Microanalytical device and use thereof for conducting chemical processes

• US 6,635,226 B1
• Filed: 02/11/2000
• Issued: 10/21/2003
• Est. Priority Date: 10/19/1994
• Status: Expired due to Term

• Current Assignee: Agilent Technologies Europe BV (Agilent Technologies, Inc.)
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Wolber, Paul K, Swedberg, Sally A., Tso, Jacqueline
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US09/502,593
• Time in Patent Office: 1,348 Days
• Field of Search: 422/129, 422/198, 422/199, 422/307, 435/283.1
• US Class Current: 422/129
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/54 using spatial temperature gradients
• CPC Class Codes: B29C 65/00 Joining or sealing of preformed parts , e.g. welding of plastics materials; Apparatus therefor general aspects of processes or apparatus for joining preformed parts B29C66/00; using porous material formed by internal pressure generated therein for joining preformed parts B29C44/1228, B29C44/326
• CPC Class Codes: B29C 66/549 said hollow-preforms being interconnected during their moulding process, e.g. by a hinge
• CPC Class Codes: G01N 2030/0035 electrical field
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 27/44721 by optical means
• CPC Class Codes: G01N 27/44773 : Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 30/60 : Construction of the column
• CPC Class Codes: G01N 30/6052 : body
• CPC Class Codes: G01N 30/606 : with fluid access or exit ports
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize

Abstract

A microanalytical device is provided for conducting chemical processes using small amounts of fluid. The devices include microstructures, e.g., microcavities, microchannels and the like, that are laser ablated or otherwise formed in a support substrate, and can be used in a variety of chemical and biochemical methods, including chromatographic, electrophoretic and electrochromatographic separations, screening and diagnostics, and chemical and biochemical synthesis. The devices are formed from a material that is thermally and chemically stable and resistant to biofouling, significantly reducing electroosmotic flow and unwanted adsorption of solute. Preferred materials are polymeric.

Claims

1. A microanalytical device in which chemical and biochemical reactions can be conducted, comprising:

a substrate fabricated from materials that are not silicon based, said substrate having first and second substantially planar opposing surfaces, and said substrate having a cavity and at least one microchannel formed in the first planar surface, wherein the cavity serves as a reaction zone that is in fluid communication with each microchannel;

a cover plate arranged over the first planar surface, said cover plate in combination with the cavity defining a reaction chamber, and with each microchannel defining a microcolumn; and

at least one inlet port and at least one outlet port communicating directly or indirectly with the reaction chamber, said ports enabling the passage of fluid from an external source into and through the reaction chamber, thereby defining a fluid flow path;

wherein a surface of the reaction chamber and/or the microcolumn is coated with or functionalized to contain a polyether.

2. The microanalytical device of claim 1, wherein the substrate is comprised of material that provides for reduced sorption of solutes compared to a substrate formed from a silicon-containing material.

3. The microanalytical device of claim 1, wherein the substrate material is polymeric.

4. The microanalytical device of claim 3, wherein the substrate material is selected from the group consisting of polyimides, polycarbonates, polyesters, polyamides, polyethers, polyurethanes, polyfluorocarbons, polystyrenes, poly(acrylonitrile-butadiene-styrene), polymethyl methacrylate, polyolefins, and copolymers thereof.

5. The microanalytical device of claim 4, wherein the substrate is comprised of polyimide.

6. The microanalytical device of claim 5, wherein the polyether is a polyethylene oxide.

7. The microanalytical device of claim 3, wherein the polyether is a polyethylene oxide.

8. The microanalytical device of claim 1, further including an additional cavity formed in the first planar surface, which in combination with the cover plate forms an additional reaction chamber.

9. The microanalytical device of claim 1, wherein the reaction chamber has an upstream region in which fluid is introduced and a downstream region from which fluid exits, and wherein the at least one microchannel comprises an upstream microchannel in fluid communication with the upstream region of the reaction chamber and a downstream microchannel in fluid communication with the downstream region of the reaction chamber.

10. The microanalytical device of claim 9, wherein the upstream microchannel in combination with the cover plate forms an upstream microcolumn, and the downstream microchannel in combination with the cover plate forms a downstream microcolumn.

11. The microanalytical device of claim 1, further including motive means to move fluid through the fluid flow path.

12. The microanalytical device of claim 11, wherein the motive means comprises a means for applying a voltage differential.

13. The microanalytical device of claim 11, wherein the motive means comprises a means for applying a pressure differential.

14. The microanalytical device of claim 1, wherein the reaction chamber is sized to contain approximately 1 μ

l to 500 μ

l of fluid.

15. The microanalytical device of claim 14, wherein the reaction chamber is sized to contain approximately 10 μ

l to 200 μ

l of fluid.

16. The microanalytical device of claim 1, wherein the at least one microchannel is approximately 1 μ

m to 200 μ

m in diameter.

17. The microanalytical device of claim 16, wherein the at least one microchannel is approximately 10 μ

m to 75 μ

m in diameter.

18. A method for conducting a chemical or biochemical reaction with small amounts of fluid, comprising:

(a) introducing a reaction fluid into a microanalytical device comprising

a substrate fabricated from materials that are not silicon based, said substrate having first and second substantially planar opposing surfaces, and said substrate having a cavity and at least one microchannel formed in the first planar surface, wherein the cavity serves as a reaction zone that is in fluid communication with each microchannel.

a cover plate arranged over the first planar surface, said cover plate in combination with the cavity defining a reaction chamber, and with each microchannel defining a microcolumn; and

at least one inlet port and at least one outlet port communicating directly or indirectly with the reaction chamber, said ports enabling the passage of fluid from an external source into and through the reaction chamber, thereby defining a fluid flow path,

wherein a surface of the reaction chamber and/or the microcolumn is coated with or functionalized to contain a polyether;

(b) applying a motive force to the device to move the reaction fluid through the flow path; and

(c) conducting the desired reaction when the reaction fluid is in the reaction chamber, resulting in a reaction product.

19. The method of claim 18, wherein step (c) is conducted by heating the reaction chamber.

20. The method of claim 18, further including collecting the reaction product at the outlet port.