Combined thermal devices for thermal cycling

• US 9,272,282 B2
• Filed: 08/13/2013
• Issued: 03/01/2016
• 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: Dale, Gregory A., Zeng, Shulin, Hasson, Kenton C.
• Primary Examiner(s): WOOLWINE, SAMUEL C
• Application Number:
  US13/966,255
• Publication Number:
  US 20140065703A1
• Time in Patent Office: 931 Days
• Field of Search: None
• US Class Current: 1/1
• 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. A method for heating a nucleic acid sample in a microfluidic device by using a heating device and an electromagnetic heating device, the 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, wherein the temperature of the sample during the second time period is caused by heat provided by both the heating device and the electromagnetic heating source heating the nucleic acid sample.

2. The method of claim 1, wherein the first time period corresponds to an extension phase of a PCR cycle, the second time period corresponds to a denaturation phase of the PCR cycle, and the third time period corresponds to an annealing phase of the PCR cycle.

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

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

5. The method of claim 1 wherein the system further comprises a temperature sensing device and a controller, the controller is operable to control the heating device and the electromagnetic heating source to provide a desired temperature based on 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 7, 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.

9. The method of claim 1 further comprising:

switching on a fan in communication with the microfluidic device, thereby increasing the rate of cooling of the sample, and

switching off the fan when a desired temperature is reached.

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

11. The method of claim 1, wherein the heating device is in contact with a micro channel containing a nucleic acid sample and the electromagnetic heating source is remote from the microfluidic device.

12. The method of claim 1, 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 1, wherein during the step of maintaining the temperature of the sample at about the third temperature for a third period of time, the amount of heat provided by the heating element is greater than the amount of heat provided by the electromagnetic heating source.