valves, pumps, fluid sensors, pressure sensors, temperature sensors, hematocrit sensors, hemoglobin sensors, calorimetric sensors, and gas (or “bubble”) sensors, fluid conditioning elements, gas injectors, gas filters, blood plasma separators, and/or communication devices (e.g., wireless devices) to permit the transfer of information within the sampling system or between sampling system  100  and a network. The illustrated sampling system  100  has a patient connector  110  and a fluid handling and analysis apparatus  140 , which analyzes a sample drawn from the patient P. The fluid handling and analysis apparatus  140  and patient connector  110  cooperate to control the flow of infusion fluid into, and/or samples withdrawn from, the patient P. Samples can also be withdrawn and transferred in other suitable manners.  
       FIG. 1A  is a close up view of the fluid handling and analysis apparatus  140  which is partially cutaway to reveal some of its internal components. The fluid handling and analysis apparatus  140  preferably includes a pump  203  that controls the flow of fluid from the container  15  to the patient P and/or the flow of fluid drawn from the patient P. The pump  203  can selectively control fluid flow rates, direction(s) of fluid flow(s), and other fluid flow parameters as desired. As used herein, the term “pump” is a broad term and means, without limitation, a pressurization/pressure device, vacuum device, or any other suitable means for causing fluid flow. The pump  203  can include, but is not limited to, a reversible peristaltic pump, two unidirectional pumps that work in concert with valves to provide flow in two directions, a unidirectional pump, a displacement pump, a syringe, a diaphragm pump, roller pump, or other suitable pressurization device.  
      The illustrated fluid handling and analysis apparatus  140  has a display  141  and input devices  143 . The illustrated fluid handling and analysis apparatus  140  can also have a sampling unit  200  configured to analyze the drawn fluid sample. The sampling unit  200  can thus receive a sample, prepare the sample, and/or subject the sample (prepared or unprepared) to one or more tests. The sampling unit  200  can then analyze results from the tests. The sampling unit  200  can include, but is not limited to, separators, filters, centrifuges, sample elements, and/or detection systems, as described in detail below. The sampling unit  200  (see  FIG. 3 ) can include an analyte detection system for detecting the concentration of one or more analytes in the body fluid sample. In some embodiments, the sampling unit  200  can prepare a sample for analysis. If the fluid handling and analysis apparatus  140  performs an analysis on plasma contained in whole blood taken from the patient P, filters, separators, centrifuges, or other types of sample preparation devices can be used to separate plasma from other components of the blood. After the separation process, the sampling unit  200  can analyze the plasma to determine, for example, the patient P&#39;s glucose level. The sampling unit  200  can employ spectroscopic methods, calorimetric methods, electrochemical methods, or other suitable methods for analyzing samples.  
      With continued reference to  FIGS. 1 and 1 A, the fluid  14  in the container  15  can flow through the tube  13  and into a fluid source passageway  111 . The fluid can further flow through the passageway  111  to the pump  203 , which can pressurize the fluid. The fluid  14  can then flow from the pump  203  through the patient connection passageway  112  and catheter  11  into the patient P. To analyze the patient&#39;s P body fluid (e.g., whole blood, blood plasma, interstitial fluid, bile, sweat, excretions, etc.), the fluid handling and analysis apparatus  140  can draw a sample from the patient P through the catheter  11  to a patient connector  110 . The patient connector  110  directs the fluid sample into the sampling passageway  113  which leads to the sampling unit  200 . The sampling unit  200  can perform one or more analyses on the sample. The fluid handling and analysis apparatus  140  can then output the results obtained by the sampling unit  200  on the display  141 .  
      In some embodiments, the fluid handling system  10  can draw and analyze body fluid sample(s) from the patient P to provide real-time or near-real-time measurement of glucose levels. Body fluid samples can be drawn from the patient P continuously, at regular intervals (e.g., every 5, 10, 15, 20, 30 or 60 minutes), at irregular intervals, or at any time or sequence for desired measurements. These measurements can be displayed bedside with the display  141  for convenient monitoring of the patient P.  
      The illustrated fluid handling system  10  is mounted to a stand  16  and can be used in hospitals, ICUs, residences, healthcare facilities, and the like. In some embodiments, the fluid handling system  10  can be transportable or portable for an ambulatory patient. The ambulatory fluid handling system  10  can be coupled (e.g., strapped, adhered, etc.) to a patient, and may be smaller than the bedside fluid handling system  10  illustrated in  FIG. 1 . In some embodiments, the fluid handling system  10  is an implantable system sized for subcutaneous implantation and can be used for continuous monitoring. In some embodiments, the fluid handling system  10  is miniaturized so that the entire fluid handling system can be implanted. In other embodiments, only a portion of the fluid handling system  10  is sized for implantation.  
      In some embodiments, the fluid handling system  10  is a disposable fluid handling system and/or has one or more disposable components. As used herein, the term “disposable” when applied to a system or component (or combination of components), such as a cassette or sample element, is a broad term and means, without limitation, that the component in question is used a finite number of times and then discarded. Some disposable components are used only once and then discarded. Other disposable components are used more than once and then discarded. For example, the fluid handling and analysis apparatus  140  can have a main instrument and a disposable cassette that can be installed onto the main instrument, as discussed below. The disposable cassette can be used for predetermined length of time, to prepare a predetermined amount of sample fluid for analysis, etc. In some embodiments, the cassette can be used to prepare a plurality of samples for subsequent analyses by the main instrument. The reusable main instrument can be used with any number of cassettes as desired. Additionally or alternatively, the cassette can be a portable, handheld cassette for convenient transport. In these embodiments, the cassette can be manually mounted to or removed from the main instrument. In some embodiments, the cassette may be a non disposable cassette which can be permanently coupled to the main instrument, as discussed below.  
      Disclosed herein are a number of embodiments of fluid handling systems, sampling systems, fluid handling and analysis apparatuses, analyte detection systems, and methods of using the same. Section I below discloses various embodiments of the fluid handling system that may be used to transport fluid from a patient for analysis. Section II below discloses several embodiments of fluid handling methods that may be used with the apparatus discussed in Section I. Section III below discloses several embodiments of a sampling system that may be used with the apparatus of Section I or the methods of Section II. Section IV below discloses various embodiments of a sample analysis system that may be used to detect the concentration of one or more analytes in a material sample. Section V below discloses methods for determining analyte concentrations from sample spectra. Section VI below discloses various embodiments of inhibiting blood clot formation that are useful in a sampling apparatus.  
      Section I—Fluid Handling System  
       FIG. 1  is a schematic of the fluid handling system  10  which includes the container  15  supported by the stand  16  and having an interior that is fillable with the fluid  14 , the catheter  11 , and the sampling system  100 . Fluid handling system  10  includes one or more passageways  20  that form conduits between the container, the sampling system, and the catheter. Generally, sampling system  100  is adapted to accept a fluid supply, such as fluid  14 , and to be connected to a patient, including, but not limited to catheter  11  which is used to catheterize a patient P. Fluid  14  includes, but is not limited to, fluids for infusing a patient such as saline, lactated Ringer&#39;s solution, or water. Sampling system  100 , when so connected, is then capable of providing fluid to the patient. In addition, sampling system  100  is also capable of drawing samples, such as blood, from the patient through catheter  11  and passageways  20 , and analyzing at least a portion of the drawn sample. Sampling system  100  measures characteristics of the drawn sample including, but not limited to, one or more of the blood plasma glucose, blood urea nitrogen (BUN), hematocrit, hemoglobin, or lactate levels. Optionally, sampling system  100  includes other devices or sensors to measure other patient or apparatus related information including, but not limited to, patient blood pressure, pressure changes within the sampling system, or sample draw rate.  
      More specifically,  FIG. 1  shows sampling system  100  as including the patient connector  110 , the fluid handling and analysis apparatus  140 , and the connector  120 . Sampling system  100  may include combinations of passageways, fluid control and measurement devices, and analysis devices to direct, sample, and analyze fluid. Passageways  20  of sampling system  100  include the fluid source passageway  111  from connector  120  to fluid handling and analysis apparatus  140 , the patient connection passageway  112  from the fluid handling and analysis apparatus to patient connector  110 , and the sampling passageway  113  from the patient connector to the fluid handling and analysis apparatus. The reference of passageways  20  as including one or more passageway, for example passageways  111 ,  112 , and  113  are provided to facilitate discussion of the system. It is understood that passageways may include one or more separate components and may include other intervening components including, but not limited to, pumps, valves, manifolds, and analytic equipment.  
      As used herein, the term “passageway” is a broad term and is used in its ordinary sense and includes, without limitation except as explicitly stated, as any opening through a material through which a fluid, such as a liquid or a gas, may pass so as to act as a conduit. Passageways include, but are not limited to, flexible, inflexible or partially flexible tubes, laminated structures having openings, bores through materials, or any other structure that can act as a conduit and any combination or connections thereof. The internal surfaces of passageways that provide fluid to a patient or that are used to transport blood are preferably biocompatible materials, including but not limited to silicone, polyetheretherketone (PEEK), or polyethylene (PE). One type of preferred passageway is a flexible tube having a fluid contacting surface formed from a biocompatible material. A passageway, as used herein, also includes separable portions that, when connected, form a passageway.  
      The inner passageway surfaces may include coatings of various sorts to enhance certain properties of the conduit, such as coatings that affect the ability of blood to clot or to reduce friction resulting from fluid flow. Coatings include, but are not limited to, molecular or ionic treatments.  
      As used herein, the term “connected” is a broad term and is used in its ordinary sense and includes, without limitation except as explicitly stated, with respect to two or more things (e.g., elements, devices, patients, etc.): a condition of physical contact or attachment, whether direct, indirect (via, e.g., intervening member(s)), continuous, selective, or intermittent; and/or a condition of being in fluid, electrical, or optical-signal communication, whether direct, indirect, continuous, selective (e.g., where there exist one or more intervening valves, fluid handling components, switches, loads, or the like), or intermittent. A condition of fluid communication is considered to exist whether or not there exists a continuous or contiguous liquid or fluid column extending between or among the two or more things in question. Various types of connectors can connect components of the fluid handling system described herein. As used herein, the term “connector” is a broad term and is used in its ordinary sense and includes, without limitation except as explicitly stated, as a device that connects passageways or electrical wires to provide communication (whether direct, indirect, continuous, selective, or intermittent) on either side of the connector. Connectors contemplated herein include a device for connecting any opening through which a fluid may pass. These connectors may have intervening valves, switches, fluid handling devices, and the like for affecting fluid flow. In some embodiments, a connector may also house devices for the measurement, control, and preparation of fluid, as described in several of the embodiments.  
      Fluid handling and analysis apparatus  140  may control the flow of fluids through passageways  20  and the analysis of samples drawn from a patient P, as described subsequently. Fluid handling and analysis apparatus  140  includes the display  141  and input devices, such as buttons  143 . Display  141  provides information on the operation or results of an analysis performed by fluid handling and analysis apparatus  140 . In one embodiment, display  141  indicates the function of buttons  143 , which are used to input information into fluid handling and analysis apparatus  140 . Information that may be input into or obtained by fluid handling and analysis apparatus  140  includes, but is not limited to, a required infusion or dosage rate, sampling rate, or patient specific information which may include, but is not limited to, a patient identification number or medical information. In an other alternative embodiment, fluid handling and analysis apparatus  140  obtains information on patient P over a communications network, for example an hospital communication network having patient specific information which may include, but is not limited to, medical conditions, medications being administered, laboratory blood reports, gender, and weight. As one example of the use of fluid handling system  10 , which is not meant to limit the scope of the present disclosure,  FIG. 1  shows catheter  11  connected to patient P.  
      As discussed subsequently, fluid handling system  10  may catheterize a patient&#39;s vein or artery. Sampling system  100  is releasably connectable to container  15  and catheter  11 . Thus, for example,  FIG. 1  shows container  15  as including the tube  13  to provide for the passage of fluid to, or from, the container, and catheter  11  as including the tube  12  external to the patient. Connector  120  is adapted to join tube  13  and passageway  111 . Patient connector  110  is adapted to join tube  12  and to provide for a connection between passageways  112  and  113 .  
      Patient connector  110  may also include one or more devices that control, direct, process, or otherwise affect the flow through passageways  112  and  113 . In some embodiments, one or more lines  114  are provided to exchange signals between patient connector  110  and fluid handling and analysis apparatus  140 . The lines  114  can be electrical lines, optical communicators, wireless communication channels, or other means for communication. As shown in  FIG. 1 , sampling system  100  may also include passageways  112  and  113 , and lines  114 . The passageways and electrical lines between apparatus  140  and patient connector  110  are referred to, with out limitation, as the bundle  130 .  
      In various embodiments, fluid handling and analysis apparatus  140  and/or patient connector  110 , includes other elements (not shown in  FIG. 1 ) that include, but are not limited to: fluid control elements, including but not limited to valves and pumps; fluid sensors, including but not limited to pressure sensors, temperature sensors, hematocrit sensors, hemoglobin sensors, calorimetric sensors, and gas (or “bubble”) sensors; fluid conditioning elements, including but not limited to gas injectors, gas filters, and blood plasma separators; and wireless communication devices to permit the transfer of information within the sampling system or between sampling system  100  and a wireless network.  
      In one embodiment, patient connector  110  includes devices to determine when blood has displaced fluid  14  at the connector end, and thus provides an indication of when a sample is available for being drawn through passageway  113  for sampling. The presence of such a device at patient connector  110  allows for the operation of fluid handling system  10  for analyzing samples without regard to the actual length of tube  12 . Accordingly, bundle  130  may include elements to provide fluids, including air, or information communication between patient connector  110  and fluid handling and analysis apparatus  140  including, but not limited to, one or more other passageways and/or wires.  
      In one embodiment of sampling system  100 , the passageways and lines of bundle  130  are sufficiently long to permit locating patient connector  110  near patient P, for example with tube  12  having a length of less than 0.1 to 0.5 meters, or preferably approximately 0.15 meters and with fluid handling and analysis apparatus  140  located at a convenient distance, for example on a nearby stand  16 . Thus, for example, bundle  130  is from 0.3 to 3 meters, or more preferably from 1.5 to 2.0 meters in length. It is preferred, though not required, that patient connector  110  and connector  120  include removable connectors adapted for fitting to tubes  12  and  13 , respectively. Thus, in one embodiment, container  15 /tube  13  and catheter  11 /tube  12  are both standard medical components, and sampling system  100  allows for the easy connection and disconnection of one or both of the container and catheter from fluid handling system  10 .  
      In another embodiment of sampling system  100 , tubes  12  and  13  and a substantial portion of passageways  111  and  112  have approximately the same internal cross-sectional area. It is preferred, though not required, that the internal cross-sectional area of passageway  113  is less than that of passageways  111  and  112  (see  FIG. 1B ). As described subsequently, the difference in areas permits fluid handling system  10  to transfer a small sample volume of blood from patient connector  110  into fluid handling and analysis apparatus  140 .  
      Thus, for example, in one embodiment passageways  111  and  112  are formed from a tube having an inner diameter from 0.3 millimeter to 1.50 millimeter, or more preferably having a diameter from 0.60 millimeter to 1.2 millimeter. Passageway  113  is formed from a tube having an inner diameter from 0.3 millimeter to 1.5 millimeter, or more preferably having an inner diameter of from 0.6 millimeter to 1.2 millimeter.  
      While  FIG. 1  shows sampling system  100  connecting a patient to a fluid source, the scope of the present disclosure is not meant to be limited to this embodiment. Alternative embodiments include, but are not limited to, a greater or fewer number of connectors or passageways, or the connectors may be located at different locations within fluid handling system  10 , and alternate fluid paths. Thus, for example, passageways  111  and  112  may be formed from one tube, or may be formed from two or more coupled tubes including, for example, branches to other tubes within sampling system  100 , and/or there may be additional branches for infusing or obtaining samples from a patient. In addition, patient connector  110  and connector  120  and sampling system  100  alternatively include additional pumps and/or valves to control the flow of fluid as described below.  
       FIGS. 1A and 2  illustrate a sampling system  100  configured to analyze blood from patient P which may be generally similar to the embodiment of the sampling system illustrated in  FIG. 1 , except as further detailed below. Where possible, similar elements are identified with identical reference numerals in the depiction of the embodiments of FIGS.  1  to  2 .  FIGS. 1A and 2  show patient connector  110  as including a sampling assembly  220  and a connector  230 , portions of passageways  111  and  113 , and lines  114 , and fluid handling and analysis apparatus  140  as including the pump  203 , the sampling unit  200 , and a controller  210 . The pump  203 , sampling unit  200 , and controller  210  are contained within a housing  209  of the fluid handling and analysis apparatus  140 . The passageway  111  extends from the connector  120  through the housing  209  to the pump  203 . The bundle  130  extends from the pump  203 , sampling unit  200 , and controller  210  to the patient connector  110 .  
      In  FIGS. 1A and 2 , the passageway  111  provides fluid communication between connector  120  and pump  203  and passageway  113  provides fluid communication between pump  203  and connector  110 . Controller  210  is in communication with pump  203 , sampling unit  200 , and sampling assembly  220  through lines  114 . Controller  210  has access to memory  212 , and optionally has access to a media reader  214 , including but not limited to a DVD or CD-ROM reader, and communications link  216 , which can comprise a wired or wireless communications network, including but not limited to a dedicated line, an intranet, or an Internet connection.  
      As described subsequently in several embodiments, sampling unit  200  may include one or more passageways, pumps and/or valves, and sampling assembly  220  may include passageways, sensors, valves, and/or sample detection devices. Controller  210  collects information from sensors and devices within sampling assembly  220 , from sensors and analytical equipment within sampling unit  200 , and provides coordinated signals to control pump  203  and pumps and valves, if present, in sampling assembly  220 .  
      Fluid handling and analysis apparatus  140  includes the ability to pump in a forward direction (towards the patient) and in a reverse direction (away from the patient). Thus, for example, pump  203  may direct fluid  14  into patient P or draw a sample, such as a blood sample from patient P, from catheter  11  to sampling assembly  220 , where it is further directed through passageway  113  to sampling unit  200  for analysis. Preferably, pump  203  provides a forward flow rate at least sufficient to keep the patient vascular line open. In one embodiment, the forward flow rate is from 1 to 5 ml/hr. In some embodiments, the flow rate of fluid is about 0.05 ml/hr, 0.1 ml/hr, 0.2 ml/hr, 0.4 ml/hr, 0.6 ml/hr, 0.8 ml/hr, 1.0 ml/hr, and ranges encompassing such flow rates. In some embodiments, for example, the flow rate of fluid is less than about 1.0 ml/hr. In certain embodiments, the flow rate of fluid may be about 0.1 ml/hr or less. When operated in a reverse direction, fluid handling and analysis apparatus  140  includes the ability to draw a sample from the patient to sampling assembly  220  and through passageway  113 . In one embodiment, pump  203  provides a reverse flow to draw blood to sampling assembly  220 , preferably by a sufficient distance past the sampling assembly to ensure that the sampling assembly contains an undiluted blood sample. In one embodiment, passageway  113  has an inside diameter of from 25 to 200 microns, or more preferably from 50 to 100 microns. Sampling unit  200  extracts a small sample, for example from 10 to 100 microliters of blood, or more preferably approximately 40 microliters volume of blood, from sampling assembly  220 .  
      In one embodiment, pump  203  is a directionally controllable pump that acts on a flexible portion of passageway  111 . Examples of a single, directionally controllable pump include, but are not limited to a reversible peristaltic pump or two unidirectional pumps that work in concert with valves to provide flow in two directions. In an alternative embodiment, pump  203  includes a combination of pumps, including but not limited to displacement pumps, such as a syringe, and/or valve to provide bi-directional flow control through passageway  111 .  
      Controller  210  includes one or more processors for controlling the operation of fluid handling system  10  and for analyzing sample measurements from fluid handling and analysis apparatus  140 . Controller  210  also accepts input from buttons  143  and provides information on display  141 . Optionally, controller  210  is in bi-directional communication with a wired or wireless communication system, for example a hospital network for patient information. The one or more processors comprising controller  210  may include one or more processors that are located either within fluid handling and analysis apparatus  140  or that are networked to the unit.  
      The control of fluid handling system  10  by controller  210  may include, but is not limited to, controlling fluid flow to infuse a patient and to sample, prepare, and analyze samples. The analysis of measurements obtained by fluid handling and analysis apparatus  140  of may include, but is not limited to, analyzing samples based on inputted patient specific information, from information obtained from a database regarding patient specific information, or from information provided over a network to controller  210  used in the analysis of measurements by apparatus  140 .  
      Fluid handling system  10  provides for the infusion and sampling of a patient blood as follows. With fluid handling system  10  connected to bag  15  having fluid  14  and to a patient P, controller  210  infuses a patient by operating pump  203  to direct the fluid into the patient. Thus, for example, in one embodiment, the controller directs that samples be obtained from a patient by operating pump  203  to draw a sample. In one embodiment, pump  203  draws a predetermined sample volume, sufficient to provide a sample to sampling assembly  220 . In another embodiment, pump  203  draws a sample until a device within sampling assembly  220  indicates that the sample has reached the patient connector  110 . As an example which is not meant to limit the scope of the present disclosure, one such indication is provided by a sensor that detects changes in the color of the sample. Another example is the use of a device that indicates changes in the material within passageway  111  including, but not limited to, a decrease in the amount of fluid  14 , a change with time in the amount of fluid, a measure of the amount of hemoglobin, or an indication of a change from fluid to blood in the passageway.  
      When the sample reaches sampling assembly  220 , controller  210  provides an operating signal to valves and/or pumps in sampling system  100  (not shown) to draw the sample from sampling assembly  220  into sampling unit  200 . After a sample is drawn towards sampling unit  200 , controller  210  then provides signals to pump  203  to resume infusing the patient. In one embodiment, controller  210  provides signals to pump  203  to resume infusing the patient while the sample is being drawn from sampling assembly  220 . In an alternative embodiment, controller  210  provides signals to pump  203  to stop infusing the patient while the sample is being drawn from sampling assembly  220 . In another alternative embodiment, controller  210  provides signals to pump  203  to slow the drawing of blood from the patient while the sample is being drawn from sampling assembly  220 .  
      In another alternative embodiment, controller  210  monitors indications of obstructions in passageways or catheterized blood vessels during reverse pumping and moderates the pumping rate and/or direction of pump  203  accordingly. Thus, for example, obstructed flow from an obstructed or kinked passageway or of a collapsing or collapsed catheterized blood vessel that is being pumped will result in a lower pressure than an unobstructed flow. In one embodiment, obstructions are monitored using a pressure sensor in sampling assembly  220  or along passageways  20 . If the pressure begins to decrease during pumping, or reaches a value that is lower than a predetermined value then controller  210  directs pump  203  to decrease the reverse pumping rate, stop pumping, or pump in the forward direction in an effort to reestablish unobstructed pumping.  
       FIG. 3  is a schematic showing details of a sampling system  300  which may be generally similar to the embodiments of sampling system  100  as illustrated in  FIGS. 1 and 2 , except as further detailed below. Sampling system  300  includes sampling assembly  220  having, along passageway  112 : connector  230  for connecting to tube  12 , a pressure sensor  317 , a calorimetric sensor  311 , a first bubble sensor  314   a , a first valve  312 , a second valve  313 , and a second bubble sensor  314   b . Passageway  113  forms a “T” with passageway  111  at a junction  318  that is positioned between the first valve  312  and second valve  313 , and includes a gas injector manifold  315  and a third valve  316 . The lines  114  comprise control and/or signal lines extending from calorimetric sensor  311 , first, second, and third valves ( 312 ,  313 ,  316 ), first and second bubble sensors ( 314   a ,  314   b ), gas injector manifold  315 , and pressure sensor  317 . Sampling system  300  also includes sampling unit  200  which has a bubble sensor  321 , a sample analysis device  330 , a first valve  323   a , a waste receptacle  325 , a second valve  323   b , and a pump  328 . Passageway  113  forms a “T” to form a waste line  324  and a pump line  327 .  
      It is preferred, though not necessary, that the sensors of sampling system  100  are adapted to accept a passageway through which a sample may flow and that sense through the walls of the passageway. As described subsequently, this arrangement allows for the sensors to be reusable and for the passageways to be disposable. It is also preferred, though not necessary, that the passageway is smooth and without abrupt dimensional changes which may damage blood or prevent smooth flow of blood. In addition, is also preferred that the passageways that deliver blood from the patient to the analyzer not contain gaps or size changes that permit fluid to stagnate and not be transported through the passageway.  
      In one embodiment, the respective passageways on which valves  312 ,  313 ,  316 , and  323  are situated along passageways that are flexible tubes, and valves  312 ,  313 ,  316 , and  323  are “pinch valves,” in which one or more movable surfaces compress the tube to restrict or stop flow therethrough. In one embodiment, the pinch valves include one or more moving surfaces that are actuated to move together and “pinch” a flexible passageway to stop flow therethrough. Examples of a pinch valve include, for example, Model PV256 Low Power Pinch Valve (Instech Laboratories, Inc., Plymouth Meeting, Pa.). Alternatively, one or more of valves  312 ,  313 ,  316 , and  323  may be other valves for controlling the flow through their respective passageways.  
      Colorimetric sensor  311  accepts or forms a portion of passageway  111  and provides an indication of the presence or absence of blood within the passageway. In one embodiment, calorimetric sensor  311  permits controller  210  to differentiate between fluid  14  and blood. Preferably, calorimetric sensor  311  is adapted to receive a tube or other passageway for detecting blood. This permits, for example, a disposable tube to be placed into or through a reusable calorimetric sensor. In an alternative embodiment, calorimetric sensor  311  is located adjacent to bubble sensor  314   b . Examples of a calorimetric sensor include, for example, an Optical Blood Leak/Blood vs. Saline Detector available from Introtek International (Edgewood, N.J.).  
      As described subsequently, sampling system  300  injects a gas—referred to herein and without limitation as a “bubble”—into passageway  113 . Sampling system  300  includes gas injector manifold  315  at or near junction  318  to inject one or more bubbles, each separated by liquid, into passageway  113 . The use of bubbles is useful in preventing longitudinal mixing of liquids as they flow through passageways both in the delivery of a sample for analysis with dilution and for cleaning passageways between samples. Thus, for example the fluid in passageway  113  includes, in one embodiment, two volumes of liquids, such as sample S or fluid  14  separated by a bubble, or multiple volumes of liquid each separated by a bubble therebetween.  
      Bubble sensors  314   a ,  314   b  and  321  each accept or form a portion of passageway  112  or  113  and provide an indication of the presence of air, or the change between the flow of a fluid and the flow of air, through the passageway. Examples of bubble sensors include, but are not limited to ultrasonic or optical sensors, that can detect the difference between small bubbles or foam from liquid in the passageway. Once such bubble detector is an MEC Series Air Bubble/Liquid Detection Sensor (Introtek International, Edgewood, N.Y.). Preferably, bubble sensor  314   a ,  314   b , and  321  are each adapted to receive a tube or other passageway for detecting bubbles. This permits, for example, a disposable tube to be placed through a reusable bubble sensor.  
      Pressure sensor  317  accepts or forms a portion of passageway  111  and provides an indication or measurement of a fluid within the passageway. When all valves between pressure sensor  317  and catheter  11  are open, pressure sensor  317  provides an indication or measurement of the pressure within the patient&#39;s catheterized blood vessel. In one embodiment, the output of pressure sensor  317  is provided to controller  210  to regulate the operation of pump  203 . Thus, for example, a pressure measured by pressure sensor  317  above a predetermined value is taken as indicative of a properly working system, and a pressure below the predetermined value is taken as indicative of excessive pumping due to, for example, a blocked passageway or blood vessel. Thus, for example, with pump  203  operating to draw blood from patient P, if the pressure as measured by pressure sensor  317  is within a range of normal blood pressures, it may be assumed that blood is being drawn from the patient and pumping continues. However, if the pressure as measured by pressure sensor  317  falls below some level, then controller  210  instructs pump  203  to slow or to be operated in a forward direction to reopen the blood vessel. One such pressure sensor is a Deltran IV part number DPT-412 (Utah Medical Products, Midvale, Utah).  
      Sample analysis device  330  receives a sample and performs an analysis. In several embodiments, device  330  is configured to prepare of the sample for analysis. Thus, for example, device  330  may include a sample preparation unit  332  and an analyte detection system  334 , where the sample preparation unit is located between the patient and the analyte detection system. In general, sample preparation occurs between sampling and analysis. Thus, for example, sample preparation unit  332  may take place removed from analyte detection, for example within sampling assembly  220 , or may take place adjacent or within analyte detection system  334 .  
      As used herein, the term “analyte” is a broad term and is used in its ordinary sense and includes, without limitation, any chemical species the presence or concentration of which is sought in the material sample by an analyte detection system. For example, the analyte(s) include, but not are limited to, glucose, ethanol, insulin, water, carbon dioxide, blood oxygen, cholesterol, bilirubin, ketones, fatty acids, lipoproteins, albumin, urea, creatinine, white blood cells, red blood cells, hemoglobin, oxygenated hemoglobin, carboxyhemoglobin, organic molecules, inorganic molecules, pharmaceuticals, cytochrome, various proteins and chromophores, microcalcifications, electrolytes, sodium, potassium, chloride, bicarbonate, and hormones. As used herein, the term “material sample” (or, alternatively, “sample”) is a broad term and is used in its ordinary sense and includes, without limitation, any collection of material which is suitable for analysis. For example, a material sample may comprise whole blood, blood components (e.g., plasma or serum), interstitial fluid, intercellular fluid, saliva, urine, sweat and/or other organic or inorganic materials, or derivatives of any of these materials. In one embodiment, whole blood or blood components may be drawn from a patient&#39;s capillaries.  
      In one embodiment, sample preparation unit  332  separates blood plasma from a whole blood sample or removes contaminants from a blood sample and thus comprises one or more devices including, but not limited to, a filter, membrane, centrifuge, or some combination thereof. In alternative embodiments, analyte detection system  334  is adapted to analyze the sample directly and sample preparation unit  332  is not required.  
      Generally, sampling assembly  220  and sampling unit  200  direct the fluid drawn from sampling assembly  220  into passageway  113  into sample analysis device  330 .  FIG. 4  is a schematic of an embodiment of a sampling unit  400  that permits some of the sample to bypass sample analysis device  330 . Sampling unit  400  may be generally similar to sampling unit  200 , except as further detailed below. Sampling unit  400  includes bubble sensor  321 , valve  323 , sample analysis device  330 , waste line  324 , waste receptacle  325 , valve  326 , pump line  327 , pump  328 , a valve  322 , and a waste line  329 . Waste line  329  includes valve  322  and forms a “T” at pump line  337  and waste line  329 . Valves  316 ,  322 ,  323 , and  326  permit a flow through passageway  113  to be routed through sample analysis device  330 , to be routed to waste receptacle  325 , or to be routed through waste line  324  to waste receptacle  325 .  
       FIG. 5  is a schematic of one embodiment of a sampling system  500  which may be generally similar to the embodiments of sampling system  100  or  300  as illustrated in  FIGS. 1 through 4 , except as further detailed below. Sampling system  500  includes an embodiment of a sampling unit  510  and differs from sampling system  300  in part, in that liquid drawn from passageway  111  may be returned to passageway  111  at a junction  502  between pump  203  and connector  120 .  
      With reference to  FIG. 5 , sampling unit  510  includes a return line  503  that intersects passageway  111  on the opposite side of pump  203  from passageway  113 , a bubble sensor  505  and a pressure sensor  507 , both of which are controlled by controller  210 . Bubble sensor  505  is generally similar to bubble sensors  314   a ,  314   b  and  321  and pressure sensor  507  is generally similar to pressure sensor  317 . Pressure sensor  507  is useful in determining the correct operation of sampling system  500  by monitoring pressure in passageway  111 . Thus, for example, the pressure in passageway  111  is related to the pressure at catheter  11  when pressure sensor  507  is in fluid communication with catheter  11  (that is, when any intervening valve(s) are open). The output of pressure sensor  507  is used in a manner similar to that of pressure sensor  317  described previously in controlling pumps of sampling system  500 .  
      Sampling unit  510  includes valves  501 ,  326   a , and  326   b  under the control of controller  210 . Valve  501  provides additional liquid flow control between sampling unit  200  and sampling unit  510 . Pump  328  is preferably a bi-directional pump that can draw fluid from and into passageway  113 . Fluid may either be drawn from and returned to passageway  501 , or may be routed to waste receptacle  325 . Valves  326   a  and  326   b  are situated on either side of pump  328 . Fluid can be drawn through passageway  113  and into return line  503  by the coordinated control of pump  328  and valves  326   a  and  326   b . Directing flow from return line  503  can be used to prime sampling system  500  with fluid. Thus, for example, liquid may be pulled into sampling unit  510  by operating pump  328  to pull liquid from passageway  113  while valve  326   a  is open and valve  326   b  is closed. Liquid may then be pumped back into passageway  113  by operating pump  328  to push liquid into passageway  113  while valve  326   a  is closed and valve  326   b  is open.  
       FIG. 6A  is a schematic of an embodiment of gas injector manifold  315  which may be generally similar or included within the embodiments illustrated in  FIGS. 1 through 5 , except as further detailed below. Gas injector manifold  315  is a device that injects one or more bubbles in a liquid within passageway  113  by opening valves to the atmosphere and lowering the liquid pressure within the manifold to draw in air. As described subsequently, gas injector manifold  315  facilitates the injection of air or other gas bubbles into a liquid within passageway  113 . Gas injector manifold  315  has three gas injectors  610  including a first injector  610   a , a second injector  610   b , and a third injector  610   c . Each injector  610  includes a corresponding passageway  611  that begins at one of several laterally spaced locations along passageway  113  and extends through a corresponding valve  613  and terminates at a corresponding end  615  that is open to the atmosphere. In an alternative embodiment, a filter is placed in end  615  to filter out dust or particles in the atmosphere. As described subsequently, each injector  610  is capable of injecting a bubble into a liquid within passageway  113  by opening the corresponding valve  613 , closing a valve on one end of passageway  113  and operating a pump on the opposite side of the passageway to lower the pressure and pull atmospheric air into the fluid. In one embodiment of gas injector manifold  315 , passageways  113  and  611  are formed within a single piece of material (e.g., as bores formed in or through a plastic or metal housing (not shown)). In an alternative embodiment, gas injector manifold  315  includes fewer than three injectors, for example one or two injectors, or includes more than three injectors. In another alternative embodiment, gas injector manifold  315  includes a controllable high pressure source of gas for injection into a liquid in passageway  113 . It is preferred that valves  613  are located close to passageway  113  to minimize trapping of fluid in passageways  611 .  
      Importantly, gas injected into passageways  20  should be prevented from reaching catheter  11 . As a safety precaution, one embodiment prevents gas from flowing towards catheter  11  by the use of bubble sensor  314   a  as shown, for example, in  FIG. 3 . If bubble sensor  314   a  detects gas within passageway  111 , then one of several alternative embodiments prevents unwanted gas flow. In one embodiment, flow in the vicinity of sampling assembly  220  is directed into line  113  or through line  113  into waste receptacle  325 . With further reference to  FIG. 3 , upon the detection of gas by bubble sensor  314   a , valves  316  and  323   a  are opened, valve  313  and the valves  613   a ,  613   b  and  613   c  of gas injector manifold  315  are closed, and pump  328  is turned on to direct flow away from the portion of passageway  111  between sampling assembly  220  and patient P into passageway  113 . Bubble sensor  321  is monitored to provide an indication of when passageway  113  clears out. Valve  313  is then opened, valve  312  is closed, and the remaining portion of passageway  111  is then cleared. Alternatively, all flow is immediately halted in the direction of catheter  11 , for example by closing all valves and stopping all pumps. In an alternative embodiment of sampling assembly  220 , a gas-permeable membrane is located within passageway  113  or within gas injector manifold  315  to remove unwanted gas from fluid handling system  10 , e.g., by venting such gas through the membrane to the atmosphere or a waste receptacle.  
       FIG. 6B  is a schematic of an embodiment of gas injector manifold  315 ′ which may be generally similar to, or included within, the embodiments illustrated in  FIGS. 1 through 6 A, except as further detailed below. In gas injector manifold  315 ′, air line  615  and passageway  113  intersect at junction  318 . Bubbles are injected by opening valve  316  and  613  while drawing fluid into passageway  113 . Gas injector manifold  315 ′ is thus more compact that gas injector manifold  315 , resulting in a more controllable and reliable gas generator.  
      Section II—Fluid Handling Methods  
      One embodiment of a method of using fluid handling system  10 , including sampling assembly  220  and sampling unit  200  of  FIGS. 2, 3  and  6 A, is illustrated in Table 1 and in the schematic fluidic diagrams of  FIGS. 7A-7J . In general, the pumps and valves are controlled to infuse a patient, to extract a sample from the patient up passageway  111  to passageway  113 , and to direct the sample along passageway  113  to device  330 . In addition, the pumps and valves are controlled to inject bubbles into the fluid to isolate the fluid from the diluting effect of previous fluid and to clean the lines between sampling. The valves in  FIGS. 7A-7J  are labeled with suffices to indicate whether the valve is open or closed. Thus a valve “x,” for example, is shown as valve “x-o” if the valve is open and “x-c” if the valve is closed.  
               TABLE 1                          Methods of operating system 10 as illustrated in FIGS. 7A-7J                                                                     Pump   Pump   Valve   Valve   Valve   Valve   Valve   Valve   Valve   Valve       Mode   Step   203   328   312   313   613a   613b   613c   316   323a   323b               Infuse   ( FIG. 7A )   F   Off   O   O   C   C   C   C   C   C       patient   Infuse patient                                                     Sample   ( FIG. 7B )   R   Off   C   O   one or more   C   C   C       patient   Clear fluid from                   are open                                                                 passageways                   O   O   O                       ( FIG. 7C )   R   Off   O   O   C   C   C   C   C   C           Draw sample until           after colorimetric           sensor 311 senses           blood           ( FIG. 7D )   Off   On   O   C   C   C   C   O   C   O           Inject sample into           bubble manifold           Alternative to   R   On   O   O   C   C   C   O   C   O                                                                     ( FIG. 7E )   Off   On   C   C   sequentially   O   C   O                                                                 Inject bubbles                   O   O   O                       ( FIG. 7F )   F   Off   C   O   C   C   C   O   O   C           Clear bubbles           from patient line           ( FIG. 7G )   F   Off   O   O   C   C   C   C   C   C           Clear blood from           patient line           ( FIG. 7H )   F   Off   C   O   C   C   C   O   O   C           Move bubbles out           of bubbler                                                         ( FIG. 7I ) Add   Off   On   C   C   sequentialy   O   C   O                                                                 cleaning bubbles                   O   O   O                       ( FIG. 7J ) Push   F   Off   C   O   C   C   C   O   O   C           sample to analyzer           until bubble sensor           321 detects bubble                         F = Forward (fluid into patient),                R = Reverse (fluid from patient),                O = Open,                C = Closed             
 
