Patent Publication Number: US-9905409-B2

Title: Devices and methods for performing mass analysis

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is the National Stage of International Application No. PCT/US2008/084608, filed Nov. 25, 2008, which claims priority to and benefit of U.S. Provisional Patent Application Ser. No. 60/991,232, filed Nov. 30, 2007. The entire contents of these applications are incorporated herein by reference. 
     RELATED APPLICATIONS 
     This application claims priority benefit of a U.S. Provisional Patent Application No. 60/991,232, filed Nov. 30, 2007. The contents of this application is expressly incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to devices and methods of performing mass analysis. And, in particular, devices for mass spectrometers that introduce ions from areas of relatively high pressure to areas of low pressure. 
     BACKGROUND OF THE INVENTION 
     As used herein, the terms “mass analyser” or “mass detector” or “mass spectrometer” refer to an apparatus, device or instrument that produces a signal or result based on a mass to charge ratio of analyte ions. Mass analysers may take several common forms, such as, by way of example, without limitation, quadrupole mass filters, ion trap mass analyzers, magnetic sector mass analyzers, time-of-flight mass analyzers, ion-cyclotron resonance (FTMS) analyzers, and Kingdon trap analysers. 
     Mass spectrometers used for the analysis of biomolecules usually employ atmospheric pressure ionization (API) sources. API sources suitable for the analysis of solutions include electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI), and pneumatically and/or thermally assisted electrospray sources. API is also used with techniques such as matrix assisted laser desorption (MALDI), desorption electrospray ionization (DESI), desorption ionization on silicon (DIOS), and “DART” (direct analysis in real time). 
     The mass analysis of ions is usually carried out at sub-atmospheric pressures, so that all API techniques require an interface for transmitting ions from the source into a region of relatively high vacuum, usually via one or more evacuated chambers. Ion transmission devices, typically comprising sets of elongated rods or apertured disks to which alternating potentials are applied, are typically provided in chambers where the pressure is sufficiently low for them to be effective. However, most interfaces between API sources and a mass analyzer also comprise a vacuum chamber without an ion transmission device through which the ions have to pass. The following discussion relates particularly to electrospray API sources, but it will be understood that the interfaces described are equally applicable to the other types of API sources listed above, or indeed to any ionization source which generates a plume or spray of ions in a region of relatively high, or atmospheric pressure. 
     Electrospray ion sources generate an aerosol comprising electrically charged droplets from a solution (often the eluent from a liquid chromatograph) by means of an electrical field applied between a counter electrode and a capillary tube through which the solution flows. The charged droplets may comprise ions characteristic of a sample dissolved in the solution. These charged droplets are at least partially desolvated through contact with gas molecules present in the source, which is usually maintained at atmospheric pressure. Desolvation may be assisted by suitably directing one or more flows of gas in relation to the electrosprayed aerosol, and/or by heating the gas and/or the capillary tube. Replacing the capillary tube with a pneumatic nebulizer (usually a concentric flow nebulizer) may further improve desolvation and additionally may increase the maximum solution flow rate which the source can accept. When a nebulizer is used, the electrospray ionization process may be replaced (or assisted) by a corona discharge (APCI) or a beam of photons (APPI), so that an electrical field between the nebulizer and the capillary may not be necessary. 
     Whatever processes of ionization and desolvation are used, the ions generated in the atmospheric pressure portion of the source must pass through an interface between the source and the vacuum system of the spectrometer. It is desirable that the interface transmit as many as possible of the ions generated in the aerosol, complete their desolvation without causing losses (for example, by thermal decomposition), and simultaneously separate and remove most of the inert gas and solvent so that the pressure in the mass analyzer is maintained low enough for its proper operation. These requirements are not easily met and many different source and interface designs have been proposed. 
     The geometrical arrangement of the API source, with respect to the relative orientations of the aerosol and the entrance aperture of the interface, may influence the sensitivity of a mass detector. The structure of the aperture and type of interface have also been found to influence performance. 
     The interface is subjected to a stream of sample and, due to the small orifices and passageways, can accumulate deposits. It is desirable to have an interface that can be readily removed, cleaned or replaced with an alternative interface. 
     As used herein, the term “high pressure” refers to relative pressure compared to parts of a mass analyser that operate at low pressures approaching vacuum conditions. The term includes, but is not limited to, “atmospheric pressure”. As used herein, “atmospheric pressure” includes the operation of a device in the presence of significant quantities of gas, perhaps with pressures several hundred torr either side of atmospheric pressure itself. The term is generally used in the art to distinguish a type of device and ionization source at or about atmospheric pressures from those that operate under high or medium vacuum, for example, an electron impact or chemical ionization source. 
