Abstract:
An improved electrospray ion source for increasing the current generated from the electrospray process and of the type having a needle ( 10 ), a counter-electrode ( 20 ), a saddle or outer electrode ( 30 ), and concurrent flow of gas ( 92 ). A method and device is disclosed that utilizes a controlled electrospray nebulizer where an aerosol comprised of charged droplets and gas-phase ions is sprayed into a field-free or near field-free desolvation or reaction region ( 120 ). This process results in the production and ultimate destination of charged aerosols and gas-phase ions in field-free or near field-free regions ( 120, 201, 210, 240, 340 ) where they can be directed towards and into a sampling aperture or tube; directed into a reaction region resulting in to the production of reaction products; or directed and deposited on surfaces resulting in the production of desorbed products by means of a concurrent flow of gas or nebulizing gas ( 92, 94, 96 ), a potential difference between the regions of production and destination, counter-current flow of gas, or a combination thereof. The method is useful for increasing the detection of analytes in solutions that are electrosprayed and analyzed with mass spectrometry.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of Provisional Patent Application Ser. No. 60/881,584, filed Jan. 22, 2007 by the present inventors. This application is related to application Ser. No. 08/946,290, filed Oct. 7, 1997, now U.S. Pat. No. 6,147,345, granted Nov. 14, 2000; application Ser. No. 09/877,167, filed Jun. 8, 2001, now U.S. Pat. No. 6,744,041, granted Jun. 1, 2004; application Ser. No. 10/449,147, filed May 31, 2003, now U.S. Pat. No. 6,818,889, granted Nov. 16, 2004; application Ser. No. 10/449,344, filed May 1, 2003, now U.S Pat. No. 6,888,132, granted May 3, 2005; application Ser. No. 10/661,842, filed Sep. 12, 2003, now U.S. Pat. No. 6,949,740, granted Sep. 27, 2005; application Ser. No. 10/688,021, filed Oct. 17, 2003, now U.S. Pat. No. 6,943,347, granted Sep. 15, 2005; application Ser. No. 10/785,441, filed Feb. 23, 2004, now U.S. Pat. No. 6,878,930, granted Apr. 12, 2005; application Ser. No. 10/862,304, filed Jun. 7, 2004, now U.S. Pat. No. 7,087,898, granted Aug. 8, 2006, application Ser. No. 10/863,130, filed Jun. 7, 2004, now U.S. Pat. No. 6,914,243, granted Jul. 5, 2005; application Ser. No. 10/989,821, filed Nov. 25, 2004, now U.S. Pat. No. 7,081,621, granted Jul. 25, 2006; application Ser. No. 11/120,363, filed May 2, 2005, now U.S. Pat. No. 7,095,019, granted Aug. 22, 2006; application Ser. No. 11/173,377, filed Jun. 2, 2005, now U.S. Pat. No. 7,060,976, granted Jun. 13, 2006; application Ser. No. 11/491,634, filed Jul. 24, 2006, now U.S. Pat. No. 7,253,406, granted Aug. 7, 2007; and provisional application Ser. No. 60/724,399, filed Oct. 7, 2005. 
    
    
     GOVERNMENT SUPPORT  
     Not Applicable 
     SEQUENCE LISTING OR PROGRAM 
     Not Applicable 
     BACKGROUND 
     1. Field of Invention 
     This invention relates to methods and devices for improved electrospray nebulization and ionization, specifically to such electrospray nebulizers which are used for the production and introduction of gas-phase ions at atmospheric pressure into mass spectrometers and other gas-phase ion analyzers and detectors. 
     2. Discription of Prior Art 
     Ion sources that utilize high electrical potentials to generate ions at or near atmospheric pressure; such as, atmospheric pressure discharge ionization and chemical ionization, and electrospray ionization; have low sampling efficiency through conductance or transmission apertures, where less than 1% [often less than 1 ion in 10,000] of the ion current emanating from the ion source make it into the lower pressure regions of the present interfaces for mass spectrometry. Thereafter, scientists have devised several means of delivering and transferring gas-phase ions from atmospheric pressure sources into the vacuum system of mass spectrometers, such as, using lower flow electrostatic sprayers to form very small droplets [referred to as nanospray], using increased heating of the aerosols to generate more gas-phase ions, increasing the sampling diameter of the sampling aperture at the atmospheric-lower pressure interface, and using electrostatic, electrodynamic, or aerodynamic lens at atmospheric and low pressure to focus highly charged liquid jets, aerosols of droplets and ion clusters, and gas-phase ions. 
