Patent Publication Number: US-2007122914-A1

Title: Obtaining measurements of light transmitted through an assay test strip

Description:
BACKGROUND  
      Assay test kits currently are available for testing a wide variety of medical and environmental conditions or compounds, such as a hormone, a metabolite, a toxin, or a pathogen-derived antigen.  FIG. 1  shows a typical lateral flow test strip  10  that includes a sample receiving zone  12 , a labeling zone  14 , a detection zone  15 , and an absorbent zone  20  on a common substrate  22 . These zones  12 - 20  typically are made of a material (e.g., chemically-treated nitrocellulose) that allows fluid to flow from the sample receiving zone  12  to the absorbent zone  22  by capillary action. The detection zone  15  includes a test region  16  for detecting the presence of a target analyte in a fluid sample and a control region  18  for indicating the completion of an assay test.  
       FIGS. 2A and 2B  show an assay performed by an exemplary implementation of the test strip  10 . A fluid sample  24  (e.g., blood, urine, or saliva) is applied to the sample receiving zone  12 . In the example shown in  FIGS. 2A and 2B , the fluid sample  24  includes a target analyte  26  (i.e., a molecule or compound that can be assayed by the test strip  10 ). Capillary action draws the liquid sample  24  downstream into the labeling zone  14 , which contains a substance  28  for indirect labeling of the target analyte  26 . In the illustrated example, the labeling substance  28  consists of an immunoglobulin  30  with a detectable particle  32  (e.g., a reflective colloidal gold or silver particle). The immunoglobulin  30  specifically binds the target analyte  26  to form a labeled target analyte complex. In some other implementations, the labeling substance  28  is a non-immunoglobulin labeled compound that specifically binds the target analyte  26  to form a labeled target analyte complex.  
      The labeled target analyte complexes, along with excess quantities of the labeling substance, are carried along the lateral flow path into the test region  16 , which contains immobilized compounds  34  that are capable of specifically binding the target analyte  26 . In the illustrated example, the immobilized compounds  34  are immunoglobulins that specifically bind the labeled target analyte complexes and thereby retain the labeled target analyte complexes in the test region  16 . The presence of the labeled analyte in the sample typically is evidenced by a visually detectable coloring of the test region  16  that appears as a result of the accumulation of the labeling substance in the test region  16 .  
      The control region  18  typically is designed to indicate that an assay has been performed to completion. Compounds  35  in the control region  18  bind and retain the labeling substance  28 . The labeling substance  28  typically becomes visible in the control region  18  after a sufficient quantity of the labeling substance  28  has accumulated. When the target analyte  26  is not present in the sample, the test region  16  will not be colored, whereas the control region  18  will be colored to indicate that assay has been performed. The absorbent zone  20  captures excess quantities of the fluid sample  24 .  
      Although visual inspection of lateral flow assay devices of the type described above are able to provide qualitative assay results, such a method of reading these types of devices is unable to provide quantitative assay measurements and therefore is prone to interpretation errors. Automated and semi-automated lateral flow assay readers have been developed in an effort to overcome this deficiency. These readers typically include a light source for illuminating the top side of a test strip on which the test and control regions are exposed, and an optical detector that measures light that reflects or fluoresces from the top surface. In these approaches, a significant source of noise is caused by reflection of the illuminating light from non-target surfaces of the test strip and other surfaces within the readers. The noise caused by such stray reflected light may be reduced by increasing the precision with which the test strip is aligned with the optical detector and by performing complex and resource intensive analyses of the measurement data. In general, however, such noise reduction measures increase the cost and complexity of the assay reader design.  
      What is needed is a diagnostic test system that is capable of obtaining optical measurements from an assay test strip in a way that reduces the susceptibility of the detection system to receive stray reflected light and thereby allows the assay test strips to be evaluated with high accuracy and precision while using relatively inexpensive components and without requiring complex and resource intensive analyses of the measurement data.  