       FIG. 7A  illustrates one embodiment of a method of infusing a patient. In the step of  FIG. 7A , pump  203  is operated forward (pumping towards the patient) pump  328  is off, or stopped, valves  313  and  312  are open, and valves  613   a ,  613   b ,  613   c ,  316 ,  323   a , and  323   b  are closed. With these operating conditions, fluid  14  is provided to patient P. In a preferred embodiment, all of the other passageways at the time of the step of  FIG. 7A  substantially contain fluid  14 .  
      The next nine figures ( FIGS. 7B-7J ) illustrate steps in a method of sampling from a patient. The following steps are not meant to be inclusive of all of the steps of sampling from a patient, and it is understood that alternative embodiments may include more steps, fewer steps, or a different ordering of steps.  FIG. 7B  illustrates a first sampling step, where liquid is cleared from a portion of patient connection passageway and sampling passageways  112  and  113 . In the step of  FIG. 7B , pump  203  is operated in reverse (pumping away from the patient), pump  328  is off, valve  313  is open, one or more of valves  613   a ,  613   b , and  613   c  are open, and valves  312 ,  316 ,  323   a , and  326   b  are closed. With these operating conditions, air  701  is drawn into sampling passageway  113  and back into patient connection passageway  112  until bubble sensor  314   b  detects the presence of the air.  
       FIG. 7C  illustrates a second sampling step, where a sample is drawn from patient P into patient connection passageway  112 . In the step of  FIG. 7C , pump  203  is operated in reverse, pump  328  is off, valves  312  and  313  are open, and valves  316 ,  613   a ,  613   b ,  613   c ,  323   a , and  323   b  are closed. Under these operating conditions, a sample S is drawn into passageway  112 , dividing air  701  into air  701   a  within sampling passageway  113  and air  701   b  within the patient connection passageway  112 . Preferably this step proceeds until sample S extends just past the junction of passageways  112  and  113 . In one embodiment, the step of  FIG. 7C  proceeds until variations in the output of calorimetric sensor  311  indicate the presence of a blood (for example by leveling off to a constant value), and then proceeds for an additional set amount of time to ensure the presence of a sufficient volume of sample S.  
       FIG. 7D  illustrates a third sampling step, where a sample is drawn into sampling passageway  113 . In the step of  FIG. 7D , pump  203  is off, or stopped, pump  328  is on, valves  312 ,  316 , and  326   b  are open, and valves  313 ,  613   a ,  613   b ,  613   c  and  323   a  are closed. Under these operating conditions, blood is drawn into passageway  113 . Preferably, pump  328  is operated to pull a sufficient amount of sample S into passageway  113 . In one embodiment, pump  328  draws a sample S having a volume from 30 to 50 microliters. In an alternative embodiment, the sample is drawn into both passageways  112  and  113 . Pump  203  is operated in reverse, pump  328  is on, valves  312 ,  313 ,  316 , and  323   b  are open, and valves  613   a ,  613   b ,  613   c  and  323   a  are closed to ensure fresh blood in sample S.  
       FIG. 7E  illustrates a fourth sampling step, where air is injected into the sample. Bubbles which span the cross-sectional area of sampling passageway  113  are useful in preventing contamination of the sample as it is pumped along passageway  113 . In the step of  FIG. 7E , pump  203  is off, or stopped, pump  328  is on, valves  316 , and  323   b  are open, valves  312 ,  313  and  323   a  are closed, and valves  613   a ,  613   b ,  613   c  are each opened and closed sequentially to draw in three separated bubbles. With these operating conditions, the pressure in passageway  113  falls below atmospheric pressure and air is drawn into passageway  113 . Alternatively, valves  613   a ,  613   b ,  613   c  may be opened simultaneously for a short period of time, generating three spaced bubbles. As shown in  FIG. 7E , injectors  610   a ,  610   b , and  610   c  inject bubbles  704 ,  703 , and  702 , respectively, dividing sample S into a forward sample S 1 , a middle sample S 2 , and a rear sample S 3 .  
       FIG. 7F  illustrates a fifth sampling step, where bubbles are cleared from patient connection passageway  112 . In the step of  FIG. 7F , pump  203  is operated in a forward direction, pump  328  is off, valves  313 ,  316 , and  323   a  are open, and valves  312 ,  613   a ,  613   b ,  613   c , and  323   b  are closed. With these operating conditions, the previously injected air  701   b  is drawn out of first passageway  111  and into second passageway  113 . This step proceeds until air  701   b  is in passageway  113 .  
       FIG. 7G  illustrates a sixth sampling step, where blood in passageway  112  is returned to the patient. In the step of  FIG. 7G , pump  203  is operated in a forward direction, pump  328  is off, valves  312  and  313  are open, and valves  316 ,  323   a ,  613   a ,  613   b ,  613   c  and  323   b  are closed. With these operating conditions, the previously injected air remains in passageway  113  and passageway  111  is filled with fluid  14 .  
       FIGS. 7H and 7I  illustrates a seventh and eighth sampling steps, where the sample is pushed part way into passageway  113  followed by fluid  14  and more bubbles. In the step of  FIG. 7H , pump  203  is operated in a forward direction, pump  328  is off, valves  313 ,  316 , and  323   a  are open, and valves  312 ,  613   a ,  613   b ,  613   c , and  323   b  are closed. With these operating conditions, sample S is moved partway into passageway  113  with bubbles injected, either sequentially or simultaneously, into fluid  14  from injectors  610   a ,  610   b , and  610   c . In the step of  FIG. 7I , the pumps and valves are operated as in the step of  FIG. 7E , and fluid  14  is divided into a forward solution C 1 , a middle solution C 2 , and a rear solution C 3  separated by bubbles  705 ,  706 , and  707 .  
      The last step shown in  FIG. 7  is  FIG. 7J , where middle sample S 2  is pushed to sample analysis device  330 . In the step of  FIG. 7J , pump  203  is operated in a forward direction, pump  328  is off, valves  313 ,  316 , and  323   a  are open, and valves  312 ,  613   a ,  613   b ,  613   c , and  323   b  are closed. In this configuration, the sample is pushed into passageway  113 . When bubble sensor  321  detects bubble  702 , pump  203  continues pumping until sample S 2  is taken into device sample analysis  330 . Additional pumping using the settings of the step of  FIG. 7J  permits the sample S 2  to be analyzed and for additional bubbles and solutions to be pushed into waste receptacle  325 , cleansing passageway  113  prior to accepting a next sample.  
      Section III—Sampling System  
       FIG. 8  is a perspective front view of a third embodiment of a sampling system  800  which may be generally similar to sampling system  100 ,  300  or  500  and the embodiments illustrated in  FIGS. 1 through 7 , except as further detailed below. The fluid handling and analysis apparatus  140  of sampling system  800  includes the combination of an instrument  810  and a sampling system cassette  820 .  FIG. 8  illustrates instrument  810  and cassette  820  partially removed from each other. Instrument  810  includes controller  210  (not shown), display  141  and input devices  143 , a cassette interface  811 , and lines  114 . Cassette  820  includes passageway  111  which extends from connector  120  to connector  230 , and further includes passageway  113 , a junction  829  of passageways  111  and  113 , an instrument interface  821 , a front surface  823 , an inlet  825  for passageway  111 , and an inlet  827  for passageways  111  and  113 . In addition, sampling assembly  220  is formed from a sampling assembly instrument portion  813  having an opening  815  for accepting junction  829 . The interfaces  811  and  821  engage the components of instrument  810  and cassette  820  to facilitate pumping fluid and analyzing samples from a patient, and sampling assembly instrument portion  813  accepts junction  829  in opening  815  to provide for sampling from passageway  111 .  
       FIGS. 9 and 10  are front views of a sampling system cassette  820  and instrument  810 , respectively, of a sampling system  800 . Cassette  820  and instrument  810 , when assembled, form various components of  FIGS. 9 and 10  that cooperate to form an apparatus consisting of sampling unit  510  of  FIG. 5 , sampling assembly  220  of  FIG. 3 , and gas injection manifold  315 ′ of  FIG. 6B .  
      More specifically, as shown in  FIG. 9 , cassette  820  includes passageways  20  including: passageway  111  having portions  111   a ,  112   a ,  112   b ,  112   c ,  112   d ,  112   e , and  112   f ; passageway  113  having portions  113   a ,  113   b ,  113   c ,  113   d ,  113   e , and  113   f ; passageway  615 ; waste receptacle  325 ; disposable components of sample analysis device  330  including, for example, a sample preparation unit  332  adapted to allow only blood plasma to pass therethrough and a sample chamber  903  for placement within analyte detection system  334  for measuring properties of the blood plasma; and a displacement pump  905  having a piston control  907 .  
      As shown in  FIG. 10 , instrument  810  includes bubble sensor units  1001   a ,  1001   b , and  1001   c , calorimetric sensor, which is a hemoglobin sensor unit  1003 , a peristaltic pump roller  1005   a  and a roller support  1005   b , pincher pairs  1007   a ,  1007   b ,  1007   c ,  1007   d ,  1007   e ,  1007   f ,  1007   g , and  1007   h , an actuator  1009 , and a pressure sensor unit  1011 . In addition, instrument  810  includes portions of sample analysis device  330  which are adapted to measure a sample contained within sample chamber  903  when located near or within a probe region  1002  of an optical analyte detection system  334 .  
      Passageway portions of cassette  820  contact various components of instrument  810  to form sampling system  800 . With reference to  FIG. 5  for example, pump  203  is formed from portion  111   a  placed between peristaltic pump roller  1005   a  and roller support  1005   b  to move fluid through passageway  111  when the roller is actuated; valves  501 ,  323 ,  326   a , and  326   b  are formed with pincher pairs  1007   a ,  1007   b ,  1007   c , and  1007   d  surrounding portions  113   a ,  113   c ,  113   d , and  113   e , respectively, to permit or block fluid flow therethrough. Pump  328  is formed from actuator  1009  positioned to move piston control  907 . It is preferred that the interconnections between the components of cassette  820  and instrument  810  described in this paragraph are made with one motion. Thus for example the placement of interfaces  811  and  821  places the passageways against and/or between the sensors, actuators, and other components.  
      In addition to placement of interface  811  against interface  821 , the assembly of apparatus  800  includes assembling sampling assembly  220 . More specifically, an opening  815   a  and  815   b  are adapted to receive passageways  111  and  113 , respectively, with junction  829  within sampling assembly instrument portion  813 . Thus, for example, with reference to  FIG. 3 , valves  313  and  312  are formed when portions  112   b  and  112   c  are placed within pinchers of pinch valves  1007   e  and  1007   f , respectively, bubble sensors  314   b  and  314   a  are formed when bubble sensor units  1001   b , and  1001   c  are in sufficient contact with portions  112   a  and  112   d , respectively, to determine the presence of bubbles therein; hemoglobin detector is formed when hemoglobin sensor  1003  is in sufficient contact with portion  112   e , and pressure sensor  317  is formed when portion  112   f  is in sufficient contact with pressure sensor unit  1011  to measure the pressure of a fluid therein. With reference to  FIG. 6B , valves  316  and  613  are formed when portions  113   f  and  615  are placed within pinchers of pinch valves  1007   h  and  1007   g , respectively.  
      In operation, the assembled main instrument  810  and cassette  820  of  FIGS. 9-10  can function as follows. The system can be considered to begin in an idle state or infusion mode in which the roller pump  1005  operates in a forward direction (with the impeller  1005   a  turning counterclockwise as shown in  FIG. 10 ) to pump infusion fluid from the container  15  through the passageway  111  and the passageway  112 , toward and into the patient P. In this infusion mode the pump  1005  delivers infusion fluid to the patient at a suitable infusion rate as discussed elsewhere herein.  
      When it is time to conduct a measurement, air is first drawn into the system to clear liquid from a portion of the passageways  112 ,  113 , in a manner similar to that shown in  FIG. 7B . Here, the single air injector of  FIG. 9  (extending from the junction  829  to end  615 , opposite the passageway  813 ) functions in place of the manifold shown in  FIGS. 7A-7J . Next, to draw a sample, the pump  1005  operates in a sample draw mode, by operating in a reverse direction and pulling a sample of bodily fluid (e.g. blood) from the patient into the passageway  112  through the connector  230 . The sample is drawn up to the hemoglobin sensor  1003 , and is preferably drawn until the output of the sensor  1003  reaches a desired plateau level indicating the presence of an undiluted blood sample in the passageway  112  adjacent the sensor  1003 .  
      From this point the pumps  905 ,  1005 , valves  1007   e ,  1007   f ,  1007   g ,  1007   h , bubble sensors  1001   b ,  1001   c  and/or hemoglobin sensor  1003  can be operated to move a series of air bubbles and sample-fluid columns into the passageway  113 , in a manner similar to that shown in  FIGS. 7D-7F . The pump  905 , in place of the pump  328 , is operable by moving the piston control  907  of the pump  905  in the appropriate direction (to the left or right as shown in  FIGS. 9-10 ) with the actuator  1009 .  
      Once a portion of the bodily fluid sample and any desired bubbles have moved into the passageway  113 , the valve  1007   h  can be closed, and the remainder of the initial drawn sample or volume of bodily fluid in the passageway  112  can be returned to the patient, by operating the pump  1005  in the forward or infusion direction until the passageway  112  is again filled with infusion fluid.  
      With appropriate operation of the valves  1007   a - 1007   h , and the pump(s)  905  and/or  1005 , at least a portion of the bodily fluid sample in the passageway  113  (which is 10-100 microliters in volume, or 20, 30, 40, 50 or 60 microliters, in various embodiments) is moved through the sample preparation unit  332  (in the depicted embodiment a filter or membrane; alternatively a centrifuge as discussed in greater detail below). Thus, only one or more components of the bodily fluid (e.g., only the plasma of a blood sample) passes through the unit  332  or filter/membrane and enters the sample chamber or cell  903 . Alternatively, where the unit  332  is omitted, the “whole” fluid moves into the sample chamber  903  for analysis.  
      Once the component(s) or whole fluid is in the sample chamber  903 , the analysis is conducted to determine a level or concentration of one or more analytes, such as glucose, lactate, carbon dioxide, blood urea nitrogen, hemoglobin, and/or any other suitable analytes as discussed elsewhere herein. Where the analyte detection system  1700  is spectroscopic (e.g. the system  1700  of  FIG. 17  or  44 - 46 ), a spectroscopic analysis of the component(s) or whole fluid is conducted.  
      After the analysis, the body fluid sample within the passageway  113  is moved into the waste receptacle  325 . Preferably, the pump  905  is operated via the actuator  1009  to push the body fluid, behind a column of saline or infusion fluid obtained via the passageway  909 , back through the sample chamber  903  and sample preparation unit  332 , and into the receptacle  325 . Thus, the chamber  903  and unit  332  are back-flushed and filled with saline or infusion fluid while the bodily fluid is delivered to the waste receptacle. Following this flush a second analysis can be made on the saline or infusion fluid now in the chamber  903 , to provide a “zero” or background reading. At this point, the fluid handling network of  FIG. 9 , other than the waste receptacle  325 , is empty of bodily fluid, and the system is ready to draw another bodily fluid sample for analysis.  
      In some embodiments of the apparatus  140 , a pair of pinch valve pinchers acts to switch flow between one of two branches of a passageway.  FIGS. 13A and 13B  are front view and sectional view, respectively, of a first embodiment pinch valve  1300  in an open configuration that can direct flow either one or both of two branches, or legs, of a passageway. Pinch valve  1300  includes two separately controllable pinch valves acting on a “Y” shaped passageway  1310  to allow switch of fluid between various legs. In particular, the internal surface of passageway  1310  forms a first leg  1311  having a flexible pinch region  1312 , a second leg  1313  having a flexible pinch region  1314 , and a third leg  1315  that joins the first and second legs at an intersection  1317 . A first pair of pinch valve pinchers  1320  is positioned about pinch region  1312  and a second pair of pinch valve pinchers  1330  is positioned about pinch region  1314 . Each pair of pinch valve pinchers  1320  and  1330  is positioned on opposite sides of their corresponding pinch regions  1312 ,  1314  and perpendicular to passageway  1310 , and are individually controllable by controller  210  to open and close, that is allow or prohibit fluid communication across the pinch regions. Thus, for example, when pinch valve pinchers  1320  (or  1330 ) are brought sufficiently close, each part of pinch region  1312  (or  1314 ) touches another part of the pinch region and fluid may not flow across the pinch region.  
      As an example of the use of pinch valve  1300 ,  FIG. 13B  shows the first and second pair of pinch valve pinchers  1320 ,  1330  in an open configuration.  FIG. 13C  is a sectional view showing the pair of pinch valve pinchers  1320  brought together, thus closing off a portion of first leg  1311  from the second and third legs  1313 ,  1315 . In part as a result of the distance between pinchers  1320  and intersection  1317  there is a volume  1321  associated with first leg  1311  that is not isolated (“dead space”). It is preferred that dead space is minimized so that fluids of different types can be switched between the various legs of the pinch valve. In one embodiment, the dead space is reduced by placing the placing the pinch valves close to the intersection of the legs. In another embodiment, the dead space is reduced by having passageway walls of varying thickness. Thus, for example, excess material between the pinch valves and the intersection will more effectively isolate a valved leg by displacing a portion of volume  1321 .  
      As an example of the use of pinch valve  1300  in sampling system  300 , pinchers  1320  and  1330  are positioned to act as valve  323  and  326 , respectively.  
       FIGS. 14A and 14B  are various views of a second embodiment pinch valve  1400 , where  FIG. 14A  is a front view and  FIG. 14B  is a sectional view showing one valve in a closed position. Pinch valve  1400  differs from pinch valve  1300  in that the pairs of pinch valve pinchers  1320  and  1330  are replaced by pinchers  1420  and  1430 , respectively, that are aligned with passageway  1310 .  
      Alternative embodiment of pinch valves includes 2, 3, 4, or more passageway segments that meet at a common junction, with pinchers located at one or more passageways near the junction.  
       FIGS. 11 and 12  illustrate various embodiment of connector  230  which may also form or be attached to disposable portions of cassette  820  as one embodiment of an arterial patient connector  1100  and one embodiment a venous patient connector  1200 . Connectors  1100  and  1200  may be generally similar to the embodiment illustrated in  FIGS. 1-10 , except as further detailed below.  
      As shown in  FIG. 11 , arterial patient connector  1100  includes a stopcock  1101 , a first tube portion  1103  having a length X, a blood sampling port  1105  to acquire blood samples for laboratory analysis, and fluid handling and analysis apparatus  140 , a second tube  1107  having a length Y, and a tube connector  1109 . Arterial patient connector  1100  also includes a pressure sensor unit  1102  that is generally similar to pressure sensor unit  1011 , on the opposite side of sampling assembly  220 . Length X is preferably from to 6 inches (0.15 meters) to 50 inches (1.27 meters) or approximately 48 inches (1.2 meters) in length. Length Y is preferably from 1 inch (25 millimeters) to 20 inches (0.5 meters), or approximately 12 inches (0.3 meters) in length. As shown in  FIG. 12 , venous patient connector  1200  includes a clamp  1201 , injection port  1105 , and tube connector  1109 .  
      Section IV—Sample Analysis System  
      In several embodiments, analysis is performed on blood plasma. For such embodiments, the blood plasma must be separated from the whole blood obtained from the patient. In general, blood plasma may be obtained from whole blood at any point in fluid handling system  10  between when the blood is drawn, for example at patient connector  110  or along passageway  113 , and when it is analyzed. For systems where measurements are preformed on whole blood, it may not be necessary to separate the blood at the point of or before the measurements is performed.  
      For illustrative purposes, this section describes several embodiments of separators and analyte detection systems which may form part of system  10 . The separators discussed in the present specification can, in certain embodiments, comprise fluid component separators. As used herein, the term “fluid component separator” is a broad term and is used in its ordinary sense and includes, without limitation, any device that is operable to separate one or more components of a fluid to generate two or more unlike substances. For example, a fluid component separator can be operable to separate a sample of whole blood into plasma and non-plasma components, and/or to separate a solid-liquid mix (e.g. a solids-contaminated liquid) into solid and liquid components. A fluid component separator need not achieve complete separation between or among the generated unlike substances. Examples of fluid component separators include filters, membranes, centrifuges, electrolytic devices, or components of any of the foregoing. Fluid component separators can be “active” in that they are operable to separate a fluid more quickly than is possible through the action of gravity on a static, “standing” fluid. Section IV.A below discloses a filter which can be used as a blood separator in certain embodiments of the apparatus disclosed herein. Section IV.B below discloses an analyte detection system which can be used in certain embodiments of the apparatus disclosed herein. Section IV.C below discloses a sample element which can be used in certain embodiments of the apparatus disclosed herein. Section IV.D below discloses a centrifuge and sample chamber which can be used in certain embodiments of the apparatus disclosed herein.  
      Section IV.A—Blood Filter  
      Without limitation as to the scope of the present disclosure, one embodiment of sample preparation unit  332  is shown as a blood filter  1500 , as illustrated in  FIGS. 15 and 16 , where  FIG. 15  is a side view of one embodiment of a filter, and  FIG. 16  is an exploded perspective view of the filter.  
      As shown in the embodiment of  FIG. 15 , filter  1500  that includes a housing  1501  with an inlet  1503 , a first outlet  1505  and a second outlet  1507 . Housing  1501  contains a membrane  1509  that divides the internal volume of housing  1501  into a first volume  1502  that include inlet  1503  and first outlet  1505  and a second volume  1504 .  FIG. 16  shows one embodiment of filter  1500  as including a first plate  1511  having inlet  1503  and outlet  1505 , a first spacer  1513  having an opening forming first volume  1502 , a second spacer  1515  having an opening forming second volume  1504 , and a second plate  1517  having outlet  1507 .  
      Filter  1500  provides for a continuous filtering of blood plasma from whole blood. Thus, for example, when a flow of whole blood is provided at inlet  1503  and a slight vacuum is applied to the second volume  1504  side of membrane  1509 , the membrane filters blood cells and blood plasma passes through second outlet  1507 . Preferably, there is transverse blood flow across the surface of membrane  1509  to prevent blood cells from clogging filter  1500 . Accordingly, in one embodiment of the inlet  1503  and first outlet  1505  may be configured to provide the transverse flow across membrane  1509 .  
      In one embodiment, membrane  1509  is a thin and strong polymer film. For example, the membrane filter may be a 10 micron thick polyester or polycarbonate film. Preferably, the membrane filter has a smooth glass-like surface, and the holes are uniform, precisely sized, and clearly defined. The material of the film may be chemically inert and have low protein binding characteristics.  
      One way to manufacture membrane  1509  is with a Track Etching process. Preferably, the “raw” film is exposed to charged particles in a nuclear reactor, which leaves “tracks” in the film. The tracks may then be etched through the film, which results in holes that are precisely sized and uniformly cylindrical. For example, GE Osmonics, Inc. (4636 Somerton Rd. Trevose, Pa. 19053-6783) utilizes a similar process to manufacture a material that adequately serves as the membrane filter. The surface the membrane filter depicted above is a GE Osmonics Polycarbonate TE film.  
      As one example of the use of filter  1500 , the plasma from 3 cc of blood may be extracted using a polycarbonate track etch film (“PCTE”) as the membrane filter. The PCTE may have a pore size of 2 μm and an effective area of 170 millimeter 2 . Preferably, the tubing connected to the supply, exhaust and plasma ports has an internal diameter of 1 millimeter. In one embodiment of a method employed with this configuration, 100 μl of plasma can be initially extracted from the blood. After saline is used to rinse the supply side of the cell, another 100 μl of clear plasma can be extracted. The rate of plasma extraction in this method and configuration can be about 15-25 μl/min.  
      Using a continuous flow mechanism to extract plasma may provide several benefits. In one preferred embodiment, the continuous flow mechanism is reusable with multiple samples, and there is negligible sample carryover to contaminate subsequent samples. One embodiment may also eliminate most situations in which plugging may occur. Additionally, a preferred configuration provides for a low internal volume.  
      Additional information on filters, methods of use thereof, and related technologies may be found in U.S. patent application Publication No. 2005/0038357, published on Feb. 17, 2005, titled SAMPLE ELEMENT WITH BARRIER MATERIAL; and U.S. patent application Ser. No. 11/122,794, filed on May 5, 2005, titled SAMPLE ELEMENT WITH SEPARATOR. The entire contents of the above noted publication and patent application are hereby incorporated by reference herein and made a part of this specification.  
      Section IV.B—Analyte Detection System  
      One embodiment of analyte detection system  334 , which is not meant to limit the scope of the present disclosure, is shown in  FIG. 17  as an optical analyte detection system  1700 . Analyte detection system  1700  is adapted to measure spectra of blood plasma. The blood plasma provided to analyte detection system  334  may be provided by sample preparation unit  332 , including but not limited to a filter  1500 .  
      Analyte detection system  1700  comprises an energy source  1720  disposed along a major axis X of system  1700 . When activated, the energy source  1720  generates an energy beam E which advances from the energy source  1720  along the major axis X. In one embodiment, the energy source  1720  comprises an infrared source and the energy beam E comprises an infrared energy beam.  
      The energy beam E passes through an optical filter  1725  also situated on the major axis X, before reaching a probe region  1710 . Probe region  1710  is portion of apparatus  322  in the path of an energized beam E that is adapted to accept a material sample S. In one embodiment, as shown in  FIG. 17 , probe region  1710  is adapted to accept a sample element or cuvette  1730 , which supports or contains the material sample S. In one embodiment of the present disclosure, sample element  1730  is a portion of passageway  113 , such as a tube or an optical cell. After passing through the sample element  1730  and the sample S, the energy beam E reaches a detector  1745 .  
      As used herein, “sample element” is a broad term and is used in its ordinary sense and includes, without limitation, structures that have a sample chamber and at least one sample chamber wall, but more generally includes any of a number of structures that can hold, support or contain a material sample and that allow electromagnetic radiation to pass through a sample held, supported or contained thereby; e.g., a cuvette, test strip, etc.  
      In one embodiment, sample element  1730  forms a disposable portion of cassette  820 , and the remaining portions of system  1700  form portions of instrument  810 , and probe region  1710  is probe region  1002 .  
      With further reference to  FIG. 17 , the detector  1745  responds to radiation incident thereon by generating an electrical signal and passing the signal to processor  210  for analysis. Based on the signal(s) passed to it by the detector  1745 , the processor computes the concentration of the analyte(s) of interest in the sample S, and/or the absorbance/transmittance characteristics of the sample S at one or more wavelengths or wavelength bands employed to analyze the sample. The processor  210  computes the concentration(s), absorbance(s), transmittance(s), etc. by executing a data processing algorithm or program instructions residing within memory  212  accessible by the processor  210 .  
      In the embodiment shown in  FIG. 17 , the filter  1725  may comprise a varying-passband filter, to facilitate changing, over time and/or during a measurement taken with apparatus  322 , the wavelength or wavelength band of the energy beam E that may pass the filter  1725  for use in analyzing the sample S. (In various other embodiments, the filter  1725  may be omitted altogether.) Some examples of a varying-passband filter usable with apparatus  322  include, but are not limited to, a filter wheel (discussed in further detail below), an electronically tunable filter, such as those manufactured by Aegis Semiconductor (Woburn, Mass.), a custom filter using an “Active Thin Films platform,” a Fabry-Perot interferometer, such as those manufactured by Scientific Solutions, Inc. (North Chelmsford, Mass.), a custom liquid crystal Fabry-Perot (LCFP) Tunable Filter, or a tunable monochrometer, such as a HORIBA (Jobin Yvon, Inc. (Edison, N.J.) H1034 type with 7-10 μm grating, or a custom designed system.  
      In one embodiment detection system  1700 , filter  1725  comprises a varying-passband filter, to facilitate changing, over time and/or during a measurement taken with the detection system  1700 , the wavelength or wavelength band of the energy beam E that may pass the filter  25  for use in analyzing the sample S. When the energy beam E is filtered with a varying-passband filter, the absorption/transmittance characteristics of the sample S can be analyzed at a number of wavelengths or wavelength bands in a separate, sequential manner. As an example, assume that it is desired to analyze the sample S at N separate wavelengths (Wavelength  1  through Wavelength N). The varying-passband filter is first operated or tuned to permit the energy beam E to pass at Wavelength  1 , while substantially blocking the beam E at most or all other wavelengths to which the detector  1745  is sensitive (including Wavelengths  2 -N). The absorption/transmittance properties of the sample S are then measured at Wavelength  1 , based on the beam E that passes through the sample S and reaches the detector  1745 . The varying-passband filter is then operated or tuned to permit the energy beam E to pass at Wavelength  2 , while substantially blocking other wavelengths as discussed above; the sample S is then analyzed at Wavelength  2  as was done at Wavelength  1 . This process is repeated until all of the wavelengths of interest have been employed to analyze the sample S. The collected absorption/transmittance data can then be analyzed by the processor  210  to determine the concentration of the analyte(s) of interest in the material sample S. The measured spectra of sample S is referred to herein in general as C s (λ i ), that is, a wavelength dependent spectra in which C s  is, for example, a transmittance, an absorbance, an optical density, or some other measure of the optical properties of sample S having values at or about a number of wavelengths λ i , where i ranges over the number of measurements taken. The measurement C s (λ i ) is a linear array of measurements that is alternatively written as Cs i .  
      The spectral region of system  1700  depends on the analysis technique and the analyte and mixtures of interest. For example, one useful spectral region for the measurement of glucose in blood using absorption spectroscopy is the mid-IR (for example, about 4 microns to about 11 microns). In one embodiment system  1700 , energy source  1720  produces a beam E having an output in the range of about 4 microns to about 11 microns. Although water is the main contributor to the total absorption across this spectral region, the peaks and other structures present in the blood spectrum from about 6.8 microns to 10.5 microns are due to the absorption spectra of other blood components. The 4 to 11 micron region has been found advantageous because glucose has a strong absorption peak structure from about 8.5 to 10 microns, whereas most other blood constituents have a low and flat absorption spectrum in the 8.5 to 10 micron range. The main exceptions are water and hemoglobin, both of which are interferents in this region.  
      The amount of spectral detail provided by system  1700  depends on the analysis technique and the analyte and mixture of interest. For example, the measurement of glucose in blood by mid-IR absorption spectroscopy is accomplished with from 11 to 25 filters within a spectral region. In one embodiment system  1700 , energy source  1720  produces a beam E having an output in the range of about 4 microns to about 11 microns, and filter  1725  include a number of narrow band filters within this range, each allowing only energy of a certain wavelength or wavelength band to pass therethrough. Thus, for example, one embodiment filter  1725  includes a filter wheel having 11 filters with a nominal wavelength approximately equal to one of the following: 3 μm, 4.06 μm, 4.6 μm, 4.9 μm, 5.25 μm, 6.12 μm, 6.47 μm, 7.98 μm, 8.35 μm, 9.65 μm, and 12.2 μm.  
      In one embodiment, individual infrared filters of the filter wheel are multi-cavity, narrow band dielectric stacks on germanium or sapphire substrates, manufactured by either OCLI (JDS Uniphase, San Jose, Calif.) or Spectrogon US, Inc. (Parsippany, N.J.). Thus, for example, each filter may nominally be 1 millimeter thick and 10 millimeter square. The peak transmission of the filter stack is typically between 50% and 70%, and the bandwidths are typically between 150 nm and 350 nm with center wavelengths between 4 and 10 μm. Alternatively, a second blocking IR filter is also provided in front of the individual filters. The temperature sensitivity is preferably &lt;0.01% per degree C. to assist in maintaining nearly constant measurements over environmental conditions.  
      In one embodiment, the detection system  1700  computes an analyte concentration reading by first measuring the electromagnetic radiation detected by the detector  1745  at each center wavelength, or wavelength band, without the sample element  1730  present on the major axis X (this is known as an “air” reading). Second, the system  1700  measures the electromagnetic radiation detected by the detector  1745  for each center wavelength, or wavelength band, with the material sample S present in the sample element  1730 , and the sample element and sample S in position on the major axis X (i.e., a “wet” reading). Finally, the processor  210  computes the concentration(s), absorbance(s) and/or transmittances relating to the sample S based on these compiled readings.  
      In one embodiment, the plurality of air and wet readings are used to generate a pathlength corrected spectrum as follows. First, the measurements are normalized to give the transmission of the sample at each wavelength. Using both a signal and reference measurement at each wavelength, and letting S i  represent the signal of detector  1745  at wavelength i and R i  represent the signal of the detector at wavelength i, the transmittance, T i  at wavelength i may computed as T i =S i (wet)/S i (air). Optionally, the spectra may be calculated as the optical density, OD i , as −Log(T i ). Next, the transmission over the wavelength range of approximately 4.5 μm to approximately 5.5 μm is analyzed to determine the pathlength. Specifically, since water is the primary absorbing species of blood over this wavelength region, and since the optical density is the product of the optical pathlength and the known absorption coefficient of water (OD=L σ, where L is the optical pathlength and σ is the absorption coefficient), any one of a number of standard curve fitting procedures may be used to determine the optical pathlength, L from the measured OD. The pathlength may then be used to determine the absorption coefficient of the sample at each wavelength. Alternatively, the optical pathlength may be used in further calculations to convert absorption coefficients to optical density.  
      Blood samples may be prepared and analyzed by system  1700  in a variety of configurations. In one embodiment, sample S is obtained by drawing blood, either using a syringe or as part of a blood flow system, and transferring the blood into sample chamber  903 . In another embodiment, sample S is drawn into a sample container that is a sample chamber  903  adapted for insertion into system  1700 .  
       FIG. 44  depicts another embodiment of the analyte detection system  1700 , which may be generally similar to the embodiment illustrated in  FIG. 17 , except as further detailed below. Where possible, similar elements are identified with identical reference numerals in the depiction of the embodiments of  FIGS. 17 and 44 .  
      The detection system  1700  shown in  FIG. 44  includes a collimator  30  located between source  1720  and filter  1725  and a beam sampling optics  90  between the filter and sample element  1730 . Filter  1725  includes a primary filter  40  and a filter wheel assembly  4420  which can insert one of a plurality of optical filters into energy beam E. System  1700  also includes a sample detector  150  may be generally similar to sample detector  1725 , except as further detailed below.  
      As shown in  FIG. 44 , energy beam E from source  1720  passes through collimator  30  through which the before reaching a primary optical filter  40  which is disposed downstream of a wide end  36  of the collimator  30 . Filter  1725  is aligned with the source  1720  and collimator  30  on the major axis X and is preferably configured to operate as a broadband filter, allowing only a selected band, e.g. between about 2.5 μm and about 12.5 μm, of wavelengths emitted by the source  1720  to pass therethrough, as discussed below. In one embodiment, the energy source  1720  comprises an infrared source and the energy beam E comprises an infrared energy beam. One suitable energy source  1720  is the TOMA TECH™ IR-50 available from HawkEye Technologies of Milford, Conn.  
      With further reference to  FIG. 44 , primary filter  40  is mounted in a mask  44  so that only those portions of the energy beam E which are incident on the primary filter  40  can pass the plane of the mask-primary filter assembly. The primary filter  40  is generally centered on and oriented orthogonal to the major axis X and is preferably circular (in a plane orthogonal to the major axis X) with a diameter of about 8 mm. Of course, any other suitable size or shape may be employed. As discussed above, the primary filter  40  preferably operates as a broadband filter. In the illustrated embodiment, the primary filter  40  preferably allows only energy wavelengths between about 4 μm and about 11 μm to pass therethrough. However, other ranges of wavelengths can be selected. The primary filter  40  advantageously reduces the filtering burden of secondary optical filter(s)  60  disposed downstream of the primary filter  40  and improves the rejection of electromagnetic radiation having a wavelength outside of the desired wavelength band. Additionally, the primary filter  40  can help minimize the heating of the secondary filter(s)  60  by the energy beam E passing therethrough. Despite these advantages, the primary filter  40  and/or mask  44  may be omitted in alternative embodiments of the system  1700  shown in  FIG. 44 .  
      The primary filter  40  is preferably configured to substantially maintain its operating characteristics (center wavelength, passband width) where some or all of the energy beam E deviates from normal incidence by a cone angle of up to about twelve degrees relative to the major axis X. In further embodiments, this cone angle may be up to about 15 to 35 degrees, or from about 15 degrees or 20 degrees. The primary filter  40  may be said to “substantially maintain” its operating characteristics where any changes therein are insufficient to affect the performance or operation of the detection system  1700  in a manner that would raise significant concerns for the user(s) of the system in the context in which the system  1700  is employed.  
      In the embodiment illustrated in  FIG. 44 , filter wheel assembly  4420  includes an optical filter wheel  50  and a stepper motor  70  connected to the filter wheel and configured to generate a force to rotate the filter wheel  50 . Additionally, a position sensor  80  is disposed over a portion of the circumference of the filter wheel  50  and may be configured to detect the angular position of the filter wheel  50  and to generate a corresponding filter wheel position signal, thereby indicating which filter is in position on the major axis X. Alternatively, the stepper motor  70  may be configured to track or count its own rotation(s), thereby tracking the angular position of the filter wheel, and pass a corresponding position signal to the processor  210 . Two suitable position sensors are models EE-SPX302-W2A and EE-SPX402-W2A available from Omron Corporation of Kyoto, Japan.  
      Optical filter wheel  50  is employed as a varying-passband filter, to selectively position the secondary filter(s)  60  on the major axis X and/or in the energy beam E. The filter wheel  50  can therefore selectively tune the wavelength(s) of the energy beam E downstream of the wheel  50 . These wavelength(s) vary according to the characteristics of the secondary filter(s)  60  mounted in the filter wheel  50 . The filter wheel  50  positions the secondary filter(s)  60  in the energy beam E in a “one-at-a-time” fashion to sequentially vary, as discussed above, the wavelengths or wavelength bands employed to analyze the material sample S. An alternative to filter wheel  50  is a linear filter translated by a motor (not shown). The linear filter may be, for example, a linear array of separate filters or a single filter with filter properties that change in a linear dimension.  
      In alternative arrangements, the single primary filter  40  depicted in  FIG. 44  may be replaced or supplemented with additional primary filters mounted on the filter wheel  50  upstream of each of the secondary filters  60 . As yet another alternative, the primary filter  40  could be implemented as a primary filter wheel (not shown) to position different primary filters on the major axis X at different times during operation of the detection system  1700 , or as a tunable filter.  
      The filter wheel  50 , in the embodiment depicted in  FIG. 45 , can comprise a wheel body  52  and a plurality of secondary filters  60  disposed on the body  52 , the center of each filter being equidistant from a rotational center RC of the wheel body. The filter wheel  50  is configured to rotate about an axis which is (i) parallel to the major axis X and (ii) spaced from the major axis X by an orthogonal distance approximately equal to the distance between the rotational center RC and any of the center(s) of the secondary filter(s)  60 . Under this arrangement, rotation of the wheel body  52  advances each of the filters sequentially through the major axis X, so as to act upon the energy beam E. However, depending on the analyte(s) of interest or desired measurement speed, only a subset of the filters on the wheel  50  may be employed in a given measurement run. A home position notch  54  may be provided to indicate the home position of the wheel  50  to a position sensor  80 .  
      In one embodiment, the wheel body  52  can be formed from molded plastic, with each of the secondary filters  60  having, for example a thickness of 1 mm and a 10 mm×10 mm or a 5 mm×5 mm square configuration. Each of the filters  60 , in this embodiment of the wheel body, is axially aligned with a circular aperture of 4 mm diameter, and the aperture centers define a circle of about 1.70 inches diameter, which circle is concentric with the wheel body  52 . The body  52  itself is circular, with an outside diameter of 2.00 inches.  
      Each of the secondary filter(s)  60  is preferably configured to operate as a narrow band filter, allowing only a selected energy wavelength or wavelength band (i.e., a filtered energy beam (Ef) to pass therethrough. As the filter wheel  50  rotates about its rotational center RC, each of the secondary filter(s)  60  is, in turn, disposed along the major axis X for a selected dwell time corresponding to each of the secondary filter(s)  60 .  
      The “dwell time” for a given secondary filter  60  is the time interval, in an individual measurement run of the system  1700 , during which both of the following conditions are true: (i) the filter is disposed on the major axis X; and (ii) the source  1720  is energized. The dwell time for a given filter may be greater than or equal to the time during which the filter is disposed on the major axis X during an individual measurement run. In one embodiment of the analyte detection system  1700 , the dwell time corresponding to each of the secondary filter(s)  60  is less than about 1 second. However, the secondary filter(s)  60  can have other dwell times, and each of the filter(s)  60  may have a different dwell time during a given measurement run.  
      From the secondary filter  60 , the filtered energy beam (Ef) passes through a beam sampling optics  90 , which includes a beam splitter  4400  disposed along the major axis X and having a face  4400   a  disposed at an included angle θ relative to the major axis X. The splitter  4400  preferably separates the filtered energy beam (Ef) into a sample beam (Es) and a reference beam (Er).  
      With further reference to  FIG. 44 , the sample beam (Es) passes next through a first lens  4410  aligned with the splitter  4400  along the major axis X. The first lens  4410  is configured to focus the sample beam (Es) generally along the axis X onto the material sample S. The sample S is preferably disposed in a sample element  1730  between a first window  122  and a second window  124  of the sample element  1730 . The sample element  1730  is further preferably removably disposed in a holder  4430 , and the holder  4430  has a first opening  132  and a second opening  134  configured for alignment with the first window  122  and second window  124 , respectively. Alternatively, the sample element  1730  and sample S may be disposed on the major axis X without use of the holder  4430 .  
      At least a fraction of the sample beam (Es) is transmitted through the sample S and continues onto a second lens  4440  disposed along the major axis X. The second lens  4440  is configured to focus the sample beam (Es) onto a sample detector  150 , thus increasing the flux density of the sample beam (Es) incident upon the sample detector  150 . The sample detector  150  is configured to generate a signal corresponding to the detected sample beam (Es) and to pass the signal to a processor  210 , as discussed in more detail below.  
      Beam sampling optics  90  further includes a third lens  160  and a reference detector  170 . The reference beam (Er) is directed by beam sampling optics  90  from the beam splitter  4400  to a third lens  160  disposed along a minor axis Y generally orthogonal to the major axis X. The third lens  160  is configured to focus the reference beam (Er) onto reference detector  170 , thus increasing the flux density of the reference beam (Er) incident upon the reference detector  170 . In one embodiment, the lenses  4410 ,  4440 ,  160  may be formed from a material which is highly transmissive of infrared radiation, for example germanium or silicon. In addition, any of the lenses  4410 ,  4440  and  160  may be implemented as a system of lenses, depending on the desired optical performance. The reference detector  170  is also configured to generate a signal corresponding to the detected reference beam (Er) and to pass the signal to the processor  210 , as discussed in more detail below. Except as noted below, the sample and reference detectors  150 ,  170  may be generally similar to the detector  1745  illustrated in  FIG. 17 . Based on signals received from the sample and reference detectors  150 ,  170 , the processor  210  computes the concentration(s), absorbance(s), transmittance(s), etc. relating to the sample S by executing a data processing algorithm or program instructions residing within the memory  212  accessible by the processor  210 .  
      In further variations of the detection system  1700  depicted in  FIG. 44 , beam sampling optics  90 , including the beam splitter  4400 , reference detector  170  and other structures on the minor axis Y may be omitted, especially where the output intensity of the source  1720  is sufficiently stable to obviate any need to reference the source intensity in operation of the detection system  1700 . Thus, for example, sufficient signals may be generated by detectors  170  and  150  with one or more of lenses  4410 ,  4440 ,  160  omitted. Furthermore, in any of the embodiments of the analyte detection system  1700  disclosed herein, the processor  210  and/or memory  212  may reside partially or wholly in a standard personal computer (“PC”) coupled to the detection system  1700 .  
       FIG. 46  depicts a partial cross-sectional view of another embodiment of an analyte detection system  1700 , which may be generally similar to any of the embodiments illustrated in  FIGS. 17, 44 , and  45 , except as further detailed below. Where possible, similar elements are identified with identical reference numerals in the depiction of the embodiments of  FIGS. 17, 44 , and  45 .  
      The energy source  1720  of the embodiment of  FIG. 46  preferably comprises an emitter area  22  which is substantially centered on the major axis X. In one embodiment, the emitter area  22  may be square in shape. However the emitter area  22  can have other suitable shapes, such as rectangular, circular, elliptical, etc. One suitable emitter area  22  is a square of about 1.5 mm on a side; of course, any other suitable shape or dimensions may be employed.  
      The energy source  1720  is preferably configured to selectably operate at a modulation frequency between about 1 Hz and 30 Hz and have a peak operating temperature of between about 1070 degrees Kelvin and 1170 degrees Kelvin. Additionally, the source  1720  preferably operates with a modulation depth greater than about 80% at all modulation frequencies. The energy source  1720  preferably emits electromagnetic radiation in any of a number of spectral ranges, e.g., within infrared wavelengths; in the mid-infrared wavelengths; above about 0.8 μm; between about 5.0 μm and about 20.0 μm; and/or between about 5.25 μm and about 12.0 μm. However, in other embodiments, the detection system  1700  may employ an energy source  1720  which is unmodulated and/or which emits in wavelengths found anywhere from the visible spectrum through the microwave spectrum, for example anywhere from about 0.4 μm to greater than about 100 μm. In still other embodiments, the energy source  1720  can emit electromagnetic radiation in wavelengths between about 3.5 μm and about 14 μm, or between about 0.8 μm and about 2.5 μm, or between about 2.5 μm and 20 μm, or between about 20 μm and about 100 μm, or between about 6.85 μm and about 10.10 μm. In yet other embodiments, the energy source  1720  can emit electromagnetic radiation within the radio frequency (RF) range or the terahertz range. All of the above-recited operating characteristics are merely exemplary, and the source  1720  may have any operating characteristics suitable for use with the analyte detection system  1700 .  
      A power supply (not shown) for the energy source  1720  is preferably configured to selectably operate with a duty cycle of between about 30% and about 70%. Additionally, the power supply is preferably configured to selectably operate at a modulation frequency of about 10 Hz, or between about 1 Hz and about 30 Hz. The operation of the power supply can be in the form of a square wave, a sine wave, or any other waveform defined by a user.  
      With further reference to  FIG. 46 , the collimator  30  comprises a tube  30   a  with one or more highly-reflective inner surfaces  32  which diverge from a relatively narrow upstream end  34  to a relatively wide downstream end  36  as they extend downstream, away from the energy source  1720 . The narrow end  34  defines an upstream aperture  34   a  which is situated adjacent the emitter area  22  and permits radiation generated by the emitter area to propagate downstream into the collimator. The wide end  36  defines a downstream aperture  36   a . Like the emitter area  22 , each of the inner surface(s)  32 , upstream aperture  34   a  and downstream aperture  36   a  is preferably substantially centered on the major axis X.  
      As illustrated in  FIG. 46 , the inner surface(s)  32  of the collimator may have a generally curved shape, such as a parabolic, hyperbolic, elliptical or spherical shape. One suitable collimator  30  is a compound parabolic concentrator (CPC). In one embodiment, the collimator  30  can be up to about 20 mm in length. In another embodiment, the collimator  30  can be up to about 30 mm in length. However, the collimator  30  can have any length, and the inner surface(s)  32  may have any shape, suitable for use with the analyte detection system  1700 .  
      The inner surfaces  32  of the collimator  30  cause the rays making up the energy beam E to straighten (i.e., propagate at angles increasingly parallel to the major axis X) as the beam E advances downstream, so that the energy beam E becomes increasingly or substantially cylindrical and oriented substantially parallel to the major axis X. Accordingly, the inner surfaces  32  are highly reflective and minimally absorptive in the wavelengths of interest, such as infrared wavelengths.  
      The tube  30   a  itself may be fabricated from a rigid material such as aluminum, steel, or any other suitable material, as long as the inner surfaces  32  are coated or otherwise treated to be highly reflective in the wavelengths of interest. For example, a polished gold coating may be employed. Preferably, the inner surface(s)  32  of the collimator  30  define a circular cross-section when viewed orthogonal to the major axis X; however, other cross-sectional shapes, such as a square or other polygonal shapes, parabolic or elliptical shapes may be employed in alternative embodiments.  
      As noted above, the filter wheel  50  shown in  FIG. 46  comprises a plurality of secondary filters  60  which preferably operate as narrow band filters, each filter allowing only energy of a certain wavelength or wavelength band to pass therethrough. In one configuration suitable for detection of glucose in a sample S, the filter wheel  50  comprises twenty or twenty-two secondary filters  60 , each of which is configured to allow a filtered energy beam (Ef) to travel therethrough with a nominal wavelength approximately equal to one of the following: 3 μm, 4.06 μm, 4.6 μm, 4.9 μm, 5.25 μm, 6.12 μm, 6.47 μm, 7.98 μm, 8.35 μm, 9.65 μm, and 12.2 μm. (Moreover, this set of wavelengths may be employed with or in any of the embodiments of the analyte detection system  1700  disclosed herein.) Each secondary filter&#39;s  60  center wavelength is preferably equal to the desired nominal wavelength plus or minus about 2%. Additionally, the secondary filters  60  are preferably configured to have a bandwidth of about 0.2 μm, or alternatively equal to the nominal wavelength plus or minus about 2%-10%.  
      In another embodiment, the filter wheel  50  comprises twenty secondary filters  60 , each of which is configured to allow a filtered energy beam (Ef) to travel therethrough with a nominal center wavelengths of: 4.275 μm, 4.5 μm, 4.7 μm, 5.0 μm, 5.3 μm, 6.056 μm, 7.15 μm, 7.3 μm, 7.55 μm, 7.67 μm, 8.06 μm, 8.4 μm, 8.56 μm, 8.87 μm, 9.15 μm, 9.27 μm, 9.48 μm, 9.68 μm, 9.82 μm, and 10.06 μm. (This set of wavelengths may also be employed with or in any of the embodiments of the analyte detection system  1700  disclosed herein.) In still another embodiment, the secondary filters  60  may conform to any one or combination of the following specifications: center wavelength tolerance of ±0.01 μm; half-power bandwidth tolerance of ±0.01 μm; peak transmission greater than or equal to 75%; cut-on/cut-off slope less than 2%; center-wavelength temperature coefficient less than 0.01% per degree Celsius; out of band attenuation greater than OD  5  from 3 μm to 12 μm; flatness less than 1.0 waves at 0.6328 μm; surface quality of E-E per Mil-F-48616; and overall thickness of about 1 mm.  
      In still another embodiment, the secondary filters mentioned above may conform to any one or combination of the following half-power bandwidth (“HPBW”) specifications:  
                                           Center Wavelength   HPBW   Center Wavelength   HPBW       (μm)   (μm)   (μm)   (μm)                                                4.275   0.05   8.06   0.3       4.5   0.18   8.4   0.2       4.7   0.13   8.56   0.18       5.0   0.1   8.87   0.2       5.3   0.13   9.15   0.15       6.056   0.135   9.27   0.14       7.15   0.19   9.48   0.23       7.3   0.19   9.68   0.3       7.55   0.18   9.82   0.34       7.67   0.197   10.06   0.2                  
 
