Abstract:
Improvements have been made for collection and focusing of ions generated from atmospheric pressure sources such as electrospray, atmospheric pressure chemical ionization, inductively coupled plasma, discharge, photoionization and atmospheric pressure matrix assisted laser desorption ionization. A high transmission electro-optical surface is placed between the source regions and the focusing regions to optimize the field geometries and strengths in each respective region. Compression ratios of greater than 5000 are capable of transferring virtually all ions from large volume dispersive ion regions into ion beam cross-sections of less than 1 mm. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when coupled to atmospheric pressure ionization sources.

Description:
GOVERNMENT SUPPORT  
       [0001] The invention described herein was made in the course of work under a grant from the Department of Health and Human Services, Grant Number: 1 R43 RR143396-1. 
     
    
     
       BACKGROUND  
         [0002]    1. Field of Invention  
           [0003]    This invention relates to methods and devices for improved collection and focusing of ions generated at atmospheric pressure for introduction into the mass spectrometer and other particle detectors.  
           [0004]    2. Description of Prior Art  
           [0005]    The generation of ions at atmospheric pressure is accomplished by a variety of means; including, electrospray (ES), atmospheric pressure chemical ionization (APCI), atmospheric pressure matrix assisted laser desorption ionization (MALDI), discharge ionization,  63 Ni sources, inductively coupled plasma ionization, and photoionization. A general characteristic of all atmospheric sources is the dispersive nature of the ions once produced. Needle sources such as electrospray and APCI disperse ions radially from the axis in high electric fields emanating from needle tips. Aerosol techniques disperse ions in the radial flow of gases emanating from tubes and nebulizers. Even desorption techniques such as atmospheric pressure MALDI will disperse ions in a solid angle from a surface. The radial cross-section of many dispersive sources can be as large as 5 or 10 centimeters in diameter. As a consequence of a wide variety of dispersive processes, efficient sampling of ions from atmospheric pressure sources to small cross-sectional targets or through small cross-sectional apertures and tubes (usually less than 1 mm) into a mass spectrometer becomes quite problematic. This is particularly amplified if the source on ions is removed from the regions directly adjacent to the aperture.  
           [0006]    The simplest approach to sampling dispersive atmospheric sources is to position the source on axis with a sampling aperture or tube. The sampling efficiency of simple plate apertures is generally less than 1 ion in 10 4 . Devices developed by Fite (U.S. Pat. No. 4,209,696) used pinhole apertures in plates with electrospray. Devices developed by Laiko and Burlingame (WO 99/63576) used aperture plates with atmospheric pressure MALDI. An atmospheric pressure source by Kazuaki et al (JP04215329) is also representative of this inefficient approach. This general approach in severely restricted by the need for precise aperture alignment and source positioning and very poor sampling efficiency.  
           [0007]    A wide variety of source configurations utilize conical skimmer apertures in order to improve collection efficiency over planar devices. This approach to focusing ions from atmospheric sources is limited by the acceptance angle of the field generated by the cone. Generally, source position relative to the cone is also critical to performance, although somewhat better than planar apertures. Conical apertures are the primary inlet geometry for commercial ICP/MS with closely coupled and axially aligned torches. Examples of conical-shaped apertures are prevalent in ES and APCI (U.S. Pat. No. 5,756,994), and ICP (U.S. Pat. No. 4,999,492) inlets. As with planar apertures, source positioning relative to the aperture is critical to performance and collection efficiency is quite low.  
           [0008]    One focusing alternative utilizes a plate lens with a large hole in front of an aperture plate or tube for transferring sample into the vacuum system. The aperture plate is generally held at a high potential difference relative to the plate lens. The configuration creates a potential well that penetrates into the source region and has a significant improvement in collection efficiency relative to the plate or cone apertures. This configuration has a clear disadvantage in that the potential well resulting from the field penetration is not independent of ion source position, or potential. High voltage needles can diminish this well. Off-axis sources can affect the shape and collection efficiency of the well. Optimal positions are highly dependent upon both flow (gas and liquid) and voltages. They are reasonable well suited for small volume sources such as nanospray. Larger flow sources become less efficient and problematic. Because this geometry is generally preferential over plates and cones, it is seen in most types of atmospheric source designs. We will call this approach the “Plate-well” design which is reported with apertures by Labowsky et al. (U.S. Pat. No. 4,531,056), Covey et al. (U.S. Pat. No. 5,412,209) and Franzen (U.S. Pat. No. 5,747,799). There are also many Plate-well designs with tubes reported by Fenn et al. (U.S. Pat. No. 4,542,293), Goodley et al. (U.S. Pat. No. 5,559,326), and Whitehouse et al. (U.S. Pat. No. 6,060,705).  
