Method for recognizing patterns from assay results

A Fourier transform optical detection system for use with a test assay that has a sensitivity pattern, the detection system including a lens having a Fourier transform plane and detectors located in the Fourier transform plane positioned in an arrangement of a Fourier transform pattern of the sensitivity pattern.

BACKGROUND

Currently, assays are read by human eye or a high cost imaging system. Assay readings done by eye are based on individual human judgment and therefore are subject to human error. Assays readings done by imaging systems require expensive detection systems. 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 that is the subject of the assay is referred to as the analyte of interest. 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 are known in the art, and the sensitive region is formed by a chemical treatment or a physical manipulation of the surface. The pattern of the sensitive region includes one or more shapes, for example, a circular shape with a diameter of approximately one centimeter (cm).

The substrate is typically made of silicon or glass and has a smooth surface. The surface of the substrate includes a sensitive region that reacts to exposure to an analyte of interest. The sensitive region is indistinguishable from the substrate outside the sensitive region until the sensitive region is exposed to the analyte of interest. The sensitive region will react to exposure of the sensitive region to an analyte of interest.

Detection of the reaction of the sensitive region upon exposure to the analyte of interest is performed by human eye or high-cost, high-resolution detection systems that determine the shape of the sensitive region upon exposure to the analyte of interest.

A human observes the sensitive region to determine if exposure to the sample resulted in a change in the appearance of the sensitive region relative to the rest of the substrate. If there was a sufficient change, the observer concludes that the sensitive region was exposed to the analyte of interest and thus, that the analyte of interest was included in the sample. When readings are made by the human eye to determine an exposure of the sensitive region to an analyte of interest, the readings may not be consistent and may be prone to error.

When assays are read by high-resolution systems, such as a charge-coupled device (CCD) systems and some CMOS-based system, the determination of an exposure of the sensitive region to of a analyte of interest is determined by a reading across the entire substrate to determine the shape and location of the sensitive region exposed to the analyte of interest. Such systems may be consistent and relatively error free. However, the equipment is expensive and such detailed determination is unnecessary.

Application Ser. No. 11/019,183 filed by the applicant on Dec. 23, 2004 (also referred to here as the “11/019,183 Application”) describes a low resolution detection system that is strategically arranged in the image plane of a lens to detect illumination from reactive regions in a test assay in which the reactive regions for different analytes have different shapes, such as circular shapes, square shapes and/or rectangular shapes. The detection is done in the image plane of the lens using a priori knowledge of the shape for each reactive material in the test assay.

A market demand exists for a simple, consistent and inexpensive system to determine whether a test sample of biological or chemical material being assayed includes an analyte of interest.

SUMMARY

A first aspect of the present invention provides a Fourier transform optical detection system for use with a test assay that has a sensitivity pattern. The detection system includes a lens having a Fourier transform plane and detectors located in the Fourier transform plane positioned in an arrangement of a Fourier transform pattern of the sensitivity pattern.

A second aspect of the present invention provides a method of increasing a signal to noise ratio during a measurement of a test assay using a Fourier transform detection system. The method includes receiving light having a sensitivity pattern at a lens having a Fourier transform plane and detecting light at intensity peaks of a Fourier transform pattern of the sensitivity pattern in the Fourier transform plane.

A third aspect of the present invention provides a test assay for detecting an analyte. The assay includes a substrate and detection regions arranged in a Fourier transformable pattern on the substrate. The detection regions react with the analyte and emit light, transmit light or reflect light in the Fourier transformable pattern. The Fourier transformable pattern has at least one intensity peak with a contrast greater than 0.5 when Fourier transformed.

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

FIGS. 1A and 1Bare views of one embodiment of a Fourier transform optical detection system20for use with a test assay60having a sensitivity pattern100. The sensitivity pattern100is also referred to as a “Fourier transformable pattern100” since the sensitivity pattern100can be Fourier transformed by a lens40. The sensitivity pattern100is segmented into quadrants100A,100B,100C and100D by the line98, which vertically bisects the sensitivity pattern100, and by the line99, which horizontally bisects the sensitivity pattern100.

