Non-contact infrared thermocycling

• US 9,630,182 B2
• Filed: 12/04/2013
• Issued: 04/25/2017
• Est. Priority Date: 12/04/2013
• Status: Active Grant

• Current Assignee: Leidos Innovations Technology, Inc.
• Original Assignee: Leidos Innovations Technology, Inc.
• Inventors: Egan, Michael Edward, Trost, Peter Karl, Landers, James, Root, Brian, Scott, Orion
• Primary Examiner(s): WOOLWINE, SAMUEL C
• Application Number:
  US14/096,273
• Publication Number:
  US 20150151302A1
• Time in Patent Office: 1,238 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2300/1872 Infrared light
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• 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 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: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2565/629 being a microfluidic device

Abstract

A microfluidic chip includes one or more reaction chambers to hold fluids for chemical or biochemical reactions, such as PCR. A non-contact heat source heats the reaction chamber and the fluid, such that the heat source does not contact the reaction chamber or the fluid. The heat source can heat the reaction chamber and the fluid separately, where the reaction chamber and the fluid separately absorb heat radiation from the heat source. A temperature sensor acquires a temperature of the reaction chamber and/or the fluid. Control circuitry controls the heat source according to a cycling profile for the reaction in the fluid to cycle the heat source between heating and not heating the reaction chamber and the fluid based on the temperature acquired by the temperature sensor. Cooling can be provided passively or actively.

Claims

1. An apparatus, comprising:

a plurality of reaction chambers, each reaction chamber to hold a fluid;

a heat source to heat the reaction chamber and the fluid, wherein the heat source does not contact the reaction chamber or the fluid, and the reaction chamber and the fluid separately absorb heat radiation from the heat source, the heat source including a plurality of infrared lasers, each infrared laser having a different wavelength, outputs of the infrared lasers being coupled together as to form a single heat source for the reaction chamber;

a temperature sensor to acquire a temperature of the reaction chamber and/or the fluid; and

control circuitry configured to control the heat source independently for each of the reaction chambers according to a corresponding cycling profile for a chemical or biochemical reaction in the fluid to cycle the heat source between heating and not heating each of the reaction chambers and the fluid based on a corresponding temperature acquired by the temperature sensor.

2. The apparatus according to claim 1, wherein:

the heat source includes an output for non-contact heating for each of the reaction chambers, and

the temperature sensor is to acquire a separate temperature for each of the reaction chambers.

3. The apparatus according to claim 2, further comprising:

a microfluidic chip that includes the plurality of reaction chambers and cyclic olefin copolymer (COC).

4. The apparatus according to claim 1, wherein at least one of the infrared lasers operates at 1720 nm+/−

10 nm center wavelength.

5. The apparatus according to claim 1, wherein the temperature sensor is a non-contact sensor that does not contact the reaction chamber or the fluid.

6. The apparatus according to claim 5, wherein the temperature sensor includes one or more pyrometers or one or more infrared cameras.

7. The apparatus according to claim 1, wherein the cycling profile includes following steps:

(a) heating to a first temperature at a first rate;

(b) holding the first temperature for a first holding time;

(c) cooling to a second temperature at a second rate;

(d) holding the second temperature for a second holding time;

(e) heating to a third temperature at a third rate; and

(f) holding the third temperature for a third holding time.

8. The apparatus according to claim 7, wherein, in the cycling profile, the steps (a)-(f) are repeated for a predetermined number of cycles.

9. The apparatus according to claim 8, wherein, for a last one of the cycles, the third temperature is held for a final extension time period that is longer than the third holding time.

10. The apparatus according to claim 9, wherein the cycling profile includes, prior to the step (a) in a first one of the cycles, a denaturing step of holding a denaturing temperature for a denaturing time period.