      In still further embodiments, the secondary filters may have a center wavelength tolerance of ±0.5% and a half-power bandwidth tolerance of ±0.02 μm.  
      Of course, the number of secondary filters employed, and the center wavelengths and other characteristics thereof, may vary in further embodiments of the system  1700 , whether such further embodiments are employed to detect glucose, or other analytes instead of or in addition to glucose. For example, in another embodiment, the filter wheel  50  can have fewer than fifty secondary filters  60 . In still another embodiment, the filter wheel  50  can have fewer than twenty secondary filters  60 . In yet another embodiment, the filter wheel  50  can have fewer than ten secondary filters  60 .  
      In one embodiment, the secondary filters  60  each measure about 10 mm long by 10 mm wide in a plane orthogonal to the major axis X, with a thickness of about 1 mm. However, the secondary filters  60  can have any other (e.g., smaller) dimensions suitable for operation of the analyte detection system  1700 . Additionally, the secondary filters  60  are preferably configured to operate at a temperature of between about 5° C. and about 35° C. and to allow transmission of more than about 75% of the energy beam E therethrough in the wavelength(s) which the filter is configured to pass.  
      According to the embodiment illustrated in  FIG. 46 , the primary filter  40  operates as a broadband filter and the secondary filters  60  disposed on the filter wheel  50  operate as narrow band filters. However, one of ordinary skill in the art will realize that other structures can be used to filter energy wavelengths according to the embodiments described herein. For example, the primary filter  40  may be omitted and/or an electronically tunable filter or Fabry-Perot interferometer (not shown) can be used in place of the filter wheel  50  and secondary filters  60 . Such a tunable filter or interferometer can be configured to permit, in a sequential, “one-at-a-time” fashion, each of a set of wavelengths or wavelength bands of electromagnetic radiation to pass therethrough for use in analyzing the material sample S.  
      A reflector tube  98  is preferably positioned to receive the filtered energy beam (Ef) as it advances from the secondary filter(s)  60 . The reflector tube  98  is preferably secured with respect to the secondary filter(s)  60  to substantially prevent introduction of stray electromagnetic radiation, such as stray light, into the reflector tube  98  from outside of the detection system  1700 . The inner surfaces of the reflector tube  98  are highly reflective in the relevant wavelengths and preferably have a cylindrical shape with a generally circular cross-section orthogonal to the major and/or minor axis X, Y. However, the inner surface of the tube  98  can have a cross-section of any suitable shape, such as oval, square, rectangular, etc. Like the collimator  30 , the reflector tube  98  may be formed from a rigid material such as aluminum, steel, etc., as long as the inner surfaces are coated or otherwise treated to be highly reflective in the wavelengths of interest. For example, a polished gold coating may be employed.  
      According to the embodiment illustrated in  FIG. 46 , the reflector tube  98  preferably comprises a major section  98   a  and a minor section  98   b . As depicted, the reflector tube  98  can be T-shaped with the major section  98   a  having a greater length than the minor section  98   b . In another example, the major section  98   a  and the minor section  98   b  can have the same length. The major section  98   a  extends between a first end  98   c  and a second end  98   d  along the major axis X. The minor section  98   b  extends between the major section  98   a  and a third end  98   e  along the minor axis Y.  
      The major section  98   a  conducts the filtered energy beam (Ef) from the first end  98   c  to the beam splitter  4400 , which is housed in the major section  98   a  at the intersection of the major and minor axes X, Y. The major section  98   a  also conducts the sample beam (Es) from the beam splitter  4400 , through the first lens  4410  and to the second end  98   d . From the second end  98   d  the sample beam (Es) proceeds through the sample element  1730 , holder  4430  and second lens  4440 , and to the sample detector  150 . Similarly, the minor section  98   b  conducts the reference beam (Er) through beam sampling optics  90  from the beam splitter  4400 , through the third lens  160  and to the third end  98   e . From the third end  98   e  the reference beam (Er) proceeds to the reference detector  170 .  
      The sample beam (Es) preferably comprises from about 75% to about 85% of the energy of the filtered energy beam (Ef). More preferably, the sample beam (Es) comprises about 80% of the energy of the filtered energy beam (Es). The reference beam (Er) preferably comprises from about 10% and about 50% of the energy of the filtered energy beam (Es). More preferably, the reference beam (Er) comprises about 20% of the energy of the filtered energy beam (Ef). Of course, the sample and reference beams may take on any suitable proportions of the energy beam E.  
      The reflector tube  98  also houses the first lens  4410  and the third lens  160 . As illustrated in  FIG. 46 , the reflector tube  98  houses the first lens  4410  between the beam splitter  4400  and the second end  98   d . The first lens  4410  is preferably disposed so that a plane  4612  of the lens  4410  is generally orthogonal to the major axis X. Similarly, the tube  98  houses the third lens  160  between the beam splitter  4400  and the third end  98   e . The third lens  160  is preferably disposed so that a plane  162  of the third lens  160  is generally orthogonal to the minor axis Y. The first lens  4410  and the third lens  160  each has a focal length configured to substantially focus the sample beam (Es) and reference beam (Er), respectively, as the beams (Es, Er) pass through the lenses  4410 ,  160 . In particular, the first lens  4410  is configured, and disposed relative to the holder  4430 , to focus the sample beam (Es) so that substantially the entire sample beam (Es) passes through the material sample S, residing in the sample element  1730 . Likewise, the third lens  160  is configured to focus the reference beam (Er) so that substantially the entire reference beam (Er) impinges onto the reference detector  170 .  
      The sample element  1730  is retained within the holder  4430 , which is preferably oriented along a plane generally orthogonal to the major axis X. The holder  4430  is configured to be slidably displaced between a loading position and a measurement position within the analyte detection system  1700 . In the measurement position, the holder  4430  contacts a stop edge  136  which is located to orient the sample element  1730  and the sample S contained therein on the major axis X.  
      The structural details of the holder  4430  depicted in  FIG. 46  are unimportant, so long as the holder positions the sample element  1730  and sample S on and substantially orthogonal to the major axis X, while permitting the energy beam E to pass through the sample element and sample. As with the embodiment depicted in  FIG. 44 , the holder  4430  may be omitted and the sample element  1730  positioned alone in the depicted location on the major axis X. However, the holder  4430  is useful where the sample element  1730  (discussed in further detail below) is constructed from a highly brittle or fragile material, such as barium fluoride, or is manufactured to be extremely thin.  
      As with the embodiment depicted in  FIG. 44 , the sample and reference detectors  150 ,  170  shown in  FIG. 46  respond to radiation incident thereon by generating signals and passing them to the processor  210 . Based these signals received from the sample and reference detectors  150 ,  170 , the processor  210  computes the concentration(s), absorbance(s), transmittance(s), etc. relating to the sample S by executing a data processing algorithm or program instructions residing within the memory  212  accessible by the processor  210 . In further variations of the detection system  1700  depicted in  FIG. 46 , the beam splitter  4400 , reference detector  170  and other structures on the minor axis Y may be omitted, especially where the output intensity of the source  1720  is sufficiently stable to obviate any need to reference the source intensity in operation of the detection system  1700 .  
       FIG. 47  depicts a sectional view of the sample detector  150  in accordance with one embodiment. Sample detector  150  is mounted in a detector housing  152  having a receiving portion  152   a  and a cover  152   b . However, any suitable structure may be used as the sample detector  150  and housing  152 . The receiving portion  152   a  preferably defines an aperture  152   c  and a lens chamber  152   d , which are generally aligned with the major axis X when the housing  152  is mounted in the analyte detection system  1700 . The aperture  152   c  is configured to allow at least a fraction of the sample beam (Es) passing through the sample S and the sample element  1730  to advance through the aperture  152   c  and into the lens chamber  152   d.    
      The receiving portion  152   a  houses the second lens  4440  in the lens chamber  152   d  proximal to the aperture  152   c . The sample detector  150  is also disposed in the lens chamber  152   d  downstream of the second lens  4440  such that a detection plane  154  of the detector  150  is substantially orthogonal to the major axis X. The second lens  4440  is positioned such that a plane  142  of the lens  4440  is substantially orthogonal to the major axis X. The second lens  4440  is configured, and is preferably disposed relative to the holder  4430  and the sample detector  150 , to focus substantially all of the sample beam (Es) onto the detection plane  154 , thereby increasing the flux density of the sample beam (Es) incident upon the detection plane  154 .  
      With further reference to  FIG. 47 , a support member  156  preferably holds the sample detector  150  in place in the receiving portion  152   a . In the illustrated embodiment, the support member  156  is a spring  156  disposed between the sample detector  150  and the cover  152   b . The spring  156  is configured to maintain the detection plane  154  of the sample detector  150  substantially orthogonal to the major axis X. A gasket  157  is preferably disposed between the cover  152   b  and the receiving portion  152   a  and surrounds the support member  156 .  
      The receiving portion  152   a  preferably also houses a printed circuit board  158  disposed between the gasket  157  and the sample detector  150 . The board  158  connects to the sample detector  150  through at least one connecting member  150   a . The sample detector  150  is configured to generate a detection signal corresponding to the sample beam (Es) incident on the detection plane  154 . The sample detector  150  communicates the detection signal to the circuit board  158  through the connecting member  150   a , and the board  158  transmits the detection signal to the processor  210 .  
      In one embodiment, the sample detector  150  comprises a generally cylindrical housing  150   a , e.g. a type TO-39 “metal can” package, which defines a generally circular housing aperture  150   b  at its “upstream” end. In one embodiment, the housing  150   a  has a diameter of about 0.323 inches and a depth of about 0.248 inches, and the aperture  150   b  may have a diameter of about 0.197 inches.  
      A detector window  150   c  is disposed adjacent the aperture  150   b , with its upstream surface preferably about 0.078 inches (+/−0.004 inches) from the detection plane  154 . (The detection plane  154  is located about 0.088 inches (+/−0.004 inches) from the upstream edge of the housing  150   a , where the housing has a thickness of about 0.010 inches.) The detector window  150   c  is preferably transmissive of infrared energy in at least a 3-12 micron passband; accordingly, one suitable material for the window  150   c  is germanium. The endpoints of the passband may be “spread” further to less than 2.5 microns, and/or greater than 12.5 microns, to avoid unnecessary absorbance in the wavelengths of interest. Preferably, the transmittance of the detector window  150   c  does not vary by more than 2% across its passband. The window  150   c  is preferably about 0.020 inches in thickness. The sample detector  150  preferably substantially retains its operating characteristics across a temperature range of −20 to +60 degrees Celsius.  
       FIG. 48  depicts a sectional view of the reference detector  170  in accordance with one embodiment. The reference detector  170  is mounted in a detector housing  172  having a receiving portion  172   a  and a cover  172   b . However, any suitable structure may be used as the sample detector  150  and housing  152 . The receiving portion  172   a  preferably defines an aperture  172   c  and a chamber  172   d  which are generally aligned with the minor axis Y, when the housing  172  is mounted in the analyte detection system  1700 . The aperture  172   c  is configured to allow the reference beam (Er) to advance through the aperture  172   c  and into the chamber  172   d.    
      The receiving portion  172   a  houses the reference detector  170  in the chamber  172   d  proximal to the aperture  172   c . The reference detector  170  is disposed in the chamber  172   d  such that a detection plane  174  of the reference detector  170  is substantially orthogonal to the minor axis Y. The third lens  160  is configured to substantially focus the reference beam (Er) so that substantially the entire reference beam (Er) impinges onto the detection plane  174 , thus increasing the flux density of the reference beam (Er) incident upon the detection plane  174 .  
      With further reference to  FIG. 48 , a support member  176  preferably holds the reference detector  170  in place in the receiving portion  172   a . In the illustrated embodiment, the support member  176  is a spring  176  disposed between the reference detector  170  and the cover  172   b . The spring  176  is configured to maintain the detection plane  174  of the reference detector  170  substantially orthogonal to the minor axis Y. A gasket  177  is preferably disposed between the cover  172   b  and the receiving portion  172   a  and surrounds the support member  176 .  
      The receiving portion  172   a  preferably also houses a printed circuit board  178  disposed between the gasket  177  and the reference detector  170 . The board  178  connects to the reference detector  170  through at least one connecting member  170   a . The reference detector  170  is configured to generate a detection signal corresponding to the reference beam (Er) incident on the detection plane  174 . The reference detector  170  communicates the detection signal to the circuit board  178  through the connecting member  170   a , and the board  178  transmits the detection signal to the processor  210 .  
      In one embodiment, the construction of the reference detector  170  is generally similar to that described above with regard to the sample detector  150 .  
      In one embodiment, the sample and reference detectors  150 ,  170  are both configured to detect electromagnetic radiation in a spectral wavelength range of between about 0.8 μm and about 25 μm. However, any suitable subset of the foregoing set of wavelengths can be selected. In another embodiment, the detectors  150 ,  170  are configured to detect electromagnetic radiation in the wavelength range of between about 4 μm and about 12 μm. The detection planes  154 ,  174  of the detectors  150 ,  170  may each define an active area about 2 mm by 2 mm or from about 1 mm by 1 mm to about 5 mm by 5 mm; of course, any other suitable dimensions and proportions may be employed. Additionally, the detectors  150 ,  170  may be configured to detect electromagnetic radiation directed thereto within a cone angle of about 45 degrees from the major axis X.  
      In one embodiment, the sample and reference detector subsystems  150 ,  170  may further comprise a system (not shown) for regulating the temperature of the detectors. Such a temperature-regulation system may comprise a suitable electrical heat source, thermistor, and a proportional-plus-integral-plus-derivative (PID) control. These components may be used to regulate the temperature of the detectors  150 ,  170  at about 35° C. The detectors  150 ,  170  can also optionally be operated at other desired temperatures. Additionally, the PID control preferably has a control rate of about 60 Hz and, along with the heat source and thermistor, maintains the temperature of the detectors  150 ,  170  within about 0.1° C. of the desired temperature.  
      The detectors  150 ,  170  can operate in either a voltage mode or a current mode, wherein either mode of operation preferably includes the use of a pre-amp module. Suitable voltage mode detectors for use with the analyte detection system  1700  disclosed herein include: models LIE 302 and 312 by InfraTec of Dresden, Germany; model L2002 by BAE Systems of Rockville, Md.; and model LTS-1 by Dias of Dresden, Germany. Suitable current mode detectors include: InfraTec models LIE 301, 315, 345 and 355; and 2×2 current-mode detectors available from Dias.  
      In one embodiment, one or both of the detectors  150 ,  170  may meet the following specifications, when assuming an incident radiation intensity of about 9.26×10 −4  watts (rms) per cm 2 , at 10 Hz modulation and within a cone angle of about 15 degrees: detector area of 0.040 cm 2  (2 mm×2 mm square); detector input of 3.70×10 −5  watts (rms) at 10 Hz; detector sensitivity of 360 volts per watt at 10 Hz; detector output of 1.333×10 −2  volts (rms) at 10 Hz; noise of 8.00×10 −8  volts/sqrtHz at 10 Hz; and signal-to-noise ratios of 1.67×10 5  rms/sqrtHz and 104.4 dB/sqrtHz; and detectivity of 1.00×10 9  cm sqrtHz/watt.  
      In alternative embodiments, the detectors  150 ,  170  may comprise microphones and/or other sensors suitable for operation of the detection system  1700  in a photoacoustic mode.  
      The components of any of the embodiments of the analyte detection system  1700  may be partially or completely contained in an enclosure or casing (not shown) to prevent stray electromagnetic radiation, such as stray light, from contaminating the energy beam E. Any suitable casing may be used. Similarly, the components of the detection system  1700  may be mounted on any suitable frame or chassis (not shown) to maintain their operative alignment as depicted in  FIGS. 17, 44 , and  46 . The frame and the casing may be formed together as a single unit, member or collection of members.  
      In one method of operation, the analyte detection system  1700  shown in  FIG. 44  or  46  measures the concentration of one or more analytes in the material sample S, in part, by comparing the electromagnetic radiation detected by the sample and reference detectors  150 ,  170 . During operation of the detection system  1700 , each of the secondary filter(s)  60  is sequentially aligned with the major axis X for a dwell time corresponding to the secondary filter  60 . (Of course, where an electronically tunable filter or Fabry-Perot interferometer is used in place of the filter wheel  50 , the tunable filter or interferometer is sequentially tuned to each of a set of desired wavelengths or wavelength bands in lieu of the sequential alignment of each of the secondary filters with the major axis X.) The energy source  1720  is then operated at (any) modulation frequency, as discussed above, during the dwell time period. The dwell time may be different for each secondary filter  60  (or each wavelength or band to which the tunable filter or interferometer is tuned). In one embodiment of the detection system  1700 , the dwell time for each secondary filter  60  is less than about 1 second. Use of a dwell time specific to each secondary filter  60  advantageously allows the detection system  1700  to operate for a longer period of time at wavelengths where errors can have a greater effect on the computation of the analyte concentration in the material sample S. Correspondingly, the detection system  1700  can operate for a shorter period of time at wavelengths where errors have less effect on the computed analyte concentration. The dwell times may otherwise be nonuniform among the filters/wavelengths/bands employed in the detection system.  
      For each secondary filter  60  selectively aligned with the major axis X, the sample detector  150  detects the portion of the sample beam (Es), at the wavelength or wavelength band corresponding to the secondary filter  60 , that is transmitted through the material sample S. The sample detector  150  generates a detection signal corresponding to the detected electromagnetic radiation and passes the signal to the processor  210 . Simultaneously, the reference detector  170  detects the reference beam (Er) transmitted at the wavelength or wavelength band corresponding to the secondary filter  60 . The reference detector  170  generates a detection signal corresponding to the detected electromagnetic radiation and passes the signal to the processor  210 . Based on the signals passed to it by the detectors  150 ,  170 , the processor  210  computes the concentration of the analyte(s) of interest in the sample S, and/or the absorbance/transmittance characteristics of the sample S at one or more wavelengths or wavelength bands employed to analyze the sample. The processor  210  computes the concentration(s), absorbance(s), transmittance(s), etc. by executing a data processing algorithm or program instructions residing within the memory  212  accessible by the processor  210 .  
      The signal generated by the reference detector may be used to monitor fluctuations in the intensity of the energy beam emitted by the source  1720 , which fluctuations often arise due to drift effects, aging, wear or other imperfections in the source itself. This enables the processor  210  to identify changes in intensity of the sample beam (Es) that are attributable to changes in the emission intensity of the source  1720 , and not to the composition of the sample S. By so doing, a potential source of error in computations of concentration, absorbance, etc. is minimized or eliminated.  
      In one embodiment, the detection system  1700  computes an analyte concentration reading by first measuring the electromagnetic radiation detected by the detectors  150 ,  170  at each center wavelength, or wavelength band, without the sample element  1730  present on the major axis X (this is known as an “air” reading). Second, the system  1700  measures the electromagnetic radiation detected by the detectors  150 ,  170  for each center wavelength, or wavelength band, with the material sample S present in the sample element  1730 , and the sample element  1730  and sample S in position on the major axis X (i.e., a “wet” reading). Finally, the processor  180  computes the concentration(s), absorbance(s) and/or transmittances relating to the sample S based on these compiled readings.  
      In one embodiment, the plurality of air and wet readings are used to generate a pathlength corrected spectrum as follows. First, the measurements are normalized to give the transmission of the sample at each wavelength. Using both a signal and reference measurement at each wavelength, and letting S i  represent the signal of detector  150  at wavelength i and R i  represent the signal of detector  170  at wavelength i, the transmission, τ i  is computed as τ i =S i (wet)/R i (wet)/S i (air)/R i (air). Optionally, the spectra may be calculated as the optical density, OD i , as −Log(T i ).  
      Next, the transmission over the wavelength range of approximately 4.5 μm to approximately 5.5 μm is analyzed to determine the pathlength. Specifically, since water is the primary absorbing species of blood over this wavelength region, and since the optical density is the product of the optical pathlength and the known absorption coefficient of water (OD=L σ, where L is the optical pathlength and σ is the absorption coefficient), any one of a number of standard curve fitting procedures may be used to determine the optical pathlength, L from the measured OD. The pathlength may then be used to determine the absorption coefficient of the sample at each wavelength. Alternatively, the optical pathlength may be used in further calculations to convert absorption coefficients to optical density.  
      Additional information on analyte detection systems, methods of use thereof, and related technologies may be found in the above-mentioned and incorporated U.S. patent application Publication No. 2005/0038357, published on Feb. 17, 2005, titled SAMPLE ELEMENT WITH BARRIER MATERIAL.  
      Section IV.C—Sample Element  
       FIG. 18  is a top view of a sample element  1730 ,  FIG. 19  is a side view of the sample element, and  FIG. 20  is an exploded perspective view of the sample element. In one embodiment, sample element  1730  includes sample chamber  903  that is in fluid communication with and accepts filtered blood from sample preparation unit  332 . The sample element  1730  comprises a sample chamber  903  defined by sample chamber walls  1802 . The sample chamber  903  is configured to hold a material sample which may be drawn from a patient, for analysis by the detection system with which the sample element  1730  is employed.  
      In the embodiment illustrated in  FIGS. 18-19 , the sample chamber  903  is defined by first and second lateral chamber walls  1802   a ,  1802   b  and upper and lower chamber walls  1802   c ,  1802   d ; however, any suitable number and configuration of chamber walls may be employed. At least one of the upper and lower chamber walls  1802   c ,  1802   d  is formed from a material which is sufficiently transmissive of the wavelength(s) of electromagnetic radiation that are employed by the sample analysis apparatus  322  (or any other system with which the sample element is to be used). A chamber wall which is so transmissive may thus be termed a “window;” in one embodiment, the upper and lower chamber walls  1802   c ,  1802   d  comprise first and second windows so as to permit the relevant wavelength(s) of electromagnetic radiation to pass through the sample chamber  903 . In another embodiment, only one of the upper and lower chamber walls  1802   c ,  1802   d  comprises a window; in such an embodiment, the other of the upper and lower chamber walls may comprise a reflective surface configured to back-reflect any electromagnetic energy emitted into the sample chamber  903  by the analyte detection system with which the sample element  1730  is employed. Accordingly, this embodiment is well suited for use with an analyte detection system in which a source and a detector of electromagnetic energy are located on the same side as the sample element.  
      In various embodiments, the material that makes up the window(s) of the sample element  1730  is completely transmissive, i.e., it does not absorb any of the electromagnetic radiation from the source  1720  and filters  1725  that is incident upon it. In another embodiment, the material of the window(s) has some absorption in the electromagnetic range of interest, but its absorption is negligible. In yet another embodiment, the absorption of the material of the window(s) is not negligible, but it is stable for a relatively long period of time. In another embodiment, the absorption of the window(s) is stable for only a relatively short period of time, but sample analysis apparatus  322  is configured to observe the absorption of the material and eliminate it from the analyte measurement before the material properties can change measurably. Materials suitable for forming the window(s) of the sample element  1730  include, but are not limited to, calcium fluoride, barium fluoride, germanium, silicon, polypropylene, polyethylene, or any polymer with suitable transmissivity (i.e., transmittance per unit thickness) in the relevant wavelength(s). Where the window(s) are formed from a polymer, the selected polymer can be isotactic, atactic or syndiotactic in structure, so as to enhance the flow of the sample between the window(s). One type of polyethylene suitable for constructing the sample element  1730  is type  220 , extruded or blow molded, available from KUBE Ltd. of Staefa, Switzerland.  
      In one embodiment, the sample element  1730  is configured to allow sufficient transmission of electromagnetic energy having a wavelength of between about 4 μm and about 10.5 μm through the window(s) thereof. However, the sample element  1730  can be configured to allow transmission of wavelengths in any spectral range emitted by the energy source  1720 . In another embodiment, the sample element  1730  is configured to receive an optical power of more than about 1.0 MW/cm 2  from the sample beam (Es) incident thereon for any electromagnetic radiation wavelength transmitted through the filter  1725 . Preferably, the sample chamber  903  of the sample element  1730  is configured to allow a sample beam (Es) advancing toward the material sample S within a cone angle of 45 degrees from the major axis X (see  FIG. 17 ) to pass therethrough.  
      In the embodiment illustrated in  FIGS. 18-19 , the sample element further comprises a supply passage  1804  extending from the sample chamber  903  to a supply opening  1806  and a vent passage  1808  extending from the sample chamber  903  to a vent opening  1810 . While the vent and supply openings  1806 ,  1810  are shown at one end of the sample element  1730 , in other embodiments the openings may be positioned on other sides of the sample element  1730 , so long as it is in fluid communication with the passages  1804  and  1808 , respectively.  
      In operation, the supply opening  1806  of the sample element  1730  is placed in contact with the material sample S, such as a fluid flowing from a patient. The fluid is then transported through the sample supply passage  1804  and into the sample chamber  903  via an external pump or by capillary action.  
      Where the upper and lower chamber walls  1802   c ,  1802   d  comprise windows, the distance T (measured along an axis substantially orthogonal to the sample chamber  903  and/or windows  1802   a ,  1802   b , or, alternatively, measured along an axis of an energy beam (such as but not limited to the energy beam E discussed above) passed through the sample chamber  903 ) between them comprises an optical pathlength. In various embodiments, the pathlength is between about 1 μm and about 300 μm, between about 1 μm and about 100 μm, between about 25 μm and about 40 μm, between about 10 μm and about 40 μm, between about 25 μm and about 60 μm, or between about 30 μm and about 50 μm. In still other embodiments, the optical pathlength is about 50 μm, or about 25 μm. In some instances, it is desirable to hold the pathlength T to within about plus or minus 1 μm from any pathlength specified by the analyte detection system with which the sample element  1730  is to be employed. Likewise, it may be desirable to orient the walls  1802   c ,  1802   d  with respect to each other within plus or minus 1 μm of parallel, and/or to maintain each of the walls  1802   c ,  1802   d  to within plus or minus 1 μm of planar (flat), depending on the analyte detection system with which the sample element  1730  is to be used. In alternative embodiments, walls  1802   c ,  1802   d  are flat, textured, angled, or some combination thereof.  
      In one embodiment, the transverse size of the sample chamber  903  (i.e., the size defined by the lateral chamber walls  1802   a ,  1802   b ) is about equal to the size of the active surface of the sample detector  1745 . Accordingly, in a further embodiment the sample chamber  903  is round with a diameter of about 4 millimeter to about 12 millimeter, and more preferably from about 6 millimeter to about 8 millimeter.  
      The sample element  1730  shown in  FIGS. 18-19  has, in one embodiment, sizes and dimensions specified as follows. The supply passage  1804  preferably has a length of about 15 millimeter, a width of about 1.0 millimeter, and a height equal to the pathlength T. Additionally, the supply opening  1806  is preferably about 1.5 millimeter wide and smoothly transitions to the width of the sample supply passage  1804 . The sample element  1730  is about 0.5 inches (12 millimeters) wide and about one inch (25 millimeters) long with an overall thickness of between about 1.0 millimeter and about 4.0 millimeter. The vent passage  1808  preferably has a length of about 1.0 millimeter to 5.0 millimeter and a width of about 1.0 millimeter, with a thickness substantially equal to the pathlength between the walls  1802   c ,  1802   d . The vent aperture  1810  is of substantially the same height and width as the vent passage  1808 . Of course, other dimensions may be employed in other embodiments while still achieving the advantages of the sample element  1730 .  
      The sample element  1730  is preferably sized to receive a material sample S having a volume less than or equal to about 15 μL (or less than or equal to about 10 μL, or less than or equal to about 5 μL) and more preferably a material sample S having a volume less than or equal to about 2 μL. Of course, the volume of the sample element  1730 , the volume of the sample chamber  903 , etc. can vary, depending on many variables, such as the size and sensitivity of the sample detector  1745 , the intensity of the radiation emitted by the energy source  1720 , the expected flow properties of the sample, and whether flow enhancers are incorporated into the sample element  1730 . The transport of fluid to the sample chamber  903  is achieved preferably through capillary action, but may also be achieved through wicking or vacuum action, or a combination of wicking, capillary action, peristaltic, pumping, and/or vacuum action.  
       FIG. 20  depicts one approach to constructing the sample element  1730 . In this approach, the sample element  1730  comprises a first layer  1820 , a second layer  1830 , and a third layer  1840 . The second layer  1830  is preferably positioned between the first layer  1820  and the third layer  1840 . The first layer  1820  forms the upper chamber wall  1802   c , and the third layer  1840  forms the lower chamber wall  1802   d . Where either of the chamber walls  1802   c ,  1802   d  comprises a window, the window(s)/wall(s)  1802   c / 1802   d  in question may be formed from a different material as is employed to form the balance of the layer(s)  1820 / 1840  in which the wall(s) are located. Alternatively, the entirety of the layer(s)  1820 / 1840  may be formed of the material selected to form the window(s)/wall(s)  1802   c ,  1802   d . In this case, the window(s)/wall(s)  1802   c ,  1802   d  are integrally formed with the layer(s)  1820 ,  1840  and simply comprise the regions of the respective layer(s)  1820 ,  1840  which overlie the sample chamber  903 .  
      With further reference to  FIG. 20 , second layer  1830  may be formed entirely of an adhesive that joins the first and third layers  1820 ,  1840 . In other embodiments, the second layer  1830  may be formed from similar materials as the first and third layers, or any other suitable material. The second layer  1830  may also be formed as a carrier with an adhesive deposited on both sides thereof. The second layer  1830  includes voids which at least partially form the sample chamber  903 , sample supply passage  1804 , supply opening  1806 , vent passage  1808 , and vent opening  1810 . The thickness of the second layer  1830  can be the same as any of the pathlengths disclosed above as suitable for the sample element  1730 . The first and third layers can be formed from any of the materials disclosed above as suitable for forming the window(s) of the sample element  1730 . In one embodiment, layers  1820 ,  1840  are formed from material having sufficient structural integrity to maintain its shape when filled with a sample S. Layers  1820 ,  1830  may be, for example, calcium fluoride having a thickness of 0.5 millimeter. In another embodiment, the second layer  1830  comprises the adhesive portion of Adhesive Transfer Tape no. 9471LE available from 3M Corporation. In another embodiment, the second layer  1830  comprises an epoxy, available, for example, from TechFilm (31 Dunham Road, Billerica, Mass. 01821), that is bound to layers  1820 ,  1840  as a result of the application of pressure and heat to the layers.  
      The sample chamber  903  preferably comprises a reagentless chamber. In other words, the internal volume of the sample chamber  903  and/or the wall(s)  1802  defining the chamber  903  are preferably inert with respect to the sample to be drawn into the chamber for analysis. As used herein, “inert” is a broad term and is used in its ordinary sense and includes, without limitation, substances which will not react with the sample in a manner which will significantly affect any measurement made of the concentration of analyte(s) in the sample with sample analysis apparatus  322  or any other suitable system, for a sufficient time (e.g., about 1-30 minutes) following entry of the sample into the chamber  903 , to permit measurement of the concentration of such analyte(s). Alternatively, the sample chamber  903  may contain one or more reagents to facilitate use of the sample element in sample assay techniques which involve reaction of the sample with a reagent.  
      In one embodiment, sample element  1730  is used for a limited number of measurements and is disposable. Thus, for example, with reference to  FIGS. 8-10 , sample element  1730  forms a disposable portion of cassette  820  adapted to place sample chamber  903  within probe region  1002 .  
      Additional information on sample elements, methods of use thereof, and related technologies may be found in the above-mentioned and incorporated U.S. patent application Publication No. 2005/0038357, published on Feb. 17, 2005, titled SAMPLE ELEMENT WITH BARRIER MATERIAL; and in the above-mentioned and incorporated U.S. patent application Ser. No. 11/122,794, filed on May 5, 2005, titled SAMPLE ELEMENT WITH SEPARATOR.  
      Section IV.D—Centrifuge  
       FIG. 21  is a schematic of one embodiment of a sample preparation unit  2100  utilizing a centrifuge and which may be generally similar to the sample preparation unit  332 , except as further detailed below. In general, the sample preparation unit  332  includes a centrifuge in place of, or in addition to a filter, such as the filter  1500 . Sample preparation unit  2100  includes a fluid handling element in the form of a centrifuge  2110  having a sample element  2112  and a fluid interface  2120 . Sample element  2112  is illustrated in  FIG. 21  as a somewhat cylindrical element. This embodiment is illustrative, and the sample element may be cylindrical, planar, or any other shape or configuration that is compatible with the function of holding a material (preferably a liquid) in the centrifuge  2110 . The centrifuge  2110  can be used to rotate the sample element  2112  such that the material held in the sample element  2112  is separated.  
      In some embodiments, the fluid interface  2120  selectively controls the transfer of a sample from the passageway  113  and into the sample element  2112  to permit centrifuging of the sample. In another embodiment, the fluid interface  2120  also permits a fluid to flow though the sample element  2112  to cleanse or otherwise prepare the sample element for obtaining an analyte measurement. Thus, the fluid interface  2120  can be used to flush and fill the sample element  2112 .  
      As shown in  FIG. 21 , the centrifuge  2110  comprises a rotor  2111  that includes the sample element  2112  and an axle  2113  attached to a motor, not shown, which is controlled by the controller  210 . The sample element  2112  is preferably generally similar to the sample element  1730  except as described subsequently.  
      As is further shown in  FIG. 21 , fluid interface  2120  includes a fluid injection probe  2121  having a first needle  2122  and a fluid removal probe  2123 . The fluid removal probe  2123  has a second needle  2124 . When sample element  2112  is properly oriented relative to fluid interface  2120 , a sample, fluid, or other liquid is dispensed into or passes through the sample element  2112 . More specifically, fluid injection probe  2121  includes a passageway to receive a sample, such as a bodily fluid from the patient connector  110 . The bodily fluid can be passed through the fluid injection probe  2121  and the first needle  2122  into the sample element  2112 . To remove material from the sample element  2112 , the sample  2112  can be aligned with the second needle  2124 , as illustrated. Material can be passed through the second needle  2124  into the fluid removal probe  2123 . The material can then pass through a passageway of the removal probe  2123  away from the sample element  2112 .  
      One position that the sample element  2112  may be rotated through or to is a sample measurement location  2140 . The location  2140  may coincide with a region of an analysis system, such as an optical analyte detection system. For example, the location  2140  may coincide with a probe region  1002 , or with a measurement location of another apparatus.  
      The rotor  2111  may be driven in a direction indicated by arrow R, resulting in a centrifugal force on sample(s) within sample element  2112 . The rotation of a sample(s) located a distance from the center of rotation creates centrifugal force. In some embodiments, the sample element  2112  holds whole blood. The centrifugal force may cause the denser parts of the whole blood sample to move further out from the center of rotation than lighter parts of the blood sample. As such, one or more components of the whole blood can be separated from each other. Other fluids or samples can also be removed by centrifugal forces. In one embodiment, the sample element  2112  is a disposable container that is mounted on to a disposable rotor  2111 . Preferably, the container is plastic, reusable and flushable. In other embodiments, the sample element  2112  is a non-disposable container that is permanently attached to the rotor  2111 .  
      The illustrated rotor  2111  is a generally circular plate that is fixedly coupled to the axle  2113 . The rotor  2111  can alternatively have other shapes. The rotor  2111  preferably comprises a material that has a low density to keep the rotational inertia low and that is sufficiently strong and stable to maintain shape under operating loads to maintain close optical alignment. For example, the rotor  2111  can be comprised of GE brand ULTEM™ (trademark) polyetherimide (PEI). This material is available in a plate form that is stable but can be readily machined. Other materials having similar properties can also be used.  
      The size of the rotor  2111  can be selected to achieve the desired centrifugal force. In some embodiments, the diameter of rotor  2111  is from about 75 millimeters to about 125 millimeters, or more preferably from about 100 millimeters to about 125 millimeters. The thickness of rotor  2111  is preferably just thick enough to support the centrifugal forces and can be, for example, from about 1.0 to 2.0 millimeter thick.  
      In an alternative embodiment, the fluid interface  2120  selectively removes blood plasma from the sample element  2112  after centrifuging. The blood plasma is then delivered to an analyte detection system for analysis. In one embodiment, the separated fluids are removed from the sample element  2112  through the bottom connector. Preferably, the location and orientation of the bottom connector and the container allow the red blood cells to be removed first. One embodiment may be configured with a red blood cell detector. The red blood cell detector may detect when most of the red blood cells have exited the container by determining the haemostatic level. The plasma remaining in the container may then be diverted into the analysis chamber. After the fluids have been removed from the container, the top connector may inject fluid (e.g., saline) into the container to flush the system and prepare it for the next sample.  
       FIGS. 22A  to  23 C illustrate another embodiment of a fluid handling and analysis apparatus  140 , which employs a removable, disposable fluid handling cassette  820 . The cassette  820  is equipped with a centrifuge rotor assembly  2016  to facilitate preparation and analysis of a sample. Except as further described below, the apparatus  140  of  FIGS. 22A-22C  can in certain embodiments be similar to any of the other embodiments of the apparatus  140  discussed herein, and the cassette  820  can in certain embodiments be similar to any of the embodiments of the cassettes  820  disclosed herein.  
      The removable fluid handling cassette  820  can be removably engaged with a main analysis instrument  810 . When the fluid handling cassette  820  is coupled to the main instrument  810 , a drive system  2030  of the main instrument  810  mates with the rotor assembly  2016  of the cassette  820  ( FIG. 22B ). Once the cassette  820  is coupled to the main instrument  810 , the drive system  2030  engages and can rotate the rotor assembly  2016  to apply a centrifugal force to a body fluid sample carried by the rotor assembly  2016 .  
      In some embodiments, the rotor assembly  2016  includes a rotor  2020  sample element  2448  ( FIG. 22C ) for holding a sample for centrifuging. When the rotor  2020  is rotated, a centrifugal force is applied to the sample contained within the sample element  2448 . The centrifugal force causes separation of one or more components of the sample (e.g., separation of plasma from whole blood). The separated component(s) can then be analyzed by the apparatus  140 , as will be discussed in further detail below.  
      The main instrument  810  includes both the centrifuge drive system  2030  and an analyte detection system  1700 , a portion of which protrudes from a housing  2049  of the main instrument  810 . The drive system  2030  is configured to releasably couple with the rotor assembly  2016 , and can impart rotary motion to the rotor assembly  2016  to rotate the rotor  2020  at a desired speed. After the centrifuging process, the analyte detection system  1700  can analyze one or more components separated from the sample carried by the rotor  2020 . The projecting portion of the illustrated detection system  1700  forms a slot  2074  for receiving a portion of the rotor  2020  carrying the sample element  2448  so that the detection system  1700  can analyze the sample or component(s) carried in the sample element  2448 .  
      To assemble the fluid handling and analysis apparatus  140  as shown in  FIG. 22C , the cassette  820  is placed on the main instrument  810 , as indicated by the arrow  2007  of  FIGS. 22A and 22B . The rotor assembly  2016  is accessible to the drive system  2030 , so that once the cassette  820  is properly mounted on the main instrument  810 , the drive system  2030  is in operative engagement with the rotor assembly  2016 . The drive system  2030  is then energized to spin the rotor  2020  at a desired speed. The spinning rotor  2020  can pass repeatedly through the slot  2074  of the detection system  1700 .  
      After the centrifuging process, the rotor  2020  is rotated to an analysis position (see  FIGS. 22B and 23C ) wherein the sample element  2448  is positioned within the slot  2074 . With the rotor  2020  and sample element  2448  in the analysis position, the analyte detection system  1700  can analyze one or more of the components of the sample carried in the sample element  2448 . For example, the detection system  1700  can analyze at least one of the components that is separated out during the centrifuging process. After using the cassette  820 , the cassette  820  can be removed from the main instrument  810  and discarded. Another cassette  820  can then be mounted to the main instrument  810 .  
      With reference to  FIG. 23A , the illustrated cassette  820  includes the housing  2400  that surrounds the rotor assembly  2016 , and the rotor  2020  is pivotally connected to the housing  2400  by the rotor assembly  2016 . The rotor  2020  includes a rotor interface  2051  for driving engagement with the drive system  2030  upon placement of the cassette  820  on the main instrument  810 .  
      In some embodiments, the cassette  820  is a disposable fluid handling cassette. The reusable main instrument  810  can be used with any number of cassettes  820  as desired. Additionally or alternatively, the cassette  820  can be a portable, handheld cassette for convenient transport. In these embodiments, the cassette  820  can be manually mounted to or removed from the main instrument  810 . In some embodiments, the cassette  820  may be a non disposable cassette which can be permanently coupled to the main instrument  810 .  
       FIGS. 25A and 25B  illustrate the centrifugal rotor  2020 , which is capable of carrying a sample, such as bodily fluid. Thus, the illustrated centrifugal rotor  2020  can be considered a fluid handling element that can prepare a sample for analysis, as well as hold the sample during a spectroscopic analysis. The rotor  2020  preferably comprises an elongate body  2446 , at least one sample element  2448 , and at least one bypass element  2452 . The sample element  2448  and bypass element  2452  can be located at opposing ends of the rotor  2020 . The bypass element  2452  provides a bypass flow path that can be used to clean or flush fluid passageways of the fluid handling and analysis apparatus  140  without passing fluid through the sample element  2448 .  
      The illustrated rotor body  2446  can be a generally planar member that defines a mounting aperture  2447  for coupling to the drive system  2030 . The illustrated rotor  2020  has a somewhat rectangular shape. In alternative embodiments, the rotor  2020  is generally circular, polygonal, elliptical, or can have any other shape as desired. The illustrated shape can facilitate loading when positioned horizontally to accommodate the analyte detection system  1700 .  
      With reference to  FIG. 25B , a pair of opposing first and second fluid connectors  2027 ,  2029  extends outwardly from a front face of the rotor  2020 , to facilitate fluid flow through the rotor body  2446  to the sample element  2448  and bypass element  2452 , respectively. The first fluid connector  2027  defines an outlet port  2472  and an inlet port  2474  that are in fluid communication with the sample element  2448 . In the illustrated embodiment, fluid channels  2510 ,  2512  extend from the outlet port  2472  and inlet port  2474 , respectively, to the sample element  2448 . (See  FIGS. 25E and 25F .) As such, the ports  2472 ,  2474  and channels  2510 ,  2512  define input and return flow paths through the rotor  2020  to the sample element  2448  and back.  
      With continued reference to  FIG. 25B , the rotor  2020  includes the bypass element  2452  which permits fluid flow therethrough from an outlet port  2572  to the inlet port  2574 . A channel  2570  extends between the outlet port  2572  and the inlet port  2574  to facilitate this fluid flow. The channel  2570  thus defines a closed flow path through the rotor  2020  from one port  2572  to the other port  2574 . In the illustrated embodiment, the outlet port  2572  and inlet port  2574  of the bypass element  2452  have generally the same spacing therebetween on the rotor  2020  as the outlet port  2472  and the inlet port  2474 .  
      One or more windows  2460   a ,  2460   b  can be provided for optical access through the rotor  2020 . A window  2460   a  proximate the bypass element  2452  can be a through-hole (see  FIG. 25E ) that permits the passage of electromagnetic radiation through the rotor  2020 . A window  2460   b  proximate the sample element  2448  can also be a similar through-hole which permits the passage of electromagnetic radiation. Alternatively, one or both of the windows  2460   a ,  2460   b  can be a sheet constructed of calcium fluoride, barium fluoride, germanium, silicon, polypropylene, polyethylene, combinations thereof, or any material with suitable transmissivity (i.e., transmittance per unit thickness) in the relevant wavelength(s). The windows  2460   a ,  2460   b  are positioned so that one of the windows  2460   a ,  2460   b  is positioned in the slot  2074  when the rotor  2020  is in a vertically orientated position.  
      Various fabrication techniques can be used to form the rotor  2020 . In some embodiments, the rotor  2020  can be formed by molding (e.g., compression or injection molding), machining, or a similar production process or combination of production processes. In some embodiments, the rotor  2020  is comprised of plastic. The compliance of the plastic material can be selected to create the seal with the ends of pins  2542 ,  2544  of a fluid interface  2028  (discussed in further detail below). Non-limiting exemplary plastics for forming the ports (e.g., ports  2572 ,  2574 ,  2472 ,  2474 ) can be relatively chemically inert and can be injection molded or machined. These plastics include, but are not limited to, PEEK and polyphenylenesulfide (PPS). Although both of these plastics have high modulus, a fluidic seal can be made if sealing surfaces are produced with smooth finish and the sealing zone is a small area where high contact pressure is created in a very small zone. Accordingly, the materials used to form the rotor  2020  and pins  2542 ,  2544  can be selected to achieve the desired interaction between the rotor  2020  and the pins  2542 ,  2544 , as described in detail below.  
      The illustrated rotor assembly  2016  of  FIG. 23A  rotatably connects the rotor  2020  to the cassette housing  2400  via a rotor axle boss  2426  which is fixed with respect to the cassette housing and pivotally holds a rotor axle  2430  and the rotor  2020  attached thereto. The rotor axle  2430  extends outwardly from the rotor axle boss  2426  and is fixedly attached to a rotor bracket  2436 , which is preferably securely coupled to a rear face of the rotor  2020 . Accordingly, the rotor assembly  2016  and the drive system  2030  cooperate to ensure that the rotor  2020  rotates about the axis  2024 , even at high speeds. The illustrated cassette  820  has a single rotor assembly  2016 . In other embodiments, the cassette  820  can have more than one rotor assembly  2016 . Multiple rotor assemblies  2016  can be used to prepare (preferably simultaneously) and test multiple samples.  
      With reference again to  FIGS. 25A, 25B ,  25 E and  25 F, the sample element  2448  is coupled to the rotor  2020  and can hold a sample of body fluid for processing with the centrifuge. The sample element  2448  can, in certain embodiments, be generally similar to other sample elements or cuvettes disclosed herein (e.g., sample elements  1730 ,  2112 ) except as further detailed below.  
      The sample element  2448  comprises a sample chamber  2464  that holds a sample for centrifuging, and fluid channels  2466 ,  2468 , which provide fluid communication between the chamber  2464  and the channels  2512 ,  2510 , respectively, of the rotor  2020 . Thus, the fluid channels  2512 ,  2466  define a first flow path between the port  2474  and the chamber  2464 , and the channels  2510 ,  2468  define a second flow path between the port  2472  and the chamber  2464 . Depending on the direction of fluid flow into the sample element  2448 , either of the first or second flow paths can serve as an input flow path, and the other can serve as a return flow path.  
      A portion of the sample chamber  2464  can be considered an interrogation region  2091 , which is the portion of the sample chamber through which electromagnetic radiation passes during analysis by the detection system  1700  of fluid contained in the chamber  2464 . Accordingly, the interrogation region  2091  is aligned with the window  2460   b  when the sample element  2448  is coupled to the rotor  2020 . The illustrated interrogation region  2091  comprises a radially inward portion (i.e., relatively close to the axis of rotation  2024  of the rotor  2020 ) of the chamber  2464 , to facilitate spectroscopic analysis of the lower density portion(s) of the body fluid sample (e.g., the plasma of a whole blood sample) after centrifuging, as will be discussed in greater detail below. Where the higher-density portions of the body fluid sample are of interest for spectroscopic analysis, the interrogation region  2091  can be located in a radially outward (i.e., further from the axis of rotation  2024  of the rotor  2020 ) portion of the chamber  2464 .  
      The rotor  2020  can temporarily or permanently hold the sample element  2448 . As shown in  FIG. 25F , the rotor  2020  forms a recess  2502  which receives the sample element  2448 . The sample element  2448  can be held in the recess  2502  by frictional interaction, adhesives, or any other suitable coupling means. The illustrated sample element  2448  is recessed in the rotor  2020 . However, the sample element  2448  can alternatively overlie or protrude from the rotor  2020 .  
      The sample element  2448  can be used for a predetermined length of time, to prepare a predetermined amount of sample fluid, to perform a number of analyses, etc. If desired, the sample element  2448  can be removed from the rotor  2020  and then discarded. Another sample element  2448  can then be placed into the recess  2502 . Thus, even if the cassette  820  is disposable, a plurality of disposable sample elements  2448  can be used with a single cassette  820 . Accordingly, a single cassette  820  can be used with any number of sample elements as desired. Alternatively, the cassette  820  can have a sample element  2448  that is permanently coupled to the rotor  2020 . In some embodiments, at least a portion of the sample element  2448  is integrally or monolithically formed with the rotor body  2446 . Additionally or alternatively, the rotor  2020  can comprise a plurality of sample elements (e.g., with a record sample element in place of the bypass  2452 ). In this embodiment, a plurality of samples (e.g., bodily fluid) can be prepared simultaneously to reduce sample preparation time.  
