Floating thermal contact enabled PCR

Patent metadata

Field	Value
Publication number	US-9683792-B2
Application number	US-201514755941-A
Country	US
Kind code	B2
Filing date	Jun 30, 2015
Priority date	Jun 30, 2014
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

Abstract

The present invention generally pertains to a system which utilizes floating thermal contact to enable PCR, in a thermal management device. Comprised of multiple thermal zones attached to a framework, each zone an individually actuated, isolated sub-assembly. The actuation of each zone ensures physical contact with an uneven, yet flat microfluidic chip to achieve effective, conductive heat transfer. The isolation of each zone serves to insulate the thermal zones from each other and minimize undesired heat transfer between adjacent zones, so that each zone is at a proper, uniform temperature.

First claim

What is claimed is:

1. A thermal management device enabling PCR reactions in a microfluidic channel, the device comprising:
a framework;
one or more thermal zone sub-assemblies coupled to the framework, each thermal zone sub-assembly having a thermal control element, and wherein each thermal zone sub-assembly is coupled to the framework by one or more thermal actuation mechanisms; and
one or more thermal spreaders configured to contact the thermal control elements of the one or more thermal zone sub-assemblies,
wherein the thermal actuation mechanisms consist essentially of insulative bearings, fasteners, and a spring, wherein the spring is configured to apply a force to drive the thermal control element toward one of the one or more thermal spreaders, wherein each fastener is a shoulder screw, and wherein each thermal actuation mechanism includes at least one polymer-based bearing, which travels up and down on the shaft of at least one of the shoulder screws that are attached to the framework and are pushed by the spring.

2. The thermal management device of claim 1 , wherein the insulative bearings are polymer-based bearings.

3. The thermal management device of claim 1 , wherein each thermal control element can be configured to have an operational temperature of from about 22° C. to about 95° C.

4. The thermal management device of claim 1 , wherein each of the thermal actuation mechanisms further comprises a first insulative fiber washer around a shoulder screw that holds the spring in place.

5. The thermal management device of claim 1 , wherein each thermal zone sub-assembly has a minimal spacing of 1 mm between itself and any other thermal zone sub-assembly or the framework.

6. The thermal management device of claim 1 , wherein at least one thermal zone assembly has a resistive heating element used to maintain a thermal zone at a temperature above room temperature.

7. The thermal management device of claim 1 , wherein at least one thermal zone assembly that has a thermoelectric element used to maintain a thermal zone at a temperature at or below room temperature.

8. The thermal management device of claim 1 , wherein at least one thermal zone assembly maintains a thermal zone at a temperature above room temperature, and wherein at least another thermal zone assembly maintains a thermal zone at a temperature at or below room temperature.

9. The thermal management device of claim 8 , wherein a first thermal zone and a fifth thermal zone are maintained at a temperature at or below room temperature, wherein a second thermal zone, fourth thermal zone, and a sixth thermal zone are maintained at a temperature above room temperature, and wherein a third thermal zone is maintained at a temperature above the temperature of at least the second thermal zone.

10. The thermal management device of claim 1 , wherein at least one of the thermal zone sub-assemblies is coupled to a heat sink.

11. The thermal management device of claim 10 , wherein the heat sink is a finned heat sink.

12. The thermal management device of claim 10 , wherein at least one of the thermal zone sub-assemblies is remotely connected to the heat sink via a heat pipe.

13. The thermal management device of claim 10 , wherein at least one of the thermal zone sub-assemblies is directly mounted on the heat sink.

14. The thermal management device of claim 1 , wherein a flexible heater circuit is configured and arranged to be the thermal control element for two or more thermal zone sub-assemblies of the thermal management device.

15. The thermal management device of claim 14 , wherein a first region of the flexible heater circuit can be moved by one of the thermal actuation mechanisms to be in contact with one of the thermal spreaders.

16. The thermal management device of claim 15 , wherein the first region of the flexible heater circuit is contact with one of the thermal spreaders and at least a second region of the flexible heater circuit is in contact with another one of the thermal spreaders.

17. The thermal management device of claim 16 , wherein the first region of the flexible heater circuit and the second region of the flexible heater circuit can flex relative to each other by a distance of about 0.75 mm to about 1.0 mm.

18. A method to perform PCR reactions in a microfluidic device comprising the following steps:
(a) providing a thermal management device comprising:
a framework;
one or more thermal zone sub-assemblies coupled to the framework, each thermal zone sub-assembly having a thermal control element, and wherein each thermal zone sub-assembly is coupled to the framework by one or more thermal actuation mechanisms; and
one or more thermal spreaders configured to contact the thermal control elements of the one or more thermal zone sub-assemblies, wherein the thermal actuation mechanisms consist essentially of insulative bearings, fasteners, and a spring, wherein the spring is configured to apply a force to drive the thermal control element toward one of the one or more thermal spreaders, wherein each fastener is a shoulder screw, and wherein each thermal actuation mechanism includes at least one polymer-based bearing, which travels up and down on the shaft of at least one of the shoulder screws that are attached to the framework and are pushed by the spring, and further wherein the thermal management device contains a plurality of droplets that contain reagents necessary for desired PCR reactions, and

(b) performing PCR in the microfluidic device.

19. A thermal management device enabling PCR reactions in a microfluidic channel, the device comprising:
a framework;
one or more thermal zone sub-assemblies coupled to the framework, each thermal zone sub-assembly having a thermal control element, and wherein each thermal zone sub-assembly is coupled to the framework by one or more thermal actuation mechanisms;
one or more thermal spreaders configured to contact the thermal control elements of the one or more thermal zone sub-assemblies; and
a flexible heater circuit, configured and arranged to be the thermal control element for two or more thermal zone sub-assemblies of the thermal management device,
wherein a first region of the flexible heater circuit can be moved by one of the thermal actuation mechanisms to be in contact with one of the thermal spreaders, wherein at least a second region of the flexible heater circuit is in contact with another one of the thermal spreaders, and wherein the first region of the flexible heater circuit and the second region of the flexible heater circuit can flex relative to each other by a distance of about 0.75 mm to about 1.0 mm.

20. The thermal management device of claim 19 , further wherein the thermal actuation mechanisms consist essentially of insulative bearings, fasteners, and a spring, wherein the spring is configured to apply a force to drive the thermal control element toward one of the one or more thermal spreaders, wherein each fastener is a shoulder screw, and wherein each thermal actuation mechanism includes at least one polymer-based bearing, which travels up and down on the shaft of at least one of the shoulder screws that are attached to the framework and are pushed by the spring.

Assignees

• Gnubio Inc
• Bio Rad Laboratories Inc

Inventors

• Possinger Christopher
• Kiani Sepehr

Classifications

• B01L3/502784

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title

• F25B21/04

  reversible · CPC title

• F28F2275/20

  with threaded elements · CPC title

• B01L2300/1883

  using thermal insulation · CPC title

• B01L2300/1822

  using Peltier elements · CPC title