System and methods for performing rotor assays

• US 6,299,839 B1
• Filed: 08/31/1995
• Issued: 10/09/2001
• Est. Priority Date: 08/31/1995
• Status: Expired due to Fees

• Current Assignee: First Medical, Inc.
• Original Assignee: First Medical, Inc.
• Inventors: Karunaratne, Arjuna R., Gustafson, Eric K., Ensler, Lawrence M., Ellsworth, Stoughton L.
• Primary Examiner(s): Le, Long V.
• Assistant Examiner(s): GABEL, GAILENE
• Application Number:
  US08/522,434
• Time in Patent Office: 2,231 Days
• Field of Search: 422/58, 422/63, 422/64, 422/72, 422/102, 435/287.1, 435/287.2, 435/287.3, 435/288.4, 435/288.5, 435/7.21, 435/7.94, 436/45, 436/164, 436/172, 436/514, 436/518, 436/807, 436/809, 436/52, 436/526, 210/205, 210/222, 210/782, 210/789, 210/745, 210/514, 210/359, 210/380.1, 210/198.1, 210/94
• US Class Current: 422/63
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/111666 Utilizing a centrifuge or compartmented rotor
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream

Abstract

An analytical system comprises a frame and movable carriage. An analytical rotor is mounted on the carriage and can be translated among a sample dispensing station, a fluid dispensing station, and a label detection zone. In order to perform assays, the analyzer system requires only the introduction of the analytical rotor, sample, and a volume of diluent solution. Sample within the analyzer is contained at all times within either a sample receptacle or the rotor. The method allows for the sequential addition of sample and diluent in order to perform multiple assay steps and is particularly suitable for performing heterogeneous immunoassays. The use of fluorescent label in the system allows multiple analyte detection reactions to be performed from a single sample applied to a single rotor.

Claims

1. A system for performing assays employing a disposable sample receptacle and a disposable rotor, said system comprising:

a frame having longitudinal, transverse, and vertical axes;

a rotational drive unit for removably receiving and selectively rotating the rotor including a non-rotating rotor support having a plurality of fixed magnets therein for agitating magnetically responsive mixing elements to effect mixing in the rotor as the rotor is rotated;

a positioning assembly on the frame which translates the rotational drive unit along a predetermined linear path within the system;

a liquid reagent dispenser disposed along the predetermined path;

a sample dispensing unit disposed along the predetermined path, wherein the sample dispensing unit removably receives the sample receptacle and includes a drive mechanism for dispensing liquid sample from the sample receptacle to a rotor;

a signal detector disposed along the predetermined path of the rotational drive unit; and

a controller operatively connected to the rotational drive unit, the positioning assembly, the liquid reagent dispenser, the sample dispensing unit, and the detector, wherein the controller controls (a) the positioning assembly to translate the rotational drive unit among the liquid reagent dispenser, the sample dispensing unit, and the detector, (b) the rotational drive unit to rotate the rotor, (c) the liquid reagent dispenser to dispense liquid reagent to the rotor, (d) the sample dispensing unit to dispense sample to the rotor, and (e) the signal detector to detect signal produced in the rotor.

2. The system as in claim 1, wherein the linear path is oriented longitudinally.

3. The system as in claim 1, wherein the rotational drive unit includes a drive motor which can be controlled to operate at at least two rotational speeds and to selectively position a rotor at stationary rotational positions.

4. The system as in claim 3 wherein the motor is servo-controlled.

5. The system as in claim 1, wherein the rotational drive unit includes a magnetic chuck for receiving the rotor.

6. The system as in claim 1, wherein the positioning assembly can also translate the rotational drive unit along a vertical axis, whereby the drive unit can be positioned in a plane defined by the longitudinal and vertical axes.

7. The system as in claim 6, wherein the positioning assembly comprises longitudinal guide tracks on the frame, a carriage slidably mounted on the longitudinal tracks, a motor connected to the controller for positioning the carriage along the longitudinal guide, a disc rotation motor and spindle on the carriage for receiving a rotor, and a vertical positioning motor mounted on the carriage and connected to the disc rotation motor for positioning the motor and spindle along a vertical axis relative to the carriage.

8. The system as in claim 1, wherein the liquid reagent dispenser includes a dispensing probe, a syringe connected to the controller for aspirating and dispensing liquid reagent through the probe, and a receptacle on the frame for removably receiving a disposable reagent container.

9. The system as in claim 8, wherein the liquid reagent dispenser further includes a vertical guide on the frame and a motor connected to the controller for positioning the probe along said vertical guide.

10. A system for performing assays employing a disposable sample receptacle and a disposable rotor, said system comprising:

a frame having longitudinal, transverse, and vertical axes;

a rotational drive unit including a magnetic chuck for removably receiving and selectively rotating the rotor;

a positioning assembly on the frame which translates the rotational drive unit along a predetermined path within the system longitudinally;

a liquid reagent dispenser disposed along the predetermined path;

a sample dispensing unit disposed along the predetermined path, wherein the sample dispensing unit removably receives the sample receptacle and includes a drive mechanism for dispensing liquid sample from the sample receptacle to the rotor;

a single detector disposed along the predetermined path of the rotational drive unit; and

a controller operatively connected to the rotational drive unit, the positioning assembly, the liquid reagent dispenser, the sample dispensing unit, and the detector, wherein the controller controls (a) the positioning assembly to translate the rotational drive unit among the liquid reagent dispenser, the sample dispensing unit, and the detector, (b) the rotational drive unit to rotate the rotor, (c) the liquid reagent dispenser to dispense liquid reagent to the rotor, (d) the sample dispensing unit to dispense sample to the rotor, and (e) the signal detector to detect signal produced in the rotor.

