Circuit board with onboard light sources

Abstract

To provide a reagent analyzer having a circuit board, an imaging system, and a processor.SOLUTION: The circuit board (34) has a substrate, and a plurality of conductive leads. The substrate has a first and a second major surface. The first major surface is opposite the second major surface. The substrate has an opening (38) extending between the first major surface and the second major surface. The reagent analyzer also includes an imaging system (22) having a field of view extending through the opening formed in the substrate and configured to capture an image of a wet reagent test device (44) positioned at a read position in the field of view, the image having a plurality of pixels. The processor is configured to receive the image, and to analyze pixels of the image to determine a presence or an absence of a target constituent being in a sample applied to the wet reagent pad.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 63 / 064,609, filed August 12, 2020, and U.S. Provisional Application No. 63 / 225,124, filed July 23, 2021. The entire contents of the above-referenced patent applications are incorporated herein by reference.

[0002] The inventive concepts disclosed herein relate generally to an analyzer for a reagent card and more particularly, but not by way of limitation, to an analyzer having an improved signal-to-noise ratio through the use of a circuit board having an aperture and a built-in light source. [Background technology]

[0003] A myriad of analytical procedures, compositions, and tools have been developed to meet the needs of the medical community and other expanding technologies such as the brewing industry, chemical manufacturing, etc. Whether the lateral flow immunoassay or dip-and-read test device is used to analyze biological fluids or tissues, or commercial or industrial fluids or substances, the general procedure involves contacting the test device with the sample or specimen to be tested and analyzing the test device manually or by instrumentation.

[0004] A lateral flow immunoassay is a diagnostic device used to confirm the presence or absence of a target analyte. A lateral flow immunoassay generally includes a flow path that carries a sample past a control line position and a test line position. The control line at the control line position determines that the test is functioning properly, and the test line at the test line position provides the result of the lateral flow immunoassay. Lateral flow immunoassays have been developed to be used in dipstick or housed test formats. Both dipstick and housed tests function similarly and generally fall into one of two categories: sandwich assays, where a positive test is indicated by the presence of a colored line at the test line position, and competitive assays, where a positive test is indicated by the absence of a colored line at the test line position.

[0005] Dip-and-read reagent test devices are widely used in many analytical applications, especially in the chemical analysis of biological fluids, due to their relatively low cost, ease of use, and fast results. For example, in the medical field, many physiological functions can be monitored by simply dipping a dip-and-read reagent test device into a sample of bodily fluid or tissue, such as urine or blood, and observing a detectable response, such as a change in color or a change in the amount of light reflected or absorbed by the test device.

[0006] Many dip-and-read reagent test devices for detecting body fluid constituents are capable of performing quantitative or at least semi-quantitative measurements. Thus, by measuring a detectable response after a predetermined time, a user can obtain not only a positive indication for the presence of a particular component in a test sample, but also an estimate as to how much of that component is present. Such dip-and-read reagent test devices provide physicians and laboratory technicians with an easy diagnostic tool and the ability to assess the extent of a disease or physical condition.

[0007] Examples of dip-and-read reagent test devices currently in use include those manufactured by Siemens Healthcare Diagnostics Inc. under the trademark MULTISTIX. Such immunochemical, diagnostic, or serological test devices typically include one or more carrier matrices, such as absorbent paper, that incorporate specific reagents or reaction systems that exhibit a distinct detectable response (e.g., a color change in the visible or ultraviolet spectrum) in the presence of specific test sample constituents or components. Depending on the reaction system incorporated in the specific matrix, these test devices can detect the presence of glucose, ketone bodies, bilirubin, urobilinogen, occult blood, nitrite, and other substances. A characteristic change in color intensity observed within a specific time range after contacting the dip-and-read reagent test device with the sample indicates the presence and / or concentration of a specific component in the sample. Several other examples of dip-and-read reagent test devices and their reagent systems can be found in U.S. Pat. Nos. 5,233,333, 5,233,625, 5,233,625, and 5,233,625, the disclosures of which are incorporated herein by reference in their entireties.

[0008] However, dip-and-read reagent test devices have several limitations. For example, dip-and-read reagent test devices generally require a technician to manually dip the test device into the sample, wait a prescribed amount of time, and then visually compare the color of the test device to a color chart provided with the test device. This process is slow, the resulting reading is highly skill-dependent (e.g., precise timing, proper comparison to the color chart, ambient lighting conditions, and the technician's eyesight), and results may be inconsistent between two different technicians performing the same test. Finally, the act of manually dipping the test device into the sample may result in cross-contamination or improper deposition of the test sample on the test device, such as by incomplete insertion of the test device into the sample, insufficient time to deposit the sample on the test device, or too much sample on the test device that drips, leaks, or splashes onto the technician's work area, person, or clothing.

[0009] There has been a need in the art for testing tools and methods for performing multiple tests economically and quickly, particularly by using automated processing. Automated analyzer systems offer advantages over manual testing in terms of cost per test, test handling volume, and / or speed of obtaining test results or other information.

[0010] Currently available automated instruments for reading individual reagent test devices, such as lateral flow immunoassays or dip-and-read reagent test devices or reagent strips (e.g., CLINITEK STATUS reflectance photometers manufactured and sold by Siemens Healthcare Diagnostics, Inc.), by the instrument require that each test device be manually loaded onto the automated instrument after contacting the test device with the specimen or sample to be tested. Manual loading requires that the reagent test device be properly positioned on the automated instrument within a limited time period after contacting the solution or substance to be tested. Once the analysis is complete, the used reagent test device is removed from the instrument and disposed of in accordance with applicable regulations.

[0011] Another development is the introduction of multi-profile reagent cards and automated analyzers of multi-profile reagent cards. A multi-profile reagent card is essentially a card-like test device that includes multiple reagent-impregnated matrices or pads for performing multiple analyses of analytes simultaneously or sequentially, as described, for example, in U.S. Pat. No. 5,399,363, the entire disclosure of which is incorporated herein by reference. The reagent pads on the multi-profile reagent card are typically arranged in a grid-like arrangement and spaced apart from each other at a distance to define several rows and columns of reagent pads. Adjacent reagent pads in the same row can be referred to, for example, as test strips, and can contain reagents for a combination of pre-set tests to be performed on each sample.

[0012] The multiple-profile reagent card provides an efficient, economical, rapid, and convenient way of performing automated analyses. An automated analyzer configured to use the multiple-profile reagent card typically retrieves the multiple-profile reagent card from a storage drawer or cassette or the like, and advances the multiple-profile reagent card, typically one step at a time, on a travel surface of the analyzer via a card movement mechanism to place one test strip (or one row of reagent pads) at a sample dispensing position and / or one or more read positions. Exemplary card movement mechanisms include a conveyor belt, a ratchet mechanism, a sliding ramp, or a card gripping or pulling mechanism. As the multiple-profile reagent card moves or advances along the travel surface and is positioned at a sample dispensing position, one or more pipettes (e.g., manually or automatically) deposit one or more sample volumes onto one or more of the reagent pads on the reagent card. The reagent pads are then placed at one or more read positions and analyzed (e.g., manually or automatically) to evaluate the test results. The reagent card is placed within the field of view of an imaging system, e.g., an optical imaging system, microscope, or spectrometer, and one or more images of the reagent pads on the card (e.g., light signals indicative of the color of the reagent pads) are captured and analyzed. Typically, the field of view of the imaging system is relatively large, allowing for the capture of multiple images of the same reagent pad as the reagent card is moved or advanced through multiple reading positions within the field of view of the imaging system. The field of view includes multiple reading positions or locations, and each reagent pad moves incrementally through these reading positions as the reagent card progresses through the field of view of the imaging system. As the analyzer moves the card between various reading positions at known time intervals, for example, multiple images obtained within the field of view of the imaging system allow the analyzer to determine a change in color of the reagent pad as a result of the reagent pad reacting with the sample at each reading position depending on the time it takes for the pad to move to each reading position. Finally, the used card is removed from the analyzer and appropriately disposed of.

[0013] Existing problems with optical imaging systems used with automated analyzers include uneven illumination of the relatively large field of view of the optical imaging system, vignetting effects of the camera lens used, noise from the large aspect ratio of the reagent test device, and light scattering between the test device and the imaging system. These factors can result in non-uniform images. However, one of these requirements of most colorimetric analysis modules is uniform illumination intensity in the acquired image across the test device. However, correction using image processing does not improve the signal-to-noise ratio (SNR). Light scattering in existing optical imaging systems can further reduce the signal-to-noise ratio by introducing noise into the image.

