Abstract:
An ion transfer device for transferring ions emerging from an electrospray ion source at atmosphere to a vacuum chamber includes an inner surface in the shape of a diverging conical duct. The ion transfer device has an entrance aperture for positioning proximate the exit port of the electrospray ion source emitter, the entrance aperture receiving the electrosprayed ions from the exit port of the electrospray ion source emitter at atmosphere, the diverging conical duct being an electrode toward which the ions migrate and having an exit aperture with an inner diameter larger than an inner diameter of its entrance aperture, the exit aperture enclosed in the vacuum chamber, the diverging conical duct transporting the ions from atmosphere to vacuum. The vacuum chamber can be a chamber of a vacuum housing enclosing a mass analyzer.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of co-pending U.S. patent application Ser. No. 13/827,727, filed on Mar. 14, 2013, which claims priority to U.S. Provisional Application No. 61/759,645, filed Feb. 1, 2013, the entirety of which is incorporated herein by reference thereto. 
     
    
     STATEMENT REGARDING FEDERALLY FUNDED RESEARCH 
       [0002]    This invention was made with government support under grants RR00862 and GM103314 awarded by the National Institutes of Health. Accordingly, the government has certain rights in the invention. 
     
    
     TECHNICAL FIELD 
       [0003]    The present disclosure relates to a method and apparatus for improving ion transmission into a mass spectrometer, and, more particularly, to a method and apparatus for improving the transfer of ions between atmosphere and a vacuum region of a mass spectrometer, and to a mass spectrometer with improved ion transfer thereto. 
       BACKGROUND 
       [0004]    The performance of scientific instruments, such as mass spectrometers, which operate under vacuum conditions with the ions of interest produced externally at atmospheric pressure are profoundly affected by the efficiency of ion transfer between the atmosphere and vacuum regions of the instrument. As transfer efficiency increases, loss of ions produced from the sample of interest is reduced, and the number of informative ions that enter the instrument is increased. This can result in increased speed of analysis, resolution, and sensitivity of the instrument. 
         [0005]    Among the most rudimentary atmosphere-vacuum interfaces is a small orifice in the first vacuum chamber evacuated by a roughing pump to pressures of about 1-10 Torr. The pumping speed of typical roughing pumps is usually a few liters/s, which places a limit on the diameter of the orifice of typically less than 0.5 mm. Ion beams created this way are usually poorly collimated, so that the beam diameter quickly increases downstream of the orifice. To avoid destroying the ion beam and incurring ion losses, a skimmer electrode is typically positioned 4-7 mm downstream of the orifice to provide a means for ion passage further into the next higher vacuum stage of the instrument, as described, for example, in a publication by Fenn, “Mass spectrometric implications of high-pressure ion sources,”  Int. J. Mass Spectrom . 2000, 200: 459-478. 
         [0006]    The first atmosphere-vacuum interfaces for coupling electrospray ionization (ESI) sources to mass spectrometers were designed on this principle, and some mass spectrometer manufacturers still use this design with little or no modifications. One disadvantage of this rudimentary interface is the absence of an efficient means to supply heat to the small charged droplets produced by ESI and the associated heavily solvated ions after they have entrained in the supersonic jet formed by gas expansion into the vacuum. 
         [0007]    The effects of adiabatic expansion cooling can be counteracted to some extent by creating a declustering potential between the orifice and the skimmer. However, the amplitude of the declustering voltage cannot be very large because it will induce dissociation of the already desolvated ions. Other modifications to this rudimentary interface previously proposed to improve the ion desolvation process include introducing a counter flow of heated gas (sometimes referred to as a heated gas curtain), heating the entire interface, and installing a heated laminar flow chamber (particle discriminator interface, PDI) in front of the orifice. However, these modifications are expensive, and/or frequently of very limited efficiency, often requiring precise controls for optimization of temperature and gas flows for the particular analyte and solvent system. Such controls are needed to insure complete desolvation and to prevent a decrease in sensitivity from ions being swept away at gas flow rates that are too high. 
