System for performing multi-formatted assays

• US 8,501,461 B2
• Filed: 12/03/2009
• Issued: 08/06/2013
• Est. Priority Date: 03/10/2005
• Status: Active Grant

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Inventors: Knight, Byron J., Li, Haitao
• Primary Examiner(s): BOWERS, NATHAN ANDREW
• Application Number:
  US12/630,302
• Publication Number:
  US 20100075336A1
• Time in Patent Office: 1,342 Days
• Field of Search: 435/287.3, 435/809, 435/307.1, 435/303.1, 435/808, 435/287.2, 435/288.7, 422/82.07, 422/82.08, 250/461.2, 250/483.1, 250/461.1, 250/459.1, 73/73, 732/46
• US Class Current: 435/288.7
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6851 Quantitative amplification
• CPC Class Codes: C12Q 2537/165 Mathematical modelling, e.g. logarithm, ratio
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2035/00346 Heating or cooling arrangements
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 2035/0097 monitoring reactions as a function of time
• CPC Class Codes: G01N 2035/0441 for samples
• CPC Class Codes: G01N 2035/0443 for reagents
• CPC Class Codes: G01N 2035/0444 for cuvettes or reaction vessels
• CPC Class Codes: G01N 2035/0455 Coaxial carousels
• CPC Class Codes: G01N 2035/0491 Position sensing, encoding; closed-loop control
• CPC Class Codes: G01N 2035/103 using disposable tips
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/0415 : Carrusel, sequential
• CPC Class Codes: G01N 35/00693 : Calibration
• CPC Class Codes: G01N 35/0092 : Scheduling
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/025 : having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/026 : having blocks or racks of reaction cells or cuvettes
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/04 : Details of the conveyor system G01N35/021 - G01N35/028 take precedence
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 435/809 : Incubators or racks or holders for culture plates or containers
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

An automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations in which discrete aspects of the assay are performed on fluid samples contained in sample vessels. The analyzer includes stations for automatically preparing a sample, incubating the sample, preforming an analyte isolation procedure, ascertaining the presence of a target analyte, and analyzing the amount of a target analyte. An automated receptacle transporting system moves the sample vessels from one station to the next. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte, and, in one embodiment, a method for real-time monitoring of the amplification process.

Claims

1. A system for detecting two or more different optical signals emitted from each of a plurality of reaction receptacles, wherein the reaction receptacles are disposed in a fixed arrangement with respect to each other, said system comprising:

a plurality of optical sensors, each of said optical sensors being configured to detect one of the two or more optical signals and being associated with one of the reaction receptacles so that each reaction receptacle has associated therewith one optical sensor for each optical signal to be detected, whereby said optical sensors associated with each of the plurality of reaction receptacles are arranged in a configuration that enables each optical sensor to detect the associated optical signal emitted from the associated reaction receptacle; and

a transport mechanism constructed and arranged to effect movement of each reaction receptacle to sequentially place each reaction receptacle into a signal-detecting position with respect to one of its associated optical sensors,

wherein (1) said plurality of optical sensors are arranged so that only one of the plurality of reaction receptacles at a time can be in a signal-detecting position with respect to one of its associated optical sensors, and (2) each of said optical sensors configured to detect one of the two or more optical signals is arranged together in a group with at least one other of said optical sensors configured to detect the same optical signal.

2. The system of claim 1, wherein said plurality of optical sensors are disposed in fixed positions, and wherein said transport mechanism comprises a receptacle transport mechanism constructed and arranged to move the reaction receptacles into signal-detecting positions with respect to said fixed optical sensors.

3. The system of claim 2, wherein said receptacle transport mechanism comprises a rotatable carousel constructed and arranged for holding, moving, and positioning the reaction receptacles with respect to said optical sensors.

4. The system of claim 3, wherein said optical sensors are arranged at different angular positions with respect to said carousel.