     The terms “charged particles” and “ions” are meant to include singly- and multiply-charged ions, solvated and or desolvated ions, adduct ions, and cluster ions, and the like. Ions and/or charged particles are typically formed from a sample in an ionization source operating at atmospheric pressure (as defined above) and potentially carry one or more analytes of interest, other carrier or sample molecules, solvents and gases, charged droplets of solvent and the like. 
     SUMMARY OF THE INVENTION 
     Embodiments of the present invention feature devices and methods for performing mass analysis. One embodiment of the present invention is directed to a device for receiving one or more ions travelling in a plume in an area of high pressure and passing the ions into a area of low pressure. The area of high pressure is separated from the area of low pressure by a first wall. The plume has a first axis, and the ions travelling in the low pressure area have a second axis. The device comprises an inlet housing for mounting on the first wall between the area of low pressure and the area of high pressure. The inlet housing has a junction point, first passage and at least one of the inlet housing and the wall has a second passage. The first passage has a first passage axis, an entrance and a terminal end. The entrance is in fluid communication with the area of high pressure and the terminal end is in communication with the junction point. The junction point is in fluid communication with the second passage. The second passage has a second passage axis and an exit. The first passage is for receiving ions from the area of high pressure and the exit is for discharging ions into the area of low pressure. The first passage axis intersects the first axis or a line extending parallel to the first axis at a point and defines a first angle. The first passage axis and said second passage axis intersect at a point and define a second angle. The second passage axis defines the second axis or extending along a line parallel to the second axis. Thus, the inlet housing receives ions at high pressure and passes such ions at low pressure. 
     One embodiment of the present invention features a device wherein the inlet housing is capable of assuming a first position on the wall and a second position on the wall. In the first position the first passage axis has a first angle of equal to or less than about 75 degrees and in the second position the first passage axis has a first angle of equal to or greater than 105 degrees. Thus, embodiments of the present invention allow the inlet housing to adjust for the plume, or different plumes from alternative sources. 
     One embodiment of the present invention features a device wherein the inlet housing is mounted to said wall by releasable mounting means. The inlet housing is capable of being removed and reattached to said wall in at least one of a first position and second position. Thus, the inlet housing can be readily serviced, replaced, or adjusted. The releasable mounting means comprises clips, vacuum retention, cams, quick release cams, interlocking flanges, and screws. 
     One embodiment of the present invention features a device wherein the inlet housing is capable of rotation between said first position and said second position. One embodiment features power means for rotating said inlet housing. Such power means comprise motors, such as stepper motors and the like with suitable gearing to effect movement of the inlet housing. One embodiment further comprises control means in signal communication with the power means. The control means is responsive to operator instructions or operating conditions to set the inlet housing in the first position or the second position. As used herein, the term control means refers to computer processing units (CPUs) and equipment containing CPUs, such as computers, servers, personal computers, and such analytical equipment such as the mass analyser itself. 
     Preferably, the device has indicia that cooperate with indicia on the wall to allow the inlet housing to be set in a first position or a second position. For example, without limitation, one embodiment features a device having a mark that cooperates with a scale on the wall or vice versa. 
     One embodiment of the device features a second passage having at least one restriction section defining an area, of at least one of the first passage and second passage, at a higher pressure than the low pressure area. Preferably, the restriction section has a restriction diameter, the first passage has a first passage diameter and the second passage has a second passage diameter. 
     The restriction diameter has a smaller diameter than at least one of the first passage diameter and the second passage diameter. 
     One embodiment of the device features a housing shroud. The housing shroud surrounds the inlet housing in a spaced relationship to define a gap. The housing shroud has an opening around the first passage entrance for applying a gas. The housing shroud, preferably, cooperates with the shape and dimensions of the inlet housing. A generally conical shape for both the inlet housing and housing shroud is preferred. 
     The first passage axis can be set to intersect a line extending with the plume or parallel to the plume. The first passage axis and said second passage axis have an angle of between 10 and 90 degrees. This angle is not readily adjustable, however, the device is simple and inexpensive to make, such that mass spectrometers can readily receive alternative inlet housings with different angles between the first passage axis and second axis passage, different restriction diameters, different first passage diameters, different second passage diameters, and different entrances. 
     One embodiment of the present invention comprises the device as part of a mass analyser comprising a high pressure area vessel and a low pressure vessel. The high pressure vessel surrounds the inlet housing to contain the plume. Preferably, the wall separating the high and the low pressure vessels have releasable mounting means and alignment indicia. 
     Preferably, the high pressure area further comprises at least one plume forming means, such as an electrospray or nebuliser, or a plurality of plume forming means. Preferably, the inlet housing has one or more positions for each of the plume forming means. 
