Integrated monolithic microfabricated electrospray and liquid chromatography system and method

• US 6,800,198 B2
• Filed: 12/21/2000
• Issued: 10/05/2004
• 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: Davis, Timothy J., Moon, James E., Galvin, Gregory J.
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US09/745,652
• Publication Number:
  US 20010001460A1
• Time in Patent Office: 1,384 Days
• Field of Search: 250/288, 250/288.A, 210/656, 210/748, 210/198.2, 210/243, 204/450, 204/600, 422/70, 436/161, 295/921
• US Class Current: 210/198.2
• 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 29/49002 Electrical device making
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

An electrospray device, a liquid chromatography device and an electrosprayliquid 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 process for fabricating an electrospray device, comprising:

providing a substrate having a first surface and a second surface;

forming a nozzle in said substrate substantially perpendicular to said first surface and substantially extending to said first surface;

forming a recessed region such that said nozzle is surrounded by and defined by said recessed region;

forming a channel through said substrate, said channel including an entrance orifice defined on said second surface and extending between said entrance orifice and an end of said nozzle, such that said channel substantially extends between said first and second surfaces; and

providing means to produce a sufficient electrical potential difference to produce an electrospray.

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

3. The process of claim 1, wherein at least one of the steps of forming said nozzle, recessed region and channel are done at least in part by reactive-ion etching.

4. The process of claim 3, further comprising providing a layer of silicon oxide to act as a mask during said reactive-ion etching.

5. The process of claim 1, further comprising aligning said entrance on said second surface to said nozzle on said first surface, or vice versa, so as to ensure that said channel is continuous between said first and second surfaces.

6. The process of claim 5, further comprising using infrared illumination and image detection to provide an image of features already formed on one side of said substrate to which features on another side are aligned during lithographic exposure.

7. The process of claim 6, wherein said substrate is polished on both first and second surfaces.

8. The process of claim 1, wherein said substrate is polished on both first and second surfaces.

9. The process of claim 1, further comprising controlling a height of said nozzle by adjusting an amount of etching on said first surface.

10. The process of claim 1, further comprising forming an injection surface in said second surface of said substrate and forming a well recessed from said injection surface, wherein said entrance orifice is defined within said well.

11. The process of claim 1, further comprising:

forming an insulating layer over at least an interior surface of said channel, interior and exterior surfaces of said nozzle, and said first surface of said substrate; and

forming an electrode in electrical contact with said substrate on said first surface.

12. The process of claim 11, wherein said insulating layer is silicon oxide and said step of forming said insulating layer includes one of growing by thermal oxidation of silicon and depositing by a deposition technique.

13. The process of claim 11, further comprising forming at least one additional electrode on said first surface, said at least one additional electrode being electrically isolated from said substrate.

14. The process of claim 1, further comprising:

forming an insulating layer over at least an interior surface of said channel, interior and exterior surfaces of said nozzle, and said second surface of said substrate; and

forming an electrode to provide electrical contact to said substrate on said second surface.

15. The process of claim 14, wherein said insulating layer is silicon oxide and said step of forming said insulating layer includes one of growing by thermal oxidation of silicon and depositing by a deposition technique.

16. The process of claim 14, further comprising:

forming an insulating layer over said first surface of said substrate; and

forming at least one additional electrode on said first surface, said at least one additional electrode being electrically isolated from said substrate.

17. The process of claim 1, further comprising providing controlling circuitry for said electrospray device, said circuitry being integrated on said substrate.

18. A process for fabricating an electrospray system, comprising:

providing a first substrate having a first surface and a second surface;

forming a nozzle in said first substrate substantially perpendicular to said first surface and substantially extending to said first surface;

forming a recessed region surrounding and defining said nozzle;

forming a nozzle channel through said substrate, said nozzle channel including a nozzle channel entrance defined on said second surface and extending between said nozzle channel entrance and an end of said nozzle, such that said nozzle channel substantially extends between said first and second surfaces; and

providing means to produce a sufficient electrical potential difference to produce an electrospray;

attaching a second substrate to said first substrate, said second substrate having a major surface; and

delivering fluid to said nozzle channel entrance wherein said second substrate, in conjunction with said first substrate, is used to confine and/or direct a flow of said fluid.

19. The process of claim 18, wherein said step of delivering fluid includes the steps of:

forming an injection channel in said first substrate, said injection channel extending from an injection orifice defined on said first surface through said first substrate to a channel exit defined on said second surface;

forming a connecting channel in said major surface of said second substrate; and

attaching said major surface of said second substrate to said second surface of said first substrate, said connecting channel interconnecting said channel exit and said nozzle channel entrance.

20. The process of claim 19, wherein said steps of forming said injection channel and said connecting channel include, at least in part, reactive-ion etching.

21. The process of claim 19, wherein said step of forming said injection channel includes using infrared illumination and image detection to provide an image of features already formed on one side of said first substrate to which features on another side of said first substrate are aligned during lithographic exposure.

22. The process of claim 19, further comprising forming a well recessed from an injection surface in said first surface of said first substrate, wherein said injection orifice is defined within said well.