     Lens for Low Pressure Sources: Liquid Metal Ion and Low Pressure Electrospray Ion Sources 
     Electrodes or lens have been disclosed to increase the ion signal of electrospray sources and liquid metal ion sources operated at lower pressures—for example, in U.S. Pat. No. 4,318,028 to Perel et al. (1982), Mahoney et al. (1987), Lee et al. (1988, 1989), and U.S. Pat. No. 7,211,805 to Kaga et al (2007). Our own patents U.S. Pat. Nos. 5,838,002 (1998), 6,278,111 B1 (2001), and World patent 98/07505 (1998) describes a sub-atmospheric source comprised of a concentric tube which surrounds the end of the electrospray capillary which was used to electrically stabilize the liquid cone-jet, directing the liquid jet into a heated high pressure region where the jet broke up into small droplets and where gas-phase ions and ion clusters were formed. This approach proved feasible but it was found to difficult to control the collection and focusing of ions formed in this higher-pressure region due to the electrical breakdown of the gases. 
     Lens for Atmospheric Pressure Electrospray Sources: Between Sprayer and Aperture or Inlet 
     Several types of ring or planar electrodes positioned between the sprayer and an inlet aperture have been proposed to focus ions and charged droplets for example—Olivares et al. (1987) disclosed a focusing ring located downstream of the electrospray sprayer; U.S. Pat. No. 5,306,910 to Jarrell et al. (1994) disclosed a gird which is operated with an oscillating electrical potential to form gas-phase ions from highly charge droplets, while allowing the electrospray needle and entrance aperture to remain at ground potential, however, most of the droplets would impact on the grid as they pass through the grid, not making it into the inlet aperture; Feng et al. (2002) describes a series of annular electrodes downstream of an induction electrode used to guide charged droplets; Alousi et al. (2002) describes a lens between the electrospray needle and the entrance aperture dividing the ion source into two discrete areas, an area for the creation of highly charged droplets and gas-phase ions and a drift region with an electrical gradient across the area, leading to an increase of 2-10 fold in the signal intensity however, most of the ion current from the sprayer was deposited on the lens; and U.S. Pat. No. 7,071,465 to Hill, Jr. et al. (2006) disclosed placing the electrospray needle inside an ion mobility spectrometer comprised of a series of ring electrodes. 
     World patent 03/010794 A2 to Forssmann et al. (2003) disclosed a series of annular electrodes for ion acceleration and then subsequent ion focusing in front of the inlet aperture, similar to the device described by Jarrell et al. (1994). Jarrell et al.&#39;s device utilize an oscillatory potential while Forssmann et al.&#39;s device utilizes a direct current potential to first accelerate charged drops away from the electrospray needle, through an aperture in an accelerating electrode [or through an accelerating grid in Jarrell et al.&#39;s device], and then into a focusing region. In both cases, droplets are accelerated away from an electrospray needle and travel up a potential gradient into a focusing region due to their momentum. Droplets and any gas-phase ions resulting from the breakup of the droplets would more than likely impact on the accelerating electrodes due to the diverging electrostatic fields along the axis of the electrodes. 
     Lens for Atmospheric Pressure Ion Sources: Lens at Electrospray Nebulizer and Discharge Source 
     Several types of ring or planar electrodes at the sprayer have been proposed to focus ions and charged droplets at atmospheric pressure. U.S. Pat. No. 4,531,056 to Labowsky et al. (1985) disclosed a perforated diaphragm used to direct the flow of a gas over an electrospray needle to aid in the evaporation of highly charged droplets emanating from the needle and sweep away gas-phase solvent molecules from the area in front of the inlet aperture. In addition, the diaphragm was used to stabilize the position of the needle to direct the liquid jet through a center aperture in the diaphragm leading into a desolvation or ionization region. 
     For discharge ion sources, such as atmospheric pressure ionization of gases and atmospheric pressure chemical ionization, several types of lenses at the discharge source have been proposed and/or implemented—for example, U.S. Pat. No. 6,147,345 to Willoughby (2000) disclosed an electrospray ion source comprised of a discharge needle, a counter electrode, a lens, and a gas source for seeding the liquid emerging from an electrospray needle with counter ions; and U.S. Pat. No. 6,949,741 to Cody et al. (2005) and U.S. Pat. No. 7,112,785 to Larame et al. (2006), and now marketed as DART™ (Direct Analysis in Real Time) by JEOL-USA, Inc. (Peabody, Mass., www.jeol.com) and IONSENSE, Inc. (Peabody, Mass.; www.ionsense.com), disclosed an atmospheric discharge source comprised of a discharge needle, a counter electrode, and a field-free reaction chamber. Our own U.S. Pat. Nos. 6,888,132 (2005), 7,095,019 (2006), and 7,253,406 (2007), all to Sheehan et al. disclosed a remote reagent ion source comprised of a laminated high-transmission lens for ionizing gas-phase species in a field-free or near field-free reaction region; and U.S. provisional patent application 60/724,389 to Karpetsky et al. (2005) marketed and introduced for sale in June 2007 at the 55th ASMS Conference on Mass Spectrometry and Allied Topics (Indianapolis, Ind.), as Remote Reagent Ion Generator (RRIG) by Chem-Space Associates, Inc. (Pittsburgh, Pa.; www.lcms.com), disclosed a remote reagent chemical ionization source comprised of a discharge needle, counter electrode, and a saddle electrode coupled to a field-free transfer region for ionization of gas-phase species in a field-free or near field-free reaction region. 
