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WO2025226778A1 - Détection automatisée de particules étrangères et de gouttelettes d'échantillon dans un chemin optique pour des analyseurs d'urine à base d'imagerie - Google Patents

Détection automatisée de particules étrangères et de gouttelettes d'échantillon dans un chemin optique pour des analyseurs d'urine à base d'imagerie

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Publication number
WO2025226778A1
WO2025226778A1 PCT/US2025/025912 US2025025912W WO2025226778A1 WO 2025226778 A1 WO2025226778 A1 WO 2025226778A1 US 2025025912 W US2025025912 W US 2025025912W WO 2025226778 A1 WO2025226778 A1 WO 2025226778A1
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WIPO (PCT)
Prior art keywords
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statistical metric
area
metric
statistical
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/025912
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English (en)
Inventor
Vaishnav Ram SAVARNI K R
John Barrett DUNN
Amlan PRAHARAJ
Sudipa BHATTACHARYA
Ethan Warner
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Siemens Healthcare Diagnostics Inc
Original Assignee
Siemens Healthcare Diagnostics Inc
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Publication date
Application filed by Siemens Healthcare Diagnostics Inc filed Critical Siemens Healthcare Diagnostics Inc
Publication of WO2025226778A1 publication Critical patent/WO2025226778A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/274—Calibration, base line adjustment, drift correction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • G01N35/00613—Quality control
    • G01N35/00623—Quality control of instruments
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • G01N35/00693—Calibration
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/15—Preventing contamination of the components of the optical system or obstruction of the light path
    • G01N2021/155—Monitoring cleanness of window, lens, or other parts
    • G01N2021/157—Monitoring by optical means

Definitions

  • inventive concepts disclosed herein generally relate to an analyzer having a transparent shield positioned between an optical reader and a sample holder, and more particularly, but not by way of limitation, to systems and methods configured to determine a degree of occlusion of the transparent shield while viewing a sample holder through the transparent shield.
  • lateral flow immunoassays and the so-called "dip-and-read" type reagent test devices.
  • dip-and-read test devices are used for the analysis of a biological fluid or tissue, or for the analysis of a commercial or industrial fluid or substance, the general procedure involves a test device coming in contact with the sample or specimen to be tested, and manually or instrumentally analyzing the test device.
  • a lateral flow immunoassay is a diagnostic device used to confirm the presence or absence of a target analyte.
  • Lateral flow immunoassays typically contain a flow path which conveys a sample past a control line position and a test line position. A control line at the control line position confirms the test is working properly, and a test line at the test line position provides the result of the lateral flow immunoassay.
  • Lateral flow immunoassays are developed to be used in a dipstick format or in a housed test format.
  • dipsticks and housed tests work in a similar way, and generally fall within one of two categories: sandwich assays - a positive test is represented by the presence of a colored line at the test line position; and competitive assays - a positive test is represented by the absence of a colored line at the test line position.
  • sandwich assays - a positive test is represented by the presence of a colored line at the test line position
  • competitive assays - a positive test is represented by the absence of a colored line at the test line position.
  • a dip-and-read reagent test device In medicine, for example, numerous physiological functions can be monitored merely by dipping a dip-and-read reagent test device into a sample of body 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 from, or absorbed by the test device.
  • dip-and-read reagent test devices for detecting body fluid components are capable of making quantitative, or at least semi-quantitative, measurements. Thus, by measuring the detectable response after a predetermined time, a user can obtain not only a positive indication of the presence of a particular constituent in a test sample, but also an estimate of how much of the constituent is present.
  • Such dip-and- read reagent test devices provide physicians and laboratory technicians with a facile diagnostic tool, as well as with the ability to gauge the extent of disease or bodily malfunction.
  • Illustrative of dip-and-read reagent test devices currently in use are products available from Siemens Healthcare Diagnostics Inc., under the trademark MULTISTIX, and others.
  • Immunochemical, diagnostic, or serological test devices such as these usually include one or more carrier matrix, such as absorbent paper, having incorporated therein a particular reagent or reactant system which manifests a detectable response (e.g., a color change in the visible or ultraviolet spectrum) in the presence of a specific test sample component or constituent.
  • a detectable response e.g., a color change in the visible or ultraviolet spectrum
  • these test devices can detect the presence of glucose, ketone bodies, bilirubin, urobilinogen, occult blood, nitrite, and other substances.
  • a specific change in the intensity of color observed within a specific time range after contacting the dip-and-read reagent test device with a sample is indicative of the presence of a particular constituent and/or its concentration in the sample.
  • dip-and-read reagent test devices suffer from some limitations.
  • dip-and-read reagent test devices typically require a technician to manually dip the test device into a sample, wait for a prescribed amount of time, and visually compare the color of the test device to a color chart provided with the test device. This process is slow and the resulting reading is highly skill-dependent (e.g., exact timing, appropriate comparison to the color chart, ambient lighting conditions, and technician vision) and may be inconsistent between two different technicians performing the same test.
  • the act of manually dipping the test device into the sample may introduce cross-contamination or improper deposition of the test sample on the test device, such as via incomplete insertion of the test device into the sample, insufficient time for the sample to be deposited onto the test device, or having too much sample on the test device which may drip, leak, or splash on the technician's work area, person, or clothing.
  • Automated instruments which are currently available for instrumentally 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 photometer, manufactured and sold by Siemens Healthcare Diagnostics, Inc.) require each test device to be manually loaded into the automated instrument after contacting the test device with specimen or sample to be tested. Manual loading requires that the reagent test device be properly positioned in the automated instrument within a limited period of time after contacting the solution or substance to be tested. At the end of the analysis, used reagent test devices are removed from the instrument and disposed of in accordance with applicable laws and regulations.
  • CLINITEK STATUS reflectance photometer manufactured and sold by Siemens Healthcare Diagnostics, Inc.
  • Multiple-profile reagent cards are essentially card-shaped test devices which include multiple reagent-impregnated matrices or pads for simultaneously or sequentially performing multiple analyses of analytes, such as the one described in U.S. Pat. No. 4,526,753, for example, the entire disclosure of which is hereby incorporated herein by reference.
  • the reagent pads on the multiple-profile reagent card are typically arranged in a grid-like arrangement and spaced at a distance from one another so as to define several rows and columns of reagent pads.
  • Adjacent reagent pads in the same row may be referred to as a test strip, and may include reagents for a preset combination of tests that is ran for each sample, for example.
  • Multiple-profile reagent cards result in an efficient, economical, rapid, and convenient way of performing automated analyses.
  • An automated analyzer configured to use multiple-profile reagent cards typically takes a multiple-profile reagent card, such as from a storage drawer, or a cassette, and advances the multiple-profile reagent card through the analyzer over a travelling surface via a card moving mechanism, typically one step at a time so that one test strip (or one row of reagent pads) is positioned at a sample-dispensing position and/or at one or more read position.
  • Exemplary card moving mechanisms include a conveyor belt, a ratchet mechanism, a sliding ramp, or a card-gripping or pulling mechanism.
  • a pipettes e.g., manual or automatic
  • the reagent pads are positioned at one or more read positions and analyzed (e.g., manually or automatically) to gauge the test result.
  • the reagent card is placed in the field of view of an imaging system, such as an optical imaging system, a microscope, or a photo spectrometer, for example, and one or more images of the reagent pads on the card (e.g., optical signals indicative of the color of the reagent pads) is captured and analyzed.
  • an imaging system such as an optical imaging system, a microscope, or a photo spectrometer, for example
  • images of the reagent pads on the card e.g., optical signals indicative of the color of the reagent pads
  • the field of view of the imaging system is relatively large to allow for the capture of multiple images of the same reagent pad as the reagent card is moved or stepped across multiple read positions in the field of view of the imaging system.
  • the field of view encompasses multiple read positions or locations, and each reagent pad is moved in a stepwise fashion through the read positions as the reagent card travels across the field of view of the imaging system.
  • the analyzer moves the card between various read positions in known intervals of time, the multiple images taken in the field of view of the imaging system allow the analyzer to determine changes in the color of the reagent pad as a result of the reagent pad reacting with the sample at each read position as a function of the time it takes the pad to be moved to the respective read position, for example. Finally, the used card is removed from the analyzer, and is disposed of appropriately.
