Automated point of care detection system including complete sample processing capabilities

• US 6,656,428 B1
• Filed: 08/03/2000
• Issued: 12/02/2003
• Est. Priority Date: 08/06/1999
• Status: Expired due to Fees

• Current Assignee: Inverness Medical-Biostar, Inc. (Abbott Laboratories)
• Original Assignee: Thermo BioStar, Inc. (Abbott Laboratories)
• Inventors: Baker, James, Clark, David D., Ghusson, Andrew, Zeis, John, Bickoff, Charles, McEachern, Richard D., Wells, Ian, Balsavich, John C. Jr., Kohga, Kunio, Dorson, John, Fujii, Alan J., Steaffens, Jeffrey W., Maynard, James E.
• Primary Examiner(s): Ludlow, Jan
• Assistant Examiner(s): SINES, BRIAN J
• Application Number:
  US09/632,343
• Time in Patent Office: 1,216 Days
• Field of Search: 422/58, 422/68.1, 422/61-64, 422/72, 422/100, 422/81, 422/101, 422/65, 422/56, 422/99, 435/7.1, 436/43, 436/46, 436/47
• US Class Current: 422/404
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: G01N 2035/0436 with pre-packaged reagents, i.e. test-packs
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 35/00 Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack

Abstract

The present invention relates to cost effective analytical instruments for determining the presence or amount of an analyte in a sample. The analytical instruments utilize an assay cartridge which has a sample receiving port and a rotatable carousel containing a plurality of reagent wells. Each reagent well includes a piston element for delivery of reagent to a test surface. The instrument is capable of indexing the assay cartridge to deliver sample and reagents to a test surface in a predetermined and flexibile manner, thus providing an assay protocol which is specific to the type of sample under analysis. The invention also relates to components, features, disposables, reagent delivery systems, accessories, and methods for using such instruments. Appropriate applications include infectious disease testing, cancer detection and monitoring, therapeutic drug level monitoring, allergy testing, environmental testing, food testing, diagnostic testing of human and veterinary samples, and off-line process testing.

Claims

1. An assay cartridge for use in an analytical instrument, the assay cartridge comprising:

a bottom member comprising an optical reading well and a test surface; and

a top member comprising a rotatable reagent carousel, said reagent carousel comprising a sample receiving port and a plurality of reagent wells, wherein one or more of said reagent wells comprise a reagent and a reagent well piston for delivery of said reagent to the test surface.

3. An assay cartridge according to claims 1 or 2, wherein said test surface comprises an analyte-specific binding layer for immobilizing an analyte on said test surface.

4. An assay cartridge according to claims 1 or 2, wherein said test surface nonspecifically immobilizes an analyte on said test surface.

5. An assay cartridge according to claims 1 or 2, wherein said test surface is an optically active test surface.

6. An assay cartridge according to claim 5, wherein said optically active test surface is adapted to generate an interference, ellipsometric, or polarization signal.

7. An assay cartridge according to claims 1 or 2, wherein said rotatable carousel further comprises a sample processing element.

8. An assay cartridge according to claim 7, wherein said sample processing element comprises a filtration surface.

9. An assay cartridge according to claims 1 or 2, wherein said sample receiving port is adapted to receive a swab type sample collection device.

10. An assay cartridge according to claims 1 or 2, wherein a bottom portion of each reagent well is sealed by a breakable seal material, and wherein a top portion of each reagent well is sealed by said reagent well piston in combination with a breakable seal material.

11. An assay cartridge according to claim 10, wherein each reagent well piston comprises a piercing element to break said breakable seal material sealing the bottom of said reagent well upon application of a sufficient force.

12. An assay cartridge according to claims 1 or 2, wherein the bottom member comprises extender tabs adapted to ensure proper registration of said assay cartridge with said analytical instrument.

13. The assay cartridge of claim 12, wherein the extender tabs further comprise a locking mechanism for carousel rotation.

14. An assay cartridge according to claims 1 or 2, wherein each reagent well piston comprises a hex boss element.

15. An assay cartridge according to claims 1 or 2, wherein said analytical instrument is a completely automated point of care instrument.

17. The assay cartridge of claims 1 or 2, further comprising an extraction reagent flow channel and a differential seal for the control of extraction reagent to the sample receiving port.

18. A method of fabricating an assay cartridge according to claims 1 or 2, the method comprising:

attaching the bottom member to the top member such that the rotatable reagent carousel may be rotated relative to the bottom member.

2. An assay cartridge for use in an analytical instrument, the assay cartridge comprising:

a bottom member comprising an optical reading well and a test surface; and

a top member comprising a rotatable reagent carousel, said reagent carousel comprising a sample receiving port, a plurality of reagent wells, a reagent flow channel, and a differential seal,

wherein said test surface lies in said optical reading well,

wherein one or more of said regent wells comprise a reagent and a reagent well piston for delivery of said reagent to the test surface, and

wherein said reagent flow channel is adjacent to said sample receiving port, a top part of said reagent flow channel is connected to a top part of said sample receiving port, and said differential seal lies between a bottom part of said reagent flow channel and a bottom part of one of said reagent wells, thereby allowing flow to occur from one of said reagent wells through said reagent flow channel to said sample receiving port.

16. An assay cartridge according to claim 2, wherein said analytical instrument is a completely automated point of care instrument.