         [0008]    One efficient solution to improving the ion desolvation process without the need for precise gas flow control is described in co-owned U.S. Pat. No. 4,977,320 to Chowdury, et al., (hereinafter, “Chowdury”), entitled “Electrospray Ionization Mass Spectrometer with New Features,” which issued on Dec. 11, 1990. In the method disclosed by Chowdury, solvated ions formed by an electrospray ionization of an analyte solution at atmospheric pressure were introduced into a first vacuum chamber of a mass spectrometer through a metal capillary heated to, for example, about 85° C. The capillary in Chowdury is about 0.5 mm in diameter and of 203 mm in length, and projects into the first vacuum chamber  21  of the mass spectrometer. Chowdury further discloses that heating of the capillary tube causes evaporation of the droplets and desolvation of the resulting molecular ions of interest for analysis. Such ion interfaces containing a heated metal capillary or an array of heated capillaries instead of a simple orifice have since became widely adopted by mass spectrometry manufacturers and researchers, especially when high flow-rate ESI ion sources are coupled to mass spectrometers. 
         [0009]    With the advent of nano-flow ESI ion sources, or low flow-rate electrospray ionization sources, the sensitivity of mass spectrometers coupled to on-line chromatography has dramatically increased (see, e.g., U.S. Pat. No. 5,788,166 to Valaskovic, et al., entitled “Electrospray ionization source and method of using the same,” issued Aug. 4, 1998). Nano-flow ESI emitters can potentially provide better conditions for sample ionization and, ultimately, higher ionization efficiency than the standard electrospray sources based on the heated metal capillary as described in Chowdury. However, little optimization has been made to ion interfaces that operate with nano-flow ESI sources to increase the efficiency of ion transfer between the atmosphere and the vacuum interface of a mass spectrometer. 
         [0010]    Accordingly, there is still a need for a method and apparatus for improving the transfer of ions from atmosphere into a vacuum region of a mass spectrometer, particularly for mass spectrometers for coupling nano-flow ESI ion sources thereto. 
       SUMMARY 
       [0011]    The present disclosure provides a method and device for improving the transfer of ions from atmosphere into a vacuum stage of a mass spectrometer. The present disclosure additionally provides a mass spectrometer including the ion transfer device for coupling an ESI ion source thereto. 
         [0012]    In one aspect, a system for the analysis of the mass spectra of ions includes an electrospray ion source generating ions for analysis, the electrospray ion source comprising an exit port from which the ions are electrosprayed at atmosphere; a mass analyzer having an inlet port enclosed in a vacuum housing for receiving the ions to be analyzed; and a diverging conical duct electrode having an entrance aperture and an exit aperture, the exit aperture having an inner diameter larger than an inner diameter of the entrance aperture, the entrance aperture positioned proximate the exit port of the electrospray ion source for receiving the ions at atmosphere from the electrospray ion source, and wherein the exit aperture is enclosed in the vacuum housing and operatively coupled to the inlet port for transporting the ions from atmosphere to the mass analyzer under vacuum. 
         [0013]    In another aspect, an ion transfer device for transferring ions emerging from an electrospray ion source, having an exit port for spraying the ions at atmosphere, to a vacuum chamber, includes an inner surface in the shape of a diverging conical duct. The ion transfer device has an entrance aperture for positioning proximate the exit port of the electrospray ion source, the entrance aperture receiving the electrosprayed ions from the exit port of the electrospray ion source at atmosphere. The diverging conical duct is an electrode toward which the ions migrate and has an exit aperture with an inner diameter larger than an inner diameter of the entrance aperture, the exit aperture configured to be operatively coupled to the vacuum chamber for transferring the ions thereto. 
         [0014]    In addition to the above aspects of the present disclosure, additional aspects, objects, features and advantages will be apparent from the embodiments presented in the following description and in connection with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0015]      FIG. 1  is a schematic representation of a prior art mass spectrometer. 
           [0016]      FIG. 2  is a schematic representation of a cross-section of an embodiment of an ion transfer device of the present disclosure. 
           [0017]      FIG. 3  is a schematic representation of a cross-section of an embodiment of a system formed in accordance with the present disclosure for the analysis of the mass spectra of ions formed from molecules of interest. 
           [0018]      FIG. 4  is a schematic representation of a cross-section of a measurement apparatus for measuring transmission efficiency and transmitted current through an electrode interface of electrosprayed ions between atmosphere and a vacuum chamber. 
           [0019]      FIG. 5A  is a perspective representation of an embodiment of an ion transfer device of the present disclosure. 
