COMBINED THERMAL DEVICES FOR THERMAL CYCLING

• US 20080124723A1
• Filed: 06/29/2007
• Published: 05/29/2008
• Est. Priority Date: 06/30/2006
• Status: Active Grant

• Current Assignee: Canon US Life Sciences Inc (Canon Inc.)
• Original Assignee: Canon US Life Sciences Inc (Canon Inc.)
• Inventors: Hasson, Kenton C., Dale, Gregory A., Zeng, Shulin
• Granted Patent: US 7,851,185 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1811 using electromagnetic induction heating
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1877 using chemical reactions
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2561/113 Real time assay
• CPC Class Codes: C12Q 2565/629 being a microfluidic device
• CPC Class Codes: G01N 21/71 thermally excited
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G06T 2207/10004 : Still image; Photographic image
• CPC Class Codes: G06T 2207/30072 : Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 7/0012 : Biomedical image inspection
• CPC Class Codes: G06T 7/11 : Region-based segmentation
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream

Abstract

The invention relates to systems and methods including a combination of thermal generating device technologies to achieve more efficiency and accuracy in PCR temperature cycling of nucleic samples undergoing amplification.

Claims

1. In a system comprising a nucleic acid sample, a heating device, and an electromagnetic heating source, a method comprising:

(a) controlling the heating device to cause a temperature of the sample to be at or about a first desired temperature for at least a first time period;

(b) after expiration of the first time period, increasing the output of the electromagnetic heating source to cause the temperature of the sample to be at or about a second desired temperature for at least a second time period;

(c) during said second time period, lowering the amount of heat the heating device provides to the sample; and

(d) immediately after expiration of the second time period, lowering the output of the electromagnetic heating source and controlling the heating device to cause the temperature of the sample to be at or about a third desired temperature for a third time period,

wherein the first temperature is less than the second temperature and the third temperature is less than the first temperature.

2. The method of claim 1 wherein the heating device is a Peltier device.

3. The method of claim 1 wherein the electromagnetic heating source is an infrared source.

4. The method of claim 1 wherein the system further comprises a controller and wherein the controlling steps are performed by the controller.

5. The method of claim 4 wherein the system further comprises a temperature sensing device and the controller is operable to control the heating device and the electromagnetic heating source as a function of a desired temperature and an output of the temperature sensing device.

6. The method of claim 5 wherein the temperature sensing device is a contact device.

7. The method of claim 5 wherein the temperature sensing device is a non-contact device.

8. The method of claim 1, wherein steps (a) through (d) occur while the sample is flowing through a channel.

9. The method of claim 1 wherein the system further comprises a switchable fan, the method further comprising:

switching on the fan, thereby increasing the rate of cooling of the sample, and

switching off the fan when a desired temperature is reached.

10. A method of amplifying a DNA sample in a polymerase chain reaction, the method comprising:

heating the sample to a first temperature for a first time period using a thermoelectric device;

heating the sample to a second temperature for a second time period using primarily an electromagnetic heat source;

cooling the sample to a third temperature; and

maintaining the third temperature for a third time period using the thermoelectric device,

wherein the second temperature is higher than the first and the first temperature is higher than the third.

11. The method of claim 10, wherein the thermoelectric device is thermostatically controlled by a controller based on an output of a temperature sensing device operable to sense a temperature of the sample.

12. The method of claim 10, wherein the first temperature is about 72°

C., the second temperature is about 95°

C., and the third temperature is about 55°

C.

13. The method of claim 10, wherein the thermoelectric device is a Peltier device.

14. The method of claim 10, further comprising:

switching on a fan to cool the sample from the second temperature to the third temperature and switching off the fan when the sample reaches the third temperature.

15. A nucleic acid sample heating system, comprising:

a nucleic acid sample container operable to receive a nucleic acid sample;

a first heating device; and

a second heating device, wherein

the first heating device is configured to heat the nucleic acid sample to at least about a first temperature,

the second heating device is configured to heat the nucleic acid sample to a second and third temperature,

the first temperature is associated with a denaturing phase of a PCR process,

the first heating device is a non-contact heating device, and

the second heating device is a contact heating device.

16. The system of claim 15, wherein:

the first heating device has a first temperature resolution;

the second heating device has a second temperature resolution, and

the second temperature resolution is finer than the first temperature resolution.

17. The system of claim 15, wherein the first heating device comprises a source configured to produce infra-red radiation and the second heating device is a Peltier heating element.

18. The system of claim 15, wherein the container comprises a microfluidic device having a microfluidic channel configured to receive the nucleic acid sample.

19. A method of heating a nucleic acid sample comprising:

(a) heating the nucleic acid sample to about a first temperature;

(b) after heating the sample to about the first temperature, maintaining the temperature of the sample at about the first temperature for a first period of time;

(c) after expiration of the first period of time, heating the sample to about a second temperature;

(d) after heating the sample to about the second temperature, maintaining the temperature of the sample at about the second temperature for a second period of time;

(e) after expiration of the second period of time, cooling the sample to about a third temperature; and

(f) after cooling the sample to about the third temperature, maintaining the temperature of the sample at about the third temperature for a third period of time, wherein

the first temperature is less than the second temperature and greater than the third temperature,

the step of maintaining the temperature of the sample at about the second temperature consists primarily of using one or more non-contact heating elements to maintain the temperature of the sample at about the second temperature, and

the step of maintaining the temperature of the sample at about the third temperature comprises using one or more contact heating elements to maintain the temperature of the sample at about the third temperature.

20. The method of claim 19, wherein the one or more non-contact heating elements comprises a source of infra-red radiation.

21. The method of claim 20, wherein the source of infra-red radiation comprises a laser.

22. The method of claim 19, wherein the one or more contact heating elements comprises a Peltier device.

23. The method of claim 19, further comprising forcing the nucleic acid sample to move through a channel.

24. The method of claim 23, wherein steps (a)-(f) occur while the sample is moving through channel.

25. The method of claim 24, wherein the channel is a microfluidic channel.

26. The method of claim 19, wherein the step of maintaining the temperature of the sample at about the third temperature for a third period of time consists primarily of using the one or more contact heating elements to maintain the temperature of the sample at about the third temperature for the third period of time.

27. The method of claim 26, wherein the step of maintaining the temperature of the sample at about the first temperature for the first period of time consists primarily of using the one or more contact heating elements to maintain the temperature of the sample at about the first temperature for the first period of time.