Patent Publication Number: US-2022229064-A1

Title: Method of using differential measurement in two or more channels to improve sensitivity

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/008,891 filed on Jun. 14, 2018 and scheduled to issue on Feb. 8, 2022 as U.S. Pat. No. 11,243,209, which is a divisional of U.S. patent application Ser. No. 11/500,626, filed on Aug. 8, 2006, now U.S. Pat. No. 10,001,486, issued on Jun. 19, 2018. The disclosures of all of the above-referenced prior applications, publications, and patents are considered part of the disclosure of this application, and are incorporated by reference herein in their entirety. 
    
    
     BACKGROUND 
     Currently, assays are read by human eye or high cost imaging system and the reading of assays are determined by individual human judgment or expensive equipment. The purpose of reading these assays is to determine whether a test sample of biological or chemical material being assayed includes a particular analyte, or a derivative or constituent of the analyte. The particular analyte, which is the subject of the assay, is referred to as a test analyte. The test sample may include biological material such as urine, saliva, blood plasma, or the like. The test sample may include chemical material such as rainwater, sludge, or the like. 
     An assay is performed using a substrate having a sensitive region patterned on the surface of the substrate. Such substrates may include channels that wick the test sample up and over the sensitive regions patterned within the channels. In some case, the substrate is made of silicon or glass and has a smooth surface. If the substrate includes channels, the channels are etched in the substrate and the sensate region is patterned within the etched channels. In other cases, the substrate is made of paper. If the paper substrate includes channels, the channels are defined by the type and/or density of the paper or by thickness variations in the paper. 
     The sensitive region reacts to exposure of a test analyte. The sensitive region is indistinguishable from the substrate outside the sensitive region until the sensitive region is exposed to the test analyte. The reaction can be a bonding of the material in the sensitive region with the test analyte. The reaction is detected by an emission of light from the reacted region. In some cases, light is incident on the assay after exposure to a test sample. If a reaction has occurred, some of the incident light is reflected from the bonded material. For example, gold atoms are attached to the test analyte and incident light is reflected from the bound gold atoms. In other cases, if a reaction has occurred, the bonded material fluoresces upon exposure to the incident light. 
     A human observes the sensitive region to determine if there was a sufficient change in the appearance of the sensitive region relative to the rest of the substrate. When readings to determine an exposure of the sensitive region to of a test analyte are made by the human eye, the readings may not be consistent and may be prone to error. When assays are read by equipment, such as a charge-coupled device (CCD), the determination of an exposure of the sensitive region to of a test analyte may be consistent and relatively error free. However, the equipment typically must be high resolution to make the accurate determination and such equipment is expensive. 
     In some instances, it is useful to determine the amount of analyte in the test sample. For example, if a physician is treating a physical condition for a patient and the patient&#39;s blood is the test sample 
     A market demand exists for a simple, inexpensive system to determine whether a test sample of biological or chemical material being assayed includes a particular analyte, or a derivative or constituent of the analyte. There is also a market demand for quantifying the amount of includes a particular analyte, or a derivative or constituent of the analyte in an inexpensive system. 
     SUMMARY 
     The invention provides in a first aspect a method to calibrate measurements of a test analyte in a test sample. The method includes measuring at least one test-light level responsive to reactions of at least one reagent group and at least one reactive test analyte in the test sample, measuring at least one control-light level responsive to reactions of at least one reagent group and at least one control analyte in a control sample. Each control analyte is a known amount of at least one reactive test analyte. The method further includes determining a presence of the reactive test analyte in the test sample based on the measured test-light levels and control-light levels. The reagent group and the reactive test analyte react by attaching to each other. 
     The invention provides in a second aspect a test strip to calibrate measurements of one or more test analytes in a test sample. The test strip includes at least two channels, each channel including reagent portions having associated reagent groups. Each channel receives either the test sample or a selected control sample. The selected control sample includes a known amount of at least one test analyte and the test sample includes either an unknown amount of at least one test analyte or an undetectable amount of the test analytes. 
     The invention provides in a third aspect a system to calibrate measurements of one or more test analytes from a test sample. The system includes a photodetector array and a processor communicatively coupled to the photodetector array. The photodetector detects light correlated to at least three reagent portions of a test strip and detects a reference light from at least one blank portion of the test strip. The processor determines reaction light levels correlated to the light detected from each of the reagent portions, determines a reference-light level correlated to the blank portion, forms calibration curves for respective reagent groups based on respective first reaction light levels and respective second reaction light levels and determines an amount of one or more test analytes in the test sample based on placements of third reaction light levels on respective calibration curves. 
     The invention provides in a fourth aspect a system to calibrate measurements of one or more test analytes in a test sample. The system includes means for measuring test-light levels from reactions of test analytes with reagent groups, means for measuring control-light levels from reactions of control analytes with reagent groups, means for forming calibration curves based on detected control-light levels, and means for determining amounts of the test analytes in the test sample from placements of the test-light levels on the calibration curves. 
    
    
     
       DRAWINGS 
         FIG. 1  is a block diagram of one embodiment of a test strip. 
         FIG. 2  is a block diagram of one embodiment of a system to calibrate measurements of one or more test analytes from a test sample. 
         FIGS. 3A and 3B  are side cross-sectional views of one embodiment of the control channel during a calibration process before and after a bonding event, respectively. 
         FIGS. 4A and 4B  are side cross-sectional views of one embodiment of a test-sample channel during a calibration process before and after a bonding event, respectively. 
         FIG. 5  is a block diagram of one embodiment of a system to calibrate measurements of one or more test analytes from a test sample. 
         FIG. 6  is a block diagram of one embodiment of a photodetector array. 
         FIG. 7  is a block diagram of one embodiment of a test strip. 
         FIG. 8  is a flow diagram of one embodiment of a method to determine a presence of a reactive test analyte in a test sample. 
         FIG. 9  is a block diagram of one embodiment of a test strip. 
         FIG. 10  is a flow diagram of one embodiment of a method to determine an amount of a reactive test analyte in a test sample. 
         FIG. 11 a    cross-sectional side view of one embodiment of a system to calibrate measurements of one or more test analytes from a test sample. 