     A further embodiment of the present invention features a method of operating a detector for determining mass to charge ratios of ions. The method comprises the steps of providing at least one high pressure vessel for creating ions and at least one low pressure vessel for creating a signal corresponding to the mass and charge of the ion. The high pressure vessel and low pressure vessel have at least one first wall and an opening allowing fluid and ionic communication between the low pressure vessel and the high pressure vessel. The high pressure vessel has at least one plume forming means. The high pressure vessel is in fluid and ionic communication with the low pressure vessel by the opening. The ions travel along the plume on a first axis and travel in the low pressure vessel on a second axis. The high pressure vessel has an inlet housing mounted on the first wall between the area of low pressure and the area of high pressure. The inlet housing has a junction point, first passage and at least one of the inlet housing and the first wall has a second passage. The first passage has a first passage axis, an entrance and a terminal end. The entrance is in fluid communication with the area of high pressure and the terminal end is in communication with the junction point. The junction point is in fluid communication with the second passage, and the second passage has a second passage axis, and a exit. The first passage is for receiving ions and the exit is for discharging ions into said area of low pressure. The first passage axis intersects the first axis or a line extending parallel to the first axis at a point and defining a first angle. The first passage axis and said second passage axis intersect at a point and define a second angle. The second passage axis defining the second axis or extending along a line parallel to the second axis. The method further comprising the step of receiving ions in the entrance of the first passage at high pressure and passing ions at low pressure into said low pressure vessel for the exit. 
     The method preferably provides an inlet housing capable of assuming at a first position on said wall and a second position on said wall. And, the method comprises the step of selecting at least one of said first position and second position for said inlet housing. Preferably, in the first position the first passage axis has a first angle of equal to or less than about 75 degrees and in the second position the passage axis has a first angle of equal to or greater than 105 degrees. 
     The method preferably provides an inlet housing mounted to the first wall by releasable mounting means. And, the method comprises affixing an inlet housing to the wall by the releasable mounting means. The method provides for adjusting the inlet housing to different positions, servicing, maintaining, and replacing the inlet housing. Preferred releasable mounting means comprises clips, vacuum retention, cams, quick release cams, interlocking flanges, and screws. Preferably, the inlet housing and the wall have alignment indicia to facilitate placement of the inlet housing in the desired position. 
     One method of the present invention provides an inlet housing capable of rotation between the first position and the second position. The method comprises the step of rotating said inlet housing to select a position. 
     One method of the present invention provides power means for rotating said inlet housing. Preferably, the method further provides control means in signal communication with said power means. The control means is responsive to operator instructions or operating conditions or programming to set the inlet housing in the first position or the second position. 
     One method of the present invention provides a housing shroud. The housing shroud surrounds the inlet housing in a spaced relationship to define a gap. The housing shroud has a shroud opening around the first passage entrance for applying a gas and the method comprises the step of introducing a gas though the shroud opening. 
     A preferred device has a shroud housing and inlet housing having cooperating size and shape. A preferred shape is conical and sized to allow the operator to remove and adjust the device within the high pressure vessel. 
     These and other features and advantages will be apparent to those skilled in the art upon reading the detailed description that follows and viewing the Figures briefly described below. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  is a schematic drawing of apparatus for generating charged particles by electrospray ionization incorporating a device according to the invention; 
         FIG. 2  is a schematic drawing of apparatus for generating charged particles by atmospheric pressure chemical ionization incorporating a device according to the invention; 
         FIG. 3  is a schematic drawing of apparatus for generating charged particles by atmospheric pressure photoionization incorporating a device according to the invention; 
         FIG. 4  is a schematic drawing of apparatus for generating charged particles by surface ionization incorporating a device according to the invention; 
         FIG. 5  is a drawing of part of a device according to the invention; 
         FIG. 6  is a drawing showing more details of a component of the device shown in  FIG. 5 ; 
         FIG. 7  is a drawing showing more details of another component of the device shown in  FIG. 5 ; 
         FIG. 8  is a simplified schematic drawing of a mass spectrometer incorporating ionization sources having a device according to the invention, and 
         FIG. 9  is a drawing showing another embodiment of a device according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION 
     Embodiments of the present invention will be described with respect to a inlet for a mass analyser with the understanding that features of the present invention have application to other equipment and analysers as well. The following description to directed to the inventors&#39; preferred embodiments and the best mode of making and using the invention. These embodiments are subject to modification and alteration which changes are understood to be part of the invention. 
