[0001] This application is a continuation-in-part of U.S. Application No. 14/292,448, filed May 30, 2014, which is a continuation-in-part of U.S. Application No. 14/146,922, filed January 3, 2014, now issued as U.S. Pat. No. 8,835,839, which claims the benefit of U.S. Provisional Application No. 61/809,660, filed April 8, 2013, and U.S. Application No. 14/528,917, filed October 30, 2014, the disclosures of which are hereby incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] The invention was made with Government support under Contract DE-AC05- 76RLO I 830, awarded by the U.S. Department of Energy. The Government has certain rights in the invention.

TECHNICAL FIELD

[0003] This invention relates to ion manipulations in gases. More specifically, this invention relates to the use of RF and/or DC fields to manipulate ions through electrodes, and building complex sequences of such manipulations in devices that include one or more such surfaces and structures built upon the surfaces. BACKGROUND OF THE INVENTION

[0004| As the roles for mass spectrometry and other technologies that involve the use, manipulation or analysis of ions continue to expand, new opportunities can become limited by approaches currently used for extended sequences of ion manipulations, including their transport through regions of elevated pressure, reaction (both ion-molecule and ion-ion), and ion mobility separations. As such manipulations become more sophisticated, conventional instrument designs and ion optic approaches become increasingly impractical, expensive and/or inefficient.

SUMMARY OF THE INVENTION

[0005] The present invention is directed to devices and methods of manipulating ions in gases. In one embodiment, an ion manipulation device is disclosed that is essentially lossless and allows extended sequences of ion manipulations. The device includes a pair of surfaces and in which a pseudopotential is formed that inhibits charged particles from approaching either of the surfaces, and the simultaneous application of DC potentials to control and restrict movement of ions between the surfaces.

[0006] in one implementation this involves two substantially or identical surfaces that have an inner array of electrodes, surrounded by a first outer array of electrodes and a second outer array of electrodes. Each outer array of electrodes is positioned on either side of the inner electrodes and contained within - and extending substantially along the length of - each parallel surface in a fashion similar to the inner array of electrodes. The DC potentials are applied to the first and second outer array of electrodes. The RF potentials, with a superimposed electric field, are applied to the array of inner electrodes.

[0007] The superimposed electric field may be a static or dynamic electric field. The static electric field may be, but is not limited to, a DC gradient. The dynamic electric field may be, but is not limited to, a traveling wave. [0008] in one embodiment, the electrode arrangements on the two surfaces are identical, such that similar or identical voltages are applied to both. However, the exact arrangement of electrodes can differ, and the precise voltages applied to the two facing surfaces can also differ.

[0009] The pair of surfaces may be substantially planar, substantially parallel or parallel, or not flat.

[0010] in one embodiment, the RF potentials are applied along with the DC potentials on the first and second outer electrode arrays. In another embodiment, the RF potentials are applied to only one of the two surfaces, in another embodiment, the RF potentials are applied to both of the surfaces.

[0011] in one embodiment, the electric field in all or a portion of the device may be replaced with a gas flow to move ions in the direction of the gas flow.

[0012] In one embodiment, the RF on at least one inner electrode is out of phase with its neighboring inner electrode. In one embodiment the RF on each electrode is phase shifted with its neighboring inner electrode to form a repulsive pseudopotential. In one embodiment, the RF on each electrode is approximately 180 degrees out of phase with its neighboring inner electrode to form the pseudopotential.

[0013] In one embodiment, the array of inner electrodes comprises at least two electrodes on the pair of surfaces. In another embodiment, the first outer array of electrodes and the second outer array of electrodes each comprise at least two electrodes on the pair of surfaces. The device can include insulating material or resistive material between the electrodes.

[0014] The RF voltage applied to the electrodes is between 0.1 kHz and 50 MHz, the electric field is between 0 and 5000 volts/mm, and operating pressures from less than 10 ^-3 torr to approximately atmospheric pressure or higher. [0015] In one embodiment, the electrodes are perpendicular to at least one of the surfaces. In an alternative embodiment, the electrodes are parallel to at least one of the surfaces. The electrodes may comprise a thin conductive layer on the surfaces.

[0016] In certain embodiments, the device comprises multiple pairs of surfaces and allows transfer of the ions through an aperture to move between different pairs of surfaces.

[0017] The electrodes on the pair of surfaces may form one or more different configurations. These configurations include, but are not limited to, the following: a substantially T-shaped configuration, allow ing ions to be switched at a junction of the T- shaped configuration; a substantially Y-shaped configuration, allow ing ions to be switched at a junction of the Y-shaped configuration; a substantially X-shaped or cross-shaped configuration, allowing ions to be switched at a junction of one or more sides of the X-shaped or cross-shaped configuration; and/or a substantially multidirectional shape, such as an asterisk (*) - shaped configuration, with multiple junction points, allowing ions to be switched at a junction to one or more sides of the configuration.

[0018] In one embodiment, the electric field allows the ions to move in a circular-shaped path, rectangular-shaped path, or other irregular path, to allow the ions to make more than one transit and, as one example, achieve higher resolution ion mobility separations.

[0019] The space between the surfaces may be filled with an inert gas or a gas that ions react with ions.

[0020] Stacks of cyclotron stages may be used with the device to, for example, allow different ranges of ion mobilities to be separated in different cyclotron stages, and in sum cover the entire range of ions in a mixture.

[0021] The electric fields can be increased to cause ions to react or dissociate.

[0022] The device may be coupled to at least one of the following: a charge detector, an optical detector, and/or a mass spectrometer. [0023] In one embodiment, the device can be fabricated and assembled using printed circuit board technology and interfaced with a mass spectrometer.

[0024] The device can be used to perform ion mobility separations and/or differential ion mobility separations (e.g., FAIMS).

[0025] Ions may be formed outside or inside the device using photoionization. Corona discharge, laser ionization, electron impact, field ionization, e!ectrospray, or any other ionization technique that generates ions to be used with the device.