         FIGS. 12A-12C  are cross-sectional front views of one embodiment of a system to calibrate measurements of one or more test analytes from a test sample at different times during a calibration process. 
     
    
    
     In accordance with common practice, the various described features are not drawn to scale but are drawn to emphasize features relevant to the present invention. Reference characters denote like elements throughout figures and text. 
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration specific illustrative embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized and that logical, mechanical and electrical changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense. 
       FIG. 1  is a block diagram of one embodiment of a test strip  32 . The test strip  32  is used to calibrate measurements of one or more test analytes in a test sample  40 . The test strip  32  is used in conjunction with a calibration system  10  or  11  as described below with reference to  FIGS. 2 and 5 . The test sample  40  is delivered from a well  55  of the sample tray  27  to a first channel  70  of the test strip  32 . The test sample  40  includes a test analyte shown as a triangle and represented generally by  47 . The test analyte  47  is also referred to here as “first test analyte  47 .” In one implementation of this embodiment, the test sample  40  is introduced to the first channel  70  through a hole in the test strip  32  that is located over the test-sample channel  70 . In an implementation of this case, the test sample  40  is pipetted into the hole. 
     The test strip  32  comprises three channels: the first channel  70 , a second channel  72 , and a third channel  74 . Each of the first channel  70 , the second channel  72 , and the third channel  74  comprise reagent portions  100  and reagent portions  110 . The reagent portion  100  includes one type of reagent group and the reagent portion  110  includes another type of reagent group. The terms “reagent group” and “reagent” are used interchangeable throughout this document. As shown in  FIG. 1 , the row  105  is a row of reagent portions  100  and the row  106  is a row of reagent portions  110 . 
     A test analyte  47  is reactive to a reagent if the test analyte  47  and the reagent attach or bond to each other when they contact each other. Such a bonding between the test analyte  47  and the reagent is referred to here as a bonding event. The contact required to initiate a bonding event occurs when the test analyte  47  flows through the first channel  70  past or through the reagent portion  100  and/or reagent portion  110 . If the test analyte  47  and the reagent group attach or bond to each other, the test analyte  47  is a reactive test analyte  47  to the respective reagent group. 
     In the embodiment of test strip  32 , the second channel  72  includes a blank portion  300 . The blank portion  300  does not include any reagent groups and is positioned between the reagent portion  100  and the reagent portion  110  within the second channel  72 . 
       FIG. 2  is a block diagram of a system  10  to calibrate measurements of one or more test analytes  47  ( FIG. 1 ) from a test sample  40 . The description of  FIG. 2  is based on the test strip  32  described with reference to  FIG. 1  although the description is relevant to other implementations of test strips. The system  10  comprises a photodetector array  200 , a processor  220 , a memory  230 , at least one light source  250 . The system  10  operates on the test strip  32 , which receives samples from the sample tray  27 . The system  10  also includes software  225 , which is executed by the processor  220  to perform the operations described in this document. The software  225  is stored or otherwise embodied in or on a storage medium  226 . In one implementation of this embodiment, the system  10  includes a test strip such as test strip  32 . In another implementation of this embodiment, the system  10  includes a test strip and a sample tray, such as the test strip  32  and the sample tray  27 . 
     As shown in  FIG. 1 , the first channel  70 , also referred to here as “test-sample channel  70 ,” receives the test sample  40 . The test sample  40  includes either an unknown amount of at least one test analyte  47  or an undetectable amount of the test analyte  47 , which is shown flowing in the first channel  70  over the reagent portions  110  and  100 . If an undetectable amount of test analyte  47  is in the test sample  40 , photodetectors in the calibration system do not sense any illumination from a reagent portion  100  in the test-sample channel  70  responsive to a bonding of the test analyte  47  and the reagent group in the reagent portion  100  during the calibration process. The calibration process is described below with reference to method  1000  of  FIG. 10 . 
     A photodetector in a photodetector array or a group of pixels in a photodetector array are both referred to here as a photodetector element. In one implementation of this embodiment, the calibration system does not sense any illumination generated responsive to a bonding event at a from a reagent portion  100  in the test-sample channel  70 , since the generated illumination from the bonding event is at or below the noise floor of the photodetector element. In another implementation of this embodiment, the photodetector element in the calibration system does not sense any illumination from a reagent portion  100  in the test-sample channel  70  because there is no test analyte in the test sample  40  and therefore no bonding event occurred. 
     The second channel  72 , also referred to here as a “first control channel  72 ,” receives a first control sample  42  that is delivered from a well  56  of the sample tray  27 . The first control sample  42  comprises control analytes, which are shown in the second channel  72  flowing over the reagent portions  110  and  100  and over the blank portion  300 . The control analyte, shown as an “X” and represented generally by  45 , is a known amount of a test analyte  45  reactive to reagents in the respective reagent portion  100 . The control analyte  45  is also known as “first control analyte  45 ” and the known amount of the reactive test analyte  45  is a first known amount of the reactive test analyte  45 . The control analyte  47 , which is shown as triangles in  FIG. 1 , is a known amount of the test analyte  47  reactive to reagents in the reagent portion  110 . The control analyte  47  is also known as “second control analyte  47 ” and the known amount of the reactive test analyte  47  is a first known amount of the reactive test analyte  47 . Bonding events occur for the first control analyte  45  and the reagents in reagent portion  100  in the first control channel  72 . Bonding events occur for the second control analyte  47  and the reagents in reagent portion  110  in the first control channel  72 . 
     The third channel  74 , also referred to here as “second control channel  74 ,” receives a second control sample  44  that is delivered from a well  57  of the sample tray  27 , which is shown in the second control channel  74  flowing over the reagent portions  110  and  100 . The second control sample  44  also comprises the first control analyte  45  and the second control analyte  47 . The second control sample  44  has a second known amount of the first test analyte  47  and a second known amount of the second test analyte  45 . The second known amount is different from the first known amount. Bonding events occur for the first control analyte  45  and the reagents in reagent portion  100  in the second control channel  74 . Bonding events occur for the second control analyte  47  and the reagents in reagent portion  110  in the second control channel  74 . 
