Ion guide with switchable operating modes

Abstract

We provide a mass spectrometer system equipped with an ion guide. [Solution] An ion guide 1202, consisting of a series of electrodes 1212 positioned between a first end 1210-1 and a second end 1210-2, operates in either an m / z separation mode for separating ions primarily based on their mass-to-charge ratio (m / z), or an ion mobility separation mode for separating ions primarily based on their mobility. A controller 1206 sets the attributes of a radio frequency (RF) voltage waveform to be applied to the series of electrodes 1212 and is further configured to apply the RF voltage waveform while the ion guide 1202 is operating in the selected mode. The RF voltage waveform causes spatial separation of ions within the ion guide 1202, generating a plurality of moving pseudopotential wells, which exert a force that biases ions to move toward the second end 1210-2 of the ion guide 1202.

Description

[Technical Field]

[0001] (Related applications) This application claims priority to U.S. Provisional Patent Application No. 63 / 716,846, filed on November 6, 2024, the entirety of which is incorporated herein by reference. [Background technology]

[0002] Mass spectrometry has often been called the "gold standard" tool for the identification and analysis of various classes of compounds. Much of the strength of mass spectrometry lies in the ability of modern mass spectrometers to separate, store, and subsequently manipulate specific ion species of interest, selected from the numerous ion species generally produced by the ionization of any given sample mixture, via ion fragmentation or ion-ion chemical reactions. In many types of mass spectrometers, quadrupole mass filters are often employed to perform ion separation. For example, in triple quadrupole or quadrupole-time-of-flight (Q-TOF) mass spectrometers, the mass filter is positioned before the mass spectrometer. The mass filter can receive ion streams consisting of various ion species with different mass-to-charge (m / z) ratios. Specific pairs of direct-current (DC) and oscillating radio-frequency (RF) voltages may be applied to the rod electrodes of the mass filter to separate specific ion species with a particular m / z. Applying appropriately sized DC and RF voltages allows only a narrow range of m / z values ​​encompassing the desired specific m / z to pass through the mass filter. This operation neutralizes and removes all other ions with different m / z values ​​from the instrument. The ion species containing the desired specific m / z are thus transmitted through the mass filter to other downstream mass spectrometer components without significant contamination from other ion species, allowing the separated ions to be manipulated and analyzed in various ways.

[0003] While mass filters perform an important function, they are still inefficient in that they always exclude all ions except for specific ions that are allowed to pass through the instrument by selecting the filter passband. As a result, more than 90 percent of potentially available compositionally relevant information can typically be wasted by mass filters at any given time.

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

[0005] As an example of such preliminary separation methods, ion mobility spectrometry (IMS) is often used to separate ionized molecules in the gas phase based on their mobility within a carrier buffer gas. For a general overview of the coupling of ion mobility spectrometers to mass spectrometers, readers should refer 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 (Non-patent Literature 1)). 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 an canceling gas flow, or along a uniform DC electric field by a canceling gas flow having a non-uniform axial velocity profile (gas velocity gradient). The captured ions are separated in space according to their ion mobility and then eluted (released) over time according to their mobility by adjusting either the gas velocity or the DC electric field. Details of the TIMS technique are described, for example, in U.S. Patent No. 6,630,662 by inventor Loboda (Patent Document 1), U.S. Patent No. 7,838,826(B1) by inventor Park (Patent Document 2), and U.S. Patent No. 11226308 by Rather and Michelmann (Patent Document 3).Further explanations are 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 (Non-Patent Literature 2)) 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 (Non-Patent Literature 3)).

[0006] Both ion mobility spectroscopy techniques and trap-type ion mobility spectroscopy techniques utilize ion guides configured to provide an axial DC electric field along their longitudinal direction. Such an axial electric field can be provided by proportionally distributing the voltage applied between the inlet and outlet ends of the ion guide among a plurality of electrodes positioned between the inlet and outlet ends of the ion guide. As an example, the voltage may be proportionally distributed among segments of the rod electrodes of a quadrupole or multipole ion guide apparatus. Alternatively, as will be described in more detail later herein, the voltage may be proportional, for example, between a plurality of mutually parallel electrode plates, or between a plurality of thin electrode wires deposited or otherwise bonded onto a substrate plate or wafer.

[0007] By providing appropriate power and electrical connections, a so-called "traveling wave" DC voltage can be supplied to various rod segments of a segmented quadrupole ion guide, plate electrodes of a multilayer plate or multilayer ring ion guide, or electrode wires of a printed circuit board (U.S. Patent No. 6,812,453 by inventors Bateman et al.). Generally, in such operation, a periodically fluctuating DC voltage is applied to individual rod segment electrodes, plate electrodes, or wires, with the phase of the periodicity shifting between pairs of electrodes, causing the potential well to move from the ion injection end to the ion outlet end of the ion guide. 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 impactor cell using DC traveling waves is the T-Wave® system offered by Waters Corporation (Milford, Massachusetts, USA). The T-Wave® system employs a multilayer ring ion guide with radial ion confinement provided by an RF voltage and axial ion propulsion provided by an added DC traveling wave.Another DC traveling wave configuration known by the acronym "SLIM" (Structures for Lossless Ion Manipulation) has been developed at the Pacific Northwest National Laboratory and is 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 (Non-Patent Document 4)) 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 ion manipulations." Analyst 142, no. 7 (2017): 1010-1021 (Non-Patent Document 5)). The SLIM ion guide employs a similar traveling wave concept for ion capture and propulsion but does so using a modified electrode configuration suitable for printed circuit board implementation. The T-Wave (trademark) and SLIM traveling wave systems are most commonly used at relatively high pressures (e.g., about 1 Torr), where axial ion motion is impeded by gas collisions, and as a result, separation is possible based in part on the collision cross section.

[0008] Recently, ion guides have been described that are implemented by operating a traveling wave as a main RF axial confinement waveform applied not by a DC voltage but instead to plate electrodes of a multi-pole rod segment or a stacked ring structure. According to these teachings, the 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, different modulated RF waveforms are applied to each electrode of the subset. Examples include RF traveling waves generated by amplitude modulation (U.S. Patent No. 9,799,503 to inventors Williams et al. (Patent Document 4)) and frequency modulation (U.S. Patent No. 10,692,710 to inventors Prabhakaran et al. (Patent Document 5)).

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Non-Patent Documents

[0010]

Non-Patent Document 1

Non-Patent Document 2

Outdoor Tools3

Outdoor Tools 4

Direct Environment 5

[0011] The following description provides a simplified overview of one or more embodiments of the systems and methods described herein. This overview is not intended to be a comprehensive overview of all intended embodiments, nor to identify the main or important elements of all embodiments, nor to clearly describe the scope of any or all embodiments. Its sole purpose is to present one or more embodiments of the systems and methods described herein as a prelude to the more detailed description presented below.

[0012] An exemplary system comprises a memory for storing instructions and one or more processors communicatively coupled to the memory, wherein one or more processors are configured to execute instructions, and the process is to determine that an ion guide will operate in a select mode of two modes, wherein the ion guide comprises a first end, a second end, and a set of electrodes positioned between the first and second ends, the set of electrodes defining an ion-occupied volume between the first and second ends, and the two modes include an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the ion-mass-to-charge ratio (m / z), and an ion-mobility separation mode configured to separate ions in the ion-occupied volume mainly based on the ion-mobility. The present invention relates to setting the attributes of a radio frequency (RF) voltage waveform to be applied to a series of electrodes so that the ion guide operates in select mode, the setting including setting the attributes of the RF voltage waveform to a first range when the ion guide operates in m / z separation mode, and setting the attributes of the RF voltage waveform to a second range when the ion guide operates in ion mobility separation mode, the setting including applying an RF voltage waveform having the set attributes to the series of electrodes while the ion guide is operating in select mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward a second end of the ion guide.

[0013] An exemplary mass spectrometer system comprises an ion guide configured to receive ions, the ion guide comprising a series of electrodes positioned at a first end, a second end, and between the first and second ends, the series of electrodes defining an ion-occupied volume between the first and second ends; one or more power supplies electrically coupled to the series of electrodes, configured to apply a set of radio frequency (RF) voltage waveforms to the series of electrodes; and a controller communicatively coupled to the one or more power supplies, the controller configured to execute instructions to carry out a process, the process being to determine to operate the ion guide in a selectable mode of two modes, the two modes being an m / z separation mode configured to separate ions in the ion-occupied volume primarily based on the ion-mass-to-charge ratio (m / z); and a mode configured to separate ions primarily based on ion-mobility The method includes determining an ion mobility separation mode configured to separate ions, and setting the attributes of a radio frequency (RF) voltage waveform to be applied to a set of electrodes to operate an ion guide in a selective mode, wherein setting includes setting the attributes of the RF voltage waveform to a first range when the ion guide is operating in m / z separation mode, and setting the attributes of the RF voltage waveform to a second range when the ion guide is operating in ion mobility separation mode, and setting and applying an RF voltage waveform having the set attributes to a set of electrodes while the ion guide is operating in selective mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases ions to move toward a second end of the ion guide.

[0014] An exemplary method for operating an ion guide comprising a first end, a second end, and a series of electrodes positioned between the first and second ends, wherein the series of electrodes define an ion-occupied volume between the first and second ends, and the method determines to operate the ion guide in a selective mode of two modes, the two modes including an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the ion mass-to-charge ratio (m / z), and an ion mobility separation mode configured to separate ions mainly based on the ion mobility, and based on the determination, a radio frequency (RF) electric current to be applied to the series of electrodes to operate the ion guide in the selective mode. A method for setting the attributes of a pressure waveform, the setting comprising setting the attributes of an RF voltage waveform within a first range when the ion guide is operating in m / z separation mode, and setting the attributes of an RF voltage waveform within a second range when the ion guide is operating in ion mobility separation mode, the setting comprising applying an RF voltage waveform having the set attributes to a series of electrodes while the ion guide is operating in selection mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward a second end of the ion guide. [Brief explanation of the drawing]

[0015] The accompanying drawings illustrate various embodiments and are part of this specification. The illustrated embodiments are merely examples and do not limit the scope of this disclosure. Throughout the drawings, the same or similar reference numerals indicate the same or similar elements. [Figure 1A] This is a schematic cross-sectional view of a known multilayer ring ion guide ion transport device. [Figure 1B] This is a schematic diagram of an exemplary plate electrode that may be used in a multilayer ring ion guide ion transport system. [Figure 1C]This is a schematic diagram of known ion manipulation and ion guide devices that can be used as ion transport devices. [Figure 1D] Figure 1C is a schematic diagram of the electrode configuration on the surface of a known ion manipulation and ion guide device. [Figure 2A] This is a schematic cross-sectional view of an embodiment of an ion tunnel stacked ring ion guide according to this instruction. By applying a static and uniform DC axial electric field to counteract the downstream movement of the pseudopotential well generated by the application of a traveling high-frequency (RF) wave, ions can be moved in different directions depending on their mass-to-charge (m / z) ratio. [Figure 2B] Figure 2A is another schematic cross-sectional view of the ion tunnel stacked ring ion guide, in which ions are moved to various different stable zones according to their respective mass-to-charge (m / z) ratios by the application of a static, non-uniform DC axial electric field that counteracts downstream movement in the pseudopotential well, and are accumulated therein. [Figure 2C] Figure 2A is a schematic diagram illustrating the extraction of ions from the stacked ring ion guide device in the order of each m / z ratio, achieved by tilting the amplitude of the RF voltage applied to the electrodes of the device. [Figure 3A] This is a schematic cross-sectional view of the first embodiment of the ion funnel stacked ring ion guide according to this instruction, in which ions are drawn toward the narrow downstream end of the funnel, and by applying a static, uniform DC axial electric field to counteract the upstream movement of the pseudopotential well generated by the application of a traveling RF wave, the ions are moved in different directions depending on the mass-to-charge (m / z) ratio. [Figure 3B] This is a modified version of the ion manipulation and ion guide device shown in Figure 1C, based on this instruction. [Figure 4A] This is a set of simulated plots of the equilibrium positions of ions with various m / z ratios in an ion-guided ion separator device under the application of an electric field gradient in the DC axis direction, with their directions opposite to the direction of the traveling wave generated by RF. [Figure 4B]This is a set of simulated plots of the equilibrium positions of ions at various m / z ratios within an ion-guided ion separator device, under the application of a gradient in the amplitude of a traveling wave-induced RF waveform in the presence of a counteracting uniform DC axial electric field. [Figure 5] This is a schematic diagram of a part of a mass spectrometer, including a quadrupole mass filter or other mass spectrometer components arranged in series with the ion optics apparatus configured and operating according to this instruction. [Figure 6A] Figure 2A is a reproduction of a schematic cross-sectional view of the apparatus and the ion packets within it, further illustrating a schematic example of how the DC voltage can be distributed between the stacked electrodes to generate a static and uniform DC axial electric field. [Figure 6B] A uniform axial electric field is provided in some embodiments of this teaching to counteract the biasing of ions by the movement of a propagating pseudopotential well (pseudowave) generated by RF,

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[0016] 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 to methods of using such ion optical components within a mass spectrometer. All patents, patent application publications, and other publications referenced herein are incorporated herein by reference in their entirety as they are described herein in their entirety.

[0017] In some examples, as a result of the pseudopotential inductive force (i.e., traveling pseudopotential well) driving ion movement in RF-modulated traveling wave devices being m / z dependent, various ion sorting and / or ion storage devices can be constructed by counteracting the m / z-dependent pseudopotential force with a counteracting m / z-independent force, such as a counteracting DC electric field. Such RF-DC ion sorting devices can be configured to provide initial coarse separation and temporary storage of ion species independently of the gas flow. Such RF-DC sorting devices can be deployed under both high vacuum and medium vacuum conditions, as disclosed herein, and are therefore more versatile than conventional ion sorting devices. Existing DC traveling wave devices require RF confinement separate from the DC traveling wave to move ions, whereas the apparatus and methods described herein utilize an RF voltage to both confine and move ions.

