Abstract:
An ion injection spray apparatus and method are provided for coupling a liquid chromatograph or other liquid flow device to a mass spectrometer. The ion injection spray assembly is composed in part of a chamber for voltage and gas input, a metal union for a liquid voltage junction, a gas distribution assembly, a vacuum seal and an ion spray needle. The position of the ion spray needle within this assembly is directly coupled to the outlet of the upstream liquid flow device through the metal union. The vacuum of the mass spectrometer pulls gas at atmospheric pressure though the gas distribution assembly to focus the sample liquid at the spray needle outlet and create a centrifugal gas funnel which helps to desolvate the sample ions and sweep them into the mass spectrometer over a wide range of flow rates.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims benefit under Title 35, United States Code §119(e) of U.S. Provisional Application No. 61/125,802 filed on Apr. 28, 2008. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to liquid chromatography (LC) and mass spectrometry (MS) systems and the analysis of chemical samples, and more particularly to ion injection spray devices for use in LC/MS. More particularly, this invention relates to ionization of a sample from an LC device that uses centrifugal gas flow to keep the ionized sample concentrated along a flow path before entering the MS device. 
     BACKGROUND OF THE INVENTION 
     The present invention relates to electrospray ionization (ESI) devices or other ion injection spray devices for use in LC/MS. LC/MS is an important tool in the analysis of many chemical compounds including biomolecules which are important to human health and longevity. Specifically, LC/MS can be used to isolate, identify, characterize and quantify a wide range of sample molecules. The analysis of samples by LC/MS consists of four main steps; 1) LC separation of the different molecules in a sample, 2) formation and desolvation of sample molecule ions, 3) mass analysis to separate the ions from one another according to their mass to charge ratios, and 4) detection of the ions. A variety of means exist in the field of LC/MS to perform each of these functions. The particular combination of means used in a given LC/MS system determines the characteristics of that specific system. 
     To mass analyze ions, for example, one might use an ion trap analyzer, where ions are trapped by a radio frequency (RF) quadrupole field and mass selective ejected by scanning RF amplitude and/or dc voltage. Other mass analyzers include the quadrupole (Q), the ion cyclotron resonance (ICR), the sector (using a magnetic or electrostatic field or both), and the time of flight (TOF) analyzers. 
     Before mass analysis can begin, however, gas phase ions must be formed from the sample molecules. If the sample molecules are sufficiently volatile, ions may be formed by electron impact (EI) or chemical ionization (CI). For solid samples, ions can be formed by desorption/ionization of the sample molecules by bombardment with high energy particles. For liquid phase sample molecules, atmospheric pressure ionization (API) is currently the technique of choice. One of the more widely used API methods, known as electrospray ionization (ESI), was first suggested by Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice, J. Chem. Phys. 49, 2240, 1968). In ESI, analytes in solution and sprayed from a needle and the spray is induced by the application of a potential difference between the spray tip (where the liquid emerges) and a counter electrode. By subjecting the emerging liquid to a strong electric field, it becomes charged, and as a result, it “breaks up” into smaller particles if the charge imposed on the liquid&#39;s surface is strong enough to overcome the surface tension of the liquid (i.e., as the particles attempt to disperse the charge and return to a lower energy state). This results in the formation of fine, charged droplets of solution containing the analyte molecules. These droplets further evaporate leaving behind gas phase analyte ions. 
     Electrospray mass spectrometry (ESI-MS) was introduced by Yamashita and Fenn (M. Yamashita and M. B. Fenn, J. Phys. Chem. 88, 4671, 1984). To establish this combination of ESI and MS, ions had to be formed at atmospheric pressure, and then introduced into the vacuum system of a mass analyzer via a differentially pumped interface. The combination of ESI and MS afforded scientists the opportunity to mass analyze a wide range of samples, and ESI-MS is now widely used in the analysis of biomolecules and other complex organic molecules. 
     Over the past two decades, a number of means and methods of electrospray useful to LC/MS have been developed. For higher LC flow rates (i.e. 50-5000 ul/min), pneumatic assisted electrospray has become the technique of choice (A. P. Bruins, T. R. Covey, and J. D. Henion, Anal. Chem., 59, 2642, 1987, and Henion et al, U.S. Pat. No. 4,861,988). This technique uses a gas flowing past the ESI spray tip to assist in the formation and desolvation of charged droplets. Although the gas assists in the formation of the spray and makes the operation of the electrospray ionization (ESI) easier and more robust, the excess gas dilutes the sample ions, resulting in lower ion transfer efficiency and a loss of sensitivity. 
