CLINICAL ANALYZER AUTOMATED SYSTEM DIAGNOSTICS

Title:

CLINICAL ANALYZER AUTOMATED SYSTEM DIAGNOSTICS

Document Type and Number:

WIPO Patent Application WO/2020/139989

Kind Code:

Abstract:

A method for operating and diagnosing faults in a laboratory instrument comprising a plurality of subsystems may comprise performing an analytic sequence and a set of diagnostic steps. Such a method may be performed using a diagnostic reagent comprising paramagnetic particles and lacking an antibody component. Such a method may also include evaluating a set of the instrument's subsystems in the opposite of the order in which those subsystems are used during analysis.

See also references of EP 3903109A4

Attorney, Agent or Firm:

MORRIS, William, S. et al. (US)

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Claims:

WHAT IS CLAIMED IS:

1. A method of operating and diagnosing faults in a laboratory instrument comprising a plurality of subsystems, the method comprising:

a) performing an analytic sequence of steps to analyze a biological sample, wherein the analytic sequence of steps utilizes a set of subsystems from the plurality of subsystems of the laboratory instrument in a first order; and b) performing a set of diagnostic steps to identify faults in the laboratory instrument, wherein:

i) performing the set of diagnostic steps comprises 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 analytic sequence of steps.

2. The method of claim 1, wherein:

a) the set of subsystems comprises:

i) a sample dispensing subsystem; and

ii) a chemiluminescence detection subsystem;

b) the first order comprises using the sample dispensing subsystem to dispense a biological fluid into a reaction vessel before using the chemiluminescence detection subsystem to detect chemiluminescent light from the reaction vessel; and

c) the second order comprises evaluating operation of the chemiluminescence detection subsystem before evaluating operation of the sample dispensing subsystem.

3. The method of claim 2, wherein:

a) evaluating the chemiluminescence detection subsystem comprises, for each of a set of one or more vessels, performing a set of substrate blank check steps comprising:

i) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to that vessel; ii) incubating that vessel after the substrate adapted to generate chemiluminescent light in reaction with ALP is added to that vessel; and iii) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that vessel after it has been incubated and placed in a luminometer vessel chamber;

and

b) each vessel from the set of one or more vessels is empty when the substrate adapted to generate chemiluminescent light in reaction with ALP is added to it.

4. The method of claim 3, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) changing a bottle used to store the substrate adapted to generate chemiluminescent light in reaction with ALP; and ii) decontaminating a line used to convey the substrate adapted to generate chemiluminescent light in reaction with ALP.

5. The method of claim 3, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

b) extending evaluation of the chemiluminescence detection subsystem by performing a set of no- vessel light check steps comprising:

i) measuring light detected in the luminometer vessel chamber by the lumonimeter when no vessel is present in the luminometer vessel chamber;

ii) causing a light source comprised by the chemiluminescence 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 comprised by the chemiluminescence detection subsystem is emitting light at that intensity.

6. The method of claim 5, wherein the method comprises:

a) determining the fault in the laboratory instrument based on light detected during the set of no- vessel light check steps; and

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) cleaning a luminometer box comprised by the chemiluminescence detection subsystem;

ii) recalibrating the luminometer; and

iii) replacing the luminometer.

7. The method of claim 3, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

b) extending evaluation of the chemiluminescence detection subsystem by performing a set of substrate volume check steps comprising: i) adding a predetermined volume of the substrate adapted to generate chemiluminescent light in reaction with ALP to a test vessel; and ii) measuring the actual volume of the substrate adapted to generate chemiluminescent light in reaction with ALP in the test vessel using one or more images of the test vessel captured with a digital camera.

8. The method of claim 7, wherein the method comprises:

a) determining the fault in the laboratory instrument based on the actual volume of the substrate adapted to generate chemiluminescent light in reaction with ALP in the test vessel; and b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing a substrate dispensing probe; and

ii) replacing a substrate dispensing syringe.

9. The method of claim 2, wherein evaluating the sample dispensing subsystem comprises performing a 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 an ALP solution to that sample vessel using a reagent pipettor;

ii) moving a portion of the ALP solution from that sample vessel to a corresponding reaction vessel from a set of one or more reaction vessels using a sample pipettor comprised by the sample dispensing subsystem; b) for each of the set of one or more reaction vessels corresponding to a sample vessel from the set of one or more sample vessels:

i) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to that reaction vessel;

ii) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that reaction vessel after it has been spun, incubated and placed in a luminometer vessel chamber.

