Patent Publication Number: US-5838002-A

Title: Method and apparatus for improved electrospray analysis

Description:
TECHNICAL FIELD 
     This invention relates to a method and apparatus for electrospraying solutions of chemical species for detection in gas phase ion detectors from liquid solutions, particularly chemical species that are separated and detected with liquid chromatography-mass spectrometry. 
     BACKGROUND ART 
     The production of intact gas phase ions from compounds dissolved in solution has been a topic of considerable attention for some time, particularly in liquid chromatography-mass spectrometry. 1  Typically, the ion production process has been problematic for labile and/or high molecular weight compounds because, in many cases, the energy input to facilitate a phase change from liquid to the gas resulted in chemical reactions, rearrangements or degradation of the analyte of interest. Many compounds separated with liquid chromatography fall into this category. In recent years electrospray (ES) and electrohydrodynamic processes (EHD) have successfully demonstrated capabilities for ion production with both labile and high molecular weight compounds. 2  6 The terms electrospray and electrohydrodynamic are sometimes used interchangeably. For the present discussion we will referred to both processes as electrospray and restrict our definition to sprays in which conical deformation of the liquid occurs as a result of high electrical potential. This is referred to as the cone-jet mode of electrospray. 
     The mechanism of ion production in ES has been the subject of considerable debate over the years. 7  The characteristic geometry of ES aerosol and ion generators is the simple cone-jet  8  as seen in FIG. 1. We can summarize the process of electrospray by describing each part of the spray as labeled. A conducting liquid usually emerges from a capillary tube held at high electrical potential (Region A). The liquid accelerates toward a counterelectrode and assumes the characteristic conical geometry (Region B). At the apex of the cone, a high velocity jet emerges (Region C) which subsequently breaks into highly charged droplets (Region D). The highly charged droplets in Region D are generally evaporated with dry gas 5  or heat 9  to produce further breakup of the liquid and formation of gas phase ionic species. In some instances ions are emitted directly from the apex of the cone instead of a jet, particularly with liquid metal emittors. 10  Cone-jet aerosol sources have been utilized for a number of applications; including, mass spectrometry sample introduction and ionization, 5 ,11 particle generation, 12  and thruster technology, 13  and liquid metal ion sources. 10  . The operation of cone-jet source of aerosols has been demonstrated at atmospheric  14  - 17  and at reduced pressure. 10 ,18 
     The production of ions from an ES source has demonstrated extremely good applicability for compounds that are labile and/or high molecular weight. Typically ES ion sources are operated at atmospheric pressure because of the efficient heat transfer at these pressures to the charged droplets which results in the evaporation of the primary droplets and concomitantly causes efficient ion production. Unfortunately, at atmospheric pressure only a fraction of the ions produced are actually sampled into the low pressure detectors because of the difficulty of focusing and sampling ions through small sampling apertures to reduced pressures. Larger apertures are sometimes used to improve sampling efficiencies; however, these require more costly and/or higher capacity pumping on the vacuum system to maintain acceptable detector operating pressures. Another limitation of atmospheric pressure ES operation is the threshold of electrical discharge across the gap between the high electrical potential capillary and the counterelectrode. This threshold is generally a function of capillary and counterelectrode spacing and geometry, surrounding gas composition, and pressure. The operating voltages are limited by the discharge threshold due to partial or complete degradation of the electrospray process during an electrical discharge. Discharges generally present a greater limitation while operating atmospheric pressure ES sources in the negative ion mode.  19 ,20 
     The operation of ES processes at reduced pressures has allowed scientists to reduce the total gas load on the vacuum system. The operating pressure must be sufficiently low to prevent electrical discharge. 21  Experimental results with ES at low pressure have demonstrated (1) instability of the liquid cone-jet resulting in the formation of multiple swirling cone-jets; (2) instability in the directionality of the resulting liquid jet; (3) freezing and (4) boiling of the liquid cone at the end of the capillary; (5) a high degree of solvent clustering of the ions leaving the electrospray cone; and (6) gas phase ions possessing a wide spread in kinetic energy making the collection and focusing of the ions difficult. 2-6 ,18,21 Solvent clustering, along with the divergence of the droplets from the axis of the tip of the liquid cone, freezing and boiling of the liquid cone and instability of the electrospray cone have made ion detection in the low pressure mode of operation irreproducible and difficult to interpret. 
