Patent Publication Number: US-6661003-B2

Title: Dielectric capillary high pass ion filter

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of application Ser. No. 09,429,063, filed Oct. 29, 1999, now U.S. Pat. No. 6,486,469. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention has been created without the sponsorship or funding of any federally sponsored research or development program. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to mass spectrometry and, particularly, to delivery of ions from a higher pressure ion source through a tubular interface to a mass analyzer operating at high vacuum. 
     BACKGROUND 
     Mass spectrometers have been shown to be particularly useful for analysis of liquid or gaseous samples, and mass spectrometry (“MS”) can be coupled with gas chromatography (“GC”) or liquid chromatography (“LC”) for analysis of substances having a wide range of polarities and molecular weights in samples obtained from a wide range of sources. 
     Mass spectrometers employing atmospheric pressure ionization (“API”) techniques can be particularly useful for obtaining mass spectra from liquid samples, and MS employing such ion sources are frequently used in conjunction with high performance liquid chromatography (“HPLC”), and combined HPLC/MS systems are commonly used for analysis of polar and ionic substances, including biomolecular species. In API techniques a liquid sample containing a mobile phase (e.g., solvent) and analytes is introduced into an ionization chamber and there converted to a charged dispersion or aerosol of fine droplets from which ions emerge as the liquid evaporates and the droplets shrink in size. The conversion of liquid to spray or aerosol can be accomplished by any of a variety of techniques. Evaporation of the liquid can be assisted, for example, by passing a flow of warm gas (“drying gas”) through the cloud of droplets. 
     In mass spectrometry apparatus, an interface must be provided between a source of ions to be analyzed, which is typically at high-pressure (at or near atmospheric pressure in API sources), and the enclosure for the mass analyzer, which is typically at very low pressure. In one approach, a tube, having a bore usually of capillary dimension, serves as a conduit for the ions. One end of the capillary opens into the ionization chamber at about atmospheric pressure, and the other end of the capillary opens into the high vacuum chamber. 
     In some such apparatus the capillary interface is constructed of a dielectric material such as a glass and is provided at the ends with electrodes that are connected with sources of electrical potential. See, for example, U.S. Pat. No. 4,542,293. In conventional operation using a dielectric capillary interface the electrode at the upstream end of the capillary, in the ionization chamber, is held at a high magnitude electrical potential (typically in the range −3000V to −6000 V for operation in a “positive ion” mode; the polarity is reversed for operation in a “negative ion” mode) and the electrode at the downstream end of the capillary, in the vacuum chamber, is held at a lower magnitude and oppositely charged electrical potential (typically in the range +50 V to +400 V for operation in a “positive ion” mode). Ions are entrained in the flow of gas into the inlet end of the capillary from the higher pressure ion source chamber and carried with the gas, against the opposing electrical field, through the lumen of the capillary and out through the exit end of the capillary into the low pressure chamber downstream. 
     Various mass spectrometry apparatus employing a capillary interface between an atmospheric pressure ionization (“API”) ion source and the mass analyzer are described, for example, in U.S. Pat. No. 5,838,003 (electrospray ionization [“ESI”]), U.S. Pat. No. 5, 736,741 (ESI and atmospheric pressure chemical ionization [“APCI”]), U.S. Pat. No. 5,726,447 (corona discharge ionization). These and any other patents and other publications referred to in this application are hereby incorporated herein in their entirety. 
     Considerable interest has developed, particularly in the pharmaceuticals and medical diagnostics industries, in employing mass spectrometry to analyze large numbers of samples that contain only a few analytes of interest. Typically the sources of the samples are biological fluids such as urine or blood. Samples from such sources contain significant quantities of substances that are not of interest in the analysis, and sample treatment for removal of these substances makes up a significant proportion of the cost of such analyses. Accordingly, some effort has been directed toward reducing the extent of sample treatment prior to introducing the sample to mass spectrometry apparatus. In one approach, tandem mass spectrometry (“MS/MS”) has been used in an effort to reduce the need for sample preparation for simple target compound analysis. MS/MS systems are significantly more costly than MS systems. 
