Apparatus and method for spatially and temporally sorting ion using RF travelling wave

Abstract

To provide a method of operating an ion optical component including a series of electrodes between first and second ends.SOLUTION: A method includes: applying a set of RF voltage waveforms to a series of electrodes and generating a plurality of moving pseudopotential wells that exert, on ions within an ion optic, forces so as to urge the ions to migrate from a first end to a second end of the ion optic; and applying, simultaneously with the application of the set of RF voltage waveforms, DC potentials to the series of electrodes and generating a DC electric field that exerts, on the ions within the ion optic, forces so as to urge the ions to migrate from the second end to the first end. Therefore, there is caused one or more of spatial separation, differential migration or filtering of ions within an ion optical component in accordance with their respective mass-to-charge (m / z) ratios.SELECTED DRAWING: Figure 10A

Description

[Technical field]

[0001] This application relates to mass spectrometers and mass spectrometry. More specifically, this application relates to ion optical components, including ion guides, ion traps, and ion separation devices employed in mass spectrometers, and methods of using such ion optical components within mass spectrometers. [Background technology]

[0002] Mass spectrometry has often been called the "gold standard" tool for the identification and analysis of various classes of compounds. The strength of mass spectrometry resides in no small part in the ability of modern mass spectrometers to separately isolate, store, and subsequently manipulate, via ion fragmentation or ion-ion chemical reactions, specific ion species of interest selected from the many ion species typically produced by ionization of any sample mixture. In many types of mass spectrometers, quadrupole mass filters are often employed to perform the ion isolation function. For example, in triple quadrupole or quadrupole-time-of-flight (Q-TOF) mass spectrometers, the mass filter is placed before the mass analyzer. The mass filter can receive an ion stream composed of various ion species with various mass-to-charge (m / z) ratios. To isolate a specific ion species with a specific m / z, a specific pair of direct-current (DC) and oscillating radio-frequency (RF) voltages may be applied to the rod electrodes of the mass filter. Application of DC and RF voltages of appropriate magnitude allows transmission through the mass filter of only a narrow range of m / z values ​​encompassing the particular m / z of interest. Such operation causes ions having all other m / z values ​​to be ejected from the device and neutralized. The ion species containing the particular m / z of interest are thus transmitted through the mass filter without significant contamination from other ion species to other downstream mass analyzer components where the ions of the separated ion species can be manipulated and analyzed in various ways.

[0003] Although mass filters perform an important function, they are nevertheless inefficient in that they always reject all ions except those specific ions that are permitted to pass through the instrument by the selection of the filter passband. As a result, typically more than 90 percent of the potentially available compositionally relevant information may be wasted by the mass filter at any particular time.

[0004] To improve the overall analytical efficiency, various types of pre-separation devices have been employed, generally upstream of the mass filter, as a means of providing a non-destructive initial coarse separation of ion species. Once separated by the pre-separation device, the various coarsely separated ion groups can then be separately transferred to the mass filter for narrowband separation of the ion species of interest. Due to the earlier pre-separation, a smaller proportion of ions will be discarded by the mass filter during each such separation.

[0005] One example of such a pre-separation method is ion mobility spectrometry. Ion mobility spectrometry (IMS) is often used to separate ionized molecules in the gas phase based on their mobility in a carrier buffer gas. The reader is referred to Kanu et al. (Kanu, Abu B., Prabha Dwivedi, Maggie Tam, Laura Matz and Herbert H. Hill Jr. “Ion mobility-mass spectrometry.” Journal of mass spectrometry 43, no. 1 (2008): 1-22) for a general review of the coupling of ion mobility spectrometers to mass spectrometers. According to another separation method known as trapped ion mobility spectrometry (TIMS), ions are trapped along a non-uniform DC electric field (electric field gradient) by a countervailing gas flow or along a uniform DC electric field by a countervailing gas flow with a non-uniform axial velocity profile (gas velocity gradient). The trapped ions are separated in space according to ion mobility and then eluted (ejected) over time according to their mobility by adjusting one of the gas velocity and the DC electric field. Details of the TIMS technique are described, for example, in U.S. Patent No. 6,630,662 to inventor Loboda, U.S. Patent No. 7,838,826 (B1) to inventor Park, and U.S. Patent No. 11226308 to Rather and Michelmann.Further explanation is provided by Michelmann et al. (Michelmann, Karsten, Joshua A. Silveira, Mark E. Ridgeway, and Melvin A. Park. "Fundamentals of trapped ion mobility spectrometry." Journal of the American Society for Mass Spectrometry 26, no. 1 (2014): 14-24) and Silveira et al. (Silveira, Joshua A., Karsten Michelmann, Mark E. Ridgeway, and Melvin A. Park. "Fundamentals of trapped ion mobility spectrometry part II: fluid dynamics." Journal of the American Society for Mass Spectrometry 27, no. 4 (2016): 585-595).

[0006] Both ion mobility spectrometry and trapped ion mobility spectrometry techniques use ion guides configured to provide an axial DC electric field along their length. Such an axial electric field may be provided by proportionally applying a voltage between the entrance and exit ends of the ion guide among a number of electrodes disposed between the entrance and exit ends of the ion guide. As an example, the voltage may be proportionally distributed among segments of rod electrodes of a quadrupole or multipole ion guide device. Alternatively, as described in more detail later in this specification, the voltage may be proportionally distributed among, for example, a number of mutually parallel electrode plates, or among a number of thin electrode wires deposited or otherwise attached onto a substrate plate or wafer.

[0007] By providing suitable power supplies and electrical connections, so-called "traveling wave" DC voltages can be supplied to the various rod segments of a segmented quadrupole ion guide, the plate electrodes of a stacked plate or stacked ring ion guide, or the electrode wires of a printed circuit board (US Pat. No. 6,812,453 to inventors Bateman et al.). Generally, in such operation, a periodically varying DC voltage is applied to the individual rod segment electrodes, plate electrodes, or wires, shifting the periodic phase between pairs of electrodes and moving the potential well from the ion inlet end of the ion guide to its ion outlet end. Traveling DC voltage waves have been used to control ions in mass spectrometers according to several different configurations. The most common commercially available ion guide and mass spectrometer collision cell using DC traveling waves is the T-Wave® system offered by Waters Corporation (Milford, Massachusetts, USA). The T-Wave® system employs a stacked ring ion guide with radial confinement of ions provided by an RF voltage and axial ion propulsion provided by a summed DC traveling wave.Other DC traveling wave configurations, known by the acronym "SLIM" (Structures for Lossless Ion Manipulation), have been developed at the Pacific Northwest National Laboratory and are described by Tolmachev et al. (Tolmachev, Aleksey V., Ian K. Webb, Yehia M. Ibrahim, Sandilya VB Garimella, Xinyu Zhang, Gordon A. Anderson, and Richard D. Smith. "Characterization of ion dynamics in structures for lossless ion manipulations." Analytical chemistry 86, no. 18 (2014): 9162-9168) and Ibrahim et al. (Ibrahim, Yehia M., Ahmed M. Hamid, Liulin Deng, Sandilya VB Garimella, Ian K. Webb, Erin S. Baker, and Richard D. Smith. "New frontiers for mass spectrometry based upon structures for lossless "SLIM ion guides" are described by Roberts in "Ion manipulations." Analyst 142, no. 7 (2017): 1010-1021. SLIM ion guides employ a similar traveling wave concept to trap and propel ions, but with a modified electrode configuration suitable for printed circuit board implementation. T-Wave® and SLIM traveling wave systems are most commonly used at relatively high pressures (e.g., around 1 Torr), where axial motion of ions is impeded by gas collisions, allowing separation based in part on collision cross section.

[0008] Recently, ion guides have been described in which traveling waves are implemented not by DC voltages, but instead by manipulation of a main RF axial containment waveform applied to the plate electrodes of multipole rod segments or stacked ring structures. According to these teachings, various electrodes of an electrode array (e.g., an array of plate electrodes, rod electrode segments, printed circuit board electrodes, etc.) can be logically grouped into successive subsets of electrodes (e.g., sets each containing three or more electrodes), whereby within each subset, a different modulated RF waveform is applied to each electrode of the subset. Examples include RF traveling waves generated by amplitude modulation (US Patent No. 9,799,503 to inventors Williams et al.) and frequency modulation (US Patent No. 10,692,710 to inventors Prabhakaran et al.).

[0009] The inventors have recognized that as a result of the m / z-dependence of the pseudopotential-induced forces (i.e., traveling pseudopotential wells) that drive ion movement in RF-modulated traveling wave devices, various ion sorting and / or ion storage devices can be constructed by countering the m / z-dependent pseudopotential forces with opposing m / z-independent forces, such as opposing DC electric fields. Such RF-DC ion sorting devices can be configured to provide initial crude separation and temporary storage of ion species without relying on gas flow. Such novel RF-DC sorting devices, as disclosed herein, can be deployed under both high and medium vacuum conditions and are therefore more versatile than conventional ion sorting devices. While existing DC traveling wave devices require RF confinement separate from the DC traveling wave to move ions, the apparatus and methods described herein utilize RF voltages to both confine and move ions. Summary of the Invention

[0010] Since the RF induced traveling wave has an m / z dependent force (i.e., greater force for lower m / z values), it is possible to counter this force with a second m / z independent force. For example, a static opposing DC axial electric field can be generated by applying a simple DC potential gradient across multiple electrodes. The combination of opposing forces can then be advantageously used to spatially sort ions within an ion guide or ion trap device. Such a pair of opposing applied forces produces three different ion behavior states, as follows: (1) First, for ions with the smallest m / z value where the force due to the RF traveling wave dominates the DC electric field force, the movement is in the direction of the traveling wave. (2) For ions with the largest m / z value where the force due to the RF traveling wave dominates the DC axial electric field, the movement is opposite to the direction of the traveling wave. (3) Finally, for ions with a certain critical m / z value, the RF induced force and the DC potential gradient induced force balance such that the ion does not move in either direction but is trapped within a certain region within the ion optical device, the location of this certain region depending on the particular m / z value and the applied voltage.

[0011] Thus, the inventors have recognized that an ion guide can be configured such that the coordinated application of an RF field and a static DC field, in some embodiments, causes low and high m / z value ions to move in opposite directions while simultaneously trapping ions with a critical m / z value at a trapping location within the ion guide. According to some other embodiments, gradients may be applied to either the RF field, the DC field, or both the RF and DC fields. In such cases, the trapping location becomes m / z dependent, thereby trapping and spatially separating ions based on their respective m / z values. Thus, in such embodiments, ions can be spatially sorted along the length of the ion guide in a manner similar to how ions in isoelectric focusing, such as in a liquid phase, move to a point in a pH gradient that neutralizes the ions. RF field gradients can be generated by varying the RF amplitude V along the length of the device, or more simply by varying the electrode geometry, either by varying the axial spacing of the electrodes or by varying the electrode opening diameter. A DC electric field gradient can be generated most simply by varying resistors in the divider network used to generate the gradient.