           [0009]    Several embodiments of atmospheric pressure sources have incorporated grids in order to control the sampling. Jarrell and Tomany (U.S. Pat. No. 5,436,446) utililized a grid that reflected lower mass ions into a collection cone and passed large particles through the grid. This modulated system was intended to allow grounded needles and float the grid at high alternating potentials. This device had limitations with duty cycle of ion collection in a modulating field (non-continuous sample introduction) and spacial and positioning restrictions relative to the sampling aperture. Andrien et al (U.S. Pat. No. 6,207,954 B1) used grids as counter electrodes for multiple corona discharge sources configured in geometries and at potentials to generated ions of opposite charge and monitor their interactions and reactions. This specialized reaction source was not configured with high field ratios across the grids and was not intended for high transmission and collection, rather for generation of very specific reactant ions. An alternative atmospheric pressure device by Yoshiaki (JP10088798) utilized hemispherical grids in the second stage of pressure reduction. Although the approach is similar to the present device in concept, it is severely limited by gas discharge that may occur at low pressures if higher voltages are applied to the electrodes and most of the ions are lost at the cone-aperture from atmospheric pressure into the first pumping stage.  
           [0010]    Grids are also commonly utilized for sampling ions from atmospheric ion sources utilized in ion mobility spectrometry (IMS). Generally, for IMS analysis ions are pulsed through grids down a drift tube to a detector as shown in Kunz (U.S. Pat. No. 6,239,428B1). Great effort is made to create planar plug of ions in order to maximize resolution of components in the mobility spectrum. These devices generally are not continuous, nor do they require focusing at extremely high compression ratios.  
         SUMMARY  
         [0011]    A preferred embodiment of the invention is the configuration of a High Transmission Element (HTE) comprising a conducting meshed-surface in the shape of a partial hemisphere. The HTE is configured downstream from any of a variety of atmospheric pressure sources and upstream from an Inner Field-shaping Electrode and a conducting collector surface (aperture plate or tube). Ions generated in a relatively large volumetric area of an atmospheric pressure source are attracted toward the HTE by an attracting potential relative to the source region.  
           [0012]    The field ratio, the field strength on the source side of the high transmission element relative to the collector side is maintained at a lower value (generally 2-10×less) than the field strength equidistant to the collector side of the HTE. In this operating condition, the field from the collector side of the HTE penetrates into the source side of the HTE and accelerates appreciably all of the ions through the openings in the HTE surface. Typically the field ratio value is calculated at a distance of several opening diameters away from the surface. A good value of a field ratio is greater than 10.  
           [0013]    The HTE is typically manufactured so to allow ions to pass easily through the HTE surface. This entails having a HTE with a low depth aspect ratio, referring to the ratio of the dimension of the openings to the thickness of the HTE surface; where the thickness of the element is as thin as mechanically possible. In addition, the openness of the HTE is also important. Typically the openness, the ratio of the dimension of the opening to the entire surface area should be as large as possible to allow the field from the collector side to penetrate through the HTE into the source side several opening diameters away from the surface of HTE.  
           [0014]    The HTE and the inner field-shaping electrode are held at approximately the same potential relative to the collector surface which is held at extremely high potential difference to attract virtually all ions that cross the HTE, through a relatively large aperture in the inner field-shaping electrode, onto the collector surface (or through an aperture into the vacuum). The combination of HTE shape, Inner Field-shaping Electrode aperture size, and potential difference (between the HTE and the collector) affect substantial compression of the dispersed ions into a small cross-sectional beam at the collector. When this beam is precisely aligned with a vacuum sampling aperture into a mass spectrometer, very high sensitivities are achieved.  
           [0015]    The physical separation of ionization source region from the deep potential-well focusing region by the HTE solves many of the efficiency problems associated with conventional approaches to ion collection at atmospheric pressure. With the present invention, dispersed ions are not required to be focused to a small diameter in the ion source region, rather, they are required to drift toward a relatively large surface of the HTE. In this way all ions from a given source can be collected across an appropriately sized and shaped HTE surface, then focused in the high field of the focusing well.  