     Techniques have been proposed for separating ions according to their mobility. In such ion mobility separation “IMS” techniques, an accelerating electrical potential is employed, to move ions against a countercurrent gas flow. In IMS, ions having higher mobility have higher drift velocities. 
     SUMMARY 
     We have discovered that high pass ion filtration can be effected within a dielectric capillary interface between a higher pressure ionization chamber and the lower pressure environment of a mass analyzer in mass spectrometry apparatus, by application of electrical potentials to end electrodes and to at least one electrode associated with the dielectric capillary between the ends, to create an end-to-end electric field generally opposing the gas flow-assisted movement of ions from the upstream end to the downstream end, and to create a steeper voltage gradient along an upstream portion than along a downstream portion of the capillary. The voltage gradient along the steeper upstream portion of the capillary is sufficiently steep to cause ions having high mobility and having drift velocities below a lower limit to stall within the capillary. The respective potentials may be adjusted to increase the steepness of the upstream voltage gradient to increase the drift velocity lower limit. 
     The apparatus is inexpensive to construct and simple to operate. Because movement of ions from the higher pressure ionization chamber to the vacuum chamber is according to the invention assisted by gas flow through the capillary interface, ions having higher mobility have lower drift velocities. The high pass ion filter according to the invention can provide for removal of lower drift velocity ions from the population of ions that are delivered to the mass analyzer. 
     Accordingly, in one general aspect the invention features a conduit for transporting ions from a higher pressure ion source to a mass analyzer at high vacuum in mass spectrometry apparatus. The conduit includes a tube constructed of a dielectric material and defining a capillary bore extending from end to end and having an end electrode associated with each end and at least one additional electrode associated with the tube between the ends. The electrodes are connected to a source of electrical potential. 
     Electrodes are connected to a source of electrical potential, as that term is used herein, when they are electrically connected to separate voltage sources, and also when any two or more of them are electrically connected to a common single source that is provided with circuitry (e.g., resistive networks) that can be used to apply different voltages to the 
     In operation, electrical potentials are applied at the end electrodes and the additional electrode to generate an end-to-end electric field having a voltage gradient that is steeper along an upstream portion of the conduit than along a downstream portion of the conduit. Ions are carried by the flow of gas from the ion source through the conduit to the high vacuum environment of the mass analyzer, against the end-to-end electrical field gradient. In a positive ion mode the upstream end is kept more electronegative than the downstream end, while in a negative ion mode the upstream end is kept more electropositive than the downstream end. According to the invention, the steeper gradient in the more upstream portion of the conduit retards the downstream movement of ions having drift velocities below a lower limit, so that they are prevented from passing through and out from the conduit. As the retarding voltage gradient is made steeper, the lower limit increases. 
     In some embodiments at least two additional electrodes are associated with the dielectric tube between the ends. 
     In another general aspect the invention features a method for delivering ions from a higher-pressure ionization chamber to a mass analyzer operating at high vacuum. The method employs a conduit that includes a tube constructed of a dielectric material and defining a capillary bore from end to end and having an electrode associated with each end and at least one additional electrode associated with the tube between the ends. According to the method, electrical potentials are applied to the electrodes to generate an end-to-end electric field having a voltage gradient that is steeper along an upstream portion of the conduit than along a downstream portion of the conduit. The steeper voltage gradient upstream retards the downstream movement of ions having lower drift velocities and thereby reduces the flow of ions having lower drift velocities through and out from the conduit to the mass analyzer. 
     The expression “drift velocity”, as that tern is used in describing the invention herein, is the mean ion velocity within the capillary in a direction from the ionization chamber toward the vacuum chamber. According to the invention, because ion movement from the ionization chamber toward the vacuum chamber is assisted by gas flow (against an opposing electrical potential gradient), ions having higher mobilities have lower drift velocities. 
     The invention is especially useful in qualitative and quantitative treatment of complex samples in analytical schemes employing mass spectrometry (“MS”) coupled with liquid chromatography (“LC”), usually high performance liquid chromatography (“HPLC”). The invention can be especially useful where an atmospheric pressure ionization (“API”) technique, such as electrospray ionization (“ESI”), or inductively coupled plasma ionization (“ICP”) or atmospheric pressure chemical ionization (“APCI”) is employed in LC/MS. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a diagrammatic sketch in a sectional view showing an embodiment of apparatus according to the invention. 