     In one implementation of this embodiment, more than two control analytes are included in the first control sample  42  and the second control sample  44 . In another implementation of this embodiment, only one control analyte of the first known amount is included in the first control sample  42  and only one control analyte of the second known amount is in the second control sample  44 . 
     In yet another implementation of this embodiment, the test strip includes more than two control channels. In yet another implementation of this embodiment, the test strip includes only one control channel. In yet another implementation of this embodiment, the test strip includes a blank channel having no reagent groups. In yet another implementation of this embodiment, the test strip includes more than one channel with a blank portion  300 . Other implementations of embodiments of test strips are described below with reference to  FIGS. 7 and 9 . 
     In yet another implementation of this embodiment, there is more than one reagent portion  100  in the first channel  70 , the second channel  72 , and the third channel  74 . In yet another implementation of this embodiment, there is more than one reagent portion  100  and more than one reagent portion  110  in the first channel  70 , the second channel  72 , and the third channel  74 . 
     The test sample  40  can be a patient sample, a forensic sample, a biological sample or a chemical sample. The test sample  40 , the first control sample  42  and the second control sample  44  are fluid samples having a viscosity to permit wicking in the respective test-sample channel  70 , first control channel  72  and third control channel  74 . In one implementation of this embodiment, the control samples  42  and  44  include a base fluid to which the known amounts of one or more control analytes are added. 
     The test sample  40  is wicked into the test-sample channel  70  by capillary action. The first control sample  42  and the second control sample  44  are wicked into the first control channel  72  and the second control channel  74 , respectively, by capillary action. The first channel  70 , the second channel  72  and the third channel  74  can be gel channels, capillary channels, glass channels, paper channels, wettable-fiber channels. One or more of the first channel  70 , the second channel  72  and the third channel  74  can be a different type of channel than the other channels. In one implementation of this embodiment, the reagent portion  100  and the reagent portion  110  are inside the capillary channels. In another implementation of this embodiment, the reagent portion  100  and the reagent portion  110  are embedded in the material that forms the capillary channels. In yet another implementation of this embodiment, the reagent portion  100  and the reagent portion  110  overlay the material that forms the capillary channels so that the sample material touches the reagent portions  100  and the reagent portions  110  when the sample is wicked through the channels. 
     As shown in  FIG. 1 , the test sample  40  and the control samples  42  and  44  are delivered to the test strip  32  by a sample tray  27 . Other methods of delivery of the test sample  40  and the control samples  42  and  44  can be used to allow the test sample  40  and the control samples  42  and  44  to wick into the respective channels. In one implementation of this embodiment, the wells  55 ,  56  and  57  are not on a single tray or substrate. In another implementation of this embodiment, hypodermic needles deliver the test sample  40  and the control samples  42  and  44  to the respective first channel  70 , the second channel  72  and the third channel  74 . 
     The light source  250  illuminates the test strip  32  with light  260 . A portion of the light  260  that is incident on the test strip  32  is reflected as light  262 . A portion of the light  260  that is incident on the test strip  32  is transmitted through the test strip  32  as light  261 . A portion of the light  260  interacts with the reagent portion  100 . The processor  220  is communicatively coupled to the photodetector array  200  and the memory  230 . In one implementation of this embodiment, the memory  230  is integral to the photodetector array  200 . The system  10  calibrates measurements of one or more test analytes  47  in a test sample  40  while the photodetector array  200 , the light source  250  and the test strip  32 , have relative positions in pre-selected locations. The relative positions include specific distances between the photodetector array  200 , the light source  250  and the test strip  32 . The relative positions also include specific angles between the surfaces of the photodetector array  200 , the light source  250  and the test strip  32 . 
     In one implementation of this embodiment, a portion of the light  260  incident on the test strip  32  is transmitted through the test strip  32  as light  261  and none of the light  260  is reflected from the test strip  32 . In another implementation of this embodiment, a portion of the light  260  is reflected as light  262  and none of the light  260  is transmitted through the test strip  32 . In yet another implementation of this embodiment, at least a portion of the light  260  is absorbed by the test strip  32 . 
     If a bonding event has occurred at one or more of the reagent portions  100  and  110  on the test strip  32 , the light  260  stimulates the emission of a reaction light having a reaction light level from the reagent portion  100  and  110  in which the bonding event occurred. In one implementation of this embodiment, if a bonding event has occurred at one or more of the reagent portions  100  and  110  on the test strip  32 , the light  260  is reflected as reaction light having a reaction light level from the reagent portion  100  and  110  in which the bonding event occurred. The bonding events and the generation of reaction light in the test strip  32  is described now with reference to  FIGS. 3A, 3B, 4A and 4B . 
       FIGS. 3A and 3B  are side cross-sectional views of one embodiment of the control channel  72  during a calibration process before and after a bonding event, respectively. The plane upon which the cross-section views of  FIGS. 3A and 3B  are taken is indicated by section line  3 - 3  in  FIG. 1 . The reagent group represented generally by  80  in the reagent portion  100  is attached to a surface  35  of the test strip  32  in first control channel  72 . The reagent group  80  is also referred to here as “first reagent group  80 .” The reagent group represented generally by  82  in the reagent portion  110  is attached to the surface  35  of the test strip  32  in first control channel  72 . The reagent group  82  is also referred to here as “second reagent group  82 .” The reagent portion  100  is spatially separated from the reagent portion  110  by the blank portion  300 . There is no reagent group attached to the surface  35  of the test strip in the blank portion  300 . As shown in  FIG. 3A , light represented generally by  260  is incident on the surface  35  of the test strip  32  before a bonding event and no reaction light is emitted from the reagent portion  100  or the reagent portion  110 . Any light  260  reflected from the surface  35  is not shown. 
     As shown in  FIG. 3B , light  260  is incident on the surface  35  of the test strip  32  after a bonding event so reaction light represented generally by  150  is emitted from the reagent portion  100  of the first control channel  72  and reaction light represented generally by  155  is emitted from the reagent portion  110  of the first control channel  72 . The control analyte represented generally by  45 , which is a first known amount of a test analyte  45  that may or may not be in the test sample  40 , is bonded to the first reagent group  80 . 
