Low volume chemical and biochemical reaction system

• US 20020110900A1
• Filed: 04/18/2002
• Published: 08/15/2002
• Est. Priority Date: 08/02/1999
• Status: Abandoned Application

• Current Assignee: Amersham Biosciences (General Electric Company)
• Original Assignee: Amersham Biosciences (General Electric Company)
• Inventors: Jovanovich, Stevan B., Roach, David J.
• Application Number:
  US10/125,045
• Publication Number:
  US 20020110900A1
• Time in Patent Office: Days
• US Class Current: 435/286.4
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2527/125 Specific component of sample, medium or buffer
• CPC Class Codes: C12Q 2535/101 Sanger sequencing method, i.e. oligonucleotide sequencing using primer elongation and dideoxynucleotides as chain terminators
• CPC Class Codes: C12Q 2565/518 characterised by the immobilisation of the nucleic acid sample or target
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• 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 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method and device for preparing nanoscale reactions. An automated system utilizes an array of reaction chambers. The ends of the chambers are temporarily sealed with deformable membranes and reactions effected by incubation of temperature cycling. Reaction mixtures may be assembled by using the reaction containers to meter reaction components. After the reaction is finished, the reaction containers may be dispensed onto a substrate and the reaction products analyzed. An automated transfer device may be used for automated transport of the reaction container array or other transportable elements.

Claims

1. A device for dispensing small quantities of liquid, the device comprising:

a capillary cassette, comprised of a plurality of capillary tube sections disposed in an array through a substrate; and

a capillary cassette dispensing means, said dispensing means receiving said capillary cassette and dispensing an array of capillaries of said capillary cassette to an array of locations.

2. The device of claim 1, wherein said dispensing means is a pressure driven dispenser.

3. The device of claim 2, wherein said pressure driven dispenser includes an enclosed area, wherein one end of said capillary tube sections in said capillary cassette may be sealed in said enclosed area, and wherein the enclosed area enclosing one end of capillaries in said capillary cassette may be pressurized.

4. The device of claim 2, wherein said pressure driven dispenser includes a centrifuge.

5. The device of claim 1, wherein said capillary cassette is an array of 96 capillaries.

6. The device of claim 1, further including a wash station and a means for transferring said capillary cassette between said dispensing means and said wash station.

7. The device of claim 6, wherein said means for transferring said capillary cassette is an automated transfer device.

8. The device of claim 7, wherein said automated transfer device is a robotic arm.

9. The device of claim 6, wherein said wash station includes a housing for receiving a capillary cassette and a liquid introduction and removal system that pumps liquid through said capillary tube sections and evacuates said liquid from said capillary tube sections.

10. The device of claim 1, wherein each capillary tube section of said capillary cassette has an interior volume of less than one microliter.

11. A device for transfer of an amount of liquid from a plurality of locations in a highly parallel manner, the device comprising:

a capillary cassette comprised of a substrate and a two dimensional array of capillary tube sections extending through said substrate, each of said capillary tube sections having a first and a second opposing open ends, said first open ends being coplanar and said second open ends being coplanar;

a capillary cassette dispenser; and

an automated capillary cassette transfer device, wherein said capillary cassette transfer device may move said capillary cassette between said a filling location and said capillary cassette dispenser.

12. The system of claim 11, wherein said substrate is bendable.

13. The system of claim 11, wherein said substrate is curved.

14. The device of claim 11, wherein said capillary cassette dispenser employs a pressure differential to dispense said capillary tube sections in said capillary cassette.

15. The device of claim 12, wherein said dispenser is a centrifuge dispenser.

16. The device of claim 12, wherein said dispenser includes an enclosed area, wherein one end of said capillary tube sections in said capillary cassette may be sealed in said enclosed area, and wherein the enclosed area enclosing one end of capillaries in said capillary cassette may be pressurized.

17. The device of claim 11, wherein said capillary cassette is comprised of a 8 by 12 array of capillary tube sections of equal length extending through a substrate.

18. The device of claim 11, further including a wash station, wherein said automated capillary cassette transfer device is disposed to transfer said capillary cassette between the capillary cassette dispenser and said wash station.

19. The device of claim 16, wherein said wash station has an enclosure that receives said capillary cassette and a fluid distribution manifold for introducing fluid through capillary tube sections of said capillary cassette.

20. The device of claim 11, wherein each capillary tube section in said capillary cassette has an interior volume of less than one microliter.

22. The method of claim 19, further including a step of washing capillary tube sections of said capillary cassette.

23. The method of claim 20, wherein all steps are repeated a plurality of times.

24. The method of claim 19, wherein said filling occurs by capillary action without mechanical force.

25. The method of claim 19, wherein said dispensing is effected by establishing a pressure differential.

26. The method of claim 23, wherein said dispensing is effected by centrifugal force.

27. The method of claim 19, wherein moving said capillary cassette is effected by gripping said capillary cassette by an automated transfer device and moving said capillary cassette to a programmed location.

28. The method of claim 19, where the step of filling said array of capillary tube sections includes filling said capillary tube sections with a volume of fluid less than one microliter.

29. The method of claim 19, wherein all steps are controlled by a central electronic control.

21. A method to dispense small quantities of fluid in a highly parallel manner, comprising:

filling an array of capillary tube sections in a capillary cassette with fluid at a filling location, moving said capillary cassette to a dispensing location; and

simultaneous dispensing said capillary tube sections at said dispensing location.

30. A device for transfer of an amount of liquid from a plurality of locations in a highly parallel manner, the device comprising:

a capillary cassette comprised of a substrate and a linear array of capillary tube sections extending through said substrate, each of said capillary tube sections having a first and a second opposing open ends, said first open ends being coplanar and said second open ends being coplanar;

a capillary cassette dispenser; and

an automated capillary cassette transfer device, wherein said capillary cassette transfer device may move said capillary cassette between said a filling location and said capillary cassette dispenser.

31. The system of claim 30, wherein said substrate is bendable.

32. The system of claim 30, wherein said substrate is curved.

33. The device of claim 30, wherein said capillary cassette dispenser employs a pressure differential to dispense said capillary tube sections in said capillary cassette.

34. The device of claim 33, wherein said dispenser is a centrifuge dispenser.

35. The device of claim 33, wherein said dispenser includes an enclosed area, wherein one end of said capillary tube sections in said capillary cassette may be sealed in said enclosed area, and wherein the enclosed area enclosing one end of capillaries in said capillary cassette may be pressurized.

36. The device of claim 30, further including a wash station, wherein said automated capillary cassette transfer device is disposed to transfer said capillary cassette between the capillary cassette dispenser and said wash station.

37. The device of claim 36, wherein said wash station has an enclosure that receives said capillary cassette and a fluid distribution manifold for introducing fluid through capillary tube sections of said capillary cassette.

38. The device of claim 30, wherein each capillary tube section in said capillary cassette has an interior volume of less than one microliter.