Device and method for ion mobility and charge separation, and for ion filtering

Abstract

Ion manipulation device for driving ions in a propulsion direction comprising an electrode support for supporting one or more electrodes; a first set of RF electrodes comprising a number n of electrodes, wherein the first set of RF electrodes comprises at least three electrodes; and an RF voltage generator operatively connected to the first set of RF electrodes. The RF voltage generator is configured to generate a plurality of phase-shifted RF voltages, each consecutive phase-shifted RF voltage of the generated plurality of phase- shifted RF voltages being phase-shifted by a value of approximately 2jt / n or 2jt / n to both confine ions in a first and / or second direction and to propel ions in the propulsion direction orthogonal or non-parallel to the first and / or second direction. The electrodes of the first set of RF electrodes are operatively connected to the RF voltage generator to simultaneously receive the plurality of phase-shifted RF voltages.

Description

[0001] DEVICE AND METHOD FOR ION MOBILITY AND CHARGE SEPARATION, AND FOR ION FILTERING

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is related to and claims priority on International patent Application PCT / IB2023 / 062887 filed December 18, 2023, the disclosure of which is hereby incorporated herein by reference in its entirety for all purposes.

[0004] FIELD OF THE INVENTION

[0005] The invention relates to devices that allow to manipulate trajectories of ions in gases. More specifically, the invention relates to the use of radiofrequency (RF) and DC electric potentials to manipulate ion trajectories, and to electrode configurations and systems that are required to generate such electric potentials. Even more specifically, the invention relates to systems and methods used for transport of ions through gases and to separate ions by their mobility and mass-to-charge ratio.

[0006] BACKGROUND

[0007] The field of mass spectrometry (MS) is ever-evolving with new challenges and today various separation techniques are applied in conjunction with MS analysis to accommodate sample complexity in scientific, medical, and industrial applications. The challenge lies in the necessity to separate the typically dilute analytes of interest from other species or impurities present in a sample, which may impede their efficient transfer to and / or detection by the MS.

[0008] In many applications where molecules are to be identified or quantified, the separation dimension can be used as a molecule-specific identifier, from which structural information about the molecules of interest is sometimes inferred. This is especially important in applications where one needs to discern multiple isomers of a molecule, which cannot be distinguished using MS alone.

[0009] One of these separation techniques is ion mobility spectrometry (IMS), which can separate molecular ions based on their size and shape. In IMS, ions are brought into an environment of inert buffer gas while an electric field exerts a force on them toward a defined direction. Travelling through the buffer gas under the influence of this electric field, ions undergo collisions with the gas molecules with a frequency that is directly linked to their molecular size or, more precisely, their collision-cross section, and therefore exhibit a specific drift velocity or so-called mobility. Ions of different mobilities will be separated after some time of exposure to the driving force of the electric field and the collisional drag imposed by the buffer gas.

[0010] A range of IMS technologies exist, and they vary in their approach to ion confinement, creation of electric fields, and handling dynamics and composition of the buffer gas. In the simplest and earliest implementation using a linear drift tube (DT) [1 , 2], pulses of ions traverse a drift cell filled with a stationary buffer gas, under the influence of an electrostatic field. While this technique allows to deduce information about the ion's collision-cross section from first principles, it is generally limited in mobility resolution, i.e. its ability to separate ions of very similar mobilities, while keeping a small footprint of the instrument.

[0011] Higher resolution per instrument size can typically be achieved on instrumentation using dynamically changing electric fields. In travelling wave (TW) ion mobility [3, 4], a local maximum of the electric potential applied to a number of electrodes that define the electric field is moving along the propagation direction of the ions. This travelling potential wave repeats periodically and ions either 'surf' the potential wave if their mobility allows them to move with the speed of the potential wave at a given maximum amplitude, or they periodically 'roll over' a travelling potential with a frequency that is governed by the mobility of a given ion. The roll-over frequency of an ion then results in a net propagation velocity, which is mobility dependent and will therefore eventually lead to the separation of ions with different mobilities. In yet other approaches, either static or dynamic electric fields are applied to drive ions through a region where a gas flow exerts a mobility-dependent drag force onto the ions thereby leading to spatial or temporal mobility separation. Such principles are used in trapped ion mobility spectrometers (TIMS) [5, 6, 7] or differential mobility spectrometers (DMS) [8, 9].

[0012] Regardless of the specific implementation of ion transport, ions need to be confined to the volume where the electric fields are defined, and a number of different approaches exist.

[0013] In TW, TIMS, and some DT analyzers, radiofrequency (RF) alternating electric potentials are applied to electrodes to create ion-confining electric fields

[0010] . While many different electrode geometries have been applied, they all operate under the principle that a first electrode carries an RF potential with a defined frequency and amplitude, and the RF potential applied to a second, neighboring electrode is shifted in phase by 180° with respect to the first one. Few examples for frequently used electrode arrangements for ion confinement are multipoles, where two sets of electrodes carry the two phase- shifted RF potentials, respectively; ring electrodes, consisting of consecutive cylindrical rings, where the RF potential applied to each ring is shifted in phase by 180° with respect to the next one; electrodes that can extend in a straight or curved path to all directions on a surface, whereas each electrode has a neighboring, parallel or 'offset' electrode, which receives the RF potential that is shifted in phase by 180° with respect to the one applied to the first electrode.

[0014] Using either option for ion confinement, the electric potentials that are intended to move ions through a defined volume need to be either superimposed to the RF potentials or applied to a second type of electrode that are interspersed between the RF electrodes, to create a superposition of electric fields that both confine ions and propel them through the buffer gas.

[0015] Electrodes on surfaces have been used to create ion-confining electric fields independently of their later use in ion-mobility devices. An array of radiofrequency electrodes on two opposing surfaces with encompassing DC-only electrodes on each surface can define an electric field to trap ions between the surfaces. Such an electrode configuration has been used to trap ions for further interrogation by laser light

[0011] , and been further developed into a cryogenically cooled ion trap for spectroscopic analysis of molecular ions inside mass spectrometers

[0012] . Similar radiofrequency electrode arrays on single surfaces are sometimes used to collect and guide ions toward small orifices. In this context such assemblies are referred to as ion- or RF-carpets

[0013] . Finally, arrays of radiofrequency electrodes on surfaces, configured to receive two radiofrequency potentials which are 180° shifted in phase to one another, interspersed with electrodes configured to receive DC or TW electric potentials, can be used to guide ions along extended pathlength and perform ion-mobility separation on them, using so-called structures for lossless ion manipulation (SLIM)

[0014] .

[0016] While technologies and systems for ion transport and ion mobility separation have significantly improved over the past 10 years, there is still a strong need for substantially improved and / or alternative methods, systems, and devices, for example to rapidly filter ions over a specific mobility band, or to guide ions effectively around corners on a surface-electrode based ion transport device.

[0017] SUMMARY

[0018] It is therefore one aspect of the present disclosure to provide an ion manipulation device. The Ion manipulation device for driving ions in a propulsion direction may comprise at least one electrode support for supporting one or more electrodes; at least one first set of radiofrequency electrodes comprising a number n of electrodes, wherein the at least one first set of radiofrequency electrodes comprises at least three electrodes; and at least one radiofrequency voltage generator operatively connected to the at least one first set of radiofrequency electrodes. The at least one radiofrequency voltage generator is configured to generate a plurality of phase-shifted radiofrequency voltages, each consecutive phase- shifted radiofrequency voltage of the generated plurality of phase-shifted radiofrequency voltages being phase-shifted by a value of about 2jt / n or by a value of 2jt / n to both (i) confine ions in a first (Y) and / or second direction (Z) and (ii) to propel ions in the propulsion direction (X) orthogonal or non-parallel to the first (Y) and / or second direction (Z). The electrodes of the at least one first set of radiofrequency electrodes are operatively connected to the at least one radiofrequency voltage generator to simultaneously receive the plurality of phase-shifted radiofrequency voltages.

[0019] It is another aspect of the present disclosure to provide an ion mobility spectrometry (IMS) system according to claim 34, a mass spectrometer instrument or Field-ion mobility device according to claim 35, an ion manipulation system according to claim 36 and an ion manipulation system according to claim 38. It is yet another aspect of the present disclosure to provide an ion manipulation method according to claim 48, and an ion manipulation method according to claim 76.

[0020] Specific embodiments and other advantageous features can be found in the dependent claims. The above and other objects, features and advantages of the present invention and the manner of realizing them will become more apparent, and the invention itself will best be understood from a study of the following description with reference to the attached drawings showing some preferred embodiments of the invention.

[0021] BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and together with the general description given above and the detailed description given below, serve to explain features of the invention.

[0023] Figure 1A schematically shows an example of a ring-electrode guide of an exemplary ion manipulation or transportation device of the present disclosure, the ring-electrode guide comprising or consisting of a stack of annular electrodes.

[0024] Figures 1 B and 1C schematically show exemplary electrode devices comprising a support or holder of the ring-electrode guide and the ring electrodes thereof.

[0025] Figure 1 D schematically shows an exemplary embodiment of an ion manipulation device of the present disclosure including the embodiment in which the RF electrodes are the ring electrodes of Figure 1A.

[0026] Figure 2 shows Electric potentials for n = 3, resulting to a phase shift of 2TT / 3, or 120°, where n is the number of phase-shifted RF potentials chosen for the specific exemplary implementation of the phase-assisted ion transportation or transmission device, and that is applied in the present example to a set of three RF electrodes.

[0027] Figure 3A is a schematic top-view showing an exemplary arrangement of electrodes for an exemplary ion manipulation or transportation device comprising two interleaved electrode arrays as included or defined on a surface for ion trajectory simulations. The array of n = 3 RF electrodes (numbered 1 to 3) for phase assisted transmission repeats into the X-direction of the surface, and an exemplary array of eight electrodes (A through H) used exclusively for ion propulsion (not for confinement) repeats into the Y-direction. Eight electrodes are provided as an exemplary embodiment, and a different of electrodes may be used. For example, more than three electrodes can work similarly well.

[0028] Figure 3B is a schematic side-view, in the direction of the arrow 3B of Figure 3A, schematically showing an exemplary arrangement first and second components of an exemplary ion manipulation or transportation device, the first and second components being located opposite one another and whose surface includes the electrode arrangement of Figure 3A, Figure 3A showing the electrode arrangement on the surface of the lower component.

[0029] Figure 3C is a schematic side-view, similar to that of Figure 3B, schematically showing another exemplary arrangement electrodes wherein the electrodes include spaced curved electrodes segments that are located to form one or more annular electrodes structure of the ion manipulation or transportation device.

[0030] Figure 3D schematically shows an exemplary serpentine ion path device comprising or formed by a plurality of corner elements for ion confinement and transmission using phase-assisted transmission permitting separation of ions based on ion mobility.

[0031] Figure 4(A) to 4(D) shows the results of SIMION trajectory simulations for ions with a m / z ratio of (A) 250, (B) 500, (C) 1000, and (D) 1500. The electrode array shown in the background is for indicative purpose only and not drawn to scale.

[0032] Figure 5 schematically shows an exemplary corner element of an ion path for phase-assisted ion transmission with superimposed travelling wave potentials. The RF electrodes for this exemplary system with n = 3 are labeled i = 1 , 2, and 3. Individual electrodes of the repeating travelling-wave electrode array are labelled A through H.

[0033] Figure 6(A) to 6(D) show the results of ion trajectory simulations inside the ion path defined in Figure 5, using phase-assisted transmission with a phase-shift of 120° (n = 3) for ions with a m / z ratio of 250 (A) and a m / z ratio of 1000 (C), respectively. Comparative ion trajectories are also shown for the same electrode geometries using a phase shift of 180° between neighboring electrodes for ions with a m / z ratio of 250 (B) and a m / z ratio of 1000 (D).

[0034] Figure 7 shows arrival time distributions of GRGDS and SDGRG ions in [M+H]+charge state after up to five separation cycles on a serpentine ion mobility device under phase-assisted transmission conditions.

[0035] Figure 8 shows comparative ion mobility resolving power of the test device using the method of phase- assisted transmission (three phase) of the present disclosure as well as traditional two-phase operation. The resolving power was determined by examining peak position and width of drift peaks of GRGDS and SDGRG 1+ ions in collision-cross section space, after up to 1 1 separation cycles.

[0036] Figure 9 shows radiofrequency potentials, provided by an RF generator, with a constant phase shift of 2TT / 3 and a frequency of 893 kHz, generated using three resonant radiofrequency circuits that are externally excited using three periodic square-wave signals of the same frequency and phase shift (only one is shown here). For simplicity, only one of the two phases Ai generated by each RF generator is shown.

[0037] Figure 10 shows an exemplary embodiment in which an electrode arrangement showing a portion of the electrode arrangement in which interleaved / deviation electrodes are (partially) encompassed or enclosed by an RF electrode, and in which the RF electrode is (partially) encompassed or enclosed by interleaved / deviation electrodes.

[0038] Figure 11 shows an exemplary apparatus or system in which the ion manipulation device and / or the ion manipulation system of the present enclosure may operate to carry out phase-assisted transmission to achieve ion separation according to the present disclosure.

[0039] Figure 12 schematically shows an embodiment of an exemplary ion manipulation device schematically showing an RF voltage generator coupled to RF electrodes and an interleaved electrode voltage generator coupled to interleaved electrodes, although not shown, the interleaved electrode voltage generator is also coupled or electrically connected to the other interleaved electrodes of the ion manipulation device.

[0040] Herein, identical reference numerals are used, where possible, to designate identical elements that are common to the Figures. Also, the images are simplified for illustration purposes and may not be depicted to scale.

[0041] DETAILED DESCRIPTION OF SEVERAL EMBODIMENTS

[0042] In order to overcome the above-mentioned drawbacks in the art, the present invention discloses herein a device, system and methods for ion transport in gases, as well as methods to generate the phase-shifted radiofrequency (RF) voltages to operate the device. The invention was first implemented in-silico and then verified experimentally, where the method of generating phase-shifted RF voltages was verified as well.

[0043] Figure 1 D schematically shows an exemplary device 1 or exemplary ion manipulation device 1 , or ion transportation or transmission device 1 of the present disclosure. Figures 1A to 1C, 3A to 3C and 5 schematically show embodiments of exemplary elements of the ion manipulation device 1 .

[0044] The ion manipulation device 1 is for driving, pushing or forcing ions into, and / or in, a first direction or an ion transport or ion propulsion / propelling direction. The ion manipulation device 1 is configured to drive, push or force ions into, and / or in, the first direction that is the ion transport or ion propulsion / propelling direction, for example the direction X shown in the exemplary illustrations of the Figures.

[0045] The ion propulsion / propelling direction is, for example, a direction in which ions (or a portion of the ions) are moved or displaced along a principal ion pathway through the device 1 or through a component of the device 1. Ions (or a portion thereof) may, for example, be repeatedly displaced or propelled (a plurality of times) along the principal ion pathway when displaced cyclically through the device 1 or a component of the device 1.

[0046] The ion manipulation device 1 includes, for example, at least one or a plurality of electrode supports 3 for supporting at least one or a plurality of electrodes EL, ELIN. The electrode support 3 may include or define the plurality of electrodes. The electrode support 3 comprises, for example, a structure or body configured to mechanically hold or support the electrodes. The electrode support 3 and the electrodes supported by the electrode support 3 form an electrode device 5 (see, for example, Figure 1 D) comprising the at least one electrode support 3 and the electrodes.

[0047] The ion manipulation device 1 includes, for example, at least one electrode device 5 or a plurality of electrode devices 5. Each electrode device 5 may form, for example, an ion guiding device 7 of the ion manipulation device 1 (see, for example, Figures 1 B to 1 D, 3B to 3C).

[0048] The plurality of electrode devices 5 and / or ion guiding devices 7 may, for example, be serially arranged as track elements in series to define, for example, an elongated ion track, or a cyclic ion track / circuit.

[0049] The ion manipulation device 1 may, for example, include at least one ion manipulation device element / component support (not shown) configured to support and hold elements and / or components of the ion manipulation device 1 is specific and / or relative positions in the ion manipulation device 1. For example, the ion manipulation device element / component support is configured to hold the plurality of electrode devices 5 and / or ion guiding devices 7 in relative positions to define the elongated ion track, or a cyclic ion track / circuit. Alternatively or additionally, the ion manipulation device element / component support is configured to hold the plurality of corner elements CNR (see, for example, Figure 3D) and associated devices in relative positions to define the ion track, or a cyclic ion track / circuit formed thereby.