     Practioners of EHD minimize the problem of freezing and boiling by dissolving there analyte in a non-volatile solvent, such as glycerine, and introducing sample into a vacuum chamber at reduced flow rates (nanoliters/min). Some low pressure ES devices included various lenses for controlling the ions (not droplets) downstream from ES needle. 3 ,4,6,18 Prior related art can be divided into four (4) groups: 
     1. low pressure electrospray without a focusing means for sampling into a low pressure detector (such as, references 4 and 23); 
     2. low pressure electrospray with a focusing means for directing the aerosol into low pressure detectors (such as, references 3 and 6); 
     3. low pressure electrospray with a focusing means for directing aerosol into a high pressure declustering region (such as, reference 6); and 
     4. low pressure electrospray without a focusing means and sampling the aerosol into a high pressure ionization region (such as, reference 22). 
     The art of Mahoney and coworkers  6  addresses declustering downstream from the spray but does not effectively deal with the evaporation of droplets produced at low pressure. 
     Platzer 22  addresses the problem of solvent declustering and wide kinetic energy spread at low pressures by directly spraying from low pressures through a heated tube into a higher pressure ionization region. The art of Platzer fails to address the inherent instability of the primary electrospray process, freezing and boiling in a vacuum; and the wide angular and spatial dispersion of the spray. The primary outcome of failing to address the low pressure spray stability will result in significant losses of analyte and droplets on the walls of their first chamber and the heated transfer tube. Although, they may collect some of the spray through the tube by virtue of large cross sectional diameters, they will still have irreproducible and unstable signal resulting from the unstable spray processes. 
     The object of the current invention is to overcome the aforementioned limitations of both atmospheric pressure and low pressure operations of electrospray. 
     REFERENCES 
     1. Neissen, W. M. A.; van der Greef, J. Liquid chromatography-Mass Spectrometry, Principles and Applications, Dekker: New York, 1992. 
     2. Smith, D. P. H. IEEE Trans. Ind. AppI. 1986, IA-22, 527-535. The electrohydrodynamic atomization of liquids. 
     3. Cook, K. D. Mass Spect. Rev. 1986 5, 467-519. Electrohydrodynamic mass spectrometry. 
     4. Duelcks, T., Roeligen, F. W. J. Mass Spectrom. 1995 30, 324-332. Ion source for electrohydrodynamic mass spectrometry. 
     5. (a) Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989, 246, 64-70. Electrospray ionization for mass spectrometry of large biomolecules. (b) Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Mass Spectrom. Rev. 1990, 9, 37-70. Electrospray ionization-principles and practice. 
     6. (a) Mahoney, J. F., Perel, J., Lee, T. D., Legesse, K.; A theoretical and experimental basis for producing very high mass biomolecular ions by electrohydrodynamic emission; presented at the 27th IEEE Industry Applications Society Annual Meeting, Atlanta, Ga, Oct. 18-23,1987. (b) Lee, T. D., Legesse, K., Mahoney, J. F., Perel, J.; An EHD source for the mass spectral analysis of peptides; Proceedings of the 36th ASMS Conference on Mass Spectrometry and Allied Topics, San Francisco, Calif. Jun. 5-10, 1988. (c) Lee, T. D., Legesse, K., Mahoney, J. F., Perel, J.; Electrohydrodynamic emission mass spectra of peptides; Proceedings of the 37th ASMS Conference on Mass Spectrometry and Allied Topics, Miami Beach, FL, May 21-26, 1989. (d) Mahoney, J. F., Perel, J., Lee, T. D., Husain, S., Todd, P. J., Cook, K.; Electrohydrodynamic ion source design for mass spectrometry: Ionization, ion optics and desolvation; Proceedings of the 38th ASMS Conference on Mass Spectrometry and Allied Topics, Tucson, AR, Jun. 3-8, 1990. 
     7. lkonomou, M. G.; Blades, A. T.; Kebarle, P. Anal. Chem. 1991, 63, 1989-1996. Electrospray-ion spray: A comparison of mechanisms and performance. 
     8. Grace, J. M.; Marijinissen, J. C. M. J. Aerosol Sci. 1994, 25, 1005-1019. A Review of liquid atomization by electrical means. 
     9. Chowdhury, S. K., Viswanatham, K., Chait, B. T. Rapid Comm. Mass Spectrom. 1990, 4, 81-87. An electrospray ionization mass spectrometer with new features. 