     When subjected to the light  260 , the control analyte  45  bonded to the reagent group  80  is stimulated to emit reaction light  150 . In one implementation of this embodiment, light  260  is reflected from the control analyte  45  bonded to the reagent group  80 . A photodetector element of the photodetector array  200  detects the reaction light  150  and the processor  220  that is communicatively coupled to the photodetector array  200  determines a first reaction light level correlated to the reaction light  150  detected from the reagent portion  100  in the first control channel  72 . 
     Based on the location of the photodetector element of the photodetector array  200  that detects the reaction light  150 , the processor  220  is able to determine that the reaction light  150  originated at the reagent portion  100  in the first control channel  72 . The determination is made because the system  10  calibrates measurements of one or more test analytes  47  in a test sample  40  when the photodetector array  200 , the light source  250  and the test strip  32  have relative positions in pre-selected locations. Based on the pre-selected relative positions and the angle subtended by the emitted light, the light emitted from known locations on the test strip  32  is correlated to known locations on the photodetector array  220 . These correlated positions are stored in the memory  230 , which is communicatively coupled to the processor  220 . The processor  220  retrieves the information as needed from memory  230  to determine that the reaction light  150  originated at the reagent portion  100  in the first control channel  72 . 
     Likewise, when subjected to the light  260 , the control analyte  47  bonded to the reagent group  82  is stimulated to emit reaction light  155 . In one implementation of this embodiment, light  260  is reflected from the control analyte  47  bonded to the reagent group  82 . A photodetector element of the photodetector array  200  detects the reaction light  155  and the processor  220  determines a first reaction light level correlated to the reaction light  155  detected from the reagent portion  110  in the second control channel  74 . 
     Based on the location of the photodetector element of the photodetector array  200  that detects the reaction light  155 , the processor  220  is able to determine that reaction light  155  originated at the reagent portion  110  in the first control channel  72  using the correlated positions stored in the memory  230 . 
     When subjected to the light  260 , the blank portion  300  reflects a portion of the light  260  as reference light represented generally by  180  into the photodetector array  200 . Reference light  180  also includes ambient light (not shown) that reflects from the surface  35 . There can be other sources of reference light  180 . The photodetector array  200  detects the reference light  180  and the processor  220  determines a reference-light level correlated to the reference light  180  detected from the blank portion  300  in the first control channel  72 . Based on the location of the photodetector element of the photodetector array  200  that detects the light, the processor  220  is able to determine by that the reference light  180  originated at the blank portion  300  in the first control channel  72  using the correlated positions stored in the memory  230 . 
       FIGS. 4A and 4B  are side cross-sectional views of one embodiment of a test-sample channel  70  during a calibration process before and after a bonding event, respectively. The plane upon which the cross-section view of  FIGS. 4A and 4B  are taken is indicated by section line  4 - 4  in  FIG. 1 . The reagent group  80  in the reagent portion  100  is attached to the surface  35  of the test strip  32  in the test-sample channel  70 . The reagent group  82  in the reagent portion  110  is attached to a surface  35  of the test strip  32  in the test-sample channel  70 . The reagent portion  110  is spatially separated from the reagent portion  110  by a region in which there is no reagent group attached to the surface  35  of the test strip  32 . In one implementation of this embodiment, the reagent portion  100  is adjacent to the reagent portion  110 . As shown in  FIG. 4A , light  260  is incident on the surface  35  of the test strip  32  before a bonding event so no reaction light is emitted from the reagent portion  100  or the reagent portion  110 . Any light  260  reflected from the surface  35  is not shown. 
     As shown in  FIG. 4B , light  260  is incident on the surface  35  of the test strip  32  after a bonding event, so test light represented generally by  160  is emitted from the reagent portion  110  of the test-sample channel  70 . 
     The test analyte  47 , from the test sample  40  having an unknown amount of a test analyte  45 , is bonded to the reagent group  82 . When subjected to the light  260 , the test analyte  47  bonded to the reagent group  82  is stimulated to emit test light  160 . A photodetector element of the photodetector array  200  detects the test light  160  and the processor  220  determines a test-light level correlated to the test light  160  emitted from the reagent portion  110  in the test-sample channel  70 . The processor  220  is able to determine by the location of the photodetector element of the photodetector array  200  that detects the test light  160 , that the test light  160  originated at the reagent portion  110  in the test-sample channel  70 . 
     However, since the exemplary test sample  40  (as shown in  FIG. 1 ) does not include any test analyte  45 , there is no bonding of test analytes to the reagent portion  100  in the test-sample channel  70 . When test-sample channel  70  is subjected to the light  260 , the reagent group  80  is not stimulated to emit (or reflect) any light. A photodetector element of the photodetector array  200  detects only ambient light but no light due to a bonding event at the reagent portion  100  in the test-sample channel  70 . The processor  220  is able to determine by the location of the photodetector element of the photodetector array  200  that detects the ambient light (or light  260  reflected from the reagent portion  100 ). Based on the determined position, the processor  220  is able to determine that only ambient light (or light  260  reflected from the reagent portion  100 ) originated at the reagent portion  100  in the test-sample channel  70 . 
     The photodetector array  200  detects light correlated to at least two reagent portions  100  and  110  of the test strip  32 . The photodetector array  200  detects a reference light from at least one blank portion  300  of the test strip  32 . 
     The photodetector array  200  is a photodetector, a one-dimensional photodetector array, a two-dimensional photodetector array, a charge-coupled device camera, an array of complimentary metal-oxide-semiconductor image sensors, or combinations thereof. 
       FIG. 5  is a block diagram of one embodiment of a system  11  to calibrate measurements of one or more test analytes  45  from a test sample  40 . The system  10  differs from the system  10  of  FIG. 2 , in that a lens system  210  is included in system  10  and a processor  221  is included in the photodetector array  200 . The system  11  also includes a display  234  and a reader  232  which are used to display calibration curves or display in text format the amount of one or more test analytes  45 . In one implementation of this embodiment, the system  11  includes a test strip such as test strip  32 . In another implementation of this embodiment, the system  11  includes a test strip and a sample tray, such as test strip  32  and the sample tray  27 . In one implementation of this embodiment, all the described functions of processor  220  are performed by the processor  221  in the photodetector array  200 . In another implementation of this embodiment, the described functions of processor  220  are shared by the processor  220  and the processor  221  in the photodetector array  200 . 
