Microfabricated diffusion-based chemical sensor

• US 5,716,852 A
• Filed: 03/29/1996
• Issued: 02/10/1998
• Est. Priority Date: 03/29/1996
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Brody, James P, Yager, Paul, Weigl, Bernhard H., Holl, Mark R.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US08/625,808
• Time in Patent Office: 683 Days
• Field of Search: 436/172, 436/177, 436/180, 436/52, 422/81, 422/82, 422/82.08
• US Class Current: 436/172
• CPC Class Codes: B01F 25/31 in conduits or tubes through which the main component flows
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3039 with mixing achieved by diffusion between layers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 30/0005 Field flow fractionation
• CPC Class Codes: G01N 30/38 Flow patterns
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J
• CPC Class Codes: G01N 35/085 : Flow Injection Analysis
• CPC Class Codes: Y10S 366/01 : Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream; c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area; and d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

Claims

1. A method for detecting the presence of analyte particles in a sample stream also comprising larger particles comprising:

a) conducting said sample stream into a laminar flow channel;

b) conducting an indicator stream into said laminar flow channel, whereby said sample stream and said indicator stream flow in adjacent laminar streams in said channel;

c) allowing analyte particles to diffuse into said indicator stream;

d) detecting the presence of analyte particles in said indicator stream.

2. The method of claim 1 wherein said indicator and sample streams are liquid streams.

3. The method of claim 1 wherein said indicator stream comprises an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with particles of said analyte, and said detecting step comprises detecting a change in property of said indicator substance.

4. The method of claim 3 wherein said indicator substance is immobilized on a particulate substrate carried within said indicator stream.

5. The method of claim 3 wherein said indicator substance is a substance which changes in fluorescence in the presence of said analyte particles.

6. The method of claim 3 wherein said indicator substance is sensitive not only to said analyte particles, but also to particles in said sample stream larger than said analyte particles.

7. The method of claim 1 wherein comprising conducting multiple sample streams into laminar flow in said flow channel.

8. The method of claim 1 comprising conducting multiple indicator streams into laminar flow in said flow channel.

9. The method of claim 1 comprising also conducting reference or calibration streams into laminar flow in said flow channel.

10. The method of claim 1 wherein specimen streams are conducted from the indicator stream at successive intervals along the length of said laminar flow channel and changes in the indicator stream measured in each specimen stream and compared with the changes measured in each other specimen stream, whereby concentration of the analyte in the sample stream is determinable.

11. The method of claim 1 wherein analyte concentration in said sample stream is determined within at most about three seconds.

12. A channel cell system for detecting the presence of analyte particles in a sample stream also comprising larger particles comprising:

a) a laminar flow channel;

b) at least two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream and (2) said sample stream;

c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area;

d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

13. The system of claim 12 wherein said indicator stream comprises an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles.

14. The system of claim 12 also comprising external detecting means for detecting changes in the indicator stream as a result of contact with analyte particles.

15. The system of claim 14 wherein said external detection means comprise a fluorescence detector.

16. The system of claim 13 comprising an analyte stream comprising a liquid carrier and substrate particles on which said indicator substance is immobilized in a liquid carrier introduced into one of said inlet means.

17. The system of claim 12 comprising means for conducting specimen streams from the indicator stream at successive intervals along the length of said laminar flow channel and means for measuring signals from the indicator stream in each specimen stream whereby concentration of the analyte in the sample stream may be determined.

18. A system for detecting the presence of particles of an analyte in a liquid sample stream also comprising larger particles, said system comprising a channel cell fabricated by etching channel grooves in the form of a "T" or a "Y" having a central trunk and two branches into the surface of a silicon microchip and covering said grooves with glass, said channel cell comprising:

a) a laminar flow channel formed of the trunk of said "T" or "Y";

b) two inlet means comprising branches of said "T" or "Y" in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream comprising an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream;

c) wherein said laminar flow channel has a depth sufficiently small such that parallel laminar flow of said streams occurs therein, and a length sufficient that particles of said analyte diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area, and said indicator and sample streams reach equilibrium within said laminar flow channel;

d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

19. The system of claim 18 also comprising channel means for conducting specimen streams from the indicator stream at successive intervals along the length of said laminar flow channel and viewport means for measuring signals from the indicator substance in each specimen stream whereby concentration of the analyte in the sample stream is determinable.