Abstract:
An apparatus for use as an ion source for mass analysis includes a nebulizing device, a vaporizing device, a chamber, an ion sampling structure, and an ionizing device. The vaporizing device includes a vaporizing interior that terminates at a vaporizing device outlet. The chamber fluidly communicates with the vaporizing device outlet. The ion sampling structure has an ion sampling inlet fluidly communicating with the chamber and spaced from the vaporizing device outlet. The ionizing device includes first and second electrodes positioned to produce an electrical discharge therebetween a location closer to the vaporizing device outlet than to the ion sampling inlet.

Description:
RELATED APPLICATIONS  
       [0001]    This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/428,802, filed Nov. 25, 2002. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention generally relates to atmospheric pressure chemical ionization (APCI) in preparation for mass analysis, as is performed in mass spectrometry (MS). More particularly, the present invention relates to an apparatus and method for improving ionization of sample molecules in an APCI source.  
         BACKGROUND OF THE INVENTION  
         [0003]    Mass spectrometry is a highly sensitive method of molecular analysis. In general, mass spectrometry is a technique that produces a mass spectrum by converting the components of a sample into rapidly moving gaseous ions, and resolving the ions on the basis of their mass-to-charge (m/e or m/z) ratios. The mass spectrum can be expressed as a plot of relative abundances of charged components as a function of mass, and thus can be used to characterize a population of ions based on their mass distribution. Mass spectrometry is often performed to determine molecular weight, molecular formula, structural identification, and the presence of isotopes. The apparatus provided for implementing mass spectrometry, i.e., a mass spectrometer (MS) system, typically consists of a sample inlet system, an ion source, a mass analyzer, and an ion detection system, as well as the components necessary for carrying out signal processing and readout tasks. Many of these functional components of the mass spectrometer, particularly the mass analyzer, are maintained at a low pressure by means of a vacuum system. The ion source converts the components of a sample into charged particles. The negative particles are ordinarily removed from the process flow in positive ion mode when analyzing positive particles. In negative ion mode the positive ions are removed. The mass analyzer disperses the charged particles based on their respective masses, and then focuses the ions on the detector. The ion currents produced by the detector are then amplified and recorded as a function of spectral scan time. The designs of the components of the mass spectrometer, and the principles by which they operate, can vary considerably. Thus, components of differing designs have distinct advantages and disadvantages when compared to each other, and the desirability of any one design can depend on, among other factors, the nature of the sample to be analyzed.  
           [0004]    The sample inlet system employed for mass spectrometry can be chromatographic. That is, the effluent from a chromatographic column can be utilized as the sample source for the MS system. The mass spectrometer in such cases can be considered as serving as the detector for the chromatographic apparatus. Such an arrangement is commercially available in systems in which a gas chromatographic (GC) apparatus is directly coupled to the mass spectrometer (GC/MS systems), or a liquid chromatographic (LC) apparatus is directly coupled to the mass spectrometer (LC/MS systems). These combined systems are particularly useful for deriving complex spectra from mixtures, as it is known that mass spectrometers alone are more or less limited to handling pure compounds and relatively simple mixtures.  