     SUMMARY  
      In one aspect, the invention features a diagnostic test method in accordance with which a test strip is held. The test strip includes a flow path for a fluid sample, a bottom side, and a top side that is opposite the bottom side and that supports a detection zone, which has at least one measurement region coupled to the flow path. The top side of the test strip is illuminated with light. The illuminating light that is transmitted through the test strip and out from the bottom side of the test strip is detected.  
      In another aspect, the invention features a diagnostic test system that includes a detection system and a retainer. The detection system includes an optical detector that produces a measurement signal in response to light. The retainer holds a test strip so that the top side of the test strip is exposed for illumination and the bottom side of the test strip faces the optical detector.  
      Other features and advantages of the invention will become apparent from the following description, including the drawings and the claims. 
    
    
     DESCRIPTION OF DRAWINGS  
       FIG. 1  is a diagrammatic view of a prior art implementation of an assay test strip.  
       FIG. 2A  is a diagrammatic view of a fluid sample being applied to a sample receiving zone of the assay test strip shown in  FIG. 1 .  
       FIG. 2B  is a diagrammatic view of the assay test strip shown in  FIG. 2A  after the fluid sample has flowed across the test strip to an absorption zone.  
       FIG. 3  is a diagrammatic side view of an embodiment of a diagnostic test system that includes a detection system and a retainer that is holding an assay test strip.  
       FIG. 4  is a diagrammatic side view of the diagnostic test system shown in  FIG. 3  in which the detection system is obtaining intensity measurements of light passing through the test strip before an assay has been performed.  
       FIG. 5  is a simulated graph of the transmitted light intensity measured by the detection system with the test strip in the state shown in  FIG. 4  plotted as a function of position along the test strip.  
       FIG. 6  is a diagrammatic side view of the diagnostic test system shown in  FIG. 3  in which the detection system is obtaining intensity measurements of light passing through the test strip after an assay has been performed.  
       FIG. 7  is a simulated graph of the transmitted light intensity measured by the detection system with the test strip in the state shown in  FIG. 6  plotted as a function of position along the test strip.  
       FIG. 8  is a simulated graph of the difference between the light intensity measurements shown in  FIGS. 5 and 7  plotted as a function of position along the test strip.  
       FIG. 9  is a diagrammatic side view of an embodiment of the diagnostic test system shown in  FIG. 3  in which the detection system includes two optical detectors.  
       FIG. 10  is a diagrammatic side view of an embodiment of the diagnostic test system shown in  FIG. 3  that is incorporated within a housing that includes an optically transparent window for illuminating the top side of the test strip with external ambient light.  
       FIG. 11  is a diagrammatic side view of an embodiment of the diagnostic test system shown in  FIG. 3  that is incorporated within a housing that includes a light source that illuminates the top side of the test strip. 
    
    
     DETAILED DESCRIPTION  
      In the following description, like reference numbers are used to identify like elements. Furthermore, the drawings are intended to illustrate major features of exemplary embodiments in a diagrammatic manner. The drawings are not intended to depict every feature of actual embodiments nor relative dimensions of the depicted elements, and are not drawn to scale.  
      I. Introduction  
      The embodiments that are described herein provide systems and methods of obtaining measurements of light transmitted through assay test strips and using these measurements to evaluate assays performed on the assay test strips. The light that is transmitted through the test strips is substantially free of light that is reflected from non-target surfaces of the test strips and other surfaces within the diagnostic test system. For this reason, the alignment constraints between the test strips and the detection system in the embodiments that are described below may be reduced relative to diagnostic test approaches that measure light from the illuminated surfaces of the test strips. The need for complex and resource intensive analyses of the measurement data in order to reduce the noise caused by reflected light also is reduced. These features allow the embodiments that are described herein to evaluate assay test strips with high accuracy and precision while using relatively inexpensive components and without requiring complex and resource intensive analyses of the measurement data.  