     10. Prewett, P. D.; Mair, G. L. R. Focused Ion Beams from Liquid Metal Ion Sources; Research Studies Press, Ltd.: Somerset, England, 1991. 
     11. Kebarle, P. and Tang, L. Anal. Chem. 1993, 65, 972A-986A. From ions in solution to ions in the gas phase, The mechanism of electrospray mass spectrometry. 
     12. Lewis, K. C., Dohmeier, D. M., Jorgenson, J. W., Kaufman, S. L., Zarrin, F., Dorman, F. D., Anal. Chem. 1994, 66, 2285-2292. Electrospray-condensation particle counter, A molecule-counting LC detector for macromolecules. 
     13. Bailey, A. G. (ed.) &#34;Chapter 8 Further Applications of Charged Drops&#34;, pp. 171-176, IN Electrostatic Spraying of Liquids, Research Studies Press Ltd.: Somerset, England, 1988. 
     14. Zeleny, J. Proc. Camb. Phil. Soc, 1915, 18, 71-83. On the conditions of instability of electrified drops, with applications to the electrical discharge from liquid points. (b) Zeleny, J. Phys. Rev. 1917, 10,1-6. Instability of electrified liquid surfaces. 
     15. Taylor, G. I. Proc. R. Soc. 1969, A313, 453-475. Electrically driven jets. 
     16. de la Mora, J. F., Loscertales, I. G. J. Fluid Mech. 1994, 260, 155-184. The current emitted by highly conducting Taylor Cones. 
     17. (a) Gomez, A., Tang, K. Phys. Fluids 1994,6, 404-414. Charge and fission of droplets in electrostatic sprays. (b) Gomez, A., Tang, K. Phys. Fluids 1994,6, 2317-2332. On the structure of an electrostatic spray of monodisperse droplets. 
     18. Luttgens, U., Dulcks, T., Roligen, F. W. Surface Science 1992, 266,197-203. Field induced disintegration of glycerol solutions under vacuum and atmospheric pressure conditions studied by optical microscopy and mass spectrometry. 
     19. Le Blanc, J. C. Y.; Guevremont, R.; Siu, K. W. M. 1993, Int. J. Mass Spectrom. Ion Proc. in press. Electrospray mass spectrometry of some proteins and the aqueous solution acid/base equilibrium model in the negative ion detection mode. 
     20. Ikonomou, M. G.; Blades, A. T.; Kebarle, P. J. Am. Soc. Mass Spectrom. 1991, 2, 497-505. Electrospray mass spectrometry of methanol and water solutions suppression of electric discharge with SF 6  gas. 
     21. Dohmeier, D. M., Ph.D. Dissertation, University of North Carolina, Chapel Hill, N.C. 1991; Chapter 4, Electrospray in vacuum as a potential interface between open tubular liquid chromatography and mass spectrometry; pp. 92-172; IN: Open tubular liquid chromatography: Studies in column efficiency and detection. 
     22. Platzer, B.; &#34;Process and device for feeding liquid samples to mass spectrometers by electrostatic nebulisation,&#34; WO Patent 95/34089 (Dec. 14, 1995). 
     23. Jorgenson, J. W. and Dohmeier, D. M.; &#34;Microelectrospray method and apparatus&#34;, U.S. Pat. No. 5,115,131 (May 19, 1992). 
     24. Fenn, J. B., Yamashita, M., Whitehouse, C.; &#34;Process and apparatus for changing the energy of charged particles contained in a gaseous medium&#34;, U.S. Pat. No. 4,542,293 (Sep. 17, 1985). 
     25. Rayleigh, Lord Proc. Phil. Mag. Series, 1882, 5, 184-186. On the equilibrium of liquid conducting masses charged with electricity. 
     SUMMARY OF INVENTION 
     The current invention is intended to overcome many of the aforementioned limitations of conventional atmospheric pressure electrospray and low pressure electrohydrodynamic (EHD) devices by physically separating the primary aerosol generation process from the secondary aerosol and ion generation processes and discretely optimizing both. The primary process of cone-jet formation is controlled by thermal and electrostatic means to facilitate the formation of a directionally stable liquid cone-jet. Once a stable cone-jet is formed, the jet and resulting droplets are introduced into a evaporation region where the secondary aerosol is generated and the ion generating processes take place. 
