Clinical analyzer automated system diagnostics

Abstract

A method for operating a laboratory instrument having multiple subsystems and diagnosing faults in the laboratory instrument can include performing an analytical sequence and a set of diagnostic steps. Such a method can be performed using a diagnostic reagent that includes paramagnetic particles and lacks an antibody component. The set of diagnostic steps can include adding, to each container in the set of containers, a diagnostic reagent that includes paramagnetic particles and lacks an antibody component. Such a method can also include evaluating the set of instrument subsystems in the reverse order that those subsystems are used during the analysis.

Description

[Technical Field]

[0001] (Related Applications) This is related to and claims the benefit of U.S. Provisional Patent Application No. 62 / 785,863, entitled "Clinical Analyzer Automated System Diagnostics," filed with the United States Patent Office on December 28, 2018, which application is incorporated herein by reference in its entirety. [Background technology]

[0002] Automated clinical analyzers are well known in the art and are generally used for the automated or semi-automated analysis of patient samples. Typically, a prepared patient sample, such as blood, urine, or spinal fluid, is placed on such an analyzer in a sample container, such as a test tube. The analyzer pipettes the patient sample and one or more reagents into a reaction cell (e.g., a reaction vessel, cuvette, or flow cell), where the sample is typically analyzed for a particular analyte of interest, and the results of the analysis are reported.

[0003] Historically, maintaining such analyzers has generally required customers, field service, and manufacturing engineers to manually perform diagnostic routines, including manually filling sample tubes with test solutions, loading them into the analyzer, requesting tests on the tubes using the analyzer user interface, and processing them through the instrument. During this process, the analyzer may be unavailable for processing actual samples, which can result in significant downtime over the life of the machine. Additionally, if there is a fault in the machine, the individual responsible for fixing it (e.g., a field service engineer) may not have any information about the root cause of the fault and may therefore have to initiate an extended diagnostic testing session to determine what type of remediation may be required, thereby further increasing instrument downtime.

[0004] Therefore, there is a need for a method for diagnosing faults in clinical analyzers that overcomes the limitations of the prior art. Summary of the Invention [Means for solving the problem]

[0005] According to certain aspects of the present disclosure, a method for operating a laboratory instrument having multiple subsystems and diagnosing faults in the laboratory instrument can be implemented. Such a method may include performing an analytical step sequence to analyze a biological sample, where the analytical step sequence may utilize a set of subsystems from the multiple subsystems in a first order. Such a method may also include performing a set of diagnostic steps to identify faults in the laboratory instrument. In such a case, performing the set of diagnostic steps may include evaluating each subsystem in the set of subsystems in a second order, where the second order in which the subsystems in the set of subsystems are evaluated may reverse the first order in which the subsystems in the set of subsystems are used in the analytical step sequence.

[0006] According to certain aspects of the present disclosure, a method for operating and diagnosing faults in a laboratory instrument can be implemented to include performing an analytical step sequence and a diagnostic step sequence. In such a method, the analytical step sequence can include adding an assay reagent to a reaction vessel that includes paramagnetic particles and an antibody adapted to bind to an analyte. A set of diagnostic steps can include, for each vessel in the set of vessels, adding a diagnostic reagent that includes paramagnetic particles and does not include an antibody component.

[0007] According to certain aspects of the present disclosure, a method for diagnosing a fault in a laboratory instrument may be implemented. Such a method may include cleaning each container from a set of containers, using a digital camera to capture one or more particle retention images, and calculating a retention value based on the one or more particle retention images.

[0008] According to certain aspects of the present disclosure, a method for diagnosing faults in a laboratory instrument having multiple subsystems may be implemented. Such a method may include performing a set of diagnostic steps to identify a fault in the laboratory instrument. In such a method, each diagnostic step in the set of diagnostic steps may correspond to a subsystem in the multiple subsystems. Such a method may also include detecting a fault in the laboratory instrument during execution of a diagnostic step from the set of diagnostic steps and providing an output identifying a subsystem in the laboratory instrument corresponding to the diagnostic step in which a fault was detected.

[0009] According to certain aspects of the present disclosure, methods for operating a laboratory instrument and diagnosing faults in the laboratory instrument may be implemented. In some aspects, such methods may include performing an analytical step sequence to analyze a biological sample. Such an analytical step sequence may include transferring a portion of the biological sample from a sample container to a reaction container, generating an analysis mixture by transferring a first reagent including alkaline phosphatase (ALP) from a reagent pack to the reaction container, removing from the reaction container a portion of the analysis mixture that is not bound to the analyte using an assay wash subsystem, adding a substrate adapted to react with the ALP to produce chemiluminescent light to the reaction container, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using a luminometer. In such methods, the method may also include performing a set of diagnostic steps, including evaluating the assay wash subsystem by performing a set of wash efficiency check steps for each of a set of one or more containers. Such wash efficiency check steps may include adding, for each container, a combination of an ALP solution, a second reagent including paramagnetic particles, and a wash buffer to the container. Such a wash efficiency check step may also include, for each of the containers, exposing the container to a magnetic field, adding additional wash buffer to the container, and spinning the contents of the container at high speed. Such a wash efficiency check step may also include, for each of the containers, aspirating a fluid from the container, adding it to the container adapted to react with ALP to produce chemiluminescent light, and using a luminometer to measure the chemiluminescent light from the container after it is placed in a luminometer container chamber.

[0010] According to certain aspects of the present disclosure, a method for operating a laboratory instrument and diagnosing faults in the laboratory instrument can be implemented. Such a method may include performing an analytical step sequence for analyzing a biological sample using multiple subsystems, including a sample dispensing subsystem, a reagent dispensing subsystem, an assay washing subsystem, and a chemiluminescence detection subsystem. In such a method, the analytical step sequence may include generating an analytical mixture by transferring a first reagent including ALP from a reagent pack to a reaction vessel using the reagent dispensing subsystem, removing from the reaction vessel a portion of the analytical mixture that is not bound to the analyte using the assay washing subsystem, adding a substrate adapted to react with the ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using the chemiluminescence detection subsystem. Such a method may also include performing a set of diagnostic steps, including evaluating the multiple subsystems using a luminometer included in the chemiluminescence detection subsystem and, in parallel with the evaluation, using machine vision to evaluate one or more of the multiple subsystems.

[0011] According to certain aspects of the present disclosure, a method for operating a laboratory instrument with multiple subsystems and diagnosing a fault in the laboratory instrument can be implemented. Such a method may include performing an analytical step sequence and a diagnostic step sequence. In such a method, the analytical step sequence may include transferring a portion of a biological sample from a sample container to a reaction container, generating an analysis mixture by transferring a first reagent including ALP from a reagent pack to the reaction container using a reagent dispensing subsystem, removing a portion of the analysis mixture that is not bound to the analyte from the reaction container using an assay wash subsystem, adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction container, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using a chemiluminescent detection subsystem. In such a method, a set of diagnostic steps may include adding the substrate to a test container and determining that a fault exists in the laboratory instrument based on the chemiluminescent light detected using the chemiluminescent detection subsystem. Such a method may also include performing a set of expanded diagnostic steps based on determining that a fault exists in the laboratory instrument. Such a set of magnified diagnostic steps may include, for each of a plurality of magnified test vessels, adding a predetermined volume of test fluid to the magnified test vessel, capturing an image of the magnified test vessel, and determining the volume of test fluid in the magnified test vessel using the image of the magnified test vessel. In such methods, the test fluid may be selected from the group consisting of a substrate adapted to react with ALP to produce chemiluminescent light, a wash buffer, a first reagent comprising ALP, and a second reagent comprising paramagnetic particles.

[0012] According to certain aspects of this disclosure, a non-transitory computer-readable medium can be implemented having stored thereon data that operatively configures a computer to perform a method as described in any of the preceding paragraphs.

[0013] According to certain aspects of the disclosure, a machine can be implemented that includes a sample dispensing subsystem, a reagent dispensing subsystem, an assay wash subsystem, a chemiluminescence detection subsystem, and means for automatically diagnosing faults in the operation of the machine.