           [0016]    One advantage of the present device is the independence of collection efficiency from source position. Multiple sources are able to be uniformly collected with this invention. Multiple focal points can also be configured if there is need to collect part of the sample and analyze another part.  
           [0017]    A primary object of the invention is to collect all the ions, all the time.  
         OBJECTS AND ADVANTAGES  
         [0018]    One object of the present invention is to increase the collection efficiency of an ions and/or charged particles at a collector, or through an aperture or tube into a vacuum system, by creating a very small cross-sectional area beam of ions and/or charged particles from highly dispersed atmospheric pressure ion sources. Another object of the present invention is to increase the transmission efficiency of ions from atmospheric pressure ion sources to a target collector, or through an aperture or tube. The present invention has a significant advantage over prior art in that the use of a High Transmission Element to separate ion generation from ion focusing allows precise shaping of fields in both regions. Ions can be generated in large ion source regions without losses to walls. Droplets have longer time to evaporate and/or desorb ions without loss from the sampling stream. Source temperatures can be lower because rapid evaporation is not required. This can prevent thermal decomposition of some labile compounds. Counter electrodes for electrospray needles do not have to be the plate lens as practices with most convention sources or even the HTE. The aerosol can be generated remotely and ions can be allowed to drift toward the HTE.  
           [0019]    Another object of the present invention is to have collection efficiency be independent of ion source position relative to the collection well. With the present invention there is no need for precise mechanical needle alignment or positioning relative to collectors, apertures, or tubes invention. Ions generated any at position in the ion source region are transmitted to the collector, aperture, or tube with similar efficiency. No existing technology has positional independence of the source. The precise and constant geometry, and alignment of the focusing well with sampling apertures will not change with needle placement. The fields inside (focusing side) the well will not change, even if they change outside (source side).  
           [0020]    Another object of the present invention is the independence of ion source type. This device is capable of transmission and collection of ions from any atmospheric (or near atmospheric) source; including, electrospray, atmospheric pressure chemical ionization, atmospheric pressure MALDI (laser desorption), inductively coupled plasma, discharge sources, nickel 63 sources, spray ionization sources, induction ionization sources and photoionization sources. The device is also capable of sampling ions of only one polarity at a time, but with extremely high efficiency.  
           [0021]    Another object of the present invention is to efficiently collect and/or divert a flow of ions from more than one source. This can be performed in a simultaneous fashion for introduction of mass calibrants from a separate source and analytes from a different source; conversely, it can be performed sequentially as is typical with multiplexing of multiple chromatographic streams introduced into one mass spectrometer.  
           [0022]    Another object of the present invention is to efficiently transmit ions to more than one target position. This would have the utility of allowing part of the sample to be collected on a surface while another part of the sample is being introduced through an aperture into a mass spectrometer to be analyzed.  
           [0023]    Another object of the present invention is to improve the efficiency of multiplexed inlets from both multiple macroscopic sources and micro-chip arrays, particularly those developed with multiple needle arrays for electrospray. Position independence of this invention make it compatible with a wide variety of needle array technologies and multi-well plates for surface desorption techniques.  
           [0024]    Another object of the present invention is to remove larger droplets and particles from aerosol sources with a counter-flow of gas to prevent contamination of apertures, tubes, and vacuum components. 
       
    
    
     DRAWING FIGURES  
       [0025]    In the drawings, closely related figures have the same number but different alphabetic suffixes.  
         [0026]    FIGS.  1  are cross-sectional illustrations of hemispherical-shaped high transmission element configurations with three alternative target collector elements; namely, (A) the target collector elements configured with an aperture into a vacuum system, (B) the target collector element configured with a tube inlet to a vacuum system, and (C) the target collector element configured with an aperture directed toward a non-vacuum ion sample collector plate.  
         [0027]    FIGS.  2  are cross-sectional illustrations of hemispherical-shaped high transmission element configurations with multiple sources of ions, (A) showing two continuous sources of ions, (B) showing time-varying or pulsed sources of ions from MALDI, and (C) showing time-varying sources of ions from electrospray.  
         [0028]    FIGS.  3  are cross-sectional illustrations of hemispherical-shaped high transmission element configurations as a rotating valve assembly for discretely sampling multiple ion sources; (A) showing valve position  1 , and (B) valve position  2 .  
