Thermal cycler for PCR

• US 8,246,243 B2
• Filed: 01/12/2010
• Issued: 08/21/2012
• 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: Atwood, John G., Fawcett, Adrian, Ferrara, Keith S., Hetherington, Paul M., Noreiks, Richard W., Olsen, Douglas E., Widomski, John R., Wittmer, Charles M.
• Primary Examiner(s): VERBITSKY, GAIL KAPLAN
• Application Number:
  US12/686,100
• Publication Number:
  US 20100173400A1
• Time in Patent Office: 952 Days
• Field of Search: 374/1, 374 10- 13, 374 4- 5, 374 43- 44, 374/100, 374/179, 374/141, 374/29, 374 30- 39, 374/208, 702/130, 702/133, 702/136, 702/99, 422/99, 422/51, 136/200, 136/201, 136/203, 136/204, 73/10.1, 436/147, 436/149, 436/157, 436/163
• 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. An apparatus comprising:

a thermal cycler comprising;

a removable assembly configured to receive a plurality of vials and cycle the plurality of vials through a series of temperatures;

a computer device configured to control cycling of the plurality of vials through a series of temperature excursions; and

a cover, the cover being configured to press against an upper portion of vials when the vials are disposed in the removable assembly;

wherein the removable assembly comprises

a sample block configured to receive the plurality of vials,

a plurality of Peltier thermal electric devices in thermal communication with the sample block,

a heat sink in thermal communication with the ample block, and

a memory device that stores data related to the removable assembly, wherein the memory device in electrical communication with the computer device, and wherein the removable assembly is configured to be removed from the apparatus and is configured to be attached to a different apparatus for cycling vials through a series of temperatures.

2. The apparatus of claim 1, wherein the removable assembly further comprises a clamping mechanism positioned so as to clamp the plurality of Peltier thermal electric devices between the sample block and the heat sink.

3. The apparatus of claim 1, wherein the data comprises thermal characteristic data.

4. The apparatus of claim 1, wherein the sample block comprises a plurality of sample wells, for receiving the plurality of sample vials, each well having a top and bottom, an upper support plate connecting the tops of the plurality of sample wells.

5. The apparatus of claim 4, wherein the upper support plate and the plurality of sample wells are provided as a single piece.

6. The apparatus of claim 4, wherein the sample block comprises silver.

7. The apparatus of claim 4, further comprising a bottom plate connecting the bottom of the sample wells.

8. The apparatus of claim 1, wherein sample block is rectangular.

9. The apparatus of claim 1, wherein the plurality of Peltier thermoelectric devices is matched to provide a temperature within 0.2°

C. for a given input current.

10. The apparatus of claim 1, wherein the plurality of Peltier thermoelectric devices each comprise:

a first ceramic layer having bonded copper traces;

a second ceramic layer having bonded copper traces, the second ceramic layer comprising a plurality of ceramic elements; and

a plurality of bismuth telluride pellets positioned between the first ceramic layer and the second ceramic layer and soldered to the bonded copper traces on the first and second ceramic layers.

11. The apparatus of claim 10, wherein the ceramic of the first and second layer is alumina.

12. The apparatus of claim 1, wherein the heat sink comprises:

a plate having a top side and a bottom side; and

a plurality of fins extending perpendicularly from the bottom side.

13. The apparatus of claim 1, further comprising a plurality of vials received in the sample block.

14. The apparatus of claim 13, wherein the plurality of vials comprises a microtiter tray.

15. The apparatus of claim 1, wherein the computer device is also configured to control a temperature of the cover.

16. A method of calibrating a removable assembly for cycling samples through a series of temperatures, the removable assembly comprising a sample block for receiving vials, a plurality of Peltier thermal electric devices, a heat sink, and a memory device capable of storing data related to the removable assembly, the method comprising:

providing a thermal cycler comprising a cover mounted to the thermal cycler;

attaching the removable assembly to the thermal cycler for cycling vials through a series of temperatures;

applying power to the plurality of Peltier thermal electric devices, causing the removable assembly to cycle through a desired series of temperature excursions;

measuring the actual temperature excursions;

comparing the actual temperature excursions with the desired temperature excursions;

adjusting the power applied to the plurality of Peltier thermal electric devices so that the actual temperature excursions match the desired temperature excursions; and

recording data in the memory device for further utilization in obtaining the desired temperature excursions.

17. The method of claim 16, further comprising removing the calibrated removable assembly from the instrument, and attaching the removable assembly to a different instrument for cycling vials through a series of temperatures.

18. The method of claim 16, wherein the assembly further comprises a clamping mechanism positioned so as to clamp the plurality of Peltier thermal electric devices between the sample block and the heat sink.

19. The method of claim 16, wherein the data comprises thermal characteristic data.

20. An apparatus comprising:

a removable assembly configured to receive a plurality of vials and cycle the plurality of vials through a series of temperatures;

a computer device configured to control cycling of the plurality of vials through a series of temperature excursions; and

a cover, the cover being configured to press against an upper portion of vials when the vials are disposed in the removable assembly;

wherein the removable assembly comprises

a sample block configured to receive the plurality of vials,

a heat sink;

a plurality of Peltier thermal electric devices in thermal contact with the sample block and the heat sink; and

a memory device that stores thermal characteristics related to the performance of the removable assembly, wherein the memory device in electrical communication with the computer device, and wherein the removable assembly is configured to be removed from the apparatus and is configured to be attached to a different apparatus for cycling vials through a series of temperatures.