  • a sample tray holds a consumable such as a reagent card to be read.
  • the sample tray is moved by a motor from outside a housing of the analyzer to inside the housing where the sample measurement occurs by an optical reader.
  • excess fluid not captured by the consumable have been found to be splattered onto any optical components above the sample holding area during this movement.
  • optics become dirty the analyzer needs to be cleaned or replaced due to risk of an incorrect result that can be used by a doctor to mis-diagnose a patient.
  • Liao models blob-like spots present on the camera module in three steps: preprocessing of the image, modeling of the background, and determination of dirt spots.
  • the background image template is obtained by dividing the image into multiple overlapping sub-regions and fitting a second-order polynomial to each subregion.
  • the dirt spots are then identified by subtracting the acquired image from the background template image and applying morphological operations such as erosion and dilation.
  • Shajahan et al. proposed a method for identifying and correcting debris on a camera lens deployed on a robot designed for dusty environments, utilizing multiple video frames to track and algorithmically correct for dust. [Shajahan, Jalaluddin & Reyes, Sandra & Xiao, Jizhong. (2021). Camera Lens Dust Detection and Dust Removal for Mobile Robots in Dusty Fields. 687-691. 10.1109/ROBIO54168.2021.9739233].
  • U.S. Patent Publication No. 2014/0232869 Al to May et al. discloses a vision system for automobiles exposed to external environments, where dirt, moisture, or water accumulation can occur, and proposes an approach for dirt detection in such systems.
  • Chen and Fuh described a method for detecting dirt defects on vignette surfaces using a basis spline (B-Spline) to generate an ideal vignette surface and subtracting the contaminated surface from the generated vignette surface to locate the defect.
  • B-Spline basis spline
  • Moeller and Nirschl proposed a closed-loop control system for cleaning intensity and a method to evaluate the cleanliness of woven filter cloth, automatically evaluating the weave's periodicity based on a reported algorithm and employing background subtraction to detect particle deposits as irregularities on the near-regular weave pattern.
  • a method, reagent analyzer and a non-transitory computer readable medium which divides an area of the image of a calibration device within a reagent analyzer into a plurality of sub-areas, computes a first statistical metric of a first sub-area of the plurality of sub-areas using first pixel data within the first sub-area, computes a second statistical metric of a second sub-area of the plurality of sub-areas using second pixel data within the second sub-area, analyzes the first statistical metric and the second statistical metric to determine if an occlusion of the calibration device exists in the first sub-area or the second sub-area; and responsive to a determination that the occlusion of the calibration device exists in the first sub-area or the second sub-area, cause an action, such as initiating an alert in a form perceivable by a human; storing data indicative of the occlusion; identifying a component within an optical path used to capture the image having the occlusion
  • FIG. 1 is a front elevation view of an exemplary embodiment of an analyzer according to the inventive concepts disclosed herein, showing a transparent shield positioned in a field of view of an imaging system thereof.
  • FIG. 2 is a side elevation view of the analyzer of FIG. 1.
  • FIG. 3 is an end elevation view of the analyzer having the transparent shield positioned within a slot formed in a housing according to the inventive concepts disclosed herein.
  • FIG. 4A is a bottom plan view of a circuit board having an aperture surrounded by onboard light sources according to the inventive concepts disclosed herein to facilitate controlled illumination of the reagent card and reduce light scattering detected by the imaging system.
  • FIG. 4B is a side elevational view of a transparent shield positioned below a circuit board, the circuit board having an aperture surrounded by one or more illumination source according to the inventive concepts disclosed herein.
  • FIG. 5 is a top plan view image of a sample holder and a test device as viewed through the transparent shield in accordance with the inventive concepts disclosed herein, wherein the test device is a reagent card.
  • FIG. 6 is a top plan view image of the sample holder and the test device shown in FIG. 5 as viewed through the transparent shield, wherein the transparent shield has an exemplary degree of occlusion based on material present on a first surface of the transparent shield in accordance with the inventive concepts disclosed herein.
  • FIG. 8 is a flow diagram of an exemplary embodiment of a method for detecting an occlusion in accordance with the inventive concepts disclosed herein.
  • FIG. 9 is a bottom plan view of the transparent shield having an aperture in accordance with the inventive concepts disclosed herein.
  • FIG. 10 is a side elevation view of the transparent shield of FIG. 9 positioned ajar on a rail constructed in accordance with the present disclosure and having an engaging member.
  • FIG. 11 is a side elevation view of the transparent shield engaging the rail and with the engaging member of the rail positioned within the aperture of the transparent shield of FIG. 9.
  • FIG. 12 is a top plan view of the transparent shield of FIG. 9 engaging the rail, the rail having the engaging member according to the inventive concepts disclosed herein positioned within the aperture of the transparent shield.
  • FIG. 13 is a top plan view image of the sample holder and a test device as viewed through the transparent shield, wherein the test device is a reagent card cassette.
  • FIG. 14 is a top plan view image of the sample holder and test device shown in FIG. 13 as viewed through the transparent shield, wherein the transparent shield has an exemplary degree of occlusion based on material present on a first surface of the transparent shield in accordance with the inventive concepts disclosed herein.
  • FIG. 15 is a top plan view image of the sample holder and a calibration device as viewed through the transparent shield in accordance with the inventive concepts disclosed herein, wherein the calibration device is a reagent card calibration device.
  • FIG. 16 is a top plan view image of the sample holder and another version of the calibration device as viewed through the transparent shield in accordance with the inventive concepts disclosed herein, wherein the calibration device is a reagent card cassette calibration device.
  • FIG. 17 is a graph depicting a statistical metric and a predicted statistical metric in accordance with the inventive concepts disclosed herein, wherein the graph does not indicate the presence of an obstruction.
  • FIG. 18 is a graph depicting the statistical metric and the predicted statistical metric shown in FIG. 17, wherein the graph indicates the presence of an obstruction.
  • the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
  • "or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by anyone of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
  • qualifiers like “substantially,” “about,” “approximately,” and combinations and variations thereof, are intended to include not only the exact amount or value that they qualify, but also some slight deviations therefrom, which may be due to manufacturing tolerances, measurement error, wear and tear, stresses exerted on various parts, and combinations thereof, for example.
  • any reference to "one embodiment” or “an embodiment” means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment.
  • the appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.
  • wet reagent test device refers to a reagent device that has a volume of sample deposited thereon such that the reagent in the reagent device may react with its target constituent if such constituent is present in the sample.
  • a wet reagent test device may also have a volume of a negative control deposited thereon.
  • reagent test device refers to a carrier having a reagent.
  • exemplary reagent devices include a reagent pad of a dip and read test strip, or a control strip or a test strip of a lateral flow immunoassay.
  • the inventive concepts disclosed herein are generally directed to an analyzer for reagent test devices and methods for reading reagent test devices, and more particularly, but not by way of limitation, an analyzer having a transparent shield in a field of view of an imaging system and a sample holder such that the imaging system is configured to capture images of the sample holder through the transparent shield.
  • the analyzer includes a processor.
  • the processor is configured to receive an image and analyze pixels of the image to determine a degree of occlusion within an optical path between the imaging system and the sample holder.
  • the processor can be configured to determine a degree of occlusion of the transparent shield in embodiments including the transparent shield.
  • inventive concepts disclosed herein will be described primarily in connection with automatic analyzers using multiple-profile reagent cards as the reagent test device, the inventive concepts disclosed herein are not limited to automatic analyzers or to multipleprofile reagent cards.
  • a method according to the inventive concepts disclosed herein may be implemented with a manual analyzer, or may be implemented with an automatic analyzer using a reagent test device other than a multiple-profile reagent card, such as a lateral flow immunoassay, dip-and-read reagent test device, or a reel of reagent test devices on a substrate, and combinations thereof, as will be appreciated by a person of ordinary skill in the art having the benefit of the instant disclosure.
  • the inventive concepts disclosed herein may be implemented with any reagent device imaging system which has a field of view with at least one read position in the field of view.
  • a signal value indicative of a color of a reagent test device changes when the reagent test device is exposed to a sample.