[0012] The spatial and temporal ion separation and sorting provided by the devices described herein is independent of gas flow. However, optimal operation of such devices may be achieved at ambient gas pressures ranging from 0.01 Torr to about 2 Torr. At lower pressures, when ions are pulled out of the pseudopotential wells by the opposing DC, there are insufficient gas collisions for the ions to settle into adjacent pseudopotential wells. In such low pressure regimes, ions may be pulled through or across several traveling RF pseudopotential wells by the opposing DC electric field. Such low pressure behavior is detrimental to the ultimate resolution of the separation. The strength of the ion mobility contribution will depend on the ion properties as well as various controllable parameters such as gas composition, gas temperature, etc. Unfortunately, this ion mobility contribution is difficult to predict as a result of the time-varying RF electric field. Therefore, under some circumstances, it may be necessary to perform a proper calibration of the response of each device under various selected experimental conditions and various classes of ions.

[0013] Thus, according to a first aspect of the present teachings, there is provided a method of operating an ion guide having first and second ends and a series of electrodes between the first and second ends, the ion guide having a gas therein at a pressure of 0.01 Torr or greater, the method comprising: applying a set of radio frequency (RF) voltage waveforms to a series of electrodes that create a plurality of moving pseudo-potential wells that exert a force on ions within the ion guide urging the ions to move away from the first end of the ion guide towards the second end; and simultaneously with the application of the set of RF voltage waveforms, applying a set of two or more direct current (DC) potentials to either a set of electrodes or a set of auxiliary electrodes that generate a mass-to-charge ratio (m / z) independent force on ions within the ion guide urging the ions to move away from the second end towards the first end of the ion guide; This causes one or more of m / z dependent spatial separation, differential movement, or filtering of ions within the ion guide.

[0014] According to a second aspect of the present teachings, a mass spectrometer system includes: an ion source configured to generate a plurality of ions by ionization of a sample, the ions comprising a plurality of mass-to-charge ratio (m / z) values; An ion guide having a gas therein at a pressure of 0.01 Torr or more, an ion inlet configured to receive a stream of ions from an ion source; Ion outlet, and an ion guide comprising: a series of electrodes disposed between an ion inlet and an ion outlet, the series of electrodes defining an ion occupied volume between the ion inlet and the ion outlet and an axis of the ion guide; one or more power sources electrically coupled to the series of electrodes, the one or more power sources comprising: applying a set of radio frequency (RF) voltage waveforms to a series of electrodes to confine ions within an ion-occupied volume and generate a plurality of moving pseudo-potential wells that exert forces on the ions urging them to move away from the inlet end toward the outlet end or away from the outlet end toward the inlet end; and one or more power sources configured to apply a set of direct current (DC) potentials to a series of electrodes or two or more auxiliary electrodes that generate a mass-to-charge ratio (m / z) independent force on ions within the ion guide that opposes the force exerted by the moving pseudo-potential well. [Brief description of the drawings]

[0015] The above and various other aspects of the present invention will become apparent from the following description, which refers to the accompanying drawings, which are given by way of example only and are not necessarily drawn to scale.

[0016] [Figure 1A] 1 is a schematic cross-sectional view of a known stacked ring ion guide ion transport device. [Figure 1B] FIG. 2 is a schematic diagram of an exemplary plate electrode as may be employed in a stacked ring ion guide ion transport device. [Figure 1C] FIG. 1 is a schematic diagram of a known ion manipulation and ion guiding device that may be employed as an ion transport apparatus. [Figure 1D] FIG. 1D is a schematic diagram of an electrode configuration on the surface of the known ion manipulation and ion guiding device of FIG. [Figure 2A] FIG. 1 is a schematic cross-sectional view of an embodiment of an ion tunnel stacked ring ion guide in accordance with the present teachings, in which ions with different mass-to-charge (m / z) ratios are forced to move in different directions by application of a static uniform DC axial electric field against the downstream movement of a pseudopotential well generated by application of a traveling radio frequency (RF) wave. [Figure 2B] FIG. 2B is another schematic cross-sectional view of the ion tunnel stacked ring ion guide of FIG. 2A, in which ions are transported to and accumulated in various different stability zones according to their respective mass-to-charge (m / z) ratios by application of a static, non-uniform DC axial electric field that opposes their downstream movement through the pseudopotential well. [Figure 2C] FIG. 2B is a schematic illustration of the extraction of ions from the stacked ring ion guide device of FIG. 2A in order of their respective m / z ratios by ramping the amplitude of the RF voltage applied to the electrodes of the device. [Figure 3A] FIG. 1 is a schematic cross-sectional view of a first embodiment of an ion funnel stacked ring ion guide in accordance with the present teachings, in which ions with different mass-to-charge (m / z) ratios are forced to move in different directions by application of a static uniform DC axial electric field that draws ions toward the downstream narrow end of the funnel and opposes the upstream movement of a pseudo-potential well created by application of a traveling RF wave. [Figure 3B] 1D is a modified version of the ion manipulation and ion guiding device of FIG. 1C in accordance with the present teachings. [Figure 4A]1 is a set of simulated plots of equilibrium positions of ions of various m / z ratios in an ion guide ion separator device under the application of a DC axial electric field gradient, the direction of which is opposite to that of the RF generated traveling wave. [Figure 4B] 1 is a set of simulated plots of equilibrium positions of ions of various m / z ratios within an ion guide ion separator apparatus under the application of a gradient in amplitude of a traveling wave induced RF waveform in the presence of an opposing uniform DC axial field. [Diagram 5] 1 is a schematic diagram of a portion of a mass spectrometer apparatus including a quadrupole mass filter or other mass spectrometer component arranged in series with an ion optics device constructed and operated in accordance with the present teachings. [Figure 6A] FIG. 2B is a schematic cross-sectional reproduction of the device of FIG. 2A and an ion packet therein, further illustrating a schematic example of how DC voltages can be distributed between stacked electrodes to generate a static, uniform DC axial electric field. [Figure 6B] A uniform axial electric field that opposes the energizing of ions by the movement of a traveling pseudo-potential well (pseudo-wave) generated by RF, according to some embodiments of the present teachings.

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[0017] The following description is presented to enable any person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the described embodiments will be readily apparent to those skilled in the art, and the general principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiments and examples shown, but is to be accorded the widest possible scope in accordance with the features and principles shown and described. For a more detailed and complete understanding of the features of the present invention, please refer to Figures 1A-1D, 2A-2C, 3, 4A, 4B, 5, 6A-6H, 7A, 7B, 8, 9, 10A-10C, 11A, and 11B in conjunction with the following description.

[0018] In the description of the invention herein, unless otherwise understood or stated, implicitly or explicitly, it is understood that words appearing in the singular include their plural equivalents, and words appearing in the plural include their singular equivalents. Furthermore, unless otherwise understood or stated, implicitly or explicitly, it is understood that for any given component or embodiment described herein, any of the possible candidates or alternatives listed for that component may generally be used individually or in combination with each other. Furthermore, it should be understood that the figures shown herein are not necessarily drawn to scale, and that some of the elements may be drawn merely to clarify the invention. Also, reference numerals may be repeated among the various figures to indicate corresponding or similar elements. Additionally, unless otherwise understood or stated, implicitly or explicitly, it is understood that any listing of candidates or alternatives is merely illustrative and not limiting.

[0019] Unless otherwise defined, all other technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification, including definitions, shall control. It will be understood that there is an implicit "about" before the quantitative terms referred to in this disclosure so that minor and insignificant deviations are within the scope of the present teachings. Similarly, the use of "comprise", "comprises", "comprising", "contain", "contains", "containing", "include", "includes", and "including" is not intended to be limiting. As used herein, "a" or "an" may refer to "at least one" or "one or more". Additionally, the use of "or" is inclusive, such that the phrase "A or B" applies when "A" is applicable, when "B" is applicable, or when both "A" and "B" are applicable.

[0020] As used herein, the term "DC," when referring to a voltage applied to one or more electrodes of a mass spectrometer component (such as an ion tunnel or ion funnel), does not necessarily imply the application or presence of a current through those electrodes. Thus, the term "DC" is used herein to distinguish the referenced voltage from applied oscillating voltages that oscillate at radio frequencies and are referred to as "RF" voltages.

[0021] As used herein, the term "static" as applied to a DC electric field (vector field) or RF amplitude refers to a DC electric field or RF amplitude that is maintained essentially unchanged over a period of time, with insignificant variations of 10 percent or less of the average electric field strength or average RF amplitude, as the case may be. The term "uniform" as applied to a DC electric field refers to a DC electric field that is maintained to have a magnitude and direction that does not vary substantially other than insignificant statistical variations over a length encompassing a series of electrodes, for example across a series of electrodes spanning the length of an ion optical component from the ion entrance end to the ion exit end. Conversely, the terms "gradient" and "non-uniform" as applied to a DC electric field refer to a spatial variation across the series of electrodes, at least in the magnitude of the DC electric field, and a DC electric field that is adapted to exhibit such variation, respectively. It should be noted that a "static" DC electric field may be either uniform or have a gradient. The term "uniform" as applied to an RF amplitude refers to an RF amplitude that is maintained substantially unchanged over a length encompassing a series of electrodes. Conversely, the terms "gradient" and "non-uniform" as applied to an RF amplitude refer to a spatial variation across the series of electrodes of the applied amplitude.

[0022] As used herein, the terms "dynamic" and "ramped" as applied to either a DC electric field or RF amplitude refer to a DC electric field or RF amplitude that is varied with time, in either a monotonically increasing or decreasing manner, over a period of time. Ramping the magnitude of a DC electric field applied across a set of electrodes requires a ramping of the DC potential applied to a subset (i.e., to one or more) of those electrodes. Similarly, ramping the RF amplitude of an RF waveform applied across a set of electrodes requires a ramping of the RF amplitude applied to one or more of those electrodes.

[0023] A DC electric field or RF amplitude that is maintained in a static state for a first period of time may be maintained in a dynamic or ramped state at other times occurring either before or after the period, and vice versa. Similarly, a DC electric field or RF amplitude that is maintained in a uniform state for a first period of time may be maintained in a non-uniform state at other times, and vice versa. As used herein, the terms "urge" and "urges," when used in reference to the effect on one or more ions of the direction of an applied force, do not necessarily imply that one or more ions are caused to move in that direction in response to the force, since the direction of movement of any ion upon application of the force depends on its initial momentum vector and the vector sum of all such applied forces.

