Microfluidic chromatography

• US 6,752,922 B2
• Filed: 04/05/2002
• Issued: 06/22/2004
• Est. Priority Date: 04/06/2001
• Status: Expired due to Term

• Current Assignee: Standard Biotools Incorporated
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc A., Chou, Hou-Pu, Huang, Jiang
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US10/118,469
• Publication Number:
  US 20020158022A1
• Time in Patent Office: 809 Days
• Field of Search: 210/635, 210/656, 210/659, 210/198.2, 422/70, 436/161, 73/615.6
• US Class Current: 210/198.2
• CPC Class Codes: B01D 15/08 Selective adsorption, e.g. chromatography
• CPC Class Codes: G01N 2030/387 Turbulent flow of mobile phase
• CPC Class Codes: G01N 2030/521 form
• CPC Class Codes: G01N 30/6065 with varying cross section
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10T 137/86863 Rotary valve unit
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention is directed to a microfluidic chromatography apparatus comprising a microfabricated fluid delivery system and a chromatography column which is in fluid communication with the fluid delivery system, and a method for producing and using the same. Preferably, the chromatography column comprises an OTLC, PCLC, or combinations thereof.

Claims

1. A microfluidic chromatography apparatus for separating an analyte in a sample fluid comprising:

(a) a microfabricated fluid delivery system which is produced from a material comprising an elastomeric polymer, wherein said fluid deliver system comprises;

(i) a microfluidic flow channel comprising a flow channel inlet for introducing the fluid into said flow channel and a flow channel outlet,

(ii) a flow control channel,

(iii) a flow control valve comprised of a flow control elastomeric segment that is disposed in between said flow channel and said flow control channel to regulate fluid flow through said flow 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, said flow control elastomeric segment when positioned in said flow channel restricting fluid flow therethrough, and

(iv) a flow control channel actuation system operatively interconnected to said flow control channel for applying an actuation force to said flow control channel; and

(b) a chromatography column comprising;

(i) a stationary phase which is capable of separating at least a portion of the analyte from the sample fluid,

(ii) a column inlet which is in fluid communication with said flow channel outlet, and

(iii) a column outlet through which a separated fluid exits the chromatography column.

2. The microfluidic chromatography apparatus of claim 1, wherein said elastomeric polymer is selected from the group consisting of poly(carborane-siloxanes), poly(bis(fluoroalkoxy)phosphazene), poly(acrylonitrile-butadiene), poly(1-butene), poly(chlorotrifluoroethylene-vinylidene fluoride) copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride), poly(vinylidene fluoride-hexafluoropropylene) copolymer, elastomeric polyvinylchloride, polysulfone, polycarbonate, polymethylmethacrylate, polytertrafluoroethylene, polydimethylsiloxane, polydimethylsiloxane copolymer, and aliphatic urethane diacrylate.

3. The microfluidic chromatography apparatus of claim 1, wherein said fluid delivery system further comprises a peristaltic pump which is comprised of one or more of said flow control valves.

4. The microfluidic chromatography apparatus of claim 3, wherein said fluid delivery system further comprises an eluent inlet which is in fluid communication with said flow channel inlet for introducing an eluent to said flow channel.

5. The microfluidic chromatography apparatus of claim 1, wherein said chromatography column is a microfluidic chromatography device comprising a chromatography channel having an inner surface.

6. The microfluidic chromatography apparatus of claim 5, wherein said stationary phase is covalently attached to said inner surface.

7. The microfluidic chromatography apparatus of claim 5, wherein said chromatography column comprises a microfabricated rotary channel comprising:

a rotary channel inlet;

(a) a rotary channel outlet;

(b) a rotary control channel;

(c) a rotary inlet control valve comprised of an elastomeric segment of said rotary inlet control channel that is disposed in between said rotary channel inlet and said rotary 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 rotary control channel, said elastomeric segment of said rotary inlet control channel when positioned in said rotary channel inlet restricting fluid flow therethrough;

(d) a rotary outlet control valve comprised of an elastomeric segment of said rotary outlet control channel that is disposed in between said rotary channel outlet and said rotary 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 rotary control channel, said elastomeric segment of said rotary control channel outlet when positioned in said rotary channel outlet restricting fluid flow therethrough;

(e) a rotary pump valve comprised of an elastomeric segment of said rotary pump that is disposed in between said rotary channel and said rotary pump 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 rotary pump control channel, said elastomeric segment of said rotary pump when positioned in said rotary channel restricting fluid flow therethrough; and

(f) a rotary control channel actuation system operatively interconnected to said rotary control channel for applying an actuation force to said rotary control channel.

8. The microfluidic chromatography apparatus of claim 4, wherein said flow channel inlet further comprises:

a sample reservoir comprising a sample reservoir inlet channel which is in fluid communication with said flow channel;

a sample reservoir inlet control channel;

a sample reservoir inlet control valve for opening and closing fluid communication between said sample reservoir and said flow channel, wherein said sample reservoir inlet control valve comprises an elastomeric segment of said sample reservoir inlet control channel that is disposed in between said sample reservoir control channel and said sample reservoir inlet channel to regulate fluid flow through said sample reservoir inlet channel, wherein said sample reservoir inlet control valve is deflectable into or retractable from said sample reservoir inlet channel upon which said sample reservoir inlet control valve operates in response to an actuation force applied to said sample reservoir inlet control channel, said elastomeric segment of said sample reservoir inlet control channel when positioned in said sample reservoir inlet channel restricting fluid flow therethrough; and

an sample reservoir inlet control channel actuation system operatively interconnected to said sample reservoir inlet control channel for applying an actuation force to said sample reservoir inlet control channel.

9. The microfluidic chromatography apparatus of claim 4, wherein said eluent inlet further comprises:

an eluent reservoir comprising an eluent reservoir inlet channel;

an eluent reservoir inlet control channel;

an eluent reservoir inlet control valve for opening and closing fluid communication between said eluent reservoir and said flow channel, wherein said eluent reservoir inlet control valve comprises an elastomeric segment of said eluent reservoir inlet control channel that is disposed in between said eluent reservoir inlet control channel and said eluent reservoir inlet channel to regulate fluid flow through said eluent reservoir inlet channel, wherein said eluent reservoir inlet control valve is deflectable into or retractable from said eluent reservoir inlet channel upon which said eluent reservoir inlet control valve operates in response to an actuation force applied to said eluent reservoir inlet control channel, said elastomeric segment of said eluent reservoir inlet control valve when positioned in said eluent reservoir inlet channel restricting fluid flow therethrough;

an eluent reservoir inlet control channel actuation system operatively interconnected to said eluent reservoir inlet control channel for applying an actuation force to said eluent reservoir inlet control channel.

10. The microfluidic chromatography apparatus of claim 1, wherein said column outlet is in fluid communication with a sample detection system inlet.

11. The microfluidic chromatography apparatus of claim 1, wherein said chromatography column is an open tubular liquid chromatography column or a packed capillary liquid column.

12. The microfluidic chromatography apparatus of claim 1, wherein said flow channel is located on an interface between a solid substrate and the elastomeric polymer such that an inner surface of said flow channel comprises an elastomeric polymer portion and a solid substrate portion.

13. The microfluidic chromatography apparatus of claim 12, wherein the stationary phase is attached to the solid substrate portion of the flow channel inner surface.

14. The microfluidic chromatography apparatus of claim 13, wherein the elastomeric polymer portion of the flow channel inner surface comprises a surface coating that reduces a non-specific binding of the analyte.