  • the change in signal value is known (or can be measured) and therefore may become an optional offset signal value. Any change outside of the offset signal value is likely caused by a reaction with a clinical component that is being measured.
  • FIGS. 1-3 shown therein is an exemplary embodiment of a reagent analyzer 10 according to the inventive concepts disclosed herein.
  • the reagent analyzer 10 may be an automatic reagent card analyzer, for example. Exemplary embodiments of automatic reagent card analyzers are described in detail in U.S. patent application Serial No. 13/712,144, filed on December 12, 2012, and in PCT application No. PCT/US2012/069621, filed on December 14, 2012, the entire disclosures of which are hereby expressly incorporated herein by reference.
  • the exemplary reagent analyzer 10 may include a housing 14, having a slot 15, the housing 14 surrounding a cavity 18.
  • the reagent analyzer 10 also includes, at least one rail 19, an imaging system 22 comprising at least a camera 26, a sample tray 30 having a sample holder 32 positioned within the cavity 18, a transparent shield 31, and a circuit board 34 having an aperture 38 and one or more illumination source 42a-n positioned within the cavity 18.
  • the housing 14 may be formed from one or more components configured to form the cavity 18 and support the at least one rail 19, imaging system 22, the sample tray 30, the transparent shield 31, and the circuit board 34.
  • the housing 14 is opaque to visible light.
  • the housing 14 is opaque to one or more wavelength of light generated by the one or more illumination source 42a-n.
  • the housing 14 may normalize ambient light.
  • the housing 14 has the slot 15 within which the transparent shield 31 may be positioned into the housing 14, and from which the transparent shield 31 may be removed from within the housing 14.
  • the transparent shield 31 has at least one sidewall 33, at least one end 35, a first surface 36 extending between the at least one sidewall 33 and the at least one end 35, a second surface 37 positioned opposite the first surface 36 extending between the at least one sidewall 33 and the at least one end 35, and an intermediate region 41 extending between the first surface 36 and the second surface 37.
  • the transparent shield 31 has a first sidewall 33a, a second sidewall 33b positioned opposite the first sidewall 33a, a first end 35a, a second end 35b positioned opposite the first end 35a, the first surface 36 extending from the first end 35a to the second end 35b, a second surface 37 positioned opposite the first surface 36 extending from the first end 35a to the second end 35b, and the intermediate region 41 extending between the first surface 36 and the second surface 37.
  • the transparent shield 31 is transparent to visible light such that light may travel through the transparent shield 31 without appreciable scattering allowing objects positioned beyond the transparent shield 31 to be seen and imaged clearly.
  • the transparent shield 31 may have a degree of translucence such that light may travel through the transparent shield 31 with scattering allowing objects positioned beyond the transparent shield 31 to be seen with varying degrees of clarity.
  • the first surface 36 and the second surface 37 may both be planar and substantially parallel so as to avoid magnifying visible light passing through the transparent shield 31.
  • the transparent shield 31 is configured to protect the imaging system 22 from splatter or other debris resulting from movement of the sample tray 30 into and out of the housing 14.
  • the transparent shield 31 may be movable within and out of the housing 14 through the slot 15.
  • the transparent shield 31 may have a grip (not shown) on at least one end 35 of the transparent shield 31.
  • the grip may be a textured surface, e.g., a frost or an etching on the first surface 36 and/or the second surface 37, or may include a handle extending from and/or connected to the first surface 36 and/orthe second surface 37, or the like.
  • the transparent shield 31 has an aperture 43 positioned on an edge of the transparent shield 31 extending from the first surface 36 through the intermediate region 41 to the second surface 37. (FIG. 9).
  • the at least one rail 19 may be positioned within the cavity 18, adjacent to the slot 15 such that upon the positioning of the transparent shield 31 within the slot 15, the surface 37 of the transparent shield 31 may be positioned on the at least one rail 19. In other non-limiting embodiments, the at least one rail 19 may be positioned within the cavity 18, adjacent to the slot 15 such that upon positioning the transparent shield 31 within the slot 15, the surface 36 of the transparent shield 31 may be positioned on the at least one rail 19. In some non-limiting embodiments, the at least one rail 19 may have an engaging member 45 (shown in FIG. 10) oriented in such a way that when the transparent shield 31 is being positioned within the cavity 18, the engaging member 45 causes the transparent shield 31 to be in an ajar position.
  • the transparent shield 31 may be removed from the cavity 18.
  • the transparent shield 31 may function as a barrier to prevent debris from the sample holder 32 from contacting the circuit board 34 and/or the imaging system 22.
  • the imaging system 22 includes the 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 or fixed at a relative distance from the sample tray 30 or the transparent shield 31, for example.
  • the imaging system 22 and/or the camera 26 may include one or more lens with a focal length selected to provide a field of view 40 to include at least the aperture 38 of the circuit board 34.
  • the imaging system 22 may be implemented and function as any desired reader such that the field of view 40 of the imaging system 22 includes substantially the entire aperture 38 of the circuit board 34, for example.
  • the imaging system 22 may be supported at a location above, below, or beside the sample tray 30.
  • the field of view 40 may extend in a linear direction from the imaging system 22 to the aperture 38.
  • the field of view 40 may extend in a non-linear direction from the imaging system 22 to the aperture 38 due to the presence of one or more optical steering component in the field of view 40.
  • Exemplary optical steering components include mirror(s), lens(es), beam splitter(s), or combinations thereof.
  • the imaging system 22 may be configured to detect or capture an image or an optical signal indicative of a reflectance value or a color value of a reagent pad, a lateral flow assay, or the like, (shown in FIGS. 5-7 and discussed in more detail below) positioned in the field of view 40 of the imaging system 22, for example.
  • the imaging system 22 may be configured to detect or capture an image or an optical signal indicative of a reflectance value or a color value of the sample holder 32 positioned in the field of view 40 of the imaging system 22, through the transparent shield 31.
  • the field of view 40 of the imaging system 22 may include only a portion of the aperture 38 of the circuit board 34.
  • the field of view 40 of the imaging system may include only a portion of the transparent shield 31.
  • the camera 26 of the imaging system 22 may include any desired digital or analog imager, such as a digital camera, an analog camera, a CMOS imager, a diode, and combinations thereof.
  • the imaging system 22 may also include a lens system, optical filters, collimators, diffusers, or any other optical-signal processing devices, for example.
  • the imaging system 22 is not limited to an optical imager in the visible spectrum, and may include an infrared imaging system, an ultra-violet imaging system, a microwave imaging system, an X-ray imaging system, and/or other desired imaging systems, for example.
  • Non-exclusive examples of the imaging system 22 include optical imaging systems, spectrophotometers, gas chromatographs, microscopes, infrared sensors, and combinations thereof, for example.
  • the imaging system 22 includes at least one camera 26 and lens wherein the at least one camera 26 is an AR0239: CMOS Image Sensor, 2.3 MP, 1/2.7" and the lens is a DSL949 Sunex lens (Sunex Inc., Carlsbad, CA), both configured to maintain a large field of view 40 while keeping geometric image distortion low, thereby providing a resolution of 1080 pixels by 1920 pixels wherein each pixel depicts approximately a 0.065mm square area of the sample tray 30 and/or the sample holder 32.
  • the at least one camera 26 is an AR0239: CMOS Image Sensor, 2.3 MP, 1/2.7"
  • the lens is a DSL949 Sunex lens (Sunex Inc., Carlsbad, CA), both configured to maintain a large field of view 40 while keeping geometric image distortion low, thereby providing a resolution of 1080 pixels by 1920 pixels wherein each pixel depicts approximately a 0.065mm square area of the sample tray 30 and/or the sample holder 32.
  • the sample tray 30 may be configured to adjust the location of the sample holder 32 within the field of view 40.
  • the sample holder 32 may be configured to receive at least one of a test device 44 (shown in FIGS. 5-7) and a calibration device 300 (shown in FIGS. 15 and 16).
  • the test device 44 may be one of a reagent card 124 (shown in FIGS. 5-7) and a reagent card cassette 304 (shown in FIGS. 13 and 14), each having a sample 46.
  • the calibration device 300 may be one of a reagent card calibration device 308 (shown in FIG. 15) and a reagent cassette card calibration device 312 (shown in FIG. 16).