[0014] Specular reflection is a specular reflection from a surface and is not related to the material below the surface. In an analyzer, specular reflection can be caused by the surface of the test sample and / or the test device being wet. When specular reflection occurs, such reflection can confound measurements due to bright specular spots that are unrelated to the signal due to the absorption of light in the reagent pad. Specular scattering interferes with the measurement of reflected light from the reagent pad by adding an extraneous variable signal that is unrelated to the analyte concentration, making measurements related to the analyte concentration inaccurate. Crossed polarizers to reduce interference from specular reflection are discussed in U.S. Pat. No. 5,399,343. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] U.S. Patent No. 3,123,443 [Patent Document 2] U.S. Patent No. 3,212,855 [Patent Document 3] U.S. Patent No. 3,814,668 [Patent Document 4] U.S. Patent No. 4,526,753 [Patent Document 5] U.S. Patent No. 4,890,926 Summary of the Invention [Problem to be solved by the invention]

[0016] Thus, there is a need in the art for an analyzer that provides controlled illumination and reduces the effects of light scattering, thereby increasing the signal-to-noise ratio.The inventive concepts disclosed herein are directed to such a reagent analyzer. [Means for solving the problem]

[0017] In one embodiment, the inventive concept disclosed herein is a reagent analyzer that addresses the deficiencies of the prior art discussed above. The reagent analyzer includes a circuit board, an imaging system, and a processor. The circuit board includes a substrate and a plurality of conductive leads extending on or into the substrate. The substrate has a first major surface and a second major surface, the first major surface being located opposite the second major surface. The substrate has an opening extending between the first major surface and the second major surface. The reagent analyzer also includes an imaging system, the imaging system having a field of view extending through the opening formed in the substrate and configured to capture an image of a wet reagent test device positioned at a read position within the field of view, the image having a plurality of pixels. The processor is configured to receive the image and analyze the pixels of the image to determine the presence or absence of a target component in a sample applied to the wet reagent pad.

[0018] To assist those skilled in the art in making and using the inventive concepts disclosed herein, reference is made to the accompanying drawings and schematic diagrams, which are not intended to be drawn to scale, and where like reference numbers are intended to refer to the same or similar elements for consistency. For clarity, not every component is shown in every drawing. For clarity and conciseness, certain configurations and certain features of these figures may be exaggerated and not drawn to scale, or may be shown in schematic form. [Brief description of the drawings]

[0019] [Figure 1] 1 is a front view of an exemplary embodiment of an analyzer in accordance with the inventive concepts disclosed herein showing a test device, such as a reagent card, positioned within the field of view of its imaging system. [Diagram 2] FIG. 2 is a side view of the analyzer of FIG. [Diagram 3] FIG. 13 is a bottom view of a circuit board having an opening surrounded by a built-in light source in accordance with the inventive concepts disclosed herein to facilitate controlled illumination of the reagent card and reduce light scattering detected by the imaging system. [Figure 4] 1 is a table showing example power levels, x, y, and z positions, and angles for a test device for a built-in light source in accordance with the inventive concepts disclosed herein. [Diagram 5] FIG. 1 illustrates an illumination graph with and without light source optimization according to the inventive concepts disclosed herein. [Figure 6] FIG. 1 is a diagram of an exemplary test device that can be read by an analyzer in accordance with the inventive concepts disclosed herein. [Figure 7] FIG. 1 illustrates an exemplary embodiment of a reagent analyzer having a controller. [Figure 8] 4 is a flow diagram of an exemplary embodiment of a calibration routine. [Figure 9] FIG. 2 is a side view of an exemplary embodiment of a reagent analyzer having a first polarizer and a second polarizer. [Figure 10] FIG. 2 is an exploded orthogonal view of a circuit board and a first polarizer. [Figure 11] FIG. 1 shows a first polarizer filtering and transmitting light towards the sample, which reflects the light towards the second polarizer, which filters and transmits the light towards the camera. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Before describing in detail at least one embodiment of the inventive concepts disclosed herein, In particular, it is to be understood that the inventive concepts are not limited in their application to the details of construction and arrangement of the components or steps or methods set forth in the following description or illustrated in the drawings. The inventive concepts disclosed herein are capable of other embodiments or of being practiced or carried out in various ways. It is also to be understood that the terms and terminology used herein are for the purpose of description and should not be construed in any way to limit the inventive concepts disclosed and claimed herein.

[0021] In the following detailed description of embodiments of the inventive concept, numerous specific details are set forth in order to provide a more thorough understanding of the inventive concept. However, it will be apparent to those skilled in the art that the inventive concept disclosed herein may be practiced without these specific details. In other instances, well-known configurations are not described in detail in order to not unnecessarily complicate the present disclosure.

[0022] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," or any other variation thereof, are intended to be non-exclusive inclusive. For example, a process, method, article, or apparatus that includes a list of elements is not necessarily limited to only those elements but may include other elements that are not expressly listed or are not inherently present.

[0023] Unless expressly stated to the contrary, "or" refers to an inclusive rather than an exclusive disjunction. For example, a condition A or B is satisfied by one of the following: A is true (or present) and B is false (or absent), A is false (or absent) and B is true (or present), or both A and B are true (or present).

[0024] In addition, elements and components of the embodiments herein are described by the use of "a" or "an." This is done merely for convenience to give a general sense of the inventive concept. This description should be interpreted as including one or at least one, and the singular also includes the plural, unless it is clear that something else is meant.

[0025] Moreover, any reference herein to "one embodiment" or "an embodiment" means that a particular element, configuration, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. References to the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment.

[0026] As used herein, a "wet reagent test device" refers to a reagent device having a volume of sample deposited thereon such that a reagent in the reagent device can react with its target component if such component is present in the sample. Wet reagent test devices can also deposit a negative control volume.

[0027] As used herein, a "reagent test device" refers to a carrier having a reagent. Exemplary reagent devices include the reagent pad of a dip-and-read test strip, or a control strip or test strip of a lateral flow immunoassay.

[0028] Finally, as used herein, modifiers such as "about," "approximately," and "substantially" are intended to mean that the modified item is not limited to the exact value specified, but also includes minor variations or deviations from that value caused by, for example, measurement errors, manufacturing tolerances, stresses experienced by various components, wear and tear, and combinations thereof.

[0029] The inventive concepts disclosed herein are directed generally to analyzers for reagent cards, and more particularly, but not limited to, analyzers that provide controlled illumination within acceptable limits and increase the signal-to-noise ratio by reducing the effects of light scattering. Examples of controlled illumination include, but are not limited to, uniform illumination, spot, flash, or time-varying illumination within acceptable limits. Although the inventive concepts disclosed herein are primarily described in the context of automated analyzers using multiple-profile reagent cards, the inventive concepts disclosed herein are not limited to automated analyzers or multiple-profile reagent cards. For example, as will be appreciated by one of ordinary skill in the art having the benefit of this disclosure, methods according to the inventive concepts disclosed herein can be implemented by manual analyzers or automated analyzers using reagent test devices such as lateral flow immunoassays, dip-and-read reagent test devices, or reels of reagent test devices on a substrate, and combinations thereof. Additionally, the inventive concepts disclosed herein can be implemented by any reagent device imaging system having at least one read position within a field of view.

[0030] In particular, when the reagent-testing device becomes wet, a signal value indicating the color of the reagent-testing device, such as a reagent pad, control line, or test line, changes. For negative solutions, the change in signal value is known (or can be measured) and can therefore be an optional offset signal value. Any change outside the range of offset signal values ​​is likely caused by a reaction with the clinical component being measured.

[0031] 1-2, an exemplary embodiment of a reagent analyzer 10 in accordance with the inventive concepts disclosed herein is shown. The reagent analyzer 10 may be, for example, an automated reagent card analyzer. Exemplary embodiments of an automated reagent card analyzer are described in detail in U.S. patent application Ser. No. 13 / 712,144, filed Dec. 12, 2012, and PCT application PCT / US2012 / 069621, filed Dec. 14, 2012, the disclosures of which are expressly incorporated herein by reference in their entireties.

[0032] Generally, the reagent analyzer 10 may include a housing 14 enclosing a cavity 18, an imaging system 22 including at least a camera 26, a sample tray 30 having a sample holder 32 disposed within the cavity 18, and a circuit board 34 having an opening 38 (also referred to as a first opening) and one or more illumination sources 42a-n disposed within the cavity 18.

[0033] The housing 14 can be formed from one or more components configured to form a cavity 18 and support the imaging system 22, the sample tray 30, and the circuit board 34. In one embodiment, the housing is opaque to visible light. In another embodiment, the housing is opaque to one or more wavelengths of light generated by the one or more illumination sources 42a-n. In one embodiment, the housing 14 can normalize to ambient light.

[0034] The imaging system 22 includes at least one camera 26 and is supported by the housing 14. In one embodiment, the imaging system 22 may be fixed to the housing 14, for example, or may be fixed at a relative distance from the sample tray 30. The imaging system 22 and / or the camera 26 may include one or more lenses having a focal length selected to provide a field of view 40 to include at least the opening 38 in the circuit board 34.

[0035] The imaging system 22 may be implemented and function as any desired reader such that, for example, the field of view 40 of the imaging system 22 includes substantially the entirety of the opening 38 in the circuit board 34. The imaging system 22 may be supported at a location above, below, or adjacent to the sample tray 30. In some embodiments, the field of view 40 may extend in a linear direction from the imaging system 22 to the opening 38. In other embodiments, the field of view 40 may extend in a non-linear direction from the imaging system 22 to the opening 38 due to the presence of one or more optical steering components in the field of view 40. Exemplary optical steering components include mirrors, lenses, beam splitters, or combinations thereof. The imaging system 22 may be configured to detect or capture images or light signals indicative of, for example, reflectance or color values ​​of a reagent pad disposed within the field of view 40 of the imaging system 22 (as shown in FIG. 6 and discussed in more detail below). However, it should be understood that in some exemplary embodiments, the field of view 40 of the imaging system 22 may include only a portion of the opening 38 of the circuit board 34. The camera 26 of the imaging system 22 may include any desired digital or analog imaging device, such as a digital camera, an analog camera, a CMOS imager, a diode, and combinations thereof. The imaging system 22 may also include, for example, a lens system, optical filters, collimators, diffusers, or any other optical signal processing devices. Additionally, the imaging system 22 is not limited to optical imagers in the visible spectrum, but may include, for example, infrared imaging systems, ultraviolet imaging systems, microwave imaging systems, x-ray imaging systems, and / or other desired imaging systems. Non-exclusive examples of the imaging system 22 include, for example, optical imaging systems, spectrophotometers, gas chromatographs, microscopes, infrared sensors, and combinations thereof.