[0018] Since RF-induced traveling waves have an m / z-dependent force (i.e., a greater force for lower m / z values), it is possible to counteract this force with a second m / z-independent force. For example, a static counteracting DC axial electric field can be generated by applying a simple DC potential gradient across multiple electrodes. The combination of counteracting forces can then be used to spatially select ions within an ion guide or ion trap device. Such a pair of counteracting applied forces produce three different ion behavior states, as follows: (1) Firstly, 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 dominating the DC axial electric field, the movement is opposite to the direction of the traveling wave. (3) Finally, for ions with a specific critical m / z value, the RF-induced force and the DC potential gradient-induced force balance out so that the ion does not move in any direction but is trapped within a specific region within the ion optical device, the location of which depends on a specific m / z value and applied voltage.

[0019] In some embodiments, the ion guide can be configured such that, by the coordinated application of an RF electric field and a static DC electric field, low m / z and high m / z ions are moved in opposite directions, while at the same time, ions with critical m / z values ​​are captured at capture positions within the ion guide. According to some other embodiments, the gradient may be applied to either the RF electric field, the DC electric field, or both. In such cases, the capture positions become m / z-dependent, thereby capturing 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, 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. The RF electric field gradient can be generated by varying the RF amplitude V along the length of the device, or more simply by changing the electrode geometry, either by varying the axial spacing of the electrodes or the electrode opening diameter. The DC electric field gradient can be most easily generated by changing the resistors in the divider network used to generate the gradient.

[0020] The spatial and temporal ion separation and sorting provided by the apparatus described herein are independent of gas flow. However, optimal operation of such apparatus can be achieved at ambient gas pressures ranging from 0.01 Torr to about 10 Torr. At lower pressures, if ions are drawn out of pseudopotential wells by opposing DC forces, gas collisions are insufficient, and ions cannot settle into adjacent pseudopotential wells. In such low-pressure regimes, ions may be pulled through or across several progressing RF pseudopotential wells by opposing DC electric fields. Such low-pressure behavior is detrimental to the final resolution of the separation. The strength of the ion mobility contribution will depend on ionic properties, as well as various controllable parameters such as gas composition and gas temperature. Unfortunately, this ion mobility contribution is difficult to predict as a result of the time-varying RF electric field. Therefore, under certain circumstances, it may be necessary to perform appropriate calibration of the response of each apparatus under various selected experimental conditions and different classes of ions. In many embodiments, even at pressures in the range of 0.01 to 0.5 Torr, the contribution of ion mobility effects between ions may be small or negligible compared to the effects caused by differences in ion mass-to-charge ratios or charge differences.

[0021] In the descriptions herein, unless otherwise implicitly or explicitly understood or stated, a singular term encompasses its plural equivalents, and a plural term encompasses its singular equivalent. Furthermore, unless otherwise implicitly or explicitly understood or stated, it is understood that for any given component or embodiment described herein, any of the possible candidates or substitutes 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 some elements may be drawn simply to illustrate the invention. Also, reference numerals may be repeated in various figures to indicate corresponding or similar elements. In addition, unless otherwise implicitly or explicitly understood or stated, any enumeration of candidates or substitutes is for illustrative purposes only and not limiting.

[0022] Unless otherwise defined, all other technical and scientific terms used herein have the meanings generally understood by those skilled in the art to which this disclosure belongs. In case of any conflict, this specification, including definitions, shall prevail. It will be understood that there is an implicit “about” before any quantitative terms referred to herein, so as to be within the scope of this teaching. Similarly, the use of “comprise,” “comprises,” “comprising,” “contain,” “contains,” “containing,” “include,” “includes,” and “including” is not intended to be limiting. Where used herein, “a” or “an” may mean “at least one” or “one or more.” Also, the use of “or” is inclusive, and as a result the phrase “A or B” means when “A” is applicable, when “B” is applicable, or when both “A” and “B” are applicable.

[0023] As used herein, the term “DC” refers to a voltage applied to one or more electrodes of a mass spectrometer component (such as an ion tunnel or ion funnel), and does not necessarily imply the application or presence of current through those electrodes. Therefore, the term “DC” is used herein to distinguish the voltage referred to from an applied oscillating voltage that oscillates at high frequencies and is called an “RF” voltage.

[0024] As used herein, the term “static” applied to a DC electric field (vector field) or RF amplitude refers to a DC electric field or RF amplitude that remains essentially constant over a period of time, with potentially insignificant fluctuations of less than 10 percent of the average electric field strength or average RF amplitude. The term “uniform” applied to a DC electric field refers to a DC electric field that is maintained to have a magnitude and direction that does not fluctuate substantially except for insignificant statistical fluctuations over a length encompassing a set of electrodes that spans the length of an ion optical component from an ion inlet to an ion outlet. Conversely, the terms “gradient” and “non-uniform” applied to a DC electric field refer to spatial fluctuations of at least the magnitude of the DC electric field across a set of electrodes, and a DC electric field that is made to exhibit such fluctuations, respectively. Note that a “static” DC electric field may be either uniform or have a gradient. The term “uniform” applied to an RF amplitude refers to an RF amplitude that is maintained to not fluctuate substantially over a length encompassing a set of electrodes. Conversely, the terms “gradient” and “non-uniform” applied to an RF amplitude refer to spatial fluctuations of the applied amplitude across a set of electrodes.

[0025] As used herein, the terms “dynamic” and “graded,” as applied to either a DC electric field or an RF amplitude, refer to a DC electric field or RF amplitude that is varied over time, either monotonically increasing or monotonically decreasing, over a period of time. The gradient of the magnitude of a DC electric field applied across a set of electrodes requires a gradient of the DC potential applied to a subset of those electrodes (i.e., one or more of them). Similarly, the gradient of the RF amplitude of an RF waveform applied across a set of electrodes requires a gradient of the RF amplitude applied to one or more of those electrodes.

[0026] A DC electric field or RF amplitude maintained in a static state over a first period may be maintained in a dynamic or tilted state at other times occurring either before or after the period, and vice versa. Similarly, a DC electric field or RF amplitude maintained in a uniform state over a first period 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 relation to the effect of the direction of an applied force on one or more ions, do not necessarily mean that one or more ions are moved in that direction in response to a force, since the direction of movement of any ion at the time of force application depends on its initial momentum vector and the vector sum of all such applied forces.

[0027] As described above, so-called "multilayer ring ion guides" are frequently employed in mass spectrometry to guide or otherwise manipulate ions. In this specification, the term "multilayer ring ion guide" is used to refer to any of the following: an ion guide comprising a series or number of rings or ring-shaped electrodes; an ion guide comprising a series or number of plates or plate-like electrodes; and / or an ion guide comprising a series or number of printed circuit boards having electrode structures printed on a substrate surface. Multilayer ring ion guides are often used as either so-called "ion tunnels" or "ion funnels." Figure 1A provides a schematic longitudinal section view of a multilayer ring ion guide apparatus 10 including both an ion tunnel portion 12a and an ion funnel portion 12b. However, it should be noted that many apparatuses simply referred to in the art as "ion funnels" have both an ion tunnel portion and an ion funnel portion, as depicted in Figure 1A.

[0028] Generally speaking, the stacked ring ion guide device 10 comprises multiple closely spaced ring electrodes or plate electrodes 2. A schematic diagram of a typical individual ring electrode or plate electrode 2 is shown in Figure 1B. For clarity, Figure 1A depicts only a small number of electrodes 2. It should be noted that in practice, a typical ion funnel or ion tunnel device may have 100 or more individual electrodes. Each ring or plate electrode 2 (Figure 1B) is typically circular and has an opening 8 defined by the inner surface 3 of the ring. Each ring electrode 2 may have one or more tabs, such as tabs 9, for mounting to a support structure (not shown) and, optionally, for providing electrical connections to one or more power sources (e.g., a voltage source and / or any other type of power source).

[0029] 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 diameters θ of the various openings generally decrease along the direction away from the ion implantation port end 13 of the device toward the ion exhaust port end 18. As used herein, the term “broad end” is used to refer to the end of the ion funnel portion where the fluctuating opening diameter, θ, is largest, and the term “narrow end” is used to refer to the opposite end of the ion funnel portion where the opening diameter is smallest. During operation, an oscillating radio frequency (RF) voltage is applied to the electrodes in a defined phase relationship to confine ions radially inside the device. According to a generally defined conventional phase relationship, the phase of the RF voltage waveform of each stacked electrode is out of phase by π radians (180 degrees) from the phase of each directly adjacent electrode. The collection of all openings of all electrodes 2 defines an ion-occupied volume 11, in which ions generally travel from the ion implantation port end 13 to the ion exhaust port end 18 of the device 10, as indicated by arrows on the longitudinal axis 16. In typical operation, a pseudopotential well, centered on axis 16 and generated by the applied RF configuration, confines ions within the ion-occupied volume 11. The relatively large electrode openings at the ion implantation port end 13 and ion tunnel section 12a of the apparatus are generally employed to capture ion dispersion or diffusion clouds. In contrast, as the electrode opening of the ion funnel section 12b narrows toward the ion outlet 18, the ion cloud is narrowed into a narrow beam that can pass through the narrow opening into the high-vacuum chamber. The movement of ions in the direction from the ion implantation port end toward the ion outlet can be facilitated by the gas flow into which the ions are drawn. Ions may also be biased in the same direction by providing a DC axial electric field generated by differentially supplying DC voltages to the electrodes 2.

[0030] Figure 1C is a schematic diagram of another known type of ion manipulating and ion guiding device 50, as taught in the aforementioned U.S. Patent No. 10,692,710. As described in that patent, the device 50 comprises two parallel substrate plates or wafers 51 and 53 spaced apart from each other, each plate or wafer having a surface on which a plurality of electrodes are arranged. For example, the plates or wafers 51 and 53 may be substrates of a printed circuit board. The electrode support surfaces may face each other across a gap between the two substrate plates or wafers, as shown. A central axis 57 is defined to pass through the device 50. Each electrode support surface has an array of inner electrodes 55 and also has outer guard electrodes 52a, 52b. The outer guard electrodes 52a, 52b are positioned on both sides 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 support surface of the substrate plates or wafers 51, 53. During operation, ions can be confined within the gap between the electrode support surfaces and guided parallel to the central axis 57, as taught in U.S. Patent No. 10,692,710.

[0031] Figure 1D schematically shows a portion of the electrode support surface of an individual substrate plate or wafer 53 of a known ion manipulating and ion guiding device 50. In the example illustrated in Figure 1D, each of the outer guard electrodes 52a, 52b includes a single elongated electrode that is elongated parallel to the central axis 57. The electrode array 55 comprises a series of individual electrodes 7a, 7b, 7c, ..., 7m. Although 12 such individual electrodes are shown, the array 55 may comprise any number of electrodes. A voltage source (not shown) can apply voltage to each electrode 7a-7m individually. As described above in the Background Art section of this specification, U.S. Patent No. 10,692,710 further teaches, using the ion manipulating 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 each electrode of each subset with differently modulated RF waveforms, a traveling wave can be generated that tends to bias ions parallel to the central axis 57 through the apparatus 50.

[0032] Figure 2A is a schematic cross-sectional view of a first embodiment of the ion tunnel stacked ring ion guide 100 according to this teaching. The stacked ring ion guide 100 is depicted as comprising only the ion tunnel portion, but alternatively, it may comprise any number of ion funnel portions and combinations of ion tunnel portions. In the 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 the ion injection port 113. Through the operation of the device 100, the original mixture of ion species can be separated into several packets, for example, ion packets 117a, 117b, and 117c as shown, each containing a different subset of the original set of ion species. These partially separated ion packets can then be exited from the device as a stream of ion packets 119 through the ion outlet 118.

[0033] The physical configuration of electrode 2 of apparatus 100 (Figure 2A) is similar to the physical configuration of the electrode in the ion tunnel portion 12a of the stacked ring ion guide 10, where each electrode has an opening of diameter θ0, and the collection of openings defines the ion-occupied volume 101. Despite this similarity, apparatus 100 differs from apparatus 10 (Figure 1A) in the following respects: (a) The electrodes are logically grouped in a stacked order of subsets of electrodes, and each subset (in this example) has exactly four electrodes. (b) The RF voltage waveform applied to the electrodes fluctuates over time within each subset of electrodes to generate multiple pseudopotential wells in which ions tend to concentrate, thereby causing the pseudopotential wells to move in a desired direction parallel to the axis of the apparatus, the set of moving pseudopotential wells being referred herein to as the RF traveling wave or equivalently the “pseudowave”, and, (c) An axial DC electric field is provided within the ion-occupied volume that tends to bias the ions in the direction opposite to the direction of movement of the pseudopotential well. Figure 6A is a schematic cross-sectional view of the apparatus and the ion packets within it of Figure 2A, and further illustrates a schematic example of how the DC voltage V can be distributed between the stacked electrodes to generate a static and uniform DC axial electric field. The axial electric field vector near the axis of the apparatus,

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[0036] Specifically, with regard to logically grouping electrodes into subsets, Figure 2A depicts two such groups (i.e., subsets), each 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 Figure 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 extending from the ion inlet 113 to the ion outlet 118. According to some alternative embodiments, some parts of the electrodes do not need to be organized into such groups. Although four electrodes per subset are illustrated, the number of electrodes per subset, N e The number of , does not necessarily have to be limited to four. More generally, N e The repeating distance along the axis of the device 100 (parallel to arrows 115 and 119), L R , is defined as the distance between consecutive electrodes 2a (or consecutive electrodes 2b, etc.).

[0037] 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 RF voltage waveform, as will be further described below. All electrodes 2a are supplied with a first RF voltage waveform, which is identical among all electrodes 2a in the embodiment. Similarly, all electrodes 2b are supplied with a second RF voltage waveform, which is identical among all electrodes 2b in the embodiment. Similarly, a third voltage waveform is applied to all electrodes 2c, and a fourth voltage waveform is applied to all electrodes 2d. Generally speaking, N eThe individual voltage waveforms are selected such that a set of moving virtual potential wells is generated along the axis of the device (which coincides with arrows 115 and 119), thereby forming a set of "traveling waves" that tend to bias the ions along the axis. According to the example shown in FIG. 2A, the voltage waveforms are configured such that the traveling waves bias the ions in a direction from the ion inlet 113 to the ion outlet 118 parallel to lines 115, 119. However, according to some other embodiments further described below herein, the voltage waveforms may be configured to bias the ions in the opposite direction.