         [0029]    [0029]FIG. 4 is a cross-sectional illustration of a two-target array of hemispherical shaped high transmission elements sampling one source of ions.  
         [0030]    FIGS.  5  are cross-sectional illustrations of hemispherical shaped high transmission elements with a counter flow of gas; (A) showing counter-flow of gas at the target region, and (B) showing counter-flow of gas at across the entire area of the high transmission element.  
         [0031]    FIGS.  6  show perspective views of six hemispherical shaped high transmission elements; showing (A) circular apertures, (B) woven mesh, (C) criss-cross mesh (D) hexagonal apertures, (E) transverse slots, and (F) radial slots.  
         [0032]    FIGS.  7  show cross-sectional illustrations various geometries of high transmission element that create effective focusing; (A) planar, (B) conical, and (C) hemispherical.  
       REFERENCE NUMBERS IN DRAWINGS  
       [0033]    [0033]                                               20   laser beam   40   high transmission       21a   first liquid inlet       element       21b   second liquid inlet   41   holes or apertures       22a   first MALDI sample   42   ring insulator       22b   second MALDI sample   42a   ring insulator       23a   first electrospray   42b   ring insulator           liquid cone-jet   44   inner field       23b   second electrospray       shaping electrode           liquid cone-jet   44a   inner field       24   MALDI sample plate       shaping electrode       25   electrospray needle array   44b   inner field       30   ion source region       shaping electrode       30a   first ion source region   46   ring insulator       30b   second ion source region   46a   first ring insulator       32   ion collection region   46b   second ring insulator       32a   first ion collection region   48a   first insulator       32b   second ion collection region   48b   second insulator       34   ion trajectory lines   50   ion focusing-       36   outer field shaping       steering region           electrode   50a   first ion focusing-       52   gas supply line       steering region       56   equipotential lines   50b   second ion focusing-       70   insulated tube or capillary       steering region       72   rotating switch   86c   inner field-shaping       74   isolation plate       electrode aperture       76   axial valve aperture   86d   inner field-shaping       78   off-axis valve aperture       electrode aperture       80   target collector element   86e   inner field-shaping       81   electrode       electrode aperture       80a   first target collector element   86f   inner field-shaping       80b   second target collector element       electrode aperture       82   collector surface   90   collector region       82a   first off-axis collector element   90a   first collector region       82b   second off-axis collector   90b   second collector region           element   92a   first off-axis       84   target collection aperture       collector region       84a   tubular target collection   92b   second off-axis           aperture       collector region       86   inner field-shaping   94   collector plate           electrode aperture       86a   inner field-shaping           electrode aperture       86b   inner field-shaping           electrode aperture                    
     
    
     DESCRIPTION  
       [0034]    Preferred Embodiment  
         [0035]    [0035]FIGS. 1A and 6A (Basic Focusing Device)  
         [0036]    One embodiment of the present invention is an ion or particle focusing device utilizing a high transmission element  40  as illustrated in FIG. 1A. The device includes an atmospheric pressure or near atmospheric pressure ion source region  30  from which ions are supplied to an ion collection region  32 . This device is intended for use in collection and focusing of ions from a wide variety of ion sources; including, but not limited to electrospray, atmospheric pressure chemical ionization, photo-ionization, electron ionization, laser desorption (including matrix assisted), inductively coupled plasma, and discharge ionization. Both gas-phase ions and charged particles emanating from region  30  are collected and focused with this device. Ions and charged particles from region  32  move through a high transmission element  40  into an ion focusing-steering region  50 . Strong electric fields in region  50  relative to region  32  cause ions in region  32  to traverse element  40  and be focused to a target collector element  80 . Movement of ions from region  30  to region  90  is indicated by a set of ion trajectory lines  34 . The focused ions at element  80  are transferred to an ion collection region  90  through a target collection aperture  84 . Aperture  84  has a diameter appropriate to restrict the flow of gas from region  50  to region  90 . In the case of vacuum detection, such as mass spectrometry in region  90 , typical aperture diameters are 100 to 500 um. Element  80  is made of a conducting material or a conductively coated insulating material such as glass. The collection region  90  in this embodiment is intended to be the vacuum system of a mass spectrometer (interface stages, optics, analyzer, and detector) or other low-pressure ion and particle detectors. In this embodiment the element  40  has a hemisphere-shaped surface of uniform cross-section (FIG. 6A). It is made of a conductive material, such as stamped sheet metal. Circular-shaped apertures or holes  41  are evenly spaced across element  40 . Element  40  is fabricated from a conducting and chemically inert material such as stainless steel. It is also possible to use molded materials that are conducting as well as non-conducting molded materials with subsequent deposition of conducting material on the surface of element  40 . An inner field-shaping electrode  44  is a conducting circular plate position between element  40  and  80 . Element  40  is electrically separated from electrode  44  by insulating ring  46 . Element  80  is electrically separated from electrode  44  by insulating ring  42 . An outer field-shaping electrode  36  comprises a conducting cylinder coaxial to and outside of element  40 . Electrode  36  is electrically separated from element  40  by insulating ring  46 . All elements and electrodes are generally made of chemically inert and conductive materials that may be stamped or machined to conform to the appropriate geometries, such as stainless steel, brass, copper, and aluminum.  