           [0020]      FIG. 5B  is a schematic representation of a cross-section of an embodiment of the ion transfer device of  FIG. 5A . 
           [0021]      FIG. 5C  is a magnified view of the tip of the ion transfer device of  FIG. 5B . 
           [0022]      FIGS. 6A-6C  are schematic representations of a cross-section of the measurement apparatus shown in  FIG. 4 , with three different electrode interfaces coupled to the vacuum chamber for measuring transmission efficiency and transmitted current through the different electrode interfaces to the vacuum chamber. 
           [0023]      FIG. 7A  is a graphical representation of the ion transmission through the ion transfer device of  FIG. 5B  compared to the ion transmission through various commercial capillary interfaces. 
           [0024]      FIG. 7B  is a graphical representation of a transmitted current through the ion transfer device of  FIG. 5B  compared to the ion current through various commercial capillary interfaces. 
           [0025]      FIG. 8A  is a graphical representation of an ion transmission through the slowest diverging conical duct portion of the ion transfer device of  FIG. 5B  compared to the ion transmission through capillary interfaces of varying lengths. 
           [0026]      FIG. 8B  is a graphical representation of the transmitted current through the slowest diverging conical duct portion of the ion transfer device of  FIG. 5B  compared to the ion transmission through capillary interfaces of varying lengths. 
           [0027]      FIG. 9A  is a graphical representation of the ion transmission through the ion transfer device of  FIG. 5B  compared to the ion transmission through various commercial rudimentary orifice interfaces. 
           [0028]      FIG. 9B  is a graphical representation of the transmitted current through the ion transfer device of  FIG. 5B  compared to the ion transmission through various commercial rudimentary orifice interfaces. 
           [0029]      FIG. 10A  is a schematic representation of the ion beam, and measured divergence of the beam, observed in the ion transfer device of  FIG. 5B . 
           [0030]      FIGS. 10B and 10C  are schematic representations of the ion beams, and measured divergence of the beams, observed in the rudimentary orifice interfaces shown in  FIGS. 6B and 6C , respectively. 
       
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0031]    The following sections describe exemplary embodiments of the present disclosure. It should be apparent to those skilled in the art that the described embodiments of the present disclosure provided herein are illustrative only and not limiting, having been presented by way of example only. All features disclosed in this description may be replaced by alternative features serving the same or similar purpose, unless expressly stated otherwise. Therefore, numerous other embodiments of the modifications thereof are contemplated as falling within the scope of the present disclosure as defined herein and equivalents thereto. 
         [0032]    The present disclosure is directed to a method and apparatus for improving the transfer of ions from the atmosphere into a vacuum of a mass spectrometer. The present disclosure is also directed to a mass spectrometer including the ion transfer apparatus of the disclosure. 
         [0033]    Referring to  FIG. 1 , a prior art electrospray ionization mass spectrometer is described in co-owned U.S. Pat. No. 4,977,320 to Chowdhury, et al., in which a long metal capillary tube  11  is used to couple the ionized spray emitted from an electrospray needle tip  14  at atmospheric pressure to a vacuum pressure chamber  21  in order to inject the ions into a mass analyzing chamber  31 . The capillary tube  11  is also heated to preferably about 85 C to cause the ionized droplets and solvated ions to undergo continuous desolvation as they pass through the tube  11 . 
         [0034]    While the use of a heated capillary advantageously improved the ion desolvation process without the need for precise gas flow control, the efficiency of ion transmission into the vacuum chamber  21  using the capillary tube disclosed in Chowdhury is still low. 
         [0035]    Referring to  FIG. 2 , the present inventors discovered that, surprisingly, a slowly diverging conical duct  52  provides a superior interface over the capillary tube of the prior art as an ion transfer device  50  for coupling electrosprayed ions from an electrospray source at atmosphere to a mass spectrometer at vacuum. In one embodiment of an ion transfer device formed in accordance with the present disclosure, about 75 to about 99% of ions from a nano-flow ESI ion source placed a distance from an inlet port  25  of the device  50  can be transferred into vacuum through the ion transfer device  50 , resulting in a total transmitted ion current of higher than 200 nA from a nano-flow ESI source. This translates to an improved total transmitted current to a mass analyzer through the ion transfer device  50  from about 10 to about 100 times higher than can be achieved under similar conditions in commercial mass spectrometers that utilize a heated capillary as a key element of the interface. 