           [0005]    An ion source commonly serving as the interface between an LC apparatus and the mass spectrometer operates according to the principle of atmospheric pressure ionization (API), a soft ionization technique in which ionization of a sample occurs outside of the vacuum region or regions associated with the mass spectrometer. An increasingly popular type of API technique is atmospheric pressure chemical ionization (APCI or APcI). Simply stated, APCI is a means for ionizing samples (e.g., analyte molecules) dissolved in a liquid (e.g., an excess of mobile-phase molecules such as solvent). The sample-containing liquid emitted from the LC apparatus is pneumatically nebulized into a fine dispersion of numerous small droplets, typically below 100 microns in diameter. Heat is applied to the droplets to vaporize the liquid and sample matrix. This nebulization/vaporization process, however, is gentle enough to preserve the molecular identity of the sample constituents at this stage. The resulting gas/vapor is subsequently passed into a chamber where electrons emitted from an electrode generate a low-current corona discharge in the ambient, atmospheric-pressure environment consisting of, for example, a background gas such as nitrogen or air. The corona discharge ionizes the mobile-phase molecules to form an energetic chemical reagent gas plasma. In the corona discharge, ion-molecule reactions occur between the charge-neutral sample and the reagent ions formed in the primary discharge. The dominant mechanisms for the ion-molecule reactions are collisions between the reagent ions and the sample molecules, enabled by the relatively high (atmospheric) pressure environment, and charge transfer reactions. The ion-molecule reactions cause the sample to become charged, and the resulting stable sample ions are passed through an opening in a vacuum chamber into the mass analyzer of the mass spectrometer for mass analysis. Unlike the API technique of electrospray ionization (ESI), in which multiple-charged molecular ions [M +nH] n+ are produced, in most applications APCI produces only single-charged molecular ions typically in the form of [M+H] + or [M−H] − as a result of protonation or deprotonation.  
           [0006]    [0006]FIG. 1 illustrates an example of a conventional APCI source, generally designated  10 , utilized in, for example, an LC/MS system. In general terms, APCI source  10  comprises a sample introduction and nebulizing section, generally designated  20 ; a vaporization section, generally designated  30 ; an ionization section, generally designated  40 ; and an ion inlet section, generally designated  50 . Ion inlet section  50  includes a front plate  52  having an ion inlet aperture  53  through which ionized products are directed into the mass analyzer of the mass spectrometer. For simplicity, the mass analyzer and other typical components of the mass spectrometer, such as its ion detection, signal processing and readout systems, are collectively designated as MS in FIG. 1.  
           [0007]    Nebulizing section  20  comprises a capillary tube  23 , typically a metal capillary, that serves as the sample inlet system of mass spectrometer MS. Capillary tube  23  conducts the LC column flow from a liquid chromatographic apparatus LC into vaporization section  30 . In addition, a length of conduit  27  for directing a suitable inert nebulizing gas such as nitrogen into vaporization section  30  is coaxially disposed about capillary tube  23 . Vaporization section  30  of APCI source  10  generally includes a vaporizing tube  33  and a heater  35  enclosed in a coaxial housing (not shown), and a conduit  37  for directing a suitable inert vaporizing (“auxiliary” or “make-up”) gas such as nitrogen into vaporizing tube  33 . Heater  35  is situated so as to ensure sufficient thermal contact with the wall of vaporizing tube  33 . The wall of vaporizing tube  33  is typically quartz, and can operate at temperatures ranging-from about 200-600° C. to rapidly vaporize effluent from capillary tube  23 . While the thermal effect on typical samples is minimal, such a technique is not compatible with very thermally labile molecules. Capillary tube  23  is disposed along the central axis of vaporizing tube  33  and terminates at a capillary tube outlet  23 A within vaporizing tube  33 . A portion of vaporizing gas conduit  37  is coaxially disposed about nebulizing gas conduit  27  as well as capillary tube  23 .  
           [0008]    Ionization section  40  of APCI source  10  generally includes an ionization chamber  42  defining an enclosed volume into which a corona needle or pin  43  is inserted. Capillary tube  23   30  and conduits  27  and  37  are often integrated in a manifold structure which, along with vaporization section  30 , is often structured as a probe that is mounted to ionization chamber  42 . Corona needle  43  typically operates at about 5-10 kV and 1-5 mA to strike a low-current corona discharge or electron cloud  45  within ionization section  40 . This electrical discharge  45  enables the generation of the afore-mentioned chemical reagent gas plasma utilized to ionize the sample molecules. Vaporizing tube  33  terminates at a vaporizing tube outlet  33 A in fluid communication with ionization chamber  42 , whereby vaporized analyte and mobile-phase constituents are transferred into chamber  42  for ionization. One or more voltage sources (not shown) are typically provided to impress a voltage between front plate  52  of ion inlet section  50  and one or more electrically conductive surfaces in ionization section  40  such as corona needle  43 , thereby establishing one or more electric fields sufficient to attract ionized products derived from the vaporized LC eluent into ion inlet section  50  through ion inlet aperture  53 .  