10. The method of claim 9, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and

b) addressing the fault by checking the sample pipettor position.

11. The method of claim 9, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and b) extending evaluation of the sample dispensing subsystem by performing a set of camera sample volume check steps comprising:

i) for each of a plurality of extended diagnostic sample vessels:

A) dispensing a first volume of wash buffer into that extended diagnostic sample vessel using a reagent pipettor;

B) aspirating a second volume of wash buffer from that extended diagnostic sample vessel using the sample pipettor; and

C) capturing one or more digital camera images of that extended diagnostic sample vessel after aspiration of the second volume of wash buffer;

ii) for each of a first set of extended diagnostic reaction vessels:

A) dispensing a third volume of wash buffer into that extended diagnostic reaction vessel using the sample pipettor; and

B) capturing one or more digital camera images of that extended diagnostic reaction vessel after dispensing of the third volume of wash buffer;

iii) for each of a second set of extended diagnostic reaction vessels:

A) dispensing a fourth volume of wash buffer into that extended diagnostic reaction vessel using the sample pipettor; and

B) capturing one or more digital camera images of that extended diagnostic reaction vessel after dispensing of the fourth volume of wash buffer.

12. The method of claim 11, wherein the method comprises:

a) determining the fault in the laboratory instrument based on images captured during performance of the set of camera sample volume check steps; and b) addressing the fault by replacing a sample dispensing syringe.

13. The method of claim 9, wherein the method comprises:

i) for each of a set of one or more test sample vessels:

A) adding a predetermined amount of an ALP solution to that test sample vessel using a reagent pipettor;

B) moving a portion of the ALP solution from that test sample vessel to a corresponding test reaction vessel from a set of one or more test reaction vessels using the sample pipettor, wherein the portion of the ALP solution moved from that test sample vessel has an amount corresponding to a subset of the set of test reaction vessels which the test reaction vessel into which the portion of ALP solution is moved;

ii) for each of the set of one or more test reaction vessels corresponding to a test sample vessel from the set of one or more test sample vessels:

A) adding the substrate adapted to generate chemiluminescent light in reaction with ALP to that reaction vessel; and

B) using the luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that reaction vessel after it has been spun, incubated and placed in a luminometer vessel chamber.

14. The method of claim 13, wherein the method comprises:

a) determining the fault in the laboratory instrument based on chemiluminescent light detected in the sample volume linearity check steps; and

b) addressing the fault by replacing a sample dispensing motor.

15. The method of claim 9, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and

b) extending evaluation of the sample dispensing subsystem by performing a set of sample dilution check steps comprising: i) adding a predetermined volume of an ALP solution to each of a plurality of test sample vessels using the reagent pipettor;

ii) for each of a first set of test dilution vessels:

A) moving a first amount of the ALP solution from a corresponding test sample vessel to that test dilution vessel using the sample pipettor;

B) adding a second amount of wash buffer to that test dilution vessel using the reagent pipettor;

C) mixing the contents of that test dilution vessel;

D) move a third amount of fluid from that dilution vessel to a corresponding reaction vessel using the sample pipettor;

iii) for each of a second set of test dilution vessels:

A) moving a fourth amount of the ALP solution from a corresponding test sample vessel to that test dilution vessel using the sample pipettor;

B) adding a fifth amount of wash buffer to that test dilution vessel using a reagent pipettor;

C) mixing the contents of that test dilution vessel;

D) move the third amount of fluid from that dilution vessel to a corresponding reaction vessel using the sample pipettor;

iv) adding, to each of the test reaction vessels that corresponds to a test dilution vessel, the substrate adapted to generate chemiluminescent light in reaction with ALP; and

v) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that test reaction vessel after it has been spun, incubated and placed in a luminometer vessel chamber.

16. The method of claim 15, wherein the method comprises:

a) determining the fault in the laboratory instrument based on chemiluminescent light detected in the set of luminometer sample volume check steps; and b) addressing the fault by checking sample dispense tip immersion height.

17. The method of claim 9, wherein the sample pipettor is selected from a set of sample pipettors consisting of:

a) a sample precision pipettor; and

b) a sample aliquot pipettor.

18. The method of claim 2, wherein:

a) the set of subsystems comprises a assay washing subsystem;

c) the set of diagnostic steps comprises evaluating operation of the assay washing subsystem between evaluating operation of the sample dispensing subsystem and evaluating operation of the chemiluminescence detection subsystem.