     For lower flow LC/MS (10-1000 nl/min), nanospray ionization (NSI) has become the technique of choice (M. S. Wilm and M. Mann, Int. J. Mass Spectrom. Ion Processes, 136-167, 1994; and M. Mann and M. S. Wilm, U.S. Pat. No. 5,504,329). U.S. Pat. No. 5,504,329 is incorporated herein by reference in its entirety, with various details of NSI being utilized with the apparatus and method of this invention. NSI utilizes very low liquid flows and a very narrow spray tip outlet placed very close to the MS inlet, which results in the formation of very small spray droplets which can be desolvated without gas assistance. Although the ion signal provided by NSI in conjunction with MS is essentially the same as with conventional ESI, MS is a concentration sensitive detection technique which makes NSI the best technique for high sensitivity applications. Since no gas is used in NSI, high ion transfer efficiency can be achieved, but at a cost of ease of use and robustness relative to pneumatic assisted electrospray. 
     When using NSI-MS, the liquid flow rate, solvent composition, spray tip voltage, spray tip design, spray tip integrity and the position of the spray tip outlet relative to the MS inlet are all critical for good spray stability which results in proper ionization, desolvation and ion transfer efficiency. NSI spray tips are generally made by pulling and cutting fused silica tubing to make the very small ID/OD tips required for stable spray at nanoliter per minute flow rates, but these tips are difficult to reproduce, fragile to handle and easy to clog. Because of these limitations, NSI can be difficult to set up and maintain, making it poorly suited for analyses requiring robust operation. 
     Since NSI is generally limited to flow rates below 1 μl/min, samples must be separated using nanoLC which has its own share of problems and limitations. NanoLC requires specialized instrumentation and careful attention to details to insure optimal performance. NanoLC columns (&lt;150 um ID) have limited sample capacity, require specialized sample injection protocols to load large sample volumes and lack the robustness of larger LC columns. Finally, the low flow rates used in nanoLC/NSI-MS typically result in longer sample analysis time, making this technique poorly suited to high throughput applications like biomarker validation and pharmaceutical development. 
     Several attempts have been made to develop commercially viable microspray ionization (MSI) sources in an effort to overcome the limitations imposed by NSI, but these MSI sources have not been very well accepted. Although these MSI sources, which are basically miniaturized versions of pneumatic assisted ESI, do offer increased stability and work at higher LC flow rates versus NSI, the added gas flow still results in a lower ion transfer efficiency and a unacceptable loss in sensitivity for most researchers. 
     The applicants have recognized the need for a LC/MS electrospray apparatus and method that can overcome the limitations imposed by ESI, MSI and NSI, without compromising the ion transfer efficiency critical to high sensitivity applications. This apparatus and method provide simple, robust operation over a wide dynamic flow range and maintain high ion transfer efficiency independent of the LC flow rate. This apparatus and method can be be simple to set up and use (“Plug and Play”), operate continually with minimal maintenance and provide both high sensitivity and high throughput operation, especially at flows from 0.1-100 ul/min. 
     SUMMARY OF THE INVENTION 
     To achieve the foregoing objectives of the present invention, an ion injection spray device and method for introducing sample ions into a mass spectrometer is presented. The assignee of this invention, Michrom BioResources, Inc. of Auburn, Calif., refers to its brand of this ion injection spray device by the trademark CAPTIVES PRAY. It is an object of the invention to provide a simply constructed, easy to operate and highly efficient mass spectrometer sample introduction apparatus for a wide range of liquid sample flow rates. An apparatus according to the present invention comprises a spray needle with an inlet opening for acceptance of a liquid flow, such as from the output of an LC device and an outlet tip for spray of said liquid into the MS. The spray needle preferably terminates in an ion injection spray device (akin to an electrospray needle) for the creation of charged particles of the liquid flow for introduction into the MS. Upon exiting the outlet tip of the spray needle, the charged particles of the liquid flow are introduced to the MS inlet. The ions are drawn by an electric field from the spray tip and are focused by gas pulled in by the vacuum of the mass spectrometer. 
     According to the invention, liquid from a liquid chromatograph (LC) or other liquid flow device flows through a column into a metal union. The device comprises a spray needle preferably of circular cross-section, encircled by a non-conductive outer tube also preferably of circular cross-section. 