     FIG. 2 is a diagrammatic sketch in a sectional view showing an alternative embodiment of apparatus according to the invention. 
     FIG. 3 is a diagrammatic sketch in a sectional view showing another alternative embodiment of apparatus according to the invention. 
     FIG. 4 is a diagrammatic sketch in a sectional view showing an example of an embodiment of mass spectrometry apparatus employing apparatus according to the invention. 
     FIG. 5A is a diagrammatic sketch in sectional view of an embodiment of apparatus according to the invention, and FIG. 5B is a diagram of an idealized electric field over the length of the capillary interface in FIG. 5A in operation according to the invention. 
     FIG. 6A is a diagrammatic sketch in sectional view of an embodiment of apparatus according to the invention, and FIG. 6B is a diagram of an idealized electric field over the length of the capillary interface in FIG. 6A in operation according to the invention. 
    
    
     DETAILED DESCRIPTION 
     Particular embodiments will now be described in detail with reference to the drawings, in which like parts are referenced by like numerals. The drawings are not to scale and, in particular, certain of the dimensions may be exaggerated for clarity of presentation. 
     Referring now to the drawings, there is shown in FIG. 1, generally indicated by the reference numeral  10 , an embodiment of a conduit according to the invention. The conduit  10  includes a tube of a dielectric material, having a tube wall  12  defining a lengthwise bore or lumen  14  of capillary dimension. The tube has an inlet opening  17  to the lumen at an inlet end  16 , and an exit opening  19  at an exit end  18 . End electrode  20  is associated with the inlet end  16  and end electrode  22  is associated with exit end  18 . An additional electrode  24  is associated with the tube at a point along the tube length between the inlet end electrode and the outlet end electrode. When the apparatus is in operation, each of the electrodes is connected to a source of electrical potential (not shown in the Fig.). 
     FIG. 4 shows by way of example API mass spectrometry apparatus generally at  80 , having apparatus  10  as in FIG. 1 installed according to an embodiment of the invention. The apparatus  80  includes walls (e.g.,  82 ) defining an ionization chamber  83  in which the enclosed volume  84  is at higher pressure, typically about atmospheric pressure, when the apparatus is in operation; and walls (e.g.,  86 ) defining a vacuum chamber  85  (shown in part in the Fig.) in which the enclosed volume  88  is at reduced pressure, typically in the range 10 torr to 10 −8  torr. In some mass spectrometer configurations the vacuum chamber  85  may contain elements (not shown in the Fig.) such as, for example, a mass analyzer, that function at very high vacuum. In other configurations the vacuum chamber  85  may constitute a stage between the ionization chamber and mass analyzer and may contain, for example, ion optical elements or ion guides which operate under vacuum but not at very high vacuum characteristic of operation of the mass analyzer. 
     In the embodiment illustrated in FIG. 4, an electrospray assembly  96  is employed. The electrospray assembly receives liquid samples (arrow S) from a sample source (not shown in the Fig.), such as for example, a liquid chromatography device, and produces at an electrospray exit  95  an aerosol directed generally into an ionization region  90 . The tip of the electrospray assembly at the exit  95  is connected to a source of electrical potential (not shown), which may be held at ground potential or at some potential above or below ground potential, as described in further detail below. Formation of the aerosol may be assisted by use, for example, of pneumatic nebulization. 
     The volume within the ionization chamber  83  is maintained at about atmospheric pressure by exhaust through port  87 , and the volume within the downstream vacuum chamber  85  is maintained at the appropriate vacuum by pumping out through vacuum port  89 . Accordingly, a steep pressure gradient is maintained between the ionization chamber and the vacuum chamber. 
