Microfluidic free interface diffusion techniques

• US 9,643,136 B2
• Filed: 04/25/2014
• Issued: 05/09/2017
• Est. Priority Date: 04/06/2001
• Status: Expired due to Term

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Hansen, Carl L., Quake, Stephen R., Berger, James M.
• Primary Examiner(s): Kunemund, Robert M
• Application Number:
  US14/262,424
• Publication Number:
  US 20140347953A1
• Time in Patent Office: 1,110 Days
• CPC Class Codes: B01F 25/00 Flow mixers; Mixers for falling materials, e.g. solid particles centrifugal mixers B04
• CPC Class Codes: B01F 33/3039 with mixing achieved by diffusion between layers
• CPC Class Codes: B01J 2219/00355 peristaltic
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00396 Membrane valves
• CPC Class Codes: B01J 2219/00398 in multiple arrangements
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 2200/025 : Align devices or objects to ensure defined positions relative to each other
• 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 2300/0681 : Filter
• 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 2300/14 : Means for pressure control
• CPC Class Codes: B01L 2300/18 : Means for temperature control
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502769 : characterised by multiphase flow arrangements
• CPC Class Codes: B01L 7/54 : using spatial temperature gradients
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B81B 1/00 : Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: C30B 29/02 : Elements
• CPC Class Codes: C30B 7/14 : the crystallising materials being formed by chemical reactions in the solution
• CPC Class Codes: F04B 43/043 : Micropumps
• CPC Class Codes: F04B 43/14 : having plate-like flexible members
• CPC Class Codes: F16K 2099/0074 : using photolithography, e.g. etching
• CPC Class Codes: F16K 2099/0078 : using moulding or stamping
• 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 2099/0086 : Medical applications
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0015 : Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0017 : Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
• CPC Class Codes: F16K 99/0059 : actuated by a pilot fluid
• CPC Class Codes: Y10T 117/1004 : with means for measuring, testing, or sensing
• CPC Class Codes: Y10T 117/1008 : with responsive control means
• CPC Class Codes: Y10T 117/1012 : with a window or port for visual observation or examination
• CPC Class Codes: Y10T 137/0318 : Processes
• CPC Class Codes: Y10T 137/0324 : With control of flow by a condition or characteristic of a fluid
• CPC Class Codes: Y10T 137/2224 : Structure of body of device
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A static fluid and a second fluid are placed into contact along a microfluidic free interface and allowed to mix by diffusion without convective flow across the interface. In accordance with one embodiment of the present invention, the fluids are static and initially positioned on either side of a closed valve structure in a microfluidic channel having a width that is tightly constrained in at least one dimension. The valve is then opened, and no-slip layers at the sides of the microfluidic channel suppress convective mixing between the two fluids along the resulting interface. Applications for microfluidic free interfaces in accordance with embodiments of the present invention include, but are not limited to, protein crystallization studies, protein solubility studies, determination of properties of fluidics systems, and a variety of biological assays such as diffusive immunoassays, substrate turnover assays, and competitive binding assays.

Claims

1. A method of performing a chemotaxis assay on a microfluidic device, comprising:

providing a microfluidic device;

establishing a microfluidic free interface in the microfluidic device between a first static fluid having a motile cell and a second static fluid having a chemical, wherein establishing the microfluidic free interface includes exposing the motile cell to a concentration gradient of the chemical in the microfluidic device; and

detecting an activity of the motile cell.

2. The method of claim 1, wherein establishing the microfluidic free interface comprises:

i) positioning the first static fluid and the second static fluid on opposite sides of a closed valve; and

ii) opening the valve.

3. The method of claim 1, wherein the motile cell is a component of the immune system.

4. The method of claim 1, wherein the chemical elicits an immune-response.

5. The method of claim 1, wherein detecting the activity of the motile cell comprises detecting movement of the cell toward or away from the chemical.

6. The method of claim 1, wherein detecting the activity of the motile cell comprises detecting a rate of movement of the cell toward or away from the chemical.

7. The method of claim 1, further comprising suppressing convective flow of the first static fluid and the second static fluid.

8. The method of claim 2, wherein positioning the first static fluid and the second static fluid on the opposite sides of the closed valve includes:

priming a first side and a second side of a channel with a gas, wherein the first side is located opposite the closed valve from the second side;

displacing the gas from the first side and the second side with the first static fluid and the second static fluid, respectively.

9. The method of claim 8, wherein the channel includes material permeable to the gas, and wherein displacing the gas includes allowing the gas to permeate through the material of the channel.

10. The method of claim 1, wherein establishing the microfluidic free interface comprises:

introducing the first static fluid into a chamber; and

introducing the second static fluid into the chamber such that at least a portion of the first static fluid remains in the chamber to form a microfluidic free interface between the first static fluid and the second static fluid.