       FIGS. 26A and 26B  illustrate a layered construction technique which can be employed when forming certain embodiments of the sample element  2448 . The depicted layered sample element  2448  comprises a first layer  2473 , a second layer  2475 , and a third layer  2478 . The second layer  2475  is preferably positioned between the first layer  2473  and the third layer  2478 . The first layer  2473  forms an upper chamber wall  2482 , and the third layer  2478  forms a lower chamber wall  2484 . A lateral wall  2490  of the second layer  2475  defines the sides of the chamber  2464  and the fluid channels  2466 ,  2468 .  
      The second layer  2475  can be formed by die-cutting a substantially uniform-thickness sheet of a material to form the lateral wall pattern shown in  FIG. 26A . The second layer  2475  can comprise a layer of lightweight flexible material, such as a polymer material, with adhesive disposed on either side thereof to adhere the first and third layers  2473 ,  2478  to the second layer  2475  in “sandwich” fashion as shown in  FIG. 26B . Alternatively, the second layer  2475  can comprise an “adhesive-only” layer formed from a uniform-thickness sheet of adhesive which has been die-cut to form the depicted lateral wall pattern.  
      However constructed, the second layer  2475  is preferably of uniform thickness to define a substantially uniform thickness or path length of the sample chamber  2464  and/or interrogation region  2091 . This path length (and therefore the thickness of the second layer  2475  as well) is preferably between 10 microns and 100 microns, or is 20, 40, 50, 60, or 80 microns, in various embodiments.  
      The upper chamber wall  2482 , lower chamber wall  2484 , and lateral wall  2490  cooperate to form the chamber  2464 . The upper chamber wall  2482  and/or the lower chamber wall  2484  can permit the passage of electromagnetic energy therethrough. Accordingly, one or both of the first and third layers  2473 ,  2478  comprises a sheet or layer of material which is relatively or highly transmissive of electromagnetic radiation (preferably infrared radiation or mid-infrared radiation) such as barium fluoride, silicon, polyethylene or polypropylene. If only one of the layers  2473 ,  2478  is so transmissive, the other of the layers is preferably reflective, to back-reflect the incoming radiation beam for detection on the same side of the sample element  2448  as it was emitted. Thus the upper chamber wall  2482  and/or lower chamber wall  2484  can be considered optical window(s). These window(s) are disposed on one or both sides of the interrogation region  2091  of the sample element  2448 .  
      In one embodiment, sample element  2448  has opposing sides that are transmissive of infrared radiation and suitable for making optical measurements as described, for example, in U.S. patent application Publication No. 2005/0036146, published Feb. 17, 2005, titled SAMPLE ELEMENT QUALIFICATION, and hereby incorporated by reference and made a part of this specification. Except as further described herein, the embodiments, features, systems, devices, materials, methods and techniques described herein may, in some embodiments, be similar to any one or more of the embodiments, features, systems, devices, materials, methods and techniques described in U.S. patent application Publication No. 2003/0090649, published on May 15, 2003, titled REAGENT-LESS WHOLE-BLOOD GLUCOSE METER; or in U.S. patent application Publication No. 2003/0086075, published on May 8, 2003, titled DEVICE AND METHOD FOR IN VITRO DETERMINATION OF ANALYTE CONCENTRATIONS WITHIN BODY FLUIDS; or in U.S. patent application Publication No. 2004/0019431, published on Jan. 29, 2004, titled METHOD OF DETERMINING AN ANALYTE CONCENTRATION IN A SAMPLE FROM AN ABSORPTION SPECTRUM, or in U.S. Pat. No. 6,652,136, issued on Nov. 25, 2003 to Marziali, titled METHOD OF SIMULTANEOUS MIXING OF SAMPLES. In addition, the embodiments, features, systems, devices, materials, methods and techniques described herein may, in certain embodiments, be applied to or used in connection with any one or more of the embodiments, features, systems, devices, materials, methods and techniques disclosed in the above-mentioned U.S. patent applications Publications Nos. 2003/0090649; 2003/0086075; 2004/0019431; or U.S. Pat. No. 6,652,136. All of the above-mentioned publications and patent are hereby incorporated by reference herein and made a part of this specification.  
      With reference to  FIGS. 23B and 23C , the cassette  820  can further comprise the movable fluid interface  2028  for filling and/or removing sample liquid from the sample element  2448 . In the depicted embodiment, the fluid interface  2028  is rotatably mounted to the housing  2400  of the cassette  820 . The fluid interface  2028  can be actuated between a lowered position ( FIG. 22C ) and a raised or filling position ( FIG. 27C ). When the interface  2028  is in the lowered position, the rotor  2020  can freely rotate. To transfer sample fluid to the sample element  2448 , the rotor  2020  can be held stationary and in a sample element loading position (see  FIG. 22C ) the fluid interface  2028  can be actuated, as indicated by the arrow  2590 , upwardly to the filling position. When the fluid interface  2028  is in the filling position, the fluid interface  2028  can deliver sample fluid into the sample element  2448  and/or remove sample fluid from the sample element  2448 .  
      With continued reference to  FIGS. 27A and 27B , the fluid interface  2028  has a main body  2580  that is rotatably mounted to the housing  2400  of the cassette  820 . Opposing brackets  2581 ,  2584  can be employed to rotatably couple the main body  2580  to the housing  2400  of the cassette  820 , and permit rotation of the main body  2580  and the pins  2542 ,  2544  about an axis of rotation  2590  between the lowered position and the filling position. The main instrument  810  can include a horizontally moveable actuator (not shown) in the form of a solenoid, pneumatic actuator, etc. which is extendible through an opening  2404  in the cassette housing  2400  (see  FIG. 23B ). Upon extension, the actuator strikes the main body  2580  of the fluid interface  2028 , causing the body  2580  to rotate to the filling position shown in  FIG. 27C . The main body  2580  is preferably spring-biased towards the retracted position (shown in  FIG. 23A ) so that retraction of the actuator allows the main body to return to the retracted position. The fluid interface  2028  can thus be actuated for periodically placing fluid passageways of the pins  2542 ,  2544  in fluid communication with a sample element  2448  located on the rotor  2020 .  
      The fluid interface  2028  of  FIGS. 27A and 23B  includes fluid connectors  2530 ,  2532  that can provide fluid communication between the interface  2028  and one or more of the fluid passageways of the apparatus  140  and/or sampling system  100 / 800 , as will be discussed in further detail below. The illustrated connectors  2530 ,  2532  are in an upwardly extending orientation and positioned at opposing ends of the main body  2580 . The connectors  2530 ,  2532  can be situated in other orientations and/or positioned at other locations along the main body  2580 . The main body  2580  includes a first inner passageway (not shown) which provides fluid communication between the connector  2530  and the pin  2542 , and a second inner passageway (not shown) which provides fluid communication between the connector  2532  and the pin  2544 .  
      The fluid pins  2542 ,  2544  extend outwardly from the main body  2580  and can engage the rotor  2020  to deliver and/or remove sample fluid to or from the rotor  2020 . The fluid pins  2542 ,  2544  have respective pin bodies  2561 ,  2563  and pin ends  2571 ,  2573 . The pin ends  2571 ,  2573  are sized to fit within corresponding ports  2472 ,  2474  of the fluid connector  2027  and/or the ports  2572 ,  2574  of the fluid connector  2029 , of the rotor  2020 . The pin ends  2571 ,  2573  can be slightly chamfered at their tips to enhance the sealing between the pin ends  2571 ,  2573  and rotor ports. In some embodiments, the outer diameters of the pin ends  2573 ,  2571  are slightly larger than the inner diameters of the ports of the rotor  2020  to ensure a tight seal, and the inner diameters of the pins  2542 ,  2544  are preferably identical or very close to the inner diameters of the channels  2510 ,  2512  leading from the ports. In other embodiments, the outer diameter of the pin ends  2571 ,  2573  are equal to or less than the inner diameters of the ports of the rotor  2020 .  
      The connections between the pins  2542 ,  2544  and the corresponding portions of the rotor  2020 , either the ports  2472 ,  2474  leading to the sample element  2448  or the ports  2572 ,  2574  leading to the bypass element  2452 , can be relatively simple and inexpensive. At least a portion of the rotor  2020  can be somewhat compliant to help ensure a seal is formed with the pins  2542 ,  2544 . Alternatively or additionally, sealing members (e.g., gaskets, O-rings, and the like) can be used to inhibit leaking between the pin ends  2571 ,  2573  and corresponding ports  2472 ,  2474 ,  2572 ,  2574 .  
       FIGS. 23A and 23B  illustrate the cassette housing  2400  enclosing the rotor assembly  2016  and the fluid interface  2028 . The housing  2400  can be a modular body that defines an aperture or opening  2404  dimensioned to receive a drive system housing  2050  when the cassette  820  is operatively coupled to the main instrument  810 . The housing  2400  can protect the rotor  2020  from external forces and can also limit contamination of samples delivered to a sample element in the rotor  2020 , when the cassette  820  is mounted to the main instrument  810 .  
      The illustrated cassette  820  has a pair of opposing side walls  2041 ,  2043 , top  2053 , and a notch  2408  for mating with the detection system  1700 . A front wall  2045  and rear wall  2047  extend between the side walls  2041 ,  2043 . The rotor assembly  2016  is mounted to the inner surface of the rear wall  2047 . The front wall  2045  is configured to mate with the main instrument  810  while providing the drive system  2030  with access to the rotor assembly  2016 .  
      The illustrated front wall  2045  has the opening  2404  that provides access to the rotor assembly  2016 . The drive system  2030  can be passed through the opening  2404  into the interior of the cassette  820  until it operatively engages the rotor assembly  2016 . The opening  2404  of  FIG. 23B  is configured to mate and tightly surround the drive system  2030 . The illustrated opening  2404  is generally circular and includes an upper notch  2405  to permit the fluid interface actuator of the main instrument  810  to access the fluid interface  2028 , as discussed above. The opening  2404  can have other configurations suitable for admitting the drive system  2030  and actuator into the cassette  820 .  
      The notch  2408  of the housing  2400  can at least partially surround the projecting portion of the analyte detection system  1700  when the cassette  820  is loaded onto the main instrument  810 . The illustrated notch  2408  defines a cassette slot  2410  ( FIG. 23A ) that is aligned with elongate slot  2074  shown in  FIG. 22C , upon loading of the cassette  820 . The rotating rotor  2020  can thus pass through the aligned slots  2410 ,  2074 . In some embodiments, the notch  2408  has a generally U-shaped axial cross section as shown. More generally, the configuration of the notch  2408  can be selected based on the design of the projecting portion of the detection system  1700 .  
      Although not illustrated, fasteners, clips, mechanical fastening assemblies, snaps, or other coupling means can be used to ensure that the cassette  820  remains coupled to the main instrument  810  during operation. Alternatively, the interaction between the housing  2400  and the components of the main instrument  810  can secure the cassette  820  to the main instrument  810 .  
       FIG. 28  is a cross-sectional view of the main instrument  810 . The illustrated centrifuge drive system  2030  extends outwardly from a front face  2046  of the main instrument  810  so that it can be easily mated with the rotor assembly  2016  of the cassette  820 . When the centrifuge drive system  2030  is energized, the drive system  2030  can rotate the rotor  2020  at a desired rotational speed.  
      The illustrated centrifuge drive system  2030  of  FIGS. 23E and 28  includes a centrifuge drive motor  2038  and a drive spindle  2034  that is drivingly connected to the drive motor  2038 . The drive spindle  2034  extends outwardly from the drive motor  2038  and forms a centrifuge interface  2042 . The centrifuge interface  2042  extends outwardly from the drive system housing  2050 , which houses the drive motor  2038 . To impart rotary motion to the rotor  2020 , the centrifuge interface  2042  can have keying members, protrusions, notches, detents, recesses, pins, or other types of structures that can engage the rotor  2020  such that the drive spindle  2034  and rotor  2020  are coupled together.  
      The centrifuge drive motor  2038  of  FIG. 28  can be any suitable motor that can impart rotary motion to the rotor  2020 . When the drive motor  2038  is energized, the drive motor  2038  can rotate the drive spindle  2034  at constant or varying speeds. Various types of motors, including, but not limited to, centrifuge motors, stepper motors, spindle motors, electric motors, or any other type of motor for outputting a torque can be utilized. The centrifuge drive motor  2038  is preferably fixedly secured to the drive system housing  2050  of the main instrument  810 .  
      The drive motor  2038  can be the type of motor typically used in personal computer hard drives that is capable of rotating at about 7,200 RPM on precision bearings, such as a motor of a Seagate Model ST380011A hard drive (Seagate Technology, Scotts Valley, Calif.) or similar motor. In one embodiment, the drive spindle  2034  may be rotated at 6,000 rpm, which yields approximately 2,000 G&#39;s for a rotor having a 2.5 inch (64 millimeter) radius. In another embodiment, the drive spindle  2034  may be rotated at speeds of approximately 7,200 rpm. The rotational speed of the drive spindle  2034  can be selected to achieve the desired centrifugal force applied to a sample carried by the rotor  2020 .  
      The main instrument  810  includes a main housing  2049  that defines a chamber sized to accommodate a filter wheel assembly  2300  including a filter drive motor  2320  and filter wheel  2310  of the analyte detection system  1700 . The main housing  2049  defines a detection system opening  3001  configured to receive an analyte detection system housing  2070 . The illustrated analyte detection system housing  2070  extends or projects outwardly from the housing  2049 .  
      The main instrument  810  of  FIGS. 23C and 23E  includes a bubble sensor unit  321 , a pump  2619  in the form of a peristaltic pump roller  2620   a  and a roller support  2620   b , and valves  323   a ,  323   b . The illustrated valves  323   a ,  323   b  are pincher pairs, although other types of valves can be used. When the cassette  820  is installed, these components can engage components of a fluid handling network  2600  of the cassette  820 , as will be discussed in greater detail below.  
      With continued reference to  FIG. 28 , the analyte detection system housing  2070  surrounds and houses some of the internal components of the analyte detection system  1700 . The elongate slot  2074  extends downwardly from an upper face  2072  of the housing  2070 . The elongated slot  2074  is sized and dimensioned so as to receive a portion of the rotor  2020 . When the rotor  2020  rotates, the rotor  2020  passes periodically through the elongated slot  2074 . When a sample element of the rotor  2020  is in the detection region  2080  defined by the slot  2074 , the analyte detection system  1700  can analyze material in the sample element.  
      The analyte detection system  1700  can be a spectroscopic bodily fluid analyzer that preferably comprises an energy source  1720 . The energy source  1720  can generate an energy beam directed along a major optical axis X that passes through the slot  2074  towards a sample detector  1745 . The slot  2074  thus permits at least a portion of the rotor (e.g., the interrogation region  2091  or sample chamber  2464  of the sample element  2448 ) to be positioned on the optical axis X. To analyze a sample carried by the sample element  2448 , the sample element and sample can be positioned in the detection region  2080  on the optical axis X such that light emitted from the source  1720  passes through the slot  2074  and the sample disposed within the sample element  2448 .  
      The analyte detection system  1700  can also comprise one or more lenses positioned to transmit energy outputted from the energy source  1720 . The illustrated analyte detection system  1700  of  FIG. 28  comprises a first lens  2084  and a second lens  2086 . The first lens  2084  is configured to focus the energy from the source  1720  generally onto the sample element and material sample. The second lens  2086  is positioned between the sample element and the sample detector  1745 . Energy from energy source  1720  passing through the sample element can subsequently pass through the second lens  2086 . A third lens  2090  is preferably positioned between a beam splitter  2093  and a reference detector  2094 . The reference detector  2094  is positioned to receive energy from the beam splitter  2093 .  
      The analyte detection system  1700  can be used to determine the analyte concentration in the sample carried by the rotor  2020 . Other types of detection or analysis systems can be used with the illustrated centrifuge apparatus or sample preparation unit. The fluid handling and analysis apparatus  140  is shown for illustrative purposes as being used in conjunction with the analyte detection system  1700 , but neither the sample preparation unit nor analyte detection system are intended to be limited to the illustrated configuration, or to be limited to being used together.  
      To assemble the fluid handling and analysis apparatus  140 , the cassette  820  can be moved towards and installed onto the main instrument  810 , as indicated by the arrow  2007  in  FIG. 22A . As the cassette  820  is installed, the drive system  2030  passes through the aperture  2040  so that the spindle  2034  mates with the rotor  2020 . Simultaneously, the projecting portion of the detection system  1700  is received in the notch  2408  of the cassette  820 . When the cassette  820  is installed on the main instrument  810 , the slot  2410  of the notch  2048  and the slot  2074  of the detection system  1700  are aligned as shown in  FIG. 22C . Accordingly, when the cassette  820  and main instrument  810  are assembled, the rotor  2020  can rotate about the axis  2024  and pass through the slots  2410 ,  2074 .  
      After the cassette  820  is assembled with the main instrument  810 , a sample can be added to the sample element  2448 . The cassette  820  can be connected to an infusion source and a patient to place the system in fluid communication with a bodily fluid to be analyzed. Once the cassette  820  is connected to a patient, a bodily fluid may be drawn from the patient into the cassette  820 . The rotor  2020  is rotated to a vertical loading position wherein the sample element  2448  is near the fluid interface  2028  and the bypass element  2452  is positioned within the slot  2074  of the detection system  1700 . Once the rotor  2020  is in the vertical loading position, the pins  2542 ,  2544  of the fluid interface  2028  are positioned to mate with the ports  2472 ,  2474  of the rotor  2020 . The fluid interface  2028  is then rotated upwardly until the ends  2571 ,  2573  of the pins  2542 ,  2544  are inserted into the ports  2472 ,  2474 .  
      When the fluid interface  2028  and the sample element  2448  are thus engaged, sample fluid (e.g., whole blood) is pumped into the sample element  2448 . The sample can flow through the pin  2544  into and through the rotor channel  2512  and the sample element channel  2466 , and into the sample chamber  2464 . As shown in  FIG. 25C , the sample chamber  2464  can be partially or completely filled with sample fluid. In some embodiments, the sample fills at least the sample chamber  2464  and the interrogation region  2091  of the sample element  2448 . The sample can optionally fill at least a portion of the sample element channels  2466 ,  2468 . The illustrated sample chamber  2464  is filled with whole blood, although the sample chamber  2464  can be filled with other substances. After the sample element  2448  is filled with a desired amount of fluid, the fluid interface  2028  can be moved to a lowered position to permit rotation of the rotor  2020 .  
      The centrifuge drive system  2030  can then spin the rotor  2020  and associated sample element  2448  as needed to separate one or more components of the sample. The separated component(s) of the sample may collect or be segregated in a section of the sample element for analysis. In the illustrated embodiment, the sample element  2448  of  FIG. 25C  is filled with whole blood prior to centrifuging. The centrifugal forces can be applied to the whole blood until plasma  2594  is separated from the blood cells  2592 . After centrifuging, the plasma  2594  is preferably located in a radially inward portion of the sample element  2448 , including the interrogation region  2091 . The blood cells  2592  collect in a portion of the sample chamber  2464  which is radially outward of the plasma  2594  and interrogation region  2091 .  
      The rotor  2020  can then be moved to a vertical analysis position wherein the sample element  2448  is disposed within the slot  2074  and aligned with the source  1720  and the sample detector  1745  on the major optical axis X. When the rotor  2020  is in the analysis position, the interrogation portion  2091  is preferably aligned with the major optical axis X of the detection system  1700 . The analyte detection system  1700  can analyze the sample in the sample element  2448  using spectroscopic analysis techniques as discussed elsewhere herein.  
      After the sample has been analyzed, the sample can be removed from the sample element  2448 . The sample may be transported to a waste receptacle so that the sample element  2448  can be reused for successive sample draws and analyses. The rotor  2020  is rotated from the analysis position back to the vertical loading position. To empty the sample element  2448 , the fluid interface  2028  can again engage the sample element  2448  to flush the sample element  2448  with fresh fluid (either a new sample of body fluid, or infusion fluid). The fluid interface  2028  can be rotated to mate the pins  2542 ,  2544  with the ports  2472 ,  2474  of the rotor  2020 . The fluid interface  2028  can pump a fluid through one of the pins  2542 ,  2544  until the sample is flushed from the sample element  2448 . Various types of fluids, such as infusion liquid, air, water, and the like, can be used to flush the sample element  2448 . After the sample element  2448  has been flushed, the sample element  2448  can once again be filled with another sample.  
      In an alternative embodiment, the sample element  2448  may be removed from the rotor  2020  and replaced after each separate analysis, or after a certain number of analyses. Once the patient care has terminated, the fluid passageways or conduits may be disconnected from the patient and the sample cassette  820  which has come into fluid contact with the patient&#39;s bodily fluid may be disposed of or sterilized for reuse. The main instrument  810 , however, has not come into contact with the patient&#39;s bodily fluid at any point during the analysis and therefore can readily be connected to a new fluid handling cassette  820  and used for the analysis of a subsequent patient.  
      The rotor  2020  can be used to provide a fluid flow bypass. To facilitate a bypass flow, the rotor  2020  is first rotated to the vertical analysis/bypass position wherein the bypass element  2452  is near the fluid interface  2028  and the sample element  2448  is in the slot  2074  of the analyte detection system  1700 . Once the rotor  2020  is in the vertical analysis/bypass position, the pins  2542 ,  2544  can mate with the ports  2572 ,  2574  of the rotor  2020 . In the illustrated embodiment, the fluid interface  2028  is rotated upwardly until the ends  2571 ,  2573  of the pins  2542 ,  2544  are inserted into the ports  2572 ,  2574 . The bypass element  2452  can then provide a completed fluid circuit so that fluid can flow through one of the pins  2542 ,  2544  into the bypass element  2452 , through the bypass element  2452 , and then through the other pin  2542 ,  2544 . The bypass element  2452  can be utilized in this manner to facilitate the flushing or sterilizing of a fluid system connected to the cassette  820 .  
      As shown in  FIG. 23B , the cassette  820  preferably includes the fluid handling network  2600  which can be employed to deliver fluid to the sample element  2448  in the rotor  2020  for analysis. The main instrument  810  has a number of components that can, upon installation of the cassette  820  on the main instrument  810 , extend through openings in the front face  2045  of cassette  820  to engage and interact with components of the fluid handling network  2600 , as detailed below.  
      The fluid handling network  2600  of the fluid handling and analysis apparatus  140  includes the passageway  111  which extends from the connector  120  toward and through the cassette  820  until it becomes the passageway  112 , which extends from the cassette  820  to the patient connector  110 . A portion  111   a  of the passageway  111  extends across an opening  2613  in the front face  2045  of the cassette  820 . When the cassette  820  is installed on the main instrument  810 , the roller pump  2619  engages the portion  111   a , which becomes situated between the impeller  2620   a  and the impeller support  2620   b  (see  FIG. 23C ).  
      The fluid handling network  2600  also includes passageway  113  which extends from the patient connector  110  towards and into the cassette  820 . After entering the cassette  820 , the passageway  113  extends across an opening  2615  in the front face  2045  to allow engagement of the passageway  113  with a bubble sensor  321  of the main instrument  810 , when the cassette  820  is installed on the main instrument  810 . The passageway  113  then proceeds to the connector  2532  of the fluid interface  2028 , which extends the passageway  113  to the pin  2544 . Fluid drawn from the patient into the passageway  113  can thus flow into and through the fluid interface  2028 , to the pin  2544 . The drawn body fluid can further flow from the pin  2544  and into the sample element  2448 , as detailed above.  
      A passageway  2609  extends from the connector  2530  of the fluid interface  2028  and is thus in fluid communication with the pin  2542 . The passageway  2609  branches to form the waste line  324  and the pump line  327 . The waste line  324  passes across an opening  2617  in the front face  2045  and extends to the waste receptacle  325 . The pump line  327  passes across an opening  2619  in the front face  2045  and extends to the pump  328 . When the cassette  820  is installed on the main instrument  810 , the pinch valves  323   a ,  323   b  extend through the openings  2617 ,  2619  to engage the lines  324 ,  327 , respectively.  
      The waste receptacle  325  is mounted to the front face  2045 . Waste fluid passing from the fluid interface  2028  can flow through the passageways  2609 ,  324  and into the waste receptacle  325 . Once the waste receptacle  325  is filled, the cassette  820  can be removed from the main instrument  810  and discarded. Alternatively, the filled waste receptacle  325  can be replaced with an empty waste receptacle  325 .  
      The pump  328  can be a displacement pump (e.g., a syringe pump). A piston control  2645  can extend over at least a portion of an opening  2621  in the cassette face  2045  to allow engagement with an actuator  2652  when the cassette  820  is installed on the main instrument  810 . When the cassette  820  is installed, the actuator  2652  ( FIG. 23E ) of the main instrument  810  engages the piston control  2645  of the pump  328  and can displace the piston control  2645  for a desired fluid flow.  
      It will be appreciated that, upon installing the cassette  820  of  FIG. 23A  on the main instrument  810  of  FIG. 23E , there is formed (as shown in  FIG. 23E ) a fluid circuit similar to that shown in the sampling unit  200  in  FIG. 3 . This fluid circuit can be operated in a manner similar to that described above in connection with the apparatus of  FIG. 3  (e.g., in accordance with the methodology illustrated in  FIGS. 7A-7J  and Table 1).  
       FIG. 24A  depicts another embodiment of a fluid handling network  2700  that can be employed in the cassette  820 . The fluid handling network  2700  can be generally similar in structure and function to the network  2600  of  FIG. 23B , except as detailed below. The network  2700  includes the passageway  111  which extends from the connector  120  toward and through the cassette  820  until it becomes the passageway  112 , which extends from the cassette  820  to the patient connector  110 . A portion  111   a  of the passageway  111  extends across an opening  2713  in the front face  2745  of the cassette  820 . When the cassette  820  is installed on the main instrument  810 , a roller pump  2619  of the main instrument  810  of  FIG. 24B  can engage the portion  111   a  in a manner similar to that described above with respect to  FIGS. 23B-23C . The passageway  113  extends from the patient connector  110  towards and into the cassette  820 . After entering the cassette  820 , the passageway  113  extends across an opening  2763  in the front face  2745  to allow engagement with a valve  2733  of the main instrument  810 . A waste line  2704  extends from the passageway  113  to the waste receptacle  325  and across an opening  2741  in the front face  2745 . The passageway  113  proceeds to the connector  2532  of the fluid interface  2028 , which extends the passageway  113  to the pin  2544 . The passageway  113  crosses an opening  2743  in the front face  2745  to allow engagement of the passageway  113  with a bubble sensor  2741  of the main instrument  810  of  FIG. 24B . When the cassette  820  is installed on the main instrument  810 , the pinch valves  2732 ,  2733  extend through the openings  2731 ,  2743  to engage the passageways  113 ,  2704 , respectively.  
      The illustrated fluid handling network  2700  also includes a passageway  2723  which extends between the passageway  111  and a passageway  2727 , which in turn extends between the passageway  2723  and the fluid interface  2028 . The passageway  2727  extends across an opening  2733  in the front face  2745 . A pump line  2139  extends from a pump  328  to the passageways  2723 ,  2727 . When the cassette  820  is installed on the main instrument  810 , the pinch valves  2716 ,  2718  extend through the openings  2725 ,  2733  in the front face  2745  to engage the passageways  2723 ,  2727 , respectively.  
      It will be appreciated that, upon installing the cassette  820  on the main instrument  810  (as shown in  FIG. 24A ), there is formed a fluid circuit that can be operated in a manner similar to that described above, in connection with the apparatus of  FIGS. 9-10 .  
      In view of the foregoing, it will be further appreciated that the various embodiments of the fluid handling and analysis apparatus  140  (comprising a main instrument  810  and cassette  820 ) depicted in  FIGS. 22A-28  can serve as the fluid handling and analysis apparatus  140  of any of the sampling systems  100 / 300 / 500 , or the fluid handling system  10 , depicted in  FIGS. 1-5  herein. In addition, the fluid handling and analysis apparatus  140  of  FIGS. 22A-28  can, in certain embodiments, be similar to the apparatus  140  of  FIGS. 1-2  or  8 - 10 , except as further described above.  
      Section V—Methods for Determining Analyte Concentrations from Sample Spectra  
      This section discusses a number of computational methods or algorithms which may be used to calculate the concentration of the analyte(s) of interest in the sample S, and/or to compute other measures that may be used in support of calculations of analyte concentrations. Any one or combination of the algorithms disclosed in this section may reside as program instructions stored in the memory  212  so as to be accessible for execution by the processor  210  of the fluid handling and analysis apparatus  140  or analyte detection system  334  to compute the concentration of the analyte(s) of interest in the sample, or other relevant measures.  
      Several disclosed embodiments are devices and methods for analyzing material sample measurements and for quantifying one or more analytes in the presence of interferents. Interferents can comprise components of a material sample being analyzed for an analyte, where the presence of the interferent affects the quantification of the analyte. Thus, for example, in the spectroscopic analysis of a sample to determine an analyte concentration, an interferent could be a compound having spectroscopic features that overlap with those of the analyte. The presence of such an interferent can introduce errors in the quantification of the analyte. More specifically, the presence of interferents can affect the sensitivity of a measurement technique to the concentration of analytes of interest in a material sample, especially when the system is calibrated in the absence of, or with an unknown amount of, the interferent.  
      Independently of or in combination with the attributes of interferents described above, interferents can be classified as being endogenous (i.e., originating within the body) or exogenous (i.e., introduced from or produced outside the body). As example of these classes of interferents, consider the analysis of a blood sample (or a blood component sample or a blood plasma sample) for the analyte glucose. Endogenous interferents include those blood components having origins within the body that affect the quantification of glucose, and may include water, hemoglobin, blood cells, and any other component that naturally occurs in blood. Exogenous interferents include those blood components having origins outside of the body that affect the quantification of glucose, and can include items administered to a person, such as medicaments, drugs, foods or herbs, whether administered orally, intravenously, topically, etc.  
      Independently of or in combination with the attributes of interferents described above, interferents can comprise components which are possibly but not necessarily present in the sample type under analysis. In the example of analyzing samples of blood or blood plasma drawn from patients who are receiving medical treatment, a medicament such as acetaminophen is possibly, but not necessarily present in this sample type. In contrast, water is necessarily present in such blood or plasma samples.  
      To facilitate an understanding of the inventions, embodiments are discussed herein where one or more analyte concentrations are obtained using spectroscopic measurements of a sample at wavelengths including one or more wavelengths that are identified with the analyte(s). The embodiments disclosed herein are not meant to limit, except as claimed, the scope of certain disclosed inventions which are directed to the analysis of measurements in general.  
      As an example, certain disclosed methods are used to quantitatively estimate the concentration of one specific compound (an analyte) in a mixture from a measurement, where the mixture contains compounds (interferents) that affect the measurement. Certain disclosed embodiments are particularly effective if each analyte and interferent component has a characteristic signature in the measurement, and if the measurement is approximately affine (i.e., includes a linear component and an offset) with respect to the concentration of each analyte and interferent. In one embodiment, a method includes a calibration process including an algorithm for estimating a set of coefficients and an offset value that permits the quantitative estimation of an analyte. In another embodiment, there is provided a method for modifying hybrid linear algorithm (HLA) methods to accommodate a random set of interferents, while retaining a high degree of sensitivity to the desired component. The data employed to accommodate the random set of interferents are (a) the signatures of each of the members of the family of potential additional components and (b) the typical quantitative level at which each additional component, if present, is likely to appear.  
      Certain methods disclosed herein are directed to the estimation of analyte concentrations in a material sample in the possible presence of an interferent. In certain embodiments, any one or combination of the methods disclosed herein may be accessible and executable processor  210  of system  334 . Processor  210  may be connected to a computer network, and data obtained from system  334  can be transmitted over the network to one or more separate computers that implement the methods. The disclosed methods can include the manipulation of data related to sample measurements and other information supplied to the methods (including, but not limited to, interferent spectra, sample population models, and threshold values, as described subsequently). Any or all of this information, as well as specific algorithms, may be updated or changed to improve the method or provide additional information, such as additional analytes or interferents.  
      Certain disclosed methods generate a “calibration constant” that, when multiplied by a measurement, produces an estimate of an analyte concentration. Both the calibration constant and measurement can comprise arrays of numbers. The calibration constant is calculated to minimize or reduce the sensitivity of the calibration to the presence of interferents that are identified as possibly being present in the sample. Certain methods described herein generate a calibration constant by: 1) identifying the presence of possible interferents; and 2) using information related to the identified interferents to generate the calibration constant. These certain methods do not require that the information related to the interferents includes an estimate of the interferent concentration—they merely require that the interferents be identified as possibly present. In one embodiment, the method uses a set of training spectra each having known analyte concentration(s) and produces a calibration that minimizes the variation in estimated analyte concentration with interferent concentration. The resulting calibration constant is proportional to analyte concentration(s) and, on average, is not responsive to interferent concentrations.  
      In one embodiment, it is not required (though not prohibited either) that the training spectra include any spectrum from the individual whose analyte concentration is to be determined. That is, the term “training” when used in reference to the disclosed methods does not require training using measurements from the individual whose analyte concentration will be estimated (e.g., by analyzing a bodily fluid sample drawn from the individual).  
      Several terms are used herein to describe the estimation process. As used herein, the term “Sample Population” is a broad term and includes, without limitation, a large number of samples having measurements that are used in the computation of a calibration—in other words, used to train the method of generating a calibration. For an embodiment involving the spectroscopic determination of glucose concentration, the Sample Population measurements can each include a spectrum (analysis measurement) and a glucose concentration (analyte measurement). In one embodiment, the Sample Population measurements are stored in a database, referred to herein as a “Population Database.” 
      The Sample Population may or may not be derived from measurements of material samples that contain interferents to the measurement of the analyte(s) of interest. One distinction made herein between different interferents is based on whether the interferent is present in both the Sample Population and the sample being measured, or only in the sample. As used herein, the term “Type-A interferent” refers to an interferent that is present in both the Sample Population and in the material sample being measured to determine an analyte concentration. In certain methods it is assumed that the Sample Population includes only interferents that are endogenous, and does not include any exogenous interferents, and thus Type-A interferents are endogenous. The number of Type-A interferents depends on the measurement and analyte(s) of interest, and may number, in general, from zero to a very large number. The material sample being measured, for example sample S, may also include interferents that are not present in the Sample Population. As used herein, the term “Type-B interferent” refers to an interferent that is either: 1) not found in the Sample Population but that is found in the material sample being measured (e.g., an exogenous interferent), or 2) is found naturally in the Sample Population, but is at abnormally high concentrations in the material sample (e.g., an endogenous interferent). Examples of a Type-B exogenous interferent may include medications, and examples of Type-B endogenous interferents may include urea in persons suffering from renal failure. In the example of mid-IR spectroscopic absorption measurement of glucose in blood, water is found in all blood samples, and is thus a Type-A interferent. For a Sample Population made up of individuals who are not taking intravenous drugs, and a material sample taken from a hospital patient who is being administered a selected intravenous drug, the selected drug is a Type-B interferent.  
      In one embodiment, a list of one or more possible Type-B Interferents is referred to herein as forming a “Library of Interferents,” and each interferent in the library is referred to as a “Library Interferent.” The Library Interferents include exogenous interferents and endogenous interferents that may be present in a material sample due, for example, to a medical condition causing abnormally high concentrations of the endogenous interferent.  
      In addition to components naturally found in the blood, the ingestion or injection of some medicines or illicit drugs can result in very high and rapidly changing concentrations of exogenous interferents. This results in problems in measuring analytes in blood of hospital or emergency room patients. An example of overlapping spectra of blood components and medicines is illustrated in  FIG. 29  as the absorption coefficient at the same concentration and optical pathlength of pure glucose and three spectral interferents, specifically mannitol (chemical formula: hexane-1,2,3,4,5,6-hexaol), N acetyl L cysteine, dextran, and procainamide (chemical formula: 4-amino-N-(2-diethylaminoethyl)benzamid).  FIG. 30  shows the logarithm of the change in absorption spectra from a Sample Population blood composition as a function of wavelength for blood containing additional likely concentrations of components, specifically, twice the glucose concentration of the Sample Population and various amounts of mannitol, N acetyl L cysteine, dextran, and procainamide. The presence of these components is seen to affect absorption over a wide range of wavelengths. It can be appreciated that the determination of the concentration of one species without a priori knowledge or independent measurement of the concentration of other species is problematic.  
      One method for estimating the concentration of an analyte in the presence of interferents is presented in flowchart  3100  of  FIG. 31  as a first step (Block  3110 ) where a measurement of a sample is obtained, a second step (Block  3120 ), where the obtained measurement data is analyzed to identify possible interferents to the analyte, a third step (Block  3130 ) where a model is generated for predicting the analyte concentration in the presence of the identified possible interferents, and a fourth step (Block  3140 ) where the model is used to estimate the analyte concentration in the sample from the measurement. Preferably the step of Block  3130  generates a model where the error is minimized for the presence of the identified interferents that are not present in a general population of which the sample is a member.  
      The method Blocks  3110 ,  3120 ,  3130 , and  3140  may be repeatedly performed for each analyte whose concentration is required. If one measurement is sensitive to two or more analytes, then the methods of Blocks  3120 ,  3130 , and  3140  may be repeated for each analyte. If each analyte has a separate measurement, then the methods of Blocks  3110 ,  3120 ,  3130 , and  3140  may be repeated for each analyte.  
      An embodiment of the method of flowchart  3100  for the determination of an analyte from spectroscopic measurements will now be discussed. Further, this embodiment will estimate the amount of glucose concentration in blood sample S, without limit to the scope of the present disclosure. In one embodiment, the measurement of Block  3110  is an absorbance spectrum, C s (λ i ), of a measurement sample S that has, in general, one analyte of interest, glucose, and one or more interferents. In one embodiment, the methods include generating a calibration constant κ(λ i ) that, when multiplied by the absorbance spectrum C s (λ i ), provides an estimate, g est , of the glucose concentration g s .  
      As described subsequently, one embodiment of Block  3120  includes a statistical comparison of the absorbance spectrum of sample S with a spectrum of the Sample Population and combinations of individual Library Interferent spectra. After the analysis of Block  3120 , a list of Library Interferents that are possibly contained in sample S has been identified and includes, depending on the outcome of the analysis of Block  3120 , either no Library Interferents, or one or more Library Interferents. Block  3130  then generates a large number of spectra using the large number of spectra of the Sample Population and their respective known analyte concentrations and known spectra of the identified Library Interferents. Block  3130  then uses the generated spectra to generate a calibration constant matrix to convert a measured spectrum to an analyte concentration that is the least sensitive to the presence of the identified Library Interferents. Block  3140  then applies the generated calibration constant to predict the glucose concentration in sample S.  
      As indicated in Block  3110 , a measurement of a sample is obtained. For illustrative purposes, the measurement, C s (λ i ), is assumed to be a plurality of measurements at different wavelengths, or analyzed measurements, on a sample indicating the intensity of light that is absorbed by sample S. It is to be understood that spectroscopic measurements and computations may be performed in one or more domains including, but not limited to, the transmittance, absorbance and/or optical density domains. The measurement C s (λ i ) is an absorption, transmittance, optical density or other spectroscopic measurement of the sample at selected wavelength or wavelength bands. Such measurements may be obtained, for example, using analyte detection system  334 . In general, sample S contains Type-A interferents, at concentrations preferably within the range of those found in the Sample Population.  
      In one embodiment, absorbance measurements are converted to pathlength normalized measurements. Thus, for example, the absorbance is converted to optical density by dividing the absorbance by the optical pathlength, L, of the measurement. In one embodiment, the pathlength L is measured from one or more absorption measurements on known compounds. Thus, in one embodiment, one or more measurements of the absorption through a sample S of water or saline solutions of known concentration are made and the pathlength, L, is computed from the resulting absorption measurement(s). In another embodiment, absorption measurements are also obtained at portions of the spectrum that are not appreciably affected by the analytes and interferents, and the analyte measurement is supplemented with an absorption measurement at those wavelengths.  
      Some methods are “pathlength insensitive,” in that they can be used even when the precise pathlength is not known beforehand. The sample can be placed in the sample chamber  903  or  2464 , sample element  1730  or  2448 , or in a cuvette or other sample container. Electromagnetic radiation (in the mid-infrared range, for example) can be emitted from a radiation source so that the radiation travels through the sample chamber. A detector can be positioned where the radiation emerges, on the other side of the sample chamber from the radiation source, for example. The distance the radiation travels through the sample can be referred to as a “pathlength.” In some embodiments, the radiation detector can be located on the same side of the sample chamber as the radiation source, and the radiation can reflect off one or more internal walls of the sample chamber before reaching the detector.  
      As discussed above, various substances can be inserted into the sample chamber. For example, a reference fluid such as water or saline solution can be inserted, in addition to a sample or samples containing an analyte or analytes. In some embodiments, a saline reference fluid is inserted into the sample chamber and radiation is emitted through that reference fluid. The detector measures the amount and/or characteristics of the radiation that passes through the sample chamber and reference fluid without being absorbed or reflected. The measurement taken using the reference fluid can provide information relating to the pathlength traveled by the radiation. For example, data may already exist from previous measurements that have been taken under similar circumstances. That is, radiation can be emitted previously through sample chambers with various known pathlengths to establish reference data that can be arranged in a “look-up table,” for example. With reference fluid in the sample chamber, a one-to-one correspondence can be experimentally established between various detector readings and various pathlengths, respectively. This correspondence can be recorded in the look-up table, which can be recorded in a computer database or in electronic memory, for example.  
      One method of determining the radiation pathlength can be accomplished with a thin, empty sample chamber. In particular, this approach can determine the thickness of a narrow sample chamber or cell with two reflective walls. (Because the chamber will be filled with a sample, this same thickness corresponds to the “pathlength” radiation will travel through the sample). A range of radiation wavelengths can be emitted in a continuous manner through the cell or sample chamber. The radiation can enter the cell and reflect off the interior cell walls, bouncing back and forth between those walls one or multiple times before exiting the cell and passing into the radiation detector. This can create a periodic interference pattern or “fringe” with repeating maxima and minima. This periodic pattern can be plotted where the horizontal axis is a range of wavelengths and the vertical axis is a range of transmittance, measured as a percentage of total transmittance, for example. The maxima occur when the radiation reflected off of the two internal surfaces of the cell has traveled a distance that is an integral multiple N of the wavelength of the radiation that was transmitted without reflection. Constructive interference occurs whenever the wavelength is equal to 2b/N, where “b” is the thickness (or pathlength) of the cell. Thus, if ΔN is the number of maxima in this fringe pattern for a given range of wavelengths λ 1 -λ 2 , then the thickness of the cell b is provided by the following relation: b=ΔN/2(λ 1 -λ 2 ). This approach can be especially useful when the refractive index of the material within the sample chamber or fluid cell is not the same as the refractive index of the walls of the cell, because this condition improves reflection.  
      Once the pathlength has been determined, it can be used to calculate or determine a reference value or a reference spectrum for the interferents (such as protein or water) that may be present in a sample. For example, both an analyte such as glucose and an interferent such as water may absorb radiation at a given wavelength. When the source emits radiation of that wavelength and the radiation passes through a sample containing both the analyte and the interferent, both the analyte and the interferent absorb the radiation. The total absorption reading of the detector is thus fully attributable to neither the analyte nor the interferent, but a combination of the two. However, if data exists relating to how much radiation of a given wavelength is absorbed by a given interferent when the radiation passes through a sample with a given pathlength, the contribution of the interferent can be subtracted from the total reading of the detector and the remaining value can provide information regarding concentration of the analyte in the sample. A similar approach can be taken for a whole spectrum of wavelengths. If data exists relating to how much radiation is absorbed by an interferent over a range of wavelengths when the radiation passes through a sample with a given pathlength, the interferent absorbance spectrum can be subtracted from the total absorbance spectrum, leaving only the analyte&#39;s absorbance spectrum for that range of wavelengths. If the interferent absorption data is taken for a range of possible pathlengths, it can be helpful to determine the pathlength of a particular sample chamber first so that the correct data can be found for samples measured in that sample chamber.  
      This same process can be applied iteratively or simultaneously for multiple interferents and/or multiple analytes. For example, the water absorbance spectrum and the protein absorbance spectrum can both be subtracted to leave behind the glucose absorbance spectrum.  
      The pathlength can also be calculated using an isosbestic wavelength. An isosbestic wavelength is one at which all components of a sample have the same absorbance. If the components (and their absorption coefficients) in a particular sample are known, and one or multiple isosbestic wavelengths are known for those particular components, the absorption data collected by the radiation detector at those isosbestic wavelengths can be used to calculate the pathlength. This can be advantageous because the needed information can be obtained from multiple readings of the absorption detector that are taken at approximately the same time, with the same sample in place in the sample chamber. The isosbestic wavelength readings are used to determine pathlength, and other selected wavelength readings are used to determine interferent and/or analyte concentration. Thus, this approach is efficient and does not require insertion of a reference fluid in the sample chamber.  
      In some embodiments, a method of determining concentration of an analyte in a sample can include inserting a fluid sample into a sample container, emitting radiation from a source through the container and the fluid sample, obtaining total sample absorbance data by measuring the amount of radiation that reaches the detector, subtracting the correct interferent absorbance value or spectrum from the total sample absorbance data, and using the remaining absorbance value or spectrum to determine concentration of an analyte in the fluid sample. The correct interferent absorbance value can be determined using the calculated pathlength.  
      The concentration of an analyte in a sample can be calculated using the Beer-Lambert law (or Beer&#39;s Law) as follows: If T is transmittance, A is absorbance, P 0  is initial radiant power directed toward a sample, and P is the power that emerges from the sample and reaches a detector, then T=P/P 0 , and A=−log T=log(P 0 /P). Absorbance is directly proportional to the concentration (c) of the light-absorbing species in the sample, also known as an analyte or an interferent. Thus, if e is the molar absorptivity (1/M 1/cm), b is the path length (cm), and c is the concentration (M), Beer&#39;s Law can be expressed as follows: A=e b c. Thus, c=A/(e b).  
      Referring once again to flowchart  3100 , the next step is to determine which Library Interferents are present in the sample. In particular, Block  3120  indicates that the measurements are analyzed to identify possible interferents. For spectroscopic measurements, it is preferred that the determination is made by comparing the obtained measurement to interferent spectra in the optical density domain. The results of this step provide a list of interferents that may, or are likely to, be present in the sample. In one embodiment, several input parameters are used to estimate a glucose concentration g est  from a measured spectrum, C s . The input parameters include previously gathered spectrum measurement of samples that, like the measurement sample, include the analyte and combinations of possible interferents from the interferent library; and spectrum and concentration ranges for each possible interferent. More specifically, the input parameters are: 
          Library of Interferent Data: Library of Interferent Data includes, for each of “M” interferents, the absorption spectrum of each interferent, IF={IF 1 , IF 2 , . . . , IF M }, where m=1, 2, . . . , M; and a maximum concentration for each interferent, Tmax={Tmax 1 , Tmax 2 , . . . , Tmax M }; and     Sample Population Data: Sample Population Data includes individual spectra of a statistically large population taken over the same wavelength range as the sample spectrum, Cs i , and an analyte concentration corresponding to each spectrum. As an example, if there are N Sample Population spectra, then the spectra can be represented as C={C 1 , C 2 , . . . , C N }, where n=1, 2, . . . , N, and the analyte concentration corresponding to each spectrum can be represented as g={g 1 , g 2 , . . . , g N }.        

