System for nucleic acid based diagnostic assay

• US 5,578,270 A
• Filed: 03/24/1995
• Issued: 11/26/1996
• Est. Priority Date: 03/24/1995
• Status: Expired due to Fees

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Antol, David J., Hildebrand, Scott D., Lamos, Michael L., Bourdelle, Peter A., Reichler, Allen S.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/409,821
• Time in Patent Office: 613 Days
• Field of Search: 436/49, 436/54, 422/67, 422/68.1, 422/81, 422/100, 422/103
• US Class Current: 422/67
• 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 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/109 with two horizontal degrees of freedom
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure

Abstract

An automated system is provided for carrying out nucleic acid based assays on a plurality of liquid samples with little or no intervention by a human operator. The system includes at least one reaction station adapted to hold and apply controlled amounts of heat to a plurality of reaction devices in which the liquid samples are receivable. Each of the reaction devices includes a sample area for receiving a liquid sample, a reaction area into which the liquid sample is movable to carry out a nucleic acid decontamination or amplification reaction on the sample, and a pneumatic port for allowing air to be aspirated from and dispensed into the reaction device to move the sample between the sample area and the reaction area. A robotically controlled aspiration and dispensing head is adapted to move into contact with the pneumatic ports of the reaction devices, and to aspirate air from and dispense air into the pneumatic ports of the reaction devices in order to move the liquid samples between the sample and reaction areas of the reaction devices. A programmable control system is provided for causing the robotically controlled aspiration and dispensing head to move into contact with the pneumatic ports of the reaction devices, and to aspirate air from and dispense air into the reaction devices in order to cause the desired movement of the liquid samples within the reaction devices. The robotically controlled aspiration and dispensing head is also adapted to transfer the liquid samples to and from the reaction devices using disposable pipettes, and to introduce liquid reagents into the reacted samples after the samples have been transferred from the reaction devices to separate assay devices. A robotically controlled wash head is also provided to aspirate and dispense wash fluids and reagent fluids from the assay devices.

Claims

1. An automated system for carrying out reactions on a plurality of liquid samples, comprising:

a plurality of reaction devices in which said liquid samples are receivable, each of said reaction devices including a sample area for receiving a liquid sample, a reaction area separate from said sample area into which said liquid sample is movable from said sample area to carry out a reaction on said sample, and a pneumatic port for allowing air to be aspirated from and dispensed into said reaction device to move said liquid sample between said sample area and said reaction area;

a reaction station adapted to hold said plurality of reaction devices;

a robotically controlled aspiration and dispensing head adapted to move into contact with said pneumatic ports of said reaction devices, and to aspirate air from and dispense air into said pneumatic ports in order to move the liquid samples in said reaction devices between said sample areas and said reaction areas; and

a programmable control device for causing said robotically controlled aspiration and dispensing head to move into contact with said pneumatic ports of said reaction devices, and to withdraw air from and dispense air into said reaction devices in order to move said liquid samples between said sample areas and said reaction areas.

2. An automated system as claimed in claim 1, wherein said robotically controlled aspiration and dispensing head is adapted to be brought into contact with the pneumatic port of only one of said reaction devices at a time, and wherein said programmable control device causes said robotically controlled aspiration and dispensing head to move into contact with each of said reaction devices in sequence.

3. An automated system as claimed in claim 1, wherein said robotically controlled aspiration and dispensing head carries a detachable pipette for engaging the pneumatic ports of said reaction devices, and wherein said system further comprises a docking station for holding said detachable pipette when said pipette is not attached to said robotically controlled aspiration and dispensing head.

4. An automated system as claimed in claim 3, wherein said programmable control device causes said robotically controlled aspiration and dispensing head to pick up said detachable pipette from said docking station before moving into contact with the pneumatic ports of said reaction devices, and to return said detachable pipette to said docking station after withdrawing air from and dispensing air into said reaction devices.

5. An automated system as claimed in claim 4, wherein said docking station includes a bracket with which said detachable pipette is engageable by means of a generally horizontal motion of said robotically controlled aspiration and dispensing head, said pipette being detachable from said aspiration and dispensing head by means of a generally upward motion of said aspiration and dispensing head while said pipette is engaged with said bracket.

6. An automated system as claimed in claim 1, wherein said programmable control device causes said robotically controlled aspiration and dispensing head to move said liquid samples from said sample areas to said reaction areas, to allow said liquid samples to remain in said reaction areas for predetermined intervals, and to return said liquid samples to said sample areas after said predetermined intervals have elapsed.