[0026] In another embodiment of the present invention, an ion manipulation device is disclosed. The device includes a pair of substantially parallel surfaces. The device further includes an array of inner electrodes contained within, and extending substantially along the length of, each parallel surface. The device also includes a first outer array of electrodes and a second outer array of electrodes, each positioned on either side of the inner electrodes, contained within, and extending substantially along the length of, each parallel surface, wherein a pseudopotential is formed that inhibits charged particles from approaching either of the parallel surfaces. The device also includes a RF voltage source and DC voltage sources, wherein a first DC voltage source is applied to the first and second outer array of electrodes and wherein a RF frequency, with a superimposed electric field, is applied to the inner electrodes by applying a second DC voltage to each electrode, such that ions move between the parallel surfaces within an ion confinement area in the direction of the electric field or can be trapped in the ion confinement area.

[0027] In one embodiment, the RF frequency applied to the electrodes is between 0.1 kHz and 50 MHz. The RF peak-to-peak voltage is approximately 10 to 2000 volts. The electric field is between about 0 and about 5000 volts/mm, and the pressure is between 10 ^-3 torr and atmospheric pressure. [0028] In one embodiment, one or more of the electrodes has 0.5 to 10 mm relief from the surface, so that degradation of device performance due to charging of the surfaces between electrodes is prevented.

[0029] in another embodiment of the present invention, a method of manipulating ions is disclosed. The method includes injecting ions between a pair of substantially parallel surfaces, wherein each pair of parallel surfaces contains an array of inner electrodes and a first and second array of outer electrodes on either side of the inner electrodes. The method further includes applying RF fields to confine the ions between the surfaces. The method also includes applying a first DC field to the outer electrodes equal to or higher than a second DC field applied to the inner electrodes to confine ions laterally. The method also includes superimposing the second DC field on the RF field to further confine and move the ions along in a direction set by the electric field.

[0030] In one embodiment, the method further includes transferring the ions through an aperture in at least one of the pairs of parallel surfaces, wherein the ions travel to between another pair of parallel surfaces.

[0031] In another embodiment of the present invention, an ion manipulation device is disclosed. The device includes multiple pairs of substantially parallel surfaces. The device further includes an array of inner electrodes contained within, and extending substantially along the length of, each parallel surface. The device also includes a plurality of outer arrays of electrodes, w herein at least one outer array of electrodes is positioned on either side of the inner electrodes. Each outer array is contained within and extends substantially along the length of each parallel surface, forming a potential that can inhibit ions moving in the direction of the outer array of electrodes, and which works in conjunction with a pseudopotential created by potentials applied to the inner array of electrodes that inhibits charged particles from approaching either of the parallel surfaces. The dev ice also includes a RF voltage source and a DC voltage source. A DC voltage is applied to the plurality of outer arrays of electrodes. The RF voltage, with a DC superimposed electric field, is applied to the inner electrodes by applying the DC voltage to each electrode, such that ions will move between the parallel surfaces within an ion confinement area in the direction of the electric field or have their motion confined to a specific area such that they are trapped in the ion confinement area. Transfer of the ions to another pair of parallel surfaces or through multiple pairs of parallel surfaces is allowed through an aperture in one or more of the surfaces.

[0032] In another embodiment of the present invention, the electrodes have significant relief from the surfaces. Regions of such relief can be used to alter the electric fields, or also to prevent effects due to charging of nonconductive regions between electrodes. Such designs have particular value in regions where ion confinement is imperfect, such as in reaction regions where ion-molecule or ion-ion reactions result in ion products that have m/z values either too high or too low for effective ion confinement. In such cases just the reaction regions may require electrodes that extend from the surfaces, and in such cases these regions may have different, often larger, spacing between the two surfaces.

[0033] In another embodiment of the present invention RF potentials having two or more distinct frequencies and different electric fields are co-applied to the arrays of electrodes on the two surfaces and with a pattern of application that creates a pseudopotential that inhibits charged particles from approaching one or both of the substantially parallel surfaces over a substantially greater m/z range than would be feasible with RF potentials of a single frequency.

[0034] In another embodiment of the present invention, each central or inner electrode is replaced by two or more electrodes with adjacent electrodes having different phase of the RF applied such that the traps formed for ions close to one of the surfaces are substantially reduced, resulting in improved performance such as a reduction of possible trapping effects or reduction in the m/z range that can be transmitted, particularly when ion currents near the upper limit are being transmitted. [0035] In another embodiment of the present invention, an ion manipulation device with electrical breakdown protection is disclosed. The device includes a pair of surfaces including an ion inlet and an ion outlet. The device also includes arrays of electrodes coupled to the surfaces to which RF potentials are applied to at least one of the surfaces in order to create a pseudopotential that inhibits charged particles from approaching the surfaces. The device further includes simultaneous application of DC potentials to control and restrict movement of ions in between each pair of surfaces, wherein the surfaces are housed in a chamber. At least one electrically insulative shield is coupled to an inner surface of the chamber for increasing a mean-free path between two adjacent electrodes in the chamber. The ion manipulation device can be, but is not limited to. an ion mobility cyclotron device.

[0036] In one embodiment, the at least one insulative shield includes a first insulative shield enclosing at least a part of the inlet and a second insulative shield enclosing at least a part of the outlet. The first insulative and the second insulative shield may be made of, but not limited, to Teflon, polyether ether ketone (PEEK), or polycarbonate.

[0037] In another embodiment, the inner surface is a side plate, and the at least one insulative shield is coupled to the plate via a sealing member.

[0038] The sealing member is. but not limited to. an O-ring. adhesive, or sealant, and the at least one insulative shield includes electrical feedthrough housing.

[0039] In one embodiment, the device includes a plurality of ion manipulation devices.

[0040] The device with electrical breakdown protection can include a first insulation plate between each ion device inside of the chamber. The first insulation plate is made of, but not limited to, ceramic. Teflon, fiberglass, PEEK, or polycarbonate.

[0041] The device with electrical breakdown protection can include a top cover located above a top ion device in the chamber, and a bottom cover located below a bottom ion device. The top cover may include bolt holes for sealing purposes, and the bottom lid may include a metal plate with an insulation plate embedded on the metal plate. [0042] In one embodiment, an inlet of each device is coupled to an ion source, and an outlet of each device is coupled to a mass spectrometer. The ion source may be, but is not limited to, an ion funnel or a dual ion funnel.