     Unlike NSI technology, the present invention allows the practitioner to easily attach the spray assembly to the MS. There is no need for microscopes, cameras or X,Y,Z positioning adjustment. Rather the spray assembly is simply attached to the MS inlet with a vacuum seal and is ready to perform its function within the MS. The present invention reduces set-up time and increases the speed in which mass spectrometry can be carried out versus NSI-MS. The present invention provides stable spray and uniform performance across a wide dynamic flow rate range (0.1-100+ ul/min). 
     Coaxial gas flow is preferably introduced around the spray needle through an annular space between the spray needle and outer tube at high velocity, typically generated by the vacuum inlet of the MS. A second gas flow is preferably introduced at the spray needle outlet to focus the spray inward and a third gas flow is introduced in a centrifugal fashion to provide funnel-shaped swirling gas flow to help desolvate and focus the ions into the MS. The device of the present invention is preferably sealed by at least one O-ring to generate vacuum assisted gas flow and prevent loss of sample ions into the atmosphere. Unlike previous electrospray technology where the spray and drying gases are open to the atmosphere, the present invention uses the vacuum from MS to guide the flow of ions and gases in the sealed spray chamber into the MS and prevent loss of sample ions to the atmosphere. 
     The metal (or other electrically conductive material) union is either connected to high voltage with the MS inlet at ground or the union is at ground and the MS inlet is connected to high voltage, and the voltage differential is generally between 500 and 5000 volts. Typically the position of the outlet tip of the spray needle is fixed at 1-5 mm from the MS inlet capillary or orifice. The combination of the electric field and the gas flows serve to nebulize the liquid stream as it exits the spray needle. The apparatus and method described by this invention and shown in the figures that follow has been tested and found to meet all of the performance criteria outlined above. 
     OBJECTS OF THE INVENTION 
     Accordingly, a primary object of the present invention is to provide an ion injection spray device which can effectively convert samples such as those discharged from a liquid chromatograph (LC) into ions before passage into a mass spectrometer (MS). 
     Another object of the present invention is to provide a method for ionizing a sample between an upstream source, such as a LC and a mass analyzer, such as a MS. 
     Another object of the present invention is to provide a sample evaluation system which includes a LC, an ion injection spray device and a MS which reliably pass samples from the LC to the MS. 
     Another object of the present invention is to provide an ion injection spray device which is easy to align with an inlet to a MS or other subatmospheric pressure mass analyzer. 
     Another object of the present invention is to provide an ion injection spray device which utilizes centrifugal flow of a gas adjacent an outlet of a spray needle to assist in keeping ions to be mass analyzed along a central axis flow path. 
     Another object of the present invention is to provide an ion injection spray device which has a wide dynamic flow range, such as for between 0.1 and 100 or more microliters per minute. 
     Other further objects of the present invention will become apparent from a careful reading of the included drawing figures, the claims and detailed description of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings. Although the illustrated embodiment is merely exemplary of systems for carrying out the present invention, both the organization and method of operation of the invention, in general, together with further objectives and advantages thereof, may be more easily understood by reference to the drawings and the following description. The drawings are not intended to limit the scope of this invention, which is set forth with particularity in the claims as appended or as subsequently amended, but merely to clarify and exemplify the invention. For a more complete understanding of the present invention, reference is now made to the following drawings in which: 
         FIG. 1  is a schematic depiction of the centrifugal flow gas within the ion spray chamber according to this invention. 
         FIG. 2  is a full sectional view of the electrospray assembly, as well as the LC column, union and MS inlet capillary according to the preferred embodiment of the present invention. 
         FIG. 3  is a more detailed full sectional view of the electrospray insert within the assembly that is coupled with the union and MS inlet capillary according to the preferred embodiment of the present invention. 
         FIG. 4  is a full sectional most detailed view of gas flow paths of the electrospray insert around the spray needle into the mass spectrometer at the electrospray chamber and for a slightly modified embodiment of the invention. 
         FIG. 5  is a sectional view taken along line 5-5 of  FIG. 4  or  FIG. 6  and showing the off center inlet embodiment to induce centrifugal gas flow within the chamber. 
         FIG. 6  is a full sectional view depicting an alternative design of the present invention for use with mass spectrometers that use an orifice as the ion inlet. 