[0014] Various additional aspects are set forth in the following description. These aspects can relate to individual features and combinations of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit the broad concepts upon which the embodiments disclosed herein are based. The present invention provides, for example, the following. (Item 1) 1. A method of operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the set of subsystems in a second order; ii) performing the second order in which each subsystem in the set of subsystems is evaluated, reversing the first order in which the set of subsystems are used in the analysis process sequence. (Item 2) a) the set of subsystems: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) The method of item 1, wherein the second sequence includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem. (Item 3) a) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with ALP to produce chemiluminescent light, followed by incubating the vessel; iii) measuring chemiluminescent light from the receptacle using a luminometer provided by the chemiluminescence detection subsystem after the receptacle has been incubated and placed in a luminometer receptacle chamber; b) The method according to item 2, wherein each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to each container. (Item 4) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) modifying the bottle used to store the substrate to be adapted to react with ALP to produce chemiluminescent light; and ii) decontaminating a line used to transport the substrate adapted to react with ALP to produce chemiluminescent light. (Item 5) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of receptacle-free optical check steps, the set of receptacle-free optical check steps comprising: i) measuring light detected in the luminometer vessel chamber by the luminometer when no vessel is present in the luminometer vessel chamber; ii) causing a light source provided by the chemiluminescent detection subsystem to emit light at one or more intensities; and iii) for each of the one or more intensities, measuring light detected by the luminometer when the light source provided by the chemiluminescent detection subsystem is emitting light at that intensity. (Item 6) The method comprises: a) determining the fault in the laboratory instrument based on light detected during the set of receptacle-free light check steps; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) cleaning a luminometer box provided by the chemiluminescence detection subsystem; ii) recalibrating the luminometer; and iii) replacing the luminometer. (Item 7) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of substrate volume check steps, the set of substrate volume check steps comprising: i) adding to a test vessel a predetermined volume of said substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the actual volume of the substrate adapted to react with ALP to produce chemiluminescent light in the test vessel using one or more images of the test vessel captured by a digital camera. (Item 8) The method comprises: a) determining the disturbance in the laboratory device based on the actual volume of the substrate adapted to react with ALP in the test container to produce chemiluminescent light; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the substrate dispensing probe; ii) replacing the substrate dispensing syringe. (Item 9) evaluating the sample dispensing subsystem, a) for each of a set of one or more sample vessels: i) adding a predetermined amount of ALP solution to the sample container using a reagent pipetter; ii) transferring a portion of the ALP solution from the sample vessel to a corresponding reaction vessel in a set of one or more reaction vessels using a sample pipettor provided by the sample dispensing subsystem; b) for each of the set of one or more reaction vessels corresponding to a sample vessel in the set of one or more sample vessels, i) adding to the reaction vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the chemiluminescent light from the reaction vessel using a luminometer provided by the chemiluminescent detection subsystem after the reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 10) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) addressing the fault by checking the sample pipetter position. (Item 11) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of camera sample volume checking steps, the set of camera sample volume checking steps comprising: i) for each of the plurality of magnified diagnostic sample containers; A) dispensing a first volume of wash buffer into the enlarged diagnostic sample container using a reagent pipettor; B) aspirating a second volume of wash buffer from the enlarged diagnostic sample container using the sample pipettor; C) capturing one or more digital camera images of the magnified diagnostic sample container after aspiration of the second volume of wash buffer; ii) for each of the first set of expanded diagnostic reaction vessels: A) dispensing a third volume of wash buffer into the expanded diagnostic reaction vessel using the sample pipettor; B) capturing one or more digital camera images of the magnified diagnostic reaction vessel after dispensing the third volume of wash buffer; iii) for each of the second set of expanded diagnostic reaction vessels: A) dispensing a fourth volume of wash buffer into the expanded diagnostic reaction vessel using the sample pipettor; B) capturing one or more digital camera images of the magnified diagnostic reaction vessel after dispensing the fourth volume of wash buffer. (Item 12) The method comprises: a) determining the fault in the laboratory instrument based on images captured during the set of camera sample volume check steps; b) dealing with the fault by replacing the sample dispensing syringe. (Item 13) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of sample volume linearity check steps, the set of sample volume linearity check steps comprising: i) for each of a set of one or more test sample containers: A) adding a predetermined amount of ALP solution to the test sample container using a reagent pipetter; B) using the sample pipettor to transfer a portion of the ALP solution from the test sample container to a corresponding test reaction vessel in a set of one or more test reaction vessels, the portion of the ALP solution transferred from the test sample container having a volume corresponding to the test reaction vessel to which the portion of the ALP solution was transferred, the subset of the set of test reaction vessels; ii) for each of the set of one or more test reaction vessels corresponding to a test sample vessel in the set of one or more test sample vessels, A) adding to the reaction vessel the substrate adapted to react with ALP to produce chemiluminescent light; B) measuring the chemiluminescent light from the reaction vessel using the luminometer provided by the chemiluminescent detection subsystem after the reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 14) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the sample volume linearity checking step; b) addressing the fault by replacing the sample dispensing motor. (Item 15) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of sample dilution check steps, the set of sample dilution check steps comprising: i) adding a predetermined volume of ALP solution to each of a plurality of test sample containers using the reagent pipettor; ii) for each of the first set of test dilution containers: A) transferring a first amount of the ALP solution from a corresponding test sample container to the test dilution container using the sample pipettor; B) adding a second amount of wash buffer to the test dilution container using the reagent pipettor; C) mixing the contents of the test dilution container; D) transferring a third amount of fluid from the dilution vessel to a corresponding reaction vessel using the sample pipettor; iii) for each of the second set of test dilution containers: A) transferring a fourth amount of the ALP solution from a corresponding test sample container to the test dilution container using the sample pipettor; B) adding a fifth volume of Wash Buffer to the test dilution container using a reagent pipettor; C) mixing the contents of the test dilution container; D) transferring the third amount of fluid from the dilution vessel to a corresponding reaction vessel using the sample pipettor; iv) adding to each of said test reaction vessels corresponding to said test dilution vessels said substrate adapted to react with ALP to produce chemiluminescent light; and v) measuring the chemiluminescent light from the test reaction vessel using a luminometer provided by the chemiluminescent detection subsystem after the test reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 16) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the set of luminometer sample volume checking steps; b) addressing the fault by checking the sample dispensing tip immersion height. (Item 17) The sample pipettor a) a precision sample pipettor; b) a sample aliquot pipettor; and c) a sample aliquot pipettor. (Item 18) a) the set of subsystems comprises an assay wash subsystem; b) the analytical process sequence includes using the assay wash subsystem to remove unbound material from the reaction vessel between using the sample dispensing subsystem to dispense the biological fluid into the reaction vessel and using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) The method of claim 2, wherein the set of diagnostic steps includes evaluating the operation of the assay washing subsystem between evaluating the operation of the sample dispensing subsystem and evaluating the operation of the chemiluminescent detection subsystem. (Item 19) a) the instrument comprises a reagent dispensing subsystem; b) the analysis step sequence includes using the reagent dispensing subsystem to dispense reagents into the reaction vessels before using the assay wash subsystem to remove unbound material from the reaction vessels; c) The method of claim 18, wherein the set of diagnostic steps includes evaluating the operation of the reagent dispensing subsystem before evaluating the operation of the assay washing subsystem. (Item 20) a) evaluating the operation of the reagent dispensing subsystem before evaluating the operation of the assay wash subsystem includes evaluating the operation of the reagent dispensing subsystem using a digital camera; b) The method of claim 19, wherein the set of diagnostic steps includes evaluating the performance of the reagent dispensing subsystem using a luminometer provided by the luminescence detection subsystem after evaluating the performance of the assay washing subsystem. (Item 21) evaluating operation of the reagent dispensing subsystem using a digital camera; a) ultrasonically mixing the diagnostic reagents in the diagnostic reagent pack using an ultrasonic probe; b) for each container in the set of containers, using the reagent pipettor to transfer the diagnostic reagent from the diagnostic reagent pack to the container; c) using the digital camera to capture one or more reagent resuspension images, each of the one or more reagent resuspension images comprising an image of a container in the set of containers after the diagnostic reagent has been added to the container; d) performing a reagent resuspension check using the one or more reagent resuspension images. (Item 22) a) the reagent dispensed into the reaction vessel prior to using the assay wash subsystem to remove unbound material from the reaction vessel comprises paramagnetic particles and an antibody component adapted by binding to an analyte; b) The method according to item 21, wherein the diagnostic reagent comprises paramagnetic particles and does not comprise an antibody component. (Item 23) The method comprises: a) determining that the laboratory instrument is faulty based on the reagent resuspension check; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the ultrasonic probe; ii) calibrating ultrasound in said laboratory instrument; iii) replacing an ultrasound transducer of the laboratory instrument. (Item 24) Evaluating the operation of the reagent dispensing subsystem using the luminance meter includes, for each of a set of one or more containers: a) adding a predetermined volume of ALP solution to the container using a reagent pipettor; b) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; c) performing a set of luminometer reagent volume check steps, including measuring chemiluminescent light from the container using the luminometer provided by the chemiluminescence detection subsystem after the container has been spun, incubated, and placed in a luminometer container chamber. (Item 25) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) addressing the fault by rearranging the position of the reagent pipettor. (Item 26) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) expanding the evaluation of the reagent dispensing subsystem by performing a set of camera reagent volume check steps for each of a plurality of test containers, the set of camera reagent volume check steps comprising: i) adding a predetermined volume of wash buffer to the test vessel using the reagent pipettor; ii) capturing one or more images of the test vessel. (Item 27) The method comprises: a) determining the fault in the laboratory instrument based on images captured during the set of camera reagent volume check steps; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the reagent dispensing syringe; ii) replacing the reagent dispensing motor. (Item 28) a) the method comprises: i) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; ii) augmenting the evaluation of the reagent dispensing subsystem by performing a set of reagent volume linearity check steps for each of a plurality of test vessels, the set of reagent volume linearity check steps comprising: A) adding a predetermined volume of a mixture of ALP solution and wash buffer to the test vessel; B) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; C) measuring chemiluminescent light from the container using a luminometer provided by the chemiluminescent detection subsystem after the container has been spun, incubated, and placed in a luminometer container chamber; b) the plurality of test vessels comprises a subset of three test vessels; c) for each of the three subsets of test vessels comprised by the plurality of test vessels, the mixture of ALP solution and wash buffer added to the test vessels comprised by the subset of test vessels has a ratio of ALP solution to wash buffer that is different from the ratio of ALP solution to wash buffer added to the test vessels comprised by the other subsets comprised by the plurality of test vessels. (Item 29) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the reagent volume linearity checking step; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) checking the perpendicularity of the reagent pipettor; ii) replacing the tip of the reagent pipettor; iii) replacing the ultrasonic transducer. (Item 30) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) expanding the evaluation of the reagent dispensing subsystem by performing a set of reagent pipettor carryover check steps for each of a plurality of test containers, the set of reagent pipettor carryover check steps comprising: i) adding ALP solution to the test vessel using the reagent pipettor; ii) adding a wash buffer to the test vessel using the reagent pipettor after adding the ALP solution; iv) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; v) adding the substrate adapted to react with ALP to produce chemiluminescent light, followed by rapid spinning of the test vessel; vi) measuring chemiluminescent light from the vessel using a luminometer provided by the chemiluminescence detection subsystem after incubation and placement in a luminometer vessel chamber. (Item 31) The method comprises: a) determining the fault in the laboratory instrument based on chemiluminescence light detected in the reagent pipetter carryover check step; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the tip of the reagent pipettor; ii) checking the status of a wash tower provided by said assay wash subsystem; iii) replacing the wash dispense pump. (Item 32) 1. A method of operating a laboratory instrument and diagnosing a fault in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, the analytical step sequence comprising adding assay reagents to a reaction vessel, the assay reagents comprising paramagnetic particles and antibodies adapted to bind to an analyte; b) performing a set of diagnostic steps to evaluate the operation of the laboratory instrument, the set of diagnostic steps including, for each container in the set of containers, adding a diagnostic reagent to the container, the diagnostic reagent including paramagnetic particles and not including an antibody component. (Item 33) a) the assay reagent has a first concentration of paramagnetic particles; b) the diagnostic reagent has a second concentration of paramagnetic particles; c) The method of claim 32, wherein the first concentration is lower than the second concentration. (Item 34) a) the first concentration is 0.3 mg / mL to 2.0 mg / mL, b) The method of claim 33, wherein the second concentration is 4.0 mg / mL. (Item 35) The set of diagnostic steps comprises: a) for each container in the set of containers: i) creating a test mixture by combining the diagnostic reagent added to the container with a portion of a wash buffer; ii) exposing the test mixture to a magnetic field in the container; iii) removing the container from the magnetic field; and iv) mixing the test mixture contained in the container after the container is removed from the magnetic field; b) using a digital camera to capture one or more particle resuspension images, each of the one or more particle resuspension images comprising an image of a container in the set of containers after the test mixture contained in the container has been mixed; c) performing a resuspension check using the one or more particle resuspension images. (Item 36) For each container in the set of containers, mixing the test mixture contained in the container; a) moving the container onto a cleaning wheel into a high speed rotational mixing position; b) mixing the test mixture contained in the container at high speed. (Item 37) The method comprises: a) determining that the laboratory instrument is faulty based on the resuspension check; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) arranging a high-speed rotating mixer at the high-speed rotating mixing position on the cleaning wheel; ii) replacing the high-speed rotating mixer. (Item 38) For each container in the set of containers, mixing the test mixture contained in the container before moving the container to the high speed rotation mixing position on the cleaning wheel includes: a) moving the container to a pipette position within the laboratory instrument; b) ultrasonically mixing the test mixture contained in the vessel using a reagent pipettor. (Item 39) The method comprises: a) determining that the laboratory instrument is faulty based on the resuspension check; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) aligning the reagent pipettor to the pipette position within the laboratory instrument; ii) checking the verticality of the reagent pipettor. (Item 40) The set of diagnostic steps comprises: a) for each container of the set of containers, ultrasonically mixing the diagnostic reagent using an ultrasonic probe before adding the diagnostic reagent to the container; b) using a digital camera to capture one or more reagent resuspension images, each of the one or more reagent resuspension images comprising an image of a container in the set of containers after the diagnostic reagent has been added to the container; c) performing a reagent resuspension check using the one or more reagent resuspension images. (Item 41) The method comprises: a) determining that the laboratory instrument is faulty based on the reagent resuspension check; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the ultrasonic probe; ii) calibrating ultrasound in said laboratory instrument; iii) replacing an ultrasound transducer of the laboratory instrument. (Item 42) 1. A method of diagnosing a fault in a laboratory instrument, the method comprising: a) cleaning each container from a set of containers; b) using a digital camera to capture one or more particle-retention images, each of the one or more particle-retention images comprising an image of a container in the set of containers after the container has been cleaned; c) performing a set of diagnostic steps including: calculating a retention value based on said one or more particle retention images. (Item 43) a) the set of containers includes a plurality of containers; b) the set of diagnostic steps includes, for each vessel in the set of vessels, generating a test mixture by combining a reagent containing paramagnetic particles added to the vessel with a portion of a wash buffer; c) The method of claim 42, wherein the test mixture in each vessel in the set of vessels comprises 50 μL of reagent and 150 μL of wash buffer. (Item 44) The method comprises: a) determining that the laboratory instrument is faulty based on the retention value; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) aligning an aspiration probe with a reaction vessel location within said laboratory instrument; ii) checking the magnetic functionality of the laboratory instrument. (Item 45) The retention value is a) grayscale values ​​derived from said one or more particle-retaining images; b) a particle retention calibration curve. (Item 46) a) the particle retention calibration curve is generated using a plurality of calibration mixtures, each of which includes a portion of a reagent comprising paramagnetic particles and a portion of a wash buffer; b) The method of claim 45, wherein the plurality of calibration mixtures comprises a set of calibration mixtures, each calibration mixture in the set of calibration mixtures having a different reagent to wash buffer ratio than any other calibration mixture in the set of calibration mixtures. (Item 47) said set of calibration mixtures comprising: a) 50:150 and b) 40:160 and c) 35:165 and d) a calibration mixture having a reagent to wash buffer ratio of 25:175. (Item 48) a) generating said particle retention calibration using said plurality of calibration mixtures; i) for each calibration mixture, A) delivering a container containing said calibration mixture to a cleaning wheel; B) spinning the container containing the calibration mixture at a substrate spin position on the cleaning wheel; C) capturing a grayscale image of the container containing the calibration mixture after it has been mixed; ii) generating the calibration curve with the captured grayscale image of the container containing the calibration mixture; b) the set of containers includes a plurality of containers; c) the set of diagnostic steps comprises, for each container in the set of containers: i) creating a test mixture by combining the reagent added to the vessel with a portion of a wash buffer; ii) washing at least two times with the wash buffer after the test mixture is prepared in the vessel; iii) aspirating fluid from the container with an aspiration probe after the container has been washed at least twice; iv) adding a volume of wash buffer to the container after the fluid has been aspirated from the container with the aspiration probe, the volume of wash buffer added to the container being equal to the volume of test mixture that was in the container prior to aspiration; v) spinning the container at a substrate spin position on the wash wheel after the volume of wash buffer has been added to the container; d) The method of claim 46, wherein the one or more particle retention images comprise a grayscale image of each container in the set of containers captured after the container has had a volume of wash buffer added to it and has been spin-mixed at the substrate spin position on the wash wheel. (Item 49) 1. A method for diagnosing faults in a laboratory instrument having multiple subsystems, the method comprising: a) performing a set of diagnostic steps to identify faults in the laboratory instrument, each diagnostic step in the set of diagnostic steps corresponding to a subsystem in the plurality of subsystems; b) detecting a fault in the laboratory instrument during execution of a diagnostic step in the set of diagnostic steps; c) providing an output identifying the subsystem corresponding to the diagnostic step during which the fault was detected in the laboratory instrument. (Item 50) a) the plurality of subsystems: i) a sample dispensing subsystem; ii) a reagent dispensing subsystem; and iii) an assay wash subsystem; and iv) a chemiluminescence detection subsystem; b) the device is adapted to analyze the biological sample for the presence of an analyte by performing a set of analytical steps, the analytical steps comprising: i) transferring a portion of the biological sample from a sample container to a reaction container using the sample dispensing subsystem; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel using the reagent dispensing subsystem; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to the analyte using the assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using the chemiluminescent detection subsystem. (Item 51) 1. A method of operating a laboratory instrument and diagnosing a fault in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, said analytical step sequence comprising: i) transferring a portion of the biological sample from a sample container to a reaction container; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to said reaction vessel; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using an assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using a luminometer; b) performing a set of diagnostic steps, including evaluating the assay wash subsystem by performing a set of wash efficiency check steps for each of a set of one or more containers, the set of wash efficiency check steps comprising: i) A) ALP solution; B) a second reagent comprising paramagnetic particles; C) Combination with washing buffer, adding to said container; ii) performing a set of cleaning steps, A) exposing the container to a magnetic field; B) adding additional wash buffer to the vessel; C) removing the contents of the container performing one or more high speed rotations; iii) aspirating fluid from said container; iv) after aspirating fluid from said container, adding said substrate adapted to react with ALP to produce chemiluminescent light; v) incubating the container; vi) using the luminometer to measure chemiluminescent light from the container after it is placed in a luminometer container chamber. (Item 52) a) the second reagent comprising paramagnetic particles does not comprise an antibody component; b) the analysis step sequence comprises adding a third reagent comprising paramagnetic particles to the reaction vessel, the paramagnetic particles provided by the third reagent being coated with an antibody component adapted to bind to the analyte. (Item 53) a) the analytical step sequence i) transferring a third reagent comprising paramagnetic particles to the reaction vessel before transferring the first reagent comprising ALP to the reaction vessel; ii) incubating the reaction vessel between transferring the third reagent comprising paramagnetic particles to the reaction vessel and transferring the first reagent comprising ALP to the reaction vessel; iii) incubating the reaction vessel between transferring the third reagent comprising ALP to the reaction vessel and detecting chemiluminescent light produced by the substrate in reaction with the ALP using the luminometer; b) The method according to item 51, wherein for each container in the set of containers, the container is incubated only once during the performance of the set of diagnostic steps. (Item 54) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) addressing the fault by aligning a pick-and-place actuator position with the container position. (Item 55) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of wash buffer volume check steps, the set of wash buffer volume check steps comprising: i) using each of one or more probes to add a predetermined volume of wash buffer to one or more test vessels; ii) transferring each of the test vessels to a camera position on a wash wheel, where the predetermined volume of wash buffer has been added; iii) capturing an image of the one or more test vessels to which the predetermined volume of wash buffer has been added; and iv) using the captured image to determine the actual volume of the wash buffer added to each of the one or more test vessels. (Item 56) The method comprises: a) determining the fault in the laboratory instrument based on the actual volume of the wash buffer added to the one or more test vessels; b) addressing the fault by replacing the one or more probes used to add the wash buffer to the one or more test vessels. (Item 57) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of residual volume check steps, the set of residual volume check steps comprising: i) using each of one or more probes to add a predetermined volume of wash buffer to one or more test vessels; ii) for each test vessel to which the predetermined volume of wash buffer has been added, A) moving the test vessel to an aspiration position corresponding to the probe used to add the predetermined amount of wash buffer to the test vessel; B) aspirating fluid from the test vessel using an aspiration probe positioned at the aspiration position to which the test vessel has been moved; C) moving the test container to a camera position after fluid has been aspirated therefrom; D) capturing one or more images of the test vessel after fluid has been aspirated therefrom; E) determining a residual volume remaining in the test vessel based on the one or more captured images of the test vessel. (Item 58) The method comprises: a) determining the fault in the laboratory instrument based on the residual volume detected in the residual volume checking step; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing one or more aspiration probes; ii) arranging one or more aspiration probes at the aspiration location where they are located; iii) replacing the peristaltic pump tubing. (Item 59) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of aspirate probe carryover check steps, the set of aspirate probe carryover check steps including, for each of a set of one or more test vessels: i) adding the ALP solution to the test vessel; ii) adding a wash buffer to the test vessel after adding the ALP solution; iii) aspirating the ALP solution from the test vessel using an aspirating probe; iv) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; v) adding the substrate adapted to react with ALP to produce chemiluminescent light, followed by rapid spinning of the test vessel; vi) using the luminometer to measure chemiluminescent light from the vessel after incubation and placement in the luminometer vessel chamber. (Item 60) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the aspirate probe carryover check step; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing one or more aspiration probes; ii) checking the status of a wash tower provided by said assay wash subsystem; iii) replacing the wash dispense pump. (Item 61) 1. A method of operating a laboratory instrument and diagnosing a fault in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, i) the analytical step sequence comprises: A) a sample dispensing subsystem; B) a reagent dispensing subsystem; C) an assay wash subsystem; D) a chemiluminescence detection subsystem; ii) performing said analytical step sequence; A) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel using the reagent dispensing subsystem; B) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using the assay wash subsystem; C) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using the chemiluminescent detection subsystem; b) performing a set of diagnostic steps, said diagnostic steps comprising: i) evaluating the plurality of subsystems using a luminometer provided by the chemiluminescence detection subsystem; ii) using machine vision to evaluate one or more subsystems among the plurality of subsystems in parallel with evaluating the plurality of subsystems using a luminometer provided by the chemiluminescence detection subsystem. (Item 62) a) the sample dispensing subsystem: i) a sample precision subsystem; ii) a sample aliquoting subsystem; b) the analytical step sequence i) transferring an aliquot of the biological sample from the sample container to the reaction vessel using the sample aliquoting subsystem; ii) transferring the portion of the biological sample from the sample container to the reaction vessel using the sample dispensing subsystem. (Item 63) a) the analysis step sequence includes adding to the reaction vessel an analysis reagent including paramagnetic particles coated with an antibody component adapted to bind to the analyte; b) The method of claim 61, wherein the set of diagnostic steps comprises adding an analytical reagent containing paramagnetic particles and lacking an antibody component to a vessel that serves as the reaction vessel in the evaluation of the device. (Item 64) 1. A method of operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence, i) transferring a portion of the biological sample from a sample container to a reaction container; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to said reaction vessel using a reagent dispensing subsystem; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using an assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to said reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with said ALP using a chemiluminescent detection subsystem; b) performing a set of diagnostic steps, i) adding to the test vessel said substrate adapted to react with ALP to produce chemiluminescent light; ii) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected using the chemiluminescent detection subsystem; c) performing a set of magnified diagnostic steps based on determining that the fault is present in the laboratory device, for each of a plurality of magnified test containers: i) adding a predetermined volume of test fluid to the enlarged test vessel; ii) capturing an image of said magnified test vessel; iii) determining a volume of the test fluid in the magnified test vessel using the image of the magnified test vessel; The test fluid is A) said substrate adapted to react with ALP to produce chemiluminescent light; B) Washing buffer; C) the first reagent containing ALP; D) a second reagent comprising paramagnetic particles. (Item 65) a) performing the set of diagnostic steps includes, for each of a set of one or more containers: i) in said container said substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with the ALP to produce chemiluminescent light, followed by incubating the vessel; iii) using the chemiluminescence detection subsystem to measure chemiluminescent light from the vessel after incubation and placement in a luminometer vessel chamber; b) determining that the fault is present in the laboratory instrument based on the chemiluminescent light detected using the chemiluminescent detection subsystem comprises determining that at least one container of a set of containers is contaminated with ALP based on detecting light emitted from the container using the chemiluminescent detection subsystem. (Item 66) Item 66. The method of item 65, wherein the test fluid added to the magnification test vessel is the substrate adapted to react with ALP to produce chemiluminescent light. (Item 67) Item 65. The method of item 64, wherein for each of the plurality of magnified test containers, determining the volume of test fluid in the magnified test container using the image of the magnified test container includes determining the volume of the fluid using the distance between the bottom of a meniscus in the magnified test container and the bottom of the magnified test container. (Item 68) performing said set of diagnostic steps a) performing ultrasonic mixing on a diagnostic reagent in a reagent pack; b) transferring a portion of the diagnostic reagent from the reagent pack to a particle testing container; c) capturing an image of the test vessel after the transfer of the portion of the diagnostic reagent; d) determining whether an obstruction exists in the laboratory instrument based on the grayscale value of the image of the test container. (Item 69) 69. The method of claim 68, wherein the diagnostic reagent comprises uncoated paramagnetic particles and does not include any paramagnetic particles coated with an antibody component. (Item 70) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the first set of subsystems in a second order; ii) performing the second order in which each subsystem in the set of subsystems is evaluated, reversing the first order in which the set of subsystems are used in the analysis process sequence. (Item 71) a) the set of subsystems: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) The non-transitory computer-readable medium of Item 70, wherein the second order includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem. (Item 72) a) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with the ALP to produce chemiluminescent light, followed by incubating the vessel; iii) using a luminometer provided by the chemiluminescence detection subsystem to measure chemiluminescent light from the vessel