19. The method of claim 18, wherein:

a) the instrument comprises a reagent dispensing subsystem;

b) the analytic sequence of steps comprises using the reagent dispensing subsystem to dispense a reagent into the reaction vessel before using the assay washing subsystem to remove unbound material from the reaction vessel; and c) the set of diagnostic steps comprises evaluating operation of the reagent dispensing subsystem before evaluating operation of the assay washing subsystem.

20. The method of claim 19, wherein:

a) evaluating operation of the reagent dispensing subsystem before evaluating operation of the assay washing subsystem comprises evaluating operation of the reagent dispensing subsystem using a digital camera; and b) the set of diagnostic steps comprises evaluating operation of the reagent dispensing subsystem using a luminometer comprised by the luminescence detection subsystem after evaluating operation of the assay washing subsystem.

21. The method of claim 20, wherein evaluating operation of the reagent dispensing subsystem using a digital camera comprises:

a) ultrasonically mixing a diagnostic reagent in a diagnostic reagent pack using an ultrasonic probe;

b) for each vessel in a set of vessels, using the reagent pipettor to transfer the diagnostic reagent from the diagnostic reagent pack to that vessel; c) using the digital camera to capture one or more reagent resuspension images, wherein each of the one or more reagent resuspension images comprises an image of a vessel from the set of vessels after the diagnostic reagent has been added to that vessel; and

d) performing a reagent resuspension check using the one or more reagent resuspension images.

22. The method of claim 21, wherein:

a) the reagent dispensed into the reaction vessel before using the assay washing subsystem to remove unbound material from the reaction vessel comprises paramagnetic particles and an antibody component adapted by bind to an analyte;

b) the diagnostic reagent comprises paramagnetic particles and does not include an antibody component.

23. The method of claim 21, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on the reagent resuspension check;

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing the ultrasonic probe;

ii) calibrating ultrasonics in the laboratory instrument; and iii) replacing an ultrasonic transducer in the laboratory instrument.

24. The method of claim 20 wherein evaluating operation of the reagent dispensing subsystem using the luminometer comprises, for each of a set of one or more vessels, performing a set of luminometer reagent volume check steps comprising:

a) adding a predetermined volume of an ALP solution to that vessel using a reagent pipettor;

b) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to that vessel;

c) using the luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that vessel after it has been, spun, incubated and placed in a luminometer vessel chamber.

25. The method of claim 24, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; and

b) addressing the fault by realigning a position of the reagent pipettor.

26. The method of claim 24, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; and

b) extending evaluation of the reagent dispensing subsystem by, for each of a plurality of test vessels, perform a set of camera reagent volume check steps comprising:

i) adding a predetermined volume of wash buffer to that test vessel using the reagent pipettor; and

ii) capturing one or more images of that test vessel.

27. The method of claim 26, wherein the method comprises: a) determining the fault in the laboratory instrument based on images captured in performance of the set of camera reagent volume check steps; and b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing a reagent dispensing syringe; and

ii) replacing a reagent dispensing motor.

28. The method of claim 24, wherein

a) the method comprises:

i) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; and

ii) extending evaluation of the reagent dispensing subsystem by, for each of a plurality of test vessels, performing a set of reagent volume linearity check steps comprising:

A) adding a predetermined volume of a mixture of ALP solution and wash buffer to that test vessel;

B) adding the substrate adapted to generate chemiluminescent light in reaction with ALP to that test vessel; and

C) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that vessel after it has been, spun, incubated and placed in a luminometer vessel chamber

b) the plurality of test vessels comprises three subsets of test vessels; and 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 test vessels comprised by that subset of test vessels has a different ratio of ALP solution to wash buffer than the mixtures of ALP solution and wash buffer added to test vessels comprised by the other subsets comprised by the plurality of test vessels.

29. The method of claim 28, wherein the method comprises: a) determining the fault in the laboratory instrument based on chemiluminescent light detected in the reagent volume linearity check steps; and

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) checking perpendicularity of the reagent pipettor;

ii) replacing a tip of the reagent pipettor; and

iii) replacing an ultrasonic transducer.