         [0037]    Additional Embodiments  
         [0038]    [0038]FIGS. 1B, 1C,  2 A,  2 B,  2 C—(Alternative Target Collectors, Multiple Sources)  
         [0039]    Additional embodiments are shown in FIGS. 1B, 1C, and  2 A through  2 C, in each case the high transmission element  40  is shown with a hemispherical surface.  
         [0040]    In FIG. 1B the ion and particle focusing device shows a similar arrangement as in FIG. 1A, however the plate-shaped collector electrode  80  is replaced by tube-shaped target collector element  80  which is located on the outside of an electrically insulated tube  70 . Flow of ions and particles through tube  70  and tubular target collector aperture  84   a  are similarly transferred to collector region  90 . Region  90  is generally the vacuum region of a mass spectrometer or other vacuum detectors. Movement of ions from region  30  to region  90  is indicated by a set of ion trajectory lines  34 .  
         [0041]    In FIG. 1C the ion and particle focusing device also shows a similar arrangement as in FIG. 1A, however, this configuration represents the collection of focused ions onto a target surface of a sample plate or probe. In this embodiment, region  90  is replaced with a collector plate  94 . The focused ions at element  80  are transferred to plate  90  through a target collection aperture  84 . Aperture  84  has a diameter appropriate to restrict the flow of gas from region  50  to plate  94 , particularly in the case of reduced pressure ion collection. Plate  94  has the purpose of collecting ions, such as, but not limited to a 96-well plate, the collector surface  82  of which is electrically conductive. Note that the entire plate  94  could be made of conductive material negating the need for surface  82 . Movement of ions from region  30  to plate  94  is indicated by a set of ion trajectory lines  34 .  
         [0042]    In FIG. 2A, a single element  40  is downstream of two discrete separate ion collection regions  32   a  and  32   b  which are downstream of ion source regions  30   a  and  30   b,  respectively. Movements of ions from regions  30   a  and  30   b  to region  90  are indicated by a set of ion trajectory lines  34 . This device allows the efficient sampling of two discrete ion source regions from two unique locations. Sampling of multiple ion sources is not limited to two regions; but three, four, five, or more may be sample through a single focal point (element  80 ).  
         [0043]    In FIG. 2B, a single element  40  is downstream of an atmospheric pressure matrix assisted laser desorption ionization (MALDI) sample plate  24 , shown at two discrete ion sampling times. At (Time  1 ) a first sample  22   a  is illuminated by laser  20  producing desorbed ions in ion source region  30   a.  At (Time  2 ) a second sample  22   b  is illuminated by laser  20  producing desorbed ions in ion source region  30   b.  Ions from both regions  30   a  and  30   b  are collected across a single element  40  and passed through aperture  84  to collection or mass analysis in region  90 .  
         [0044]    In FIG. 2C, a single element  40  is downstream of an electrospray needle array  25  at two different time points. At (Time  1 ) an electrospray source  21   a  forms a liquid cone-jet  23   a  and produces an aerosol of highly charged liquid droplets and ions in ion source region  30   a.  At (Time  2 ) a second electrospray source  21   b  forms a liquid cone-jet  23   b  producing an aerosol of highly charged liquid droplets and of ions in ion source region  30   b.  Ions from both regions  30   a  and  30   b  are collected across a single element  40  and passed through aperture  84  to collection or mass analysis in region  90 .  
