Apparatus for a fluid impingement thermal cycler

• US 5,942,432 A
• Filed: 10/07/1997
• Issued: 08/24/1999
• Est. Priority Date: 10/07/1997
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Perkinelmer Incorporated
• Inventors: Smith, Douglas H., Woudenberg, Timothy M., Shigeura, John
• Primary Examiner(s): Redding, David A.
• Application Number:
  US08/946,512
• Time in Patent Office: 686 Days
• Field of Search: 422/129, 422/131, 422/134, 422/138, 435/285.1, 435/287.2, 435/288.4, 435/303.1, 263/2, 165/58, 165/61, 935/77, 935/88
• US Class Current: 435/303.1
• 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

Abstract

Apparatus are disclosed that thermally cycles samples between at least two temperatures. These apparatus operate by impinging fluid jets onto the outer walls of a sample containing region. Because the impinging fluid jets provide a high heat transfer coefficient between the jet and the sample containing region, the sample containing regions are uniformly cycled between the two temperatures. The heat exchange rate between the jets and the sample regions are substantially uniform.

Claims

1. An apparatus for thermally cycling a plurality of samples between at least two temperatures where each of said samples is held in one of a plurality of sample regions in an array, where each of said sample regions defines an outer heat-exchange wall expanse, said apparatus comprising:

a source for providing a pressurized fluid at a selected first and second temperatures; and

a chamber containing;

(a) a structure adapted for supporting said array;

(b) a manifold for receiving said pressurized fluid and distributing same in the form of a plurality of fluid jets directed against said wall expanses, and substantially normal thereto, when said array is held by said structure, to produce substantially uniform heat exchange between said fluid jets and said samples; and

(c) an outlet for venting said fluid from said fluid jets out of said chamber.

2. The apparatus of claim 1 for use with a microtiter plate, comprising said array, wherein said sample regions are composed of a plurality of wells each having a bottom surface defining said wall expanse wherein said fluid jets impinge on said bottom surface when said plate is held by said structure.

3. The apparatus of claim 1 for use with a plurality of tubes, comprising said array, each of said tubes having an elongated sample-holding portion defining said wall expanse and said manifold having a plurality of pockets each adapted to enclose said wall expanse of one of said tubes;

each of said pockets distributing said fluid jets onto said wall expanse, said pockets open at the top to allow said fluid from said fluid jets to exit said pockets; and

said structure comprising a plate adapted to support said tubes descending into said pockets.

4. The apparatus of claim 1, wherein said samples are polynucleotides and said apparatus is used for thermal cycling a polymerase chain reaction.

5. The apparatus of claim 1 further comprising fluid recycling means operativily connecting said outlet to said source for recycling said fluid there between.

6. The apparatus of claim 5 further comprising a sterile filter to filter said fluid.

7. The apparatus of claim 1, wherein said structure is adapted to form a fluid-tight seal between the structure and the array.

8. The apparatus of claim 1, wherein said pressurized fluid is a liquid.

9. The apparatus of claim 1, wherein said pressurized fluid is a gas.

10. An apparatus for thermally cycling a plurality of samples between at least two temperatures comprising:

a source for providing a pressurized fluid at a selected first and second temperatures; and

a chamber containing;

(a) an array of a plurality of sample regions where each of said samples is adapted to be held in one of said sample regions and each of said sample regions defines an outer heat-exchange wall expanse;

(b) a structure supporting said array;

(c) a manifold for receiving said pressurized fluid and distributing same in the form of a plurality of fluid jets directed against said wall expanses and substantially normal thereto, to produce substantially uniform heat exchange between said fluid jets and said samples; and

(d) an outlet for venting said fluid from said fluid jets out of said chamber.

11. The apparatus of claim 10 wherein said array is contained in a microtiter plate wherein said sample regions are composed of a plurality of wells, each having a bottom surface defining said wall expanse wherein said fluid jets impinge on said bottom surface.

12. The apparatus of claim 10 wherein said array is formed by a plurality of tubes, each of said tubes having an elongated sample-holding portion defining said wall expanse and said manifold having a plurality of pockets each adapted to enclose said wall expanse of one of said tubes;

each of said pockets distributing said fluid jets onto said wall expanse, said pockets open at the top to allow said fluid from said fluid jets to exit said pockets; and

said structure comprising a plate to support said tubes descending into said pockets.

13. The apparatus of claim 10 wherein said samples are polynucleotides and said apparatus is used for thermal cycling a polymerase chain reaction.

14. The apparatus of claim 10 further comprising fluid recycling means operativily connecting said outlet to said source for recycling said fluid there between.

15. The apparatus of claim 14 further comprising a sterile filter to filter said fluid.

16. The apparatus of claim 10, wherein said structure is adapted to form a fluid-tight seal between the structure and the array.

17. The apparatus of claim 10, wherein said pressurized fluid is a liquid.

18. The apparatus of claim 10, wherein said pressurized fluid is a gas.