after incubation and placement in a luminometer vessel chamber; b) each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to each container. (Item 73) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) modifying the bottle used to store said substrate adapted to react with ALP to produce chemiluminescent light; ii) decontaminating a line used to transport the substrate adapted to react with ALP to produce chemiluminescent light. (Item 74) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of receptacle-free optical check steps, the set of receptacle-free optical check steps comprising: i) measuring light detected in the luminometer vessel chamber by the luminometer when no vessel is present in the luminometer vessel chamber; ii) causing a light source contained by said chemiluminescent detection subsystem to emit light at one or more intensities; iii) for each of the one or more intensities, measuring light detected by the luminometer when the light source provided by the chemiluminescence detection subsystem is emitting light at that intensity. (Item 75) The method comprises: a) determining the fault in the laboratory instrument based on light detected during the set of receptacle-free light check steps; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) cleaning a luminometer box provided by the chemiluminescence detection subsystem; ii) recalibrating the luminometer; and 75. The non-transitory computer-readable medium of claim 74, comprising: providing a non-transitory computer-readable medium selected from the group consisting of: and iii) replacing the luminometer. (Item 76) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of substrate volume check steps, the set of substrate volume check steps comprising: i) adding to a test vessel a predetermined volume of said substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the actual volume of the substrate adapted to react with ALP to produce chemiluminescent light in the test vessel using one or more images of the test vessel captured by a digital camera. (Item 77) The method comprises: a) determining the disturbance in the test chamber based on the actual volume of the substrate adapted to react with ALP in the test vessel to produce chemiluminescent light; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) replacing the substrate dispensing probe; ii) replacing the substrate dispensing syringe. (Item 78) Evaluating the sample dispensing subsystem includes performing a set of luminometer sample volume check steps, the set of luminometer sample volume check steps comprising: a) for each of a set of one or more sample vessels: i) adding a predetermined amount of ALP solution to the sample container using a reagent pipetter; ii) transferring a portion of the ALP solution from the sample vessel to a corresponding reaction vessel in a set of one or more reaction vessels using a sample pipettor provided by the sample dispensing subsystem; b) for each of the set of one or more reaction vessels corresponding to a sample vessel in the set of one or more sample vessels, i) adding to the reaction vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the chemiluminescent light from the reaction vessel using a luminometer provided by the chemiluminescent detection subsystem after the reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 79) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and b) providing a notification that addresses the fault by checking the sample pipetter position. (Item 80) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of camera sample volume checking steps, the set of camera sample volume checking steps comprising: i) for each of the plurality of magnified diagnostic sample containers; A) dispensing a first volume of wash buffer into the enlarged diagnostic sample container using a reagent pipettor; B) aspirating a second volume of wash buffer from the enlarged diagnostic sample container using the sample pipettor; C) capturing one or more digital camera images of the magnified diagnostic sample container after aspiration of the second volume of wash buffer; ii) for each of the first set of expanded diagnostic reaction vessels: A) dispensing a third volume of wash buffer into the expanded diagnostic reaction vessel using the sample pipettor; B) capturing one or more digital camera images of the magnified diagnostic reaction vessel after dispensing the third volume of wash buffer; iii) for each of the second set of expanded diagnostic reaction vessels: A) dispensing a fourth volume of wash buffer into the expanded diagnostic reaction vessel using the sample pipettor; B) capturing one or more digital camera images of the magnified diagnostic reaction vessel after dispensing the fourth volume of wash buffer. (Item 81) The method comprises: a) determining the fault in the laboratory instrument based on images captured during the set of camera sample volume check steps; b) providing a notification to address the fault by replacing the sample dispensing syringe. (Item 82) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of sample volume linearity check steps, the set of sample volume linearity check steps comprising: i) for each of a set of one or more test sample containers: A) adding a predetermined amount of ALP solution to the test sample container using a reagent pipetter; B) using the sample pipettor to transfer a portion of the ALP solution from the test sample container to a corresponding test reaction vessel in a set of one or more test reaction vessels, wherein the portion of the ALP solution transferred from the test sample container has a volume corresponding to the subset of the set of test reaction vessels to which the portion of the ALP solution was transferred; ii) for each of the set of one or more test reaction vessels corresponding to a test sample vessel in the set of one or more test sample vessels, A) adding to the reaction vessel the substrate adapted to react with ALP to produce chemiluminescent light; B) measuring chemiluminescent light from the reaction vessel using the luminometer provided by the chemiluminescence detection subsystem after the reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 83) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the sample volume linearity checking step; b) providing a notification to address the fault by replacing the sample dispense motor. (Item 84) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; b) augmenting the evaluation of the sample dispensing subsystem by performing a set of sample dilution check steps, the set of sample dilution check steps comprising: i) adding a predetermined volume of ALP solution to each of a plurality of test sample containers using the reagent pipettor; ii) for each of the first set of test dilution containers: A) transferring a first amount of the ALP solution from a corresponding test sample container to the test dilution container using the sample pipettor; B) adding a second amount of wash buffer to the test dilution container using the reagent pipettor; C) mixing the contents of the test dilution container; D) transferring a third amount of fluid from the dilution vessel to a corresponding reaction vessel using the sample pipettor; iii) for each of the second set of test dilution containers: A) transferring a fourth amount of the ALP solution from a corresponding test sample container to the test dilution container using the sample pipettor; B) adding a fifth volume of Wash Buffer to the test dilution container using a reagent pipettor; C) mixing the contents of the test dilution container; D) transferring the third amount of fluid from the dilution vessel to a corresponding reaction vessel using the sample pipettor; iv) adding to each of said test reaction vessels corresponding to said test dilution vessels said substrate adapted to react with ALP to produce chemiluminescent light; and v) measuring chemiluminescent light from the test reaction vessel using a luminometer provided by the chemiluminescent detection subsystem after the test reaction vessel has been spun, incubated, and placed in a luminometer vessel chamber. (Item 85) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the set of luminometer sample volume checking steps; b) providing a notification to address the fault by checking the sample dispensing tip immersion height. (Item 86) The sample pipettor a) a precision sample pipettor; b) a sample aliquot pipettor; and c) a sample aliquot pipettor. (Item 87) a) the set of subsystems comprises an assay wash subsystem; b) the analysis step sequence includes using the assay wash subsystem to remove unbound material from the reaction vessel between using the sample dispensing subsystem to dispense the biological fluid into the reaction vessel and using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) the set of diagnostic steps includes evaluating the operation of the assay wash subsystem between evaluating the operation of the sample dispense subsystem and evaluating the operation of the chemiluminescence detection subsystem. (Item 88) a) the instrument comprises a reagent dispensing subsystem; b) the analysis step sequence includes using the reagent dispensing subsystem to dispense reagents into the reaction vessels before using the assay wash subsystem to remove unbound material from the reaction vessels; c) the set of diagnostic steps includes evaluating the operation of the reagent dispensing subsystem before evaluating the operation of the assay washing subsystem. (Item 89) a) evaluating the operation of the reagent dispensing subsystem before evaluating the operation of the assay wash subsystem includes evaluating the operation of the reagent dispensing subsystem using a digital camera; Item 89. The non-transitory computer-readable medium of Item 88, wherein the set of diagnostic steps includes evaluating the operation of the reagent dispensing subsystem using a luminometer provided by the luminescence detection subsystem after evaluating the operation of the assay washing subsystem. (Item 90) evaluating operation of the reagent dispensing subsystem using a digital camera; a) ultrasonically mixing the diagnostic reagents in the diagnostic reagent pack using an ultrasonic probe; b) for each container in the set of containers, using the reagent pipettor to transfer the diagnostic reagent from the diagnostic reagent pack to the container; c) using the digital camera to capture one or more reagent resuspension images, each of the one or more reagent resuspension images comprising an image of a container in the set of containers after the diagnostic reagent has been added to the container; d) performing a reagent resuspension check using the one or more reagent resuspension images. (Item 91) a) the reagent dispensed into the reaction vessel prior to using the assay wash subsystem to remove unbound material from the reaction vessel comprises paramagnetic particles and an antibody component adapted by binding to an analyte; b) The non-transitory computer-readable medium of item 90, wherein the diagnostic reagent comprises paramagnetic particles and does not comprise an antibody component. (Item 92) The method comprises: a) determining that the laboratory instrument is faulty based on the reagent resuspension check; b) addressing said impairment by performing one or more actions, said one or more actions comprising: i) replacing the ultrasonic probe; ii) calibrating ultrasound in said laboratory instrument; iii) replacing an ultrasound transducer of the laboratory instrument. (Item 93) Evaluating the operation of the reagent dispensing subsystem using the luminance meter includes, for each of a set of one or more containers: a) adding a predetermined volume of ALP solution to the container using a reagent pipettor; b) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; c) performing a set of luminometer reagent volume check steps, including: measuring chemiluminescent light from the container using the luminometer provided by the chemiluminescence detection subsystem after the container has been spun, incubated, and placed in a luminometer container chamber. (Item 94) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) providing a notification that addresses the fault by rearranging the position of the reagent pipettor. (Item 95) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) expanding the evaluation of the reagent dispensing subsystem by performing a set of camera reagent volume check steps for each of a plurality of test containers, the set of camera reagent volume check steps comprising: i) adding a predetermined volume of wash buffer to the test vessel using the reagent pipettor; ii) capturing one or more images of the test vessel. (Item 96) The method comprises: a) determining the fault in the laboratory instrument based on images captured during the set of camera reagent volume check steps; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) replacing the reagent dispensing syringe; ii) replacing the reagent dispensing motor. (Item 97) a) the method comprises: i) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; ii) augmenting the evaluation of the reagent dispensing subsystem by performing a set of reagent volume linearity check steps for each of a plurality of test vessels, the set of reagent volume linearity check steps comprising: A) adding a predetermined volume of a mixture of ALP solution and wash buffer to the test vessel; B) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; C) measuring chemiluminescent light from the container using a luminometer provided by the chemiluminescent detection subsystem after the container has been spun, incubated, and placed in a luminometer container chamber; b) the plurality of test vessels comprises a subset of three test vessels; c) for each of the subsets of three test vessels comprised by the plurality of test vessels, the mixture of ALP solution and wash buffer added to the test vessels comprised by the subset of test vessels has a different ratio of ALP solution to wash buffer than the mixture of ALP solution and wash buffer added to the test vessels comprised in the other subsets comprised by the plurality of test vessels. (Item 98) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the reagent volume linearity checking step; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) checking the perpendicularity of the reagent pipettor; ii) replacing the tip of the reagent pipettor; Item 98. The non-transitory computer-readable medium of item 97, comprising providing a method selected from the group consisting of: and iii) replacing the ultrasound transducer. (Item 99) The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; b) expanding the evaluation of the reagent dispensing subsystem by performing a set of reagent pipettor carryover check steps for each of a plurality of test containers, the set of reagent pipettor carryover check steps comprising: i) adding ALP solution to the test vessel using the reagent pipettor; ii) adding a wash buffer to the test vessel using the reagent pipettor after adding the ALP solution; iv) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; v) adding the substrate adapted to react with ALP to produce chemiluminescent light, followed by rapid spinning of the test vessel; vi) measuring chemiluminescent light from the vessel after incubation and placement in a luminometer vessel chamber using a luminometer provided by the chemiluminescent detection subsystem. (Item 100) The method comprises: a) determining the fault in the laboratory instrument based on chemiluminescence light detected in the reagent pipetter carryover check step; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) replacing the tip of the reagent pipettor; ii) checking the status of a wash tower provided by said assay wash subsystem; Item 100. The non-transitory computer-readable medium of Item 99, comprising providing a method selected from the group consisting of: and iii) replacing the wash dispense pump. (Item 101) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, the analytical step sequence comprising adding assay reagents to a reaction vessel, the assay reagents comprising paramagnetic particles and antibodies adapted to bind to an analyte; b) performing a set of diagnostic steps to evaluate operation of the laboratory instrument, the set of diagnostic steps including, for each container in the set of containers, adding a diagnostic reagent to the container, the diagnostic reagent including paramagnetic particles and not including an antibody component. (Item 102) a) the assay reagent has a first concentration of paramagnetic particles; b) the diagnostic reagent has a second concentration of paramagnetic particles; c) the first concentration is less than the second concentration. (Item 103) a) the first concentration is 0.3 mg / mL to 2.0 mg / mL, b) The non-transitory computer-readable medium of Item 102, wherein the second concentration is 4.0 mg / mL. (Item 104) The set of diagnostic steps comprises: a) for each container in the set of containers: i) creating a test mixture by combining the diagnostic reagent added to the container with a portion of a wash buffer; ii) exposing the test mixture to a magnetic field in the container; iii) removing the container from the magnetic field; and iv) mixing the test mixture contained in the container after removing the container from the magnetic field; b) using a digital camera to capture one or more particle resuspension images, each of the one or more particle resuspension images comprising an image of a container in the set of containers after the test mixture contained in the container has been mixed; c) performing a resuspension check using the one or more particle resuspension images. (Item 105) For each container in the set of containers, mixing the test mixture contained in the container includes: a) moving the container onto a cleaning wheel into a high speed rotational mixing position; b) high-speed spin-mixing of the test mixture contained in the container. (Item 106) The method comprises: a) determining that the laboratory instrument is faulty based on the resuspension check; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) arranging a high-speed rotating mixer at the high-speed rotating mixing position on the cleaning wheel; ii) replacing the high-speed rotating mixer. (Item 107) For each container in the set of containers, mixing the test mixture contained in the container includes: a) moving the container to a pipette position within the laboratory instrument; b) ultrasonically mixing the test mixture contained in the vessel using a reagent pipettor. (Item 108) The method comprises: a) determining that the laboratory instrument is faulty based on the resuspension check; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) aligning the reagent pipettor to the pipette position within the laboratory instrument; ii) checking the verticality of the reagent pipettor. (Item 109) The set of diagnostic steps comprises: a) for each container of the set of containers, ultrasonically mixing the diagnostic reagent using an ultrasonic probe before adding the diagnostic reagent to the container; b) using a digital camera to capture one or more reagent resuspension images, each of the one or more reagent resuspension images comprising an image of a container in the set of containers after the diagnostic reagent has been added to the container; c) performing a reagent resuspension check using the one or more reagent resuspension images. (Item 110) The method comprises: a) determining that the laboratory instrument is faulty based on the reagent resuspension check; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) replacing the ultrasonic probe; ii) calibrating ultrasound in said laboratory instrument; iii) replacing the ultrasound transducer of the laboratory instrument. (Item 111) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for diagnosing faults in a laboratory instrument having multiple subsystems, the method comprising: a) cleaning each container from a set of containers; b) using a digital camera to capture one or more particle-retention images, each of the one or more particle-retention images comprising an image of a container in the set of containers after the container has been cleaned; and c) calculating a retention value based on the one or more particle retention images. (Item 112) a) the set of containers includes a plurality of containers; b) the set of diagnostic steps includes, for each vessel in the set of vessels, generating a test mixture by combining a reagent containing paramagnetic particles added to the vessel with a portion of a wash buffer; c) The non-transitory computer-readable medium of Item 111, wherein the test mixture in each container in the set of containers comprises 50 μL of reagent and 150 μL of wash buffer. (Item 113) The method comprises: a) determining that the laboratory instrument is faulty based on the retention value; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) aligning an aspiration probe with a reaction vessel location within the laboratory instrument; ii) checking the magnetic functionality of the laboratory instrument. (Item 114) The retention value is a) grayscale values ​​derived from said one or more particle-retaining images; b) a particle retention calibration curve. (Item 115) a) the particle retention calibration curve is generated using a plurality of calibration mixtures, each of which includes a portion of a reagent comprising paramagnetic particles and a portion of a wash buffer; b) the plurality of calibration mixtures comprises a set of calibration mixtures, each calibration mixture in the set of calibration mixtures having a different reagent to wash buffer ratio than any other calibration mixture in the set of calibration mixtures. (Item 116) said set of calibration mixtures comprising: a) 50:150 and b) 40:160 and c) 35:165 and d) a calibration mixture having a reagent to wash buffer ratio of 25:175. (Item 117) a) generating said particle retention calibration using said plurality of calibration mixtures; i) for each calibration mixture, A) delivering a container containing said calibration mixture to a cleaning wheel; B) spinning the container containing the calibration mixture at a substrate spin position on the cleaning wheel; C) capturing a grayscale image of the container containing the calibration mixture after it has been mixed; ii) generating the calibration curve with the captured grayscale image of the container containing the calibration mixture; b) the set of containers includes a plurality of containers; c) the set of diagnostic steps comprises, for each container in the set of containers: i) creating a test mixture by combining the reagent added to the vessel with a portion of a wash buffer; ii) washing at least two times with the wash buffer after the test mixture is prepared in the vessel; iii) aspirating fluid from the container with an aspiration probe after the container has been washed at least twice; iv) adding a volume of wash buffer to the container after the fluid has been aspirated from the container with the aspiration probe, the volume of wash buffer added to the container being equal to the volume of test mixture that was in the container prior to aspiration; v) spinning the container at a substrate spin position on the wash wheel after the volume of wash buffer has been added to the container; d) the one or more particle retention images comprise a grayscale image of each container in the set of containers captured after the container has had a volume of wash buffer added to it and has been spin-mixed at the substrate spin position on the wash wheel. (Item 118) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for diagnosing faults in a laboratory instrument having multiple subsystems, the method comprising: a) performing a set of diagnostic steps to identify faults in the laboratory instrument, each diagnostic step in the set of diagnostic steps corresponding to a subsystem in the plurality of subsystems; b) detecting faults in the laboratory instrument during performance of a diagnostic step from the set of diagnostic steps; and c) providing an output identifying the subsystem corresponding to the diagnostic process during which the fault in the laboratory instrument was detected. (Item 119) a) the plurality of subsystems: i) a sample dispensing subsystem; ii) a reagent dispensing subsystem; and iii) an assay wash subsystem; and iv) a chemiluminescence detection subsystem; b) the device is adapted to analyze the biological sample for the presence of an analyte by performing a set of analytical steps, the analytical steps comprising: i) transferring a portion of the biological sample from a sample container to a reaction container using the sample dispensing subsystem; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel using the reagent dispensing subsystem; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to the analyte using the assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using the chemiluminescent detection subsystem. (Item 120) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, said analytical step sequence comprising: i) transferring a portion of the biological sample from a sample container to a reaction container; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to said reaction vessel; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using an assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using a luminometer; b) performing a set of diagnostic steps, including evaluating the assay wash subsystem by performing a set of wash efficiency check steps for each of a set of one or more containers, the set of wash efficiency check steps comprising: i) A) ALP solution; B) a second reagent comprising paramagnetic particles; C) Combination with washing buffer, adding to said container; ii) performing a set of cleaning steps, A) exposing the container to a magnetic field; B) adding additional wash buffer to the vessel; C) removing the contents of the container performing one or more high speed rotations; iii) aspirating fluid from said container; iv) after aspirating fluid from said container, adding said substrate adapted to react with ALP to produce chemiluminescent light; v) incubating the container; vi) using the luminometer to measure chemiluminescent light from the container after it is placed in a luminometer container chamber. (Item 121) a) the second reagent comprising paramagnetic particles does not comprise an antibody component; b) the analysis step sequence includes adding a third reagent to the reaction vessel, the third reagent comprising paramagnetic particles, the paramagnetic particles provided by the third reagent being coated with an antibody component adapted to bind to the analyte. (Item 122) a) the analytical step sequence i) transferring a third reagent comprising paramagnetic particles to the reaction vessel before transferring the first reagent comprising ALP to the reaction vessel; ii) incubating the reaction vessel between transferring the third reagent comprising paramagnetic particles to the reaction vessel and transferring the first reagent comprising ALP to the reaction vessel; iii) incubating the reaction vessel between transferring the third reagent comprising ALP to the reaction vessel and detecting chemiluminescent light produced by the substrate in reaction with the ALP using the luminometer; b) For each container in the set of containers, the container is incubated only once during the execution of the set of diagnostic steps. (Item 123) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) providing a notification to address the fault by aligning a pick-and-place actuator position with the container location. (Item 124) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of wash buffer volume check steps, the set of wash buffer volume check steps comprising: i) using each of one or more probes to add a predetermined volume of wash buffer to one or more test vessels; ii) transferring each of the test vessels to a camera position on a wash wheel, where the predetermined volume of wash buffer has been added; iii) capturing an image of the one or more test vessels to which the predetermined volume of wash buffer has been added; and iv) using the captured image to determine the actual volume of the wash buffer added to each of the one or more test vessels. (Item 125) The method comprises: a) determining the failure in the laboratory device based on the actual volume of the wash buffer added to the one or more test vessels; b) providing a notification that addresses the fault by replacing one or more of the probes used to add the wash buffer to the one or more test vessels. (Item 126) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of residual volume check steps, the set of residual volume check steps comprising: i) using each of one or more probes to add a predetermined volume of wash buffer to one or more test vessels; ii) for each test vessel to which the predetermined volume of wash buffer has been added, A) moving the test vessel to an aspiration position corresponding to the probe used to add the predetermined amount of wash buffer to the test vessel; B) aspirating fluid from the test vessel using an aspiration probe positioned at the aspiration position to which the test vessel has been moved; C) moving the test container to a camera position after fluid has been aspirated therefrom; D) capturing one or more images of the test vessel after fluid has been aspirated therefrom; and E) determining a residual volume remaining in the test vessel based on the one or more captured images of the test vessel. (Item 127) The method comprises: a) determining the fault in the laboratory instrument based on the residual volume detected in the residual volume checking step; b) providing a notification to address the fault by taking one or more actions, the one or more actions including: i) replacing one or more aspiration probes; ii) arranging one or more aspiration probes at the aspiration location where they are located; iii) replacing the peristaltic pump tubing. (Item 128) The method comprises: a) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected while performing the set of cleaning efficiency check steps; b) expanding the evaluation of the assay wash subsystem by performing a set of aspirate probe carryover check steps, the set of aspirate probe carryover check steps including, for each of a set of one or more test vessels: i) adding the ALP solution to the test vessel; ii) adding a wash buffer to the test vessel after adding the ALP solution; iii) aspirating the ALP solution from the test vessel using an aspirating probe; iv) adding to the test vessel the substrate adapted to react with ALP to produce chemiluminescent light; v) adding the substrate adapted to react with ALP to produce chemiluminescent light, followed by rapid spinning of the test vessel; vi) using a luminometer to measure chemiluminescent light from the container after incubation and placement within the luminometer container chamber. (Item 129) The method comprises: a) determining the fault in the laboratory instrument based on the chemiluminescent light detected in the aspirate probe carryover check step; b) providing a notification to address the fault by taking one or more actions; i) replacing one or more aspiration probes; ii) checking the status of a wash tower provided by said assay wash subsystem; iii) replacing the wash dispense pump. (Item 130) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical step sequence for analyzing a biological sample, i) the analytical step sequence comprises: A) a sample dispensing subsystem; B) a reagent dispensing subsystem; C) an assay wash subsystem; D) a chemiluminescence detection subsystem; ii) performing said analytical step sequence; A) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel using the reagent dispensing subsystem; B) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using the assay wash subsystem; C) adding a substrate adapted to react with ALP to produce chemiluminescent light to the reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with the ALP using the chemiluminescent detection subsystem; b) performing a set of diagnostic steps, said diagnostic steps comprising: i) evaluating the plurality of subsystems using a luminometer provided by the chemiluminescence detection subsystem; ii) using machine vision to evaluate one or more subsystems among the plurality of subsystems in parallel with evaluating the plurality of subsystems using a luminometer provided by the chemiluminescence detection subsystem. (Item 131) a) the sample dispensing subsystem: i) a sample precision subsystem; ii) a sample aliquoting subsystem; b) the analytical step sequence i) transferring an aliquot of the biological sample from the sample container to the reaction vessel using the sample aliquoting subsystem; ii) transferring the portion of the biological sample from the sample container to the reaction vessel using the sample dispensing subsystem. (Item 132) a) the analysis step sequence includes adding to the reaction vessel an analysis reagent including paramagnetic particles coated with an antibody component adapted to bind to an analyte; b) the set of diagnostic steps includes adding an analytical reagent containing paramagnetic particles and lacking an antibody component to a vessel that serves as the reaction vessel in the evaluation of the device. (Item 133) 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence, i) transferring a portion of the biological sample from a sample container to a reaction container; ii) generating an assay mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to said reaction vessel using a reagent dispensing subsystem; iii) removing from the reaction vessel the portion of the assay mixture that is not bound to an analyte using an assay wash subsystem; and iv) adding a substrate adapted to react with ALP to produce chemiluminescent light to said reaction vessel, and detecting the chemiluminescent light produced by the substrate upon reaction with said ALP using a chemiluminescent detection subsystem; b) performing a set of diagnostic steps, i) adding to the test vessel said substrate adapted to react with ALP to produce chemiluminescent light; ii) determining that a fault exists in the laboratory instrument based on chemiluminescent light detected using the chemiluminescent detection subsystem; c) performing a set of magnified diagnostic steps based on determining that the fault is present in the laboratory device, for each of a plurality of magnified test containers: i) adding a predetermined volume of test fluid to the enlarged test vessel; ii) capturing an image of said magnified test vessel; iii) determining a volume of the test fluid in the magnified test vessel using the image of the magnified test vessel; The test fluid is A) a substrate adapted to react with ALP to produce chemiluminescent light; B) Washing buffer; C) the first reagent containing ALP; D) a second reagent comprising paramagnetic particles. (Item 134) a) performing the set of diagnostic steps includes, for each of a set of one or more containers: i) in said container said substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with the ALP to produce chemiluminescent light, followed by incubating the vessel; iii) using the chemiluminescence detection subsystem to measure chemiluminescent light from the vessel after incubation and placement in a luminometer vessel chamber; Item 134. The non-transitory computer-readable medium of Item 133, wherein determining that the fault exists in the laboratory instrument based on chemiluminescent light detected using the chemiluminescent detection subsystem comprises determining that at least one container of a set of containers is contaminated with ALP based on detecting light emitted from the container using the chemiluminescent detection subsystem. (Item 135) Item 135. The non-transitory computer-readable medium of Item 134, wherein the test fluid added to the magnification test vessel is the substrate adapted to react with ALP to produce chemiluminescent light. (Item 136) Item 134. The non-transitory computer-readable medium of Item 133, wherein for each of the plurality of magnified test containers, determining the volume of test fluid in the magnified test container using the image of the magnified test container includes determining the volume of the fluid using the distance between the bottom of a meniscus in the magnified test container and the bottom of the magnified test container. (Item 137) performing said set of diagnostic steps a) performing ultrasonic mixing on a diagnostic reagent in a reagent pack; b) transferring a portion of the diagnostic reagent from the reagent pack to a particle testing container; c) capturing an image of the test vessel after the transfer of the portion of the diagnostic reagent; d) determining whether an obstruction is present in the laboratory instrument based on the grayscale value for the image of the test container. (Item 138) Item 138. The non-transitory computer-readable medium of Item 137, wherein the diagnostic reagent comprises uncoated paramagnetic particles and does not include any paramagnetic particles coated with an antibody component. (Item 139) 1. A machine for testing a biological sample for the presence of an analyte and having self-diagnostic capabilities, said machine comprising: a) a sample dispensing subsystem; b) a reagent dispensing subsystem; c) an assay wash subsystem; d) a chemiluminescence detection subsystem; and e) means for automatically diagnosing faults in said operation of said machine. [Brief explanation of the drawings]