     In  FIG. 5 , the test strip  32 , the lens system  210  and the photodetector array  200  are shown in a side cross-sectional view. The side cross-sectional view of the test strip  32  is similar to the side cross-sectional view of  FIG. 3B . In  FIG. 5 , the reagent groups  80  and  82  are not shown. The photodetector array  200  and the operation of system  11  are discussed with reference to  FIG. 5  and  FIG. 6 . 
       FIG. 6  is a block diagram of one embodiment of a photodetector array  200 . The photodetector elements  201 ,  202  and  203  on or at the surface  212  of the photodetector array  200  as shown in the side cross-sectional view of  FIG. 5 . The photodetector elements  201 - 209  of the photodetector array  200  are shown arranged on the surface  212  in a rectangular array. 
     The column  174  of the photodetector array  200  includes photodetector elements  207 ,  208  and  209 . Test light from the reagent portion  100  ( FIG. 2 ) in the test-sample channel  70  is focused by the lens system  210  onto the photodetector element  207 . Test light from the reagent portion  110  ( FIG. 2 ) in the test-sample channel  70  is focused by the lens system  210  onto the photodetector element  209 . In one implementation of this embodiment, the photodetector element  208  is not in the photodetector array  200 . 
     The column  172  of the photodetector array  200  includes photodetector elements  201 ,  202  and  203 . Reaction light  150  from the reagent portion  100  in the second channel  72  is focused by the lens system  210  onto the photodetector element  201 . Reference light  180  from the blank portion  300  in the second channel  72  is focused by the lens system  210  onto the photodetector element  202 . Reaction light  155  from the reagent portion  100  in the second channel  72  is focused by the lens system  210  onto the photodetector element  203 . As shown in  FIG. 5 , a portion of the light  260  from the light source  250  is transmitted through the test strip  32 . Light  260  incident on the photodetector array  200  is detected at the photodetector element  208  ( FIG. 6 ) and the light intensity is normalized for the intensity of the light transmitted through the blank portion  300  of the test strip  32 . 
     The column  171  of the photodetector array  200  includes photodetector elements  204 ,  205  and  206 . Reaction light represented generally by  170  from the reagent portion  100  ( FIG. 2 ) in the third channel  74  is focused by the lens system  210  onto the photodetector element  204 . Reaction light represented generally by  175  from the reagent portion  110  ( FIG. 2 ) in the third channel  74  is focused by the lens system  210  onto the photodetector element  206 . In one implementation of this embodiment, the photodetector element  205  is not in the photodetector array  200 . 
     These correlated positions, such as the correlation between reagent portion  100  and the photodetector element  201  shown in  FIG. 5 , are stored in the memory  230 , which is communicatively coupled to the processor  220 . The processor  220  retrieves the information as needed from memory  230  to determine that the reaction light  150  originated at the reagent portion  100  in the first control channel  72 . 
     In one implementation of this embodiment, the photodetector elements  201 - 209  are single photodetectors positioned in an array on the surface  212 . In another implementation of this embodiment, the photodetector elements  201 - 209  are each a group of pixels in a photodetector array  220 . In yet another implementation of this embodiment, the photodetector elements  201 - 209  are each a pixel in a photodetector array  220 . 
     In yet another implementation of this embodiment, each sensor element is a complementary metal-oxide-semiconductor (CMOS) sensor element. Each sensor element may alternatively be a charge-coupled device (CCD) sensor element or another suitable type of sensor element that generates an electrical signal in response to incident light. In one implementation of this embodiment, the lens system  210  is an array of diffractive optical elements etched or molded in a plastic substrate. In another implementation of this embodiment, the lens system  210  is an array of lenses positioned in securing framework. There are other ways to form the lens system  210 . The lenses in the lens system  210  are designed based on the specific distances between the photodetector array  200 , the light source  250  and the test strip  32 , the wavelengths of the light being focused and the specific angles between the surfaces of the photodetector array  200 , the light source  250  and the test strip  32 . In another implementation of this embodiment, the lens system  210  is coated with a coating to prevent the transmission of the wavelength or wavelengths of the light  260 . 
       FIG. 7  is a block diagram of one embodiment of a test strip  30 . Test strip  30  is used to calibrate measurements of one analyte in a test sample  40 . The test strip  32  can be used in conjunction with a calibration system  10  or  11  as described above below with reference to  FIGS. 2 and 5 , respectively. The test sample  40  is delivered from a well  55  of the sample tray  25  to a first channel  70  of the test strip  30 . The test sample  40  includes a test analyte as described above with reference to  FIGS. 1 and 2 . 
     The test strip  30  comprises two channels: the first channel  50 , a second channel  52 . Each of the first channel  50  and the second channel  52  comprise a reagent portion  100 . The reagent portion  100  includes one type of reagent group. In the embodiment of test strip  30 , the second channel  52  includes a blank portion  300 . The blank portion  300  does not include any reagent groups. 
       FIG. 8  is a flow diagram of one embodiment of a method  800  to determine a presence of a reactive test analyte  45  in a test sample  40 . The particular embodiment of method  800  shown in  FIG. 8  is described here as being implemented using the test strip  30  in the system  11  described above with reference to  FIG. 5 . Specifically method  800  is implemented using the test-sample channel  70  and one control channel  72 . In one implementation of this embodiment, the software  225  is executed by the processor  220  to perform the operations described with reference to method  800 . In another implementation of this embodiment, the software  225  is executed by the processor  221  in the photodetector array  200  to perform the operations described with reference to method  800 . 
     At block  802 , a test sample  40  including an unknown amount of the test analyte  45  is introduced into the test-sample channel  70 . The test sample  40  is wicked into the test-sample channel  70  from the well  55  of the sample tray  27 . At block  804 , the control sample  42  including at least one control analyte  45  and/or control analyte  47  into the control channel  72 . The control sample  42  is wicked into the control channel  72  from the well  56  of the sample tray  27 . 
