Integrated monolithic microfabricated electrospray and liquid chromatography system and method

• US 6,780,313 B1
• Filed: 10/31/2000
• Issued: 08/24/2004
• Est. Priority Date: 09/17/1998
• Status: Expired due to Term

• Current Assignee: Rheonix, Inc.
• Original Assignee: Advion BioSciences Incorporated, Kionix Incorporated (ROHM Co., Ltd.)
• Inventors: Corso, Thomas N., Lowes, Stephen, Schultz, Gary A., Davis, Timothy J., Moon, James E., Galvin, Gregory J.
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US09/702,955
• Time in Patent Office: 1,393 Days
• Field of Search: 250/288, 250/288.A, 210/656, 210/748, 210/198.2, 210/243, 204/600, 422/70, 436/161
• US Class Current: 210/198.2
• CPC Class Codes: G01N 2030/6013 interfaces to detectors
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray
• CPC Class Codes: H01J 49/0018 Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
• CPC Class Codes: H01J 49/167 Capillaries and nozzles specially adapted therefor; electrostatic spraying per se B05B5/00
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An electrospray device, a liquid chromatography device and an electrospray-liquid chromatography system are disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The liquid chromatography device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow; a cover substrate bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate; and, optionally, electrode(s) for application of a electric potential to the fluid. The exit orifice of the liquid chromatography device may be homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. An array of multiple systems may be fabricated in a single monolithic chip for rapid sequential fluid processing and generation of electrospray for subsequent analysis, such as by positioning the exit orifices of the electrospray devices near the sampling orifice of a mass spectrometer.

Claims

1. A chemical separation device comprising:

a substrate defining a channel,

a plurality of posts fabricated from said substrate and extending from said channel, an electrically insulating layer grown on the surface of the substrate and

a stationary phase bound to the posts, said posts providing interaction with an analyte introduced into said channel for producing separation, wherein said analyte is electrically insulated from said substrate.

2. The device of claim 1, wherein said substrate is of silicon.

3. The device of claim 1, wherein said insulation layer is silicon oxide.

4. The device of claim 3, wherein said silicon oxide is grown by thermal oxidation of silicon.

5. The device of claim 3, wherein said silicon oxide layer is deposited using a deposition technique.

6. The device of claim 1, wherein said plurality of posts are spaced apart from each other by no more than 5 microns measured edge to edge.

7. The device of claim 1, wherein said plurality of posts in said separation channel are arranged at least one of periodically, semi-periodically, and randomly.

8. The device of claim 1, further comprising means for applying electrical potential to a fluid at one or more locations in said channel.

9. The device of claim 1, wherein said substrate defines at least one additional channel, said at least one additional channel containing a plurality of posts fabricated from said substrate and extending from and perpendicular to a bottom of said at least one additional channel.

10. The device of claim 9, further comprising means for applying electrical potential to fluids at one or more locations in said at least one additional channel.

11. The device of claim 1, further comprising controlling circuitry for said chemical separation device integrated on said substrate.

12. A chemical separation system, comprising:

a first substrate having a first surface and a second surface, said first substrate defining

(a) an entrance opening on said first surface,

(b) a fluid reservoir recessed from said second surface,

(c) a first channel extending between said entrance opening and said reservoir,

(d) a second channel recessed from said second surface, and

(e) a plurality of posts extending from and perpendicular to a bottom of said second channel;

a cover substrate attached to said first substrate to enclose said reservoir and said second channel adjacent said cover substrate; and

an insulating layer grown on the surface of said substrate, said cover, said reservoir, said first channel, said second channel, and said plurality of posts;

wherein at least one of said first substrate and said cover substrate defines an exit; and

wherein said second channel extends between said exit and said reservoir.

13. The system of claim 12, wherein at least one of said first substrate and said cover substrate is of silicon.

14. The system of claim 12, wherein said insulating layer is silicon oxide.

15. The system of claim 14, wherein said silicon oxide is grown by thermal oxidation of silicon.

16. The system of claim 14, wherein said silicon oxide is deposited by a deposition technique.

17. The system of claim 12, further comprising a stationary phase bound to said plurality of posts, said plurality of posts providing interaction with an analyte introduced into said second channel for producing separation in said analyte.

18. The system of claim 12, further comprising means for applying electrical potential to a fluid in at least one location, said location selected from the group consisting of said fluid reservoir, said second channel, and said exit.

19. The system of claim 12, wherein each of said plurality of posts are spaced apart from each other by no more than 5 microns, measured edge to edge.

20. The system of claim 12, wherein said plurality of posts in said second channel are arranged at least one of periodically, semi-periodically, and randomly.

21. The system of claim 12, further comprising:

a multiplicity of entrance openings on said first surface;

an equal multiplicity of fluid reservoirs recessed from said second surface;

a multiplicity of first channels extending between each of said multiplicity of entrance openings and a corresponding one of said multiplicity of fluid reservoirs;

wherein said second channel recessed from said second surface extends between said exit and every one of said multiplicity of fluid reservoirs.

22. The system of claim 12, further comprising:

a plurality of additional entrance openings on said first surface;

a plurality of additional reservoirs recessed from said second surface, each additional reservoir corresponding to one of said plurality of additional entrance openings;

a plurality of additional first channels, each corresponding to and extending between one of said plurality of additional entrance openings and its corresponding additional reservoir; and

a plurality of additional second channels recessed from said second surface, wherein one of said first substrate and said cover substrate defines a plurality of additional exits, each additional exit corresponding to one of said plurality of additional reservoirs;

wherein each additional second channel corresponds to and extends between one of said plurality of additional reservoirs and said corresponding additional exit.

23. The system of claim 22, further comprising at least one means for applying electrical potential to fluids at one or more locations in said plurality of additional fluid reservoirs, additional second channels and additional exits.

24. The system of claim 22, further comprising controlling circuitry for said chemical separation system, said circuitry being integrated on at least one of said first and said second substrate.