Systems and methods for the amplification of DNA

Patent metadata

Field	Value
Publication number	US-9540686-B2
Application number	US-23319408-A
Country	US
Kind code	B2
Filing date	Sep 18, 2008
Priority date	Sep 18, 2008
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

A system for amplifying nucleic acids is disclosed which, in one embodiment, includes a fluidic device having a sample channel and a heat exchange channel disposed sufficiently close to the sample channel such that a heat exchange fluid in the heat exchange channel can cause a sample in the sample channel to gain or lose heat at desired levels. In one illustrative embodiment, the system further includes three reservoirs coupled to the heat exchange channel and a temperature control system configured to heat fluids stored in the respective reservoirs at different temperatures. One or more pumps and a controller are configured to cause fluid stored in the reservoirs to enter and flow through the heat exchange channel at different times.

First claim

What is claimed is:

1. A system for amplifying DNA, comprising:
a microfluidic chip comprising a sample channel and a heat exchange channel formed within the microfluidic chip and sufficiently close to the sample channel such that a heat exchange fluid in the heat exchange channel can cause a sample in the sample channel to gain or lose heat at desired levels, wherein the heat exchange channel is configured to exchange heat with two sides of the sample channel;
a first reservoir having an output port coupled to an input of the heat exchange channel through a first forward valve and having an input port coupled to an output of the heat exchange channel through a first return valve, said first reservoir storing a first heat exchange fluid;
a second reservoir having an output port coupled to the input of the heat exchange channel through a second forward valve and having an input port coupled to the output of the heat exchange channel through a second return valve, said second reservoir storing a second heat exchange fluid;
a third reservoir having an output port coupled to the input of the heat exchange channel through a third forward valve and having an input port coupled to the output of the heat exchange channel through a third return valve, said third reservoir storing a third heat exchange fluid, wherein each of the first, second, and third reservoirs is divided into two chambers fluidly connected with each other by a valve, the fluid being released into the heat exchange channel from a first chamber and returned back from the heat exchange channel into the second chamber;
a temperature control system configured to: (a) regulate the heat exchange fluid stored in the first reservoir at a first temperature, (b) regulate the heat exchange fluid stored in the second reservoir at a second temperature, and (c) regulate the heat exchange fluid stored in the third reservoir at a third temperature;
one or more pumps;
an imaging system including an excitation source and an image capturing device configured to image a biological reaction within the sample channel through a sample channel region unobstructed by the heat exchange channel; and
a controller configured to operate said valves and said one or more pumps such that:
(a) for a first period of time, the first heat exchange fluid stored in the first reservoir enters the heat exchange channel, but the second and third heat exchange fluids stored in the second and third reservoirs, respectively, do not enter the heat exchange channel;
(b) for a second period of time, the second heat exchange fluid stored in the second reservoir enters the heat exchange channel, but the first and third heat exchange fluids stored in the first and third reservoirs, respectively, do not enter the heat exchange channel; and
(c) for a third period of time, the third heat exchange fluid stored in the third reservoir enters the heat exchange channel, but the first and second heat exchange fluids stored in the first and second reservoirs, respectively, do not enter the heat exchange channel, wherein
the first period of time is different than the second period of time, which is different than the third period of time, and
the first temperature is different than the second temperature, which is different than the third temperature, wherein the first heat exchange fluid is returned back to the first reservoir prior to directing the second heat exchange fluid to the heat exchange channel and the second heat exchange fluid is returned back to the second reservoir prior to directing the third heat exchange fluid to the heat exchange channel.

2. The system of claim 1 , wherein the controller is further configured to operate said return valves such that the first heat exchange fluid returns to the second chamber of the third reservoir after exiting the heat exchange channel.

3. The system of claim 2 , wherein the controller is further configured to operate said return valves such that the second heat exchange fluid returns to the second chamber of the first reservoir after exiting the heat exchange channel.

4. The system of claim 3 , wherein the controller is further configured to operate said return valves such that the third heat exchange fluid returns to the second chamber of the second reservoir after exiting the heat exchange channel.

5. The system of claim 1 , wherein the controller is further configured to operate said return valves such that the first heat exchange fluid returns to the second chamber of the first reservoir after exiting the heat exchange channel.

6. The system of claim 5 , wherein the controller is further configured to operate said return valves such that the second heat exchange fluid returns to the second chamber of the second reservoir after exiting the heat exchange channel.

7. The system of claim 6 , wherein the controller is further configured to operate said return valves such that the third heat exchange fluid returns to the second chamber of the third reservoir after exiting the heat exchange channel.

8. The system of claim 1 , wherein the first temperature is a temperature such that when the first heat exchange fluid moves through the heat exchange channel said fluid heats a sample in the sample channel to a temperature over 80 degrees Celsius, the second temperature is a temperature such that when the second heat exchange fluid moves through the heat exchange channel said fluid cools a sample in the sample channel to a temperature under 60 degrees Celsius, and the third temperature is a temperature such that when the third heat exchange fluid moves through the heat exchange channel said fluid heats a sample in the sample channel to a temperature between 60 and 80 degrees Celsius.

9. The system of claim 1 , wherein at least a portion of the heat exchange channel is beneath the sample channel and parallel with the sample channel.

10. The system of claim 1 , wherein at least one dimension of the heat exchange channel and the sample channel is less than 3000 micrometers.

11. The system of claim 10 , wherein the heat exchange channel has a width between about 20 and 2000 micrometers and a depth between about 20 and 2000 micrometers.

12. The system of claim 1 , wherein said heat exchange fluids comprise a gas, a liquid or a gas and liquid mixture.

13. The system of claim 1 , wherein said heat exchange fluids comprise water and/or compressed air with pressure from 1 to 200 psia.

14. The system of claim 12 , wherein said first heat exchange fluid is different than the second heat exchange fluid, which can be the same or different than the third heat exchange fluid.

15. A system for amplifying DNA, comprising:
a microfluidic chip comprising a sample channel and a heat exchange channel formed within the microfluidic chip sufficiently close to the sample channel such that a heat exchange fluid in the heat exchange channel can cause a sample in the sample channel to gain or lose heat at desired levels, wherein the heat exchange channel is configured to exchange heat with two sides of the sample channel;
a first reservoir having an output port coupled to an input of the heat exchange channel through a first forward valve and having an input port coupled to an output of the heat exchange channel through a first return valve, said first reservoir storing a first heat exchange fluid;
a second reservoir having an output port coupled to the input of the heat exchange channel through a second forward valve and having an input port coupled to the output of the heat exchange channel through a second return valve, said second reservoir storing a second heat exchange fluid;
a third reser

Assignees

• Zeng Shulin
• Hasson Kenton C
• Dale Gregory A
• Canon Us Life Sciences Inc

Inventors

• Zeng Shulin
• Hasson Kenton C
• Dale Gregory A

Classifications

• B01L2300/0883

  Serpentine channels · CPC title

• B01L2300/1838

  using fluid heat transfer medium · CPC title

• C12Q2527/101

  Temperature · CPC title

• B01L2300/1827

  using resistive heater · CPC title

• B01L2300/0816

  Cards, e.g. flat sample carriers usually with flow in two horizontal directions · CPC title