Traveling wave IMS with countercurrent of gas

Abstract

Methods for separating ions, which include: Providing a separation device comprising multiple electrodes; Applying one or more transient DC voltages to at least some of the electrodes to drive ions through the separation device in a first direction; Providing a gas flow in a second direction that is inclined or opposite to the first direction; Performing a first operating mode in which one or more transient DC voltages are traversed along at least a part of the axial length of the separation device at a first speed to cause ions to be separated according to their ion mobilities; and Performing a second mode of operation in which one or more transient DC voltages are traversed along at least a part of the axial length of the separation device at a second speed higher than the first speed in order to cause ions to be separated according to their mass-to-charge ratios; the gas flow is provided during the first and second operating modes.

Description

Background of the present invention

[0001] The present invention relates to an ion separation device.

[0002] Ion mobility spectrometers or ion mobility separators are well-known. One particular well-known ion mobility separator is described in relation to… Fig. 7 of US 6,630,662 B1 (Loboda). The known ion mobility separator comprises a segmented quadrupole ion mobility separator. An axial DC voltage gradient is maintained along the length of the ion mobility separator, and a countercurrent of gas is provided.

[0003] One problem with the known arrangement is that the ion mobility separator is essentially equivalent to a conventional ion mobility separator with a longer drift length. Although the arrangement described in US 6,630,662 Bloffenbart allows for a more compact ion mobility separator, it offers no other improvement.

[0004] US 2009 / 0302209 A1 discloses an ion conductor or mass analyzer at the output of which a pseudo-potential barrier is generated. The depth of the pseudo-potential barrier is inversely proportional to the mass-to-charge ratio of an ion. One or more transient DC voltages are applied to drive ions along the ion conductor, with the amplitude being increased over time to separate ions.

[0005] It is desirable to provide an improved method for separating ions and an improved separation device. Summary of the present invention

[0006] According to a first aspect, the present invention provides a method for separating ions, comprising the following: Providing a separation device comprising multiple electrodes; Applying one or more transient DC voltages or DC potentials to at least some of the electrodes to drive ions through the separation device in a first direction; Providing a gas flow in a second direction that is substantially inclined or opposite to the first direction; Performing a first operating mode in which one or more transient DC voltages are traversed, shifted, or sequentially applied along at least a portion of the axial length of the separation device at a first speed to cause ions to be separated according to their ion mobilities; and Performing a second operating mode in which one or more transient DC voltages are traversed, shifted, or sequentially applied along at least a part of the axial length of the separation device at a second speed higher than the first speed to cause ions to be separated according to their mass-to-charge ratios; wherein the gas flow is provided during the first and second operating modes.

[0007] A particular advantage of the separation device according to the present invention is that the separation device offers improved functionality compared to conventional ion mobility separators such as the ion mobility separator disclosed in US 6 630 662 B1.

[0008] The present invention is particularly advantageous in that the preferred ion separator features improved ion mobility and mass-to-charge ratio separation and can be easily switched between different operating modes. In one operating mode, ions are separated according to their ion mobility (or their collision cross-section), and in another operating mode, ions are separated according to their mass or their mass-to-charge ratio. This is not possible with the arrangement disclosed in US 6,630,662 B1.

[0009] As experts in the field will understand, conventional ion mobility separators using a DC drift tube cannot be operated in a mode where separation depends predominantly on mass or mass-to-charge ratio, because the separation mechanism is fundamentally different compared to traveling-wave ion mobility separators (i.e., devices in which one or more transient DC voltages or DC potentials are applied to the electrodes that form the ion mobility separator).

[0010] A countercurrent of gas is used to provide an ion mobility separator or filter and a mass or mass-to-charge ratio separator or filter capable of separating ions over time, preferably from a continuous ion beam.

[0011] The use of a counter-gas flow to improve mass-to-charge ratio resolution is counterintuitive, since it is generally desirable for mass-to-charge ratio separation to be performed at low pressures, whereas the use of a counter-gas flow has usually been associated with the effect of increasing the pressure in the apparatus.

[0012] The preferred separation device preferably comprises an RF-limited ion guide. Ions are driven along and through the axial length of the ion guide by applying a traveling wave or one or more transient DC voltage potentials or voltages to the electrodes of the ion guide. The ion guide is supplied with a buffer gas (for example, helium or nitrogen) so that ions that are taken up into the ion guide and allowed to pass forward through it are separated over time according to their ion mobility or their collision cross-section as they traverse the ion guide.The buffer gas is supplied or caused to flow in a direction opposite to or inclined to the direction in which the traveling wave or one or more transient DC voltages or potentials are applied to the electrodes, and to the direction in which an axial DC potential barrier is displaced along the length of the ion guide. For example, according to one embodiment, one or more transient DC voltages or potentials can be progressively applied to the electrodes, such that an axial DC potential barrier moves from an input of the device to an output of the device, and at the same time a buffer gas is preferably designed to move from the output of the device towards the input of the device, i.e.,to flow in a direction opposite to the direction of movement of the transient DC voltages or DC potentials applied to the electrodes.

[0013] In an ion mobility separator that uses a traveling wave or one or more transient DC voltages or potentials to drive ions along the axial length of the device, it is natural that ions do not experience a continuous force driving them toward the device's output. The traveling wave or transient DC voltage or potential barriers overtake the ions as they are separated over time, and thus they experience a driving force toward the output only for a portion of the time it takes them to traverse the device. For the remainder of the time, the ions experience either no force or a net force driving them back toward the device's input.

[0014] It will therefore be recognized by those skilled in the field that the nature of the ion mobility separation used by a traveling-wave ion mobility separator according to the preferred embodiment differs significantly from the mechanism that separates ions in a conventional ion mobility separator. As those skilled in the field will understand, a conventional ion mobility separator uses a drift cell in combination with a static DC voltage field that is maintained along the axial length of the ion mobility separator.

[0015] The different nature of ion mobility separation used by a traveling-wave ion mobility separator is fundamental to its operation. If the ion mobility separator is operated such that waves, or transient DC voltages or potentials, are shifted along the length of the device at relatively low velocities, then ions reach a terminal velocity and are separated predominantly over time according to their ion mobility or collision cross-section.

[0016] Applying a countercurrent of gas in a direction essentially opposite to the direction in which the traveling wave propagates along the length of the ion mobility separator increases the ion mobility separation efficiency and extends the ion mobility drift time. Furthermore, the ion mobility separator can be easily adapted to change the mechanism by which the ions are separated over time; that is, the device can be easily controlled to separate ions according to their ion mobility or collision cross-section, and then adapted to separate ions according to their mass or mass-to-charge ratio.

[0017] When a countercurrent of gas is applied to the ion mobility separator, the drift time is prolonged for a given wave amplitude and velocity. This is because an ion of a specific ion mobility or collision cross-section is overtaken by the traveling wave or the transient DC voltages or potentials, as these are applied sequentially to adjacent electrodes multiple times during its drift time. The same effect can be achieved by increasing the traveling wave velocity or decreasing the time between the application of transient DC voltages or potentials to adjacent electrodes.