           [0009]    In operation, a liquid sample comprising the LC column flow from liquid chromatographic apparatus LC is introduced into the heated vaporizing tube  33  via capillary tube  23 , typically at a flow rate of about 0.1-2.0 ml/min. Nebulizing and vaporizing gas streams are introduced into vaporizing tube  33  through nebulizing gas conduit  27  and vaporizing gas conduit  37 , respectively. The nebulizing gas flows concentrically around centrally disposed capillary tube  23  at a high velocity and a typical pressure of about 0.8 MPa, thereby nebulizing the liquid sample into small liquid droplets as the nebulizing gas and liquid sample enter vaporizing tube  33 . Because the wall of vaporizing tube  33  is heated by heater  35  and consequently transfers heat energy into the interior of vaporizing tube  33 , the liquid droplets of the nebulized sample entering vaporizing tube  33  are converted into vapor. The vaporizing gas is added to the system at a typical flow rate of about 1 -3 L/min by means of vaporizing gas conduit  37 . The flow of vaporizing gas assists in sweeping or transporting the liquid-droplet and vapor phases of the sample-containing aerosol through vaporizing tube  33 . The resulting vapor temperature of the aerosol is about 100° C. The heated gas/vapor then passes in a sample exhaust stream  60  into chamber  42  and into the low-current corona discharge  45  established by corona needle  43  in ionization section  40 , where the charge-neutral sample is ionized by ion-molecule reactions with the reagent ions formed in corona discharge  45 .  
           [0010]    In a typical configuration of conventional APCI source  10 , corona needle  43  is oriented toward and in relatively close proximity with ion inlet aperture  53 . Accordingly, a relatively large space or gap exists between vaporizing tube outlet  33 A and the ionization volume defined by corona discharge  45 . Moreover, corona discharge  45  is typically established by electrically  30  coupling corona needle  43  with front plate  52  of ion entry section  50 . As a result, vapor flow in ionization chamber  42  is characterized by an undesirably large volumetric time constant, which in turn results in a large-volume mixture of vapor-phase sample and vapor-phase background species (i.e., non-sample constituents). This mixture leads to an increase in the formation of background ions and in the splitting of peak components of the sample, a concomitant reduction in reaction volume and thus a reduction in sample ions, and an increase in chemical noise (i.e., a reduction in signal-noise ratio) and peak tailing or broadening as generated by mass spectrometer MS. In addition, corona needle  43  extends into sample exhaust  60  and thus is subject to contamination, especially at high flow rates.  
           [0011]    It would therefore be advantageous to provide an ion source and ionization method that minimizes the amount of background vapor mixing with sample vapor, increases reaction volume, reduces the number of background ions entering a mass spectrometer, and reduces sample peak tailing. It would be further advantageous to provide an ion source in which the electrode or electrodes employed are not directly exposed to the vaporizer discharge and to the chemical environment of the source chamber into which the contents of the vaporizing tube are exhausted.  
           [0012]    The present invention is provided to address, in whole or in part, these and other problems associated with the prior art.  
         SUMMARY OF THE INVENTION  
         [0013]    In general terms, the present invention provides an apparatus and method for ionizing a sample in preparation for mass analysis. The sample is first nebulized by pneumatic means and then vaporized by heating means. The vaporized sample is then ionized by directing the sample through an electrical discharge. The ionized sample is then directed toward the inlet section of an appropriate mass analysis device such as a mass spectrometer. The electrical discharge is formed at a location within the apparatus that enables the sample to be ionized without any significant mixing with background gases or vapors, and thus background noise and peak tailing is avoided or reduced during mass analysis. In some embodiments the electrical discharge has a DC potential, while in other embodiments the electrical discharge has an AC potential.  