     Turning now to  FIG. 1  and  FIG. 5 , such Figures depict an embodiment of a device, generally designated by the numeral  17 , according to the invention. It comprises an inlet housing  32  and a shroud housing  37  disposed as shown so that a gap  40  exists between them. As depicted in  FIG. 1 , both housings are mounted on a wall  14  by wall mounting means comprising items  34 ,  38 ,  41  and  42 , described in more detail below. 
     The wall  14  encloses a region  1  of high gas pressure and separates it from a region  7  of lower gas pressure, and is provided with a wall opening  69 . The device  17  may be used to receive one or more charged particles travelling along a first axis  4  and pass them through a first passage  5  in the inlet housing  32 . The first passage  5  has a first passage axis  18  and comprises an entrance  64  and an exit  65 . Device  17  further comprises a second passage  66  that has a second passage axis  9 . Second passage  66  further comprises an exit  68  ( FIG. 1 ) and an entrance  67  ( FIG. 5 ) that adjoins the exit  65  of the first passage  5  at a junction point. The first passage axis  18  is inclined to the second passage axis  9 . In the  FIG. 1  embodiment, the angle  12  between the axes of the first and second passages is 20°. Other angles can be selected from the range of about 10° to 90°. These other angles can be made in alternative substitutable devices  17 . 
     In use, the device  17  may provide fluid communication between the region  1  of high gas pressure and the region  7  of lower gas pressure via the wall opening  69 . In order to allow a substantial pressure difference to be maintained between these regions, a restrictor section  6  is incorporated at the entrance  67  of the second passage  66 , aligned with the second passage axis  9 . It will be appreciated, however, that the restrictor section  6  could equally well be incorporated in the first passage  5 , for example close to its exit  65 . One embodiment of the present invention features a restrictor section  6  formed in an insert  36  fitted in a counterbore  35  in the exit face  34  of the inlet housing  32 . Insert  36  may be a press fit in the counterbore  35 , or may be welded in position. Alternatively, it may be a sliding fit to allow different inserts to be used, each having different restrictor sections  6 . These may be selected to adjust the gas flow between the regions  1  and  7  to control the pressure in the region of lower pressure  7 . Alternative devices  17  are preferably provided with different restrictor sections  6  to allow the device  17  to be selected for conditions and samples. 
     The restrictor section  6  may form any part or the whole of either or both of the first passage  5  and the second passage  66 . However, it is preferred that it is shorter than the passage in which it is comprised and that it is disposed so that at least a portion of the first passage  5  adjacent to its entrance  64  is at substantially the same pressure as that in the region  1  of high gas pressure. 
     As shown in  FIG. 6 , an embodiment of the inlet housing  32  has a tapered member  44  having an exit face  34  and an entrance face  46 . The tapered member  44  may have a substantially rectangular cross section and may carry a circular boss  63  on which its entrance face  46  is formed. The first passage  5  formed within the tapered member  44  may have a circular cross section and have its entrance  64  in the entrance face  46 . To facilitate its mounting on the wall  14 , the inlet housing  32  may further comprise a flange portion  33  on which the exit face  34  is formed. The entrance face  46  is smaller in area than the exit face  34 . The exit face  34  engages with the wall opening  69  ( FIG. 1 ). The first passage  5  may comprise an internally tapered portion  47  to provide a smooth transition between the diameter of the first passage  5  and the smaller diameter of the restrictor section  6 . 
     Device  17  has a shroud housing  37  to surround the inlet housing  32  and define a gap  40  between them. As shown in  FIG. 7 , shroud housing  37  may comprise a tapered body portion  39  and a flange portion  38  adapted for mounting on the wall  14 . Flange portion  38  is fitted with two dowels  41  which locate in corresponding holes in wall  14 , and is secured to the wall by screws in holes  42 . Spacers  43  are provided on the tapered body portion to hold the inlet housing  32  in position on wall  14  when the device  17  is assembled. Together, these components comprise wall mounting means for holding the inlet housing  32  to the wall  14  so that the first passage  5  and second passage  66  cooperate to pass through the wall opening  69  at least some of the charged particles into the region  7  of lower gas pressure. The wall mounting means further ensures that the first passage axis  18  is inclined to the first axis  4  and defines a first angle  11  therebetween. In the illustrated embodiment, the first axis  4  and the first passage axis  18  lie in the same plane, but in other embodiments the two axes may lie in different planes so that the first passage axis  18  is inclined to a line extending parallel to the first axis  4 . 
     Conveniently, the wall mounting means is such that the first angle  11  is less than 75° or greater than 105°. This angle can be adjusted by turning the device  17 . As depicted in  FIG. 1 , device  17  has a mark or pointer  101   a  which cooperates with indicia  101   b  on the wall or associated with the wall  69  to align the device in a desired position. 