[0050] An electrode device 5 may form, for example, a component or an ion guiding component of the ion guiding device 7. As shown exemplarily in Figure 3B, the ion guiding device 7 includes a first electrode device 5A (or a first ion guiding component) and a second electrode device 5B (or a second ion guiding component). The ion guiding device 7 may thus include, for example, a plurality of ion guiding components. The ion guiding components are arranged, with their outer electrode surfaces facing inwards from the perspective of the ion guiding device 7, to define an ion transport channel TC located between the ion guiding components and / or the electrode devices 5. The ions are displaced in the ion propulsion / propelling direction in the transport channel TC, which for example contains a buffer gas (for example, nitrogen or helium) when the ion manipulation device 1 is in use.

[0051] The Ion manipulation device 1 includes, for example, at least one enclosed gas cell 31 in which the ion guiding device 7 and / or the electrode device 5 is placed or contained in, and in which the ions are displaced by the applied electric fields. The enclosed gas cell may have, for example, a pressure between O.l mBar and 1000 mBar.

[0052] As shown exemplarily in Figure 3B, the first electrode device 5A is arranged with its electrodes facing or located opposite the second electrode device 5B, the electrodes facing inwardly and defining the ion transport channel TC located between the electrode devices 5A, 5B. It is to be noted that the ion guiding components of the ion guiding device 7 are not necessarily identical, or not each the same electrode device 5. The ion guiding device 7 may, for example, include one or at least one electrode device 5, 5A and an electrode component device comprising an electrode arrangement configured to repel or direct ions in a direction towards the electrode device 5, 5A, to locate ions in the transport channel TC for propulsion in the ion manipulation device 1 by the electrode device 5.

[0053] As mentioned, the electrode support 3 may include or define the plurality of electrodes. The electrode support 3 may include at least one surface SF that includes the electrodes or to which the electrodes are fixed, or that defines the electrode outer surface.

[0054] The support 3 comprises or consists of, for example, a material configured to hold and / or receive electrically conductive material (for example, a material comprising or consisting of at least one metal, for example copper or aluminium) that forms the electrodes, and / or that forms electrical circuits and / or connections that are in electrical connection with the electrodes permitting to apply operating voltage signals or potentials to the electrodes from voltage generators and / or voltage sources.

[0055] The support 3 may comprise or consist of an insulating material such a ceramic material, a polymer, a glass, or a semiconductor material.

[0056] The support 3 may comprise or consist of a printed circuit board (PCB). The printed circuit board may, for example, comprise or consist of fibers such as glass fibers, and resins or epoxies.

[0057] The support 3 includes or defines the at least one surface SF upon which the electrodes are provided and / or fixed. The surface SF may, for example, extend to define a length L where, for example, 0.25m>L>10cm, or 1 m>L>10cm, and / or define a width W where, for example, 0.5m>W>1cm.

[0058] The support 3 may, for example, include or define a (substantially) planar surface or planar inner surface SF, as for example shown in Figure 3B. The support 3 may also, for example, be or define a planar support or an elongated planar support. The electrodes may, for example, also extend to include or define a (substantially) planar outer electrode surface ESF, as for example also shown in Figure 3B. Alternatively, the electrodes may, for example, extend to include or define a curved outer electrode surface ESF.

[0059] In an embodiment, an ion guiding device 7 of the ion manipulation device 1 may, for example, be formed by or comprise two electrode device 5A, 5B arranged opposite each other and / or arranged with (at least some of) their electrodes facing one another as shown, for example, in Figure 3B. A first support 3A is included in a first ion guiding device component that is the first electrode device 5A, and a second support 3B is included in a second ion guiding device component that is the second electrode device 5B.

[0060] The electrodes of the first support 3A are located opposite or directly opposite or facing or directly facing the electrodes of the second support 3A. The ion manipulation device element / component support of the ion manipulation device 1 is, for example, configured to support and hold the first and second ion guiding device components or the devices 5A, 5B at a separation distance SD to define the ion transport channel TC between the ion guiding device components. The principal ion pathway extends, for example, through the defined ion transport channel TC. The supports 3A, 3B of the ion guiding device components or devices 5A, 5B include, for example, the electrical circuits and / or connections in electrical connection with the electrodes. The electrical circuits and / or connections, when connected to the voltage generators and / or voltage sources permit the application of operating voltage signals or potentials to displace the ions, for example, in the ion transport channel TC.

[0061] In an embodiment, the support (or supports) 3 may, for example, include or define at least one curved surface or curved inner surface SF, as for example shown in Figure 3C. The support 3 may, for example, be or define a hollow support or an elongated hollow support, as for example, shown in Figure 1 B and 3C. The support 3 may, for example, be or define a concave or curved-cavity support, as for example, shown in Figure 1 C. The electrodes are curved electrodes or define a curved outer electrode surface ESF, or extend to include or define a (substantially) curved outer electrode surface ESF, as for example also shown in Figures 1C and 3C.

[0062] The curved electrodes may include a plurality of full annular or ring electrodes, as shown in Figure 1A to 1 D. Alternatively or additionally, an annular electrode may be formed by a plurality of fragmented curved electrodes FG, or include spaced-apart curved electrode segments FG, as shown in Figure 3C that are located to form a segmented or fragmented annular electrode structure of the ion manipulation or transportation device 1. The support 3 may include a plurality of such fragmented annular electrodes FG. The number of electrode fragments FG may, for example, be between 2 and 16, Figure 3 showing an annular electrode consisting of four curved electrode segments FG.

[0063] The ion manipulation device 1 and / or the at least one electrode device 5 includes at least one set or a plurality of sets S1 , S2, S3, S4, S5 of radiofrequency (RF) electrodes EL (see, for example, Figures 1 A, 1 D and 3A). Five sets S1 , S2, S3, S4, S5 are shown for explanatory purposes, and it is noted that device 1 can include fewer or more sets of electrodes EL.

[0064] In an embodiment, first and / or second sets, or the plurality of sets S1 , S2, S3, S4, S5 of RF electrodes may form a ring-electrode assembly comprising at least three coaxially stacked annular or ring electrodes, as shown in the exemplary embodiment of Figure 1 D. The annular or ring electrodes may, for example, be concentric and / or may have different diameters.

[0065] The ion manipulation device 1 (and / or the electrode device 5) includes at least one first set of RF electrodes EL comprising a number n of electrodes EL. The first set (or each set) comprises at least three electrodes EL (n >3) that are located along the propulsion direction of the ions, for example, the X-direction, as shown in Figures 1A and 1 D. The exemplary embodiment of Figures 1 D and 3A show a set including three RF electrodes EL1 , EL2, EL3.

[0066] In an exemplary embodiment, as shown for example in Figures 1 D and 3A, the electrodes EL1 , EL2, EL3 or each electrode EL1 , EL2, EL3 of the set are, for example, sequentially located on the electrode support 3 in a direction extending parallel to the propulsion direction X. The sets S1 , S2, S3, S4, S5 of electrodes EL are, for example, also sequentially located in a direction extending parallel to the propulsion direction X.

[0067] The ion manipulation device 1 may also include at least one or a plurality of radiofrequency voltage generators 9 operatively connected to the first set of RF electrodes EL, and / or to the plurality of sets of RF electrodes EL.

[0068] The RF voltage generator 9 is configured to generate a plurality of phase-shifted RF voltages, such as phase-shifted RF voltages PH1 , PH2, PH3 (see, for example, Figure 2). Each consecutive phase-shifted RF voltage of the generated plurality of phase-shifted RF voltages is phase-shifted by a value of 2jt / n, or a value of about / approximately 2jt / n, where n is the number of RF electrodes EL in a set, as mentioned previously.

[0069] The value of about / approximately 2jt / n is a value within ± 5% of 2jt / n, or ± 10% of 2jt / n or ± 15% of 2jt / n or ± 20% of 2jt / n.

[0070] The RF voltage generator 9 is configured to generate and / or apply a time dependent phase-shifted radiofrequency electric potential to the RF electrodes EL. The time dependent phase-shifted RF electric potential can be, for example, defined by an alternating current (AC) waveform. The AC waveform may, for example, be in the form of a sine wave, a cosine wave, or a combination of multiple sine and / or cosine waves. The AC waveform may, for example, be in the form of a sawtooth waveform, or a square wave.

[0071] In an exemplary embodiment, the RF voltage generator 9 is configured to generate and / or apply a time dependent radiofrequency electric potential to the RF electrodes i, with the electric potential being defined by: where U is a DC bias voltage of the RF potentials, V is an amplitude, to = 2nf is the angular frequency with a frequency or RF frequency f, n is the number of electrodes EL of the set (or sets) to which a phase- shifted RF potential is applied, n > 3, and i is a positive integer number enumerating consecutive electrodes with i = (1 ... n).

[0072] While the waveform is defined by a sine function in the above equation, the sine function can be replaced by any one of the previously mentioned functions, such as a cosine wave, or a combination of multiple sine and / or cosine waves, or replaced by a sawtooth waveform, or a square waveform.

[0073] The generated phase-shifted RF voltages may respectively have a positively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes EL and to displace ions in a first propulsion direction, for example the positive X-direction X+. The generated plurality of phase-shifted RF voltages may respectively have a negatively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes EL and to displace ions in a second propulsion direction, for example the negative X-direction X-, opposite to the first propulsion direction X+.

[0074] The generated phase-shifted RF voltages applied to the RF electrodes RF preferably have for example, substantially or approximately, the same frequency and / or amplitude.

[0075] A frequency of the phase-shifted radiofrequency voltages can be, for example, between (i) 400kHz or 500kHz and (ii) 2MHz or 3MHz or 4MHz or 5MHz (the extremity values included for example). An amplitude of the phase-shifted radiofrequency voltages may, for example, be between (i) 100V and (ii) 500V (the extremity values included for example).

[0076] The generated plurality of phase-shifted RF voltages is respectively applied to all electrodes of the one set, or all electrodes of each set (see, for example, Figure 1 D) to both (i) confine (or repel) ions in a first direction (for example the Y direction) and / or confine (or repel) ions in a second direction (for example the Z direction) and (ii) to propel ions in the propulsion direction (for example the X direction), where the propulsion direction is orthogonal or non-parallel to the first (Y-direction) and / or the second direction (Z-direction).

[0077] The electrodes EL of the at least one set (or of the plurality of sets, or of each set of RF electrodes EL) are operatively connected to the RF voltage generator 9 to simultaneously receive the plurality of phase-shifted RF voltages PH1 , PH2, PH3. That is, the generated plurality of phase-shifted RF voltages PH1 , PH2, PH3 are respectively applied to the electrodes EL1 , EL2, EL3 of the at least one set of RF electrodes EL. In the case of a plurality of sets, for example sets S1 to S5, the generated plurality of phase-shifted RF voltages PH1 , PH2, PH3 are respectively applied to the electrodes EL1 , EL2, EL3 of the set S1 , and to the electrodes EL1 , EL2, EL3 of the second set S2, and to the electrodes EL1 , EL2, EL3 of the third set S3, of the fourth set S4 and of the fifth set S5.

[0078] The RF voltage generator 9 is configured to simultaneously apply the generated phase-shifted RF voltages to each electrode of each set of the RF electrodes, with each RF electrode simultaneously receiving a RF voltage that is phase-shifted by a value of 2jt / n (or by a value of about / approximately 2jt / n) with respect to its neighboring RF electrode, or with respect to each of its neighboring RF electrodes.

[0079] In the exemplary embodiment where n=3 and a set includes three RF electrodes EI1 , EL2, EL3; RF electrode EL2 receives a RF voltage that is phase-shifted by a value of 120° (or about 120°) with respect to its neighboring RF electrode EL1 (and vice-versa), and RF electrode EL3 receives a RF voltage that is phase-shifted by a value of 120° (or about 120°) or with respect to its neighboring RF electrode EL3 (and vice-versa). The RF electrodes EL of the set receive or have, for example, such phase-shifted RF voltages applied simultaneously to the electrodes of the set. For a plurality of sets S1 , S2, S3, S4, S5, the RF electrodes EL of the sets (or of each set) receive or have, for example, such phase-shifted RF voltages applied simultaneously to the electrodes inside the sets, or applied simultaneously to the electrodes inside each set and simultaneously to each set S1 , S2, S3, S4, S5.

[0080] In exemplary embodiments where the RF electrodes EL comprises an annular or ring electrode, for example, fully annular as shown in Figures 1A and 1 D, or annular comprising a plurality of fragmented curved electrodes FG as shown in Figure 3C, this permits to both (i) confine (or repel) ions in the first direction (the Y direction) and the second direction (the Z direction) as well as (ii) to propel ions in the propulsion direction (the X direction), where the propulsion direction is orthogonal or non-parallel to the first (Y-direction) and the second directions (Z-direction). This permits ions to be propelled in the propulsion direction and through the transmission channel TC of the electrode device 5.

[0081] The propulsed or transmitted ions, displaced in the propulsion direction by the RF electrodes EL, can then be acted upon by deviation or separation means such as deviation or separation electrodes ELIN to filter or separate ions based on, for example, a m / z ratio of the ions. Exemplary deviation or separation electrodes ELIN are shown for example in Figure 3A.

[0082] The device 1 can employ the phase-assisted transmission and comprise or form an m / z ratio and / or ion mobility filter device, or an ion dispersion device. Such a device can, for example, be realized using the arrangement of electrodes where ions are being propelled through a buffer gas in the device with, for example, two (approximately) orthogonal velocity components. At least one of the orthogonal velocity components is m / z dependent and / or ion mobility dependent to permit a separation of ions. Such a device can be implemented using an arrangement of electrodes including the RF electrodes EL and deviation or separation electrodes ELIN.

[0083] Deviation or separation electrodes ELIN are not shown in Figure 1 D to avoid encumbering the schematic illustration, the deviation or separation electrodes ELIN may for example be located relative to the annular RF electrodes EL in the same manner as that of Figure 3A. Deviation or separation electrodes ELIN may include a curved outer surface facing inwards towards an annular center of an annular arrangement formed or defined by one or more sets SI and / or arrays AR of deviation or separation electrodes ELIN forming segments or fragments of the annular arrangement. An annular arrangement is, for example, located between or adjacent the annular RF electrodes EL of Figure 1 D. The deviation or separation electrodes ELIN of the annular arrangement may be positioned or laid out relative to the annular RF electrodes EL in the manners described below concerning the RF electrodes EL and the deviation or separation electrodes.

[0084] The or each electrode EL of the set (or sets) of RF electrodes EL may extend, at least partially or fully, in a direction (substantially or approximately) orthogonal to the propulsion direction X in which ions are driven (see, for example, Figures 1 D and 3A). The or each electrode EL of the set (or sets) of RF electrodes EL may, for example, be or comprise an elongated electrode whose elongated direction of extension extends in a direction (substantially or approximately) orthogonal to the propulsion direction X in which ions are driven (see, for example, Figures 1 D and 3A).

[0085] In an embodiment, the RF electrode EL may, for example, have or define a (substantially) rectangular shape as shown, for example, in Figure 3A, however, other shapes are possible, as detailed further below.

[0086] As mentioned, the Ion manipulation device 1 may include a plurality of sets of RF electrodes EL, for example, the first set S1 and at least one second set S2. Similarly, the second set S2 includes the number n of RF electrodes EL operatively connected to the RF voltage generator 9 to also simultaneously receive the plurality of phase-shifted RF voltages. The RF electrodes EL of the first and second sets are operatively connected to the RF voltage generator 9 to simultaneously both receive the plurality of phase-shifted RF voltages. The RF voltage generator 9 is configured to simultaneously apply the phase-shifted RF voltages PH1 , PH2, PH3 to each RF electrode EL1 , EL2, EL3 of the second set, and / or the first and second sets (or all sets). Each electrode EL1 , EL2, EL3 of the sets simultaneously receives a RF voltage that is phase- shifted by a value of 2jt / n (or about 2jt / n) with respect to its neighboring electrode, or with respect to each of its neighboring electrodes.

[0087] The Ion manipulation device 1 and the RF voltage generator 9 are configured to simultaneously apply RF voltages of the same phase to a first electrode EL1 of the first set and to a first electrode EL1 of the second set, or to a first electrode EL1 of each set. The Ion manipulation device 1 and the RF voltage generator 9 are configured to simultaneously apply RF voltages having the same phase shift relative to the first electrodes EL1 to a second electrode EL2 of the first and second sets, or to the first and second electrodes of each set. The Ion manipulation device 1 and / or the RF voltage generator 9 are configured to simultaneously apply RF voltages having the same phase shift relative to the second electrodes EL2 to a third electrode EL3 of the first set and the second set, or to a third electrode EL3 of each set. The first EL1 , second EL2 and third EL3 electrodes are consecutive electrodes.