      Preferably, the Sample Population does not have any of the M interferents present, and the material sample has interferents contained in the Sample Population and none or more of the Library Interferents. Stated in terms of Type-A and Type-B interferents, the Sample Population has Type-A interferents and the material sample has Type-A and may have Type-B interferents. The Sample Population Data are used to statistically quantify an expected range of spectra and analyte concentrations. Thus, for example, for a system  10  or  334  used to determine glucose in blood of a person having unknown spectral characteristics, the spectral measurements are preferably obtained from a statistical sample of the population.  
      The following discussion, which is not meant to limit the scope of the present disclosure, illustrates embodiments for measuring more than one analyte using spectroscopic techniques. If two or more analytes have non-overlapping spectral features, then a first embodiment is to obtain a spectrum corresponding to each analyte. The measurements may then be analyzed for each analyte according to the method of flowchart  3100 . An alternative embodiment for analytes having non-overlapping features, or an embodiment for analytes having overlapping features, is to make one measurement comprising the spectral features of the two or more analytes. The measurement may then be analyzed for each analyte according to the method of flowchart  3100 . That is, the measurement is analyzed for each analyte, with the other analytes considered to be interferents to the analyte being analyzed for.  
      Interferent Determination  
      One embodiment of the method of Block  3120  is shown in greater detail with reference to the flowchart of  FIG. 32 . The method includes forming a statistical Sample Population model (Block  3210 ), assembling a library of interferent data (Block  3220 ), comparing the obtained measurement and statistical Sample Population model with data for each interferent from an interferent library (Block  3230 ), performing a statistical test for the presence of each interferent from the interferent library (Block  3240 ), and identifying each interferent passing the statistical test as a possible Library Interferent (Block  3250 ). The steps of Block  3220  can be performed once or can be updated as necessary. The steps of Blocks  3230 ,  3240 , and  3250  can either be performed sequentially for all interferents of the library, as shown, or alternatively, be repeated sequentially for each interferent.  
      One embodiment of each of the methods of Blocks  3210 ,  3220 ,  3230 ,  3240 , and  3250  are now described for the example of identifying Library Interferents in a sample from a spectroscopic measurement using Sample Population Data and a Library of Interferent Data, as discussed previously. Each Sample Population spectrum includes measurements (e.g., of optical density) taken on a sample in the absence of any Library Interferents and has an associated known analyte concentration. A statistical Sample Population model is formed (Block  3210 ) for the range of analyte concentrations by combining all Sample Population spectra to obtain a mean matrix and a covariance matrix for the Sample Population. Thus, for example, if each spectrum at n different wavelengths is represented by an n×1 matrix, C, then the mean spectrum, μ, is a n×1 matrix with the (e.g., optical density) value at each wavelength averaged over the range of spectra, and the covariance matrix, V, is the expected value of the deviation between C and μ as V=E((C−μ)(C−μ) T ). The matrices μ and V are one model that describes the statistical distribution of the Sample Population spectra.  
      In another step, Library Interferent information is assembled (Block  3220 ). A number of possible interferents are identified, for example as a list of possible medications or foods that might be ingested by the population of patients at issue or measured by system  10  or  334 , and their spectra (in the absorbance, optical density, or transmission domains) are obtained. In addition, a range of expected interferent concentrations in the blood, or other expected sample material, are estimated. Thus, each of M interferents has spectrum IF and maximum concentration Tmax. This information is preferably assembled once and is accessed as needed.  
      The obtained measurement data and statistical Sample Population model are next compared with data for each interferent from the interferent library (Block  3230 ) to perform a statistical test (Block  3240 ) to determine the identity of any interferent in the mixture (Block  3250 ). This interferent test will first be shown in a rigorous mathematical formulation, followed by a discussion of  FIGS. 33A and 33B  which illustrates the method.  
      Mathematically, the test of the presence of an interferent in a measurement proceeds as follows. The measured optical density spectrum, C s , is modified for each interferent of the library by analytically subtracting the effect of the interferent, if present, on the measured spectrum. More specifically, the measured optical density spectrum, C s , is modified, wavelength-by-wavelength, by subtracting an interferent optical density spectrum. For an interferent, M, having an absorption spectrum per unit of interferent concentration, IF M , a modified spectrum is given by C′ s (T)=C s −IF M  T, where T is the interferent concentration, which ranges from a minimum value, Tmin, to a maximum value Tmax. The value of Tmin may be zero or, alternatively, be a value between zero and Tmax, such as some fraction of Tmax.  
      Next, the Mahalanobis distance (MD) between the modified spectrum C′ s  (T) and the statistical model (μ, V) of the Sample Population spectra is calculated as: 
 