  • the reagent card calibration device 308 may be similar in size and dimension to the reagent card 124, and the reagent cassette card calibration device 312 may be similar in size and dimension to the reagent card cassette 304, except that the reagent card calibration device 308 and the reagent cassette card calibration device 312 are white in color and do not contain the sample 46.
  • the sample 46 may be any bodily fluid, tissue, or any other chemical or biological sample, and combinations thereof, such as urine, saliva, or blood, for example.
  • the sample 46 may be in liquid form and may contain one or more target constituents such as bilirubin, ketones, glucose, or any other desired target constituent, for example.
  • the circuit board 34 having the aperture 38 may be positioned within the cavity 18 and interposed 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, the calibration device 300, and/or the sample 46.
  • the circuit board 34 is described in FIGS. 1-2, and FIG. 4B and in more detail below.
  • the circuit board 34 is positioned at 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 (described below) would have to be performed after any adjustment.
  • the circuit board 34 may be positioned between the imaging system 22 and the transparent shield 31, such that the field of view 40 of the imaging system 22 is substantially unobstructed from the sample holder 32, the test device 44, the calibration device 300, and/or the sample 46.
  • the reagent analyzer 10 includes a calibration bar48 within the field of view 40 of the imaging system.
  • the calibration bar 48 can be a flat white plastic strip within the housing 14 of the reagent analyzer 10 that spans the width of the test device 44, such as a reagent strip, and is used as a reference measurement to compute percent reflectance for test devices 44 (e.g., strips).
  • the sample holder 32 supports the calibration bar 48 within the field of view 40 of the imaging system 22 such that the calibration bar 48 is adjacent to the test device 44.
  • the housing 14 may include a plurality of connected sidewalls 80, 82, 84 and 86 cooperating to surround the cavity 18.
  • the sidewall 80 is spaced from the sidewall 82, and the sidewall 84 is spaced from the sidewall 86.
  • the transparent shield 31 may be sized and dimensioned to traverse the cavity 18 between the sidewalls 80 and 82, and the sidewalls 84 and 86 thereby dividing the cavity 18 into a first portion 88 and a second portion 90.
  • the transparent shield 31 may have a length L between approximately 5 cm and approximately 21 cm.
  • the transparent shield 31 may be a protecting device for the lens, wherein the transparent shield 31 may have a length of approximately 5 cm. In other non-limiting embodiments, the transparent shield 31 may be a protecting device for the lens and the optical components, wherein the transparent shield 31 may have a length of approximately 14 cm. In some non-limiting embodiments, wherein the transparent shield 31 is a protecting device for the lens and the optical components, the transparent shield 31 may not be removable from the reagent analyzer 10.
  • the housing 14 has the slot 15, and the transparent shield 31 is positioned within the cavity 18 adjacent to the slot 15, the slot having a width W1 and a height dl, the transparent shield 31 having a width W2 less than the width W1 of the slot 15 and a thickness d2 less than the height dl of the slot 15.
  • the slot may have a width W1 of approximately 4.5 cm, a height dl of approximately 0.2 cm, and the transparent shield 31 may have a width W2 of approximately 4.3 cm and a thickness d2 of approximately 0.1 cm.
  • the height dl of the slot 15 may be greater than 0.1 cm. In some non-limiting embodiments, the thickness d2 of the transparent shield 31 may be between approximately 0.1 cm and approximately .3 cm. In some embodiments, the width W1 of the slot 15 may be between approximately 1.7 cm and approximately 4.5 cm. In some non-limiting embodiments, the width W2 of the transparent shield 31 may be between approximately 1.5 cm and approximately 4.3 cm. In some embodiments, the transparent shield 31 is movably supported within the housing 14 and aligned with the slot 15 such that the transparent shield 31 is movable through the slot 15.
  • the surface 36 and the surface 37 of the transparent shield 31 are planar and parallel within the intermediate region 41 to avoid distorting or scattering light passing through the transparent shield 31.
  • the transparent shield 31 may be separate from the imaging system 22 and configured to block debris originating from the sample tray 30 from coming into contact with the imaging system 22.
  • the transparent shield 31 may be constructed of glass, ceramic, plastic, such as acrylic, polycarbonate, and the like.
  • control and/or power signals may be supplied to the illumination source 42a-n by the controller 144.
  • the intensity of the optical signal emitted by the illumination source 42a-n is maintained substantially constant through the operation of the reagent analyzer 10, such as by control and power signals supplied by the controller 144.
  • the optical signals emitted by the illumination source 42a- n may be conditioned or processed by one or more optical or other systems (not shown), such as filters, diffusers, polarizers, lenses, lens systems, collimators, and combinations thereof, for example.
  • the sample holder 32 may be adapted to accept the test device 44 in the form of a reagent card cassette 304 having one or more multiple-profile reagent cards 124 therein, for example.
  • An exemplary reagent card 124 is shown in FIGS. 5-7 and described in more detail below, and an exemplary reagent card cassette 304 is shown in FIGS. 13 and 14 and described in more detail below.
  • Each reagent card 124 (detailed below) may include a substrate 128 and one or more reagent pads 132a-n positioned thereon, or otherwise associated therewith.
  • Each reagent card cassette 304 may include a reagent pad 132 and a reading area 316.
  • the reagent pads 132a-n may include fluidic or microfluidic compartments (not shown).
  • the sample holder 32 may be further adapted to accept the calibration device 300 in the form of the reagent card calibration device 308 and/or the reagent card cassette calibration device 312.
  • An exemplary reagent card calibration device 308 is shown in FIG. 15 and described in more detail below, and an exemplary reagent card cassette calibration device 312 is shown in FIG. 16 and described in more detail below.
  • Y1 such as a certain type of analyte.
  • the color developed by a reaction of a particular constituent with a particular reagent may define a characteristic discrete spectrum for absorption and/or reflectance of light for that particular constituent.
  • the extent of color change of the reagent and the sample 46 may depend on the amount of the target constituent present in the sample 46, for example. In some embodiments, the color change may be viewed through the reading area 316 of the reagent card cassette 304.
  • the presence and concentrations of these target constituents in the sample 46 may be determinable by an analysis of the color changes undergone by the one or more reagent pads 132a-n at predetermined times after application of the sample 46 to the reagent pads 132a-n and/or at predetermined read positions in the field of view of the imaging system 22, for example, such as the reading area 316 of the reagent card cassette 304.
  • This analysis may involve a color comparison of each reagent pad 132a-n to itself at different time periods after application of the sample 46 and/or at different read positions in the field of view 40 of the imaging system 22.
  • the sample 46 may be assigned to one of a number of categories, e.g., a first category corresponding to no target constituent present in the sample 46, a second category corresponding to a small concentration of target constituent present in the sample 46, a third category corresponding to a medium concentration of target constituent present in the sample 46, and a fourth category corresponding to a large concentration of target constituent present in the sample 46, for example.
  • a first category corresponding to no target constituent present in the sample 46
  • a second category corresponding to a small concentration of target constituent present in the sample 46
  • a third category corresponding to a medium concentration of target constituent present in the sample 46
  • a fourth category corresponding to a large concentration of target constituent present in the sample 46, for example.
  • the imaging system 22 may detect an optical signal indicative of a color or a reflectance value of a reagent pad 132a-n, the calibration bar 48, and/or a test strip at any time interval after a volume of sample 46 has been dispensed on the test device 44, e.g., the reagent pad 132a-n and/or test strip, and regardless of location of the particular reagent pad 132a-n and/or test strip, for example.
  • a video, or a sequence of images may be captured of the reagent pad 132a-n, the calibration bar 48, and/or test device 44 at a variety of time intervals after a volume of sample 46 is deposited on the reagent pad 132a-n and/or test strip.
  • Controlled illumination will be described herein by way of example as uniform illumination across an extent, i.e., length and width, of the sample holder 32 and/or sample 46 within acceptable limits. It should be understood, however, that the present disclosure is not limited to uniform illumination.
  • the circuit board 34 is comprised of a substrate 60 having a bottom surface 61a and a top surface 61b, a plurality of conductive leads extending on or in the substrate 60, and the aperture 38 extending between the bottom surface 61a and the top surface 61b.
  • the one or more illumination source 42a-n is a plurality of LEDs 64a-n and one or more IR LED 68.
