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

• US 8,105,824 B2
• Filed: 01/10/2011
• Issued: 01/31/2012
• Est. Priority Date: 01/25/2004
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Facer, Geoffrey, Grossman, Robert, Unger, Marc, Lam, Phillip, Chou, Hou-Pu, Kimball, Jake, Pieprzyk, Martin, Daridon, Antoine
• Primary Examiner(s): Marcheschi, Michael
• Assistant Examiner(s): Doe, Shanta G
• Application Number:
  US12/987,787
• Publication Number:
  US 20110265304A1
• Time in Patent Office: 386 Days
• Field of Search: 4352871-2873, 435/288.4, 435/303.1
• US Class Current: 435/303.1
• 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 operating a carrier for holding a microfluidic device comprising:

(a) providing the carrier for holding the microfluidic device, wherein the carrier comprises;

a non-elastomeric substrate comprising a plurality of wells, wherein each of the plurality of wells has a well opening with a center point and the plurality of wells is spatially arranged such that the center point to center point spacing is about 4.5 mm;

a plurality of channels within the substrate wherein each of the plurality of wells is in fluid communication with at least one of the plurality of channels; and

a receiving portion on the non-elastomeric substrate for receiving the microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells, wherein the microfluidic device comprises an elastomeric material;

(b) providing the microfluidic device, the microfluidic device comprising a chamber wherein the chamber is coupled to a well through a channel in the substrate;

(c) providing a platen with an interface plate comprising one or more ports;

(d) introducing a reagent into at least one of the wells;

(e) urging the platen against an upper face of the substrate to form a pressure cavity;

(f) applying a pressure to at least one of the one or more ports; and

(g) driving fluid from the well containing the reagent into the chamber in the microfluidic device.

2. The method of claim 1 wherein the pressure is between about 1 and about 35 psi.

3. A method of operating a carrier for holding a microfluidic device comprising:

(a) providing the carrier for holding the microfluidic device, wherein the carrier comprises;

a non-elastomeric substrate comprising a plurality of wells, wherein each of the plurality of wells has a well opening with a center point and the plurality of wells is spatially arranged such that the center point to center point spacing is about 4.5 mm;

a plurality of channels within the substrate wherein each of the plurality of wells is in fluid communication with at least one of the plurality of channels; and

a receiving portion on the non-elastomeric substrate for receiving the microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells, wherein the microfluidic device comprises an elastomeric material;

(b) providing the microfluidic device comprising a chamber and a valve wherein the chamber is coupled to a well through a channel in the substrate and wherein the valve is coupled to an accumulator through a channel in the substrate;

(c) providing a platen with an interface plate comprising more than one port,

(d) introducing a reagent into at least one of the wells,

(e) urging the platen against an upper face of the substrate to form a pressure cavity,

(f) applying a pressure to a first port,

(g) driving fluid from the well containing the reagent into the chamber in the microfluidic device, and

(h) applying a pressure a second port to apply a pressure to the accumulator.

4. The method of claim 3 wherein the pressure is between about 1 and about 35 psi.

5. A method of operating a carrier for holding a microfluidic device comprising:

(a) providing the carrier for holding the microfluidic device, wherein the carrier comprises;

a non-elastomeric substrate comprising a plurality of wells, wherein each of the plurality of wells has a well opening with a center point and the plurality of wells is spatially arranged such that the center point to center point spacing is about 4.5 mm;

a plurality of channels within the substrate wherein each of the plurality of wells is in fluid communication with at least one of the plurality of channels; and

a receiving portion on the non-elastomeric substrate for receiving the microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells, wherein the microfluidic device comprises an elastomeric material;

(b) providing the microfluidic device comprising a chamber and a valve wherein the chamber is coupled to a well through a channel in the substrate and wherein the valve is coupled to an accumulator through a channel in the substrate;

(c) providing a platen with an interface plate comprising one or more ports,

(d) introducing a reagent into at least one of the wells,

(e) urging the platen against an upper face of the substrate to form a pressure cavity,

(f) applying a pressure to at least one of the one or more ports,

(g) driving fluid from the well containing the reagent into the chamber in the microfluidic device, and

(h) releasing a pressure in the accumulator.

6. A method of operating a carrier for holding a microfluidic device comprising:

(a) providing the carrier for holding the microfluidic device, wherein the carrier comprises;

a non-elastomeric substrate comprising a plurality of wells, wherein each of the plurality of wells has a well opening with a center point and the plurality of wells is spatially arranged such that the center point to center point spacing is about 4.5 mm;

a plurality of channels within the substrate wherein each of the plurality of wells is in fluid communication with at least one of the plurality of channels;

a pressure accumulator; and

a receiving portion on the non-elastomeric substrate for receiving the microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells, wherein the receiving portion comprises a thermal control device and the microfluidic device comprises an elastomeric material;

(b) providing the microfluidic device, the microfluidic device comprising a chamber and a valve wherein the chamber is coupled to a well through a channel in the substrate and wherein the valve is coupled to the accumulator through a channel in the substrate,

(c) providing a platen with an interface plate comprising more than one port,

(d) providing a thermal control source,

(e) introducing a reagent into at least one of the wells,

(f) urging the platen against an upper face of the substrate to form a pressure cavity,

(g) applying a pressure to a first port,

(h) driving fluid from the well containing the reagent into a chamber in the microfluidic device,

(i) applying a pressure to a second port to apply a pressure in an accumulator, and

(j) placing the thermal control device in thermal communication with the thermal control source so that a temperature in the chamber is changed as a result of a change in temperature of the thermal control source.

7. The method of claim 6 wherein the pressure is between about 1 and about 35 psi.