[0036] In one embodiment, the imaging system 22 includes at least one camera 26 and a lens, where the at least one camera 26 is an OnSemi MT9D131 CMOS sensor (ON Semiconductor, Phoenix, Arizona) and the lens is a DSL949 Sunex lens (Sunex Inc., Carlsbad, CA), both configured to maintain a wide field of view 40 while reducing geometric image distortion, thereby providing a resolution of 1600 pixels by 1200 pixels, with each pixel representing an approximately 0.065 mm square area of ​​the sample tray 30 and / or sample holder 32.

[0037] The sample tray 30 can be configured to adjust the location of the sample holder 32 within the field of view 40. The sample holder 32 can be configured to receive at least one of the test devices 44, which can be reagent cards and reagent card cassettes, each having a sample 46. The sample 46 can be, for example, any bodily fluid, such as urine, saliva, or blood, tissue, or any other chemical or biological sample, and combinations thereof. The sample 46 can be, for example, in a liquid form, and can contain one or more target components, such as bilirubin, ketones, glucose, or any other desired target component.

[0038] A circuit board 34 having an opening 38 may be positioned within the cavity 18 to be placed between the imaging system 22 and the sample tray 30 such that the field of view 40 of the imaging system 22 is substantially unobstructed from the sample holder 32, the test device 44, and / or the sample 46. The circuit board 34 is described in more detail in FIG. 3 and below. In one embodiment, the circuit board 34 is located in a fixed location between the imaging system 22 and the sample tray 30, however, in another embodiment, the circuit board 34 may be adjusted to varying locations between the imaging system 22 and the sample tray 30. If the circuit board 34 is adjustable, a calibration routine 170 (described below) should be performed after any adjustment.

[0039] Illumination sources 42a-n may be, for example, light emitting diodes, light bulbs, lasers, incandescent light bulbs or tubes, fluorescent light bulbs or tubes, halogen light bulbs or tubes, or any other desired light source configured to emit light signals having any desired intensity, wavelength, frequency, or direction of propagation. or objects. The illumination sources 42a-n can be mounted on the circuit board 34 and oriented such that substantially the entire field of view 40 of the imaging system 22 is illuminated by the illumination sources 42a-n. In some exemplary embodiments, the illumination sources 42a-n can be operatively coupled to a controller 144 (see FIG. 7, described in more detail below), such that control and / or power signals can be provided to the illumination sources 42a-n by the controller 144. It is desirable for the intensity of the optical signals emitted by the illumination sources 42a-n to be maintained substantially constant throughout operation of the reagent analyzer 10, such as by the control and power signals provided by the controller 144. In one embodiment, the optical signals emitted by the illumination sources 42a-n can be conditioned or processed by one or more optical or other systems (not shown), such as, for example, filters, diffusers, polarizers, lenses, lens systems, collimators, and combinations thereof.

[0040] In some exemplary embodiments, one or more illumination sources 42a-n may be implemented, such as a first illumination source 42a and a second illumination source 42b, which may have different locations and / or orientations, whereby the first illumination source 42a and the second illumination source 42b cooperate to illuminate substantially the entire field of view 40 of the imaging system 22 (e.g., substantially the entire sample holder 32 and / or sample 46). The first illumination source 42a and the second illumination source 42b may, for example, emit light signals having different illumination intensities.

[0041] In one embodiment, the sample holder 32 can be adapted to receive a test device 44 in the form of, for example, a reagent card cassette having one or more multi-profile reagent cards. Each reagent card (described in more detail below) can include a substrate and one or more reagent pads disposed on or otherwise associated with the substrate. In an exemplary embodiment, the reagent pads can include fluidic or microfluidic compartments (not shown).

[0042] Each reagent pad may include a reagent configured to produce a color change in response to the presence of a target component, such as a molecule, cell, or substance, in a specimen sample 46 deposited on the reagent pad. Different reagents may be provided in the reagent pads to detect the presence of different target components. The different reagents may produce one or more color changes in response to the presence of a particular component in the sample 46, such as a particular type of analyte. The color produced by the reaction of a particular component to a particular reagent may define a distinct spectrum characteristic of the light absorption and / or reflection for that particular component. The extent of the color change of the reagent and sample 46 may depend, for example, on the amount of the target component present in the sample 46.

[0043] The presence and concentration of these target components in sample 46 may be determinable, for example, by analysis of the color change produced by one or more reagent pads after a predetermined time after application of sample 46 to the reagent pads and / or at a predetermined read location within the field of view 40 of imaging system 22. This analysis may involve a color comparison of each reagent pad after different time periods after application of sample 46 and / or at different read locations within the field of view 40 of imaging system 22.

[0044] Based on an analysis of the magnitude of the optical signals detected by the imaging system 22, the sample 46 may be classified into one of a number of categories, e.g., a first category corresponding to the absence of the target component in the sample 46, a second category corresponding to a low concentration of the target component present in the sample 46, a third category corresponding to a medium concentration of the target component present in the sample 46, and a fourth category corresponding to a high concentration of the target component present in the sample 46. , sample 46 can be assigned.

[0045] Additionally, the imaging system 22 can detect light signals indicative of the color or reflectance value of a reagent pad and / or test strip at any time interval after a volume of sample 46 is dispensed onto the testing device 44, e.g., the reagent pad and / or test strip, regardless of the location of the particular reagent pad and / or test strip. In one exemplary embodiment, a video or series of images of the reagent pad and / or test strip can be captured at various time intervals after a volume of sample 46 is deposited onto the reagent pad and / or test strip.

[0046] The imaging system 22 may be operated intermittently, continuously, or periodically, for example, to detect one or more reflectance signals indicative of the color or reflectance value of one or more test devices 44, e.g., reagent pads, at any time and at any location within the field of view of the camera 26. In some exemplary embodiments, the imaging system 22 may capture an image indicative of the color or reflectance value of a test device 44, e.g., a reagent pad, before any sample 46 is deposited on the reagent pad or at any known time after a volume of sample 46 has been deposited on the reagent pad.

[0047] 3, there is shown a bottom view of a circuit board 34 having an aperture 38 surrounded by one or more illumination sources 42a-n in accordance with the inventive concepts disclosed herein to facilitate controlled illumination of the sample holder 32 and / or sample 46 and reduce light scattering detected by the imaging system 22. Controlled illumination is described herein by way of example as uniform illumination across the extent, i.e., length and width, of the sample holder 32 and / or sample 46 within acceptable limits. However, it should be understood that the present disclosure is not limited to uniform illumination. The circuit board 34 includes a substrate 60 having a bottom surface 61a and a top surface 61b, a plurality of conductive leads extending on or into the substrate 60, and an aperture 38 extending between the bottom surface 61a and the top surface 61b.

[0048] The circuit board 34 shown in FIG. 3 depicts a bottom side 61a of the circuit board 34 having one or more illumination sources 42a. When placed in the reagent analyzer 10, the bottom side 61a is oriented to face the sample tray 30, and thus can provide light generated by the one or more illumination sources 42a-n directly to the sample holder 32 and / or the sample 46. The illumination sources 42a-n are connected to a plurality of conductive leads of the circuit board 34, which thus provide electricity to each illumination source 42a-n. In one embodiment, the circuit board 34 further includes an illumination source circuit (not shown) connected to the plurality of conductive leads, the illumination source circuit configured to apply electricity independently of each illumination source 42a-n. For example, the illumination source circuit can be configured to provide a first power to the first illumination source 42a and a second power to the second illumination source 42b, where the first power and the second power are different, thereby causing a difference in illumination intensity across the sample. The illumination sources 42a-n are positioned to provide a substantially uniform illumination intensity across the field of view 40 of the camera 26, thereby illuminating the reagent pad with a substantially uniform intensity, thereby increasing the accuracy of reading the color change of the reagent pad (as shown below and in more detail in FIG. 5). As shown in FIG. 3, the substrate 60 of the circuit board 34 is substantially planar, whereby each of the one or more illumination sources 42a-n is located a similar distance from the sample tray 30. Depending on the location of the illumination source 42a-n relative to the sample 46, the distance between the illumination source 42a-n and the sample 46 may be different for some of the illumination sources 42a-n. However, in other embodiments, the circuit board 34 may be non-planar, whereby one or more of the illumination sources 42a-n are located a different distance from the sample tray 30. In one embodiment, the one or more illumination sources 42a-n may be mounted on posts (not shown), with each post mounted to the circuit board 34 and providing one or more conductive paths to a particular one of the illumination sources 42a-n. When a support is used, this This brings a portion of one or more illumination sources 42a-n closer to the sample 46 and / or sample tray 30.

