Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control

• US 20060269641A1
• Filed: 05/12/2006
• Published: 11/30/2006
• Est. Priority Date: 11/29/1990
• Status: Abandoned Application

• Current Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Ragusa, Robert P., Woudenberg, Timothy M., Williams, Fenton, Margulies, Marcel, Leath, Richard, Miles, Clive, Mossa, Albert Carmelo, Atwood, John Girdner, Goven, Lisa May
• Application Number:
  US11/433,892
• Publication Number:
  US 20060269641A1
• Time in Patent Office: Days
• US Class Current: 425/286
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• 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 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• 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: G05D 23/1917 using digital means
• CPC Class Codes: Y10S 435/809 Incubators or racks or holders for culture plates or containers

Abstract

A thermal cycler for automatic performance of the polymerase chain reaction is provided. The thermal cycler comprises a heater control that provides close temperature control of the reaction.

Claims

1. An apparatus comprising:

a heating and cooling system,

a heat exchanger in heat transfer communication with the heating and cooling system and adapted to hold at least one sample tube in heat transfer communication with the heat exchanger, wherein the at least one sample tube is adapted to contain a known volume of a sample;

a temperature sensor adapted to determine the temperature of the heat exchanger in a first sample interval, wherein the first sample interval is an interval of time designated as time n; and

a computing apparatus adapted to control the heating and cooling system and wherein the computing apparatus is adapted to determine the temperature of a sample as a function of the temperature of the heat exchanger over time by utilizing the relationship;

Tsampn=Tsampn-1+(TBn−

Tsampn-1)*tinterval/tau

where Tsampn is equal to the sample temperature in the first sample interval, Tsampn-1 is a sample temperature in a second sample interval immediately preceding the first sample interval, the second sample interval designated as time n-1, TBn is equal to the temperature of the heat exchanger in the first sample interval, tinterval is a time in seconds between consecutive sample intervals, and tau is a function of thermal characteristics of the apparatus.

2. The apparatus of claim 1, wherein the heat exchanger comprises a conical cavity.

3. The apparatus of claim 1, wherein the shape of the heat exchanger complements a shape of a respective sample tube.

4. The apparatus of claim 1, wherein the heat exchanger comprises a block.

5. The apparatus of claim 1, wherein the heat exchanger comprises a block with wells formed therein.

6. The apparatus of claim 1, wherein the heat exchanger comprises a liquid bath.

7. The apparatus of claim 1, wherein the heat exchanger comprises an oven.

8. The apparatus of claim 1, wherein the thermal characteristics comprise a first thermal time constant corresponding to at least one sample tube and a volume of a sample, and a second thermal time constant corresponding to a temperature sensor thermally coupled to the heat exchanger, and tau equals approximately the first thermal time constant minus the second thermal time constant.

9. The apparatus of claim 1, further comprising an input device for receiving user defined setpoints defining a hold time/temperature profile, wherein the computing apparatus includes a controller adapted to control the heating and cooling system as a function of the user defined setpoints and a sample temperature.

10. The apparatus of claim 1, wherein the heat exchanger is adapted to receive at least one sample tube containing a volume of sample in the range of from approximately 20 microliters to approximately 100 microliters.

11. The apparatus of claim 1, wherein the heat exchanger further comprises an enclosure, the enclosure defining an enclosed ambient atmosphere, and wherein the heat exchanger is in heat transfer communication with the enclosed ambient atmosphere.

12. The apparatus of claim 11, wherein the heating and cooling system comprises a heater thermally coupled to the enclosed ambient atmosphere.

13. The apparatus of claim 1, wherein the heat exchanger is in heat transfer communication with cooling channels.

14. The apparatus of claim 1, wherein the means for determining the temperature of the heat exchanger in the first sample interval comprises means for determining the temperature of the heat exchanger in the first sample interval as a function of at least one temperature of the heat exchanger in a previous sample interval.

15. The apparatus of claim 1, further comprising an input device for receiving a tube type and a reaction volume, and wherein the computing apparatus comprises means for determining the thermal time constant for a sample tube as a function of the tube type and a sample volume.

16. An apparatus comprising:

a heating and cooling system;

a heat exchanger thermally coupled with the heating and cooling system and adapted to hold at least one sample tube, the at least one sample tube being thermally coupled with the heat exchanger and being adapted to contain a known volume of a sample;

a temperature sensor adapted to determine the temperature of the heat exchanger in a first period of time; and

a computing apparatus adapted to control the heating and cooling system and determine the temperature of a sample in the first period of time and in a second earlier period of time that precedes the first period of time by a third period of time, with the temperature of the sample in the first period of time determined as a function of the difference between the temperature of the heat exchanger in the first period of time and the temperature of the sample in the second earlier period of time.

18. The apparatus of claim 16, wherein the function comprises a factor by which the difference between the temperature of the heat exchanger in the first period of time and the temperature of the sample in the second earlier period of time is multiplied.

21. The apparatus of claim 16, wherein the heat exchanger comprises a liquid bath.

22. The apparatus of claim 16, wherein the heat exchanger comprises an oven.

19. The apparatus of claim 17, wherein the factor comprises the third period of time.

20. The apparatus of claim 17, wherein the factor comprises thermal characteristics of the apparatus.