5. The system of claim 3, wherein each of said reaction receptacles is positioned at a different radial position with respect to the axis of rotation of said carousel, and wherein the optical sensors associated with each reaction receptacle are positioned at different angular locations and at the radial position corresponding to the associated reaction receptacle.

6. The system of claim 5, further comprising baffles configured to optically isolate each of said optical sensors from the other optical sensors, wherein said baffles comprise walls arranged concentrically and at different radial positions with respect to the axis of rotation of said carousel so as to be located between radially-adjacent reaction receptacles.

7. The system of claim 5, wherein each of said reaction receptacles comprises a test tube, and wherein said test tubes are connected to each other in an aligned arrangement and an upright orientation and further wherein said connected arrangement of test tubes is carried on said carousel in a generally radial orientation so that each test tube is located at a different radial position.

8. The system of claim 4, wherein said system comprises three optical sensors associated with each reaction receptacle, each of the three optical sensors being configured to detect a different one of three different optical signals.

9. The system of claim 8, comprising fifteen optical sensors to detect three different optical signals emitted by each of at least five reaction receptacles.

10. The system of claim 9, wherein said optical sensors are equally spaced at 24 degree increments about said carousel.

11. The system of claim 1, comprising three optical sensors associated with each reaction receptacle, each of the three optical sensors being configured to detect a different one of three different optical signals.

12. The system of claim 1, wherein each of said reaction receptacles comprises a test tube, and wherein said test tubes are connected to each other in an aligned arrangement and an upright orientation.

13. The system of claim 1, further comprising baffles configured to optically isolate each of said optical sensors from the other optical sensors.

14. The system of claim 1, wherein each of said optical sensors comprises a fluorometer constructed and arranged to detect fluorescent emissions from the reaction receptacles.

15. The system of claim 1, wherein the two or more different optical signals are optical signals having different wavelengths.

16. The system of claim 1, wherein the amount of each different optical signal emitted from each reaction receptacle is indicative of the presence or amount of a different target nucleic acid within the contents of the reaction receptacle, and wherein the system is configured to process detected optical signal data so as to determine the presence or amount, within the contents of each receptacle, of the target nucleic acid associated with each optical signal based on the detected optical signals.

17. The system of claim 1, wherein each of the reaction receptacles is placed in a signal-detecting position with respect to an associated optical sensor configured to detect one optical signal before the reaction receptacle is placed in signal-detecting position with respect to an associated optical sensor configured to detect a different optical signal.

18. A system for detecting two or more different optical signals emitted from each of a plurality of reaction receptacles, wherein the reaction receptacles are disposed in a fixed arrangement with respect to each other, said system comprising:

a plurality of optical sensors, each of said optical sensors being configured to detect one of the two or more optical signals and being associated with one of the reaction receptacles so that each reaction receptacle has associated therewith one optical sensor for each optical signal to be detected, whereby said optical sensors associated with each of the plurality of reaction receptacles are arranged in a configuration that enables each optical sensor to detect the associated optical signal emitted from the associated reaction receptacle; and

a transport mechanism constructed and arranged to effect relative movement between the plurality of reaction receptacles and the optical sensors to sequentially place each reaction receptacle into a signal-detecting position with respect to one of its associated optical sensors,

wherein (1) said plurality of optical sensors are arranged so that only one of the plurality of reaction receptacles at a time can be in a signal-detecting position with respect to one of its associated optical sensors, (2) each of said optical sensors configured to detect one of the two or more optical signals is arranged together in a group with at least one other of said optical sensors configured to detect the same optical signal, and (3) wherein the relative movement comprises changing the physical location of the optical sensors, the reaction receptacles, or both the optical sensors and the reaction receptacles, within the system.