         FIG. 7  is a schematic of a typical LC/MS injections system of this invention incorporated therein. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     As required, detailed illustrative embodiments of the present invention are disclosed herein. However, techniques, systems and operating structures in accordance with the present invention may be embodied in a wide variety of sizes, shapes, forms and modes, some of which may be quite different from those in the disclosed embodiments. The specific structural and functional details disclosed herein are merely representative, yet in that regard, they are deemed to afford the best embodiment for purposes of disclosure and to provide a basis for the claims which define the scope of the present invention. 
     The following presents a detailed description of a preferred embodiment of the present invention, as well as some alternate embodiments of the invention. As discussed above, the present invention relates generally to the mass spectroscopic analysis of chemical samples and more particularly to the coupling of liquid chromatography (LC) equipment to mass spectrometry (MS) equipment. Specifically, an apparatus and method are described for the production of ions and subsequent transport of said ions into a MS. Reference is herein made to the figures, wherein the numerals representing particular parts are consistently used throughout the figures and accompanying discussion. 
     As shown in  FIGS. 1 ,  2  and  3 , the ion injection spray device  100  resides between an LC column or other connection tubing  11  from a fluid flow source  15  ( FIG. 1 ) and a MS  200  capillary inlet  10 . The ion spray  100  is housed in a non-conductive body  14 , which supplies gas and voltage inputs and holds the entire assembly in place. Liquid phase samples introduced at the liquid flow source  15  have been separated (such as in an LC column) and exit the flow source  15  into the conductive union  1  through the connection tubing  11 . Within the union  1 , a high voltage liquid junction  21  is formed in the “Zero Dead Volume” (ZDV) center  22  of the conductive union  1 . High voltage is supplied through a connector  12  and a conductive electrode  4  to the conductive union  1 . 
     The charged liquid exits the conductive union  1  through an ion spray needle  3  which is attached to the conductive union  1 . The needle  3  is supported by a non-conductive tip housing  2  ( FIG. 2 ) and exits the needle  3  outlet in the ion injection spray chamber  6  where electrospray of the charged liquid takes place. The chamber  6  is formed between the non-conductive needle housing  2  and the MS capillary inlet  10 , which are surrounded by the gas distribution manifold  27 . 
     The MS capillary inlet  10  is preferably fitted with a mounting flange  9  to seal it to the gas distribution manifold  27  using O-rings  26  and the non-conductive needle housing  2  is also sealed in the gas distribution manifold  27  using O-rings. The vent holes  8  on the mounting flange  9  provide tip cooling and temperature differential when using a heated MS capillary inlet  10 . This design lowers the temperature in the ion injection spray chamber  6  and reduces the chance of sample precipitation that could cause the spray tip to clog when using a heated capillary MS inlet  10  at elevated temperatures. 
     The gas distribution manifold  27  ( FIGS. 3 and 4 ) is designed to distribute gas from the gas input  13  ( FIGS. 1 and 2 ) to the chamber  6  using the vacuum of the MS  200 . The first vacuum assisted coaxial gas flow  33  ( FIG. 4 ) is introduced through a rear opening  23  in the gas distribution manifold  27  around the needle  3 . The gas flow  33  enters an annular space  7  ( FIGS. 3 and 4 ) between the needle  3  and a non-conductive outer tube  5  at high velocity, as developed by the vacuum inlet of the MS. The outer tube  5  and the coaxial gas flow annular space  7  are specifically designed to assist electrospray and prevent large droplets from forming at the tip of the needle  3 . 
     In the preferred embodiment, the needle  3  is made of fused silica capillary tubing. The non-conductive needle housing  2  and non-conductive outer tube  5  are made of PEEK. The union  1  is made of metal. Due to the high voltage involved, the silica tubing is sufficiently electrically conductive to facilitate ion formulation. 
     A second vacuum assisted gas flow  34  ( FIG. 4 ) is preferably introduced through a middle opening  24  in the gas distribution manifold  27  ( FIG. 3 ) at the needle  3  tip to focus the spray from the tip inward. This second gas flow  34  can be introduced radially toward a central axis X ( FIGS. 4 and 5 ) of the chamber  6  or introduced in a centrifugal fashion at least partially circumferentially about the central axis X. 
     A third vacuum assisted gas flow  35  ( FIGS. 4 and 5 ) is preferably introduced through a front opening  25  in the gas distribution manifold  27 . The third gas flow  35  is introduced in a centrifugal fashion to provide funnel shaped swirling gas flow  37  to help desolvate and focus the sample ions  36  into the MS  200 ,  210 . 