[0049] In one embodiment, the substrate 60 has a first region 62a, a second region 62b opposite the first region 62a, and an intermediate region 62c between the first region 62a and the second region 62b. One or more illumination sources 42a-n may be attached to the substrate 60 in each of the first region 62a, the second region 62b, and the intermediate region 62c, or in some combination thereof. In one embodiment, a first power may be applied to one or more illumination sources 42a-n in the first region 62a and the second region 62b, such that the one or more illumination sources 42a-n in the first region 62a and the second region 62b may provide a first illumination intensity, and a second power may be applied to one or more illumination sources 42a-n in the intermediate region 62c, such that the one or more illumination sources 42a-n in the intermediate region 62c may provide a second illumination intensity, where the first power and the second power are different, and the first illumination intensity and the second illumination intensity are different.

[0050] The opening 38 extends from the top surface 61b to the bottom surface 61a and provides an aperture for the field of view 40 of the imaging system 22 to pass from the imaging system 22 to the sample holder 32 and provides the camera 26 with a controlled view of the test device 44 associated with the sample holder 32. The opening 38 may be further configured such that the bottom surface 61a of the circuit board 34 may include one or more illumination sources 42a-n on each side of the opening 38. In one embodiment, the opening 38 is located substantially within the intermediate region 62c. In one embodiment, the opening 38 has a first major axis and a first minor axis, the sample holder 32 has a second major axis and a second minor axis, and the first major axis is aligned with the second major axis. 3 as a rectangle to provide a controlled field of view of a rectangular reagent test device, it will be understood that the opening 38 can be configured in any shape such that the field of view 40 is a controlled field of view of the sample tray 30, and the illumination source 42 can be calibrated to provide substantially uniform illumination of the sample 46. In the example of FIG. 3, the opening 38 does not extend to the edge of the circuit board 34.

[0051] In one embodiment, opening 38 extends to the edge of circuit board 34 without bisecting circuit board 34, while in another embodiment opening 38 extends through the entire circuit board 34 and bisects the circuit board into first and second halves, which are mounted in separate locations and supported by housing 14 such that field of view 40 is a controlled field of view of the sample tray and illumination source 42.

[0052] In one embodiment shown in FIG. 3, the one or more illumination sources 42a-n are a plurality of LEDs 64a-n and one or more infrared LEDs 68a-n. The LEDs 64a-n shown in FIG. 3 include 20 visible light LEDs arranged as shown in FIG. 3 and one or more infrared LEDs 68. The LEDs 64a-n include any LEDs required to produce a substantially uniform light intensity across the sample holder 32 and / or reagent card or cassette. The infrared LEDs 68 can be used, for example, to apply heat to the sample 46 or to identify an ID pad on the test device 44. In one embodiment, the ID pad is utilized to correlate the sample on the test device supported by the sample holder 32 to data acquired by the reagent analyzer 10.

[0053] In one embodiment, the plurality of LEDs 64a-n are selected to provide a fixed color, visible light, ultraviolet light, infrared light, or white light, or some combination thereof. In another embodiment, each LED 64a-n is positioned at an angle relative to the reagent card. In yet another embodiment, each LED 64a-n is positioned one or more distances away from the test device 44 supported by the sample holder 32, such that the first LED 64 and the second LED 64 are spaced apart from each other by a distance of 0.05 mm. The LEDs 64 are positioned at different distances from the test device 44 and / or the sample holder 32 .

[0054] 4-5, FIG. 4 shows a table 80 indicating power level 84, x-position 88, y-position 90, z-position 92, and relative angle 94, which is the angle with respect to the sample holder 32 for each LED 64a-t, and FIG. 5 shows an illumination intensity graph 100, where an optimized normalized illumination intensity measurement 104 shows the optimization of the LEDs 64a-t, and an unoptimized illumination intensity measurement 108 shows the LEDs 64a-t that have not been subjected to optimization according to the inventive concepts disclosed herein. By adjusting the power level of each LED 64, a substantially uniform light intensity is achieved as shown in the optimized illumination intensity measurement 104. The substantially uniform light intensity can be between 85% and 100% uniform. In the example shown in FIG. 5, the optimized normalized illumination intensity is between 85% and 95%.

[0055] Referring now to FIG. 6, there is shown a diagram 120 of a portion of an exemplary test device 44 in the form of a reagent card 124 that can be read by a reagent analyzer 10 in accordance with the inventive concepts disclosed herein.

[0056] The reagent card 124 can include a substrate 128 and one or more or a plurality of reagent pads 132a-n disposed on or otherwise associated with the substrate 128. The substrate 128 can be constructed of any suitable material, such as, for example, paper, photographic paper, polymers, fibrous materials, and combinations thereof. The reagent pads 132a-n can be arranged on the substrate 128 in a grid-like configuration, for example, to define one or more test strips. In an exemplary embodiment, the reagent pads 132a-n can include fluidic or microfluidic compartments (not shown). The reagent pads 132a-n can be spaced apart from one another, for example, such that the test strips are spaced apart, such that adjacent test strips and / or reagent pads 132a-n can be simultaneously positioned at separate locations within the field of view 40 of the imaging system 22. The reagent card 124 can be a multi-profile reagent card having multiple reagent pads 132a-n with different reagents and / or multiple different test strips. Additionally, in some exemplary embodiments, the reagent card 124 can include, for example, one or more calibration chips or reference pads, which do not have reagents and can act as color standards. In another embodiment, the reagent card 124 includes an ID pad having an identifier that is visible under infrared light.

[0057] Each reagent pad 132a-n may include a reagent configured to produce a color change in response to the presence of a target component, such as a molecule, cell, or substance, in the specimen sample 46 deposited on the reagent pad 132a-n. Different reagents may also be provided on the reagent pads 132a-n to detect the presence of different target components. The different reagents may produce one or more color changes in response to the presence of a particular component in the sample 46, such as a particular type of analyte. The color produced by the reaction of a particular component to a particular reagent may define a distinct spectrum characteristic of the light absorption and / or reflection for that particular component. The extent of the color change of the reagent and sample may depend, for example, on the amount of the target component present in the sample 46.

[0058] The color change can be read by the imaging system 22. Signals indicative of the color of the reagent pads 132a-n can be received by the imaging system 22, which can analyze those signals to determine a color change in the reagent pads 132a-n that occurs as a result of the reagent pads 132a-n reacting with a volume of sample 46 deposited on the reagent pads 132a-n. Such a color change can be, for example, The color change can be analyzed according to the read position of the reagent pad 132a-n when the indicative optical signal or image was detected, and / or the known duration that the volume of sample 46 was deposited on the reagent pad 132a-n, and combinations thereof. The color change can be interpreted as a quantitative, qualitative, and / or semi-qualitative indication of the presence and / or concentration or amount of the target component within the volume of sample 46 deposited on the reagent pad 132a-n, as described above.

[0059] 7, an analyzer diagram 140 is shown depicting a reagent analyzer 10 including an analyzer controller 144. The analyzer controller 144 has at least a processor 148 and a non-transitory computer readable memory 152. The memory 152 can store computer executable instructions that, when executed by the processor 148, cause the processor 148 to communicate with and / or be operatively coupled to other elements of the reagent analyzer 10. Although the analyzer controller 144 is depicted separate from the reagent analyzer 10, it will be understood that in some embodiments the analyzer controller 144 can be integrated into the reagent analyzer 10, for example, for purposes of illustration only, the analyzer controller 144 can be an additional component of the reagent analyzer 10 or can be integrated with another component of the reagent analyzer 10, such as the circuit board 34.

[0060] In one embodiment, the imaging system 22 can be operatively coupled to, for example, the analyzer controller 144 and / or the processor 148 such that the controller 144 can transmit one or more power and / or control signals to the camera 126 and / or one or more illumination sources 42a-n and transmit one or more signals from the camera 126 to the processor 148. The analyzer controller 144 can be configured to evaluate a test result when a reagent card is extracted within the reagent analyzer 10, for example, by receiving one or more signals from the camera 126. The camera 126 can be configured to detect or capture one or more optical or other signals indicative of a reflectance value of a test device 44, such as, for example, a reagent pad, and transmit signals indicative of the reflectance value of the test device 44, e.g., a reagent pad, to the processor 148. For example, the camera 126 can detect one or more optical signals having wavelengths indicative of a reflectance value of the reagent pad and / or test strip at each read location. The camera 126 can detect, for example, optical signals indicative of the reflectance value of the reagent pad and / or test strip at any desired read position, location, or area within the field of view 40, or any other desired location or areas. The signals transmitted by the camera 126 to the processor 148 can be, for example, electrical signals, optical signals, and combinations thereof. In one embodiment, the signals are in the form of an image file having a matrix of pixels, each pixel having a color code indicative of a reflectance value. In an exemplary embodiment, the image file can have two or more predefined regions of pixels, each predefined region of pixels corresponding to a read position of one of the reagent pads and / or test strips within the field of view 40 of the camera 126. In one embodiment, the processor 148 can store the transmitted signals and / or image files in one or more databases 156 and / or memory 152.