19. A method for detecting two or more different optical signals emitted from each of a plurality of reaction receptacles, disposed in a fixed arrangement with respect to each other using an instrument comprising optical sensors configured to detect one of two or more optical signals from each of a plurality of reaction receptacles, wherein each optical sensor is associated with one of the reaction receptacles and each reaction receptacle has associated therewith one optical sensor for each optical signal to be detected and wherein the optical sensors are arranged so that only one of the plurality of reaction receptacles at a time can be in a signal-detecting position with respect to one of its associated optical sensors and the optical sensors are grouped so that each of the reaction receptacles is placed in a signal-detecting position with respect to an associated optical sensor configured to detect one optical signal before the reaction receptacle is placed in signal-detecting position with respect to an associated optical sensor configured to detect a different optical signal, said method comprising, for each of the two or more different optical signals to be detected the steps of:

(a) effecting movement of the plurality of reaction receptacles to sequentially place each reaction receptacle of the fixed arrangement of reaction receptacles into a signal-detecting position with respect to one of its associated optical sensors configured to detect one of the two or more optical signals; and

(b) sequentially measuring an amount of the one optical signal emitted by the contents of each reaction receptacle as each reaction receptacle is placed in the signal detecting position with respect to its associated optical sensor configured to detect the one optical signal.

20. The method of claim 19, wherein the plurality of optical sensors are disposed in fixed positions, and wherein effecting relative movement comprises moving the reaction receptacles into signal-detecting positions with respect to the fixed optical sensors.

21. The method of claim 20, wherein moving the reaction receptacles comprises moving each of the reaction receptacles in a circular path.

22. The method of claim 21, wherein the optical sensors are arranged at different angular positions with respect to the circular path of the associated reaction receptacle.

23. The method of claim 21, wherein all of the reaction receptacles are moved in a circular path having a common axis of rotation and each of the reaction receptacles is positioned at a different radial position with respect to the axis of rotation, and wherein the optical sensors associated with each reaction receptacle are positioned at different angular locations and at the radial position corresponding to the associated reaction receptacle.

24. The method of claim 23, wherein each of the reaction receptacles comprises a test tube, and wherein the test tubes are connected to each other in an aligned arrangement and an upright orientation and further wherein moving the reaction receptacles in a circular path comprises carrying the connected arrangement of test tubes in a generally radial orientation with respect to the axis of rotation.

25. The method of claim 19, comprising providing three optical sensors associated with each reaction receptacle, each of the three optical sensors being configured to detect a different one of three different optical signals.

26. The method of claim 19, wherein each of the reaction receptacles comprises a test tube, and wherein the test tubes are connected to each other in an aligned arrangement and an upright orientation.

27. The method of claim 19, further comprising optically isolating each of the optical sensors from the other optical sensors.

28. The method of claim 19, wherein each of the optical sensors comprises a fluorometer constructed and arranged to detect fluorescent emissions from the reaction receptacles.

29. The method of claim 19, wherein each different optical signal is generated by a different fluorescent dye contained in the reaction receptacle.

30. The method of claim 29, wherein the fluorescent dyes comprise rhodamine dyes in combination with a DABCYL quencher.

31. The method of claim 30, wherein the fluorescent dyes further comprise fluorescein dyes in combination with a DABCYL quencher.

32. The method of claim 31, wherein the dyes comprise two or more dyes selected from the group consisting of tetramethyl-6-rhodamine (“

TAMRA”

), tetrapropano-6-carboxyrhodamine (“

ROX”

), 6-carboxyfluorescein (“

FAM”

), and 2′

,7′

-dimethoxy-4′

,5′

-dichloro-6-carboxyrhodamin (“

JOE”

).

33. The method of claim 19, wherein the two or more different optical signals are optical signals having different wavelengths.

34. The method of claim 19, wherein the amount of each different optical signal emitted by the contents of each reaction receptacle is indicative of the presence or amount of a different target nucleic acid within the contents of the reaction receptacle, and wherein the method further comprises the step of determining the presence or amount, within the contents of each reaction receptacle, of the target nucleic acid associated with each measured optical signal based upon the measurements obtained in step b).

35. The method of claim 34, further comprising the step of periodically measuring the amount of each optical signal emitted by the contents of each reaction receptacle prior to determining an amount of the target nucleic acid associated with each measured optical signal.