[0015] [Figure 1] An exemplary assay is shown.

[0016] [Figure 2A] 1 shows a cross-sectional perspective view of a luminance meter. [Figure 2B] 1 shows a cross-sectional perspective view of a luminance meter.

[0017] [Figure 3A] 1 illustrates an exemplary cleaning wheel. [Figure 3B] 1 illustrates an exemplary cleaning wheel.

[0018] [Figure 4] 1 illustrates an exemplary pipetting system.

[0019] [Figure 5] 1 shows an exemplary probe wash sequence.

[0020] [Figure 6] 1 illustrates an exemplary computer system.

[0021] [Figure 7] 1 illustrates an exemplary process that can be used to evaluate the performance of a clinical analyzer.

[0022] [Figure 8] 1 illustrates steps that can be used to generate a calibration curve.

[0023] [Figure 9] 1 illustrates a process that can be used to perform a cleaning efficiency check. DETAILED DESCRIPTION OF THE INVENTION

[0024] Various embodiments are described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims appended hereto. Additionally, any examples set forth herein are not intended to be limiting, but merely set forth some of the many possible embodiments of the appended claims.

[0025] Referring now to FIG. 1, that figure shows an exemplary assay 100 as may be performed by an automated clinical analyzer. Assay 100 begins at step 1. A reaction vessel 105 (e.g., a cuvette) may be used for assay 100. A pipette 110 is used to place a first reagent 115, which includes iron particles 120 at a concentration of 0.3-2.0 mg / mL, into reaction vessel 105. First reagent 115 also includes an antibody or antigen adapted to bind only to the analyte in patient sample 165 that the assay is intended to measure. In assay 100, iron particles 120 are coated with the antibody or antigen.

[0026] In step 2, the patient sample 165 is added to the reaction vessel 105 with a pipette 110. The pipette 110 may be cleaned, renewed, or have a new tip at each step. Additionally, in some analyzers, different pipettes may be used at different steps (e.g., a first pipette for dispensing the patient sample, a second pipette for dispensing reagents, a third pipette for aspirating and / or washing, etc.).

[0027] In step 3, the reaction vessel 105 containing the patient sample 165 and the first reagent 115 (including the iron particles 120) is mixed to produce a mixture 170. Additionally (or alternatively), in some analyzers, the contents of the vessel 105 may be mixed as well as, or instead, exposed to a heat source (i.e., incubation). During the binding process, the antibodies or antigens on the iron particles 120 of the first reagent 115 bind to the analyte of interest in the patient sample 165. The binding process can result in the analyte of the patient sample 165 binding to the antigen or antibody coated on the iron particles 120.

