Multilevel microfluidic systems and methods

• US 9,316,331 B2
• Filed: 11/27/2013
• Issued: 04/19/2016
• Est. Priority Date: 01/25/2005
• Status: Active Grant

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Facer, Geoffrey, Fowler, Brian, Quan, Emerson Cheung, Unger, Marc
• Primary Examiner(s): Alexander, Lyle
• Assistant Examiner(s): Wecker, Jennifer
• Application Number:
  US14/091,342
• Publication Number:
  US 20140318633A1
• Time in Patent Office: 874 Days
• US Class Current: 1/1
• CPC Class Codes: B01F 25/20 Jet mixers, i.e. mixers using high-speed fluid streams using jets to create vortex flow B01F25/10
• CPC Class Codes: B01F 33/30 Micromixers
• 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 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• 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 3/502707 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: F16K 2099/008 Multi-layer fabrications
• CPC Class Codes: F16K 2099/0084 Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0015 Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0026 Valves using channel deformation
• CPC Class Codes: F16K 99/0059 : actuated by a pilot fluid
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: Y10T 137/0329 : Mixing of plural fluids of diverse characteristics or conditions
• CPC Class Codes: Y10T 137/2164 : Plural power inputs to single device
• CPC Class Codes: Y10T 137/2169 : Intersecting at interaction region [e.g., comparator]
• CPC Class Codes: Y10T 137/2559 : Self-controlled branched flow systems
• CPC Class Codes: Y10T 137/2655 : Biased open isolation valve
• CPC Class Codes: Y10T 137/2688 : Flow rate responsive
• CPC Class Codes: Y10T 137/87249 : Multiple inlet with multiple outlet

Abstract

Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.

Claims

1. A method for reducing mixing times associated with using a microfluidic device, the method comprising:

providing a microfluidic device having a reaction cell, the reaction cell including a first chamber having a first volume and a second chamber having a second volume, the first chamber and the second chamber being in fluid communication through a reaction channel having an interface valve for controlling fluid communication between the first chamber and the second chamber, wherein said reaction channel and said interface valve are not located within the same plane or level as the first chamber and the second chamber;

introducing a first material into the first chamber so as to pressurize the first material in the first chamber to a first pressure;

introducing a second material into the second chamber so as to pressurize the second material in the second chamber to a second pressure; and

mixing first material from the first chamber with second material from the second chamber by opening the interface valve, wherein the first pressure and the second pressure are sufficiently different to cause the mixing.

2. The method of claim 1 wherein the first material is expelled from the first chamber and into the second chamber.

3. The method of claim 1, wherein the first pressure is greater than the second pressure.

4. The method of claim 3, wherein the first pressure is about 10 psi and the second pressure is about 0 psi.

5. The method of claim 1 wherein the first chamber has a dimension between 1000 μ

m and 1 μ

m and the second chamber has a dimension between 1000 μ

m and 1 μ

m.

6. The method of claim 5 wherein the second chamber is smaller than first chamber.

7. The method of claim 1 wherein the second material comprises patient DNA and the first material comprises an oligonucleotide primer and probe set.

8. The method of claim 1, wherein the second chamber or first chamber has a volume within a range from about 0.1 nanoliters to about 10 nanoliters.

9. The method of claim 1, wherein the second chamber or first chamber has a volume within a range from about 1 nanoliters to about 20 nanoliters.

10. The method of claim 6, wherein the second chamber has a volume within a range from about 0.1 nanoliters to about 10 nanoliters and the first chamber has a volume within a range from about 1 nanoliters to about 20 nanoliters.

11. The method of claim 1, wherein a center-to-center distance between the first chamber and the second chamber is 250 μ

m to 350 μ

m.

12. The method of claim 1, wherein the first material is an assay reagent and the second material is an assay sample.