Microfluidic devices and methods of using same

• US 7,476,363 B2
• Filed: 05/02/2004
• Issued: 01/13/2009
• Est. Priority Date: 04/03/2003
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc, Quan, Emerson, Huang, Jiang
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Levkovich; Natalia
• Application Number:
  US10/837,885
• Publication Number:
  US 20050084421A1
• Time in Patent Office: 1,717 Days
• Field of Search: 422/100, 422/102, 422/103
• US Class Current: 422/504
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 3/00 Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
• CPC Class Codes: B01L 3/0248 Prongs, quill pen type dispenser
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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 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: C12Q 1/686 Polymerase chain reaction [PCR]

Abstract

An M×N matrix microfluidic device for performing a matrix of reactions, the device having a plurality of reaction cells in communication with one of either a sample inlet or a reagent inlet through a via formed within an elastomeric block of the device. Methods provided include a method for forming vias in parallel in an elastomeric layer of an elastomeric block of a microfluidic device, the method comprising using patterned photoresist masks and etching reagents to etch away regions or portions of an elastomeric layer of the elastomeric block.

Claims

1. A microfluicic device for reacting a plurality of different samples with a plurality of different reagents comprising:

a) a first layer;

b) a second layer;

c) a plurality of reaction cells located in said second layer;

wherein each reaction cell comprises;

i) a first chamber located in the second layer; and

ii) a second chamber located in the second layer connected to the first chamber via an interface channel;

iii) a first valve in said interface channel between said first chamber and said second chamber that, when actuated, fluidically isolates said first chamber and said second chamber from each other;

wherein each said first chamber is in fluid communication with a first fluid channel located in said second layer, each said first fluid channel is in fluid communication with a plurality of first chambers, and each said first fluid channel is in fluid communication with a corresponding fluid inlet through which solution can be introduced into said channel;

wherein each said second chamber is in fluid communication with a second fluid channel that traverses an interface between said first and second layers; and

wherein a plurality of said second fluid channels are in fluid communication with a corresponding third fluid channel, and each said third fluid channel is located in said first layer and is in fluidic communication with a corresponding fluid inlet through which solution can be introduced into said channel.

2. The device of claim 1 wherein said reaction cells are formed within an elastomeric block formed from a plurality of layers bonded together and said valve is a deflectable membrane.

3. The device of claim 1 comprising a plurality of first containment valves and a plurality of second containment valves, wherein for each reaction cell

said first chamber is associated with a first containment valve that, when actuated, fluidically isolates said first chamber form a first fluid channel;

said second chamber is associated with a second containment valve that, when actuated, fluidically isolates said second chamber from a second fluid channel; and

said first and second containment valves are controlled by a common control channel.

4. A microfluidic device for reacting M number of different samples with N number of different reagents comprising:

a first layer and a second layer;

a plurality of reaction cells in the second layer, each reaction cell comprising a first chamber and a second chamber, said first chamber and said second chamber being in fluid communication through an interface channel having an interface valve associated therewith for controlling fluid communication between said first chamber and said second chamber;

a set of inlets denoted first chamber inlets, wherein each first chamber inlet is in fluid communication with a first chamber and through which solution can be introduced into said device and into said first chamber through a via connecting said first layer to said second layer; and

a set of inlets denoted second chamber inlets through which solution can be introduced into said device and into said second chamber;

wherein each said first channel inlet is in communication with said first chamber through a first channel and each said second channel inlet is in fluid communication with said second chamber through a second channel, a portion of said first channel and a portion of said second channel being oriented parallel to each other and each having a containment valve associated therewith for controlling fluid communication therethrough, wherein said valve associated with said first channel and said valve associated with said second channel are in operable communication with each other through a common containment control channel.

5. The microfluidic device of claim 4 wherein said reaction cells are formed within an elastomeric block formed from a plurality of layers bonded together and said interface valve is a deflectable membrane.

6. The microfluidic device of claim 4 wherein said containment common control channel located along a line normal to one of said first channel or said second channel.

7. The microfluidic device of claim 4 formed from polydimethylsiloxane (PDMS).

8. The microfluidic device of claim 4 that comprises at least 1000 reaction cells.

9. A microfluidic device for reacting a plurality of different samples with a plurality of different reagents comprising:

a) a first layer;

b) a second layer;

c) a plurality of reaction cells located in said second layer;

wherein each reaction cell comprises;

i) a first chamber located in the second layer;

ii) a second chamber located in the second layer connected to the first chamber via an interface channel;

iii) a first valve in said interface channel between said first chamber and said second chamber that, when actuated, fluidically isolates said first chamber and said second chamber from each other;

wherein each said first chamber is in fluid communication with a first fluid channel located in said second layer, each said first fluid channel is in fluid communication with a plurality of first chambers, and each said first fluid channel is in fluid communication with a corresponding fluid inlet through which solution can be introduced into said channel;

wherein each said second chamber is in fluid communication with a second fluid channel connecting said second chamber in said second layer with a third fluid channel in said first layer and wherein a plurality of said second fluid channels are in fluid communication with a corresponding third fluid channel, and each said third fluid channel is located in said first layer and is in fluidic communication with a corresponding fluid inlet through which solution can be introduced into said channel.

10. The device of claim 9 wherein said reaction cells are formed within an elastomeric block formed from a plurality of layers bonded together and said valve is a deflectable membrane.

11. The device of claim 9 comprising a plurality of first containment valves and a plurality of second containment valves, wherein for each reaction cell said first chamber is associated with a first containment valve that, when actuated, fluidically isolates said first chamber from a first fluid channel;

said second chamber is associated with a second containment valve that, when actuated, fluidically isolates said second chamber from a second fluid channel; and

said first and second containment valves are controlled by a common control channel.