     Apparatus  10  is installed in mass spectrometry apparatus  80  as an interface between the ionization chamber and the vacuum chamber. The inlet end  16  with associated electrode  20  is located in ionization chamber  83  downstream from ionization region  90 , and the exit end  18  with associated electrode  22  is located in vacuum chamber  85 . A source  92  of drying gas provides a flow of heated gas to an enclosure formed by a cowl  94 , which directs the drying gas generally upstream (arrows DG) through an opening  97  toward the ionization region  90 , where it passes through the cloud of droplets formed by the electrospray assembly  96 . The cowl may be connected to a source of electrical potential, and may be employed to generate and to shape an electric field within the ionization chamber. 
     Gas (including vapor) together with ions formed in the ionization region  90  flows (arrow G +I in ) from the higher-pressure volume  84  into the inlet opening in the inlet end  16  of the capillary. In conventional operation, ions entrained in the gas flow within the lumen of the capillary are carried toward the lower pressure volume  88 , and emerge from the exit opening in the exit end  18  of the capillary into the downstream vacuum chamber  85 . 
     According to the invention, electric potentials are applied to the inlet and exit end electrodes  20 ,  22  and to the additional electrode  24 , to produce a steeper voltage gradient in an upstream portion than along a downstream portion of the capillary. Reference is now made to FIGS. 5A,  5 B. FIG. 5A shows apparatus  10 , generally as described with reference to FIG. 1, and FIG. 5B shows diagrammatically at  50  an idealized gradient of electrical potentials (V) generated over the length (L) of the capillary by application of selected electrical potentials at the electrodes. An electrical potential V cl  is applied at the additional electrode  24 , and an electrical potential V, is applied at the inlet electrode  20 , and an electrical potential V 0  is applied at the exit electrode  22 . The different voltages are set, according to the invention, so that the portion  52  of the voltage gradient generally upstream from the additional electrode  24  is steeper than the portion  54  of the voltage gradient more downstream. The voltages are set so that the steeper upstream portion  52  of the voltage gradient (over an upstream portion  53  of the capillary length) is sufficiently steep to cause ions having drift velocities below a selected lower limit to stall within the capillary lumen, and to drift to the walls of the capillary. As a result, the subpopulation I f  of ions emerging in the gas flow from the capillary exit (G+I f  in FIG. 4) and entering the free jet expansion in the vacuum chamber has a higher proportion of ions having drift velocities above the selected limit, than were present in the population I in  that had flowed into the capillary inlet. 
     In FIG. 5B the gradients are shown as relative absolute values. For operation in positive ion mode, for example, the input end voltage V i  is electronegative as compared with the exit end voltage V o . For operation in negative ion mode, for example, the input end voltage V i  is electropositive as compared with the exit end voltage V o . The additional electrode voltage V c1  is selected, according to the position of the electrode along the length of the capillary, and according to the operational mode, to provide a voltage gradient from the input electrode that is sufficiently steep to retard the passage of ions having drift velocities below the selected limit. In some embodiments the end-to-end potential difference (absolute value) is in the range 500 V to 8 kV, or in some embodiments 500 V to 5 kV. The potential difference (absolute value) between the additional electrode voltage V c1  and the inlet electrical potential V i  can be determined for a desired lower drift velocity threshold and for a particular device configuration readily and as a matter of routine. For example, an assortment of molecules having known masses may be tested using various potentials, and the extent to which the test molecules pass through the conduit can be determined by measuring the signal produced by ions arriving at a detector. The results can provide a voltage range calibration for the particular device for filtration of ions having a range of masses. 
     The drift velocities of ions passing through the conduit depend in part upon the kinetic energy of the ions, the drift velocities of a population of ions passing through the capillary can be raised or lowered by increasing or decreasing the temperature. This can be accomplished, for example, by heating or cooling the capillary, or by changing the temperature of the drying gas. 
     The effectiveness of the filter according to the invention can be improved providing more than one additional electrode at points along the length of the capillary and, in particular, by setting the voltages of any two or more pairs of electrodes to generate two or more retarding voltage gradients. Referring now to FIG. 2, there is shown generally at  11  apparatus according to the invention in which two separate retarding voltage gradients can be maintained. As in FIG. 1, the apparatus  11  in FIG. 2 includes a tube of a dielectric material, having tube wall  12  defining a lengthwise bore or lumen  14  of capillary dimension. The tube has an inlet opening  17  to the lumen at an inlet end  16 , and an exit opening  19  at an exit end  18 . End electrode  20  is associated with the inlet end  16  and end electrode  22  is associated with the exit end  18 . Additional electrodes  24 ,  26 ,  28  are associated with the tube at points along the tube length between the inlet end electrode and the outlet end electrode. Each of the electrodes is connected to a source of electrical potential (not shown in the Fig.). 
