Combined thermal devices for thermal cycling
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.
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.