Patent Publication Number: US-10324025-B2

Title: Optical flow cell and test head apparatus

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application is a divisional of U.S. application Ser. No. 15/134,528, filed on Apr. 21, 2016, and claims priority from it. This application is related to a co-pending continuation-in-part U.S. application Ser. No. 15/694,083, filed on Sep. 1, 2017. The entire content of the U.S. application Ser. No. 15/134,528 and U.S. application Ser. No. 15/694,083 are incorporated herein in their entireties by reference for all purposes. 
    
    
     FIELD OF TECHNOLOGY 
     Aspects of the present disclosure are directed to the field of spectroscopic determination of analyte content in a sample, and more particularly to the field of presenting a body fluid sample for spectroscopic analysis in an optical flow cell. 
     BACKGROUND 
     In a variety of clinical settings, it is important to measure certain chemical characteristics of blood, for example, the analytes Hemoglobin (e.g., Carboxyhemoglobin, Oxyhemoglobin, Methemoglobin), proteins, lipids, bilirubin. These settings range from a routine visit of a patient to a physician&#39;s office, an emergency room, or monitoring of a hospitalized patient, for example. Measurement of an analyte in a body fluid sample may be accomplished by numerous methods one of which is by spectroscopic determination. 
     Spectroscopic determination of analyte content in a body fluid sample, such as a blood sample for example, involves presenting the body fluid sample to a light source and analyzing properties of light transmitted through the sample or reflected from the sample. A structure for presenting a fluid sample in a spectroscopic measurement instrument such as a clinical analyzer is generally called an optical flow cell. In certain implementations, a sample chamber in the sample cell is preferably configured with a precise depth dimension during measurements so that a path-length of light through the sample is predetermined. The optical path-length through an optical flowcell may preferably be maintained within a few microns during a measurement, for example. Following a measurement, the sample may be flushed from the flow cell to prepare for analysis of another sample. During the flushing process the optical flow cell may be opened or partially opened for more efficient flushing, for example. 
     Two alternative sample cell configurations for optical spectroscopy as previously known are described in U.S. Pat. No. 6,188,474. In one configuration, a previously described sample cell is selectively adjustable between a first position having a predetermined optical path-length adapted for analyte measurement while the sample is in the measurement zone, and a second position having a predetermined other path-length adapted for clearing the sample from the flow path. This previously known sample cell includes two cell portions that are maintained in a slidable fluid tight engagement with one another so that adjustability of the fluid flow path from a small cross section flow path for measurement to a larger cross section flow path for flushing is accomplished by sliding the mating surfaces relative to another. The slidable engagement in this configuration detrimentally may trap sample portions between the first cell portion and the second cell portion which may cause contamination to a sample under measurement and may affect the dimensional consistency of the path-length. In another configuration, the previously described sample cell is selectively adjustable between a first position having a predetermined optical path-length for measurement and a second position for clearing the sample by applying and relaxing a compressive force between the first cell portion and the second cell portion. In this configuration, the path-length may be detrimentally affected by compression of an elastomeric gasket between the first cell portion and a second cell portion. 
     SUMMARY 
     Aspects of the present disclosure include a variable path length optical flow cell such as the type of optical flow cell used for measuring an analyte in a clinical analyzer. The analytes are typically found in a body fluid including but not limited to blood, plasma and serum. Analytes measured in optical flow cell include but are not limited to Hemoglobins, proteins, lipids, and bilirubin, for example. The disclosed flow cell expands and closes like a bellows to achieve a first depth for cleaning and a shallower second depth for measurement. In one embodiment, sealing in the disclosed flow cell is achieved by a diamond shaped seal surrounding an inner fluid chamber. The diamond shaped seal is operative to seal the inner fluid chamber by expanding laterally against walls of a seal channel containing the seal in the flow cell throughout the movement of the two portions of the optical flow cell. The seal is not compressed between the first portion of the cell and the second portion of the cell. This improves precision and repeatability of an optical path-length through the flow cell. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing will be apparent from the following more particular description of example embodiments of the present disclosure, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings, which are not necessarily to scale, emphasis illustrative embodiments of the present disclosure. 
         FIGS. 1A-1C  illustrate an example of an optical flow cell according to an aspect of the present disclosure. 
         FIG. 2  illustrates an optical flow cell including cantilever arms configured to provide an opening force between portions of the optical flow cell according to an aspect of the present disclosure. 
         FIG. 3  illustrates a test head apparatus for locating and actuating an optical flow cell according to an aspect of the present disclosure. 