11. The apparatus according to claim 10, wherein the control circuitry is configured to control the heat source according to the cycling profile such that following conditions are satisfied:

volume of the fluid ≦

10 ml;

the predetermined number of cycles=20-35;

the first temperature=50-96°

C.;

the first holding time=2-20 seconds;

the first rate=>

2°

C./s;

the second temperature=50-96°

C.;

the second holding time=5-60 seconds;

the second rate;

<

−

1°

C./s;

the third temperature=50-96°

C.;

the third holding time=5-60 seconds;

the third rate=>

2°

C./s; and

the final extension time period=1-15 minutes.

12. The apparatus according to claim 11, wherein the control circuitry is configured to control the heat source according to the cycling profile such that the following conditions are satisfied:

denaturing temperature=50-96°

; and

denaturing time period is equal to or more than 60 seconds.

13. The apparatus according to claim 10, wherein the control circuitry is configured to control the heat source according to the cycling profile such that following conditions are satisfied:

volume of the fluid ≦

10 ml;

the predetermined number of cycles is approximately 27;

the first temperature is approximately 95°

C.,

the first holding time is approximately 5 seconds;

the first rate is approximately >

3°

C./s;

the second temperature is approximately 60°

C.;

the second holding time is approximately 10 seconds;

the second rate is approximately −

2.1°

C./s;

the third temperature is approximately 72°

C.;

the third holding time is approximately 10 seconds; and

the third rate is approximately 3.7°

C./s.

14. The apparatus according to claim 10, wherein the control circuitry is configured to control the heat source according to the cycling profile such that following conditions are satisfied:

the first temperature is higher than the second and third temperatures;

the third temperature is higher than the second temperature; and

the first holding time is less than the second and third holding times.

15. The apparatus according to claim 1, further comprising:

an active or passive cooler to cool the reaction chamber and/or the fluid, wherein

when the active cooler is provided, the control circuit is configured to control the active cooler to provide cooling in accordance with the cycling profile.

16. The apparatus according to claim 1, wherein:

the heat source includes a fiber optic channel to output infrared light to the reaction chamber and the fluid to heat the reaction chamber and the fluid, and

the fiber optical channels include corrective lenses at output ends thereof.

17. A method for a reaction, comprising:

independently controlling, by control circuitry, heating and cooling of each of a plurality of reaction chambers, each contains a fluid in which an reaction is to occur, in accordance with a corresponding cycling profile based on sensing a corresponding temperature of each of the reaction chambers or the fluid, each cycling profile including;

(a) heating to a first temperature at a first rate;

(b) holding the first temperature for a first holding time;

(c) cooling to a second temperature at a second rate;

(d) holding the second temperature for a second holding time;

(e) heating to a third temperature at a third rate; and

(f) holding the third temperature for a third holding time, wherein a reaction chamber is heated by a heat source including a plurality of infrared lasers, each infrared laser having a different wavelength, outputs of the infrared lasers being coupled together as to form a single heat source for the reaction chamber.

18. A non-transitory computer-readable medium including computer-executable instructions, which when executed by control circuitry, cause the control circuitry to perform the method according to claim 17.

19. An apparatus, comprising:

a reaction chamber to hold a fluid;

a non-contact heat source to heat the reaction chamber and the fluid, wherein the heat source does not contact the reaction chamber or the fluid, and the reaction chamber and the fluid separately absorb heat radiation from the heat source;

a temperature sensor to acquire a temperature of the reaction chamber and/or the fluid; and

control circuitry configured to control the heat source according to a cycling profile for a chemical or biochemical reaction in the fluid to cycle the heat source between heating and not heating the reaction chamber and the fluid based on the temperature acquired by the temperature sensor, wherein the heat source includes an output for non-contact heating for each of the reaction chambers, the temperature sensor is to acquire a separate temperature for each of the reaction chambers, and the control circuitry is configured to control the heat source independently for each of the reaction chambers based on the respective temperatures acquired by the temperature sensor and the cycling profile, wherein the heat source includes one or more infrared lasers and the one or more infrared lasers operate at 1720 nm+/−

10 nm center wavelength.