[0043] in another embodiment of the present invention, an ion manipulation device with electrical breakdown protection is disclosed. The device includes a pair of surfaces including an ion inlet and an ion outlet. The device also includes arrays of electrodes coupled to the surfaces to which RF potentials are applied to at least one of the surfaces in order to create a pseudopotential that inhibits charged particles from approaching the surfaces. The device further includes simultaneous application of DC potentials to control and restrict movement of ions in between each pair of surfaces, wherein the surfaces are housed in a chamber. At least one electrically insulative shield is coupled to a side plate of the chamber via a sealing member for increasing a mean-free-path between two adjacent electrodes in the chamber.

[0044] In another embodiment of the present invention, an ion manipulation device with electrical breakdown protection is disclosed. The device includes a pair of surfaces including an ion inlet and an ion outlet. The device also includes arrays of electrodes coupled to the surfaces to which RF potentials are applied to at least one of the surfaces in order to create a pseudopotential that inhibits charged particles from approaching the surfaces. The device further includes simultaneous application of DC potentials to control and restrict movement of ions in between each pair of surfaces, wherein the surfaces are housed in a chamber. A first insulative shield encloses at least part of the inlet and a second insulative shield encloses at least a part of the outlet.

[0045] In another embodiment of the present invention, an ion manipulation device with electrical breakdow n protection is disclosed. The device includes a pair of surfaces including an ion inlet and an ion outlet. The device also includes arrays of electrodes coupled to the surfaces to which RF potentials are applied to at least one of the surfaces in order to create a pseudopotential that inhibits charged particles from approaching the surfaces. The device further includes simultaneous application of DC potentials to control and restrict movement of ions in between each pair of surfaces, wherein the surfaces are housed in a chamber. The device also includes a plurality of insulative shields for increasing a mean-free-path between two adjacent electrodes in the chamber, wherein the plurality of shields includes: i. one or more inner surface insulative shields coupled to one or more side plates of the chamber; and one or more inlet and outlet insulative shields, wherein the inlet insulative shield encloses at least a part of the inlet, and the outlet insulative shield encloses at least a part of the outlet.

[0046] In another embodiment of the present invention, an ion manipulation device to prevent loss of ions is disclosed. The device includes a pair of surfaces and an inner array of electrodes coupled to the surfaces. The device also includes a RF voltage and a DC voltage. The RF and DC voltages are alternately applied to the inner array of electrodes. The applied RF voltage is alternately positive and negative so that immediately adjacent or nearest neighbor RF applied electrodes are supplied with RF signals that are approximately 180 degrees out of phase.

[0047] In one embodiment, the device includes a first outer electrode array coupled to the surface and positioned on one side of the inner array of electrodes, and a second outer electrode array coupled to the surface and positioned on the other side of the inner array of electrodes. A second DC voltage is applied to the first and second outer electrode arrays.

[0048] The device can include multiple pairs of surfaces, wherein transfer of the ions is allowed through an aperture and guided by a series of electrodes to move between different pairs of surfaces of the multiple pairs of surfaces.

[0049] The DC voltage may be a static or a time-varying DC voltage. In one embodiment, the time-varying DC voltage is a traveling wave voltage.

[0050] In one embodiment, the pair of surfaces is a pair of substantially parallel surfaces. [0051] In one embodiment, the array of inner electrodes is contained within and extends substantially along the length of each surface. In one embodiment, the arrays of outer electrodes are contained within and extend substantially along the length of each surface.

[0052] In another embodiment of the present invention, a method of manipulating ions is disclosed. The method includes injecting ions between a pair of surfaces. Each pair of surfaces contains an array of inner electrodes. The method also includes applying a RF voltage and a DC voltage alternately to the inner array of electrodes. The applied RF voltage is alternately positive and negative so that immediately adjacent or nearest neighbor RF applied electrodes are supplied with RF signals that are approximately 180 degrees out of phase.

[0053] In another embodiment of the present invention, an ion manipulation device to prevent loss of ions is disclosed. The device includes a pair of surfaces and an inner array of electrodes coupled to the surfaces. The device also includes a RF voltage applied to only one of the surfaces and a DC voltage applied to only the other surface. In one embodiment, the device includes first outer electrode array coupled to the surface and positioned on one side of the inner array of electrodes, and a second outer electrode array coupled to the surface and positioned on the other side of the inner array of electrodes, wherein a second DC voltage is applied to the first and second outer electrode arrays.

[0054] In another embodiment of the present invention, a method of manipulating ions is disclosed. The method includes injecting ions between a pair of surfaces, wherein each pair of surfaces contains an array of inner electrodes. The method also includes applying a RF voltage to only one of the surfaces and a DC voltage to only the other surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] Figure 1 A is a schematic of a portion of an individual parallel surface containing an arrangement of electrodes for an ion manipulation device, in accordance with one embodiment of the present invention.

[0056] Figure 1 B is a schematic of a portion of an ion manipulation device, in accordance with one embodiment of the present invention.

[0057] Figure 2 is a schematic of a portion of an individual parallel surface containing an arrangement of electrodes, and also showing an ion confinement area, for an ion manipulation device, in accordance with one embodiment of the present invention.

[0058] Figure 3A is a schematic of an individual parallel surface containing an arrangement of electrodes for an ion manipulation device, in accordance with one embodiment of the present invention.

[00591 Figure 3B is a schematic of an ion manipulation dev ice, in accordance with one embodiment of the present invention.

[0060] Figure 4A is a schematic of an ion manipulation device, in accordance w ith one embodiment of the present invention.

[0061] Figure 4B shows where the ions will be confined when DC and RF potentials are applied to the device of Figure 4 A, in accordance w ith one embodiment of the present invention.

[0062] Figures 5A, 5B, and 5C show simulations for an ion switch in a T-shaped configuration of an ion manipulation device, in accordance with one embodiment of the present invention.

[0063] Figure 6 shows dual polarity trapping regions for ion -ion reactions in an ion manipulation device, in accordance with one embodiment of the present invention. [0064] Figure 7 shows simulations of an ion switch in an "elevator' configuration where ions are transferred through one or more apertures to move between different pairs of parallel surfaces in an ion manipulation device, in accordance with one embodiment of the present invention.

[0065] Figure 8 shows simulations of an ion switch in an "elevator" configuration having multiple levels where ions are transferred through one or more apertures to move between different pairs of parallel surfaces in an ion manipulation device, in accordance with one embodiment of the present invention.

[0066] Figure 9 shows an ion manipulation device implemented as an ion mobility cyclotron for high resolution separations, in accordance with one embodiment of the present invention.