     The gas flow  35  and any other gas flows into the ion spray chamber  6  can be introduced in a centrifugal fashion in a variety of different ways. In one form of the invention, the gas flow  35  comes in through a front opening  25  which is broken into separate outlets ( FIG. 5 ) at the junction between the chamber  6  and the front opening  25 , which gas entry ports are offset laterally from a center line X of the chamber  6 . If more than one entry port for the gas flow  35  is provided, they are preferably offset in a common direction, such as each being offset to a left side of the center line X of the chamber  6  when viewed in a common direction with the direction of flow of ions through the chamber  6 . 
     In such an instance, the gas flow  35  into the chamber  6  would be centrifugal and curving in a counter-clockwise direction (along arrows  35  of  FIG. 5 ). The flow would transition from being centrifugal within a plane perpendicular to the centerline of the chamber  6  into axial in a common direction with flow of ions through the chamber  6  as the centrifugal gas flow  35  is drawn into the vacuum within the MS  200 ,  210  ( FIGS. 1-3 ). Thus, the flow would actually be in somewhat of a funnel transitioning from purely centrifugal to primarily axial. This funnel-like flow helps to keep all of the ions exiting the tip of the needle  3  in a tight column adjacent the central axis X of the chamber  6 , and passing from the tip of the needle  3  into the capillary inlet  10  of the MS  200 ,  210 . 
     As another alternative, centrifugal flow into the chamber  6  can be achieved by forming vanes in walls of the forward opening  25  or other openings in which it is desired that the gas flow be at least somewhat centrifugal. Such veins could be fixed and curve in the direction desired for swirl within the chamber  6 . As another alternative, the veins could be formed on a rotor which would spin to generate the centrifugal flow as desired. While more complex, such a rotor could be varied in speed to allow for adjustment in the degree of centrifugal flow within the chamber  6 . 
     Most preferably, at least one gas flow, typically the most upstream gas flow  33  is configured to be primarily coaxial with the centerline of the chamber  6  and the centerline of the needle  3 . At least one downstream gas flow (and two gas flows  34 ,  35  in the embodiment of  FIGS. 1-3 ) is provided in a more centrifugal fashion than the first primarily coaxial gas flow. However, in simplified or varied forms of this invention the gas flow might be limited to as few as one gas flow with at least some centrifugal component ( FIG. 1 ) to the gas flow about the centerline of the chamber  6  and the needle  3 , and still provide some benefit according to this invention. 
     While  FIG. 4  depicts a more detailed view of the chamber  6  generally similar to the ion injection spray device  100  of  FIGS. 2 and 3 ,  FIG. 4  actually depicts a slightly modified embodiment in that the inlet end of the MS  210  has a tapering conical form about a central axis X of the capillary inlet  10  of the MS  210  and a diameter of the chamber  6  has been altered slightly. The diameter of the chamber  6  can be customized to coordinate with the configuration of the inlet end of the particular MS with which the ion injection spray device  100 ,  110  of this invention is configured to operate with. Also, conceivably for different specific ions it might be desirable to provide custom different sizes for the chamber  6  which would further optimize injection of the ions into the MS in a tight column adjacent the central axis X of the chamber  6  and with a minimum of sample loss. 
     While the voltage for the ion injection spray device  100 ,  110  can be provided in a variety of different ways, often the most convenient manner for providing such voltage is to utilize high voltage leads from the MS  200 ,  210 ,  220  (as depicted in  FIG. 6 ). In this way, the proper desired potential difference is provided between the relevant portions of the MS  200 ,  210 ,  220  and the union  1  where the sample is initially caused to experience a voltage which ultimately leads to ionization of the sample as it leaves the tip of the needle  3 . Depending on the particular voltage provided by the MS  200 ,  210 ,  220 , and other design parameters for the ion injection spray device  100 ,  110 ,  120 ,  53 , the material forming the needle  3  can also be adjusted to optimize formation of ions from the sample. For instance, the needle could be formed of fused silica as is common with nanospray mass spectrometry. As an alternative, the spray needle could be made of metal capillary tubing or polymeric capillary tubing, altering the electric performance of the needle  3  and tuning the ion injection spray device  100 ,  110 ,  120 ,  53  to the particular configuration of the MS  200 ,  210 ,  220  and other design parameters of the device  100 ,  110 ,  120 ,  53 . Depending on the material and other design parameters of the needle  3 , the voltage can optionally be adjusted as a further design parameter for optimization of the device  100 ,  110 ,  120 ,  53 . 