           [0014]    According to one embodiment, an apparatus for use as an ion source for mass analysis comprises a nebulizing device for nebulizing a flowing sample, a vaporizing device for vaporizing the sample flowing from the nebulizing device, a chamber, an ion sampling structure, and an ionizing device. The vaporizing device comprises a vaporizing interior that terminates at a vaporizing device outlet. The chamber fluidly communicates with the vaporizing device outlet. The ion sampling structure has an ion sampling inlet that fluidly communicates with the chamber and is spaced from the vaporizing device outlet. The ionizing device comprises first and second electrodes. The electrodes are positioned so as to produce an electrical discharge therebetween at a location closer to the vaporizing device outlet than to the ion sampling inlet.  
           [0015]    In one aspect of this embodiment, the first electrode is positioned in the chamber in close proximity to the vaporizing device outlet. The second electrode is disposed within the vaporizing interior such that an electrical discharge is produced that extends into the vaporizing interior through the vaporizing device outlet. The second electrode can be a point-charge device such as a needle or pin, or can take the form of an electrically conductive portion of the nebulizing device or the vaporizing device. Alternatively, the second electrode is positioned in the chamber in the close proximity to the vaporizing device outlet opposite to the first electrode, such that the electrical discharge traverses a sample exhaust flow from the vaporizing device outlet. As another alternative, the first and second electrodes are disposed along an axial length of the vaporizing device outside of the vaporizing interior and are coupled by an AC voltage to produce an electrical discharge substantially entirely within the vaporizing interior. Preferably, the AC voltage is a high frequency voltage such as an RF voltage.  
           [0016]    According to any of the embodiments described herein, the components of the apparatus serving as electrodes are positioned so as not to contact the sample in order to prevent contamination of the electrodes.  
           [0017]    According to another embodiment, an apparatus for use as an ion source for mass analysis comprises a nebulizing device, a vaporizing device, a chamber, an ion sampling structure, and an ionizing device. The ionizing device comprises an electrode disposed in the chamber for creating an electrical discharge between the electrode and an electrically conductive component disposed in an interior of the vaporizing device. In one aspect, a DC voltage source is connected between the electrode and the conductive portion. In another aspect, an AC voltage source is connected between the electrode and the conductive portion.  
           [0018]    According to yet another embodiment, an apparatus for use as an ion source or mass analysis comprises a nebulizing device, a vaporizing device, a chamber, an ion sampling structure, and a ionizing device. The ionizing device comprises first and second electrodes disposed in the chamber for creating an electrical discharge therebetween, across a sample exhaust flow received in the chamber from the vaporizing device, and proximal to an outlet of the vaporizing device into the chamber.  
           [0019]    In one aspect of this embodiment, an RF voltage source is connected between the first and second electrodes. In another aspect, in addition to the RF voltage source, a DC voltage source is connected between one or both of the electrodes and the ion sampling structure for establishing an electrical field for directing sample ions toward an inlet of the ion sampling structure.  
           [0020]    According to another embodiment, an apparatus for use as an ion source for mass analysis comprises a nebulizing device, a vaporizing device, a chamber, an ion sampling structure, and an ionizing device. The ionizing device comprises a first electrode disposed in the chamber approximate to an outlet of the vaporizing device, and a second electrode disposed in an interior of the vaporizing device. The configuration of these electrodes creates an electrical discharge through the vaporizing device outlet and into the interior of the vaporizing device.  
           [0021]    According to another embodiment, an apparatus for use as an ion source for mass analysis comprises a nebulizing device, a vaporizing device, a chamber, an ion sampling structure, and an ionizing device. The ionizing device comprises a first and second electrodes that are driven by a RF voltage. The first and second electrodes are disposed outside of the interior of the vaporizing device along a length of the vaporizing device for creating an electrical discharge substantially entirely within the interior. In one aspect of this embodiment, an additional, polarizing electrode is disposed in the chamber for establishing an electrical field by which ionized sample components can be directed toward an inlet of the ion sampling structure.  
           [0022]    A method is provided for ionizing sample molecules at atmospheric pressure, comprising the following steps. A nebulized sample is flowed through an interior of a vaporizing device to vaporize the sample. The vaporized sample is exhausted through an outlet of the vaporizing device into a chamber. An ion sampling inlet is disposed in the chamber and is spaced from the vaporizing device outlet. The sample is ionized by forming an electrical discharge at a location that is closer to the vaporizing device outlet than to the ion sampling inlet.  