      The terms “assay test strip” and “lateral flow assay test strip” encompass both competitive types of assay test strips in which an increase in the concentration of the analyte in the sample results in an increase in the concentration of labels in the test region and non-competitive types of assay test strips in which an increase in the concentration of the analyte in the fluid sample results in a decrease in the concentration of labels in the test region. A lateral flow assay test strip generally includes a sample receiving zone and a detection zone, and may or may not have a labeling zone. In some implementations, a lateral flow assay test strip includes a sample receiving zone that is located vertically above a labeling zone, and additionally includes a detection zone that is located laterally downstream of the labeling zone.  
      The term “analyte” refers to a substance that can be assayed by the test strip. Examples of different types of analytes include organic compounds (e.g., proteins and amino acids), hormones, metabolites, antibodies, pathogen-derived antigens, drugs, toxins, and microorganisms (e.g., bacteria and viruses).  
      As used herein the term “label” refers to a substance that has specific binding affinity for an analyte and a detectable characteristic feature that can be distinguished from other elements of the test strip. The label may include a combination of a labeling substance (e.g., a fluorescent particle, such as a quantum dot) that provides the detectable characteristic feature and a probe substance (e.g., an immunoglobulin) that provides the specific binding affinity for the analyte. In some implementations, the labels have distinctive optical properties, such as luminescence (e.g., fluorescence) or reflective properties, which allow regions of the test strip containing different labels to be distinguished from one another.  
      The term “reagent” refers to a substance that reacts chemically or biologically with a target substance, such as a label or an analyte.  
      The term “capture region” refers to a region on a test strip that includes one or more immobilized reagents.  
      The term “test region” refers to a capture region containing an immobilized reagent with a specific binding affinity for an analyte.  
      The term “control region” refers to a capture region containing an immobilized reagent with a specific binding affinity for a label.  
      The term “measurement region” refers to any region of interest on an assay test strip, such as a capture region or a calibration region, that may be measured for the purpose of evaluating the assay test strip. The term “baseline region” refers to any region of an assay test strip outside of a measurement region.  
      The term “measurement signal” refers to a signal that is produced by an optical detector in response to light received from a measurement region of an assay test strip. The term “baseline signal” refers to a signal that is produced by an optical detector in response to light received from a baseline region of an assay test strip.  
      The phrase “quantifying a first value with respect to a second value” refers to a process of deriving a final quantified value from a function that compares the first and second values or that compares values that are derived respectively from the first and second values. The comparison function may include a ratio between the first and second values, a difference between the first and second values, or some other mathematical function of the first and second values.  
      II. General Diagnostic Test System Architecture  
       FIG. 3  shows an embodiment of a diagnostic test system  40  that includes a detection system  42  and a retainer  44  that holds a test strip  46 . The test strip  46  has a bottom side  48  and a top side  50  that is opposite the bottom side  48  and supports a detection zone  52 , which includes a test region  54  and a control region  56 . The detection system  42  includes an optical detector  58  that has a field of view  60  that corresponds to an area on the bottom side  48  of the test strip  46 . When the test strip  46  is held by the retainer  44 , the optical detector  58  obtains intensity measurements of light that passes from a region above the top side  50  of the test strip  46 , through the test strip  46 , and out the bottom side  48  of the test strip  46 . The light intensity measurements typically are transmitted to a data analyzer (not shown in  FIG. 3 ), which computes at least one parameter from one or more of the light intensity measurements. A results indicator (not shown in  FIG. 3 ) typically provides an indication of one or more of the results of an assay of the test strip  46 . In some implementations, the diagnostic test system  40  is fabricated from relatively inexpensive components enabling it to be used for disposable or single-use applications.  