[0018] Intuitively, this might be considered equivalent to applying a countercurrent of gas, since the drift time for an ion of a given mobility is increased, thus increasing the number of times ions are overtaken by the traveling wave or the transient DC voltages or potentials. However, unlike applying a countercurrent of gas, the measure of increasing the traveling wave velocity does not actually lead to a significant increase in the ion mobility separation performance or ion mobility resolution of the system. In fact, when the velocity of the traveling wave or the transient DC voltages or potentials is significantly increased, the device begins to separate ions predominantly according to their mass or mass-to-charge ratio, rather than their ion mobility.

[0019] The application of a countercurrent of gas in conjunction with a traveling wave ion mobility separator has several advantages over conventional arrangements, including conventional arrangements that use a countercurrent of gas.

[0020] The resolution of conventional ion mobility separators, which drive ions along the length of the ion mobility separator against a static buffer gas, depends on the square root of the electric field applied along the axial length of the ion mobility separator and on the square root of the length of the device.

[0021] For conventional ion mobility separators that employ static DC fields, the potential drop across the ion mobility separator becomes relatively large in order to maintain the electric field over longer ion mobility separation cells, and ultimately becomes impractical due to discharge. In contrast, traveling-wave ion mobility separators according to the preferred embodiment do not suffer from this limitation, and furthermore, the amplitude of the transient DC voltage or transient DC potential, preferably applied to the electrodes, can be relatively small, and the amplitude of the transient DC voltage or transient DC potential is preferably independent of the length of the device.

[0022] An advantageous aspect of the present invention is that it preferably provides an enhanced high-resolution ion mobility separation device that can be operated using transient DC voltages of relatively low amplitude. The amplitude of the transient DC voltages or DC potentials applied to the electrodes is relatively low compared to conventional devices that utilize an axial DC driving force.

[0023] Furthermore, increasing the speed of the traveling wave or the rate at which the transient DC voltages or DC potentials are applied along the length of the device can lead to a separation that is strongly correlated with mass and mass-to-charge ratio, instead of a separation that is governed by ion mobility or collision cross-section.

[0024] In the preferred operating mode, where ions are separated according to their ion mobility or collision cross-section, the ions do not reach their final velocity while being accelerated by the traveling wave potential or the transient DC voltages or potentials. Once ions are overtaken by the traveling wave or the transient DC voltages or potentials while being displaced along the length of the device, they lose most or all of their forward velocity. On average, the forward velocity of the ions is related to their mass-to-charge ratio. This results in the drift time of the ions being much more strongly correlated with the mass-to-charge ratio of the ions than with their ion mobility or collision cross-section.

[0025] Switching from ion mobility separation to mass-to-charge ratio separation by increasing the speed of the traveling wave is a unique feature of traveling wave ion mobility separation and cannot be reproduced using conventional ion mobility separators that utilize a static DC field in combination with a conventional drift tube.

[0026] As a result, the ion separation device according to the present invention makes it possible to use the same device to separate ions predominantly based on their ion mobility or their collision cross-section, or alternatively to a greater extent based on their mass-charge ratio, by simply changing the operating parameters of the traveling wave or the transient DC voltages or DC potentials applied to the electrodes.

[0027] This property can be useful if the separator is to be used as part of a linked sampling arrangement to improve the duty cycle of a sampling mass-to-charge ratio filter, such as a quadrupole mass filter.

[0028] Switching between ion mobility separation or collision cross-section separation to mass-to-charge ratio separation can be achieved by changing the traveling wave parameters.

[0029] Preferably, the second operating mode causes ions to leave the separation device in order of increasing or decreasing mass-to-charge ratio; wherein the second operating mode further comprises: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer.

[0030] This second operating mode can be advantageous, for example, in that it makes it possible to optimize or improve the duty cycle of the ion analyzer.

[0031] The ion analyzer can include an ion filter that only allows ions to pass through that have a certain value or range of values ​​of a physicochemical property at a given time, and the value or range of values ​​that passes through the ion filter can be varied over time in the second operating mode based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer.

[0032] The ions that pass through the ion filter can be detected, so that the physicochemical properties of any detected ions can be determined from the knowledge of the physicochemical properties that are passing through the filter at the time of detection.

[0033] The ion filter can be a quadrupole or other multipole mass filter.

[0034] Alternatively, the ion analyzer can be a batch ion analyzer that receives ions from the separation device and repeatedly pulses ions into an analysis area. The time between pulses can be varied over time based on and synchronized with the mass-to-charge ratios of the ions leaving the separation device and arriving at the ion analyzer. Alternatively, the time between the emission of a given ion from the separation device and its pulse into the analysis area can be varied based on and synchronized with the mass-to-charge ratios of the ions leaving the separation device and arriving at the ion analyzer as a function of time.

[0035] Accordingly, the time between the exit of ions of a first mass-to-charge ratio (or a first range of mass-to-charge ratios) from the separation device and their pulse into the analysis area differs from the time between the exit of ions of a second mass-to-charge ratio (or a second range of mass-to-charge ratios) from the separation device and their pulse into the analysis area. This can allow the pulsed extraction area of ​​the ion analyzer to be filled with ions more efficiently and can thus improve the duty cycle of the ion analyzer.

[0036] The ion analyzer can be a time-of-flight mass analyzer, and the analysis range can be a time-of-flight range.

[0037] The ion analyzer described here can be a mass analyzer and / or the physicochemical property can be a mass-to-charge ratio.

[0038] The first operating mode can cause ions to leave the separation device in order of increasing or decreasing ion mobility; and the first operating mode can further include: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronously with the ion mobilities of the ions leaving the separation device and received at the ion analyzer.

[0039] In the first operating mode, the ion analyzer can include an ion filter that only allows ions to pass through that have a certain value or range of values ​​of a physicochemical property at a given time, and the value or range of values ​​that passes through the ion filter can be varied over time in the first operating mode based on and synchronously with the ion mobilities of the ions leaving the separation device and received at the ion analyzer.

[0040] The ions that pass through the ion filter can be detected, so that the physicochemical properties of any detected ions can be determined from the knowledge of the physicochemical properties that are passing through the filter at the time of detection.

[0041] The ion filter can be a quadrupole or other multipole mass filter.

[0042] The ion analyzer operating in the first mode can be a mass analyzer and / or the physicochemical property can be a mass-to-charge ratio.

[0043] In the first operating mode, the one or more mass-to-charge ratios of the ions passed through the ion filter can be varied over time and as a function of the ion mobilities received at the ion filter from the separation device in order to allow only ions of a selected charge state to pass through.

[0044] The ion analyzer can be a discontinuous ion analyzer that receives ions from the separation device and repeatedly pulses ions into an analysis area; wherein the duration of the time between the pulses is varied over time as a function of time based on and synchronously with the ion mobilities of the ions leaving the separation device and received at the ion analyzer; or wherein the duration of the time between the exit of a given ion from the separation device and the pulse into the analysis area is varied over time based on and synchronously with the ion mobilities of the ions leaving the separation device and received at the ion analyzer as a function of time.Accordingly, the length of time between the exit of ions of a first ion mobility (or a first range of ion mobilities) from the separation device and the pulse into the analysis area differs from the length of time between the exit of ions of a second ion mobility (or a second range of ion mobilities) from the separation device and the pulse into the analysis area.