30. The method of claim 24, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer reagent volume check steps; and

b) extending evaluation of the reagent dispensing subsystem by, for each of a plurality of test vessels, performing a set of reagent pipettor carryover check steps comprising:

i) adding a ALP solution to that test vessel using the reagent pipettor; ii) after adding the ALP solution, adding wash buffer to that test vessel using the reagent pipettor;

iv) adding the substrate adapted to generate chemiluminescent light in reaction with ALP to that test vessel;

v) spinning that test vessel after adding the substrate adapted to generate chemiluminescent light in reaction with ALP; and vi) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that vessel after it has been incubated and placed in a luminometer vessel chamber.

31. The method of claim 30, wherein the method comprises:

a) determining the fault in the laboratory instrument based on chemiluminescent light detected in the reagent pipettor carryover check steps; and b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing a tip of the reagent pipettor; ii) investigating a condition of a wash tower comprised by the assay washing subsystem; and

iii) replacing a wash dispense pump.

32. A method of operating and diagnosing faults in a laboratory instrument, the method comprising:

a) performing an analytic sequence of steps to analyze a biological sample, wherein the analytic sequence of steps comprises adding, to a reaction vessel, an assay reagent comprising paramagnetic particles and an antibody adapted to bind to an analyte; and

b) performing a set of diagnostic steps to evaluate operation of the laboratory instrument, wherein the set of diagnostic steps comprises, for each vessel in a set of vessels, adding a diagnostic reagent to that vessel, wherein the diagnostic reagent comprises paramagnetic particles and does not include an antibody component.

33. The method of claim 32, wherein:

a) the assay reagent has a first concentration of paramagnetic particles;

b) the diagnostic reagent has a second concentration of paramagnetic particles; and c) the first concentration is lower than the second concentration.

34. The method of claim 33, wherein:

a) the first concentration is between 0.3 mg/mL and 2.0 mg/mL; and

b) the second concentration is 4.0 mg/mL.

35. The method of claim 32, wherein the set of diagnostic steps comprises:

a) for each vessel in the set of vessels:

i) creating a testing mixture by combining the diagnostic reagent added to that vessel with a portion of wash buffer;

ii) subjecting the testing mixture in that vessel to a magnetic field;

iii) removing that vessel from the magnetic field; and iv) after that vessel has been removed from the magnetic field, mixing the testing mixture contained in that vessel;

b) using a digital camera to capture one or more particle resuspension images, wherein each of the one or more particle resuspension images comprises an image of a vessel from the set of vessels after the testing mixture contained in that vessel has been mixed;

c) performing a resuspension check using the one or more particle resuspension images.

36. The method of claim 35, wherein, for each vessel in the set of vessels, mixing the testing mixture contained in that vessel comprises:

a) moving that vessel to a spin mixing position on a wash wheel;

b) spin mixing the testing mixture contained in that vessel.

37. The method of claim 36, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on the resuspension check;

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) aligning a spin mixer to the spin mixing position on the wash wheel; and ii) replacing the spin mixer.

38. The method of claim 35, wherein, for each vessel in the set of vessels, mixing the testing mixture contained in that vessel comprises, before moving that vessel to the spin mixing position on the wash wheel:

a) moving that vessel to a pipetting position in the laboratory instrument; and b) ultrasonically mixing the testing mixture contained in that vessel using a reagent pipettor.

39. The method of claim 38, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on the resuspension check; b) addressing the fault by performing one or more actions selected from the group consisting of:

i) aligning the reagent pipettor to the pipetting position in the laboratory instrument; and

ii) checking perpendicularity of the reagent pipettor.

40. The method of claim 32, wherein the set of diagnostic steps comprises:

a) for each vessel in the set of vessels, before adding the diagnostic reagent to that vessel, ultrasonically mixing the diagnostic reagent using an ultrasonic probe; b) using a digital camera to capture one or more reagent resuspension images, wherein each of the one or more reagent resuspension images comprises an image of a vessel from the set of vessels after the diagnostic reagent has been added to that vessel; and

c) performing a reagent resuspension check using the one or more reagent resuspension images.

41. The method of claim 40, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on the reagent resuspension check;

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing the ultrasonic probe;

ii) calibrating ultrasonics in the laboratory instrument; and iii) replacing an ultrasonic transducer in the laboratory instrument.

42. A method of diagnosing faults in a laboratory instrument, the method comprising performing a set of diagnostic steps comprising:

a) washing each vessel from a set of vessels;

b) using a digital camera to capture one or more particle retention images, wherein each of the one or more particle retention images comprises an image of a vessel from the set of vessels after that vessel has been washed; and

c) calculating a retention value based on the one or more particle retention images.