23. The process of claim 18, wherein the step of delivering fluid includes the steps of:

forming an injection channel in said first substrate, said injection channel extending from an injection orifice defined on said first surface through said first substrate to a channel exit defined on said second surface;

forming a connecting channel in said second surface of said first substrate, extending from said channel exit to said nozzle channel entrance; and

attaching said major surface of said second substrate to said second surface of said first substrate, said major surface enclosing said connecting channel interconnecting said channel exit and said nozzle channel entrance in said first substrate.

24. The process of claim 23, wherein said steps of forming said injection channel and said connecting channel include, at least in part, reactive-ion etching.

25. The process of claim 23, wherein said step of forming said injection channel includes using infrared illumination and image detection to provide an image of features already formed on one side of said first substrate to which features on another side of said first substrate are aligned during lithographic exposure.

26. The process of claim 23, further comprising forming a well recessed from an injection surface in said first surface of said first substrate, wherein said injection orifice is defined within said well.

27. The process of claim 18, wherein the step of delivering fluid includes the steps of:

forming an injection channel in said second substrate, said injection channel extending from an injection orifice defined on a minor surface of said second substrate through said second substrate to a channel exit defined on said major surface;

forming a connecting channel in said second surface of said first substrate; and

attaching said major surface of said second substrate to said second surface of said first substrate, said connecting channel of said first substrate interconnecting said channel exit and said nozzle channel entrance.

28. The process of claim 27, wherein said steps of forming said injection channel and said connecting channel include, at least in part, reactive-ion etching.

29. The process of claim 27, wherein said step of forming said injection channel includes using infrared illumination and image detection to provide an image of features already formed on one side of said second substrate to which features on another side of said second substrate are aligned during lithographic exposure.

30. The process of claim 27, further comprising forming a well recessed from an injection surface in said minor surface of said second substrate, wherein said injection orifice is defined within said well.

31. The process of claim 18, wherein said step of delivering fluid includes:

forming an injection channel in said second substrate, said injection channel extending from an injection orifice defined on a minor surface of said second substrate through said second substrate to a channel exit defined on said major surface;

forming a connecting channel in said major surface of said second substrate; and

attaching said major surface of said second substrate to said second surface of said first substrate, said connecting channel interconnecting said channel exit and said nozzle channel entrance.

32. The process of claim 31, wherein said steps of forming said injection channel and said connecting channel include, at least in part, reactive-ion etching.

33. The process of claim 31, wherein said step of forming said injection channel includes using infrared illumination and image detection to provide an image of features already formed on one side of said second substrate to which features on another side of said second substrate are aligned during lithographic exposure.

34. The process of claim 31, further comprising forming a well recessed from an injection surface in said minor surface of said second substrate, wherein said injection orifice is defined within said well.

35. The process of claim 18, wherein at least one of said first and second substrates is of silicon.

36. The process of claim 18, wherein said steps of forming said nozzle, said recessed region, and said nozzle channel include, at least in part, reactive-ion etching.

37. The process of claim 36, further comprising providing a layer of silicon oxide to act as a mask during said reactive-ion etching.

38. The process of claim 36, further comprising controlling a height of said nozzle by adjusting relative amounts of etching on said first and second surfaces of said first substrate.

39. The process of claim 18, wherein said step of forming said nozzle channel includes the step of aligning said nozzle channel entrance on said second surface of said first substrate to said nozzle on said first surface, or vice versa, to ensure that said nozzle channel is continuous between said first and second surfaces.

40. The process of claim 39, wherein said step of aligning includes using infrared illumination and image detection to provide an image of features already formed on one side of said first substrate to which features on another side of said first substrate are aligned during lithographic exposure.

41. The process of claim 18, wherein at least one of said first and second substrates on both surfaces is polished before the steps of forming and attaching.

42. The process of claim 18, further comprising the steps of forming an insulating layer over at least an interior surface of said channel, interior and exterior surfaces of said nozzle, and said first surface of said first substrate;

and

forming an electrode in electrical contact with said first substrate on said first surface.

43. The process of claim 42, wherein said insulating layer is silicon oxide and said step of forming said insulating layer includes one of growing by thermal oxidation of silicon and depositing by a deposition technique.

44. The process of claim 42, further comprising forming at least one additional electrode on said first surface, said at least one additional electrode being electrically isolated from said first substrate.

45. The process of claim 18, further comprising:

forming an insulating layer over at least an interior surface of said channel, interior and exterior surfaces of said nozzle, and said second surface of said substrate; and

forming an electrode in electrical contact with said first substrate on said second surface.

46. The process of claim 45, wherein said insulating layer is silicon oxide, and said step of forming said insulating layer includes one of growing by thermal oxidation of silicon and depositing by a deposition technique.

47. The process of claim 45, further comprising:

forming an insulating layer over said first surface of said substrate; and

forming at least one additional electrode on said first surface, said at least one additional electrode being electrically isolated from said first substrate.

48. The process of claim 18, wherein said step of attaching includes bonding said first substrate to said second substrate by one of anodic bonding, sodium-silicate bonding, eutectic bonding, glass frit bonding, polyimide bonding, and low-temperature fusion bonding.

49. The process of claim 18, further comprising providing controlling circuitry for said electrospray system integrated on at least one of said first and second substrates.