Abstract:
Ions that are transported from an ion source to a mass spectrometer for mass analysis are often accompanied by background particles such as photons, neutral species, and cluster or aerosol ions which originate in the ion source. Background particles are also produced by scattering and neutralization of ions during collisions with background gas molecules in higher pressure regions with line-of-sight to the mass spectrometer detector. In either case, such background particles produce noise in mass spectra. Apparatus and methods are provided in which a multipole ion guide is configured to efficiently transport ions through multiple vacuum stages, while preventing background particles, produced both in the ion source and along the ion transport pathway, from reaching the detector, thereby improving signal-to-noise in mass spectra.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to mass spectrometry and in particular to apparatus and methods for transporting ions with a multipole ion guide through multiple vacuum pumping stages with reduced background particle noise. 
       BACKGROUND OF THE INVENTION 
       [0002]    Mass analyzers are used to analyze solid, liquid, and gaseous samples by measuring the mass-to-charge (m/z) ratio of ions produced from a sample in an ion source. Many types of ion sources operate at relatively high pressure, that is, higher than vacuum pressure required by the mass analyzer and/or detector. For example, some types of ion sources operate at or near atmospheric pressure, such as electrospray (ES), atmospheric pressure chemical ionization (APCI), inductively coupled plasma (ICP), and atmospheric pressure (AP-) MALDI and laser ablation ion sources. Other types of ion sources operate at intermediate vacuum pressures, such as glow discharge or intermediate pressure (IP-) MALDI and laser ablation ion sources. Still other types of ion sources are configured in a vacuum region in which the vacuum pressure may increase during operation of the ion source, such as electron ionization and chemical ionization ion sources. 
         [0003]    Ion sources operated at higher pressures are usually configured to deliver ions into the vacuum region of the mass analyzer via one or more differential pumping vacuum stages that isolate the mass analyzer and detector from the higher pressure of the upstream stages. In such configurations, an ion optical arrangement is typically configured between the ion source and the mass analyzer entrance in order to facilitate transfer of ions from the ion source to the mass analyzer entrance through the multiple vacuum pumping stages, while restricting the flow of background gas into the mass analyzer region. 
         [0004]    Apart from efficiently transferring ions from the ion source to the mass analyzer, such ion optical arrangements are also often configured to prevent background particles originating in the ion source from reaching the mass analyzer detector, where they would produce background noise in the mass spectra. Depending on the type of ion source, such particles may include photons, undesolvated cluster ions and neutral species, electrons, and charged and uncharged aerosol particles. Such particles may not be effectively eliminated by the mass analyzer, if at all, in which case they may produce background noise in the recorded mass spectra, thereby limiting the achievable signal-to-noise ratio. Consequently, depending on the type of ion source employed and the instrument configuration, various approaches to preventing such background particles from reaching the mass analyzer detector have been devised. 
         [0005]    One approach that is now common practice is to locate the detector outside the field of view from the ion source, as described, e.g., in Dawson, “Quadrupole Mass Spectrometry and Its Applications”, pp. 34-35 and 138-139. In these so-called ‘off-axis’ detector configurations, most photons and neutral species emanating from the ion source follow flight paths that miss the detector, while mass analyzed ions of interest are deflected with electric fields to intersect with the detector. Most of these configurations consist simply of misaligning the detector with the exit of the mass analyzer, possibly combined with some electrostatic deflector for steering ions to the detector. However, relatively complicated versions of such arrangements were also proposed, for example, by Brubaker in U.S. Pat. No. 3,410,997, in which curved ion guides were configured to transport the mass-analyzed ions from the exit of a quadrupole mass analyzer to a detector. 
         [0006]    It is usually more advantageous, however, to remove undesirable particles from the ion path before they enter the mass analyzer. One reason for this is that the impingement of such particles on surfaces in the mass analyzer may result in the buildup of an electrically insulating layer of contamination on surfaces, which may accumulate charge that distorts electric fields and degrade performance. Another reason is that the impact of such particles on surfaces may create secondary particles which may, in turn, find their way to the mass spectrometer detector and create noise. Hence, for example, Brubaker further described in U.S. Pat. No. 3,473,020 a number of arrangements in which curved ion guides are configured before the entrance to a quadrupole mass filter, whereby ions of interest are guided to the mass filter entrance, while photons and neutral species proceed undeflected and thus do not enter the mass filter. 
         [0007]    A number of alternative configurations have since been developed with at least one of the objectives being to prevent background particles originating with the ion source, such as photons, neutrals, charged droplets, etc., from reaching a mass analyzer detector. For example, Mylchreest et al. describe in U.S. Pat. No. 5,171,990 apparatus and methods for preventing high velocity droplets or particles, emanating from a capillary orifice into vacuum from an atmospheric pressure ion (API) source, from proceeding into the lens region at the entrance of a mass analyzer. Essentially, Mylchreest et al. describe orienting the capillary so that its axis is offset from a skimmer orifice or aperture separating the capillary exit vacuum region from the vacuum region of the mass analyzer entrance lens. Hence, high velocity droplets and particles traveling along the axis of the capillary are blocked from proceeding into the mass analyzer region, while ions of interest are deviated from the axis to travel through the orifice or aperture by virtue of their free jet expansion from the capillary exit. However, such a configuration would suffer from contamination buildup on the orifice or aperture, leading to unstable operation due to electrostatic charging. Also, the transmission efficiency of ions would degrade due to scattering of ions out of the deviated flight path from background gas molecules in this relatively high pressure region. 
         [0008]    Takada et al. describe in U.S. Pat. No. 5,481,107 the incorporation of an electrostatic lens disposed between an API source and the entrance to a mass analyzer. The mass analyzer axis and that of the ion source and interface optics is offset so as to prevent droplets and neutral species from proceeding past the entrance aperture of the mass analyzer, while the electrostatic lens is configured to re-direct ions of interest from the axis of the ion source and interface optics into the mass analyzer entrance aperture. One difficulty with such an arrangement is that ions entering vacuum via such AP/vacuum interfaces typically exhibit similar velocity distributions, more or less independent of their mass. This results in ion kinetic energies that depend strongly on ion mass, and, because the focusing action of electrostatic lenses in vacuum depends only on ion kinetic energy and ion charge, and not ion mass, such a configuration leads to severe mass discrimination effects. 
         [0009]    Mordehai et al. describe in U.S. Pat. Nos. 5,672,868, 5,818,041, and 6,069,355, configurations in which a multipole RF ion guide is located between an ion source and the entrance to a mass analyzer. Ions are transported from the ion source to the input end of the ion guide along an axis that is at an angle with respect to the axis of the ion guide. The ions enter the input end of the ion guide while they are entrained in an aerodynamic jet emanating from the ion source, or from an ion transport device such as a capillary. Ions entering the input region of the ion guide are re-directed to move along the ion guide axis via the action of the RF fields in the ion guide, and are transported by the ion guide to the entrance of the mass analyzer. Neutral and energetic charged particles continue more or less along their original trajectories and are lost to the surrounding surfaces. However, as with the apparatus and methods of Takada et al. &#39;107, described above, ions entrained in an aerodynamic jet have ion kinetic energies that depend on ion mass. Hence, the re-directing of ions by the RF fields in the ion guide with good efficiency requires that the ions be quickly collisionally cooled by collisions with background gas molecules, which is increasingly more important the greater the ion mass, hence ion energy. Hence, Mordehai et al. provide a separate gas inlet to let in extra ‘buffer’, or collision, gas for this purpose. Because the ion guide is located entirely within a single vacuum stage, the gas pressure would not be substantially different from one end of the ion guide to the other end. Hence, the probability of collisions between ions and background gas molecules as ions exit the ion guide would have to be substantial in the apparatus of Mordehai et al., resulting in degraded transport efficiency in this region. Such scattering is also known to lead to increased background noise at the detector, due to the acceleration of scattered ions in the RF fringe fields in this region, as well as the production of energetic neutral species due charge-exchange neutralization of such accelerated ions (as discussed below). 
         [0010]    Wells describes in U.S. Pat. No. 6,730,904 a multipole ion guide that is configured in segments, where different segments may be operated with independent voltages. This allows ions traversing the ion guide to be guided along different optical axes within the ion guide from one segment to the next, where the different axes are offset with respect to each other. Wells describes such segmented ion guide configurations in which ions and neutral particles enter the ion guide along an entrance axis, and the ions are then guided so as to exit the ion guide along an exit axis that is offset from the entrance axis. The neutrals proceed along the entrance axis direction and are thereby prevented from proceeding past the ion guide exit. Again, the efficiency of ion transport depends on collisionally cooling energetic ions as they enter the ion guide. For example, Wells demonstrates through computer simulations of one embodiment that many more ions are lost to the ion guide electrodes when the gas pressure in the ion guide is reduced from a pressure corresponding to a mean free path of 1 mm to a pressure corresponding to a mean free path of 10 mm. Hence, as with the apparatus and methods described by Mordehai et al., as discussed above, a significant background gas pressure is expected in the region where ions exit the ion guide, resulting in collisions between ions and background gas molecules in this region, which ultimately leads to increased background noise at a downstream detector. 