     The tapered body portion  39  is of rectangular cross section such that the gap  40  between it and the inlet housing  32  is of approximately constant width. Tapered body portion  39  has an entrance face  48  which comprises a circular orifice  49  which is disposed adjacent to the entrance face  46  of tapered member  44  when the shroud housing  37  and inlet housing  32  are assembled on the wall  14 , as shown in  FIG. 5 . A gas inlet pipe  45  is provided to allow gas to be introduced into the gap  40  and to flow out of the circular orifice  49  around the entrance  64  of the first passage  5 , as discussed in more detail below. 
     Referring next to  FIG. 1 , the device  17  may be incorporated in apparatus for generating charged particles, generally indicated by  13 . Typically, apparatus  13  may be an atmospheric pressure ionization source, for example an electrospray ionization source, suitable for use in a mass spectrometer. In such apparatus, a fluid comprising a sample to be analyzed (for example, the eluent from a liquid chromatograph) may flow into the region  1  of high gas pressure through an inlet conduit  3 . Region  1  is typically maintained at atmospheric pressure, but other pressures are within the scope of the invention, as discussed above. The region  1  of high gas pressure is surrounded by the wall  14 , which also separates region  1  from the region  7  of lower gas pressure. A wall opening  69  is provided between the two regions, as explained above. A gas inlet  60  is fitted to the wall  14  and a flow of a heated gas (typically air or nitrogen) is admitted into region  1  and exits through a vent  15 . As in prior types of electrospray ionisation sources, an aerosol is generated from a solution of a sample admitted through the inlet conduit  3  and a plume  2  of charged particles is generated. The inlet conduit  3  is maintained at a high potential relative to a counter electrode  16 . The plume  2  of charged particles has a first axis  4 , as shown in  FIG. 1 . In the this embodiment, the angle  11  between the first axis  4  and the first passage axis  18  is less than 75°, (shown as 60° in  FIG. 1 ), but other angles can be used. (See the description of the  FIG. 2  embodiment, below). Gas, which may optionally be heated and may also be used to assist nebulization, may be introduced into the region  1  through a conduit  61  disposed concentrically with the inlet conduit  3 , additionally or alternatively to the gas introduced through the inlet  60 . Gas flowing in the region  1  of high gas pressure assists the desolvation of the droplets comprised in the aerosol formed from the inlet conduit  3 , but may not always be necessary. Further improvement in the desolvation efficiency, especially at high flow rates, may be obtained by replacing the inlet conduit  3  with a nebulizer similar to those used in APCI ionization sources, as discussed below. 
     Material (including charged particles, neutral molecules and droplets of solution) may be sampled from the plume  2  into a first passage  5  in the device  17 . A second passage  66 , in fluid communication with the first passage  5 , conveys at least some charged particles from the first passage  5 , though the wall opening  69  and into the region  7  of lower gas pressure. Region  7  is maintained at a lower pressure than that in region  1  by a vacuum pump  10 . A restrictor section  6  is disposed at the entrance  67  of the second passage  66 , as discussed above. The restrictor  6  has a lower conductance than the first passage  5 , so that the impedance it presents to a flow of gas between the region  1  and the second passage  66  is largely responsible for the pressure difference between them. This ensures that the pressure in the first passage  5  is substantially that in the region  1 . 
       FIG. 2  shows another embodiment of the invention which is similar to that shown in  FIG. 1  but which has an atmospheric pressure chemical ionization source (APCI) in place of the electrospray ionization source shown in  FIG. 1 . In an APCI source, a nebulizer  20  comprising a sample inlet pipe  21  concentrically disposed in an outer pipe  22  replaces the sample inlet conduit  3  of the  FIG. 1  embodiment. A nebulizing gas is introduced into the outer pipe  22  to generate an aerosol from the liquid flowing through the sample inlet pipe  21 . Other types of nebulizer, for example a cross-flow pneumatic nebulizer, may also be used. A corona discharge is established in region  1  by means of a potential difference maintained between a discharge electrode  23  (supported in an insulator  25 ) and the wall  14  and/or the device  17 . The corona discharge produces from the aerosol produced by the nebulizer  20  a plume of charged particles  2  directed along the first axis  4 . Additional heating means (not shown for clarity) may be used to assist in aerosol desolvation. 
     As in the embodiment shown in  FIG. 1 , gas may be introduced into region  1  through a gas inlet  60  and may leave through the vent  15 , and may advantageously be heated. Heated desolvation gas may also be caused to flow around nebulizer  20  in a concentric manner through a second gas inlet  62 . This arrangement may improve the desolvation of the aerosol, but may not always be necessary. 
