Separation media, multiple electrospray nozzle system and method

• US 6,956,207 B2
• Filed: 04/01/2003
• Issued: 10/18/2005
• Est. Priority Date: 01/18/2000
• Status: Expired due to Term

• Current Assignee: Advion, Inc. (Beijing Bohui Innovation Biotechnology Group Co., Ltd.)
• Original Assignee: Advion BioSciences Incorporated
• Inventors: Huang, Xian, Schultz, Gary A., Corso, Thomas N., Prosser, Simon J.
• Primary Examiner(s): Lee, John R.
• Assistant Examiner(s): Vanore, David A.
• Application Number:
  US10/405,689
• Publication Number:
  US 20030201390A1
• Time in Patent Office: 931 Days
• Field of Search: 250/281, 250/282, 250/288, 250/423.R, 210/198.2, 210/243, 210/656, 210/748
• US Class Current: 250/288
• CPC Class Codes: B01J 20/103 comprising silica
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/281 Sorbents specially adapted for preparative, analytical or investigative chromatography
• CPC Class Codes: B01J 20/283 based on silica
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/82 Shaped bodies, e.g. monoliths, plugs, tubes, continuous beds
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 2030/528 Monolithic sorbent material
• CPC Class Codes: G01N 27/44717 Arrangements for investigating the separated zones, e.g. localising zones
• CPC Class Codes: G01N 30/463 for multidimensional chromatography
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/467 all columns being identical
• 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

Abstract

A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths in its microchannels is disclosed. The polymer monoliths are liquid-permeable and serve as microcolumns for liquid chromatography, which are prepared by in situ radical polymerization of a mixture containing vinyl monomers and solvents (porogen) in the microchannels. A method and system are disclosed to generate one or more electrospray plumes from one or more nozzles that provide an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analyses contained within the fluid. A plurality of electrospray devices can be used in the form of an array of miniaturized separate electrospray devices for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid for analysis. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods. The silicon chip having the packed microchannels disclosed herein finds application in coupling with mass spectrometry for sample analysis. Also disclosed is a separation block having multiple through-substrate channels filled with a separation material such as polymer monolith which can be stacked in multiple blocks for sequential two-dimensional chromatographic separation and integrated with the electrospray device.

Claims

1. A method of producing an electrospray device comprising:

providing a substrate having opposed first and second surfaces, at least the first surface coated with a photoresist over an etch-resistant material;

exposing the photoresist on the first surface to an image to form a pattern in the form of at least one ring on the first surface;

removing the exposed photoresist on the first surface which is outside and inside the at least one ring to form an annular portion;

removing the etch-resistant material from the first surface of the substrate where the exposed photoresist was removed to form holes in the etch-resistant material;

optionally, removing all photoresist remaining on the first surface;

exposing the photoresist on the second surface to an image to from a pattern circumscribing extensions of the at least one ring formed in the etch-resistant material of the first surface;

removing the exposed photoresist on the second surface;

removing the etch-resistant material on the second surface where the photoresist was removed;

removing material from the substrate coincident with where the etch-resistant material on the second surface was removed to form a reservoir extending partially into the substrate;

optionally, removing the remaining photoresist on the second surface;

coating the second surface with an etch-resistant material;

coating the first surface with a second coating of photoresist;

exposing the second coating of photoresist within the at least ring to an image;

removing the exposed second coating of photoresist from within the at least one ring to form at least one hole;

removing material from the substrate coincident with the at least one hole in the second layer of photoresist on the first surface to form at least one passage extending through the second layer of photoresist on the first surface and into the substrate to the extent needed to reach the etch-resistant material coating the reservoir;

removing photoresist from at least the first surface;

applying an etch-resistant layer to all exposed surfaces of the substrate;

removing the etch-resistant layer from the first surface that is around the at least one ring;

removing material from the substrate exposed by the removed etch-resistant layer around the at least one ring to define at least one nozzle on the first surface;

removing from the substrate at least the etch-resistant material coating the reservoir;

applying an etch-resistant material to all surfaces of the substrate;

filling at least one of the reservoir and the at least one passage with a polymerizable material; and

polymerizing the polymerizable material.

2. The method according to claim 1, wherein the substrate is made from silicon and the etch-resistant material is silicon dioxide.

3. The method according to claim 1, further comprising:

applying a silicon nitride layer over all surfaces after said applying an etch-resistant material to all uncoated portions of the substrate.

4. The method according to claim 1, wherein the polymerizable material comprises styrene, acrylic acid and its esters, methacrylic acid and it esters, vinyl pyridine, maleate, vinylester, vinyl ether, and vinylalcohol derivatives, crosslinked with divinylbenzene, ethylene dimethacrylate or diacrylate, diethylene glycol dimethacrylate or diacrylate, divinylpyridine, bis-N-vinyl-2-pyrrolidone, N,N-methylene-bisacrylamide or bismethacrylamide, or trimethylolpropane trimethacrylate.

5. The method according to claim 4, wherein the polymerizable material further comprises a porogen and an initiator.

6. The method according to claim 1, wherein at least one passage is filled with the polymerizable material.

7. The method according to claim 1, wherein the reservoir is filled with the polymerizable material.

8. The method according to claim 1, wherein the reservoir and at least one passage are filled with the polymerizable material.

9. The method according to claim 1, wherein multiple passages are filled with the polymerizable material.