      In the illustrated embodiments, each of the test strips  46  is a non-competitive type of assay test strip that supports lateral flow of a fluid sample along a lateral flow direction  62 . Each of the test strips  46  includes a labeling zone  64 , a detection zone  52 , and an absorbent zone  65  that are formed on a common substrate  67 . The labeling zone  64  contains a labeling substance that binds a label to a target analyte that may be present in a fluid sample to be assayed. The detection zone  52  includes a membrane  69  that supports at least one test region  54  containing an immobilized substance that binds the target analyte and at least one control region  56  containing an immobilized substance that binds the label. One or more areas of the detection zone  52 , including at least a portion of the test region  54  and the control region  56 , are exposed for illumination from a region above the top side  50  of the test strip  46 . The source of the illumination may be ambient light or an active light source, such as a light emitting diode.  
      The membrane  69  and the substrate  67  are formed of respective materials that are translucent with respect to light within a target wavelength range (e.g., visible light or infrared light) that is detectable by the optical detector  58 . Exemplary materials from which the membrane  69  and the substrate may be formed include nitrocellulose (cellulose nitrate), paper, glass fibers, polypropylene, and cellulose acetate. In some embodiments, the various zones  52 ,  64 , and  65  may be formed on a single translucent sheet of material and the substrate  67  may be omitted. In other embodiments, the substrate  67  may include one or more windows that are aligned vertically (i.e., orthogonally with respect to the top and bottom sides  50 ,  48  of the test strip) with respective measurement and baseline regions of the detection zone  52 .  
      In other embodiments, the test strips  46  are competitive type of lateral flow assay test strips in which the concentration of the label in the test region decreases with increasing concentration of the target analyte in the fluid sample. Some of these embodiments include a labeling zone, whereas others of these implementations do not include a labeling zone.  
      Some of these competitive lateral flow assay test strip embodiments include a labeling zone that contains a label that specifically binds target analytes in the fluid sample, and a test region that contains immobilized target analytes as opposed to immobilized test reagents (e.g., antibodies) that specifically bind any non-bound labels in the fluid sample. In operation, the test region will be labeled when there is no analyte present in the fluid sample. However, if target analytes are present in the fluid sample, the fluid sample analytes saturate the label&#39;s binding sites in the labeling zone, well before the label flows to the test region. Consequently, when the label flows through the test region, there are no binding sites remaining on the label, so the label passes by and the test region remains unlabeled.  
      In other competitive lateral flow assay test strip embodiments, the labeling zone contains only pre-labeled analytes (e.g., gold adhered to analyte) and the test region contains immobilized test reagents with an affinity for the analyte. In these embodiments, if the fluid sample contains unlabeled analyte in a concentration that is large compared to the concentration of the pre-labeled analyte in the labeling zone, then label concentration in the test region will appear proportionately reduced.  
      The detection system  46  includes one or more optoelectronic components for optically inspecting the exposed areas of the detection zone of the test strip  50 . In some implementations, the detection system  46  includes at least one optical detector  58 , which includes a respective optoelectronic transducer  66 . The optoelectronic transducer  66  produces electrical measurement signals in response to receipt of light that is transmitted through the test strip  46 . The optoelectronic transducer  66  may be implemented by any type of photodetector device, including a one-dimensional optical detector (e.g., a photodiode device) and a two-dimensional optical detector (e.g., a CCD or CMOS image sensor device). The optical detector  58  also may include an optical system  68  that guide light from the bottom side  50  of the test strip  46  onto the respective active areas of the optoelectronic transducer  66 . The optical system  68  may include one or more optical elements (e.g., refractive lenses, diffractive lenses, and optical filters) that intercept and modify the light received from respective regions of the bottom side  50  of the test strip  46 .  
      In some implementations, the optical detector  58  may be designed to selectively capture light that is transmitted though the test strip  46 . For example, the optical detector  58  may be designed to selectively capture light corresponding to the light illuminating the top side  50  of the test strip  46 . For example, if the illuminating light is provided by a light source that produces light within a specified wavelength range or that has a specified polarization, the optical detector  58  may be designed to selectively capture light within the specified wavelength range or having the specified polarization. In these embodiments, the optical detector  58  may include one or more optical filters that define the wavelength ranges or polarizations axes of the detected light.  
