Microfluidic free interface diffusion techniques

• US 8,021,480 B2
• Filed: 04/16/2010
• Issued: 09/20/2011
• Est. Priority Date: 04/06/2001
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Original Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Inventors: Berger, James M., Quake, Stephen R., Hansen, Carl L.
• Primary Examiner(s): Kunemund; Robert M
• Application Number:
  US12/762,170
• Publication Number:
  US 20100263732A1
• Time in Patent Office: 522 Days
• Field of Search: 117/68, 117/69, 117/70
• US Class Current: 117/68
• 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 mixing two fluids comprising:

providing a first static fluid having a total volume;

providing a second static fluid having a total volume;

disposing a portion of the first static fluid in contact with a portion of the second static fluid to form a fluidic interface, such that a minimum volume of the first and second fluids is exposed to a steepest concentration gradient present immediately along the fluidic interface.

2. The method of claim 1 wherein portions of the first and second fluids along the interface are restricted by a dimension of a microfluidic flow channel.

3. The method of claim 2 wherein the first fluid is positioned in a first chamber, the second fluid is positioned in a second chamber, and the microfluidic flow channel connects the chambers, such that a ratio of a cross-sectional area of the first chamber to a cross-sectional area of the microfluidic flow channel is between 500 and 25,000.

4. The method of claim 1 wherein the first static fluid and the second static fluid are maintained at different temperatures.

5. The method of claim 1 wherein the minimum volume is between 1 aL to 1 uL.

6. The method of claim 1 wherein the minimum volume is between 100 aL to 100 nL.

7. The method of claim 1 wherein the minimum volume is between 1 fL to 10 nL.

8. The method of claim 1 wherein the minimum volume is between 100 fL to 1 nL.

9. The method of claim 1 wherein the minimum volume is between and 1 pL to 100 pL.

10. The method of claim 1 further comprising opening a valve to form the fluidic interface.

11. The method of claim 1 further comprising providing an elastomeric device to contain the first and second static fluids.

12. The method of claim 1 wherein providing at least the first or second static fluid comprises blind filing a fluid up to a valve.

13. The method of claim 1 further comprising utilizing a break-through value to form the fluidic interface.

14. The method of claim 1 wherein the first fluid and the second fluid are positioned in a channel, the first fluid is positioned on a first side of the channel and the second fluid is positioned on a second side of the channel with a valve positioned between the first and second sides.

15. The method of claim 14 further comprising utilizing one or more control channels overlapping at least a portion of the first side or the second side of the channel to create a plurality of chambers within the channel.

16. The method of claim 1 wherein total volume of the first static is greater than the total volume of the second static fluid.

17. The method of claim 16 wherein a ratio of the total volume of the first static to the total volume of the second static fluid is between 2 and 10.

18. The method of claim 2 wherein the dimension of the microfluidic flow channel is a width dimension of the microfluidic flow channel.