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

• US 20050214173A1
• Filed: 02/14/2005
• Published: 09/29/2005
• Est. Priority Date: 01/25/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc, Facer, Geoffrey, Pieprzyk, Martin, Daridon, Antoine, Chou, Hou-Pu, Lam, Phillip, Grossman, Robert, Kimball, Jake
• Granted Patent: US 7,867,763 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• 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 for containing a plurality of separate reaction chambers, the array device comprising an elastomeric block formed from a plurality of layers, wherein at least one layer has at least one recess formed therein, the recess having at least one deflectable membrane integral to the layer with the recess, the array device further comprising a thermal transfer device proximal to at least one of the reaction chambers, the thermal transfer device being formed to contact a thermal control source;

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

contacting the array device 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 chambers is changed as a result of a change in temperature of the thermal control source.

2. The method recited in claim 1 wherein the thermal transfer device comprises a semiconductor.

3. The method recited in claim 1 wherein the thermal transfer device comprises silicon.

4. The method recited in claim 1 wherein the thermal transfer device comprises a reflective material.

5. The method recited in claim 1 wherein the thermal transfer device comprises a metal.

6. The method recited in claim 1 wherein the thermal control device is adapted to apply a force to the thermal transfer device to urge the thermal transfer device towards the thermal control source.

7. The method recited in claim 6 wherein the force comprises a magnetic, electrostatic, or vacuum force.

8. The method recited in claim 7 wherein the force comprises a vacuum force applied towards the thermal transfer device through channels formed in a surface of the thermal control device or the thermal transfer device.

9. The method recited in claim 8 further comprising detecting a level of vacuum achieved between the surface of the thermal control device and a surface of the thermal transfer device.

10. The method recited in claim 9 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.

11. The method recited in claim 10 wherein when the level of vacuum does not exceed a preset level an alert is manifested or a realignment protocol is engaged.

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

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

14. The method recited in claim 13 wherein automatically controlling and monitoring the carrying out of the method is performed with an automatic control system in operable communication with a robotic control system for introducing and removing the array device from the thermal control device.

15. The method recited in claim 1 further comprising monitoring progress of the reactions.

16. A device comprising the array device described in claim 1.

17. A unit comprising the thermal control device as described in claim 9.

18. A system comprising the array device of claim 1 and the thermal control device of claim 9.

19. A microfluidic system comprising:

an array device for containing a plurality of separate reaction chambers disposed within a reaction area and in fluid communication with fluid inlets to the array device disposed outside the reaction area, the array device comprising an elastomeric block formed from a plurality of layers, wherein at least one layer has at least one recess formed therein, the recess having at least one deflectable membrane integral to the layer with the recess;

a carrier adapted to hold the array device and having a plurality of fluid channels interfaced with the fluid inlets; and

a thermal transfer interface comprising a thermally conductive material disposed to provide substantially homogeneous thermal communication from a thermal control source to the reaction area.

20. The microfluidic system recited in claim 19 wherein the thermally conductive material is reflective.

21. The microfluidic system recited in claim 19 wherein the thermally conductive material comprises a semiconductor.

22. The microfluidic system recited in claim 19 wherein the thermally conductive material comprises silicon.

23. The microfluidic system recited in claim 19 wherein the thermally conductive material comprises polished silicon.

24. The microfluidic system recited in claim 19 wherein the thermally conductive material comprises a metal.

25. The microfluidic system recited in claim 19 wherein the reaction area is located within a central portion of the array device and the fluid inlets are disposed at a periphery of the array device.

26. The microfluidic system recited in claim 25 wherein the array device is coupled with the carrier at the periphery of the array device and the thermally conductive material is coupled with a surface of the array device at the reaction area.

27. The microfluidic system recited in claim 19 further comprising means for applying a force to the thermal transfer interface to urge the thermal transfer interface towards the thermal control source.

28. The microfluidic system recited in claim 27 wherein the means for applying a force comprises a means for applying a vacuum source towards the thermal transfer interface through channels formed in a surface of a thermal control device or in the thermal transfer device.

29. The microfluidic system recited in claim 28 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 device.

30. The microfluidic system recited in claim 29 wherein the vacuum level detector is located at a position along the channel or channels distal from a location of a source of vacuum.

31. The microfluidic system recited in claim 19 further comprising an automatic control system in operable communication with a robotic control system for introducing and removing the array device from the thermal control source.