      The retainer  44  holds the test strip  46  so that the top side  50  is exposed for illumination and the bottom side  48  is faced by the optical detector  58 . In some embodiments, the retainer  44  is configured to move the test strip  46  relative to the detection system  42 . In other embodiments, the detection system  42  is configured to move relative to the test strip  46 . In some embodiments, both the retainer  44  and the detection system  42  move relative to each other. In some embodiments, the movable ones of the retainer  44  and the detection system  42  are moved manually by a user of the diagnostic test system  40 . Other embodiments of the diagnostic test system  40  include at least one motor that moves the movable ones of the retainer  44  and the detection system  42 . These embodiments typically include a position encoder (e.g., an optical encoder) that produces signals that track the relative position of the retainer  44  with respect to the detection system  42 . These embodiments also typically include a data analyzer that is operable to correlate the measurements obtained by the detection system  42  with locations along the test strip  46  based on the signals produced by the position encoder.  
      As shown in  FIG. 3 , the retainer  44  includes a window  70  that allows light that is transmitted through the test strip  46  to reach the optical detector  58  when the test strip  46  is held by the retainer  44 . In some implementations, the window  70  may consist of an opening in the support structure of the retainer  44 , as shown in  FIG. 3 . In other implementations, the window  70  may include a material that is optically transparent to light within a target wavelength range (e.g., visible light or infrared light) that is detectable by the optical detector  58 . In some implementations, the retainer  44  is formed of a material (e.g., glass or quartz) that is optically transparent to light within the target wavelength range.  
      III. Obtaining Measurement Signals for Evaluating Assay Test Strips  
       FIG. 4  shows the diagnostic test system  40  and the test strip  46  in a state before an assay has been performed. In this state, the test region  54  and the control region  56  have not immobilized any of the label from the labeling zone  64 . Consequently, the transmittance (i.e., the ratio of the transmitted optical power to the incident optical power) of light  72  through the thickness of the test strip  46  at the locations of the test and control regions  54 ,  56  will correspond to the transmittance through the test strip  46  at other locations in the detection zone  52 , except for attenuations that might be caused by the presence of the immobilized substances in the test and control regions  54 ,  56  that bind the target analyte and the label, respectively. In typical implementations of the test strip  46 , however, the attenuation of the transmitted light  72  by the immobilized substances is expected to be substantially smaller than the light attenuation that is caused by the presence of the label in the test and control regions  54 ,  56 . In some embodiments, one or more of the properties of the illuminating light  72  and the immobilized substances may be selected so that the attenuation of the light  72  caused by the presence of the immobilized substances the test and control regions  54 ,  56  is substantially smaller than the light attenuation that is caused by the presence of the label in the test and control regions  54 ,  56 .  
       FIG. 5  shows an exemplary simulated graph of the transmitted light intensity measured by the optical detector  58  with the test strip  46  in the state shown in  FIG. 4  plotted as a function of position along the test strip  46 . In this example, the light intensity measured by the optical detector  58  is substantially uniform across the detection zone  52 , except in the positions  74 ,  76  corresponding to the test and control regions  54 ,  56 . At these positions  74 ,  76 , the graph is intended to show the relatively small reductions in the transmitted light intensity that are expected to be caused by the immobilized substances in the test and control regions  54 ,  56  of the detection zone  52 .  
       FIG. 6  shows the diagnostic test system  40  and the test strip  46  in a state after an assay has been performed. In this state, the test region  54  will contain ones of the labeling compounds that are bound to the target analyte in the fluid sample that is the subject of the assay. In addition, the control region  56  will contain excess ones of the labeling compounds that are transported from the labeling zone  64  by the capillary migration of the fluid sample across the detection zone  52 . In this state, the transmittance of light  72  through the thickness of the test strip  46  at locations corresponding to the test and control regions  54 ,  56  will not correspond to the transmittance through the thickness of the test strip  46  at other locations of the detection zone  52  due to the presence of the immobilized label in the test and control regions  54 ,  56 . In particular, the presence of the label in the test and control regions  54 ,  56  blocks or substantially reduces the intensity of illuminating light that is transmitted through the test strip  46 , as shown diagrammatically in  FIG. 6 .  