         [0045]    Alternative Embodiments  
         [0046]    [0046]FIGS. 3, 4,  5 A,  5 B,  6 B,  6 C,  6 D,  7 A,  7 B,  7 C (Ion Switching Valve, Multiple Targets, Counter-Flow Gas)  
         [0047]    There are a variety of alternative embodiments of the present invention in terms of accommodating multiple ionization sources and multiple collectors (type and number). In addition, the device is capable of accommodating various geometries of element  40  (FIGS. 7), and accommodating a wide variety of possible aperture types for element  40  (FIGS. 6).  
         [0048]    FIGS.  3  show a high efficiency atmospheric pressure focusing device operating in an ion valve-switching configuration. Here two discrete and continuous ion sources  30   a  and  30   b  are shown. Ions from each source are continually being sampled across element  40  into focusing regions  50   a  and  50   b  respectively. The hemisphere-shaped element  40  is partitioned in half by isolation plate  74  separating regions  50   a  and  50   b  and allowing ions from each source to be collected and focused uniquely. A rotating switch  72  is rotated about the axis of tube  70  to present an axial valve aperture  76  to region  50   a  and an off-axis valve aperture  78  to region  50   b  in valve (Position  1 ) show in FIG. 3A. Switch  72  is rotated 180° about the axis of tube  70  to present aperture  76  to region  50   b  and aperture  78  to region  50   a  in valve (Position  2 ) show in FIG. 3B. In valve (Position  1 ), ions from region  32   a  are focused toward element  80  through aperture  76  and sampled into region  90  for collection or mass detection. In this position, the ions from region  32   b  are focused toward a second off-axis collector element  82   b  through aperture  78  and collected or discarded into a second off-axis collector region  92   b.  In valve (Position  2 ), ions from region  32   b  are focused toward element  80  through aperture  76  and sampled into region  90  for collection or mass detection. In this position, the ions from region  32   a  are now focused toward a first off-axis collector element  82   a  through aperture  78  and collected or discarded into a first off-axis collector region  92   a.  In this embodiment, the field shaping electrodes  44   a  and  44   b  comprise the surface of the rotating switch  72 . Electrode  36  is isolated from element  40  by insulator  46 . Element  80  is isolated from switch  72  by insulator  42 . Elements  82   a  and  82   b  are insulated from switch  72  by insulators  48   a  and  48   b,  respectively. It is the intent of FIG. 3 to illustrate a two-position ion valve switching configuration; however, four, six, eight, and larger position valves using additional off-axis valve apertures and partitioning plates will accommodate additional ionization sources for multiplexing applications. Rotation and aperture positioning would be 90°, 60°, and 45°, respectively.  
         [0049]    In FIG. 4, a single source  30  supplies ions to two discrete focusing regions. Part of the ions from region  30  traverse element  40   a  and are focused in region  50   a  toward element  80   a  to collection region  90   a.  Conversely, another portion of the ions from region  32  traverse element  40   b  and are focused in region  50   b  toward element  80   b  to collection region  90   b.  The object of this embodiment is the transfer of ions to more than one target. More than one target could entail multiple detectors, one in region  90   a  and one in region  90   b.  Alternatively, there may be applications where ions (e.g. proteins, reagents) from one source may be required to be collected in two or more focal points such as the wells of multiple sample trays (e.g. 96-well plates). This device can supply efficient and real-time sample splitting for micro-collection.  
         [0050]    In FIG. 5A the ion and particle focusing device shows a hemisphere-shaped element  40  in the same manor as FIG. 1A with the addition of a flow of gas counter to the direction of motion of ions and charged particles (trajectory lines  34 ). The gas is introduced from an external gas supply through tube  52  into the space between electrode  44  and element  80 . The counter-flow of gas travels through an inner field-shaping electrode aperture  86 , across region  50 , traversing element  40  into region  32 . The relative diameter of aperture  86  is significantly larger than aperture  84 . The counter-flow gas is generally composed of, but not limited to nitrogen.  