[0045] The discontinuous ion analyzer can be a mass analyzer.

[0046] The ion analyzer can be a time-of-flight mass analyzer, and the analysis range can be a time-of-flight range.

[0047] The method can include determining the mass-to-charge ratios of the separated ions in the second operating mode.

[0048] The separation device may comprise a flight area or form part thereof, and the second mode of operation may include: driving the ions through the flight area in the first direction using one or more transient DC voltages or DC potentials, determining the flight times of the ions through the flight area, and determining the mass-to-charge ratios of the ions from the flight times of the ions through the flight area.

[0049] The step of determining the mass-to-charge ratios of the ions may include detecting the ions leaving the flight area.

[0050] The gas flows through the flight time area in the second direction.

[0051] The method can include measuring the ion mobilities of the separated ions in the first operating mode.

[0052] The separation device may comprise a flight area or form part thereof, and the first mode of operation may include: driving the ions through the flight area in the first direction using one or more transient DC voltages or DC potentials, determining the flight times of the ions through the flight area, and determining the ion mobilities of the ions from the flight times of the ions through the flight area.

[0053] The step of determining the ion mobilities of the ions may include detecting the ions that leave the flight area.

[0054] The gas flows through the flight time area in the second direction.

[0055] Ions that have the same mass-to-charge ratio but different ion mobilities are preferably separated in the first operating mode; and / or ions that have the same ion mobility but different mass-to-charge ratios are preferably separated in the second operating mode.

[0056] The method preferably separates the ions in the first operating mode with a higher ion mobility resolution than in the second operating mode; and / or the method preferably separates the ions in the second operating mode with a higher mass-to-charge ratio resolution than in the first operating mode.

[0057] In the first operating mode, ions are predominantly separated by ion mobility, and in the second operating mode, predominantly by mass-to-charge ratio.

[0058] Preferably, during the first operating mode, one or more transient DC voltages or potentials are repeatedly traversed or moved along the device to drive the ions in the first direction. Preferably, during the second operating mode, one or more transient DC voltages or potentials are repeatedly traversed or moved along the device to drive the ions in the first direction.

[0059] The speed of one or more transient DC voltages in the first operating mode can be ≤ x % of the speed of one or more transient DC voltages in the second operating mode, where X is selected from the following group: 90; 80; 70; 60; 50; 40; 30; 20; 10; or 5.

[0060] In the first operating mode, one or more DC voltage or DC potential barriers and a counter-gas current preferably cause the ions to reach their final velocities; and in the second operating mode, the one or more DC voltage or DC potential barriers and the counter-gas current preferably do not cause the ions to reach their final velocities.

[0061] The first speed can be chosen from the following group: (i) < 100 m / s; (ii) 100-200 m / s; (iii) 200-300 m / s; (iv) 300-400 m / s; (v) 400-500 m / s; (vi) 500-600 m / s; (vii) 600-700 m / s; (viii) 700-800 m / s; (ix) 800-900 m / s; (x) 900-1000 m / s; (xi) 1000-1100 m / s; (xii) 1100-1200 m / s; (xiii) 1200-1300 m / s; (xiv) 1300-1400 m / s; (xv) 1400-1500 m / s; (xvi) 1500-1600 m / s; (xvii) 1600-1700 m / s; (xviii) 1700-1800 m / s; (xix) 1800-1900 m / s; (xx) 1900-2000 m / s; (xxi) 2000-2100 m / s; (xi) (xxii) 2100-2200 m / s; (xxiii) 2200-2300 m / s; (xxiv) 2300-2400 m / s; (xxv) 2400-2500 m / s; (xxvi) 2500-2600 m / s; (xxvii) 2600-2700 m / s; (xxviii) 2700-2800 m / s; (xxix) 2800-2900 m / s; (xxx) 2900-3000 m / s; and (xxxi) > 3000 m / s.

[0062] Preferably, the first speed is less than 1000 m / s.

[0063] The second speed can be chosen from the following group: (i) < 100 m / s; (ii) 100-200 m / s; (iii) 200-300 m / s; (iv) 300-400 m / s; (v) 400-500 m / s; (vi) 500-600 m / s; (vii) 600-700 m / s; (viii) 700-800 m / s; (ix) 800-900 m / s; (x) 900-1000 m / s; (xi) 1000-1100 m / s; (xii) 1100-1200 m / s; (xiii) 1200-1300 m / s; (xiv) 1300-1400 m / s; (xv) 1400-1500 m / s; (xvi) 1500-1600 m / s; (xvii) 1600-1700 m / s; (xviii) 1700-1800 m / s; (xix) 1800-1900 m / s; (xx) 1900-2000 m / s; (xxi) 2000-2100 m / s; (xi) (xxii) 2100-2200 m / s; (xxiii) 2200-2300 m / s; (xxiv) 2300-2400 m / s; (xxv) 2400-2500 m / s; (xxvi) 2500-2600 m / s; (xxvii) 2600-2700 m / s; (xxviii) 2700-2800 m / s; (xxix) 2800-2900 m / s; (xxx) 2900-3000 m / s; and (xxxi) > 3000 m / s.

[0064] Preferably, the second speed is less than 1000 m / s.

[0065] The method may include varying, sampling, or grading the amplitude of one or more transient DC voltages or potentials as a function of time during the first operating mode and / or the second operating mode; and / or wherein the one or more transient DC voltages or potentials have different amplitudes during the first and second operating modes.

[0066] The method may include increasing and / or decreasing the amplitude of one or more transient DC voltages or potentials as a function of time during the first operating mode and / or second operating mode; and / or wherein the one or more transient DC voltages or potentials may have a higher amplitude during the first operating mode than during the second operating mode or a lower amplitude during the first operating mode than during the second operating mode.

[0067] It is understood that the step of separating ions according to their ion mobility in the first operating mode may include separating ions according to their collision cross-section (“CCS”) or their differential ion mobility.

[0068] In the first and / or second operating mode, ions can be separated in a separation range maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; (ix)> 1000 mbar; (x) ≤ 5 mbar; and (xi) ≤ 10 mbar.

[0069] Pressures of ≤ 5 mbar or ≤ 10 mbar are particularly advantageous in the second operating mode. More precisely, it has been found that it is desirable to maintain gas pressures at or below these values ​​during the mass-to-charge ratio separation operating mode and to apply a counter-gas flow, rather than increasing the gas pressure, to improve separation.

[0070] The gas flow can have a velocity in the second direction selected from the following group: (i) < 10 m / s; (ii) 10-20 m / s; (iii) 20-30 m / s; (iv) 30-40 m / s; (v) 40-50 m / s; (vi) 50-60 m / s; (vii) 60-70 m / s; (viii) 70-80 m / s; (ix) 80-90 m / s; (x) 90-100 m / s; and (xi) > 100 m / s.

[0071] Ions can enter a separation region, be separated in the first and second operating modes according to ion mobility or mass-to-charge ratio, and then leave the separation region; wherein the first direction is either: (i) from an ion exit end of the separation region towards an ion entry end of the separation region; or (ii) from an ion entry end of the separation region towards an ion exit end of the separation region.

