MICROFLUIDIC DEVICE AND METHODS OF USING SAME

• US 20070004031A1
• Filed: 09/12/2006
• Published: 01/04/2007
• Est. Priority Date: 11/30/2001
• Status: Abandoned Application

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Yi, Yong, Unger, Marc, Facer, Geoffrey, Miyashita-Lin, Emily, Wienecke, Anja, Lucero, Michael, Manger, Ian
• Application Number:
  US11/531,155
• Publication Number:
  US 20070004031A1
• Time in Patent Office: Days
• US Class Current: 435/287.200
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 2219/00337 Valves
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00403 in multiple arrangements
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/06 Valves, specific forms thereof
• 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 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: C12M 1/38 Temperature-responsive control
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: F16K 11/20 operated by separate actuating members with one plug turning in another F16K11/12
• CPC Class Codes: G01N 2035/00366 : Several different temperatures used
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10T 137/2076 : Utilizing diverse fluids
• CPC Class Codes: Y10T 137/2496 : Self-proportioning or correlating systems
• CPC Class Codes: Y10T 137/86292 : System with plural openings, one a gas vent or access opening
• CPC Class Codes: Y10T 137/87249 : Multiple inlet with multiple outlet
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses.

Claims

1. The microfluidic device, comprising:

(a) a first plurality of flow channels formed in an elastomeric substrate;

(b) a second plurality of flow channels formed in the elastomeric substrate that intersect the first plurality of flow channels to define an array of reaction sites, each reaction site located at an intersection of one of the first and second flow channels; and

(c) a plurality of isolation valves disposed along the first and second plurality of flow channels and spaced between the reaction sites that can be actuated to isolate a solution within each of the reaction sites from solutions at other reaction sites, wherein the isolation valves comprise one or more control channels that each overlay and intersect one or more of the flow channels.

2. The microfluidic device of claim 1, wherein.

the first plurality of flow channels are substantially parallel to one another, and

the second plurality of flow channels are substantially parallel to one another and orthogonal to the first plurality of flow channels.

3. The microfluidic device of claim 1, wherein each of the first plurality of flow channels and each of the second plurality of flow channels comprise a separate inlet.

4. The microfluidic device of claim 1, wherein at least some of the first plurality of flow channels are in fluid communication with a first inlet and/or at least some of the second plurality of flow channels are in fluid communication with a second inlet.

7. The microfluidic device of claim 1, further comprising one or more temperature controllers, each operatively disposed to regulate temperature at one or more of the reaction sites.

8. The microfluidic device of claim 1, further comprising one or more temperature sensors, each operatively disposed to detect the temperature at one or more of the reaction sites.

9. The microfluidic device of claim 1, further comprising:

one or more temperature controllers, each operatively disposed to regulate temperature at one or more of the reaction sites; and

one or more temperature sensors, each operatively disposed to detect the temperature at one or more of the reaction sites.

11. The microfluidic device of claim 1, wherein the guard channels are present at a density of 25 channels/cm².

5. The microfluidic device, comprising:

(a) a first plurality of flow channels formed in an elastomeric substrate;

(b) a second plurality of flow channels formed in the elastomeric substrate that intersect the first plurality of flow channels to define an array of reaction sites, each reaction site located at an intersection of one of the first and second flow channels;

(c) a plurality of isolation valves disposed along the first and second plurality of flow channels and spaced between the reaction sites that can be actuated to isolate a solution within each of the reaction sites from solutions at other reaction sites, wherein the isolation valves comprise one or more control channels that each overlay and intersect one or more of the flow channels; and

(d) a plurality of guard channels overlaying one or more of the flow channels and/or one or more of the reaction sites, wherein the guard channels are sized and positioned to reduce evaporation of solution from the flow channel and/or reaction sites.

6. The microfluidic device, comprising:

(a) a first plurality of flow channels formed in an elastomeric substrate;

(b) a second plurality of flow channels formed in the elastomeric substrate that intersect the first plurality of flow channels to define an array of reaction sites, each reaction site located at an intersection of one of the first and second flow channels; and

(c) a plurality of isolation valves disposed along the first and second plurality for flow channels and spaced between the reaction sites that can be actuated to isolate a solution within each of the reaction sites from solutions at other reaction sites, wherein the isolation valves comprise one or more control channels that each overlay and intersect one or more of the flow channels;

wherein at least some of the isolation valves further comprise an elastomeric membrane that separates one of the control channels from the flow channel upon which the isolation valve operates.

10. The microfluidic device, comprising:

(a) a first plurality of flow channels formed in an elastomeric substrate;

(b) a second plurality of flow channels formed in the elastomeric substrate that intersect the first plurality of flow channels to define an array of reaction sites, each reaction site located at an intersection of one of the first and second flow channels;

(c) a plurality of isolation valves disposed along the first and second plurality of flow channels and spaced between the reaction sites that can be actuated to isolate a solution within each of the reaction sites from solutions at other reaction sites, wherein the isolation valves comprise one or more control channels that each overlay and intersect one or more of the flow channels; and

(d) a plurality of guard channels overlaying one or more of the flow channels and/or one or more of the reaction sites, wherein the guard channels are sized and positioned to reduce evaporation of solution from the flow channel and/or reaction sites;

wherein the guard channels have a cross-sectional area that is less than 50,000 μ

m².