     Also as in the embodiment shown in  FIG. 1 , some of the charged particles in the plume  2  enter the first passage  5  in the inlet housing  32  and pass into the second passage  66  through the restrictor  6 . In the  FIG. 2  embodiment, the first passage  5  is disposed so that the angle  24  between the first axis  4  and the first passage axis  18  is greater than 105°, (shown as 120° in  FIG. 2 ). It will be appreciated that this disposition of the first passage  5  relative to the first axis  4  may also be used with the  FIG. 1  embodiment, and that the disposition shown in  FIG. 1  may be used with the  FIG. 2  embodiment. The choice of the angle to be used may be made according to the flow rate of sample through the inlet  3  or the nebulizer  20 . A greater angle (for example, angle  24  in  FIG. 2 ), which inclines the first passage axis  18  towards the direction of travel of the charged particles in the plume  2 , is most suitable for higher flow rates. A smaller angle, for example angle  11  in  FIG. 1 , has been found to be more suitable for lower flow rates. 
     It will be appreciated that the illustration of the electrospray and APCI ion sources in  FIGS. 1 and 2 , and the descriptions above, are simplified. The detailed design of such sources is well established and further elaboration is unnecessary. Any prior type of APCI or electrospray ion source may be adapted for use in apparatus according to the invention. 
       FIG. 3  shows another embodiment of the invention that comprises an atmospheric pressure photoionization (APPI) source. As in the case of the  FIG. 2  embodiment, a nebulizer  20  generates an aerosol in the region  1  from a liquid containing a sample. Region  1  contains gas, typically air or nitrogen at high pressure (as defined above). Typically, atmospheric pressure may be used. A UV lamp  26  generates a beam of photons (schematically shown at  27 ) that intersects the aerosol. The various chemical processes associated with the known process of APPI, including the introduction of dopants by means not shown but known in the art, thereby generate a plume of charged particles  2  directed along the first axis  4 . Charged particles in the plume may enter the first passage  5  which may be disposed in either of the positions illustrated in  FIG. 1  or  FIG. 2 . The angle between the first axis  4  and the first passage axis  18  is less than 75° or greater than 105°. However, different devices  17  can be substituted with different angles. 
     An electrical field may also be provided in region  1  to assist the transfer of charged particles into the passage  5 , for example by application of a potential difference between a lamp electrode  28  and the shroud housing  37 . A restrictor  6  and a second passage  66  are provided and operate as described for the embodiments shown in  FIGS. 1 and 2 . 
     As in the embodiment shown in  FIG. 1 , gas may be introduced into region  1  through the gas inlet  60  and may leave through the vent  15 , and may advantageously be heated. Heated desolvation gas may also be caused to flow around nebulizer  20  in a concentric manner through a second gas inlet  62 . This arrangement may improve the desolvation of the aerosol, but may not always be necessary. 
     Another embodiment of the invention is shown ion  FIG. 4 , wherein a surface  29  is provided in region  1 . A sample to be analysed is supported on the surface  29  and a plume of charged particles  2  directed along a first axis  4  is generated from the sample by the impact of a beam of primary particles  30  from a source  31 . The  FIG. 4  embodiment may comprise a matrix-assisted laser desorption (MALDI) source that operates at a first pressure that is equal to atmospheric pressure (as defined above). Such sources are well known in the art. Briefly, a sample may be either dissolved in a suitable matrix before it is deposited on the surface  29 , or in a matrix previously deposited on the surface  29 . The source  31  may comprise a laser and the beam of primary particles  30  may comprise photons from the laser. These photons impact the matrix and sample present on the surface  29  and release charged particles therefrom. These charged particles form the plume  2  directed along the first axis  4 . As in the embodiments previously described, charged particles from the plume  2  may enter the first passage  5  in the inlet housing  32 . This is disposed relative to the first axis  4  as described for the embodiments of  FIGS. 1-3 . An electrical field (not shown in  FIG. 4 ) may be provided in region  1  to assist the entry of charged particles into the first passage  5 . A shroud housing  37 , a first restrictor  6 , and a second passage  66  are also provided and may be disposed as previously described. A gas inlet  60  is provided in the enclosure  14 , through which a gas may be introduced to maintain region  1  at the first pressure. It is sometimes useful to heat this gas and control the direction of its flow. 