[0072] It may be arranged so that ions progressively exit or elute from the separation device over a period of time as follows: (i) substantially in order of their ion mobility, collision cross-section or differential ion mobility during the first operating mode; (ii) substantially in reverse order of their ion mobility, collision cross-section or differential ion mobility during the first operating mode; (iii) substantially in order of their mass, mass-to-charge ratio or flight time during the second operating mode; or (iv) substantially in reverse order of their mass, mass-to-charge ratio or flight time during the second operating mode.

[0073] The method can switch between the first and second operating modes, preferably while the same sample is being analyzed in a single test run.

[0074] The force to drive ions in the first direction can be provided by a multiphase alternating or RF voltage applied to the electrodes, instead of by one or more transient DC voltages or DC potentials.

[0075] Accordingly, according to a second aspect, the present invention provides a method for separating ions, comprising the following: Providing a separation device comprising multiple electrodes; Applying multiphase alternating or RF voltages or potentials to at least some of the electrodes, switching the phase of the voltages or potentials applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages or potentials successively along the device such that a pseudo-potential barrier moves along the device, the potential barrier driving ions in a first direction through the separating device; and Providing a gas flow in a second direction that is substantially inclined or opposite to the first direction; Performing a first operating mode in which one or more alternating or RF voltages or potentials are applied along at least a part of the axial length of the separation device such that the potential barrier moves along the device at a first velocity to cause ions to be separated according to their ion mobilities; and Performing a second mode of operation in which one or more alternating or RF voltages or potentials are applied along at least a part of the axial length of the separation device such that the potential barrier moves along the device at a second speed higher than the first speed in order to cause ions to be separated according to their mass-to-charge ratios; the gas flow is provided during the first and second operating modes.

[0076] The electrodes to which the different phases of the multiphase alternating or RF voltages or potentials are applied are chosen so that the ions are driven in the first direction.

[0077] The multiphase AC or RF voltages or potentials preferably comprise a 3-phase, 4-phase, 5-phase, 6-phase, 7-phase, 8-phase, 9-phase, or 10-phase AC or RF voltage supply to function as an RF drive. According to other embodiments, the AC or RF voltage supply may comprise more than ten phases.

[0078] The method according to the second aspect may include one of the preferred or optional features discussed in connection with the first aspect, except that the ions are driven in the first direction by the multiphase AC or RF voltages or potentials instead of by the one or more DC voltage or DC potential barriers.

[0079] The method may include varying, sampling, or grading the amplitude of the polyphase AC or RF voltages as a function of time during the first operating mode and / or the second operating mode; and / or wherein the polyphase AC or RF voltages have different amplitudes during the first and second operating modes.

[0080] The method may involve increasing and / or decreasing the amplitude of the multiphase AC or RF voltages as a function of time during the first operating mode and / or second operating mode; and / or wherein the multiphase AC or RF voltages may have a higher amplitude during the first operating mode than during the second operating mode or a lower amplitude during the first operating mode than during the second operating mode.

[0081] The concept of using one or more transient DC voltages or DC potentials and a counter-gas flow to mass to improve the mass-to-charge ratio separation is assumed to be novel in itself.

[0082] Accordingly, according to a third aspect, the present invention provides a method for separation according to mass-to-charge ratio, comprising: Providing a separation device comprising multiple electrodes; Applying one or more transient DC voltages or DC potentials to at least some of the electrodes to drive ions through the separation device in a first direction; Providing a gas stream in a second direction that is substantially inclined or opposite to the first direction, wherein ions are separated according to their mass-to-charge ratios by the one or more transient DC voltages and the counter-gas stream.

[0083] Preferably, ions are arranged to leave the separation device in order of increasing or decreasing mass-to-charge ratio; the method further comprising: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronized with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer.

[0084] This operating mode can be advantageous, for example, in that it makes it possible to optimize or improve the duty cycle of the ion analyzer.

[0085] The ion analyzer may include an ion filter that only allows ions to pass through that have a certain value or range of values ​​of a physicochemical property at a given time, and the value or range of values ​​that passes through the ion filter may be varied over time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and being received at the ion analyzer.

[0086] The ions that pass through the ion filter can be detected, so that the physicochemical properties of any detected ions can be determined from the knowledge of the physicochemical properties that are passing through the filter at the time of detection.

[0087] The ion filter can be a quadrupole or other multipole mass filter.

[0088] Alternatively, the ion analyzer can be a batch ion analyzer that receives ions from the separation device and repeatedly pulses ions into an analysis area. The time between pulses can be varied over time based on and synchronized with the mass-to-charge ratios of the ions leaving the separation device and arriving at the ion analyzer. Alternatively, the time between the emission of a given ion from the separation device and its pulse into the analysis area can be varied based on and synchronized with the mass-to-charge ratios of the ions leaving the separation device and arriving at the ion analyzer as a function of time.

[0089] Accordingly, the time between the exit of ions of a first mass-to-charge ratio (or a first range of mass-to-charge ratios) from the separation device and their pulse into the analysis area differs from the time between the exit of ions of a second mass-to-charge ratio (or a second range of mass-to-charge ratios) from the separation device and their pulse into the analysis area. This can allow the pulsed extraction area of ​​the ion analyzer to be filled with ions more efficiently and can thus improve the duty cycle of the ion analyzer.

[0090] The ion analyzer can be a time-of-flight mass analyzer, and the analysis range can be a time-of-flight range.

[0091] The ion analyzer described here can be a mass analyzer and / or the physicochemical property can be a mass-to-charge ratio.

[0092] The method preferably includes determining the mass-to-charge ratios of the separated ions.

[0093] The separation device may include or form part of a flight region, and the method may include: driving the ions through the flight region in the first direction using one or more transient DC voltages or DC potentials, determining the flight times of the ions through the flight region, and determining the mass-to-charge ratios of the ions from the flight times of the ions through the flight region.

[0094] The step of determining the mass-to-charge ratios of the ions may include detecting the ions leaving the flight area.

[0095] The gas flows through the flight time area in the second direction.

[0096] Ions that have the same mass-to-charge ratio but different ion mobilities are preferably separated by the device.

[0097] Preferably, the one or more DC voltage or DC potential barriers and the counter-gas current do not cause the ions to reach their final velocities while passing through the device.

[0098] The one or more transient DC voltages or DC potentials are applied to at least some of the electrodes such that the one or more DC voltage or DC potential barriers are preferably traversed, shifted or applied sequentially along at least a part of the axial length of the separating device at a first speed.

[0099] Preferably, one or more transient DC voltages or DC potentials are repeatedly traversed or moved along the device to drive the ions in the first direction.

[0100] The method may involve varying, sampling, or grading the amplitude of one or more transient DC voltages or DC potentials as a function of time.

[0101] Preferably, the ions are separated with higher mass-to-charge ratio resolution if one or more transient DC voltages or DC potentials have a higher velocity, and with lower mass-to-charge ratio resolution if one or more transient DC voltages or DC potentials have a lower velocity.