The test assay60is also referred to as “assay60.” The Fourier transform optical detection system20is also referred to as “detection system20.” The detection system20comprises a lens40having a Fourier transform plane fFTand a detector array30. The detector array30is segmented into quadrants30A,30B,30C and30D by the line28, which vertically bisects the detector array30, and by the line29, which horizontally bisects the detector array30.

The detector array30includes first detectors32A,32B,32C and32D, also referred to here as “first detectors32” and “first detector32.” The detector array30additionally includes second detectors34A,34B,34C, and34D, also referred to here as “second detectors34” and “second detector34.” The first detectors32A,32B,32C and32D are each centered in the respective quadrant30A,30B,30C and30D of the photodetector array30. The second detectors34A,34B,34C, and34D are each in the respective quadrant30A,30B,30C and30D of the photodetector array30in a location offset from the first detectors32A,32B,32C and32D. The first detectors32and the second detectors34are all located in the Fourier transform plane fFT.

The first detectors32and the second detectors34are positioned in an arrangement of a Fourier transform pattern of the sensitivity pattern100so that the first detectors32detect light at peak-intensity regions of the Fourier transform pattern of the sensitivity pattern100in the Fourier transform plane50(FIG. 1B) and the second detectors34detecting light in at least one low-intensity region of the Fourier transform pattern of the sensitivity pattern100in the Fourier transform plane50. The intersection of lines98and99, the center42of the lens40, and the intersection of lines28and29are all aligned with each other on the optical axis41of the lens40.

The sensitivity pattern100is a checkerboard pattern of detection regions represented generally by the numeral71and non-detection regions represented generally by the numeral72in test assay60. The detection regions71are regions which are able to react to the presence of a test analyte in a test sample, when the test assay60is exposed to the test sample having the test analyte. In order to facilitate visualization of the sensitivity pattern100, the detection regions71are darker than the non-detection regions71inFIG. 1A. In this embodiment, the sensitivity pattern comprises100a uniform array of a pattern. Other patterns are possible.

FIG. 1Ais an oblique view of the detection system20.FIG. 1Bis a side view of the detection system20. The test assay60is located at an object distance dofrom the lens40. The top surface75of the assay substrate70, also referred to as “substrate70,” is in an object plane51(FIG. 1B) of the lens40. The object plane51(shown in cross-section inFIG. 1B) is perpendicular to the optical axis41of the lens40.

The detector array30is located at a distance fFTfrom the lens40opposing the test assay60in the Fourier transform plane50(shown in cross-section inFIG. 1B) of the lens40. The front surface of the detector array30is in the Fourier transform plane50. The Fourier transform of the sensitivity pattern100is imaged by the lens40in the Fourier transform plane50.

The detection system20also includes a processor25communicatively coupled to the detector array30. The first detector32and the second detector34each generate signals indicative of the intensity of light incident on the first detector32and the second detector34, respectively. The processor25receives the signals and determines if the first detector32and the second detector34are receiving light in a pattern of a Fourier transform of the sensitivity pattern100.

The detection system20also includes a memory26communicatively coupled to the processor25. At least a portion of software and/or firmware executed by the processor25and any related data structures are stored in memory26.

FIGS. 2A and 2Bare enlarged views of a portion of the test assay60(FIG. 1) before and after exposure to a test sample, respectively.FIG. 2Ashows a portion61of the test assay60, which includes two detection regions71and two non-detection regions72, before exposure of reagents (shown as curved lines and generally represented as numeral92) to a test sample that includes reactive test analytes.FIG. 2Bis an enlarged view a portion62, which includes two detection regions71and two non-detection regions72, of the test assay60(FIG. 1) after exposure to the test sample that includes reactive test analytes, also referred to as “test analytes94,” shown as X's, and represented generally by the numeral94. The test analytes94are bonded to the reagents92in the detection regions71. The detection regions71include the reagents92attached to the top surface75of the substrate70. The reagents92in detection regions71are able to bond to a reactive test analyte94when the test analytes94come into contact with the reagents92. The non-detection regions72do not have any attached reagents92.