[0038] According to some embodiments of the present teachings, the RF voltage waveforms applied to the electrodes of device 100 may be selected as described in U.S. Patent No. 9,799,503. This patent provides an example of a subset of four electrodes of a stacked ring ion guide, and each RF voltage waveform is supplied to the four electrodes such that a plurality of moving virtual 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 to 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 jωt Third RF drive signal Equation 1c V D =V4F(ω m t - Φ4)e jωt Fourth RF drive signal Equation 1d In the formula, t is time, V1 to V4 are amplitudes from zero to the peak, j is the imaginary unit, the function F is a complex function of its argument, periodic with a period of 2π, the scalar value Φ1 is the first phase, the scalar value Φ2 is the second phase shifted by 90 degrees (π / 2 radians) relative to the first phase, the scalar value Φ3 is the third phase shifted by 180 degrees (π radians) relative to the first phase, the scalar value Φ4 is the third phase shifted by 270 degrees (3π / 2 radians) relative to the first phase, and the scalar values ​​ω and ω m ω>ω m The angular frequency may be in radians per second. The applied voltage is understood to be described by the real part of any resulting complex representation. The patent also provides specific examples of implementations of the representations of Equations 1a to 1d, with the applied voltage being as follows: V A =V0cos(ω m t)cos(ωt) First RF drive signal formula 2a V B =V0cos(ω m t-π / 2)cos(ωt) Second RF drive signal formula 2b V C =V0cos(ω m t-π)cos(ωt) Third RF drive signal formula 2c V D =V0cos(ω m t - 3π / 2)cos(ωt)f4th RF drive signal f C formula 2d

[0039] As mentioned above, the number of electrodes per subset is not limited to four electrodes per subset, but can be any integer N. e (Here, N e It may include ≥3). In such a case, the various electrodes R of each subset and the various voltage waveforms V(t) supplied to the electrodes of each subset can be enumerated by the index variable i in order from the electrode closest to the inlet, as follows:

[0040]

number

[0041] Next, all electrodes designated as R1 are supplied with the same identical waveform, V1(t). Similarly, all electrodes designated as R2 are supplied with the same identical waveform, V2(t), and so on. According to some embodiments, the phase shift, ΔΦ, between any two consecutive electrodes in the subset is constant across the subset and is given by the following equation. ΔΦ = 2π / N e formula 3

[0042] However, according to some other embodiments, the phase shift is not necessarily uniform across each subset.

[0043] According to some other embodiments of this teaching, the RF voltage waveform supplied to the electrodes of the apparatus 100 is a frequency-modulated signal, S, represented by the following equation. FM , which may be selected as described in U.S. Patent No. 10,692,710, which describes the generation of a traveling wave by supplying a frequency-modulated waveform driven by , S FM =V c cos(2πf c +βS MS ) In the formula, f C V is the "carrier frequency" (i.e., the frequency of an unmodulated standard RF voltage waveform), and V C is the voltage amplitude of the RF waveform, β is the frequency modulation index, and S MS The frequency is a frequency-modulated period waveform, f M , and this is f C This is a lower frequency. This latter patent describes how the electrodes of a stacked ring ion guide are organized into subsets of eight electrodes each, and how they produce a frequency-modulated periodic waveform, S MS This provides a specific example where the phase changes by only 2π / 8 radians (45 degrees) between each pair of electrodes.

[0044] Referring again to Figure 2A, arrow 110 indicates the direction of movement of the RF-generated pseudopotential well (i.e., the traveling wave) that 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 ion that tends to bias the ion in a “forward” direction, generally from the ion inlet 113 toward the ion outlet 118. However, in alternative embodiments, the direction of pseudopotential well movement may be reversed relative to the direction of movement shown in Figure 2A by reversing the phase relationship of the driving waveforms applied within each subset of electrodes. Figure 2A also shows that this teaching also generates a static, uniform DC axial electric field that exerts a force on the ion that tends to counteract the force exerted by the pseudopotential well movement. A schematic example of the magnitude of the static, uniform DC axial electric field is provided by plot 508 in Figure 6A. Thus, arrow 111 indicates the direction in which the same ion is biased to move by the applied static, uniform DC axial electric field. Therefore, according to the operation shown in Figure 2A, the DC axial electric field is applied in such a way that it tends to bias the ions in the "reverse" direction from the ion outlet 118 towards the ion inlet 113. However, it should be noted that if the direction of pseudopotential well movement is reversed from the direction shown in Figure 2A, and the traveling wave instead tends to bias the ions towards the ion inlet 113, the direction of the DC axial electric field is also reversed relative to the direction shown in Figure 2A, and the DC axial electric field thus reversed will bias the ions towards the ion outlet 118.

[0045] 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 along the length of the apparatus by including 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.

[0046] As shown in Figure 2A, the opposing pseudopotential and DC axial electric field forces applied produce three different ion behavior states, namely: (1) Firstly, for ions with the smallest m / z value such that the force due to the RF traveling wave exceeds the DC electric field force (e.g., ions in ion packet 117a), the movement will be in the direction of the traveling wave, as indicated by the motion vector 118a; (2) For ions with the largest m / z value such that the DC axial electric field is dominant (e.g., ions in ion packet 117c), the motion will be opposite to the direction of the traveling wave, as indicated by the motion vector 118c; and (3) Finally, for ions with a specific critical m / z value dependent on the applied voltage (e.g., ions in ion packet 117b), the RF-induced force and the DC gradient-induced force are in equilibrium, and such ions will not move in either direction. Therefore, when the apparatus 100 operates as shown in Figure 2A, it simultaneously operates as (a) a mass filter that allows only ions with relatively low m / z values ​​(i.e., below critical values) to pass through the outlet flow 119 to downstream devices (such as quadrupole mass filters and / or collision cells and / or mass spectrometers), (b) a single mass-charged ion trap or ion accumulator for ions with critical m / z values, and (c) a filter that removes all ions with m / z values ​​greater than critical values.

[0047] Figure 2B is another schematic cross-sectional view of the ion tunnel stacked ring ion guide 100 as introduced in Figure 2A, but configured and operating in an alternative mode that causes differential movement of ions through the ion guide, as well as spatially separated capture of ion species according to their respective mass-to-charge (m / z) ratios. According to the operating mode shown in Figure 2B, the applied static DC axial electric field counteracting the pseudopotential-induced traveling wave is not uniform, but instead decreases in magnitude in the overall direction from the ion outlet 118 to the ion injection port 113. Specifically, as indicated by arrow 112, the DC axial electric field continues to generate a force that tends to bias the ions in the "upstream" direction, opposite to the "downstream" direction (as indicated by arrow 110) in which the ions are biased 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 the m / z range will be trapped within the ion-occupied volume as each such ion species moves to an axial position where the upstream DC axial electric field precisely balances with the downstream pseudopotential inductive force exerted on the mass-charge value of the ion species, and accumulates there. For example, Figure 2B shows the mass-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, and a mass-to-charge ratio, (m / z) H The approximate axial equilibrium position of the third ion packet 117c having , is shown, where (m / z) H >(m / z) M >(m / z) LAlthough only three packets of ions with a specific m / z value are illustrated in Figure 2B, in reality, there is generally a substantially continuous range of equilibrium positions for ions with a specific m / z value, and the m / z value within the equilibrium m / z range decreases in the overall direction toward the ion outlet 118. Additionally, certain ion species with small m / z values ​​outside the range may move toward the ion outlet, and certain other ion species with large m / z values ​​outside the range may move toward the ion inlet. Thus, in the operating mode schematically illustrated in Figure 2B, the device 100 functions as a multi-mass-charged ion sorting ion trap.

[0048] As shown in Figure 2B, in order to extract ions trapped at various equilibrium positions, the amplitude of the phase-shifted and / or frequency-modulated main RF voltage can be tilted upward over time (i.e., gradually increased) as described above, so that the equilibrium positions corresponding to all m / z values ​​move toward the ion outlet as the RF voltage amplitude is tilted, as shown by the displacement vectors 118a, 118b, and 118c in Figure 2C. Additionally or alternatively, the magnitude of the opposing DC electric field may be tilted downward (i.e., gradually decreased). In this example, the trapped ions with the smallest m / z value (e.g., the ions in packet 117a) pass through the ion outlet first, and the ions with the largest m / z value (e.g., the ions in packet 117c) exit last.

[0049] It should be noted that in alternative embodiments, the direction 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 discharged from the apparatus if the "direction" of the slope of the RF amplitude (of the traveling wave biasing the ions toward the ion injection port 113) (i.e., either an "upward" or "downward" slope) and the "direction" of the slope of the magnitude of the DC electric field (biasing the ions toward the ion outlet 118) are reversed. While many of the basic examples discussed herein refer to the slope of either the RF amplitude or the DC electric field, it should be further noted that more generally, the RF amplitude and the DC electric field may be sloped simultaneously, thereby increasing or decreasing both the RF amplitude and the magnitude of the DC electric field while they are sloped simultaneously. In other examples, simultaneous slope may include an increase in the RF amplitude and a simultaneous decrease in the magnitude of the DC electric field. In yet another example, simultaneous slope may include a decrease in the RF amplitude and a simultaneous increase in the magnitude of the DC electric field.

[0050] As described above, a stacked ring ion guide in the form of an ion tunnel may be constructed to function as either a single-mass-charged ion trap or ion accumulator (as described with reference to Figure 2A) by (a) providing a uniform DC axial electric field to counteract a traveling wave uniformly applied over the length of the device, or (b) a multi-mass-charged ion sorting ion trap when there is a longitudinal spatial gradient in either the counteracting DC electric field and / or the propulsion force of the pseudowave. In the case of an ion tunnel device, the operation that generates the “longitudinal spatial gradient in the propulsion force of the pseudowave” requires providing different RF waveforms (e.g., different RF amplitudes) to the electrodes of the device at various different locations between the ion inlet and ion outlet. In such cases, the required electronics can 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 depicted in Figure 3A, the gradient of the pseudopotential well depth and the resulting gradient of the propulsion force are generated by the geometry of the device. Specifically, within the ion funnel apparatus 200, the depths of the various pseudopotential wells increase in the direction of ion funnel convergence (see, for example, Figure 1 of U.S. Patent No. 9,799,503), which essentially increases the proximity of the electrode edges to the ion beam in the same direction (centered near the device axis). Thus, using the direction of the RF-generated traveling wave (arrow 210) directed to bias the ions toward the ion implantation port 213 and the direction of the DC electric field (arrow 211) directed to bias the ions toward the ion outlet 218, the apparatus 200 can operate as a multi-mass-charge ion-selective ion trap without applying any electric field gradient. Using the configuration shown in Figure 3A, relatively "light" (small m / z) ions can be trapped in region 117a adjacent to the ion implantation port 213, while at the same time, relatively "heavy" (large m / z) ions can be trapped in region 117c adjacent to the ion outlet 218. As mentioned above, the intermediate m / z ions are trapped within region 117b.The captured ions can be released in reverse order of their m / z ratio by either tilting the magnitude of the DC electric field upward (i.e., to a larger value) and / or tilting the applied RF amplitude downward (i.e., to a smaller value).

[0051] Figure 3B shows a modified version of the ion manipulation and ion guiding device in Figure 1C, according to this instruction. The ion manipulation and ion guiding device 250 depicted in Figure 3B is modified from device 50 (Figure 1C) so that it can be operated in the same manner as 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 toward each other along the direction away from the ion injection port 313 toward the ion outlet 318. For example, as shown in Figure 3B, plates / wafers 251 and 253 are separated from each other by a first separation distance, s1, at the ion implantation port 313, and by a second separation distance, s2, at the ion outlet 318, where s1 > s2, and there is continuous convergence of plates / wafers 251 and 253 between the ion implantation port 313 and the ion outlet 318.

[0052] In some examples of U.S. patents, it is taught that an RF traveling wave can be generated along the axis 57 of device 50 by manipulating a principal RF axial confinement waveform applied to a series of individual electrodes 7a, 7b, 7c, ... (see Figure 1D) of a series of mutually opposing electrode arrays 55. Additionally, a DC electric field to counteract the motion of ions subsequently energized by the RF traveling wave can also be generated within either device 50 (Figure 1C) or a modified device 250 (Figure 3B). For example, a static and uniform DC electric field can be generated within either device 50 or the modified device 250 by distributing the DC potential difference imposed between an ion injection port 313 and an ion outlet 318 among a plurality of inner electrodes of each plate / wafer 251, 253. The distribution of the voltage difference can be achieved by a voltage divider system in known ways. Additionally or alternatively, an axial DC electric field may be generated, or otherwise, the generated axial electric field may be supplemented by providing guard electrodes 52a, 52b on each plate / wafer composed of an electrically resistive material (as opposed to a conductive material such as metal). For example, the resistive guard electrodes 52a, 52b may be formed from any one of several suitable materials having electrically resistive properties (e.g., doped glass, cermet, polymer, etc., but not limited to these).

[0053] This is because, within the device 250, the electrodes of the two electrode arrays 55 (one electrode array supported on each of the plates / wafers 251 and 253) gradually approach each other along the direction from the ion injection port 313 to the ion outlet 318, and thus a gradient exists in the depth of the pseudopotential well, with the well depth increasing in the same direction. The increasing well depth creates a gradient in the propulsion force provided by the traveling wave generated by the RF. Thus, if the RF-generated traveling wave is configured to bias ions away from the ion outlet 318 towards the ion injection port 313 within the device 250, and the biasing of the traveling wave is counteracted by a static, uniform DC electric field that biases ions towards the ion outlet 318, then different ion species with different respective m / z values ​​will establish different respective equilibrium positions within the device. In this situation, the distribution of equilibrium positions is similar to that depicted in Figure 3A, with ions 117a having a smaller mass-to-charge ratio being closer to the ion injection port than ions 117b and 117c having a larger mass-to-charge ratio, and ion 117c having the largest mass-to-charge ratio being closest to the ion outlet. The captured ions can then be emitted from device 250 in reverse order of their m / z ratio by either tilting the magnitude of the DC electric field upward (i.e., to a larger value) and / or tilting the applied RF amplitude downward (i.e., to a smaller value).