     At block  806 , processor  220  measures at least one test-light level responsive to reactions of at least one reagent group  80  and/or reagent group  82  ( FIG. 4B ) and at least one reactive test analyte  47  ( FIG. 4B ) in the test sample  40 . The test light  160  is incident on a photodetector element  209  ( FIG. 6 ) in the photodetector array  200 . The photodetector element  209  generates a signal responsive to the incident test light  160 . The signal is input to processor  220 . The processor  220  generates a test-light level that is correlated to the signal received from the photodetector element  209 . In this manner the processor  220  measures a test-light level responsive to reactions of at least one reagent group  82  ( FIG. 4B ) and at least one reactive test analyte  47  ( FIG. 4B ) in the test sample  40 . 
     At block  808 , processor  220  measures at least one control-light level responsive to reactions of at least one reagent group  80  and/or reagent group  82  ( FIG. 4B ) and at least one control analyte  47  and/or  47  ( FIG. 3B ) in the control sample  42 . Each control analyte is a known amount of at least one reactive test analyte as described above with reference to  FIGS. 2, 3A, 3B, 4A and 4B . 
     The reaction light  150  is incident on the photodetector element  201  ( FIG. 5 ) in the photodetector array  200 . The photodetector element  201  generates a signal responsive to the reaction light  150 . The signal is input to processor  220 . The processor  220  generates a control-light level that is correlated to the signal received from the photodetector element  201 . In one implementation of this embodiment, the reference-light level is measured by the processor  220  in a manner similar to the manner in which the control-light level is measured. 
     At block  810 , the processor  220  determines a presence of the reactive test analyte  47  in the test sample  40  based on the measured test-light levels and control-light levels. If the test-light level is below the control-light level, then the amount of the test analyte is less than the amount of test analyte in the control sample. If the test-light level is above the control-light level, then the amount of the test analyte is greater than the amount of test analyte in the control sample. If the test-light level is above the reference-light level, then the test analyte is present in the test sample. Likewise, if the test-light level is at or below the reference-light level, then the test analyte is not present in the test sample. 
     The wavelength of the lights  260 ,  150 ,  155 ,  180 ,  160 ,  170  and  175  described here are dependent upon the reagent groups and the analytes. For all the implementations described herein, the wavelength of the light  260  is suited to cause an attached reagent group and the reactive test analyte to emit light of a known wavelength. In one implementation of this embodiment, the light source  250  emits light  260  having more than one wavelength from different spectral regions. In another implementation of this embodiment, the light source  250  emits light  260  having wavelengths over a continuous range of wavelengths. 
     The photodetector elements  201 - 209  are suited to detect the wavelengths of the emitted test light  160  and control light  150 ,  155 ,  170  and  175  and reference light  180 . In one implementation of this embodiment, the photodetector elements  201 - 209  detect different ranges of wavelengths. The systems  10  and  11  are designed for various test analytes reacting with specific reagents that emit light or reflect light of a known wavelength based on the wavelength of the light  260  emitted from the light source  250 . 
       FIG. 9  is a block diagram of one embodiment of a test strip  31 . The test strip  31  is used to calibrate measurements of one or more test analytes in a test sample  40 . The test strip  31  is used in conjunction with a calibration system  10  or  11  as described below with reference to  FIGS. 2 and 5 , respectively. 
     The test strip  31  comprises four channels: the first channel  60 , a second channel  62 , a third channel  64  and a fourth channel  66 . Each of the first channel  60 , the second channel  62 , and the third channel  64  comprise reagent portions  100  and reagent portions  110 . The fourth channel  66  does not include any reagent portions and as such is equivalent to the blank portion  300  in the test strip  32 . 
     The first channel  60 , also referred to here as “test-sample channel  60 ,” receives the test sample  40  as described above with reference to  FIG. 1 . The second channel  62 , also referred to here as a “first control channel  62 ,” receives a first control sample  42  that is delivered from a well  56  of the sample tray  26 . The third channel  64 , also referred to here as “second control channel  64 ,” receives a second control sample  44  that is delivered from a well  57  of the sample tray  26 . The fourth channel  66 , also referred to here as “blank channel  66 ,” receives the second control sample  44  that is delivered from a well  58  of the sample tray  26 . 
       FIG. 10  is a flow diagram of one embodiment of a method  1000  to determine an amount of a reactive test analyte  45  in a test sample  40 . The particular embodiment of method  1000  shown in  FIG. 10  is described here as being implemented using either system  10  or  11  described above with reference to  FIGS. 2 and 5 , respectively, operating on the test strip  31  described above with reference to  FIG. 9 . The exemplary test strip  31  is similar to the exemplary test strip  32  in that the reagent portions  100  and  110  react to control analytes  45  and  47 , respectively. The blank portion  300  of test strip  32  is equivalent to the blank channel  66  of test strip  31 . 
     Method  1000  is implemented for a system having at least two control channels. The software  225  is executed by the processor  220  to perform the operations described with reference to method  1000 . 
     Method  1000  is implemented with portions of method  800 . Method  1000  begins after block  802  of method  800  is implemented for the test strip  31 , so that the test sample  40  including an unknown amount of the test analyte  45  has been introduced into the test-sample channel  60  from the well  55  of the sample tray  26  prior to step  1002 . In one implementation of this embodiment, the process at blocks  802  and  1002  occur at the same time. 
     At block  1002 , the first control sample  42  including the first known amount of control analyte  47  is introduced into the first control channel  62 . In one implementation of this embodiment, the first control sample  42  also includes a first known amount of control analyte  45  so both the control analyte  45  and  47  are introduced into the first control channel  62 . 
     At block  1004 , the second control sample  44  including the second control analyte  47  having a second known amount of the first test analyte  47  is introduced into the second control channel  64 . In one implementation of this embodiment, the second control sample  44  also includes a second known amount of control analyte  45  so both the control analyte  45  and  47  are introduced into the second control channel  64 . 
     At block  1006 , the second control sample  44  including the second control analyte  47  having a second known amount of the first test analyte  47  is introduced into the blank channel  66 . In one implementation of this embodiment, the first control sample  42  including the first control analyte  47  having a first known amount of the first test analyte  47  is introduced into the blank channel  66 . 
     Before block  1008  is implemented, blocks  806  and  808  in the method  800  of  FIG. 8  are implemented and the processor  220  determines reaction light levels correlated to the light detected from each of the reagent portions  100  and  110 . The processor  220  also determines the reference-light levels correlated to the blank channel  66  (or blank portion  300  of test strip  32 ). 
