Integrated monolithic microfabricated dispensing nozzle and liquid chromatography-electrospray system and method
First Claim
1. An electrospray device comprising:
- a substrate having an injection surface and an ejection surface opposing the injection surface, wherein the substrate is an integral monolith comprising;
an entrance orifice on the injection surface;
an exit orifice on the ejection surface;
a channel extending between the entrance orifice and the exit orifice;
a recess extending into the ejection surface and surrounding the exit orifice, thereby defining a nozzle on the ejection surface; and
an electric field application system defining an electric field consisting essentially of;
a first electrode imparting a first electrical potential to fluid passing through the electrospray device and a second electrode substantially co-planar with the exit orifice imparting a second electrical potential, wherein the first and the second electrodes are positioned to define an electric field surrounding the exit orifice.
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Abstract
A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/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 droplets or an electrospray. A plurality of these electrospray devices can be used in the form of an array of miniaturized nozzles. The liquid chromatography-electrospray 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 is bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate. The exit orifice of the liquid chromatography device is homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. Procedures for fabrication of the electrospray devices of the present invention are also disclosed.
150 Citations
66 Claims
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1. An electrospray device comprising:
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a substrate having an injection surface and an ejection surface opposing the injection surface, wherein the substrate is an integral monolith comprising;
an entrance orifice on the injection surface;
an exit orifice on the ejection surface;
a channel extending between the entrance orifice and the exit orifice;
a recess extending into the ejection surface and surrounding the exit orifice, thereby defining a nozzle on the ejection surface; and
an electric field application system defining an electric field consisting essentially of;
a first electrode imparting a first electrical potential to fluid passing through the electrospray device and a second electrode substantially co-planar with the exit orifice imparting a second electrical potential, wherein the first and the second electrodes are positioned to define an electric field surrounding the exit orifice. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
an electrospray device according to claim 14; and
a daughter plate having a plurality of fluid receiving wells at least one positioned to receive fluid droplets/spray ejected from a respective one of the plurality of exit orifice.
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25. A system for processing droplets/sprays of fluid comprising:
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an electrospray device according to claim 14; and
a mass spectrometry device having a plurality of ion sampling orifices at least one positioned to receive droplets/sprays of fluid ejected from a respective one of the plurality of exit orifices.
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26. A system for processing droplets/sprays of ink comprising:
an ink jet printer which comprises an electrospray device according to claim 14, that ejects droplets/sprays of ink from the plurality of exit orifices.
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27. A system for processing droplets/sprays of fluid comprising:
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an electrospray device according to claim 14; and
a device to provide fluid to the plurality of entrance orifices of the electrospray device.
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28. A method of liquid separation analysis comprising:
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providing the system according to claim 27, where the device to provide fluid to the entrance orifice of said electro spray device is a liquid separation device, wherein said method comprises;
passing a fluid through the liquid separation device so that the fluid is subjected to liquid separation analysis and passing a fluid into the entrance orifice, through the channel, and through the exit orifice under conditions effective to produce an electrospray.
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29. The method according to claim 28, wherein the liquid separation analysis is selected from the group consisting of capillary electrophoresis, capillary dielectrophoresis, capillary electrochromatography, and liquid chromatography.
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30. The electrospray device according to claim 1, further comprising:
a nozzle positioned between the exit orifice and the recess, wherein the nozzle has a cross-sectional area of less than about 3000 μ
m2.
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31. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of up to 50 μ
- m.
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32. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of up to 30 μ
- m.
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33. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of from 2 μ
- m to 50 μ
m.
- m to 50 μ
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34. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of from 2 μ
- m to 30 μ
m.
- m to 30 μ
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35. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of 15 μ
- m.
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36. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of 5 μ
- m.
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37. The electrospray device according to claim 1, wherein the nozzle has an inner diameter of 2 μ
- m.
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38. The electrospray device according to claim 1, wherein the nozzle has an outer diameter of up to 60 μ
- m.
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39. The electrospray device according to claim 1, wherein the nozzle has an outer diameter of up to 40 μ
- m.
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40. The electrospray device according to claim 1, wherein the nozzle has an outer diameter of 20 μ
- m.
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41. The electrospray device according to claim 1, wherein the nozzle has an outer diameter of 5 μ
- m.
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42. The electrospray device according to claim 1, wherein the nozzle has an outer diameter of from 5 to 60 μ
- m.
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43. A system for processing droplets/sprays of fluid comprising:
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an electrospray device according to claim 1, and a mass spectrometry device to receive droplets/sprays of fluid from the exit orifice of the electrospray device.
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44. A method of mass spectrometric analysis comprising:
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providing the system according to claim 43, wherein the device to receive fluid droplets/sprays of fluid from the exit orifice of said electrospray device is a mass spectrometer, wherein said method comprises;
passing a fluid into the entrance orifice, through the channel, and through the exit orifice under conditions effective to produce an electrospray and passing the electrospray into the mass spectrometer, whereby the fluid is subjected to a mass spectrometry analysis.
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45. A system for processing droplets/sprays of fluid comprising:
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an electrospray device according to claim 1; and
a conduit positioned to direct fluid into the entrance orifice.
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46. The system according to claim 45, where the conduit contains a plurality of spaced apart posts.
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47. The system according to claim 46, wherein the plurality of posts are spaced apart by no more than 2 μ
- m.
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48. The system according to claim 46, wherein the posts have an outer coating of an insulating material.
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49. The system according to claim 48, wherein the insulating material is selected from the group consisting of silicon dioxide, silicon nitride, and combinations thereof.
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50. The system according to claim 45, wherein the substrate further comprises:
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a fluid reservoir in fluid communication with the fluid passage;
a fluid inlet to direct fluid entering said substrate into the fluid reservoir; and
a fluid outlet to direct fluid from the fluid passage to the entrance orifice of said electrospray device.
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51. The system according to claim 50, wherein the substrate has opposed first and second surfaces with the fluid reservoir and the fluid passage being depressions in the first surface of the substrate, said system further comprising:
a second substrate joined to the first surface of the substrate to cover the fluid reservoir and the fluid passage.
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52. The system according to claim 51, wherein the fluid inlet and the fluid outlet extend through the surface of the substrate.
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53. The system according to claim 50, wherein the substrate comprises a plurality of fluid passages, a plurality of fluid reservoirs each in fluid communication with one of the plurality fluid passages, a plurality of fluid inlets to direct fluid entering said second substrate into one of the plurality of fluid reservoirs, and a plurality of fluid outlets to direct fluid from the fluid passages to an entrance orifice of said electrospray device.
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54. The system according to claim 50, wherein the substrate has opposed first and second surfaces and the device to provide fluid comprises:
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a second substrate comprising;
a fluid reservoir in fluid communication with the fluid passage;
a fluid inlet to direct fluid entering said second substrate into the fluid reservoir; and
a fluid outlet to direct fluid from the fluid passage to the entrance orifice of said electrospray device, wherein substrate is joined to the second substrate to cover the fluid reservoir and the fluid passage.
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55. A method of generating an electrospray comprising:
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providing an electro spray device according to claim 1;
passing a fluid into the entrance orifice, through the channel, and through the exit orifice;
applying a first potential to the first electrode; and
applying a second potential to the second electrode, whereby fluid discharged from the exit orifice forms an electrospray.
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56. The method according to claim 55, wherein the electrospray is in the form of droplets.
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57. The method according to claim 55, wherein the electrospray is in the form of a spray.
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58. The method according to claim 55, further comprising:
detecting components of the electrospray by spectroscopic detection.
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59. The method according to claim 58, wherein the spectroscopic detection is selected from the group consisting of UV absorbance, laser induced fluorescence, and evaporative light scattering.
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60. A method of mass spectrometric analysis comprising:
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providing an electrospray device according to claim 1;
providing a liquid separation device to provide fluid to the entrance orifice of said electrospray device;
providing a mass spectrometer to receive fluid droplets/sprays of fluid from the exit orifice of said electrospray device;
passing a fluid through the liquid separation device so that the fluid is subjected to liquid separation analysis;
passing a fluid into the entrance orifice, through the channel, and through the exit orifice under conditions effective to produce an electrospray; and
passing the electrospray into the mass spectrometer, whereby the fluid is subjected to a mass spectrometry analysis.
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61. The method according to claim 60, wherein the liquid separation analysis is selected from the group consisting of capillary electrophoresis, capillary dielectrophoresis, capillary electrochromatography, and liquid chromatography.
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62. A method for processing multiple sprays of fluid comprising:
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providing an electrospray device according to claim 1;
providing a device to provide at least one fluid sample to at least one entrance orifice of said electrospray device;
providing a device to receive multiple sprays of fluid or droplets from said electrospray device;
passing a fluid from said fluid providing device to said electrospray device;
generating an electric filed surrounding the exit orifice of said at least one spray unit such that fluid discharged therefrom forms an electrospray or droplets; and
passing said electrospray or droplets from said electrospray device to said receiving device.
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63. The method of claim 62 further comprising using said receiving device for performing mass spectrometry analysis;
- liquid chromatography analysis;
protein, DNA, or RNA, combinatorial chemistry analysis;
proteomic screening; and
ink jet printing.
- liquid chromatography analysis;
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64. A system for processing droplets/sprays of fluid comprising:
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an electrospray device comprising;
a substrate having an injection surface and an ejection surface opposing the injection surface, wherein the substrate comprises;
an entrance orifice on the injection surface;
an exit orifice on the ejection surface;
a channel extending between the entrance orifice and the exit orifice; and
a recess extending into the ejection surface and surrounding the exit orifice; and
a device to provide fluid to the electrospray device comprising;
a fluid passage;
a fluid reservoir in fluid communication with the fluid passage;
a fluid inlet to direct fluid entering the device into the fluid reservoir; and
a fluid outlet to direct fluid from the fluid passage to the entrance orifice of said electrospray device, wherein the cross-sectional area of the entrance orifice of said electrospray device is equal to or less than the cross-sectional area of the fluid passage. - View Dependent Claims (65, 66)
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Specification