The reagents92in the detection regions71react with the test analyte94such that the optical characteristics of the surface are changed and light is emitted, reflected or transmitted in the Fourier transformable pattern100(FIG. 1). In one implementation of this embodiment, the reagents92in the detection regions71bond to the test analyte94and the bonded material emits light from the detection regions71. In another implementation of this embodiment, gold atoms are attached to the test analyte94and the bonding of the reagents92to the test analyte94is detected as reflected light when light is incident on the test assay60. In yet another implementation of this embodiment, if a reaction has occurred, the bonded reagents92and test analytes94fluoresce upon exposure to the incident light. In another implementation of this embodiment, each test analyte94includes an attached fluorescent molecule. The Fourier transformable pattern100has at least one intensity peak with a contrast greater than 0.5 when Fourier transformed by lens40(FIG. 1).

FIG. 3Ais a Fourier transform pattern80of the sensitivity pattern100(FIG. 1A). The Fourier transform pattern80is shown as viewed from the position of the lens40inFIG. 1A. After the test assay60is exposed to a test sample (not shown) that includes reactive test analyte94, light is emitted, transmitted or reflected from the top surface75of the test assay60in the pattern of the sensitivity pattern100. The light emitted, transmitted or reflected from the top surface75(FIG. 1B) of the test assay60is transmitted through the lens40. The light transmitted through the lens40is Fourier transformed by the lens40and focused in the resulting Fourier transform pattern80at the Fourier transform plane55located the distance fFTfrom the lens40(FIGS. 1A and 1B). Since the sensitivity pattern100is a checkerboard, two dimensionally shaped peak-intensity regions (represented as white squares labeled with numerals82A,82B,82C, and82D in a crosshatch background) are imaged in the Fourier transform plane50(FIG. 1B). The two dimensionally shaped peak-intensity regions82A,82B,82C, and82D are also referred to here as “peak-intensity regions82.” At the peak-intensity regions82, a peak intensity of light is incident on the first detectors32(FIGS. 1A and 1B) located in the Fourier transform plane50.

When the Fourier transform pattern80is imaged on the photodetector array30inFIG. 1A, the second detectors34are positioned in a low-intensity region of the Fourier transform pattern80of the sensitivity pattern100. The low-intensity region is represented generally by the numeral83and indicated by the cross hatching. The low-intensity region83includes all of the Fourier transform pattern80outside of the peak-intensity regions82and the average signal region84referred to here as the “DC-component region84.” The second detectors34can be placed anywhere in the low-intensity region83of the Fourier transform pattern80.

The intensity of light at the peak-intensity regions82, referred to here as Ipeak, is much higher than the intensity of the light at the low-intensity region83, referred to here as Ilow, therefore the Fourier transformable pattern100, when Fourier transformed, has at least one high contrast peak at peak-intensity regions82. The peak-intensity regions82are intensity peaks in the Fourier transformed pattern with a contrast greater than 0.5. The contrast of the Fourier transform pattern80is defined here as (Ipeak−Ilow)/(Ipeak+Ilow). In one implementation of this embodiment, the peak-intensity regions82are intensity peaks in the Fourier transformed pattern with a contrast that is discernable by the human eye.

The optical axis40(FIGS. 1A and 1B) intersects the Fourier transform plane50at the average signal region84. The DC-component region84is a two dimensionally shaped light pattern (shown as a square white box) located in the center of the Fourier transform pattern80in the Fourier transform plane50(FIG. 1B). The DC-component region84has an intensity level that correlates to the mean intensity of the contrast between the intensity of light from the detection region71and the non-detection region72. If the average light intensity emitted, transmitted or reflected from the top surface75of the test assay60from the detection region71is Ihiand the average light intensity emitted, transmitted or reflected from the non-detection region72is Ilow, the intensity of light in the DC-component region84is proportional to (Ihi+Ilow)/2.