     To provide two retarding voltage gradients using apparatus according to the invention as in the embodiment of FIG. 2, electric potentials are applied to the inlet and exit end electrodes  20 ,  22 ; and to the additional electrode  24 , to produce a first steeper voltage gradient in the portion of the capillary between the inlet electrode  20  and the additional electrode  24 , and also to the additional electrodes  26 ,  28  to produce a second steeper voltage in the portion of the capillary between additional electrodes  26  and  28 . Reference is now made to FIGS. 6A,  6 B. FIG. 6A shows apparatus  11 , generally as described with reference to FIG. 2, and FIG. 6B shows diagrammatically at  60  an idealized gradient of electrical potentials (V) generated over the length (L) of the capillary by application of selected electrical potentials at the electrodes. Electrical potentials V c1 , V, c2 , V c3  are applied at the additional electrodes  24 ,  26 ,  28 , respectively, and electrical potentials V i , V o  are applied at the inlet and exit electrodes  20 ,  22 . The different voltages are set, according to the invention, so that the portion  62  of the voltage gradient generally upstream from the additional electrode  24  and the portion  66  of the voltage gradient generally between the additional electrodes  26 ,  28  are steeper than other portions, e.g.,  64 ,  68  of the voltage gradient elsewhere along the length of the capillary. The voltages are set so that the steeper upstream portion  62  of the voltage gradient (over an upstream portion  63  of the capillary length) is sufficiently steep to cause ions having drift velocities below a selected lower limit to stall within the capillary lumen, and to drift to the walls of the capillary, and, similarly, so that the steeper portion  66  of the voltage gradient (over a second portion  65  of the capillary length) is sufficiently steep to cause ions having drift velocities below a selected lower limit (which may be the same as or different from the lower limit selected for the upstream retarding gradient) to stall within the capillary lumen, and to drift to the walls of the capillary,. As a result, the subpopulation I f  of ions emerging in the gas flow from the capillary exit (G+I f  in FIG. 4) and entering the free jet expansion in the vacuum chamber has a higher proportion of ions having drift velocities above the selected limit(s), than were present in the population I in  that had flowed into the capillary inlet. Where the selected lower limits are the same, the second retarding gradient can remove ions below the limit that may have escaped the upstream retarding gradient. In the voltage profile shown in FIG. 6B the voltages are set so that a less steep voltage gradient is present between the steeper portions. As may be appreciated, the respective voltages may be set such that the voltage gradient between the steeper portions is flat, or such that a nonopposing gradient is created between the steeper portions. Also, in the voltage profile shown in FIG. 6B the voltages are set so that the retarding voltage gradients have about the same steepness. As may be appreciated, retarding voltage gradients of different steepness may be applied, either to more completely remove ions having drift velocities below a particular limit, or to remove ions having drift velocities below a different limit, in a more downstream segment of the capillary. Other voltage profiles may be created using a configuration as in FIG.  6 A. For example, the voltages may be set so that the voltage profile has a first shallower voltage gradient (generally between electrodes  20  and  24 ), followed downstream by a first steeper voltage gradient (generally between electrodes  24  and  26 ) sufficient to retard movement of ions having drift velocities below a selected lower limit, in turn followed downstream by a next shallower voltage gradient (generally between electrodes  26  and  28 ), finally followed downstream by a next steeper voltage gradient (generally between electrodes  28  and  22 ) sufficient to retard movement of ions having drift velocities below a selected lower limit. 