 MD   2 ( C   s −( T t ),μ;ρ   )=( C   s )−( T IF   m )−μ) T   V   −1 ( C   s −( T IF   m )−μ)  Eq. (1) 
 
      The test for the presence of interferent IF is to vary T from Tmin to Tmax (i.e., evaluate C′ s  (T) over a range of values of T) and determine whether the minimum MD in this interval is in a predetermined range. Thus for example, one could determine whether the minimum MD in the interval is sufficiently small relative to the quantiles of a χ 2  random variable with L degrees of freedom (L=number of wavelengths).  
       FIG. 33A  is a graph  3300  illustrating the steps of Blocks  3230  and  3240 . The axes of graph  3300 , OD i  and OD j , are used to plot optical densities at two of the many wavelengths at which measurements are obtained. The points  3301  are the measurements in the Sample Population distribution. Points  3301  are clustered within an ellipse that has been drawn to encircle the majority of points. Points  3301  inside ellipse  3302  represent measurements in the absence of Library Interferents. Point  3303  is the sample measurement. Presumably, point  3303  is outside of the spread of points  3301  due the presence of one or more Library Interferents. Lines  3304 ,  3307 , and  3309  indicate the measurement of point  3303  as corrected for increasing concentration, T, of three different Library Interferents over the range from Tmin to Tmax. The three interferents of this example are referred to as interferent # 1 , interferent # 2 , and interferent # 3 . Specifically, lines  3304 ,  3307 , and  3309  are obtained by subtracting from the sample measurement an amount T of a Library Interferent (interferent # 1 , interferent # 2 , and interferent # 3 , respectively), and plotting the corrected sample measurement for increasing T.  
       FIG. 33B  is a graph further illustrating the method of  FIG. 32 . In the graph of  FIG. 33B , the squared Mahalanobis distance, MD 2  has been calculated and plotted as a function of t for lines  3304 ,  3307 , and  3309 . Referring to  FIG. 33A , line  3304  reflects decreasing concentrations of interferent # 1  and only slightly approaches points  3301 . The value of MD 2  of line  3304 , as shown in  FIG. 33B , decreases slightly and then increases with decreasing interferent # 1  concentration.  
      Referring to  FIG. 33A , line  3307  reflects decreasing concentrations of interferent # 2  and approaches or passes through many points  3301 . The value of MD 2  of line  3307 , as shown in  FIG. 33B , shows a large decrease at some interferent # 2  concentration, then increases. Referring to  FIG. 33A , line  3309  has decreasing concentrations of interferent # 3  and approaches or passes through even more points  3303 . The value of MD 2  of line  3309 , as shown in  FIG. 33B , shows a still larger decrease at some interferent # 3  concentration.  
      In one embodiment, a threshold level of MD 2  is set as an indication of the presence of a particular interferent. Thus, for example,  FIG. 33B  shows a line labeled “original spectrum” indicating MD 2  when no interferents are subtracted from the spectrum, and a line labeled “95% Threshold”, indicating the 95% quantile for the chi 2  distribution with L degrees of freedom (where L is the number of wavelengths represented in the spectra). This level is the value which should exceed 95% of the values of the MD 2  metric; in other words, values at this level are uncommon, and those far above it should be quite rare. Of the three interferents represented in  FIGS. 33A and 33B , only interferent # 3  has a value of MD 2  below the threshold. Thus, this analysis of the sample indicates that interferent # 3  is the most likely interferent present in the sample. Interferent # 1  has its minimum far above the threshold level and is extremely unlikely to be present; interferent # 2  barely crosses the threshold, making its presence more likely than interferent # 1 , but still far less likely to be present than interferent # 1 .  
      As described subsequently, information related to the identified interferents is used in generating a calibration constant that is relatively insensitive to a likely range of concentration of the identified interferents. In addition to being used in certain methods described subsequently, the identification of the interferents may be of interest and may be provided in a manner that would be useful. Thus, for example, for a hospital based glucose monitor, identified interferents may be reported on display  141  or be transmitted to a hospital computer via communications link  216 .  
      Calibration Constant Generation Embodiments  
      Once Library Interferents are identified as being possibly present in the sample under analysis, a calibration constant for estimating the concentration of analytes in the presence of the identified interferents is generated (Block  3130 ). More specifically, after Block  3120 , a list of possible Library Interferents is identified as being present. One embodiment of the steps of Block  3120  are shown in the flowchart of  FIG. 34  as Block  3410 , where synthesized Sample Population measurements are generated, Block  3420 , where the synthesized Sample Population measurements are partitioned in to calibration and test sets, Block  3430 , where the calibration are is used to generate a calibration constant, Block  3440 , where the calibration set is used to estimate the analyte concentration of the test set, Block  3450  where the errors in the estimated analyte concentration of the test set is calculated, and Block  3460  where an average calibration constant is calculated.  
      One embodiment of each of the methods of Blocks  3410 ,  3420 ,  3430 ,  3440 ,  3450 , and  3460  are now described for the example of using identifying interferents in a sample for generating an average calibration constant. As indicated in Block  3410 , one step is to generate synthesized Sample Population spectra, by adding a random concentration of possible Library Interferents to each Sample Population spectrum. The spectra generated by the method of Block  3410  are referred to herein as an Interferent-Enhanced Spectral Database, or IESD. The IESD can be formed by the steps illustrated in  FIGS. 35-38 , where  FIG. 35  is a schematic diagram  3500  illustrating the generation of Randomly-Scaled Single Interferent Spectra, or RSIS;  FIG. 36  is a graph  3600  of the interferent scaling;  FIG. 37  is a schematic diagram illustrating the combination of RSIS into Combination Interferent Spectra, or CIS; and  FIG. 38  is a schematic diagram illustrating the combination of CIS and the Sample Population spectra into an IESD.  
      The first step in Block  3410  is shown in  FIGS. 35 and 36 . As shown schematically in flowchart  3500  in  FIG. 35 , and in graph  3600  in  FIG. 36 , a plurality of RSIS (Block  3540 ) are formed by combinations of each previously identified Library Interferent having spectrum IF m  (Block  3510 ), multiplied by the maximum concentration Tmax m  (Block  3520 ) that is scaled by a random factor between zero and one (Block  3530 ), as indicated by the distribution of the random number indicated in graph  3600 . In one embodiment, the scaling places the maximum concentration at the 95 th  percentile of a log-normal distribution to produce a wide range of concentrations with the distribution having a standard deviation equal to half of its mean value. The distribution of the random numbers in graph  3600  are a log-normal distribution of μt=100, σ50.  
      Once the individual Library Interferent spectra have been multiplied by the random concentrations to produce the RSIS, the RSIS are combined to produce a large population of interferent-only spectra, the CIS, as illustrated in  FIG. 37 . The individual RSIS are combined independently and in random combinations, to produce a large family of CIS, with each spectrum within the CIS consisting of a random combination of RSIS, selected from the full set of identified Library Interferents. The method illustrated in  FIG. 37  produces adequate variability with respect to each interferent, independently across separate interferents.  
      The next step combines the CIS and replicates of the Sample Population spectra to form the IESD, as illustrated in  FIG. 38 . Since the Interferent Data and Sample Population spectra may have been obtained at different pathlengths, the CIS are first scaled (i.e., multiplied) to the same pathlength. The Sample Population database is then replicated M times, where M depends on the size of the database, as well as the number of interferents to be treated. The IESD includes M copies of each of the Sample Population spectra, where one copy is the original Sample Population Data, and the remaining M−1 copies each have an added random one of the CIS spectra. Each of the IESD spectra has an associated analyte concentration from the Sample Population spectra used to form the particular IESD spectrum.  
      In one embodiment, a 10-fold replication of the Sample Population database is used for 130 Sample Population spectra obtained from 58 different individuals and 18 Library Interferents. Greater spectral variety among the Library Interferent spectra requires a smaller replication factor, and a greater number of Library Interferents requires a larger replication factor.  
      The steps of Blocks  3420 ,  3430 ,  3440 , and  3450  are executed to repeatedly combine different ones of the spectra of the IESD to statistically average out the effect of the identified Library Interferents. First, as noted in Block  3420 , the IESD is partitioned into two subsets: a calibration set and a test set. As described subsequently, the repeated partitioning of the IESD into different calibration and test sets improves the statistical significance of the calibration constant. In one embodiment, the calibration set is a random selection of some of the IESD spectra and the test set are the unselected IESD spectra. In a preferred embodiment, the calibration set includes approximately two-thirds of the IESD spectra.  
      In an alternative embodiment, the steps of Blocks  3420 ,  3430 ,  3440 , and  3450  are replaced with a single calculation of an average calibration constant using all available data.  
      Next, as indicted in Block  3430 , the calibration set is used to generate a calibration constant for predicting the analyte concentration from a sample measurement. First an analyte spectrum is obtained. For the embodiment of glucose determined from absorption measurements, a glucose absorption spectrum is indicated as    G . The calibration constant is then generated as follows. Using the calibration set having calibration spectra  ={c 1 , c 2 , . . . , c n } and corresponding glucose concentration values  ={g 1 , g 2 , . . . , g n }, then glucose-free spectra  ′={c′ 1 , c′ 2 , . . . , c′ n } can be calculated as: c′ j =c j −   G g j . Next, the calibration constant, κ, is calculated from  ′ and    G , according to the following 5 steps: 
          1)  ′ is decomposed into  ′=A   Δ ′ B ′ , that is, a singular value decomposition, where the A-factor is an orthonormal basis of column space, or span, of  ′;     2) A ′  is truncated to avoid overfitting to a particular column rank r, based on the sizes of the diagonal entries of Δ (the singular values of  ′). The selection of r involves a trade-off between the precision and stability of the calibration, with a larger r resulting in a more precise but less stable solution. In one embodiment, each spectrum C includes 25 wavelengths, and r ranges from 15 to 19;     3) The first r columns of A ′  are taken as an orthonormal basis of span (  ′);     4) The projection from the background is found as the product P ′ =A ′ A ′   T  that is the orthogonal projection onto the span of  ′, and the complementary, or nulling projection P ′   ⊥ =1−P ′ , which forms the projection onto the complementary subspace  ′ ⊥ , is calculated; and     5) The calibration vector κ is then found by applying the nulling projection to the absorption spectrum of the analyte of interest: κ RAW P ′   ⊥     G , and normalizing: κ=κ RAW /  κ RAW ,    G   , where the angle brackets  ,   denote the standard inner (or dot) product of vectors. The normalized calibration constant produces a unit response for a unit    G  spectral input for one particular calibration set.        