In this manner as shown inFIGS. 1A,1B,2A,2B and3A, the first detectors32and the second detectors34of detector array30are positioned in an arrangement of a Fourier transform pattern80of the sensitivity pattern100. Specifically, the first detector32A is located to detect light in the peak-intensity region82A, the first detector32B is located to detect light in the peak-intensity region82B, the first detector32C is located to detect light in the peak-intensity region82C, and the first detector32D is located to detect light in the peak-intensity region82D. Likewise, the second detector34A is located to detect light in the low-intensity region83that is offset from the peak-intensity region82A, the second detector34B is located to detect light in the low-intensity region83that is offset from the peak-intensity region82B, the second detector34C is located to detect light in the low-intensity region83that is offset from the peak-intensity region82C, and the second detector34D is located to detect light in the low-intensity region83that is offset from the peak-intensity region82D.

In one implementation of this embodiment, the Fourier transform optical detection system20includes only one second detector34A,34B,34C or34D that detects the light level in the low-intensity region83and only one first detector32A,32B,32C or32D that detects the light level in the respective peak-intensity region82A,82B,82C, or82D.

The first detectors32and the second detectors34do not need to be high resolution detectors. The first detectors32and the second detectors34do not need to be positioned as closely to each other as the detection regions71are positioned to each other on the test assay60, since the detector array30is not resolving the image of the light emitted, transmitted or reflected from the test assay60in the sensitivity pattern100. In one implementation of this embodiment, the first detectors32and the second detectors34are large area semiconductor photodetectors. The detection system20(FIGS. 1A and 1B) includes first detectors32and the second detectors34that are operable to detect the wavelength of the light emitted, transmitted or reflected from the test assay60.

FIG. 3Bis an upper-right hand quadrant81of the Fourier transform pattern80ofFIG. 3A. The upper-right hand quadrant81is also referred to here as “quadrant81.” The DC-component region84is now in the lower-left hand corner of the Fourier transform pattern and the peak-intensity region82C is centered in the quadrant81. Likewise, the peak-intensity regions82A,82B and82D are centered in their respective quadrants of the Fourier transform pattern80. The discussion related toFIGS. 5A-5Dis based on a software modeling of quadrant81of the Fourier transform pattern80.

FIG. 4is a flow diagram of one embodiment of a method400to increase the signal to noise ratio SNR during a measurement of a test assay60using the Fourier transform detection system20. The particular embodiment of method400shown inFIG. 4is described here as being implemented for use with the detection system20described above in connection withFIGS. 1A,1B,2A,2B and3B. Other embodiments are possible.

At block402, the detection regions71are formed on the test assay60in the sensitivity pattern100. In one implementation of this embodiment, detection regions71are formed by patterning the substrate70to expose all the detection regions71shown inFIG. 1Aand then attaching the reagent92to exposed detection regions71of the substrate70. The methods of attaching the reagent92are set by the type of substrate70and by the type of reagent92. The detection regions71are operable to react to a test analyte94so the test assay60emits, transmits or reflects light in the sensitivity pattern100. In one implementation of this embodiment, more than one type of reagent is attached to the exposed areas of the substrate70.

At block404, the test assay60is exposed to a test material that includes reactive test analyte94. The test analyte94and the reagent92bond to each other when they come into contact. In one implementation of this embodiment, a test sample including test analyte94is washed over the top surface75of the test assay60in order to expose the test assay60to the test analyte94. In another implementation of this embodiment, the test assay60is dipped into the test sample including test analyte94, in order to expose the test assay60to the test analyte94. In another implementation of this embodiment, capillary forces are implemented in channels on the test assay60in order to expose the test assay60to the test analyte94. Other exposure techniques are possible.