     In certain embodiments of the invention the wall mounting means may be such as to allow the inlet housing  32  to assume either a first position or a second position on the waif  14 . such that in the first position the first angle is less than 90° and in the second position the first angle is greater than 90°. In these embodiments, the wall mounting means is such that the housings  32  and  37  are capable of locating only in these two positions. The flange portion  33  of the inlet housing  32  may have an exit face  34  shaped as shown in  FIG. 5 . This shaped exit face may locate in the wall opening  69  in wall  14 , which has a similar shape. This shape allows the inlet housing  32  to be positioned in either of the two positions that are illustrated in  FIGS. 1 and 2 . Flange  38  of the shroud housing  37  is fitted with two dowels  41  which locate in holes in the wall  14 . These dowels are disposed at 180° to one another so that the shroud housing  37  may be located in two different positions, corresponding to the two positions of the inlet housing  32 . 
       FIG. 6  illustrates in more detail an embodiment of the inlet housing  32 . It comprises the flange  33  and a tapered member  44  that has a substantially rectangular cross section, as described above. The first passage  5  is perpendicular to the entrance face  46 . As shown in  FIG. 1 , when housing  32  is in position on the wall of the enclosure  14 , its exit face  34  is located in a plane that is approximately parallel to the plane in which lies the first axis  4 . This disposition allows the angle between the first axis  4  and the first passage axis  18  to be changed by repositioning the housing  32 , as explained above. The first passage  5  comprises a circular bore through the tapered member  44 , and a circular boss  63  comprising the entrance face  46  is formed on the narrow end of the tapered member  44  as shown. The restrictor section  6  may comprise a small tube of circular cross-section, for example 0.0135″ diameter and 0.016″ long) formed in the insert  36 . The first passage  5  may be 0.062″ diameter. These dimensions allow the pressure in the second passageway  66  to be maintained at a pressure of approximately 1 to 3 torr when the pump  10  is a small rotary vacuum pump, (for example 20 ft 3 ·min −1 ) when region  1  contains gas at approximately atmospheric pressure. 
     When mounted as shown in  FIGS. 1-4  the second passage axis  9  extends from the restrictor section  6  and along the second passageway itself. Conveniently, the second passage axis  9  is perpendicular to the exit face  34  of the inlet housing  32 , as shown in the figures. 
     An embodiment of the shroud housing  37  is shown in more detail in  FIG. 7 . It comprises a flange portion  38  and a tapered body portion  39  of rectangular cross section. The body portion  39  has an entrance face  48  that closes the narrowest end of the tapered body portion  39  and comprises a circular orifice  49 . Tapered body portion  39  further comprises an exit face  70 , as shown. The area of the entrance face  48  is smaller than the area of the exit face  70 . 
     As explained, the flange portion  38  may be secured to the wall  14  by screws in the holes  42  in a first position or a second position, corresponding to the first and second positions of the inlet housing  32 , and may hold the inlet housing  32  in position by means of spacers  43 . Alternatively, machined structural elements (for example a “quick-lock” coupling) may be used to secure both the housing  37  and the housing  32  to the wall  14 , and to space them apart. 
     A desolvation gas (typically a heated flow of nitrogen or other inert gas) may be introduced into the space  40  through the inlet  45  so that it flows around the tapered member  44  of the housing  32 , around the entrance of the first passageway  5  in the circular boss  46  and into region  1  through the orifice  49 . Such a gas flow may further assist desolvation of the charged particles as they enter the first passage  5 , and help reduce the unwanted admission of contaminants which may be present in the region  1  of high gas pressure. 
     The inlet housing  32  and shroud housing  37  may be manufactured from metals such as stainless steel, brass, titanium and ceramics. 
     It will be appreciated that although  FIGS. 1-7  are drawn with particular example angles  11 ,  12  and  24 , the device  17  can be constructed with any desired angles that fall within the ranges specified. Further, although the embodiment illustrated in the figures provides two positions for the inlet housing  32  on the wall of enclosure  14 , it is also within the scope of the invention to provide more than two positions (corresponding to different angles  11 ,  12  and  24 ), or to provide only one position. The invention may also provide several different housings, each having different angles  11 ,  12  and  24 , which can be installed according to the requirements of any particular analysis. 
       FIG. 9  is a drawing of an embodiment in which the wall mounting means permits the inlet housing  32  and the shroud housing  37  to be rotated between at least first and second positions. The housings  32  and  37  are secured to a motion plate  73  that carries a spigot  74 . A bearing  72  for the spigot  74  is located in the wall opening  69  in the wall  14 , and a thrust bearing  71  is disposed between the motion plate  73  and the wall  14  to allow the motion plate to rotate freely about an axis of rotation  81 . An ‘O’ ring seal (not shown) is provided around the spigot in the wall opening  69 . The motion plate  73  is provided with teeth  79  around its circumference that mesh with a worm gear  75  mounted on a shaft  77 . Power means for rotating the motion plate  73  (and with it the housings  32  and  37 ) between the first and second positions comprise a motor  76 , which drives the shaft  77 . Control means  78  are in signal communication with the power means comprising the motor  76  via an electrical connection  80 , and may be responsive to operator&#39;s instructions to set the housings in the desired positions. The first and second positions may correspond to those illustrated in  FIGS. 1 and 2 , but other positions are within the scope of the invention. The control means  78  may be implemented in software adapted to run on a computer used to control a mass spectrometer incorporating the apparatus shown in  FIG. 9 . The control means  78  may be also be responsive to the operating conditions or the results being obtained for a given analysis, to set the housings in a position most appropriate for an analysis being carried out. 