[0102] The velocity of one or more transient DC voltages or DC potentials can be selected from the following group: (i) < 100 m / s; (ii) 100-200 m / s; (iii) 200-300 m / s; (iv) 300-400 m / s; (v) 400-500 m / s; (vi) 500-600 m / s; (vii) 600-700 m / s; (viii) 700-800 m / s; (ix) 800-900 m / s; (x) 900-1000 m / s; (xi) 1000-1100 m / s; (xii) 1100-1200 m / s; (xiii) 1200-1300 m / s; (xiv) 1300-1400 m / s; (xv) 1400-1500 m / s; (xvi) 1500-1600 m / s; (xvii) 1600-1700 m / s; (xviii) 1700-1800 m / s; (xix) 1800-1900 m / s; (xx) 1900-2000 m / s; (xxi) 2000-2100 m / s; (xi) (xxii) 2100-2200 m / s; (xxiii) 2200-2300 m / s; (xxiv) 2300-2400 m / s; (xxv) 2400-2500 m / s; (xxvi) 2500-2600 m / s; (xxvii) 2600-2700 m / s; (xxviii) 2700-2800 m / s; (xxix) 2800-2900 m / s; (xxx) 2900-3000 m / s; and (xxxi) > 3000 m / s. Preferably the speed is > 1000 m / s.

[0103] The method may involve varying, sampling, or grading the amplitude of one or more transient DC voltages or DC potentials as a function of time.

[0104] The method may involve increasing and / or decreasing the amplitude of one or more transient DC voltages or DC potentials as a function of time.

[0105] The separating device can be maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; (ix)> 1000 mbar.

[0106] Preferably the pressure is ≤ 5 mbar or ≤ 10 mbar.

[0107] The gas flow can have a velocity in the second direction selected from the following group: (i) < 10 m / s; (ii) 10-20 m / s; (iii) 20-30 m / s; (iv) 30-40 m / s; (v) 40-50 m / s; (vi) 50-60 m / s; (vii) 60-70 m / s; (viii) 70-80 m / s; (ix) 80-90 m / s; (x) 90-100 m / s; and (xi) > 100 m / s.

[0108] The first direction can either: (i) be from an ion exit end of the separation device towards an ion entry end of the separation device; or (ii) be from an ion entry end of the separation device towards an ion exit end of the separation device.

[0109] It can be arranged so that ions progressively exit or elute from the separation device over a period of time as follows: (i) substantially in order of their mass, mass-to-charge ratio or flight time; or (ii) substantially in reverse order of their mass, mass-to-charge ratio or flight time.

[0110] The force to drive ions in the first direction can be provided by a multiphase alternating or RF voltage applied to the electrodes, instead of by one or more transient DC voltages or DC potentials.

[0111] Accordingly, according to a fourth aspect, the present invention provides a method for separation according to mass-charge ratio or ion mobility, comprising: Providing a separation device comprising multiple electrodes; Applying multiphase alternating or RF voltages or potentials to at least some of the electrodes, switching the phase of the voltages or potentials applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages or potentials successively along the device such that a pseudo-potential barrier moves along the device, the potential barrier driving ions in a first direction through the separating device; and Providing a gas flow in a second direction that is substantially inclined or opposite to the first direction.

[0112] The electrodes to which the different phases of the multiphase alternating or RF voltages or potentials are applied are chosen so that the ions are driven in the first direction.

[0113] The multiphase AC or RF voltages or potentials preferably comprise a 3-phase, 4-phase, 5-phase, 6-phase, 7-phase, 8-phase, 9-phase, or 10-phase AC or RF voltage supply to function as an RF drive. According to other embodiments, the AC or RF voltage supply may comprise more than ten phases.

[0114] The method according to the fourth aspect may include one of the preferred or optional features discussed in connection with the third aspect, except that the ions are driven in the first direction by the multiphase alternating or RF voltages or potentials instead of by the one or more DC voltage or potential barriers.

[0115] The method may involve varying, sampling, or grading the amplitude of multiphase alternating or RF voltages as a function of time.

[0116] The method may involve increasing and / or decreasing the amplitude of multiphase alternating or RF voltages as a function of time.

[0117] The present invention also provides a method for mass spectrometry or ion mobility spectrometry, comprising a method as described herein.

[0118] The present invention also provides a separation device for carrying out the methods described herein.

[0119] Accordingly, the present invention, according to the first aspect, provides a separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages or to apply DC voltage potentials to at least some of the electrodes in order to drive ions through the separation device in a first direction; a second device designed and adapted to provide a gas flow in a second direction that is substantially inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices for the following: Performing a first operating mode in which one or more transient DC voltages are traversed, shifted, or sequentially applied along at least a part of the axial length of the separation device at a first speed to cause ions to be separated according to their ion mobilities; Performing a second mode of operation in which one or more transient DC voltages are traversed, shifted, or sequentially applied along at least a portion of the axial length of the separation device at a first velocity higher than the first velocity, in order to cause ions to be separated according to their mass-to-charge ratios; and Providing the gas flow during the first and second operating modes.

[0120] The device can be designed and adapted to perform any of the preferred or optional methods described in relation to the first aspect of the present invention.

[0121] According to the second aspect, the present invention provides a separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply multiphase alternating or RF voltages or potentials to at least some of the electrodes and to determine the phase of the voltages or potentials applied to successive electrodes along the device, to switch such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages or potentials successively along the device such that a pseudo-potential barrier moves along the device, the potential barrier driving ions in a first direction through the separation device; a second device designed and adapted to provide a gas flow in a second direction that is substantially inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices for the following: Performing a first operating mode in which one or more alternating or RF voltages or potentials are applied along at least a part of the axial length of the separation device such that the potential barrier moves along the device at a first velocity to cause ions to be separated according to their ion mobilities; and Performing a second mode of operation in which one or more alternating or RF voltages or potentials are applied along at least a portion of the axial length of the separation device such that the potential barrier moves along the device at a second velocity higher than the first velocity to cause ions to be separated according to their mass-to-charge ratios; and Providing the gas flow during the first and second operating modes.

[0122] According to the third aspect, the present invention provides a separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages or DC potentials to at least some of the electrodes in order to drive ions in a first direction through the separation device; and a second device designed and adapted to provide a gas flow in a second direction that is substantially inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices such that the one or more transient DC voltages or DC potentials drive the ions against the gas flow in such a way that the ions are separated according to their mass-to-charge ratios.

[0123] According to the fourth aspect, the present invention provides a separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply multiphase alternating or RF voltages or potentials to at least some of the electrodes and to switch the phase of the voltages or potentials applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages or potentials successively along the device such that a pseudo-potential barrier moves along the device, the potential barrier driving ions in a first direction through the separation device; a second device designed and adapted to provide a gas flow in a second direction that is substantially inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices in such a way that the potential barrier drives the ions against the gas flow in such a way that the ions are separated according to their mass-to-charge ratios.

[0124] The separating devices disclosed herein can have a number of general properties.

[0125] For example, the multiple electrodes can include ring electrodes, an ion tunnel, or multiple electrodes, each with an opening through which ions are allowed to pass during use.

[0126] The multiple electrodes can include axially segmented rod electrodes.