           [0023]    In one aspect of this method, at least a portion of the electrical discharge is directed through the vaporizing device outlet into the vaporizing device interior to initiate ionizing reactions prior to the sample being exhausted into the chamber. In another aspect, the sample is exhausted into the chamber in a sample exhaust stream and the electrical discharge traverses the sample exhaust stream at a location immediately downstream from the vaporizing device outlet. The sample becomes ionized immediately after being exhausted from the vaporizing device outlet. In a further aspect, the electrical discharge is formed substantially and entirely within the vaporizing device interior to initiate ionizing reactions prior to the sample being exhausted into the chamber.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0024]    [0024]FIG. 1 is an axial cross-sectional schematic view of a conventional APCI source;  
         [0025]    [0025]FIG. 2A is a perspective view of an APCI source provided in accordance with one embodiment of the present invention;  
         [0026]    [0026]FIG. 2B is an axial cross-sectional schematic view of the APCI source shown in FIG. 2A;  
         [0027]    [0027]FIG. 3A is a perspective view of an APCI source provided in accordance with another embodiment of the present invention;  
         [0028]    [0028]FIG. 3B is an axial cross-sectional schematic view of the APCI source shown in FIG. 3A;  
         [0029]    [0029]FIG. 4 is an axial cross-sectional schematic view of an APCI source in accordance with an alternative of the embodiment shown in FIG. 3B;  
         [0030]    [0030]FIG. 5 is an axial cross-sectional schematic view of an APCI source provided in accordance with a further embodiment of the present invention;  
         [0031]    [0031]FIG. 6A is a perspective view of an APCI source provided in accordance with yet another embodiment of the present invention;  
         [0032]    [0032]FIG. 6B is an axial cross-sectional schematic view of the APCI source shown in FIG. 6A; and  
         [0033]    [0033]FIG. 6C is a transverse cross-sectional schematic view of the APCI source shown in FIG. 6A. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0034]    Referring to FIGS. 2A and 2B, an APCI source, generally designated  100 , is illustrated in accordance with one embodiment of the present invention. APCI source  100  finds particular use as an interface between a liquid chromatographic apparatus LC and a mass spectrometer MS. The invention, however, is not limited to the use of an LC instrument or any other particular input source of sample analytes to be ionized and processed by mass spectrometer MS. APCI source  100  comprises a sample introduction and nebulizing section or device, generally designated  120 ; a vaporization section or device, generally designated  130 ; an ionization section or device, generally designated  140 ; and an ion entry section or device, generally designated  150 , including a front plate or wall  152 . Front plate  150  has an ion sampling inlet  153  through which ionized products from a sample exhaust flow, generally designated E, are directed into mass spectrometer MS. Ion sampling inlet  153  can be an orifice or a conduit. As appreciated by persons skilled in the art, the structures defining the interface between ionization section  140  of APCI source  100  and ion entry section  150  are configured (such as through the use of appropriate flanges, seals, fasteners, and so on) to maintain a vacuum environment within mass spectrometer MS and an atmospheric or near-atmospheric pressure environment within APCI source  100 .  
         [0035]    Nebulizing section  120  comprises a sample conduit  123 , preferably in the form of a capillary tube, for introducing a sample-containing solution from an appropriate source such as a liquid chromatographic apparatus LC. Sample conduit  123  is disposed generally along the central axis of a vaporizing tube  133 , and terminates at a sample conduit outlet  123 A that serves as the inlet for introducing the sample-containing solution directly into vaporizing tube  133 . Nebulizing section  120  also comprises a conduit  127  for directing a suitable inert nebulizing gas such as nitrogen into vaporizing tube  133 . Nebulizing gas conduit  127  terminates at a nebulizing gas conduit outlet  127 A positioned to conduct nebulizing gas into vaporizing tube  133  in the vicinity of the point of entry of the sample-containing solution emitted from sample conduit  127 , and thus to efficiently nebulize the sample-containing solution. Nebulization is preferably accomplished by positioning nebulized gas outlet  127 A concentrically around sample outlet  123 A of sample conduit  123 . Sample conduit outlet  123 A and nebulizing gas conduit outlet  127 A can be structured as concentric orifices or as a nozzle. The path of the nebulized sample analyte components as they are nebulized, vaporized, ionized, and directed toward ion entry section  150  is schematically indicated in FIG. 2B by a line S. It will be understood, however, that the path of the sample as it flows through vaporizing tube  133  is not necessarily linear and can involve vortical components, and that means can be provided to force a vortical or otherwise non-linear flow if desired to enhance vaporization.  