       FIG. 8  is a drawing of an example mass spectrometer according to the invention. Charged particles, which have entered the region  7  of lower gas pressure along the second passage axis  9 , travel towards the pump  10  as shown in  FIG. 1 . A second restrictor  19  connects the region  7  with a region  52  of still lower pressure ( FIG. 8 ) that is maintained at a pressure below that of region  7  by a turbomolecular pump  53 . Charged particles entering the second restrictor  19  pass along a second axis  51  that is inclined to the second passage axis  9 . Conveniently, the second axis  51  is perpendicularly disposed to the second passage axis  9 . 
     A mass analyser and interface  8  ( FIGS. 1-4 and 8 ) is disposed to receive charged particles travelling along the second axis  51 . Mass analyser and interface  8  may produce mass spectral information relating to the charged particles or species derived form them. 
     The second restrictor  19  ( FIGS. 1-4 and 8 ) may comprise a hollow conical member  50  aligned with the second axis  51 . The region  52  of still lower pressure may be maintained at a pressure of less than about 10 −2  torr. Mass analyser and interface  8  may comprise an ion guide  54  comprising a stack of annular electrodes to which appropriate AC voltages are applied may be provided in region  52  to assist the transmission of charged particles through an orifice  55  into an analyser vacuum chamber  56 . Chamber  56  may be maintained at a pressure of less than about 10 −5  torr by a turbomolecular vacuum pump  57 . Mass analyser and interface  8  may further comprise a conventional quadrupole mass filter comprising four electrodes (of which three are shown at  58  in  FIG. 8 ) that receives at least some of the charged particles are transmitted by the ion guide  54  through the orifice  55 . A charged particle detector  59  receives charged particles exiting from the mass filter. 
     The mass analyser and interface  8  described above and shown in  FIG. 8  is by way of example only. It is within the scope of the invention to use different configurations of mass filters, ion guides, and vacuum chambers. For example, the single quadrupole mass filter shown in  FIG. 8  may be replaced by a conventional triple quadrupole mass filter comprising two quadrupole mass filters and one or more gas collision cells, a time-of-flight mass analyser, a magnetic sector mass analyser, an ion trap mass analyser, a Fourier Transform mass analyser, or any combination of such mass analysers and/or collision cells. Ion trap mass analysers that may be employed include, but are not limited to, 3-D quadrupole ion traps (“Quistors”), cylindrical ion traps, and “Kingdon” orbital trapping devices (also known as “Orbitraps”). The combination of mass analysers and collision cells may be determined by the type of analyses to be carried out. 
     Similarly, the ion guide  54  in region  52  may be replaced by any other type of ion transmission device, for example quadrupole, hexapole or octupole rod sets, or more than one stack of annular electrodes. Alternatively, the ion guide may be replaced by focussing electrodes supplied only with direct potentials, or omitted altogether. It is also within the scope of the invention to provide more than one intermediate vacuum chamber between the second passage  66  and the analyser vacuum chamber  56 , or even omit region  52  so that the second passage  66  communicates directly with the analyser vacuum chamber  56 . 
     In  FIG. 8  the apparatus downstream of the second restrictor  19  is shown in a highly simplified form, omitting many features that may be necessary for the proper operation of a high performance mass analyser. Such analysers are well known in the art, however, so that a more detailed description is not required. 
     Although in  FIG. 8  the second axis  51  is shown perpendicularly disposed to the second passage axis  9 , this is not an essential feature. It is within the scope of the invention to provide any angle between these two axes, including a linear disposition such that the second axis  51  is an extension of the second passage axis  9 . 
     Thus, preferred embodiments of the present invention have been described in detail with the understanding that the features of the present description are capable of being modified and altered without departing from the teaching. 
     Therefore, the present invention should not be limited to the precise details but should encompass the subject matter of the claims and their equivalents. 
     For example, housings  32  and  37  may be mounted directly on element  101  which contains passageway  7  if element  103  is sufficiently large. Wall  14  could then mount on an outer portion of element  101 .