         [0011]    In European Patent Application 0 237 259 A2, Syka describes tandem quadrupole mass spectrometer configurations, some of which include a bent or tilted quadrupole ion guide positioned just before the final quadrupole mass analyzer and detector. The bent or tilted quadrupole ion guide is described to reduce noise by preventing excited and fast neutral particles and fast ions emanating from an ion source from reaching the detector, because the tilted or bent quadrupole removes the detector from line-of-sight of the ion source. The entrance and exit ends of such bent quadrupole ion guide reside in the same vacuum stage limiting the ions within the bent quadrupole ion guide to traverse a single background pressure region constrained by the single vacuum stage pumping speed. 
         [0012]    Kalinitchenko describes in U.S. Pat. No. 6,614,021 a configuration of an ICP/MS instrument that incorporates an electrostatic mirror between an ICP ion source and a quadrupole mass analyzer. The mirror provides an electrostatic focusing field that deflects ions from the ion source, for example, by 90 degrees, and focuses them through an aperture at the entrance of the quadrupole mass analyzer. Such an arrangement avoids any line-of-sight from the ion source to the detector, thereby preventing background particles originating in the ion source, such as photons and energetic neutral species, from reaching the detector. Kalinitchenko reports a substantial increase in sensitivity relative to prior art, measured as counts/sec per parts-per-million (ppm) of analyte. However, the increase was achieved “without attendant increase in background” noise, implying that significant background noise persisted as in previous configurations, in spite of the reflecting mirror. 
         [0013]    All of the prior art discussed above describe apparatus and methods to reduce or eliminate background noise caused primarily by undesirable particles emanating from an ion source. However, it is now appreciated that background particle noise can also originate from other sources besides the ion source. For example, while the reflecting mirror arrangement of Kalinitchenko described in U.S. Pat. No. 6,614,021, discussed above, provided for no possible line-of-sight between the ion source and the detector, the significant background noise that was previously observed nevertheless persisted, demonstrating that such background particle noise must in fact originate from processes separate from the ion source itself. The observed non-source-related background noise was reduced substantially, as described subsequently by Kalinitchenko in U.S. Pat. No. 6,762,407, by incorporating a set of curved, or tilted, ‘fringe’ electrodes between the entrance of the quadrupole mass analyzer and the quadrupole entrance aperture. Kalinitchenko suggests that energetic neutral particles are produced as ions are accelerated through residual gas in the apparatus. That is, some ions inevitably interact with background gas molecules, for example, via resonant charge exchange processes, resulting in conversion of the accelerating ions into energetic neutral species. Another possible explanation is that such acceleration leads to some degree of ion fragmentation, resulting in energetic neutral fragments that are on a favorable trajectory to reach the mass analyzer detector. 
         [0014]    Kalinitchenko further describes that such collisions occur not only during acceleration of ions along their axial motion direction, such as in the reflecting mirror region, but also along directions orthogonal to their axial direction, for example, in the fringe fields between the end of an RF multipole ion guide and an aperture proximal to the end. Hence, the curved or tilted ‘fringe’ electrodes described by Kalinitchenko in the &#39;407 patent prevented energetic neutrals created in the electrostatic mirror vacuum region, and in the region of the entrance aperture and the upstream section of the ‘fringe’ electrode structure, from reaching the detector. 
         [0015]    On the other hand, it is well known that the interactions between ions and background gas molecules involve not only the neutralization of the ions, but also scattering of ions out of the beam path, resulting in additional ion loss. Ion losses also occur due to scattering by oscillating fringe fields proximal to the entrance or exit of an RF multipole ion guide. In any case, the ion transmission efficiency in the apparatus and methods described in the &#39;407 patent by Kalinitchenko would be reduced due to ions lost by scattering with background gas molecules as they move from the relatively higher background pressure vacuum region of the reflecting mirror, through the vacuum interface aperture, and traverse the region between the interface aperture and the RF ‘fringe’ field electrodes. 
         [0016]    The loss of ions due to scattering with background gas molecules in vacuum regions of higher background gas pressure is frequently minimized by transporting ions through such regions within an RF multipole ion guide. The RF fields within such ion guides generate an effective repelling force directed orthogonally to the ion beam direction, that is, orthogonal to the ion guide axis, thereby counteracting such scattering out of the beam path. Further, such collisions serve to dampen the ions&#39; kinetic energy, which allows the ions to settle closer to the ion guide axis, thereby improving transport efficiency. However, significant scattering losses nevertheless occur when ions must exit the ion guide in a region where collisions with background gas molecules are likely. This is a problem typically encountered in conventional multiple vacuum stage vacuum systems, in which static electric field vacuum partitions separate the different vacuum stages. Ions traveling within an ion guide through one vacuum stage with a relatively higher vacuum pressure must exit the ion guide and traverse an aperture provided in the vacuum partition to move into the next vacuum stage that has a lower gas pressure, with such conventional vacuum stage configurations. Ions are lost due to scattering in collisions with background gas molecules once they exit the ion guide, and ions are also lost due to scattering by fringe fields between the aperture and the ion guide exit in the upstream vacuum stage, or between the aperture and the ion guide entrance in the downstream vacuum stage. Even if the gas pressure in the next vacuum stage is low enough, on average, that collisions between ions and gas molecules are rare, nevertheless, ions may experience frequent collisions with gas molecules that flow from the upstream, higher background gas pressure vacuum stage into the lower pressure downstream vacuum stage in the vicinity to the interface aperture. 
         [0017]    The problem of ion loss during transit between vacuum stages has been effectively addressed by Whitehouse, et al. in U.S. Pat. Nos. 5,652,527; 5,962,851; 6,188,066; and 6,403,953, which describe extending an RF multipole ion guide through the vacuum partitions between two or more vacuum stages. Essentially, these patents describe RF multipole ion guides that effectively transport ions through and between vacuum stages at high and low background gas pressures, and are configured with a small enough cross-section to act as an effective restriction to gas flow between vacuum stages, similar to an aperture or orifice in a vacuum partition. Whitehouse et al. further describes in these documents the incorporation of multipole ion guides extending through multiple vacuum pumping stages between API sources and mass analyzers. 
         [0018]    This same situation also exists at the entrance and exit of a conventional collision cell, in which a multipole ion guide is located in a region of gas pressure that is high enough so that ions collide with background gas molecules as they traverse the ion guide. Although ions are prevented from scattering out of the beam path by the RF fields of the ion guide while traversing the ion guide, the ions typically must enter and exit the ion guide via apertures at the ends of the collision cell that help maintain a pressure differential between the region internal to the collision cell and vacuum regions external to the collision cell. Hence, ions are scattered by collisions with collision gas molecules as the ions enter and leave the collision cell, resulting in ion losses. Furthermore, background particles in the form of energetic neutral species may be created as a result of ions being accelerated into the collision cell for the purpose of collision-induced fragmentation. Some of these energetic neutral species may continue through the exit of the collision cell, and into a mass analyzer and detector located downstream, thereby creating background particle noise. Furthermore, ions exiting the collision cell must pass through the RF fringe fields between the ion guide exit end and the exit aperture of the collision cell. This is also a region where collisions between ions and gas molecules occur, resulting in ion scattering losses, as well as ion neutralization via charge exchange, for example. As discussed above, it is known that ions may be accelerated to higher energies in such RF fringe fields, and neutralization of energetic ions creates energetic neutral species, which then also may continue on downstream to create background noise in a mass analyzer and detector. 
         [0019]    The problem of ion loss during ion transit into and out of a conventional collision cell has also been addressed by Whitehouse, et al. in U.S. Pat. No. 7,034,292, which describes configurations that include a multipole ion guide that extends continuously from inside a collision cell to outside the collision cell, where the multipole ion guide terminates in a region of background pressure that is low enough that collisions between ions and background gas molecules essentially do not occur. In such configurations, ions do not experience RF fringe fields until they are in a vacuum region with low enough background gas pressure that collisions with background gas molecules essentially do not occur. Nevertheless, energetic neutral species that are created by collisions between ions and collision gas molecules as the ions are accelerated into the collision cell remain a potential source of background particle noise at a mass analyzer detector located downstream of the collision cell. 