         [0036]    Vaporization section  130  comprises a structure suitable for defining an interior space through which the nebulized sample can travel to ionization section  140  and be efficiently vaporized prior to reaching ionization section  140 . Accordingly, FIG. 2 illustrates a vaporizing space-defining structure provided in the form of vaporizing tube  133 , although the invention is not limited to providing a tube-like or cylindrical profile. Vaporization section  130  can further comprise a heater  135  (FIG. 2B) of any suitable type (e.g., resistive elements, inductive coils, or the like) disposed in thermal contact with the wall of vaporizing tube  133 . Heater  135  is enclosed in an outer housing  136  (FIG. 2A) of vaporization section  130 . Heater  135  can operate according to a pre-determined temperature profile, and vaporizing tube  133  can have a specified axial length, for the purpose of maximizing vaporization of the contents of vaporizing tube  133 . If desired, a sample pre-heating device (not shown) could also be included in vaporization section  130  or nebulizing section  120 . A conduit  137  coaxial with nebulizing gas conduit  127  and capillary tube  123  supplies a flow of a suitable inert vaporizing gas such as nitrogen to assist in transporting the nebulized sample components through vaporizing tube  133 . Vaporizing tube  133  terminates at a vaporizing tube outlet  133 A that serves as the vaporized sample inlet into an ionization chamber  142 . While the axis of ion sampling inlet  153  can be inline with the axis of vaporizing tube outlet  133 A, it is preferable that these two axes either be parallel and offset to each other or oriented at an angle α to each other. Angle α can be any value between 0 and 90°, and in one exemplary embodiment is 74°. The offset or angled orientation of vaporizing tube outlet  133 A relative to ion sampling inlet  153  prevents large droplets that are not fully vaporized or ionized and background gas from entering ion entry section  150 . This in turn reduces contamination of mass spectrometer MS, peak tailing, and background noise.  
         [0037]    Similar to the conventional system illustrated in FIG. 1, ionization section  140  of APCI source  100  generally includes an enclosed chamber (ionization chamber  142 ) into which an electrode  143 , such as a corona needle or other point-charge supply means, is inserted to strike a low-current corona discharge D. At least one voltage source V is connected between corona needle  143  and front plate  152  or some other proximal, electrically conductive portion of ion inlet section  150  (at ground or some other reference potential) to establish an electric field (typically at a DC potential) suitable for directing ionized sample products toward front plate  152  and through ion sampling inlet  153  for introduction into mass spectrometer MS.  
         [0038]    Unlike the conventional system, however, electrode  143  is not positioned near or coupled with front plate  152 . Instead, electrode  143  is positioned close enough to vaporizing tube outlet  133 A to enable the establishment of a voltage potential of, for example, approximately 1-approximately 6 kV, between electrode  143  and an electrically conductive portion of nebulizing section  120  that is grounded or at some other suitable reference voltage. For example, capillary tube  123  can be constructed from a metal and serve as a counter-electrode that becomes coupled with electrode  143  upon the energizing of electrode  143 . As a result, electrical discharge D, or at least a portion thereof, is created in vaporizing tube  133  as illustrated in FIGS. 2A and 2B, and travels from electrode  143  to capillary tube  123  or other portion of nebulizing section  120 . This electrical discharge D ionizes the vaporized or vaporizing constituents residing within vaporization tube  133 . The reagent ions needed for chemical ionization are created mostly in vaporizing tube  133  and in sample exhaust E just outside of vaporizing tube outlet  133 A. In some cases, ionization of at least some of the sample molecules through collision with the reagent ions can also occur within vaporizing tube  133 .  