         [0036]    Though not wishing to be bound by any particular theory, the inventors contemplate that the phenomenon of flow separation may be at least partially responsible for this surprising discovery of improved ion transmission through the slowly diverging conical duct of the present disclosure. It is surmised that the flow separation likely occurs when the gas/liquid moves in the diverging duct with a velocity higher than some critical velocity. The present inventors have demonstrated that an ion beam  54  produced from embodiments of the ion transfer device  50  has advantageous properties, including that: (i) it does not interact with inner walls  56  of the device  50  (presumably after flow separation takes place); and (ii) as the ion beam  54  propagates, it diverges very slowly. For example, measurements of a divergence of the ion beam  54  relative to a central longitudinal axis  58  of one embodiment of the diverging conical duct  52  were taken, showing a divergence angle of about 0.6 degrees. Such narrow ion beams can be efficiently heated, for example, by radiative heat from an encompassing heated sleeve, to provide ion desolvation. 
         [0037]    In one embodiment of the present disclosure, the ion transfer device includes a diverging conical duct with an inner diameter of the inlet port between about 0.1-1 mm and an inner diameter of an exit port between about 0.2-5 mm, an inner diameter of an exit port of the device being greater than the inner diameter of the inlet port. 
         [0038]    Preferably, the inner diameter of the inlet port is from about 0.3 mm to about 0.6 mm. 
         [0039]    In another embodiment of the present disclosure, the ion transfer device includes a diverging conical duct with inner walls forming an angle of divergence  55  with the longitudinal axis  58  of the diverging conical duct  52  of from about 0.6 to about 1.0 degrees. 
         [0040]    Preferably, the angle of divergence  55  is from about 0.7 degrees to about 0.9 degrees. 
         [0041]    In other various embodiments, the angle of divergence  55  is less than about 1.0 degree and greater than about 0.6 degree and the inner diameter of the inlet port is about 0.4 mm. 
         [0042]    In various additional embodiments of the present disclosure, a length of the diverging conical duct of the ion transfer device is from about 1 to about 200 mm. Preferably, the length is from about 5 to about 10 mm. 
         [0043]    In a preferred embodiment, an inner diameter of the inlet port is between about 0.3 mm and about 0.5 mm, the angle of divergence  55  is between about 0.6 and about 0.9 degree, and the length of the diverging conical duct of the ion transfer device is at least about 7 mm. 
         [0044]    The diverging conical duct of the ion transfer device is preferably maintained at a voltage of between about 0 and about 1000 V. The diverging conical duct is also preferably heated by any means known in the art to a temperature between about 273K and about 600K. 
         [0045]    The diverging conical duct can be formed of any material appropriate for forming an electrode, which also conducts heat, including metals, conductive plastics, conductive glass, and so on. In a preferred embodiment the diverging conical duct is formed of conductive plastic. 
         [0046]    Referring to  FIG. 3 , an embodiment of a system  100  for the analysis of the mass spectra of ions formed from molecules of interest includes the ion transfer device  50  of the present disclosure for coupling electrosprayed ions  40  from atmosphere to a mass spectrometer or analyzer  80  maintained in a vacuum housing  70 . The electrosprayed ions  40  can be produced by introducing a dilute solution of the molecules of interest  30  into an inlet port  35  of the electrospray ion source  110 . The ion source  110 , which can be a nano-electrospray ion source, transports the dilute solution  30  and charges droplets of the solution to produce a divergent cone of electrosprayed ions  40  emitted from an exit port  45 . A high voltage source maintains the ion source  110  at a high voltage relative to the ion transfer device  50 , preferably at about 1kV to about 2 kV. The system  100  also preferably includes a heating device  75  for heating the diverging conical duct  52  and a voltage source  155  for maintaining or altering a voltage applied to the diverging conical duct  52  of the ion transfer device  50 , preferably between 0 and 400V. The diverging conical duct  52  forms an electrode, the voltage differential formed between the ion source  110  and the diverging conical duct  52  causing the charged droplets emitted from the ion source to migrate along electric field lines toward the entrance  25  of the diverging conical duct  52 . 
         [0047]    The mass analyzer  80  can be a quadrupole mass analyzer, like that shown in  FIG. 1 , an ion trap mass analyzer, a time-of-flight mass analyzer, or any mass analyzer known in the art. 