         FIG. 4  illustrates a test head apparatus for locating and actuating an optical flow cell according to another aspect of the present disclosure. 
         FIG. 5  illustrates a test head apparatus for locating and actuating an optical flow cell according to another aspect of the present disclosure. 
         FIG. 6  is a graph of test data illustrating optical path length repeatability in a test head apparatus according to an aspect of the present disclosure. 
         FIG. 7  illustrates a test head apparatus for locating and actuating an optical flow cell according to another aspect of the present disclosure. 
         FIG. 8  is a process flow diagram describing a method for spectroscopic determination of an analyte in a body fluid sample, according to an aspect of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     Aspects of the present disclosure include a variable path length optical flow cell for optical measurement of analytes in a body fluid sample in a clinical analyzer such as but not limited to GEM 4000 and GEM 5000 clinical analyzers (Instrumentation Laboratory Company, Bedford, Mass.). In an embodiment, the disclosed flow cell closes to provide chamber having an optical path through the chamber having a path-length of about 80 micrometers to about 90 micrometers for optical determination of one or more analytes of a body fluid sample in the chamber. When the flow cell is in the closed configuration for sample analysis, the optical path-length through an upper portion of the flow cell and a lower portion of the flow cell is very accurate due to a very small tolerance of displacement between an upper portion of the flow cell and a lower portion of the flow cell. When a measurement is complete, the flow cell can be opened for washing out the body fluid sample from the sample chamber. When the flow cell is in the open configuration for cleaning, the tolerance of displacement between the upper portion of the flow cell and the lower portion of the flow cell is not critical and the gap between the upper portion and lower portion of the flow cell may be significantly greater than 80-90 micrometers. In an illustrative embodiment, when the flow cell is in the open configuration for wash out, gap between the upper portion of the flow cell and the lower portion of the flow cell may provide a chamber depth of about 250-400 micrometers, for example. 
     Aspects of the present disclosure include a floating seal surrounding the sample chamber. The seal is effective by lateral compression of the seal against sidewalls of a seal channel surrounding the sample chamber. Some extra space is provided above and below the seal in the seal channel. The extra space prevents the seal from being compressed vertically, or from bottoming-out to form face seal between the top portion and bottom portion of the sample cell. 
     Sample cell configurations that employ face seals do not exhibit repeatable measurement lengths within one micron tolerance. By avoiding compression of the seal between the top portion and bottom portion of the sample cell, the disclosed floating seal configuration allows the sample cell to be closed to a repeatable chamber height within about one micron. This closed chamber height provides an optical measurement distance that is accurate and repeatable within about one micron in a height range of about 0.09 mm in some embodiments to about 0.5 mm distance in other embodiments. 
     In an illustrative embodiment, closing of the disclosed flow cell may be actuated using low cost shape memory alloy such as nitinol, for example. Alternatively, the flow cell maybe closed by an actuation mechanism that includes a solenoid or an electric motor such as a stepper motor, for example. The flow cell halves are urged away from each other toward the open configuration by a spring force when the actuation mechanism is retracted or relaxed. 
     Referring to  FIGS. 1A-1C , aspects of the present disclosure include a sample cell apparatus  100  for use in spectroscopic determination of an analyte in a body fluid sample. The sample cell apparatus  100  includes a first plate member  10  made from an optically clear material and a second plate member  20  made from an optically clear material and opposing the first plate member  10 . A first surface of the first plate member  10  faces the second plate member  20 . The first surface includes a first well portion  19 , a first seal channel portion  12  adjacent to the first well portion  19 , and a first abutment surface  15  outside of the first well portion  19  and outside of the first seal channel portion  12 . A second surface of the second plate member  20  faces the first plate member  10 . The second surface includes a second well portion  29  aligned with the first well portion  19  to form a sample chamber  50 , a second seal channel portion  23  aligned with the first seal channel portion  12  and adjacent to the second well portion  29 , and a second abutment surface  25  outside of the second well portion  29  and outside of the second seal channel portion  23  and aligned with the first abutment surface  15 . The first well portion  19  has a fixed depth relative to the first abutment surface  15 , and the second well portion  29  has a fixed depth relative to the second abutment surface  25 . One or more spring members  40  are configured between the first plate member  10  and the second plate member  20  to urge the first plate member  10  away from the second plate member  20 . A floating seal  30  extends into the first seal channel portion  12  and the second seal channel portion  22 . The floating seal  30  is compressed transversely between sidewalls of the first seal channel and the second seal channel. According to an aspect of the present disclosure, the floating seal  30  defines a periphery of the sample chamber. A fluid inlet path  60  extends through the first plate member  10  or the second plate member  20  into the sample chamber  50 . A fluid outlet path  70  also extends through the first plate member  10  or the second plate  20  into the sample chamber  50 . 