[0054] The following discussion relates to Figures 6A–6H, which are schematic graphs of various voltages and DC electric fields within an ion guide operating according to this instruction. In 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 pseudowaves is applied to the electrodes of each ion guide to bias the ions from the ion inlet to the ion outlet. Note that the absolute magnitude of the applied DC voltage is plotted in Figures 6C and 6E, respectively. When positively charged ions are introduced into an ion guide or ion separator device operating as described herein, the overall movement of ions within the device will be as described, provided that the applied DC voltage profile is in a general form such as the profiles shown in Figures 6C and 6E. However, when negatively charged ions are introduced into the apparatus, if the applied DC voltage profile has a general form that is 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 apparatus will be as described.

[0055] As described above, a uniform DC electric field can be applied to counteract the motion of a set of moving RF potential wells (i.e., a set of pseudowaves) in order to separate ions containing a specific m / z range within the ion guide (see, for example, Figure 2A). For example, plot 508 in Figure 6A depicts a uniform axial DC electric field that can be generated by applying a series of DC voltages to various individual electrodes of the ion guide, where the applied voltage increases linearly from the ion inlet to the ion outlet (i.e., plot 501 in Figure 6A). Alternatively, as described above, a non-uniform axial DC electric field can be applied to counteract the motion of pseudowaves in order to cause the ion guide to emit ions from the ion outlet in either increasing or decreasing m / z order (see, for example, Figure 2C).

[0056] Figure 6B shows the absolute size,

[0057]

number

[0058]

number

[0059]

number

[0060] Regarding the use of an ion guide as an ion separation and sorting device (e.g., Figure 2C) in which ions are emitted in order of their m / z values, the mass spectral resolution R of the device can be adjusted by utilizing a non-uniform electric field profile, as schematically depicted in Figure 6D, which can be generated by applying a DC voltage to the electrodes according to the voltage profile shown by segments 504a and 504b in Figure 6E. Specifically, the magnitude of the axial DC electric field that counteracts the ion motion caused by the pseudowave,

[0061]

number

[0062] Ions are introduced into an ion guide device, which can be configured using a traveling RF voltage and a static DC voltage as shown in Figures 6D and 6E, via an ion inlet 113. The location 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 traveling RF waves that create a pseudopotential well that energizes the ions through the device from the ion inlet 113 to the outlet 118 located at position L. Simultaneously, a DC voltage is applied to the electrodes, having a general form shown by the dashed lines 503a and 503b in Figure 6D, which generates an axial electric field that energizes the ions toward the ion inlet 113. After the introduction of the ions, the amplitude A of the applied RF voltage... RF The mass-to-charge ratio (m / z) is tilted (i.e., increased) over time. Under such conditions, as previously described herein, packets of ions having different respective m / z values ​​separate from each other and move through the apparatus toward the ion outlet 118 at different velocities. Figure 6D shows the mass-to-charge ratio, (m / z) within the apparatus. L (m / z) M , and (m / z) H The positions of the three ion packets 517a, 517b, and 517c, each possessing the respective characteristics, are schematically described, where (m / z) at a specific time t1. H >(m / z) M >(m / z) LThis refers to the sloping state before any ion reaches the plateau region 503b of the DC electric field profile. The instantaneous position of any such ion packet at any given time represents the axial position in the device where the instantaneous forward bias of the ion packet by the pseudowave, such as that produced by the sloped RF amplitude at a given time, slightly overcomes the reverse bias of the ion by the electrostatic field along the electric field segment 503a. As previously stated, these opposing forces cause the ion with the smallest m / z value (e.g., the ion in packet 517a) to move most rapidly towards the ion outlet, and as a result, these ions reach point p1 at time t1. The ion with the largest m / z value (e.g., the ion in packet 517c) moves most slowly, and as a result, only arrives at point p3 at time t1. Simultaneously, the ion with an intermediate m / z value (e.g., the ion in packet 517b) reaches point p2.

[0063] Figure 6F is a schematic diagram of the position of the ion packet in Figure 6D at a second time t2 following time t1, where the applied RF amplitude is such that the forward biasing pseudopotential force on the ion in ion packet 517a is E along electric field intensity segment 503b. maxThe electrostatic force is initially equal to the maximum reverse biasing electrostatic force corresponding to the point, and then slopes to substantially exceed it. As a result, multiple portions of the ion packet 517a are collected by individual progressing pseudopotential wells, thereby transported downstream in a conveyor belt manner from position pc to the ion outlet 118 at position L. This ion movement along the flat electric field strength profile 503b is relatively rapid compared to movement along the rising voltage profile 503a, because the additional slope of the RF amplitude is not satisfied by the corresponding increase in the DC electric field biasing in the reverse direction. Simulations of ion motion show that some of the ions in each ion packet may move in the reverse direction (i.e., towards the ion inlet 113) within the constant electric field region 503b, but they move less frequently than in the variable electric field region 503a. On average, the progressing pseudopotential wells move the ions forward away from point pc towards the ion outlet 118, so the ions can efficiently escape from the region 503a near point pc.

[0064] As 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. Since the forward-biasing pseudopotential force at these positions is only slightly above (i.e., nearly above) the reverse-biasing DC electric field force, the RF amplitude is further tilted until the subsequent time t3 when packet 517b reaches position pc, so that the ions in both of these packets continue to move relatively slowly toward position pc. As shown in Figure 6G, further tilting of the RF amplitude causes relatively rapid transport of the ions in packet 517b from position pc to position L. Further additional tilting similarly transports the ions in packet 517c (not shown).

[0065] Referring to Figures 6G to 6H, the transport of ions through the ion guide, in the manner described above, temporally separates the appearance of ion packets with different m / z values ​​from the ion outlet 118 of the device 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 precise, as shown in Figures 6D, 6F, and 6G. For example, a general form of voltage profile shown in Figure 6H, where the profile along the second segment 503b is not constant, can also be usefully employed. Simulations of ion motion and distribution showed that the precise form of the electric field within the "constant" region (i.e., the region shown by the voltage profile segment 503b) is not important. The simulations show that the best m / z resolution is achieved when the electric field within the profile segment 503b is constant, but small fluctuations have little effect on performance. In any case, any gradient of the DC electric field within profile segment 503b should be smaller than the gradient of the DC electric field within profile region 503a, which is used for the initial spatial separation of ion species by m / z.

[0066] Furthermore, the amplitude A of the applied RF waveform RF The gradient of may be selected according to the requirements of the specific measurement. For example, if the ion guide device is employed as a mass spectrometer of the type operating in general inspection mode and involves the detection of all ions emerging from the ion outlet, then A, as schematically depicted in Figure 7A, RF A continuous slope may be adopted. Figure 7A shows the difference in A over time. RFWhile a linear variation is illustrated, alternatively, the variation may be nonlinear, having a steeper slope (i.e., a faster increase in amplitude) at times during the gradient when ions emerging from the instrument are not expected to require detection at the maximum achievable resolution, and a shallower slope (i.e., a slower rate of amplitude increase) at other times when emerging ions are expected to require a higher level of m / z discrimination. For example, Figure 8 shows the expected achievable mass spectral resolution of an ion as a function of m / z at a constant RF gradient velocity. Figure 9 shows that a longer duration allocated to the completion of the gradient is expected to result in higher resolution. Figure 7B shows, for example, a longer residence time Δt at the time when a particular ion of interest is expected to emerge from the instrument, and a variable amplitude jump ΔA at the time when the ion of interest is not expected. RF This illustrates a discontinuous, stepwise gradient. The expected time of appearance of an ion with a particular m / z value can be predetermined by calibrating the passage time of known standard ions through the instrument under various conditions.

[0067] Figures 4A and 4B represent the simulated performance of an ion sorting apparatus configured and operating according to this instruction. The simulated apparatus is 160 mm wide and has 320 electrodes and 160 pseudopotential wells. The simulation assumed a typical separation / equilibrium time of 40 milliseconds and operation in the presence of 100 mTorr nitrogen gas. The plots in Figure 4A represent the equilibrium positions of ions with various m / z ratios in such an apparatus, under the application of a DC axial electric field gradient and simultaneously an RF waveform that does not vary over the length of the apparatus. In contrast, the plots in Figure 4B represent the equilibrium positions of the same ions under the application of an RF amplitude gradient over the length of the apparatus, in the presence of a uniform DC axial electric field. Traces 301 (Figure 4A) and 351 (Figure 4B) both represent ions with a virtual m / z value of 500 Th. Similarly, traces 302 and 352 represent ions with an m / z ratio of 600 Th, traces 303 and 353 represent ions with an m / z ratio of 700 Th, traces 304 and 354 represent ions with an m / z ratio of 800 Th, traces 305 and 352 represent ions with an m / z ratio of 900 Th, and traces 306 and 356 represent ions with an m / z ratio of 1000 Th.

[0068] Figure 5 is a schematic diagram of a part of a mass spectrometer, including an ion filter 400 or other mass spectrometer components arranged in series with an ion transporter 500, configured according to the instructions described above. Apparatus 500 may comprise any of the embodiments illustrated in the accompanying drawings, and may comprise any other apparatus not illustrated in this teaching that operates in accordance with this teaching, including, but not limited to, other ion guides that can provide both axial electric field gradients (end-to-end or over only a portion of the device length) and longitudinal gradients (end-to-end or over only a portion of the device length) in RF amplitude or any other RF parameter.

[0069] As illustrated, the apparatus 400 is a quadrupole mass filter comprising four mutually parallel rod electrodes 401, which are maintained in alignment by a support structure 415 and which may also provide electrical connections to the rods. In other cases, the apparatus may comprise, but is not limited to, a multipole ion trap, a multipole fragmentation cell, an ion guide, or any type of mass spectrometer. Preferably, a controllable ion gate 410 is located between the ion outlet of the apparatus 500 and the ion inlet of the apparatus 400.

[0070] In the operation of the system depicted in Figure 5, the apparatus 500 provides an ion outlet stream 119, where, at any given point in time, the range of mass-charge (m / z) values ​​of the ions constituting the outlet stream 119 is reduced compared to a wider range of m / z values ​​provided at the inlet end of the apparatus 500 in the inlet ion stream 115, where the range of (m / z) values ​​constituting the outlet stream 119 changes over time to either a larger or smaller m / z value. Thus, in practice, the operation of the apparatus 500 is similar to that of a conventional mass filter, where the mass-charge passband of the mass filter is scanned over time, except that the passband of the apparatus 500 is wider than that of a conventional mass filter, and ions within each passband range can be accumulated and temporarily stored in the apparatus 500 before being released from the apparatus. Thus, the apparatus 500 performs the function of ion accumulation, as well as the function of partially pre-separating ions before transferring them to the conventional apparatus 400. If a conventional instrument 400 is equipped with a quadrupole mass filter, such a mass filter can separate a narrower m / z range, and each separation range contains ion species for a specific analytical purpose.

[0071] The ion outlet flow 119 may be either continuous or discontinuous in time. The continuity of delivery of the ion outlet flow to the apparatus 400 can be controlled by the operation of the ion gate 410, thereby limiting the m / z range of ions that can be transferred to the downstream apparatus during any given time interval. During the time when the ion gate 410 is closed (thereby limiting transfer), new ion packets from the inlet ion flow 115 may be accumulated and sorted within the upstream apparatus 500 as described above herein. At such times, the applied RF waveform and DC voltage are adjusted to cause sorting (e.g., Figure 2B). When the ion gate 410 is open, the internal RF waveform and DC voltage are adjusted to allow the accumulated ions to move out of the apparatus in either an increasing order of their m / z values ​​(e.g., Figure 2C) or a decreasing order (e.g., Figure 3A).

[0072] Figure 10A is a flowchart of a first method (Method 800) for operating an ion guide according to this teaching. In the first step, step 801 of Method 800, a pulse of ions containing a range of mass-to-charge ratios (m / z) is input to the 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 the end of the ion guide adjacent to the first port. The ions may be trapped and / or stored there by temporarily creating a transient static potential well near the port by applying a DC voltage to the electrode near the first port. In the next step 803 (which may be performed before or simultaneously with steps 801 and 802), a radio frequency (RF) voltage waveform is applied to a series of electrodes of the ion guide, which generates a number of pseudopotential wells configured to bias the ions in a first direction, either away from the first ion port toward the second ion port or, alternatively, toward the first ion port. In step 805, performed concurrently with step 803, a DC potential is applied to each of the two or more electrodes, generating a DC electric field that biases the ions in the opposite direction to the biasing of the ions by the pseudopotential well. The DC electric field may be uniform (i.e., constant magnitude that does not vary with position) or non-uniform (i.e., magnitude that varies with position) along the length of the ion guide. In an optional step 807, the applied RF amplitude and / or one or more applied DC potentials are gradually sloped over time, either increasing or decreasing, to facilitate the differential movement of ions toward the second ion port. Finally, in step 809, ions containing a range of m / z ratios that is reduced (i.e., a subset of the range) of the initially input ions are extracted from the second port of the ion guide. The extracted ions may be injected into another component of a mass spectrometer, such as a mass filter, collision cell, or mass spectrometer.

[0073] Figure 10B is a flowchart of a second method (Method 810) for operating an ion guide according to this teaching. In step 811 of Method 810, a radio frequency (RF) voltage waveform is applied to a series of electrodes positioned between the ion inlet and ion outlet of the ion guide, generating a number of pseudopotential wells configured to bias ions away from the ion inlet towards the ion outlet. In step 813, performed concurrently with step 811, each DC potential is applied to each of two or more electrodes that generate a DC electric field configured to bias ions away from the ion outlet towards the ion inlet. The DC electric field may be uniform (i.e., constant magnitude with no position variation) or non-uniform (i.e., magnitude with position variation) along the length of the ion guide. Subsequently, in step 815, pulses of ions containing a range of mass-charge values ​​are 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 the ions through the ion guide toward the ion outlet. In step 819, the ions are extracted from the ion outlet in order of increasing mass-to-charge ratio. The extracted ions may be injected into another component of a mass spectrometer, such as a mass filter, collision cell, or mass spectrometer. According to a modification of method 810, step 815 may be performed before steps 811-813, and an additional step of capturing pulses of ions within the region of the ion guide adjacent to the ion inlet may be performed before steps 811-813.