         [0020]    In all of the configuration described by Whitehouse in U.S. Pat. Nos. 5,652,527; 5,962,851; 6,188,066; 6,403,953; and 7,034,292, multipole ion guides were configured to be in axial alignment between the ion source and the entrance to a mass analyzer. In other words, no provision was made for preventing background particles emanating from an ion source, or created along the beam path from collisions with background gas molecules, from entering a mass analyzer or from reaching a mass analyzer detector. Hence, there has not been available a solution to the problem of providing efficient transport of ions between a region of higher background gas pressure, at which collisions between ions and background gas molecules occur, and a region of lower background gas pressure, at which such collisions essentially do not occur, while simultaneously preventing background particles originating either from an ion source, and/or created in collisions between ions and background gas molecules during ion transit, from reaching a mass analyzer detector and thereby causing background noise in mass spectra. 
       SUMMARY OF THE INVENTION 
       [0021]    Accordingly, it is one object of the present invention to reduce the number of background particles emanating from an ion source that reach a mass analyzer detector, while improving the transmission efficiency of ions to the mass analyzer. 
         [0022]    Another object of the present invention is to reduce the number of background particles, created from collisions between ions and background gas molecules, that reach a mass analyzer detector, while improving the transmission efficiency of ions to the mass analyzer. 
         [0023]    Another object of the present invention is to simultaneously reduce the number of background particles, created both from collisions between ions and background gas molecules, as well as background particles that emanate from an ion source, that reach a mass analyzer detector, while improving the transmission efficiency of ions to the mass analyzer. 
         [0024]    A still further object of the present invention is to reduce the number of background particles, both emanating from an ion source and created by collisions between ions and background gas molecules, that are able to enter a mass analyzer, while improving the transmission efficiency of ions to the mass analyzer. 
         [0025]    These and other objectives are achieved by providing an RF multipole ion guide, in a multiple-vacuum pumping stage vacuum system, that extends continuously through at least one vacuum partition between an upstream region (farther from a mass analyzer detector) of higher gas pressure and a downstream region of lower gas pressure. The ion guide is configured with an axis that is tilted, bent or curved, with respect to the subsequent direction of an ion beam as it enters a mass analyzer, so as to prevent, simultaneously, any line-of-sight between an upstream ion source region, as well as any and all higher pressure regions in which collisions between ions and background gas molecules occur, and the mass analyzer detector. In particular, the disclosed invention prevents background particles from reaching the mass analyzer detector which are created in the vicinity of the vacuum partition, through which the RF multipole ion guide extends, which separates an upstream region of higher background gas pressure at which collisions between ions and background gas molecules occur, and subsequent downstream vacuum regions at lower background gas pressure at which such collisions are insignificant. Consequently, this vacuum partition will be referred to herein as a ‘high pressure vacuum partition’. Some embodiments of the invention also eliminate any line-of-sight between any such regions in which background particles are created, and the entrance to the mass analyzer, in addition to the mass analyzer detector. 
         [0026]    Hence, the embodiments of the invention uniquely provide for the efficient transport of ions through and between vacuum pumping stages, while simultaneously eliminating background noise that originates from background particles emanating from an ion source, as well as background particles that are created from collisions between ions and background gas molecules during ion transport. Consequently, the invention provides apparatus and methods that both improve signal and reduce background particle noise simultaneously, with reduced cost and complexity, compared to prior art. 
         [0027]    Four categories of background noise particles are distinguished here: (1) background particles that emanate directly from an ion source, such as charged and uncharged droplets, and energetic neutral species and ions, and which create background noise by impinging on the detector directly; (2) background particles that emanate directly from an ion source and which impact surfaces within the mass analyzer or near the detector, thereby creating secondary particles that subsequently impinge on the detector and create background noise; (3) background particles, such as energetic neutral and ionic species, that are created as ions collide with background gas molecules during transit toward a mass analyzer entrance, and which create background noise by impinging on the detector directly; and (4) background particles that are created as ions collide with background gas molecules during transit, and which impact surfaces within the mass analyzer or near the detector, thereby creating secondary particles that subsequently impinge on the detector and create background noise. All embodiments of the subject invention prevent background noise from particles of categories (1) and (3), that is, which prevent background particles of any origin outside the mass analyzer from reaching the mass analyzer detector directly. Some embodiments of the subject invention also prevent background noise from particles of categories (2) and (4), as well, that is, which prevent background particles of any origin from even passing through the entrance to a mass analyzer. Still other embodiments also prevent any background particles that are created upstream of the ‘high pressure vacuum partition’ from passing beyond this vacuum partition and into the downstream low pressure vacuum region. 
         [0028]    In some embodiments, a linear multipole ion guide is configured to extend continuously from an upstream vacuum pumping stage into a downstream vacuum pumping stage, and through a vacuum partition, that is, a ‘high pressure vacuum partition’, between the two vacuum pumping stages, such that the central axis of the ion guide is configured with a tilted orientation angle with respect to the entrance axis of a mass analyzer located downstream. The background gas pressure in the vacuum pumping stage in which the ion guide exit is located is low enough to allow ions to move without collisions with background gas molecules from the ion guide exit into the entrance of the mass analyzer. However, the background gas pressure in the immediately preceding vacuum pumping stage may be high enough that such collisions can occur with significant frequency. The ion guide is configured such that the mounting structure that supports the rods or poles of the multipole ion guide is integrated as an extension of the vacuum partition between the vacuum stage in which the ion guide exit is located, and the immediately preceding vacuum stage, so that the ion guide acts as an effective restriction to the flow of gas between these vacuum pumping stages, as described by Whitehouse et al., in U.S. Pat. Nos. 5,652,527; 5,962,851; 6,188,066; and 6,403,953. This partition is configured in the embodiments of the present invention at a distance from the mass analyzer entrance that is far enough away to ensure that any background particles that may be created by collisions between ions and background gas molecules in the vicinity of this partition do not have any line-of-sight trajectory to the mass analyzer detector, due to the tilted angle between the ion guide axis and the axis of the mass analyzer entrance. Such a configuration also ensures that there is no line-of-sight between any region upstream of this vacuum partition and the mass analyzer detector, thereby also ensuring that any background particles originating with an upstream ion source or higher pressure region such as a collision cell, or the entrance region of the ion guide, have no line-of-sight to the mass analyzer detector as well. Hence, the embodiments disclosed herein that incorporate such a multipole ion guide configuration, will prevent background noise from particles of categories (1) and (3) from reaching the mass analyzer detector. 
         [0029]    In some embodiments, the ion guide exit may be positioned proximal to the mass analyzer entrance, so that ions are directed into the mass analyzer immediately after exiting the ion guide, possibly with the help of an electrostatic steering or deflecting electrode located at the ion guide exit. However, the ion guide exit may also be positioned some distance away from the mass analyzer entrance, in which case, one or more additional ion transport devices, such as electrostatic lenses and/or deflection devices, and/or one or more additional multipole ion guides, all of which are well-known in the art, may be employed to efficiently transport ions from the ion guide exit to the mass analyzer entrance. Depending on the separation distance between the exit of the ion guide and the entrance to the mass analyzer, the tilt angle between the linear ion guide axis and the axis of the mass analyzer entrance, combined with the separation between the ion guide exit and the mass analyzer entrance, also prevents background particles from even passing through the mass analyzer entrance, thereby providing further protection from background particle noise by eliminating background particles of categories (2) and (4) as well as (1) and (3). 
         [0030]    In other embodiments of the disclosed invention, a multipole ion guide that extends continuously through a ‘high pressure vacuum partition’ may be configured with a bend or curve located downstream of the vacuum partition, such that the axis of the ion guide at its exit end is coaxial with a mass analyzer entrance. The axis of the mass analyzer entrance will be oriented at an angle with respect to the tangent to the axis of the ion guide at the point at which the ion guide extends through the ‘high pressure vacuum partition’, as in the previously-described embodiments. However, a bend or curve in the ion guide eliminates the requirement in the previously-described embodiments that ions exit the multipole ion guide before they are re-directed to the axis of the mass analyzer entrance, since the ions are re-directed to move along the mass analyzer entrance axis while still within the multipole ion guide, in these other embodiments. This alternative configuration may provide better ion transport efficiency into the mass analyzer entrance, while reducing complexity and cost, relative to the previously-described tilted linear ion guide configurations. 
         [0031]    Further, some embodiments also incorporate a tilted orientation angle between the central axis of an ion guide at the point where it passes through a ‘high pressure vacuum partition’, and the axis of the ion beam as it enters the ion guide. Such a configuration prevents background particles originating upstream of the ion guide, such as from an ion source or higher pressure region such as a collision cell, or even background particles created at the ion guide entrance region, from passing beyond the vacuum partition, and therefore provides additional assurance that such particles are unable to create noise at a mass analyzer detector. Again, additional electrostatic and/or RF ion guide devices may optionally be employed to ensure maximum ion transport efficiency into the ion guide entrance end, for embodiments that incorporate a tilted linear multipole ion guide, or, alternatively, a bend or curve in an ion guide axis upstream of the vacuum partition, similar to such downstream bends or curves described above, may be incorporated to optimize ion transport efficiency through this upstream portion of the ion guide. 