[0061] The processor 148 can, for example, determine a reflectance or color change of the reagent pad and / or test strip along with a sample (e.g., urine) placed thereon based on signals detected by the camera 126. Each optical signal or other signal indicative of one or more reflectance readings detected by the camera 126 can have a magnitude related to a different wavelength of light (i.e., color). The color of the sample and / or the one or more test strips for the target component in the reagent pad can be determined. The drug response can be determined based on the relative magnitudes of the reflected signals of various color components, e.g., red, green, and blue reflected component signals. For example, the color of each reagent pad can be converted to a standard color model, which typically includes three or four values ​​or color components that combine to represent a particular color (e.g., the RGB color model, which includes hue, saturation, and brightness (HLS) and hue, saturation, and value (HSV) point representations, and / or the CMYK color model, or any other suitable color model). In some embodiments, the camera 126 can detect multiple light signals at each reading position, each detected signal having one or more color components, e.g., a red component signal, a green component signal, and a blue component signal, and each of these component signals can be transmitted to the processor 148. In some exemplary embodiments, for example, the camera 126 can detect a single light signal at each reading position, and the processor 148 can convert the signal received from the camera 126 into separate color component signals, e.g., a red component signal, a green component signal, and a blue component signal.

[0062] In one embodiment, the processor 148 can select or otherwise designate a reagent pad as a reference reagent pad and reference each of the remaining reagent pads to the reference reagent pad, thereby calculating a calibration factor for each reagent pad at each read location based on the ratio of the reflectance value of the optical signal or image detected at the reference reagent pad to the respective optical signal or image detected at each reagent pad by the camera 126. Additionally, in some exemplary embodiments, rather than selecting a reference reagent pad, each reagent pad can be referenced to a conceptual color or color standard for each reagent pad, as will be appreciated by those skilled in the art.

[0063] Calibration routine 170 (described below and shown in FIG. 8 ) may be implemented as a set of processor-executable instructions or logic stored on non-transitory computer-readable medium 154 that, when executed by processor 148, causes processor 148 to perform logic to calculate or determine calibration coefficients. Calibration routine 170 may be performed periodically, for example, at preset time intervals, with each new lot of reagent cards, when desired in accordance with specific quality control procedures applicable to reagent analyzer 10, and combinations thereof.

[0064] 8, an exemplary process flow diagram of a calibration routine 170 is shown, which generally comprises the steps of: acquiring at least one image of a calibration test strip, where only one of the one or more illumination sources is enabled for each image (step 174); pre-processing the image (step 178); updating the "A" matrix with the pre-processed image (step 182); determining intensity values ​​for each of the one or more illumination sources 42a-n (step 186); generating an illumination source intensity file (step 190); acquiring test images of the calibration test strip using the illumination source intensity file (step 194); and determining a non-uniformity value (step 198). The calibration routine 170 is used to maximize light intensity uniformity with the minimum number of illumination sources 42a-n required and to determine the illumination source status for each illumination source 42a-n on the circuit board 34. The calibration routine 170 is described below with each illumination source 42a-n as an LED 64a-n, although it is understood that each LED 64a-n may be replaced with other illumination sources 42a-n. Further, for example, the illumination source status for each LED may be stored as LED status data, which may include data describing the LED, such as intensity, power level, location, LED identifier, and / or combinations thereof.

[0065] At step 174, the camera 126 may detect a first light signal or a first image indicative of a reflectance value of a calibration test strip disposed within the sample holder 32 with the first LED 64a enabled and, for example, all remaining LEDs 64b-t disabled. In one embodiment, the camera 126 can detect an image having pixel regions with colors or reflectance values ​​representative of the color of the calibration test strip and transmit such image to the controller 144. The camera 126 can then detect a second image different from the first image or a second light signal different from the first light signal indicative of the reflectance value of the calibration test strip position in the sample holder 32 with the second LED 64b enabled and, for example, all remaining LEDs 64a and 64c-t disabled. The calibration test strip can be a dry reagent card having one or more dry reagent pads. Each image can include metadata stored therein, such as an LED identifier associated with an LED 64 having an enabled state, i.e., a state in which the LED power level is set to a value that enables the LED to generate light. Because no sample is deposited on the calibration test strip, no reaction occurs and the color of the calibration test strip should be uniform across the calibration test strip. Thus, the difference in reflectance values ​​detected in the first image and the second image is due to non-uniform illumination.

[0066] At step 178, each image is pre-processed. Pre-processing may include one or more modifications of each image to enable comparison between the images. For example, pre-processing may include rotating the image and / or cropping the image so that only a portion of the image is utilized in the calibration routine 170.

[0067] In step 182, the "A" matrix is ​​updated with the pre-processed image. In the "A" matrix, the i-th column of "A" is the intensity distribution of the i-th LED powered illumination intensity or brightness on the object plane (e.g., the plane corresponding to the top surface of the reagent card). The vignetting V can be calibrated separately. Similarly, A i The i-th column of is the illumination intensity distribution of the i-th LED measured at unit power in the image plane.

[0068] An example "A" matrix is ​​P 1×m =V m×m Am×n W 1×n It can be described in matrix form as, where v is the vignetting function, w is the LED illumination intensity or brightness, m is the number of grid points on the object and image planes, and n is the number of LEDs. To adapt the image plane intensity, we use the weights w i needs to be determined.

[0069] For a single LED placed on an object plane with a radiant intensity distribution given by L(q), the irradiance at any point (x,y) on the plane is:

number

number

[0070] Illumination by one or more uniformly powered LEDs tapers at the edges of the object plane, which is the image plane, exacerbated by vignetting. To obtain uniform illumination intensity, the LED power is increased for LEDs closer to the edges of the object plane, thus increasing the illumination intensity. In one embodiment, adjusting the power of each LED is performed by using different current limiting resistors and / or pulse width modulation.

[0071] At step 186, the number of LEDs, LED positions, and and for a given vector, 0 ≤ w ≤ w to optimize the LED lighting intensity or brightness. max Subject to, c 1×m and A I =VA minimize(||A IAn optimization problem is solved where λ||w||1) is the total incident power, λ||w ... cvx_begin variable w(led.count) minimize(norm(A*wb)) subject to 0<=w<=1 cvx_end

[0072] At step 190, the LED intensities are compiled into an LED intensity file and stored by the processor 148 in the memory 152, database 156, or another suitable storage medium, or a combination thereof. The LED intensity file may store LED state data for each of the LEDs 64a-t. The LED intensities may be stored in the LED intensity file as a single LED intensity for each LED 64a-n, or as LED intensities for each channel of a desired color model. For example, a red component LED intensity, a green component LED intensity, and a blue component LED intensity may be stored for each LED 64a-t and for each channel of an RGB color model or any other desired color model.

[0073] At step 194, the camera 126 may detect a test light signal or capture a test image indicative of a reflectance value of a calibration test strip placed in the sample holder 32, for example, with each LED 64a-t enabled per the unique LED state data in the LED intensity file. The camera 126 may detect a test image having a region of pixels having a color or reflectance value representative of the color of the calibration test strip, and transmit such image to the controller 144.

[0074] At step 198, the controller 144 may evaluate the test image to determine a non-uniformity value. The non-uniformity value may be expressed as a percentage of illumination intensity non-uniformity in the test image. In an exemplary embodiment, the non-uniformity percentage is less than 5%. If the non-uniformity percentage is greater than 5%, the controller 144 may indicate a failure to successfully complete the calibration routine 170, attempt to re-run the calibration routine 170, and / or some combination of these, or may do nothing.

[0075] Additionally, as will be appreciated by those skilled in the art, for example, to reduce downtime for the reagent analyzer 10, the calibration routine 170 can be performed on one or more calibration test strips on the reagent card, with the remaining test strips being used to test samples as described above. In one embodiment, the reagent analyzer 10 can determine a non-uniformity value before a sample is analyzed to verify the current calibration. If it is determined that the reagent analyzer 10 is not calibrated, the calibration routine 170 can be executed.

[0076] 9, there is shown a diagram of an exemplary embodiment of a reagent analyzer 10a constructed similarly to the reagent analyzer 10 discussed above, but with a first polarizer 202a and a second polarizer 202b. Elements common between the reagent analyzer 10 and the reagent analyzer 10a are indicated with the same reference numbers. The first polarizer 202a and the second polarizer 202b can be linear absorbing (or dichroic) polarizing filters constructed from any suitable material, such as, for example, polyvinyl alcohol (PVA), cellulose triacetate (CTA), and combinations thereof.

[0077] The first polarizer 202a can have a first transmission axis 206a, a first boundary 210a, a second boundary 210b opposite the first boundary 210a, and an opening 214 (also referred to herein as a second opening), and can be disposed within the cavity 18 and positioned between the circuit board 34 and the sample holder 32 such that light generated by one or more illumination sources 42a-n is provided to the first boundary 210a and a portion of the light passes through the first polarizer 202a and the second boundary 210b. In some embodiments, the light generated by the one or more illumination sources 42a-n is provided directly to the first boundary 210a.

[0078] When light is provided to the first boundary 210a, the first polarizer 202a can be configured to transmit a portion of the light that is linearly polarized parallel to the first transmission axis 206a out of the second boundary 210b and to absorb a portion of the light that is linearly polarized perpendicular to the first transmission axis 206a.

[0079] In one embodiment, the first polarizer 202a is mounted to the bottom surface 61a of the circuit board 34 and covers one or more illumination sources 42a-n, and in another embodiment, the first polarizer 202a is mounted within the cavity 18 below the circuit board 34 and above the sample holder 32.