[0088] As mentioned, the ion manipulation device 1 may include deviation or separation means configured to displace the ions driven in the propulsion direction or to displace at least a portion of the ions driven in the propulsion direction into one or more deviation directions or separation directions based on, for example, ion mobility. The deviation direction or separation direction are directions that are different or non-parallel to the ion propulsion direction in which the RF electrodes propulse or force the ions. The deviation direction or separation direction is, for example, in the Y-direction in the exemplary embodiments of Figures 1A to 1 D and Figure 3A.

[0089] The deviation direction or separation direction is determined by the arrangement of the deviation or separation means employed and is a direction that permits separation or deviation of a portion of the propelled ions, propelled by the RF electrodes and sets thereof, into a direction that is different to that of the propulsion direction. The ion manipulation device 1 may include a plurality of different deviation or separation means permitting separation of ions into a plurality of different separation or deviation directions.

[0090] In an embodiment, the deviation or separation means comprises deviation / separation electrodes ELIN or interleaved electrodes ELIN. The deviation / separation electrodes ELIN or interleaved electrodes ELIN are arranged or configured to receive or have applied thereto one or more interleaved or deviation electrode voltages to displace ions into the deviation or separation direction. This allows ions of different mobilities to be deviated or separated out ions driven in the propulsion direction by the RF electrodes. The deviation / separation electrodes ELIN or interleaved electrodes ELIN are arranged on the support 3 and located on the support 3 with respect to the RF electrodes to displace ions into the deviation or separation direction when a deviation voltage is applied to the deviation / separation electrodes ELIN or interleaved electrodes ELIN.

[0091] A deviation / separation electrode ELIN may, for example, extend to define a length LIN where, for example, 0.1 mm> LIN >10mm, define a width WIN where, for example, 0.1 mm> WIN >5mm. An RF electrode EL may, for example, extend to define a length LEL where, for example, 0.1 mm> LEL >100mm, define a width WEL where, for example, 0.1 mm> WEL >2mm.

[0092] The electrode device 5 or the ion guiding device 7 (or a surface SF thereof) comprises at least one or a plurality of deviation or interleaved electrodes ELIN, or at least one or a plurality of arrays AR of deviation or interleaved electrodes ELIN (see, for example, Figure 3A).

[0093] For example, at least one or a plurality of interleaved / deviation electrodes ELIN can be, for example, located between RF electrodes of a set of RF electrodes, or between RF electrodes of a first and second set. A plurality of interleaved electrodes ELIN can be, for example, additionally or alternatively located adjacent to one RF electrode or adjacent to a plurality of RF electrodes of a set of RF electrodes, or adjacent to RF electrode(s) of a first and second set.

[0094] An interleaved / deviation electrode (or electrodes) ELIN may alternatively or additionally, for example, be within or around or be enclosed or encompassed by one or more RF electrodes EL of one or more sets (see, for example, Figure 10). The interleaved / deviation electrode ELIN may be located within the RF electrode or electrodes EL, or the RF electrode or electrodes EL may be located around the interleaved / deviation electrode or electrodes ELIN. Alternatively, or additionally, one or more RF electrodes EL may for example be enclosed or encompassed by one or more interleaved / deviation electrodes ELIN. The RF electrodes EL may be located within the interleaved / deviation electrode or electrodes ELIN, or the interleaved / deviation electrode (or electrodes) ELIN may be located around the RF electrode or electrodes EL.

[0095] In an embodiment, the deviation or interleaved electrode ELIN may, for example, be elongated, or may have or define a (substantially) rectangular shape as shown, for example, in Figure 3A, however, other shapes are possible, as detailed further below and it is not necessary that the electrodes have a rectangular shape. The deviation or interleaved electrode ELIN has or defines a shape that extends into a direction (substantially) orthogonal to the propulsion direction of the ions by the RF electrodes E. The deviation or interleaved electrode ELIN may extend in a linear and / or curved manner in this direction.

[0096] In the exemplary embodiments of Figures 1 D and 3A, the interleaved electrodes ELIN extend in the same elongated direction of extension as that of the RF electrodes RF. The electrodes have exemplary rectangular shape, it being nevertheless noted that the RF electrodes and the interleaved electrodes ELIN may have different shapes.

[0097] The deviation or interleaved electrodes ELIN are coupled or attached to, or are included on a surface SF of the electrode support 3, for example, in the same manner previously described in relation to the RF electrodes EL.

[0098] The deviation or interleaved electrodes ELIN are arranged or configured to receive or have applied thereto one or more deviation or interleaved electrode voltages to displace or repel ions into the deviation or separation direction based on, for example, ion mobility. The Ion manipulation device 1 includes at least one or a plurality of deviation or interleaved electrode voltage generators 15 configured to generate the electrode voltages applied to the deviation or interleaved electrodes ELIN to displace or propel ions into the deviation direction or separation direction. Figure 12 schematically shows, along with an RF voltage generator 9 coupled to RF electrodes, an electrode voltage generator 15 coupled to deviation or interleaved electrodes ELIN. Although not shown, the interleaved electrode voltage generator 15 is coupled or electrically connected to the other deviation or interleaved electrodes ELIN of the ion manipulation device 1 to provide interleaved or deviation voltages thereto.

[0099] In an embodiment, the deviation or interleaved electrode voltage generator(s) 15 is configured to generate or provide interleaved or deviation electrode voltages as electrostatic potentials or voltages which are configured to generate electric fields to displace or propel ions into the deviation direction or the separation direction different to that of the ion propulsion direction imposed on the ions by the voltage signals applied to the RF electrodes EL.

[0100] The amplitude and polarity of the electrostatic potential or voltage that is applied may, for example, be set so as to drive or direct the ions in the deviation direction or the separation direction. The electrostatic potential or voltage may be applied to the electrode or electrodes ELIN. Alternatively, an electrostatic potential or voltage may, for example, be applied so as to generate a potential or voltage difference between at least two electrodes ELIN to generate an electric field in the deviation or separation direction.

[0101] In an embodiment, the deviation or interleaved electrode voltage generator 15 is configured to generate or provide a travelling electric potential wave or a travelling wave electric potential TW configured to generate electric fields to displace or propel ions into the deviation direction or the separation direction. The travelling wave electric potential TW is described herein further below and also described in US patent US10804089 (reference 14), the disclosure of which is hereby incorporated herein by reference in its entirety for all purposes.

[0102] The electrode device 5 or the ion guiding device 7 includes at least one or a plurality of deviation / interleaved electrode sets SI1 ,SI2,SI3 where a deviation / interleaved electrode set SI or each deviation / interleaved electrode set SI includes at least one or a plurality of deviation or interleaved electrodes ELIN.

[0103] The or each set S11 ,SI2,SI3 of deviation or interleaved electrodes ELIN comprises for example segmented electrodes A, B, C, D, F, G, H to which deviation or interleaved electrode voltages are applied to displace or propel ions into the deviation direction or the separation direction.

[0104] The deviation / interleaved electrode sets SI1.SI2, SI3 and / or the deviation or interleaved electrodes ELIN of the set extend, for example, in the deviation direction or the separation direction or in a direction non-parallel or different to that of the propulsion direction imposed on the ions by the RF electrodes EL.

[0105] The deviation / interleaved electrode sets SI1.SI2, SI3 and / or the deviation or interleaved electrodes ELIN of the set may extend, for example, in an elongated direction that is the same as an elongated direction of extension of the RF electrodes EL (see, for example, Figure 3A).

[0106] The deviation / interleaved electrodes ELIN may, for example, be arranged or located relative to the RF electrodes in the same manner previously described herein. The deviation / interleaved electrode set or sets SI may, for example, also be arranged or located relative to the RF electrodes in this same manner. They are, for example located between or adjacent or within or around the RF electrodes EL of the set (S1 , of RF electrodes EL of the electrode device 5 or the ion guiding device 7.

[0107] The array AR of deviation or interleaved electrodes ELIN of the electrode device 5 or the ion guiding device 7 may include at least one or a plurality deviation / interleaved electrode sets S11 ,SI2, SI3. In the exemplary embodiment of Figure 3A, the array AR or each array AR is shown to include three deviation / interleaved electrode sets SI1.SI2, SI3 in the illustrated exemplary embodiment. Three deviation / interleaved electrode sets SI1.SI2, SI3 are shown enclosed by a dashed-line box.

[0108] As mentioned, an electrostatic potential or an electrodynamic electric potential can be applied to these deviation / interleaved electrodes to deviate ions into the deviation direction or the separation direction. In the case of electrodynamic electric potentials, electric potentials are applied to electrodes of the deviation / interleaved electrode set or sets to implement a travelling electric potential that is displaced along the deviation / interleaved electrodes of the deviation / interleaved electrode set or sets. This is, for example, done for and for example repeated for the deviation / interleaved electrode set or sets of each array AR located along the electrode device 5 or the ion guiding device 7 so that the ions driven in the propulsion direction experience the resulting dynamic or displacing electric field as these driven ions are displaced in the propulsion direction by the RF electrodes. For example, the electric potentials that have the form of a travelling potential wave are applied to an exemplary predefined number of electrodes A through H of the deviation / interleaved electrode set or sets, for example, to set SI1. A travelling wave TW electric potential applied to the exemplary number of eight electrodes (electrodes A through H) may, for example, be in the form of a square wave, represented as a bit pattern 11110000, where 1 and 0 represent two different DC levels of the square potential wave, respectively, and the position in the string of eight binary numbers is represented by the electrodes A through H. After a predefined time interval, the applied voltage / potential changes and the bit pattern changes for example to 01 111000, then to 00111100, then to 00011110, then to 0000111 1 , then to 1000011 1 , then to 11000011 , and then to 11 100001 . This is done to each sequential set, for example, SI2 and then SI3 (of an array AR) to displace the travelling wave electric potential from one set to the next set. This can be repeated to continuously propagate the travelling wave across the set or sets. This is for example done for each array AR.

[0109] In an embodiment, the ion manipulation device 1 and / or ion guiding device 7 includes at least first and second electrode devices 5A, 5B (see, for example, Figure 3B). The first electrode device 5A includes the plurality of deviation / interleaved electrodes ELIN, for example, enclosed by, located between and / or adjacent the RF electrodes of the sets of RF electrodes EL1 , EL2, EL3. As mentioned, the deviation / interleaved electrodes ELIN are arranged to receive the interleaved / deviation electrode voltages to displace ions into the at least one deviation direction or separation direction based on, for example, ion mobility. The RF electrodes EL and the interleaved / deviation electrodes ELIN are coupled to the surface SF1 of the electrode support 3A of the electrode device 5A, or the surface SF1 includes the interleaved / deviation electrodes ELIN and the RF electrodes, as previously mentioned.

[0110] The second electrode devices 5B may, for example, be identical in electrode layout or configuration to the first electrode devices 5A on the surface SF’, SF2 of the electrode support 3B of the second electrode devices 5B. The electrode arrangement on the surface SF’, SF2 of the electrode support 3B may, for example, be a mirror image of the electrode arrangement of the surface SF1 of the first electrode device 5A.

[0111] The electrode support 3B of the second electrode devices 5B may, for example, comprise one or more second sets S1 ’, S2’, S3’, S4’, S5’ of RF electrodes EL’ (EL1 ’, EL2’, EL3 ') coupled or attached to the surface SF’, SF2 of the second electrode support 3B, and / or interleaved / deviation electrodes ELIN that are, for example, enclosed by, or located between and / or adjacent the RF electrodes EL’ of the one or more second sets S1 ’, S2’, S3’, S4’, S5’ of RF electrodes EL’.

[0112] The electrode supports 3A, 3B and their surfaces may, for example, include the exemplary electrode arrangement shown in Figure 3A.

[0113] The Ion manipulation device 1 , in addition to including RF voltage generator(s) 9, may also include one or more electrode voltage generators 15 operatively connected to the interleaved / deviation electrodes of each electrode support and configured to generate electrodes voltages or interleaved / deviation electrode voltages to displace or propel ions into the deviation direction or separation direction.

[0114] Alternatively, the electrode support 3B of the second electrode device 5B may comprise at least one or a plurality of electrodes coupled to or included by the surface SF’, SF2 of the electrode support 3B. The electrode or electrodes are configured and / or arranged to receive a potential or voltage to repel ions inwardly or towards the first electrode support 5A, and / or towards the surface SF1 of the first electrode support 3A. The Ion manipulation device 1 includes one or more electrode voltage generators operatively connected to the electrodes of the second electrode support 3B and configured to generate repel electrode voltages or to displace or propel the ions inwardly or towards the first electrode support 5A where the ions are displaced into the deviation direction or separation direction by the interleaved / deviation electrodes of the first electrode support 5A.

[0115] As previously mentioned, in relation to Figure 3B, the electrode devices 5A, 5B are arranged with their outer electrode surfaces facing inwardly to define an ion transport channel TC located between the electrode devices 5A, 5B. The first electrode device 5A is arranged with its electrodes facing or located opposite the second electrode device 5B, the electrodes facing inwardly and defining the ion transport channel TC located between the electrode devices 5A, 5B. The ion guiding device 7 may also include two more electrode devices 5, that is, a plurality of electrode devices 5 arranged and held so that their electrodes face inwardly and define the ion transport channel TC located between the electrode devices 5.

[0116] The surface SF1 of the first electrode support 3A may, for example, be located opposite / facing or directly opposite / facing the second surface SF’, SF2 of the second electrode support 3B, or the surface SF1 may for example be located in (approximately or substantially) parallel to the second surface SF2 of the second electrode support 3B.

[0117] The surface SF1 of the first and second electrode supports 3A, 3B (or of each electrode support 3) may for example be a (substantially) flat surface or a planar surface defined by a plane. These surfaces can be arranged relative to each other as previously described above in relation to Figure 3B.

[0118] The ion manipulation device 1 is configured to drive ions in the propulsion direction (X) between the surfaces of the electrode supports, for example, between the surface SF1 of the first electrode support 3A and the surface SF2 of the second electrode support 3B.

[0119] In an embodiment, opposing RF electrode surfaces or nominally opposing RF electrode surfaces of RF electrodes EL may have, for example, a RF voltage of the same phase applied to them. A RF voltage of different phases may alternatively be applied.

[0120] As described previously, the ion manipulation device 1 and / or the ion guiding device 7 is configured displace ions in the propulsion direction (for example, the X-direction) via the plurality of RF electrodes EL and the phase-shifted RF voltages PH1 , PH2, PH3 applied to the RF electrodes EL. In addition to displacement of ions in the propulsion direction (for example, the X-direction), interleaved electrodes displace ions into the deviation direction or the separation direction (for example, the Y-direction), based for example on ion mobility.

[0121] In an embodiment, the deviation or separation means may alternatively or additionally comprise gas flow means or a gas dispenser configured to displace a portion of the ions driven in the propulsion direction into the separation or deviation direction based on ion mobility. The gas dispenser may for example comprise one or more nozzles arranged to dispense flowing gas at a velocity in a direction non-parallel or orthogonal to the propulsion direction of the ions driven by the RF electrodes EL. Collision of the propelled ions with flowing gas molecules displaces a portion of the ions driven in the propulsion direction into the separation or deviation direction based on ion mobility. The gas may, for example, be nitrogen gas.

[0122] The ion manipulation device 1 may include one or more ion detectors 17 configured to detect the deviated or separated ions, and / or to detect ions driven in the propulsion direction by the RF electrodes EL. The or each ion detector 17 may, for example, include or have an associated ion aperture. The ion detector 17 is positioned relative to the ion guiding device 7 and / or electrode device 5 to receive displaced ions displaced by the voltage signals applied to the electrodes of the ion manipulation device 1 .

[0123] The ion detector 17 may, for example, be an ion detector 17A configured for spatial sensitivity operation to detect the mobility and / or m / z dependent displacement of the ions to obtain information about the content of the ion ensemble.

[0124] The ion manipulation device 1 may alternatively or additionally include one or more mass or mobility filter devices (for example, an ion transmission window) configured to filter or select ions for subsequent analysis by, for example, an ion analysis device, or for further manipulation or displacement by a further ion device.