         [0032]    There need not be any particular relation between the direction nor magnitude of this ‘upstream tilt angle’ between the central axis of an ion guide at the point where it passes through a ‘high pressure vacuum partition’, and the axis of the ion beam as it enters the ion guide, and the ‘downstream tilt angle’ defined by the axis of the ion guide at the point where it passes through the ‘high pressure vacuum partition’, and the mass analyzer entrance axis, in order realize maximum reduction in background noise. However, it typically proves to be more straightforward, and therefore less complex and costly, to configure the ‘upstream tilt angle’ to be equal in magnitude and opposite in direction to the ‘downstream tilt angle’. In this special case, the ion beam directions upstream of the ion guide entrance and downstream of the ion guide exit will be parallel, but displaced laterally (orthogonally to the axial beam direction). Such an arrangement facilitates instrument design and fabrication. 
         [0033]    Another special embodiment of the present invention incorporates a multipole ion guide extending continuously through a ‘high pressure vacuum partition’, where the multiplole ion guide is structured with a continuously curving axis, for example, where the ion guide axis extends through a 90 degree segment of a circle. In such an embodiment, the ion guide extends through vacuum partitions while the axis curves. 
         [0034]    An even further embodiment of the present invention incorporates an ‘S’ curve downstream of the ‘high pressure vacuum partition’, for example, such that the ion guide entrance is coaxial with upstream portion of the ion beam path, and extends straight through the ‘high pressure vacuum partition’. An ‘S’ curve in the ion guide axis downstream of the ‘high pressure vacuum partition’ then translates the ion guide axis such that the axis of the ion guide at its exit is parallel to, but displaced laterally from, the ion guide axis at its entrance. Hence, the ion beam is guided through the curves to the ion guide exit, and then subsequently into a mass analyzer located downstream, while all background particles created in the vicinity of, and upstream of, the ‘pressure vacuum partition’ do not negotiate the curves in the ion guide axis and fail to enter the mass analyzer. 
         [0035]    Additionally, in all cases, it is typically more advantageous to orient the rods, or poles, of the multipole ion guide such that background particles from an upstream source are more likely to pass through a gap between poles, rather than strike a pole, in order to minimize contamination and consequential electrostatic charging effects. 
         [0036]    Furthermore, depending on the vacuum requirements of the mass analyzer and/or detector employed, it may be advantageous to provide one or more additional vacuum partitions between the ion guide exit and the mass analyzer entrance, that is, locate the mass analyzer and detector in a vacuum pumping stage downstream of the vacuum pumping stage in which the exit end of the multipole ion guide is positioned or located, in order to provide an even lower pressure within the space of the mass analyzer and/or detector. In such cases, the multipole ion guide may be extended continuously through such additional vacuum partitions to facilitate ion transport through the partition, or separate ion guide may be employed which then extend continuously through the additional vacuum partitions, instead. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0037]      FIG. 1  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and are then transported to a quadrupole mass analyzer by a multipole ion guide that extends through a vacuum partition to provide optimum ion transport, and which is tilted at an angle with respect to the entrance axis of the mass filter in order to prevent background particles from reaching the mass analyzer detector. The tilt in the ion guide relative to the capillary axis also reduces background particles. 
           [0038]      FIG. 2  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through an aperture lens and then directly into a multipole ion guide that extends continuously through two vacuum partitions, to transport the ions to a quadrupole mass analyzer, where the ion guide is tilted at an angle with respect to the entrance axis of the mass filter in order to prevent background particles from reaching the mass analyzer detector. 
           [0039]      FIG. 2A  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through an aperture lens and then directly into a multipole ion guide that extends continuously through three vacuum partitions, to transport the ions to a quadrupole mass analyzer, where the ion guide is tilted at an angle with respect to the entrance axis of the mass filter, and also includes a bend in the ion guide, in order to prevent background particles from reaching the mass analyzer detector. 
           [0040]      FIG. 3  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through an aperture lens and then directly into a multipole ion guide segment that extends continuously through one vacuum partition. A second segment then transports the ions through a second vacuum partition to a quadrupole mass analyzer. The two segments are coaxial, and they are tilted at an angle with respect to the entrance axis of the mass filter, in order to prevent background particles from reaching the mass analyzer detector. 
           [0041]      FIG. 4  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through an aperture lens and then directly into a first multipole ion guide segment that extends continuously through two vacuum partitions. A second segment then transports the ions through a second vacuum partition to a quadrupole mass analyzer. The first segments is coaxial with the capillary axis, but the second segment is tilted at an angle with respect to the entrance axis of the mass filter, in order to prevent background particles from reaching the mass analyzer detector. 
           [0042]      FIG. 5  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and are then transported to a quadrupole mass analyzer by a multipole ion guide that extends through three vacuum partitions to provide optimum ion transport. The ion guide contains two bends along its length, such that entrance portion of the ion guide is coaxial with the capillary axis, the central portion is at an angle relative to the first portion, and the exit portion is coaxial with the entrance axis of the mass filter, thereby preventing background particles from reaching the mass analyzer detector. 
           [0043]      FIG. 5A  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through an aperture lens and then directly into a multipole ion guide that extends continuously through four vacuum partitions to provide optimum ion transport to a quadrupole mass analyzer. The ion guide contains two bends along its length, such that entrance portion of the ion guide is coaxial with the capillary axis, the central portion is at an angle relative to the first portion, and the exit portion is coaxial with the entrance axis of the mass filter, thereby preventing background particles from reaching the mass analyzer detector. 
           [0044]      FIG. 6  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and then into a multipole ion guide that extends continuously through one vacuum partitions to provide optimum ion transport to a quadrupole mass analyzer. The ion guide contains two bends along its length, such that entrance portion of the ion guide is coaxial with the capillary axis, the central portion is at an angle relative to the first portion, and the exit portion is coaxial with the entrance axis of the mass filter, thereby preventing background particles from reaching the mass analyzer detector. 
           [0045]      FIG. 7  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and then into a multipole ion guide that extends continuously through one vacuum partitions to provide optimum ion transport to a quadrupole mass analyzer. The ion guide is configured with a continuous curve along its length, such that entrance portion of the ion guide is coaxial with the capillary axis, and the exit portion is coaxial with the entrance axis of the mass filter, and at an angle of ninety degrees with respect to the axis of the capillary, thereby preventing background particles from reaching the mass analyzer detector. 
           [0046]      FIG. 7A  schematically illustrates an embodiment of the invention in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and then into a multipole ion guide that extends continuously through two vacuum partitions to provide optimum ion transport to a quadrupole mass analyzer. The ion guide is configured with a continuous curve along its length, such that entrance portion of the ion guide is coaxial with the capillary axis, and the exit portion is coaxial with the entrance axis of the mass filter, and at an angle of ninety degrees with respect to the axis of the capillary, thereby preventing background particles from reaching the mass analyzer detector. 
           [0047]      FIG. 8  schematically illustrates an embodiment of the invention in a ‘triple-quadrupole’ configuration, in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and are then transported to a first quadrupole mass analyzer by a multipole ion guide that extends through a vacuum partition to provide optimum ion transport, and which is tilted at an angle with respect to the entrance axis of the mass filter in order to prevent background particles from proceeding into a collision cell downstream of the first mass analyzer. The collision cell is configured with an ion guide with a continuous curve along its length, such that entrance portion of the ion guide is coaxial with the first quadrupole mass filter, and the exit portion is coaxial with the entrance axis of a second quadrupole mass filter, and at an angle of ninety degrees with respect to the axis of the first mass quadrupole mass filter, thereby preventing background particles from the collision cell, or upstream of the collision cell, from reaching the detector located downstream of the second quadrupole mass filter. 
           [0048]      FIG. 9  schematically illustrates an embodiment of the invention in a ‘triple-quadrupole’ configuration, in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and are then transported to a first quadrupole mass analyzer by a multipole ion guide that extends through a vacuum partition to provide optimum ion transport, and which is tilted at an angle with respect to the entrance axis of the mass filter in order to prevent background particles from proceeding into a collision cell downstream of the first mass analyzer. The collision cell is configured with an ion guide with a continuous curve along its length, such that entrance portion of the ion guide is coaxial with the first quadrupole mass filter, and the exit portion is coaxial with the entrance axis of a second quadrupole mass filter, and at an angle of ninety degrees with respect to the axis of the first mass quadrupole mass filter, thereby preventing background particles from the collision cell, or upstream of the collision cell, from reaching the detector located downstream of the second quadrupole mass filter. The exit portion of the collision cell ion guide extends continuously through the collision cell exit partition to provide optimum ion transport through the collision cell exit partition. 