     A liquid solution is introduced through a needle, held at high electrical potential, into a first chamber maintained at reduced pressure to produce a stable electrospray cone-jet. The product of this primary process is intended to be a highly charged liquid jet and droplets from an electrospray source directed on the axis of a counterelectrode (see FIG. 1). In contrast, other devices used in low pressure ES systems are typically operated to produce ions directly from the primary cone. 43 ,4,6 The pressure in the first chamber of the present device is maintained below the pressure at which electrical discharge occurs, typically less than 0.1 Torr. Ancillary heating of the tube may be required in the first chamber to prevent freezing of the liquid from evaporative cooling. 
     The liquid cone-jet in the present device is stabilized by the electrostatic lens surrounding the capillary resulting in a constant (in time) conical geometry with a constant (in space) axial direction associated with the liquid jet. The liquid jet under influence of surface tension will break into droplets that will continue in the axial direction of the jet. The present invention takes advantage of the extremely small axial cross-section of the liquid jet and droplets and their high axial velocity, to sample all of this jet of liquid across a high pressure gradient through a small cross sectional aperture into a higher pressure region. The aperture size is selected for efficient transfer of liquid through the aperture and in order to maintain pressure requirements in both the first chamber (to prevent discharge) and the second chamber (to desolvate, breakup ion clusters, form ions, react species, and focus ions). 
     A key aspect of the present method of ion generation is the precise alignment of the liquid jet with the sampling aperture located in the wall of the first chamber leading into the second chamber. This alignment allows virtually all analyte in solution to be introduced into the second chamber. The alignment of the jet may be accomplished with either mechanical translational adjustment, and/or electrostatic or magnetic steering. The stability of the cone-jet is also dependent upon the geometry and spatial relationship of the stabilizing electrode; and the stability of the liquid flow. 
     Once the liquid jet is aligned with the aperture, the high velocity highly charged jet and primary droplets are introduced into the higher pressure chamber (the second chamber) in order to more efficiently conduct heat to the droplets causing the evaporation of the volatile components in the droplets. The extent of evaporation in the second chamber is regulated by a controlled heat supply, the gas composition, gas pressure and the geometry of the region. As the droplet decreases in size, due to the evaporation of the volatile components, the density of charges on the surface of the droplet increases, driving the highly charged droplets to the limit of charging, sometimes called the &#34;Rayleigh limit&#34;. 25  At this point the primary droplets deform and emit secondary droplets, ion clusters, or ions. The secondary droplets undergo further evaporation and a subsequent emission of droplets, ion clusters and ions. The ions that leave the droplets may be highly solvated or clustered. Collision of ions and/or ion clusters with the residual background gas(es) or other ions in this higher pressure region will be sufficiently energetic to decluster the adducts and leave intact gas phase molecular ions formed from the electrospray process. These ions can then be focused, analyzed, and detected by conventional means, such as a mass spectrometer. Examples of mass spectrometers; include, (but are not limited to) time-of-flight, ion traps, fourier transform, quadrupole, magnetic sector, and tandem instruments. 
     Because the second chamber affords a degree of isolation of the ion generation processes from the primary droplet charging process, alternative operating conditions are compatible with the present device. For example, the second chamber can be pressurized with helium (a highly conductive gas) to induce efficient desolvation. This gas results in a gas discharge when used with conventional electrospray devices, at atmospheric pressure. Another example, would be the use of high energy sources, such as, dc and rf discharges, to augment both desolvation, ionization processes, and fragmentation. The second chamber could also serve as a reaction chamber for a variety of processes, as a collector or trap of selected ions for storage and/or subsequent analyze (e.g. quadrupole trap, potential well trap). 
     The restriction of the total mass flow into the vacuum system with the present devise significantly reduces the system pumping requirements when compared to conventional ES devices. The production of a stable cone-jet at reduced pressures minimizes the problems associated with gas discharge in atmospheric pressure modes of operation, particularly in negative ion mode. The collection of virtually the entire primary aerosol into a higher pressure region allows efficient ion production and declustering and eliminates problems associated with other low pressure ES devices, such as, spatial and directional instabilities and cluster formation. Since ion production occurs in close proximity to the mass analyzer or other gas phase ion detectors, the transport losses compared with atmospheric ES operation are not as significant. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring to FIG. 2, a preferred embodiment of the invention, which may be  but is not limited to! the effluent from a liquid chromatograph, flows within tube 17 in the direction of the arrow and all or a portion of the liquid is caused to flow out of capillary tube 10. Excess liquid flows out of splitter tube 16 in a flow splitter configuration. Insulator tube 15 joins onto tee 14 and is composed of an electrically insulating material. Insulator tube 15 is of sufficient length, internal diameter, and total resistance to maintain an electrical potential difference between the high voltage power supply and the liquid chromatograph, which is at ground. Tee 14 is composed of electrically conducting material, usually stainless steel. Tee 14 is connected to a high voltage power supply which can be regulated in terms of voltage, current, a combination of current and voltage, and possibly modulated. Tee 14 may be kept at several thousand volts, but is not limited to this. The portion of the liquid that flows through capillary tube 10 also flows into vacuum chamber 1, through a vacuum seal 13 composed of an electrically insulating material, such as glass, or lexan, which also provides mechanical support for capillary tube 10. Capillary tube 10 may be composed of an insulating or metallic material. 