         [0048]    In various embodiments of the system, the diverging conical duct  52  can be coupled to the front of the (first) vacuum stage of the mass spectrometer. In other embodiments, the diverging conical duct  52  can extend into the vacuum chamber. 
         [0049]    In various embodiments of the system of the present disclosure, a gap  120  between the exit port  45  of the ion source  110  and an inlet port  25  of the ion transfer device  50  can preferably be varied as necessary to obtain optimum coupling efficiency of ions to the analyzer  80 . 
         [0050]    In one embodiment, a gap between the exit port  45  and the inlet port  25  is between about 10 mm and about 0.1 mm. In another embodiment, the gap is less than about 4 mm. 
         [0051]    In one preferred embodiment the ion source  110  is a nano-flow ESI. 
         [0052]    In other embodiments, the nanoflow ion source can be coupled to the end of a liquid chromatography system, to a liquid pumping system, or simply to a tube containing the liquid to be electrosprayed. 
         [0053]    Referring still to  FIG. 3 , the vacuum housing  70  can include a first vacuum chamber  72 , to which an exit port  165  of the ion transfer device  50  is coupled, and a second vacuum chamber  74 , as well as various elements including ion optics  76 , such as a skimmer, lenses, RF guides and so on between the exit port  65  of the ion transfer device  50  and a receiving port  75  of the analyzer  80 . 
         [0054]    Referring to  FIG. 4 , an experimental measurement apparatus  130  was assembled to compare an embodiment of the ion transfer device  50  of the present disclosure with other types of interfaces for coupling electrosprayed ions  132  from atmosphere to a vacuum chamber  134 , representing a vacuum stage of a mass spectrometer. A Faraday cup  136  was positioned in place of an analyzer of a mass spectrometer for measuring the ion current transmitted (I 8 ). The ion source  138  for generating the ions  132  from a diluted sample  140  was a standard liquid junction nano-flow ESI ion source mounted on an x-y-z-stage. New Objective PicoTip capillary emitters having 10±1 μm pulled tip orifices (unless otherwise noted) were used for the nano-ESI ion source. For the high voltage supply  142 , a Bertran supply was used. Two different solutions were electrosprayed: 60%/39%/1% MeOH/H2O/acetic acid (from Fisher) and 0.1% v/w brilliant blue R dye (from Sigma-Aldrich) in 50/50 MeOH/H2O. The solutions were introduced into the emitter  138  by a Harvard syringe pump with a flow rate of about 100/hour. The x-y-z-stage was used to align the exit tip  144  of the emitter  138  relative to the entrance  146  of the particular atmosphere/vacuum interface under test, for optimizing alignment of the ESI-produced spray  132  of ions and droplets through each of the atmosphere/vacuum interfaces tested. 
         [0055]    Referring to  FIG. 5A , in one embodiment the diverging conical duct of an ion transfer device of the present disclosure is provided by a standard conductive plastic 0.3-10 μl pipette tip  150 . A representation of a cross-section of one example of the pipette tip, exposing internal walls that form a slowly diverging conical duct, is provided in  FIG. 5B . 
         [0056]    The pipette tip  150  is made from conductive plastic, is about 30 mm long, and is available from Advion, 10 Brown Road, Suite 101, Ithaca, N.Y. 14850 USA, as Part No. Catalog: CS109. The tip  150  contains a 7 mm-long section  160  of slowly diverging conical duct at its inlet tip  155 , with an angle of divergence of about 0.8°. It was found that this section  160  alone can transmit ions better than any other type of electrode tested. The pipette  150  also contains additional diverging ducts with larger angles of divergence that have an effect on ion transmission, improving the transmission further over the 7 mm section alone. Referring to the circular inset  162  of  FIG. 5B , the inner passage at the inlet  155  was additionally shaped (using a pin) to widen an inner diameter  164  at the inlet  155  of the ion transfer device to improve the suction flow of air into the diverging conical duct  152 . 