         [0051]    In FIG. 5B the ion and particle focusing device shows a hemisphere-shaped element  40  in the same manor as FIG. 1A with the addition of a flow of gas counter to the direction of motion of ions and charged particles. The gas is introduced from an external gas supply through tube  52  into the space between electrode  44  and element  81 . The counter-flow of gas travels through an array of apertures  86   a,  across region  50 , traversing element  40  into region  32 . This counter-flow configuration has as an object the removal of a much broader area of interfering gases and particles. The relative diameters of apertures  86   a  are significantly larger than aperture  84   a.  The counter-flow gas is also generally composed of, but not limited to nitrogen.  
         [0052]    [0052]FIG. 6B shows a hemisphere-shaped element  40  made of single strands of metal wire woven to produce a pattern of square openings, commonly referred to as a plain square weave;  
         [0053]    [0053]FIG. 6C shows a hemisphere-shaped element  40  made of two sets of single strands of metal wire with equal diameters, one set overlaying the other, producing a pattern of square openings;  
         [0054]    [0054]FIG. 6D shows a hemisphere-shaped element  40  made of a surface with apertures  41  fabricated in a manner to produce a pattern of hexagon-shaped openings;  
         [0055]    [0055]FIG. 6E shows a hemisphere-shaped element  40  made of a surface with transverse slotted apertures  41  across the surface.  
         [0056]    [0056]FIG. 6F shows a hemisphere-shaped element  40  made of a surface with radial slotted apertures  41  across the surface.  
         [0057]    Alternatively, the element  40  may be manufactured by using the techniques of microelectronics fabrication: photolithography for creating patterns, etching for removing material, and deposition for coating the surfaces with specific materials;  
         [0058]    [0058]FIG. 7A shows element  40  as a cross-section of a planar-shaped surface of radial slotted apertures  41  as in FIG. 6F. Element  40  is attached to the electrode  44  isolated from the planar-shaped collector element  80  by insulator  42 ;  
         [0059]    [0059]FIG. 7B shows element  40  as a cross-section of a cone-shaped surface of radial slotted apertures  41  as in FIG. 6F. Element  40  is attached to the electrode  44  isolated from the planar-shaped collector element  80  by insulator  42 ; and  
         [0060]    [0060]FIG. 7C shows element  40  as a cross-section of a hemisphere-shaped surface of radial slotted apertures  41  as in FIG. 6F. Element  40  is attached to the electrode  44  isolated from the planar-shaped collector element  80  by insulator  42 .  
       OPERATION  
       [0061]    Operation of the Basic Device (As shown in FIGS. 1, 5,  6 , and  7 )  
         [0062]    Ions supplied or generated from an atmospheric pressure source are attracted to the high transmission element  40  by an electrical potential difference between the ion source region  30  and the potential on element  40 . The ions will tend to follow the field lines through region  32 . We distinguish regions  30  and  32  in that the ion source region  30  may comprise a plasma with ill-defined or uncontrollable fields. Region  32  contains gas such as air or nitrogen below the threshold for discharge ionization and fields defined by the shape and potential on element  40 . The ions moving toward element  40  are diverted away from the conducting surfaces of element  40  through apertures  41  by the presence of the electrical field penetrating through element  40  into the part of region  32  that is close to the outer surface of element  40 . This field penetration is due to the requisite field strength on the focusing side of element  40  being larger than the field strength in region  32 . The field in region  50  must be higher than that in region  32 . Under conditions of a high field ratio (field in region  50 /field in region  32 ) a significant percentage up to 100% of ions from region  32  are transferred into region  50 . This effectively makes element  40  transparent to ions moving from region  32  to region  50 .  
         [0063]    The shape of element  40  and the potential difference between elements  40  and  80  will cause the ions that traversed element  40  to be focused at or near a small cross-sectional area at the center of element  80 . In the operation of this device as an atmospheric inlet to the mass spectrometer, the target collection element  80  will have an aperture  84  through which focused ions will travel on their path into the vacuum system. Both focusing fields and viscous forces will cause ions in the region of aperture  84  to travel into the vacuum system of the mass spectrometer. It is intended that this focusing device be coupled to the vacuum inlet of any conventional mass spectrometer or the atmospheric pressure inlet to any ion mobility spectrometer. Alternatively, this device may be operated as a collection and focusing device to move gas-phase ions and charged particulate materials from diffuse atmospheric sources onto small focal areas of collector surfaces. We envision applications for laying down materials in printing, semiconductor, and micro-chemistry applications. In addition, this device can operate to collect sample onto surfaces for subsequent surface analysis (e.g. depositing sample onto MALDI targets, SIMS targets, or X-ray targets). In addition, collection onto surfaces of reaction wells may allow for gas-phase ion production to be a useful tool for placing charge chemical species into a discrete and small reaction well. This technique could be useful for automated collection and specification of complex reagents and reactant for applications in combinatorial chemistry.  