[0024] As mentioned above, so-called "stacked ring ion guides" are frequently employed in mass spectrometry to guide or otherwise manipulate ions. In this specification, the term "stacked ring ion guide" is used to refer to either an ion guide including a series or a number of rings or ring-shaped electrodes, an ion guide including a series or a number of plates or plate-like electrodes, and / or an ion guide including a series or a number of printed circuit boards having electrode structures printed on the substrate surface. Stacked ring ion guides are often referred to as either so-called "ion tunnels" or "ion funnels". FIG. 1A provides a schematic longitudinal cross-sectional view of a stacked ring ion guide device 10 including both an ion tunnel portion 12a and an ion funnel portion 12b. However, it should be noted that many devices referred to in the art simply as "ion funnels" have both an ion tunnel portion and an ion funnel portion, as shown in FIG. 1A.

[0025] Generally described, a stacked ring ion guide device 10 comprises a plurality of closely spaced ring or plate electrodes 2. A schematic diagram of a typical individual ring or plate electrode 2 is shown in FIG. 1B. For clarity, FIG. 1A shows only a small number of electrodes 2. It should be noted that in practice a typical ion funnel or ion tunnel device may comprise 100 or more individual electrodes. Each ring or plate electrode 2 (FIG. 1B) is typically circular and has an opening 8 defined by an inner ring surface 3. Each ring electrode 2 may comprise one or more tabs, such as tabs 9 for attachment to a support structure (not shown) and possibly for providing an electrical connection to a power supply (not shown).

[0026] Within the ion tunnel, as exemplified by ion tunnel section 12a, all openings of the electrodes in this section have a constant diameter θ TIn contrast, within the ion funnel portion 12b, the diameter θ of the various apertures generally decreases along a direction away from the ion inlet end 13 toward the ion outlet end 18 of the device. As used herein, the term "wide end" is used to indicate the end of the ion funnel portion where the varying aperture diameter θ is largest, and the term "narrow end" is used to indicate the opposite end of the ion funnel portion where the aperture diameter is smallest. In operation, an oscillating radio frequency (RF) voltage is applied to the electrodes with a defined phase relationship to confine ions radially within the device. According to a commonly defined conventional phase relationship, the phase of the RF voltage waveform of each stacked electrode is π radians (180 degrees) out of phase with that of each immediately adjacent electrode. The collection of all apertures of all electrodes 2 defines an ion-occupied volume 11 within which ions travel, generally as indicated by the arrow on the longitudinal axis 16, from the ion inlet end 13 to the ion outlet end 18 of the device 10. In typical operation, the pseudopotential well centered on axis 16 and created by the applied RF configuration serves to confine ions within the ion occupied volume 11. The relatively large electrode openings at the ion inlet end 13 and ion tunnel portion 12a of the device are generally employed to trap a dispersed or diffuse cloud of ions. In contrast, the electrode openings at the ion funnel portion 12b shrink towards the ion outlet 18, constricting the ion cloud into a narrow beam that can pass through a narrow opening into the high vacuum chamber. The movement of ions in the direction from the ion inlet end towards the ion outlet may be assisted by a gas flow into which the ions are drawn. The ions may also be urged in the same direction by the provision of a DC axial electric field, generated by differentially providing DC voltages to the electrodes 2.

[0027] FIG. 1C is a schematic diagram of another known type of ion manipulation and ion guiding device 50, as taught in the aforementioned U.S. Pat. No. 10,692,710. As described in that patent, the device 50 comprises two spaced apart parallel substrate plates or wafers 51 and 53, each having a surface on which a plurality of electrodes are disposed. For example, the plates or wafers 51 and 53 may be printed circuit board substrates. The electrode-bearing surfaces may face each other across a gap between the two substrate plates or wafers, as shown. A central axis 57 is defined through the device 50. Each of the electrode-bearing surfaces has an array of inner electrodes 55 and also has outer guard electrodes 52a, 52b. The outer guard electrodes 52a, 52b are disposed on either side of the array of inner electrodes 55. The array of inner electrodes 55 and the outer electrodes 52a, 52b extend substantially along the length of the electrode-bearing surfaces of the substrate plates or wafers 51, 53. In operation, ions can be confined within the gap between the electrode bearing surfaces and directed parallel to the central axis 57 as taught in US Pat. No. 10,692,710.

[0028] FIG. 1D shows a schematic representation of a portion of an electrode-bearing surface of an individual substrate plate or wafer 53 of a known ion manipulation and ion guiding device 50. In the example illustrated in FIG. 1D, each of the outer guard electrodes 52a, 52b includes a single elongated electrode elongated parallel to a central axis 57. The array of electrodes 55 comprises a series of individual electrodes 7a, 7b, 7c, ..., 7m. Although twelve such individual electrodes are shown, the array 55 may comprise any number of electrodes. A voltage source (not shown) can apply a voltage to each electrode 7a-7m individually. As discussed above in the Background section of this specification, U.S. Pat. No. 10,692,710 further teaches, using the ion manipulation device 50 as an example, that the various electrodes of the inner electrode array 55 can be logically grouped into successive subsets of electrodes (e.g., sets each comprising three or more electrodes). The patent further teaches that by providing differently modulated RF waveforms to each electrode of each subset, a traveling wave can be created that tends to urge ions parallel to the central axis 57 through the device 50.

[0029] 2A is a schematic cross-sectional view of a first embodiment of an ion tunnel stacked ring ion guide 100 according to the present teachings. The stacked ring ion guide 100 is shown to include only an ion tunnel portion, but may alternatively include any number of combinations of ion funnel and ion tunnel portions. In general operation of the device 100, an ion stream 115 containing an unseparated mixture of ion species is delivered to the ion-occupied volume 101 of the device through an ion inlet 113. Operation of the device 100 can separate the original mixture of ion species into multiple packets, for example, ion packets 117a, 117b, and 117c as shown, each of which contains a different subset of the original set of ion species. These partially separated packets of ions can then be forced to exit the device as a stream of ion packets 119 through an ion outlet 118.

[0030] The physical configuration of the electrodes 2 of device 100 (FIG. 2A) is similar to that of the electrodes of the ion tunnel portion 12a of the stacked ring ion guide 10, with each electrode having an aperture of diameter θ0, the collection of the apertures defining an ion-occupied volume 101. Despite this similarity, device 100 differs from device 10 (FIG. 1A) in the following ways: (a) The electrodes are logically grouped into a stacked order of subsets of electrodes, each of which comprises (in this example) exactly four electrodes. (b) the RF voltage waveform applied to the electrodes is varied in time within each subset of electrodes to generate a plurality of pseudo-potential wells in which ions tend to concentrate, whereby the pseudo-potential wells are caused to move in a desired direction parallel to the axis of the device, the set of moving pseudo-potential wells being referred to herein as an RF traveling wave or equivalently a "pseudo-wave"; and (c) An axial DC electric field is provided within the ion occupancy that tends to urge the ions in a direction opposite to the direction of travel of the pseudopotential well. Figure 6A is a schematic cross-sectional reproduction of the device of Figure 2A and an ion packet therein, further illustrating a schematic example of how a DC voltage V can be distributed between the stacked electrodes to generate a static, uniform DC axial electric field. The axial electric field vector in the vicinity of the axis of the device

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[0031] Specifically, with regard to logical grouping of electrodes into subsets, FIG. 2A shows two such groups (i.e., subsets), each group comprising a first electrode 2a, a second electrode 2b, a third electrode 2c, and a fourth electrode 2d. Although only two such groups are labeled in FIG. 2A, it should be understood that in the illustrated embodiment, each grouping of four electrodes into subsets relates to all electrodes 2 of the device that extend from the ion inlet 113 to the ion outlet 118. According to some alternative embodiments, some portions of the electrodes may not be so organized into groups. Although four electrodes per subset are illustrated, the number of electrodes per subset N may vary. e is not necessarily limited to 4. More generally, N e ≧3. The repeat distance L along the axis of the device 100 (parallel to the arrows 115 and 119) R is defined as the distance between successive electrodes 2a (or successive electrodes 2b, etc.).

[0032] Within each subset of electrodes of the device 100, the four electrodes of the subset differ in that, during operation, each electrode is supplied with a different respective RF voltage waveform, as will be further described below. All electrodes 2a are supplied with a first RF voltage waveform, which in an embodiment is the same between all electrodes 2a. Similarly, all electrodes 2b are supplied with a second RF voltage waveform, which in an embodiment is the same between all electrodes 2b. Similarly, a third voltage waveform is applied to all electrodes 2c, and a fourth voltage waveform is applied to all electrodes 2d. Generally described, N e The voltage waveforms are selected such that a set of moving pseudo-potential wells are generated along the axis of the device (coincident with arrows 115 and 119), thereby forming a set of "traveling waves" that tend to urge ions along the axis. According to the example shown in Figure 2A, the voltage waveforms are configured such that the traveling waves urge ions in a direction parallel to lines 115, 119 from the ion inlet 113 towards the ion outlet 118. However, according to some other embodiments described further herein below, the voltage waveforms may be configured to urge ions in the opposite direction.

[0033] According to some embodiments of the present teachings, the RF voltage waveforms applied to the electrodes of the apparatus 100 may be selected as described in U.S. Patent No. 9,799,503, which provides an example of a subset of four electrodes of a stacked ring ion guide, with respective RF voltage waveforms supplied to the four electrodes such that a plurality of moving pseudo-potential wells generate traveling waves within the ion guide. According to the aforementioned U.S. Patent No. 9,799,503, the four RF voltage waveforms may be supplied according to the following first through fourth drive signals: V A =V1F(ω m t-Φ1)e jωt First RF Drive Signal Equation 1a V B =V2F(ω m t-Φ2)e jωt Second RF drive signal Equation 1b V C =V3F(ω m t-Φ3)e jωtThird RF drive signal Equation 1c V D =V4F(ω m t-Φ4)e jωt Fourth RF drive signal Equation 1d where t is time, V1 through V4 are amplitudes from zero to peak, j is the imaginary unit, the function F is a complex function of its argument and is periodic with a period of 2π, the scalar value Φ1 is a first phase, the scalar value Φ2 is a second phase shifted 90 degrees (π / 2 radians) relative to the first phase, the scalar value Φ3 is a third phase shifted 180 degrees (π radians) relative to the first phase, the scalar value Φ4 is a third phase shifted 270 degrees (3π / 2 radians) relative to the first phase, and ω>ω m Scalar values ​​ω and ω m may be an angular frequency in radians / second. It is understood that the applied voltage is described by the real part of any resulting complex expression. The patent also provides a specific example of an implementation of the expressions in Equations 1a-1d, where the applied voltage is: V A =V0cos(ω m t)cos(ωt) First RF drive signal Equation 2a V B =V0cos(ω m t-π / 2)cos(ωt) Second RF drive signal Equation 2b V C =V0cos(ω m t-π)cos(ωt) Third RF drive signal Equation 2c V D =V0cos(ω m t-3π / 2)cos(ωt) 4th RF drive signal f C formula 2d As mentioned above, the number of electrodes per subset is not limited to four electrodes per subset, but can be any integer N e (where N e In such a case, the various electrodes R in each subset and the various voltage waveforms V(t) supplied to the electrodes in each subset may be enumerated by index variable i in order starting with the electrode closest to the inlet inlet as follows:

number

[0034] According to some other embodiments of the present teachings, the RF voltage waveform supplied to the electrodes of the device 100 is a frequency modulated signal S represented by the following equation: FM The frequency of the input pulse may be selected as described in US Pat. No. 10,692,710, which describes the generation of a traveling wave by supplying a frequency modulated waveform driven by a S FM =V c cos(2πf c +βS MS ) where f C is the "carrier frequency" (i.e., the frequency of the standard unmodulated RF voltage waveform), and V C is the voltage amplitude of the RF waveform, β is the frequency modulation index, and S MS is a frequency modulated periodic waveform with frequency f M f C This latter patent describes how the electrodes of a stacked ring ion guide are organized into subsets of eight electrodes each to generate a frequency modulated periodic waveform S MS provides a specific example where the phase of varies by 2π / 8 radians (45 degrees) between each pair of electrodes.