           [0049]      FIG. 10  schematically illustrates an embodiment of the invention in a ‘triple-quadrupole’ configuration, in which ions from an ESI ion source are carried into vacuum via a dielectric capillary, pass through a skimmer, and are then transported to a first quadrupole mass analyzer by a multipole ion guide that extends through a vacuum partition to provide optimum ion transport, and which is tilted at an angle with respect to the entrance axis of the mass filter in order to prevent background particles from proceeding into a collision cell downstream of the first mass analyzer. The collision cell is configured with two ion guide segments along a continuous curve, such that entrance portion of the first ion guide segment is coaxial with the first quadrupole mass filter, and the exit portion of the second segment is coaxial with the entrance axis of a second quadrupole mass filter, and at an angle of ninety degrees with respect to the axis of the first mass quadrupole mass filter, thereby preventing background particles from the collision cell, or upstream of the collision cell, from reaching the detector located downstream of the second quadrupole mass filter. The exit portion of the second collision cell ion guide segment extends continuously through the collision cell exit partition to provide optimum ion transport through the collision cell exit partition. The segmented collision cell ion guide provides additional analytical functionality, such as the capability of MS/MS n . 
           [0050]      FIG. 11  schematically illustrates cross-sectional views for a variety of possible ion guide configurations according to the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0051]    A preferred embodiment of the invention is shown in  FIG. 1 . This embodiment is configured with a conventional Electrospray Ionization (ESI) ion source  1  with pneumatic nebulization assist, operating essentially at atmospheric pressure, and mounted to a vacuum system comprising four vacuum pumping stages  2 ,  3 ,  4  and  5 . The source  1  includes a pneumatic nebulization assisted electrospray probe  6  essentially comprising a liquid sample delivery tube which delivers liquid sample  7  to sample delivery tube end  8 . A voltage differential between tube end  8  and the entrance end  9  of capillary vacuum interface  10  is provided by a high voltage DC power supply (not shown). The resulting electrostatic field in the vicinity of sample delivery tube end  8  results in the formation of an electrospray plume  11  from sample liquid  7  emerging from sample delivery tube end  8 . In order to enhance nebulization and ionization efficiencies, nebulization gas  12  may be delivered though a nebulization gas tube with an exit opening that is proximal to and, ideally, coaxial with liquid sample delivery tube exit end  8 . Counter-current drying gas  13  is heated in drying gas heater  14  and flows past the entrance end  9  of capillary vacuum interface  10  as heated counter-current drying gas  15  to assist with the evaporation of droplets in electrospray plume  11 . Sample ions are released from evaporating charged droplets within plume  11 , and the ions, along with any remaining charged and uncharged droplets and aerosol particles, are entrained in background gas flowing into capillary vacuum orifice  16 . The ions, droplets, and aerosol particles are carried through the capillary  10  bore  17  along with the gas to the capillary exit end  18 , and pass through capillary  10  exit orifice  19  into the first vacuum pumping stage  2 . Typically, the gas undergoes a supersonic expansion upon exiting the capillary exit orifice  19 , and the ions, droplets, and aerosol particles typically acquire velocity distributions that are similar to that of the gas molecules in the expanding gas. Hence, the kinetic energy acquired by any such species will be more or less proportional to the mass of the species. Consequently, droplets and aerosol particles may acquire kinetic energies orders of magnitude larger than the ions of interest. 
         [0052]    The ions, droplets, and aerosol particles pass through the orifice  20  of skimmer  21 , which is mounted via electrical insulator  22  so that a voltage may be applied to the skimmer to focus charged particles into pumping stage  3  downstream of the skimmer. Ions, droplets, and aerosol particles that pass through the skimmer  21  orifice  20  proceed into the entrance end  23  of linear multipole ion guide  24  along ion beam axis  36 , which is essentially the axis of the capillary  10  bore  17 , as well as that of skimmer  21  orifice  20 . Linear multipole ion guide  24  is a hexapole ion guide comprising six rods  25  arranged symmetrically about a common axis  26 . Multipole ion guides comprising four, eight, or more than eight such rods may be used as well. In the embodiment of the invention illustrated in  FIG. 1 , the linear multipole ion guide  24  axis  26  and the axis  36  are oriented at an angle  37  relative to each other. However, in other embodiments of the invention, the linear multipole ion guide axis  26  may be coaxial with the axis  36  of capillary  10  bore  17  and skimmer  21  aperture  20 . 
         [0053]    Multipole ion guide  24  rods  25  are supported via insulators  27  and vacuum partition  28  in such a configuration that essentially the only conduit for gas flow between vacuum stages  3  and  4  is the spaces within and between the rods  25 . In some constructions, gas may also flow through spaces proximal to and outboard of the rods  25 . Hence, multipole ion guide  24  is configured to extend continuously between vacuum pumping stages  3  and  4  while restricting the flow of gas between the vacuum pumping stages  3  and  4 . Ions which enter the multipole ion guide  24  at entrance end  23  are guided along the multipole ion guide  24  axis  26  by oscillating RF electric fields generated by alternating RF voltages applied to the rods  25  of multipole ion guide  24 . The RF fields within the ion guide  24  prevent ions from passing beyond the rods  25  in directions orthogonal to the ion guide  24  axis  26 , while ions move along essentially parallel to the ion guide axis  26  to the ion guide exit end  29 . 
         [0054]    Ions exit the multipole ion guide  24  through exit end  29  and are directed through aperture  30  in vacuum partition  31 . The ions then proceed into the entrance  32  of a quadrupole mass filter  33 . Ions are filtered in quadrupole mass filter  33  in according to their mass-to-charge values, and ions which successfully traverse the quadrupole mass filter  33  then pass through the quadrupole mass filter  33  exit aperture  34 . These ions are then detected by directing them into detector  35 , or by directing them to impact conversion dynode  36 , which creates secondary charged particles, which are then directed into detector  35  for detection. 
         [0055]    In the embodiment illustrated in  FIG. 1 , the large majority of background particles, such as charged and uncharged droplets and aerosol particles, energetic ions and neutral species, which may originate in the ion source  1 , and/or capillary  10  bore  17 , and or in the region between the capillary  10  exit  18  and the skimmer  21  aperture  20 , and/or between the skimmer  21  aperture  20  and the ion guide entrance  23 , fail to respond, or respond poorly, to the RF fields in the ion guide  24 , and proceed more or less along their trajectories past the ion guide  24  entrance  23  to impact surfaces before reaching quadrupole entrance  32  of quadrupole mass filter  33 . Such surfaces may include the surfaces of ion guide  24  rods  25 , vacuum partition  28 , insulators  27 , and vacuum partition  31 . 
         [0056]    Simultaneously, ions which do respond adequately to the RF fields within the ion guide  24  are guided along ion guide axis  26 . The background gas pressure within the portion of ion guide  24  that extends into vacuum pumping stage  3  is at a pressure high enough that collisions between the ions and background gas molecules occurs, which reduced the kinetic energies of the ions as they traverse ion guide  24 . Generally, the average background gas pressure within this portion of ion guide  33  is at least high enough that the mean free path between collisions between ions and background gas molecules is greater than approximately the distance that the ions must traverse between the ion guide  24  entrance end  23  to the location  40  proximal to where ion guide  24  passes through vacuum partition  28 . Hence, ions that are guided along the axis  26  of ion guide  24 , and lose kinetic energy due to such collisions, will settle closer to axis  26  as their kinetic energy decreases, due to the action of the well-known, so-called ‘pseudopotential’ well that is formed by the RF fields within the ion guide  24  along ion guide  24  axis  26 . 
         [0057]    Once the ions move through ion guide  24  into vacuum pumping stage  4 , which is at a lower background gas pressure such that collisions between ions and background gas molecules essentially do not occur, the ions move from the vicinity of vacuum partition  28  to the ion guide  24  exit end  29  without any significant collisions with background gas molecules. Hence, the last location in the apparatus illustrated in  FIG. 1  at which background particles may be created by collisions between ions and background gas molecules is location  40  within ion guide  24  proximal to and downstream of vacuum partition  28 . 
         [0058]    As the ions reach the exit end  29  of ion guide  24 , they are directed through aperture  30  in vacuum partition  31 , and then into quadrupole mass filter  33  through quadrupole mass filter entrance  32 , while the ion beam direction is changed through angle  39  from axis  26  of ion guide  24  to axis  37  of mass filter  33 . Any background particles that had been created at location  40 , or any background particles which may originate upstream of location  40 , may have a line-of-sight trajectory through quadrupole entrance  32 , but will not have line-of-sight trajectory past aperture  34  to the detector  35  or any surface in the region of detector  35 , due to the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and the location  40 . Hence, such background particles are prevented from creating background particle noise by impacting detector  35  or conversion dynode  36  or surrounding surfaces in the region of detector  35  and conversion dynode  36 . 