  • the LEDs 64a-n shown in FIG. 4A include twenty (20) visible light LEDs arranged as shown in FIG. 4A, and one or more IR LED 68.
  • the LEDs 64a-n includes any LED that is needed to produce a substantially uniform light intensity across the sample holder 32 and/or reagent card 124 or reagent cassette.
  • the IR LED 68 may be used to apply heat to the sample 46, or identify an ID pad on the test device 44, for example. In one embodiment, the ID pad is utilized to correlate the sample 46 on the test device 44 supported by the sample holder 32 with a data obtained by the reagent analyzer 10.
  • the plurality of LEDs 64a-n are selected to provide a fixed color, visible light, ultra-violet light, infrared light, or white light, or some combination thereof.
  • each LED 64a-n is positioned at an angle relative to the reagent card 124.
  • each LED 64a-n is positioned at one or more distance from the test device 44 and/or the calibration device 300 supported by the sample holder 32 such that a first LED 64 and a second LED 64 are different distances from the test device 44, the calibration device 300, and/or the sample holder 32.
  • a substantially uniform light intensity may be achieved.
  • the substantially uniform light intensity may be between 85% - 100% uniform.
  • the illumination source circuitry may be configured to supply a first power to a first illumination source 42a and a second power to a second illumination source 42b wherein 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 arranged such that the illumination intensity across the field of view 40 of the camera 26 is substantially uniform, thereby increasing accuracy of readings of color changes of the reagent pads as the reagent pads are illuminated with a substantially uniform intensity (depicted in more detail below and in FIGS. 5-7).
  • the substrate 60 of circuit board 34 as shown in FIG. 4B, is substantially planar thereby causing each of the one or more illumination source 42a-n to be a similar distance from the sample tray 30.
  • the distance between the illumination source 42a-n and the sample 46 may be different for certain of the illumination sources 42a-n.
  • the circuit board 34 may be non-planar thereby causing one of more of the illumination source 42a-n to be located at different distances from the sample tray 30.
  • one or more illumination source 42a-n may be affixed to a standoff (not shown) where each standoff is affixed to the circuit board 34 and provides one or more conductive paths to a particular one of the illumination source 42a-n. When a standoff is used, this causes a portion of the one or more illumination source 42a-n to be closer to the sample 46 and/or the sample tray 30.
  • 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.
  • the one or more illumination source 42a-n may be affixed to the substrate 60 in each of the first region 62a, second region 62b, and intermediate region 62c, or some combination thereof.
  • a first power may be applied to the one or more illumination source 42a-n within the first region 62a and within the second region 62b thereby causing the one or more illumination source 42a-n within the first region 62a and within the second region to provide a first illumination intensity
  • a second power may be applied to the one or more illumination source 42a-n within the intermediate region 62c thereby causing the one or more illumination source 42a-n within the intermediate region 62c to provide a second illumination intensity, the first power and the second power being different and the first illumination intensity and the second illumination intensity being different.
  • the aperture 38 of the circuit board 34 extends from the top surface 61b to the bottom surface 61a to provide an opening for the field of view 40 of the imaging system 22 to pass through from the imaging system 22 through the transparent shield 31 to the sample holder 32 and provide the camera 26 with a controlled view of the test device 44 and/or the calibration device 300 associated with the sample holder 32.
  • the aperture 38 may be further configured such that the bottom surface 61a of the circuit board 34 may include one or more illumination source 42a-n on each side of the aperture 38.
  • the aperture 38 is located substantially within the intermediate region 62c.
  • the aperture 38 has a first major axis and a first minor axis and the sample holder 32 has a second major axis and a second minor axis wherein the first major axis is aligned with the second major axis. While the aperture 38 is depicted as a rectangle in FIG. 4A for providing a controlled view of a rectangular reagent test device, it is understood that the aperture 38 may be configured of any shape such that the field of view 40 is a controlled view of the sample tray 30 and the illumination source 42 can be calibrated to provide a substantially uniform illumination of the sample 46. In the example of FIG. 4A, the aperture 38 does not extend to an edge of the circuit board 34.
  • the aperture 38 extends to an edge of the circuit board 34 without bisecting the circuit board 34 whereas in another embodiment, the aperture 38 extends through the entire circuit board 34, bisecting the circuit board into a first half and a second half, wherein the first half and the second half are mounted at separate locations and supported by the housing 14 such that the field of view 40 is a controlled view of the sample tray and the illumination source 42.
  • the reagent card 124 may include a substrate 128 and one or more, or a plurality of reagent pads 132a-n positioned thereon, or otherwise associated therewith.
  • the substrate 128 may be constructed of any suitable material, such as paper, photographic paper, polymers, fibrous materials, and combinations thereof, for example.
  • the reagent pads 132a-n may be arranged in a grid-like configuration on the substrate 128 so as to define one or more test strip, for example.
  • the reagent pads 132a-n may include fluidic or microfluidic compartments (not shown).
  • the reagent pads 132a-n may be spaced apart a distance from one another so that the test strips are spaced apart such that adjacent test strips and/or reagent pads 132a-n may be simultaneously positioned at separate positions within the field of view 40 of the imaging system 22, for example.
  • the reagent card 124 may be a multipleprofile reagent card having multiple reagent pads 132a-n having different reagents and/or multiple different test strips. Further, in some exemplary embodiments, the reagent card 124 may include one or more calibration chips or reference pads, which may have no reagent and may serve as color references, for example. In another embodiment, the reagent card 124 includes an ID pad having an identifier visible under IR light.
  • Each reagent pad 132a-n may include a reagent configured to undergo a color change in response to the presence of a target constituent such as a molecule, cell, or substance in the sample 46 of a specimen deposited on the reagent pad 132a-n.
  • the reagent pads 132a-n may be provided with different reagents for detecting the presence of different target constituents. Different reagents may cause one or more color change in response to the presence of a certain constituent in the sample 46, such as a certain type of analyte.
  • the color developed by a reaction of a particular constituent with a particular reagent may define a characteristic discrete spectrum for absorption and/or reflectance of light forthat particular constituent.
  • the extent of color change of the reagent and the sample may depend on the amount of the target constituent present in the sample 46, for example.
  • the color change may be read by the imaging system 22. Signals indicative of the colorof the reagent pads 132a-n may be received and/orcaptured in an image by the imaging system 22, which may analyze the signals and determine a change in the color of the reagent pad 132a-n as a result of the reagent pad 132a-n reacting with the volume of sample 46 deposited thereon.
  • Such color change may be analyzed as a function of the read position of the reagent pad 132a-n when the optical signal or image indicative of the color of the reagent pad 132a-n was detected and/or as a function of the known duration of time the volume of sample 46 has been deposited onto the reagent pad 132a-n, and combinations thereof, for example.
  • the color change may be interpreted as a quantitative, qualitative, and/or semi- qualitative indication of the presence and/or concentration or amount of a target constituent in the volume of sample 46 deposited on the reagent pad 132a-n as described above.
  • FIG. 4B shown therein is an analyzer diagram 140 depicting the reagent analyzer 10 including the transparent shield 31 and an analyzer controller 144.
  • the analyzer controller 144 has at least a processor 148 coupled to a non-transitory computer readable medium 152.
  • the non-transitory computer readable medium 152 can be random access memory, read-only memory or the like and can be located locally with the processor 148 or remotely (e.g., in the cloud).
  • the non-transitory computer readable medium 152 can be formed of any suitable medium, such as a magnetic medium, semiconductor medium, or optical medium.
  • the non-transitory computer readable mediuml52 may store computer executable instructions, such as one or more software application 154 (hereinafter, the "software application 154") that, when executed by the processor 148, causes the processor 148 to communicate with and/or be operably coupled to other elements of the reagent analyzer 10. While the analyzer controller 144 is depicted separately from the reagent analyzer 10, it is understood that in some embodiments, the analyzer controller 144 may be integrated into the reagent analyzer 10, such as, by way of example only, the analyzer controller 144 may be an additional component of the reagent analyzer 10 or may be integrated with another component of the reagent analyzer 10, for example, the circuit board 34.
