Microfluidic sample separation device

• US 20020164816A1
• Filed: 04/05/2002
• Published: 11/07/2002
• Est. Priority Date: 04/06/2001
• Status: Abandoned Application

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Quake, Stephen R.
• Application Number:
  US10/118,461
• Publication Number:
  US 20020164816A1
• Time in Patent Office: Days
• US Class Current: 436/161
• CPC Class Codes: G01N 2030/205 Diaphragm valves, e.g. deformed member closing the passage
• CPC Class Codes: G01N 2030/565 slurry packing
• CPC Class Codes: G01N 30/38 Flow patterns
• CPC Class Codes: G01N 30/44 using recycling of the fraction to be distributed
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10T 436/25 including sample preparation
• 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 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention provides microfluidic chromatography devices for separating an analyte from a sample solution, and methods for producing and using the same. In particular, the present invention relates to microfluidic devices which comprise a microfabricated flow channel and a material delivery system for transporting a material through the flow channel. The flow channel comprises a chromatography column portion having a solid stationary phase which is capable of separating at least a portion of the analyte from the sample solution.

Claims

1. A microfluidic device for separating an analyte from a sample fluid comprising:

(a) a microfabricated flow channel comprising;

(i) an inlet for introducing a material into said flow channel;

(ii) an outlet for removing the material from said flow channel;

(iii) a chromatography column portion located within said flow channel and in between the inlet and the outlet, and

(iv) a solid stationary phase within at least a portion of said chromatography column portion, wherein said solid stationary phase is capable of separating at least a portion of an analyte from a sample fluid; and

(b) a flow control system for regulating fluid flow through said flow channel.

2. The microfluidic device of claim 1, wherein said device is produced from a material comprising an elastomeric polymer.

3. The microfluidic device of claim 2, wherein said flow control system comprises:

(i) a flow control channel;

(ii) a flow control valve comprised of an elastomeric segment that is disposed in between said flow channel and said flow control channel, wherein said flow control valve is deflectable into or retractable from said flow channel upon which said flow control valve operates in response to an actuation force applied to said flow control channel, the elastomeric segment when positioned in said flow channel restricting fluid flow therethrough, and

(iii) a flow control channel actuation system operatively interconnected to said flow control channel for applying the actuation force to said flow control channel.

4. The microfluidic device of claim 3 further comprising:

a solid stationary phase inlet in fluid communication with said flow channel for introducing said solid stationary phase into said chromatography column portion;

a solid stationary phase inlet channel interconnecting said solid stationary phase inlet and said flow channel; and

a solid stationary phase inlet control valve comprised of an elastomeric segment that is disposed in between said solid stationary phase inlet channel and said control channel to regulate flow of solid stationary phase through said solid stationary phase inlet channel, wherein said solid stationary phase inlet control valve is deflectable into or retractable from said solid stationary phase inlet channel upon which said solid stationary phase inlet control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said solid stationary phase inlet control valve when positioned in said solid stationary phase inlet channel restricting flow of solid stationary phase material therethrough.

5. The microfluidic device of claim 3 further comprising:

a solid stationary phase reservoir in fluid communication with said flow channel for storing the solid stationary phase material; and

a solid stationary phase reservoir control valve comprised of an elastomeric segment that is disposed in between said solid stationary phase reservoir and said control channel to regulate flow of solid stationary phase into said flow channel, wherein said solid stationary phase reservoir control valve is deflectable into or retractable from said flow channel upon which said solid stationary phase reservoir control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said solid stationary phase reservoir control valve when positioned in said flow channel restricting flow of solid stationary phase material therethrough.

6. The microfluidic device of claim 4 further comprising:

an excess solid stationary phase outlet located downstream from said chromatography column portion and in fluid communication with said flow channel for removing any excess solid stationary phase flowing out of said chromatography column portion; and

an excess solid stationary phase outlet control valve comprised of an elastomeric segment that is disposed in between said excess solid stationary phase outlet and said control channel to regulate flow of solid stationary phase from said chromatography column portion to said excess solid stationary phase outlet, wherein said excess solid stationary phase outlet control valve is deflectable into or retractable from said flow channel upon which said excess solid stationary phase outlet control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said excess solid stationary phase outlet control valve when positioned in said flow channel restricting flow of excess solid stationary phase material therethrough.