         [0057]    To compare the ion transmission through the conductive plastic tip  150 , an embodiment of an ion transfer device of the present disclosure, with the transmission through other types of interfaces commonly used to transmit ions into a vacuum stage of a mass spectrometer, the conductive plastic tip  150  was replaced with different types of electrode interfaces and tested with the same apparatus  130 . All of the electrodes were heated during the measurements. The electrode holder  60  was changed as needed to accommodate the different sizes of interfaces tested. Both custom-made capillaries having an Inner Diameter (ID) of about 0.5 mm, Outer Diameter (OD) of about 1.64 mm, and length of about 5 to about 200 mm, and commercial capillaries taken from various commercial electrospray instruments (from LCQ, LTQ and Velos mass spectrometers, available from Thermo Fisher Scientific) were tested, including: a capillary from an LCQ-IT mass spectrometer (manufacturing year ˜2000) with dimensions: ID ˜0.5 mm, OD ˜1.56 mm, length ˜184.4 mm; a capillary from an LTQ-IT mass spectrometer (manufacturing year ˜2005) with dimensions: ID ˜0.5 mm, OD ˜1.56 mm, length ˜101.7 mm; and a capillary from a Velos-IT mass spectrometer (manufacturing year ˜2011) with dimensions: ID ˜0.05 mm, OD ˜1.56 mm, length ˜58.6 mm. A representative capillary  180  mounted with an electrode holder  62  to the vacuum chamber  134  is shown in  FIG. 6A . 
         [0058]    Referring to  FIG. 6B , also tested was an electrode  190  from a commercial Synapt QqTOF mass spectrometer (available from Waters Corporation, 34 Maple Street, Milford, Mass. 01757), which has a ˜0.3 mm diameter inlet orifice for accepting electrosprayed ions, followed by a short cone-shaped section that opens into a 8.3 mm ID tube for transferring the ions into the vacuum stage of a mass spectrometer. Referring to  FIG. 6C , also measured was the ion transmission through a 0.5 mm diameter hole in a flat electrode  200  of thickness 0.03 mm. This electrode is a good example of the electrodes used in rudimentary, orifice-type ion interfaces, as for example in the mass spectrometers manufactured by AB Sciex 71 Four Valley Drive, Concord, Ontario, L4K 4V8, Canada. In each case, an appropriate electrode holder  62 ,  64 ,  66  was used to couple the interface to the vacuum chamber  134 , as shown in  FIGS. 6A ,  6 B, and  6 C, respectively. 
         [0059]    To test the efficiency of ion transmission through the various interfaces into the vacuum chamber  134 , the value of the emitted ion current  148  was measured (I 5  in  FIGS. 6A-C ;  FIG. 4 ) from the nano-flow ESI ion source  138  and were compared with the current of ions that passed through the orifices or channels in the different electrodes as detected and measured (I 8  in  FIGS. 6A-C ;  FIG. 4 ) by the Faraday cup  136 . 
         [0060]    The currents were measured with a picoammeter (Keithley, Model 480). The vacuum chamber  148  was evacuated with an Edwards  12  two-stage rotary pump with an effective speed of ˜12.8 l/s (the nominal pumping speed of ˜14.2 l/s was corrected for the experimentally measured conductance of the hose connecting the vacuum chamber  134  with the pump. The typical pressure in the chamber was in the range of about 3-8 Torr, depending on the geometry and type of electrode interface being measured. 
         [0061]    The various metal capillaries  180  and the electrode holder  62  were heated by an electric heater to between about 80-200° C. The plastic tips can also be heated by heating an electrode holder ( 6 ), but the distribution of temperature along the tip was not measured. 
         [0062]    Referring to  FIGS. 7A ,  7 B,  9 A and  9 B, the ion transmission efficiency of the full conical duct was measured, as shown in  FIG. 4 , and compared with the measured transmission efficiency of a variety of metal capillaries collected from the different commercial mass spectrometers, as described above for the capillary  180  shown in  FIG. 6A . Referring to  FIGS. 8A and 8B , the ion transmission efficiency was also similarly measured for just the 7 mm front section of the pipette. 
         [0063]    Referring to  FIGS. 7A and 7B , the transmission efficiency  250  and absolute transmitted current  270  through the different types of capillaries and through an embodiment of the diverging conical duct of the present disclosure, based on the conductive plastic pipette  150  described above. The transmission efficiency  262  of the conductive plastic pipette  150  was measured to be at least 5 times higher than that measured for the various capillaries tested  264  (Velos),  266  (LTQ), and  268  (LCQ), for voltages in a normal operating range of about 1200-1500 volts used for most typical nano-flow ESI liquid chromatography/mass spectrometry (LC/MS) experiments. As shown in  FIG. 7B , the transmitted current was measured to be 10-100 times higher for the conical duct electrode  272  than that measured for the straight capillaries  274 ,  276 ,  278  in the same operating voltage range  279 . 