     Several types of electrostatic lens or electrodes at the tip of the electrospray needle have been proposed, for example—Schneider et al. (2001, 2002) disclosed a ring shaped electrode incorporated near the tip of the electrospray needle which increased the detected ion signal and the stability of the signal and at the same time decreasing the dependence of the ion signal on the sprayer position; U.S. Pat. No. 7,067,804 to Chen et al. (2006) and G.B. patent application 2428514 to Syms (2007) both disclosed an individual lens and a series of lenses to shape the electric fields in the atmospheric pressure region to cause more ions from the source to reach a downstream ion detector; U.S. Pat. No. 6,462,337 to Li et al. (2002) disclosed an auxiliary electrode so as to increase the electric field gradient from the capillary to the inlet thereby focusing and decreasing the beam divergence; U.S. Pat. No. 6,992,299 to Lee et al. (2006) disclosed an aerodynamic ion focusing system that uses a high-velocity converging gas flow to focus a diverging aerosol ion plume; and U.S. Pat. No. 7,015,466 to Takats, et al. (2006) disclosed aerodynamic desolvation and focusing of the electrospray plume. 
     Two types of electrospray nebulizers with lens have been disclosed and are available for sale. An electrospray probe manufactured and sold by Thermo Scientific (San Jose, Calif.; www.thermo.com), H-ESI™ (Heated Electrospray Ionization) discloses aerodynamic desolvation and focusing using a supersonic flow of gas through a tube surrounding the electrospray needle. While U.S. Pat. Nos. 6,998,605 (2006), 7,041,966 (2006), 7,259,368 (2007), all to Frazer et al. disclosed an electrospray assembly at or near ground potential. The sample is introduced into the ionization chamber from an electrospray assembly at approximately ground potential. Two electrodes are provided within the chamber such that three electric fields are generated, a first field extending from the electrospray assembly to the first electrode, a second field extending from the second electrode to the first electrode, and a third field extending from the second electrode to the vacuum interface. Ionization takes place between the electrospray assembly and the second electrode. Ions are forces to travel through the three fields by a concurrent flow of gas and the electric fields generated by the electrodes and the vacuum interface, before entering the vacuum chamber. This design is incorporated into a multimode (electrospray and atmospheric pressure chemical ionization) source, G1978A™, offered by Agilent Technologies, Inc. (Santa Clara, Calif.; www.agient.com). 
     Nevertheless atmospheric lens, electrodes, and grids in electrospray ion sources heretofore known suffer from a number of disadvantages: 
     (a) Electrospray nebulizers where lens and electrodes are disposed in the ionization region where gas-phase ions are formed from charged droplets, droplets and ion-clusters are lost due to impaction on these structures. 
     (b) The use of lenses in the ionization region to focus ions and charged droplets leads to the dispersion of these ions as they past through each subsequent lens, such as the dispersion at the entrance to capillary tubes or apertures. Ions, droplets, and ion-clusters can be lost due to these dispersive forces. 
     (c) The use of multiple lenses in the ionization region requires the use of greater and greater potentials on the lens to focus the ions from one region to another. This creates a large electrostatic gradient across the ionization region which can lead to possible electrostatic breakdown of the gases in the region, the requirement for high voltage power supplies, and dispersive loses as the ions pass through the lens. In essence, the more you try to focus ions with larger potentials the more they will disperse as they leave the area of large potentials and enter areas of lower or no potentials, such as passing through an aperture or into a tube. 
     (d) If one uses high velocity flows of gas to focus ions there is a need for a large volume of gas and since larger droplets are influences more so than smaller droplets and gas-phase ions by these viscous forces, larger droplets are lost due to impaction on lens and walls of the ionization chamber and are thereby lost from the gas-phase ion production process. 