[0125] Ion detectors 17 may be located relative to the ion guiding device 7 or electrode device 5 to receive displaced ions displaced by the voltage signals applied to the electrodes of the ion manipulation device 1. For example, one or more ion detectors 17 may be positioned to receive and detect ions that are principally displaced in the propulsion direction by the RF electrodes EL (see, for example, Figures 4A to 4D in which ion detectors are schematically shown relatively positioned with respect to the electrode device 5) and that have a relatively low ion mobility or relatively low m / z ratio such that these ions are little deviated or not deviated / separated away from the propulsion direction (X-direction). One or more ion detectors 17 can be laterally located (see, for example, Figures 4C and 4D) to receive and detect ions that are more strongly displaced from the propulsion direction and that have a relatively higher ion mobility or relative higher m / z ratio such that these ions are deviated or separated strongly into a deviation or separation direction and away from the propulsion direction (X-direction). As mentioned, the ion detector may be an ion detector 17A configured for spatial sensitivity operation to detect the mobility and / or m / z dependent displacement of the ions, as schematically illustrated in Figure 4D. The present disclosure also concerns an ion manipulation system including a plurality of ion manipulation devices 1. The ion manipulation system may form an m / z and / or ion mobility filter device / apparatus, or an ion dispersion device / apparatus. The ion manipulation devices 1 can, for example, be arranged to define a cyclic ion-mobility separation device. The ion manipulation device 1 can be arranged in a similar manner to the corner elements CNR (described herein further below) of a cyclic ion-mobility separation device / system 19 (see, for example Figure 3D). The ion manipulation system may also include the system elements of the serpentine ion path device of Figure 3D, including a plurality of ion detectors 17, 17A. The serpentine ion path device comprising or formed by a plurality of corner elements may also include at least one or a plurality of ion manipulation devices 1 , for example, located between a first and second corner element.

[0126] The ion manipulation device or system of the present disclosure can be, for example, a glycomic or metabololmic ion manipulation device / system, or an inorganic compound manipulation device / system, or a polymer manipulation device / system, or a peptide / protein manipulation device / system.

[0127] As described above, the ion transport approach and method exploited in this invention is based on the use of three or more RF voltages of essentially the same frequency and amplitude, that are shifted in their phases with respect to each other by a value that is substantially different from 180°, and are applied to consecutive electrodes to generate electrodynamic fields that both confine ions, i.e. exert a net repelling force onto the ions, but also exert a net force on the ions toward a pre-defined direction.

[0128] The direction of this net driving force depends on the sign of the phase shift that the RF voltage applied to one electrode has with respect to the phase of the RF potential applied to the neighboring electrode, and / or on the specific geometries of the electrodes.

[0129] This mode of ion propulsion is referred herein to as phase-assisted ion transmission. The strength of the net force acting on ions inside a buffer gas is both mass-to-charge (m / z) ratio dependent and size dependent, or collision-cross section (CCS) dependent, so that ions of different CCS and / or m / z ratio separate in space after a certain time being subjected to such electric fields.

[0130] To date, radiofrequency ion confining devices utilize a pair of radiofrequency potentials that are shifted in their phase by 180°. These electrical potentials, applied to neighboring electrodes of appropriate shape, create an ion confining electric field, which exerts a force onto the ions that repels them from the electrodes but does not transport the ions through the device. To actively transport ions through a radiofrequency device, electrostatic or electrodynamic fields need to be superimposed to these RF confining fields. In contrast, the herein disclosed invention is an innovative way to confine and transmit ions in a buffer gas. As opposed to conventional approaches, the herein disclosed invention does not require the superposition of electrostatic or electrodynamic potentials over the confining RF potentials, but the phase-shifted radiofrequency potentials of the present disclosure themselves, when applied to appropriate electrode configurations, provide a means of both ion confinement and ion propulsion. In realizing the experimental verification of the present invention, a previously undocumented manner of creating three or more phase-locked / phase-shifted radiofrequency electric potentials with phase shifts different from 180°, using capacitively coupled, resonant radiofrequency circuits was implemented.

[0131] The ion transporting properties of radiofrequency potentials that are shifted, for example, by 120° (or approximately 120°) or less have not previously been reported and were surprising. This effect is exploited for directed ion transport. The ion propelling properties of phase-shifted radiofrequency potentials are only useful or even noticeable under careful consideration of the direction / sign of the phase shift between potentials applied to neighboring electrodes. The configuration of the electrodes that the potentials are applied to is planned or predetermined to exploit the effect of phase-assisted transmission.

[0132] As previously mentioned, in an embodiment, phase-assisted ion transmission can be applied to, for example, a ring-electrode structure consisting of a stack of cylindrical rings to transmit ions through a buffer gas without the need to apply or superimpose other electric potentials to manipulate ion trajectories and to achieve propulsion of ions.

[0133] The action of a minimum of three radiofrequency potentials that are shifted in their phase with respect to one another can be sufficient to propel ions through the structure.

[0134] Generally speaking, electrodes EL can be configured such that a first electrode EL1 receives a first radiofrequency potential, a second neighboring electrode EL2 receives a second radiofrequency potential that is shifted in phase by for example 120° or approximately 120° with respect to the first potential, and a third electrode EL3 is configured to receive a third radiofrequency potential that is shifted in phase by for example 120° or approximately 120° with respect to the second potential. All potentials are preferably similar (or approximately similar) in their amplitude. Configurations using more than three phase-shifted radiofrequency potentials are similarly possible and the phase shift between potentials applied to neighboring electrodes EL shall be approximately 2?r / n, where n is the periodicity of the structure, i.e. the number of different radiofrequency potentials and electrodes EL chosen for the application.

[0135] An embodiment employing such phase-assisted transmission concerns an m / z and / or ion mobility filter device, or an ion dispersion device. Such a device can be realized using an electrode structure where ions are being propelled through a buffer gas with two orthogonal velocity components. At least one of the orthogonal velocity components is m / z dependent and / or ion mobility dependent for a separation of ions to occur.

[0136] An array of electrodes on a surface SF, SF1 (such as the one depicted in Figures 3A and 3B), where multiple parallel RF electrodes EL extend into one direction and are interspersed with multiple shorter electrodes that receive a travelling wave electric potential, can be configured as a m / z and / or ion mobility filter device. A second surface SF’, SF2 with an electrode arrangement configured to receive voltages that repel ions, for example, but not necessarily, one that can represent or is a mirror image of the electrode arrangement of the first surface SF1 , can be placed in parallel to the first surface SF1 to ensure that ions remain within or inside the action of the electric fields that provide the ion-propulsion force, and to aid ion transmission.

[0137] While a travelling wave potential can transport ions along one direction, the m / z and / or mobility dependent force exerted by the operation of the RF electrodes EL for phase-assisted transmission displaces ions into the other. The total distance traveled into the second direction will therefore depend on the m / z and / or mobility of the ions. For example, an aperture placed at the end of the array may therefore only be reached by a certain type of ions under the travelling wave and RF conditions applied. Scanning one or more of those conditions will result in an adjustable m / z and / or mobility filter unit. Alternatively, an ion detector with spatial sensitivity can detect the mobility and / or m / z dependent displacement of the ions to obtain information about the content of the ion ensemble.

[0138] In an embodiment, another m / z and mobility filter unit may be realized using an array of extended, parallel RF electrodes on a surface SF, SF1 , configured to receive RF voltages for phase-assisted transmission. A second surface SF2 may be placed (substantially) in parallel to the first surface SF1 with an electrode arrangement that, with the appropriate electric potential applied, repels ions from this surface SF2, for example, but not necessarily with an electrode arrangement that presents a mirror image of the first surface SF1.

[0139] A flow of gas in the direction of the extended parallel RF electrodes can transport ions by drag force along the same direction. The RF electrodes EL, operated under conditions of phase-assisted transmission can displace ions in a direction orthogonal to the drag force. The total distance travelled in this orthogonal direction will depend on the m / z and / or mobility of the ions. An aperture placed at the end of the RF electrodes will only receive ions for transmission that were not displaced out of its acceptance window.

[0140] By scanning transmission parameters, such as the RF amplitude, frequency, gas flow, etc., the m / z ratio and / or the mobility of the transmitted ions can be scanned and filtered. Also in this embodiment, an ion detector with spatial sensitivity can detect the mobility and / or m / z dependent displacement of the ions to obtain information about the content of the ion ensemble.

[0141] In embodiments where electrodes on a surface SF are provided and utilized to create electric fields to repel and transport ions. The electrodes EL that are configured to receive RF voltages for phase- assisted transmission may not extend on the surface SF in a linear fashion or a rectangular manner (as illustrated in the exemplary embodiment of Figure 3A) but may extend non-linearly, or be curved, oval, round, or otherwise irregular in shape. Alternatively or additionally, neighboring electrodes may or may not be of the same size for RF phase- assisted transport to take effect, as illustrated by an electrode arrangement consisting of a number of concentric rings that are of the same size or radius or that are of different sizes or radii, with each ring, or ring segment, receiving an RF potential that is phase shifted with respect to the RF potential applied to a neighboring electrode ring, or ring segment. As a result, ions can be transported either to the center or away from the center of the assembly, depending on the direction of the RF phase shift.

[0142] Electrodes ELIN can be interspersed / interleaved in such an electrode arrangement of electrodes EL configured for RF phase-assisted ion transport as for example illustrated in Figure 3A to superimpose additional electric fields that allow ion manipulation. The shape of such interspersed / interleaved electrodes ELIN may also differ from the illustrated exemplary rectangular shape, and may be curved, oval, round, or of irregular shape.

[0143] The interspersed / interleaved electrodes ELIN may be placed between RF electrodes EL, and be located to partially or fully encompass the electrode or electrodes EL, or located to be partially or fully encompassed by the RF electrode or electrodes EL (see, for example, Figure 10).

[0144] When replacing the RF electrodes of a traditional device for ion mobility separation that has structures for lossless ion manipulation (SLIM) with RF electrodes EL that are configured for phase-assisted transmission according to the present disclosure, ions can, for example, be displaced orthogonal to the direction of the traveling wave potential through the action of the phase-shifted RF potentials. As a result of a narrower transversal ion distribution, the final longitudinal ion distribution will be narrower as well, because a wide transversal ion distribution leads to ions of the same type experiencing larger variations in total path length, especially when the ion path contains multiple corners. As a result, phase-assisted transmission RF operation leads to better ion mobility resolution when compared to operation using traditional two-phase RF.

[0145] The devices, systems and methods according to the present disclosure are particularly suitable for certain fields of applications including inter alia Glycomics (biomarker research, characterization and process control of biotherapeutics, characterization of milk and other food oligosaccharides) and Metabolomics (identification of isomeric metabolites).

[0146] As anticipated, and to better clarify the subject-matter of the present invention, Figure 1 A schematically depicts an exemplary and simple illustration of an exemplary electrode geometry configured to apply the method of phase-assisted ion transmission of the present disclosure in the exemplary form of a ringelectrode assembly, which comprises or consists of, for example, at least three coaxially stacked, annular rings.

[0147] The time dependent electric RF potentials applied to the individual electrodes i are, for example, of the form where U is the DC bias voltage of the RF potentials, V is the amplitude, to = 2nf is the angular frequency with the frequency f, n is the number of phase-shifted RF potentials chosen for the specific implementation, whereas n > 3, and i is a positive integer number enumerating consecutive electrodes with i = (1 ... n).

[0148] If more than n electrodes are used, this enumeration simply repeats, so that the potential applied to the (n + l)thelectrode i on.

[0149] Figure 2 shows an example of <Pn i(t) f°rn = 3, leading to a phase shift between potentials of 2TT / 3 or 120°, for an exemplary frequency of f = 1 MHz and arbitrary DC bias and amplitude. A configuration with n = 6 leads to a phase shift of 2n / 6 or 60°.

[0150] It is noteworthy that no effect of ion propulsion is observed when n = 2, i.e. when the phase shift between the RF potentials applied to two neighboring electrodes is approximately n, or 180°, which is the case for virtually all RF potential based ion confinement and transfer technologies described in the art to date.

[0151] Conversely, phase-shifted RF potentials with n > 3 leading to a phase shift of 120° or smaller do not lose their ion confining properties. In addition, alternating electric potentials that do not strictly resemble a trigonometric function, such as a square wave or a sawtooth wave, also provide ion confining and propulsion properties.

[0152] In the example of the ring-electrode assembly shown in Figure 1 for the case of n = 3 , the electrodynamic potential <Pn i(t) would be applied to three neighboring electrodes i = 1 , 2, and 3 as 4>3 i (t), 4»3i2(t)>ar|d ^3,3(0 according to equation (1 ).

[0153] As shown in the results of the ion trajectory simulations (see for example Figures 4A to 4D, and 6A to 6D), such an operation will result in a net driving force by the electric field in the direction of X. The sign of the phase shift, i.e. the definition of electrodes 1 , 2, and 3 in +X or -X direction will define the direction of motion in +X or -X direction.

[0154] Concerning phase-assisted ion dispersion, the SIMION ion optics simulator suite was used for the in- silico verification of the invention, and a m / z and ion mobility filter based on phase-assisted ion transmission is now first discussed.

[0155] An exemplary surface-based electrode design was simulated, as it can be readily manufactured and implemented in an experiment for verification. The (substantially) planar-based design and / or substantially flat surface-based design (see for example, Figures 3A and 3B) can be relatively easily manufactured and implemented in a device.

[0156] In this approach, the electric fields that confine ions and affect their motion are generated by two interleaved arrays of rectangular electrodes on a first surface SF1 , one array or a first array of electrodes EL for phase-assisted ion confinement and propulsion into a defined direction (for example, an X- direction), and one array or a second array of electrodes ELIN for ion propulsion into a second direction (for example, a Y-direction), as well as electrodes on a second surface SF’, SF2 placed in parallel (or substantially parallel) to the first surface SF1 , which leads ions to be confined between the two surfaces, or the first surface SF1 and the second surface SF’, SF2.

[0157] The electrode geometry and electric potentials applied on the second surface SF’, SF2 are suitable to repel ions from this second surface SF2. The ions are repelled back towards the first surface SF1 to be manipulated by the electrodes of the first surface SF1 and electric fields generated by the voltage / potential signals applied thereto.

[0158] The electrode geometries on the second surface SF’, SF2 may represent, for example, a mirror image of the electrodes and electric potentials of the first surface SF1 , which is the case for the implementation discussed here.

[0159] A schematic of the electrode geometry or arrangement implemented on the first and the second surface used in this ion trajectory simulation is schematically shown in Figure 3A.

[0160] The number of RF phases used here is n = 3, which results in a repeating array or set S1 , S2, S3. . . of three parallel RF electrodes EL1 , EL2, EL3 in the X-direction. Each RF electrode EL extends into the Y- direction on the surface at a constant width in this simulation.

[0161] A second array or set of electrodes ELIN labeled A through H is interleaved with the first array or set and its role is to generate electric fields that propel ions in Y-direction. This can be achieved using electrostatic as well as electrodynamic electric potentials, and the latter one was chosen here for the simulation.

[0162] The electric potentials applied to electrodes A through H have the form of a travelling potential wave. An example for a travelling wave (TW) electric potential applied to the eight electrodes may, for example, be a square wave, represented as a bit pattern (1 1110000), where 1 and 0 represent two different DC levels of the square potential wave, respectively, and the position in the string of eight numbers represents one specific electrode A through H. After a predefined time interval, the bit pattern changes to (0111 1000), (001 11100), (00011110), (0000111 1 ), (100001 11 ), (11000011 ), and finally (11100001 ). It should be noted that electrodynamic potentials other than the exemplary square waves (such as a sine wave or a sawtooth potential) and a number of TW electrodes that is different from the exemplary eight will also generate electric fields that propel ions in the Y-direction.

[0163] The TW electrodes ELIN used here are elongated and have an exemplary width of approximately 0.4 mm in X-direction and extend 1 mm into the Y-direction. The exemplary RF electrodes EL are also elongated and are of the same width but extend for example 20 mm into Y-direction, at which point ion trajectories were terminated in the simulation. The exemplary dimensions of the surface electrodes implemented here are such so as to create the travelling wave electric fields that are equivalent to those discussed in reference

[0014] , the disclosure of which is hereby incorporated herein by reference in its entirety for all purposes.

[0164] Representative ion trajectories for ions created or generated by simulation in the lower left corner of the device or electrode array are shown in Figures 4A to 4D, for 15 ions with a ratio m / z of (Figure 4A) 250, (Figure 4B) 500, (Figure 4C) 1000, and (Figure 4D) 1500, respectively; with the ions being influenced under the following exemplary conditions: RF frequency 1 MHz, RF amplitude 125 VPP, TW amplitude 10V, TW velocity 3.4 m / s, and no difference between the DC bias potential applied to the RF and the TW potential.

[0165] Nitrogen was used as a buffer gas at an exemplary pressure of 2.5 torr, and the statistical diffusion simulation (SDS) model was used.