[0080] The second opening 214 can be aligned (i.e., overlap) with the first opening 38. The second opening 214 can extend from the first boundary 210a to the second boundary 210b and can be aligned with the first opening 38 to allow a field of view 40 of the imaging system 22 to pass from the imaging system 22 through the circuit board 34 and the first polarizer 202a to the sample holder 32 and provide a controlled field of view of the test device 44 associated with the sample holder 32 to the camera 26. The second opening 214 can be configured in any shape such that the field of view 40 is a controlled field of view of the sample holder 32 and light generated by one or more illumination sources 42a-n is provided to the first polarizer 202a.

[0081] For example, in some embodiments, the first polarizer 202a includes multiple separate polarizers that cover one or more of the one or more illumination sources 42a-n. In this embodiment, the second opening 214 may be formed by eliminating the separate polarizer that was aligned with the first opening 38.

[0082] The second polarizer 202b can have a second transmission axis 206b, a third boundary 210c, and a fourth boundary 210d, and can be disposed within the cavity 18 and positioned between the imaging system 22 and the circuit board 34 such that the field of view 40 of the imaging system 22 passes through the second polarizer 202b, and light reflected from the sample holder 32, the test device 44, and / or the sample 46 is received by the third boundary 210c and directed through the second polarizer 202b and the fourth boundary 210d to the imaging system 22 and / or the camera 26.

[0083] When light is provided to the third boundary 210c, the second polarizer 202b can be configured to transmit a portion of the light that is linearly polarized parallel to the second transmission axis 206b out of the fourth boundary 210d and to absorb a portion of the light that is linearly polarized perpendicular to the second transmission axis 206b. do.

[0084] In one embodiment, the second polarizer 202b has a fixed orientation such that the second transmission axis 206b is substantially perpendicular to the first transmission axis 206a, while in another embodiment, the second polarizer 202b is movably (e.g., rotatably) mounted to the imaging system 22 and / or camera 26 such that the orientation of the second transmission axis 206b can be adjusted.

[0085] 10, a diagram showing an exploded orthogonal view of an exemplary embodiment of the circuit board 34 and the first polarizer 202a is shown. The circuit board 34 is comprised of a substrate 60 having a bottom surface 61a and a top surface 61b, a first aperture 38 extending between the bottom surface 61a and the top surface 61b, and one or more illumination sources 42a-n. The one or more illumination sources 42a-n may be attached to the bottom surface 61a. The first polarizer 202a is comprised of a first boundary 210a and a second boundary 210b, a first transmission axis 206a, and a second aperture 214 extending between the first boundary 210a and the second boundary 210b. The second aperture 214 is aligned with the first aperture 38. A first polarizer 202a may be attached to the bottom surface 61a of the circuit board 34 and may cover one or more illumination sources 42a-n.

[0086] 11, a diagram is shown illustrating a first polarizer 202a filtering unpolarized light 218 generated by one or more illumination sources 42a-n and transmitting polarized light 222 directly toward a test device 44 having a sample 46. The test device 44 having a sample 46 reflects the polarized light 222 and directs diffuse reflection 226 and specular reflection 230 toward a second polarizer 202b. The second polarizer 202b filters the diffuse reflection 226 and specular reflection 230 and transmits the polarized light 222 toward the camera 26.

[0087] A first polarizer 202a having a first transmission axis 206a can filter the unpolarized light 218 and transmit the polarized light 222 directly towards the sample 46, where the polarized light 222 is linearly polarized parallel to the first transmission axis 206a. The polarized light 222 can be reflected by the sample 46, producing diffuse reflection 226 and specular reflection 230.

[0088] The diffuse reflection 226 may be unpolarized or may be polarized in a different direction (i.e., cross the first transmission axis 206a) than the polarized light 222. The specular reflection 230 may be polarized in the same direction as the polarized light 222 (i.e., parallel to the first transmission axis 206a).

[0089] Both the diffuse reflection 226 and the specular reflection 230 are directed towards the second polarizer 202b, which can filter the diffuse reflection 226 and the specular reflection 230 and transmit the polarized light 222 directly towards the camera 26, where the polarized light 222 is linearly polarized parallel to the second transmission axis 206b.

[0090] The inclusion of the first polarizer 202a and the second polarizer 202b is particularly important when the angle θ provided between the one or more illumination sources 42a-n and the camera 26 is relatively small (e.g., about 5 degrees). However, the angle θ can be any angle that enables the reagent analyzer 10a to function according to the present disclosure. For example (without limitation), the angle θ can be about 10 degrees, about 20 degrees, about 30 degrees, about 40 degrees, about 50 degrees, about 60 degrees, about 70 degrees, about 80 degrees, about 90 degrees, or more, as well as a range of combinations of two integers between the two aforementioned values ​​(i.e., a range of about 13 degrees to about 87 degrees, etc.).

[0091] When unpolarized light 218 is provided to the first polarizer 202a, the polarized light 222 transmitted by the first polarizer 202a is linearly polarized parallel to the first transmission axis 206a,

number

[0092] When polarized light 222 is provided to the second polarizer 202b, the light transmitted by the second polarizer 202b is linearly polarized parallel to the second transmission axis 206b, and I=Icos 2 11, when the polarization of the polarized light 222 is substantially orthogonal to the second transmission axis 206b (i.e., Φ≈90°), the intensity of the light transmitted by the second polarizer 202b is given by I2=I1cos 2 (90°)=0, and the second polarizer 202 b does not transmit any of the polarized light 222 .

[0093] In one embodiment, the second transmission axis 206b is substantially orthogonal to the first transmission axis 206a. Thus, the polarization of the specular reflection 230 is substantially orthogonal to the second transmission axis 206b, but the polarization of the diffuse reflection 226 is not, thereby blocking the specular reflection 230 while allowing a portion of the diffuse reflection 226 to pass through the second transmission axis 206b. In another embodiment, the second polarizer 202b is movable (e.g., rotatable) such that the orientation of the second transmission axis 206b can be adjusted to absorb more or less of the diffuse reflection 226 and / or the specular reflection 230.

[0094] In some embodiments, the test device 44 includes one or more reagent pads on a reagent card or reagent strip. In some cases, a portion of the sample 46 pools or remains on the surface of the test device 44 (e.g., the reagent pad) causing a specular reflection 230. By incorporating the first polarizer 202a and the second polarizer 202b, the polarized light 222 can be related solely to the absorption and scattering of light in the reagent pad of the test device 44, providing an improved reading of the concentration of the analyte.

[0095] The following is a numbered list of non-limiting exemplary embodiments of the inventive concepts disclosed herein:

[0096] 1. A method comprising: placing a wet reagent test device within a field of view of a camera sensor, the field of view of the camera sensor passing through an opening extending between a first major surface and a second major surface of a substrate of the circuit board, and depositing a volume of sample into the wet reagent test device so that, if a target component is present in the sample, a reagent in the wet reagent test device can react with the target component; illuminating the wet reagent test device with light produced by a plurality of light sources mounted on a second major surface of the substrate of the circuit board; the portion of the light is a reflected light signal formed by light reflecting from the wet reagent test device pad through an opening in the substrate of the circuit board; The method further comprises: The method includes detecting the reflected light signal with a camera sensor to generate an image of at least a portion of the reagent pad.

[0097] 2. The method of exemplary embodiment 1, further comprising: a processor analyzing the image by executing processor executable code stored in a non-transitory computer readable medium to determine the presence or absence of a target component in the sample.

[0098] 3. The method of exemplary embodiment 2, wherein analyzing the image by the processor executing the processor executable code is further defined as analyzing pixels in the image for a predetermined color indicative of the presence of a target component in the sample.

[0099] 4. The method of any one of exemplary embodiments 1 to 3, wherein illuminating the wet reagent test device with light generated by the multiple light sources is further defined as supplying a level of electricity to each of the light sources such that each light source contributes an amount of illumination calculated to provide controlled illumination at the wet reagent test device.

[0100] 5. The method of exemplary embodiment 4, wherein the controlled illumination is illumination having a substantially uniform intensity in the wet reagent test device.

[0101] 6. The method of exemplary embodiment 4, wherein the controlled illumination is an intensity designed in the wet reagent test device.

[0102] 7. The method of any one of exemplary embodiments 4 to 6, wherein the substrate has a first surface, a second surface opposite the first surface, and an intermediate region between the first surface and the second surface, the first group of light sources is disposed adjacent to the first surface of the substrate, and the second group of light sources is disposed within the intermediate region of the substrate, and illuminating the wet reagent test device with light includes providing a first amount of electricity to the first group of light sources and providing a second amount of electricity to the second group of light sources, the first amount of electricity being greater than the second amount of electricity.

[0103] 8. The method of exemplary embodiment 7, wherein a first amount of electricity operates a first light source of a first group of light sources at a first brightness, and a second amount of electricity operates a second light source of a second group of light sources at a second brightness, the first brightness being greater than the second brightness.

[0104] 9. The method according to any one of exemplary embodiments 1 to 8, wherein the light sources are arranged in a planar relationship.