         [0064]    It is worth noting that at low electrospray voltages, around ˜700 V, the transmission efficiency of the Velos-IT capillary  264  is almost as high as the transmission of the plastic tip  262  (˜100%). This, perhaps, can be explained by a rather unidirectional “dripping” mode of electro-spraying at lower voltages. This tendency is quickly broken as the voltages are increased to the operating values between 1200 to 1500 volts needed to reach the “Cone-Jet” mode of spraying needed for robust performance of nano-flow ESI LC/MS experiments. 
         [0065]    Referring to  FIG. 8A  and  FIG. 8B , the transmission efficiency and absolute transmitted current were measured through 0.5-mm ID metal capillaries of varying lengths and compared to those measured for the 7-mm section  160  of the conductive plastic tip  150 , which was cut from the end portion of the plastic pipette  150 . This slowly diverging section  160  has a divergence angle of ˜0.8°. The transmission efficiency  280  and the transmitted current  290  of this slowly diverging section  160  were measured to be at least 2 times higher than the transmission efficiency  282  and transmitted current  292  measured for the shortest metal capillary (5 mm), and even higher than those measured for an 11-mm long capillary  284 ,  294  and a 56-mm long capillary  286 ,  296  in the operating voltage range of 1200-1500 Volts  279 . This result shows that the slowly diverging conical duct  160  at the tip of the full conical conductive pipette  150  plays an important role in maximizing the ion current transmitted. 
         [0066]    Accordingly, the tendency of shortening metal capillaries to improve transmission was shown to have limited potential, in that the ion transmission efficiency and the total transmitted current increases rather slowly as the metal 0.5 mm ID capillary was shortened from 56 mm ( 286 ,  296 ), down to 11 mm ( 284 ,  294 ), and then to 5 mm in length ( 282 ,  292 ) as shown in  FIGS. 8A and 8B . 
         [0067]    Referring to  FIGS. 9A and 9B , the ion transmission efficiency  300  of the same slowly diverging conical section  160  of the plastic pipette  150  was found to be only slightly higher than that  302  of the electrode  190  (as shown in  FIG. 6B ), or than the transmission efficiency  304  through a rudimentary flat electrode  200  with a 0.5 mm orifice (as shown in  FIG. 6C ). However, under similar conditions, the transmitted current  306  for the slowly diverging conical section  160  was about 2 times higher than that  308 ,  310  measured through these other electrodes  190 ,  200  over the operating voltage range  279  of 1200-1500 Volts. 
         [0068]    The higher ion transmission efficiency of the “orifice” type of interfaces (as compared to a capillary type) may stem from the very limited time for interaction of the ions with the walls of an orifice of the order of fraction of a 1 μs. Beams formed by passing through capillaries, on the other hand, may spend 0.1-1 ms in the duct. The longer ion residence time in the capillaries have both positive and negative consequences. On the positive side, the long residence time in the heated capillary can ensure efficient desolvation of heavily solvated ions and small droplets by radiation heating. On the other hand, the longer opportunity for interaction of the beam with the capillary walls may lead to more substantial ion losses. 
         [0069]    The proposed method of forming an ion beam in a slowly diverging conical duct in accordance with the present disclosure preferably accomplishes the following: (i) the beams formed in the diverging duct do not interact excessively with the inner walls, especially after flow separation takes place, and (ii) as the beam propagates it diverges very slowly. Referring to  FIGS. 10A-10C , measurements were performed to characterize the ion beam that forms in the various electrode interfaces measured. Referring to  FIG. 10A , the ion beam  320  that forms in the full-length conductive plastic duct  150  has a very small angle of divergence (a) of about 0.6 degrees. On the other hand, beams  322  and  324  ( FIGS. 10B and 10C ) formed by passing through the orifices of the commercial interfaces  190  and  200 , shown in  FIGS. 6B and 6C , diverge more quickly and are consequently much wider, with divergences, a, of about 1.8 degrees and 7 degrees, respectively. Also importantly, the tightly focused beam  320  can travel a longer distance before the beam is dissipated by collisions with the residual buffer gas. Such a narrow beam can be efficiently heated by radiation, for example, emitted from an encompassing heated sleeve that is still large enough to prevent losses via interactions with the walls. Alternatively, the holder that couples the tip to the vacuum chamber can be heated. 
