Integrated chip carriers with thermocycler interfaces and methods of using the same

• US 9,623,413 B2
• Filed: 04/16/2010
• Issued: 04/18/2017
• Est. Priority Date: 04/05/2000
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Chou, Hou-Pu, Facer, Geoffrey, Grossman, Robert, Unger, Marc, Lam, Phillip, Kimball, Jake, Pieprzyk, Martin, Daridon, Antoine
• Primary Examiner(s): Joyner, Kevin
• Assistant Examiner(s): MULL, HOLLY MICHAELA
• Application Number:
  US12/761,917
• Publication Number:
  US 20100311060A1
• Time in Patent Office: 2,559 Days
• Field of Search: 435 5, 435 6, 4352851, 4353031, 4352831, 4352862-2887, 4352861, 435 61, 422 52, 422502, 422503, 422547
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• 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 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0605 check valves
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/06 Crystallising dishes
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/5635 : connecting two containers face to face, e.g. comprising a filter
• CPC Class Codes: B01L 3/565 : Seals in general F16L
• 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 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C12M 1/00 : Apparatus for enzymology or microbiology
• CPC Class Codes: C30B 29/58 : Macromolecular compounds
• CPC Class Codes: C30B 7/00 : Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: Y10T 29/49826 : Assembling or joining
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Claims

1. A method of conducting a reaction at a selected temperature or range of temperatures over time, the method comprising:

providing an array device comprising (i) a plurality of separate reaction chambers, each chamber comprising a chamber bottom, and (ii) a bottom surface, wherein a thermal transfer element is bonded to the bottom surface, the thermal transfer element being formed to contact a thermal control device and adapted to create a homogeneous thermal field for the plurality of separate reaction chambers, wherein the array device includes an elastomeric valve actuatable to control fluidic actions within the array device;

introducing into the array device reagents for carrying out a desired reaction; and

contacting the thermal transfer element with the thermal control device such that the thermal control device is in thermal communication with the thermal transfer element and so that a temperature of the reaction in the plurality of separate reaction chambers is homogeneously changed by the homogeneous thermal field as a result of a change in temperature of the thermal control device, wherein the thermal control device is adapted to apply a force to the thermal transfer element to urge the thermal transfer element towards the thermal control device without actuating the valve.

2. The method recited in claim 1, wherein the force comprises a magnetic, electrostatic, or vacuum force.

3. The method recited in claim 1, wherein the force comprises a vacuum force applied towards the thermal transfer element through channels formed in a surface of the thermal control device or the thermal transfer element.

4. The method recited in claim 3 further comprising detecting a level of vacuum achieved between the surface of the thermal control device and a surface of the thermal transfer element.

5. The method recited in claim 4 wherein detecting the level of vacuum is performed with a vacuum level detector located at a position along the channel or channels distal from a location of a source of vacuum.

6. The method recited in claim 5 wherein when the level of vacuum does not exceed a preset level an alert is manifested or a realignment protocol is engaged.

7. The method recited in claim 1 wherein contacting the thermal transfer element with the thermal control device is carried out by employment of one or more mechanical or electromechanical positioning devices.

8. The method recited in claim 1 further comprising automatically controlling and monitoring the carrying out of the method.

9. The method recited in claim 1 wherein the thermal transfer element comprises a semiconductor.

10. The method recited in claim 1 wherein the thermal transfer element comprises silicon.

11. The method recited in claim 1 wherein the thermal transfer element comprises a reflective material.

12. The method recited in claim 1 wherein the thermal transfer element comprises a metal.

13. A microfluidic system comprising:

an array device comprising a plurality of separate reaction chambers disposed within a reaction area and in fluid communication with fluid inlets of the array device, the fluid inlets being disposed outside the reaction area, wherein each reaction chamber comprises a chamber bottom and is in fluid communication with at least one of the fluid inlets via at least one channel;

such that fluid introduced into at least one of the fluid inlets is delivered to at least one of the plurality of separate reaction chambers, wherein the array device includes an elastomeric valve actuatable to control fluidic actions within the array device; and

a thermal transfer interface comprising a thermally conductive material bonded to a bottom surface of the array device and arranged to create a homogeneous thermal field within the reaction area from energy received from a thermal control device such that there is homogeneous heating of the plurality of separate reaction chambers, wherein the thermal control device is adapted to apply a force to the thermal transfer interface to urge the thermal transfer interface towards the thermal control device without actuating the valve.

14. The microfluidic system recited in claim 13 wherein the thermally conductive material is reflective.

15. The microfluidic system recited in claim 13 wherein the thermally conductive material comprises a semiconductor.

16. The microfluidic system recited in claim 13 wherein the thermally conductive material comprises silicon.

17. The microfluidic system recited in claim 13 wherein the thermally conductive material comprises polished silicon.

18. The microfluidic system recited in claim 13 wherein the thermally conductive material comprises a metal.

19. The microfluidic system recited in claim 13 wherein the thermal transfer interface is further arranged to form a thermally-isolating gap between the thermal transfer interface and a carrier supporting the array device.

20. The microfluidic system recited in claim 13 wherein the thermal control device includes a plurality of thermal controls controllable to induce a thermal gradient within the reaction area.

21. The microfluidic system recited in claim 13 wherein the thermal control device is adapted for applying a vacuum source towards the thermal transfer interface through channels formed in a surface of the thermal control device or in the thermal transfer interface to apply the force to the thermal transfer interface to urge the thermal transfer interface towards the thermal control device.

22. The microfluidic system recited in claim 21 further comprising a vacuum level detector for detecting a level of vacuum achieved between the surface of the thermal control device and a surface of the thermal transfer interface.

23. The microfluidic system recited in claim 22 wherein the vacuum level detector is located at a position along the channel or channels distal from a location of a source of vacuum.

24. The microfluidic system recited in claim 13 further comprising an automatic control system in operable communication with a robotic control system for introducing and removing the array device and the thermal transfer interface from the thermal control device.