      In some embodiments, the label is a reflective label that reflects the illuminating light  72  away from the top side  50  of the test strip  46 . For example, some labels (e.g., colloidal gold and silver particles) have reflectivities that are greater than 90% with respect to light within a target wavelength range corresponding to visible light (i.e., 390 nm to 770 nm). In other embodiments, the label is an absorptive label that blocks light from being transmitted through the test strip  46 . For example, some labels (e.g., quantum dots) may absorb the illuminating light within a target wavelength range and emit secondary fluorescent light at longer wavelengths. In these embodiments, the intensities of the secondary fluorescent emissions that may be detected by the optical detector  58  are expected to be substantially lower than the intensity of the primary illuminating light  72  that is transmitted through the test strip  46 .  
       FIG. 7  is an exemplary simulated graph of the transmitted light intensity measured by the optical detector  58  with the test strip  46  in the state shown in  FIG. 6  plotted as a function of position along the test strip  46 . In this example, the light intensity measured by the optical detector  58  is substantially uniform across the detection zone  52 , except in the positions  74 ,  76  corresponding to the locations of the test and control regions  54 ,  56 . At these positions  74 ,  76 , the graph is intended to show the relatively large reductions in the transmitted light intensity that are expected to be caused by the presence of the label in the test and control regions  54 ,  56  of the detection zone  52 .  
       FIG. 8  shows an exemplary simulated graph of the intensity difference (I M1 -I M2 ) between the light intensity measurements (I M1  and I M2 ) shown in  FIGS. 5 and 7  plotted as a function of position along the test strip. The intensity difference graph shows peaks in the positions  74 ,  76  along the test strip  46  corresponding to the locations of the test and control regions  74 ,  76 . In this example, the slight reductions in the transmitted light intensities that were caused by the presence of the immobilized substances in the test and control regions  54 ,  56  have only insubstantial effects on the intensity difference graph shown in  FIG. 8 . In some embodiments, an empirically determined threshold (I TH ) is applied to the intensity difference graph to identify the presence of the label in the test and the control regions  54 ,  56 . In these embodiments, the presence of the label is detected if the intensity difference is greater than the threshold. In some embodiments, the presence of the labels in the test and control regions  54 ,  56  is determined by application different thresholds to the portions  74 ,  76  of the intensity difference graph corresponding to the locations of the test and control regions  54 ,  56 .  
      IV. Exemplary Implementations of the Diagnostic Test System  
       FIG. 9  shows an embodiment  80  of the diagnostic test system  40  in which the detection system  42  includes a first optical detector  58  and a second optical detector  82 . In the illustrated embodiment, the second optical detector  82  is implemented in the same way as the first optical detector  58 . In other embodiments, the second optical detector  82  may include different components or a different configuration of the same components as the first optical detector  82 .  
      In the diagnostic test system embodiment  80 , the first optical detector  58  produces measurement signals in a measurement data channel in response to the receipt of light that is transmitted through the test strip  46  in areas of the bottom side  48  that are aligned with (or shadowed by) measurement regions of the test strip  46 . The second optical detector  82  produces baseline signals in a baseline data channel separate from the measurement data channel in response to the receipt of light that is transmitted through the test strip in areas of the bottom side  48  of the test strip  46  that are aligned with respective regions of the test strip that are outside of any measurement region. Producing the measurement and baseline signals in separate data channels allows the assay test strip  46  to be evaluated with high accuracy and precision while using relatively inexpensive detectors and processing components.  