         [0039]    As another advantage of this configuration, the amount of background vapor mixing with the sample vapor is minimized, because all or virtually all sample molecules are ionized before or in the immediate vicinity of vaporizing tube outlet  133 A and thus can be immediately attracted to ion sampling inlet  153  without first recirculating with background gas in ionization chamber  142 . This in turn minimizes ionization of background vapor components and thus reduces the number of background ions that enter mass spectrometer MS. In effect, the volumetric time constant for APCI source  100  is reduced with this configuration. Another advantage is that sample tailing is reduced, and thus the quality of data produced by mass spectrometer MS is improved. In addition, the creation of discharge D along the axial length of vaporizing tube  133  is believed to increase the reaction volume for chemical ionization, in effect extending the ionization region into vaporizing tube  133 . Also, the close proximity of electrode  143  to vaporizing tube outlet  133 A enables electrode  143  to be positioned outside of sample exhaust stream E, thereby preventing contamination of electrode  143 .  
         [0040]    In one example of the embodiments illustrated herein, vaporizing tube  133  is 4.5 mm in inside diameter and 50 mm in length, and has a volume of approximately 0.8 ml. If auxiliary gas (e.g., nitrogen) is flowed through vaporizing tube  133  from conduit  137  at a rate of approximately 2 L/min, a volumetric time constant of approximately 0.02 second is obtained, which is a much lower volumetric time constant than is obtained by conventional APCI or ESI sources.  
         [0041]    Other embodiments yielding similar advantages will now be described with reference to FIGS.  3 A- 6 C. These other embodiments can share many common features with APCI source  100  of FIGS. 2A and 2B. Common features thus are designated by like reference numerals, and only the primary differences between the embodiments are described further. For simplicity, heater  135  and ionization chamber  142  are not shown in FIGS.  3 A- 6 C.  
         [0042]    Referring now to FIGS. 3A and 3B, an APCI source, generally designated  200 , is illustrated according to another embodiment. In addition to a first electrode  143 A such as a corona needle, APCI source  200  comprises a second electrode or counter-electrode  143 B. Counter-electrode  143 B can be structured similarly to first electrode  143 A, or can be any electrically conductive structure provided with vaporization section  130  or ionization section  140  near vaporizing tube outlet  133 A. Both electrodes  143 A and  143 B and thus the ionization region are located downstream of vaporizing tube  133  and just outside of vaporizing tube outlet  133 A. As schematically illustrated in FIG. 3B, one or more DC voltage sources V are provided as necessary to initiate a corona discharge between electrodes  143 A and  143 B, as well to couple one or both electrodes  143 A and  143 B with a suitable surface of ion entry section  150  to direct sample ions from sample exhaust flow E into ion sampling inlet  153 . As a result, electrical discharge D traverses vaporizer exhaust stream E from electrode  143 A to counter-electrode  143 B in the immediate vicinity of vaporizing tube outlet  133 A. Because electrical discharge D is located in close proximity to vaporizing tube outlet  133 A, the effective ionization region is confined to this area. Consequently, the volume in which background vapors can mix with sample vapor is small, with the advantage that background ions and peak tailing are minimized.  
         [0043]    Referring now to FIG. 4, an APCI source, generally designated  300 , is illustrated according to another embodiment that can be considered as a variation of APCI source  200  of FIGS. 3A and 3B. In the embodiment of FIG. 4, an RF generator RF is connected between electrodes  143 A and  143 B to form electrical discharge D at an RF frequency of, for example, approximately 10-1000 kHz. The application of an RF voltage to electrodes  143 A and  143 B instead of a DC voltage can provide better spatial stability and can support an “electrodeless” discharge, i.e., one in which the discharge does not contact electrodes  143 A and  143 B. As further shown schematically in FIG. 4, a DC potential is applied by a DC voltage source V or equivalent circuitry between one or both electrodes  143 A and  143 B and an electrically conductive portion of ion entry section  150  to direct the product ions toward ion sampling inlet  153 . The superposition of the DC voltage on the alternating RF voltage can be accomplished by known circuitry means.  