      Next, the calibration constant is used to estimate the analyte concentration in the test set (Block  3440 ). Specifically, each spectrum of the test set (each spectrum having an associated glucose concentration from the Sample Population spectra used to generate the test set) is multiplied by the calibration vector κ from Block  3430  to calculate an estimated glucose concentration. The error between the calculated and known glucose concentration is then calculated (Block  3450 ). Specifically, the measure of the error can include a weighted value averaged over the entire test set according to 1/rms 2 .  
      Blocks  3420 ,  3430 ,  3440 , and  3450  are repeated for many different random combinations of calibration sets. Preferably, Blocks  3420 ,  3430 ,  3440 , and  3450  are repeated are repeated hundreds to thousands of times. Finally, an average calibration constant is calculated from the calibration and error from the many calibration and test sets (Block  3460 ). Specifically, the average calibration is computed as weighted average calibration vector. In one embodiment the weighting is in proportion to a normalized rms, such as the κ ave =κ*rms 2 /Σ(rms 2 ) for all tests.  
      With the last of Block  3130  executed according to  FIG. 34 , the average calibration constant κ ave  is applied to the obtained spectrum (Block  3140 ).  
      Accordingly, one embodiment of a method of computing a calibration constant based on identified interferents can be summarized as follows: 
          1. Generate synthesized Sample Population spectra by adding the RSIS to raw (interferent-free) Sample Population spectra, thus forming an Interferent Enhanced Spectral Database (IESD)—each spectrum of the IESD is synthesized from one spectrum of the Sample Population, and thus each spectrum of the IESD has at least one associated known analyte concentration     2. Separate the spectra of the IESD into a calibration set of spectra and a test set of spectra     3. Generate a calibration constant for the calibration set based on the calibration set spectra and their associated known correct analyte concentrations (e.g., using the matrix manipulation outlined in five steps above)     4. Use the calibration constant generated in step 3 to calculate the error in the corresponding test set as follows (repeat for each spectrum in the test set): 
            a. Multiply (the selected test set spectrum)×(average calibration constant generated in step 3) to generate an estimated glucose concentration     b. Evaluate the difference between this estimated glucose concentration and the known, correct glucose concentration associated with the selected test spectrum to generate an error associated with the selected test spectrum    
            5. Average the errors calculated in step 4 to arrive at a weighted or average error for the current calibration set—test set pair     6. Repeat steps 2 through 5 n times, resulting in n calibration constants and n average errors     7. Compute a “grand average” error from the n average errors and an average calibration constant from the n calibration constants (preferably weighted averages wherein the largest average errors and calibration constants are discounted), to arrive at a calibration constant which is minimally sensitive to the effect of the identified interferents        

     EXAMPLE 1  
      One example of certain methods disclosed herein is illustrated with reference to the detection of glucose in blood using mid-IR absorption spectroscopy. Table 2 lists 10 Library Interferents (each having absorption features that overlap with glucose) and the corresponding maximum concentration of each Library Interferent. Table 2 also lists a Glucose Sensitivity to Interferent without and with training. The Glucose Sensitivity to Interferent is the calculated change in estimated glucose concentration for a unit change in interferent concentration. For a highly glucose selective analyte detection technique, this value is zero. The Glucose Sensitivity to Interferent without training is the Glucose Sensitivity to Interferent where the calibration has been determined using the methods above without any identified interferents. The Glucose Sensitivity to Interferent with training is the Glucose Sensitivity to Interferent where the calibration has been determined using the methods above with the appropriately identified interferents. In this case, least improvement (in terms of reduction in sensitivity to an interferent) occurs for urea, seeing a factor of 6.4 lower sensitivity, followed by three with ratios from 60 to 80 in improvement. The remaining six all have seen sensitivity factors reduced by over 100, up to over 1600. The decreased Glucose Sensitivity to Interferent with training indicates that the methods are effective at producing a calibration constant that is selective to glucose in the presence of interferents.  
               TABLE 2                          Rejection of 10 interfering substances                                     Glucose   Glucose               Sensitivity to   Sensitivity to       Library   Maximum   Interferent   Interferent       Interferent   Concentration   w/o training   w/ training                                     Sodium Bicarbonate   103   0.330   0.0002       Urea   100   −0.132   0.0206       Magnesium Sulfate   0.7   1.056   −0.0016       Naproxen   10   0.600   −0.0091       Uric Acid   12   −0.557   0.0108       Salicylate   10   0.411   −0.0050       Glutathione   100   0.041   0.0003       Niacin   1.8   1.594   −0.0086       Nicotinamide   12.2   0.452   −0.0026       Chlorpropamide   18.3   0.334   0.0012                  
 
     EXAMPLE 2  
      Another example illustrates the effect of the methods for 18 interferents. Table 3 lists of 18 interferents and maximum concentrations that were modeled for this example, and the glucose sensitivity to the interferent without and with training. The table summarizes the results of a series of 1000 calibration and test simulations that were performed both in the absence of the interferents, and with all interferents present.  FIG. 39  shows the distribution of the R.M.S. error in the glucose concentration estimation for 1000 trials. While a number of substances show significantly less sensitivity (sodium bicarbonate, magnesium sulfate, tolbutamide), others show increased sensitivity (ethanol, acetoacetate), as listed in Table 3. The curves in  FIG. 39  are for calibration set and the test set both without any interferents and with all 18 interferents. The interferent produces a degradation of performance, as can be seen by comparing the calibration or test curves of  FIG. 39 . Thus, for example, the peaks appear to be shifted by about 2 mg/dL, and the width of the distributions is increased slightly. The reduction in height of the peaks is due to the spreading of the distributions, resulting in a modest degradation in performance.  
               TABLE 3                          List of 18 Interfering Substances with maximum concentrations and       Sensitivity with respect to interferents, with/without training                                             Glucose   Glucose                   Sensitivity   Sensitivity to           Library   Conc.   to Interferent w/o   Interferent w/           Interferent   (mg/dL)   training   training                                         1   Urea   300   −0.167   −0.100       2   Ethanol   400.15   −0.007   −0.044       3   Sodium Bicarbonate   489   0.157   −0.093       4   Acetoacetate Li   96   0.387   0.601       5   Hydroxybutyric Acid   465   −0.252   −0.101       6   Magnesium Sulfate   29.1   2.479   0.023       7   Naproxen   49.91   0.442   0.564       8   Salicylate   59.94   0.252   0.283       9   Ticarcillin Disodium   102   −0.038   −0.086       10   Cefazolin   119.99   −0.087   −0.006       11   Chlorpropamide   27.7   0.387   0.231       12   Nicotinamide   36.6   0.265   0.366       13   Uric Acid   36   −0.641   −0.712       14   Ibuprofen   49.96   −0.172   −0.125       15   Tolbutamide   63.99   0.132   0.004       16   Tolazamide   9.9   0.196   0.091       17   Bilirubin   3   −0.391   −0.266       18   Acetaminophen   25.07   0.169   0.126                  
 
     EXAMPLE 3  
      In a third example, certain methods disclosed herein were tested for measuring glucose in blood using mid-IR absorption spectroscopy in the presence of four interferents not normally found in blood (Type-B interferents) and that may be common for patients in hospital intensive care units (ICUs). The four Type-B interferents are mannitol, dextran, n-acetyl L cysteine, and procainamide.  
      Of the four Type-B interferents, mannitol and dextran have the potential to interfere substantially with the estimation of glucose: both are spectrally similar to glucose (see  FIG. 1 ), and the dosages employed in ICUs are very large in comparison to typical glucose levels. Mannitol, for example, may be present in the blood at concentrations of 2500 mg/dL, and dextran may be present at concentrations in excess of 5000 mg/dL. For comparison, typical plasma glucose levels are on the order of 100-200 mg/dL. The other Type-B interferents, n-acetyl L cysteine and procainamide, have spectra that are quite unlike the glucose spectrum.  
       FIGS. 40A, 40B ,  40 C, and  40 D each have a graph showing a comparison of the absorption spectrum of glucose with different interferents taken using two different techniques: a Fourier Transform Infrared (FTIR) spectrometer having an interpolated resolution of 1 cm −1  (solid lines with triangles); and by 25 finite-bandwidth IR filters having a Gaussian profile and full-width half-maximum (FWHM) bandwidth of 28 cm −1  corresponding to a bandwidth that varies from 140 nm at 7.08 μm, up to 279 nm at 10 μm (dashed lines with circles). Specifically, the figures show a comparison of glucose with mannitol ( FIG. 40A ), with dextran ( FIG. 40B ), with n-acetyl L cysteine ( FIG. 40C ), and with procainamide ( FIG. 40D ), at a concentration level of 1 mg/dL and path length of 1 μm. The horizontal axis in  FIGS. 40A-40D  has units of wavelength in microns (μm), ranging from 7 μm to 10 μm, and the vertical axis has arbitrary units.  
      The central wavelength of the data obtained using filter is indicated in  FIGS. 40A, 40B ,  40 C, and  40 D by the circles along each dashed curve, and corresponds to the following wavelengths, in microns: 7.082, 7.158, 7.241, 7.331, 7.424, 7.513, 7.605, 7.704, 7.800, 7.905, 8.019, 8.150, 8.271, 8.598, 8.718, 8.834, 8.969, 9.099, 9.217, 9.346, 9.461, 9.579, 9.718, 9.862, and 9.990. The effect of the bandwidth of the filters on the spectral features can be seen in  FIGS. 40A-40D  as the decrease in the sharpness of spectral features on the solid curves and the relative absence of sharp features on the dashed curves.  
       FIG. 41  shows a graph of the blood plasma spectra for 6 blood samples taken from three donors in arbitrary units for a wavelength range from 7 μm to 10 μm, where the symbols on the curves indicate the central wavelengths of the 25 filters. The 6 blood samples do not contain any mannitol, dextran, n-acetyl L cysteine, and procainamide—the Type-B interferents of this Example, and are thus a Sample Population. Three donors (indicated as donor A, B, and C) provided blood at different times, resulting in different blood glucose levels, shown in the graph legend in mg/dL as measured using a YSI Biochemistry Analyzer (YSI Incorporated, Yellow Springs, Ohio). The path length of these samples, estimated at 36.3 μm by analysis of the spectrum of a reference scan of saline in the same cell immediately prior to each sample spectrum, was used to normalize these measurements. This quantity was taken into account in the computation of the calibration vectors provided, and the application of these vectors to spectra obtained from other equipment would require a similar pathlength estimation and normalization process to obtain valid results.  
      Next, random amounts of each Type-B interferent of this Example are added to the spectra to produce mixtures that, for example could make up an Interferent Enhanced Spectral. Each of the Sample Population spectra was combined with a random amount of a single interferent added, as indicated in Table 4, which lists an index number N, the Donor, the glucose concentration (GLU), interferent concentration (conc(IF)), and the interferent for each of 54 spectra. The conditions of Table 4 were used to form combined spectra including each of the 6 plasma spectra was combined with 2 levels of each of the 4 interferents.  
               TABLE 4                          Interferent Enhanced Spectral Database for Example 3.                                         N   Donor   GLU   conc (IF)   IF                                                     1   A   157.7       N/A           2   A   382       N/A           3   B   122       N/A           4   B   477.3       N/A           5   C   199.7       N/A           6   C   399       N/A           7   A   157.7   1001.2   Mannitol           8   A   382   2716.5   Mannitol           9   A   157.7   1107.7   Mannitol           10   A   382   1394.2   Mannitol           11   B   122   2280.6   Mannitol           12   B   477.3   1669.3   Mannitol           13   B   122   1710.2   Mannitol           14   B   477.3   1113.0   Mannitol           15   C   199.7   1316.4   Mannitol           16   C   399   399.1   Mannitol           17   C   199.7   969.8   Mannitol           18   C   399   2607.7   Mannitol           19   A   157.7   8.8   N Acetyl L Cysteine           20   A   382   2.3   N Acetyl L Cysteine           21   A   157.7   3.7   N Acetyl L Cysteine           22   A   382   8.0   N Acetyl L Cysteine           23   B   122   3.0   N Acetyl L Cysteine           24   B   477.3   4.3   N Acetyl L Cysteine           25   B   122   8.4   N Acetyl L Cysteine           26   B   477.3   5.8   N Acetyl L Cysteine           27   C   199.7   7.1   N Acetyl L Cysteine           28   C   399   8.5   N Acetyl L Cysteine           29   C   199.7   4.4   N Acetyl L Cysteine           30   C   399   4.3   N Acetyl L Cysteine           31   A   157.7   4089.2   Dextran           32   A   382   1023.7   Dextran           33   A   157.7   1171.8   Dextran           34   A   382   4436.9   Dextran           35   B   122   2050.6   Dextran           36   B   477.3   2093.3   Dextran           37   B   122   2183.3   Dextran           38   B   477.3   3750.4   Dextran           39   C   199.7   2598.1   Dextran           40   C   399   2226.3   Dextran           41   C   199.7   2793.0   Dextran           42   C   399   2941.8   Dextran           43   A   157.7   22.5   Procainamide           44   A   382   35.3   Procainamide           45   A   157.7   5.5   Procainamide           46   A   382   7.7   Procainamide           47   B   122   18.5   Procainamide           48   B   477.3   5.6   Procainamide           49   B   122   31.8   Procainamide           50   B   477.3   8.2   Procainamide           51   C   199.7   22.0   Procainamide           52   C   399   9.3   Procainamide           53   C   199.7   19.7   Procainamide           54   C   399   12.5   Procainamide                      
 
       FIGS. 42A, 42B ,  42 C, and  42 D contain spectra formed from the conditions of Table 4. Specifically, the figures show spectra of the Sample Population of 6 samples having random amounts of mannitol ( FIG. 42A ), dextran ( FIG. 42B ), n-acetyl L cysteine ( FIG. 42C ), and procainamide ( FIG. 42D ), at a concentration levels of 1 mg/dL and path lengths of 1 μm.  
      Next, calibration vectors were generated using the spectra of  FIGS. 42A-42D , in effect reproducing the steps of Block  3120 . The next step of this Example is the spectral subtraction of water that is present in the sample to produce water-free spectra. As discussed above, certain methods disclosed herein provide for the estimation of an analyte concentration in the presence of interferents that are present in both a sample population and the measurement sample (Type-A interferents), and it is not necessary to remove the spectra for interferents present in Sample Population and sample being measured. The step of removing water from the spectrum is thus an alternative embodiment of the disclosed methods.  
      The calibration vectors are shown in  FIGS. 43A-43D  for mannitol ( FIG. 43A ), dextran ( FIG. 43B ), n-acetyl L cysteine ( FIG. 43C ), and procainamide ( FIG. 43D ) for water-free spectra. Specifically each one of  FIGS. 43A-43D  compares calibration vectors obtained by training in the presence of an interferent, to the calibration vector obtained by training on clean plasma spectra alone. The calibration vector is used by computing its dot-product with the vector representing (pathlength-normalized) spectral absorption values for the filters used in processing the reference spectra. Large values (whether positive or negative) typically represent wavelengths for which the corresponding spectral absorbance is sensitive to the presence of glucose, while small values generally represent wavelengths for which the spectral absorbance is insensitive to the presence of glucose. In the presence of an interfering substance, this correspondence is somewhat less transparent, being modified by the tendency of interfering substances to mask the presence of glucose.  
      The similarity of the calibration vectors obtained for minimizing the effects of the two interferents n-acetyl L cysteine and procainamide, to that obtained for pure plasma, is a reflection of the fact that these two interferents are spectrally quite distinct from the glucose spectrum; the large differences seen between the calibration vectors for minimizing the effects of dextran and mannitol, and the calibration obtained for pure plasma, are conversely representative of the large degree of similarity between the spectra of these substances and that of glucose. For those cases in which the interfering spectrum is similar to the glucose spectrum (that is, mannitol and dextran), the greatest change in the calibration vector. For those cases in which the interfering spectrum is different from the glucose spectrum (that is, n-acetyl L cysteine and procainamide), it is difficult to detect the difference between the calibration vectors obtained with and without the interferent.  
      It will be understood that the steps of methods discussed are performed in one embodiment by an appropriate processor (or processors) of a processing (i.e., computer) system executing instructions (code segments) stored in appropriate storage. It will also be understood that the disclosed methods and apparatus are not limited to any particular implementation or programming technique and that the methods and apparatus may be implemented using any appropriate techniques for implementing the functionality described herein. The methods and apparatus are not limited to any particular programming language or operating system. In addition, the various components of the apparatus may be included in a single housing or in multiple housings that communication by wire or wireless communication.  
      Further, the interferent, analyte, or population data used in the method may be updated, changed, added, removed, or otherwise modified as needed. Thus, for example, spectral information and/or concentrations of interferents that are accessible to the methods may be updated or changed by updating or changing a database of a program implementing the method. The updating may occur by providing new computer readable media or over a computer network. Other changes that may be made to the methods or apparatus include, but are not limited to, the adding of additional analytes or the changing of population spectral information.  
      One embodiment of each of the methods described herein may include a computer program accessible to and/or executable by a processing system, e.g., a one or more processors and memories that are part of an embedded system. Thus, as will be appreciated by those skilled in the art, embodiments of the disclosed inventions may be embodied as a method, an apparatus such as a special purpose apparatus, an apparatus such as a data processing system, or a carrier medium, e.g., a computer program product. The carrier medium carries one or more computer readable code segments for controlling a processing system to implement a method. Accordingly, various ones of the disclosed inventions may take the form of a method, an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. Furthermore, any one or more of the disclosed methods (including but not limited to the disclosed methods of measurement analysis, interferent determination, and/or calibration constant generation) may be stored as one or more computer readable code segments or data compilations on a carrier medium. Any suitable computer readable carrier medium may be used including a magnetic storage device such as a diskette or a hard disk; a memory cartridge, module, card or chip (either alone or installed within a larger device); or an optical storage device such as a CD or DVD.  
      Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.  
      Similarly, it should be appreciated that in the above description of embodiments, various features of the inventions are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that any claim require more features than are expressly recited in that claim. Rather, inventive aspects lie in a combination of fewer than all features of any single foregoing disclosed embodiment.  
      Further information on analyte detection systems, sample elements, algorithms and methods for computing analyte concentrations, and other related apparatus and methods can be found in U.S. patent application Publication No. 2003/0090649, published May 15, 2003, titled REAGENT-LESS WHOLE BLOOD GLUCOSE METER; U.S. patent application Publication No. 2003/0178569, published Sep. 25, 2003, titled PATHLENGTH-INDEPENDENT METHODS FOR OPTICALLY DETERMINING MATERIAL COMPOSITION; U.S. patent application Publication No. 2004/0019431, published Jan. 29, 2004, titled METHOD OF DETERMINING AN ANALYTE CONCENTRATION IN A SAMPLE FROM AN ABSORPTION SPECTRUM; U.S. patent application Publication No. 2005/0036147, published Feb. 17, 2005, titled METHOD OF DETERMINING ANALYTE CONCENTRATION IN A SAMPLE USING INFRARED TRANSMISSION DATA; and U.S. patent application Publication No. 2005/0038357, published on Feb. 17, 2005, titled SAMPLE ELEMENT WITH BARRIER MATERIAL. The entire contents of each of the above-mentioned publications are hereby incorporated by reference herein and are made a part of this specification.  
      A number of applications, publications and external documents are incorporated by reference herein. Any conflict or contradiction between a statement in the bodily text of this specification and a statement in any of the incorporated documents is to be resolved in favor of the statement in the bodily text.  
      Section VI—Inhibiting Blood Clot Formation  
      The coagulation of blood may affect the operation of extracorporeal blood systems. In general, coagulation proceeds according to a series of complex chemical reactions within the blood. In extracorporeal systems, coagulation may begin upon the contact of blood with most types of surfaces, and may collect on surfaces or within crevices or changes in surface type or flow conditions. Thus, for example, blood flowing through passageways may build up on the passageway walls or may form clots that restrict or block the flow of blood, hindering the operation of the system. This section is directed to several devices and methods for inhibiting blood clot formation in system  10 .  
      Section VI.A—Ultrasonic Inhibition of Blood Clots  
      It has been found by the inventors that the application of vibrations to an extracorporeal system inhibits the formation of blood clots within the system. The vibrations are preferably at frequencies above the range of human hearing, such as greater than 15 kHz, and are referred to herein and without limitation as ultrasonic vibrations or waves, or as “ultrasound.” 
      An illustrative embodiment will now be presented with reference to  FIG. 49 . The discussion in terms of the following embodiment is not meant to limit the scope of either the apparatus or methods of the present disclosure. Specifically,  FIG. 49  is a perspective view of an embodiment anti-clotting device  4900  including an ultrasonic horn  4901  and ultrasonic generator  4903 , positioned adjacent flow passageways  4910  adjacent to sample element  2310 . Ultrasonic generator  4903  is connected to a power supply and electronics (not shown). Ultrasonic horn  4901  is movable and may be placed in contact with a blood-containing portion of an extracorporeal system, for example passageways  4901 , with vibrations directed towards a location where clots are known or expected to form.  
      In one embodiment, the frequency transmitted through ultrasonic horn  4901  is from 15 to 60 kHz and transmits from 2 to 200 Watts of ultrasonic power. In one preferred embodiment, a model VC24 ultrasonic system obtained from Sonics &amp; Materials, Inc (Newtown, Conn.) was operated at a frequency of 40 kHz and 25 Watts of power.  
      As an example of the use of the apparatus of  FIG. 49 , repeated filling of sample element  2310  with whole blood in the absence of ultrasound resulted in visible clotting. Device  4900  was then tested by repeatedly filling sample element  2310  with whole blood and bringing horn  4901  in contact with passageway  4910  and activating generator  4903  to deliver a 10 second pulse of 40 kHz, 25 Watt ultrasound between each filling of sample element  2301 . The filling and providing of ultrasound was repeated every 30 minutes for 69 hours, after which there was very little evidence of clotting, either visually or by measuring the inhibition of blood flowing through the passageway.  
      Section VI.B—Inhibition of Blood Clots with Anticoagulants  
      Alternative embodiments prevent clotting by providing a cleansing solution to the flow passageways. In one such embodiment, a cleaning solution S is provided at intervals to some or all of passageways  20 . One illustration of this concept is now presented with reference to  FIG. 50 . The discussion in terms of the following embodiment is not meant to limit the scope of either the apparatus or methods of the present disclosure. Specifically,  FIG. 50  is a schematic showing details of a sampling system  5000  which may be generally similar to the embodiments of sampling system  100  or  300  as illustrated in  FIG. 1, 2 , or  3 , except as further detailed below.  
      Sampling system  5000  includes an embodiment of an anti-clotting device  5100  to provide cleaning solution S contained in cleaning solution container  5107  and delivered through a passageway  5113  into passageway  113  and sample analysis device  330 . In particular, device  5100  includes a pump  5109  and a valve  5111  on passageway  5113 , a valve  5101  on passageway  113 , and a bypass  5103  having a valve  5105 . The valves and pumps of device  5100  are connected to and controlled by controller  210  through electrical control lines that are not shown in  FIG. 50 .  
      Device  5100  may be used to flush cleaning solution S through passageway  113  and sample analysis device  330  as follows. After the steps described with reference to  FIG. 7J , valves  5101 ,  323 , and  326  closed, valves  5111  and  5105  open, and pump  5109  activated, cleaning solution S is pumped from container  5107 , through passageways  5113 ,  113 , and  324  and device  330 . This pumping action is a backflow—that is it is in the reverse direction of the normal flow of system  5000 . After a sufficient amount of cleaning solution has been provided to system  5000 , valves  5101 ,  323 , and  326  are opened, valves  5111  and  5105  are closed, and pump  5109  is stopped. Residual blood, saline, or other fluids are then pumped, using pump  203 , into waste receptacle  325 . The steps with reference to one or more of  FIGS. 7A-7J  may then be carried out.  
      In one embodiment the cleaning solution S is effective in removing blood, blood components, and/or clotted blood from the surfaces of the passageways, sample elements, or other blood contacting surfaces. It is preferred that solution S is thermally stable at room temperatures. Such solutions are typically used for cleaning hospital and laboratory instruments, and may include nonspecific protease enzymes for digesting blood. One type of cleaning solution S is a mixture of approximately 1% TERGAZYME™ (manufactured by Alconox, Inc., White Planes, N.Y.) in saline.  
      Section VI.C—Anticoagulant Inhibition of Blood Clots  
      Another alternative embodiment prevents clotting by providing an anticoagulant solution to bodily fluids in passageways  20 . One illustration of this embodiment is now presented with reference to  FIG. 51 , which is not meant to limit the scope of the present disclosure.  FIG. 51  is a schematic showing details of a sampling system  5100  which may be generally similar to the embodiments of sampling systems  100  or  300  as illustrated in  FIG. 1, 2 , or  3 , except as further detailed below. Sampling assembly  5120  of sampling system  5100  may be generally similar to the embodiments of sampling assembly  220  as illustrated in  FIGS. 1A, 2 ,  3 ,  5 , and  8 , except as further detailed below.  
      Sampling system  5100  includes an embodiment of an anticoagulant supply  5101  to provide a solution, referred to herein and without limitation as an “anticoagulant solution” AC, to bodily fluids within passageway  113 . In the embodiment of  FIG. 51 , the anticoagulant solution AC has blood anticoagulant properties and is delivered through a passageway  5103  into passageway  113  at a junction  5105 . It is preferred that anticoagulant supply  5101  includes an amount of anticoagulant solution AC to operate for some period of time, such as up to 1 hour, 6 hours, 1 day, 2 days, 3 days, or more.  
      Sampling system  5100  also includes line  114  to controller  210 . Anticoagulant supply  5101 , under the control of controller  210  delivers the solution through passageway  5103 , where it mixes with fluid in passageway  113  at junction  5103 . In one embodiment, anticoagulant supply  5101  includes a mechanism to deliver a controlled and/or repeatable quantity of anticoagulant solution AC. Thus, for example, anticoagulant supply  5101  includes a positive displacement pump, including but not limited to an ink jet-type or automated syringe pump. In another embodiment, anticoagulant supply  5101  includes a valve and anticoagulant solution AC is supplied by a low pressure in passageway  113 .  
      As described subsequently, the term “anticoagulant solution” refers to a solution that is added to a material sample of bodily fluid that has anticoagulant properties, and is not meant to be limiting as to the composition of anticoagulant solution AC. In general, anticoagulant solution AC includes one or more anticoagulants and may optionally include a solvent, such as water, and other components that may be necessary to stabilize the anticoagulants. In addition, alternative embodiments anticoagulant solution AC include components that aid in quantifying the amount of anticoagulant solution AC added to passageway  113  and that may have little or no anticoagulant properties or be related to the functioning or use of the anticoagulants, as discussed subsequently.  
      Preferably, the solution provided into passageway  5103  contains a sufficient amount of one or more anticoagulants to inhibit or prevent the coagulation of blood in passageway  113 . Anticoagulants that may be used in various embodiments include, but are not limited to sodium heparin, ethylenediaminetetraacetic acids, including but not limited to, dipotassium dthylenediamine tetraacetic acid (K2EDTA) and tripotassium ethylenediamine tetraacetic acid (K3EDTA), potassium oxalate, and sodium citrate in an aqueous solution. The concentration of these anticoagulants sufficient for inhibiting coagulation is well known in the field, and is summarized in the following table. It is preferred that the flow of anticoagulant in passageway  5103  and the flow of blood in passageway  113  be selected so that the anticoagulant concentration in the blood is sufficient to inhibit coagulation. The solution provided into passageway  5103  may contain one or more of the anticoagulants listed in Table 5 and/or other compounds.  
               TABLE 5                          Partial List of Suitable Anticoagulants.                         Concentration       Anticoagulant   in mg/dL               Sodium Heparin   10.2 mg/dL           (150Units/10 mL)       K2EDTA   175 mg/dL       K3EDTA   175 mg/dL       Potassium Oxalate/sodium fluoride (for glycolic   200 mg/dL/250 mg/dL       inhibition)       Sodium Citrate/Citric acid (buffered solution)   355 mg/dL/46.7           mg/dL                  
 
      The operation of sampling system  5100  is generally similar to the method of operating shown in  FIGS. 7A-7J  and described previously with reference to these figures except for the steps required to inject anticoagulant AC. Junction  5105 , which is not shown in  FIGS. 7A-7J , is located near valve  316 , as shown in  FIG. 51 . Controller  210  provides instructions to sampling system  5120  to supply anticoagulant AC into all or some of sample S just after passing valve  316  (at the step between that shown in  FIGS. 7E and 7F ). The sample measured by sampling unit  200  is a mixture of sample S and anticoagulant solution AC, referred to herein as mixture S/AC.  
      Obtaining measurements on mixture S/AC may require a change of the method used to analyze the measurements over making measurements on pure sample S alone. The following is a list of several methods, which is not meant to be limiting, on analyzing mixture S/AC to obtain measurements of one or more analytes in mixture S.  
      In one embodiment, the components of anticoagulant solution AC are of a sufficiently small concentration or volume when mixed with sample S, or do not have a signature detectable by sampling unit  200 , then the methods described herein can be used to measure analytes in mixture S/AC.  
      In another embodiment, the components anticoagulant solution AC are detectable by sampling unit  200  at levels that affect the measurement of analytes, then the anticoagulant solutions components are exogenous interferents that need to be accounted for. Thus, for example components of anticoagulant solution AC that affect the measurement of analytes may be included as a Library Interferent. The method described herein can then be used to measure analytes in mixture S/AC.  
      The addition of a volume of anticoagulant solution AC to solution S changes the concentration of analyte being measured. Thus, for example a concentration of an analyte in solution S may be diluted to a lower concentration in the mixture S/AC. In one embodiment, the dilution is not accounted for—that is the system measures and reports the concentration of analyte in mixture S/AC. This is the preferable method for conditions where the dilution is small enough so that the resulting dilution error is below a threshold level. In another embodiment, the measured analyte concentration in mixture S/AC is corrected to provide an estimate of the analyte concentration in the undiluted mixture S.  
      There are several alternative embodiments for correcting for dilution due to the addition of anticoagulant solution anticoagulant solution AC based on determining the amount of dilution that occurs from adding a volume of anticoagulant solution. One embodiment includes using an anticoagulation solution AC that has a component that is quantifiable in sampling system  100 . In general, a mixture of compounds used for anticoagulation purposes, including, possibly, a solvent and a stabilizer (an “anticoagulation mixture”), are either quantifiable or are not quantifiable in sampling system  100 . It is preferable that the quantifiable compound (referred to herein, without limitation, as an “anticoagulation analyte”), be it an anticoagulant or added quantifiable compound, is neither an endogenous interferent nor an endogenous analyte.  
      For infrared spectroscopic analyte detection systems, including but not limited to analyte detection system  1700 , examples of anticoagulant solutions that are quantifiable include, but are not limited to, mixtures of one or more of sodium heparin, K2EDTA, K3EDTA, potassium oxalate, and sodium citrate.  
      Anticoagulant analytes useful in infrared spectroscopic analyte detection systems, including but not limited to analyte detection system  1700 , are compounds that are inert, water-soluble, stable and that have identifiable infrared spectrum. In one embodiment, added anticoagulation analytes have a small number of infrared absorbance peaks that preferably do not overlap those of the analytes or interferents. In one embodiment, the added anticoagulation analyte has a distinctive spectrum in a range of from 4 to 6 μm and/or from 7.5 to 8.5 μm.  
      In another embodiment, sodium bicarbonate is added as an anticoagulation analyte. Sodium bicarbonate is relatively inert towards blood analytes of interest, and has a simple absorption spectrum with a major peak around 8.5 micrometers. In yet another embodiment, sodium borate salts are another added anticoagulation analyte. Other anticoagulation analytes include, but are not limited to, small, symmetric compounds of preferably two elements, including but not limited to oxides of B, C, N, Al, Si, P, S, and Se.  
      The following discussion is directed to methods for correcting for dilution due to the addition of an anticoagulant that contains an anticoagulation analyte. For discussion purposes, assume that the mixture S/AC is an ideal mixture. As one example, assume that an analyte having a concentration C 0  in volume V 0  of sample S is diluted with 6V of anticoagulant solution AC. Equating the amount of analyte in the undiluted sample S and diluted mixture S/AC gives: 
 
 C 0= C 0′(1+δ V/V 0).  Equation (1) 
 
      In a first embodiment, sampling system  5100  supplies reproducible volumes of either solution AC (δV) and solution S (V 0 ), or ratio of volumes (δV/V 0 ). The ratio δV/V 0  is then determined directly or by calibration using known sample concentrations, and Equation (1) is used to correct for dilution.  
      In a second embodiment, sampling system  5100  supplies accurately measured volumes of either anticoagulant solution AC (δV) or solution S (V) and a measurement is made of the amount of anticoagulation analyte in sampling system  100 . Assume, for example, that anticoagulation analyte has a known concentration C 1  in anticoagulant solution AC. Upon dilution of a volume δV of anticoagulant solution AC in mixture S/AC, the concentration of the anticoagulation analyte in mixture S/AC will be diluted to a value of C 1 ′. Conservation of mass of the measurable anticoagulant analyte gives: 
 
 C 1 ′=C 1 δV /( V 0+δ V ),  Equation (2) 
 
      and the volume ratio δV/V 0  in mixture can be calculated from Equation (2) as: 
 
δ V/V 0 =C 1′/( C 1 −C 1′).  Equation (3) 
 
      Equations (1) and (3) then give: 
 
 C 0 =C 0 ′C 1/( C 1 −C 1′).  Equation (4) 
 
 Given the known anticoagulation analyte concentration in the anticoagulation solution (C 1 ) and the measured anticoagulation analyte concentration and analyte concentration in the mixture S/AC (C 1 ′ and C 0 ′, respectively), Equation (4) can be used to calculate the concentration of the analyte in the material sample S. 
 