43. The method of claim 42, wherein:

a) the set of vessels comprises a plurality of vessels;

b) the set of diagnostic steps comprises, for each vessel in the set of vessels, creating a testing mixture by combining a reagent comprising paramagnetic particles added to that vessel with a portion of wash buffer;

c) the testing mixture in each vessel from the set of vessels comprises 50 pL of the reagent and 150 pL of wash buffer.

44. The method of claim 42, wherein the method comprises:

a) based on the retention value, determining that there is a fault in the laboratory instrument;

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) aligning an aspiration probe to a reaction vessel position in the laboratory instrument; and

ii) inspecting magnetic functions of the laboratory instrument.

45. The method of claim 42, wherein the retention value is calculated based on:

a) a grayscale value derived from the one or more particle retention images; and b) a particle retention calibration curve.

46. The method of claim 45, wherein:

b) the plurality of calibration mixtures comprises a set of calibration mixtures, wherein each calibration mixture from the set of calibration mixtures has a reagent to wash buffer ratio that is different from any other calibration mixture in the set of calibration mixtures.

47. The method of claim 46, wherein the set of calibration mixtures comprises calibration mixtures having the following reagent to wash buffer ratios:

a) 50 : 150;

b) 40 : 160;

c) 35 : 165; and

d) 25: 175.

48. The method of claim 46, wherein:

a) creating the particle retention calibration using the plurality of calibration mixtures comprises:

i) for each calibration mixture:

A) sending a vessel containing that calibration mixture to a wash wheel;

B) spin mixing the vessel comprising that calibration mixture at a substrate spin position on the wash wheel; and

C) capturing a grayscale image of the vessel comprising that calibration mixture after it has been mixed;

and

ii) creating the calibration curve with the captured grayscale images of the vessels comprising the calibration mixtures;

b) the set of vessels comprises a plurality of vessels;

c) the set of diagnostic steps comprises, for each vessel in the set of vessels: i) creating a testing mixture by combining the reagent added to that vessel with a portion of wash buffer;

ii) after the testing mixture is created in that vessel, washing it with the wash buffer at least twice;

iii) after that vessel has been washed at least twice, aspirating fluid from that vessel with an aspirate probe;

iv) after the fluid has been aspirated from that vessel with the aspirate probe, adding a volume of wash buffer to that vessel, wherein the volume of wash buffer added to that vessel is equal to the volume of test mixture that had been in that vessel prior to aspiration; and v) after the volume of wash buffer has been added to that vessel, spin mixing that vessel at a substrate spin position on the wash wheel; and

d) the one or more particle retention images comprises a grayscale image of each vessel from the set of vessels captured after that vessel had had the volume of wash buffer added to it and had been spin mixed at the substrate spin position on the wash wheel.

49. A method of diagnosing faults in a laboratory instrument comprising a plurality of subsystems, the method comprising:

a) performing a set of diagnostic steps to identify faults in the laboratory instrument, wherein each diagnostic step from the set of diagnostic steps corresponds to a subsystem from the plurality of subsystems;

b) detecting a fault 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 step during which the fault in the laboratory instrument was detected.

50. The method of claim 49, wherein

a) the plurality of subsystems comprises:

i) a sample dispensing subsystem;

ii) a reagent dispensing subsystem;

iii) a assay washing subsystem; and

iv) a chemiluminescence detection subsystem;

b) the instrument is adapted to analyze a biological sample for presence of an analyte by performing a set of analytic steps comprising:

i) transferring a portion of the biological sample from a sample vessel to a reaction vessel using the sample dispensing subsystem;

ii) creating an analytic 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 portions of the analytic mixture that are not bound to the analyte from the reaction vessel using the assay washing subsystem; and iv) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to the reaction vessel and detecting chemiluminescent light generated by substrate in reaction with the ALP using the chemiluminescence detection subsystem.