     The apparatus of the invention may be fabricated from any of a variety of materials, in any of a variety of ways. The dielectric material of which the conduit is constructed can be a glass such as a borosilicate glass, or a quartz, or a ceramic, or a plastic such as a polytetrafluoroethylene (“PTFE”, Teflon®) or a polyimid (Vespel®). The electrodes can be constructed as fittings or as coatings of an electrically conductive material, or as a combination of coatings and fittings. The electrically conductive material can be a relatively nonreactive electrically conductive metal such as, for example, chromium or silver or gold or platinum. Where a fitting is used the fitting may be, for example, a metal cap or sleeve configured to slip over the tube, or a metallized cap or sleeve constructed of a nonconductive material which may conveniently be a deformable (such as a elastic or resilient material) to provide for a secure fit onto the tube. Where a coating is used it may be preferable to employ two or more electrically conductive coatings, a first one of which has characteristics of good adherence to the surface of the dielectric material, and an additional one of which has desirable mechanical and other properties not provided by the first-applied electrically conductive material. And, where a coating is used it can be applied, for example, by conventional sputter coating or vapor coating, by electrodeless plating, or by a conventional chemical deposition technique, using for example a ceramic paint or a metal paint such as a gold paint or silver paint, or, for example, chrome hexacarbonate in an organic solvent such as chloroform. 
     As described above, the retarding voltage gradient causes ions having drift velocities below a lower limit to stall out of the gas flow in the bore of the tube and to impact the lumenal wall of the tube. Ordinarily, their electrical charge dissipates. Where the quantity of ions impacting the tube wall is high, the dielectric material of the tube may be unable to carry the charge away, and undesirable charging effects may result. As is described in co-pending U.S. patent application Ser. No. 09/352,467, filed Jul. 14, 1999, pertinent parts of which are hereby incorporated by reference herein, end-charging within the bore of the conduit can be reduced by providing that the lumenal surface of an end portion of the tube be of an electrically conductive material that carries away electrical charge resulting from ion collisions with the lumenal surface. The electrically conductive portion of the lumenal surface may be constructed as an endpiece defining a bore having an electrically conductive lumenal surface and contiguous with the lumenal surface of the capillary tube at that end; or it may be constructed by providing an electrically conductive coating within a portion of the lumenal surface. 
     Similarly, undesirable charging effects resulting from impact of stalled ions within the tube according to the present invention can be reduced by providing an electrically conductive surface within the lumen of the tube in regions along the tube length where collision of stalled ions may be expected to result from application of a retarding voltage gradient, and providing for electrical connection of the electrically conductive surface to a charge sink. One embodiment of apparatus according to the present invention, which is provided over a portion of its lumen with an electrically-conductive surface for carrying away charge and reducing charging effects, is shown by way of example generally at  30  in FIG.  3 . In this embodiment the dielectric capillary is provided in two sections,  32  and  33 , the walls of which define lengthwise bores or lumens  34  and  35 , respectively. The capillary sections are joined end-to-end with the axes of the bores aligned, so that together they define a straight bore of substantially uniform diameter having an inlet  37  and an exit  39 . An inlet end  36  of capillary section  32  is provided with an inlet end electrode  40 , and an exit end  38  of capillary section  33  is provided with an exit end electrode  42 . Where the other ends, respectively  46 ,  48 , of capillary sections  32  and  33  are joined, an additional electrode  44  is provided. A portion of the surface of the lumen  34  of the inlet end of capillary section  32  is provided with an electrically conductive coating  41 . And portions of the surfaces of the lumens  34 ,  35  near the ends  46 ,  48  are similarly provided with an electrically conductive coating  45 . The respective lumenal surface coatings are formed in electrically conductive contact with the respective electrodes, as described in detail in U.S. Ser. No. 09/352,467. The electrodes are connected to a source of electrical potential. In operation, the voltages are set so that a retarding voltage gradient is established over the upstream portion of the capillary (generally, that is, over the length of capillary segment  32 ), sufficiently steep to retard the downstream movement of ions having drift velocities below the desired lower limit. As the stalling ions impact the electrically conductive lumenal surface  45  near the additional electrode  44 , the charges are carried away from the lumenal surface by way of the electrode  44 . 
     EXAMPLE 
     By way of example, a prototype was constructed using a glass capillary having length 180 mm, and bore diameter 0.5 mm. The end electrodes were formed by metallizing the glass surface over a portion of the ends. The additional electrode was constructed as a metallized ball seal press-fitted over the capillary and positioned at a distance about 75 mm from the inlet end and connected by wire to a voltage source. The apparatus was installed in a Hewlett-Packard G 1946A, employing pneumatic nebulizer N 2  assisted ESI. 