[0074] Figure 10C is a flowchart of a third method (Method 830) for operating an ion guide according to this teaching. In step 831, a radio frequency (RF) voltage waveform is applied to multiple electrodes of an ion funnel having an ion inlet end, an ion outlet end, and multiple plate or ring electrodes between the inlet and outlet ends, each having an opening whose diameter decreases from the inlet end to the outlet end, and the RF voltage waveform generates multiple pseudopotential wells configured to bias ions toward the ion inlet and away from the ion outlet. In step 833, performed concurrently with step 831, a DC potential is applied to each of the electrodes, thereby generating a DC electric field configured to bias ions away from the inlet end toward the outlet end. Then, in step 835, pulses of ions containing a range of mass-charge values ​​flow into the ion funnel through its ion inlet end. In the optional step 837, the magnitude (i.e., intensity) of the DC electric field toward the ion outlet end of the ion funnel can be increased by grading the DC voltage applied to the electrodes to facilitate the movement of ions toward the ion outlet end of the ion funnel. Finally, in step 839, the ions are extracted from the outlet end of the ion funnel in decreasing order of their m / z ratio. The extracted ions may be injected into another component of a mass spectrometer, such as a mass filter, impaction cell, or mass spectrometer.

[0075] The descriptions contained herein are intended to serve as a basic explanation. The present invention is not intended to be limited in scope by the specific embodiments described herein, which are intended as single examples of individual aspects of the invention. Functionally equivalent methods and components are within the scope of the invention as defined by the claims. In addition to those shown and described herein, various other variations of the invention 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 proportionally distributed (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 within an ion guide are described, many of which utilize a set of auxiliary electrodes to generate the axial electric field. Such auxiliary electrodes are often separate from and added to a series or number of main electrodes that receive the RF voltage waveform. U.S. Patents 7,675,031 (Konicek et al.), 5,847,386 (Thomson et al.), 7,985,951 (Okumura et al.), 7,064,322 (Crawford et al.), 7,064,322 (Crawford et al.), and 6,417,511 (Russ, IV et al.) describe many alternative methods for generating axial or drag electric fields. Adapting one or more of these known axial electric field generation techniques to the methods and apparatus described herein would be considered and would be within the capabilities of those skilled in the art.

[0076] As another example of a modification of the above teaching, variations in the spacing between adjacent ring electrodes 2 (Figures 1A, 2A, 2B, and 2C), or variations in the spacing between adjacent electrodes of an array 55 supported on a substrate (Figure 1C), may be used as an additional method for generating a longitudinal spatial gradient in the propulsion force of the RF-induced traveling wave. For example, the inter-electrode spacing can be varied continuously or discontinuously along the axial length of the ion guide or ion separator device by this teaching, and this variation generates a corresponding variation in the depth of the pseudopotential well along the length of the device.

[0077] Refer to Figures 11A and 11B as yet another example of a modification of the above teaching. The virtual voltage plots depicted in Figures 11A and 11B, when considered together, provide an example of the application of two separate DC voltage profiles 930 and 940 to an ion guide device that alternate in time with respect to each other. 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. During operation, each DC profile is supplied simultaneously with the supply of an RF-modulated traveling wave that generates an RF-induced pseudopotential well that biases the ion toward the downstream end of the device to which the DC profile is supplied. DC voltage profiles 930 and 940 are supplied to provide the ion with a force that counteracts the pseudopotential inductive force and thus biases the ion toward the upstream end of the device. Thus, the algebraic sign of the slopes of profiles 930 and 940 implicitly assumes that the ion is positively charged.

[0078] Each voltage profile in Figures 11A and 11B includes a series of steep segments 932 separated from each other by a series of shallow segments 933. The terms “steep” and “shallow” are used herein in a relative sense only and do not imply any specific numerical value of the gradient or applied voltage. The steep segments of the voltage profile represent the upstream electric field vector

[0079]

number

[0080]

number

[0081]

number

[0082] The transition from voltage profile 930 (Figure 11A) to voltage profile 940 (Figure 11B) and vice versa is equivalent to a simple leftward or rightward shift of a single profile, and the shift can be observed to be equal to a constant spatial width of the profile segment. However, by appropriately and finely controlling the distribution of voltage supplied to various individual electrode segments that generate the electric field, and the circulation of voltage supplied to those electrodes, the shift can be made much smaller than the segment width. In such cases, the positional changes of the "peaks" 936 and "troughs" 937 of the voltage profile and the electric field magnitude profile may be made to more closely approximate a continuous profile shift, and the positional changes of the peaks and troughs 936, 937 may be referred to as "DC traveling waves." If the upstream moving velocity of peak 936 is controlled to match the moving velocity of target ions along the length of the device, providing such an upstream moving DC traveling wave, in conjunction with the simultaneous provision of a downstream moving RF traveling wave, can facilitate the separation and concentration of a certain targeted "heavy" ion species at the upstream end of the ion guide device. Generally, "light" ions also move toward the downstream end of the apparatus under such conditions, but with less efficiency. Conversely, downstream moving DC traveling waves can facilitate the separation and concentration of "light" ions at the downstream end of the apparatus, as well as their removal from the apparatus at the ion outlet. Various operating parameters can be controlled as needed.

[0083] It should be noted that as the gas pressure gradually increases beyond 0.01 Torr, the performance of the ion guide device described above gradually changes. This change is expected to result from the increased probability of collisions between ions and gas molecules as the gas pressure increases. Beyond a slight increase in pressure above 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 move through the device change. Generally, higher gas pressures counteract both the downstream and upstream biases generated by the applied voltage, but the effect of pressure is maximal with respect to RF traveling waves because the depth of the pseudopotential well decreases with increasing gas pressure. Consequently, 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 pronounced with respect to the bias exerted by the RF traveling wave. Therefore, at such gas pressures, the performance of the ion guide device described above (e.g., m / z resolution, ion residence time) can be advantageously modified by controlling the gas pressure, depending on the requirements of a particular measurement, experiment, or analysis program.

[0084] As the gas pressure inside the ion guide device increases further, the ion-molecular collision effect becomes increasingly pronounced relative to the effects of the applied DC and RF voltages. Consequently, beyond a certain gas pressure, which depends on the device configuration (e.g., length, cross-sectional area, gas composition, etc.), the collision effect becomes dominant over the effect dependent on the m / z of the applied voltage, and the device's performance tends to resemble that of an ion mobility separator, with its performance being modulated 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 applied RF voltage waveforms, or by controlling one or more of the frequencies of the applied voltage waveforms, according to the requirements of a specific measurement, experiment, or analysis program.

[0085] Therefore, gas pressure can be considered an additional parameter to be taken into account during the calibration of the performance of an instrument operating as described by this instruction. More generally, gas pressure is one of many operating parameters that can affect mass spectral results (e.g., mass spectral resolution and measurement rate), such as instrument length, instrument cross-sectional area, gas composition, and RF frequency, but which are difficult to model theoretically when combined. Consequently, the behavior of the instrument should be calibrated for each specific instrument before operation so that the effects of these parameters are well understood in each case.

[0086] As described herein, most mass spectrometry experiments are inherently inefficient, with mass filters sometimes excluding more than 99% of available ions. To mitigate this inefficiency, "ion scheduling" can be performed, as described herein, by accumulating ions before the ion filter in an ion guide (also known as an ion sorter). The ions can then be selectively separated and released so that a smaller proportion of them are ultimately lost in the mass filter.

[0087] In some experiments, or during certain stages of an experiment, it may be beneficial to separate ions primarily based on their m / z. For example, selected precursor ions may have known m / z values ​​(e.g., based on data-dependent investigation spectra), and / or the selected ion m / z range may be known (e.g., based on data-independent experiments). In other experiments, or during certain stages of an experiment, it may be beneficial to separate ions primarily based on their mobility. For example, ions with the same m / z may have different charge states that allow them to separate from each other based on their mobility. Therefore, it may be desirable to selectively operate the ion guide in an ion separation mode where ions are separated primarily based on m / z, or in an ion mobility separation mode where ions are separated primarily based on their mobility.

[0088] In some examples, the controller sets the attributes of the RF voltage waveform (e.g., magnitude, frequency, leading well velocity, etc.) to operate the ion guide in either m / z separation mode or ion mobility separation mode. For example, the controller sets the attributes of the RF voltage waveform to be within a first range when the ion guide is operating in m / z separation mode, or sets the attributes of the RF voltage waveform to be within a second range when the ion guide is operating in ion mobility separation mode. Based on the set attributes of the RF voltage waveform, the RF voltage waveform causes spatial separation of ions within the ion guide (e.g., mainly based on m / z in m / z separation mode, and mainly based on mobility in ion mobility separation mode), generating multiple moving pseudopotential wells, which exert a force that moves ions through the ion guide. For example, in m / z separation mode, ion separation is mainly caused by the m / z-dependent effect of the applied RF voltage waveform rather than collision effects. Alternatively, in ion mobility separation mode, ion separation is primarily caused by collision effects rather than the m / z-dependent effects of the applied RF voltage waveform. (For example, ion molecular collision effects become increasingly prominent in ion mobility separation mode). For instance, as ions experience an increasing number of collisions per cycle of the RF voltage waveform (e.g., more than one collision per cycle), the ion's ion mobility behavior takes precedence over the m / z-dependent effects. Alternatively, as ions experience an increasing number of collisions per cycle of the RF voltage waveform (e.g., less than one collision per cycle), the ion's m / z behavior takes precedence over ion mobility. The ion guide's select operating mode can be set before and / or during the experiment by configuring the attributes of the RF voltage waveform.

[0089] Furthermore, by setting the attributes of the RF voltage waveform to various ranges, the ion guide can be operated in selective mode without significantly changing the gas pressure within the ion guide. Alternatively, in some embodiments, the gas pressure within the ion guide is set in combination with the attributes of the RF voltage waveform to selectively operate the ion guide in either m / z separation mode or ion mobility separation mode. For example, the gas pressure is set to a first pressure range when the ion guide operates in m / z separation mode, and the gas pressure is set to a second pressure range when the ion guide operates in ion mobility separation mode. Such settings of the gas pressure within the ion guide can selectively increase the m / z-dependent effect for separating ions in m / z separation mode and / or the collision effect for separating ions in ion mobility separation mode.

[0090] Figure 12 shows an exemplary configuration 1200 configured to selectively operate the ion guide in either m / z separation mode or ion mobility separation mode. As shown, configuration 1200 may include an ion guide 1202, a power supply 1204, a controller 1206, and a pressure controller 1208. Configuration 1200 may include additional or alternative components to serve a particular implementation.

[0091] The ion guide 1202 may be implemented by any of the ion guides described herein, as shown in Figure 12 as a cross-sectional side view. As shown, the ion guide 1202 includes a first end 1210-1, a second end 1210-2, and a series of electrodes 1212 (e.g., electrodes 1212-1 to 1212-n) positioned between the first end 1210-1 and the second end 1210-2. The electrodes 1212 define the ion-occupied volume 1214 within the ion guide 1210 and the axis 1216 of the ion guide between the first end 1202-1 and the second end 1210-2. The series of electrodes 1212 may include any preferred number of electrodes (e.g., 100 electrodes).

[0092] The power supply 1204 is electrically coupled to the electrodes 1212 and may be implemented by any number of individually controllable power supplies. The individually controllable power supplies may be configured to generate and apply RF voltage waveforms and DC voltages, which may be applied to various combinations of electrodes 1212 as described herein. As depicted in Figure 12, the power supply 1204 can simultaneously apply RF voltage waveforms and DC voltages to a series of electrodes 1212.

[0093] The pressure controller 1208 is fluidically coupled to the ion-occupied volume 1214 and is configured to modify the gas pressure within the ion-occupied volume 1214. The pressure controller 1208 may be implemented by any suitable pumping device (e.g., a vacuum pump) configured to reduce the gas pressure within the ion-occupied volume 1214, and / or by a gas source configured to increase the gas pressure within the ion-occupied volume 1214. In some examples, the pressure controller 1208 is configured to modify the gas pressure by controlling the flow of gas into the ion-occupied volume 1214 and / or by controlling the flow of gas out of the ion-occupied volume 1214, thereby increasing and / or decreasing the gas pressure within the ion-occupied volume 1214. The pressure controller 1208 can control the gas pressure within the ion-occupied volume 1214 to a value in the range of about 0.01 Torr to about 10 Torr. Increasing the gas pressure within the ion-occupied volume 1214 provides an increase in the number of collisions of ions moving through the gas, thereby increasing the collision effect for ion separation based on ion mobility. Alternatively, a decrease in gas pressure within the ion-occupied volume 1214 provides a reduction in the number of collisions between ions moving through the gas, thereby reducing the collision effect for ion separation based on ion mobility.

[0094] As shown in the figure, the controller 1206 may be coupled to the power supply 1204 and the pressure controller 1208 and configured to control the operation of the power supply 1204 and / or the pressure controller 1208 in any preferred manner. For example, with respect to the power supply 1204, the controller 1206 can specify attributes of the RF voltage waveform (e.g., magnitude, frequency, direction, type, etc.) to apply an RF voltage waveform having the specified attributes to a series of electrodes 1212. For example, the frequency of the RF voltage waveform may be applied in the range of about 100 kilohertz (kHz) to about 1000 kHz. A decrease in the frequency of the RF voltage waveform may provide an increase in collision effects for ion separation based on ion mobility, which may result in ion separation that is primarily based on ion mobility. A decrease in the frequency of the RF voltage waveform may provide a decrease in collision effects for ion separation based on ion mobility, which may result in ion separation that is primarily based on the m / z of the ions.