         [0070]    The divergence of the beams  320 ,  322 , and  324  formed in each of the interfaces were observed by electrospraying a solution of brilliant blue R dye through the different electrodes and allowing the ions and small droplets to interact with a 72 line/inch mesh (90% transmission) positioned at various distances from the entrances. The mesh was then removed and the picture of the spot formed by the beam was taken and analyzed for each electrode interface  150 ,  190 ,  200 , respectively. The beam  320  formed in the diverging conical duct of the conductive tip  150  was measured to be about 3-10 times tighter than the beams formed in the other interface. 
       Example 
       [0071]    We have discovered a way to increase the efficiency of ion transfer from atmosphere into vacuum to almost 100%. This high efficiency was achieved using a novel configuration for the electrode through which ions enter the mass spectrometer. We term this a “ConDuct” electrode because it contains a narrow, slowly diverging conical duct that is able to transmit a large ion current into the vacuum with minimal losses, surpassing performance of all other types of atmosphere vacuum interfaces that utilize orifices or heated metal capillaries. We have constructed a new atmosphere-vacuum ion transmission interface based on the ConDuct electrode and have demonstrated that it can transmit 100-to-1000 times more ions than a typical heated-capillary-skimmer based interface. 
         [0072]    Method: 
         [0073]    We have modified an LCQ-DECAXP ion trap mass spectrometer (Thermo) by equipping the instrument with two atmosphere-vacuum interfaces that can operate simultaneously. One of these is the original interface of the mass spectrometer containing an 18 cm-long heated metal capillary and a skimmer. The other interface contains a heated holder supporting the ConDuct electrode, a quadrupole ion guide and a skimmer identical to that used in the first interface. Ions from both interfaces are mixed in a T-shaped quadrupole ion guide and transferred to the ion trap. To directly compare the relative ion transmission efficiencies, we used peptides labeled with heavy or light isotopes to distinguish between ions coming from the ConDuct interface and the original interface of the mass spectrometer. 
         [0074]    Preliminary Data: 
         [0075]    Firstly, we found that a conductive plastic 0.1-10 μl pipette tip can be used as one practical implementation of the ConDuct electrode. The tip contains a 7 mm-long section of slowly diverging conical duct at its tip (the diameter of the entrance is ˜0.4 mm), with an angle of divergence ˜0.8 degrees. 
         [0076]    Secondly, we showed that such a ConDuct electrode transmits 80-99% of the total ion current emitted from a typical nanospray ion source into the vacuum of the mass spectrometer, resulting in absolute transmitted currents &gt;200 nA. We determined that this total ion current was at least 10 times larger than the current transmitted through all the heated capillary geometries in current use and at least several times larger than through the orifice-type interfaces of even larger diameter. 
         [0077]    Thirdly, we built a new atmosphere-vacuum interface based on the ConDuct electrode and demonstrated that it can transmit 100-to-1000 times more ions than a typical heated-capillary-skimmer based interface. 
         [0078]    We also obtained some experimental evidence that supports our speculations that the phenomenon of flow separation is responsible for the improved ion transmission. Flow separation occurs when a gas moves in a diverging duct with a velocity higher than some critical velocity. We also demonstrated that the ion beam produced this way has the following advantageous properties: (i) it does not interact with the inner walls; and (ii) the beam diverges very slowly as it leaves the duct and propagates through the vacuum. 
         [0079]    Our results encourage further exploration of the phenomena involved in the formation of molecular and ion beams as they move through the slow diverging conical ducts and utilization of these phenomena for designing and implementing new atmosphere-vacuum interfaces with increased ion transfer efficiencies into mass spectrometers. 
         [0080]    While the invention has been particularly shown and described with reference to specific embodiments, it should be apparent to those skilled in the art that the foregoing is illustrative only and not limiting, having been presented by way of example only. Various changes in form and detail may be made therein without departing from the spirit and scope of the invention. Therefore, numerous other embodiments are contemplated as falling within the scope of the present invention as defined by the accompanying claims and equivalents thereto.