         [0059]    Such background particles may include, for example, any background particles emerging through capillarylo exit orifice  19 , or background particles created between capillary  10  exit orifice  19  and ion guide  24  entrance  23 , which may have trajectories that were skewed relative to capillary  10  bore  17  axis  16 , such that some of them may have line-of-sight from regions upstream of the ion guide  24  entrance  23  through mass analyzer  33  entrance  32 . Alternatively, other embodiments of the invention may be configured with angle  38  equal to zero, in which case many more of these background particles would be expected to pass through mass analyzer  33  entrance  32 . In either configuration, the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and the locations upstream of ion guide  24  entrance  23  where such background particles may be created, prevents any such particles from passing through aperture  34  to the detector  35  or any surface in the region of detector  35 . 
         [0060]    Other background particles that are prevented from reaching detector  35  or surrounding surfaces, according to the invention, include energetic neutral species that may be created by collisions between ions and background gas molecules within the portion of ion guide  24  that is located in higher gas pressure regions where such collisions occur. According to the invention, the creation of such background particles in regions such as in vacuum pumping stage  3  and in regions proximal to vacuum partition  28  up to location  40 , are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and the locations within ion guide  24  upstream of location  40  where such background particles may be created. Consequently, according to the invention, such background particles will also be prevented from creating background particle noise by impacting detector  35  or conversion dynode  36  or surrounding surfaces in the region of detector  35  and conversion dynode  36 . 
         [0061]    Hence, in the embodiment of the invention illustrated in  FIG. 1 , a linear multipole ion guide is configured to uniquely provide improved ion transport through a vacuum partition, while simultaneously reducing background particle noise caused by background particles created in collisions between ions and background gas molecules, as well as background particles originating with an ion source. 
         [0062]    An alternative embodiment of the invention is illustrated in  FIG. 2 , where elements corresponding to the same functional elements as in  FIG. 1  are labeled the same.  FIG. 2  illustrates an embodiment of the invention in which a linear multipole ion guide  24  extends continuously through two vacuum partitions  42  and  28 , from the first vacuum stage  2  in which the capillary  10  exit orifice  19  is located, through the second vacuum pumping stage  3  and into the third vacuum pumping stage  4 . In this embodiment, the skimmer  21  of  FIG. 1  has been eliminated, and a flat lens electrode  41  with aperture  43  is positioned between capillary  10  exit orifice  19  and ion guide  24  entrance  23 . This arrangement allows improved ion transport efficiency between the capillary  10  exit orifice  19  and ion guide  24  entrance  23  than the configuration of  FIG. 1 , due primarily to the closer proximity allowed by the configuration of  FIG. 2 , compared to that of  FIG. 1 , between capillary  10  exit orifice  19  and ion guide  24  entrance  23 . The ions are re-directed by the RF fields within ion guide  24  to move along ion guide  24  axis  26  rather than capillary  10  axis  36  upon entering ion guide  24  entrance  23 . Again, background particles originating upstream of location  40 , are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and any locations upstream of location  40  where background particles may be created. Consequently, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise according to this embodiment of the invention. 
         [0063]    Alternative embodiments of the invention may incorporate additional features, including ion guides which extend continuously into more than three vacuum pumping stages, as well as ion guides which incorporate a bend or curved section along the ion guide axis. Such features are illustrated in the embodiment of the invention shown in  FIG. 2A , which illustrates a four-stage vacuum pumping system, in which, similar to the configuration of  FIG. 2 , the entrance  23  of multipole ion guide  24  begins in the first vacuum pumping stage  2 . Ions flowing from capillary  10  exit orifice  19  pass through aperture  43  in lens electrode  41  and into entrance  23  of multipole ion guide  24 . The ions are re-directed by the RF fields within ion guide  24  to move along ion guide  24  axis  26  rather than capillary  10  axis  36  upon entering ion guide  24  entrance  23 . As in the embodiment of  FIG. 2 , ion guide  24  is configured to extend continuously from the first vacuum pumping stage  2 , through vacuum partition  42 , the second vacuum pumping stage  3 , and through vacuum partition  28 . However, in the configuration illustrated in  FIG. 2A , ion guide  24  also extends continuously through the third vacuum pumping stage  4 , through the vacuum partition  45 , and into vacuum pumping stage  5 , in which the mass analyzer  33  and detector  35  are located. Once the ion guide  24  has extended into vacuum pumping stage  5 , ion guide  24  is configured with a bend  44  in the ion guide axis  26 , where the bend is configured with a bend angle that is equal to the angle  39  between the ion guide  24  axis  26  along the portion of ion guide  24  upstream of the bend  44  and the mass analyzer axis  37 , so that the ion guide axis  26  of the portion of the ion guide  24  downstream of the bend  44  is coaxial with the mass analyzer axis  37 . Hence, the bend  44  in the ion guide  24  may provide better ion transmission as ions are re-directed through angle  39  from their direction along ion guide  24  axis  26  upstream of the bend  44  and mass analyzer axis  37 , relative to the configuration illustrated in  FIG. 2 . Again, background particles originating upstream of location  40 , are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and any locations upstream of location  40  where background particles may be created. Consequently, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise according to this embodiment of the invention. 
         [0064]    An alternative modification of the embodiment of  FIG. 2  is shown in  FIG. 3 .  FIG. 3  illustrates that the invention may be configured similar to the embodiment of  FIG. 2 , the primary difference being that a tilted linear multipole ion guide is segmented into two separate and independent ion guide segments along a common tilted ion guide axis  26 . The first ion guide segment  48  is configured with ion guide rods  49  and extends continuously from the ion guide entrance  23  in the first pumping stage  2 , through vacuum partition  42 , and into vacuum pumping stage  3 , where the first ion guide segment ends at ion guide segment  48  exit end  50 . After a small gap  51 , the second ion guide segment  52  extends continuously from the ion guide segment  52  entrance end  54  in vacuum stage  3 , through vacuum partition  28  into vacuum pumping stage  4 . 
         [0065]    Ions exiting capillary  10  exit orifice  19  pass into ion guide segment  49  entrance end  23  and are guided by RF fields within ion guide segment  49 , through vacuum partition  42  to ion guide segment  49  exit end  50 . From ion guide segment  49  exit end  50 , the ions are directed across the gap  51  into the entrance end  54  of ion guide segment  52 . The RF fields within ion guide segment  52  act to guide the ions to ion guide segment  52  exit end  29 . The ions are then directed through orifice  30  into mass analyzer entrance  32  for mass analysis and detection with detector  35 . 
         [0066]    Because the ion guide segments  48  and  52  are operated independently, they may have different RF and DC voltages applied. In particular, they may have the same RF voltages applied, but different DC offset voltages applied to each of them, which results in acceleration of ions from ion guide segment  49  exit end  50 , across gap  51 , and into the entrance end of ion guide segment  52 . The vacuum stage  3  in which gap  51  is located has a background gas pressure that is high enough that collisions occur between ions and background gas molecules. If the acceleration of ions across gap  51  is strong enough, then collisions between ions and background gas molecules will result in collision induced dissociation (CID) of the ions into fragment ions and neutrals. The fragment ions, and any remaining ‘parent’ ions, will be guided through ion guide  52 , and their kinetic energy, which may have been increased as a result of accelerating across gap  51 , will be damped by subsequent collisions with background gas molecules as the ions move between gap  51  and location  40 , after which the background gas pressure is low enough that collisions between ions and background gas molecules do not occur. Again, background particles originating upstream of location  40 , in this case, in particular, energetic neutral species created as a result of the CID collisions, are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and any locations upstream of location  40  where background particles may be created. Consequently, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise according to the invention. 
         [0067]      FIG. 4  illustrates a modification of  FIG. 3 , in which the first ion guide segment  48  in  FIG. 3  is oriented coaxial with capillary  10  axis  36 , and extends not only through the vacuum partition  42  between the first vacuum pumping stage  2  and the second vacuum pumping stage  3 , but also extends through an additional vacuum partition  56  (compared to the embodiment of  FIG. 3 ) that divides the vacuum pumping stage  3  of  FIG. 3  into an additional vacuum pumping stage, which is shown in  FIG. 4  as vacuum pumping stage  55 . Ion guide segment  58  exit end  59  is positioned in the third vacuum pumping stage  55  in  FIG. 4 . The second ion guide segment  52  is then oriented at an angle  38  with respect to the axis  36 , and the configuration of this embodiment is the same as in  FIG. 3  downstream of the gap  51 . 