      In some embodiments, for each measurement region in the detection zone  15 , at least one of the detection system  42  and the retainer  44  are moved into a respective measurement position in which the test strip  46  is aligned vertically (i.e., orthogonally to the top and bottom sides  50 ,  48  of the test strip  46 ) with the detection system  42  such that the first optical detector  58  is positioned directly under an area of the bottom side  48  of the test strip that corresponds to a measurement region of the detection zone  52 . For example,  FIG. 9  shows the test strip  46  and the detection system  42  in a first measurement position in which the first optical detector  58  is positioned directly under the control region  56  and the second optical detector  82  is positioned directly under a baseline region of the detection zone  15  that is adjacent to the control region  18  but outside of any measurement region (i.e., the test region  54  and the control region  56 ). In a second measurement position, the first optical detector  58  would be positioned directly under the test region  54  and the second optical detector  82  would be positioned directly under a baseline region of the detection zone  15  that is adjacent to the test region  54  but outside of the test region  54  and the control region  56 .  
      Some embodiments of the diagnostic test system  40  may include an alignment system that is configured cooperatively with the detection system  42  to guide the movement of at least one of the retainer  44  and the detection system  42  into a respective measurement position in which the test strip  46  is aligned with the detection system  42  for each measurement region in the detection zone  15 . In each measurement position, the first optical detector  58  receives light predominantly from an area of the bottom side  48  of the test strip that is aligned vertically with a respective one of the measurement regions and the second optical detector  82  receives light predominantly from an area of the bottom side  48  of the test strip that is aligned vertically with baseline region outside of any measurement region.  
       FIG. 10  shows an embodiment  90  of the diagnostic test system  40  that includes a housing  92 , the detection system  42 , a data analyzer  94 , a memory  96 , a results indicator  98 , and a power supply  100 . The housing  92  includes a port  102  for receiving the test strip  46  and a window  104  for illuminating the test strip  46  with external light  106  (e.g., ambient light). The window  104  may consist of an opening in the housing  92  or it may include a material that is optically transparent to ambient light  106  within a target wavelength range (e.g., visible light or infrared light). In some implementations, the diagnostic test system  90  is fabricated from relatively inexpensive components enabling it to be used for disposable or single-use applications.  
      The housing  92  may be made of any one of a wide variety of materials, including plastic and metal. The housing  92  forms a protective enclosure for the detection system  42 , the retainer  44 , the data analyzer  94 , the memory  96 , the power supply  100 , and other components of the diagnostic test system  90 . The housing  92  also may include the above-described alignment system, which mechanically registers the test strip  46  with respect to the detection system  42 .  
      The results indicator  98  may include any one of a wide variety of different mechanisms for indicating one or more results of an assay test. In some implementations, the results indicator  98  includes one or more lights (e.g., light-emitting diodes) that are activated to indicate, for example, a positive test result and the completion of the assay test (i.e., when sufficient quantity of the labeling substance has accumulated in the control region). In other implementations, the results indicator  98  includes an alphanumeric display (e.g., a two or three character light-emitting diode array) for presenting assay test results.  
      The power supply  100  supplies power to the active components of the diagnostic test system  90 , including the detection system  42 , the data analyzer  94 , and the results indicator  98 . The power supply  100  may be implemented by, for example, a replaceable battery or a rechargeable battery. In other embodiments, the diagnostic test system may be powered by an external host device (e.g., a computer connected by a USB cable).  
      The data analyzer  94  processes the light intensity measurements that are obtained by the detection system  42 . In general, the data analyzer  94  may be implemented in any computing or processing environment, including digital electronic circuitry or computer hardware, firmware, or software. In some embodiments, the data analyzer  94  includes a processor (e.g., a microcontroller, a microprocessor, or ASIC) and an analog-to-digital converter. In the illustrated embodiment, the data analyzer  94  is incorporated within the housing  92  of the diagnostic test system  90 . In other embodiments, the data analyzer  94  is located in a separate device, such as a computer, that may communicate with the diagnostic test system  90  over a wired or wireless connection.  