      As one example that is not meant to limit the scope of the present disclosure, analytes are determined by absorption spectroscopy and the anticoagulation analyte is a substance that mixes with the fluid containing the analytes, and that has one or more absorption features that are detectable with an analyte detection system, such as analyte detection system  1700 . In one embodiment, the anticoagulation solution AC contains an anticoagulant analyte of known concentration (e.g., C 1 ). In addition, the anticoagulant of this embodiment is treated as an analyte by sampling system  100 , and thus has a concentration that is measured in mixture S/AC (e.g., C 1 ′). The concentration of the sample analyte is measured as C 0 ′, and thus the undiluted sample analyte concentration may be computed, as in Equation (4).  
      Section VII—Multiple Fluid Handling Cassette System  
       FIGS. 52-54  depict additional embodiments of the sampling system  800 , which in some variations can be similar to the embodiments of the sampling system  800  described elsewhere herein, except as further described below. In the sampling system  800  of  FIGS. 52-54 , the cassette  820  comprises two separate or separately-housed cassettes, an instrument cassette  4000  and a patient cassette  4002 . The instrument and patient cassettes are interconnected by at least one transfer coupling  4080  which facilitates passage of fluids between the cassettes  4000  and  4002 . As will be discussed in further detail below, the instrument and patient cassettes  4000 ,  4002  are separately removably attachable to the instrument  810  (and/or to each other), and are removably interconnectable to each other via the transfer coupling  4080 . In certain circumstances, it may be desirable to have certain portions of the cassette  820  disposed of at a greater frequency than other portions. The cassette  820  of  FIGS. 52-54  may allow the disposable components of the sampling system  800  to be replaced at a more economical frequency and avoid unnecessary disposal of components that may be necessary to replace only relatively infrequently. For convenience similar components are referred to by the same reference numerals in  FIGS. 52-54  as in  FIGS. 1-52 .  
      The present embodiment of the sampling system  800  is described with reference to relative directions and positions depicted in  FIGS. 52-54 . This is done so for convenience to describe the sampling system  800  and is not intended to limit the scope of the technology disclosed herein. Also,  FIGS. 52-54  are schematic illustrations which are intended merely to show a broad scope of the present embodiment and not to limit component position, structure, or function.  
      Although the term “disposable” is used in reference to the sampling system  800  of  FIGS. 52-54 , when applied to a system or a component, such as the patient cassette  4002  or the instrument cassette  4000 , “disposable” is a broad term and means, without limitation, that the component or group of components in question is used a finite number of times and then discarded. Some disposable components are used only once and then discarded. Other disposable components are used more than once and then discarded. For example, a new patient cassette  4002  may be replaced each time a new patient is connected to the sampling system  800 , whereas the instrument cassette  4000  may be replaced only after it has been used for many patients.  
      With reference to  FIG. 52 , the patient cassette  4002  includes the fluid source passageway  111  and the connector  120  to facilitate connection to the saline (or other infusate) reservoir  15 , and the patient connection passageway  112  and the connector  110  to facilitate connection to the catheter  11 .  
      With reference to  FIG. 53 , further details of the instrument cassette  4000  are shown within the dashed line  4003 . The instrument cassette  4000  generally comprises the centrifuge rotor  2020  with the sample element  2448  mounted thereon, the fluid interface  2028  (not shown in  FIGS. 52-54 ), and the waste reservoir  325 . The instrument cassette  4000  also generally comprises a number of fluid passageways: a portion of the sampling passageway  113  which extends from a sampling passageway connector  4014  to the fluid interface; a portion of a cleanser passageway  4006  which extends from the fluid interface to a cleanser passageway connector  4012 ; a first waste passageway  4008  which extends from a junction  4009  with the sampling passageway  113  to the waste reservoir  325 ; and a second waste passageway  4004  which extends from a junction  4021  with the cleanser passageway  4006  to the waste reservoir  325 .  
      When the instrument cassette  4000  is attached to the main instrument  810 , components of the instrument cassette  4000  interface with components of the main instrument  810  as follows. The centrifuge rotor  2020  is coupled to the centrifuge drive  2030  of the main instrument  810  to facilitate rotation of the rotor and sample element  2448  as described elsewhere herein, and the fluid interface  2028  is positioned for actuation by the actuator of the main instrument  810 , as discussed above. The main instrument  810  includes valve pinchers  4020 ,  4016 , and  4018  which interface with the cleanser passageway  4006 , first waste passageway  4008  and second waste passageway  4004 , respectively, of the instrument cassette  4000 , when the instrument cassette  4000  is attached to the main instrument  810 . When the passageways  4006 ,  4008 , and  4004  are placed within the valve pinchers  4020 ,  4016 , and  4018  pinch valves are formed respectively.  
      The instrument cassette  4000  includes the waste reservoir  325  that is configured to receive waste material from the sampling and analysis processes of the sampling system  800 . After a fluid, such as blood, has been analyzed inside the centrifuge rotor  2020  and sample element  2448  as described in detail in previous embodiments, it is then discarded and placed into the waste reservoir  325 . The waste reservoir  325  may be, but is not limited to, a soft malleable IV bag, a hard rigid container, or any other suitable container for storing sample waste.  
      When the instrument cassette  4000  is attached to the main instrument  810 , the cassette  4000  is interconnected with the patient cassette  4002  via the cleanser passageway connector  4012  and the sampling passageway connector  4014 . The connectors  4012 ,  4014  may thus comprise part of the transfer coupling  4080 , which may further comprise a length of double-lumen tubing which forms the portions of the sampling passageway  113  and the cleanser passageway  4006  extending between the instrument cassette  4000  and the patient cassette  4002 . In certain embodiments, the connectors  4012 ,  4014  may be embodied in a single, double-lumen coupling which can be positioned at either end of the transfer coupling  4080  (i.e. where the transfer coupling  4080  couples to the patient cassette  4002  or to the instrument cassette  4000 ), or elsewhere along the length of the transfer coupling  4080 .  
       FIG. 54  illustrates another embodiment of the sampling system  800  which is similar to that of  FIGS. 52-53 , but with a different configuration of the instrument cassette  4000 . In the arrangement shown in  FIG. 54  the instrument cassette  4000  primarily includes the centrifuge rotor  2020  with the sample element  2448  mounted thereon, and the fluid interface (not shown). When the instrument cassette  4000  of  FIG. 54  is attached to the main instrument  810 , the centrifuge rotor  2020  is coupled to the centrifuge drive  2030  of the main instrument  810  to facilitate rotation of the rotor and sample element  2448  as described elsewhere herein. In yet another embodiment, the instrument cassette  4000  includes only the sample element  2448  itself. Such an instrument cassette  4000  can be installed on the main instrument  810  by mounting the sample element  2448  on the centrifuge rotor  2020 , which forms a permanent (or more permanent) part of the main instrument  810 , and/or otherwise installing the sample element  2448  on or in the main instrument  810  in a manner which facilitates analysis of the contents of the sample element  2448  by the main instrument  810 .  
      The other components as described above relating to the instrument cassette  4000  of  FIGS. 52-53  become a part of the patient cassette  4002  when configured as shown in  FIG. 54 . These components include the passageways  4006 ,  4004 , and  4008  which are configured to mate with valve pinchers  4020 ,  4018 , and  4016 . The instrument cassette portions that become part of the patient cassette further include the waste container  325 .  
      Although the waste container  325  is shown as a replaceable container it is also possible that the waste container my simply be a coupling that mates to an external vacuum or disposal system (not shown).  
      With continued reference to  FIG. 53 , the components of the patient cassette  4002  are located outside the dashed line  4003 . The patient cassette  4002  thus comprises a cleanser pump body  4022 , a saline (or other infusate) pump body  4030 , and a heparin (or other anticoagulant) pump body  4026 ; a cleanser reservoir  4066 ; and a number of connecting passageways and junctions as discussed further below. When the patient cassette  4002  is attached to the main instrument  810 , a cleanser pump actuator  4023  of the main instrument  810  is coupled to the cleanser pump body  4022 , a saline pump actuator  4031  of the main instrument  810  is coupled to the saline pump body  4030 , and a heparin pump actuator  4027  of the main instrument  810  is coupled to the heparin pump body  4026 . The main instrument  810  also includes valve pinchers  4034 ,  4038 ,  4044 ,  4058 ,  4054 ,  4056 , and  4052 , each of which engages a passageway of the patient cassette  4002  upon attachment of the cassette  4002  to the main instrument  810 ; and a hemoglobin sensor  4046 , bubble sensors  4040 ,  4050 , and  4051 , and pressure sensors  4024 ,  4032 , each of which engages a passageway of the patient cassette  4002  upon attachment of the cassette  4002  to the main instrument  810 .  
      The patient cassette  4002  includes the patient connection passageway  112  which is connectable to the catheter  11  (which in turn is insertable into the patient P) with the patient connector  110 . The patient connection passageway  112  travels away from the connector  110  (and through the bubble sensor  4040  and the valve pincher  4058 , when the patient cassette  4002  is engaged with the main instrument  810 ), through a four-way passageway junction  4048  (and through a valve pincher  4044  and a hemoglobin sensor  4046 , when the patient cassette  4002  is engaged with the main instrument  810 ), and continues to a passageway junction  4013 . The passageway  112  is configured to pass through the valve pinchers  4058  and  4044 , thus forming pinch valves that are preferably substantially similar to the pinch valves of the previous embodiments described in detail above.  
      The patient connection passageway  112  is also configured to pass through the bubble sensor  4040  and hemoglobin sensor  4046  of the main instrument  810  thus forming a bubble detector and a hemoglobin detector, respectively. Examples of suitable bubble sensors for use in the sampling system  800  include but are not limited to ultrasonic or optical sensors that may detect the difference between small bubbles or foam liquid in the passageway. The bubble sensors of  FIGS. 52-53  can be substantially similar to the bubble sensors of other embodiments described in detail above.  
      The patient cassette also includes the fluid source passageway  111  which extends between the saline pump body  4030  (and through the pressure sensor  4032  and valve pincher  4038  when the patient cassette  4002  is engaged with the main instrument  810 ) and the connector  120  which facilitates connection to the saline reservoir  15  as shown in  FIG. 52 . The fluid source passageway  111  connects to the patient connection passageway  112  at the junction  4013  and is configured to draw saline (or other infusate) from the saline container  15  and then to conduct the saline or other infusate through the fluid source passageway  111 , into the patient connection passageway  112 , and into the patient P (see  FIG. 1 ). Similar to the configuration of the patient connection passageway  112 , the fluid source passageway  111  is preferably configured to mate with the pressure sensor  4032  and with the valve pincher  4038  to form a pinch valve, thus desirably allowing the pressure sensor  4032  and the valve pincher  4038  to remain on the main instrument  810  for indefinite reuse.  
      From the four-way passageway junction  4048 , the sampling passageway  113  of the patient cassette  4002  extends to the sampling passageway connector  4014  (and passes through the valve pinchers  4056 ,  4052  and bubble sensors  4050 ,  4051  when the patient cassette  4002  is engaged with the main instrument  810 .). This sampling passageway  113  is configured to mate with the bubble sensors  4050 ,  4051  and the valve pinchers  4052 ,  4056  which are parts of the main instrument  810 . This passageway  113  continues past the connector  4014  into the instrument cassette  4000  and is configured to transport the sample, such as blood, into the centrifuge rotor  2020  and sample element  2448  for sample analysis.  
      The patient cassette  4002  also includes an air passageway  4053  which extends from the four-way passageway junction  4048  (and passes through the valve pincher  4054  when the patient cassette  4002  is engaged with the main instrument  810 ) to an open end opposite the junction  4048 . Thus is formed an air injector when the cassette  4002  and main instrument  810  are engaged.  
      From a passageway junction  4068  with the sampling passageway  113 , a heparin passageway  4060  of the patient cassette extends to the heparin pump body  4026 , which can be similar to the saline pump body  4030  or the cleanser pump body  4026 . The heparin pump body  4026  is configured to mate with the heparin pump actuator of the main instrument  810 . The heparin pump body  4026  is configured to infuse heparin and/or any other suitable anticoagulant fluid into the system in order to prevent clotting of the sample, such as blood, in the various passageways. Although the depicted heparin pump is a syringe, any suitable pump (e.g. a roller pump) that produces a pressure to induce fluid flow may be used.  
      In some embodiments, a heparin source passageway (not shown) is connected at one end to the heparin passageway  4060  between the junction  4068  and the heparin pump body  4026 , and extends to a source (not shown) of heparin or another suitable anticoagulant. The heparin source passageway can extend to or beyond the patient cassette housing or frame (discussed in more detail below) and terminate in a connector to facilitate connection to a heparin/anticoagulant source located externally of the patient cassette  4002 .  
      Although heparin is used in the depicted heparin pump body  4026 , any appropriate anti-coagulant may be used. In certain embodiments, it may not be necessary to include an anti-coagulant pump body  4026  or passageway where the samples are processed sufficiently soon after they are drawn, that it becomes possible to complete the analysis without the addition of anti-coagulants.  
      The patient cassette  4002  also preferably includes a cleanser branch. The cleanser branch includes the cleanser pump body  4022 , a cleanser reservoir passageway  4028 , a portion of the cleanser passageway  4006 , and a cleanser reservoir  4066 . The cleanser pump body  4022  mates to the cleanser pump actuator  4023  on the main instrument  810  when the patient cassette  4002  is attached to the main instrument  810 . In addition, upon attachment of the patient cassette  4002 , the cleanser reservoir passageway  4028  mates with the valve pincher  4034  on the main instrument  810  and thus forms a pinch valve, and the cleanser passageway  4006  engages the pressure sensor  4024 . The cleanser passageway  4006  extends from the cleanser pump body to the cleanser passageway connector  4012  where it is connectable to the instrument cassette  4000 .  
      The cleanser branch of the patient cassette  4002  is configured to draw cleanser from the cleanser reservoir  4066  into the cleanser pump body  4022 . After the cleanser has been drawn into the pump body  4024  it is then infused into various parts of the sampling system such as the instrument cassette  4000  generally, or the sample element  2448 , in order to clean away any undesirable remnants of the sample drawn from patient P of  FIG. 1 .  
      Preferably the cleanser in the cleaning reservoir  4066  is effective in removing blood, blood components, and/or clotted blood from the surfaces of the passageways, sample elements, or other blood contacting surfaces. It is preferred that the cleanser is thermally stable at room temperature. Such cleansers are frequently used in cleaning hospital and laboratory instruments and may include non-specific protease enzymes for digesting blood. One type of cleanser is a mixture of approximately one percent TERGAZYME (Alconox, Inc. of White Plains, N.Y.). The cleanser is preferably mixed in the cleanser reservoir  4066  with saline or other infusate from the saline reservoir  15 .  
      The embodiment of the sampling system  800  shown in  FIGS. 52 and 53  allows the patient cassette  4002  to be replaced at a relatively high frequency (e.g., each time the sampling system  800  is connected to a new patient, or after a given number of measurements have been made with a particular patient cassette  4002 , or after a specified amount of time has lapsed since a particular patient cassette  4002  was placed in service) in order to assure that the passageways, etc. of the patient cassette  4002  remain sufficiently clean and sanitary. The instrument cassette  4000  can be replaced at a relatively low frequency, e.g. after the instrument cassette  4000  has been used with a relatively high specified number of patients, or for a relatively high specified time period or number of measurements.  
      Preferably, the components of the instrument cassette  4000 , but for any portions of the centrifuge rotor  2020  and/or transfer coupling  4080  extending from the cassette  4000 , are housed in an instrument cassette housing (not shown) and/or mounted on an instrument cassette frame (not shown). In addition, the components of the patient cassette  4002 , but for the portions of the fluid source passageway  111 , patient connection passageway  112  and/or transfer coupling  4080  extending from the cassette  4002 , are preferably housed in a patient cassette housing (not shown) and/or mounted on a patient cassette frame (not shown). The instrument cassette housing/frame is preferably separate from the patient cassette housing frame to facilitate replacement of the cassettes at differing frequencies as discussed above, and each of the cassette housings/frames is preferably separate from the housing of the main instrument  810 .  
      The instrument cassette housing and/or the patient cassette housing can include one or more openings configured and located (preferably on the side(s) of the housing that engage the main instrument  810  or the housing of the other cassette) to permit appropriate portions of the main instrument  810  to engage portions of the cassettes. For example, such opening(s) can be configured and located to permit valve pincher(s), hemoglobin sensor(s), bubble sensor(s), and/or pressure sensor(s) of the main instrument  810  to engage appropriate portions of the passageways within the cassettes, upon engagement of the cassette housing(s) with the main instrument  810 . In addition, such opening(s) can be located and configured to permit syringe pump actuator(s) of the main instrument  810  to engage the syringe pump bodies of the cassettes, and/or permit the centrifuge drive  2030  of the main instrument  810  to engage the centrifuge rotor  2020 .  
      Although three syringe pumps are depicted in  FIGS. 52-53  as usable for fluid handling within the depicted sampling system  800 , any suitable alternative pump type (such as roller pumps and the like) may be used in place of some or all of the depicted syringe pumps. In addition, while the instrument cassette  4000  and main instrument  810  are depicted as employing a centrifuge, any other suitable fluid component separator (filter, membrane, etc.) may be employed in place of the centrifuge.  
      In view of the above described sampling system  800  it will be appreciated by one skilled in the art that the above described system  800 , in one embodiment, is a fluid handling system  800  for use in bodily fluid analysis. The system  800  includes a first fluid handling module  4002  configured to interface with the main instrument  810 . The first fluid handling module  4002  includes a first fluid handling network which includes an infusate passage  112 ; and an infusion fluid pressure member  4030  which is suitable for moving fluid within the passage  112 . The system  800  also includes a second fluid handling module  4000  which is separate from the first module  4002  and is also configured to interface with the main instrument  810 . The second fluid handling module  4000  includes at least one sample analysis cell  2448 . The first and second modules  4002  and  4000  are configured to interconnect and provide fluid communication between the first fluid handling network of module  4002  and the sample cell  2448 .  
      In another embodiment the body fluid analysis system  800  includes a body fluid analysis instrument  810  and a first fluid handling module  4002  comprising a first housing and a first fluid handling network. The first fluid handling module  4002  is removably connected to the instrument  810  such that the first housing engages the instrument  810 . The system  800  also includes a second fluid handling module  4000  comprising a second housing which is separate from the first housing of the module  4002 , and a sample analysis cell  2448 . The second fluid handling module  4000  is removably connected to the instrument  810  such that the second housing of the second module  4000  engages the instrument  810 . The first and second fluid handling modules  4002 ,  4000  are connected to each other and are in fluid communication with each other.  
      The second fluid handling module  4000  may also include its own second fluid handling network, and the sample analysis cell  2448  can be accessible via the second fluid handling network. The second fluid handling module  4000  may also include a bodily fluid component separator  2020  which may be a centrifuge rotor or a suitable filter, membrane, etc. as described above.  
      In some embodiments, the infusion fluid pressure member  4030  of the first fluid handling network may comprise a pump, or a syringe pump body. The pressure member may alternatively comprise a portion of the first fluid handling network which is configured to engage a roller pump actuator. This can take the form of a fluid passage (e.g. similar to the fluid passageway  111   a ) which extends across an opening in the housing/frame which facilitates engagement of the fluid passage with the roller pump actuator  2620   a . The pressure member may also comprise an infusion pump  4030 , a cleanser pump  4022 , or an anticoagulant pump  4026 .  
      The first fluid handling module  4002 , in some embodiments, may also include a cleanser fluid source  4066  and/or a anticoagulant fluid source  4026 , which is/are accessible via the fluid handling network of the first module  4002 . In such embodiments, the first module  4002  may further include cleanser and/or anticoagulant pressure sources which are suitable to move the cleanser and the anticoagulant from the fluid sources  4066  and  4026  respectively.  
      In some embodiments of the system  800  the first and second modules  4002  and  4000  are interconnected and their respective first and second fluid handling networks are in fluid communication. This communication may be facilitated by the transfer coupling  4080  which includes parts of the sampling passageway  112  and cleanser passageway  4028 .  
      In further view of the above described sampling system  800 , some embodiments comprise a method of using a bodily fluid analysis system  800  having a main instrument  810  and first and second replaceable fluid handling modules  4002 ,  4000  removably connected to the main instrument  810 . The analysis system  800  has a pump at least partially formed by the first fluid handling module  4002 , and a sample analysis chamber in the second fluid handling module  4000 . The method comprises replacing the first fluid handling module  4002  at a first replacement frequency and replacing the second fluid handling module  4000  at a second replacement frequency. The first replacement frequency differs from the second replacement frequency.  
      The first replacement frequency is preferably higher than the second replacement frequency. Replacing the first fluid handling module  4002  can optionally comprise replacing the first module (a) each time a new patient is associated with or connected to the analysis system  800 ; (b) after a specified number of measurements have been made with the first fluid handling module  4002 ; or (c) after a specified time has elapsed since the first module  4002  was placed in service.  
      Replacing the first fluid handling module  4002  can further optionally comprise replacing at least a portion of the pump. This can take the form of (a) replacing a syringe pump body; or (b) replacing a portion of a fluid passageway which is configured to engage a roller pump actuator.  
      Except as further described herein, the function of the sampling system  800  of  FIGS. 52-53 , including patient sampling, sample analysis, patient infusion, and system cleansing and anticoagulation, can be similar to the functions described herein with regard to the other embodiments described in detail herein.  
      In one embodiment, a sample of blood is drawn from the patient P with the sampling system  800  of  FIGS. 52-53  as follows. The infusate pump  4030  is operated in a “draw” mode while the appropriate pinch valves remain open or closed as needed, until a column of blood (with a volume of, in various embodiments, 5 ml or less, 4 ml or less, 3 ml or less, 2 ml or less, 400 microliters or less, or between 400 microliters and 5 ml) enters the patient connection passageway  112  and extends from the connector  110  past the four-way passage junction  4048 , to a location adjacent to or just past the hemoglobin sensor  4046 . As this initial volume of blood is drawn into the passageway  112 , the hemoglobin sensor  4046  is monitored until the output of the sensor  4046  reaches a desired plateau level indicating the presence of undiluted blood in the passageway  112  adjacent the sensor  4046 . Of this initially drawn blood volume in the passageway  112 , a relatively small sample (in various embodiments, 100 microliters or less, 80 microliters or less, 60 microliters or less, 40 microliters or less, 20 microliters or less, or between 20 microliters and 100 microliters) is pulled or otherwise moved from the four-way junction  4048  through the sampling passageway  113  toward the centrifuge rotor  2020  and sample element  2448  for analysis. After this relatively small sample is drawn from the initially drawn volume in the passageway  112 , the remainder of the initially drawn volume of blood is preferably immediately returned to the patient through the patient connection passageway  112 . This return can be performed by operating the infusate pump in an “infuse” mode, thereby pushing a column of infusate (e.g. saline) from the infusate source  15  toward the connector  110 . The advancing column of saline pushes the remainder of the initially drawn volume of blood back to the patient from the passageway  112  through the connector  110 , ahead of the saline column.  
      Preferably, as the blood sample is moved toward the sample element  2448  from the four-way junction  4048 , the air passageway  4053  is operated to divide the blood sample in the passageway  113  into portions separated by air slugs, and/or the heparin pump  4026  is operated to infuse the blood sample in the passageway  113  with heparin or other suitable anticoagulant to prevent clotting. In one embodiment, a column comprising four such heparinized portions of blood separated by air slugs is created and moved toward the sample element  2448 . The first three portions are moved through or past the sample element  2448 , through the cleanser passageway  4006  and second waste passageway  4004 , and into the waste receptacle  325 . The fourth portion is moved into the sample element  2448 , where it remains for centrifuging and analysis as described elsewhere herein.  
      After analysis of the fourth portion, the portion is moved to the waste receptacle  325 , preferably by operation of the cleanser pump  4022 . The cleanser pump  4022  pushes a column of cleanser through the cleanser passageway  4006 , the sample element  2448  and the first waste passageway  4008  to the waste receptacle  325 . The cleanser column thus pushes the fourth portion to the waste receptacle  325  from the sample element  2448  through the first waste passageway  4008 . Cleanser is pumped in this manner through the sample element  2448  to the waste receptacle  325  for a duration sufficient to cleanse the sample element  2448  and passageways as needed.  
      When this cleanser cycle is complete, the cleanser pump  4022  is stopped and the infusion pump  4030  is operated in the “infuse” mode once again to move the infusate or saline from the infusate source  15 , through the passageways  112  and  113 , through the sample element  2448 , through the cleanser passageway  4006  and second waste passageway  4004  to the waste receptacle  325 . Infusate is pumped in this manner for a time sufficient to remove the cleanser from the sample element  2448  and relevant passageways. After cleanser removal, the infusate pump remains in the “infuse” mode and infuses saline to the patient through the connector  110 .  
      Preferably, the sampling system  800  does not wait for analysis of the portion of the blood sent through the sampling passageway  113  before returning the remainder of the initially drawn volume of blood to the patient. By separating a small sample for analysis from the initial draw volume, the remainder of the initial draw volume can be returned to the patient quickly, and clotting and blood cell damage can be avoided. Preferably, this remainder of the initially drawn column of blood is returned to the patient in less than five minutes, less than four minutes, less than three minutes, less than two minutes, or between two minutes and five minutes, after the initial blood draw is commenced.  
      In addition, the separation of a sample for analysis from the initially drawn volume permits the duration of the sample analysis to be independent of the time that the initially drawn volume remains outside the patient. Thus, sufficient time (e.g., more than five minutes, more than eight minutes, between eight minutes and twelve minutes, or about ten minutes) is available to separate/centrifuge the sample and analyze it, enhancing accuracy. The (optional) addition of an anticoagulant such as heparin to the blood sample, as discussed above, also facilitates a long analysis time and thus high accuracy. Thus is achieved a relatively long sample analysis time and high measurement accuracy, while the initially drawn volume of blood remains outside the patient for only a relatively short time.  
      In view of the above described sampling system  800  and methods of use and operation thereof, it will be appreciated that the presently disclosed technology includes a method of handling a bodily fluid. In certain embodiments, the method comprises drawing a volume of bodily fluid from a patient P into a fluid handling network and retaining a sample of the drawn volume in the fluid handling network. The retained sample is preferably less than half of the drawn volume. The method also includes returning the balance of the drawn volume to the patient P in less than five minutes. The method also includes analyzing at least a portion of the sample.  
      This method may also include additional steps including disposing of the sample after the analysis, and/or transferring the sample to a waste container  325 . The method may also include separating a component of the bodily fluid sample and then analyzing only the separated component of the bodily fluid sample. The method may further include infusing a liquid into the patient P via the fluid handling network of the sampling system  800 , and occasionally interrupting the infusing to facilitate the above described sample draw.  
      In various embodiments of this method, returning the balance of the drawn volume to the patient comprises returning the balance in less than four minutes, less than three minutes, or less than two minutes after the draw was commenced, or between two minutes and five minutes after the draw was commenced.  
      In various embodiments of this method, the drawn volume is less than 5 milliliters, less than 400 microliters, or between 400 microliters and 5 milliliters. The sample can be less than 100 microliters in volume, or between 20 microliters and 100 microliters in volume.  
      In various embodiments of this method, the analysis can be a spectroscopic analysis.  
      In view of the above described sampling system  800  and methods of use and operation thereof, it will be appreciated that the presently disclosed technology includes a method of handling a bodily fluid. In some embodiments, the method comprises drawing a volume of the bodily fluid from a patient P into a fluid handling network, and retaining a sample of the drawn volume in the fluid handling network. The retained sample preferably comprises less than half of the drawn volume. The method further comprises returning the balance of the drawn volume to the patient, and analyzing at least a portion of the sample. The analyzing preferably takes at least 10 seconds to complete.  
      In various embodiments of this method, the analysis can be a spectroscopic analysis, and the analyzing commences upon first emitting a beam of electromagnetic radiation into at least a portion of the sample. The analyzing can be considered to be complete upon completion of the emitting.  
      In various embodiments of this method, the analyzing can take at least thirty seconds, one minute, two minutes, three minutes or five minutes to complete, or between 10 seconds and five minutes to complete.  
      In various embodiments, this method may further include infusing a liquid into the patient P via the fluid handling network of the sampling system  800 , and occasionally interrupting the infusing to facilitate the above described sample draw. The method may also include separating a component of the bodily fluid sample and then analyzing only the separated component of the bodily fluid sample.  
      In view of the above described sampling system  800  and methods of use and operation thereof, it will be appreciated that the presently disclosed technology includes a bodily fluid analyzer  800  comprising a fluid handling network configured for fluid communication with a bodily fluid within a patient; and an analyte detection system  1700  configured to examine a sample of bodily fluid in the fluid handling network. The analyzer further comprises a processor  210  and stored program instructions executable by the processor  210  so that the analyzer  800  is operable to draw a volume of the bodily fluid into the fluid handling network and retain a sample of the drawn volume in the fluid handling network. The retained sample preferably comprises less than half of the drawn volume. The analyzer  800  is further operable to return the balance of the drawn volume to the patient in less than five minutes after the drawing was commenced, and analyze at least a portion of the sample.  
      In various embodiments, this analyzer  800  can be further operable to move the sample to a waste container  325  after analyzing the sample. The analyzer  800  can be further operable to occasionally interrupt infusing the liquid to draw the volume.  
      In various embodiments, the fluid handling network of this analyzer  800  is in communication with an infusion liquid source  15  and the analyzer is further operable to infuse the liquid via the fluid handling network.  
      In various embodiments, this analyzer  800  can be further operable to return the balance of the drawn volume to the patient in less than four minutes, less than three minutes, or less than two minutes after the analyzer has commenced drawing the volume; or between two and five minutes after the analyzer has commenced drawing the volume.  
      In various embodiments, the drawn volume is less than 5 milliliters, or less than 400 microliters, or between 400 microliters and 5 milliliters. The sample can be less than 100 microliters in volume, or between 20 microliters and 100 microliters in volume.  
      In various embodiments, the analyte detection system  1700  comprises a spectroscopic analyte detection system. The analyzer can further comprise a fluid component separator accessible via the fluid handling network.  
      In view of the above described sampling system  800  and methods of use and operation thereof, it will be appreciated that the presently disclosed technology includes a bodily fluid analyzer  800  comprising a fluid handling network configured for fluid communication with a bodily fluid within a patient, and an analyte detection system  1700  configured to examine a sample of bodily fluid in the fluid handling network. The analyzer can further comprise a processor and stored program instructions executable by the processor so that the analyzer is operable to draw a volume of the bodily fluid from a patient into a fluid handling network, and retain a sample of the drawn volume in the fluid handling network. The retained sample preferably comprises less than half of the drawn volume. The analyzer is further operable to return the balance of the drawn volume to the patient, and analyze at least a portion of the sample. The analyzing takes at least 10 seconds to complete.  
      In various embodiments of this analyzer, the analyte detection system  1700  comprises a spectroscopic analyte detection system. The analyzing commences upon first emitting a beam of electromagnetic radiation into at least a portion of the sample. The analyzing can be considered to be complete upon completion of the emitting.  
      In various embodiments of this analyzer, the analyzing takes at least two minutes, at least three minutes, or at least five minutes to complete, or between ten seconds and five minutes to complete.  
      In various embodiments, the fluid handling network of this analyzer  800  is in communication with an infusion liquid source  15  and the analyzer is further operable to infuse the liquid via the fluid handling network. The analyzer  800  can be further operable to occasionally interrupt infusing the liquid to draw the volume. The analyzer can further comprise a fluid component separator accessible via the fluid handling network.  
      Although the invention(s) presented herein have been disclosed in the context of certain preferred embodiments and examples, it will be understood by those skilled in the art that the invention(s) extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses of the invention(s) and obvious modifications and equivalents thereof. Thus, it is intended that the scope of the invention(s) herein disclosed should not be limited by the particular embodiments described above.