         [0064]    An important alternative-operating mode of this device is illustrated in FIGS. 5. The flow of gas in a direction that is counter to the movement of ions will serve to reduce or eliminate contamination from particulate materials and neutral gases. The operation with counter-flow of gas is accomplished by adding sufficient flow to purge or remove unwanted materials. This to some extent will have some dependency on the volatility of neutral gases and the size of interfering particulate material originating from the source region  30 . Lower mobility charged particles may also be swept away in the counter-flow of gas.  
         [0065]    Operation of the of Multiple Source Devices (As shown in FIGS. 2 and 3)  
         [0066]    The operation of the present invention will accommodate collection of ions from more than one source. The multi-source device operated under the same principles as a single-source device with the addition of more than one source of ions. Multiple sources of ions can be sampled from multiple sources derived from different locations (FIG. 2A), derived at different times (FIGS. 2B &amp; 2C), and controlled through ion valve switching (FIGS. 3A &amp; 3B). Ions move from their respective source toward element  40  due to the electrical potential difference between the source and element  40  creating attractive forces. High fields from region  50  penetrates the apertures of element  40  to direct the motion of the ions from regions of  32   a  and  32   b  into the respective regions of  50   a  and  50   b.  Selection of a specific source of ions to be focused can be accomplished in the time dependent manner by controlling the generation process of ions (e.g. pulse of laser, application of voltage to needle).  
         [0067]    There may be operating modes where simultaneous collection of ions from two sources is desirable. An example would be the addition of a mass calibration standard in one source while introducing analytical sample in the other ion source. This simultaneous source application would of course have it primary application in high-resolution mass spectrometry.  
         [0068]    There are also noteworthy alternative operating modes of multiple sources in terms of spatial orientation of the ionization source. One configuration may fix the location of the sample and collect ions from differing spatial origins such as illustrated in FIGS. 2. Alternatively, the samples could be moved so that the location of ion generation is fixed and the sample is moved (e.g. move the sample plate instead of the laser beam).  
         [0069]    An important alternative-operating mode of the multi-source embodiment of this device is found in the ion switch configuration illustrated in FIGS. 3. The switch is operated by rotating switch  72  about the axis tube  70 . As switch  72  rotates, the alignment of off-axis valve aperture  78  with either element  82   a  or  82   b  will determine which direction the ions will travel in the two-source configuration. The valve is operated by switching switch  72  back and forth 180° from (Position  1 ) to (Position  2 ) thereby selecting either ion source for collection into the mass spectrometer or other collection device. The device does not require off-axis collection in either of regions  92   a  or  92   b  to be to discard or waste. There may be applications of this device where off-axis collection of diverted materials is important for isolation, purification, or other processing and analysis. The rate of rotation of switch  72  will determine the frequency of discrete sampling. High-speed sampling at many rpm will allow ion sampling at frequencies compatible with conventional chromatographic peak widths for applications in LC/MS or GC/MS. This operation of the present device within LC/MS or GC/MS would of course require that the ion source region be coupled to a chromatographic system. We envision that this is done in the wide variety of conventional configurations, which are not explicitly part of this invention.  
         [0070]    Operation of a larger number of sources and valve ports are not illustrated in these figures but would operate in the same fashion as the two-source valve with rotating off-axis apertures spaced around a central sampling aperture.  
         [0071]    Operation of the of Multiple Collector or Target Devices (As shown in FIG. 4)  
         [0072]    This invention may also operate in a mode whereby the ions from a single ion source region  30  are collected and focused across multiple high transmission elements with multiple discrete collection regions. This mode is useful for delivering ions from a single source to multiple focal points. FIG. 4 shows the multi-target embodiment with only two targets,  90   a  and  90   b.  The intent of this disclosure is to describe the application of a single source ion focusing device with two or more high transmission elements and companion targets up to a large array of high transmission elements and target foci which may have application in a wide variety of applications including loading reagents onto reaction wells, printing, micro-fabrication, and semi-conductor manufacture.