[0067] Figure 10 shows an ion mobility device coupled between an array of ion sources and an array of mass spectrometer devices, in accordance with one embodiment of the present invention.

[0068] Figure 1 1 shows one example of an electrical interface for an ion manipulation device in a chamber, including a side lid, electrical insulation housings and electrical feedthroughs, in accordance with one embodiment of the present invention.

[0069] Figure 12 shows one example of an insulation shield coupled to inlet and outlet openings of an ion manipulation device inside of a chamber, in accordance with one embodiment of the present invention.

[0070] Figure 13 shows a plurality of vacuum chambers arranged in a stack for housing one or more ion manipulation devices, in accordance with one embodiment of the present invention.

[0071] Figures 14 A is a schematic of one surface of an ion manipulation device with RF inner electrodes having widths of approximately 0.9 mm and the gap between the electrodes is approximately 0.7 mm. in accordance with one embodiment of the present invention. [0072] Figure 14B is a schematic of one surface of an ion manipulation device with RF inner electrodes, similar to Figure 14A, having larger widths and a narrower gap between the electrodes, in accordance with one embodiment of the present invention.

[0073] Figure 1 5A is a schematic of one surface of an ion manipulation device with alternating RF and DC inner electrodes hav ing similar widths and a gap of approximately 0.3 mm between the electrodes, in accordance with one embodiment of the present invention.

[0074] Figure 15B is a schematic of one surface of an ion manipulation device with alternating RF and DC inner electrodes, similar to Figure 15 A, with the RF electrodes having widths larger than the w idths of the DC electrodes and a gap of approximately 0.2 mm between the electrodes, in accordance with one embodiment of the present invention.

[0075] Figure 15C is a schematic of one surface of an ion manipulation device with alternating RF and DC inner electrodes, similar to Figures 15 A and 15B. with the RF electrodes having widths smaller than the widths of the DC electrodes and a gap of approximately 0.2 mm between the electrodes, in accordance with one embodiment of the present invention.

[0076] Figure 16 shows the effective field, calculated for a range of distances from the midplane (Y=0 mm) to the surface of the device (Y=2.2), with f = 1 MHz, V _RF = 1 00 V _0p , and m/'z = 1000, using the ion manipulation devices of Figure 14A (denoted as "c l ' on the figure), Figure 14B (denoted as 'c2' on the figure), Figure 15A (denoted as 'c3' on the figure). Figure 15B (denoted as 'c4' on the figure), and Figure 15C (denoted as 'c5' on the figure).

[0077) Figures 17 A and 17B show the effective potential z-profiles for various off-board distances 'h' using the ion manipulation device of Figure 14A, with f = 1 MHz, VRF = 100 V _0p , and m/z = 1000. [0078] Figures 18A and 18B show the effective potential profiles along the ion path, z axis, for various off-board distances using the ion manipulation device of Figure 14B, with f = 1 MHZ, VRF = 100 Vop, and m/z = 1000.

[0079] Figures 19A and 19B show the effective potential z-profiles for various off-board distances using the ion manipulation device of Figure 15 A, with f = 1 MHZ, V _RF = 100 Vo _P , and m/z = 1000.

[0080] Figures 20 A and 20B show the effective potential z-profiles for various off-board distances using the ion manipulation device of Figure 15B, with f = 1 MHZ, VRF = 100 V _0p , and m/z = 1000.

[0081] Figures 21A and 21B show the effective potential z-profiles for various off-board distances using the ion manipulation device of Figure 15C, with f = 1 MHZ. V _RF = 100 V _0p , and m/z = 1000.

[0082] Figures 22A and 22B show the DC potential z-pro files for various off-board distances using the ion manipulation device of Figure 15 A, with potential 100 V applied to DC inserts or electrodes.

[0083] Figures 23A and 23 B show the DC potential z-profiles for various off-board distances using the ion manipulation device of Figure 15B, with DC potential 100 V applied to DC inserts or electrodes.

[0084] Figures 24 A and 24B show the DC potential z-profiles for various off-board distances using the ion manipulation device of Figure 15C, with DC potential 100 V applied to DC inserts or electrodes.

[0085] Figure 25 is a schematic of a top and bottom surface of an ion manipulation device with DC only inner electrodes on the top surface and RF only inner electrodes on the bottom surface, in accordance with one embodiment of the present invention.

[0086] Figure 26A is a schematic of the RF only inner electrode surface, similar to the bottom surface of Figure 25, with wider RF electrodes. [0087] Figure 26B is a schematic of the RF only inner electrode surface, similar to Figure 26A, with narrower RF electrodes.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0088] The present invention is directed to devices, apparatuses, and method of manipulating ions. The present invention uses electric fields to create field-defined pathways, traps, and switches to manipulate ions in the gas phase, and with minimal or no losses.- Embodiments of the device enable complex sequences of ion separations, transfers, path switching, and trapping to occur in the space between two surfaces positioned apart and each patterned with conductive electrodes, in one embodiment, the present invention uses the inhomogeneous electric fields created by arrays of closely spaced electrodes to which readily generated peak-to-peak RF voltages (V _p-p ~ 100 V; ~ 1 MHz) are applied with opposite polarity on adjacent electrodes to create effective potential or pseudopotential fields that prevent ions from approaching the surfaces. These ion confining fields result from the combination of RF and DC potentials, with the RF potentials among other roles creating a pseudopotential that prevents loss of ions and charged particles over certain m/z ranges to a surface, and the DC potentials among other roles being used to confine ions to particular defined paths of regions between the two surfaces, or to move ions parallel to the surfaces. The confinement functions over a range of pressures (< 0.001 torr to - 1000 torr), and over a useful, broad, and adjustable mass to charge (m/z) range. Of particular interest is the ability to manipulate ions that can be analyzed by mass spectrometers, and where pressures of <0.1 to ~ 50 torr can be used to readily manipulate ions over a useful m/z range, e.g., m/z 20 to > 5,000. This effective potential works in conjunction with DC potentials applied to side electrodes to prevent ion losses, and allows the creation of ion traps and/or conduits in the gap between the two surfaces for the effectively lossless storage and/or movement of ions as a result of any gradient in the applied DC fields. [0089] In one embodiment, the invention discloses the use of RF and DC fields to manipulate ions. The manipulation includes, but is not limited to, controlling the ion paths, separating ions, reacting ions, as well as trapping and accumulating the ions by the addition of ions to the trapping region(s). The ion manipulation device, which may be referred to as an "ion conveyor" or Structure for Lossless ion Manipulation (SLIM), uses arrays of electrodes on substantially parallel surfaces to control ion motion. Combinations of RF and DC potentials are applied to the electrodes to create paths for ion transfer and ion trapping. The parallel surfaces may be fabricated using, but not limited to, printed circuit board technologies or 3D printing.