51. A method of operating and diagnosing faults in a laboratory instrument, the method comprising:

a) performing an analytic sequence of steps to analyze a biological sample, wherein the analytic sequence of steps comprises:

i) transferring a portion of the biological sample from a sample vessel to a reaction vessel;

ii) creating an analytic mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel; iii) removing portions of the analytic mixture that are not bound to an analyte from the reaction vessel using a assay washing subsystem; and iv) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to the reaction vessel and detecting chemiluminescent light generated by the substrate in reaction with the ALP using a luminometer;

b) performing a set of diagnostic steps that comprises evaluating the assay washing subsystem by, for each of a set of one or more vessels, performing a set of wash efficiency check steps comprising:

i) adding a combination of:

A) an ALP solution;

B) a second reagent comprising paramagnetic particles; and

C) a wash buffer

to that vessel;

ii) performing a set of washing steps comprising:

A) subjecting that vessel to a magnetic field;

B) adding additional wash buffer to that vessel; and C) spinning the contents of that vessel

one or more times;

iii) aspirating fluid from that vessel;

iv) after aspirating fluid from that vessel, adding the substrate adapted to generate chemiluminescent light in reaction with ALP;

v) incubating that vessel; and

vi) using the luminometer, measuring chemiluminescent light from that vessel after it has been placed in a luminometer vessel chamber.

52. The method of claim 51, wherein:

a) the second reagent comprising paramagnetic particles does not include an antibody component; and

b) the analytic sequence of steps comprises adding a third reagent comprising paramagnetic particles to the reaction vessel, wherein the paramagnetic particles comprised by the third reagent are coated with an antibody component adapted to bind to the analyte.

53. The method of claim 51, wherein:

a) the analytic sequence of steps comprises:

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; and iii) incubating the reaction vessel between transferring the third reagent comprising ALP to the reaction vessel and detecting chemiluminescent light generated by the substrate in reaction with the ALP using the luminometer;

b) for each vessel from the set of vessels, that vessel is incubated only one time during performance of the set of diagnostic steps.

54. The method of claim 51, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of wash efficiency check steps; and

b) addressing the fault by aligning a pick and place actuator position to a vessel position.

55. The method of claim 51, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of wash efficiency check steps;

b) extending evaluation of the assay washing subsystem by performing a 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) moving each of the test vessels to which the predetermined volume of wash buffer was added to a camera position on a wash wheel;

iii) capturing images of the one or more test vessels to which the predetermined volume of wash buffer was added; and

iv) using the captured images to determine the actual volume of wash buffer added to each of the one or more test vessels.

56. The method of claim 55, wherein the method comprises:

a) determining the fault in the laboratory instrument based on the actual volume of wash buffer added to the one or more test vessels; and

b) addressing the fault by replacing one or more of the probes used to add the wash buffer to the one or more test vessels.

57. The method of claim 51, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of wash efficiency check steps; b) extending evaluation of the assay washing subsystem by performing a 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 was added:

A) moving that test vessel to an aspiration position corresponding to the probe used to added the predetermined volume of wash buffer to that test vessel;

B) aspirating fluid from that test vessel using an aspiration probe located at the aspiration position to which that test vessel was moved;

C) moving that test vessel to a camera position after fluid is aspirated from it;

D) capturing one or more images of that test vessel after fluid is aspirated from it; and

E) determining a residual volume remaining in that test vessel based on the one or more images captured of that test vessel.

58. The method of claim 57, wherein the method comprises:

a) determining the fault in the laboratory instrument based on residual volume detected in the residual volume check steps; and

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing one or more aspiration probes;

ii) aligning one or more aspiration probes with the aspiration position at which it is located; and

iii) replacing peristaltic pump tubing.

59. The method of claim 51, wherein the method comprises: a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of wash efficiency check steps; and

b) extending evaluation of the assay washing subsystem by performing a set of aspirate probe carryover check steps comprising, for each of a set of one or more test vessels:

i) adding the ALP solution to that test vessel;

ii) after adding the ALP solution, adding wash buffer to that test vessel; iii) aspirating the ALP solution from that test vessel using an aspiration probe;

iv) adding the substrate adapted to generate chemiluminescent light in reaction with ALP to that test vessel;

v) spinning that test vessel after adding the substrate adapted to generate chemiluminescent light in reaction with ALP; and vi) using the luminometer, measuring chemiluminescent light from that vessel after it has been incubated and placed in the luminometer vessel chamber.

60. The method of claim 59, wherein the method comprises:

a) determining the fault in the laboratory instrument based on chemiluminescent light detected in the aspirate probe carryover check steps; and

b) addressing the fault by performing one or more actions selected from the group consisting of:

i) replacing one or more aspiration probes;

ii) investigating a condition of a wash tower comprised by the assay washing subsystem; and

iii) replacing a wash dispense pump.