At block406, light is emitted, transmitted or reflected from the test assay60in the sensitivity pattern100from the object plane51of the lens40. In one implementation of this embodiment, the bonded reagents92and test analytes94emit light of a first wavelength when an external light of a second wavelength is incident on the test assay60. In another implementation of this embodiment, the bonded reagents92and test analytes94spontaneously emit light after the reagents92and test analytes94bond to each other.

At block408, the lens40lens having a Fourier transform plane50receives the light having the sensitivity pattern100. The lens40is positioned an object distance dofrom the top surface75of the test assay60so that the optical axis41is perpendicular to the top surface75of the substrate70(FIG. 1B).

At block410, the detector array30detects light from least one peak-intensity region82and at least one low-intensity region83of the Fourier transform pattern80(FIG. 3A) of the sensitivity pattern100in the Fourier transform plane50. For example, the first detector32C (FIG. 1A) is located at the peak intensity82C (FIG. 3B) of the quadrant81of the Fourier transform pattern80. The second detector34C (FIG. 1A) is located away from the peak intensity82C in the low-intensity region83(FIG. 3B) of the quadrant81of the Fourier transform pattern80.

At block412, the processor25determines an occurrence of a reaction on the test assay60based on the detecting during block410. If light is detected by first detectors32and little or no light is detected by second detectors34, the processor25determines that the first detectors32are receiving light from the peak-intensity regions82of the sensitivity pattern100and the test analyte94is attached to the reagent92in the detection regions71of the test assay60.

If similar low light levels are detected by the first detectors32and the second detectors34, the processor25determines that the first detectors32are not receiving peak intensity light where the peak-intensity regions82of the sensitivity pattern100is expected and that the test analyte94is not attached to the reagent92in the detection regions71of the test assay60.

In one implementation of this embodiment, the detector array30is operable to detect more than one Fourier transform pattern. In this case, the processor25receives input indicative of the sensitivity pattern of the test assay60positioned in the object plane51of the lens40in detection system20. The processor25evaluates the signals from the set of detectors or photodetector elements in a photodetector array that are needed to determine if the sensitivity pattern of interest is in the object plane51of the lens40. When a new test assay60with a different sensitivity pattern is placed in the object plane51of the lens40in detection system20, the processor25receives input indicative of the sensitivity pattern of the new test assay60and evaluates signals from a new set of detectors in the detector array30or photodetector elements in a photodetector array.

The processor25executes software and/or firmware that causes the processor25to determine if a reaction occurred between the test analyte94and the reagent92. At least a portion of such software and/or firmware executed by the processor25and any related data structures are stored in memory26during execution. Memory26comprises any suitable memory now known or later developed such as, for example, random access memory (RAM), read only memory (ROM), and/or registers within the processor25. In one implementation, the processor25comprises a microprocessor or microcontroller. Moreover, although the processor25and memory26are shown as separate elements inFIG. 1, in one implementation, the processor25and memory26are implemented in a single device (for example, a single integrated-circuit device). The software and/or firmware executed by the processor25comprises a plurality of program instructions that are stored or otherwise embodied on the memory26or another storage medium from which at least a portion of such program instructions are read for execution by the processor25. In one implementation, the processor25comprises processor support chips and/or system support chips such as ASICs.

The detection system20determines an occurrence of a reaction on the test assay60even if the sensitivity pattern100has a small intensity variation between the light emitted, transmitted or reflected from the detection regions71and the light emitted, transmitted or reflected from the non-detection regions72. The Fourier transform of a well-chosen sensitivity pattern has relatively high intensity variation (between the peak-intensity region and the low-intensity region) with respect to the intensity variation of the sensitivity pattern (between the detection regions and the non-detection regions).

A human observer has difficulty seeing a 2% intensity variation in the checkerboard pattern as is shown inFIG. 5C. In some cases, a human observer has difficulty seeing a 10% intensity variation in the checkerboard pattern. In order to illustrate that the Fourier transform of a sensitivity pattern has a relatively high intensity variation with respect to the intensity variation of the sensitivity pattern,FIGS. 5A-5Dshow patterns for paired sensitivity patterns and the resultant Fourier transform patterns in which the sensitivity patterns100have various intensity variations and noise levels.

