Thermal cycler for PCR

• US 20070230535A1
• Filed: 05/17/2007
• Published: 10/04/2007
• Est. Priority Date: 03/28/1997
• Status: Active Grant

• Current Assignee: Applied Biosystems, Inc. (Thermo Fisher Scientific Incorporated), Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Fawcett, Adrian, Ferrara, Keith, Atwood, John, Noreiks, Richard, Hetherington, Paul, Olsen, Douglas, Wittmer, Charles, Widomski, John
• Granted Patent: US 7,645,070 B2
• Time in Patent Office: Days
• US Class Current: 374/1
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 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 for calibrating an assembly, the assembly comprising a sample block, thermoelectric devices, and a heat sink, all clamped together, the system comprising:

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

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.

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 memory device is located on the assembly.

8. A method for calibrating an assembly comprising a sample block, thermoelectric devices, and a heat sink, all clamped together, the method comprising:

applying power to the thermoelectric devices to ramp the assembly through a series of known temperature profiles;

measuring the actual temperature profiles of the 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 assembly; and

storing the thermal characteristics in a memory device.

9. The method of claim 8, wherein the thermoelectric devices comprise at least one Peltier thermoelectric device.

10. The method of claim 8, wherein the adjusting comprises repeating the steps of applying, measuring, comparing, and adjusting.

11. The method of claim 8, wherein the temperature sensor is present in the heat sink.

12. The method of claim 8, wherein the applying power comprises applying power with a bi-polar amplifier.

13. The method of claim 8, wherein the power source comprises a class D switch-mode amplifier.

14. The method of claim 8, wherein the memory device is located on the assembly.

15. A system for measuring the AC resistance of a Peltier thermoelectric device comprising a first heating and cooling surface and a second heating and cooling surface, said system comprising:

a first temperature sensor in thermal communication with said first heating and cooling surface;

a second temperature sensor in thermal communication with said second heating and cooling surface;

a power source for providing power to said Peltier thermoelectric device;

a circuit for sensing AC voltage across said thermoelectric device and producing a DC voltage representing said AC voltage;

a circuit for sensing AC current through said thermoelectric device and producing a DC voltage representing said AC current;

a microcontroller programmed to receive said signals from said first and second temperature sensors, said microcontroller being programmed to

cause said power source to provide power to said thermoelectric device so that said first and second temperature sensor signals are equal,

cause an AC voltage to be superimposed on said power source power,

receive said DC voltages produced by said circuit for sensing AC voltage and from said circuit for sensing AC current,

calculate the AC resistance of said thermoelectric device from said DC voltages,

compensate for ambient temperature error by performing a polynomial calculation, to obtain a compensated AC resistance measurement, and

store said compensated AC resistance measurement.