Integrated monolithic microfabricated electrospray and liquid chromatography system and method

• US 6,790,354 B1
• Filed: 10/27/2000
• Issued: 09/14/2004
• 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: Lowes, Stephen, Schultz, Gary A., Davis, Timothy J., Moon, James E., Corso, Thomas N., Galvin, Gregory J.
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US09/698,329
• Time in Patent Office: 1,418 Days
• Field of Search: 250/288, 250/283, 250/282, 210/656, 210/748, 210/198.2, 210/243, 204/600, 422/70, 436/161, 436/173, 436/183
• 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. An electrospray device comprising:

a monolithic substrate having a plurality of entrance orifices on an injection side and a plurality of nozzles on an ejection surface on an opposite planar side from the injection side, a plurality of channels each extending continuously through the monolithic substrate in communication with one of the plurality of entrance orifices and a corresponding one of the plurality of nozzles, and a region surrounding each nozzle recessed from the ejection surface;

said plurality of nozzles disposed in an array for ejecting a plurality of analytes at a mass spectrometry device interface; and

a plurality of electrodes for the application of electric potentials for generating and controlling an electric field at each nozzle to direct the ejection of the analytes from the nozzles within an acceptance region of the mass spectrometry device.

2. The device of claim 1, further comprising

an insulating layer provided over at least an interior surface of said channels and the interior and exterior surfaces of said nozzles to electrically isolate said surfaces from said substrate.

3. The device of claim 2, wherein said insulating 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 is deposited by a deposition technique.

6. The device of claim 1, wherein said nozzles are coplanar with or below said ejection surface.

7. The device of claim 1, wherein an array of said plurality of nozzles are positioned in a circular pattern on said ejection surface.

8. The device of claim 7, wherein said circular pattern comprises 96 nozzles having widths of up to 50 μ

m positioned around a circle 2 mm in diameter such that the spacing between each adjacent pair of nozzles is approximately 65 μ

m.

9. The device of claim 1, further comprising a conduit in fluid communication with at least one entrance orifice such that said device delivers fluid to said entrance orifice.

10. The device of claim 9, wherein said conduit is selected from the group consisting of capillary, chip, and micropipette tip.

11. The device of claim 1, wherein the substrate is silicon.

12. The device of claim 1, wherein the plurality of nozzles are capable of being rotated within the acceptance region of the mass spectrometry device.

13. The device of claim 1, wherein the plurality of nozzles are in a fixed position relative to the acceptance region of the mass spectrometry device.

14. The device of claim 1, wherein said generating and controlling an electric field at each nozzle includes generating an electrospray simultaneously, sequentially, or randomly at one, more than one, or all of the nozzles.