FIG. 5Ais a portion of a sensitivity pattern102exemplary of a modeled sensitivity pattern having about a 10% intensity variation between the detection regions71and non-detection regions72and +/−1.5% uniform random noise. Thus, each of the detection regions71and the non-detection regions72in the test assay60emit, transmit or reflect an intensity of light that can vary in a random uniform manner by ±1.5%.FIG. 5Bis a quadrant182of the modeled Fourier transform pattern of the modeled sensitivity pattern102ofFIG. 5A. The complete Fourier transform pattern is similar to the Fourier transform pattern80ofFIG. 3A. The intensity ratio between the peak-intensity region82C and the low-intensity region83(FIG. 3A) is about 20/1.

InFIG. 5A, the checkerboard pattern is a schematic representation of the modeled checkerboard pattern having about a 10% intensity variation between the detection regions71and non-detection regions72and +/−1.5% non-uniform random noise. In the modeling for the sensitivity pattern102ofFIG. 5A, the intensity of light from the detection regions71is 100±1.5 and the intensity of light from non-detection regions72is about 90±1.5 for an intensity ratio of about 100/90=1.11. Specifically for the modeled sensitivity pattern inFIG. 5A, the intensity ratio ranges from about 101.5/88.5=1.15 to about 98.5/91.5=1.07.

The Fourier transform optical detection system20(FIGS. 1A and 1B) detects the 20/1 intensity ratio of the Fourier transformed sensitivity pattern102with first detectors32and at least one of the second detectors34in the Fourier transform pattern in Fourier transform plane50(FIG. 1B) of the lens40. For example, the two detectors32C and34C detect light in the quadrant182of the Fourier transform pattern in Fourier transform plane50(FIG. 1B) of the lens40and the other first detectors32detect light in the other quadrants of the Fourier transform pattern. In one implementation of this embodiment, only the two detectors32C and34C are included in the photodetector array30to detect light in the Fourier transform pattern80in Fourier transform plane50(FIG. 1B) of the lens40. Thus, the Fourier transform optical detection system20is simpler than an optical detection system needed to detect a checkerboard pattern having 10% intensity variation that is imaged in an image plane of a lens.

InFIG. 5C, the checkerboard pattern is a schematic representation of a portion of the modeled checkerboard pattern having about a 2% intensity variation between the detection regions71and non-detection regions72and +/−1.5% non-uniform random noise. InFIG. 5C, the intensity of light from the detection regions71is 100±1.5 and the intensity of light from non-detection regions72is about 98±1.5 for an intensity ratio of about 100/98=1.02.

FIG. 5Dis a quadrant183of the modeled Fourier transform pattern of the modeled sensitivity pattern103ofFIG. 5C. The complete Fourier transform pattern of sensitivity pattern103is similar to the Fourier transform pattern80ofFIG. 3A. InFIG. 5D, the smallest intensity ratio between the peak-intensity region82C and the low-intensity region83(FIG. 3A) is about 3/1.

A Fourier transform optical detection system, such as the system20described above with reference toFIGS. 1A and 1B, is able detect the intensity ratio ofFIG. 5Dwith two detectors in the quadrant183of the Fourier transform plane50. Thus, the low cost detection system20is able to determine the occurrence of a reaction between the test analyte94and the regent92for this low contrast sensitivity pattern, such as sensitivity pattern103ofFIG. 5C, using between 2 to 8 low cost large area detectors and a processor25that determines a ratio between the light levels in the two detectors32and34. The human eye could not distinguish the sensitivity pattern100at 2% intensity variation with certainty.