[0028] In step 4, the reaction vessel 105 is moved near one or more magnets 130, which attract the iron particles 120 to one or more sides (e.g., peripheral portions) of the reaction vessel 105. The pipette 110 is used to wash the reaction vessel 105 with a cleaning agent 150. During washing, the magnets 130 hold the iron particles 120 to one or more sides of the reaction vessel 105. The iron particles 120 and the bound analytes of the patient sample 165 remain in the reaction vessel 105 after washing is completed by the magnets 130. Other components of the patient sample 165 may be absent from the reaction vessel 105 after washing is completed, having been washed away by the cleaning agent 150.

[0029] In step 5, a second reagent 155 including alkaline phosphatase ("ALP") (generally at a concentration of 0.01 mg / L to 2.0 mg / L) can be placed into the reaction vessel 105 using a pipette 110 with the iron particles 120 and the bound analyte of the patient sample 165. The second reagent 155 and iron particles 120 can be mixed and / or incubated. The second reagent 155 can include an antibody attached to the ALP that binds to the analyte of the patient sample 165 still attached to the iron particles 120.

[0030] In step 6, magnet 130 attracts iron particles 120 to one or more sides of reaction vessel 105. The iron particles 120 now have bound analytes from patient sample 165 and ALPs from second reagent 155 bound to them. Unbound portions of second reagent 155 are washed away with additional wash agent 150 added to reaction vessel 105 with pipette 110, and unbound fluid can be aspirated from reaction vessel 105.

[0031] In step 7, substrate material 180 is added to reaction vessel 105 with pipette 110. The substrate material 180 is mixed and incubated using heat source 125 (e.g., reaction vessel 105 is placed in an incubator). The substrate material 180 reacts with the ALP enzyme, thereby producing light 135 (i.e., photons).

[0032] In step 8, light 135 emitted by the reaction of the substrate material 180 with the ALP attached to the iron particles 120 can be measured using a luminometer such as discussed below in the context of Figure 2 to generate an output signal that can be processed to generate a relative light unit ("relative light unit" (RLU") value (i.e., output response) indicative of the result of the assay 100. For example, a larger RLU value indicates more light, which indicates a greater amount of analyte in the patient sample 165, than a smaller RLU value indicates.

[0033] 2A and 2B, FIG. 2A shows a cross-sectional perspective view of a luminometer for performing assay 100, and FIG. 2B provides an enlarged view of a portion of FIG. 2A, as indicated by the dashed circle in FIG. 2A. The cut-away portion of the cross-sectional perspective view is indicated by cross-hatching. The cross-sectional perspective view shows cap 415, chassis 405, luminometer computer system compartment 435, PMT cover 450, stand 440, motor 425, thermal barrier 445, reaction vessel chamber 610, and calibration unit 460. Luminometer output signal socket 465a and luminometer output signal socket 465b are also shown.

[0034] FIG. 2A provides a view of the chamber opening 430 that provides access to the reaction vessel chamber 610. The reaction vessel 105 is shown seated within the reaction vessel chamber 610. An optical path 640 intersects the reaction vessel chamber 610 near the bottom of the reaction vessel chamber 610. The PMT 630 may be a photomultiplier tube or any other suitable light-detecting device or detector. The PMT 630 may include a sensing element (not shown in detail) that detects light from the optical path 640 and / or the reaction vessel chamber 610. The PMT 630 is aligned with the optical path 640 and adjacent to an aperture 635 that passes through the intersection of the optical path 640 and the reaction vessel chamber 610. The aperture 635 allows light to enter the PMT 630 and be received by the sensing element. The reaction vessel chamber 610 intersects with a light path 640 when the reaction vessel 105 is placed within the reaction vessel chamber 610, and the material or sample within the reaction vessel 105 can emit photons that are visible within the light path 640 and at the aperture 635. The aperture 635 can be limited to a diameter of, for example, 8.5 centimeters to limit the field of view of the meniscus within the reaction vessel 105. At the other end of the light path 640, a calibration unit aperture 645 can be aligned with the light path 640. The calibration unit 460 can include a light emitting diode (LED) 620 and a photodiode 625. The LED 620 and photodiode 625 can provide a regulated internal light source used to calibrate the PMT 630. The reaction vessel 105 is not required in the luminometer, for example, during calibration. Although the luminometer is described as including the reaction vessel 105, it is an optional component of the system that may not necessarily be part of the luminometer.

[0035] 3A-3B, these figures illustrate a wash wheel 270 that can be used in performing the assay 100 as shown in FIG. 1. The wash wheel 270 includes a plurality of holders 272 (e.g., holes, etc.). As shown, the wash wheel 270 includes 27 holders 272. In other embodiments, the wash wheel 270 may include fewer than or more than 27 holders 272. Each holder 272 is configured to receive a vessel 105 (e.g., a reaction vessel), such that the vessel 105 and the received holder 272 are axisymmetric and, when mated, are axisymmetric with respect to one another.

[0036] In the example of Figures 3A-3B, 27 stations S are defined that are mounted on the frame 262 of the clinical analyzer, around which the wash wheel 270 moves the holders 272. Specifically, the wash wheel 270 rotates about axis A1, thereby moving the holders 272 from station to station about a rotational displacement R1. In the exemplary wash wheel 270 of Figures 3A-3B, the wash wheel 270 indexes 13 1 / 3 degrees per cycle, thereby advancing each of the 27 holders 272 one station per cycle.

[0037] In FIG. 3A, stations S are labeled with respect to the wash wheel 270 at a given location, and individual stations are designated using the letter "S" followed by the station number. Not all stations S are labeled, but can be determined by counting between labeled stations S. In FIG. 3B, the station designations using the letter "S" followed by the station number are omitted. However, a correspondence between the figures can be established by mapping the IN / OUT stations in FIG. 3B to station S1 in FIG. 3A and the station labeled QS in FIG. 3B to station S2 in FIG. 3A. A description of the various stations and the roles they can play in an assay 100 such as that shown in FIG. 1 is provided below.

[0038] In some clinical analyzers, station S0 may be a non-functional station but may transfer containers 105 between adjacent stations. Station S1 is an entry / exit station. At station S1, containers 105 are introduced into one of the holders 272 of the wash wheel 270. This may occur, for example, after a first reagent 115 (step 1) and a sample 165 (step 2) are added to a reaction vessel (e.g., in a reaction build carriage, not shown in FIGS. 3A-3B ) and then the contents of the vessel are mixed or incubated (step 3) (e.g., in an incubation wheel, not shown in FIGS. 3A-3B ). From station S1, containers 105 are rotated to other stations S and finally returned to station S1, where they are removed from the holders 272 of the wash wheel 270.

[0039] After a container 105 is added to the wash wheel 270 at station S1, it is rotated to station S2, where wash solution 150 is dispensed (start of stage 4). The contents of the container 105 are then rotated through stations S3-S8, where the paramagnetic particles 120 in the reaction vessel are drawn to the side of the vessel. The container is then rotated to station S9 (labeled as station A1 in FIG. 3B), where the contents of the vessel that are not bound to the paramagnetic particles drawn to the side of the vessel by the magnet are aspirated. The container is then moved to station S10 (labeled as station D1 in FIG. 3B), where wash buffer is added to it and the contents of the vessel are spin-mixed. This is then repeated for stations S11-S18 (i.e., the container can be magnetized at stations S11-S16, its contents aspirated at position S17 / A2, and then additional buffer is added and mixed at position S18 / D2). The vessel is then subjected to another magnetization / attraction procedure at positions S19-S25, at which point stage 4 of the assay 100 can be fully addressed.

[0040] After step 4, the vessel can be moved to position S1, from where it can be moved using a pick-and-place device to a reaction build carriage for dispensing a second reagent 155 (step 5). At this point, it can then be returned to the wash wheel for an additional magnetization+aspiration cycle (i.e., step 6), either directly or with additional mixing and / or incubation (e.g., in an incubation wheel). Generally, the additional magnetization+aspiration cycle of step 6 is performed in the same manner as described above for step 4 (i.e., wash buffer is dispensed at positions QS, D1, and D2, and the contents of the buffer are aspirated at positions A1, A2, and A3, etc.). However, at the end of step 4, rather than moving directly to the In / Out position and being removed from the wash wheel, the reaction vessel is moved to station S26, where substrate 180 is dispensed (i.e., start of step 7) and the contents of the vessel are mixed. From there, the vessel can be rotated to the In / Out position, from which it can be moved to another part of the analyzer (e.g., an incubation wheel) to further advance the ALP / substrate reaction, thereby completing step 7. Finally, at the end of step 7, the reaction vessel can be moved to a luminometer such as shown in Figures 2A-2B to measure the light produced by the ALP / substrate reaction, as shown in step 8 of assay 100 from Figure 1.

[0041] Referring now to FIG. 4, that figure illustrates an exemplary pipetting system 510 that can be used to move pipettes between various probe-receiving stations for dispensing and / or aspirating various fluids, as previously described in the context of performing assay 100. In FIG. 4, the exemplary pipetting system 510 is configured to transfer fluids between a first probe-receiving station PS1 (e.g., a reagent pack, sample container, etc.) and a second probe-receiving station PS2 (e.g., a station along the periphery of wash wheel 270). This may be done in part using a first actuator 514 mounted to a first frame 512 that is mounted to the frame of the instrument. In the example of FIG. 4, the first actuator 514 is a linear actuator that provides movement along a displacement d1. Sign conventions are defined with respect to the displacement d1. Specifically, a first direction d1+ and an opposite second direction d1− are defined with respect to the displacement d1.

[0042] In addition to the first frame 512, the exemplary pipetting system 510 of FIG. 4 also includes a second frame 516. The second frame 516 can be attached to a first actuator 514, and a second actuator 518 can be attached to the second frame 516. As shown, the second actuator 518 is a linear actuator that provides movement along a displacement d2. A sign convention is defined with respect to the displacement d2. Specifically, a first direction d2+ and an opposite second direction d2− are defined with respect to the displacement d2. As shown, the displacements d1 and d2 are perpendicular. In other embodiments, the displacements d1 and d2 can be non-perpendicular (e.g., skewed, parallel, etc.).

[0043] 4, the probe P, including the probe tip PT, may be mounted to a second actuator 518. Thus, in the exemplary pipetting system 510 of FIG. 4, by actuating the first and second actuators 514 and 518, the probe P and the probe tip PT can be moved to multiple positions in two-dimensional space, including between the probe-receiving stations PS1 and PS2. In other embodiments, additional frames and / or additional actuators may be provided (e.g., between the first frame 512 and the frame of the instrument), thereby allowing the probe P and the probe tip PT to be moved to multiple positions in three-dimensional space.

[0044] The probe P may define an axis A. The probe receiving station PS may define an axis A0. The probe P may be aligned to a corresponding probe receiving station PS when the axes A and A0 are aligned within an acceptable tolerance.

[0045] In a typical use, such as dispensing and aspirating fluids as described in the context of Figures 1 and 3, the first actuator 514 axially aligns the probe P with the desired probe receiving station PS, PS1, thereby aligning it with axes A and A0. As shown in Figure 4, the probe P and probe receiving station PS1 of the exemplary pipetting system 510 are aligned when the first actuator 514 is in an actuated position dp1. Upon alignment between the probe P and the probe receiving station PS, PS1, the second actuator 518 may move the probe P along its axis A, and thereby along the probe path 300 (e.g., away from the actuated position ap1 of the second actuator 518). Once the probe P has dispensed and / or aspirated fluid at its active position within the probe receiving station, the probe P may be retracted along the probe path 300, and the first actuator 514 then moves the second frame 516, thereby moving the probe P, the probe tip PT, and the probe path 300 to an additional receiving station within the range of the pipette system.

[0046] It should be understood that in practice, a clinical analyzer may incorporate multiple pipetting systems for such purposes as to allow for the specialization of various assemblies. For example, in some cases, the pipetting system used to transfer reagents from a reagent pack to a reaction vessel may be different from the pipetting system used to transfer samples from a sample container to a reaction vessel. In this type of system, the pipettor used to transfer reagents may have additional specialization to assist in this task. As an example, a reagent pipettor may be equipped with tips that allow for ultrasonic mixing of the reagents in the reagent pack before aspirating them for transport to a reaction vessel, thereby ensuring that the aspirated reagents are not affected by any precipitation that may occur in the reagent pack. Sample pipettors may be similarly specialized. As an example, there may be multiple sample pipettors adapted to transfer portions of a sample directly to a specific test (performed by a sample precision pipettor) or directly to a holding area (e.g., a sample wheel) where a portion of the sample can be held for use in a subsequent test (possibly including a reflex test). Multiple pipetting systems may also be incorporated for purposes other than supporting multiple workflows, for example, some instruments may be provided with multiple pipetting systems to avoid individual pipetting systems becoming a bottleneck.

[0047] It should also be understood that, while one or more pipetting system(s) such as that shown in FIG. 4 may be present in a clinical analyzer implemented according to this disclosure, such a pipetting system is not a requirement, and other types of pipette arrangements may be present in combination with or as an alternative to a system such as that shown in FIG. 4. For example, in some embodiments, various container positions (e.g., positions S0-S27 from FIG. 3) may have dedicated pipettors that can move up and down to interact with (e.g., dispense fluids and aspirate fluids from) containers at their respective positions (e.g., wash buffer dispense positions in a wash wheel as shown in FIGS. 3A-3B), but do not have the additional degrees of freedom shown in FIG. 4. Therefore, the discussion of the above variations, such as the discussion of pipetting system 510 of FIG. 4, should be understood to be merely exemplary and should not be treated as limiting.

[0048] Referring now to FIG. 5, that figure shows an exemplary arrangement that can be used to wash a probe in a pipette system 510 such as that shown in FIG. 4. The probe washing arrangement includes a hollow probe P, a frame 516, a probe actuator 518, a probe washer 530, and a probe washer actuator 520. The probe actuator 518 actuates the hollow probe P relative to the frame 516. The hollow probe P includes a tip PT. The probe actuator 518 moves the hollow probe P vertically along a probe path 300. The probe washer 530 includes a cavity 532 adapted to receive at least a portion of the hollow probe P when the probe washer 530 is disposed in the deployed position pw2, cleans the hollow probe P, which intersects with the probe path 300 when the probe washer 530 is disposed in the deployed position pw2 (shown by the dashed line), and cleans the probe path 300 when the probe washer 530 is disposed in the stowed position pw1. The probe washer actuator 520 moves the probe washer 530 between the deployed position pw2 and the stowed position pw1. The probe washer actuator 520 actuates the probe washer 530 relative to the frame 516.

[0049] In certain embodiments, the probe actuator 520 is adapted to move the hollow probe P between a stowed probe position and a probe cleaning position. The probe washer can be correspondingly moved with respect to the probe path 300 by the third actuator 520 (e.g., to an actuation position pw2) so that the probe washer 530 (e.g., the cleaning cavity 532 of the probe washer 530 and / or the bottom wall 534 of the cleaning cavity 532) intersects with the probe path 300 when the probe P is to be washed or primed for cleaning, thereby allowing the probe P to enter and exit the cleaning cavity 532. The probe washer 530 can also be moved with respect to the probe path 300 by the third actuator 120 (e.g., to an actuation position pw1) so that the probe washer 530 purges the probe path 300 when the probe P is to dispense, aspirate, prime for dispense, and / or prime for aspirate, thereby allowing the probe P to pass through the probe washer 530.

[0050] Once axis A and the cavity axis are aligned, second actuator 518 may advance probe P to a cleaning position where at least a portion of probe P is within cleaning cavity 532 of probe washer 530. Once probe P or a portion thereof is in the cleaning cavity, probe P may be cleaned internally and / or externally. Once probe P has been cleaned, second actuator 518 may retract probe P to a stowed position, thereby removing probe P or a portion thereof from cleaning cavity 532 of probe washer 530.

[0051] As with the examples provided previously herein, it should be understood that the probe washing arrangement of FIG. 5 is intended to be illustrative and should not be treated as limiting. As an example, in some analyzers, the probe washing arrangement may include a cleaning fluid supply, a pump for transferring cleaning fluid into and / or out of the probe washer 530, and one or more valves for configuring fluid flow through the probe washer. The fact that these additional components are not explicitly shown in FIG. 5 should not be treated as meaning that an analyzer implemented according to this disclosure necessarily lacks such features. Similarly, in some cases, an analyzer may be equipped with a washing station separate from the pipette assembly as an alternative to, or in addition to, the washing arrangement shown in FIG. 5. Such a washing station may include, for example, a wash tower into which a probe can be inserted for cleaning and washing dispense pumps for dispensing dispense fluid into and / or within the wash tower. Thus, while the mobile cleaning arrangement of FIG. 5 may be present in some analyzers implemented to include the functionality described in this document, it should be understood that such mobile cleaning configurations are exemplary only and should not be treated as limiting the scope of protection provided by this (or any related) document.