  • the analyzer controller 144 may be integrated into the reagent analyzer 10, such as, by way of example only, the analyzer controller 144 may be an additional component of the reagent analyzer 10 or may be integrated with another component of the reagent analyzer 10, for example, the circuit board 34.
  • the imaging system 22 may be operably coupled with the analyzer controller 144 and/or the processor 148 so that one or more power and/or control signals may be transmitted to the camera 26 and/or to the one or more illumination source 42a-n by the controller 144, and so that one or more signals may be transmitted from the camera 26 to the processor 148, for example.
  • the analyzer controller 144 may be configured to gauge test results as a reagent card is sampled within the reagent analyzer 10, for example, by receiving one or more signals from the camera 26.
  • the camera 26 may be configured to detect or capture one or more optical or other signals through the transparent shield 31 that are indicative of a reflectance value of the calibration bar 48, the test device 44, such as a reagent pad 132a-n, and/or the calibration device 300, and to transmit a signal indicative of the reflectance value of the calibration bar 48, the test device 44, e.g., the reagent pad 132a- n, and/or the calibration device 300, to the processor 148, for example.
  • One or more optical signals having wavelengths indicative of a reflectance value of the calibration bar 48 may be detected through the transparent shield 31 by the camera 26.
  • One or more optical signals having wavelengths indicative of a reflectance value of the reagent pads 132a-n and/or the test strip may be detected through the transparent shield 31 by the camera 26 at each read position, for example.
  • the camera 26 may detect an optical signal through the transparent shield 31 indicative of a reflectance value of a reagent pad 132a-n and/or test strip at any desired read position, location, or area within the field of view 40, or any other desired location or area or multiple locations or areas, for example.
  • the signal transmitted to the processor 148 by the camera 26 may be an electrical signal, an optical signal, and combinations thereof, for example.
  • the signal is in the form of an image file having a matrix of pixels, with each pixel having a color code indicative of a reflectance value.
  • the image file may have two or more predetermined regions of pixels with one predetermined region corresponding to the calibration bar 48, and other predetermined regions of pixels corresponding to a read position of one of the reagent pads and/or the test strip in the field of view 40 of the camera 26.
  • the processor 148 may calculate normalized values of the predetermined regions of pixels corresponding to a read position of one of the reagent pads by determining a percent reflectance as a ratio of the color space pixel values of the pixels corresponding to a read position to color space pixel values of the region corresponding to the calibration bar. This normalization step can be performed separately for each color channel in the color space.
  • an RGB digital image includes three color channels, i.e. Red, Green and Blue.
  • the processor 148 may store the signal transmitted and or the image file in one or more database 156 and/or in the non-transitory computer readable mediuml52. [0090] The processor 148 may determine the reflectance value or the color change of reagent pad and/or a test strip along with a sample (e.g., urine) disposed on the reagent pad and/or test strips based on the signals detected by the camera 26, for example. Each optical or other signal indicative of one or more reflectance value readings detected by the camera 26 may have a magnitude relating to a different wavelength of light (i.e., color).
  • the color of the sample(s) and/or the reaction of the one or more reagents with a target constituent in a reagent pad may be determined based upon the relative magnitudes of the reflectance signals of various color components, for example, red, green, and blue reflectance component signals.
  • the color of each reagent pad may be translated into a standard color model, which typically includes three or four values or color components (e.g., RGB color model, including hue, saturation, and lightness (HLS) and hue, saturation, and value (HSV) representation of points and/or CMYK color model, or any other suitable color model) whose combination represents a particular color.
  • RGB color model typically includes three or four values or color components (e.g., RGB color model, including hue, saturation, and lightness (HLS) and hue, saturation, and value (HSV) representation of points and/or CMYK color model, or any other suitable color model) whose combination represents a particular color.
  • HLS hue, saturation, and lightness
  • HVS hue, saturation
  • the camera 126 may detect multiple optical signals at each read position, with each detected signal having one or more color components, such as a red component signal, a green component signal, and a blue component signal, for example, and each of the component signals may be transmitted to the processor 148.
  • the camera 26 may detect a single optical signal at each read position, and the processor 148 may translate a signal received from the camera 26 into separate color component signals such as a red component signal, a green component signal, and a blue component signal, for example.
  • the method 200 for determining the degree of occlusion 178 (also referred to herein as a presence of one or more "environmental agent 178") in the field of view 40.
  • the occlusion 178 may be caused by dirt, a urine spot(s), debris and combinations thereof.
  • the occlusion 178 can be on the calibration bar 48 or the transparent shield 31 (described below and shown in FIG. 8).
  • the method 200 may be implemented as a set of processor executable instructions or logic (i.e., the software application 154) stored in the non-transitory computer readable medium 152, which instructions or logic when executed by the processor 148, cause the processor 148 to determine the degree of occlusion in the field of view, e.g., of the calibration bar 48, the transparent shield 31 or of a lens of the camera 26.
  • the method 200 for determining the degree of occlusion 178 may be performed periodically such as at a preset internal time as desired according to specific quality control procedures applicable to the reagent analyzer 10, and combinations thereof, for example. In other embodiments, however, the method 200 for determining the degree of occlusion 178 may be performed prior to each use of the reagent analyzer 10.
  • the processor 148 is further configured to have a set of processor executable instructions or logic stored in the non-transitory computer readable medium, wherein when the instructions or logic are executed by the processor 148, cause the processor 148 to cause an action on at least one periodic interval selected from a group comprising: initiate an alert in a form perceivable by a human, initiate a cleaning process configured to clean the transparent shield 31 or a lens of the camera 26, and replace the transparent shield 31 or a lens of the camera 26.
  • the periodic interval is based on a period of time or a number of tests performed by the reagent analyzer 10.
  • FIGS. 5-7 shown therein are exemplary images 170a-c illustrating a top plan view of the sample holder 32, the calibration bar 48, and test device 44, in the form of the reagent card 124, as viewed through the exemplary transparent shield 31 positioned within the housing 14 of the reagent analyzer 10 in accordance with the present disclosure.
  • the imaging system 22 may capture the image 170 of the sample holder 32, the calibration bar 48, and test device 44 through the exemplary transparent shield 31 having varying degrees of occlusion due to debris on the transparent shield 31 which may be caused by splatter from the test device 44 being moved by the sample holder 32.
  • the calibration bar 48 being attached to the sample tray 32, has the risk of having varying degrees of occlusion due to accumulating dirt / urine droplets / debris. Varying degrees of occlusion has a direct impact on the results of a patient sample.
  • any of the occlusions such as dirt / urine droplets / debris, can be detected with precise location of the occlusion within the field of view 40. Because the precise location of the occlusion within the field of view 40 can be determined, the algorithm may provide very definitive action steps to the user to carry out maintenance activities / replacement.
  • FIG. 5 illustrates an exemplary top plan view image 170a of the sample holder 32 having the test device 44, in the form of a reagent card 124, as viewed through the transparent shield 31 that does not have an environmental agent 178 present on the surface 36 or surface 37 of the transparent shield 31.
  • FIG. 6 illustrates an exemplary top plan view image 170b of the sample holder 32 having the test device 44 in the form of the reagent card 124, as viewed through the transparent shield 31 having environmental agents 178, such as dust, present on the surface 36 or the surface 37 of the transparent shield 31. Although many environmental agents 178 are shown in FIG. 6, only one environmental agent 178 is numbered for purposes of clarity.
  • the method 200 for detecting the occlusion within the optical path of the field of view 40 generally comprises the steps of: dividing an area of an image 170 of a test device 44 (e.g., calibration device 300) within the reagent analyzer 10 into a plurality of sub-areas 400a-n (shown in FIGS. 15 and 16) (step 204); computing a first statistical metric 512a (shown in FIGS.
  • the plurality of sub-areas 400a-n have a pre-defined size.
  • the pre-defined size may be stored in the non-transitory computer readable mediuml52, the database 156, or the like.
  • the first statistical metric 512a and the second statistical metric 512b may be selected from a group comprising: a minimum, maximum, median, or mean pixel value for one or more of a red channel, a green channel, and a blue channel of the image 170; a minimum, maximum, median, or mean pixel value for one or more of a hue, a saturation, and a value of the image 170; a minimum, maximum, median, or mean pixel value for one or more of a luma component, a blue-difference chroma component, and a red-difference chroma component of the image 170; a minimum, maximum, median, or mean pixel value for one or more of a perceptual lightness, a position between red and green, and a position between yellow and blue of the image 170.
