Tangential flow planar microfabricated fluid filter

• US 6,387,290 B1
• Filed: 07/02/1999
• Issued: 05/14/2002
• Est. Priority Date: 06/16/1995
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Osborn, Thor D., Brody, James P.
• Primary Examiner(s): Gulakowski, Randy
• Assistant Examiner(s): KORNAKOV, MIKHAIL
• Application Number:
  US09/346,717
• Time in Patent Office: 1,047 Days
• Field of Search: 216/2, 216/41-45, 216/99, 210/433.1, 435/2
• US Class Current: 216/99
• CPC Class Codes: B01D 2323/081 Heating
• CPC Class Codes: B01D 2323/12 Specific ratios of components used
• CPC Class Codes: B01D 2323/62 Cutting the membrane
• CPC Class Codes: B01D 39/1692 Other shaped material, e.g. perforated or porous sheets
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 67/0058 by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 67/0062 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 71/0213 Silicon
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A microfilter utilizing the principles of tangential flow to prevent clogging, and sloped channel sides to overcome surface tension effects is provided which has feed inlet and exit connected by a feed flow channel; a barrier channel parallel to the feed flow channel, and a filtrate collection channel parallel to the barrier channel so that liquid can flow from the feed flow channel through the barrier channel which is too small to accommodate the particles, into the filtrate collection channel, and from then through a filtrate flow channel to a filtrate exit. Several picoliters of cell-free plasma are recovered from one drop of blood for analysis.

Claims

1. A method for making a microfilter useful for treating a feed liquid to separate liquid from particles contained therein, said method comprising:

a) providing a {100} silicon wafer;

b) etching a feed flow channel and a filtrate collection channel into the silicon wafer of step a) with an etchant capable of attacking the {100} planes of said silicon wafer to form substantially V-shaped channels; and

c) etching a barrier channel in said wafer.

2. The method of claim 1 wherein steps a), b) and c) are performed sequentially using the same etchant.

3. The method of claim 1 wherein following the etching steps, a glass lid is bonded to the etched surface of the silicon wafer.

4. The method of claim 1 wherein the etchant used is an anisotropic etchant providing a gradual widening of the channels at the inlet and exits such that flow therethrough by means of capillary action alone is facilitated.

5. A microfilter useful for treating a feed liquid to separate liquid from particles contained therein comprising the following elements formed into the surface of a horizontal substrate:

a) a feed inlet;

b) a feed exit;

c) a microfluidic feed flow channel having a minimum dimension sufficient to permit flow of the particles and liquid therethrough, disposed between and in fluid communication with the feed inlet and the feed exit;

d) a microfluidic filtrate collection channel parallel to the feed flow channel;

e) a single barrier channel parallel to, between, and in fluid communication with the feed flow channel and the filtrate collection channel;

the barrier channel having a depth sufficiently small to permit flow of the liquid therethrough but not the particles; and

f) a filtrate exit in fluid communication with the filtrate collection channel.

6. The microfilter of claim 5 also comprising a filtrate outlet channel connecting the filtrate collection channel and the filtrate exit.

7. The microfilter of claim 5 also comprising means for applying pressure to the flow of the feed liquid through the microfilter.

8. The microfilter of claim 5 having hydrophilic surfaces whereby the liquid flows through the microfilter from the feed inlet to the filtrate exit without the application of pressure.

9. The microfilter of claim 5 adapted for the separation of plasma from whole blood.

10. The microfilter of claim 5 wherein the feed flow channel and the filtrate collection channel are substantially V-shaped.

11. The microfilter of claim 6 wherein the feed flow channel, the filtrate collection channel and the filtrate outlet channel are substantially V-shaped.

12. The microfilter of claim 5 wherein the feed flow channel and the filtrate collection channel are approximately 100 microns wide.

13. The microfilter of claim 6 wherein the barrier channel has a depth of less than about 0.1 micron.

14. The microfilter of claim 5 wherein the substrate is a silicon wafer.

15. The microfilter of claim 14 wherein the channels are etched by an anisotropic etchant to provide gradual widening at the inlet and exits whereby flow therethrough by means of capillary action alone is facilitated.

16. The microfilter of claim 5 comprising a lid which comprises a glass sheet.

17. The microfilter of claim 5 adapted to separate an analyzable quantity of plasma from one microliter of blood.

18. An analytical system comprising the microfilter of claim 5 and also comprising injection means for introducing the feed liquid into the feed inlet.

19. The microfilter of claim 5 comprising means in fluid communication with the filtrate exit for detecting the presence of an analyte in the filtrate.

20. The microfilter of claim 5 wherein the width of the barrier channel is greater than or about equal to the width of the feed flow channel.

21. The microfilter of claim 20 wherein the width of the barrier channel is about equal to the width of the feed flow channel.

22. A method for recovering a quantity of liquid separated from particles from a feed liquid containing said particles comprising introducing the feed liquid into the feed inlet of the microfilter of claim 5 and withdrawing separated liquid from the filtrate exit.

23. The method of claim 22 wherein the feed liquid is blood, the particles are blood cells, and the separated liquid is plasma.

24. The method of claim 23 wherein pressure is applied to the microfilter following withdrawal of separated liquid from the filtrate exit to clear the barrier channel of particles.