[0052] Referring now to FIG. 6 , that figure illustrates an exemplary computer system 49 that can be integrated with or connected to a clinical analyzer and can control various actions of the analyzer, such as by sending commands to the wash wheel 270, the pipettor assembly 110, and / or other components. As shown in FIG. 6 , such a computer system 49 can include a processor 51, a memory 53, a mass storage memory device 55, an input / output (I / O) interface 57, and a human machine interface (HMI) 59. The computer system 49 can also be operatively coupled to one or more external resources 61 via a network 63 or the I / O interface 57. The external resources can include, but are not limited to, a server, a database, a mass storage device, a peripheral device, a cloud-based network service, or any other suitable computer resource that can be used by the computer system 49.

[0053] The processor 51 may include one or more devices selected from a microprocessor, microcontroller, digital signal processor, microcomputer, central processing unit, field programmable gate array, programmable logic device, state machine, logic circuit, analog circuit, digital circuit, or any other device that manipulates signals (analog or digital) based on operational instructions stored in memory 53. The memory 53 may include a single memory device or multiple memory devices, including, but not limited to, read-only memory (ROM), random access memory (RAM), volatile memory, non-volatile memory, static random access memory (SRAM), dynamic random access memory (DRAM), flash memory, cache memory, or any other device capable of storing information. The mass storage memory device 55 may include a data storage device such as a hard drive, optical drive, tape drive, non-volatile solid-state device, or any other device capable of storing information.

[0054] Processor 51 may operate under the control of operating system 65, which resides in memory 53. Operating system 65 may manage computer resources such that computer program code embodied as one or more computer software applications, such as applications 67, resident in memory 53 may have instructions executed by processor 51. In alternative embodiments, processor 51 may execute applications 67 directly, in which case operating system 65 may be omitted. One or more data structures 69 may also reside in memory 53 and may be used by processor 51, operating system 65, or applications 67 to store or manipulate data.

[0055] The I / O interface 57 may provide a machine interface that operatively couples the processor 51 to other devices and systems, such as a network 63 or external resources 61. The applications 67 may thereby function cooperatively with the network 63 or external resources 61 by communicating via the I / O interface 57 to provide various features, functions, applications, processes, or modules that comprise embodiments of the present invention. The applications 67 may also include program code executed by one or more external resources 61 or otherwise rely on functions or signals provided by other systems or network components external to the computer system 49. Indeed, given the nearly limitless number of hardware and software configurations possible, those skilled in the art will understand that different versions of the present invention may include applications provided by computing resources (hardware and software) that are distributed among multiple computers or other external resources 61 located outside the computer system 49 or that are provided as a service via the network 63, such as a cloud computing service.

[0056] The HMI 59 may be operatively coupled to the processor 51 of the computer system 49 in a known manner to allow a user to directly interact with the computer system 49. The HMI 59 may include a video or alphanumeric display, a touch screen, a speaker, and any other suitable audio and visual indicators capable of providing data to a user. The HMI 59 may also include input devices and controls, such as an alphanumeric keyboard, a pointing device, a keypad, push buttons, control knobs, a microphone, etc., capable of accepting commands or input from a user and transmitting the entered input to the processor 51.

[0057] Database 71 may reside on mass storage memory device 55 and may be used to collect and organize data used by the various systems and modules described herein. Database 71 may include data and supporting data structures that store and organize the data. Specifically, database 71 may be arranged in any database organization or structure, including, but not limited to, a relational database, a hierarchical database, a network database, or combinations thereof. A database management system in the form of a computer software application executed as instructions on processor 51 may be used to access information or data stored in records of database 71 in response to queries, which may be dynamically determined and executed by operating system 65, other applications 67, or one or more modules.

[0058] Referring now to Figure 7, that figure illustrates steps that may be performed under the control of a computer such as that shown in Figure 6 to identify and / or remedy faults in an analyzer comprising components such as those illustrated and discussed in the context of Figures 1-5. In various embodiments, the performance of these steps may be triggered manually (e.g., by actuation of controls provided by a computer), performed on a scheduled basis (e.g., periodically), or performed based on external factors (e.g., when the disclosed technology is used to facilitate quality assurance as part of the manufacturing process, processes such as those shown in Figure 7 may be performed automatically at the end of the device's manufacturing process to confirm its proper functioning). Their performance may also be triggered in other ways, such as based on a combination of scheduling and external factors (e.g., performed periodically, but only when the instrument is not being used to analyze samples).

[0059] At a high level, the steps in FIG. 7 can be understood to be organized into two broad categories: a first category of steps that detect faults using machine vision and images captured by a digital camera; and a second category of steps that detect faults using a luminometer, as described in the context of FIGS. 2A-2B, used to detect chemiluminescent light during stage 8 of assay 100 shown in FIG. 1. As shown in FIG. 7, some approaches to automated diagnosis can take advantage of the presence of multiple diagnostic modes, i.e., camera- and luminometer-based fault detection, and can allow various diagnostic sequences (shown in FIG. 7 as steps 1a-4a and steps 1b-5b) to be performed in parallel. Similarly, because the luminometer-based diagnostic step generally consumes more time to allow for incubation or similar activities, in some embodiments that also include camera-based fault detection, the entire camera-based fault detection sequence can be performed during the initial check from the luminometer-based diagnostic step. As an example, the embodiment following Figure 7 may complete all of camera steps 1a-4a while the first illuminometer diagnostic step 1b is being performed. Thus, while the spatial relationships in the diagram of Figure 7 may be viewed as generally indicating various temporal relationships (e.g., the fact that sequences 1a-4a and 1b-5b are adjacent to one another reflects that the steps in those sequences may be performed in parallel), it should be understood that having temporal relationships corresponding to the spatial relationships of Figure 7 is not required and should not be viewed as limiting the protection provided by this document or any related document.

[0060] Referring now to the sequence of steps 1a-4a in FIG. 7, these steps can be generally understood as identifying a fault in the instrument's handling of paramagnetic particles using machine vision analysis of digital camera images. Starting with step 1a, the steps determine whether there is a fault in the instrument's extraction of reagents containing paramagnetic particles from a reagent pack. To make this determination, some embodiments may utilize specialized diagnostic reagents from specialized diagnostic reagent packs (referred to as ASD packs in FIG. 7) that differ from assay reagents in that they lack any type of antibody component that may bind to the analyte in the patient sample, and may also have higher concentrations than the reagents used in the assay (e.g., 2.0 mg / mL or more of paramagnetic particles in the diagnostic paramagnetic particle reagent versus 0.2-2.0 mg / mL of paramagnetic particles in the paramagnetic particle reagent, 4.2 mg / L of ALP in the diagnostic ALP solution used in the assay versus 0.1-2.0 mg / L of ALP in the ALP solution). Such diagnostic reagent packs may have similar external factors as standard reagent packs and may be loaded similarly.

[0061] In embodiments in which a diagnostic reagent pack such as those described above is used, the instrument may be configured to store the diagnostic reagent pack in a reagent storage area upon loading, and then automatically transfer it from the storage area to the reagent aspiration area when a diagnosis is to be performed. Then, once the diagnostic reagent pack is removed from storage, step 1a may be performed using a two-step process. First, the PmP diagnostic reagent 115 is processed and transferred to a reaction vessel in the same manner as the first reagent 115 is present during an assay. For example, this may involve applying an ultrasonic mixture to the PmP diagnostic reagent in the reagent pack and, after mixing, transferring a predetermined volume of the PmP diagnostic reagent (e.g., 50 μL) to the reaction vessel using a reagent pipettor. Second, the mixed reagent in the reaction vessel is imaged by a digital camera (e.g., a camera positioned proximate the dispense location of the reaction vessel or a camera positioned elsewhere on the instrument where the reaction vessel is moved for imaging purposes), and a shade check is performed on the captured image(s) to determine if there has been a fault in the handling of the PmP diagnostic reagent (e.g., if the mixed reagent in the reaction vessel has a lighter or darker grayscale value than expected). Additionally, in some embodiments, this can be performed on multiple vessels (e.g., five vessels) either in parallel or serially to provide additional information that can be used to determine if there has been a fault in the handling of the PmP diagnostic reagent.

[0062] After the handling of the PmP diagnostic reagents in the reagent pack has been evaluated, the embodiment following FIG. 7 may proceed with remediation (if a fault is identified) or to the next diagnostic step 2a. In the scenario where a fault is identified, remediation may proceed by a computer such as that shown in FIG. 6 providing a message to its interface indicating that there has been a fault in the handling of the PmP diagnostic reagents in the reagent pack (e.g., a fault in the paramagnetic particle resuspension). This type of message may also include information about one or more steps to perform to remedy the fault, such as replacing the reagent pipettor tips used in performing ultrasonic mixing, recalibrating the ultrasound, or replacing the instrument's ultrasonic transducer. If this remediation is unsuccessful, a call can be placed to request that a remote service engineer be dispatched to the instrument, and the remote service engineer can be informed of where the fault occurred (e.g., in the paramagnetic particle resuspension in the reagent pack) and what remedial actions have already been attempted. In this way, the remote service engineer is eliminated from having to perform an initial diagnostic check of the equipment when he or she arrives; instead, he or she can be pre-equipped with knowledge of where the fault occurred and potentially the tools and / or spare parts that can be used to correct the fault (e.g., a replacement camera in the case of a fault in the photograph taken rather than the operation of the equipment). Alternatively, if the remedy is successful (e.g., as can be confirmed by re-running diagnostic step 1a), the process can proceed to the subsequent diagnostic step 2a.

[0063] Referring now to step 2a, which checks for defects in the resuspension in the reaction vessel, this step can be used to determine the instrument's ability to resuspend paramagnetic particles in the reaction vessel after they have been magnetized. This can be done, for example, by using a reagent pipettor to process 50 μL of PmP diagnostic reagent (e.g., ultrasonically mixed in the reagent pack) and supplying it to the reaction vessel along with 150 μL of wash buffer. This combination can then be sent to a wash wheel where it can be magnetized (potentially without any additional reagent dispensing, fluid aspiration, or high-speed spin mixing) under computer control, as shown in Figure 6. After magnetization, the reaction vessel can be returned to the pipette position and subjected to ultrasonic mixing to resuspend the particles in solution. Finally, the resuspended mixture can be imaged by a digital camera for a darkness check, in the same manner as described for the previous diagnostic step 1a. Also, in some embodiments, checking for defects in the resuspension in the reaction vessel can be performed on multiple (e.g., five) reaction vessels, just as step 1a checking for proper handling of reagents in a reagent pack can be performed on multiple reaction vessels to provide additional data for identifying defects.

[0064] After the functionality of the instrument for resuspension in the reaction vessel has been evaluated, the embodiment following FIG. 7 can proceed to remediation (if a fault is identified) or to the next diagnostic step 3a. In the scenario where a fault is identified, remediation can proceed by the computer, as shown in FIG. 6, providing a message on its interface indicating that there was a fault in the resuspension of particles in the reaction vessel and accompanying that message with one or more steps that can be used to remediate the fault, such as ensuring that the reagent pipettor is properly aligned with the reaction vessel at the pipette position and checking to ensure that the reagent pipettor is properly vertical. As with remediation in the context of the previous step 1a, if this is unsuccessful, service can be referred to a service engineer, who can be pre-equipped to handle it directly if a fault is detected, without having to go through the diagnostic process themselves upon arrival. Alternatively, if remediation is successful (as can be verified by re-running diagnostic step 2a in which the fault was identified), the process can proceed to the next diagnostic step 3a.

[0065] Referring now to step 3a, which checks for defects in resuspension within the wash wheel, this step can be used to determine whether there is a defect in the instrument's ability to resuspend paramagnetic particles without resorting to ultrasonic mixing. This can be done, for example, by using a reagent pipettor to process 50 μL of PmP diagnostic reagent (e.g., ultrasonically mixed in the reagent pack) and deliver it to a reaction vessel along with 150 μL of wash buffer. This combination can then be sent to the wash wheel, where it can be subjected to magnetization and high-speed spin mixing (potentially without activities related to dispensing additional wash buffer or aspirate, or two or more aspiration + magnetization steps). After high-speed spin mixing, the reaction vessel can be imaged (e.g., using a camera at the reagent pipette position after being returned to its position, or using a camera positioned close to the high-speed spin mixing station of the wash wheel), and the image(s) can be used for a darkness check, as described in the context of the previous diagnostic steps 1a-2a. Similarly, as with the previous diagnostic steps 1a-2a, this evaluation can be performed multiple times (e.g., with five different reaction vessels) to provide additional data for diagnosing a fault, or, if there are multiple high-speed spinning mixing locations on the cleaning wheel, to ensure that each of those locations has been properly evaluated.

[0066] After the functionality of the equipment for resuspension within the wash wheel has been evaluated, the embodiment following FIG. 7 can proceed to remediation (if a fault is identified) or to the next diagnostic step 4a. In the scenario where a fault is identified, remediation can proceed by a computer, such as that shown in FIG. 6, providing a message on its interface indicating that there was a fault in the resuspension of particles within the wash wheel and accompanying that message with one or more steps that can be used to ensure that the high-speed mixer is properly aligned with the reaction vessel and / or replace the high-speed mixer. As with remediation in the context of the preceding steps 1a-2a, if this is unsuccessful, service can be referred to a service engineer, who can be pre-equipped to handle the fault directly if it is detected, without having to go through the diagnostic process themselves upon arrival. Alternatively, if remediation is successful (as can be verified by re-running diagnostic step 3a in which the fault was identified), the process can proceed to the next diagnostic step 4a.

[0067] Referring now to step 4a, checking for impairments in paramagnetic particle retention, that step can be used to determine whether there is an impairment in the instrument's ability to flush reaction vessels after an assay. In some embodiments, performing this step can involve performing two subprocesses: one to create a particle retention calibration curve (which may be performed simultaneously with other diagnostic steps, or may be performed in advance, such as before or at the time the instrument is installed), and another to use that calibration curve to identify impairments in the instrument's operation. Starting with the creation of the calibration curve, FIG. 8 illustrates a set of steps that may be performed in some embodiments to create this curve. As shown in FIG. 8, creating a calibration curve can begin with creating 801 multiple calibration mixtures and dispensing 802 those calibration mixtures into multiple vessels. This may include adding PmP diagnostic reagent (also referred to herein as ASD reagent) and wash buffer to each of a plurality of containers, e.g., adding 50 μL of ASD reagent and 150 μL of wash buffer to five containers, adding 40 μL of ASD reagent and 160 μL of wash buffer to five containers, adding 35 μL of ASD reagent and 165 μL of wash buffer to five containers, and adding 25 μL of ASD reagent and 175 μL of wash buffer to five containers, for a total of 20 containers with ASD reagent solutions of various concentrations. After the calibration mixture is dispensed 802 into the containers, each container can be moved 803 to the instrument's wash wheel and spun 804 to a station on the wash wheel to a substrate spin position (i.e., the position on the wash wheel where substrate 180 is dispensed during step 7 of FIG. 1 during assay 100). There, the container is spun and imaged 805. Then, if there are more vessels 806, the process is repeated until all vessels have been spun and imaged 805, at which point the images of the various vessels with their various concentrations of ASD solution are used to create 807 a calibration curve of grayscale values ​​representing various concentrations of paramagnetic particles in the mixture.

[0068] To use the calibration curve, once it is available, a computer such as that shown in FIG. 6 can cause the instrument to generate a test mixture of ASD reagent and wash buffer (e.g., 50 μL of ASD reagent and 150 μL of wash buffer) in each of multiple containers (e.g., five containers) and then send those containers to the wash wheel to undergo a complete wash process (e.g., adding wash buffer, spin-mixing, and aspirating the container to be tested at least twice) without adding substrate or ALP. The washed containers can then be returned to the wash buffer dispense position where another portion of wash buffer (e.g., 200 μL) can be dispensed into them, at which point they can be sent to the substrate spin position of the wash wheel, spun, and imaged. The images can then be compared to the previously generated calibration curve to determine whether there was a fault in the wash process, such as excessive particles being retained. If a fault is detected, remediation can then proceed as described for the previous diagnostic steps 1a-3a, with remediation steps including aligning the aspiration probe with the reaction vessel and / or checking the magnetic functions of the instrument to ensure they are functioning properly.

