Thermal cycler for PCR

• US 7,645,070 B2
• Filed: 05/17/2007
• Issued: 01/12/2010
• Est. Priority Date: 03/28/1997
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Fawcett, Adrian, Atwood, John G., Hetherington, Paul M., Wittmer, Charles M., Widomski, John R., Olsen, Douglas E., Ferrara, Keith S., Noreiks, Richard W.
• Primary Examiner(s): KAPLAN VERBITSKY, GAIL
• Application Number:
  US11/804,298
• Publication Number:
  US 20070230535A1
• Time in Patent Office: 971 Days
• Field of Search: 374 10- 12, 374 29- 36, 374/141, 374/137, 374/44, 374 4- 5, 374/1, 374/13, 374100-102, 374/112, 374/142, 702/130, 702/133, 702/136, 702/99, 422/99, 422/63, 422/67, 435/287.1
• US Class Current: 374/137
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/50853 with covers or lids
• 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 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: F25B 21/04 reversible
• CPC Class Codes: F25B 2321/021 Control thereof
• CPC Class Codes: G01R 27/205 Measuring contact resistance of connections, e.g. of earth connections
• CPC Class Codes: G05D 23/1919 characterised by the type of controller
• CPC Class Codes: H10N 10/13 characterised by the heat-exchanging means at the junction
• CPC Class Codes: Y10T 137/1516 Thermo-electric

Abstract

An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.

Claims

1. A system comprising:

a polymerase chain reaction detection instrument;

an assembly electrically connected to the polymerase chain reaction detection instrument and adapted to be removed from the polymerase chain reaction detection instrument, the assembly comprising a sample block, thermoelectric devices, and a heat sink;

a clamping mechanism that clamps together the sample block, the thermoelectric devices, and the heat sink to form a clamped assembly, wherein the clamped assembly is adapted to be removed from the polymerase chain reaction detection instrument and connected to a different polymerase chain reaction detection instrument;

a power source configured to supply power to the thermoelectric devices and ramp the assembly through a series of known temperature profiles configured to effect a polymerase chain reaction;

a temperature sensor in thermal communication with the assembly and configured to measure an actual temperature profile of the assembly;

a programmed device for receiving a measurement signal from the temperature sensor, the programmed device being programmed to carry out a characterization process whereby a comparison is made between the actual measured temperature profiles and the series of known temperature profiles, the programmed device being programmed to adjust the power supplied to the thermoelectric devices until the actual measured temperature profiles match the series of known temperature profiles; and

a memory device configured to store thermal characteristics obtained by the characterization process, the memory device being configured to operatively interface with the different polymerase chain reaction detection instrument such that the stored thermal characteristics adjust power supplied to the thermoelectric devices to control a temperature profile of the different polymerase chain reaction detection instrument.

2. The system of claim 1, wherein the temperature sensor is attached to the sample block.

3. The system of claim 1, wherein the thermoelectric devices comprise at least one Peltier thermoelectric device.

4. The system of claim 1, wherein the temperature sensor is present in the heat sink.

5. The system of claim 1, wherein the power source comprises a bi-polar amplifier.

6. The system of claim 1, wherein the power source comprises a class D switch-mode amplifier.

7. The system of claim 1, wherein the assembly further comprises a sample located within the sample block and the programmed device is programmed to thermally cycle the sample between temperatures within the range of from 35°

C. to 96°

C.

8. The system of claim 1, wherein the memory device comprises an on-board memory device residing on the removable assembly.

9. The system of claim 1, further comprising the different polymerase chain reaction detection instrument.

10. The system of claim 1, wherein the clamped assembly is adapted to be removed in clamped form from the polymerase chain reaction detection instrument and connected to a different polymerase chain reaction detection instrument.

11. A method comprising:

providing a removable assembly in a polymerase chain reaction detection instrument, the removable assembly comprising a sample block, thermoelectric devices, and a heat sink;

clamping together the sample block, the thermoelectric devices, and the heat sink to form a clamped assembly, wherein the clamped assembly is adapted to be removed from the polymerase chain reaction detection instrument and connected to a different polymerase chain reaction detection instrument;

applying power to the thermoelectric devices to ramp the assembly through a series of known temperature profiles configured to effect a polymerase chain reaction;

measuring the actual temperature profiles of the removable assembly during the ramping;

comparing the actual temperature profiles with the known temperature profiles;

adjusting the power applied to the thermoelectric devices so that the actual temperature profiles match the known temperature profiles;

generating thermal characteristics related to the removable assembly;

storing the thermal characteristics in a memory device, the memory device being configured to operatively interface with the different polymerase chain reaction detection instrument such that the stored thermal characteristics adjust power supplied to the thermoelectric devices to control a temperature profile of the different polymerase chain reaction detection instrument; and

removing the removable assembly from the polymerase chain reaction detection instrument after storing the thermal characteristics.

12. The method of claim 11, wherein the thermoelectric devices comprise at least one Peltier thermoelectric device.

13. The method of claim 11, wherein the adjusting comprises repeating the steps of applying, measuring, comparing, and adjusting.

14. The method of claim 11, wherein the measuring comprises measuring with a temperature sensor present in the heat sink.

15. The method of claim 11, wherein the applying power comprises applying power with a bi-polar amplifier.

16. The method of claim 11, wherein the applying power comprises applying power with a class D switch-mode amplifier.

17. The method of claim 11, further comprising electrically connecting the removable assembly to the different polymerase chain reaction detection instrument.

18. The method of claim 11, wherein the storing comprises storing the thermal characteristics in an on-board memory device residing on the removable assembly.

19. The method of claim 11, wherein the assembly further comprises a sample located within the sample block and the method further comprises thermally cycling the sample between temperatures within the range of from 35°

C. to 96°

C.

20. The method of claim 11, wherein the removing comprises removing the removable assembly in clamped form from the polymerase chain reaction detection instrument after storing the thermal characteristics.