Thermal cycling apparatus and method for providing thermal uniformity

• US 8,859,271 B2
• Filed: 02/16/2011
• Issued: 10/14/2014
• Est. Priority Date: 05/30/2003
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Shin, Hon Siu, Ngui, Jew Kwee, Lim, Chee Kiong, Lau, Ching Ong, Tan, Lim Hi, Kee, Yang Hooi
• Primary Examiner(s): BOWERS, NATHAN ANDREW
• Application Number:
  US13/029,085
• Publication Number:
  US 20110136219A1
• Time in Patent Office: 1,336 Days
• Field of Search: 435/303.1, 435/305.1, 435/287.2, 435/288.3, 435/6.12, 136/203, 136/205, 219/386, 219/521
• US Class Current: 435/303.1
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• 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

An apparatus and method for rapid thermal cycling including a thermal diffusivity plate. The thermal diffusivity plate can provide substantial temperature uniformity throughout the thermal block assembly during thermal cycling by a thermoelectric module. An edge heater can provide substantial temperature uniformity throughout the thermal block assembly during thermal cycling.

Claims

1. An apparatus for thermally cycling biological samples comprising:

a thermal block assembly for receiving said biological samples;

a thermoelectric module coupled to said thermal block assembly;

a frame comprising a printed circuit board material positioned around the thermoelectric module and configured to align the thermoelectric module with the thermal block assembly;

a heat sink, wherein said heat sink is coupled to said thermoelectric module with a thermal interface medium, wherein said heat sink comprises a base plate and fins;

a rigid thermal diffusivity plate, wherein said rigid thermal diffusivity plate (a) comprises a different material than said base plate and fins, (b) is positioned between the thermoelectric module and heat sink and contacts the thermoelectric module and the heat sink and (c) is configured to provide temperature uniformity to said thermal block assembly during thermal cycling.

2. The apparatus of claim 1, wherein said thermal diffusivity plate is positioned to couple to said thermoelectric module with the thermal interface medium.

3. The apparatus of claim 1, wherein said thermal block assembly comprises at least one of silver, gold, aluminum, silicon carbide, and magnesium.

4. The apparatus of claim 1, wherein said base plate and fins comprise aluminum.

5. The apparatus of claim 1, wherein said thermoelectric module comprises a thermoelectric gap, wherein said thermoelectric gap provides additional temperature uniformity throughout said thermal block assembly.

6. The apparatus of claim 5, wherein said thermoelectric gap is less than 5 millimeters.

7. The apparatus of claim 1, further comprising an edge heater, wherein said edge heater is coupled to the perimeter of said thermal block assembly.

8. The apparatus of claim 1, wherein said apparatus provides a PCR cycle time of less than thirty seconds.

9. The apparatus of claim 1, wherein said thermoelectric module comprises at least two power regions.

10. The apparatus of claim 1, further comprising a seal positioned on top of said thermal block assembly.

11. The apparatus of claim 1, wherein the thermal interface medium is thermal grease.

12. An apparatus of claim 1, wherein said thermal diffusivity plate is positioned within said base plate.

13. An apparatus of claim 1, wherein said thermoelectric module'"'"'s horizontal surface area overlaps said thermal diffusivity plate'"'"'s horizontal surface area.

14. An apparatus of claim 13, wherein said thermoelectric module'"'"'s horizontal surface area is larger than said thermal diffusivity plate'"'"'s horizontal surface area.

15. An apparatus of claim 13, wherein said thermal diffusivity plate'"'"'s horizontal surface area is larger than said thermoelectric module'"'"'s horizontal surface area.

16. The apparatus of claim 1, wherein the diffusivity plate comprises at least one of copper, silver, gold and silicon carbide.

17. The apparatus of claim 16, wherein the diffusivity plate is copper.

18. The apparatus of claim 3, wherein the copper is 99.9% EDM copper.

19. The apparatus of claim 1, wherein said diffusivity plate is about 8 mm thick.

20. The apparatus of claim 1, wherein the diffusivity plate has a thermal capacity greater than silver, gold or magnesium.

21. An apparatus for thermally cycling biological samples comprising:

a thermal block assembly for receiving said biological samples;

a thermoelectric module capable of heating and cooling, wherein the thermoelectric module is coupled to said thermal block assembly;

a printed circuit board positioned around the thermoelectric module and configured to align the thermoelectric module with the thermal block assembly;

a heat sink;

a frame positioned around the thermoelectric module; and

a rigid thermal diffusivity plate comprising copper coupled to said thermoelectric module with a thermal interface medium and coupled to said heat sink, wherein said rigid thermal diffusivity plate is positioned between said thermoelectric module and said heat sink, has at least 25% greater thermal diffusivity than said heat sink and is configured to provide temperature uniformity to said thermal block assembly during thermal cycling.

22. The apparatus of claim 21, wherein the temperature uniformity provides cooling of at least 10°

C. in at most ten seconds for said thermal block assembly.

23. The apparatus of claim 21, wherein said thermal block assembly comprises silver and gold.

24. The apparatus of claim 21, wherein said thermoelectric module comprises a thermoelectric gap, wherein said thermoelectric gap provides additional temperature uniformity throughout said thermal block assembly.

25. The apparatus of claim 24, wherein said thermoelectric gap is less than 5 millimeters.

26. The apparatus of claim 21, further comprising an edge heater, wherein said edge heater is coupled to the perimeter of said thermal block assembly.

27. An apparatus of claim 21, wherein said thermal interface medium is thermal grease.

28. An apparatus of claim 21, wherein said thermoelectric module'"'"'s horizontal surface area overlaps said thermal diffusivity plate'"'"'s horizontal surface area.

29. An apparatus of claim 28, wherein said thermoelectric module'"'"'s horizontal surface area is larger than said thermal diffusivity plate'"'"'s horizontal surface area.

30. An apparatus of claim 28, wherein said thermal diffusivity plate'"'"'s horizontal surface area is larger than said thermoelectric module'"'"'s horizontal surface area.

31. An apparatus of claim 21, wherein said thermal diffusivity plate is positioned within a base plate of said heat sink.

32. An apparatus for thermally cycling biological samples comprising:

a thermal block assembly for receiving biological samples;

a thermoelectric module in direct contact with a printed circuit board and coupled to said thermal block assembly;

a frame positioned around the thermoelectric module and configured to align the thermoelectric module with the thermal block assembly;

a heat sink, wherein said heat sink is coupled to said thermoelectric module with a thermal interface medium, wherein said heat sink comprises a baseplate and fins, is structured and arranged to provide a heat sink uniformity to the block assembly;

a rigid thermal diffusivity plate, wherein said rigid thermal diffusivity plate comprises a different material from the baseplate and fins, is positioned between the thermoelectric module and heat sink, structured and arranged to provide temperature uniformity to said thermal block assembly during thermal cycling, and wherein the rigid thermal diffusivity plate has a thickness less than the baseplate; and

wherein the uniformity provided by the diffusivity plate is greater than the heat sink thermal uniformity at an at least one specified point during a thermal cycle.

33. The apparatus of claim 32, whereby the at least one specified point in the thermal cycle is an at least one specified region during the thermal cycle.

34. The apparatus of claim 33, wherein the at least one specified region is a setpoint region of the thermal cycle.

35. The apparatus of claim 34, wherein the setpoint region is a steady state region of the thermal cycle.