[0090] Figure 1 A is a schematic of a portion of an individual parallel surface 100 containing a first and second array of outer electrodes 120 and an array of inner electrodes 330 for an ion manipulation device, in accordance with one embodiment of the present invention. The array of inner electrodes 130 is contained within and extends substantially along the length of the surface 100. The array of outer electrodes 120, positioned on either side of the inner electrodes 130, is also contained within and extends substantially along the length of the surface 100.

[0091] Figure 1 B is a schematic of a portion of an ion manipulation device 200, in accordance with one embodiment of the present invention. The device 200 includes a pair of substantially parallel surfaces 210 and 2 15. Each surface contains an array of inner electrodes 230 and a first and second array of outer electrodes 220. The arrays of outer electrodes 220 are positioned on either side of the array of inner electrodes 230. The arrays of electrodes 220 and 230 are contained within and extend substantially along the length of each parallel surface 210 and 215. The arrangement of electrodes on the opposing surfaces can be identical as well as the electric field applied. Alternately, either the detailed electrode arrangements or the electric fields applied can be different in order to affect ion motion and trapping between the device. [0092] The portion of the device 200 also includes a RF voltage source and DC voltage sources (not shown). In one embodiment, the DC voltages are applied to the first and second outer array of electrodes 220. The RF voltage, of opposite polarity upon adjacent electrodes, with a superimposed DC electric field, is applied to the inner array of electrodes 220. In the arrangement of Figure 2, with the RF and DC fields applied as such, ions either move between the parallel surfaces 210 and 215 within an ion confinement area in the direction of the electric field or can be trapped in the ion confinement area depending on the DC voltages applied.

[0093] in one embodiment, the RF on at least one inner electrode is out of phase with its neighboring inner electrode, in another embodiment, each inner electrode is 180 degrees out of phase with its neighboring inner electrode to form a pseudopoiential that inhibits charged particles from approaching either of the parallel surfaces. In another embodiment each inner electrode is replaced by two or more electrodes to which RF is applied to each and with one or more the electrodes being out of phase with its neighboring inner electrodes.

[0094] The electric field also allows the ions to move in a circular-shaped or a rectangular-shaped path, to allow the ions to make more than one transit. Stacks of cyclotron stages can be used with the device 200. Arrangements with cyclotrons, where the ions traverse a circular path, will allow very high-resolution mobility separations with small physical size.

[0095] In one embodiment, the array of inner electrodes 220 comprises at least two electrodes on the pair of parallel surfaces 210 and 215. The first outer array of electrodes and the second outer array of electrodes 220 may each comprise at least two electrodes on the pair of parallel surfaces 210 and 21 5. [0096] In one embodiment the RF is simultaneously applied with DC potentials to the electrodes 220, and in another embodiment the RF applied to adjacent outer electrodes has opposite polarity.

[0097] In one embodiment the space between the surfaces 210 and 215 may include a gas or otherwise vaporized or dispersed species that ions react with.

[0098] In one embodiment the electrodes 220 are augmented by an additional set of electrodes further displaced from the central electrodes that has DC potentials applied that are opposite in polarity to allow the confinement or separation of ions of opposite polarity.

[0099] The device 200 can be coupled to other devices, apparatuses and systems. These include, but are not limited to, a charge detector, an optical detector, and/or a mass spectrometer. The ion mobility separation possible with the device 200 can be used for enrichment, selection, collection and accumulation over multiple separations of any mobility resolved species.

[00100] The device 200 may be used to perform ion mobility separations.

[00101] In one embodiment, the RF frequency applied to the electrodes 230 is between 0.1 kHz and 50 MHz, and the electric field is between 0 and 5000 volts/mm.

[00102] In one embodiment, the electrodes 220 and 230 are perpendicular to at least one of the surfaces and may comprise a thin conductive layer on the surfaces 210 and 215.

[00103] The device 200 can include multiple pairs of substantially parallel surfaces, allowing transfer of the ions through an aperture to move between diiTerent pairs of parallel surfaces.

[00104] The electrodes on the pair of surfaces 210 and 215 can form one of many different configurations. In one embodiment, the surfaces 2 10 and 215 form a substantially T-shaped configuration, allowing ions to be sw itched at a junction of the T-shaped configuration. In another embodiment, the surfaces 210 and 215 form a substantially Y-shaped configuration, ai!owing ions to be switched at a junction of the Y-shaped configuration. In another embodiment, the surfaces 210 and 21 5 form a substantially X-shaped or cross-shaped configuration, allowing ions to be switched at a junction or one or more sides of the X-shaped configuration. In another embodiment, the surfaces 210 and 215 form a substantially multidirectional shape, such as an asterisk (*)-shaped configuration, with multiple junction points, allowing ions to be switched at a junction to one or more sides of the configuration. Devices may be constituted from any number of such elements.

[00105] The electrodes on the surfaces can have any shape, not being limited to the rectangular shapes such as in Figure 1. For example, the electrodes can be round, have ellipse or oval shapes, or be rectangles with rounded corners.

[00106] Figure 2 is a schematic of an individual parallel surface 300 containing an arrangement of electrodes 320 and 330 with an ion confinement area 340 for an ion manipulation device, in accordance with one embodiment of the present invention. Static DC voltages may be applied to the outer electrodes 320 with RF applied to the inner electrodes 330. Each central electrode can have RF applied out of phase with its neighboring electrode.

[00107] A DC or other electric field is superimposed on the RF and applied to the inner electrodes 330 to move ions through the device of Figure 2, in addition to successively lower voltages applied on each outer electrode 320 - moving from left to right or alternatively from right to left, depending on the polarity and the desired direction of motion. This electric field forces ions to the right, while the RF and DC fields also confine ions to a central region of the device as shown. Voltage polarities can be changed to allow manipulation of both negative and positive ions.