[0035] Referring again to FIG. 2A, arrow 110 represents the direction of movement of the pseudo-potential well (i.e., traveling wave) generated by RF, which may be generated as described above. As indicated by arrow 110, the application of the RF waveform may be configured such that the traveling wave exerts a force on the ions that tends to urge the ions in a "forward" direction generally from the ion inlet 113 toward the ion outlet 118. However, in an alternative embodiment, the direction of pseudo-potential well movement may be reversed relative to the movement direction shown in FIG. 2A by reversing the phase relationship of the driving waveforms applied within each subset of electrodes. FIG. 2A also illustrates that the present teachings also generate a static, uniform DC axial electric field that exerts a force on the ions that tends to counter the force exerted by the pseudo-potential well movement. A schematic example of the magnitude of the static, uniform DC axial electric field is provided by plot 508 in FIG. 6A. Thus, arrow 111 indicates the direction in which the same ions would be urged to move by the applied static, uniform DC axial electric field. Thus, in accordance with the operation shown in Figure 2A, a DC axial electric field is applied which tends to urge ions in the "reverse" direction, from the ion outlet 118 towards the ion inlet 113. Note, however, that if the direction of pseudo-potential well travel is reversed from that shown in Figure 2A, such that the traveling wave instead tends to urge ions towards the ion inlet 113, then the direction of the DC axial electric field is also reversed relative to the direction shown in Figure 2A, and the so-reversed DC axial field urges ions towards the ion outlet 118.

[0036] The DC axial electric field generated within the ion-occupied volume 101 may be generated in a known manner by dividing the end-to-end voltage difference across the length of the device through the inclusion of a series of resistors between the electrical connections to the various electrodes 2. Alternatively, the DC axial electric field may be generated by any one of several other known methods.

[0037] The opposing pseudopotential and DC axial electric field forces applied as shown in FIG. 2A produce three different ion behavior states: (1) first, for ions with the smallest m / z values ​​where the forces due to the RF traveling wave exceed the DC electric field forces (e.g., ions in ion packet 117a), the movement will be in the direction of the traveling wave as indicated by motion vector 118a; (2) for ions with the largest m / z values ​​where the DC axial electric field dominates (e.g., ions in ion packet 117c), the movement will be opposite to the direction of the traveling wave as indicated by motion vector 118c; and (3) finally, for ions with a certain critical m / z value (e.g., ions in ion packet 117b) that depends on the applied voltage, the RF and DC gradient induced forces are balanced and such ions will not move in either direction. Thus, when operated as shown in FIG. 2A , the device 100 simultaneously operates (a) as a mass filter, allowing only ions having relatively low m / z values ​​(i.e., below a critical value) to be transmitted along the outlet stream 119 to downstream devices (such as a quadrupole mass filter and / or collision cell and / or mass analyzer), (b) as a single mass-to-charge ion trap or ion accumulator for ions having a critical m / z value, and (c) as a filter that removes all ions having m / z values ​​greater than the critical value.

[0038] FIG. 2B is another schematic cross-sectional view of the ion tunnel stacked ring ion guide 100 as introduced in FIG. 2A, but configured and operated in an alternative mode that causes differential movement of ions through the ion guide and spatially separated trapping of ion species according to their respective mass-to-charge (m / z) ratios. According to the mode of operation shown in FIG. 2B, the applied static DC axial electric field that opposes the pseudopotential-induced traveling wave is not uniform, but instead decreases in magnitude in the general direction from the ion outlet 118 toward the ion inlet 113. Specifically, as indicated by arrow 112, the DC axial electric field continues to generate a force that tends to urge ions in an "upstream" direction opposite to the "downstream" direction (as indicated by arrow 110) in which ions are urged by the traveling wave. However, the magnitude of the DC axial electric field vector is non-uniform and decreases in the upstream direction. Under such operation, various ion species within a range of m / z values ​​will be trapped within the ion-occupied volume as each such ion species migrates to and accumulates at an axial position where the upstream DC axial field exactly balances the downstream pseudopotential-induced force on the mass-to-charge value of the ion species. For example, in FIG. 2B, the mass-to-charge ratio (m / z) L A first ion packet 117a having a mass to charge ratio (m / z) M A second ion packet 117b having a mass to charge ratio (m / z) H 10 is a schematic axial equilibrium position for a third ion packet 117c having (m / z) H >(m / z) M >(m / z) L2B, the equilibrium positions of only three packets of ions having a particular m / z value are illustrated, in practice there will generally be a substantially continuous range of equilibrium positions for ions having a particular m / z value, with the m / z values ​​within the equilibrium m / z range decreasing in the general direction towards the ion outlet 118. Additionally, certain ion species having small m / z values ​​outside the range may move towards the ion outlet, and certain other ion species having large m / z values ​​outside the range may move towards the ion inlet. Thus, in the mode of operation illustrated diagrammatically in FIG. 2B, the apparatus 100 functions as a multiple mass-to-charge ion selective ion trap.

[0039] As shown in Figure 2B, to extract trapped ions at various equilibrium positions, the amplitude of the phase-shifted and / or frequency-modulated main RF voltage as described above can be ramped upward (i.e., gradually increased) over time such that the equilibrium positions corresponding to all m / z values ​​move toward the ion outlet during the ramping of the RF voltage amplitude as shown by displacement vectors 118a, 118b, and 118c in Figure 2C. Additionally or alternatively, the magnitude of the opposing DC electric field can be ramped downward (i.e., gradually decreased). In this example, trapped ions with the smallest m / z values ​​(e.g., ions in packet 117a) pass through the ion outlet first, and ions with the largest m / z values ​​(e.g., ions in packet 117c) come out last.

[0040] It should be noted that in alternative embodiments, the direction of travel of the traveling wave and the direction of the opposing DC electric field may be reversed from the directions shown in Figures 2A-2C. In such alternative embodiments, the ion species with the largest m / z value will be the first to be ejected from the device if the "direction" of the ramp of the RF amplitude (of the traveling wave urging ions towards the ion inlet 113) (i.e., either an "up" ramp or a "down" ramp) and the "direction" of the ramp of the DC electric field magnitude (urging ions towards the ion outlet 118) are reversed. It should be further noted that while many of the basic examples discussed herein refer to ramping of either the RF amplitude or the DC electric field, more generally, the RF amplitude and the DC electric field may be ramped simultaneously, whereby during the simultaneous ramping, the RF amplitude and the DC electric field magnitude are both increased or both decreased. In other examples, the simultaneous ramping may include an increase in the RF amplitude and a simultaneous decrease in the DC electric field magnitude. In still other cases, the simultaneous ramping may include a decrease in the RF amplitude and a simultaneous increase in the DC electric field magnitude.

[0041] As mentioned above, a stacked ring ion guide in the form of an ion tunnel may be made to function as either (a) a single mass charge ion trap or ion accumulator (as described with reference to FIG. 2A) by providing a uniform DC axial electric field that opposes the traveling wave, which is applied uniformly over the length of the device, or (b) a multiple mass charge ion sorting ion trap, if there is a longitudinal spatial gradient in either the provided opposing DC electric field and / or the pseudo-wave transport motive force. In the case of an ion tunnel device, the act of creating a "longitudinal spatial gradient in the pseudo-wave transport motive force" requires providing different RF waveforms (e.g., different RF amplitudes) to the electrodes of the device at various different positions between the ion inlet and the ion outlet. In such cases, the required electronics may be complex, expensive, and / or difficult to design or manufacture. However, in the case of an ion funnel ion guide device, such as the ion funnel device 200 shown in FIG. 3A, the gradient in the depth of the pseudo-potential well, and hence the transport motive force, is created by the geometry of the device. Specifically, in the ion funnel device 200, the depth of the various pseudopotential wells increases in the direction of the ion funnel convergence (see, for example, FIG. 1 of U.S. Pat. No. 9,799,503), essentially due to the increasing proximity of the electrode edges to the ion beam in the same direction (centered near the device axis). Thus, with the RF-generated traveling wave direction (arrow 210) directed to urge ions toward the ion inlet 213 and the DC electric field direction (arrow 211) directed to urge ions toward the ion outlet 218, the device 200 can be operated as a multiple mass-charge ion-selecting ion trap without applying any electric field gradient. Using the configuration shown in FIG. 3A, relatively "light" (small m / z) ions can be trapped in the region 117a proximate to the ion inlet 213, while at the same time, relatively "heavy" (large m / z) ions are trapped in the region 117c proximate to the ion outlet 218. As previously described, intermediate m / z ions are trapped in region 117b.The trapped ions can be ejected in the reverse order of their m / z ratios by either ramping up (i.e., to a larger value) the magnitude of the DC electric field and / or ramping down (i.e., to a smaller value) the applied RF amplitude.

[0042] Figure 3B is a modified version of the ion manipulation and ion guiding device of Figure 1C in accordance with the present teachings. The ion manipulation and ion guiding device 250 shown in Figure 3B has been modified with respect to device 50 (Figure 1C) so that it can be operated similarly to the operation of the ion funnel 200 (Figure 3A), as described above. In contrast to device 50, in which parallel plates or wafers 51 and 53 are configured to support an array of inner electrodes 55 and a set of outer guard electrodes 52a, 52b, the modified device 250 is configured such that the plates or wafers 251 and 253 converge towards each other along a direction away from the ion inlet 313 and towards the ion outlet 318. For example, as shown in FIG. 3B, the plates / wafers 251 and 253 are separated from each other by a first separation distance s1 at the ion inlet 313 and a second separation distance s2 at the ion outlet 318, where s1>s2 and there is a continuous convergence of the plates / wafers 251, 253 between the ion inlet 313 and the ion outlet 318.