[0166] Phase-shifted RF potentials according to Equation (1 ) were applied, with n = 3, resulting in a phase shift in the potential applied to electrode i with respect to that applied to electrode i + 1 of +120°. The RF electrode EL numbering i increases in direction of X in Figures 4A to 4D.

[0167] In all four cases (see Figures 4A to 4D), ions are successfully transmitted toward the outer bounds of the simulated electrode array, where their trajectories are terminated.

[0168] The ion confining electric field is the one created by the RF electrodes EL because the travelling wave (provided by the TW electrodes ELIN) alone does not show any ion confining properties.

[0169] Each ion is displaced in X direction as well as in Y direction, albeit by different values or amounts. The displacement in Y direction is caused by the travelling potential wave (provided by the TW electrodes ELIN) and its amplitude was chosen such that all ions undergo multiple roll-over events, i.e. their mobility does not allow them to follow at the speed of the potential wavefront but causes them to lag behind, to experience the next wavefront.

[0170] As discussed above, this effect is mobility as well as m / z ratio dependent. More interestingly, and an innovative aspect of this present invention, is the displacement in X direction, which is caused by the phase shift of the RF potentials applied on the RF electrodes EL.

[0171] Also, this effect shows a strong m / z dependency and results in a larger velocity component in X direction for smaller m / z than for larger m / z. One can also envision a mobility dependence of this effect.

[0172] It is important to note that a phase shift in the opposite direction, i.e. a shift in the potentials of electrode i to i + 1 of -120° will lead to ion propulsion in the opposite direction, that is, the -X direction in the illustrated examples of Figures 3 and 4.

[0173] This simulation demonstrates how a phase shift 180° between RF potentials applied to neighboring electrodes EL can be used to both confine ions and propel them into a direction defined by the sign of the phase shift.

[0174] The combination of phase-assisted ion transport and travelling-wave ion transport allows for a mixture of ions of different m / z and mobilities to be separated and dispersed in two dimensions.

[0175] A spatially resolving ion detector located for example on the far-right side of the electrode array (of Figures 3 and 4) can detect the separated ions and the resulting data would be equivalent to a mass spectrum or an ion mobility chromatogram (if conditions are set to separate different mobilities).

[0176] Alternatively, such a device can act as a mass or mobility filter to prepare ions for further interrogation, for example, if the transmission of ions were granted in Y-direction over a small window in the X- direction. In Figure 4, this could be a transmission window in Y-direction for ions within the range of X = 10...15 mm. Under the conditions presented here in the present example and shown in Figure 4D, only the ions with m / z 1500 would be transmitted further along the Y-axis. The remining ions would, for example, continue to be transported in the X-direction.

[0177] Such a device would present a simple and compact alternative to other solutions currently employed in commercial mass spectrometers and field devices. Additionally, the TW potentials responsible for displacement in Y-direction are provided as an exemplary implementation and may be replaced by electrostatic potentials and / or by a gas flow to drag ions in a direction perpendicular to the motion caused by the phase-assisted transmission.

[0178] Figure 5 schematically shows an exemplary corner element CNR of the present disclosure. A plurality of such corner elements CNR can, for example, be arranged to form a serpentine ion path device / system 19 (see for example Figure 3D) comprising or formed by a plurality of corner elements CNR, for example, arranged end-to-end. As mentioned previously, the serpentine ion path device / system 19 may also include at least one or a plurality of ion manipulation devices 1 , for example, located between first and second corner elements CNR. The corner element CNR is configured to provide an ion path or direct the ions around or through the corner using phase-assisted ion transmission with superimposed travelling wave potentials. The corner element CNR includes a plurality of RF electrodes EL and a plurality of interleaved / deviation electrodes ELIN for generating or providing travelling-waves TW.

[0179] The corner element CNR is an ion manipulation system including a first ion manipulation device 1 , D1 and a second ion manipulation device 1 , D2.

[0180] The first ion manipulation device D1 and the second ion manipulation device D2 each have an electrode arrangement as previously described in relation to the ion manipulation device 1.

[0181] Each ion manipulation device D1 , D2 includes, for example, one or more sets of RF electrodes EL extending in a first direction as well as one or more arrays AR interleaved / deviation electrodes ELIN also extending in the first direction, the or each array AR of interleaved / deviation electrodes ELIN including at least one or a plurality of sets SI of interleaved / deviation electrodes ELIN also extending in the first direction. The relative arrangement, shape and positioning of the interleaved / deviation electrodes ELIN and the RF electrodes EL being as previously described above.

[0182] The first ion manipulation device D1 is positioned with respect to the second ion manipulation device D2 so that the sets of RF electrodes EL of the first ion manipulation device D1 are positioned adjacent to the sets of RF electrodes EL of the second ion manipulation device D2 to define at least one corner intersection element CIE or a V-shaped or L-shaped corner intersection element CIE (see, for example, Figure 5). The sets of RF electrodes EL of the first ion manipulation device D1 are, for example, positioned non-parallel or substantially / approximately perpendicular to the sets of RF electrodes of the second ion manipulation device D2.

[0183] The V-shaped or L-shaped corner intersection element CIE includes a first leg that extends to intersect or contact a second leg of the V-shaped or L-shaped element. The RF electrodes EL and / or the sets of RF electrodes EL of the first ion manipulation device D1 extend in a direction of the first leg and the sets of RF electrodes EL of the second ion manipulation device D2 extend in a direction of the second leg of the V- shaped or L-shaped element.

[0184] The sets of RF electrodes EL of the first ion manipulation device D1 are, for example, positioned nonparallel or substantially / approximately perpendicular to the elongated direction of extension a first RF electrode EL1 of the set S1 of RF electrodes of the second ion manipulation device D2.

[0185] In the illustrated exemplary embodiment of Figure 5, the elongated direction of extension the first RF electrode EL1 of the set S1 of RF electrodes of the second ion manipulation device D2 extends in the Y- direction while the RF electrodes EL of the first ion manipulation device D1 extend in the X-direction. It is noted that in an embodiment of the ion manipulation device comprising a plurality of electrode supports 3A, 3B each having surfaces SF include electrode arrangements, the first electrode supports 3A and second electrode supports 3B of each device D1 , D2 are positioned to arrange their RF electrodes in the manner described above to form the corner intersection element CIE. For example, two planar or flat surfaced SF first electrode supports 3A are positioned side-by-side, and two planar or flat surfaced SF second electrode supports 3B are positioned side-by-side to be located opposite or facing the first electrode supports 3A. This is similarly done in the case where the second electrode supports 3B comprise electrodes configured to simply repel ions back towards the first electrode support 3A, as described previously in relation to the ion manipulation device 1.

[0186] The first ion manipulation device D1 is, for example, positioned with respect to the second ion manipulation device D2 so that the arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the first ion manipulation device D1 are positioned adjacent to the arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the second ion manipulation device D2 to define the corner intersection element CIE or the V-shaped or L-shaped corner intersection element CIE. The arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the first ion manipulation device D1 are, for example, positioned non-parallel or substantially / approximately perpendicular to the arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of of the second ion manipulation device D2.

[0187] The arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the first ion manipulation device D1 are, for example, positioned non-parallel or substantially / approximately perpendicular to the elongated direction of extension the first RF electrode EL1 of the set S1 of RF electrodes of the second ion manipulation device D2.

[0188] In the illustrated exemplary embodiment of Figure 5, the elongated direction of extension the first RF electrode EL1 of the set S1 of RF electrodes of the second ion manipulation device D2 extends in the Y- direction while the arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the first ion manipulation device D1 extend in the X-direction.

[0189] The arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the first ion manipulation device D1 extend in a direction of the first leg and arrays AR and / or set(s) of interleaved / deviation electrodes ELIN of the second ion manipulation device D2 extend in a direction of the second leg of the V-shaped or L-shaped element.

[0190] The corner element CNR may include, for example, at least one or a plurality of (outer) boundary electrodes BE1 , BE2 configured to receive a DC ion confinement electric potential to push ions inwardly towards or to the manipulation electrodes EL, ELIN and away from outer edges or outer boundaries of the corner element CNR. The corner element CNR may include, for example, at least a first boundary electrode BE1 and a second boundary electrode BE2. The manipulation electrodes EL, ELIN of the first and / or second device devices D1 , D2 are located between the first boundary electrode BE1 and the second boundary electrode BE2. The first boundary electrode BE1 and the second boundary electrode BE2 define or form V-shaped or L-shaped electrodes between which the manipulation electrodes EL, ELIN are located.

[0191] The corner element CNR and / or Ion manipulation system or device may include, for example, at least one or a plurality of DC voltage source operatively connected to the outer boundary electrodes BE1 , BE2 to apply thereto a DC ion confinement electric potential.

[0192] The RF electrodes EL of the set or sets of RF electrodes of the first ion manipulation device D1 and / or the second ion manipulation device D2 are operatively connected to one or more RF voltage generators 9 to simultaneously receive the plurality of phase-shifted RF voltages PH1 , PH2, PH3 to propulse ions or to steer the ions through the corner element CNR and / or the intersection element CIE, and into an elongated direction of extension (for example, the Y-direction) of the second ion manipulation device D2. The elongated direction of extension of the second ion manipulation device D2 extends, for example, parallel to the elongated direction of extension of the RF electrodes EL or sets (and / or the sets SI of electrodes ELIN) thereof of the second ion manipulation device D2.

[0193] The plurality of interleaved electrodes ELIN of the first ion manipulation device D1 and / or the second ion manipulation device D2 are arranged to receive one or more interleaved electrode voltages from one or more interleaved electrode voltage waveform generators 15 to displace ions in a first displacement direction (for example the X-direction) across the first ion manipulation device D1 and / or to displace ions in a second displacement direction (for example the Y-direction) across the second ion manipulation device D2. The first displacement direction is non-parallel to the first displacement direction, or approximately or substantially orthogonal to the first displacement direction. The first and second displacement directions intersect to form the V-shaped or L-shaped profile. The interleaved electrode voltages are those configured to receive and implement the traveling wave, as previously described herein.

[0194] The RF voltage generator or generators 9 are configured to simultaneously provide the plurality of phase- shifted radiofrequency RF voltages PH1 , PH2, PH3 to interact with the ions being displaced in the first displacement direction (X) across the first ion manipulation device D1 to steer the ions through the corner element CNR and / or the intersection element CIE and into the elongated direction of extension of the second ion manipulation device D2.

[0195] The RF electrodes EL of the first and the second ion manipulation devices D1 , D2 are arranged to simultaneously receive a plurality of phase-shifted RF voltages (PH1 , PH2, PH3) having a positively increasing phase-shift value or a negatively increasing phase-shift value to act on the ions undergoing displacement to steer the ions through the corner element CNR and / or the intersection element CIE and into the elongated direction of extension (Y) of the second ion manipulation device D2.

[0196] The voltage signals applied are, for example, configured so that the plurality of interleaved electrodes ELIN of the first ion manipulation device D1 displace the ions along first displacement direction (or in the X- direction of the CNR, see for example Figure 5) and the arrangement of the RF electrodes EL of the first ion manipulation device D1 and / or the second ion manipulation device D2 propulse and confine the ions to displace the ions in a manner to direct the ions off the device D1 and onto the device D2 and around the angled corner formed by the devices D1 and D2 and / or direct the ions into and along the second displacement direction (or in the Y-direction of the CNR, see for example Figure 5), and the plurality of interleaved electrodes ELIN of the second ion manipulation device D2 displace the ions along second displacement direction or in the Y-direction.

[0197] A plurality of corner or intersection elements CNR arranged to define or form a cyclic ion-mobility separation system 19 (see for example, Figure 3D). The cyclic ion-mobility separation system 19 may form the serpentine ion path device / system 19. The cyclic ion-mobility separation system 19 may also include at least one or a plurality of ion manipulation devices 1 , for example, located between first and second corner elements CNR to extend the length of the ion track / path along which the ions are transported in / by the device / system.

[0198] The system may also include ion switching means 21 configured to divert ions to at least one exit 23 of the cyclic ion-mobility separation system and to at least one ion detector 17. The ion switching means 21 may, for example, be an electrostatic potential or electric field generator comprising first and second terminals between which a voltage is applied to generate or switch on an electrostatic potential or an electric field to force the ions to or in the direction of the exit 23. The electrostatic potential or electric field generator can for example be in the form of a T-junction.

[0199] The system may also include an ionization source 25, for example but not limited to an electrospray ionization (ESI) ionization source, or a proton transfer reaction (PTR) ionization source, or a plasma ionization source, or a matrix-assisted laser desorption / ionization (MALDI) source.

[0200] The ion manipulation system 19 may be, for example, a glycomic or metabololmic ion manipulation system, or an inorganic compound manipulation system or a polymer manipulation system or a peptide / protein manipulation system.

[0201] The present disclosure also concerns an ion mobility spectrometry (IMS) system including one or more of the ion manipulation devices, and / or one or more of the ion manipulation systems described herein The present disclosure also concerns a mass spectrometer instrument or field-ion mobility device including one or more of the ion manipulation devices and / or one or more ion manipulation systems.

[0202] Concerning phase-assisted cornering, a second electrode geometry was simulated using the SIMION simulation tool to investigate the effect of phase-assisted transmission technology on the transmission of ions through corners or 90° corners of electrode array configurations that create a path that ions follow by means of travelling potential wave transport. Such corners are frequently used in the art in structures for lossless ion manipulation, such as described in reference

[0014] . A corner element CNR of such an ion path, using essentially the same electrode dimensions as in the previously discussed simulation (shown in Figures 3 and 4), is depicted in Figure 5 for n = 3, with RF electrodes EL and travelling wave electrodes ELIN labelled equivalent to labelling used in Figures 4A to 4D.

[0203] Two sets S1 , S2 of three RF electrodes EL are, for example, used to define the ion path and these RF electrodes EL are interleaved with travelling wave electrodes ELIN, which repeat in a pattern of, for example, eight (labelled A through H).

[0204] As shown in Figure 5, the RF electrodes EL with n = 3 are labeled i = 1 , 2, and 3. Individual electrodes ELIN of the repeating travelling-wave electrode array, or sets SI, are labelled A through H.

[0205] Ion transport in a direction parallel to the elongated direction of extension of the RF electrodes EL is, for example, established using the travelling potential wave approach, with the travelling potential having for example the form of a square wave as in the simulation described above in relation to Figures 3 and 4.

[0206] Both the RF electrodes EL and the interleaved travelling wave electrodes ELIN are used to direct the ions around the corner element CNR. The RF electrodes EL use phase-assisted ion transmission, and the travelling wave electrodes ELIN use the travelling potential wave approach to implement an ion cornering by phase-assisted ion transmission with superimposed travelling wave potentials.

[0207] There is no substantial electric DC potential bias applied between the RF electrodes EL and the TW electrodes ELIN. However, the DC bias of electrodes BE1 , BE2 that define the boundaries of the RF / TW electrode array is held above the DC level of the other electrodes EL, ELIN (for positive ions, vice-versa for negative ions), to confine ions in the X-Y directions into or along the ion track. No other potentials are applied to these DC-only electrodes in this exemplary simulation.

[0208] The TW electrodes ELIN are configured and / or arranged such that the potential wave propagates in the positive direction of X (from left to right in Figure 5) for the electrode array element A1 with RF electrodes EL extending in the X direction, and the potential wave propagates in the positive direction of Y (from bottom to top in Figure 5) for the array A2 with RF electrodes EL extending in the Y direction.

[0209] Trajectories were simulated for n = 3 under the following exemplary conditions: RF amplitude 200 VPP, RF frequency 750 kHz, TW amplitude 5 V, TW velocity 8 m / s, DC-only confining bias 5 V, pressure 2.5 torr, buffer gas helium.

[0210] A total number of 75 ion trajectories were simulated per m / z ratio and the statistical diffusion simulation (SDS) model was used. Resulting ion trajectories are displayed in Figure 6(A) and 6(C) for ions with m / z 250 and m / z 1000, respectively, and the trajectories were started in the lower left corner of the electrode array or corner element CNR .

[0211] While ions move toward the corner CR following the direction of the travelling potential wave, they are shown by the results to be pushed toward the lower edge ED1 (see Figures 6A, 6C) of the electrode array A1 , i.e. toward the DC-only boundary electrode BE1 in the (negative) -Y direction. This effect is more pronounced for m / z 250 ions (Figure 6A) than for m / z 1000 ions (Figure 6C), which indicates or stems from the m / z-dependency of the phase-assisted ion propulsion effect.

