Microfabricated diffusion-based chemical sensor

• US 5,972,710 A
• Filed: 03/31/1997
• Issued: 10/26/1999
• Est. Priority Date: 03/29/1996
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Hixson, Gregory, Zebert, M. Diane, Yager, Paul, Weigl, Bernhard H., Altendorf, Eric, Kamholz, Andrew, Brody, James P., Holl, Mark R., Kenny, Margaret, Wu, Caicai, Schutte, David
• Primary Examiner(s): Snay, Jeffrey
• Application Number:
  US08/829,679
• Time in Patent Office: 939 Days
• Field of Search: 436/172, 436/177, 436/180, 436/52, 436/34, 422/81, 422/82, 422/82.08, 356/246, 356/440
• US Class Current: 436/34
• 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 inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of the analyte particles by a detectable change in property when contacted with the analyte particles, and (2) the sample stream; c) wherein the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to the substantial exclusion of the larger particles in the sample stream to form a detection area; and d) an outlet for conducting the streams out of the laminar flow channel to form a single mixed stream.

Claims

1. 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 inlets 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 width greater than about 20 microns, 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) an outlet for conducting said streams out of said laminar flow channel to form a single mixed stream.

2. The system of claim 1 also comprising a fluorescence detector for detecting changes in an indicator substance carried within said indicator stream as a result of contact with analyte particles.

3. The system of claim 1 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.

4. The channel cell system of claim 1 wherein said indicator stream comprises reporter beads.

5. 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; and

d) a v-groove channel in fluid connection with said laminar flow channel.

6. The channel cell system of claim 5 wherein said indicator stream comprises reporter beads.

7. The channel cell system of claim 5 further comprising at least one branching flow channel in fluid connection with said laminar flow channel and said v-groove channel.

8. The channel cell system of claim 7 wherein said sample stream comprises both dissolved and undissolved particles and said dissolved particles are detected in said laminar flow channel and said undissolved particles are detected in said v-groove channel.

9. 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; and

d) a sheath flow module in fluid connection with said laminar flow channel.

10. The channel cell system of claim 9 wherein said indicator stream comprises reporter beads.

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

a) a convoluted 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.

12. The channel cell system of claim 11 wherein said convoluted laminar flow channel comprises a coiled shape.

13. The channel cell system of claim 11 wherein said convoluted laminar flow channel comprises a square wave shape.

14. The channel cell system of claim 11 further comprising a v-groove channel in fluid connection with said convoluted laminar flow channel.

15. The channel cell system of claim 11 further comprising a sheath flow module in fluid connection with said convoluted laminar flow channel.

16. 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 inlets 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 width greater than about 20 microns, 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) an outlet for conducting said streams out of said laminar flow channel to form a single mixed stream; and

e) an optical analyte detection area.

17. A method of determining a kinetic rate constant for a reaction using the channel cell system of claim 16, comprising the steps of:

(a) conducting said sample stream and said indicator stream into said laminar flow channel having an inlet;

(b) allowing analyte particles to diffuse into said indicator stream to form an analyte detection area; and

(c) detecting the presence of said analyte in said indicator stream at a known distance from said inlet.

18. A channel cell system formed in a substrate plate for detecting by transmission 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;

e) at least one analyte detection area between said inlet means and said outlet means;

f) optically transparent plates sealed to both sides of said substrate plate; and

g) wherein said analyte detection area lies between said transparent plates in a space cut through the width of said substrate plate.

19. The channel cell system of claim 18 wherein said laminar flow channel lies between said transparent plates in a space cut through the width of said substrate plate.