11. The system as in claim 10, wherein the positioning assembly translates the rotational drive unit along a linear path on the frame.

12. The system as in claim 11 wherein the linear path is oriented longitudinally.

15. The system as in claim 10, wherein the rotational drive unit includes a non-rotating rotor support having a plurality of fixed magnets therein for interacting with magnetically responsive mixing elements in the rotor as the rotor is rotated.

16. The system as in claim 10, wherein the positioning assembly can also translate the rotational drive unit along a vertical axis, whereby the drive unit can be positioned in a plane defined by the longitudinal and vertical axes.

17. The system as in claim 16, wherein the positioning assembly comprises longitudinal guide tracks on the frame, a carriage slidably mounted on the longitudinal tracks, a motor connected to the controller for positioning the carriage along the longitudinal guide, a disc rotation motor and spindle on the carriage for receiving a rotor, and a vertical positioning motor mounted on the carriage and connected to the disc rotation motor for positioning the motor and spindle along a vertical axis relative to the carriage.

18. The system as in claim 10, wherein the liquid reagent dispenser includes a dispensing probe, a syringe connected to the controller for aspirating and dispensing liquid reagent through the probe, and a receptacle on the frame for removably receiving a disposable reagent container.

19. The system as in claim 18, wherein the liquid reagent dispenser further includes a vertical guide on the frame and a motor connected to the controller for positioning the probe along said vertical guide.

20. A system for performing assays employing a disposable sample receptacle and a disposable rotor, said system comprising:

a frame having longitudinal, transverse, and vertical axes;

a rotational drive unit having a magnetic chuck for removably receiving and selectively rotating the rotor;

a positioning assembly on the frame which translates the rotational drive unit along a predetermined path within the system longitudinally,

a liquid reagent dispenser disposed along the predetermined path;

a sample dispensing unit disposed along the predetermined path, wherein the sample dispensing unit removably receives the sample receptacle and includes a drive mechanism for dispensing liquid sample from the sample receptacle to a rotor;

a signal detector disposed along the predetermined path of the rotational drive unit; and

a controller operatively connected to the rotational drive unit, the positioning assembly, the liquid reagent dispenser, the sample dispensing unit, and the detector, wherein the controller controls (a) the positioning assembly to translate the rotational drive unit among the liquid reagent dispenser, the sample dispensing unit, and the detector, (b) the rotational drive unit to rotate the rotor, (c) the liquid reagent dispenser to dispense liquid reagent to the rotor, (d) the sample dispensing unit to dispense sample to the rotor, and (e) the signal detector to detect signal produced in the rotor.

13. The system as in claim 25, wherein the rotational drive unit includes a drive motor which can be controlled to operate at least two rotational speeds and to selectively position a rotor at stationary rotational positions.

14. The system as in claim 13, wherein the motor is servo-controlled.

21. The system as in claim 20, wherein the positioning assembly translates the rotational drive unit along a linear path.

22. The system as in claim 21, wherein the linear path is oriented longitudinally.

23. The system as in claim 20, wherein the motor is servo-controlled.

24. The system as in claim 20, wherein the rotational drive unit includes a non-rotating rotor support having a plurality of fixed magnets therein for interacting with magnetically responsive mixing elements in the rotor as the rotor is rotated.

25. The system as in claim 20, wherein the positioning assembly can also translate the rotational drive unit along a vertical axis, whereby the drive unit can be positioned in a plane defined by the longitudinal and vertical axes.

26. The system as in claim 25, wherein the positioning assembly comprises longitudinal guide tracks on the frame, a carriage slidably mounted on the longitudinal tracks, a motor connected to the controller for positioning the carriage along the longitudinal guide, a disc rotation motor and spindle on the carriage for receiving a rotor, and a vertical positioning motor mounted on the carriage and connected to the disc rotation motor for positioning the motor and spindle along a vertical axis relative to the carriage.

27. The system as in claim 20, wherein the liquid reagent dispenser includes a dispensing probe, a syringe connected to the controller for aspirating and dispensing liquid reagent through the probe, and a receptacle on the frame for removably receiving a disposable reagent container.

28. The system as in claim 27, wherein the liquid reagent dispenser further includes a vertical guide on the frame and a motor connected to the controller for positioning the probe along said vertical guide.

29. The system as in claim 20, wherein the sample dispensing unit includes:

a clamp structure for removably securing a flexible tube having an inlet end and an outlet end, which tube is part of the disposable sample receptacle; and

a peristaltic drive wheel which engages the flexible tube when the sample receptacle is secured in the clamp structure, wherein rotation of the drive wheel causes sample to flow from the inlet end to the outlet end of the flexible tube.

30. The system as in claim 29, wherein the sample dispensing unit further comprises a collar for supporting the inlet end of the flexible tube.

31. The system as in claim 20, wherein the sample dispensing unit further comprises one or more rods which extend transversely from the collar, wherein the clamp structure comprises first and second opposed clamping elements at least one of which is translatably mounted on the rods, and wherein the sample dispensing unit further comprises at least one motor for translating one or both of the clamp elements to selectively secure and release the flexible tube when in place in the collar.

32. The system as in claim 29, wherein the drive wheel is mounted on one of the clamping elements and the other clamping element has an arcuate surface which is aligned with the drive wheel, wherein the flexible tube is captured between the drive wheel and the arcuate surface.

33. The system as in claim 32, herein the drive wheel comprises a plurality of peripherally spaced-apart rollers.

34. The system as in claim 20, wherein the signal detector includes a light source and an emitted light detector, wherein the light source is positioned to focus light within the preselected fluorescent excitation wavelength band at a focal point and wherein the emitted light detector is positioned to receive emitted fluorescence from a reaction zone while said zone is positioned at the focal point and receiving focused excitation light.