[0212] When entering the corner, ions are again pushed toward the outer boundary ED2 (see Figures 6A, 6C) of the array A2 in +X direction, leading to a smooth transition into the perpendicular electrode path and a narrow distribution of ions as they travel along the +Y-direction. All trajectories are terminated at Y=19 mm.

[0213] In contrast, Figure 6(B) and 6(D) show ion trajectories for the same ion types, i.e. m / z 250 and m / z 1000, respectively, however, using traditional two-phase RF confinement where the phase shift between RF potentials applied to neighboring RF electrodes is approximately 180°. It is interesting to compare the difference in the resulting ion trajectories compared to the here-disclosed phase-assisted transmission approach.

[0214] One can observe that ions are distributed over a wider area throughout the simulation using the traditional RF confinement compared to the more confined distributions using the phase-assisted transmission approach of the present disclosure.

[0215] In addition, in the traditional approach, ions traverse the travelling wave interface simply by being pushed into the side of the perpendicularly moving potential wave, which gives them the chance to reside in this area for a number of cycles if they are not fully captured by the new potential. In contrast, in the phase- assisted transmission approach of the present disclosure, ions are actively transmitted toward the outside of the corner or edge ED2, where they are effectively transported along the ion path by the perpendicular travelling potential (in the +Y direction of Figure 5).

[0216] As a result of the overall narrower ion distribution and the more effective cornering, the variation in pathlength that ions of the same type experience over multiple such corners and turns will be smaller than in the traditional two-phase approach. Consequently, the spatial spread along the travel direction of an ion cloud consisting of ions of the same type will also be smaller, which will ultimately lead to an improved mobility resolving power when the phase-assisted transmission method is applied to an electrode arrangement featuring multiple corner elements CNR.

[0217] Experimental validation of ion transmission was carried out. To validate the concept or method of ion confinement and transmission using the phase-assisted transmission method of the present disclosure, an electrode arrangement was designed that features (around) 56 of the corner elements CNR depicted in Figure 5 arranged in a serpentine ion path of a total length of approximately 5 meters.

[0218] At the end of the path, an electrostatic potential can be switched on a T-junction to either divert ions toward an exit region that leads to an ion detector, or to have ions remain on the ion path, which then returns to the beginning of the path.

[0219] Such a device or such an electrode array allows cyclic ion-mobility separation, which has the advantage over linear separation that each additional separation cycle will increase the ion-mobility resolving power of the device.

[0220] The RF electrodes EL of the device were configured such that the performance of the traditional two- phase setup and the phase-assisted transmission method of the present disclosure could be compared back-to-back.

[0221] For this experiment, ions were produced in an electrospray ion source and transmitted to the ion mobility separation region, where a small pulse of ions was released at a time, in approximately 2 mbar pressure of nitrogen buffer gas. Subsequently, ions were transferred to high vacuum, where mass-to-charge analysis occurred in a time-of-flight analyzer. The transmission and mobility-resolution test was carried out using the isomeric reversed-peptide mixture GRGDS and SDGRG, which are standards in the field of ion mobility spectrometry. Singly charged ions were observed, which differ in their ion mobility by a small percentage. For transmission and mobility separation, the following parameters were used in both two-phase and phase-assisted transmission operation: RF amplitude 150 VPP, frequency 900 kHz, TW amplitude 30 V, TW velocity 160 m / s.

[0222] Figure 7 shows arrival time distributions of singly protonated GRGDS and SDGRG ions after 1 , 2, 3, 4, and 5 separation cycles. Each additional cycle increases the separation between the two different species. The ion mobility resolution after each separation cycle can be estimated by the ratio of the position of a mobility peak and its width, after converting drift times into a collision-cross section. The result is shown in Figure 8 for both the phase-assisted transmission of the present disclosure with n = 3, as well as traditional two-phase RF conditions.

[0223] A single cycle is not sufficient to separate the two isomers as can be observed in Figure 7, however, a second cycle shows separation and reveals a mobility resolution of approximately 90 in the case of phase-assisted transmission with n=3, whereas a resolution of approximately 75 is observed under traditional two-phase conditions. After 11 cycles, the resolution increases to around 330 when three RF phases are used, while only 275 was achieved under two-phase conditions, when the same RF amplitude and frequency is applied in both experiments. These results experimentally verify and confirm that the phase-assisted transmission method can successfully confine and transmit ions over pathlength of several meters in length aided by travellingwave potentials. The performance of electric RF potentials with a phase-shift of 120° with respect to the phase of potentials on neighboring electrodes EL was compared to the performance of traditional RF potentials that are 180° out-of-phase between neighboring electrodes, and the former was found to exceed the latter in terms of ion mobility resolving power under otherwise same conditions.

[0224] Concerning the generation of phase-shifted RF potentials, realization of the phase-assisted transmission experiment and the generation of the three RF potentials by the RF voltage generator 9 that exhibit a constant shift in phase of approximately 2TT / 3 at the desired frequency range of, for example, 400 kHz to 2 MHz, was realized by using three equivalent, resonant RF generators, which work according to the principle of a circuit known in the art as a 'tank circuit', essentially comprising or consisting of an inductor and a capacitor in parallel, whereas the capacitor represents the capacitive load of the electrode array where the RF potentials need to be applied to. Such a circuit, when externally excited at its resonant frequency, can generate two phases of an oscillatory potential (phase A and phase B), which have a constant phase shift of 180° to one another. An example for a resonant RF device that is capable of generating two RF potentials that are shifted in their phase by approximately 180° is described in reference

[0015] . To achieve the potentials for phase-assisted transmission with n = 3, three such RF generating devices were used to generate potentials Ai, A2, and A3, as well as Bi, B2, and B3, whereas each phase of A and Bi is shifted with respect to Ai+i and Bi+i by 120°, respectively, and each pair of potentials Ai and Bi are shifted in phase by 180° to each other. The latter is the result of the potential pair Ai and Bi being generated by one resonant circuit using the tank-circuit approach as described in

[0015] . The three resonant circuits and RF generators are equivalent to each other, whereas phase Ai of each circuit is connected to RF electrodes for potential <P3 iof the first surface, and phase Bi of each circuit is connected to electrodes for potential <P3 ;of the second surface. As a result of this setup, each phase A is strongly capacitively coupled to the other phases Aj i and each phase Bi is capacitively coupled to the other phases Bj i.

[0225] Each of the three RF circuits is excited with a driving potential that is approximately 120° shifted in phase with respect to the driving potential of the next RF generator. Air-variable capacitors connected in parallel to the capacitive load (i.e. the RF electrodes on the two surfaces to receive the potentials Ai and Bi that are shifted in phase by 180°) of each RF circuit can be used to fine-tune the phase and amplitudes of the three RF voltage pairs. Exemplary radiofrequency potentials Ai generated using the here described setup are displayed in Figure 9, together with the driving potential used for phase A1 / B1 and their phase shift with respect to the potential applied to neighboring electrodes is indicated. Potentials Bi are equivalent, albeit with a phase shift of 180° with respect to potentials Ai. Equivalent setups with n > 3, i.e. setups with more than three capacitively coupled RF generating circuits to achieve phase-shifted RF potentials with phase shifts of less than 120°, can be constructed.

[0226] Figure 1 1 shows an exemplary apparatus or system 27 in which the ion manipulation device and / or the ion manipulation system may operate to carry out phase-assisted transmission to achieve ion separation according to the present disclosure. The apparatus or system 27 includes, for example, the enclosed gas cell 31 inside which the ion manipulation device(s) and / or the ion manipulation system(s) described herein are located. The apparatus or system 27 includes the ionization source 25 and a detection, measurement or analysis device such as an ion detector 17 such as a mass spectrometer and / or an IR spectroscopy device. A vacuum system 102 can also be included that includes vacuum pumps and buffer gas flow controllers or valves. The vacuum system 102 is configured to set the buffer gas pressure. A power source 108 is provided for generating the different voltages or electric potentials for the electrodes. A computing device 104 and a controller 108 are configured to monitor and control the conditions of the process, for example but not limited to the pressures and gas flows, and to monitor and define the electric DC, RF, and TW potentials applied to the ionization source 25, the electrodes on the ion manipulation device and / or the ion manipulation system, and the detection / analysis device(s) 17.

[0227] Another aspect of the present disclosure concerns an ion manipulation method for driving ions in the propulsion direction. A plurality of the phase-shifted RF voltages PH1 , PH2, PH3 are generated, and applied simultaneously to the RF electrodes EL of at least one set or sets S1 , S2, S3, S4, S5 (or of a first and / or second set) of the RF electrodes EL to drive ions in the propulsion direction to both (i) confine and / or repel ions in a first direction (for example the Y-direction) and / or a second direction (for example, the Z-direction) and to propulse ions in the propulsion direction (for example the X-direction) orthogonal or non-parallel to the first and / or second directions.

[0228] The Ion manipulation method may include providing at least one ion manipulation device, or ion manipulation system as disclosed herein, and applying, to the at least one first set and / or second set of radiofrequency electrodes EL, the plurality of phase-shifted radiofrequency voltages to drive ions in a propulsion direction (X).

[0229] The phase-shifted RF voltages PH1 , PH2, PH3 may be simultaneously applied to each electrode EL of the set or sets S1 , S2, S3, S4, S5 of RF electrodes with each electrode simultaneously receiving a RF voltage that is phase-shifted by a value of 2jt / n or approximately 2jt / n with respect to its neighboring electrode EL, or with respect to each of its neighboring electrodes EL. Electrodes EL or each electrode EL of the set (S1 , S2, S3, S4, S5) of RF electrodes may be or comprise an electrode EL extending in a direction (substantially or approximately) orthogonal to the propulsion direction in which ions are driven.

[0230] The plurality of phase-shifted radiofrequency RF voltages may be simultaneously applied to the set or sets (or the first and second set) of RF electrodes. The electrodes EL of the first and second sets of RF electrodes may simultaneously receive the plurality of phase-shifted radiofrequency voltages. Each electrode EL of the first and second sets may receive a RF voltage that is phase-shifted by a value of 2jt / n or approximately 2jt / n with respect to its neighboring electrode EL, or with respect to each of its neighboring electrodes EL. Radiofrequency (RF) voltages (PH1 , PH2, PH3) of the same phase can be simultaneously applied to a first electrode EL1 of the sets (or first and second sets). RF voltages having the same phase shift relative to the first electrodes EI1 are, for example, simultaneously applied to a second electrode EL2 of the sets (or of the first and second set). RF voltages having the same phase shift relative to the second electrodes EL2 are, for example, simultaneously applied to a third electrode EL3 of the sets (or of the first and second set)

[0231] The plurality of phase-shifted radiofrequency voltages PH1 , PH2, PH3 are, for example, applied simultaneously to drive ions in the propulsion direction (X) between the at least one surface SF of the first electrode support 3A and the at least one surface SF’, SF2 of the second electrode support 3B.

[0232] Each of the generated plurality of phase-shifted radiofrequency voltages PH1 , PH2, PH3 may be defined by a time dependent phase-shifted radiofrequency (RF) electric potential that is defined by an AC waveform, as previously described herein.

[0233] Phase-shifted radiofrequency voltages PH1 , PH2, PH3 may be respectively applied to a first plurality of RF electrodes having a positively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a first propulsion direction (for example X+); and / or applied to a second plurality of RF electrodes having a negatively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a second propulsion direction (for example X-) opposite to the first propulsion direction (X+).

[0234] The method further includes displacing the ions driven in the propulsion direction (for example X- direction) or at least a portion thereof into at least one, or one or more deviation direction or separation directions based on ion mobility or m / z ratio. Interleaved or deviation electrode voltages are generated to displace or propel ions into the deviation direction or separation direction, and applied to interleaved or deviation electrodes ELIN to displace ions into the deviation directions or separation directions based on ion mobility or m / z ratio.

[0235] The interleaved electrode voltages are, for example, provided by the interleaved electrode voltage waveform generator 15 as a travelling potential wave configured to generate electric fields to displace or propel ions into the deviation directions or separation directions. Alternatively, the interleaved electrode voltages are, for example, provided by electrostatic potentials configured to generate electric fields to displace or propel ions into the deviation directions or separation directions. Alternatively, or additionally, a gas flow is performed to displace a portion of the ions driven in the propulsion direction by the RF electrodes into the deviation or separation directions based on ion mobility or m / z ratio.

[0236] Ion detecting is, for example, performed of the deviated or separated ions using one or more ion detectors 17.

[0237] In the ion manipulation system or corner element CNR formed including at least two ion manipulation devices that are the first ion manipulation device D1 and the second ion manipulation device D2, the plurality of phase-shifted radiofrequency voltages are, for example, simultaneously applied to the electrodes of the sets of RF electrodes EL of the first ion manipulation device D1 and / or the second ion manipulation device D2 to propulse the ions or to steer the ions through the at least one corner CR or intersection element CIE and into an elongated direction of extension (for example, the Y-direction) of the second ion manipulation device D2.

[0238] A DC voltage source is, for example, operatively connected to the outer boundary electrodes BE1 , BE2 to apply a DC ion confinement electric potential to the outer boundary electrodes BE1 , BE2.

[0239] Interleaved electrode voltages are, for example, provided from the interleaved electrode voltage waveform generator 15 and to the plurality of interleaved electrodes ELIN of the first ion manipulation device D1 and / or the second ion manipulation device D2 to displace ions in the first displacement direction (for example, the X-direction) across the first ion manipulation device D1 and / or to displace ions in the second displacement direction (for example, the Y-direction) across the second ion manipulation device D2. The plurality of phase-shifted radiofrequency voltages are for example simultaneously provided to the radiofrequency electrodes to interact with the ions being displaced in the first displacement direction (X) across the first ion manipulation device D1 to steer the ions through the corner or the corner intersection element (CIE) and into the elongated direction of extension of the second ion manipulation device D2.

[0240] The plurality of phase-shifted radiofrequency voltages may have a positively increasing phase-shift value or a negatively increasing phase-shift value to act on the ions undergoing displacement to steer the ions through the corner CR or the corner intersection element (CIE) and into the elongated direction of extension (Y) of the second ion manipulation device D2.

[0241] It is to be understood that a singular form of a noun corresponding to an item may include one or more of the things, unless the relevant context clearly indicates otherwise. As used herein, "A or B", "at least one of A and B", "at least one of A or B", "A, B or C", "at least one of A, B and C", and "A, B, or C," each of which may include any one of the items listed together in the corresponding one of the phrases, or all possible combinations thereof. Terms such as “first”, “second”, or “first” or “second” may simply be used to distinguish the component from other components in question, and do not limit the components in other aspects (e.g., importance or order). Terms, such as “first”, “second”, and the like, may be used herein to describe various components. Each of these terminologies is not used to define an essence, order or sequence of a corresponding component but used merely to distinguish the corresponding component from other component(s). For example, a "first" component may be referred to as a "second" component, and similarly, the "second" component may be referred to as the "first" component.

[0242] It should be noted that if it is described that one component is "connected", "coupled", or "joined" to another component, at least a third component(s) may be "connected", "coupled", and "joined" between the first and second components. Thus, terms such as “connected” and “coupled” cover both direct and indirectly connections and couplings.

[0243] It will be further understood that the terms "comprises / comprising" and / or "includes / including" when used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or populations thereof.

[0244] The word “about” or “approximately” as used herein means the identified value plus / minus 5%, unless otherwise specified herein.

[0245] “On” as used herein covers both directly on, and indirectly on with intervening element(s) therebetween. Thus, for example, if element A is stated to be “on” element B, this covers element A being directly and / or indirectly on element B. Likewise, “supported by” as used herein covers both in physical contact with, and indirectly supported by with intervening element(s) therebetween.

[0246] Implementations described herein are not intended to limit the scope of the present disclosure but are just provided to illustrate possible or exemplary realizations. While the invention has been disclosed with reference to certain preferred embodiments or to various example embodiments, numerous modifications, alterations, and changes to the described embodiments, and equivalents thereof, are possible without departing from the sphere and scope of the disclosure. Accordingly, it is intended that the invention not be limited to the described embodiments and be given the broadest reasonable interpretation in accordance with the language of the appended claims.

[0247] The features of any one of the above-described embodiments may be included in any other embodiment described herein. Each embodiment herein may be used in combination with any other embodiment(s) described herein.