     A solution in methanol:water (1:1) of three different analytes having known molecular weights of about 200, 400, and 600 were introduced at a rate about 50 μL/min. employing a nebulizer pressure about 20 p.s.i. Nitrogen was employed as a drying gas, at a flow rate about 10 L/min., and in separate runs at about 300° C. and about 200° C. The capillary inlet voltage was set at 6 kV and the exit voltage was set at 65 V, and the retarding voltage at the additional electrode was varied in the range from about +7 kV to ground. The 
     The results, generally, were as follows. At each of the drying gas temperatures, application of a sufficiently steep retarding voltage gradient removed ions from the population passing through the capillary. Within a range of retarding potential gradient steepness, lower molecular weight ions were removed in higher proportions than higher molecular weight ions, providing for removal of lower molecular weight ions while permitting passage of higher molecular weight ions. Moreover, at the higher drying gas temperature a shallower voltage gradient is effective to remove ions of a given molecular weight than at the lower drying gas temperature. 
     Other embodiments are within the claims. 
     For example, any desired number of additional electrodes can be arranged along the length of the capillary and associated closely with it, all of them connected to sources of electrical potential. In operation of the apparatus according to the invention, the voltages at any selected two of such electrodes or at any selected one of such electrodes in addition to an end electrode, can be provided to generate a retarding voltage gradient in the capillary segment between them. 
     Additionally, the voltages at selected ones of the electrodes may be varied over the course of treatment of a sample, to progressively change the slope of the potential gradient, accordingly changing the lower limit of drift velocity of ions passing the retarding gradient. 
     Time varying potentials (including alternating sign potentials) may be applied to any selected two of the electrodes; the electrodes can be separated at a suitable distance along the capillary length, and the voltage ranges and the frequencies and phase differences can be selected to provide an effective trap within the capillary for ions having selected lower drift velocities. 
     Alternatively the potential across any two electrodes can be held at a fixed point for a time, and the temperature of the ions traversing the capillary bore can be changed, for example by changing the temperature of the drying gas. An increase in the temperature of the gas traversing the capillary increases the respective drift velocities of the ions, so that some of the ions, which have lower mass and cross section and which stall out in the retarding voltage segment at a higher temperature are able to pass through the retarding voltage gradient at a lower temperature. 
     Moreover, ions having a given mass that are moving near the axial center of the capillary bore can have faster drift velocities than those nearer to the wall, and the result is a gradually degrading drift velocity profile farther downstream along the tube. In such a case, selectively warming or cooling the tube itself at one or more locations along its length may have the effect of making the drift velocity profile more uniform throughout the cross section of the bore. The conduit wall may be heated or cooled by any of a variety of means, as will be apparent to the skilled artisan, such as an electrical heating element arranged about the tube. Application of a retarding potential gradient according to the invention may result in a sharper ion mass cutoff where the velocity profile has been adjusted in this way. 
     Typically, the voltages of elements within the ionization chamber will be set so that the electric field about the ionization region is shaped to attract ions of the desired polarity toward the inlet end of the capillary interface. Particularly, for example, where a cowl is present as illustrated in FIG. 4, the voltage at the cowl is set electronegative (for operation in “positive ion” mode) with respect to the ion source. The ion source (for example, the corona discharge needle for APCI; the electrospray needle for ESI, etc.) may be set at ground or, depending upon the configuration of the apparatus and the environment in which it is operated, at a convenient voltage above or below ground. The other electrodes are then set or varied in relation to the voltage of the ion source. 
     The apparatus of the invention can be employed with any of a variety of ionization techniques, including for example atmospheric pressure ionization techniques such as electrospray ionization or inductively coupled plasma ionization or atmospheric pressure chemical ionization. The apparatus can be employed with any of a variety of mass analytical techniques, including for example magnetic sector, quadrupole (and other multipole), ion trap, time-of-flight, and Fourier-transform (ion cyclotron resonance) techniques, and tandem MS/MS techniques.