[0043] US Patent No. 10,692,710 teaches that an RF traveling wave can be generated along the axis 57 of the device 50 by manipulation of a main RF axial containment waveform applied to a series of individual electrodes 7a, 7b, 7c, ... (see Fig. 1D) of an electrode array 55 facing each other. Additionally, the inventors of the present invention have subsequently recognized that a DC electric field that opposes the motion of ions driven by the RF traveling wave can also be generated inside either the device 50 (Fig. 1C) or the modified device 250 (Fig. 3B). For example, a static and uniform DC electric field can be generated inside either the device 50 or the modified device 250 by distributing a DC potential difference imposed between the ion inlet 313 and the ion outlet 318 among multiple internal electrodes of each plate / wafer 251, 253. The distribution of the voltage difference can be achieved by a voltage divider system in a known manner. Additionally or alternatively, an axial DC electric field may be generated or otherwise supplemented by providing the guard electrodes 52a, 52b of each plate / wafer to be constructed from an electrically resistive material (as opposed to a conductive material such as a metal). For example, the resistive guard electrodes 52a, 52b may be formed from any one of a number of suitable materials having electrically resistive properties (such as, but not limited to, doped glass, cermets, polymers, etc.).

[0044] Because the electrodes 55 of the two electrode arrays (one electrode array supported on each of the plates / wafers 251, 253) in the device 250 gradually approach each other along the direction from the ion inlet 313 towards the ion outlet 318, a gradient exists in the depth of the pseudo-potential well, with the well depth increasing in the same direction. The increasing well depth creates a gradient in the movement motive force provided by the RF generated traveling wave. Thus, if the RF generated traveling wave is configured to urge ions in the device 250 away from the ion outlet 318 towards the ion inlet 313, and if the urging of the traveling wave is opposed by a static uniform DC electric field that urges ions towards the ion outlet 318, different ion species with different respective m / z values ​​will establish different respective equilibrium positions in the device. In this situation, the distribution of equilibrium positions will resemble that depicted in Figure 3A, with ions 117a having smaller mass to charge ratios closer to the ion inlet than ions 117b, 117c having larger mass to charge ratios, and ion 117c having the largest mass to charge ratio closest to the ion outlet. The trapped ions can then be ejected from the device 250 in reverse order of their m / z ratios by either ramping the DC electric field magnitude upwards (i.e., to a larger value) and / or ramping the applied RF amplitude downwards (i.e., to a smaller value).

[0045] The following discussion refers to Figures 6A-6H, which are various schematic graphs of voltages and DC electric fields within an ion guide operated in accordance with the present teachings. For each of these figures, it is assumed that the ion inlet 113 at position 0 corresponds to the left side of the respective graph, and the ion outlet 118 at position L corresponds to the right side of the plot. It is also assumed that a set of pseudo-waves is applied to the electrodes of each ion guide to urge ions from the ion inlet towards the ion outlet. Note that the absolute magnitude of the applied DC voltages is plotted in each of Figures 6C and 6E. When positively charged ions are introduced into an ion guide or ion separator device operated as described herein, if the applied DC voltage profile is of the general form as the profiles shown in Figures 6C and 6E, the overall movement of the ions within the device will be as described. However, when negatively charged ions are introduced into the device, if the applied DC voltage profile has the general form of a mirror image (i.e., reflected across the horizontal axis) of the profiles shown in Figures 6C and 6E, the overall movement of ions within the device will be as described.

[0046] As mentioned above, to separate ions comprising a particular m / z range within an ion guide (see, e.g., FIG. 2A), a uniform DC electric field can be applied that opposes the motion of a set of traveling RF potential wells (i.e., a set of pseudo-waves). For example, plot 508 of FIG. 6A illustrates a uniform axial DC electric field as may be generated by applying a series of DC voltages to various individual electrodes of an ion guide, where the applied voltages increase linearly from the ion inlet to the ion outlet (i.e., plot 501 of FIG. 6A). Also, as mentioned above, a non-uniform axial DC electric field may be applied that opposes the pseudo-wave motion to cause the ion guide to eject ions from the ion outlet in either order of increasing or decreasing m / z value (see, e.g., FIG. 2C).

[0047] Figure 6B shows the absolute magnitude

number

number

number

[0048] The inventors have determined that with respect to the use of an ion guide as an ion separation and sorting device (e.g., FIG. 2C) in accordance with the present teachings, where ions are ejected in order of their m / z value, the mass spectral resolution R of the device may be optimized by utilizing a non-uniform electric field profile as shown diagrammatically in FIG. 6D, which may be produced by applying DC voltages to the electrodes according to the voltage profile shown by segments 504a and 504b in FIG. 6E. Specifically, the inventors have determined that the magnitude of the DC axial electric field that opposes the spurious wave induced ion motion may be optimized by utilizing a non-uniform electric field profile as shown diagrammatically in FIG. 6D, which may be produced by applying DC voltages to the electrodes according to the voltage profile shown by segments 504a and 504b in FIG. 6E.

number

[0049] Ions are introduced into the ion guide device through the ion inlet 113, which can be configured with a traveling RF voltage and a static DC voltage as shown in Figures 6D and 6E. The position of the ion inlet 113 is shown as position 0 in Figures 6D and 6E. A radio frequency (RF) voltage waveform is applied to the electrodes of the device to generate a set of RF traveling waves that create a pseudo-potential well that urges the ions through the device from the ion inlet 113 to the outlet 118, located at position L. At the same time, a DC voltage is applied to the electrodes, which has the general form shown by the dashed lines 503a, 503b in Figure 6D, and generates an axial electric field that urges the ions towards the ion inlet 113. After the introduction of the ions, the amplitude A of the applied RF voltage is RF is ramped (i.e., increased) with time. Under such conditions, packets of ions having different respective m / z values ​​separate from one another and travel at different velocities through the device towards the ion outlet 118, as previously described herein. Figure 6D shows diagrammatically the positions of three packets of ions 517a, 517b, 517c within the device. L , (m / z) M , and (m / z) H At a particular time t1 during the gradient before any of the ions reach the plateau region 503b of the DC electric field profile, (m / z) H >(m / z) M >(m / z) LThe instantaneous position of any such ion packet at any particular time represents the axial position within the device where the instantaneous forward bias of the ion packet due to the pseudo-wave as generated by the ramped RF amplitude at that particular time slightly overcomes the reverse bias of the ions due to the electrostatic field along the electric field segment 503a. As previously mentioned, these opposing forces cause the ions with the smallest m / z values ​​(e.g., ions of packet 517a) to move most quickly toward the ion outlet, so that these ions reach point p1 at time t1. The ions with the largest m / z values ​​(e.g., ions of packet 517c) move most slowly, so that they only reach point p3 at time t1. At the same time, ions with intermediate m / z values ​​(e.g., ions of packet 517b) reach point p2.

[0050] FIG. 6F is a schematic diagram of the position of the ion packet of FIG. 6D at a second time t2 subsequent to time t1, at which time the applied RF amplitude is such that the forward biasing pseudopotential force on the ion packet 517a is equal to E along the electric field strength segment 503b. maxThe electric field strength of the ions 517a is initially equal to and then substantially exceeds the maximum reverse biasing electrostatic force corresponding to pc. As a result, portions of the ion packet 517a are collected by the individual moving pseudopotential wells and transported downstream in a conveyor belt fashion from position pc to the ion outlet 118 at position L. This movement of ions along the flat electric field strength profile 503b is relatively rapid compared to the movement along the rising voltage profile 503a because the additional ramp in RF amplitude is not met by a corresponding increase in the reverse biasing DC electric field. Simulations of ion motion performed by the inventors show that although a portion of the ions of each ion packet may move in the reverse direction (i.e., toward the ion inlet 113) in the constant electric field region 503b, they move less frequently than in the variable electric field region 503a. On average, the traveling pseudopotential wells move ions away from point pc and forward toward the ion outlet 118, so that the ions can efficiently escape from the region 503a near point pc.

[0051] At the same time that ion packet 517a is transported from position pc to position L, ion packets 517b and 517c remain at positions p1 and p2 upstream of position pc as a result of the previous spatial separation of the various ion packets. Because the forward biasing pseudopotential forces at these positions are only sufficient to approximately balance (i.e., slightly exceed) the reverse biasing DC electric field forces, the ions of both these packets continue to move relatively slowly toward position pc as the RF amplitude is further ramped until a subsequent time t3 when packet 517b reaches position pc. As shown in FIG. 6G, the further ramping of the RF amplitude causes the relatively rapid transport of ions of packet 517b from position pc to position L. Yet another ramp transports ions of packet 517c in a similar manner (not shown).

[0052] The transport of ions through the ion guide, in the manner described above with reference to Figures 6G-6H, causes the emergence of ion packets with different respective m / z values ​​from the ion outlet 118 of the device to be separated in time by at least the flight time of the ions from position pc to the ion outlet 118. The axial electric field profile opposing the forward motion of the ions does not need to be exactly as shown in Figures 6D, 6F and 6G. For example, a voltage profile of the general form shown in Figure 6H, in which the profile along the second segment 503b is not constant, can also be usefully employed. Simulations of ion motion and distribution carried out by the inventors have shown that the exact form of the electric field in the "constant" region (i.e. the region represented by voltage profile segment 503b) is not important. The simulations show that the best m / z resolution is achieved when the electric field in profile segment 503b is constant, but that small variations have little effect on performance. In any event, any gradient of the DC electric field in profile segment 503b should be less than the gradient of the DC electric field in the profile region 503a used for the initial spatial separation of ion species by m / z.

[0053] Furthermore, the amplitude A of the applied RF waveform RF The ramp rate of A may be selected according to the requirements of a particular measurement. For example, if the ion guide device is employed as a mass spectrometer of the type operated in a general inspection mode, involving detection of all ions emerging from the ion outlet, then A may be selected as shown diagrammatically in FIG. 7A. RF A continuous gradient of A over time may be employed. RFWhile a linear variation of is illustrated, alternatively the variation may be non-linear, having a steeper slope (i.e., a more rapid increase in amplitude) at times during the ramp where ions emerging from the instrument are not expected to require detection at maximum achievable resolution, and a shallower slope (i.e., a slower rate of increase in amplitude) at other times where emerging ions are expected to require a higher level of m / z discrimination. For example, FIG. 8 shows the expected achievable mass spectral resolution of ions as a function of m / z at a constant RF ramp rate. FIG. 9 shows that the longer the duration allotted for completion of the ramp, the higher the expected resolution. FIG. 7B shows, for example, the longer dwell time Δt at times when a particular ion of interest is expected to emerge from the instrument, and a variable amplitude jump ΔA at times when ions of interest are not expected. RF Such expected times of appearance of ions of particular m / z values ​​may be predetermined by calibration of the transit times of known standard ions through the instrument under various conditions.