[0248] REFERENCES

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[0250] [2] Ujma, J.; Giles, K.; Morris, M.; Barran, P. E. New High Resolution Ion Mobility Mass Spectrometer Capable of Measurements of Collision Cross Sections from 150 to 520 K. Anal. Chem. 2016, 88, 9469- 9478, DOI: 10.1021 / acs.analchem.6b01812

[0251] [3] Giles, K.; Pringle, S. D.; Worthington, K. R.; Little, D.; Wildgoose, J. L.; Bateman, R. H. Applications of a Travelling Wave-Based Radio-Frequency-Only Stacked Ring Ion Guide. Rapid Commun. Mass Spectrom. 2004, 18, 2401- 2414, DOI: 10.1002 / rcm.1641

[0252] [4] Giles, K. Travelling wave ion mobility. International Journal for Ion Mobility Spectrometry 2013, 16, 1-3, DOI: 10.1007 / sl 2127-013-0125-5

[0253] [5] Ridgeway, M. E.; Lubeck, M; Jordens, J; Mann, M;, Park, M. A.; Trapped ion mobility spectrometry: A short review. Int J. Mass Spectrom. 2018, 425, 22-35, DOI: 10.1016 / j .ijms.2018.01 .006

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[0012] Warnke, S.; Ben Faleh, A.; Rizzo, T. R.; Toward High-Throughput Cryogenic IR Fingerprinting of Mobility-Separated Glycan Isomers. ACS Meas. Sci. Au 2021 , 1 , 3, 157-164, DOI: 10.1021 / acsmeasuresciau.1c00018

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[0013] Wada, M.; Ishida, Y.; Nakamura, T.; Yamazaki, Y.; Kambara, T.; Ohyama, H.; Kanai, Y.; Kojima, T. M.; Nakai, Y.; Ohshima, N.; Yoshida, A.; Kubo, T.; Matsuo, Y.; Fukuyama, Y.; Okada, K.; Sonoda, T.; Ohtani, S.; Noda, K.; Kawakami, H.; Katayama, I.; Slow Rl-beams from projectile fragment separators. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 2003, 204, 570-581 , DOI: 10.1016 / S0168-583X(02)02151-1

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[0014] Ibrahim, Y. M.; Smith, R. D.; Methods and systems for integrating ion manipulation devices 2018, US10804089B2

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[0015] Robbins, M. D.; Yoon, O. K.; Zuleta, I.; Barbula, G. K.; Zare, R. N.; Computer-controlled, variablefrequency power supply for driving multipole ion guides. Review of Scientific Instruments 79, 2008, 034702, DOI: 10.1063 / 1.2884148

[0264] Each one of the above references being fully incorporated herein by reference. The disclosure of each one is hereby incorporated herein by reference in its entirety for all purposes.

[0265] GOVERNMENT INTERESTS

[0266] This invention was made with U.S. government support under grant No. R01 GM140129 awarded by National Institutes of Health and grant No. 2003042 awarded by National Science Foundation. The U.S. government has certain rights in the invention.

Claims

CLAIMS1 . Ion manipulation device (1 ) for driving ions in a propulsion direction (X) comprising: at least one electrode support (3) for supporting one or more electrodes; at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) comprising a number n of electrodes (EL), wherein the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) comprises at least three electrodes (EL); at least one radiofrequency (RF) voltage generator (9) operatively connected to the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL); wherein the at least one radiofrequency (RF) voltage generator (9) is configured to generate a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3), each consecutive phase-shifted radiofrequency (RF) voltage (PH 1 , PH2, PH3) of the generated plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) being phase-shifted by a value of about 2jt / n or by a value of 2jt / n to both (i) confine ions in a first (Y) and / or second direction (Z) and (ii) to propel ions in the propulsion direction (X) orthogonal or non-parallel to the first (Y) and / or second direction (Z); and wherein the electrodes (EL) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) are operatively connected to the at least one radiofrequency (RF) voltage generator (9) to simultaneously receive the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3).

2. Ion manipulation device (1 ) according to claim 1 , wherein the at least one radiofrequency (RF) voltage generator (9) is configured to simultaneously apply the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to each electrode (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes, each electrode (EL1 , EL2, EL3) simultaneously receiving a radiofrequency (RF) voltage (PH1 , PH2, PH3) that is phase-shifted by a value of 2jt / n or by a value of about 2jt / n with respect to its neighboring electrode (EL1 , EL2, EL3), or with respect to each of its neighboring electrodes (EL1 , EL2, EL3).

3. Ion manipulation device (1 ) according to claim 1 or 2, wherein each electrode (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) comprises an electrode extending in a direction orthogonal to the propulsion direction (X) in which ions are driven.

4. Ion manipulation device (1 ) according to any one of the previous claims, including at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes comprising the number of electrodes n, wherein the electrodes (EL1 , EL2, EL3) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) are operatively connected to the at least one radiofrequency (RF) voltage generator (9) to simultaneously receive the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3).

5. Ion manipulation device (1 ) according to the previous claim, wherein the electrodes (EL1 , EL2, EL3) of the at least one first and second sets (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) are operatively connected to the at least one radiofrequency (RF) voltage generator (9) to simultaneously both receive the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3).

6. Ion manipulation device (1 ) according to claim 4 or 5, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to simultaneously apply the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to each electrode (EL1 , EL2, EL3) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes, each electrode (EL1 , EL2, EL3) simultaneously receiving a radiofrequency (RF) voltage (PH1 , PH2, PH3) that is phase-shifted by a value of 2jt / n or about 2jt / n with respect to its neighboring electrode (EL1 , EL2, EL3), or with respect to each of its neighboring electrodes (EL1 , EL2, EL3).

7. Ion manipulation device (1 ) according to the previous claim, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to simultaneously apply the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to each electrode (EL1 , EL2, EL3) of the at least one first and second set of radiofrequency (RF) electrodes, each electrode of the at least one first and second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) receiving a radiofrequency (RF) voltage (PH1 , PH2, PH3) that is phase- shifted by a value of 2jt / n or about 2jt / n with respect to its neighboring electrode (EL1 , EL2, EL3), or with respect to each of its neighboring electrodes (EL1 , EL2, EL3).

8. Ion manipulation device (1 ) according to any one of the previous clams 4 to 7, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to simultaneously apply radiofrequency (RF) voltages (PH1 , PH2, PH3) of the same phase to a first electrode (EL1 ) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) and to a first electrode (EI1 ) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), and to simultaneously apply radiofrequency (RF) voltages (PH1 , PH2, PH3) having the same phase shift relative to the first electrodes (EL1 ) to a second electrode (EL2) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) and to a second electrode (EL2) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), and to simultaneously apply radiofrequency (RF) voltages (PH1 , PH2, PH3) having the same phase shift relative to the second electrodes (EL2) to a third electrode (EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes and to a third electrode (EL3) of the at least one second set S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), the first (EL1 ), second (EL2) and third (EL3) electrodes being consecutive electrodes (EL1 , EL2, EL3).

9. Ion manipulation device (1 ) according to any one of the previous claims 4 to 8, wherein each electrode (EL1 , EL2, EL3) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) comprises an electrode extending in a direction orthogonal to the propulsion direction (X) in whichions are driven.

10. Ion manipulation device (1) according to any one of the previous claims, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to generate and / or apply a time dependent phase- shifted radiofrequency (RF) electric potential to the electrodes, the time dependent phase-shifted radiofrequency (RF) electric potential being defined by an AC waveform.

11. Ion manipulation device (1 ) according to the previous claim, wherein the AC waveform is in the form of a sine wave, a cosine wave, or a combinations of multiple sine and / or cosine waves, a sawtooth waveform, or a square wave.

12. Ion manipulation device (1) according to any one of the previous claims, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to generate and / or apply a time dependent radiofrequency (RF) electric potentialto the electrodes i, the electric potentialbeing defined by:where U is a DC bias voltage of the RF potentials, V is an amplitude, to = 2nf is the angular frequency with a frequency f, n is the number of electrodes (EL) of the at least one first or second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) to which a phase-shifted RF potential is applied, where n > 3, and i is a positive integer number enumerating consecutive electrodes with i = (1 ... n).

13. Ion manipulation device (1) according to any one of the previous claims, wherein the at least one radiofrequency (RF) voltage generator (9) is configured to generate a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) wherein the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) respectively have a positively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a first propulsion direction (X+); and to generate a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) wherein the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) respectively have a negatively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a second propulsion direction (X-) opposite to the first propulsion direction (X+).

14. Ion manipulation device (1) according to any one of the previous claims 1 to 13, including deviation or separation means configured to displace the ions driven in the propulsion direction (X) or at least a portion of the ions driven in the propulsion direction (X) into at least one deviation direction or separation direction based on ion mobility, the at least one deviation direction and separation direction being different or nonparallel to the propulsion direction (X).

15. Ion manipulation device (1 ) according to any one of the previous claims, including at least one interleaved electrode voltage generator (15) configured to generate one or more interleaved electrode voltages to displace or propel ions into at least one deviation direction or separation direction based on ion mobility, and further including a plurality of interleaved electrodes (ELIN) enclosed by or located between and / or adjacent the radiofrequency (RF) electrodes (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), the plurality of interleaved electrodes (ELIN) being arranged to receive the one or more interleaved electrode voltages to displace ions into the at least one deviation direction or separation direction based on ion mobility, the radiofrequency (RF) electrodes (EL1 , EL2, EL3) and the interleaved electrodes (ELIN) being coupled to at least one surface (SF1 ) of a first electrode support (3A), wherein the ion manipulation device (1 ) further includes:(i) at least one second set of radiofrequency (RF) electrodes (EL’) coupled to at least one surface (SF’, SF2) of a second electrode support (3B), and / or a plurality of interleaved electrodes (ELIN) enclosed by or located between and / or adjacent the radiofrequency (RF) electrodes (EL’) of the at least one second set of radiofrequency (RF) electrodes (EL’); or(ii) a second electrode support (3B) comprising at least one or a plurality of electrodes coupled to at least one surface (SF’, SF2) of the second electrode support (3B), the at least one or a plurality of electrodes being configured and / or arranged to repel ions towards the first electrode support (3A) or towards the at least one surface (SF1 ) of the first electrode support (3A).

16. Ion manipulation device (1 ) according to the previous claim, wherein the at least one surface (SF1 ) of the first electrode support (3A) is located opposite the at least one surface (SF’, SF2) of the second electrode support (3B), or is located in parallel to the at least one surface (SF’, SF2) of the second electrode support (3B); or wherein the at least one surface (SF1 ) of the first electrode support (3B) is located opposite the at least one surface (SF’, SF2) of the second electrode support (3B), or is located in parallel to the at least one surface (SF’, SF2) of the second electrode support (3B) and wherein nominally opposing RF surfaces have the same phase.

17. Ion manipulation device (1 ) according to the previous claim 15 or 16, wherein the one or more interleaved electrode voltages are provided by at least one interleaved electrode voltage waveform generator (15) as a travelling potential wave (TW) configured to generate electric fields to displace or propel ions into the at least one deviation direction or the at least one separation direction, the at least one separation direction or the at least one deviation direction being a direction different to that of the propulsion direction (X); or one or more interleaved electrode voltages are provided by electrostatic potentials configured to generate electric fields to displace or propel ions into the at least one deviation direction or the at least one separation direction, the at least one separation direction or the at least one deviation direction being a direction different to that of the propulsion direction (X).

18. Ion manipulation device (1 ) according to any one of the previous claims 15 to 17, wherein one or more sets (SI1.SI2) of interleaved electrodes (ELIN) are located within or around or between or adjacent the electrodes (EL) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) of the first electrode support (3A), and / or are located within or around or between or adjacent the electrodes (EL’) of the at least one second set of radiofrequency (RF) electrodes (EL’) of the second electrode support (3B), each set (SI1 ,SI2) of interleaved electrodes (ELIN) comprising segmented electrodes (A, B, C, D, F, G, H) to which one or more interleaved electrode voltages are applied to displace or propel ions into the at least one deviation direction or separation direction.

19. Ion manipulation device (1 ) according to any one of the previous claims 1 to 14, including gas flow means configured to displace a portion of the ions driven in the propulsion direction (X) into the at least one separation direction based on ion mobility, the at least one separation direction being a direction different to that of the propulsion direction (X).

20. Ion manipulation device (1 ) according to any one of the previous claims 14 to 19, wherein the ion manipulation device (1 ) is further configured, in addition to displacing ions in the propulsion direction (X), to apply the generated plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to the radiofrequency (RF) electrodes to displace ions into at least one deviation direction or separation direction based on ion mobility, the at least one deviation direction or separation direction being different or nonparallel to the propulsion direction (X).

21. Ion manipulation device (1 ) according to any one of the previous claims 1 to 14, wherein the ion manipulation device (1 ) is further configured, in addition to displacing ions in the propulsion direction (X), to displace ions into at least one deviation direction or separation direction based on ion mobility, the at least one deviation direction or separation direction being different or non-parallel to the propulsion direction (X); and wherein the ion manipulation device (1 ) further includes at least one interleaved electrode voltage generator (15) configured to generate one or more interleaved electrode voltages to displace or propel ions, and further including a plurality of interleaved electrodes (ELIN) within or around or enclosed by or located between and / or adjacent the radiofrequency (RF) electrodes (EL1 , EL2, EL3), the one or more interleaved electrode voltages are provided by the at least one interleaved electrode voltage waveform generator (15) as a travelling potential wave configured to generate electric fields to displace or propel ions; or the one or more interleaved electrode voltages are provided by electrostatic potentials configured to generate electric fields to displace or propel ions, the plurality of phase-shifted radiofrequency (RF) voltages applied to the radiofrequency (RF) electrodes permitting to disperse, into the at least one deviation direction or separation direction, the ions displaced or propelled by the one or more interleaved electrode voltages and provided by the at least one interleaved electrode voltage waveform generator (15), the at least one deviation direction or separation direction beingdifferent or non-parallel to the direction in which the ions are displaced or propelled by the one or more interleaved electrode voltages.

22. Ion manipulation device (1 ) according to any one of the previous claims 1 to 21 , further including one or more ion detectors (17) configured to detect the deviated or separated ions, and / or ions driven in the propulsion direction (X).

23. Ion manipulation device (1 ) according to any one of the previous claims, wherein the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes and / or the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes form a ring-electrode assembly comprising at least three coaxially stacked annular or ring electrodes.

24. Ion manipulation device (1 ) according to any one of the previous claims 1 to 22, wherein the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) is coupled to at least one surface (SF1 ) of a first electrode support (3A), and(i) the ion manipulation device (1 ) further includes at least one second set of radiofrequency (RF) electrodes (EL’) coupled to at least one surface (SF’, SF2) of a second electrode support (3B), or(ii) the ion manipulation device (1 ) further includes a second electrode support (3B) comprising at least one or a plurality of electrodes coupled to at least one surface (SF’, SF2) of the second electrode support (3B), the at least one or a plurality of electrodes being configured and / or arranged to repel ions towards the first electrode support (3A) or towards the at least one surface (SF1 ) of the first electrode support (3A), and the ion manipulation device (1 ) is configured to drive ions in the propulsion direction (X) between the at least one surface (SF1 ) of the first electrode support (3A) and the at least one surface (SF’, SF2) of the second electrode support (3B).

25. Ion manipulation device (1 ) according to the previous claim, wherein the at least one surface (SF1 ) of the first electrode support (3A) is located opposite the at least one surface (SF’, SF2) of the second electrode support (3B), or is located in parallel to the at least one surface (SF’, SF2) of the second electrode support (3B).

26. Ion manipulation device (1 ) according to the previous claim 24 or 25, further including a plurality of interleaved electrodes (ELIN) enclosed by or located between and / or adjacent the electrodes (EL’) of the at least one second set of radiofrequency (RF) electrodes (EL’), the plurality of interleaved electrodes (ELIN) being arranged to receive one or more interleaved electrode voltages to displace ions.

27. Ion manipulation device (1 ) according to any one of the previous claims, wherein the value ofapproximately 2jt / n is a value within ± 20% of 2jt / n.

28. Ion manipulation device (1 ) according to any one of the previous claims, wherein a frequency of the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) is between 400kHz and 5MHz.

29. Ion manipulation device (1 ) according to any one of the previous claims, wherein an amplitude of the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) is between 80V and 500V.

30. Ion manipulation device (1 ) according to any one of the previous claims, including at least one enclosed gas cell in which the ions are displaced by the applied electric fields, wherein the at least one enclosed gas cell has a pressure between O.l mBar and 1000 mBar.

31. Ion manipulation device (1 ) according to any one of the previous claims, wherein the at least one electrode support (3) or each electrode support (3) is formed from an insulating material, or a semiconductor, or a ceramic, or a polymer.

32. Ion manipulation device (1 ) according to any one of the previous claims 1 to 30, wherein the at least one electrode support (3) or each electrode support (3) comprises or consists of a printed circuit board (PCB).