         [0068]    The advantage of the embodiment shown in  FIG. 4 , relative to the embodiment of  FIG. 3 , is that ions that enter the first ion guide segment  58  along axis  36  may proceed along ion guide segment  58  and experience collisional cooling of ion kinetic energy before their beam direction is re-directed from the capillary  10  axis  36  to the ion guide segment  52  axis  26 . Cooling the ion‘s kinetic energy improves the efficiency with which the RF fields within an ion guide are able to re-direct the ions’ beam path, because the effectiveness of a particular RF field strength for guiding or re-directing ions decreases as the kinetic energy of the ions increases. Hence, allowing the ions’ kinetic energy to dampen in collisions with background gas molecules in vacuum stage  3  of  FIG. 4  ensures better capture and re-direction efficiency with the ion guide segment  58  of  FIG. 4 , relative to the ion guide segment  48  of  FIG. 3 , for example. This becomes particularly important for higher mass-to-charge ions, which have kinetic energies roughly proportional to their mass as they exit the capillary  10  exit orifice  19  with the velocity distribution similar to that of the expanding gas. Also, as in the embodiment of  FIG. 3 , the RF and DC voltages applied to the ion guide segments  58  and  52  may be different, allowing CID to be performed similarly to the embodiment of  FIG. 3  as discussed above. 
         [0069]    Another alternative embodiment of the present invention is illustrated in  FIG. 5 . This embodiment is configured with an ion guide  24  that is configured with two bends  60  and  44  in the ion guide  24  axis  26  such that the ion guide  24  axis  26  at the ion guide  24  entrance end  23  is coaxial with capillary  10  axis  36 , and the ion guide  24  axis  26  at the ion guide  24  exit end  29  is coaxial with mass analyzer  33  axis  37 . Hence, the ion beam direction may be changed from capillary  10  axis  36  to the ion guide  24  axis  26  at the ion guide  24  entrance end  23 , and from the ion guide  24  axis  26  at the ion guide  24  exit end  29  to the mass analyzer  33  axis  37 , while the ions remain within the guiding RF fields of the ion guide  24 , thereby ensuring efficient ion transport during such changes in beam direction. Also, the portion of the ion guide  24  between the ion guide entrance  23  and the bend  60 , which is coaxial with the capillary  10  axis  36 , allows ion kinetic energy to cool before the beam is re-directed at bend  44 , thereby further ensuring efficient ion transport through the bend  44  even for higher mass ions. As discussed above, such higher mass ions will have higher kinetic energy upon exiting through capillary  10  exit orifice  19 , making them more difficult to re-direct with RF fields prior to collisional cooling of their kinetic energy. 
         [0070]    Again, background particles originating upstream of location  40 , are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  between the ion guide bends  44  and  60 , and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and any locations upstream of location  40  where background particles may be created. Consequently, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise according to this embodiment of the invention. 
         [0071]    For the sake of lower manufacturing cost and more straightforward instrument design, the angles  38  and  39  may be arranged to be essentially equal and opposite in direction, thereby configuring the capillary  10  axis  19  to be parallel to the mass analyzer  33  axis  37 . Also, the embodiment of  FIG. 5  is shown to be configured with an insulator  65  supporting the exit end  29  of ion guide  24  and increasing the gas flow restriction between vacuum pumping stages  4  and  5 , in addition to the gas flow restriction provided by aperture  30  in vacuum partition  31 . 
         [0072]    Additional modifications of the embodiment of the invention shown in  FIG. 5  may be incorporated. For example, the embodiment of the invention illustrated in  FIG. 5A  shows an ion guide also configured with two bends  60  and  44 , as in  FIG. 5 , but where the skimmer  21  is removed, and is replaced by vacuum partition  42  through which ion guide  24  extends such that ion guide  24  entrance  23  is located in the first vacuum pumping stage  2 , while ion guide  24 , along with ion guide  24  insulator  22 , forms the restricted conduit for gas flow between vacuum pumping stages  2  and  3 . Also, flat lens electrode  41  with aperture  43  is positioned between capillary  10  exit orifice  19  and ion guide  24  entrance  23 . This arrangement allows better ion transport efficiency between the capillary  10  exit orifice  19  and ion guide  24  entrance  23  than the skimmer  21  configuration of  FIG. 5 , due primarily to the closer proximity allowed by the configuration of  FIG. 5A , compared to that of  FIG. 5 , between capillary  10  exit orifice  19  and ion guide  24  entrance  23 . Further, the insulator support  65  and vacuum partition  31  with aperture  30  of the embodiment of  FIG. 5  is reconfigured in  FIG. 5A . As vacuum partition  66  and insulator  67 , which supports ion guide  24  proximal to ion guide exit end  29 , and, together with ion guide  24 , forms the gas flow restriction between vacuum pumping stages  4  and  5 . 
         [0073]    Again, background particles originating upstream of location  40 , are prevented from having line-of-sight trajectory paths from their point of creation through to the detector  35 , or to regions surrounding detector  35 , due to the angle  39  between the axis  26  of ion guide  24  between the ion guide bends  44  and  60 , and the axis  37  of mass analyzer  33 , in combination with the distance between mass analyzer  33  entrance  32  and any locations upstream of location  40  where background particles may be created. Consequently, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise according to this embodiment of the invention. 
         [0074]    An additional embodiment of the invention is depicted in  FIG. 6 , which illustrates essentially the configuration that was shown in  FIG. 1 , but where the ion guide  24  is replaced by one which incorporates two bends  44  and  60  similar to the bends  44  and  60  in the ion guide  24  of  FIGS. 5 and 5A . Because ion guide  24  of  FIG. 6  extends only through one vacuum partition  28 , the construction of this embodiment may be less costly and more straightforward to manufacture and assemble than the embodiments shown in  FIGS. 5 and 5A . However, the background gas pressure in vacuum stage  5  where the mass analyzer is located may not be as low as in the embodiments of  FIGS. 5 and 5A . 
         [0075]    All of the embodiments of the invention discussed above have incorporated an ion guide where at least one portion of the ion guide is configured as a linear ion guide portion. Alternatively, according to the present invention, the entire ion guide may be configured completely curved. For example,  FIG. 7  illustrates another embodiment of the present invention which incorporates a multipole ion guide  24  with a central axis  26  that follows the path of a ninety-degree segment of a circle, and which also extends through a vacuum partition  28 . Ions exiting capillary  10  orifice  19  pass through skimmer  21  aperture  20  and into the entrance  23  of curved ion guide  24 . The axis of curved ion guide  24  is configured to be coaxial with axis  36  of capillary  10  at the entrance  23  of curved ion guide  24 . The background gas pressure in vacuum stage  2  is high enough that collisions between ions and background gas molecules occur as ions traverse the ion guide within this vacuum stage. However, the background gas pressure within vacuum stage  4  is low enough that collisions between ions and background gas molecules essentially do not occur as ions traverse the ion guide  24  within the vacuum stage  4 , at least downstream of location  40 . In the configuration of  FIG. 7 , background particles originating upstream of location  40  do not have line-of-sight trajectories that allow them to pass through aperture  30  in lens  70 , which forms part of vacuum partition  68  along with insulator  69 . Consequently, according to this embodiment of the invention, all background particles will be prevented from impacting detector  35 , or conversion dynode  36 , or surrounding surfaces in the region of detector  35  and conversion dynode  36 , and are thereby are prevented from creating background particle noise. 
         [0076]    An alternative arrangement to the embodiment illustrated in  FIG. 7  is shown in  FIG. 7A . The difference between the embodiments of  FIGS. 7 and 7A  is that lens  70  of  FIG. 7  is removed, and curved ion guide  24  extends continuously through vacuum partition  68 , where insulator  69  now not only forms part of the vacuum partition, but also provides support for the rods  25 . Hence, the conductance restriction to gas flow that had been provided by aperture  30  in lens  70 , in  FIG. 7 , is now provided by the limited open spaces within, between, and otherwise proximal to the rods  25  of ion guide  24 . This configuration may provide better ion transmission from the ion guide  24  exit  29  into the mass analyzer  33  entrance  32  due to the elimination of aperture  30 . 
         [0077]    Another alternative embodiment of the invention is illustrated in  FIG. 8 .  FIG. 8  depicts an embodiment of the present invention in a so-called ‘triple quad’ configuration, in which ions from an ion source  1  are transported via a tilted ion guide  24  to a quadrupole mass filter  33  in vacuum pumping stage  5 . ‘Parent’ ions to be subsequently fragmented to produce ‘daughter’ ions are selected in quadrupole mass filter  33 , and are focused and accelerated through lens  71 , which is shown in  FIG. 8  as a three-element lens, along the quadrupole mass filter axis  72  into collision cell  73 . The accelerated parent ions collide with collision gas molecules in collision cell  73  with enough kinetic energy that the parent ions fragment into daughter ion fragments and neutral fragments. Collision cell  73  comprises curved quadrupole ion guide  77  within enclosure  84 , and is provided within the enclosure  84  with collision gas  76  via regulator valve  75  and gas delivery tube  74 . Curved ion guide  77  could alternatively be configured with six, or eight, or more than eight rods. Fragment ions and any remaining parent ions are guided to the collision cell exit aperture  85  by curved ion guide  77 , where the ions are focused through three-element focus lens  80  into quadrupole mass filter  81  in vacuum pumping stage  6 , and then the mass analyzed ions are detected with detector  35 . 