61. A method of operating and diagnosing faults in a laboratory instrument, the method comprising:

a) performing an analytic sequence of steps to analyze a biological sample, wherein: i) the analytic sequence of steps utilizes a plurality of subsystems comprising:

A) a sample dispensing subsystem;

B) a reagent dispensing subsystem;

C) a assay washing subsystem; and

D) a chemiluminescence detection subsystem;

and

ii) performing the analytic sequence of steps comprises:

A) creating an analytic 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 portions of the analytic mixture that are not bound to an analyte from the reaction vessel using the assay washing subsystem; and

C) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to the reaction vessel and detecting chemiluminescent light generated by substrate in reaction with the ALP using the chemiluminescence detection subsystem; and

b) performing a set of diagnostic steps that comprises:

i) evaluating the plurality of subsystems using a luminometer comprised by the chemiluminescence detection subsystem; and ii) in parallel with evaluating the plurality of subsystems using the luminometer comprised by the chemiluminescence detection subsystem, using machine vision to evaluate one or more subsystems from the plurality of subsystems.

62. The method of claim 61, wherein:

a) the sample dispensing subsystem comprises:

i) a sample precision subsystem; and

ii) a sample aliquoting subsystem;

and b) the analytic sequence of steps comprises transferring a portion of the biological sample from a sample vessel to the reaction vessel by performing a step selected from the group consisting of:

i) transferring an aliquot of the biological sample from the sample vessel to the reaction vessel using the sample aliquoting subsystem; and ii) transferring the portion of the biological sample from the sample vessel to the reaction vessel using the sample dispensing subsystem.

63. The method of claim 61, wherein:

a) the analytic sequence of steps comprises adding, to the reaction vessel, an analytic reagent comprising paramagnetic particles coated with an antibody component adapted to bind to the analyte; and

b) the set of diagnostic steps comprises adding, to a vessel acting as the reaction vessel in the evaluation of the instrument, an analytic reagent comprising paramagnetic particles and lacking an antibody component.

64. A method of operating and diagnosing faults in a laboratory instrument comprising a plurality of subsystems, the method comprising:

a) performing an analytic sequence steps comprising:

i) transferring a portion of a biological sample from a sample vessel to a reaction vessel;

ii) creating an analytic mixture by transferring a first reagent comprising alkaline phosphatase (ALP) from a reagent pack to the reaction vessel using a reagent dispensing subsystem;

iii) removing portions of the analytic mixture that are not bound to an analyte from the reaction vessel using a assay washing subsystem; and iv) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to the reaction vessel and detecting chemiluminescent light generated by substrate in reaction with the ALP using a chemiluminescence detection subsystem;

b) performing a set of diagnostic steps comprising: i) adding the substrate adapted to generate chemiluminescent light in reaction with ALP to a testing vessel; and

ii) based on chemiluminescent light detected using the chemiluminescence detection subsystem, determining that a fault exists in the laboratory instrument;

and

c) based on determining that the fault exists in the laboratory instrument, performing a set of extended diagnostic steps comprising, for each of a plurality of extended testing vessels:

i) adding a predetermined volume of testing fluid to that extended testing vessel;

ii) capturing an image of that extended testing vessel; and iii) determining volume of the testing fluid in that extended testing vessel using the image of that extended testing vessel

wherein the testing fluid is selected from a group consisting of:

A) the substrate adapted to generate chemiluminescent light in reaction with ALP;

B) wash buffer;

C) the first reagent comprising ALP; and

D) a second reagent comprising paramagnetic particles.

65. The method of claim 64, wherein:

a) performing the set of diagnostic steps comprises, for each of a set of one or more vessels, performing a set of substrate blank check steps comprising:

i) the substrate adapted to generate chemiluminescent light in reaction with ALP to that vessel;

ii) incubating that vessel after the substrate adapted to generate chemiluminescent light in reaction with ALP is added to that vessel; and iii) using the chemiluminescence detection subsystem to measure chemiluminescent light from that vessel after it has been incubated and placed in a luminometer vessel chamber;

and b) determining that the fault exists in the laboratory instrument based on chemiluminescent light detected using the chemiluminescence detection subsystem comprises determining that at least one vessel from the set of vessels was contaminated with ALP based on detecting light emitted from that vessel using the chemiluminescence detection subsystem.