[0069] Referring now to the sequence of steps 1b-5b in Figure 7, these steps can be understood as testing various subsystems of the instrument generally in the reverse order in which they are used in the assay, with each subsequent test generally leveraging one or more previously validated subsystems. Following this general framework, the substrate blank check 1b can test the chemiluminescent detection subsystem of the instrument (i.e., the luminometer as shown in Figures 2A-2B, along with the components used to dispense into the reaction vessels in step 7 of assay 100 as shown in Figure 1) to ensure that it does not generate spurious light detection signals. This can be done, for example, by adding a substrate adapted to generate chemiluminescent light in the presence of ALP to multiple vessels (e.g., 10 vessels), incubating the vessels as if they were being used in the assay (e.g., incubating for 48 seconds), and then using the luminometer to detect the luminance for each vessel after incubation. In this case, if the luminometer detects an unexpectedly high amount of light (e.g., greater than approximately 6,000 RLU) being produced from the vessel, this would indicate a fault because ALP must be present in the vessel to produce more light than would be expected from the blank reading. Thus, if a fault is detected, it can be remedied by changing the instrument's substrate bottle (i.e., the bottle that holds the substrate before it is dispensed into the vessel) and / or decontaminating the instrument's substrate line (i.e., the tubing or other carrier that transfers the substrate from the substrate bottle to the reaction vessel) to ensure that none of these components act as a source of contamination. If these steps are successful, the process can proceed to the next diagnostic step, step 2b. Otherwise, second-line support (e.g., a support engineer) may call in or perform an escalated diagnostic step to help further identify and / or remedy the fault.

[0070] In embodiments where remediation of a substrate blank check 1b failure can be addressed by performing expanded diagnostic and / or remedial steps, the expanded steps include performing dark count, LED, and linearity checks 1.1 to determine whether the unexpected (and unwanted) light readings are caused by the luminometer itself, rather than contamination causing the chemiluminescent reaction. This includes taking a reading in the luminometer when no container is present to confirm that no unexpected signal was detected; turning on LED 620 and reading the signal in the luminometer to confirm that the detected signal corresponds to illumination from the LED; and varying the light intensity of the LED (e.g., illuminating using 0.5, 0.8, and 1.2 pW) to confirm that the readings obtained by the luminometer at each illuminance level correspond to the expected signal value. If these expanded diagnostic checks 1.1 then fail, remedial steps can be performed (or, as with the other remedial steps, a computer, such as that shown in FIG. 6, can indicate that they should be performed), including cleaning the luminometer box, recalibrating the luminometer, and / or replacing the luminometer. Alternatively, if this extended diagnostic check 1.1 does not identify the root cause of the fault in the substrate blank check 1b, a second line support resource (e.g., a field service engineer) may be called or, in some embodiments, an additional extended diagnostic and remedial sequence 1.2 may be initiated.

[0071] In embodiments in which failures of the dark intensity count, LED, and linearity checks 1.1 are addressed to trigger additional, expanded diagnostic / remedial steps to identify the root cause of the failure in the substrate blank check 1b, these additional steps may include a substrate volume check 1.2 performed by a camera. In embodiments in which this type of check is performed, it may be performed by dispensing a predetermined volume of substrate into multiple containers (e.g., dispensing 200 μL of substrate into each of 10 containers), then capturing images of the containers and calculating the volume of substrate in each of them (e.g., based on the distance between the substrate meniscus and the bottom of the container along the cross-section of the container). If this check reveals that the substrate is not properly dispensed, it can be remedied by performing an action such as replacing the substrate dispensing probe. If the substrate volume check 1.2 does not identify the root cause of the failure in the substrate blank check 1b, or if additional remedial action does not address the failure, second-line support resources can be called in to address the failure. Alternatively, if Substrate Volume Check 1.2 identifies the root cause of the fault in Substrate Blank Check 1b (if a root cause is identified), and the remedial steps successfully address the root cause and eliminate the fault in Substrate Blank Check 1b (or if there was no fault in Substrate Blank Check 1b), the diagnostic process can continue to next step 2b to evaluate assay wash subsystem (i.e., components on the instrument that ensure unbound particles are properly removed from the reaction vessel during the assay, such as the aspiration probe, wash tower, and / or probe wash system as shown in Figure 5) operation.

[0072] Referring now to wash efficiency check step 2b, in some embodiments, this may be performed by a process such as that shown in Figure 9. First, in the process of that figure, ASD reagent and ALP solution (preferably ALP solution from an ASD pack) are dispensed into a reaction vessel using a reagent pipettor to create a test mixture (e.g., a mixture of 50 μL of ASD reagent and 150 μL of ALP solution) 901. An additional volume of wash buffer (e.g., 300 μL of wash buffer) can then be dispensed into the vessel 902. The same process used during the assay to remove unbound particles and resuspend the remainder (i.e., magnetizing the vessel (e.g., for 48 seconds), aspirating fluid from the vessel, adding an additional 500 μL of wash buffer, and spin-mixing the vessel to resuspend the contents) can then be performed on the combined contents of the vessel 903. A check 904 is then performed to determine whether this has been repeated more than once (as would be the case during assay 100, as shown in FIG. 1); if not, the unbound removal and resuspension process can be repeated. If not, the fluid can be aspirated 905 from the vessel and prepared for the chemiluminescence reaction by adding substrate (e.g., 200 μL of substrate), spin-mixing it, and incubating (e.g., for 48 seconds) 906. Finally, the vessel can be read with a luminometer 907 to determine whether an unexpectedly high amount of light was detected (indicating a fault in the wash process and an excessive amount of ALP solution remaining in the vessel to react with the substrate (e.g., more than would react with the substrate to produce 20,000 RLU)). Additionally, like other diagnostic steps, wash efficiency check step 2b can be performed in multiple vessels (e.g., 10 vessels) to provide additional data that can be used in determining whether there is a fault in the system.

[0073] If a fault is identified in wash efficiency check step 2b, support resources (e.g., a field service engineer) can be enlisted, or in some embodiments, one or more remedial steps can be implemented to address the fault. For example, the alignment of the wash wheel pick-and-place device (i.e., the device that transfers reaction vessels to the wash wheel) relative to the in / out stations on the wash wheel can be checked. Additionally, if this does not remedy the fault, one or more extended diagnostic steps can be implemented. For example, as shown in FIG. 7, this can include performing wash buffer volume check 2.1 using a camera. In some embodiments, this check 2.1 can be performed by using the probe used to dispense wash buffer into reaction vessels during the assay to dispense a known volume (e.g., 200 μL) of wash buffer into a corresponding set of test vessels, then rotating those test vessels into a position on the wash wheel (e.g., a substrate dispensing position) adjacent to the camera, imaging the vessels, and using the image to calculate the volume of wash buffer actually added to the vessels. This may involve dispensing 200 μL of wash buffer into each of five vessels using the QS probe (i.e., the probe used to add wash buffer to the reaction vessel at the QS position shown in FIG. 3B), into each of five vessels using the D1 probe (i.e., the probe used to add wash buffer to the reaction vessel at the D1 position shown in FIG. 3B), and into each of five vessels using the D2 probe (i.e., the probe used to add wash buffer to the reaction vessel at the D2 position shown in FIG. 3B). If the captured images then indicate that the volume actually dispensed by one or more probes differs from that expected, the process can proceed with one or more extended remedial steps, such as replacing the wash dispense syringe (i.e., the probe) used to dispense wash buffer into the reaction vessel where the discrepancy was noted.Alternatively, if the camera wash buffer volume check 2.1 does not identify the root cause of the failure of the wash efficiency check 2b, an additional extended diagnostic step 2.2 of checking the residual volume by camera can be performed.

[0074] It can be seen that failure of wash efficiency check 2b leads to an expanded diagnostic step 2.2 which checks residual volume by camera. In embodiments, this check 2.2 is used to ensure that the probe used to aspirate fluid from the reaction vessel during the assay is functioning as expected. This can include, for example, 1) using each of the probes (e.g., QS, D1, and D2 probes) that dispense wash buffer into the reaction vessels to assay a known amount of wash buffer (e.g., 500 μL of wash buffer) into each vessel from a set of corresponding vessels (e.g., each probe can have a set of five corresponding vessels); 2) spinning the vessels at an aspiration position on the wash wheel that corresponds to the probe used to dispense wash buffer into that vessel (e.g., moving the vessel that had wash buffer dispensed by the QS probe to a first aspiration position, the vessel that had wash buffer dispensed by the D1 probe to a second aspiration position, and the vessel that had wash buffer dispensed by the D2 probe to a third aspiration position; alternatively, in an instrument where reaction vessels can have wash buffer dispensed and aspirated at the same position, such vessels may not be moved at all); 3) aspirating fluid from the vessels; and 4) spinning the vessels to a camera position (i.e., a position on the wash wheel adjacent to a digital camera) where an image can be taken and used for volume calculation. If the volume calculation indicates an obstruction in the aspiration (i.e., in some embodiments, any fluid remaining in the vessel after aspiration is treated as an obstruction in the aspiration), one or more remedial steps may be performed to address the obstruction. These steps may include replacing the aspiration probes corresponding to the vessels in which the obstruction was detected, ensuring that the aspiration probes corresponding to the vessels in which the obstruction was detected are properly aligned with their reaction vessel stations, and / or replacing the peristaltic pump tubing used by the aspiration probes to move unbound liquid from the reaction vessels to the waste vessel.

[0075] Alternatively, if the residual volume check by camera 2.2 did not identify the root cause of the wash efficiency check failure, in some embodiments, the diagnostic process as shown in FIG. 7 can proceed with an additional extended diagnostic step of performing an aspiration probe carryover check 2.3. In embodiments in which such an additional extended diagnostic step is present, it can be performed, for example, by adding diagnostic ALP solution and wash buffer to each of multiple vessels (e.g., adding 200 μL of diagnostic ALP solution and 200 μL of wash buffer to each of 10 vessels), sending the vessels to a position where fluid is aspirated from reaction vessels to be washed between assays, aspirating the fluid, preparing the vessels for a chemiluminescence reaction (e.g., adding substrate, spin-mixing, and incubating, as described in the context of FIG. 9), and then reading them with a luminometer. If these luminometer readings detect chemiluminescent light, this can be treated as an indication that there was a problem with the aspiration probe; otherwise, all ALP can be removed before being prepared for the chemiluminescence reaction, and various remedial measures can be taken. These may include replacing the aspiration probe, investigating the condition of the wash tower should the probe involved in the failed test be cleaned, and / or replacing the pump used to dispense the wash buffer. If these measures fail to address the root cause of Wash Efficiency Check Fault 2b, additional resources (such as a field service engineer who was informed of the fault and steps taken to diagnose and remedy the fault or its root cause) can be deployed. Alternatively, if the measures are successful, the process can proceed to the next diagnostic step, 3b.

[0076] Referring now to luminometer reagent volume check step 3b, this step can be used to evaluate the functionality of the instrument's reagent dispensing subsystem (i.e., components used to handle reagents during an assay, such as the reagent pipettor and ultrasonic transducer). In some embodiments, this reagent volume check step 3b can be performed by using a reagent pipettor to add a predetermined volume of diagnostic ALP solution (e.g., 50 μL of ALP solution) to each of a plurality of vessels (e.g., 10 vessels), preparing the vessels for a chemiluminescent reaction by adding substrate (e.g., 200 μL of substrate), spinning and incubating them as described in the context of FIG. 9, and then using a luminometer to read the chemiluminescent light produced by the reaction of the substrate with the ALP solution. If this reading does not match (e.g., within 10%) the expected amount of light based on the volumes of ALP solution and substrate added to the vessels, one or more remedial actions, such as aligning the reagent pipettor with the reaction vessel and / or reagent pack, can be taken to address the discrepancy. If these measures are successful (or if no discrepancy is detected), the process as shown in Figure 7 can proceed to the next diagnostic step 4b. Otherwise, one or more extended diagnostic steps can be performed to try and identify the root cause of the discrepancy and, if identified, remedy it.

[0077] If luminometer reagent volume check 3b identifies a fault in the reagent dispensing subsystem, in some embodiments, one or more extended diagnostic actions may be performed. As shown in FIG. 7, these extended diagnostic actions may include performing camera reagent volume check 3.1, which in some embodiments may be performed in a manner similar to previously described substrate volume check 1.2; instead of dispensing substrate, camera reagent volume check 3.1 is preferably performed with a less expensive type of fluid, such as wash buffer. That is, in a camera reagent volume check, a known volume of wash buffer may be dispensed into multiple containers using a reagent pipettor (e.g., 200 μL of wash buffer may be dispensed into each of five containers using a reagent pipettor), the containers may be imaged, and the volume of wash buffer in the image may be compared to the expected volume to determine whether there was an error in the operation of the reagent pipettor. If this Camera Reagent Volume Check 3.1 identifies an error, various remedial actions can be taken to address it, such as replacing the syringe used for reagent dispensing (i.e., the reagent pipettor) and / or replacing the motor used to generate the pressure differential to transport reagent from the reagent pack to the reagent pipettor and from the reagent pipettor to the reaction vessel (i.e., the reagent dispense motor). If these remedial actions are sufficient to address the root cause of the failure of the Luminometer Reagent Volume Check 3b, the diagnostic procedure can proceed to the next step, 4b. Otherwise, an additional extended diagnostic measure in the form of the Reagent Volume Linearity Check 3.2 can be performed.

[0078] In embodiments in which a failure in luminometer reagent volume check 3b leads to an expanded diagnostic check that performs reagent volume linearity check 3.2, reagent volume linearity check 3.2 can include adding various combinations of diagnostic ALP solution and wash buffer to various sets of containers, preparing them for chemiluminescence reactions as described in the context of Figure 9, and then reading the light emitted from the containers using a luminometer. For example, in some embodiments, this can include adding 50 μL of ALP solution to 10 containers, adding 25 μL of ALP solution and 25 μL of wash buffer to 10 containers, adding 10 μL of ALP solution and 40 μL of wash buffer to 10 containers, then adding 200 μL of substrate to each of the containers and measuring the light produced by the reaction between the ALP and substrate in each of the containers. If, after performing the light measurements, there is a discrepancy between the measured light and that expected based on the volume of ALP solution in the various containers, this can be treated as an indicator of the root cause of the failure in the luminometer reagent volume check, and one or more remedial actions can be taken to address it. These remedial actions can include checking the verticality of the reagent pipettor, replacing the reagent pipettor tip, and / or replacing the ultrasonic transducer. Alternatively, if the reagent volume linearity check 3.2 did not indicate the root cause of the failure in the luminometer reagent volume check 3b, an additional extended diagnostic step can be performed in the form of the reagent pipettor carryover check 3.3.

[0079] In embodiments where a failure in luminometer reagent volume check 3b leads to reagent pipettor carryover check 3.3, the reagent volume carryover check can be performed in a manner very similar to the previously discussed aspiration probe carryover check 2.3. For example, in some embodiments, 50 μL of diagnostic ALP solution and wash buffer can be added alternately to each of 10 vessels, and the vessels can then be prepared for the chemiluminescence reaction by adding 200 μL of substrate, mixing and incubating them, and then reading the chemiluminescent light produced using a luminometer. If the light measured by the luminometer is then greater than expected based on the volumes of ALP and substrate, this can be treated as an indicator of the root cause of the failure of luminometer reagent volume check 3b, and one or more remedial actions can be implemented to address it. These remedial actions can include replacing the reagent pipettor tips, investigating the condition of the wash column, and / or replacing the wash dispense pump. If these remedial actions are not successful in remedying the fault (or if Reagent Pipettor Carryover Check 3.3 did not indicate the root cause of the fault), additional resources (e.g., a field service engineer) can be called in to address the problem. Otherwise, if the remedial actions are successful in addressing the root cause of the fault in Luminometer Reagent Volume Check 3b, the diagnostic procedure can proceed with Luminometer Sample Volume Check 4b.