     OBJECTS AND ADVANTAGES 
     Accordingly several objects and advantages of the present invention are: 
     (a) to provide an electrospray nebulizer which will present a field-free or near field-free desolvation and ionization region for collecting and focusing charged droplets or gas-phase ions resulting from the desolvation process; 
     (b) to provide an electrospray nebulizer which will present a field-free or near field-free desolvation region where downstream electrostatic lens can compress the charged species, gas-phase ions, charged droplets, ion-clusters, etc., into a small cross-sectional area without the potentials of the ion source influencing the movement of the charged species; 
     (c) to provide an electrospray nebulizer which will present a field-free or near field-free region 100&#39;s of cm 3  in volume; 
     (d) to provide an electrospray nebulizer which will present a field-free or near field-free desolvation region where viscous forces can dominate the movement of gas-phase charged species, such as gas-phase ions, charged droplets, ion-clusters, etc.; 
     (e) to provide an electrospray nebulizer which will present a field-free or near field-free region for reacting charged droplets with gas-phase ions or aerosols of charged or neutral species, forming new charged species which can then be sampled by a gas-phase ion focusing device or analyzer, such as but not limited to, AC focusing devices, ion mobility, differential mobility, or mass spectrometers, etc.; 
     (f) to provide an electrospray nebulizer which will present a field-free or near field-free region where neutrals and charged droplets or gas-phase ions can reside for prolong periods of time allowing reactions between these species to occur over long periods of time; 
     (g) to provide an electrospray nebulizer which will present a field-free or near field-free region where the position of the nebulizer relative to the ion detector is not critical and independent of each other; 
     (h) to provide an electrospray nebulizer which will present an array of electrospray nebulizers to a single or multiple field-free regions; 
     (i) to provide an electrospray nebulizer which is independent of electrospray ion source type, such as but not limited to, nanospray, pneumatically assisted electrospray, etc.; 
     (j) to provide an electrospray nebulizer which will present a gas flowing between the electrospray needle and counter-electrode to aid in the production of a highly charged aerosol of charged droplets and then subsequently sweeping this highly charged aerosol into a field-free or near field-free region; 
     (k) to provide an electrospray nebulizer which will present a decoupling of the processes required for electrospraying a liquid, such as electrical potential, the magnitude of gas flow and temperature of the nebulizing gas, etc.; from the processes needed for ion evaporation, ion desorption, ion collection, focusing, and transport of ions into the vacuum chamber of a mass spectrometer; 
     (l) to provide an electrospray nebulizer which can be used to deposit charged droplets onto a surface in a field-free or near field-free region for the purpose of charging-up the surface or charging and subsequently ionizing any chemical species contained on the surface; 
     (m) to provide an electrospray nebulizer that can be incorporated along with a field-free or near field-free reaction or desolvation chamber, gases, electronics, controller, high voltage supplies, and gas-phase ion detector into a portable or benchtop chemical analyzer; and 
     (n) to provide an a chemical analyzer which will present the processes required for analyzing components on a surface by delivering charged droplets to the surface in a field-free or near field-free region, collecting ionized products, and subsequently identifying surface components; by controlling the production and transport of the highly charged aerosol of droplets to the surface. 
     Further objects and advantages are to provide a field-free electrospray nebulizer which can be used easily and conveniently to generate charged particles or droplets, which is inexpensive to manufacture, which can be supplied in a variety of configurations to accommodate liquid flows of several microliters to hundreds of microliters, which can be manufactured as a small probe the size of one&#39;s finger or as a larger assembly depending on the application; where the outside of the nebulizer is at ground potential, thereby allowing the probe to be handled without the risk of an electric shock; which can easily replace existing nebulizers; etc. Still further objects and advantages will become apparent from a consideration of the ensuing description and drawings. 
     SUMMARY 
     In accordance with the present invention a field-free electrospray nebulizer comprises a needle or capillary for delivering a liquid, a counter-electrode, a saddle electrode, and a concurrent flow of gas; for introducing charged droplets into a field-free region. The novelty of this device is the manner in which the charged droplets or aerosols in a field-free region are both physically and electrically isolated from the high electric fields of the aerosol or charged droplet generation region. This is accomplished through the utilization of a saddle electrode. 
    
    
     
       DRAWINGS FIGURES 
       In the drawings, closely related figures have the same number but different alphabetic suffixes. 
         FIG. 1  shows a cross-sectional view of a field-free electrospray nebulizer. 
         FIG. 2  show a similar view of the field-free electrospray nebulizer with an additional concurrent flow of gas incorporated into the nebulizer. 
         FIG. 3  show a similar field-free electrospray nebulizer configured as a pneumatically assisted electrospray nebulizer. 
         FIGS. 4   a  and  4   b  shows perspective cut-aways of field-free electrospray nebulizers incorporated into an atmospheric desolvation/ionization or reaction chamber:  4   a , showing the nebulizer configured on-axis and orthogonal with an emersion lens and funnel-well; and  4   b , shows two nebulizers incorporated into a reaction chamber with a sample inlet and ion optics. 
         FIG. 5  shows a perspective cut-away of a surface ionization and detection device. 
         FIGS. 6   a  (side view),  6   b  (front view), and  6   c  (top view) show bilateral views of the equipotential surfaces of the electrospray nebulizer, illustrating the relative potentials of the needle, counter-electrode, and saddle electrode; and the open ended saddle-field region flaring out into a field-free or near field free region. 