Other sensitivity patterns having least one high contrast peak when Fourier transformed by a lens40or lens system are possible.FIG. 6is an oblique view of one embodiment of a test assay62having three sensitivity patterns on the top surface75of the substrate70. The test assay62shown inFIG. 6includes sensitivity patterns represented generally by the numerals90,91and95. When the test assay62replaces test assay60in the system20, each sensitivity pattern90,91and95has a different Fourier transform pattern in the Fourier transform plane55(FIG. 1B). In one implementation of this embodiment, the detection regions71in each of the sensitivity patterns90,91and95react to different test analytes94. In order to detect the presence of various test analytes, a photodetector array is designed with at least one detector in a high-intensity region of the Fourier transform pattern of the respective sensitivity pattern and with at least one detector in a low-intensity region of the Fourier transform pattern of the respective sensitivity pattern. The processor determines if each of the various test analytes are present.

Sensitivity pattern90includes four detection regions71that are alternating with four non-detection regions72in a row along the width dimension W. Thus, when the reagents92in the detection regions71in the sensitivity pattern90are bonded with the test analyte94(FIG. 2B), the sensitivity pattern90emits, transmits or reflects light as a spatial filter having a spatial frequency in one dimension. As used herein, a row forms a spatial filter in one dimension. A matrix such as the sensitivity pattern100forms a spatial filter in two dimensions. Also, two rows form a spatial filter in two dimensions. In one implementation of this embodiment, the sensitivity pattern90includes detection regions71that bond to a first test analyte (not shown).

Sensitivity pattern91includes four detection regions71that are the same size as the detection regions71of sensitivity pattern90. The four detection regions71alternate two by two with four non-detection regions72in a row along the width dimension W. Sensitivity pattern91is offset in the height dimension H from the sensitivity pattern90. Thus, when the detection regions71in the sensitivity pattern90are bonded with the test analyte94(FIG. 2B), the sensitivity pattern90emits light as a spatial filter having a spatial frequency in one dimension that is half the spatial frequency in one dimension as that in sensitivity pattern90. In one implementation of this embodiment, the sensitivity pattern91includes detection regions71that bond to a second test analyte (not shown).

Sensitivity pattern95includes detection regions71that are the same size as the detection regions71of sensitivity pattern90and91. Sensitivity pattern95is offset in the height dimension H from the sensitivity pattern91. Sensitivity pattern95includes detection regions71that are alternating four by four in the dimension along the width W of the substrate70with non-detection regions72so the rows have the one fourth the spatial frequency of sensitivity pattern90in the dimension along the width W of the substrate70. In one implementation of this embodiment, the sensitivity pattern95includes detection regions71that bond to a third test analyte.

As known in the art, many other appropriate sensitivity patterns are possible in one or two dimensions. Specifically, the sensitivity patterns can be in the form of a spatial filter having a spatial frequency in one dimension, multiples of the spatial frequency in one dimension, submultiples of the spatial frequency in one dimension, the spatial frequency in two dimensions, multiples of the spatial frequency in two dimensions, submultiples of the spatial frequency in two dimensions, and combinations thereof. In one implementation of this embodiment, the sensitivity pattern90, the sensitivity pattern91and/or the sensitivity pattern95are in two dimensions, that is in two or more rows.

FIG. 7is an oblique view of one embodiment of a Fourier transform optical detection system22for use with the test assay62having many sensitivity patterns90,91and95on a top surface75of a substrate70as described above with reference toFIG. 6. The many sensitivity patterns90,91and95are also referred to as a “Fourier transformable patterns90,91and95.” The test assay62is also referred to as “assay62.” The Fourier transform optical detection system22is also referred to as “detection system22.” The test assay62was described above with reference toFIG. 6.

The detection system22comprises a cylindrical lens200, a detector array represented generally by the numeral38, a processor25and a memory26. The detector array38includes a first linear detector array110, a second linear detector array111and a third linear detector array112, all located in the Fourier transform plane fFT. Each of the first linear detector array110, the second linear detector array111and the third linear detector array112include at least two detectors. All the detectors in the first linear detector array110, the second linear detector array111and the third linear detector array112together are positioned in an arrangement of a Fourier transform pattern of the many sensitivity patterns90,91and95. The detectors in the first linear detector array110, the second linear detector array111and the third linear detector array112are communicatively coupled to the processor25.