     According to another aspect of the present disclosure, the sample cell apparatus  100  includes an actuator member  80  configured to controllably overcome the spring member(s) to urge the first plate member  10  against the second plate member  20  by a displacement defined by abutment between the first abutment surface  15  and the second abutment surface  25 . 
     According to an aspect of the present disclosure, the actuator member  80  may include a shape memory member. The shape memory member may be made from nitinol, or another shape memory material, for example. According to another aspect of the present disclosure, the actuator member  80  may include an electric motor or a solenoid, for example. 
     According to another aspect of the present disclosure, the spring members  40  may be cantilever springs. The cantilever springs may be monolithically formed with the first plate member  10  and/or the second plate member  20 , for example. According to another aspect of the present disclosure, the spring members may be compression springs, or the like. 
     In certain embodiments, the sample chamber  50  may be elongated. The inlet path  60  may be located proximate to a first end of the elongated sample chamber  50 , and the outlet path  70  may be located proximate to a second end of the sample chamber  50  opposite the first end of the sample chamber  50 . In certain embodiments, the sample chamber  50  and the floating seal  30  may be substantially diamond shaped. 
     According to an aspect of the present disclosure, a light source is directed through the first plate member  10  into the sample chamber  50 . A light detector apparatus is directed to receive light from the light source that has passed through the first plate member  10 , the sample chamber  50  and the second plate member  60 . 
     In certain embodiments, the light detector apparatus may be a spectroscope, for example. The light source and/or the light detector may be integrated with actuator member. 
     According to an aspect of the present disclosure, the sample cell apparatus  100  may include an outer surface having a detent structure configured for engaging a mating detent structure in the actuator member  80  for locating the sample cell apparatus relative to the actuator member and/or relative to the light source and light detector apparatus. 
     Referring to  FIG. 2 , in an illustrative embodiment of the disclosed flow cell  200 , one or more finger portions  240 ,  242  are integrally molded with the first plate member  210  and the second plate member  220  respectively to form cantilever spring members configured to urge the first plate member  210  away from the second plate member  210 . The cantilever spring members may be used instead of or in addition to compression springs ( 40  in  FIGS. 1A-1C ), for example. Because the gap dimension between the first plate member and the second plate member is not as critical while the flow cell  200  is in the open cleaning configuration as it is in when the flow cell  200  is in the closed measurement configuration, simple spring members such as the described cantilever spring arms are sufficient to meet design requirements for applying a separating force. Alternative embodiments may provide a spring force to separate the first plate member from the second plate member with compression springs or an elastomeric pad such as a foam rubber pad, or a combination of spring types, for example. 
     Referring to  FIG. 3 , an embodiment of the disclosed flow cell  302  may be configured for removably mounting in a test head apparatus  300 . The test head apparatus  300  may include a flow cell support structure  304  and an actuating member  306 . The actuating member  306  is configured to controllably apply a force to the flow cell  302 , which compresses the top portion  310  of the flow cell  302  against the bottom portion  320  of the flow cell by overcoming the separating force of the compression spring(s)  340 . The actuating member  306  may be coupled to one or more mechanical actuators. Various types of mechanical actuators including, pneumatic actuators, hydraulic actuators, electric motors, are well known and may suitable for controllably driving the actuating member  360  in the test head apparatus, for example. 
     In an illustrative embodiment, the test head apparatus  300  may also include a light source configured for directing light though the test cell  302  and a spectrometer configured for receiving light from the light source that has passed through the test cell  302 . The light source may include a neon light source and/or an LED light source for example. The spectrometer may include spectrometer optics and/or a diffuser, for example. 
     In another aspect of the disclosure, an optical diffuser may be integrally part of first plate member  10  and/or the second plate member  20  shown in  FIGS. 1A-1C , for example. For example, a thin diffuser can be affixed to the plates or, alternatively, the surface of the plates can be frosted to diffuse the light. 