[0054] 4A and 4B represent simulated performance of an ion sorting device constructed and operated in accordance with the present teachings. The simulated device is 160 mm wide, has 320 electrodes, and 160 pseudopotential wells. The simulations assumed a typical separation / equilibration time of 40 ms and assumed operation in the presence of 100 mTorr of nitrogen gas. The plot in FIG. 4A represents the equilibrium positions of ions of various m / z ratios in such a device under an applied DC axial field gradient and simultaneously under an applied RF waveform that does not vary over the length of the device. In contrast, the plot in FIG. 4B represents the equilibrium positions of the same ions under an applied RF amplitude gradient over the length of the device in the presence of a uniform DC axial field. Trace 301 (FIG. 4A) and trace 351 (FIG. 4B) both represent ions with a hypothetical m / z value of 500 Th. Similarly, traces 302 and 352 represent ions having an m / z ratio of 600 Th, traces 303 and 353 represent ions having an m / z ratio of 700 Th, traces 304 and 354 represent ions having an m / z ratio of 800 Th, traces 305 and 352 represent ions having an m / z ratio of 900 Th, and traces 306 and 356 represent ions having an m / z ratio of 1000 Th.

[0055] FIG. 5 is a schematic diagram of a portion of a mass spectrometer apparatus including an ion filter 400 or other mass spectrometer component arranged in series with an ion guide ion transport device 500, constructed in accordance with the teachings above. The apparatus 500 may comprise any of the embodiments illustrated in the accompanying drawings, or any apparatus not shown that is operated in accordance with the present teachings, including, but not limited to, an ion guide comprising a series of electrodes disposed or otherwise attached on parallel plates or wafers (e.g., FIGS. 1C, 1D), an ion guide comprising a series of electrodes disposed or otherwise attached on non-parallel plates or wafers (e.g., FIG. 3B), an ion tunnel (e.g., FIGS. 2A-2C), an ion funnel (e.g., FIG. 3A), an ion guide having any number of both ion tunnel and ion funnel portions (e.g., FIGS. 1A-1B), an ion guide comprising a series of segments of quadrupole rods into which a series of electrodes are segmented, and other ion guides that can provide both an axial electric field gradient (either across or over only a portion of the length of the device) and a longitudinal gradient (either across or over only a portion of the length of the device) in RF amplitude or some other RF parameter.

[0056] As illustrated, the device 400 is a quadrupole mass filter comprising four mutually parallel rod electrodes 401 maintained in mutual alignment by a support structure 415, which may also provide electrical connections to the rods. In other cases, the device may comprise, but is not limited to, a multipole ion trap, a multipole fragmentation cell, an ion guide, or any type of mass analyzer. Preferably, a controllable ion gate 410 is located between the ion outlet of the device 500 and the ion inlet of the device 400.

[0057] In operation of the system shown in Figure 5, the device 500 provides an outlet stream 119 of ions where at any one time the range of mass-to-charge (m / z) values ​​of the ions making up the outlet stream 119 is reduced compared to the wider range of m / z values ​​provided at the inlet end of the device 500 in the inlet ion stream 115, where the (m / z) values ​​making up the outlet stream 119 change over time to either larger or smaller m / z values. Thus, in effect, the operation of the device 500 is similar to that of a conventional mass filter in which the mass-to-charge passband of the mass filter is scanned over time, except that the passbands of the device 500 are wider than those of a conventional mass filter, and ions within each passband range may be accumulated and temporarily stored within the device 500 before being ejected from the device. Thus, the device 500 performs the function of ion accumulation as well as the function of partially pre-separating ions before they are transferred to the conventional device 400. If the conventional instrument 400 includes a quadrupole mass filter, such a mass filter can isolate narrower m / z ranges, each isolation range containing ion species of particular interest.

[0058] The ion outlet stream 119 may be either continuous in time or discontinuous in time. The continuity of delivery of the ion outlet stream to the device 400 may be controlled by operation of the ion gate 410, thereby limiting the m / z range of ions that may be transferred to the downstream device during any particular time interval. During the time that the ion gate 410 is closed (thereby limiting transmission), new ion packets from the inlet ion stream 115 may accumulate and be sorted within the upstream device 500, as described hereinabove. At such times, the applied RF waveform and DC voltages are adjusted to cause sorting (e.g., FIG. 2B). When the ion gate 410 is open, the internal RF waveform and DC voltages are adjusted to allow the accumulated ions to move out of the device in either increasing (e.g., FIG. 2C) or decreasing (e.g., FIG. 3A) order of their m / z values.

[0059] FIG. 10A is a flow diagram of a first method (method 800) of operating an ion guide in accordance with the present teachings. In a first step, step 801 of method 800, a pulse of ions comprising a range of mass-to-charge ratios (m / z) is input to a first of two separate ion ports of the ion guide. In step 802, the ions are temporarily trapped and / or stored in the ion guide at an end of the ion guide adjacent the first port. The ions may be temporarily trapped and / or stored there by applying a DC voltage to electrodes near the first port to temporarily create a temporary static potential well near the port. In a next step 803, a radio frequency (RF) voltage waveform is applied to a series of electrodes of the ion guide that creates a plurality of pseudo-potential wells configured to urge the ions in a first direction, either away from the first ion port toward a second ion port or alternatively toward the first ion port. In step 805, which occurs simultaneously with step 803, a DC potential is applied to each of two or more respective electrodes to generate a DC field that biases the ions in a direction opposite to the bias of the ions by the pseudopotential well. The DC field may be either uniform (i.e., constant magnitude that does not vary with position) or non-uniform (i.e., has a magnitude that varies with position) over the length of the ion guide. In optional step 807, either the applied RF amplitude and / or one or more applied DC potentials are gradually ramped over time, either in an increasing or decreasing manner, to facilitate differential movement of ions towards the second ion port. Finally, in step 809, ions that include a reduced m / z ratio range relative to (i.e., a subset of) the range of m / z ratios of the originally input ions are extracted from the second port of the ion guide. The extracted ions may be injected into another component of the mass spectrometer apparatus, such as a mass filter, a collision cell, or a mass analyzer.

[0060] FIG. 10B is a flow diagram of a second method (method 810) of operating an ion guide in accordance with the present teachings. In step 811 of method 810, a radio frequency (RF) voltage waveform is applied to a series of electrodes disposed between the ion inlet and the ion outlet of the ion guide, the RF voltage waveform generating a plurality of pseudo-potential wells configured to urge ions away from the ion inlet and toward the ion outlet. In step 813, which is performed simultaneously with the performance of step 811, a respective DC potential is applied to each of two or more of the electrodes generating a DC electric field configured to urge ions away from the ion outlet and toward the ion inlet. The DC electric field may be either uniform (i.e., of a constant magnitude that does not vary with position) or non-uniform (i.e., having a magnitude that varies with position) over the length of the ion guide. Then, in step 815, a pulse of ions comprising a range of mass-to-charge values ​​is injected into the ion guide through the ion inlet. In step 817, (a) the amplitude of the applied RF waveform is increased and / or (b) the magnitude of the applied DC electric field is gradually decreased to differentially move ions through the ion guide towards the ion outlet. In step 819, ions are extracted from the ion outlet in order of increasing their mass to charge ratio. The extracted ions may be injected into another component of the mass spectrometer apparatus such as a mass filter, collision cell, or mass analyzer. According to a variation of method 810, step 815 may be performed before steps 811-813, and an additional step of trapping a pulse of ions in a region of the ion guide adjacent the ion inlet may be performed before the execution of steps 811-813.

[0061] 10C is a flow diagram of a third method (method 830) of operating an ion guide in accordance with the present teachings. In step 831, a radio frequency (RF) voltage waveform is applied to a plurality of electrodes of an ion funnel having an ion inlet end, an ion outlet end, and a plurality of plate or ring electrodes between the inlet and outlet ends with respective openings that decrease in diameter from the inlet end to the outlet end, the RF voltage waveform generating a plurality of pseudo-potential wells configured to urge ions toward the ion inlet and away from the ion outlet. In step 833, which is performed simultaneously with the performance of step 831, a respective DC potential is applied to each of the electrodes, whereby the applied potentials generate a DC electric field configured to urge ions away from the inlet end and toward the outlet end. Thereafter, in step 835, a pulse of ions comprising a range of mass-to-charge values ​​is flowed into the ion funnel through the ion inlet end. In optional step 837, the magnitude (i.e., strength) of the DC electric field toward the ion outlet end of the ion funnel can be increased by ramping the DC voltage applied to the electrodes to facilitate movement of ions toward the ion outlet end of the ion funnel. Finally, in step 839, ions are extracted from the outlet end of the ion funnel in order of decreasing m / z ratio. The extracted ions may be injected into another component of the mass spectrometer apparatus, such as a mass filter, collision cell, or mass analyzer.

[0062] The description contained in this application is intended to serve as a basic description. The present invention is not intended to be limited in scope by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention. Functionally equivalent methods and components are within the scope of the invention, as defined by the claims. Various other modifications of the present invention, in addition to those shown and described herein, will be apparent to those skilled in the art. For example, a method for generating an axial DC electric field is described herein, in which an end-to-end DC voltage is proportioned (e.g., by using a voltage divider) across a series or number of electrodes to which an RF voltage is also applied. However, many other means of generating an axial electric field in an ion guide have been described, many of which utilize a set of auxiliary electrodes to generate the axial electric field. Such auxiliary electrodes are often separate from and in addition to the series or number of main electrodes that receive the RF voltage waveform. Many alternative methods of generating axial or drag electric fields are described in U.S. Patent No. 7,675,031 (Konicek et al.), U.S. Patent No. 5,847,386 (Thomson et al.), U.S. Patent No. 7,985,951 (Okumura et al.), U.S. Patent No. 7,064,322 (Crawford et al.), U.S. Patent No. 7,064,322 (Crawford et al.), and U.S. Patent No. 6,417,511 (Russ, IV et al.). Adapting one or more of these known axial electric field generating techniques to the methods and apparatus described herein is contemplated and would be within the capabilities of one of ordinary skill in the art.

[0063] As another example of a modification of the above teachings, variation of the spacing between adjacent ring electrodes 2 (FIGS. 1A, 2A, 2B, 2C), or between adjacent electrodes of an array 55 supported on a substrate (FIG. 1C), may be used as an additional method to generate a longitudinal spatial gradient in the dynamics of RF induced traveling waves. For example, the inter-electrode spacing may be varied continuously or discontinuously along the axial length of an ion guide or ion separator apparatus in accordance with the present teachings, which variation produces a corresponding variation in the depth of the pseudopotential well along the length of the device.

[0064] As yet another example of a modification of the above teachings, the reader is referred to Figures 11A-11B. The hypothetical voltage plots shown in Figures 11A-11B, when considered together, provide an example of the application to an ion guide device of two separate DC voltage profiles 930, 940 that alternate in time with one another. The left end of each voltage profile corresponds to the ion inlet or "upstream" end of the ion guide device, and the right end of each profile corresponds to the ion outlet or "downstream" end of the device. In operation, each DC profile is applied simultaneously with the application of an RF modulated traveling wave that creates an RF induced pseudopotential well that urges ions toward the downstream end of the device to which the DC profile is applied. The DC voltage profiles 930, 940 are applied to provide a force on the ions that opposes the pseudopotential induced force and thus urges the ions toward the upstream end of the device. Thus, the algebraic sign of the slope of the profiles 930, 940 implicitly assumes that the ions are positively charged.