[0080] Referring now to luminometer sample volume check 4b, that check, in some embodiments, can be used to evaluate the performance of the sample dispensing subsystem (i.e., components used within the instrument to transfer portions of patient samples from sample containers to reaction containers, such as various sample pipettors and sample dispense motors that create pressure differentials to aspirate and / or dispense sample portions into / from the containers). This can be done by performing an activity that includes using a reagent pipettor to add a predetermined volume of diagnostic ALP solution (e.g., 100 μL) to each of a plurality of containers (e.g., 10 containers) that serve as sample containers. Luminometer sample volume check 4b can also include aliquoting a portion (e.g., 50 μL) of the ALP solution from each of the containers that serve as sample containers into another container within a plurality of containers that serve as reaction containers using the instrument's sample precision pipettor. Each of the vessels serving as reaction vessels can then be prepared for the chemiluminescent reaction previously described in the context of FIG. 9 (i.e., substrate is added, then mixed and incubated), and the light provided by the contents of the reaction vessel can be measured by the luminometer. In the event that there is a discrepancy between the light detected by the luminometer and the light expected based on the volume of ALP and substrate dispensed into the reaction vessel, this can be treated as a failure, and remedial actions, such as checking the position of the sample precision pipettor relative to the reaction vessel, can be implemented to try and address it. If these actions are successful, the diagnostic process, as shown in FIG. 7, can continue using the luminometer to check other pipettors (e.g., sample aliquot pipettors) that may be used to transfer portions of patient samples from the sample vessel. Otherwise, one or more expanded diagnostic and remedial actions can be implemented to identify and address the root cause of the luminometer sample volume check failure.

[0081] As shown in FIG. 7 , in some embodiments, extended diagnostic activities to identify the root cause of a luminometer sample volume check failure may include a camera sample volume check 4.1. Such a camera sample volume check 4.1 may involve using a reagent pipettor to add a first volume of wash buffer to multiple containers that will serve as sample containers for this test (e.g., adding 100 μL of wash buffer to each of five containers), aspirating a portion of that wash buffer using a sample precision pipettor (e.g., removing 30 μL of wash buffer from each of the containers acting as sample containers), and then imaging the containers to determine the actual volume of wash buffer remaining after aspiration (e.g., by measuring the distance between the bottom of the wash buffer meniscus and the base of the container and multiplying that distance by the cross-sectional area of ​​the container). Additionally, in some embodiments, camera sample volume check 4.1 may also dispense the wash buffer aspirated from the sample containers into a new container that will serve as a reaction container for this test. As an example, in some embodiments, in addition to (or instead of) aspirating wash buffer from a sample container and imaging the sample container, the wash buffer (or a portion thereof) may be dispensed into a new container (by itself or in combination with additional wash buffer aspirated from the sample container) that is treated as a reaction container for testing purposes. For example, in some embodiments, for each container that is treated as a sample container for testing purposes, 25 μL of wash buffer may be dispensed into a first container that acts as a reaction container, and 10 μL of wash buffer may be dispensed into a second container that acts as a reaction container. In this type of embodiment, an image may be captured of each container that acts as a reaction container after wash buffer has been dispensed into it, and an image may also be captured of the sample container after (and possibly after) any additional wash buffer has been aspirated from it.

[0082] Finally, images captured as part of Camera Sample Volume Check 4.1 can be analyzed to determine the volume of wash buffer in the imaged vessel. These volumes can then be compared to the volume that should be present based on the amount of fluid that was (or should have been) aspirated and / or dispensed, and any discrepancies can be treated as indicating a potential root cause for the failure of Luminometer Sample Volume Check 4b. This can then be followed by swapping the sample dispensing syringe on a precision pipettor, and / or may trigger remedial action, such as contacting a field service engineer and informing that person of the subsystem in which the fault was detected, what the root cause of the fault appeared to be, and what remedial action (if any) was attempted to address the root cause. Alternatively, if there was no discrepancy between the actual volume and the predicted volume within the imaged vessel, the diagnostic process as shown in Figure 7 may continue with additional extended diagnostic action to continue searching for the root cause of the fault in luminometer sample volume check 4b.

[0083] In some embodiments that include extended diagnostic steps that can be performed to determine the root cause of a failure in luminometer sample volume check 4b, as shown in FIG. 7, these extended diagnostic steps can include luminometer sample volume linearity check 4.2. Performance of this type of check 4.2 can begin using a reagent pipettor to add a predetermined volume of diagnostic ALP solution to each of multiple containers that will serve as sample vessels for this test (e.g., adding 100 μL of ALP solution to each of 30 containers). A sample precision pipettor can then be used to transfer a portion of that solution to the containers that will serve as reaction vessels for the test, and a reagent pipettor can be used to add wash buffer to those containers so that the total amount of liquid in each is the same, regardless of how much ALP solution was added by the sample precision pipettor. For example, in some embodiments, 10 reaction vessels can be filled with 50 μL of ALP solution, 10 more can be filled with 25 μL of ALP solution and 25 μL of wash buffer, and the final 10 can be filled with 10 μL of ALP solution and 40 μL of wash buffer. After the appropriate amounts of ALP solution and wash buffer are then added to the vessels serving as reaction vessels, the vessels can be prepared for a chemiluminescence reaction, as described in the context of FIG. 9 , and a luminometer can be used to measure the light emitted by the contents of those vessels. If this measured light does not match the expected amount of light based on the various volumes of ALP solution in each of the vessels, this can be treated as an indication of a potential root cause of the failure of the luminometer sample volume check, and remedial action, such as replacing the sample dispense motor, can be triggered. Alternatively, if no discrepancy exists, an additional luminometer sample dilution check 4.3 can be performed to attempt to identify the root cause of the failure of the luminometer sample volume check 4b.

[0084] In embodiments where it exists, luminometer sample dilution check 4.3 can expand on the basic concept of transferring fluid from a container acting as a sample container to a container acting as a reaction container by adding an intermediate container in which the fluid is diluted. Thus, luminometer sample dilution check 4.3 can begin using a reagent pipettor to transfer predetermined amounts of ALP solution to multiple containers acting as sample containers for that test (e.g., adding 100 μL of ALP solution to each of 20 containers). Varying amounts of wash buffer can then be added to each of multiple containers acting as dilution containers using the reagent pipettor, and then, for each sample container, a portion of the ALP solution can be transferred using a sample precision pipettor to one of the dilution containers in an amount corresponding to the previously added wash buffer. For example, in some embodiments, 10 dilution containers are added with 245 μL of wash buffer and 5 μL of ALP, and 10 dilution containers are added with 180 μL of wash buffer and 20 μL of ALP. The dilution vessels can then be mixed, and a portion of the mixture from each vessel (e.g., 50 μL) can be transferred from each dilution vessel to a corresponding reaction vessel using a sample precision pipettor. Each of the reaction vessels can then be prepared for the chemiluminescence reaction described in Figure 9, and the light emitted from the vessel can be measured using a luminometer.

[0085] In the luminometer sample dilution check 4.3, if the amount of light measured by the luminometer is inconsistent with the expected light value based on the amount of ALP that must react with the substrate in that vessel (e.g., in a situation where 20-fold (x) and 50-fold (x) dilutions of ALP are produced, the expected light values ​​from these dilutions will be 1 / 20 and 1 / 50 compared to the undiluted signal), this can be treated as indicating a root cause of failure of the luminometer sample volume check. This can then be addressed by implementing one or more remedial actions, such as checking whether the immersion height of the tip of the sample precision pipettor differs from that expected given the instrument's design parameters. This information can then be used to address the issue (e.g., by adjusting the operation of the sample precision pipettor so that the immersion height matches the instrument's design parameters). Alternatively, it can be used to proceed with further remedial / diagnostic actions, if necessary, such as calling a field service engineer and notifying them that there appears to be a problem with the immersion height of the sample precision pipettor or that there has been a failure of the luminometer sample volume check for which no root cause was properly found. Finally, once the fault in the luminometer sample volume check 4b has been remedied, the process of evaluating the operation of the remaining systems of the instrument, if any, can proceed.

[0086] Referring now to luminometer sample aliquot volume check 5b, that step can be used to check the operation of the instrument's sample aliquot subsystem. In some embodiments, this can be performed in essentially the same manner as luminometer sample volume check 4b, except that the ALP is transferred from the sample container to the reaction container with a sample precision pipettor; instead, the transfer can be performed using a sample aliquot pipettor. If the chemiluminescent light detected by the luminometer in the reaction container then does not match the expected light value based on the amount of ALP to be transferred, this can be treated as indicating a fault in the sample aliquot subsystem. This can then trigger one or more remedial actions, such as investigating the level-sensing function of the sample aliquot pipettor and / or replacing the sample aliquot syringe used on that pipettor (i.e., the pipettor tip) to either avoid or as a prelude to invoking additional support resources to address the detected fault.

[0087] The various features of the various embodiments may be combined with one another in various combinations to yield further embodiments according to the principles of the present disclosure.

[0088] Various modifications and alterations of this disclosure will become apparent to those skilled in the art without departing from the scope and spirit of this disclosure, and it should be understood that the scope of this disclosure is not to be unduly limited to the illustrative embodiments described herein. Instead, the protection afforded by any document related to this document should be determined by the claims of that document when claim terms not expressly defined therein are given their broadest reasonable interpretation as provided by a general dictionary.

[0089] For purposes of understanding the claims set forth herein, the following terms and phrases should be understood to have the following meanings:

[0090] When used in the claims, the term "based on" should be understood to mean something that is determined at least in part by stating "based on." Anything that is determined entirely by this will be described as "based exclusively on" to indicate that something must be determined entirely on something else.

[0091] As used in the claims, "computer-readable medium" should be understood to refer to any object, substance, or combination of objects or substances capable of storing data or instructions in a form that can be retrieved and / or processed by a device. Computer-readable media should not be limited to any particular type or organization and should be understood to include distributed and non-centralized systems, but they are storage objects of systems physically or logically arranged and located within a defined and / or circumscribed physical and / or logical space. The "computer-readable medium" being "non-transitory" should be understood to be synonymous with the statement that the "computer-readable medium" is "tangible," and should be understood to exclude non-tangible transmission media, such as a vacuum capable of transmitting transient electromagnetic carrier waves. Examples of "tangible" or "non-transitory" "computer-readable medium" include random access memory (RAM), read-only memory (ROM), hard drives, and flash drives.

[0092] As used in the claims, "means for automatically diagnosing faults in the operation of a machine" should be understood as a limitation recited in means+function form as provided in 35 U.S.C. §112(f) where the function is "automatically diagnoses faults in the operation of a machine," and the corresponding structure is a computer as shown in FIG. 6 configured to execute the process shown in FIG. 7.

Claims

1. 1. A method of operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the set of subsystems in a second order; ii) the second order in which each subsystem in the set of subsystems is evaluated reverses the first order in which the set of subsystems are used in the analytical process sequence; Koto and Including, a) the set of subsystems comprises: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; and Equipped with b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) the second sequence includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem; d) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with ALP to produce chemiluminescent light, followed by incubating the vessel; iii) measuring the chemiluminescent light from the receptacle using a luminometer provided by the chemiluminescent detection subsystem after the receptacle has been incubated and placed in a luminometer receptacle chamber; performing a set of substrate blank check steps including: e) each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to said each container; The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of receptacle-free optical check steps, the set of receptacle-free optical check steps comprising: i) measuring light detected in the luminometer vessel chamber by the luminometer when no vessel is present in the luminometer vessel chamber; ii) causing a light source provided by the chemiluminescent detection subsystem to emit light at one or more intensities; iii) for each of the one or more intensities, measuring the light detected by the luminometer when the light source provided by the chemiluminescent detection subsystem is emitting light at that intensity; Including The method further comprises:

2. 1. A method of operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the set of subsystems in a second order; ii) the second order in which each subsystem in the set of subsystems is evaluated reverses the first order in which the set of subsystems are used in the analytical process sequence; Koto and Including, a) the set of subsystems comprises: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; and Equipped with b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) the second sequence includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem; d) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with ALP to produce chemiluminescent light, followed by incubating the vessel; iii) measuring the chemiluminescent light from the receptacle using a luminometer provided by the chemiluminescent detection subsystem after the receptacle has been incubated and placed in a luminometer receptacle chamber; performing a set of substrate blank check steps including: e) each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to said each container; The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of substrate volume check steps, the set of substrate volume check steps comprising: i) adding to a test vessel a predetermined volume of said substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the actual volume of the substrate adapted to react with ALP to produce chemiluminescent light in the test vessel using one or more images of the test vessel captured by a digital camera; Including The method further comprises:

3. a) the set of subsystems comprises an assay wash subsystem; b) the analysis step sequence includes using the assay wash subsystem to remove unbound material from the reaction vessel between using the sample dispensing subsystem to dispense the biological fluid into the reaction vessel and using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) The method of claim 1 or 2, wherein the set of diagnostic steps includes evaluating the operation of the assay washing subsystem between evaluating the operation of the sample dispensing subsystem and evaluating the operation of the chemiluminescent detection subsystem.

4. 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the set of subsystems in a second order; ii) the second order in which each subsystem in the set of subsystems is evaluated reverses the first order in which the set of subsystems are used in the analytical process sequence; Koto and Including, a) the set of subsystems comprises: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; and Equipped with b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) the second sequence includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem; d) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with ALP to produce chemiluminescent light, followed by incubating the vessel; iii) measuring the chemiluminescent light from the receptacle using a luminometer provided by the chemiluminescent detection subsystem after the receptacle has been incubated and placed in a luminometer receptacle chamber; performing a set of substrate blank check steps including: Including, e) each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to said each container; The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of receptacle-free optical check steps, the set of receptacle-free optical check steps comprising: i) measuring light detected in the luminometer vessel chamber by the luminometer when no vessel is present in the luminometer vessel chamber; ii) causing a light source contained by said chemiluminescent detection subsystem to emit light at one or more intensities; iii) for each of the one or more intensities, measuring the light detected by the luminometer when the light source provided by the chemiluminescent detection subsystem is emitting light at that intensity; Including 10. A non-transitory computer-readable medium, further comprising:

5. 1. A non-transitory computer-readable medium having stored thereon data operatively configuring a computer to perform a method for operating a laboratory instrument having a plurality of subsystems and diagnosing faults in the laboratory instrument, the method comprising: a) performing an analytical process sequence to analyze a biological sample, the analytical process sequence utilizing a set of subsystems of the plurality of subsystems of the laboratory instrument in a first order; b) performing a set of diagnostic steps to identify faults in the laboratory instrument; i) performing the set of diagnostic steps includes evaluating each subsystem in the set of subsystems in a second order; ii) the second order in which each subsystem in the set of subsystems is evaluated reverses the first order in which the set of subsystems are used in the analytical process sequence; Koto and Including, a) the set of subsystems comprises: i) a sample dispensing subsystem; ii) a chemiluminescence detection subsystem; and Equipped with b) the first sequence includes using the sample dispensing subsystem to dispense a biological fluid into the reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) the second sequence includes evaluating the operation of the chemiluminescence detection subsystem before evaluating the operation of the sample dispensing subsystem; d) evaluating the chemiluminescent detection subsystem includes, for each of a set of one or more containers: i) adding to said vessel a substrate adapted to react with ALP to produce chemiluminescent light; ii) adding to the vessel the substrate adapted to react with ALP to produce chemiluminescent light, followed by incubating the vessel; iii) measuring chemiluminescent light from the receptacle using a luminometer provided by the chemiluminescence detection subsystem after the receptacle has been incubated and placed in a luminometer receptacle chamber; Including, e) each container in the set of one or more containers is empty when the substrate adapted to react with ALP to produce chemiluminescent light is added to said each container; The method comprises: a) determining that the laboratory instrument is faulty based on chemiluminescent light detected while performing the set of substrate blank check steps; b) expanding the evaluation of the chemiluminescent detection subsystem by performing a set of substrate volume check steps, the set of substrate volume check steps comprising: i) adding to a test vessel a predetermined volume of said substrate adapted to react with ALP to produce chemiluminescent light; ii) measuring the actual volume of the substrate adapted to react with ALP to produce chemiluminescent light in the test vessel using one or more images of the test vessel captured by a digital camera; Including 10. A non-transitory computer-readable medium, further comprising:

6. a) the set of subsystems comprises an assay wash subsystem; b) the analysis step sequence includes using the assay wash subsystem to remove unbound material from the reaction vessel between using the sample dispensing subsystem to dispense the biological fluid into the reaction vessel and using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; c) evaluating the operation of the assay washing subsystem between evaluating the operation of the sample dispensing subsystem and evaluating the operation of the chemiluminescence detection subsystem.

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