     The processor  220  measures at least one first control-light level responsive to reactions of at least one first reagent group  80  and/or second reagent group  82  ( FIG. 4B ) and at least one control analyte  45  and/or  47  ( FIG. 3B ) in the control sample  42  after it flows through the first control channel  62 . As described above, the first control light is emitted from the test strip  31  after light  260  is incident on the test strip  31  and the processor  220  determines a first reaction light level for the first control light. 
     The processor  220  also measures at least one second control-light level responsive to reactions of at least one first reagent group  80  and/or second reagent group  82  and at least one control analyte  45  and/or  47  in the control sample  44  after it flows through the second control channel  64 . As described above, the second control light is emitted from the test strip  31  after light  260  is incident on the test strip  31  and the processor  220  determines the second reaction light level for the second control light. 
     The processor  220  also measures at least one test-light level responsive to reactions of at least one reagent group  80  and/or reagent group  82  and at least one reactive test analyte  45  and/or  47  in the test sample  40 . As described above, the test light is emitted from the test strip  31  after light  260  is incident on the test strip  31  and the processor  220  determines a third reaction light level (also referred to here as test-light level) for the test light. 
     The processor  220  also determines at least one reference-light level responsive to at least one control analyte  45  and/or  47  in the control sample  44  flowing through the blank channel  66 . The control sample  44  may have absorptive or reflective qualities that modify the control light emitted (or reflected) from the test strip  31 . The reference light from the blank channel  66  (or from the blank portion  300 ) is dependent upon such absorptive or reflective qualities of the control sample. The reference light from the blank channel  66  is independent upon the qualities of the reaction between any analytes and reagents. 
     In one implementation of this embodiment, the processor  220  adjusts each reaction light level by the reference-light level. The processor  220  subtracts the reference-light level from the reaction light levels for each reagent group to form adjusted reaction light levels. The processor  220  subtracts the reference-light level from the test-light levels to form adjusted test-light levels. The processor  220  subtracts the reference-light level from the control-light levels to form adjusted control-light levels. 
     At block  1008 , the processor  220  forms calibration curves for each of the reagent groups based on the control-light levels from spatially separate reactions of each of the reagent groups and at least two control analytes having two known amounts of the test analyte. 
     The processor  220  uses the adjusted control-light level for the reagent portion  100  in the first control channel  62  and the first known level of the control analyte  45  as the first point of the calibration curve for the test analyte  45 . The processor  220  uses the adjusted control-light level for the reagent portion  100  in the second control channel  64  and the second known level of the control analyte  45  as the second point of the calibration curve for the test analyte  45 . 
     The processor  220  uses the adjusted control-light level for the reagent portion  110  in the first control channel  62  and the first known level of the control analyte  47  as the first point of the calibration curve for the test analyte  47 . The processor  220  uses the adjusted control-light level for the reagent portion  110  in the second control channel  64  and the second known level of the control analyte  47  as the second point of the calibration curve for the test analyte  47 . 
     In an embodiment in which the test strip does not include a blank portion or a blank channel, the processor  220  operates on the unadjusted light levels. In such a case, the processor  220  uses the control-light level for the reagent portion  100  in the first control channel  62  and the first known level of the control analyte  45  as the first point of the calibration curve for the test analyte  45 . The processor  220  uses the control-light level for the reagent portion  100  in the second control channel  64  and the second known level of the control analyte  45  as the second point of the calibration curve for the test analyte  45 . 
     The processor  220  uses the control-light level for the reagent portion  110  in the first control channel  62  and the first known level of the control analyte  47  as the first point of the calibration curve for the test analyte  47 . The processor  220  uses the control-light level for the reagent portion  110  in the second control channel  64  and the second known level of the control analyte  47  as the second point of the calibration curve for the test analyte  47 . 
     In one implementation of this embodiment, there are more than two points for every calibration curve. In this case, there is an additional control channel in the test strip for each additional point on the calibration curve. 
     In another implementation of this embodiment, there are more than two calibration curves. For each additional calibration curve there is an additional reagent portion for a different reagent group in the test-sample channel and in each of the control channels. 
     At block  1010 , the processor  220  determines an amount of the test analytes  47  in the test sample  40  from a placement of the test-light level for each test analyte  47  on the respective calibration curve for the control analytes  47 . 
     The processor  200  determines if test light is detected for a test analyte  47 , determines the test-light level for the detected test light and adjusts the test-light level by the reference-light level. Then the processor  200  determines where the adjusted light level is situated in the calibration curve for the test analyte. 
     Consider an exemplary case in which the test analyte  45  is reactive with the reagent group in the reagent portion  100  and the adjusted test-light level from the reagent portion  100  in the test-sample channel  60  is midway between two adjusted control-light levels in the calibration curve for the test analyte  45 . In this case, the adjusted test-light level from the reagent portion  100  in the test-sample channel  60  is equal to (CLL2−CLL1)/2+CLL1, where CLL1 is the adjusted lower control-light level from the reagent portion  100  and CLL2 is the adjusted higher control-light level from the reagent portion  100 . Then the amount of the test analyte  45  equals (KA2−KA1)/2+KA1, where KA1 is the first known amount of test analyte  45  in the first control channel  62  and KA2 is the second higher known amount of test analyte  45  in the second control channel  64 . 
     To extend the exemplary case, the test analyte  47  is reactive with the reagent group in the reagent portion  110 . The adjusted test-light level from the reagent portion  110  in the test-sample channel  60  is between the two adjusted control-light levels in the calibration curve for the test analyte  47 . The two adjusted control-light levels have a difference ΔCLL. The adjusted test-light level from the reagent portion  110  has a value that is a quarter of the difference ΔCLL above the lower adjusted control-light level. In this case, the adjusted test-light level from the reagent portion  110  in the test-sample channel  60  is equal to (CLL4−CLL3)/4+CLL3, where CLL3 is the adjusted lower control-light level for the light from the reagent portion  110 , CLL4 is the adjusted higher control-light level from the reagent portion  110  and ΔCLL=CLL4−CLL3. Then the amount of the test analyte  47  equals (KA4−KA3)/2+KA3, where KA3 is the first known amount of test analyte  47  in the first control channel  62  and KA4 is the higher second known amount of test analyte  47  in the second control channel  64 . 