     An electrode or coaxial cylindrical tube 11 is located coaxially to the capillary tube 10. For liquid cone-jet stability, electrode 11 is a coaxial cylindrical tube but not limited to this specific geometry (e.g., plate(s), quadrupole, octopole). Coaxial cylindrical tube 11 is composed of electrically conducting material, usually stainless steel. Coaxial cylindrical tube 11 is also at a high electrical potential which is adjustable to maintain a stable axial spray. Adjuster 12 is affixed to both tubes 10 and 11 and allows mechanical alignment of these tubes relative to one another and relative to the entrance lens 21. 
     FIG. 3 is an expanded view of the cone-jet region of the preferred embodiment. Liquid cone 76 emerges from the tip 9 of the capillary tube 10 and forms a liquid jet 19 moving in the direction of entrance lens 21. The alignment of the liquid jet 19 with exit or pinhole aperture 28 is performed with adjuster 12 to ensure the liquid flows into chamber 2. 
     As seen in FIG. 2, the second chamber 2 is separated from chamber 1 by means of an entrance lens 21 and skimmer lens 22. Inside chamber 2 is an additional focusing lens 20. All three lens are made of metal and serve as focusing lens for ions and charged particles. Entrance lens 21 is isolated from focusing lens 20 by insulator 23 and in turn, focusing lens 20 is isolated from chamber 2 by insulator 27. Skimmer lens 22 is isolated from chamber 2 by insulator 24. The housing of chamber 2 is made of metal and serves as a focusing lens for ions and charged particles contained in chamber 2. The volume, length and geometry is chosen to minimize surface losses of analyte and maximize transport of ions. 
     A conductive gas, such as nitrogen or helium but not limited to such gases, is added to chamber 2 through gas tube 52 from a gas supply source 50 in sufficient quantity to maintain chamber 2 at a pressure greater than either chambers 1 or 3. Gas tube 52 enters chamber 1 through vacuum feedthrough 53 and is electrically isolated from gas inlet tube 55 by means of an electrically insulating union 54. Electrically insulating union 54 is composed of a gas impermeable electrically insulating material such as glass, or ceramic but not limited to this specific material. Gas inlet tube 55 then joins chamber 2. Gas tube 52 and gas inlet tube 55 are made of a material impermeable to gas such as metal, but not limited to this specific material. 
     Gas may be removed from chamber 2 through pump out line 72. This pump out line 72 is pumped by a mechanical pump (not shown) to maintain an effective pressure in chamber 2 greater than either chambers 1 or 3. Pump out line 72 enters chamber 1 through vacuum feedthrough 73 and is electrically isolated from gas outlet tube 75 by an electrical insulating union 74. Electrically insulating union 74 is composed of a gas impermeable electrically insulating material such as glass, or ceramic but not limited to this specific material. Gas outlet tube 75 then joins chamber 2. Pump out line 72 and gas outlet tube 75 are made of a material impermeable to gas such as metal, but not limited to this specific material. The flow, pressure and composition of gas(es) into chamber 2 are controlled by a combination of the gas manifold (not shown), gas inlet valve 51, gas outlet valve 71, and sizes of apertures 28 and 29. Chamber 2 is heated by a heater cartridge 26 imbedded in the chamber wall 25, and a thermocouple (not shown) attached to the chamber indicates the temperature and couples to a temperature controller to adjust the heater power to maintain the desired temperature. 
     Ions, any residual charged droplets or particles and the added gas exit from chamber 2 through skimmer lens 22 located on axis with the entrance lens 21 into chamber 1. Skimmer lens 22 is electrically isolated from the chamber 2 so that a potential can be applied to cause ions to drift toward lens 22 and thus increase the fraction of ions that exit through aperture or pinhole aperture 29 of said skimmer lens 22. The ions exit from chamber 2 into associated ion optics (planar lens 30, planar entrance lens 33, extractor lens 38) used for focusing ions into the mass analyzer 34. 