[00108] Figure 3 A is a schematic of an individual parallel surface 400 containing an arrangement of electrodes for an ion manipulation device, in accordance with one embodiment of the present invention. The surface 400 includes electrodes 450 that are individually programmable by a DC voltage, electrodes 430 associated with a negative RF voltage, and electrodes 435 associated with a positive RF voltage - where negative and positive RF refers to the phase of the RF waveform .

[00109] Figure 3B is a schematic of an ion manipulation device 500. in accordance with one embodiment of the present invention. The ion manipulation dev ice 500 includes substantially parallel surfaces 5 10 and 5 15 that are similar to the surface 400 of Figure 3 A. The device 500 includes electrodes 550 that are individually programmable by a DC voltage, electrodes 530 associated with a negative RF voltage, and electrodes 535 associated with a positive RF voltage. In this arrangement, ions are confined between the surfaces 5 10 and 5 15. The ions move in the direction defined by an electric field.

[00110] Figure 4A is a schematic of an ion manipulation device, in accordance with one embodiment of the present invention. The central or inner electrodes hav e RF fields applied with opposite polarity to adjacent electrodes to create fields that prevent ions from closely approaching the surfaces. Ions are moved according to their mobilities under DC fields applied to the outer electrodes.

[00111] Figure 4B shows the trapping volume of ions between the surfaces containing electrodes of an ion manipulation device, in accordance with one embodiment of the present invention. Both positive and negative charged ion particles are confined in overlapping areas of the ion manipulation device. This can be accomplished using multiple arrays of outer electrodes and applying both RF and DC potentials.

[00112] The devices of the present invention provide for at least the following: lossless (a) linear ion transport and mobility separation, (b) ion transport around a corner (e.g., a 90 degree bend), (c) ion switches to direct ions to one of at least two paths, (d) ion elevators for transporting ions between different levels of multilevel ion manipulation devices, (e) ion traps for trapping, accumulation, and reaction of ions of one polarity. These devices can be combined to create a core module for more complex ion manipulation devices such as an ion mobility cyclotron. In one implementation, integrating several modules will allow fabrication of a single level device that will enable the separation of ions over periods on the order of 0.1 to 10 seconds while achieving resolutions of up to approximately 1000 for species over a limited range of mobilities. The range of mobilities, and the fractions of the total biomolecule ion mixture that can be separated, decreases as the resolution is increased. Thus, an ion mobility cyclotron module can provide a useful and targeted separation/analysis capability - where information is desired for a limited subset of species.

[00113] The integrated device can consist of a stack of modules each covering a different portion of the full mobility spectrum. In combination, they provide separations that cover the full range of ion mobilities needed for a sample, while at the same time making efficient use of all the ions from the sample. The integrated device can draw upon the ion switch, elevator, and trap components to provide a low resolution separation that partitions ions from the sample into fractions that are delivered to different cyclotrons using the ion elevator.

[00114] Figures 5A, 5B, and 5C show simulations of an ion switch in a T-shaped configuration of an ion manipulation device, in accordance with one embodiment of the present invention. These ion paths can be controlled using switch elements. As shown in Figures 5A. 5B, and 5C, the ion path can be dynamically or statically changed by modifying the electrode arrangement of the device and/or vary ing the RF and DC voltages. The ions can be switched at a junction as shown in Figure 5A, move in a straight path as shown in Figure 5B, and/or curve or bend around a corner at the junction as shown in Figure 5C.

Alternatively, the pair of parallel surfaces of the device can form other configurations such as, but not limited to, Y-shaped configurations, X-shaped or cross-shaped configurations, and other multidirectional shapes. [00115] Figure 6 shows dual polarity trapping regions for ion -ion reactions in an ion manipulation device, in accordance with one embodiment of the present invention. Different polarity of ions, positive and negative, can be trapped at the same time in at least partially overlapping physical volumes between the two surfaces of the device using multiple sets of electrodes and applying both RF and DC potentials. Additional RF or DC potentials can be applied to heat and excite either the positive or negatively charged ions in order to change the reaction rate or reaction products.

[00116] Figure 7 shows simulations of an ion switch in an "elevator" configuration where ions are transferred through one or more apertures to move between different pairs of parallel surfaces in an ion manipulation dev ice, in accordance with one embodiment of the present invention. This allows multi-dimensional ion manipulation using the ion manipulation device. In some embodiments additional electrodes are added to increase the efficiency of transfer between different levels, including electrodes with DC and/or RF potentials with different polarities on adjacent electrodes.

[00117] Figure 8 shows simulations of an ion switch in an "elevator" configuration having multiple levels where ions are transferred through one or more apertures to move between different pairs of parallel surfaces in an ion manipulation device, in accordance with one embodiment of the present invention.

[00118] Figure 9 is a schematic showing an ion manipulation device implemented as an ion mobility cyclotron. Ions entering from the ion source are initially trapped before a first low resolution separation. Separated ions of interest are trapped and then injected for cyclotron separations, potentially achieving resolutions greater than 1000. The switching points direct ions to one of at least two paths. All four points - the switching points and the bends - are where changes in the rotating DC electric field can be applied to create the cyclotron motions. [001 19] Figure 10 shows an ion mobility dev ice coupled between an array of ion sources and an array of mass spectrometer devices, in accordance with one embodiment of the present invention. As shown in Figure 10, the present invention also enables multiplexed sample analyses using an array of ion sources and multiple ion separations in parallel - separated during travel through the device - and detected using an array of high speed, high dynamic range time-of-flight (TOF) mass spectrometers (MS).

[00120] The pair of surfaces of the ion manipulat ion device can be housed in a vacuum chamber. In one embodiment, at least one electrically insulative shield is coupled to an inner surface of the chamber for increasing a mean-free-path between two adjacent electrodes in the chamber.

[00121] Figure 1 1 shows one example of an electrical interface for an ion manipulation device in a chamber, including a side lid 610, electrical insulation housings 600 and electrical feedthroughs 620, in accordance with one embodiment of the present invention. The side lid is made of a nonconductive material. The bottom or flange side 605 of the electrical insulation housing 600 includes a sealing member to isolate the mean-free-path between adjacent electrodes on the chamber side of t he feedthroughs 620. T he sealing member is, but not limited to, an O-ring, an adhesive, or a sealant. The flange 605 is coupled to the side lid 610 via the sealing member.