[0095] With respect to the pressure controller 1208, controller 1206 may instruct the pressure controller 1208 to modify the gas pressure within the ion-occupied volume 1214. Controller 1206 may be further configured to specify the flow of gas into and / or the flow of gas out of the ion-occupied volume 1214.

[0096] The controller 1206 can be implemented by any combination of one or more computing devices. For example, the controller 1206 can be implemented by a computing device included in the mass spectrometer system, one or more computing devices configured to be communicatively connected to the mass spectrometer system and / or the ion guide, and / or other local and / or remote computing devices that are useful for a particular implementation.

[0097] Figure 13 shows exemplary components of controller 1206. For example, controller 1206 may include, but is not limited to, memory facilities 1302 and processing facilities 1304 that are selectively and communicatively coupled to each other. Facilities 1302 and 1304 each include, or can be implemented by, hardware and / or software components (e.g., a processor, memory, a communication interface, instructions stored in memory for execution by the processor). In some examples, facilities 1302 and 1304 may be distributed among multiple devices and / or multiple locations to take advantage of a particular implementation. For example, facility 1302 may be distributed between one or more local computing resources and one or more remote computing resources that are communicatively coupled to the local computing resources via a network.

[0098] The storage unit 1302 may maintain (e.g., store) executable data used by the processing unit 1304 to perform any of the operations described herein. For example, the storage unit 1302 may store instruction 1306 which can be executed by the processing unit 1304 to perform any of the operations described herein. Instruction 1306 can be implemented by any suitable application, software, code, and / or other executable data instance. The storage unit 1302 may also maintain any data that is acquired, received, generated, managed, used, and / or transmitted by the processing unit 1304.

[0099] The processing unit 1304 may be configured to perform various processing operations described herein (for example, executing instructions 1306 stored in the storage unit 1302 for the purpose of performing the operation). It will be recognized that the operations and examples described herein are merely illustrative of the many different types of operations that may be performed by the processing unit 1304. In this description, any reference to an operation performed by the controller 1206 should be understood as being performed by the processing unit 1304 of the controller 1206. Furthermore, in this description, any operation performed by the controller 1206 may include the controller 1206 instructing or commanding another computing system, device, or apparatus to perform the operation.

[0100] Figure 14 shows an exemplary method 1400 for selectively setting the operating mode of an ion guide (e.g., ion guide 1202), which may be performed by the controller 1206. While Figure 14 shows exemplary operation according to one embodiment, other embodiments may omit, add, rearrange, and / or modify any of the operations shown in Figure 14.

[0101] In operation 1402, the controller 1206 determines that the ion guide will operate in a selected mode of two modes, the two modes being an m / z separation mode configured to separate ions in the ion-occupied volume primarily based on the m / z of the ions, and an ion-mobility separation mode configured to separate ions in the ion-occupied volume primarily based on the mobility of the ions. In some examples, the decision that the ion guide will operate in a selected mode is based on a user input specifying the selected mode. For example, a user device (e.g., a computing device) may be coupled communicatively to the controller 1206 so that the controller 1206 can receive a user input specifying the selected mode via the user device. In some examples, the user input is a selection between the two modes. Additionally or alternatively, the user input may specify one or more attributes of the RF voltage waveform and / or the gas pressure of the ion guide.

[0102] In some other examples, determining the operating mode of the ion guide is performed automatically by the controller 1206, without user input, for example. For instance, the controller 1206 may determine one or more conditions associated with the analysis of a sample containing ions received by the ion guide, and based on one or more conditions, select an operating mode for operating the ion guide. If the controller 1206 identifies conditions that prioritize m / z separation over ion mobility separation, the controller 1206 may select the m / z separation mode. If the controller 1206 identifies conditions that prioritize ion mobility separation over m / z separation, the controller 1206 may select the ion mobility separation mode.

[0103] As an exemplary example, the ion guide may be determined to operate in selection mode based on determining the attributes of the sample containing the ions to be received by the ion guide. The sample attributes may include one or more of the following: m / z range, charge state, mobility, chromatographic retention time or retention index, or collision cross-section of the ions contained in the sample. If the sample contains multiple ions with different charge states and the same m / z range, the controller 1206 may determine to operate the ion guide in ion mobility separation mode. Alternatively, if the sample does not contain multiple ions with a m / z range, the controller 1206 may determine to operate the ion guide in m / z separation mode. Further preferred configurations may be used to determine the operating mode of the ion guide. For example, if the m / z and / or desired m / z window of the ions selected to be separated are known, the controller 1206 may determine to operate in m / z separation mode.

[0104] In operation 1404, the controller 1206 sets, based on the decision, the attributes of the RF voltage waveform applied to a set of electrodes (e.g., electrode 1212) to operate the ion guide in selected mode. The attributes of the RF voltage waveform may include, but are not limited to, the magnitude of the RF voltage waveform, the magnitude range of the RF voltage waveform, the frequency of the RF voltage waveform, the frequency range of the RF voltage waveform, the direction of the RF voltage waveform, the velocity of the RF voltage waveform, the electrode to which the RF voltage waveform is applied, or one or more of the types of RF voltage waveforms, such as sinusoidal, pulsed, stepped, or sawtooth waveforms.

[0105] In some examples, the configuration involves setting the RF voltage waveform attributes to be within a first range when the ion guide operates in m / z separation mode, or within a second range when the ion guide operates in ion mobility separation mode. For example, the attributes may include a range of RF voltage waveform frequencies (e.g., about 100 kHz to about 1000 kHz), such that the first range of RF voltage waveform attributes includes a first range of RF voltage waveform frequencies for operation in m / z separation mode, and the second range of RF voltage waveform attributes includes a second range of RF voltage waveform frequencies for operation in ion mobility separation mode. In such cases, the RF voltage waveform frequencies in the second range are lower than those in the first range.

[0106] In operation 1406, the controller 1206 causes the ion guide to apply an RF voltage waveform having set attributes to a series of electrodes while the ion guide is operating in selection mode. The application of the RF voltage waveform is configured to cause spatial separation of ions within the ion guide and generate a number of moving pseudopotential wells that exert a force moving the ions toward a second end of the ion guide. Applying an RF voltage waveform having set attributes to a series of electrodes may include applying the RF voltage waveform having set attributes to a first series of electrodes located on the surface of a first substrate plate or wafer and to a second series of electrodes located on the surface of a second substrate plate or wafer, 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.

[0107] In m / z separation mode, the applied RF voltage waveform generates multiple moving pseudopotential wells that exert m / z-dependent forces that move ions from a first end of the ion guide (e.g., first end 1210-1) to a second end (e.g., second end 1210-2). In some examples, the controller 1206 applies two or more sets of DC potentials to either a set of electrodes or a set of auxiliary electrodes that generate a force independent of m / z that biases ions in the ion guide to move from the second end to the first end, simultaneously with the application of the RF voltage waveform. The ions can then be spatially separated within the ion guide using the combination of opposing forces. For example, for the ion with the smallest m / z value, the force due to the RF traveling wave prevails over the DC electric field force, and the movement is in the direction of the traveling wave. For the ion with the largest m / z value, the DC axial electric field becomes dominant, and the movement is in the opposite direction to the traveling wave. For ions with a specific critical m / z value, the force originating from the RF and the force originating from the DC potential gradient equilibrium such that the ions do not move in either direction but are trapped within a specific region within the ion guide, the location of which depends on the specific m / z value and applied voltage. Therefore, by the coordinated application of the RF electric field and the static DC electric field, the ion guide is configured such that ions with low m / z values ​​and ions with high m / z values ​​move in opposite directions, while at the same time, ions with critical m / z values ​​are trapped at the trapping location within the ion guide, thereby allowing for the spatial separation of ions along the length of the ion guide, primarily based on m / z.

[0108] In some examples, the gradient may be applied to either an RF electric field, a DC electric field, or both RF and DC electric fields. In such cases, the capture location becomes m / z dependent, thereby capturing and spatially separating ions based on their respective m / z values. In some examples, applying two or more DC potentials involves applying potentials that generate a static, uniform DC electric field within the ion guide, thereby causing ions with a particular mass-to-charge ratio (m / z) to accumulate within the ion guide and ions with other mass-to-charge ratios to move out of the ion guide. Additionally or alternatively, the magnitude of the applied DC potential and / or the amplitude of the applied RF voltage waveform may be sloped to move accumulated ions with a particular m / z through either the first or second end of the ion guide.

[0109] In ion mobility separation mode, ions are spatially separated primarily based on their mobility within the ion-occupied volume of the ion guide (e.g., ion-occupied volume 1214). As ions move under the influence of the applied field and collide with the background gas within the ion-occupied volume 1214, they spatially separate and move to stable capture locations. Ions move through the gas flow region of the ion-occupied volume according to their ion mobility characteristics, spatially separating from one another during their movement (e.g., by collisions with the gas within the ion-occupied volume). For example, larger ions (e.g., ions with larger collision cross-sections) are more affected by collisions and may move more slowly under the influence of the applied field than smaller ions (e.g., ions with smaller collision cross-sections), which results in ion separation. Capture locations depend at least partially on mobility, thereby capturing and spatially separating ions based partly on their respective mobility attributes. For example, ions with higher mobility may advance further into the ion guide than ions with lower mobility (i.e., they may advance further from the first end 1210-1 to the second end 1210-2). This separation allows ions leaving the ion-occupied volume of the ion guide to have a different range of ion mobility than other ions leaving the ion-occupied volume.

[0110] In other embodiments, the ion mobility separation mode can increase the size of the mobility separation effect by additionally introducing a gas flow having an ion-occupied volume. For example, the ion-occupied volume may have a gas flow, such as in a first direction, and an electric field gradient (e.g., caused by an RF voltage waveform and / or DC potential), such as in a second direction different from the first direction. In some examples, the gas flow may be generated by the operation of a pressure controller 1208.

[0111] Therefore, in m / z separation mode, the m / z-dependent effect of the applied RF voltage waveform is greater than the collision shock related to ion mobility, causing ion separation within the ion guide. In some examples, increasing the applied RF voltage waveform frequency can reduce the collision shock related to ion mobility and increase ion separation based on m / z. Thus, the RF voltage waveform frequency may be applied within a first range of RF voltage waveform frequencies in m / z separation mode to cause ion separation within the ion guide based on m / z rather than ion mobility. For example, the RF voltage waveform frequency applied in m / z separation mode may not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on ion mobility to the extent that it does not cause ion separation based on m / z.

[0112] Alternatively, in ion mobility separation mode, collision shocks related to ion mobility are greater than the m / z-dependent effect of the applied RF voltage waveform, causing ion separation within the ion guide. In some examples, decreasing the applied RF voltage waveform frequency can increase collision shocks related to ion mobility, thereby increasing ion separation based on mobility. Thus, the RF voltage waveform frequency may be applied within a second range of RF voltage waveform frequencies in ion mobility separation mode to cause ion separation within the ion guide based on mobility rather than m / z. For example, the applied RF voltage waveform frequency in ion separation mode may cause a portion of ion separation based on mobility that is greater than the portion of ion separation based on m / z.

[0113] In some examples, the attributes of the RF voltage waveform may be adjusted to switch between m / z separation mode and ion mobility separation mode. For example, the frequency of the RF voltage waveform applied to a series of electrodes of an ion guide may be decreased to switch from m / z separation mode to ion mobility separation mode, and / or the frequency of the RF voltage waveform may be increased to switch from ion mobility separation mode to m / z separation mode. As an exemplary example, an ion guide may be configured to operate in m / z separation mode, for example, to determine the m / z range of ions contained in a sample. If multiple ions contained in the sample have the same m / z range and different charge states, the controller 1206 may adjust (e.g., decrease) the frequency of the RF voltage waveform from a first range to a second range to switch the operation of the ion guide from m / z separation mode to ion mobility separation mode. The ion guide can then separate ions having the same m / z range and different charge states based on the ion mobility.

[0114] Figure 15 shows another exemplary method 1500 for selectively setting the operating mode of an ion guide (e.g., ion guide 1202), which may be performed by the controller 1206. While Figure 15 shows exemplary operation according to one embodiment, other embodiments may omit, add, rearrange, and / or modify any of the operations shown in Figure 15.

[0115] In operation 1502, the controller 1206 receives user input and / or data representing the attributes of the sample. For example, user input may specify a selection mode for the m / z separation mode or ion mobility separation mode for operating the ion guide. Additionally or alternatively, user input may specify attributes of the RF voltage waveform applied to a series of electrodes of the ion guide and / or attributes of the sample containing the ions received by the ion guide, such as the m / z range, charge state, mobility, and / or collision cross-section of the ions contained in the sample. Additionally or alternatively, the controller 1206 may receive data representing the attributes of the sample, such as the sample containing multiple ions having the same m / z range and different charge states. The data can be retrieved, for example, from a database containing the analyte or other sample components and the relevant attributes of each analyte or sample component.

[0116] In operation 1504, the controller 1206 determines whether to operate the ion guide in m / z separation mode, which is configured to separate ions within an ion-occupied volume, primarily based on the m / z of the ions. For example, if the user input specifies m / z separation mode and / or the sample does not contain multiple ions having the same m / z range, the controller 1206 may decide to operate the ion guide in m / z separation mode. Alternatively, if the user input specifies ion mobility separation mode and / or the sample contains multiple ions having the same m / z range, the controller 1206 may decide to operate the ion guide in ion mobility separation mode, which is configured to separate ions within an ion-occupied volume, primarily based on the ion mobility.