[0127] The multiple electrodes can comprise a stack or arrangement of planar electrodes, plate electrodes, or mesh electrodes.

[0128] The separation device may include a third device for applying RF voltages to the multiple electrodes in order to create a radial pseudo-potential barrier, which serves to restrict ions radially within the separation device.

[0129] The first device may be designed and adapted to apply one or more transient DC voltages or DC potentials in the first direction, wherein the first direction is either: (i) from an outlet end of the isolating device to an inlet end of the isolating device; or (ii) from an inlet end of the isolating device to an outlet end of the isolating device.

[0130] The second device can be designed and adapted to cause gas to flow in the second direction, wherein the second direction is either: (i) from an outlet end of the separating device to an inlet end of the separating device; or (ii) from an inlet end of the separating device to an outlet end of the separating device.

[0131] It may be arranged such that ions progressively exit or elute from the separation device over a period of time as follows: (i) substantially in order of their ion mobility, collision cross-section or differential ion mobility; (ii) substantially in reverse order of their ion mobility, collision cross-section or differential ion mobility; (iii) substantially in order of their mass, mass-to-charge ratio or flight time; or (iv) substantially in reverse order of their mass, mass-to-charge ratio or flight time.

[0132] The present invention provides a mass spectrometer or ion mobility spectrometer comprising a separation device as described herein.

[0133] It is counterintuitive that introducing a countercurrent of gas into a separation device designed to separate ions according to their mass-to-charge ratio should improve the separation performance of the device without substantially altering the mass-to-charge ratio correlation. One would expect that a gas current directed opposite to that in which the ions are forced by the traveling wave or one or more transient DC voltages or potentials would increase the number of ion gas collisions per unit time (i.e., reduce the mean free path of the ions) and thus cause a fraction of the ions to reach terminal velocity, reverting the separation to being related to ion mobility or collision cross-section rather than being more strongly correlated with the mass-to-charge ratio.This hypothesis would be supported by the previous observation that the ion mobility separation performance of a traveling wave device can be improved under mobility separation conditions by applying a countercurrent of gas.

[0134] The fact that this does not happen can be explained by considering the required velocity of the counterflow of gas compared to the inherent thermal velocity of the target gas.

[0135] The mean free path of an ion in a buffer gas is inversely proportional to the relative velocity of the buffer gas and the ion. The velocity v(rms) of a gas molecule at room temperature (293 K) is given by: ν(rms)=kTm where k is the Boltzmann constant, m is the mass and T is the temperature in Kelvin.

[0136] For nitrogen, the thermal velocity is approximately 680 m / s. Assuming a typical ion velocity in a traveling wave separation device is 30 m / s, a counter-gas flow of 30 m / s would completely stop this ion moving along the device. This gas velocity is only 5% of the ions' thermal velocity and therefore has a very small effect on the mean free path.

[0137] In an operating mode according to a preferred embodiment of the present invention, the force due to the traveling wave or the application of transient DC voltages or DC potentials to the electrodes is initially small compared to the force due to the gas flow, and thus ions are trapped at the inlet of the ion mobility separator. The displacement of ions from the ion mobility separator can be prevented by applying a DC voltage or pseudo-potential barrier to an input and / or output electrode.To cause ions to elute from the device, the traveling wave amplitude or the amplitude of the transient DC voltages or DC potentials applied to the electrodes can be increased and / or the speed of the traveling wave or the rate at which the transient DC voltages or DC potentials are shifted or applied along the length of the separation device can be decreased (increased) and / or the gas flow velocity can be decreased (increased).

[0138] It should be noted that, according to a less preferred embodiment, the gas may be designed to flow from the inlet of the device to the outlet of the device, and the traveling wave or the transient DC voltages or potentials may be applied to the electrodes in one direction such that ions are driven by the traveling wave or the applied transient DC voltages or potentials from the outlet to the inlet of the device. According to this embodiment, ions preferably elute from the outlet of the device in reverse order of ion mobility, i.e., ions with a relatively low ion mobility elute before ions with a relatively high ion mobility.

[0139] According to the preferred embodiment, the gas flow acts from the outlet of the device to the inlet of the device, and the traveling wave or the transient DC voltages or DC potentials are preferably applied to electrodes from the inlet end of the device to the outlet end of the device, so that ions elute from the outlet of the device in ion mobility order, i.e., ions with a relatively high ion mobility elute before ions with a relatively low mobility.

[0140] According to a less preferred embodiment, the direction of motion of the traveling wave or of the applied transient DC voltages or potentials applied to the electrodes and the direction of the gas flow may not be directly opposite to each other, i.e., not exactly 180° to each other. Embodiments of the present invention are considered in which only one component of the force due to the gas flow is opposite to the direction in which ions are forced by the traveling wave or the transient DC voltages or potentials.

[0141] According to embodiments of the present invention, the angle θ between the direction of the gas flow and the direction along which the traveling wave or the transient DC voltages or DC potentials are applied can be < 10°, 10-20°, 20-30°, 30-40°, 40-50°, 50-60°, 60-70°, 70-80°, 80-90°, 90-100°, 100-110°, 110-120°, 120-130°, 130-140°, 140-150°, 150-160°, 160-170°, 170-180° or substantially 180°.

[0142] In this case, the ions will distribute themselves spatially and the device can be used as an ion mobility or mass-to-charge ratio filter.

[0143] According to another aspect, the present invention provides a method for filtering ions, which comprises: Providing an ion filter that includes multiple electrodes; Applying one or more transient DC voltages or DC potentials to the electrodes to drive ions in a first direction along the filter; and Providing a gas flow along the filter in a second direction to counteract the movement of ions in the first direction; wherein the first and second directions are angled relative to each other at a different angle than orthogonal, so that ions with different physicochemical property values ​​migrate along different paths through the filter and so that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path.

[0144] The physicochemical property is preferably an ion mobility or a mass-to-charge ratio.

[0145] Preferably, only ions that leave the filter along the desired output path are allowed to pass through to a downstream ion analyzer, ion detector or ion trap.

[0146] Preferably, the multiple electrodes to which one or more transient DC voltages or DC potentials are applied are arranged in parallel and in a third direction, wherein the first and the third direction are angled relative to each other at an angle other than orthogonal.

[0147] The method may involve varying one or more operating parameters of the filter to select or vary one or more physicochemical property values ​​of the ions leaving the filter along the desired exit path, wherein the one or more operating parameters are: gas flow velocity; gas flow direction; velocity of the transient DC voltage or transient DC potential along the filter; amplitude of the transient DC voltage or transient DC potential; and direction of motion of the transient DC voltage or transient DC potential.

[0148] The force to drive ions in the first direction can be provided by a multiphase alternating or RF voltage applied to the electrodes, instead of by one or more transient DC voltages or DC potentials.

[0149] Accordingly, the present invention, in another aspect, provides a method for filtering ions, comprising: Providing an ion filter that includes multiple electrodes; Applying multiphase alternating or RF voltages or potentials to at least some of the electrodes, switching the phase of the voltages or potentials applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages or potentials successively along the device such that a pseudo-potential barrier moves along the device, the potential barrier driving ions in a first direction along the filter; and Providing a gas flow along the filter in a second direction to counteract the movement of ions in the first direction; wherein the first and second directions are angled relative to each other at a different angle than orthogonal, so that ions with different physicochemical property values ​​migrate along different paths through the filter and so that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path.