[0105] 10. Directing light to a first boundary of a first polarizer, the first polarizer having a first transmission axis and configured to transmit a portion of the light polarized in a direction parallel to the first transmission axis from a second boundary of the first polarizer; directing the reflected optical signal to a third boundary of a second polarizer, the second polarizer having a second transmission axis and configured to transmit a portion of the reflected optical signal polarized in a direction parallel to the second transmission axis from a fourth boundary of the second polarizer; The method of any one of exemplary embodiments 1 to 9, further comprising:

[0106] 11. The method of exemplary embodiment 10, wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

[0107] 12. The method of exemplary embodiment 10, wherein the second polarizer is movably mounted to the camera sensor such that a second transmission axis of the second polarizer is adjustable.

[0108] 13. A reagent analyzer comprising: A circuit board having a substrate and a plurality of conductive leads extending on or through the substrate, the substrate having a first major surface and a second major surface, the first major surface being positioned opposite the second major surface. a circuit board having a first major surface and a second major surface, the circuit board having an opening extending between the first major surface and the second major surface; an imaging system having a field of view extending through an opening formed in the substrate and configured to capture an image of a wet reagent test device positioned at a read position within the field of view, the image having a plurality of pixels; a processor configured to receive the image and analyze pixels of the image to determine the presence or absence of a target component in the sample applied to the wet reagent pad.

[0109] 14. The reagent analyzer of exemplary embodiment 13, wherein the first major surface faces the imaging system and further includes a light source mounted on the second major surface of the substrate.

[0110] 15. The reagent analyzer of exemplary embodiment 14, wherein the light source is a first light source and the reagent analyzer further includes a second light source and circuitry configured to supply electricity to the first and second light sources, such that the first and second light sources contribute an amount of illumination to the wet reagent test device calculated to provide controlled illumination.

[0111] 16. The reagent analyzer of exemplary embodiment 15, wherein the controlled illumination is of substantially uniform intensity.

[0112] 17. A reagent analyzer as described in exemplary embodiment 15, wherein the substrate has a first surface, a second surface opposite the first surface, and an intermediate region between the first surface and the second surface, the first light source is disposed adjacent to the first surface of the substrate, the second light source is disposed within the intermediate region of the substrate, and the circuit is configured to provide a first amount of electricity to the first light source and a second amount of electricity to the second light source, the first amount of electricity being greater than the second amount of electricity.

[0113] 18. The reagent analyzer of exemplary embodiment 17, wherein a first amount of electricity operates a first light source at a first brightness and a second amount of electricity operates a second light source at a second brightness, the first brightness being greater than the second brightness.

[0114] 19. The reagent analyzer of exemplary embodiment 14, wherein the second major surface of the substrate is planar.

[0115] 20. The opening is a first opening: a first polarizer having a first transmission axis, a first boundary facing the light source such that light generated by the light source is incident on the first boundary, a second boundary facing the wet reagent test device, and a second opening extending between the first and second boundaries, the first polarizer being configured to transmit a portion of the light generated by the light source that is polarized in a direction parallel to the first transmission axis from the second boundary, the first opening overlapping the second opening; The reagent analyzer of exemplary embodiment 14 further includes a second polarizer having a second transmission axis, a third boundary facing the first opening of the substrate such that light reflected by the wet reagent device is incident on the third boundary, and a fourth boundary facing the imaging system, the second polarizer being configured to transmit a portion of the light reflected by the wet reagent device that is polarized in a direction parallel to the second transmission axis from the fourth boundary.

[0116] 21. The reagent analyzer of exemplary embodiment 20, wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

[0117] 22. The reagent analyzer of exemplary embodiment 21, wherein the second polarizer is movably mounted to the imaging system such that a second transmission axis of the second polarizer is adjustable.

[0118] 23. An apparatus comprising: a housing surrounding the cavity and opaque to visible light; a camera sensor having a field of view within the cavity; a sample tray disposed within the cavity and having a sample holder within a field of view of the camera sensor and spaced a distance from the camera sensor; a circuit board disposed within the cavity between the camera sensor and the sample tray, the circuit board having a substrate and a plurality of conductive leads extending on or through the substrate, the substrate having a first major surface facing the camera sensor and a second major surface facing the sample tray, the first major surface being located opposite the second major surface, the substrate having an opening extending between the first and second major surfaces, the opening being positioned within the field of view of the camera sensor such that the field of view of the camera passes through the opening to provide the camera sensor with a controlled field of view of a sample holder in the sample tray; a light source attached to the second major surface of the substrate and connected to at least a portion of the plurality of conductive leads extending over the substrate; and a circuit attached to the conductive leads and configured to supply electricity to the light source via the conductive leads.

[0119] 24. The apparatus of exemplary embodiment 23, wherein the light source includes a plurality of light sources arranged and supported in a planar configuration.

[0120] 25. The apparatus of exemplary embodiment 24, wherein the second major surface of the substrate is planar.

[0121] 26. The apparatus of exemplary embodiment 24 or 25, wherein the circuitry is configured to supply electricity to each of the light sources such that each light source contributes an amount of illumination of the sample holders of the sample tray calculated to provide controlled illumination at the sample holders.

[0122] 27. The apparatus of exemplary embodiment 26, wherein the controlled illumination is of substantially uniform intensity across the extent of the sample tray.

[0123] 28. The apparatus of exemplary embodiment 24, wherein the substrate has a first surface, a second surface opposite the first surface, and an intermediate region between the first surface and the second surface, a first group of light sources is disposed adjacent to the first surface of the substrate, a second group of light sources is disposed within the intermediate region of the substrate, and a circuit provides a first amount of electricity to the first group of light sources and a second amount of electricity to the second group of light sources, the first amount of electricity being greater than the second amount of electricity.

[0124] 29. The device of exemplary embodiment 28, wherein a first amount of electricity operates a first light source of a first group of light sources at a first brightness and a second amount of electricity operates a second light source of a second group of light sources at a second brightness, the first brightness being greater than the second brightness.

[0125] 30. An apparatus according to any one of exemplary embodiments 23 to 29, wherein the sample holder has a first major axis and a first minor axis, and the opening in the substrate has a second major axis parallel to the first major axis.

[0126] 31. The opening is a first opening comprising: a first polarizer disposed within the cavity between the light source and the sample tray, the first polarizer having a first transmission axis, a first boundary facing the light source such that light generated by the light source is incident on the first boundary, a second boundary facing the sample tray, and a second opening extending between the first and second boundaries, the first polarizer being configured to transmit a portion of the light generated by the light source from the second boundary that is polarized in a direction parallel to the first transmission axis; a second polarizer attached to the camera sensor, the second polarizer having a second transmission axis, a third boundary facing the first opening in the substrate such that light reflected by the sample tray is incident on the third boundary, and a fourth boundary facing the camera sensor; The device of any one of exemplary embodiments 23 to 30, further comprising a second polarizer configured to transmit a portion of the first polarized light from the fourth boundary that is polarized in a direction parallel to the second transmission axis.

[0127] 32. The apparatus of exemplary embodiment 31, wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

[0128] 33. The apparatus of exemplary embodiment 32, wherein the second polarizer is movably mounted to the camera sensor such that a second transmission axis of the second polarizer is adjustable.

[0129] 34. An apparatus comprising: a circuit board having a substrate, the substrate having a first major surface and a second major surface, the first major surface located opposite the second major surface, and a first opening extending between the first major surface and the second major surface; a light source attached to the second major surface of the substrate; a first polarizer having a first transmission axis, a first boundary facing the light source, a second boundary facing the first boundary, and a second opening extending between the first boundary and the second boundary, the second opening overlapping the first opening; a camera sensor having a field of view extending through a first opening formed in the substrate and a second opening formed in the first polarizer; a sample tray having a sample holder within the field of view of the camera sensor and spaced a distance from the camera sensor; a second polarizer having a second transmission axis substantially orthogonal to the first transmission axis and attached to the camera sensor.

[0130] It should be understood that the steps disclosed herein can be performed simultaneously or in any desired order. For example, one or more of the steps disclosed herein can be omitted, one or more steps can be further divided into one or more substeps, and two or more steps or substeps can be combined into a single step. Furthermore, in some exemplary embodiments, one or more steps can be repeated one or more times, and such repetitions can be performed sequentially or interspersed with other steps or substeps. In addition, one or more other steps or substeps can be performed, for example, before, after, or between the steps disclosed herein.

[0131] Although the inventive concepts disclosed herein have been described with respect to detecting reflectance values ​​of a reagent pad, it should be understood that in some exemplary embodiments of the inventive concepts, the calibration may also be calculated using absorption values, transmission values, or any other value or characteristic related to the color or color change of the reagent pad.

[0132] From the foregoing description, it is apparent that the inventive concepts disclosed herein are well adapted to carry out these objects and attain the advantages set forth herein, as well as those inherent therein. While illustrative embodiments of the inventive concepts disclosed herein have been described for purposes of this disclosure, it will be understood that numerous modifications, readily apparent to those skilled in the art, may be made therein and that such modifications are within the scope of the inventive concepts as disclosed and defined in the appended claims.

Claims

1. 13. A method comprising: placing a wet reagent test device within a field of view of a camera sensor, the field of view of the camera sensor passing through an opening extending between a first major surface and a second major surface of a substrate of the circuit board, and depositing a volume of sample into the wet reagent test device so that, if a target component is present in the sample, a reagent in the wet reagent test device can react with the target component; illuminating the wet reagent test device with light produced by a plurality of light sources mounted on a second major surface of the substrate of the circuit board; the portion of the light is a reflected light signal formed by the light reflecting off the wet reagent test device pad and passing through an opening in the substrate of the circuit board; The method further comprises: The method includes detecting the reflected light signal with a camera sensor to generate an image of at least a portion of the reagent pad.

