Microfabricated devices and methods

• US 6,454,945 B1
• Filed: 11/01/2000
• Issued: 09/24/2002
• Est. Priority Date: 06/16/1995
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Altendorf, Eric, Holl, Mark R., Hixson, Gregory, Forster, Fred K., Schutte, David, Yager, Paul, Weigl, Bernhard H., Galambos, Paul C., Kamholz, Andrew, Brody, James P., Kenny, Margaret, Zebert, Diane, Wu, Caicai
• Primary Examiner(s): Drodge, Joseph W.
• Application Number:
  US09/703,764
• Time in Patent Office: 692 Days
• Field of Search: 210/134, 210/137, 210/143, 210/198.1, 210/243, 210/511, 210/634, 210/639, 210/739, 210/748, 422/62, 422/69, 422/70, 422/81, 422/101, 422/63, 436/177, 436/178, 436/180, 436/43, 436/52, 436/53, 204/600, 209/1, 209/155, 73/617.1
• US Class Current: 210/634
• CPC Class Codes: A61M 1/14 Dialysis systems; Artificial kidneys; Blood oxygenators semi-permeable membranes characterised by the material, manufacturing processes therefor B01D71/00 ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
• CPC Class Codes: B01D 11/0492 Applications, solvents used
• CPC Class Codes: B01D 11/0496 by extraction in microfluidic devices
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

This invention provides microfabricated systems for extraction of desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers. Such diffusion-based mixing or sensing devices are preferably channel cell systems for detecting the presence and/or measuring the quantity of analyte particles in a sample stream.

Claims

1. A microfluidic system comprising:

(a) a plurality of inlets;

(b) a microfluidic flow channel in fluid communication with said inlets;

(c) at least two outlets in fluid communication with said microfluidic flow channel; and

(d) flow control means connected to all but one of said inlets and said outlets.

2. The microfluidic system of claim 1 comprising means for controlling fluid flow through each of said outlets.

3. The microfluidic system of claim 1 having two inlets.

4. The microfluidic system of claim 1 having two outlets.

5. The microfluidic system of claim 1 having at least three outlets.

6. The microfluidic system of claim 1 having at least four outlets.

7. The microfluidic system of claim 1 having at least six inlets and at least six outlets.

8. The microfluidic system of claim 1 wherein said means for controlling fluid flow are connected to all of said inlets.

9. The microfluidic system of claim 1 wherein said means for controlling fluid flow are connected to all of said outlets.

10. The microfluidic system of claim 1 wherein said means for controlling fluid flow are pressure control means.

11. The microfluidic system of claim 1 wherein said pressure control means is selected from the group consisting of include columns of water, electroendoosmotic forces, optical forces, gravitational forces and surface tension forces.

12. The microfluidic system of claim 1 wherein said flow channel contains at least a first and second fluid stream in side-by-side laminar flow.

13. The microfluidic system of claim 12 wherein particles contained in said first fluid stream diffuse into said second fluid stream within said channel.

14. A microfluldic system comprising:

(a) a plurality of inlets;

(b) a microfluidic flow channel in fluid communication with said inlets;

(c) at least three outlets in fluid communication with said microfluidic flow channel; and

(d) flow control means connected to all but one of said inlets and said outlets.

15. The system of claim 14 having at least four outlets.

16. The system of claim 14 having at least six inlets and at least six outlets.

17. The microfluidic system of claim 14 wherein said means for controlling fluid flow are connected to all of said inlets.

18. The microfluidic system of claim 14 wherein said means for controlling fluid flow are connected to all of said outlets.

19. The microfluidic system of claim 14 wherein said means for controlling fluid flow are pressure control means.

20. The microfluidic system of claim 19 wherein said pressure control means is chosen from the group consisting of columns of water, electroendoosmotic forces, optical forces, gravitational forces and surface tension forces.

21. The microfluidic system of claim 14 wherein said flow channel contains at least a first and second fluid stream in side-by-side laminar flow.

22. The microfluidic system of claim 21 wherein particles contained in said first fluid stream diffuse into said second fluid stream within said channel.

23. A method for creating a fluid interface between two or more streams flowing within a microfluidic channel comprising:

(a) providing an inlet for each of said streams in fluid communication with said inlets;

(b) providing at least two outlets in fluid communication with said microfluidic flow channel;

(c) providing flow control means at all but one of said inlets and said outlets;

(d) simultaneously flowing each of said streams through an inlet into said microfluidic flow channel;

(e) allowing said streams to flow in side-by-side laminar flow within said channel; and

(f) removing said streams through the at least two outlets.

24. The method of claim 23 wherein said streams are of equal volume.

25. The method of claim 23 wherein said streams are of equal flow rate.

26. The method of claim 23 comprising forming a fluid barrier between said streams.

27. The method of claim 26 wherein said fluid barrier is formed by flowing a greater volume of one stream than the other stream into said channel.

28. The method of claim 26 wherein the fluid barrier is formed by allowing a lesser volume of one stream that the other to exit said channel.

29. The method of claim 23 wherein said streams comprise a particle-containing stream and a particle-receiving stream, and particles contained in the particle-containing stream are allowed to diffuse into the particle-receiving stream.