         [0044]    Referring now to FIG. 5, an APCI source, generally designated  400 , is illustrated according to another embodiment. An RF generator RF is connected between electrode  143 A and counter-electrode  143 B to form electrical discharge D, with at least a portion of electrical discharge D being formed within vaporizing tube  133 . Counter-electrode  143 B can be any structure having an electrical discharging surface disposed within vaporizing tube  133 . As indicated by dashed and dotted lines in FIG. 5, an electrically conductive portion of nebulizing section  120  such as capillary tube  123  can serve as the counter-electrode, in which case electrical discharge D is coupled between electrode  143 A and nebulizing section  120 . Ion mobility toward ion sampling inlet  153  can be accomplished either by applying a DC potential between one of electrodes  143 A and  143 B and ion entry section  150  as shown in FIG. 4, or by employing an additional polarizing electrode  180  as shown for example in FIGS. 6A and 6B.  
         [0045]    Referring now to FIGS. 6A and 6B, an APCI source, generally designated  500 , is illustrated according to another embodiment. An electrode  173 A and counter-electrode  173 B are mounted outside of vaporizing tube  133  along a length thereof. As further shown in FIG. 6C, electrodes  173 A and  173 B generally conform to the shape of the outer surface of vaporizing tube  133 , and thus can be provided in the form of a split cylinder. An RF generator RF connected between electrodes  173 A and  173 B is set to apply a high-frequency alternating RF voltage therebetween. This enables capacitive coupling between electrodes  173 A and  173 B across the wall of vaporizing tube  133 , which typically is constructed from a dielectric material such as quartz. As a result, an electrode-less, high-frequency (for example, approximately 10-1000 kHz) RF discharge D is created entirely within vaporizing tube  133 , and without the need for electrodes  173 A and  173 B to be directly exposed to the interior environment of vaporizing tube  133 . Ionized products discharged from vaporizing tube outlet  133 A are directed toward ion sampling inlet  153  by applying a DC potential between a polarizing electrode  180 , located downstream from vaporizing tube  133 , and ion entry section  150 . By forming electrical discharge D as well as the resultant chemical ionization reagent ions entirely within vaporizing tube  133 , the formation of background ions in ionization section  140  is avoided and the reaction volume available for the primary, intermediate, and in some cases the collision-dominated final reactions of APCI is increased. As a consequence, more sample ions are produced. As an additional advantage, because electrodes  173 A and  173 B are not directly exposed to discharge D and to the chemical environment in vaporizing tube  133  and ionization chamber  142  (schematically depicted as an enclosed volume in FIG. 2B, into which the contents of vaporizer tube  133  are exhausted through vaporizing tube outlet  133 A), electrodes  173 A and  173 B are not contaminated during the operation of APCI source  500 .  
         [0046]    It will be understood that the APCI sources described herein can be configured so as to also be capable of performing ESI, with little or no modification or reconfiguration. The subject matter disclosed herein is applicable to LC-API-MS systems in general. It will also be understood that various operating parameters for the APCI systems disclosed herein, such as effluent and gas flow rates, fluid pressures and temperatures, voltages and currents, solvent composition, and so on will depend on the nature of the sample to be mass analyzed among other factors. As a general matter, it is known that optimization of operating parameters is less critical for APCI interfaces as compared with ESI interfaces.  
         [0047]    In the operation of one or more of the embodiments disclosed herein, some ionization may occur as a result of ion ejection, which is the dominant ionizing mechanism in ESI interfaces. This is particularly true when the sample solution contains highly polar or ionic analytes. Moreover, in the case of moderately polar and/or non-volatile analytes, some ionization may occur as a result of the triboelectric effect, in which an electric charge is generated by the shearing action of the nebulizing process.  
         [0048]    It will be further understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.