2. 10. The method of claim 1, further comprising: analyzing the image by a processor executing processor executable code stored in the non-transitory computer readable medium to determine the presence or absence of a target component in the sample.

3. 3. The method of claim 2, wherein analyzing the image by the processor executing the processor executable code is further defined as analyzing pixels in the image for a predetermined color indicative of the presence of a target component in the sample.

4. The method of any one of claims 1 to 3, wherein illuminating the wet reagent test device with light produced by the multiple light sources is further defined as supplying each of the light sources with a level of electricity such that each light source contributes an amount of illumination calculated to provide controlled illumination at the wet reagent test device.

5. 5. The method of claim 4, wherein the controlled illumination is illumination having a substantially uniform intensity at the wet reagent test device.

6. 5. The method of claim 4, wherein the controlled illumination is an intensity designed into the wet reagent test device.

7. The method of any one of claims 4 to 6, wherein the substrate has a first surface, a second surface opposite the first surface, and an intermediate region between the first surface and the second surface, the first group of light sources is disposed adjacent to the first surface of the substrate, and the second group of light sources is disposed within the intermediate region of the substrate, and illuminating the wet reagent test device with light comprises providing a first amount of electricity to the first group of light sources and providing a second amount of electricity to the second group of light sources, the first amount of electricity being greater than the second amount of electricity.

8. 8. The method of claim 7, wherein a first amount of electricity causes a first light source in a first group of light sources to operate at a first brightness and a second amount of electricity causes a second light source in a second group of light sources to operate at a second brightness, the first brightness being greater than the second brightness.

9. A method according to any one of claims 1 to 8, wherein the light sources are arranged in a planar relationship.

10. directing the light to a first boundary of a first polarizer, the first polarizer having a first transmission axis and configured to transmit a portion of the light polarized in a direction parallel to the first transmission axis from a second boundary of the first polarizer; directing the reflected optical signal to a third boundary of a second polarizer, the second polarizer having a second transmission axis and configured to transmit a portion of the reflected optical signal polarized in a direction parallel to the second transmission axis from a fourth boundary of the second polarizer; The method of any one of claims 1 to 9, further comprising:

11. The method of claim 10 , wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

12. The method of claim 10 , wherein the second polarizer is movably mounted to the camera sensor such that the second transmission axis of the second polarizer is adjustable.

13. 1. A reagent analyzer comprising: a circuit board having a substrate and a plurality of conductive leads extending on or through the substrate, the substrate having a first major surface and a second major surface, the first major surface being located opposite the second major surface, the substrate having an opening extending between the first and second major surfaces; an imaging system having a field of view extending through an opening formed in the substrate and configured to capture an image of a wet reagent test device positioned at a read position within the field of view, the image having a plurality of pixels; a processor configured to receive the image and analyze pixels of the image to determine the presence or absence of a target component in the sample applied to the wet reagent pad.

14. 14. The reagent analyzer of claim 13, wherein the first major surface faces the imaging system and further comprises a light source mounted to a second major surface of the substrate.

15. 15. The reagent analyzer of claim 14, wherein the light source is a first light source and the reagent analyzer further includes a second light source and circuitry configured to supply electricity to the first and second light sources, such that the first and second light sources contribute an amount of illumination to the wet reagent test device calculated to provide controlled illumination.

16. 16. The reagent analyzer of claim 15, wherein the controlled illumination is of substantially uniform intensity.

17. 16. The reagent analyzer of claim 15, wherein the substrate has a first side, a second side opposite the first side, and an intermediate region between the first side and the second side, the first light source is disposed adjacent the first side of the substrate and the second light source is disposed within the intermediate region of the substrate, and the circuit is configured to provide a first amount of electricity to the first light source and a second amount of electricity to the second light source, the first amount of electricity being greater than the second amount of electricity.

18. 20. The reagent analyzer of claim 17, wherein a first amount of electricity operates the first light source at a first brightness and a second amount of electricity operates the second light source at a second brightness, the first brightness being greater than the second brightness.

19. 15. The reagent analyzer of claim 14, wherein the second major surface of the substrate is planar.

20. The opening is a first opening having: a first polarizer having a first transmission axis, a first boundary facing the light source such that light generated by the light source is incident on the first boundary, a second boundary facing the wet reagent test device, and a second opening extending between the first and second boundaries, the first polarizer being configured to transmit a portion of the light generated by the light source that is polarized in a direction parallel to the first transmission axis from the second boundary, the first opening overlapping the second opening; a second transmission axis, such that light reflected by the wet reagent device is incident on a third boundary; 15. The reagent analyzer of claim 14, further comprising: a second polarizer having a third boundary facing the first opening of the substrate and a fourth boundary facing the imaging system, the second polarizer being configured to transmit a portion of the light reflected by the wet reagent device that is polarized in a direction parallel to the second transmission axis from the fourth boundary.

21. 21. The reagent analyzer of claim 20, wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

22. 22. The reagent analyzer of claim 21, wherein the second polarizer is movably mounted to the imaging system such that a second transmission axis of the second polarizer is adjustable.

23. 13. An apparatus comprising: a housing surrounding the cavity and opaque to visible light; a camera sensor having a field of view within the cavity; a sample tray disposed within the cavity and having a sample holder within the field of view of the camera sensor and spaced a distance from the camera sensor; a circuit board disposed within the cavity between the camera sensor and the sample tray, the circuit board having a substrate and a plurality of conductive leads extending on or through the substrate, the substrate having a first major surface facing the camera sensor and a second major surface facing the sample tray, the first major surface being located opposite the second major surface, the substrate having an opening extending between the first and second major surfaces, the opening being positioned within the field of view of the camera sensor such that the field of view of the camera passes through the opening to provide the camera sensor with a controlled field of view of a sample holder in the sample tray; a light source attached to the second major surface of the substrate and connected to at least a portion of the plurality of conductive leads extending over the substrate; and a circuit attached to the conductive leads and configured to supply electricity to the light source via the conductive leads.

24. 24. The apparatus of claim 23, wherein the light source comprises a plurality of light sources arranged and supported in a planar configuration.

25. 25. The apparatus of claim 24, wherein the second major surface of the substrate is planar.

26. 26. The apparatus of claim 24 or 25, wherein the circuitry is configured to supply electricity to each of the light sources such that each light source contributes an amount to the illumination of a sample holder in the sample tray calculated to provide controlled illumination at the sample holder.

27. 27. The apparatus of claim 26, wherein the controlled illumination is of substantially uniform intensity across the extent of the sample tray.

28. 25. The apparatus of claim 24, wherein the substrate has a first surface, a second surface opposite the first surface, and an intermediate region between the first surface and the second surface, the first group of light sources are disposed adjacent the first surface of the substrate and the second group of light sources are disposed within the intermediate region of the substrate, and the circuit provides a first amount of electricity to the first group of light sources and a second amount of electricity to the second group of light sources, the first amount of electricity being greater than the second amount of electricity.

29. 30. The apparatus of claim 28, wherein a first amount of electricity causes a first light source in a first group of light sources to operate at a first brightness and a second amount of electricity causes a second light source in a second group of light sources to operate at a second brightness, the first brightness being greater than the second brightness.

30. An apparatus according to any one of claims 23 to 29, wherein the sample holder has a first major axis and a first minor axis, and the opening in the substrate has a second major axis parallel to the first major axis.

31. The opening is a first opening having: a first polarizer disposed within the cavity between the light source and the sample tray, the first polarizer having a first transmission axis, a first boundary facing the light source such that light generated by the light source is incident on the first boundary, a second boundary facing the sample tray, and a second opening extending between the first and second boundaries, the first polarizer being configured to transmit a portion of the light generated by the light source from the second boundary that is polarized in a direction parallel to the first transmission axis; 31. The apparatus of any one of claims 23 to 30, further comprising: a second polarizer attached to the camera sensor, the second polarizer having a second transmission axis, a third boundary facing the first opening in the substrate such that light reflected by the sample tray is incident on the third boundary, and a fourth boundary facing the camera sensor, the second polarizer being configured to transmit from the fourth boundary a portion of the light reflected by the sample tray that is polarized in a direction parallel to the second transmission axis.

32. 32. The apparatus of claim 31 , wherein the second transmission axis of the second polarizer is substantially orthogonal to the first transmission axis of the first polarizer.

33. 33. The apparatus of claim 32, wherein the second polarizer is movably mounted to the camera sensor such that a second transmission axis of the second polarizer is adjustable.

34. 13. An apparatus comprising: a circuit board having a substrate, the substrate having a first major surface and a second major surface, the first major surface opposite the second major surface, and a first opening extending between the first major surface and the second major surface; a light source attached to the second major surface of the substrate; a first polarizer having a first transmission axis, a first boundary facing the light source, a second boundary facing the first boundary, and a second opening extending between the first boundary and the second boundary, the second opening overlapping the first opening; a camera sensor having a field of view extending through a first opening formed in the substrate and a second opening formed in the first polarizer; a sample tray having a sample holder within a field of view of the camera sensor and spaced a distance from the camera sensor; a second polarizer having a second transmission axis substantially orthogonal to the first transmission axis and attached to the camera sensor.

Images