     
    
    
     DRAWING 
     Reference Numbers 
     
         
           10  electrospray needle or capillary 
           12  electrohydrodynamic spray 
           13  inner tube or capillary 
           14  co-axial tube 
           20  counter-electrode or inner electrode 
           22  aperture or passage 
           30  saddle or outer electrode 
           32  aperture or passage 
           40  insulated transfer tube 
           60  connector flange 
           70  liquid connectors 
           80  liquid sample inlet 
           90  gas-inlet 
           92  concurrent flow gases 
           94  concurrent gas 
           96  nebulizing gas 
           100  high-voltage feed-through 
           102  high-voltage connection 
           104  high-voltage connecting wire 
           110  insulator 
           120  field-free or near field-free region 
           130  open ended saddle-field region 
           200  nebulizer 
           201  chamber 
           210  desolvation/ionization region 
           220  ion optics assembly 
           230  sample inlet 
           240  desolvation/ionization-reaction region 
           250  exhaust 
           260  x, y, z adjustment stages 
           300  grounded housing 
           310  transfer tubing 
           320  aerosol beam 
           330  high-transmission element (HTE) 
           340  field-free or near field-free region 
           350  gas-phase ion detector 
           360  surface 
           361  gas-phase ions or charged droplets 
       
    
     DESCRIPTION 
     FIGS.  1  and  6 —Preferred Embodiment 
     The present invention may be used to generate electrospray aerosols in a field-free or near field-free region with higher total spray current and higher gas-phase ion production efficiency in order to detect a wide variety of ionized analytes in solution. Typical solvents include, but are not limited to water, methanol, isopropyl alcohol, ethanol, acetonitrile or solutions containing some or all of the mentioned solvents; delivered to the nebulizer from a liquid source, such as but not limited to, a high-performance liquid chromatograph (HPLC). Typical analytes are drugs and their metabolites or degradation products, biopolymers, metals, or any ionic species soluble in the solvents or mixtures of the solvents. Preferred liquid flow rates for the electrospray process are from 0.05 to 200 micro-liters per minute but may be as low as 0.001 micro-liters per minute, commonly referred to as nanospray. 
     A preferred embodiment of the present invention is a field-free electrospray nebulizer assembly or just nebulizer as illustrated in  FIG. 1 . The nebulizer is comprised of an electrospray needle or capillary  10 , a counter-electrode or inner electrode  20 , a saddle or outer electrode  30 , a connector flange  60 , liquid connectors  70   a ,  70   b ,  70   c  for connecting or joining tubing, liquid sample inlet  80 , gas-inlet  90 , and high-voltage feed-through  100 . The needle  10  is connected to the downstream end of an insulated transfer tube  40 , which electrically isolates the needle  10  from the connector flange  60 . The electrospray needle  10 , counter-electrode  20 , and saddle electrode  30  are made of electrically conductive materials, such as but not limited to stainless steel, etc. While the connectors  70  can be made of electrically conductive or insulating material. 
     Co-axial to and surrounding the needle is the counter-electrode  20  while the saddle electrode  30  is co-axial and downstream of both the needle  10  and counter-electrode  20 . Both the counter-electrode  20  and the saddle electrode  30  have passages or apertures  22 ,  32 . Insulator  110  isolates needle  10 , counter-electrode  20 , and saddle electrode  30  from each other. 
     Voltage power supplies (shown as Voltage Source) are connected to the electrospray needle  10 , the counter-electrode  20 , and saddle electrode  30  at high-voltage connections  102   a ,  102   b ,  102   c  through a high-voltage connecting wires  104 . For the electrospray needle  10  the high voltage connection is made through either direct contact with the needle  10 , in the case where the capillary  10  is a conductor; or alternatively the electrospray needle  10  may be made of insulating material, such as but limited to fused silica, glass, PEEK, etc; in which case the high-voltage connection can be made through the connector flange  60 , or the transfer tube  40  which would be further comprised of an insulated tube and a metal tube. Electrical potentials are established to produce an electrohydrodynamic spray  12  at the outlet of the needle  10  and to establish an open ended saddle-field region  130  flaring out into a field-free or near field-free region  120 . 
     The needle  10  is typically 0.5 to 3 mm in diameter (outside diameter) tapering to a point or tip. The counter-electrode  20  and saddle electrode  30  are 0.5 to 2 mm thick with the apertures  22 ,  32  configured as circular-shaped openings typically 0.5 to 1 mm in diameter. In other embodiments, the geometry of the apertures  22 ,  32  can be, but are not limited to, slotted, rectangular, diamond, or trapezoidal shapes, etc.; and the thickness of the electrodes  20 ,  30  can also vary depending on the particular gases used, shape of the needle  10 , flow of the liquid, etc. 
     All components of the device are generally made of chemically inert materials. The needle  10 , counter-electrode  20 , saddle electrode  30 , connector flange  60 , and wiring are comprised of conductive materials, such as stainless steel, brass, copper, gold, or aluminum. Circular electric insulator  110 , electrically isolate metal layers, respectively. 
     Gas or mixtures of concurrent flow gases  92  are supplied to the nebulizer and flow (along with the liquid) between the needle  10  and the counter-electrode  20  downstream towards and through the saddle electrode  30  out into the field-free or near field-free region  120 . Gases are supplied to the nebulizer from metered gas reservoirs (shown as Gas Source) through a gas in-let  90 . Gases or gas mixtures, such as but not limited to nitrogen or air can be used. 