     In this manner, the processor  220  determines reaction light levels correlated to the light detected from each of the reagent portions, determines a reference-light level correlated to the blank portion  300  or blank channel  66 , forms calibration curves for respective reagent groups based on respective first reaction light levels and respective second reaction light levels and determines an amount of one or more test analytes  47  in the test sample  40  based on placements of third reaction light levels on respective calibration curves. 
     In one implementation of this embodiment, the processor  220  adjusts each reaction light level by the reference-light level, forms calibration curves for respective reagent groups based on respective first adjusted reaction light levels and respective second adjusted reaction light levels and determines an amount of one or more test analytes in the test sample based on placements of third adjusted reaction light levels on respective calibration curves. 
       FIG. 11 a    cross-sectional side view of one embodiment of a system  9  to calibrate measurements of one or more test analytes from a test sample.  FIGS. 12A-12C  are cross-sectional front views of one embodiment of the system  9  to calibrate measurements of one or more test analytes from a test sample at different times during a calibration process. In this implementation of system  9 , the test strip  32  is scanned through the system  9  after being exposed to the test sample  40 , control sample  42  and control sample  44 . 
     As shown in  FIG. 11 , the test strip  32  moves through the reader system  400  in the direction of the arrow  5 . The reader system  400  includes the light source  250 , a 3×1 linear array of lenses  211 , a one-dimensional photodetector array  310 , processor  220 , memory  230  and display  234 . The one-dimensional photodetector array  310  comprises photodetector elements  306 ,  301  and  304  positioned in a 3×1 linear array. 
     The light  260  from the light source  250  shines on a single row  105  or  106  of the reagent portions  100  or  110 , respectively, ( FIG. 1 ) of the test strip  32 . At the moment of scanning shown in  FIG. 12A , the light  260  is incident on the reagent portions  100  in the row  105  of the test strip  32  ( FIG. 1 ). Reaction light  150  emitted from the reagent portion  100  of the first control channel  72  ( FIG. 2 ) is focused by the linear array of lenses  211  onto the photodetector element  301  while reaction light  170  from the reagent portion  100  in the second control channel  74  ( FIG. 2 ) is focused by the lens system  210  onto the photodetector element  304 . The processor  220  is communicatively coupled to the one-dimensional photodetector array  310  and operates as described above to form a calibration curve  410  and to determine a presence and/or amount of a test analyte in the test sample  40 . The calibration curve  410  is shown in the display  234  as a function of intensity (INT) and amount of test analyte. Exemplary text “0 TEST ANALYTE” indicates that there was no test analyte  45  ( FIG. 4B ) in the test sample  40 . 
     The test strip  32  moves further through the reader system  400  so that, as shown in  FIG. 12B , the light  260  is incident on the blank portion  300  in the test strip  32  ( FIG. 1 ). The blank portion  300  transmits a portion of the light  260  as reference light  180  into the photodetector array  200 . The reference light  180  and the processor  220  is focused by the linear array of lenses  211  onto the photodetector element  301  The processor  220  operates as described above to determine a reference-light level correlated to the reference light  180  detected from the blank portion  300  in the first control channel  72 . The reference-light level is shown in the display  234  as a circle. 
     The test strip  32  moves further through the reader system  400  so that, as shown in  FIG. 12C , the light  260  is incident on the reagent portions  110  in the row  106  of the test strip  32  ( FIG. 1 ). As described above with reference to  FIG. 2 , reaction light  160  emitted from the reagent portion  110  of the test-sample channel  70 . Reaction light  160  is focused by the linear array of lenses  211  onto the photodetector element  306 . Reaction light  155  is emitted from the reagent portion  110  of the first control channel  72  and is focused by the linear array of lenses  211  onto the photodetector element  301 . Reaction light  175  is emitted from the reagent portion  110  ( FIG. 2 ) in the second control channel  74  is focused by the linear array of lenses  211  onto the photodetector element  304 . The processor  220  is communicatively coupled to the one-dimensional photodetector array  310  and operates as described above to form a calibration curve  412  and to determine a presence and/or amount of a test analyte in the test sample  40 . The calibration curve  412  is shown in the display  234 . The test-light level is indicated as an asterisk (*) on the calibration curve  412  and the text “Z TEST ANALYTE” indicates that there was test analyte  47  in an amount “Z” in the test sample  40 . 
     Other methods of scanning a test strip  32  across a one-dimensional photodetector array  310  are possible. In one implementation of this embodiment, the test strip  32  is manually scanned across a one-dimensional photodetector array  310 . In another implementation of this embodiment, the test strip  32  is inserted into a slot in a reader system and is ejected from the same slot after all the reagent portions  100  and blank portions  300  of the test strip have been scanned by the light  260  and the reaction light was subsequently detected at the one-dimensional photodetector array  310  for each row  105  and  106  of reagent portions  100  and  110 , respectively. 
     The methods and techniques described here may be implemented in digital electronic circuitry, or with a programmable processor (for example, a special-purpose processor or a general-purpose processor such as a computer) firmware, software, or in combinations of them. Apparatus embodying these techniques may include appropriate input and output devices, a programmable processor, and a storage medium tangibly embodying program instructions for execution by the programmable processor. A process embodying these techniques may be performed by a programmable processor executing a program of instructions to perform desired functions by operating on input data and generating appropriate output. The techniques may advantageously be implemented in one or more programs that are executable on a programmable system including at least one programmable processor coupled to receive data and instructions from, and to transmit data and instructions to, a data storage system, at least one input device, and at least one output device. Generally, a processor will receive instructions and data from a read-only memory and/or a random access memory. 
     Storage devices suitable for tangibly embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, such as EPROM, EEPROM, and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; and DVD disks. Any of the foregoing may be supplemented by, or incorporated in, specially-designed application-specific integrated circuits (ASICs). 
     A number of embodiments of the invention defined by the following claims have been described. Nevertheless, it will be understood that various modifications to the described embodiments may be made without departing from the spirit and scope of the claimed invention. Accordingly, other embodiments are within the scope of the following claims.