66. The method of claim 65, wherein the testing fluid added to the extended testing vessel is the substrate adapted to generate chemiluminescent light in reaction with ALP.

67. The method of claim 64, wherein, for each of the plurality of extended testing vessels, determining volume of testing fluid in that extended testing vessel using the image of that extended testing vessel comprises determining the volume of fluid using a distance between a bottom of a meniscus in that extended testing vessel and that extended testing vessel’s bottom.

68. The method of claim 64, wherein performing the set of diagnostic steps comprises: a) performing an ultrasonic mix on a diagnostic reagent inside a reagent pack; b) transferring a portion of the diagnostic reagent from the reagent pack to a particle testing vessel;

c) capturing an image of the testing vessel after the transfer of the portion of the diagnostic reagent; and

d) based on a grayscale value for the image of the testing vessel, determining whether a fault exists in the laboratory instrument.

69. The method of claim 68, wherein the diagnostic reagent comprises uncoated paramagnetic particles, and does not comprise any paramagnetic particles coated with an antibody component.

70. A non-transitory computer readable medium having stored thereon data operable to configure a computer to perform a method of operating and diagnosing faults in a laboratory instrument comprising a plurality of subsystems, the method comprising: a) performing an analytic sequence of steps to analyze a biological sample, wherein the analytic sequence of steps utilizes a set of subsystems from the plurality of subsystems of the laboratory instrument in a first order; and b) performing a set of diagnostic steps to identify faults in the laboratory instrument, wherein:

i) performing the set of diagnostic steps comprises evaluating each subsystem in the first 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 analytic sequence of steps.

71. The non-transitory computer readable medium of claim 70, wherein:

a) the set of subsystems comprises:

i) a sample dispensing subsystem; and

ii) a chemiluminescence detection subsystem;

c) the second order comprises evaluating operation of the chemiluminescence detection subsystem before evaluating operation of the sample dispensing subsystem.

72. The non-transitory computer readable medium of claim 71, wherein:

a) evaluating the chemiluminescence detection subsystem comprises, for each of a set of one or more vessels, performing a set of substrate blank check steps comprising:

i) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to that vessel;

ii) incubating that vessel after the substrate adapted to generate chemiluminescent light in reaction with ALP is added to that vessel; and iii) using a luminometer comprised by the chemiluminescence detection subsystem, measuring chemiluminescent light from that vessel after it has been incubated and placed in a luminometer vessel chamber;

and

b) each vessel from the set of one or more vessels is empty when the substrate adapted to generate chemiluminescent light in reaction with ALP is added to it.

73. The non-transitory computer readable medium of claim 72, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

b) providing a notification to address the fault by performing one or more actions selected from the group consisting of:

74. The non-transitory computer readable medium of claim 72, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

b) extending evaluation of the chemiluminescence detection subsystem by performing a set of no- vessel light 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;

75. The non-transitory computer readable medium of claim 74, wherein the method comprises:

a) determining the fault in the laboratory instrument based on light detected during the set of no- vessel light check steps; and

b) providing notification to address the fault by performing one or more actions selected from the group consisting of:

i) cleaning a luminometer box comprised by the chemiluminescence detection subsystem;

ii) recalibrating the luminometer; and

iii) replacing the luminometer.

76. The method of claim 72, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of substrate blank check steps;

77. The non-transitory computer readable medium of claim 76, wherein the method comprises: a) determining the fault in the laboratory instrument based on the actual volume of the substrate adapted to generate chemiluminescent light in reaction with ALP in the test vessel; and

b) providing a notification to address the fault by performing one or more actions selected from the group consisting of:

i) replacing a substrate dispensing probe; and

ii) replacing a substrate dispensing syringe.

78. The non-transitory computer readable medium of claim 71, wherein evaluating the sample dispensing subsystem comprises performing a 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 an ALP solution to that sample vessel using a reagent pipettor;

i) adding a substrate adapted to generate chemiluminescent light in reaction with ALP to that reaction vessel;

79. The non-transitory computer readable medium of claim 78, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and b) providing a notification to address the fault by checking the sample pipettor position.

80. The non-transitory computer readable medium of claim 78, wherein the method comprises:

a) determining that there is a fault in the laboratory instrument based on chemiluminescent light detected while performing the set of luminometer sample volume check steps; and

b) extending evaluation of the sample dispensing subsystem by performing a set of camera sample volume check steps comprising: