Separation media, multiple electrospray nozzle system and method

• US 6,596,988 B2
• Filed: 01/18/2001
• Issued: 07/22/2003
• 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: Schultz, Gary A., Corso, Thomas N., Prosser, Simon J., Huang, Xian
• Primary Examiner(s): Lee, John R.
• Assistant Examiner(s): Wells, Nikita
• Application Number:
  US09/764,698
• Publication Number:
  US 20020000517A1
• Time in Patent Office: 915 Days
• Field of Search: 250/288, 250/281, 250/282, 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. An electrospray device comprising:

a substrate having;

a) an injection surface;

b) an ejection surface opposing the injection surface, wherein the substrate has at least one spray unit which comprises;

an entrance orifice on the injection surface,

an exit orifice on the ejection surface,

a channel extending through the substrate between the entrance orifice and the exit orifice, and

a recess extending into the ejection surface and surrounding the exit orifice;

c) polymerized separation material associated with said electrospray device at a location suitable to effect chromatographic separation of analytes passing through said electrospray device; and

d) an electric field generating source positioned to define an electric field surrounding at least one exit orifice.

2. The electrospray device according to claim 1, wherein the polymerized separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, or particles containing a stationary phase, non-porous silica, or silica particles encapsulated in a polymer matrix.

3. The electrospray device according to claim 1, wherein the electric field generating source comprises:

a first electrode attached to said substrate to impart a first potential to said substrate and

a second electrode to impart a second potential, wherein the first and the second electrodes are positioned to define an electric field surrounding the exit orifice.

4. The electrospray device according to claim 3, wherein the first electrode is electrically insulated from fluid passing through said electrospray device and the second potential is applied to the fluid.

5. The electrospray device according to claim 3, wherein the first electrode is in electrical contact with fluid passing through said electrospray device fluid and the second electrode is positioned on the ejection surface.

6. The electrospray device according to claim 3, wherein application of potentials to said first and second electrodes causes fluid passing through said electrospray device fluid to discharge from the exit orifice in the form of a spray.

7. The electrospray device according to claim 3, wherein application of potentials to said first and second electrodes causes fluid passing through said electrospray device fluid to discharge from the exit orifice in the form of droplets.

8. The electrospray device according to claim 1, wherein said substrate is silicon.

9. The electrospray device according to claim 1, wherein said substrate is polymeric.

10. The electrospray device according to claim 1, wherein said substrate is glass.

11. The electrospray device according to claim 1 wherein said substrate is an integral monolith.

12. The electrospray device according to claim 1, wherein the entrance orifice, the exit orifice, and the channel have a coating of an insulating material.

13. The electrospray device according to claim 12, wherein the insulating material is selected from the group consisting of silicon dioxide, silicon nitride, and combinations thereof.

14. The electrospray device according to claim 1, wherein the entrance orifice, the exit orifice, and the channel are filled with said separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

15. The electrospray device according to claim 14, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, or particles containing a stationary phase, non-porous silica, or silica particles encapsulated in a polymer matrix.

16. The electrospray device according to claim 1, wherein at least one spray unit is capable of generating a single electrospray plume.

17. The electrospray device according to claim 1, wherein at least one spray unit is capable of generating multiple electrospray plumes.

18. The electrospray device according to claim 1, wherein said substrate has a plurality of said spray units.

19. The electrospray device according to claim 18, wherein at least one of the exit orifices is capable of generating one plume of material passing through the electrospray device.

20. The electrospray device according to claim 18, wherein at least one of the exit orifices is capable of generating a plurality of plumes of material passing through the electrospray device.

21. The electrospray device according to claim 18, wherein a plume of material passing through the electrospray device is generated by a plurality of the exit orifices.

22. The electrospray device according to claim 18, wherein the electrospray is generated from a single fluid stream.

23. The electrospray device according to claim 1, further comprising:

a conduit positioned to provide fluid to the entrance orifice.

24. The electrospray device according to claim 1, further comprising:

a reservoir upstream of and in fluid communication with the entrance orifice.

25. The electrospray device according to claim 24, wherein the reservoir is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

26. The electrospray device according to claim 25, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

27. The electrospray device according to claim 24, further comprising:

a well positioned in fluid communication with the reservoir so that fluid in the well is dischargeable into the reservoir.

28. The electrospray device according to claim 27, wherein the well is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

29. The electrospray device according to claim 28, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

30. The electrospray device according to claim 1, wherein the separation material is a monolithic polymer bed formed by in situ polymerization of a monomer solution containing a porogen and an initiator.

31. The electrospray device according to claim 30, wherein the monomer comprises styrene, acrylic acid and its esters, methacrylic acid and its 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.

32. The electrospray device according to claim 18, wherein the exit orifices of the spray units are present on the ejection surface at a density of up to about 10,000 exit orifices/cm².

33. The electrospray device according to claim 18, wherein the exit orifices of the spray units are present on the ejection surface at a density of up to about 15,625 exit orifices/cm².

34. The electrospray device according to claim 18, wherein the exit orifices of the spray units are present on the ejection surface at a density of up to about 27,566 exit orifices/cm².

35. The electrospray device according to claim 18, wherein the exit orifices of the spray units are present on the ejection surface at a density of up to about 40,000 exit orifices/cm².

36. The electrospray device according to claim 18, wherein the exit orifices of the spray units are present on the ejection surface at a density of up to about 160,000 exit orifices/cm².

37. The electrospray device according to claim 18, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the spray units is less than about 500 μ

m.

38. The electrospray device according to claim 18, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the spray units is less than about 200 μ

m.

39. The electrospray device according to claim 18, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the spray units is less than about 100 μ

m.

40. The electrospray device according to claim 18, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the spray units is less than about 50 μ

m.

41. The electrospray device according to claim 3, wherein said first electrode is positioned within 500 microns of the exit orifice.

42. The electrospray device according to claim 3, wherein said first electrode is positioned within 200 microns of the exit orifice.

43. The electrospray device according to claim 3, wherein said second electrode is positioned within 500 microns of the exit orifice.

44. The electrospray device according to claim 3, wherein said second electrode is positioned within 200 microns of the exit orifice.

45. The electrospray device according to claim 1, wherein the exit orifice has a distal end in conductive contact with the substrate.

46. The electrospray device according to claim 1, wherein the device is configured to permit an electrospray of fluid at a flow rate of up to about 2 μ

L/minute.

47. The electrospray device according to claim 1, wherein the device is configured to permit an electrospray of fluid at a flow rate of from about 100 nL/minute to about 500 nL/minute.

48. An electrospray system for spraying fluid comprising an array of a plurality of electrospray devices of claim 1.

49. The electrospray system according to claim 48, wherein the device is configured to permit an electrospray of fluid at a flow rate of up to about 2 μ

L/minute.

50. The electrospray system according to claim 48, wherein the device is configured to permit an electrospray of fluid at a flow rate of from about 100 nL/minute to about 500 nL/minute.

51. The electrospray system according to claim 48, wherein the device is configured to permit an electrospray of fluid at a flow rate of greater than about 2 μ

L/minute.

52. The electrospray system according to claim 48, wherein the flow rate is from about 2 μ

L/minute to about 1 mL/minute.

53. The electrospray system according to claim 48, wherein the electrospray device density in the array exceeds about 5 devices/cm².

54. The electrospray system according to claim 48, wherein the electrospray device density in the array exceeds about 16 devices/cm².

55. The electrospray system according to claim 48, wherein the electrospray device density in the array exceeds about 30 devices/cm².

56. The electrospray system according to claim 48, wherein the electrospray device density in the array exceeds about 81 devices/cm².

57. The electrospray system according to claim 48, wherein the electrospray device density in the array is from about 30 devices/cm² to about 100 devices/cm².

58. The electrospray system according to claim 48, wherein said array is an integral monolith of said devices.

59. The electrospray system according to claim 48, wherein at least two of the devices are in fluid communication with different fluid streams.

60. The electrospray system according to claim 48, wherein at least one spray unit is configured to generate multiple electrospray plumes of fluid.

61. The electrospray system according to claim 48, wherein at least one of the electrospray devices is configured to generate a single combined electrospray plume of fluid.

62. The electrospray system according to claim 48, wherein at least one spray unit is configured to generate a single electrospray plume of fluid.

63. The electrospray system according to claim 48, wherein at least one spray unit is configured to generate multiple electrospray plumes of fluid which remain discrete.

64. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 9 mm or less.

65. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 4.5 mm or less.

66. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 2.2 mm or less.

67. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 1.1 mm or less.

68. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 0.56 mm or less.

69. The electrospray system according to claim 48, wherein the spacing on the ejection surface between adjacent devices is about 0.28 mm or less.

70. A system for processing droplets/sprays of fluid comprising:

an electrospray device according to claim 1 and

a device to receive droplets/sprays of fluid from the exit orifice of said electrospray device.

71. The system according to claim 70, wherein said substrate has a plurality of spray units and said device to receive fluid droplets/sprays comprises:

a daughter plate having a plurality of fluid receiving wells each positioned to receive fluid ejected from a respective one of the exit orifices.

72. The system according to claim 71, wherein said device to receive fluid is a mass spectrometry device.

73. A system for preparing samples for analysis comprising:

a multi-well plate having opposed surfaces and comprising a plurality of wells, each defined by an entrance opening at one of the surfaces and an exit opening at the other surface and having a wall extending between the entrance and exit openings and

a plurality of electrospray devices according to claim 1, each positioned to receive fluid from a well of the multi-well plate.

74. The system according to claim 73, wherein each of the plurality of electrospray devices further comprises:

a reservoir between an exit opening of a well of the multi-well plate and an entrance orifice.

75. The system according to claim 74, wherein the reservoir is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

76. The system according to claim 75, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

77. The system according to claim 74, wherein the well is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

78. The system according to claim 77, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

79. A system for processing droplets/sprays of fluid comprising:

a system according to claim 73 and

a device to receive droplets/sprays of fluid from the exit orifice of each of said electrospray devices.

80. The system according to claim 79, wherein said substrate has a plurality of spray units and said device to receive fluid droplets/sprays comprises:

a daughter plate have a plurality of fluid receiving wells each positioned to receive fluid ejected from a respective one of the exit orifices.

81. The system according to claim 79, wherein said device to receive fluid is a mass spectrometry device.

82. A method of generating an electrospray comprising:

providing an electrospray device according to claim 1;

passing at least one analyte of a fluid into at least one spray unit; and

generating an electric field around at least one exit orifice,

whereby each analyte of the fluid discharged from the at least one exit orifice forms an electrospray.

83. The method according to claim 82, wherein the entrance orifice, the exit orifice, and the channel of said at least one spray unit are filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

84. The method according to claim 83, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, or particles containing a stationary phase, non-porous silica, or silica particles encapsulated in a polymer matrix.

85. The method according to claim 82, further comprising:

loading a discrete sample of said at least one analyte of fluid into the entrance orifice of said at least one spray unit.

86. The method according to claim 82, further comprising:

loading a continuous sample of at least one analyte of fluid into the entrance orifice of said at least one spray unit.

87. The method according to claim 82, wherein the electric field is generated in a manner so as to produce an electrospray in the form of droplets.

88. The method according to claim 82, wherein the electric field is generated in a manner so as to produce an electrospray in the form of a spray.

89. The method according to claim 82, further comprising:

detecting at least one analyte in the electrospray fluid by spectroscopic detection.

90. The method according to claim 89, wherein the spectroscopic detection is selected from the group consisting of UV absorbance, laser induced fluorescence, and evaporative light scattering.

91. The method according to claim 89, wherein said detecting comprises sequentially spraying each electrospray while simultaneously placing each electrospray in communication with said detector.

92. The method according to claim 89, wherein said detecting comprises simultaneously spraying a plurality of electrosprays and sweeping said electrosprays in communication with said detector.

93. The method according to claim 82, further comprising:

passing the at least one analyte of a fluid through a reservoir which is upstream of and in fluid communication with the entrance orifice of said at least one spray unit.

94. The method according to claim 93, further comprising:

passing the at least one analyte of a fluid through a well which is positioned in fluid communication with the reservoir so that fluid in the well is dischargeable into the reservoir.

95. The method according to claim 93, further comprising:

passing the at least one analyte through a separation material which is contained in the reservoir, wherein the separation material is suitable to effect chromatographic separation of analytes passing through said electrospray device.

96. The method according to claim 94, further comprising:

passing the at least one analyte through a separation material which is contained in the well, wherein the separation material is suitable to effect chromatographic separation of analytes passing through said electrospray device.

97. The method according to claim 96, further comprising:

passing the at least one analyte through a separation material which is contained in the reservoir, wherein the separation material is suitable to effect chromatographic separation of analytes passing through said electrospray device.

98. The method according to claim 95, further comprising:

applying a discrete quantity of fluid containing a plurality of analytes to the reservoir and

applying a series of eluent solvents to sequentially carry each analyte in the fluid from the reservoir and through the entrance orifice, the channel, and exit orifice of said at least one spray unit.

99. The method according to claim 95, further comprising:

applying a continuous stream of fluid containing a plurality of analytes to the reservoir and

applying a series of eluent solvents to sequentially carry each analyte in the fluid from the reservoir and through the entrance orifice, the channel, and exit orifice of said at least one spray unit.

162. A method for processing samples of fluid comprising:

passing at least one sample through a respective one of a first array of multiple through-substrate channels containing a first polymerized separation material suitable to effect chromatographic separation of analytes passing through the channel;

passing said at least one sample from said first array through a respective one of a second array of multiple through-substrate channels containing a second polymerized separation material having the same or different separation characteristics than said first polymerized separation material;

optionally repeating the previous step sequentially with one or a plurality of arrays of multiple through-substrate channels;

passing said at least one sample to corresponding entrance orifices of electrospray devices of the system of claim 48,

electrospraying the at least one sample;

passing the electrospray to a detector; and

detecting at least one analyte in the electrospray.

163. The method according to claim 162, wherein said passing the electrospray to a detector comprises sequentially spraying each electrospray while simultaneously placing each electrospray in communication with said detector.

164. The method according to claim 162, wherein said passing the electrospray to a detector comprises simultaneously spraying a plurality of electrosprays and sweeping said electrosprays in communication with said detector.

165. The method according to claim 162, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, non-porous silica, or silica or particles encapsulated in a polymer matrix.

166. The method according to claim 162, wherein said separation comprises liquid chromatography, ion chromatography, affinity chromatography, capillary electrophoresis, or capillary electrochromatography.

167. The method according to claim 162, wherein the separation material comprises a porous polymer which is a product of the polymerization of a monomer comprising styrene, acrylic acid and its esters, methacrylic acid and its 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.

168. The method according to claim 162, detecting comprises:

detecting at least one analyte in the electrospray fluid by spectroscopic detection.

169. The method according to claim 162, wherein the spectroscopic detection is selected from the group consisting of UV absorbance, laser induced fluorescence, and evaporative light scattering.

100. A method of producing an electrospray device comprising:

providing an electrospray device having;

a) an injection surface having an entrance orifice and a reservoir in fluid communication with the entrance orifice,

b) an ejection surface opposing the injection surface having an exit orifice,

c) a channel extending through the device between the entrance orifice and the exit orifice,

d) a recess extending into the ejection surface and surrounding the exit orifice, and

e) an electric field generating source positioned to define an electric field surrounding the exit orifice;

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

polymerizing the polymerizable material.

101. The method according to claim 100, wherein the passage is filled with the polymerizable material.

102. The method according to claim 100, wherein the reservoir is filled with the polymerizable material.

103. The method according to claim 100, wherein the reservoir and the passage are filled with the polymerizable material.

104. The method according to claim 100, wherein the polymerizable material comprises styrene, acrylic acid and its esters, methacrylic acid and its 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.

105. The method according to claim 104, wherein the polymerizable material further comprises a porogen and an initiator.

106. The method according to claim 105, wherein the initiator comprises a thermal initiator.

107. The method according to claim 105, wherein the initiator comprises an ultraviolet initiator.

108. A separation block comprising:

a) an injection surface having a plurality of entrance orifices,

b) an ejection surface opposing the injection surface and having a plurality of exit orifices each corresponding to a respective one of the plurality of entrance orifices, and

c) a plurality of channels extending through the block between one of the plurality of entrance orifices and the corresponding one of the plurality of exit orifices, wherein a plurality of channels are filled with a polymerized separation material suitable to effect chromatographic separation of analytes passing through said block.

109. The separation block according to claim 108, wherein the polymerized separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, or particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

110. The separation block according to claim 109, wherein the porous polymeric material is a product of the polymerization of a monomer comprising styrene, acrylic acid and its esters, methacrylic acid and its 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.

111. The separation block according to claim 108, further comprising:

an array of multiple electrospray devices, each device having at least one through-substrate channel in fluid communication with a corresponding one of the plurality of exit orifices of the separation block.

112. The separation block according to claim 111, wherein at least one electrospray channel is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

113. The separation block according to claim 112, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

114. The separation block according to claim 111, further comprising:

a reservoir positioned in fluid communication with the electrospray channel so that fluid in the reservoir is dischargeable into the electrospray channel.

115. The separation block according to claim 114, wherein the reservoir is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

116. The separation block according to claim 115, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

117. The separation block according to claim 114, further comprising:

a well positioned in fluid communication with the reservoir so that fluid in the well is dischargeable into the reservoir.

118. The separation block according to claim 117, wherein the well is filled with a separation material suitable to effect chromatographic separation of analytes passing through said electrospray device.

119. The separation block according to claim 118, wherein the separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

120. The separation block according to claim 111, wherein the exit orifices of the device are present on the ejection surface at a density of up to about 10,000 exit orifices/cm².

121. The separation block according to claim 111, wherein the exit orifices of the device are present on the ejection surface at a density of up to about 15,625 exit orifices/cm².

122. The separation block according to claim 111, wherein the exit orifices of the device are present on the ejection surface at a density of up to about 27,566 exit orifices/cm².

123. The separation block according to claim 111, wherein the exit orifices of the device are present on the ejection surface at a density of up to about 40,000 exit orifices/cm².

124. The separation block according to claim 111, wherein the exit orifices of the device are present on the ejection surface at a density of up to about 160,000 exit orifices/cm².

125. The separation block according to claim 111, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the device is less than about 500 μ

m.

126. The separation block according to claim 111, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the device is less than about 200 μ

m.

127. The separation block according to claim 111, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the device is less than about 100 μ

m.

128. The separation block according to claim 111, wherein the spacing on the ejection surface between the centers of adjacent exit orifices of the device is less than about 50 μ

m.

129. The separation block according to claim 111, wherein the system is configured to permit an electrospray of fluid at a flow rate of up to about 2 μ

L/minute.

130. The separation block according to claim 111, wherein the system is configured to permit an electro spray of fluid at a flow rate of from about 100 nL/minute to about 500 nL/minute.

131. The separation block according to claim 111, wherein the device is configured to permit an electrospray of fluid at a flow rate of greater than about 2 μ

L/minute.

132. The separation block according to claim 111, wherein the flow rate is from about 2 μ

L/minute to about 1 mL/minute.

133. The separation block according to claim 111, wherein the electrospray device density in the array exceeds about 5 devices/cm².

134. The separation block according to claim 111, wherein the electrospray device density in the array exceeds about 16 devices/cm².

135. The separation block according to claim 111, wherein the electrospray device density in the array exceeds about 30 devices/cm².

136. The separation block according to claim 111, wherein the electrospray device density in the array exceeds about 81 devices/cm².

137. The separation block according to claim 111, wherein the electrospray device density in the array is from about 30 devices/cm² to about 100 devices/cm².

138. The separation block according to claim 111, wherein said array is an integral monolith of said devices.

139. The separation block according to claim 111, wherein at least two of the devices are in fluid communication with different fluid streams.

140. The separation block according to claim 111, wherein at least one spray unit is configured to generate multiple electrospray plumes of fluid.

141. The separation block according to claim 111, wherein at least one of the electrospray devices is configured to generate a single combined electrospray plume of fluid.

142. The separation block according to claim 111, wherein at least one spray unit is configured to generate a single electrospray plume of fluid.

143. The separation block according to claim 111, wherein at least one spray unit is configured to generate multiple electrospray plumes of fluid which remain discrete.

144. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 9 mm or less.

145. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 4.5 mm or less.

146. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 2.2 mm or less.

147. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 1.1 mm or less.

148. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 0.56 mm or less.

149. The separation block according to claim 111, wherein the spacing on the ejection surface between adjacent devices is about 0.28 mm or less.

150. The separation block according to claim 111, further comprising:

a device to receive fluid droplets/sprays of fluid from the exit orifice of the system of electrospray devices.

151. The separation block according to claim 150, wherein said device to receive fluid droplets/sprays comprises:

a daughter plate having a plurality of fluid receiving wells each positioned to receive fluid ejected from a respective one of the device exit orifices.

152. The separation block according to claim 150, wherein said device to receive fluid is a mass spectrometry device.

153. A separation block system comprising:

a plurality of separation blocks according to claim 108, wherein the separation blocks are stacked one upon the other and each of the plurality of exit orifices of a block above another are aligned with the corresponding one of the plurality of entrance orifices of the block below.

154. The system according to claim 153, wherein the separation material in one block has the same separation characteristics as the separation material in the other blocks.

155. The system according to claim 153, wherein the separation material in at least one block has different separation characteristics than the separation material in the other blocks.

156. The system according to claim 153, wherein the separation material in a first block effects an ion exchange separation and the separation material in a second block downstream of the first block effects a reversed-phase separation.

157. The system according to claim 153, wherein samples that are separated in the first separation block are separated by fractionation.

158. The system according to claim 153, wherein the method of fractionation is isocratic, step or gradient separation.

159. The system according to claim 153, wherein elution fractions from the first separation block are sequentially transferred to an array of different separation blocks.

160. The system according to claim 153, wherein the polymerized separation material comprises a porous polymer, polymer monolith, non-monolith polymer particles, particles containing a stationary phase, silica particles, non-porous silica, or silica particles encapsulated in a polymer matrix.

161. The system according to claim 153, wherein said separation comprises liquid chromatography, ion chromatography, affinity chromatography, capillary electrophoresis, or capillary electrochromatography.