      In operation, the test strip  46  is loaded onto the retainer  44  and moved into the port  102 . The detection system  42  obtains intensity measurements of light passing through the test strip  46 . In particular, the detection system  42  produces measurement signals in response to light received from respective areas of the bottom side  48  of the test strip  46  that are aligned with respective measurement regions of the detection zone  52 . The detection system  42  also produces baseline signals in response to light received from respective areas of the bottom side  48  of the test strip  46  that are aligned with baseline regions of the detection zone  52 .  
      The measurement and baseline signals may be obtained by a single optical detector or by multiple optical detectors, as explained above. The data analyzer  94  computes at least one parameter from one or more of the light intensity measurements. In particular, the data analyzer  94  quantifies the respective ones of the measurement signals with respect to respective ones of the baseline signals for each measurement position of the test strip  46  relative to the detection system  42 . In this process, the data analyzer  94  derives a final quantified value from a function that compares the measurement region values and baseline region values. The measurement region value is derived from the measurement signals (e.g., an average or a peak signal value) and optionally may be calibrated with respect to a dark value that is measured when the top side  50  of the test strip  46  is not illuminated (e.g., when the light source is turned off). Similarly, the baseline region value is derived from the baseline signals (e.g., an average or a peak signal value) and optionally may be calibrated with respect to a dark value that is measured when the top side  50  of the test strip  46  is not illuminated.  
      The comparison function may include a ratio between the measurement region value and the baseline region value, a difference between the measurement region value and baseline region value, or some other mathematical function of the measurement region value and the baseline region value. For example, in some embodiments, the data analyzer  94  quantifies the measurement region value in terms of the baseline region value to determine a measure of the transmission density of a respective one of the measurement regions of the test strip  46 . The transmission density is the logarithm of the transmittance to the base  10 , where the transmittance is the ratio of the measurement region value to the baseline region value. The data analyzer  94  may use the transmission density value as an index into a lookup table that maps transmission density values to analyte concentration values.  
      The results indicator  98  provides an indication of one or more of the results of an assay of the test strip  46  based on the parameters that are computed by the data analyzer  94 .  
       FIG. 11  shows an embodiment  110  of the diagnostic test system  40  that corresponds to the embodiment  80  that is shown in  FIG. 10 , except that the window  104  is replaced by a light source  112  that is configured to illuminate the top side  50  of the test strip  46  with light within a target wavelength range (e.g., visible light or infrared light). In some implementations, the light source  112  includes a semiconductor light-emitting diode. Depending on the nature of the label that is used by the test strip  46 , the light source  112  may be a broadband light source or it may be designed to emit light within a particular wavelength range or with a particular polarization, in which case the light source  112  may include one or more optical filters that define the wavelength ranges or polarizations axes of the light.  
      Some embodiments of the diagnostic test system  40  include one or more of the systems for aligning the detection system with the assay test strip. These alignment systems may be used by the data analyzer  94  to correlate the measurement and baseline signals that are produced by the detection system  42  with positions along the test strip  46 , which enables the data analyzer  94  to associate the measurement signals with the corresponding measurement regions in the detection zone.  
     V. CONCLUSION  
      The embodiments that are described in detail above provide systems and methods of obtaining measurements of light transmitted through assay test strips and using these measurements to evaluate assays performed on the assay test strips. The light that is transmitted through the test strips is substantially free of light that is reflected from non-target surfaces of the test strips and other surfaces within the diagnostic test system. For this reason, the alignment constraints between the test strips and the detection system in the embodiments that are described below may be reduced relative to diagnostic test approaches that measure light from the illuminated surfaces of the test strips. The need for complex and resource intensive analyses of the measurement data in order to reduce the noise caused by reflected light also is reduced. These features allow the embodiments that are described above to evaluate assay test strips with high accuracy and precision while using relatively inexpensive components and without requiring complex and resource intensive analyses of the measurement data.  
      Other embodiments are within the scope of the claims.