[00122] Figure 12 shows one example of an insulation shield 700 coupled to inlet and outlet openings of an ion manipulation device inside of a chamber 710, in accordance with one embodiment of the present invention. The insulation shield 700 is made of. but not limited to, Teflon, PEEK, or polycarbonate.

[00123] Figure 13 shows a plurality of vacuum chambers 810 arranged in a stack 800 for housing one or more ion manipulation devices, in accordance w ith one embodiment of the present invention. Although six chambers are shown in Figure 13, it should be noted that the stack 800 is not limited to any specific number of chambers.

[00124] The chambers 810 include at least one inlet and at least one outlet. The inlet may be coupled to an ion source interface such as, but not limited to, an ion funnel or a dual ion funnel 820. The outlet may be coupled to a mass spectrometer or analyzer directly or indirectly via another ion device 830 for manipulating and/or focusing ions. In the embodiment of Figure 13, the bottom chamber of the stack 800 is coupled through an ion funnel chamber 820 to a mass spectrometer 830 at the outlet. In the inlet, two ion funnel chambers 820 are connected as the ion source interface. One or more of the chambers 810 can include a sensor such as, but not limited to, a pressure sensor.

[00125] Figures 14A is a schematic of one surface of an ion manipulation device 1400 with RF inner electrodes 1420 hav ing widths of approximately 0.9 mm and the gap between the electrodes is approximately 0.7 mm. The surface also includes DC outer electrodes 1410. At least one RF voltage is applied to the RF inner electrodes 1420 and at least one DC voltage is applied to the DC outer electrodes 1410.

[00126] Figure I 4B is a schematic of one surface of an ion manipulation device 1450 with RF inner electrodes 1470. similar to Figure 14A, having larger widths and a narrower gap between the electrodes 1470. The surface also includes DC outer electrodes 1460. As with Figure 14 A, a RF voltage or voltages are applied to the RF inner electrodes 1470 and a DC voltage or voltages are applied to the DC outer electrodes 1460.

[00127] In another embodiment, as shown in Figures 15A-C, RF and DC voltages are alternately applied to the inner array of electrodes, and the applied RF voltage is alternately positive and negative so that immediately adjacent or nearest neighbor RF applied electrodes are supplied with RF signals that are approximately 180 degrees out of phase. [00128] Figure 15 A is a schematic of one surface of an ion manipulation device 1500 with alternating RF inner electrodes 1520 and DC inner electrodes 1530, In this example, the electrodes 1520 and 1530 having similar widths of approximately 0.5 mm and a gap of approximately 0.3 mm between the electrodes 1520 and 1530. The surface also includes outer electrodes 1510 adjacent or positioned on either side of the inner electrodes 1520 and 1530. DC voltages are applied to the outer electrodes 15 10. It should be noted that the widths or diameters of the electrodes, as well as the gap dimensions between each electrode, may vary by length.

[00129] Figure 15B is a schematic of one surface of an ion manipulation device w ith alternating RF inner electrodes 1570 and DC inner electrodes 1575, similar to Figure 15A, with the RF electrodes having widths larger than the widths of the DC electrodes and a gap of approximately 0.2 mm between the electrodes. In this example, the RF electrodes have a width of approximately 0.9 mm, and the DC electrodes have a width of approximately 0.3 mm. The surface also includes outer electrodes 1560 adjacent or positioned on either side of the inner electrodes 1570 and 1575. DC voltages are applied to the outer electrodes 1 560.

[00130] Figure 1 5C is a schematic of one surface of an ion manipulation device 1580 with alternating RF inner electrodes 1592 and DC inner electrodes 1595. similar to Figures 1 5 A and 15B. In this example, the RF electrodes 1592 have w idths smaller than the w idths of the DC electrodes 1595. The width of the RF electrodes 1592 is approximately 0.3 mm. and the width of the DC electrodes 1595 is approximately 0.9 mm. The surface includes a gap of approximately 0.2 mm between each inner electrode 1592 and 1595.

[00131] The ion manipulation device of Figures 15A- 15C may be coupled, but not limited to. a charge detector, an optica! detector, and a mass spectrometer. In one embodiment, the ion manipulation device is used to perform ion mobility separations. [00132] The DC voltages on the inner electrodes of Figures 15 A- 15C is a static or time- varying DC voltage. The time- varying voltage may be a traveling wave voltage.

[00133] The ion manipulation device of Figures 15A-15C includes a pair of surfaces. The pair of surfaces are substantially parallel or substantially planar. In one embodiment, the surfaces are not flat.

[00134] Figure 16 shows the effective field, calculated for a range of distances from the midp!ane (Y= 0 mm) to the surface of the device (Y= 2.2 mm), with f = 1 MHz, VRF = 100 V _0p , and m/z = 1000, using the ion manipulation devices of Figure 14A (denoted as 'el ' on the figure), Figure 14B (denoted as 'c2' on the figure), Figure 15A (denoted as 'c3' on the figure). Figure 15B (denoted as 'c4' on the figure), and Figure 15C (denoted as 'c5' on the figure). An effective field of E _v ~ 100 V/cm was achievable at approximately 1 .6 mm or 0.6 mm from the surface of the ion manipulation device, where y _max is approximately 2.2 mm.

[00135] Figures 17Λ and 17B show the effective potential z-profiles for various off-board distances 'h' using the ion manipulation device of Figure 14A, with f = 1 MHz, VRF = 100 V _0p , and m/z = 1000. Smooth profiles are obtained for h > 0.5 mm.

[00136] Figures 18A and 18B show the effective potential z-profiles for various off-board distances from 0.1 mm to 1 .2 mm using the ion manipulation device of Figure 34B, with f = 1 MHZ, VRF = 100 V _0P , and m/z = 1000.

[00137] Figures 19A and 19B show the effective potential z-profiles for various off-board distances using the ion manipulation device of Figure 15 A, with f = 1 MHZ, VRF = 100 V _0p , and m/z = 1000.