[0150] The physicochemical property is preferably an ion mobility or a mass-to-charge ratio.

[0151] Preferably, only ions that leave the filter along the desired output path are allowed to pass through to a downstream ion analyzer, ion detector or ion trap.

[0152] Preferably, the multiple electrodes to which multiphase alternating or RF voltages or potentials are applied are arranged in parallel and in a third direction, wherein the first and the third direction are angled relative to each other at an angle other than orthogonal.

[0153] The method preferably comprises varying one or more operating parameters of the filter to select or vary one or more physicochemical property values ​​of the ions leaving the filter along the desired exit path, wherein the one or more operating parameters are: gas flow velocity; gas flow direction; potential barrier velocity; potential barrier amplitude; and potential barrier movement direction.

[0154] The present invention also provides a method for mass spectrometry or ion mobility spectrometry, which includes a method for filtering ions as described herein.

[0155] The present invention also provides an ion filter comprising: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages or DC potentials to the electrodes to drive ions in a first direction along the filter; a second device designed and adapted to provide a gas flow in a second direction to counteract the movement of the ions in the first direction, wherein the first and second directions are angled relative to each other at an angle other than orthogonal; and a controller designed and adapted to control the first and second devices in such a way that ions with different physicochemical property values ​​migrate through the filter along different paths and that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path.

[0156] The present invention also provides an ion filter comprising: multiple electrodes; a first device designed and adapted to apply multiphase alternating or RF voltages or potentials to the electrodes, to switch the phase of the voltages or potentials applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages or potentials successively along the device such that a potential barrier moves along the device, the potential barrier driving ions in a first direction along the filter; a second device designed and adapted to provide a gas flow in a second direction to counteract the movement of the ions in the first direction, wherein the first and second directions are angled relative to each other at an angle other than orthogonal; and a controller designed and adapted to control the first and second devices in such a way that ions with different physicochemical property values ​​migrate through the filter along different paths and that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path.

[0157] The present invention provides a mass spectrometer or ion mobility spectrometer comprising an ion filter as described herein.

[0158] According to a preferred embodiment, the force provided by the traveling wave or by applying the transient DC voltages or potentials to the electrodes and the force due to the moving gas can be designed to balance each other, so that at least some ions are retained within the ion guide for a period of time and can be caused to elute from the ion guide by adjusting at least one of the parameters of the traveling wave or the transient DC voltages or potentials applied to the electrodes and / or one or more parameters of the gas flow.

[0159] According to one embodiment, the mass spectrometer may further include the following: (a) an ion source selected from the following group: (i) an electrospray ion source (“ESI” ion source); (ii) an atmospheric pressure photoionization ion source (“APPI ion source”), (iii) an atmospheric pressure chemical ionization ion source (“APCI ion source”), (iv) a matrix-assisted laser desorption ionization ion source (“MALDI ion source”), (v) a laser desorption ionization ion source (“LDI ion source”), (vi) an atmospheric pressure ionization ion source (“API ion source”), (vii) a desorption / ionization-on-silicon ion source (“DIOS ion source”), (viii) an electron impact ion source (“EI ion source”), (ix) a chemical ionization ion source (“CI ion source”), (x) a field ionization ion source (“FI ion source”), (xi) a field desorption ion source (“FD ion source”), (xii) a inductively coupled plasma ion source (“ICP ion source”), (xiii) a fast atom bombardment ion source (“FAB ion source”),(xiv) a liquid secondary ion mass spectrometry ion source (“LSIMS ion source”), (xv) a desorption electrospray ionization ion source (“DESI ion source”), (xvi) a radioactive nickel-63 ion source, (xvii) a matrix-assisted atmospheric pressure laser desorption ionization ion source, (xviii) a thermospray ion source, (xix) an atmospheric sampling glow discharge ionization ion source (“ASGDI ion source”), (xx) a glow discharge ion source (“GD ion source”), (xxi) an impactor ion source, (xxii) a direct analysis in real time ion source (“DART ion source”), (xxii) a laser spray ionization ion source (LSI ion source), (xxiv) a sonic spray ionization ion source (SSI ion source), (xxv) a matrix-assisted inlet ionization ion source (MAII ion source), (xxvi) a solvent-assisted inlet ionization ion source (SAII ion source); and / or, (b) one or more continuous or pulsed ion sources and / or (c) one or more ion guides and / or (d) one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices and / or (e) one or more ion traps or one or more ion confinement regions and / or (f) one or more collision, fragmentation or reaction cells selected from the following group: (i) a collision-induced dissociation fragmentation device (“CID fragmentation device”), (ii) a surface-induced dissociation fragmentation device (“SID fragmentation device”), (iii) an electron transfer dissociation fragmentation device (“ETD fragmentation device”), (iv) an electron capture dissociation fragmentation device (“ECD fragmentation device”), (v) an electron impact or collision dissociation fragmentation device, (vi) a photo-induced dissociation fragmentation device (“PID fragmentation device”), (vii) a laser-induced dissociation fragmentation device, (viii) an infrared radiation-induced dissociation device, (ix) an ultraviolet radiation-induced dissociation device, (x) a Nozzle-skimmer interface fragmentation device, (xi) an in-source fragmentation device, (xii) an in-source impact-induced dissociation fragmentation device,(xiii) a thermal or temperature source fragmentation device, (xiv) a device for fragmentation induced by an electric field, (xv) a device for fragmentation induced by a magnetic field, (xvi) an enzyme digestion or enzyme degradation fragmentation device, (xvii) an ion-ion reaction fragmentation device, (xviii) an ion-molecule reaction fragmentation device, (xix) an ion-atom reaction fragmentation device, (xx) an ion-metastable ion reaction fragmentation device, (xxi) an ion-metastable molecule reaction fragmentation device, (xxii) an ion-metastable atom reaction fragmentation device, (xxiii) an ion-ion reaction device for reacting ions to form adducts or productions, (xxiv) an ion-molecule reaction device for Reacting ions to form adducts or productions, (xxv) an ion-atom reaction device for reacting ions to form adducts or productions,(xxvi) an ion-metastable ion reaction device for reacting ions to form adducts or productions, (xxvii) an ion-metastable molecule reaction device for reacting ions to form adducts or productions, (xxviii) an ion-metastable atom reaction device for reacting ions to form adducts or productions, and (xxix) an electron ionization dissociation fragmentation device (“EID fragmentation device”) and / or, (g) a mass analyzer selected from the following group: (i) a quadrupole mass analyzer, (ii) a 2D or linear quadrupole mass analyzer, (iii) a Paul or 3D quadrupole mass analyzer, (iv) a Penning trap mass analyzer, (v) an ion trap mass analyzer, (vi) a magnetic sector mass analyzer, (vii) an ion cyclotron resonance mass analyzer (“ICR mass analyzer”), (viii) a Fourier transform ion cyclotron resonance mass analyzer (“FTICR mass analyzer”), (ix) an electrostatic mass analyzer designed to generate an electrostatic field with a quadrologarithmic potential distribution, (x) an electrostatic Fourier transform mass analyzer, (xi) a Fourier transform mass analyzer, (xii) a time-of-flight mass analyzer, (xiii) an orthogonal acceleration time-of-flight mass analyzer and (xiv) a linear acceleration time-of-flight mass analyzer and / or (h) one or more energy analyzers or electrostatic energy analyzers and / or (i) one or more ion detectors and / or (j) one or more mass filters selected from the following group: (i) a quadrupole mass filter, (ii) a 2D or linear quadrupole ion trap, (iii) a Paul or 3D quadrupole ion trap, (iv) a Penning ion trap, (v) an ion trap, (vi) a magnetic sector mass filter, (vii) a time-of-flight mass filter, and (viii) a Wien filter and / or (k) a device or ion gate for pulsing ions and / or (1) a device for converting a substantially continuous ion beam into a pulsed ion beam.