[0117] If controller 1206 selects the m / z separation mode (e.g., yes in operation 1504), in operation 1506, controller 1206 sets the attributes of the RF voltage waveform to be within a first range. For example, the frequency of the RF voltage waveform may be set to be within the first range (e.g., approximately 400kHz to approximately 1000kHz, approximately 500kHz to approximately 1000kHz, approximately 600kHz to approximately 1000kHz, approximately 700kHz to approximately 1000kHz, approximately 800kHz to approximately 1000kHz, etc.). Alternatively, if controller 1206 does not select the m / z separation mode (e.g., no in operation 1504), in operation 1508, controller 1206 may choose to operate the ion guide in ion mobility separation mode and set the attributes of the RF voltage waveform to be within a second range. For example, the frequency of the RF voltage waveform can be set to a second range lower than the first range (e.g., approximately 100kHz to 1000kHz, approximately 100kHz to 800kHz, approximately 100kHz to 700kHz, approximately 100kHz to 600kHz, approximately 100kHz to 500kHz, etc.).

[0118] In operation 1510, the controller 1206 causes a set RF voltage waveform having specified attributes to be applied to a set of electrodes while the ion guide is operating in selection mode. For example, the controller 1206 may cause a power supply (e.g., power supply 1204) electrically coupled to the set of electrodes to have an RF voltage waveform having specified attributes. The RF voltage waveform is configured to cause spatial separation of ions within the ion guide and generate multiple moving pseudopotential wells that exert a force moving the ions toward a second end of the ion guide. In m / z separation mode, the RF voltage waveform is configured to cause ion separation primarily based on the m / z of the ions. In mobility separation mode, the RF voltage waveform is configured to cause ion separation primarily based on the mobility of the ions. For example, lower RF voltage waveform frequencies within the second range may increase ion collision shock, thereby increasing ion separation based on mobility in ion mobility separation mode.

[0119] In some examples, the ion guide contains a gas (e.g., a gas pressure of 0.01 Torr or greater, such as about 0.01 Torr to about 10 Torr) within the ion-occupied volume, and a combination of gas attributes within the ion-occupied volume and RF voltage waveform attributes can be set so that the ion guide operates selectively in m / z separation mode or ion mobility separation mode. As an exemplary example, Figure 16 shows an exemplary method 1600 for selectively setting gas attributes based on the operating mode of the ion guide (e.g., ion guide 1202) which can be carried out by the controller 1206. Figure 16 shows exemplary operation according to one embodiment, but other embodiments may omit, add, rearrange, and / or modify any of the operations shown in Figure 16.

[0120] In operation 1602, the controller 1206 receives user input and / or data representing the attributes of the sample. For example, user input may specify a selection mode for the m / z separation mode or ion mobility separation mode for operating the ion guide. Additionally or alternatively, user input may specify the attributes of the RF voltage waveform applied to a series of electrodes of the ion guide and / or the attributes of the sample containing the ions received by the ion guide, such as the m / z range of the ions contained in the sample. Additionally or alternatively, the controller 1206 may receive data representing the attributes of the sample such that the sample contains multiple ions having the same m / z range.

[0121] In operation 1604, the controller 1206 determines whether to operate the ion guide in m / z separation mode, which is configured to separate ions within an ion-occupied volume, primarily based on the m / z of the ions. For example, if the user input specifies m / z separation mode and / or the sample does not contain multiple ions having the same m / z range, the controller 1206 may decide to operate the ion guide in m / z separation mode. Alternatively, if the user input specifies ion mobility separation mode and / or the sample contains multiple ions having the same m / z range, the controller 1206 may decide to operate the ion guide in ion mobility separation mode, which is configured to separate ions within an ion-occupied volume, primarily based on the ion mobility.

[0122] If controller 1206 selects the m / z separation mode (e.g., yes in operation 1604), in operation 1606, controller 1206 sets the gas attributes within the ion-occupied volume of the ion guide (e.g., gas pressure, gas flow velocity, gas type, gas flow direction, etc.) to a first range (in addition to setting the RF voltage waveform attributes to a first range for the RF voltage waveform). For example, the gas pressure of the gas may be set to a first range (e.g., approximately 0.1 Torr to approximately 1 Torr, approximately 0.1 Torr to approximately 0.5 Torr, approximately 0.1 Torr to approximately 0.2 Torr, etc.). Alternatively, if controller 1206 does not select the m / z separation mode (e.g., no in operation 1604), in operation 1608, controller 1206 may choose to operate the ion guide in ion mobility separation mode and set the gas attributes to be within a second range (in addition to setting the RF voltage waveform attributes to a second range for the RF voltage waveform). For example, the gas pressure of the gas can be set within a second range that includes gas pressures higher than a first range (e.g., about 0.2 Torr to about 10 Torr, about 0.5 Torr to about 10 Torr, about 1 Torr to about 10 Torr, etc.). In some examples, the ion guide does not employ a gas that flows actively within the ion-occupied volume (i.e., it does not impart a non-zero mean velocity to the buffer or background gas with respect to the ion-occupied volume). In such examples, the ability to modulate certain "static" attributes independent of the active gas flow, such as gas pressure and gas type, can still advantageously enable selection between ion mobility and m / z separation modes, as taught herein.

[0123] In operation 1610, the controller 1206 causes a gas having set attributes to be applied to the ion-occupied volume while the ion guide is operating in selection mode. For example, the controller 1206 can cause a pressure controller (e.g., pressure controller 1208) fluidly coupled to the ion-occupied volume to apply a gas having set attributes. The gas having set attributes is configured to cause ion separation in the ion guide, in addition to the applied RF voltage waveform. For example, a higher gas pressure within a second range may increase the ion collision impact, thereby increasing ion separation based on mobility. In some examples, a higher gas pressure may provide further ion separation with respect to the ion charge state.

[0124] In some cases, the m / z separation mode and the ion mobility separation mode can be switched by adjusting one or both of the gas attributes or the RF voltage waveform attributes. For example, the gas pressure of the gas applied to the ion occupancy volume of the ion guide may be increased to switch from m / z separation mode to ion mobility separation mode, and / or the gas pressure may be decreased to switch from ion mobility separation mode to m / z separation mode. Thus, adjusting the gas pressure can switch the operating mode of the ion guide with little or no change to the RF voltage waveform. Additionally or alternatively, the frequency of the RF voltage waveform applied to a series of electrodes of the ion guide may be decreased to switch from m / z separation mode to ion mobility separation mode, and / or the frequency of the RF voltage waveform may be increased to switch from ion mobility separation mode to m / z separation mode. Additionally or alternatively, the frequency of the RF voltage waveform applied to a series of electrodes of the ion guide may be decreased to switch from m / z separation mode to ion mobility separation mode, and / or the frequency of the RF voltage waveform may be increased to switch from ion mobility separation mode to m / z separation mode. Thus, adjusting the RF voltage waveform frequency and / or RF traveling wave velocity can switch the operating mode of the ion guide with little or no change in gas pressure. In some examples, the controller 1206 may change the gas pressure and / or RF voltage waveform over time in either m / z separation mode or ion mobility separation mode.

[0125] In some cases, the ion guide may first be operated in m / z separation mode to determine the m / z range and / or the relationship between the m / z, charge, and mobility of ions contained in the sample received by the ion guide. The ion guide can then be switched to operate in ion mobility separation mode to separate, for example, ions in the sample that have the same m / z and different charge states (e.g., and / or another sample containing the same ions). In some cases, the ions contained in the sample may be passed through a mass filter prior to being received by the ion guide, and the ions contained in the sample may be filtered to a selective m / z range for subsequent separation, for example, mainly based on ion mobility by the ion guide. In such cases, an MS / MS spectrum with improved resolution can be achieved for ions exclusively separated by m / z.

[0126] Figures 17A and 17B show the results of a simulation of exemplary m / z linearity when various RF voltage waveform frequencies are applied to a series of electrodes (e.g., electrode 1212) within an ion guide (e.g., ion guide 1202).

[0127] Figure 17A shows an exemplary m / z linearity of the simulation plotted as a function of m / z along the X axis and 1 / electric field along the Y axis (for example, a value representing the reciprocal of the intensity of the DC electric field at which ions are eluted from the ion guide). In the simulation, the gas pressure of the gas in the ion-occupied volume was set to 0.2 Torr, and multiple RF voltage waveform frequencies in the range of 400 kHz to 1000 kHz were applied to a series of electrodes of the ion guide to obtain different curves. As shown, RF voltage waveforms with higher frequencies provide a more linear function of m / z than RF voltage waveforms with lower frequencies, which may indicate that RF voltage waveforms with higher frequencies provide a greater m / z-dependent effect for separating ions based on m / z (e.g., higher RF voltage waveform frequencies reduce the overall effect of collisions).

[0128] Figure 17B shows an exemplary m / z linearity of the simulation plotted as a function of m / z along the X axis and 1 / Field along the Y axis. In the simulation, the gas pressure of the gas in the ion-occupied volume was set to 1 Torr, and multiple RF voltage waveform frequencies in the range of 400 kHz to 1000 kHz were applied to a series of electrodes of the ion guide to obtain different curves. As shown, RF voltage waveforms with lower frequencies provide a lower linear function of m / z than RF voltage waveforms with higher frequencies, and can even produce a significant inflection point, which may indicate that RF voltage waveforms with lower frequencies provide more collision effects for separating ions based on ion mobility. Additionally, increasing the gas pressure of the gas in the ion-occupied volume further increased the collision effect and further improved ion separation based on ion mobility. The simulations shown in Figures 17A and 17B may further indicate that changes in RF voltage waveform frequency may have more effect on m / z-based separation and ion mobility-based separation at higher gas pressures. For example, each curve obtained at a gas pressure set to 0.2 Torr (e.g., Figure 17A) has a linear approximation R-squared value greater than 0.999, while the curve obtained at a gas pressure set to 1 Torr (e.g., Figure 17B) has a lower R-squared value, indicating greater nonlinearity. Deviations from the linear relationship indicate a larger mobility component contributing to ion separation. For example, the curve associated with an RF voltage waveform frequency of 400 kHz and a gas pressure set to 1 Torr has an R-squared value of 0.9705, while the curve associated with an RF voltage waveform frequency of 1000 kHz and a gas pressure set to 1 Torr has an R-squared value of 0.9913. Therefore, the RF voltage waveform frequency can be adjusted from the second range to the first range while the gas pressure remains within the second range, in order to switch from ion mobility separation mode to m / z separation mode, or vice versa.

[0129] In some examples, computer program products embodied in non-temporary computer-readable storage media may be supplied. In such examples, the non-temporary computer-readable storage media may store computer-readable instructions in accordance with the principles described herein. When executed by the processor of a computing device, the instructions can instruct the processor and / or the computing device to perform one or more operations, including one or more of the operations described herein. Such instructions may be stored and / or transmitted using any of a variety of known computer-readable media.

[0130] Non-temporary computer-readable media as referred to herein include any non-temporary storage media involved in providing data (e.g., instructions) that can be read and / or executed by a computing device (e.g., by the processor of the computing device). For example, non-temporary computer-readable media may include, but are not limited to, any combination of non-volatile storage media and / or volatile storage media. Exemplary non-volatile storage media include, but are not limited to, read-only memory, flash memory, solid-state drives, magnetic storage devices (e.g., hard disks, floppy disks, magnetic tapes, etc.), ferroelectric random-access memory ("RAM"), and optical discs (e.g., compact discs, digital video discs, Blu-ray discs, etc.). Exemplary volatile storage media include, but are not limited to, RAM (e.g., dynamic RAM).

[0131] Figure 18 shows an exemplary computing device 1800 that may be specifically configured to perform one or more of the operations, methods, and processes described herein. Any of the systems, computing devices, and / or other components described herein may be implemented by computing device 1800.

[0132] As shown in Figure 18, the computing device 1800 may include a communication interface 1802, a processor 1804, a storage device 1806, and an input / output ("I / O") module 1808, all connected to each other via a communication infrastructure 1810. While Figure 18 shows an exemplary computing device 1800, the components illustrated in Figure 18 are not intended to be limiting. Additional or alternative components may be used in other embodiments. The components of the computing device 1800 shown in Figure 18 will now be described in more detail.

[0133] The communication interface 1802 may be configured to communicate with one or more computing devices. Examples of the communication interface 1802 include, but are not limited to, a wired network interface (such as a network interface card), a wireless network interface (such as a wireless network interface card), a modem, an audio / video connection, and any other suitable interface.

[0134] The processor 1804 generally represents any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing the execution of one or more instructions, processes, and / or operations as described herein. The processor 1804 may perform operations by executing computer executable instructions 1812 (e.g., applications, software, code, and / or other executable data instances) stored in the storage device 1806.

[0135] The storage device 1806 may include one or more data storage media, devices, or configurations, and may employ any type, form, and combination of data storage media and / or devices. For example, the storage device 1806 may include any combination of non-volatile media and / or volatile media described herein, but is not limited to the following. Electronic data, including the data described herein, may be stored temporarily and / or permanently within the storage device 1806. For example, data representing a computer executable instruction 1812 configured to instruct a processor 1804 to perform one of the operations described herein may be stored within the storage device 1806. In some examples, the data may be arranged in one or more databases residing within the storage device 1806.

[0136] The I / O module 1808 may include one or more I / O modules configured to receive user input and provide user output. One or more I / O modules may be used to receive input for a single virtual experience. The I / O module 1808 may include any hardware, firmware, software, or combination thereof that supports input and output capabilities. For example, the I / O module 1808 may include hardware and / or software for capturing user input, including, but not limited to, a keyboard or keypad, a touchscreen component (e.g., a touchscreen display), a receiver (e.g., an RF or infrared receiver), a motion sensor, and / or one or more input buttons.

[0137] The I / O module 1808 may include, but is not limited to, a graphics engine, a display (e.g., a display screen), one or more output drivers (e.g., display drivers), one or more audio speakers, and one or more audio drivers, one or more devices for presenting output to the user. In certain embodiments, the I / O module 1808 is configured to provide graphical data to the display for presentation to the user. The graphical data may represent one or more graphical user interfaces and / or any other graphical content, as may be useful for a particular implementation.