19. An analytical instrument for determining the presence or amount of an analyte in a sample, the analytical instrument comprising:

an assay cartridge comprising

(i) a bottom member comprising an optical reading well and a test surface; and

(ii) a top member comprising a reagent carousel, said reagent carousel comprising a sample receiving port and a plurality of reagent wells, wherein one or more of said reagent wells comprise a reagent and a reagent well piston for delivery of said reagent to the test surface, said top member attached to said bottom member such that the reagent carousel may be rotated relative to the bottom member.

a mechanism for receiving said assay cartridge;

a rotation element for rotating and indexing said reagent carousel;

a plunger element for engaging said reagent well pistons to deliver reagent from said reagent wells to said sample receiving port and/or said test surface;

a vacuum element for directing sample and/or reagent to said test surface;

a detector for detecting a signal from said test surface;

a control processor for controlling the rotating, plunger, and vacuum elements according to an assay algorithm; and

a signal processor for relating the generated signal to the presence or amount of said analyte.

20. An analytical instrument according to claim 19 further comprising a mechanism for linear translation mechanism for translating the assay cartridge within the analytical instrument.

21. An analytical instrument according to claim 19 further comprising a presser foot for stabilizing said assay cartridge.

22. An analytical instrument according to claim 19 further comprising an optical control element for determining cartridge orientation.

23. An analytical instrument according to claim 19, wherein said rotation element comprises a mechanical arm and motor.

24. An analytical instrument according to claim 19, wherein said plunger element comprises a push rod attached to a vertical drive element.

25. An analytical instrument according to claim 24 wherein said push rod is adapted to seat in a hex boss element on said reagent well piston.

26. An analytical instrument according to claim 25, wherein said push rod returns said reagent well piston to about its original position in the reagent well following delivery of said reagent.

27. An analytical instrument according to claim 19, wherein said detector is selected from the group consisting of a color sensor, a color detector, an image detector, a spectrophotometer, a luminometer, a fluorometer, a potentiometer, an interferometer, a polarimeter, and an ellipsometer.

28. An analytical instrument according to claim 19, wherein said detector is a fixed polarizer ellipsometer.

29. An analytical instrument according to claim 19, wherein said control processor and said signal processor consist of a single general purpose computer programmed to perform instrument control and data processing algorithms.

30. An analytical instrument according to claim 19, wherein said assay cartridge comprises an identifying element which identifies the analyte and/or the sample to the analytical instrument.

31. An analytical instrument according to claim 30, wherein said identifying element is a bar code, and said analytical instrument comprises a bar code reader configured to read said bar code.

32. An analytical instrument according to claim 19, wherein said sample receiving port is adapted to receive a swab type sample collection device.

33. An analytical instrument according to claim 19, wherein said analytical instrument is a completely automated point of care instrument.

34. A method of determining the presence or amount of an analyte in a sample, the method comprising:

providing an assay cartridge comprising

(i) a bottom member comprising an optical reading well and a test surface; and

(ii) a top member comprising a reagent carousel, said reagent carousel comprising a sample receiving port and a plurality of reagent wells, wherein one or more of said reagent wells comprise a reagent and a reagent well piston for delivery of said reagent to the test surface, said top member attached to said bottom member such that the reagent carousel may be rotated relative to the bottom member;

providing an analytical instrument comprising

(i) a mechanism for receiving said assay cartridge;

(ii) a rotation element for rotating and indexing said rotatable carousel;

(iii) a plunger element for engaging said reagent well pistons to deliver reagent from said reagent wells to said test surface;

(iv) a vacuum element for directing sample and/or reagent to said test surface;

(v) a detector for generating a signal from said test surface;

(vi) a control processor for controlling the rotating, plunger, and vacuum mechanisms according to an assay algorithm; and

(vii) a signal processor for relating the generated signal to the presence or amount of said analyte;

placing said sample into the sample receiving port of said cartridge;

placing said assay cartridge into said receiving mechanism;

performing an assay using said analytical instrument according to said assay algorithm, whereby said signal processor determines the presence or amount of said analyte in said sample.

35. A method according to claim 34, wherein said sample is selected from the group consisting of a throat swab, a vaginal swab, an endocervical swab, a rectal swab, a urethral swab, a nasal swab, a nasopharyngeal swab, a fluid, water, urine, blood, sputum, serum, plasma, an aspirate, a wash, a tissue homogenate, and a process fluid.

36. A method of determining the presence or amount of an analyte in a sample, the method comprising:

providing an assay cartridge comprising

a test surface;

a sample receiving port;

all reagents necessary for performing an assay;

a bottom member comprising an optical reading well and said test surface; and

a top member comprising a rotatable reagent carousel, said reagent carousel comprising said sample receiving port and a plurality of reagent wells, wherein one or more of said reagent wells comprise a reagent and a reagent well piston for delivery of said reagent to the test surface; and

providing an analytic instrument comprising

(i) a mechanism for receiving said assay cartridge;

(ii) a mechanism for delivering said sample to said test surface;

(iii) a mechanism for delivering said reagents to said test surface;

(iv) a detector for generating a signal from said test surface;

(v) a control processor for controlling said delivery mechanisms according to an assay algorithm; and

(vi) a signal processor for relating the generated signal to the presence or amount of said analyte;

placing said sample into the sample receiving port of said cartridge;

placing said assay cartridge into said receiving mechanism; and

performing said assay automatically using said analytical instrument according to said assay algorithm, whereby said signal processor determines the presence or amount of said analyte in said sample.

37. The method of claim 36, wherein one of said reagents comprises a sample extraction reagent, and said analytical instrument further comprises a mechanism for delivering said sample extraction reagent to said sample receiving port and allowing for extraction of one or more analyte from said sample, and said mechanism for delivering said sample to said test surface further comprises a mechanism for delivering said extracted sample to said test surface.

38. The method of claim 36, wherein said sample is selected from the group consisting of urine, water, blood, sputum, plasma, serum, aspirates, washes, tissue homogenate, process fluids, throat swabs, vaginal swabs, endocervical swabs, rectal swabs, urethral swabs, nasopharyngeal swabs, and biological fluids.