     FIGS.  2 ,  3 ,  4   a , and  4   b —Additional Embodiments 
     Additional embodiments are shown in  FIGS. 2 ,  3 ,  4   a , and  4   b.    
     Adding Concurrent Gas Flow 
       FIG. 2  shows a modified saddle electrode  30  for adding additional gas into the field-free region  120 . A second supply of gas  94  is supplied and flows through an opening or a series of openings and out into the filed-free region  120 . The concurrent gas  94  may be comprised of nitrogen, air, gas mixtures, heated gas, etc. to aide in the evaporation of the aerosol, gas saturated with solvent vapor to suppress evaporation, or combination thereof. The flow or velocity of gas  94  may be slower than the flow of the aerosol emerging from aperture  32 , the same speed so as to establish iso-kinetic flow downstream of the saddle electrode  30 , or faster so as to cause more extensive mixing of the aerosol with the drying gas and also to impart a directionality to the total flow of gas and aerosol. 
     Pneumatically Assisted Electrospray 
       FIG. 3  shows an electrospray needle comprised of an inner tube or capillary  13  and on co-axial tube  14 . Nebulizing gas  96  is supplied between these tubes to aid the electrospray process. 
     Field-Free Nebulizer Desolation Assembly Incorporated into an Atmospheric or Near Atmospheric Desolvation/Ionization Chamber and a Reaction Chamber 
       FIG. 4   a  shows the nebulizer  200   a  incorporated into an atmospheric or near atmospheric cylindrical desolvation/ionization chamber  201   a  with the nebulizer positioned on-axis  200   a  or alternatively orthogonal  200   b  to an ion optics assembly  220 . The chamber  201   a  encloses a desolvation/ionization region  210 . Where the ion optics assembly  220  can be comprised of, but limited to, an emersion lens; an atmospheric pressure interface comprised of skimmers, metal or glass tubes, or arrays of tubes leading into a vacuum chamber occupied by a mass spectrometer; other low pressure ion optic components, such as, lens and radio-frequency (RF) ion guide; atmospheric or near atmospheric ion optics such as high-transmission elements or lens as described in our U.S. Pat. Nos. 6,744,041 (2004), 6,818,889 (2004), and 7,081,621 (2006); a laminated lens as described in our U.S. Pat. No. 6,949,740 (2005); a laminated tube or arrays of laminated tubes as described in our U.S. Pat. No. 6,943,347 (2005); ion selective aperture arrays as described in our U.S. Pat. Nos. 6,914,243 (2005) and 7,060,976 (2006); radio-frequency (RF) devices as described in our U.S. Pat. Nos. 6,784,424 (2004) 7,312,444 (2007); or combinations thereof. 
       FIG. 4   b  show two nebulizers  200   c ,  200   d , but not limited to two, incorporated into a similar chamber where the chamber  201   b  is used as a desolvation/ionization chamber or a reaction chamber as described in our previous U.S. Pat. Nos. 6,878,930 (2005), 6,888,132 (2005), 7,087,898 (2006), 7,095,019 (2006), and 7,253,406 (2006). In addition, the chamber  201   b  is comprised of a sample inlet  230 ; a desolvation/ionization-reaction region  240  where gas-phase ions or highly charged aerosols from the nebulizers  200   c ,  200   d  reacts with gas-phase neutral molecules, ionic or highly charged aerosol components introduced into the chamber  201   b  from the sample inlet  230 ; an exhaust  250   a ,  250   b  where excess gases can be removed from the chamber  201   b ; and x,y,z adjustment stages  260   a ,  260   b ,  260   c  for adjusting the position of both nebulizers  200   c ,  200   d  and sample inlet  230 , respectively. The sample inlet  230  can be comprised of, but not limited to, an electrospray nebulizer; remote ion sources as describe in our U.S Pat. Nos. 6,888,132 (2005), 7,095,019 (2006), and 7,253,406 (2007), and provisional patent 60/724,399 (2005); a nebulizer as described in the preferred embodiment above; transfer tube from a gas chromatograph; a heated liquid inlet as part of an HPLC system, such as a thermospray nebulizer or an APCI (atmospheric pressure chemical ionization) nebulizer; a probe, such as a solid samples probe which can be heated, a desorption probe, or a MALDI target where the sample is desorbed by means of directing photons onto the sample; the outlet of a collector of gas-phase neutral or ionic molecules or particles; atmospheric or near atmospheric pressure ion optics as describe in our U.S. Pat. Nos. 6,744,041 (2004), 6,784,424 (2004), 6,818,889 (2004), 6,914,243 (2005), 6,943,347 (2005), 6,949,740 (2005), 7,060,976 (2006). 7,081,621 (2006), 7,312,444 (2007); and combinations thereof. Additional gases may be added to the chamber  201   b  through inlet  230  or other inlets attached to the chamber  201   b  which are directed to intersect the flow of the aerosol emerging from the nebulizer  200   c ,  200   d  to aide in the further evaporation of the aerosol producing gas-phase ions, such as helium, heated or unheated; or reactive gases, such as metastable helium, oxygen, which can react with the particles or droplets in the aerosol producing charged reactant products. In both situations, the gas-phase ions and charged reactant products can be sampled and focused with the ion optics  220 . 