7. The microfluidic device of claim 1 further comprising a sample reservoir located upstream from said chromatography column portion and in fluid communication with said flow channel.

8. The microfluidic device of claim 3 further comprising:

a sample inlet control valve comprised of an elastomeric segment that is disposed in between said inlet and said control channel to regulate flow of the sample into said flow channel, wherein said sample inlet control valve is deflectable into or retractable from said flow channel upon which said sample inlet control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said sample inlet control valve when positioned in said flow channel restricting sample flow therethrough.

9. The microfluidic device of claim 3 further comprising:

an eluent inlet located upstream from said chromatography column portion and in fluid communication with said flow channel for introducing an eluent into said chromatography column portion; and

an eluent inlet control valve comprised of an elastomeric segment that is disposed in between said eluent inlet and said control channel to regulate flow of the eluent into said flow channel, wherein said eluent inlet control valve is deflectable into or retractable from said flow channel upon which said eluent inlet control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said eluent inlet control valve when positioned in said flow channel restricting eluent flow therethrough.

10. The microfluidic device of claim 3 further comprising an eluent reservoir located upstream from said chromatography column portion and in fluid communication with said flow channel.

11. The microfluidic device of claim 1, wherein said microfabricated flow channel comprises a plurality of said chromatography column portions.

12. The microfluidic device of claim 1, wherein the distal end of said chromatography column portion is tapered for preventing or reducing the amount of solid stationary phase from flowing out of said chromatography column portion.

13. The microfluidic device of claim 3, wherein said chromatography column portion comprises a microfabricated rotary channel in fluid communication with said flow channel, wherein said rotary channel comprises:

a rotary channel inlet;

a rotary channel outlet;

a rotary inlet control valve comprised of an elastomeric segment disposed in between said rotary channel inlet and said control channel to regulate fluid flow into said rotary channel, wherein said rotary inlet control valve is deflectable into or retractable from said rotary channel inlet upon which said rotary inlet control valve operates in response to an actuation force applied to said control channel, said elastomeric segment of said rotary inlet control valve when positioned in said rotary channel inlet restricting fluid flow therethrough;

a rotary outlet control valve comprised of an elastomeric segment disposed in between said rotary channel outlet and said control channel to regulate fluid flow out of said rotary channel, wherein said rotary outlet control valve is deflectable into or retractable from said rotary channel outlet upon which said rotary outlet control valve operates in response to an actuation force applied to said control channel, said elastomeric segment of said rotary control channel outlet valve when positioned in said rotary channel outlet restricting fluid flow therethrough; and

a rotary pump valve comprised of an elastomeric segment disposed in between said rotary channel and said control channel to regulate fluid flow through said rotary channel, wherein said rotary pump valve is deflectable into or retractable from said rotary channel upon which said rotary pump valve operates in response to an actuation force applied to said control channel, said elastomeric segment of said rotary pump valve when positioned in said rotary channel restricting fluid flow therethrough.

15. The method of claim 14, wherein said microfluidic device is produced from a material comprising an elastomeric polymer.

16. The method of claim 15, wherein the flow control system comprises:

(i) a flow control channel;

(ii) a flow control valve comprised of an elastomeric segment that is disposed in between the flow channel and the flow control channel, wherein the flow control valve is deflectable into or retractable from the flow channel upon which the flow control valve operates in response to an actuation force applied to the flow control channel, the elastomeric segment when positioned in the flow channel restricting fluid flow therethrough, and

(iii) a flow control channel actuation system operatively interconnected to the flow control channel for applying the actuation force to the flow control channel.

17. The method of claim 16, wherein the sample solution is eluted through the chromatography column by actuating the one or more of the control control channels.