[0065] 11A-11B includes a series of steeper slope segments 932 separated from one another by a series of shallower slope segments 933. The terms "steep" and "shallow slope" are used herein in a relative sense only and do not imply a particular numerical value of the slope or applied voltage. The steeper slope segments of the voltage profile are separated from one another by a series of shallower slope segments 933.

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[0066] It can be observed that the change from voltage profile 930 (FIG. 11A) to voltage profile 940 (FIG. 11B) and vice versa is equivalent to either a simple left or right shift of a single profile, with the shift being equal to a certain spatial width of the profile segment. However, by appropriately finely controlling the distribution of voltages supplied to the various individual electrode segments that generate the electric field, and the cycling of the voltages supplied to those electrodes, the shift can be made much smaller than the segment width. In such a case, the change in the location of the "peaks" 936 and "valleys" 937 of the voltage profile and the electric field magnitude profile may be made to more closely approximate a continuous profile shift, and the change in the location of the peaks and valleys 936, 937 may be referred to as a "DC traveling wave". If the upstream travel speed of the peak 936 is controlled to match the travel speed of the target ions along the length of the device, the provision of such an upstream traveling DC traveling wave in conjunction with the simultaneous provision of a downstream traveling RF traveling wave may facilitate the separation and concentration of certain targeted "heavy" ion species at the upstream end of the ion guide device. Generally, "light" ions also migrate toward the downstream end of the device under such conditions, but with less efficiency. Conversely, a downstream-moving DC traveling wave can facilitate separation of "light" ions and concentration of those ions at the downstream end of the device, and / or expulsion of those ions from the device at the ion outlet. Various operating parameters can be controlled as required.

[0067] It should be noted that as the gas pressure is gradually increased beyond 0.01 Torr, the performance of the ion guide device described above gradually changes. Such changes are expected to result from the increased probability of collisions between ions and gas molecules as the gas pressure increases. For small increases in pressure beyond 0.01 Torr, the overall characteristics of the device performance remain as described above, but the m / z resolution and the speed at which ion species travel through the device change. In general, larger gas pressures counteract both the downstream and upstream biases generated by the applied voltage, but the effect of pressure is greatest with respect to the RF traveling wave because the depth of the pseudopotential well decreases with increasing gas pressure. As a result, as the internal pressure increases, the effect of the m / z-independent force exerted on all ions by the applied DC electric field becomes more significant with respect to the bias exerted by the RF traveling wave. Thus, at such gas pressures, the performance of the ion guide device as described above (e.g., m / z resolution, ion residence time) can be advantageously modified by control of the gas pressure according to the requirements of a particular measurement, experiment or analysis program.

[0068] As the gas pressure inside the ion guide device is further increased, ion-molecule collision effects become more and more significant relative to the effects of the applied DC and RF voltages, so that above a certain gas pressure that depends on the device configuration (e.g. length, cross-sectional area, gas composition, etc.), collision effects dominate the m / z dependent effects of the applied voltages and the performance of the device tends to resemble an ion mobility separator, whose performance is moderated by the applied DC and RF voltages. The performance of such an ion mobility device can be advantageously modified by controlling the magnitude of one or more of the applied RF voltage waveforms or by controlling one or more of the frequencies of the applied voltage waveforms, depending on the requirements of a particular measurement, experiment or analysis program.

[0069] Thus, gas pressure can be considered as an additional parameter to be taken into account during calibration of the performance of an apparatus operated as described by the present teachings. More generally, gas pressure is one of many operating parameters, such as apparatus length, apparatus cross-sectional area, gas composition, RF frequency, etc., that can affect mass spectral results (e.g., mass spectral resolution and measurement speed) but that are difficult to model theoretically in combination. As a result, the behavior of the apparatus should be calibrated for each specific apparatus prior to operation so that the effects of these parameters are fully understood in each case.

[0070] Furthermore, various embodiments of the present teachings can be described by one or more of the following clauses. Item 1. A method of operating an ion guide having a series of electrodes, first and second ends, and a gas therein at a pressure of 0.01 Torr or greater, the method comprising: applying a set of radio frequency (RF) voltage waveforms to a series of electrodes that create a plurality of moving pseudo-potential wells that exert a force on ions within the ion guide urging the ions to move from a first end to a second end of the ion guide; concurrently with the application of the set of RF voltage waveforms, applying a set of two or more direct current (DC) potentials to either a series of electrodes or a set of auxiliary electrodes that generate a mass-to-charge ratio (m / z) independent force on ions within the ion guide urging the ions to move from the second end to the first end; A method whereby one or more of m / z dependent spatial separation, differential movement, or filtering of ions within the ion guide is caused. Clause 2. The method of clause 1, wherein the m / z dependent spatial separation, differential movement or filtering of ions within the ion guide is controlled, in part, by controlling the gas pressure. Clause 3. The method of clause 1, wherein the ion guide is an ion mobility ion separator and the m / z dependent spatial separation, differential movement or filtering of ions within the ion guide is controlled, in part, by controlling either the magnitude or frequency of the applied RF voltage waveform. Item 4. The method of item 1, wherein the force on the ions generated by application of two or more DC potentials is generated by a dynamic DC electric field. Item 5. The method of item 4, wherein the dynamic DC electric field comprises a DC traveling wave. Clause 6. The method of clause 1, wherein the application of the two or more DC electric fields produces a static DC electric field in the ion guide. Item 7. The first end of the ion guide is an ion inlet and the second end of the ion guide is an ion outlet, and a static DC electric field is a first segment adjacent the first end, the DC electric field magnitude of the first segment gradually increasing along a direction away from the first end; and a second segment adjacent the second end, the second segment having a DC electric field magnitude equal to or greater than any of the DC electric field magnitudes in the first segment. Clause 8. The method of clause 7, wherein within the second segment, the variation in magnitude of the DC electric field as a function of distance from the first end of the ion guide is substantially linear. Clause 9. The method of clause 1, wherein applying the set of RF voltage waveforms to the series of electrodes comprises applying the set of RF voltage waveforms to a series of ring electrodes. Clause 10. The method of clause 9, wherein applying the set of RF voltage waveforms to the series of ring electrodes comprises applying the set of RF voltages to ring electrodes of an ion tunnel device. Item 11. The application of a set of RF voltage waveforms to a series of electrodes applying a set of RF voltage waveforms to a first series of electrodes disposed on a surface of a first substrate plate or wafer and to a second series of electrodes disposed on a surface of a second substrate plate or wafer; Item 10. The method of item 1, wherein the first substrate plate or wafer is substantially parallel to the second substrate plate or wafer and separated from the second substrate plate or wafer by a gap. Item 12. Applying two or more DC potentials includes applying potentials that create a static, uniform DC electric field within the ion guide, thereby directing ions of a particular mass-to-charge ratio (m / z). M 2. The method of claim 1, wherein ions having a mass to charge ratio of 1 are accumulated within the ion guide and ions having other mass to charge ratios are moved out of the ion guide. Item 13. The method further includes ramping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby detecting a specific mass-to-charge ratio (m / z). M Item 13. The method of item 12, wherein accumulated ions having a magnitude of .gtoreq..times ... Clause 14. The method of clause 1, wherein applying two or more DC potentials comprises applying potentials that generate a static, non-uniform DC electric field within the ion guide, whereby ions are accumulated at a plurality of different locations within the ion guide according to their respective mass-to-charge ratio values. Clause 15. The method of clause 14, further comprising ramping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, whereby accumulated ions are caused to move out of the ion guide through either the first or second end in either ascending or reverse order of the ions' respective mass to charge ratios. Section 16. applying the set of RF voltage waveforms to the series of ring electrodes comprises applying the set of RF voltages to a ring electrode of an ion funnel device, the first end being a wide end of the ion funnel device and the second end being a narrow end of the ion funnel device; applying the two or more DC potentials includes applying potentials that create a static, uniform DC electric field within the ion guide that exerts a force on the ions urging them towards a narrow end of the ion funnel device; 10. The method of claim 9, whereby ions are accumulated at a number of different positions within the ion guide according to their respective mass to charge ratio values. Clause 17. The method of clause 16, further comprising ramping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, whereby the accumulated ions are caused to move out of the ion guide through the narrow end of the ion funnel device in reverse order of the ions' respective mass to charge ratios. Item 18. A mass spectrometer system, comprising: an ion source configured to generate a plurality of ions by ionization of a sample, the ions comprising a plurality of mass-to-charge ratio (m / z) values; An ion guide having a gas therein at a pressure of 0.01 Torr or more, an ion inlet configured to receive a stream of ions from an ion source; Ion outlet, and an ion guide comprising: a series of electrodes disposed between an ion inlet and an ion outlet, the series of electrodes defining an ion occupied volume between the ion inlet and the ion outlet and an axis of the ion guide; one or more power sources electrically coupled to the series of electrodes, the one or more power sources comprising: applying a set of radio frequency (RF) voltage waveforms to a series of electrodes to confine ions within an ion-occupied volume and generate a plurality of moving pseudo-potential wells that exert forces on the ions urging them to move either from the inlet end to the outlet end or from the outlet end to the inlet end; and one or more power supplies configured to apply a set of direct current (DC) potentials to a series of electrodes or two or more auxiliary electrodes that generate a force on ions in the ion guide that is mass-to-charge ratio (m / z) independent and counters a force exerted by a moving pseudo-potential well, simultaneously with the application of the set of RF voltage waveforms. Clause 19. The mass spectrometer system of clause 18, wherein the one or more power supplies are configured to apply a set of DC potentials to generate a dynamic DC electric field within the ion guide. Item 20. The mass spectrometer system of item 19, wherein the dynamic DC electric field comprises a DC traveling wave. Clause 21. The mass spectrometer system of clause 18, wherein the one or more power supplies are configured to apply a set of DC potentials to generate a static DC electric field in the ion guide. Item 22. A DC electric field generates a force on the ions configured to urge the ions towards the ion inlet, the static DC electric field: a first segment adjacent the first end, the magnitude of the DC electric field gradually increasing along a direction away from the ion inlet and toward the ion outlet; and a second segment adjacent the second end, the second segment having a DC electric field magnitude equal to or greater than any of the DC electric field magnitudes in the first segment. Clause 23. The mass spectrometer system of clause 22, wherein within the second segment, the variation in magnitude of the DC electric field as a function of distance from the first end of the ion guide is substantially linear. Item 24. The mass spectrometer system of item 18, wherein the series of electrodes comprises a series of ring electrodes of a stacked ring ion guide. Item 25. A series of electrodes, a first series of electrodes disposed on a surface of a first substrate plate or wafer; and a second series of electrodes disposed on a surface of a second substrate plate or wafer. Clause 26. The mass spectrometer system of clause 25, wherein the first substrate plate or wafer is substantially parallel to the second substrate plate or wafer and separated from the second substrate plate or wafer by a gap. Item 27. A mass spectrometer system according to item 25, wherein the first substrate plate or wafer and the second substrate plate or wafer converge towards each other along a direction from the ion inlet to the ion outlet. Item 28. The one or more power sources are further configured to apply a DC potential such that the generated DC electric field is a static, uniform electric field, thereby detecting a specific mass-to-charge ratio (m / z). M 20. The mass spectrometer system of claim 18, wherein ions having a mass to charge ratio of 1 are accumulated within the ion guide and ions having other mass to charge ratios are moved out of the ion guide. Item 29. The one or more power sources are further configured to vary the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby varying the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby varying the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby varying the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby varying the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby varying the magnitude of the applied RF voltage ... M 29. The mass spectrometer system of claim 28, wherein accumulated ions having a magnitude of 0.01 to 0.1 are moved out of the ion guide through an ion ejection port. Clause 30. The mass spectrometer system of clause 18, wherein the one or more power supplies are further configured to apply a set of DC potentials such that the generated DC electric field is a static, non-uniform electric field, thereby causing ions to accumulate at a plurality of different locations within the ion guide according to their respective mass to charge ratio values. Clause 31. The mass spectrometer system of clause 30, wherein the one or more power supplies are further configured to ramp the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, whereby the accumulated ions are moved out of the ion guide through the ion outlet either in order of the ions' respective mass to charge ratios increasing or in order of the ions' respective mass to charge ratios decreasing. Clause 32. The mass spectrometer system of clause 18, further comprising a mass filter device configured to receive ions transmitted out of the ion guide through the outlet end of the ion guide. Item 33. The mass spectrometer system of Item 32, further comprising an ion gate disposed between the outlet end of the ion guide and the mass filter. Item 34. A mass spectrometer system according to Item 18, wherein the inter-electrode spacing between the ion inlet and the ion outlet is not constant.

