Microfluidic chromatography

• US 7,217,367 B2
• Filed: 06/21/2004
• Issued: 05/15/2007
• Est. Priority Date: 04/06/2001
• Status: Expired due to Fees

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Unger, Marc A., Chou, Hou-Pu, Huang, Jiang
• Primary Examiner(s): Therkorn; Ernest G.
• Application Number:
  US10/874,103
• Publication Number:
  US 20050000900A1
• Time in Patent Office: 1,058 Days
• Field of Search: 210/635, 210/656, 210/659, 210/198.2, 422/70, 436/161, 73/615.6, 137/625.46
• US Class Current: 210/656
• 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 method for producing a microfluidic chromatography apparatus comprising:

(a) producing a microfabricated fluid delivery system from a material comprising an elastomeric polymer, wherein the fluid delivery 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;

(b) producing a microfabricated rotary channel comprising;

a rotary channel inlet;

a rotary channel outlet;

a rotary control channel;

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;

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;

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

a rotary control channel actuation system operatively interconnected to said rotary control channel for applying an actuation force to said rotary control channel;

(c) microfabricating a chromatography column which comprises a column inlet, a column outlet, and a chromatography channel having an inner surface which comprises a functional group;

(d) attaching a stationary phase compound capable of separating at least a portion of an analyte in the fluid to at least a portion of the inner surface by reacting the stationary phase compound with the functional group under conditions sufficient to form a covalent bond between the functional group and the stationary phase compound; and

(e) connecting the fluid delivery system to the chromatography column such that the column inlet is in fluid communication with the flow channel outlet.

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

3. The method of claim 2, wherein the stationary phase is attached to the solid substrate portion of the flow channel inner surface.

4. The method of claim 3, wherein the elastomeric polymer portion of the flow channel inner surface comprises a surface coating that reduces a non-specific binding of the analyte.

5. The method of claim 1, wherein the functional group is silane.

6. The method of claim 5, wherein the stationary phase compound is 1-octadecene.

7. The method of claim 1 wherein the functional group comprises an active functional group.

8. The method of claim 1 wherein the functional group is selected from the group consisting of alkene, isocyanate, epoxide, and hydroxyl.

9. The method of claim 1 wherein the stationary phase compound is in the form of a solution in an inert solvent.

10. The method of claim 9 wherein:

the functional group is a silane; and

the inert solvent is selected from the group consisting of a hydrocarbon, ethyl ether, tetrahydrofuran, dimethoxyethane, dimethyl formaldehyde, chloroform, dichloromethane, toluene, and xylene.

11. The method of claim 1 wherein the stationary phase compound is selected from the group consisting of 1-octodecanol, octadecylsilane, octadecyltrichlorosilane, octadecyl isocyanate, and trioctedecylsilane.

12. The method of claim 1 wherein the 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.

13. The method of claim 1 wherein the microfluidic flow channel has a width less than 1000 μ

m.

14. The method of claim 1 wherein the microfluidic flow channel has a width between 10 and 200 μ

m.

15. The method of claim 1 wherein the control channel has a width less than 1000 μ

m.

16. The method of claim 1 wherein the control channel has a width between 10 and 200 μ

m.

17. The method of claim 1 wherein the microfluidic channel has a width-to-depth ratio between 3:

1 and 15;

1.

18. The method of claim 1 wherein the control channel has a width-to-depth ratio between 3:

1 and 15;

1.

19. The method of claim 1 wherein the fluid delivery system further comprises an eluent inlet in fluid communication with the flow channel for introducing an eluent to the flow channel.