     Adjacent to chamber 2 and along the longitudinal axis of chamber 2, inside chamber 1 at high vacuum, is an element or extractor lens 38 to which electrical potentials are applied for accelerating the ions away from the aperture 29 of skimmer lens 22. Adjacent to extractor lens 38 and along the longitudinal axis of chamber 2 and extractor lens 38, are one or more planar lenses 30 which are used to focus ions into planar entrance lens 33, from whence they proceed into the mass analyzer 34 and are detected by a detector which is normally an electron multiplier but can be a Faraday cage or other conventional device for registering the arrival of ions (not shown). A quadrupole mass filter is shown to be the mass analyzer. 
     The mass analyzer is located in vacuum chamber 3 which must be maintained at 10 -5  torr or below for normal operation. An isolator wall 37 divides chambers 1 and 3 and contains a planar entrance lens 33. Planar entrance lens 33 is electrically isolated from isolator wall 37. Chamber 3 is evacuated through pumping port 61. In this differently pumped embodiment, higher pressures and associated gas loads can be accommodated in chamber 1 while still maintaining normal operating pressures in chamber 3. 
     FIG. 4 illustrates a second embodiment of the invention where chamber 2, mass analyzer 34 and associated ion optics (planar lens 30, extractor lens 38) all reside inside the same chamber, chamber 1. Chamber 1 is a region of high vacuum, evacuated through pumping port 60. In contrast to the said first embodiment (a differentially pumped system, as shown in FIG. 2), a larger pump would be required to evacuate chamber 1 through pumping port 60 to maintain a normal operating pressure of 10 -5  torr or below if the same size apertures (28 and 29) for entrance lens 21 and skimmer lens 22 are used in this said second embodiment. 
     A third embodiment of the invention is a variation of the second embodiment, where apertures 28 and 29 for entrance lens 21 and skimmer lens 22 are smaller than those used in either the first or second embodiments. In this said third embodiment the pressure in chamber 1 could be maintained at normal operating pressure for the mass analyzer with a similar pump use in said first embodiment (a differentially pumped system). In said second and third embodiments of the invention, the planar lens 30 focuses ions directly into the mass analyzer 34 rather than through planar entrance lens 33. 
     REFERENCE NUMBERS IN DRAWINGS 
     1. chamber 1 
     2. chamber 2 
     3. chamber 3 
     9. tip of capillary tube 
     10. capillary tube 
     11. electrode or coaxial cylindrical tube 
     12. adjuster 
     13. vacuum seal 
     14. tee 
     15. insulator tube 
     16. splitter tube 
     17. tube 
     19. liquid jet 
     20. focusing lens 
     21. entrance lens 
     22. skimmer lens 
     23. insulator 
     24. insulator 
     25. chamber wall 
     26. heater cartridge 
     27. insulator 
     28. exit or pinhole aperture 
     29. aperture or pinhole aperture 
     30. planar lens 
     33. planar entrance lens 
     34. mass analyzer 
     37. isolator wall 
     38. extractor lens 
     50. gas supply source 
     51. gas inlet valve 
     52. gas tube 
     53. vacuum feedthrough 
     54. electrically insulating union 
     55. gas inlet tube 
     60. pumping port 
     61. pumping port 
     71. gas outlet valve 
     72. pump out line 
     73. vacuum feedthrough 
     74. electrically insulating union 
     75. gas outlet tube 
     76. liquid cone 
     BRIEF DESCRIPTION OF THE DRAWINGS 
     This invention will be described in greater detail by reference to the drawings, in which: 
     FIG. 1 is a schematic diagram of the regions (Region A: Needle, Region B: Cone, Region C: Jet, Region D: Plume) associated with electrospray aerosol generation and ionization. 
     FIG. 2 is a schematic cross-sectional diagram of the present invention with a differentially pumped vacuum system in a liquid chromatography mass spectrometer implementation. 
     FIG. 3 is a detailed cross-sectional diagram of a preferred embodiment of the invention showing an expanded view of the capillary tube, the cone-jet in chamber 1 being steered through an entrance lens into the higher pressure chamber, chamber 2. 
     FIG. 4 is a detailed cross-sectional diagram of an alternative vacuum configuration for the present device.