     Chambers  201   a ,  201   b  can be heated by any conventional means, such as but not limited to a cartridge heater (not shown). The temperature of the chambers  201   a ,  201   b  and therefore the region enclosed within the chambers, can be regulated by means of a thermocouple (not shown) attached to the chamber; with the thermocouple and cartridge heater coupled to a temperature controller to adjust the heater power to maintain the desired temperature. Alternatively, the chambers,  201   a ,  201   b  and respective regions  210 ,  240  can be heated by heating the gas flowing into the region from the nebulizers  200   a ,  200   b ,  200   c ,  200   d , the sample inlet  230 , ion optics assembly  220 , or combinations thereof. 
     FIG.  5 —Alternate Embodiment (Surface Ionization and Detector) 
     There are various possibilities with regard to configuring the nebulizer for ionizing components on surfaces and subsequently collecting and detecting the components.  FIG. 5  illustrates an embodiment of a surface ionization device that can be portable or stationary comprised of the nebulizer  200   e , a grounded housing  300 , transfer tubing  310  for directing a highly charged aerosol beam  320   a ,  320   b  comprised of liquid droplets to a surface  360 , collection optics comprised of a high-transmission element (HTE)  330  and ion optics assembly  230   b  (as disclosed in our U.S. Pat. Nos. 6,744,041 (2004), 6,818,998 (2004), 6,914,243 (005), 6,940,740 (2005), 6,943,347 (2005), 7,081,621 (2005), and 7,060,976 (2006)) for collecting, focusing, and delivering gas-phase ions or charged droplets  361  resulting from the highly charged aerosol reacting with a sample or samples on the surface  360 ; a field-free or near field-free region  340  sandwiched between the surface  360  and the HTE  330 ; and a gas-phase ion detector  350  such as but not limited, to a mobility analyzer (ion mobility spectrometer or a differential ion mobility spectrometer); an ion detector in a vacuum chamber comprised of an atmospheric pressure interface to the vacuum chamber, a mass spectrometer (MS); or combinations thereof. 
     OPERATION 
     FIGS.  1  thru  6   
     The nebulizer is operated as a field-free or near field-free electrospray nebulizer for liquid chromatography analysis by establishing a DC potential difference between the needle  10  and the counter-electrode  20 . A liquid solution from the sample inlet  80  is pumped through the tube  40  into the needle  10 . As the liquid exits the needle it forms an electrohydrodynamic spray  12  or a liquid cone-jet geometry at the outlet of the capillary. The highly-charged aerosol resulting from the electrospray nebulizing/ionization process and the gas  92  flowing between the needle  10  and the counter-electrode  20  are directed into the aperture  32  in the saddle electrode  30 . By also establishing a DC potential on the saddle electrode  30  that is greater then the potential on the counter-electrode  20  but less than the potential on the needle  10 , region  120  is maintained field-free or near field-free, as shown in  FIGS. 6   a  thru  6   c.    
     For example, the needle  10  may have a potential of +2,500 volts while the counter-electrode  20 , saddle electrode  30 , and walls enclosing the field-free or near field-free region  120  are at −2,500, ˜0, and ˜0 volts, respectively. This results in a highly charge aerosol of positive droplets being propelled by electrostatic and viscous forces into the field-free region  120 . Other operating parameters are possible, the needle  10  can be ˜0 volts, the counter-electrode  20  −5,000 volts, and saddle electrode  30  and walls −2,500 volts resulting a highly charged aerosol of positive ions; or the needle  10  ˜0 volts, the counter-electrode  20  +5,000 volts, and saddle electrode and walls  30  +2,500 volts resulting in a highly charged aerosol of negative ions. In each situation region  120  is maintain field-free or near field-free. 
     The evaporation of the aerosol may be further enhanced by adding gasses to the field-free or near field-free region  120 , desolvation/ionization region  210 , or combinations thereof. Any resulting gas-phase ions being produced from the electrospray or pneumatically assisted electrospray process can be sampled and focused with ion optics  220  and introduced into an atmospheric interface to a mass spectrometer. 
     Alternatively, as shown in  FIG. 4   b , the aerosol may be directed into reaction region  240  resulting in the production of reaction products; or as shown in  FIG. 5 , the high-charged aerosol flowing out of the nebulizer may be directed onto the surface  360  where components on the surface may desorbed off as described in U.S. patent publication 2005/0230635 (2005) entitled “Method and system for desorption electrospray ionization”. But unlike publication 2005/0230635 where the process of deposition and desorption is performed in a region with highly dispersive electrostatic fields, here the electrospray aerosol is deposited and ions are desorbed in a field-free region  340 . 