  • the method 200 further comprises, prior to dividing the area of the image 170 of the calibration device 300 (step 204), transforming the image 170.
  • Transforming the image 170 may include transforming the image 170 from a red-green-blue (RGB) image 170 having an RGB color space to a hue-saturation-value (HSV) image 170 having an HSV color space, a YCbCr image 170 having a YCbCr color space, and an International Commission on Illumination (CIE) LAB image 170 having a CIELAB color space.
  • RGB red-green-blue
  • HSV hue-saturation-value
  • YCbCr image 170 having a YCbCr color space
  • CIE International Commission on Illumination
  • the plurality of sub-areas 400a-n form a row 404 of subareas 400a-n, and the first sub-area 400a and the second sub-area 400b are within the row 404 of sub-areas 400a-n (shown in FIG. 15).
  • analyzing the first statistical metric 512a and the second statistical metric 512b in the row 404 of sub-areas 400a-n further comprises computing a first predicted statistical metric 516a for the first sub-area 400a and a second predicted statistical metric 516b for the second sub-area 400b.
  • the baseline value can be set as a value corresponding to a percentage difference, such as 1.5 to 2% of a maximum value of the first statistical metric 512a or the second statistical metric 512b.
  • the method 200 further comprises assigning a unique value (shown on the x-axis 520 in FIGS. 17 and 18) to each of the sub-areas 400a-n and using the unique values in the computation of the first predicted statistical metric 516a for the first sub-area 400a and the second predicted statistical metric 516b for the second sub-area 400b.
  • the baseline value can be set as a value corresponding to a percentage difference, such as 1.5 to 2% of a maximum value
  • the first predicted statistical metric 516a and the second predicted statistical metric 516b may be determined by fitting a curve 504 (shown in a first graph 500a in FIG. 17 and a second graph 500b in FIG. 18) to the plurality of statistical metrics 512a-n including the first statistical metric 512a and the second statistical metric 512b, wherein each of the points on the curve 504 correspond to a particular one of the plurality of predicted statistical metrics 516a-n.
  • the curve 504 is defined by a polynomial function.
  • the polynomial function is a seventh-degree polynomial function.
  • the polynomial function may have a degree that is more or less than seven. As shown in FIG.
  • analyzing the first statistical metric 512a and the second statistical metric 512b includes: comparing the first statistical metric 512a to the first statistical baseline metric to generate a first value (i.e., the first value indicative of the difference between the first statistical metric 512a and the first statistical baseline metric); comparing the second statistical metric 512b to the second statistical baseline metric to generate a second value (i.e., the second value indicative of the difference between the second statistical metric 512b and the second statistical baseline metric); and responsive to the first value or the second value exceeding a baseline value, determining that the occlusion 178 of the calibration device 300 exists.
  • the baseline value can be within a range of 1.5% to 2% of a maximum value of the first statistical metric 512a or the second statistical metric 512b.
  • comparing the first statistical metric 512a to the first predicted statistical metric 516a, comparing the second statistical metric 512b to the second predicted statistical metric 516b, comparing the first statistical metric 512a to the second statistical metric 512b, comparing the first statistical metric 512a to the first statistical baseline metric, and/or comparing the second statistical metric 512b to the second statistical baseline metric is performed using a statistical metric selected from a group comprising: absolute difference; root mean square (RMS) error; relative deviation; mean squared error (MSE); mean absolute error (MAE); R 2 error; mean absolute percentage error (MAPE); combinations thereof; and/or the like.
  • dividing the area of the image 170 of the calibration device 300 is defined further as executing a program (e.g., the software application 154) having a first boundary forthe first sub-area 400a pre-defined.
  • the predefined first boundary for the first sub-area 400a may be stored in the non-transitory computer readable mediuml52, the database 156, or the like.
  • cleaning or replacing the transparent shield 31 improves the accuracy of the analysis provided by the reagent analyzer 10.
  • cleaning the transparent shield 31 can be implemented by moving the transparent shield 31 out of the housing 14 through the slot 15 (without the need to disassemble the analytical device or access the optical system directly), cleaning the surface 36 or the surface 37 of the transparent shield 31 and moving the transparent shield 31 into the housing 14 through the slot 15.
  • Cleaning the transparent shield 31 can be implemented manually by a human gripping the transparent shield 31, or in an automated fashion. In the automated version, a motor-driven wiper can be used to wipe and clean the surface 36 or the surface 37.
  • replacing the transparent shield 31 can be implemented by moving the transparent shield 31 out of the housing 14 through the slot 15, discarding the transparent shield 31, and moving a replacement transparent shield 31 into the housing 14 through the slot 15.
  • the data indicative of the degree of occlusion 178 may be stored in the non- transitory computer readable mediuml52, the database 156, or the like.
  • the data indicative of the transparent shield 31 (for example) having a degree of occlusion 178 may have a time stamp.
  • the method 200 for determining the degree of occlusion 178 of the optical path of the field of view 40 may be implemented as a set of processor executable instructions or logic (i.e., the software application 154) stored in the non-transitory computer readable medium 152, which instructions or logic when executed by the processor 148, cause the processor 148 to carry out the logic to calculate or determine the degree of occlusion 178 of the optical path of the field of view 40.
  • the method 200 for determining the degree of occlusion 178 of the optical path of the field of view 40 may be carried out periodically, such as at a preset interval of time or may be according to specific quality control procedures applicable to the reagent analyzer 10, and combinations thereof, for example.
  • the processor 148 may be configured to process an image 170 of the sample holder 32 through the transparent shield 31 having the degree of translucence positioned within the housing 14 of the reagent analyzer 10, and detect the degree of translucence of the transparent shield 31.
  • the analyzer 10 may be configured to calibrate the degree of translucence of the transparent shield 31 to a known transparency standard of the transparent shield 31 stored in the non- transitory computer readable mediuml52 to normalize or correct for any inadvertent optical influence caused by light passing through the transparent shield 31.
  • the calibration of the degree of translucence of the transparent shield 31 may be conducted at periodic intervals during use of the analyzer 10 or by operator command.
  • the processor 148 is further configured have a set of processor executable instructions or logic stored in the non-transitory computer readable mediuml52, wherein when the instructions or logic are executed by the processor 148, cause the processor 148 to cause an action on at least one periodic interval selected from a group comprising: initiate an alert in a form perceivable by a human, initiate a cleaning process configured to clean the transparent shield 31, and replace the transparent shield 31.
  • the periodic interval is based on a period of time or a number of tests performed by the reagent analyzer 10.
  • FIG. 13 illustrates an exemplary top plan view image 170d of the sample holder 32 having the test device 44 in the form of the reagent card cassette 304, as viewed through the transparent shield 31 that does not have an environmental agent 178 present on the surface 36 or surface 37 of the transparent shield 31.
  • FIG. 14 illustrates an exemplary top plan view image 170e of the sample holder 32 having the test device 44 in the form of the reagent card cassette 304, as viewed through the transparent shield 31 having environmental agents 178, such as a urine droplet or dust, present on the surface 36 or the surface 37 of the transparent shield 31. Although many environmental agents 178 are shown in FIG. 14, only one environmental agent 178 is numbered for purposes of clarity.
  • FIG. 15 illustrates an exemplary top plan view image 170f of the sample holder 32 having the calibration device 300 in the form of the reagent card calibration device 308, as viewed through the transparent shield 31 having environmental agents 178, such as dust, present on the surface 36 or the surface 37 of the transparent shield 31. Although many environmental agents 178 are shown in FIG. 15, only one environmental agent 178 is numbered for purposes of clarity.
  • FIG. 16 illustrates an exemplary top plan view image 170f of the sample holder 32 having the calibration device 300 in the form of the reagent card cassette calibration device 312, as viewed through the transparent shield 31 having environmental agents 178, such as dust, present on the surface 36 orthe surface 37 of the transparent shield 31. Although many environmental agents 178 are shown in FIG. 15, only one environmental agent 178 is numbered for purposes of clarity.