33. Ion manipulation device (1 ) according to any one of the previous claims, wherein in the Ion manipulation device (1 ) is a glycomic or metabololmic ion manipulation device or an inorganic compound manipulation device or a polymer manipulation device or a peptide / protein manipulation device.

34. Ion mobility spectrometry (IMS) system including one or more ion manipulation devices (1 ) according to any one of the previous claims.

35. Mass spectrometer instrument or Field-ion mobility device including one or more ion manipulation devices (1 ) according to any one of the previous claims.

36. Ion manipulation system including a plurality of ion manipulation devices (1 ) according to any one of the previous claims.

37. Ion manipulation system according to the previous claim, wherein the ion manipulation devices (1 ) are arranged to define a cyclic ion-mobility separation device.

38. Ion manipulation system including a first ion manipulation device (D1 ) according to any one of the previous claims 24 to 26, and a second ion manipulation device (D2) according to any one of the previous claims 24 to 26, wherein the sets of radiofrequency (RF) electrodes (EL) (EL’) of the first ion manipulation device (D1 ) are positioned adjacent to the sets of radiofrequency (RF) electrodes (EL) (EL’) of the second ion manipulation device (D2) to define at least one corner or intersection element (CNR),the sets of radiofrequency (RF) electrodes (EL) (EL’) of the first ion manipulation device (D1 ) being positioned non-parallel or substantially perpendicular to the sets of radiofrequency (RF) electrodes of the second ion manipulation device (D2).

39. Ion manipulation system according to the previous claim, including at least one DC voltage source operatively connected to outer boundary electrodes (BE1 , BE2) to apply thereto a DC ion confinement electric potential.

40. Ion manipulation system according to the previous claim 38 or 39, wherein electrodes (EL)(EL’) of the sets of radiofrequency (RF) electrodes (EL)(EL’) of the first ion manipulation device (D1 ) and / or the second ion manipulation device (D2) are operatively connected to the at least one radiofrequency (RF) voltage generator 9 to simultaneously receive the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

41. Ion manipulation system according to the previous claim, wherein the plurality of interleaved electrodes (ELIN) of the first ion manipulation device (D1 ) and / or the second ion manipulation device (D2) are arranged to receive one or more interleaved electrode voltages from at least one interleaved electrode voltage waveform generator (15) to displace ions in a first displacement direction (X) across the first ion manipulation device (D1 ) and / or to displace ions in a second displacement direction (Y) across the second ion manipulation device (D2), and the at least one radiofrequency (RF) voltage generator (9) is configured to simultaneously provide the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to interact with the ions being displaced in the first displacement direction (X) across the first ion manipulation device (D1 ) to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

42. Ion manipulation system according to the previous claim, wherein radiofrequency (RF) electrodes (EL)(EL’) of the first and second ion manipulation devices (D1 , D2) are arranged to simultaneously receive a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) having a positively increasing phase-shift value or a negatively increasing phase-shift value to act on the ions undergoing displacement to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

43. Ion manipulation system according to any one of the previous claims 38 to 42, including a plurality of corner or intersection elements (CNR) arranged to define a cyclic ion-mobility separation system.

44. Ion manipulation system according to the previous claim, wherein the ion manipulation system includesion switching means (21 ) configured to divert ions to at least one exit (23) of the cyclic ion-mobility separation system and to at least one ion detector (17).

45. Ion manipulation system according to any one of the previous claims 36 to 44, wherein the ion manipulation system is a glycomic or metabololmic ion manipulation system, or an inorganic compound manipulation system or a polymer manipulation system or a peptide / protein manipulation system.

46. Ion mobility spectrometry (IMS) system including one or more ion manipulation systems according to any one of the previous claims 36 to 44.

47. Mass spectrometer instrument or Field-ion mobility device including one or more ion manipulation systems according to any one of the previous claims 36 to 44.

48. Ion manipulation method for driving ions in a propulsion direction (X) including the steps of: generating a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3), each consecutive phase-shifted radiofrequency (RF) voltage (PH1 , PH2, PH3) of the generated plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) being phase-shifted by a value of 2jt / n or about 2jt / n to both (i) confine ions in a first (Y) and / or second (Z) direction and (ii) to propulse ions in the propulsion direction (X) orthogonal or non-parallel to the first (Y) and / or second direction (Z), wherein n is a number of electrodes (EL) of a set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL); and applying the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) simultaneously to the electrodes (EL) of at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) to drive ions in the propulsion direction (X).

49. Ion manipulation method according to claim 48, wherein the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) are simultaneously applied to each electrode (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes, each electrode (EL1 , EL2, EL3) simultaneously receiving a radiofrequency (RF) voltage (PH1 , PH2, PH3) that is phase-shifted by a value of 2jt / n or about 2jt / n with respect to its neighboring electrode (EL1 , EL2, EL3), or with respect to each of its neighboring electrodes (EL1 , EL2, EL3).

50. Ion manipulation method according to claim 48 or 40, wherein each electrode (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) comprises an electrode extending in a direction orthogonal to the propulsion direction (X) in which ions are driven.

51. Ion manipulation method according to anyone of claims 48 to 50, further comprising simultaneously applying the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes comprising the number of electrodes n; theelectrodes (EL1 , EL2, EL3) of the at least one first and second sets (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) simultaneously receiving the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3).

52. Ion manipulation method according to the previous claim, wherein the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) are simultaneously applied to each electrode (EL1 , EL2, EL3) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes, each electrode (EL1 , EL2, EL3) receiving a radiofrequency (RF) voltage (PH1 , PH2, PH3) that is phase-shifted by a value of 2jt / n or about 2jt / n with respect to its neighboring electrode (EL1 , EL2, EL3), or with respect to each of its neighboring electrodes (EL1 , EL2, EL3).

53. Ion manipulation method according to any one of the previous claims 51 or 52, wherein radiofrequency (RF) voltages (PH1 , PH2, PH3) of the same phase are simultaneously applied to a first electrode (EL1 ) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) and to a first electrode (EL1 ) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), and radiofrequency (RF) voltages (PH1 , PH2, PH3) having the same phase shift relative to the first electrodes (EI1 ) are simultaneously applied to a second electrode (EL2) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) and to a second electrode (EL2) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), and radiofrequency (RF) voltages (PH1 , PH2, PH3) having the same phase shift relative to the second electrodes (EL2) are simultaneously applied to a third electrode (EL3) of the at least one first set (S1 , S2,53. S4, S5) of radiofrequency (RF) electrodes and to a third electrode (EL3) of the at least one second set S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3), the first (EL1 ), second (EL2) and third (EL3) electrodes being consecutive electrodes (EL1 , EL2, EL3).

54. Ion manipulation method according to any one of the previous claims 51 to 53, wherein each electrode (EL1 , EL2, EL3) of the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) comprises an electrode extending in a direction orthogonal to the propulsion direction (X) in which ions are driven.

55. Ion manipulation method according to any one of the previous claims 48 to 54, wherein each of the generated plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) are defined by a time dependent phase-shifted radiofrequency (RF) electric potential that is defined by an AC waveform.

56. Ion manipulation method according to the previous claim, wherein the AC waveform is in the form of a sine wave, a cosine wave, or a combinations of multiple sine and / or cosine waves, or a sawtooth waveform, or a square wave.

57. Ion manipulation method according to any one of the previous claims 48 to 56, wherein the generated plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) are defined by a time dependent radiofrequency (RF) electric potential n i(t) applied to the electrodes i, the electric potential <Pn i(t) being defined by:where U is a DC bias voltage of the RF potentials, V is an amplitude, to = 2nf is the angular frequency with a frequency f, n is the number of electrodes (EL) of the at least one first or second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) to which a phase-shifted RF potential is applied, where n > 3, and i is a positive integer number enumerating consecutive electrodes with i = (1 ... n).

58. Ion manipulation method according to any one of the previous claims 48 to 57, wherein the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) respectively have a positively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a first propulsion direction (X+); and / or the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) respectively have a negatively increasing phase-shift value to create an effective potential to both repel ions from the RF electrodes and to displace ions in a second propulsion direction (X-) opposite to the first propulsion direction (X+).

59. Ion manipulation method according to any one of the previous claims 48 to 58, further including displacing the ions driven in the propulsion direction (X) or at least a portion of the ions driven in the propulsion direction (X) into at least one deviation direction or separation direction based on ion mobility, the at least one deviation direction and separation direction being different or non-parallel to the propulsion direction (X).

60. Ion manipulation method according to any one of the previous claims 48 to 59, further including:- generating one or more interleaved electrode voltages to displace or propel ions into at least one deviation direction or separation direction based on ion mobility, and- applying the one or more interleaved electrode voltages to a plurality of interleaved electrodes (ELIN) located between and / or adjacent the electrodes (EL1 , EL2, EL3) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL1 , EL2, EL3) to displace ions into the at least one deviation direction or separation direction based on ion mobility.61 . Ion manipulation method according to the previous claim, wherein the one or more interleaved electrode voltages are provided by at least one interleaved electrode voltage waveform generator (15) as a travelling potential wave configured to generate electric fields to displace or propel ions into the at least one deviationdirection or separation direction, the at least one separation or deviation direction being a direction different to that of the propulsion direction (X); or the one or more interleaved electrode voltages are provided by electrostatic potentials configured to generate electric fields to displace or propel ions into the at least one deviation direction or separation direction, the at least one separation or deviation direction being a direction different to that of the propulsion direction (X).

62. Ion manipulation method according to the previous claim 60 or 61 , wherein one or more sets (SI1 ,SI2) of interleaved electrodes (ELIN) are located enclosed by or between or adjacent the electrodes (EL) of the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) and / or are located enclosed by or between or adjacent the electrodes (EL’) of the at least one second set of radiofrequency (RF) electrodes (EL’), each set (S11 ,SI2) of interleaved electrodes (ELIN) comprising segmented electrodes (A, B, C, D, F, G, H) to which one or more interleaved electrode voltages are applied to displace or propel ions into the at least one deviation direction or separation direction.

63. Ion manipulation method according to any one of the previous claims 48 to 62, including applying a gas flow to displace a portion of the ions driven in the propulsion direction (X) into the at least one separation direction based on ion mobility.

64. Ion manipulation method according to any one of the previous claims 48 to 63, further including applying the plurality of generated phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to the radiofrequency (RF) electrodes to displace ions into at least one deviation direction or separation direction based on ion mobility, the at least one deviation direction or separation direction being different or non-parallel to the propulsion direction (X).

65. Ion manipulation method according to any one of the previous claims 48 to 64, further including detecting, using one or more ion detectors, the deviated or separated ions, and / or ions driven in the propulsion direction (X).

66. Ion manipulation method according to any one of the previous claims 48 to 65, wherein the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes and / or the at least one second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes form a ring-electrode assembly comprising at least three coaxially stacked annular or ring electrodes.

67. Ion manipulation method according to any one of the previous claims 48 to 66, wherein the at least one first set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL) are coupled to at least one surface (SF) of a first electrode support (3A), and either (i) at least one second set of radiofrequency (RF) electrodes (EL’) are coupled to at least one surface (SF’, SF2) of a second electrode support (3B) to form an ion manipulation device comprising the first and second electrode supports (3A, 3B), or (ii) a second electrode support (3B) is provided comprising at leastone or a plurality of electrodes coupled to at least one surface (SF’, SF2) of the second electrode support (3B), the at least one or a plurality of electrodes being configured and / or arranged to repel ions towards the first electrode support (3A) or towards the at least one surface (SF) of the first electrode support (3A) to form an ion manipulation device comprising the first and second electrode supports (3A,3B), and the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) are applied simultaneously to drive ions in the propulsion direction (X) between the at least one surface (SF) of the first electrode support (3A) and the at least one surface (SF’, SF2) of the second electrode support (3B).

68. Ion manipulation method according to the previous claim, wherein the at least one surface (SF) of the first electrode support (3A) is located opposite the at least one surface (SF’, SF2) of the second electrode support (3B), or is located in parallel to the at least one surface (SF’, 3B) of the second electrode support (3B).

69. Ion manipulation method according to the previous claim 67 or 68, wherein a plurality of interleaved electrodes (ELIN) are located enclosed by or between and / or adjacent the electrodes (EL’) of the at least one second set of radiofrequency (RF) electrodes (EL’), the plurality of interleaved electrodes (ELIN) being arranged to receive one or more interleaved electrode voltages to displace ions.

70. Ion manipulation method according to any one of the previous claims 67 to 69, wherein an ion manipulation system is formed including at least two ion manipulation devices that are the first ion manipulation device (D1 ) and the second ion manipulation device (D2), wherein the sets of radiofrequency (RF) electrodes (EL) (EL’) of the first ion manipulation device (D1 ) are positioned adjacent to the sets of radiofrequency (RF) electrodes (EL) (EL’) of the second ion manipulation device (D2) to define at least one corner or intersection element (CNR), the sets of radiofrequency (RF) electrodes (EL) (EL’) of the first ion manipulation device (D1 ) being positioned non-parallel or substantially perpendicular to the sets of radiofrequency (RF) electrodes of the second ion manipulation device (D2).

71. Ion manipulation method according to the previous claim, wherein at least one DC voltage source is operatively connected to outer boundary electrodes (EL)(EL’) to apply thereto a DC ion confinement electric potential.

72. Ion manipulation method according to the previous claim 70 or 71 , including simultaneously applying the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to the electrodes (EL)(EL’) of the sets of radiofrequency (RF) electrodes (EL)(EL’) of the first ion manipulation device (D1 ) and / or the second ion manipulation device (D2) to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

73. Ion manipulation method according to any one of the previous claims 70 to 72, including providing one or more interleaved electrode voltages from at least one interleaved electrode voltage waveform generator (15) to the plurality of interleaved electrodes (ELIN) of the first ion manipulation device (D1 ) and / or the second ion manipulation device (D2) to displace ions in a first displacement direction (X) across the first ion manipulation device (D1 ) and / or to displace ions in a second displacement direction (Y) across the second ion manipulation device (D2), and simultaneously providing the plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) to the radiofrequency (RF) electrodes to interact with the ions being displaced in the first displacement direction (X) across the first ion manipulation device (D1 ) to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

74. Ion manipulation method according to any one of the previous claims 70 to 73, wherein radiofrequency (RF) electrodes of the first and second ion manipulation devices (D1 , D2) are arranged to simultaneously receive a plurality of phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) having a positively increasing phase-shift value or a negatively increasing phase-shift value to act on the ions undergoing displacement to steer the ions through the at least one corner or intersection element (CNR) and into an elongated direction of extension (Y) of the second ion manipulation device (D2).

75. Ion manipulation method according to any one of the previous claims 70 to 74, wherein a plurality of corner or intersection elements (CNR) are arranged to define a cyclic ion-mobility separation system, and the ion manipulation method includes activating an ion switching means (21 ) to divert ions to at least one exit (23) of the cyclic ion-mobility separation system and to at least one ion detector (17).

76. Ion manipulation method including the steps of: providing at least one ion manipulation device (1 ) according to any one of the previous claims 1 to 35, or at least one ion manipulation system according to any one of the previous claims 35 to 47; and applying, to the at least one first set (S1 , S2, S3, S4, S5) and / or second set (S1 , S2, S3, S4, S5) of radiofrequency (RF) electrodes (EL), the plurality of phase-shifted radiofrequency (RF) voltages to drive ions in a propulsion direction (X).

77. Ion manipulation method according to any one of the previous claims 48 to 76, wherein the value of approximately 2jt / n is a value within ± 20% of 2jt / n.

78. Ion manipulation method according to any one of the previous claims 48 to 77, wherein a frequency of the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) is between (i) 400kHz and (ii) 5MHz.

79. Ion manipulation method according to any one of the previous claims 48 to 78, wherein an amplitude of the phase-shifted radiofrequency (RF) voltages (PH1 , PH2, PH3) is between (i) 80V and (ii) 500V.

80. Ion manipulation method according to any one of the previous claims 48 to 79, including at least one enclosed gas cell in which the ions are displaced by the applied electric fields, wherein the at least one enclosed gas cell has a pressure between O.l mBar and 1000 mBar.81 . Ion manipulation method according to any one of the previous claims 48 to 80, wherein the at least one electrode support (3) or each electrode support (3) is formed from an insulating material, or a semiconductor, or a ceramic, or a polymer.

82. Ion manipulation method according to any one of the previous claims 48 to 81 , wherein the at least one electrode support (3) or each electrode support (3) comprises or consists of a printed circuit board (PCB).

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