[0138] The advantages and features of this disclosure can be further described by the following statement. 1. A system comprising a memory for storing instructions and one or more processors communicatively coupled to the memory, wherein one or more processors are configured to execute instructions, and the process determines to operate an ion guide in a select mode of two modes, wherein the ion guide comprises a first end, a second end, and a series of electrodes positioned between the first and second ends, the series of electrodes defining an ion-occupied volume between the first and second ends, and the two modes include an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the ion-mass-to-charge ratio (m / z), and an ion-mobility separation mode configured to separate ions in the ion-occupied volume mainly based on the ion-mobility. A system comprising setting the attributes of a radio frequency (RF) voltage waveform to be applied to a series of electrodes so that the ion guide operates in select mode, the setting including setting the attributes of the RF voltage waveform to a first range when the ion guide operates in m / z separation mode, and setting the attributes of the RF voltage waveform to a second range when the ion guide operates in ion mobility separation mode, and applying an RF voltage waveform having the set attributes to the series of electrodes while the ion guide is operating in select mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward a second end of the ion guide. 2. A system as described in any of the preceding statements, in which setting the attributes of the RF voltage waveform includes setting one or more of the frequency of the RF voltage waveform, the magnitude of the RF voltage waveform, or the speed of the RF voltage waveform. 3. A system as described in any of the preceding statements, wherein a first range of RF voltage waveform attributes includes a first range of RF voltage waveform frequencies, and a second range of RF voltage waveform attributes includes a second range of RF voltage waveform frequencies lower than the first range of RF voltage waveform frequencies. 4. A system as described above, wherein the ion guide contains gas within the ion-occupied volume at a gas pressure of 0.01 Torr or greater. 5. The system as described in any of the preceding statements, further comprising setting the gas pressure of the gas in the ion-occupied volume so that the ion guide operates in select mode, based on the determination that the process is to set the gas pressure to a first pressure range when the ion guide is operating in m / z separation mode, and to set the gas pressure to a second pressure range when the ion guide is operating in ion mobility separation mode. 6. A system as described in any of the preceding statements, wherein the first pressure range includes gas pressures lower than the gas pressures included in the second pressure range. 7. A system as described in any of the preceding descriptions, further comprising adjusting the attributes of the RF voltage waveform so that the process switches between m / z separation mode and ion mobility separation mode. 8. A system as described above in which the ion guide determines to operate in a selection mode based on user input specifying the selection mode. 9. A system as described in any of the preceding statements, in which the decision to operate the ion guide in a selective mode is based on determining the attributes of the sample containing the ions received by the ion guide. 10. A system as described in any of the preceding statements, wherein the sample attributes include multiple ions having the same m / z range. 11. The system according to any of the foregoing descriptions, further comprising, simultaneously with the application of an RF voltage waveform, the application of a direct current (DC) potential to either a series of electrodes or a set of auxiliary electrodes that generate a force that biases ions in an ion guide to move from a second end to a first end, in a manner independent of m / z. 12. A system according to any of the foregoing descriptions, comprising applying a set of two or more potentials to move ions from a second end to a first end and generate a static, uniform DC electric field within an ion guide, thereby causing ions having a particular m / z to accumulate within the ion guide and ions having other mass-to-charge ratios to move away from the ion guide. 13. The system according to any of the foregoing descriptions, further comprising the process of sloping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby moving accumulated ions having a specific m / z through either the first or second end out of the ion guide. 14. The system according to any of the preceding descriptions, wherein applying an RF voltage waveform to a series of electrodes includes applying an RF voltage waveform to a first series of electrodes disposed on the surface of a first substrate plate or wafer and to a second series of electrodes disposed on the surface of a second substrate plate or wafer, 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. 15. A mass spectrometer system comprising an ion guide configured to receive ions, the ion guide comprising a series of electrodes positioned at a first end, a second end, and between the first and second ends, the series of electrodes defining an ion-occupied volume between the first and second ends; one or more power supplies electrically coupled to the series of electrodes, configured to apply a set of radio frequency (RF) voltage waveforms to the series of electrodes; and a controller communicatively coupled to the one or more power supplies, the controller configured to perform a process, the process of determining to operate the ion guide in a selectable mode of two modes, the two modes being an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the ion-mass-to-charge ratio (m / z), and a mode configured to separate ions mainly based on ion-mobility. A mass spectrometer system comprising: determining an ion mobility separation mode configured such as; setting the attributes of a radio frequency (RF) voltage waveform to be applied to a series of electrodes so as to operate an ion guide in a selection mode, wherein setting includes setting the attributes of the RF voltage waveform to a first range when the ion guide is operating in m / z separation mode; setting the attributes of the RF voltage waveform to a second range when the ion guide is operating in ion mobility separation mode; and applying an RF voltage waveform having the set attributes to a series of electrodes while the ion guide is operating in selection mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases ions to move toward a second end of the ion guide. 16. A method for operating an ion guide, comprising: a first end, a second end, and a series of electrodes positioned between the first and second ends, wherein the series of electrodes define an ion-occupied volume between the first and second ends, and the method determines to operate the ion guide in a selective mode of two modes, the two modes including an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the mass-to-charge ratio (m / z) of the ions, and an ion-mobility separation mode configured to separate ions mainly based on the ion mobility, and a high frequency to be applied to the series of electrodes to operate the ion guide in the selective mode based on the determination, A method for setting the attributes of an (RF) voltage waveform, the setting comprising setting the attributes of the RF voltage waveform to a first range when the ion guide is operating in m / z separation mode, and setting the attributes of the RF voltage waveform to a second range when the ion guide is operating in ion mobility separation mode, the setting comprising applying an RF voltage waveform having the set attributes to a series of electrodes while the ion guide is operating in selection mode, wherein the RF voltage waveform is configured to cause spatial separation of ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward a second end of the ion guide. 17. The method described in any of the preceding statements, wherein setting the attributes of the RF voltage waveform includes setting one or more of the frequency of the RF voltage waveform, the magnitude of the RF voltage waveform, or the velocity of the RF voltage waveform. 18. The method described in any of the preceding descriptions, wherein a first range of RF voltage waveform attributes includes a first range of RF voltage waveform frequencies, and a second range of RF voltage waveform attributes includes a second range of RF voltage waveform frequencies lower than the first range of RF voltage waveform frequencies. 19. The method of any of the foregoing descriptions, further comprising setting the gas pressure of the gas in the ion-occupied volume to cause the ion guide to operate in select mode, wherein setting the gas pressure includes setting the gas pressure within a first pressure range when the ion guide is operating in m / z separation mode, and setting the gas pressure within a second pressure range when the ion guide is operating in ion mobility separation mode. 20. The method of any of the foregoing descriptions, further comprising adjusting the attributes of the RF voltage waveform to switch between m / z separation mode and ion mobility separation mode.

[0139] In the above description, various exemplary embodiments have been described with reference to the accompanying drawings. However, it will be apparent that various modifications and changes can be made thereto, and additional embodiments can be realized, without departing from the scope of the invention as described in the following claims. For example, certain features of one embodiment described herein can be combined with or replaced by features of another embodiment described herein. Therefore, this specification and the drawings should be considered in an exemplary sense, not in an restrictive sense.

Claims

1. It is a system, Memory for storing instructions, The system comprises one or more processors communicably coupled to the memory, wherein the one or more processors are configured to execute the instructions that carry out a process, and the process, The determination to operate an ion guide in a selectable mode of two modes, wherein the ion guide comprises a first end, a second end, and a series of electrodes positioned between the first and second ends, the series of electrodes defining an ion-occupied volume between the first and second ends, and the two modes include an m / z separation mode configured to separate ions within the ion-occupied volume primarily based on the mass-to-charge ratio (m / z) of the ions, and an ion-mobility separation mode configured to separate ions within the ion-occupied volume primarily based on the mobility of the ions. Based on the above determination, the attributes of the radio frequency (RF) voltage waveform to be applied to the series of electrodes are set so that the ion guide operates in the selected mode, the setting being, When the ion guide operates in the m / z separation mode, the attributes of the RF voltage waveform are set to a first range, Setting includes setting the attribute of the RF voltage waveform within a second range when the ion guide operates in the ion mobility separation mode. A system comprising applying the RF voltage waveform having the set attributes to the set electrodes while the ion guide is operating in the selection mode, wherein the RF voltage waveform is configured to cause spatial separation of the ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward the second end of the ion guide.

2. The system according to claim 1, wherein setting the attributes of the RF voltage waveform includes setting one or more of the frequency of the RF voltage waveform, the magnitude of the RF voltage waveform, or the speed of the RF voltage waveform.

3. The system according to claim 1, wherein the first range of the attributes of the RF voltage waveform includes a first range of RF voltage waveform frequencies, and the second range of the attributes of the RF voltage waveform includes a second range of RF voltage waveform frequencies lower than the first range of RF voltage waveform frequencies.

4. The system according to claim 1, wherein the ion guide contains gas within the ion-occupied volume at a gas pressure of 0.01 Torr or more.

5. The process further includes setting the gas pressure of the gas in the ion-occupied volume so that the ion guide operates in the selected mode based on the determination, and setting the gas pressure is When the ion guide operates in the m / z separation mode, the gas pressure is set to a first pressure range. The system according to claim 4, comprising setting the gas pressure within a second pressure range when the ion guide is operating in the ion mobility separation mode.

6. The system according to claim 5, wherein the first pressure range includes a gas pressure lower than the gas pressure included in the second pressure range.

7. The system according to claim 1, further comprising adjusting the attributes of the RF voltage waveform so that the process switches between the m / z separation mode and the ion mobility separation mode.

8. The system according to claim 1, wherein the determination that the ion guide operates in the selection mode is based on user input specifying the selection mode.

9. The system according to claim 1, wherein determining that the ion guide operates in the selection mode is based on determining the attributes of a sample containing ions received by the ion guide.

10. The system according to claim 9, wherein the attribute of the sample includes a plurality of ions having the same m / z range.

11. The system according to claim 1, further comprising, at the same time as the application of the RF voltage waveform, applying a direct current (DC) potential to either the series of electrodes or a set of auxiliary electrodes that generate a force that biases the ions in the ion guide to move from the second end to the first end, in an independent of m / z.

12. The system according to claim 11, wherein the application of the DC potential includes applying a set of two or more potentials, one of which generates a static and uniform DC electric field within a portion of the ion guide, thereby causing ions having a specific m / z to accumulate within the ion guide and ions having other mass-to-charge ratios to move out of the ion guide.

13. The system according to claim 12, wherein the process further includes sloping the magnitude of the applied DC potential or the amplitude of the applied RF voltage waveform, thereby moving the accumulated ions having a specific m / z through either the first or second end to the outside of the ion guide.

14. The system according to claim 1, wherein applying the RF voltage waveform to the series of electrodes includes applying the RF voltage waveform to a first series of electrodes disposed on the surface of a first substrate plate or wafer and a second series of electrodes disposed on the surface of a second substrate plate or wafer, 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.

15. A mass spectrometer system, An ion guide configured to receive ions, wherein the ion guide is The first end, The second end, and A series of electrodes positioned between the first end and the second end, the series of electrodes defining the ion-occupied volume between the first end and the second end, and an ion guide, One or more power supplies electrically coupled to the series of electrodes, configured to apply a set of high-frequency (RF) voltage waveforms to the series of electrodes, The system comprises one or more power sources and a controller that is communicatively coupled, wherein the controller is configured to perform a process, and the process is The determination to operate the ion guide in a selectable mode of two modes, wherein the two modes include an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the mass-to-charge ratio (m / z) of the ions, and an ion mobility separation mode configured to separate the ions mainly based on the mobility of the ions. Based on the above determination, the attributes of the radio frequency (RF) voltage waveform to be applied to the series of electrodes are set so that the ion guide operates in the selected mode, the setting being, When the ion guide operates in the m / z separation mode, the attributes of the RF voltage waveform are set to a first range, Setting includes setting the attribute of the RF voltage waveform within a second range when the ion guide operates in the ion mobility separation mode. A mass spectrometer system comprising applying the RF voltage waveform having the set attributes to the set electrodes while the ion guide is operating in the selection mode, wherein the RF voltage waveform is configured to cause spatial separation of the ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exerting a force that biases the ions to move toward the second end of the ion guide.

16. A method for operating an ion guide, wherein the ion guide comprises a first end, a second end, and a series of electrodes positioned between the first end and the second end, the series of electrodes defining the ion-occupied volume between the first end and the second end, and the method The determination to operate the ion guide in a selectable mode of two modes, wherein the two modes include an m / z separation mode configured to separate ions in the ion-occupied volume mainly based on the mass-to-charge ratio (m / z) of the ions, and an ion mobility separation mode configured to separate the ions mainly based on the mobility of the ions. Based on the above determination, the attributes of the radio frequency (RF) voltage waveform to be applied to the series of electrodes are set so that the ion guide operates in the selected mode, the setting being, When the ion guide operates in the m / z separation mode, the attributes of the RF voltage waveform are set to a first range, Setting includes setting the attribute of the RF voltage waveform within a second range when the ion guide operates in the ion mobility separation mode. A method comprising applying the RF voltage waveform having the set attributes to the set electrodes while the ion guide is operating in the selection mode, wherein the RF voltage waveform is configured to cause spatial separation of the ions in the ion guide and generate a plurality of moving pseudopotential wells, the plurality of moving pseudopotential wells exert a force that biases the ions to move toward the second end of the ion guide.

17. The method according to claim 16, wherein setting the attributes of the RF voltage waveform includes setting one or more of the frequency of the RF voltage waveform, the magnitude of the RF voltage waveform, or the speed of the RF voltage waveform.

18. The method according to claim 16, wherein the first range of the attributes of the RF voltage waveform includes a first range of RF voltage waveform frequencies, and the second range of the attributes of the RF voltage waveform includes a second range of RF voltage waveform frequencies lower than the first range of RF voltage waveform frequencies.

19. Based on the above determination, the gas pressure of the gas in the ion-occupied volume is further set to cause the ion guide to operate in the selected mode, and the setting of the gas pressure is When the ion guide operates in the m / z separation mode, the gas pressure is set to a first pressure range. The method according to claim 16, comprising setting the gas pressure within a second pressure range when the ion guide operates in the ion mobility separation mode.

20. The method according to claim 16, further comprising adjusting the attributes of the RF voltage waveform so as to switch between the m / z separation mode and the ion mobility separation mode.

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