Side-wall heater for thermocycler device

• US 20030106682A1
• Filed: 10/01/2002
• Published: 06/12/2003
• Est. Priority Date: 10/02/2001
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Stratagene California
• Inventors: Brown, Larry, Taylor, Roger, Reid, Taylor
• Granted Patent: US 7,459,302 B2
• Time in Patent Office: Days
• US Class Current: 165/206
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0858 Side walls
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• 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: Y10S 435/809 Incubators or racks or holders for culture plates or containers

Abstract

The invention relates to an apparatus and methods for preventing condensation on the interior surfaces of sample tubes which are being exposed to temperature cycles, such as during a PCR amplification reaction. In particular, the invention relates to apparatus comprising a sample block comprising a plurality of sample wells for receiving sample tubes and heating elements disposed in the sample wells for heating at least a portion of the sides of sample tubes (e.g., at least the portion which forms the head space after a tube is filled with a PCR reaction mixture). In a preferred aspect, the sample block is part of a thermocycling device for performing PCR and the side-wall heater is used to enhance uniformity and speed of amplification reactions. For example, by decreasing or eliminating condensation, signal strength jumps in a real-time PCR assay can be minimized as can reaction non-homogeneity.

Claims

1. An apparatus for heating an upper portion of the interior surface of a sample tube, said upper portion extending from the top of the tube to a point above a lower portion of the tube which is filled with a fluid, said apparatus comprising:

a) a side-wall heating block comprising a heat-conducting material, said heat-conducting material comprising at least one sample hole for receiving the sample tube;

wherein said sample hole runs from an upper surface of the block through a lower surface of said block, said sample hole alignable with a sample well of a sample block for a thermocycler apparatus, wherein the height of said side-wall heating block is substantially the same as the longitudinal length of the upper portion of the sample tube; and

(b) a heating element disposed on or in said side-wall heating block, said heating element connectable to a power supply for activating said heating element to thereby provide heat to the heat-conducting material.

2. The apparatus according to claim 1, wherein the heating block further comprises a

(c) a temperature sensor for detecting the temperature of the block, said temperature sensor connectable to a processor for monitoring the temperature of the block, said processor connectable to said power supply and for providing instructions to said power supply to activate said heating element to maintain the temperature of the block to a level which is the same or higher than the temperature of the fluid in said lower portion of said tube for a selected period of time.

3. The apparatus according to claim 1, wherein said side-wall heating block comprises a plurality of sample holes for receiving a plurality of sample tubes.

4. The apparatus according to claim 1, wherein at least one sample hole is conformed to fit a sample tube for use in a PCR reaction.

5. The apparatus according to claim 4, wherein said sample tube can receive up to 0.2 ml of a fluid.

6. The apparatus according to claim 4, wherein said sample tube can receive up to 0.6 ml of a fluid.

7. The apparatus according to claim 4, wherein said sample tube can receive up to 1.5 ml of a fluid.

8. The apparatus according to claim 4, wherein said sample tube is connected to a plurality of other sample tubes, each other sample tube received by a sample hole in the side-wall heating block, and wherein the top of each tube extends from the portion of the tube which rests at the top of the sample hole.

9. The apparatus according to claim 1, wherein said block comprises 24 sample holes.

10. The apparatus according to claim 1, wherein said block comprises 32 sample holes.

11. The apparatus according to claim 1, wherein said block comprises 48 sample holes.

12. The apparatus according to claim 1, wherein said block comprises 96 sample holes.

13. The apparatus according to claim 1, wherein said block comprises 384 sample holes.

14. The apparatus according to claim 1, wherein said sample holes are arrayed in 8 rows.

15. The apparatus according to claim 13, wherein said sample holes are arrayed in three, four, six, or twelve columns.

16. The apparatus according to claim 1, wherein said heating element is a resistive heating element.

17. An assembly comprising the apparatus of claim 1 and a sample block for a thermocycler said sample block comprising at least one sample well, wherein any sample holes in said side-wall heating block are aligned with openings of any sample wells in said sample block.

18. The assembly according to claim 17, wherein said sample block for said thermocycler comprises a heating element and said heating element in said side-wall heating block is controllable independently of said heating element in said sample block.

19. The assembly according to claim 17, wherein said sample block further comprises a cooling element.

20. The assembly according to claim 17, wherein said at least one sample well in said sample block is beveled to receive a conical portion of a sample tube.

21. The assembly according to claim 20, wherein said sample hole of said side-wall heating block is conformed to receive a cyclindrical portion of a sample tube comprising a cyclindrical upper portion and a conical lower portion.

22. A thermocycler device comprising the assembly according to claim 17.

23. The thermocycler device according to claim 22, wherein said device further comprises a hot top assembly for heating the external surface of the top of said at least one sample tube placed in a sample hole in said side-wall heating block

24. The thermocycler device according to claim 22, wherein said device is connectable to a detector for detecting optical signals from said at least one sample tube disposed in said assembly.

25. The thermocycler device according to claim 24, wherein said detector enables detection of a signal generated during an amplification reaction.

26. A method for heating the upper portion of a sample tube above a portion of the tube which is filled with a fluid, said method comprising:

a) placing said sample tube in a sample hole of the apparatus of claim 1, said portion of said tube comprising said fluid protruding past said lower surface of said side-wall heating block;

b) activating said heating element, to heat said upper portion of said sample tube.

27. The method according to claim 26, wherein said side-wall heating block is heated to a temperature which is the same or above the temperature of said portion of said tube comprising said fluid.

28. The method according to claim 26, wherein heating of said side-wall heating block prevents condensation on interior walls of said sample tube.

29. The method according to claim 26, wherein said portion of said tube comprising said fluid is within a sample well of a sample block said sample block comprising a heating element which controlled independently of said heating element in said side-wall heating block.

30. The method according to claim 26, wherein said sample block cycles said portion of said tube comprising said fluid through a least one change of temperature.

31. The method according to claim 30, wherein said sample block cycles said portion of said tube comprising said fluid through cycles of a PCR reaction.

32. The method according to claim 29 or 30, wherein heating element maintains said side-wall heating block at a temperature which is the same or above the temperature of the sample block for a selected period of time.

33. The method according to claim 31, wherein said heating element maintains said side-wall heating block at a temperature which is above the highest temperature through which the sample block is cycling.

34. The method according to claim 32, wherein said highest temperature is greater than 90°

C.

35. The method according to claim 33, wherein said highest temperature is 94°

C.

36. The method according to claim 32, wherein said side-wall heating block maintains a uniform temperature while said sample block is cycling through changes of temperature.