         [0078]    The configuration of the embodiment depicted in  FIG. 8  is shown to be essentially the same as the configuration of  FIG. 1  from the ion source through quadrupole mass filter  33 . Therefore, background particles produced upstream of location  40  in ion guide  24  are prevented from line-of-sight past the aperture of lens  71  at the exit end of quadrupole mass filter  33 , due to the tilt angle  39 , as well as tilt angle  38  in this case, as discussed above in relation to the embodiment of  FIG. 1 . Consequently, such background particles are prevented from entering collision cell  73 . Energetic background particles, which would not have been filtered very well with quadrupole mass filter  33  due to their high energy and/or lack of charge, if allowed to enter collision cell  73 , would have collided with collision gas molecules to produce background fragment ions from the background particles. Such background fragment ions would appear in the fragment ion mass spectra produced by quadrupole mass filter  81 , and would complicate the analysis. 
         [0079]    Moreover, the curved collision cell, according to this embodiment of the invention, prevents a line-of-sight from anyplace along axis  72  within collision cell  73 , to mass analyzer detector  35  or surfaces in the vicinity of detector  35  downstream of exit lens  88 . Hence, any energetic fragment ions or neutral fragments that are created as a result of collisions between ions and collision gas molecules in the collision cell  73 , will not have line-of-sight to the detector  35 , and therefore will be prevented from created background particle noise, according to this embodiment of the invention. Additionally, the transmission for ions between vacuum stage  5  and vacuum stage  6  is enhanced by configuring the collision cell  73  to extend continuously between vacuum stages  5  and  6 . 
         [0080]    The embodiment of the invention illustrated in  FIG. 9  is essentially identical to the embodiment of  FIG. 8 , except that the curved rods  78  of curved ion guide  77  are mounted via insulator  79  which forms an extension of the collision cell  73  enclosure  84 . This configuration allows curved collision cell ion guide  77  to extend continuously from inside the collision cell to outside the collision cell, as illustrated in  FIG. 9 . Such a configuration, according to the present invention, provides better ion transport efficiency for ions exiting the collision cell, as well as lower background particle noise, in comparison with the conventional arrangement of an exit aperture  85  which forms an extension to collision cell enclosure  84  as shown in  FIG. 8 . The reason for the better ion transport efficiency of  FIG. 9  is that, in the embodiment of  FIG. 8 , ions may be scattered by the RF fringe fields at the exit aperture  85  due to the RF voltages applied to the curved rods  78  of curved ion guide  77 . Ions are also scattered, in the embodiment of  FIG. 8 , by collisions with collision gas molecules in the regions proximal to exit aperture  85  as they pass out of the guiding RF fields within curved ion guide  77  and through the exit aperture  85  in the embodiment of  FIG. 8 , resulting in ion loss, as well as the creation of background particles that are created from such collisions. In contrast, in the embodiment of  FIG. 9 , ions are guided by the RF fields within curved ion guide  77  through the exit  87  of curved collision cell  84  of  FIG. 9 , and only pass out of these guiding RF fields and through exit aperture  85  within vacuum stage  6 , that is, within a background gas pressure that is low enough that collisions between ions and background gas molecules essentially do not occur, resulting in better ion transport efficiency, as well as the avoidance of the creation of background particles as ions pass through the RF fringe fields proximal to aperture  85 . 
         [0081]    Furthermore, lower background particle noise is provided by the configuration of  FIG. 9 , compared to that of  FIG. 8 , also because the last location at which ions may collide with collision gas molecules is location  86  in  FIG. 9 , just downstream of collision cell exit  87 . Location  86  occurs in ion guide  77  some distance upstream of exit aperture  85 , that is, where curved ion guide  77  is still curving. Because of this arrangement, background particles created in collisions between ions and collision gas molecules at location  86  do not have line-of-sight to detector  35 , or surfaces in the region of detector  35  downstream of quadrupole exit lens  88 . Hence, the extension of ion guide  77  continuously through collision cell partition  84  via mounting insulator  79  provides both improved ion transport from collision cell  73  into subsequent quadrupole mass filter  81 , while preventing background particles resulting from collisions between ions and collision gas molecules from creating background particle noise at the detector  35 , according to the embodiment of the invention of  FIG. 9 . 
         [0082]      FIG. 10  illustrates an embodiment of the invention which is essentially the same as the embodiment of  FIG. 9 , except that the collision cell  73  ion guide  77  of  FIG. 9  is segmented into three separate and independent ion guide segments  90 ,  91 , and  92  in the embodiment of  FIG. 10 , where any or all ion guide segment  90 ,  91 , and  92  may have the possibility of separate DC and RF voltages applied. Configuring the ion guide in collision cell  73  into segments  90 ,  91 , and  92  affords additional capabilities relative to the embodiment of  FIG. 9 . For example, fragment ions may be produced via CID by accelerating parent ions into ion guide segment  90  from quadrupole mass filter  33 . Simultaneously, RF voltages may be applied to the rods of ion guide segment  90  which cause resonant-frequency excitation radial ejection of all ions except fragment ions with a selected m/z value. These m/z selected fragment ions may then be axially-accelerated by a DC offset voltage difference between ion guide segments  90  and  91 , resulting in CID of the selected fragment ions. The resulting second generation fragment ions may then be m/z analyzed by directing them through ion guide segment  92  and into mass analyzer  81  and detector  35 . 
         [0083]    In any of the embodiments of the invention described above, it is to be understood that any of the ion guides or ion guide segments may be configured as a quadrupole ion guide, having four poles, or rods, arranged symmetrically about a central axis, as shown in cross-section in  FIG. 11A . Alternatively, a greater number of rods, or poles, may be utilized in any of the RF ion guides or ion guide segments described previously. For example six rods or poles may be incorporated, as illustrated in  FIG. 11D , or eight poles or rods as depicted in  FIG. 11C , or more than eight rods or poles may be used in any of the ion guides or ion guide segments described herein. Also, it is to be understood that any of the ion guides or ion guide segments described herein may be configured with poles that are not circular in cross-section. For example, flat plates are also within the scope of the present invention, as illustrated in the quadrupole arrangement of  FIG. 11B . Further, it is also within the scope of the invention that so-called ‘stacked-ring’ RF ion guides may be incorporated as an ion guide for the transport of ions in any of the embodiments of the invention. 
         [0084]    It should also be understood that, while the embodiments described herein have incorporated an ESI ion source as the source of ions, any ion source may be used in any of the embodiments‘instead, within the scope of the invention. In particular, other ion sources that operate at or near atmospheric pressure, such as atmospheric pressure chemical ionization (APCI), inductively coupled plasma (ICP), and atmospheric pressure (AP-) MALDI and laser ablation ion sources, may be incorporated within the scope of the invention. Other types of ion sources which operate at intermediate vacuum pressures, such as glow discharge or intermediate pressure (IP-) MALDI and laser ablation ion sources, or other types of ion sources that are configured in a vacuum region in which the vacuum pressure rises significantly during operation of the ion source, such as electron ionization and chemical ionization ion sources, may also be used within the scope of the invention. 
         [0085]    In addition, it is to be further understood that the method and/or apparatus that is employed to transport ions from the ion source to the entrance of the first ion guide is not limited to a dielectric capillary interface as described in the aforementioned embodiments, but may also include, within the scope of the invention, a metal capillary, a nozzle or orifice, an array of orifices, or any other conduit that may be used for this purpose, as appropriate for the ion source and vacuum conditions at hand. 
         [0086]    Furthermore, it is to be understood that, while a quadrupole mass filter has been configured in the embodiments described herein, the scope of the invention also encompasses other types of mass analyzers, including three-dimensional ion traps, magnetic sector mass analyzers, time-of-flight mass analyzers with either axial pulsing or orthogonal pulsing, two-dimensional ion traps with axial resonant ejection. 
         [0087]    Although the present invention has been described in accordance with the embodiments shown, one of ordinary skill in the art will recognize that there could be variations to the embodiments, and those variations would be within the spirit and scope of the present invention. 
         [0088]    It should be understood that the preferred embodiment was described to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth to which they are fairly legally and equitably entitled.