  • Illustrative Embodiment 1 A method performed by at least one processor executing processor executable instructions stored in a non-transitory computer readable medium that causes the at least one processor to: divide an area of an image of a calibration device within a reagent analyzer into a plurality of sub-areas; compute a first statistical metric of a first sub-area of the plurality of sub-areas using pixel data within the first sub-area; compute a second statistical metric of a second sub-area of the plurality of sub-areas using pixel data within the second sub-area; analyze the first statistical metric and the second statistical metric to determine if an occlusion of the calibration device exists in the first sub-area or the second sub-area; and responsive to a determination that the occlusion of the calibration device exists in the first sub-area or the second sub-area, cause an action selected from a group comprising: initiating an alert in a form perceivable by a human; storing data indicative of the occlusion
  • Illustrative Embodiment 2 The method of illustrative embodiment 1, wherein the plurality of sub-areas form a row of sub-areas, and wherein the first sub-area and the second sub-area are within the row of sub-areas.
  • Illustrative Embodiment 3 The method of illustrative embodiment 2, wherein analyzing the first statistical metric and the second statistical metric in the row of sub-areas further comprises computing a first predicted statistical metric for the first sub-area and a second predicted statistical metric for the second sub-area, and wherein analyzing the first statistical metric and the second statistical metric further comprises: comparing the first statistical metric to the first predicted statistical metric to generate a first value; comparing the second statistical metric to the second predicted statistical metric to generate a second value; and responsive to the first value or the second value exceeding a baseline value, determining that the occlusion of the calibration device exists.
  • Illustrative Embodiment 4 The method of illustrative embodiment 3, further comprising the step of assigning a unique value to each of the sub-areas and using the unique values in the computation of the first predicted statistical metric for the first sub-area and the second predicted statistical metric for the second sub-area.
  • Illustrative Embodiment 5 The method of illustrative embodiment 1, wherein analyzing the first statistical metric and the second statistical metric is defined further as assigning unique values to the first sub area and the second sub area, and computing a mathematical model based on the unique values, the first statistical metric, and the second statistical metric, and wherein the mathematical model is used to generate a first predicted statistical metric and a second predicted statistical metric, and wherein analyzing fu rther comprises: comparing the first statistical metric to the first predicted statistical metric to generate a first value; comparing the second statistical metric to the second predicted statistical metric to generate a second value; and responsive to the first value or the second value exceeding a baseline value, determining that the occlusion of the calibration device exists.
  • Illustrative Embodiment 6 The method of illustrative embodiment 1, wherein the first sub-area is adjacent to the second sub-area, and wherein analyzing the first statistical metric and the second statistical metric further comprises: comparing the first statistical metric to the second statistical metric; and responsive to a difference between the first statistical metric and the second statistical metric being above a threshold, determining that the occlusion of the calibration device exists within at least one of the first sub-area and the second sub-area.
  • Illustrative Embodiment 7 The method of illustrative embodiment 1, further comprising the steps of storing a first statistical baseline metric associated with the first sub-area in the non-transitory computer readable medium and storing a second statistical baseline metric associated with the second sub-area in the non-transitory computer readable medium prior to the step of computing the first statistical metric, and wherein analyzing the first statistical metric and the second statistical metric includes: comparing the first statistical metric to the first statistical baseline metric to generate a first value; comparing the second statistical metric to the second statistical baseline metric to generate a second value; and responsive to the first value or the second value exceeding a baseline value, determining that the occlusion of the calibration device exists.
  • Illustrative Embodiment 8 The method of illustrative embodiment 1, further comprising the step of inserting the calibration device into the reagent analyzer prior to dividing the area of the image of the calibration device.
  • Illustrative Embodiment 9. The method of illustrative embodiment 1, wherein dividing the area of the image of the calibration device is defined further as executing a program having a first boundary pre-defined for the first sub-area.
  • a reagent analyzer comprising: a housing; a sample holder configured to support a calibration device, the sample holder movable into the housing and out of the housing; a transparent shield; an imaging system having a field of view extending through the transparent shield and configured to capture an image of the calibration device positioned within the sample holder through the transparent shield at a read position in the field of view, the image having a plurality of pixels; at least one processor; and a non-transitory computer readable medium storing processor executable instructions that when executed by the at least one processor causes the at least one processor to: divide an area of the image of the calibration device within the reagent analyzer into a plurality of sub-areas; compute a first statistical metric of a first sub-area of the plurality of sub-areas using first pixel data within the first sub-area; compute a second statistical metric of a second sub-area of the plurality of sub-areas using second pixel data within the second sub-area
  • processor executable instructions when executed by the at least one processor further causes the at least one processor to assign a unique value to each of the sub-areas and use the unique values in the computation of the first predicted statistical metric for the first sub-area and the second predicted statistical metric for the second sub-area.
  • analyzing the first statistical metric and the second statistical metric in the row of sub-areas is defined further as computing a mathematical model based on the unique values, the first statistical metric, and the second statistical metric, and wherein the mathematical model is used to generate the first predicted statistical metric and the second predicted statistical metric.
  • Illustrative Embodiment 15 The reagent analyzer of illustrative embodiment 10, wherein the first sub-area is adjacent to the second sub-area, and wherein analyzing the first statistical metric and the second statistical metric further comprises: comparing the first statistical metric to the second statistical metric; and responsive to a difference between the first statistical metric and the second statistical metric being above a threshold, determining that the occlusion of the calibration device exists within at least one of the first sub-area and the second sub-area.
  • Illustrative Embodiment 16 The reagent analyzer of illustrative embodiment 10, wherein the processor executable instructions when executed by the at least one processor further causes the at least one processor to store a first statistical baseline metric associated with the first sub-area in the non-transitory computer readable medium and store a second statistical baseline metric associated with the second sub-area in the non-transitory computer readable medium prior to the step of computing the first statistical metric, and wherein analyzing the first statistical metric and the second statistical metric includes: comparing the first statistical metric to the first statistical baseline metric to generate a first value; comparing the second statistical metric to the second statistical baseline metric to generate a second value; and responsive to the first value or the second value exceeding a baseline value, determining that the occlusion of the calibration device exists.
  • Illustrative Embodiment 17 The reagent analyzer of illustrative embodiment 10, wherein the processor executable instructions when executed by the at least one processor further causes the at least one processor to insert the calibration device into the reagent analyzer prior to dividing the area of the image of the calibration device.

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Abstract

Sont décrits un procédé, un analyseur de réactif et un support lisible par ordinateur non transitoire qui divise une zone de l'image du dispositif d'étalonnage à l'intérieur d'un analyseur de réactif en une pluralité de sous-zones, calcule une première métrique statistique d'une première sous-zone de la pluralité de sous-zones à l'aide de premières données de pixel à l'intérieur de la première sous-zone, calcule une seconde métrique statistique d'une seconde sous-zone de la pluralité de sous-zones à l'aide de secondes données de pixel à l'intérieur de la seconde sous-zone, analyse la première métrique statistique et la seconde métrique statistique pour déterminer si une occlusion du dispositif d'étalonnage existe dans la première sous-zone ou la seconde sous-zone ; et en réponse à une détermination selon laquelle l'occlusion du dispositif d'étalonnage existe dans la première sous-zone ou la seconde sous-zone, provoquer une action pour remédier à l'occlusion.
PCT/US2025/025912 2024-04-26 2025-04-23 Détection automatisée de particules étrangères et de gouttelettes d'échantillon dans un chemin optique pour des analyseurs d'urine à base d'imagerie Pending WO2025226778A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150276613A1 (en) * 2012-10-25 2015-10-01 Chrm Sciences, Inc. Definitive development diagnostic analysis
US20210215615A1 (en) * 2010-08-26 2021-07-15 Charm Sciences, Inc. Assay analysis
US20220274103A1 (en) * 2017-10-31 2022-09-01 The Penn State Research Foundation Biochemical analysis system

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210215615A1 (en) * 2010-08-26 2021-07-15 Charm Sciences, Inc. Assay analysis
US20150276613A1 (en) * 2012-10-25 2015-10-01 Chrm Sciences, Inc. Definitive development diagnostic analysis
US20220274103A1 (en) * 2017-10-31 2022-09-01 The Penn State Research Foundation Biochemical analysis system

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