18. The method of claim 16 further comprising placing the solid stationary phase into the chromatography column portion prior to introducing the sample solution into the chromatography column portion.

19. The method of claim 18, wherein the solid stationary phase is placed into the chromatography column portion using the flow control system.

20. The method of claim 18, wherein the microfluidic device further comprises:

a solid stationary phase inlet in fluid communication with said flow channel for introducing said solid stationary phase into said chromatography column portion;

a solid stationary phase inlet channel interconnecting said solid stationary phase inlet and said flow channel;

a solid stationary phase inlet control valve comprised of an elastomeric segment that is disposed in between said solid stationary phase inlet channel and said control channel to regulate flow of solid stationary phase through said solid stationary phase inlet channel, wherein said solid stationary phase inlet control valve is deflectable into or retractable from said solid stationary phase inlet channel upon which said solid stationary phase inlet control valve operates in response to an actuation force applied to said control channel, the elastomeric segment of said solid stationary phase inlet control valve when positioned in said solid stationary phase inlet channel restricting flow of solid stationary phase material therethrough.

21. The method of claim 16, wherein the chromatography column portion comprises a microfabricated rotary channel in fluid communication with the flow channel, wherein the rotary channel comprises:

a rotary channel inlet;

a rotary channel outlet;

a rotary inlet control valve comprised of an elastomeric segment disposed in between the rotary channel inlet and the control channel to regulate fluid flow into the rotary channel, wherein the rotary inlet control valve is deflectable into or retractable from the rotary channel inlet upon which the rotary inlet control valve operates in response to an actuation force applied to the control channel, the elastomeric segment of the rotary inlet control valve when positioned in the rotary channel inlet restricting fluid flow therethrough;

a rotary outlet control valve comprised of an elastomeric segment disposed in between the rotary channel outlet and the control channel to regulate fluid flow out of the rotary channel, wherein the rotary outlet control valve is deflectable into or retractable from the rotary channel outlet upon which the rotary outlet control valve operates in response to an actuation force applied to the control channel, the elastomeric segment of the rotary control channel outlet valve when positioned in the rotary channel outlet restricting fluid flow therethrough; and

a rotary pump valve comprised of an elastomeric segment disposed in between the rotary channel and the control channel to regulate fluid flow through the rotary channel, wherein the rotary pump valve is deflectable into or retractable from the rotary channel upon which the rotary pump valve operates in response to an actuation force applied to the control channel, the elastomeric segment of the rotary pump valve when positioned in the rotary channel restricting fluid flow therethrough.

22. The method of claim 21 further comprising:

introducing the sample solution into the rotary channel;

eluting a first eluent through the rotary channel to removed materials that are not bound to the solid stationary phase that is present within the rotary channel; and

eluting a second eluent through the rotary channel to removed materials that were bound to the solid stationary phase.

23. The method of claim 22 further comprising actuating both of the a rotary outlet control valve and the rotary inlet control valve after introducing the sample solution into the rotary channel and circulating the sample solution through the rotary channel prior to said step of eluting with the first eluent.

24. The method of claim 22 further comprising actuating both of the rotary outlet control valve and the rotary inlet control valve after introducing the second eluent into the rotary channel and circulating the second eluent through the rotary channel prior to removing the material from the rotary channel.

14. A method for separating an analyte from a sample solution, said method comprising the steps of:

(a) introducing a sample solution into a microfluidic device comprising;

(i) a microfabricated flow channel comprising;

(A) an inlet for introducing a material into said flow channel;

(B) an outlet for removing the material from said flow channel;

(C) a chromatography column portion located within said flow channel and in between the inlet and the outlet, and

(D) a solid stationary phase within at least a portion of said chromatography column portion, wherein said solid stationary phase is capable of separating at least a portion of an analyte from a sample fluid; and

(ii) a flow control system for regulating fluid flow through said flow channel; and

(b) eluting the sample solution through the chromatography column portion with an eluent using the flow control system, whereby at least a portion of the analyte is separated from the sample solution.