Claims

1. 1. A method of operating an ion guide comprising a series of electrodes, first and second ends, and having a gas therein at a pressure of 0.01 Torr or greater, the method comprising: applying a set of radio frequency (RF) voltage waveforms to the series of electrodes that create a plurality of moving pseudo-potential wells that exert a force on ions within the ion guide urging the ions to move from the first end to the second end of the ion guide; concurrently with said application of said set of RF voltage waveforms, applying a set of two or more direct current (DC) potentials to either the series of electrodes or a set of auxiliary electrodes that generate a force on the ions within the ion guide that is mass to charge ratio (m / z) independent and urges the ions to move from the second end to the first end; thereby causing one or more of m / z dependent spatial separation, differential movement or filtering of ions within said ion guide.

2. 10. The method of claim 1, wherein the m / z dependent spatial separation, differential movement, or filtering of ions within the ion guide is controlled, in part, by controlling gas pressure.

3. 2. The method of claim 1 , wherein the ion guide is an ion mobility ion separator, and the m / z dependent spatial separation, differential movement, or filtering of ions within the ion guide is controlled, in part, by controlling either the magnitude or frequency of an applied RF voltage waveform.

4. The method of claim 1 , wherein the force on the ions generated by the application of the two or more DC potentials is generated by a dynamic DC electric field.

5. The method of claim 4 , wherein the dynamic DC electric field comprises a DC traveling wave.

6. The method of claim 1 , wherein the application of the two or more DC electric fields creates a static DC electric field in the ion guide.

7. the first end of the ion guide is an ion inlet and the second end of the ion guide is an ion outlet, and the static DC electric field a first segment adjacent the first end, the magnitude of the DC electric field gradually increasing along a direction away from the first end; a second segment adjacent the second end, the magnitude of the DC electric field being equal to or greater than any magnitude of the DC electric field in the first segment.

8. 8. The method of claim 7, wherein within the second segment, the variation in magnitude of the DC electric field as a function of distance from the first end of the ion guide is substantially linear.

9. The method of claim 1 , wherein the applying the set of RF voltage waveforms to the series of electrodes comprises applying the set of RF voltage waveforms to a series of ring electrodes.

10. 10. The method of claim 9, wherein said applying said set of RF voltage waveforms to said series of ring electrodes comprises applying a set of RF voltages to a ring electrode of an ion tunnel device.

11. said applying said set of RF voltage waveforms to said series of electrodes applying the set of RF voltage waveforms to a first series of electrodes disposed on a surface of a first substrate plate or wafer and to a second series of electrodes disposed on a surface of a second substrate plate or wafer; The method of claim 1 , wherein the first substrate plate or wafer is substantially parallel to the second substrate plate or wafer and separated from the second substrate plate or wafer by a gap.

12. The application of the two or more DC potentials includes applying potentials that create a static, uniform DC electric field within the ion guide, thereby generating a specific mass to charge ratio (m / z) Ｍ 2. The method of claim 1, wherein ions having a mass to charge ratio of 1 are accumulated within the ion guide and ions having other mass to charge ratios are moved out of the ion guide.

13. The method further includes ramping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby detecting the specific mass to charge ratio (m / z). Ｍ 13. The method of claim 12, wherein the accumulated ions having a .DELTA..times ...

14. 2. The method of claim 1 , wherein the application of the two or more DC potentials comprises applying potentials that create a static, non-uniform DC electric field within the ion guide, whereby the ions are accumulated at a plurality of different locations within the ion guide according to their respective mass to charge ratio values.

15. 15. The method of claim 14, further comprising ramping the magnitude of an applied DC potential or the amplitude of an applied RF voltage waveform, whereby the accumulated ions are caused to move out of the ion guide through either the first or second end in either ascending or reverse order of their respective mass to charge ratios.

16. said applying the set of RF voltage waveforms to the series of ring electrodes comprises applying a set of RF voltages to a ring electrode of an ion funnel device, said first end being a wide end of said ion funnel device and said second end being a narrow end of said ion funnel device; said applying of the two or more DC potentials comprises applying potentials that create a static uniform DC electric field within the ion guide that exerts a force on the ions urging them towards the narrow end of the ion funnel device; whereby ions are accumulated at a number of different locations within the ion guide according to their respective mass to charge ratio values.

10. The method of claim 9.

17. ramping the magnitude of an applied DC potential or the amplitude of an applied RF voltage waveform, whereby the accumulated ions are caused to move out of the ion guide through the narrow end of the ion funnel device in reverse order of their respective mass to charge ratios.

17. The method of claim 16.

18. 1. A mass spectrometer system comprising: an ion source configured to generate a plurality of ions by ionization of a sample, the ions comprising a plurality of mass-to-charge ratio (m / z) values; An ion guide having a gas therein at a pressure of 0.01 Torr or more, an ion inlet configured to receive the stream of ions from the ion source; Ion outlet, and an ion guide comprising: a series of electrodes disposed between the ion inlet and the ion outlet, the series of electrodes defining an ion occupied volume between the ion inlet and the ion outlet and an axis of the ion guide; one or more power sources electrically coupled to the series of electrodes, the one or more power sources comprising: applying a set of radio frequency (RF) voltage waveforms to the series of electrodes to confine the ions within the ion-occupied volume and generate a plurality of moving pseudo-potential wells that exert forces on the ions urging them to move either from the inlet end to the outlet end or from the outlet end to the inlet end; and one or more power supplies configured to apply a set of direct current (DC) potentials to the series of electrodes or two or more auxiliary electrodes that generate a mass-to-charge ratio (m / z) independent force on the ions in the ion guide that opposes the force exerted by the moving pseudo-potential well, simultaneously with the application of the set of RF voltage waveforms.

19. 20. The mass spectrometer system of claim 18, wherein the one or more power supplies are configured to apply the set of DC potentials to generate a dynamic DC electric field within the ion guide.

20. 20. The mass spectrometer system of claim 19, wherein the dynamic DC electric field comprises a DC traveling wave.

21. 20. The mass spectrometer system of claim 18, wherein the one or more power sources are configured to apply the set of DC potentials to generate a static DC electric field in the ion guide.

22. the DC electric field generates a force on the ions configured to urge the ions towards the ion inlet, the static DC electric field: a first segment adjacent a first end, the magnitude of the DC electric field gradually increasing along a direction away from the ion inlet toward the ion outlet; a second segment adjacent a second end, the magnitude of the DC electric field being equal to or greater than any magnitude of the DC electric field in the first segment.

23. 23. The mass spectrometer system of claim 22, wherein within the second segment, the variation in magnitude of the DC electric field as a function of distance from the first end of the ion guide is substantially linear.

24. 20. The mass spectrometer system of claim 18, wherein the series of electrodes comprises a series of ring electrodes of a stacked ring ion guide.

25. The series of electrodes a first series of electrodes disposed on a surface of a first substrate plate or wafer; a second series of electrodes disposed on a surface of a second substrate plate or wafer.

26. 26. The mass spectrometer system of claim 25, wherein the first substrate plate or wafer is substantially parallel to the second substrate plate or wafer and separated from the second substrate plate or wafer by a gap.

27. 26. The mass spectrometer system of claim 25, wherein the first substrate plate or wafer and the second substrate plate or wafer converge towards each other along a direction from the ion inlet to the ion outlet.

28. The one or more power sources are further configured to apply the DC potential such that the generated DC electric field is a static, uniform electric field, thereby detecting a particular mass to charge ratio (m / z). Ｍ 20. The mass spectrometer system of claim 18, wherein ions having a mass to charge ratio of 1 are accumulated within the ion guide and ions having other mass to charge ratios are moved out of the ion guide.

29. The one or more power sources are further configured to vary the magnitude of an applied DC potential or the amplitude of an applied RF voltage waveform, thereby determining the specific mass to charge ratio (m / z). Ｍ 30. The mass spectrometer system of claim 28, wherein the accumulated ions having a magnitude of .gtoreq..times ...

30. 20. The mass spectrometer system of claim 18, wherein the one or more power sources are further configured to apply the set of DC potentials such that a generated DC electric field is a static, non-uniform electric field, whereby ions are caused to accumulate at a plurality of different locations within the ion guide according to their respective mass to charge ratio values.

31. 31. The mass spectrometer system of claim 30, wherein the one or more power supplies are further configured to ramp the magnitude of an applied DC potential or the amplitude of an applied RF voltage waveform, whereby the accumulated ions are moved out of the ion guide through the ion outlet in either order of increasing respective mass to charge ratios of the ions or decreasing respective mass to charge ratios of the ions.

32. 20. The mass spectrometer system of claim 18, further comprising a mass filter device configured to receive ions transmitted out of the ion guide through an outlet end of the ion guide.

33. 33. The mass spectrometer system of claim 32, further comprising an ion gate located between the outlet end of the ion guide and a mass filter.

34. 20. The mass spectrometer system of claim 18, wherein the inter-electrode spacing between the ion inlet and the ion outlet is not constant.

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