7. An automated system as claimed in claim 6, wherein said predetermined intervals are equal for all of said reaction devices.

8. An automated system as claimed in claim 1, further comprising:

a disposable pipette tip station adapted to hold a plurality of disposable pipette tips which are individually attachable to said robotically controlled aspiration and dispensing head; and

a sample receptacle station adapted to hold a plurality of sample receptacles in which said liquid samples are initially provided;

wherein said programmable control device causes said robotically controlled aspiration and dispensing head to pick up disposable pipette tips from said disposable pipette tip station, to move to said sample receptacle station and aspirate liquid samples into said disposable pipette tips from said sample receptacles, and to move to said reaction station and dispense said liquid samples into said reaction devices.

9. An automated system as claimed in claim 8, wherein said robotically controlled aspiration and dispensing head is adapted to pick up only one of said disposable pipette tips at a time, and wherein said programmable control device causes said robotically controlled aspiration and dispensing head to move to said disposable pipette tip station and to pick up a new disposable pipette tip before aspirating a liquid sample from each of said sample receptacles.

10. An automated system as claimed in claim 1, further comprising:

a disposable pipette tip station adapted to hold a plurality of disposable pipette tips which are individually attachable to said robotically controlled aspiration and dispensing head; and

a reagent station adapted to hold a plurality of reagent containers which contain liquid reagents to be added to said liquid samples;

wherein said programmable control device causes said robotically controlled aspiration and dispensing head to pick up disposable pipette tips from said disposable pipette tip station, to move to said reagent station and aspirate liquid reagents into said disposable pipette tips from said reagent containers, and to move to said reaction station and dispense said liquid reagents into said liquid samples.

11. An automated system as claimed in claim 10, wherein said robotically controlled aspiration and dispensing head is adapted to pick up only one of said disposable pipette tips at a time, and wherein said programmable control device causes said robotically controlled aspiration and dispensing head to move to said disposable pipette tip station and pick up a new disposable pipette tip before aspirating a liquid reagent from each of said reagent containers.

12. An automated system as claimed in claim 10, wherein said reaction station is adapted to hold a plurality of assay devices to which said liquid samples are transferred after reactions are carried out on said samples in said reaction devices, and wherein the dispensing of said liquid reagents into said liquid samples is carried out by dispensing said reagents into said assay devices.

13. An automated system as claimed in claim 12, wherein prior to aspiration and dispensing of said liquid reagents into said assay device, said programmable control device causes said robotically controlled aspiration and dispensing head to pick up disposable pipette tips from said disposable pipette tip station, to move to said reaction station and aspirate reacted liquid samples from said reaction devices, and to dispense said reacted liquid samples into said assay devices.

14. An automated system as claimed in claim 13, wherein said robotically controlled aspiration and dispensing head is adapted to pick up only one of said disposable pipette tips at a time, and wherein said programmable control device causes said robotically controlled aspiration and dispensing head to move to said disposable pipette tip station and pick up a new disposable pipette tip before aspirating a reacted liquid sample from each of said reaction devices.

15. An automated system as claimed in claim 12, wherein each of said assay devices includes a plurality of separate portions, each of said portions being adapted to receive part of the same liquid sample, and wherein the dispensing of said reagents into each of said assay devices is carried out by dispensing a different one of said reagents into each portion of said assay device.

16. An automated system as claimed in claim 12, further comprising a robotically controlled wash head adapted to dispense a wash fluid into said assay devices and to aspirate fluids from said assay devices, said robotically controlled wash head being controlled by said programmable control device.

17. An automated system as claimed in claim 16, wherein each of said assay devices includes a plurality of separate portions, each of said portions being adapted to receive part of the same liquid sample, and wherein said robotically controlled wash head includes separate aspiration/dispensing nozzles for washing all of said portions simultaneously.

18. An automated system as claimed in claim 12, wherein each of said assay devices is held adjacent to a corresponding one of said reaction devices at said reaction station, with the number of assay devices and reaction devices being equal.

19. An automated system as claimed in claim 18, wherein said assay devices and said reaction devices are carried by a tray which is removable from said automated system.

20. An automated system as claimed in claim 1, wherein said reaction station includes a heating platen for heating said plurality of reaction devices.

21. An automated system as claimed in claim 1, wherein said reaction station is one of a plurality of reaction stations in said automated system, and wherein said programmable control device causes said robotically controlled aspiration and dispensing head to carry out substantially the same functions at each of said reaction stations.