[00138] Figures 20A and 20B show the effective potential z-profiles for various off-board distances using the ion manipulation device of Figure 15B. with f = 1 MHZ, VRF = 100 V _0P , and m/z = 1000. The profiles are close to ideal when h > 0.5 mm. where E _y is >

approximately 100 V/cm. [00139] Figures 2 1 A and 2 1 B show the effective potential z-pro files for various off-board distances using the ion manipulation device of Figure 1 5C, with f = 1 MHZ, VRF = 1 00 V _0p , and m/z = 1 000. in this example, the profiles were less than ideal, as the effective fields were weak.

|00140] Figures 22A and 22B show the DC potential z-profiles for various off-board distances using the ion manipulation device of Figure 15 A, with f = 1 MHZ, V _RF = 100 V _0p , and m/z = 1000. Uniform profiles were obtained at h > 1 .2 mm. with a penetration of 43% of the DC potential into the central volume.

[00141 ] Figures 23A and 23B show the DC potential z-pro files for various off-board distances using the ion manipulation device of Figure 15B, with f = 1 MHZ, VRF = 100 V _0p , and m/z = 1000. The narrower DC electrodes in this example led to a reduced penetration of approximately 27% to the center.

[00142] Figures 24A and 24B show the DC potential z-profiles for various off-board distances using the ion manipulation device of Figure 1 5C, with f = 1 MHZ, VRF = 1 00 V _0p , and m/z = 1 000. The wider DC electrodes in this example led to an increased penetration of approximately 55% to the center.

[00143] Figure 25 is a schematic of a top surface 1 600 and a bottom surface 1650 of an ion manipulation device with DC only inner electrodes 1 620 on the top surface 1 600 and RF only inner electrodes 1 670 on the bottom surface 1 650. The top surface 1 600 includes outer electrodes 1610 on either side of the inner electrodes 1620. Similarly, the bottom surface 1650 also includes outer electrodes 1 660 on either side of the inner electrodes 1 670. In this embodiment or example, a RF voltage is applied to only the inner electrodes 1 670 of the bottom surface 1650, and only a DC voltage is applied to the inner electrodes 1620 of the top surface 1600. It should be noted that the top surface can have "RF only" inner electrodes, while the bottom surface has "DC only" inner electrodes. A DC voltage is applied to the outer electrodes of each surface 1600 and 1650. The DC voltage applied to the outer electrodes may be different or the same voltage applied to the DC only inner electrodes.

[00144| Figure 26A is a schematic of the RF only inner electrode surface 1700, similar to the bottom surface of Figure 25. with wider RF inner electrodes 1720. The surface 1700 also includes a first and second array of outer electrodes 1710. In this example, the RF electrodes or strips 1720 are approximately 0.8 mm wide with approximately 0.4 mm spaces between the strips.

[00145| Figure 26B is a schematic of the RF only inner electrode surface 1750, similar to Figure 26A, with narrower RF electrodes 1770. The surface 1750 also includes a first and second array of outer electrodes 1760. In this example, the RF electrodes or strips 1 770 are approximately 0.4 mm wide with approximately 0.4 mm spaces between the strips.

[00146] The ion manipulation devices, particularly the embodiments shown in Figures 15A-C, 25 and 26, address the need for reduced complexity, control electronics, and expense of power supplies needed to enable complex sequences of ion manipulations. This is mainly- due to the separation of electrodes to which RF and DC voltages are applied.

[00147| The devices also enable the use of longer path length ion mobility separations and/or other manipulations, providing much higher resolutions, as large differences in electric fields are not required - the potential needed for, for example, separations typically increase in proportion with the length of the ion manipulation path. The devices cover the full mobility range, which does not require a limited mobility range as would be required for separations in a cyclotron or other receptive path of limited length. EXAMPLE

[00148| The following examples serve to illustrate certain embodiments and aspects of the present invention and are not to be construed as limiting the scope thereof.

[00149] A device, as shown in Figure IB, was used to manipulate ions injected from an external ESI source. Simulations were performed to refine the design of the device; e.g. electrode sizes and spacing between the planar surfaces were adjusted. Boards were fabricated with electrode regions to test capabilities that included efficient ion transportation, ion mobility separations, ion trapping, and ion switching between alternative corridors or paths.

[00150] In one test, ions were introduced from the external ESI source and injected into one of the ion corridors at a pressure of - 4 torr. RF frequencies of approximately 1.4 MHz and 140 Vp-p were applied to create repulsive fields to confine ions within the ion corridors between the opposing board surfaces. The RF fields were combined with DC for further confinement to the corridors and also to move the ions along the corridors based upon their ion mobilities. Separate electrodes were used to measure ion currents at various locations and evaluate ion transmission efficiency through different areas of the device. Initial measurements showed that ions can be efficiently introduced into such devices, as well as transported through them with minimal losses.

[00151] The device of the present invention, including its various embodiments, can be manufactured at very low cost and is very flexible, allowing application to many different areas in mass spectrometry. As one example, the device can be fabricated and assembled using printed circuit board technology and interfaced with a mass spectrometer. The device can also be lossless. Ion mobility separation and complex ion manipulation strategies can be easily implemented with the device. [00152| The device of the present invention, including its various embodiments, can be altered in its performance by the use of electrodes that have significant thickness and thus substantial relief from one or both of the surfaces. The thickness can vary between electrodes, and individual electrodes can have variable thickness. These electrodes can be used to create electric fields not practical for very thin electrodes (e.g. surface deposited such as on conventional printed circuit boards). Regions of devices with such electrodes have particular value when incomplete or inefficient ion confinement may occur, such as for very low or high m/z ions created by reactions that can provide a well-controlled electric field and prevent degraded performance from distorted electric fields due to the charging of surfaces between electrodes.

[00153] Embodiments of the present invention can improve and extend analysis capabilities in, for example, proteomics, metabolomics, lipidomics, glycomics, as well as their applications to a broad range of biological and chemical measurements and applicable research areas. Utilization of the ion manipulation device can lead to faster, cheaper, and more sensitive measurements relevant to understanding chemical, environmental, or biological systems. The present invention enables MS-based approaches involving complex ion manipulations in the gas phase capable of augmenting or completely displacing conventional liquid phase approaches. The present invention also enables separations and other ion manipulations over extended periods in a nearly lossless fashion. These capabilities lead to very fast and high resolution gas phase separations of ions.

[00154] The present invention has been described in terms of specific embodiments incorporating details to facilitate the understanding of the principles of construct ion and operation of the invention. As such, references herein to specific embodiments and details thereof are not intended to limit the scope of the claims appended hereto. It will be apparent to those skilled in the art that modifications can be made in the embodiments chosen for illustration without departing from the spirit and scope of the invention.