     Referring to  FIG. 4 , according to an aspect of the present disclosure, the disclosed flow cell  406  may include an alignment portion  404  for aligning the flow cell properly when it is mounted in the test head apparatus  400 . The alignment portion  404  may include a depression or detent in the surface of the top portion  410  or bottom portion  420  of the flow cell  406 . The alignment portion  404  is configured for engaging an alignment and retention portion  402  of the test head apparatus  400 . In an illustrative embodiment, the alignment and retention portion  402  may include a wheel configured to sit in the depression/detent of the alignment portion  404  of the flow cell  406  when the flow cell  406  is properly located in the test had apparatus  400 . The wheel may be spring biased against the alignment and retention portion  402  of the flow cell  406 , for example. 
     Referring to  FIG. 5 , an embodiment of the disclosed test head apparatus  500  includes an actuating member  506  operatively coupled to a nitinol wire  508 . The nitinol wire changes length upon application of electrical energy applied to the nitinol wire, and returns to an original length upon removal of the electrical energy. This shape memory characteristic of the nitinol wire enables a simple and reliable electro-mechanical actuation mechanism for controlling movement of the actuating member  506  by applying and removing a voltage and/or electrical current to the nitinol wire. 
       FIG. 6  is a graph  600  of test data including measurements of the optical path length through a flow cell  502  using an embodiment of the test head apparatus as shown in  FIG. 5  in which actuation was implemented by energizing the nitinol wire  508 . In this configuration the gap was repeatable with +/−1.5 microns. 
     In previously known optical test heads, a light detector portion of a spectrometer device has typically been mounted in the test head and connect to an external portion of the spectrometer with a fiber optic cable. This adds cost and complexity to the test head apparatus. Aspects of the present disclosure include an optical light engine integrated in a test head apparatus. The disclosed integrated optical light engine combines a light emitting diode (LED), a neon lamp source, a spectrometer, optics with diffuser, and a mechanism for actuating a variable path length flow cell. The disclosed test head apparatus head is compact and rugged and avoids optical fibers for coupling the LED and spectrometer to the test head. The integrated optical head enables portable blood gas instruments to be constructed with lower costs and greater simplification, for example. 
     In one example, disclosure, a small spectrometer, such as modular spectrometer by Ocean Optics, Inc. of Dunedin, Fla., USA, may be mounted in the test head and directly coupled to external processing equipment, for example without employing fiber optic cables. An illustrative embodiment of the disclosed test head apparatus  700  as shown in  FIG. 7 , includes a spectrometer  710 , such as spectrometer model STS by Ocean Optics, Inc., mounted directly in the test head apparatus  700 . The spectrometer  710  is configured for analyzing light that is transmitted through a flow cell  702  mounted in the test head apparatus  700 . The disclosed configuration including an incorporated spectrometer  710  in the test head apparatus  700  is significantly less expensive than previously known test head configurations that couple a spectrometer light detector portion to a spectrometer device with expensive fiber optic cable bundles, for example. 
     Referring to  FIG. 8 , another aspect of the present disclosure includes a method  800  for spectroscopic determination of an analyte in a body fluid sample. At block  810 , the method  800  includes providing a sample cell having a sample path extending between a first plate member and an opposing second plate member. The sample path is adapted for communicating the body fluid sample from a fluid inlet path through a sample chamber between the first plate member and the second plate member to a fluid outlet path. At block  820 , the method includes inserting the body fluid sample into the chamber. At block  830 , the method  800  includes providing one or more spring members between the first plate member and the second plate member. The spring members apply a spring force configured to separate the first plate member from the second plate member. At block  840 , the method  800  includes moving the first plate member along a normal axis of the first plate and the second plate to a closed configuration by applying a compressive force that overcomes the spring force and urges an abutment surface of the first plate member against an abutment surface of the second plate member. In the closed configuration a predetermined optical path length is provided through the sample chamber for conducting optical measurements. 
     In block  830 , the method  800  may also include mechanically limiting the predetermined optical path length within a range of +/−1 micron based on a first fixed depth of the chamber into the first plate member relative to the abutment surface of the first plate member and second fixed depth of the chamber into the second plate member relative to the abutment surface of the second plate member. According to aspects of the present disclosure, the method  800  also includes spectroscopically determining the presence of analyte in the sample at block  850  by applying light along the predetermined optical path length. 
     According to aspects of the present disclosure, the method  800  also includes removing the compressive force after spectroscopically determining the presence of the analyte in the body fluid sample at bloc  860  and allowing the first plate member to be displaced by the spring force along the normal axis away from the second plate member to an open configuration. The method  800  further includes clearing the body fluid sample from the chamber at block  870  while the first plate member is displaced away from the second plate member in the open configuration.