     Other details of the needle  3  could also be modified as design parameters to optimize for different performance characteristics desired for the ion injection spray device  100 ,  110 ,  120 ,  53 . For instance, while the needle  3  preferably has both a cylindrical inner diameter and outer diameter along its length, the needle  3  could have tapering inner and/or outer diameters. Also, a difference between the inner and outer diameters can vary so that a thickness of the wall of the needle  3  can be selected to optimize performance. For instance, decreasing the wall thickness of the needle  3  at the tip can cause greater charge concentration at the tip, effecting ionization of the sample as it leaves the needle  3 . Modifying the inside diameter of the needle  3  affects flow rate of the sample and thus affects throughput through the MS  200 ,  210 ,  220  and duty cycle for the LC/MS system. 
     The needle  3  is preferably supported adjacent the union  1  so that the needle  3  does not contact the needle housing  2  or the outer tube  5 . This support for the needle  3  is upstream of where the rear opening  23  in the gas distribution manifold  27  allows the first coaxial gas flow  33  to approach the needle  3  and pass coaxially along an exterior of the needle  3  and toward the chamber  6 . This mount for the needle  3  is preferably fixed. As an alternative, this mount for the needle  3  can be adjustable so that a position of the tip of the needle  3  can be adjusted axially along the center line X to bring it closer to the capillary inlet  10  of the MS or further from the capillary inlet  10  of the MS. Such needle position adjustability provides a further parameter which can either be designed into the ion injection spray device  100 ,  110 ,  120 ,  53  or configured to be adjustable for tuning of the device  100 ,  110 ,  120 ,  53 . 
     The typically un-tapered inner diameter of the spray needle  3  is typically 0.02-0.05 millimeters, and its typically un-tapered outer diameter is typically 0.05-0.15 millimeters. The inner diameter of the outer tube  5  is typically 0.15 to 0.25 millimeters, leaving an annular space between the two tubes of thickness about 0.05 to 0.10 mm. The outer diameter of the outer tube is not critical and the outer tube can be made of any desired thickness depending on the material from which it is formed. Typically the outer tube is made of PEEK and the tip of the spray needle typically protrudes 1-5 mm from the outer tube. 
       FIG. 6  shows an alternative embodiment of the ion injection spray device  120  for use with MSs that utilize a MS inlet orifice  46  rather than a MS capillary inlet  10 . This embodiment consists of a non-conductive ion injection spray needle  40 , a non-conductive outer cylinder  41 , focusing coaxial gas flow  42 , entering upstream of the needle  40  tip and centrifugal gas flow  44  generally near the tip to help desolvate and focus the desolvated sample ions  47  into the MS. A curtain gas  45  from the MS  220  may also be used to help desolvate and focus sample ions. 
       FIG. 7  depicts a typical LC/MS system for use with the present invention. A HPLC or other liquid separation device  55  provides liquid phase sample flow through a separation column  52  to the ion injection spray device  53  and into the MS  200 . An optional gas source  51  can be used to supply gas to the device  53 . Although ambient air can also be used as the gas source pulled in by the MS  200  vacuum, high purity gas (nitrogen, air, helium, etc.) is recommended when contaminants are present in the ambient air around the MS  200 . Ambient air or high purity gas may also be presaturated with solvent vapors (methanol, formic acid, ammonia, etc.) for specific types of MS  200  analytes which respond better in the presence of such solvent vapors. A high voltage supply  54  from the MS  200  provides the necessary voltage differential for electrospray ionization of the liquid sample. 
     It should be noted that any other method known in the prior art might be used in conjunction with the device according to the present invention. For example, the ion inlet could be an orifice, a glass capillary or a metal capillary and the high voltage could be applied on the MS inlet while the spray tip is at ground potential. 
     This disclosure is provided to reveal a preferred embodiment of the invention and a best mode for practicing the invention. Having thus described the invention in this way, it should be apparent that various different modifications can be made to the preferred embodiment without departing from the scope and spirit of this invention disclosure. When structures are identified as a means to perform a function, the identification is intended to include all structures which can perform the function specified. When structures of this invention are identified as being coupled together, such language should be interpreted broadly to include the structures being coupled directly together or coupled together through intervening structures. Such coupling could be permanent or temporary and either in a rigid fashion or in a fashion which allows pivoting, sliding or other relative motion while still providing some form of attachment, unless specifically restricted.