The cylindrical lens200has a Fourier transform plane fFT. The cylindrical lens200has a cylindrical axis201and an optical axis202. The optical axis202is positioned to be perpendicular to the top surface75of the test assay62and perpendicular to the Fourier transform plane (distinguished at an edge of the plane as dashed line50) in which the detector array38is positioned. The front faces of the first linear detector array110, the second linear detector array111and the third linear detector array112are all positioned in the Fourier transform plane50. The optical axis202is aligned to the center of the top surface75of the test assay62and the point113in the second linear array111in the detector array38. The cylindrical axis201is perpendicular to the optical axis202and is parallel to the height dimension H of the test assay62(FIG. 6). The cylindrical axis201and the optical axis202lie in a plane that is perpendicular to the top surface75of the test assay62and perpendicular to the Fourier transform plane50.

In one implementation of this embodiment, the first linear detector array110, the second linear detector array111and the third linear detector array112are each an electronic imaging device, such as a charge-coupled device (CCD) systems or a CMOS-based system. In another implementation of this embodiment, the first linear detector array110, the second linear detector array111and the third linear detector array112are a single electronic imaging device, such as a charge-coupled device (CCD) systems or a CMOS-based system.

The processor25determines the presence of any test analytes that bond to the test assay62as described above with reference to method400ofFIG. 3. The processor25is communicatively coupled to the memory26.

The detectors comprise linear arrays of detectors, a two dimensional array of detectors, imaging devices having arrays of pixels, detectors having one size, detectors having various sizes, and combinations thereof. The lens systems comprise a cylindrical lens, a spherical lens, an array of cylindrical lenses, an array of spherical lenses, and combinations thereof.

In one implementation of this embodiment, the sensitivity pattern comprises a sinusoidal pattern in one dimension or two dimensions.FIG. 8shows plots of amounts of reagent versus a width of a substrate70(FIG. 6). By varying the amount of reagent in a sinusoidal manner, the intensity of light emitted from the reagent after it bonds to a test analyte varies in the same sinusoidal pattern. In an exemplary case, a first sinusoidal sensitivity pattern is located at a first region of the test assay (for example, the first sinusoidal sensitivity pattern replaces the sensitivity pattern90inFIG. 6so that the first region is the first row along dimension W of the test assay62inFIG. 6). The first sinusoidal sensitivity pattern includes a first reagent is in an amount that varies sinusoidally at a first frequency 3/W as represented by the solid sinusoidal curve indicated with the label A.

In one implementation of this embodiment, a second sensitivity pattern is also located at the first region of the test assay. In this exemplary case, the second sinusoidal sensitivity pattern and the second sinusoidal sensitivity pattern replace the sensitivity pattern90. The second sinusoidal sensitivity pattern includes a second reagent in an amount that varies sinusoidally at a second frequency of 2/W as represented by the dashed sinusoidal curve indicated with the label B. In this manner, the first sensitivity pattern varies sinusoidally at the first frequency 3/W and detects the presence of the first test analyte located at the first region of the test assay while the second sensitivity pattern varies sinusoidally at the second frequency 2/W and detects the presence of the second test analyte. The first sensitivity pattern and the second sensitivity pattern and are co-located at the first region, which is the first row along dimension W of the test assay62inFIG. 6.

In another implementation of this embodiment, the first sinusoidal sensitivity pattern of the first reagent and the second sinusoidal sensitivity pattern of the second reagent are offset from each other on the substrate70. In this case, the first reagent in an amount that varies sinusoidally at a first frequency of 3/W as represented by the solid sinusoidal curve A is located at the first row of test assay62(FIG. 6) replacing sensitivity pattern90and the second reagent in an amount that varies sinusoidally at a second frequency of 2/W as represented by the dashed sinusoidal curve B is located at the second row of the test assay62(FIG. 6) replacing sensitivity pattern91.

In yet another implementation of this embodiment shown inFIG. 8, the second sensitivity pattern has a frequency that is half that of the first sensitivity pattern.