     ADVANTAGES 
     From the description above, a number of advantages of our field-free electrospray nebulizer become evident: 
     (a) The presence of a saddle electrode will permit charged droplets and gas-phase ions resulting from the electrospray process to pass through the saddle electrode without impacting on the electrode and reside in a field-free or near field-free region. 
     (b) The use of a saddle electrode will provide a field-free or near field-free region downstream of the electrospray nebulizer where the dispersive forces of the ion source are minimal. 
     (c) The use of a saddle electrode will permit the use of low electrical potential optics in the field-free or near field-free region, thus avoiding the need for high electrical potentials to focus and collect charged species. 
     (d) With a saddle electrode, one can add various gases to the field-free or near field-free region for drying droplets, thus avoiding the possible breakdown of these gases that occur in the high electric fields of the electrospray nebulizer. 
     (e) The use of the saddle electrode will permit the use of prescribed gases (in terms of the nature of gases, composition, temperature, velocity, directional flow, degree of saturation, etc.) to determine the production of, trajectories, and ultimately deliver charged droplets, gas-phase ions, or combinations thereof onto distal surface, into tubes, openings, etc. 
     (f) Although electrospray nebulizers are high-field ionization devices that influence the trajectories of ions downstream of the nebulizer, the saddle electrode of our electrospray nebulizer prevent these fields from influencing the trajectories of ions in the field-free or near field-free region. 
     (g) The presence of co-axial counter and saddle electrodes will permit adding gas between the electrospray needle and the counter-electrode to assist in the nebulization the liquid and also sweep the resulting highly charged aerosol through the saddle electrode into the field-free or near-field free region. 
     CONCLUSION, RAMIFICATION, AND SCOPE 
     Accordingly, the reader will see that the field-free electrospray nebulizer of this invention can be used to introduce a highly charged aerosol and subsequently generate gas-phase ions in a field-free desolvation region from a distal source of charged aerosol or droplet generation, can be used to generate gas-phase ions in an isokinetic flow of gas, and can be use to deliver charged droplets to a surface. In addition, when a field-free electrospray nebulizer has been used to deliver charged droplets to a surface, the resulting analyte ions from the surface are produced in a field-free or near field-free region without the dispersive electric fields of a ion source impairing the ability to collect and focus these analyte ions. Furthermore, the field-free electrospray nebulizer has the additional advantages in that:
         it permits the production and collection of highly charged aerosols, comprised of charged droplets and gas-phase ions, from the electrospray nebulizer to be collected in the field-free region where the charged species can focused into a small cross-section area;   it allows the volume of the field-free desolvation region to be 100&#39;s cm 3 ;   it provides an electrospray nebulizer with a field-free or near field-free desolvation and reaction chamber where species, charged, and uncharged can react producing new charged species which are detected with a gas-phase analyzer;   it provides an electrospray nebulizer with co-axial electrodes, counter and saddle electrodes, where gas can be introduced between the electrospray needle and the counter-electrode aiding in the nebuliziation of the liquid and eventual transport of the highly charged aerosol into a fireld-free or near field-free region;   it permits long residence time of the species in the field-free or near field-free desolvation region;   it allows the relative position of the electrospray nebulizer to be independent of any ion detector present;   it allows the electrospray nebulizer to be comprised of multiple nebulizers, arranged in an array;   it provides an electrospray nebulizer which can be comprised of various types of nebulizers, such as but not limited to nanospray, pneumatically assisted electrospray to be used;   it provides an electrospray nebulizer which can deposit a highly charged aerosol onto a surface, distal to the nebulizer; and   it allows the electrospray nebulizer along with a field-free or near field-free desolvation region to be incorporated into a portable or benchtop chemical analyzer, the analyzer itself comprised of gases or gas inlets, electronics, gas and electronic controllers, and a gas-phase ion detector, such as but not limited to mass, ion mobility, or differential mobility spectrometers, etc;       

     Although the description contains many specifications, these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention. For example, the nebulizer and field-free desolvation region can be constructed as a totally integrated or monolithic structure or as separate components which can easily be disassembled and reassembled as necessary; the position of the electrospray needle can be adjustable relative to the counter-electrode; the size of the aperture of the counter-electrode and saddle electrode can be variable, either adjusted manually or by computer control; the potentials of the electrospray needle, counter-electrode, saddle electrode, and field-free or near field-free desolvation reaction region can be adjusted manually or by computer control to obtain optimum performance; various gases may be used, such as but not limited to, nitrogen, air, helium, and mixtures thereof; the nebulizer and field-free region can be constructed of electrically conductive and insulating materials, such as but limited to composites, silica, glass, glass coated with di-electrics, metal coated insulator, stainless steel, Teflon, Vespel, composites, and combination thereof; etc. 
     Thus the scope of the invention should be determined by the appended claims and their legal equivalents, rather than by the examples given.