[0160] The mass spectrometer may also include the following: (i) a C-trap and a mass analyzer comprising an outer tubular electrode and a coaxial inner spindle-shaped electrode forming an electrostatic field with a quadrologarithmic potential distribution, wherein in a first operating mode ions are allowed to pass through to the C-trap and then injected into the mass analyzer, and wherein in a second operating mode ions are allowed to pass through to the C-trap and then to a collision cell or electron transfer dissociation device, fragmenting at least some ions into fragment ions, and wherein the fragment ions are then allowed to pass through to the C-trap before being injected into the mass analyzer, and / or (ii) a ring-stack ion guide comprising several electrodes, each having an opening through which ions pass during use, wherein the distance between the electrodes increases along the length of the ion path, wherein the openings in the electrodes in an upstream section of the ion guide have a first diameter, and wherein the openings in the electrodes in a downstream section of the ion guide have a second diameter which is smaller than the first diameter, and wherein opposite phases of an alternating or RF voltage are applied to successive electrodes during use.

[0161] According to one embodiment, the mass spectrometer further comprises a device designed and adapted to supply an alternating or RF voltage to the electrodes. The AC or RF voltage preferably has an amplitude selected from the following group: (i) < 50 V peak-to-peak, (ii) 50-100 V peak-to-peak, (iii) 100-150 V peak-to-peak, (iv) 150-200 V peak-to-peak, (v) 200-250 V peak-to-peak, (vi) 250-300 V peak-to-peak, (vii) 300-350 V peak-to-peak, (viii) 350-400 V peak-to-peak, (ix) 400-450 V peak-to-peak, (x) 450-500 V peak-to-peak and (xi) > 500 V peak-to-peak.

[0162] The alternating or RF voltage preferably has a frequency selected from the following group: (i) < 100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1.5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0-3.5 MHz, (xii) 3.5-4.0 MHz, (xiii) 4.0-4.5 MHz, (xiv) 4.5-5.0 MHz, (xv) 5.0-5.5 MHz, (xvi) 5.5-6.0 MHz (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7.5-8.0 MHz, (xxi) 8.0-8.5 MHz, (xxii) 8.5-9.0 MHz, (xxiii) 9.0-9.5 MHz, (xxiv) 9.5-10.0 MHz and (xxv) > 10.0 MHz.

[0163] The mass spectrometer may also include a chromatography or other separation device upstream of an ion source. According to one embodiment, the chromatography separation device comprises a liquid chromatography or gas chromatography device.

[0164] According to another embodiment, the separation device may include: (i) a capillary electrophoresis separation device (“CE separation device”), (ii) a capillary electrochromatography separation device (“CEC separation device”), (iii) a separation device with an essentially rigid ceramic-based multilayer microfluidic substrate (“ceramic tile”), or (iv) a supercritical fluid chromatography separation device. Brief description of the drawings

[0165] Various embodiments of the present invention, together with other arrangements shown for illustrative purposes only, are now described by way of example with reference to the drawing, wherein: Fig. Figure 1A shows an ion mobility separator according to a preferred embodiment, wherein ions are driven from the input to the output of the ion mobility separator by applying several transient DC voltages or DC potentials to the electrodes forming the ion mobility separator, and wherein an opposing current or countercurrent of gas is also applied, such that the gas pushes ions back towards the input, and Fig. 1B shows a single ring electrode of the preferred device; Fig. 2 shows a graph in which a mass-to-charge ratio is plotted against a drift time for ions modeled using a conventional traveling wave ion mobility separator operated under conventional ion mobility conditions without countercurrent of gas and with a traveling wave velocity of 300 m / s; Fig. Figure 3 shows a graph plotting a mass-to-charge ratio against a drift time for the same ions, which are in Fig. 2 were modeled, however, according to a preferred embodiment of the present invention using a counterflow of gas and with a traveling wave speed of 300 m / s; Fig. Figure 4 shows a graph plotting a mass-to-charge ratio against a drift time for the same ions, which are in Fig. 2 were modeled under the same pressure of 1 Torr helium without a countercurrent of gas and with a traveling wave speed of 600 m / s; Fig. Figure 5 shows a graph plotting a mass-to-charge ratio against a drift time for the same ions, which are in Fig. 2 were modeled under the same pressure of 1 Torr helium without a countercurrent of gas, but with the traveling wave speed increased to 1500 m / s; Fig. Figure 6 shows a graph plotting a mass-to-charge ratio against a drift time for the ions listed in Tables 1 and 3 below, with a static gas and a traveling wave velocity of 300 m / s; Fig. Figure 7 shows a graph in which a mass-to-charge ratio is plotted against a drift time for the ions, which are in Fig. Figure 6 shows, again with a static gas, but with the traveling wave speed increased to 1500 m / s; Fig. Figure 8 shows a graph in which a mass-to-charge ratio is plotted against a drift time for the ions, which are in Fig. 5 are shown, but with a countercurrent of gas and where the traveling wave speed was 1500 m / s; Fig. 9A shows an ion separation device according to an alternative embodiment of the present invention in the (y,z) plane, wherein a counterflow of gas was provided, but wherein the gas flow was directed in a direction which was not completely opposite to the direction along which the ions are driven by the traveling wave, Fig. 9B shows the device in the (x,y) plane and Fig. 9C shows the device in the (x,z) plane; Fig. 10A shows the same device in the (y,z) plane and indicates the path that the ions take through the device in the absence of a countercurrent of gas and Fig. 10B shows the device in the (y,z) plane and indicates the path taken by ions in the presence of a countercurrent of gas through the device; and Fig. 11 shows a further embodiment of the present invention, which is similar to the embodiment in Fig. 1 is, except that the gas flow runs in one direction from the inlet to the outlet of the ion mobility separator and the traveling wave or the transient DC voltages or DC potentials are applied in one direction from the outlet to the inlet of the ion mobility separator. Detailed description of the preferred embodiment

[0166] A preferred embodiment of the present invention will now be described with reference to Fig. 1A described.

[0167] Fig. Figure 1A shows a preferred embodiment of the invention, wherein an ion mobility separator or other separation device is provided, comprising an RF-constrained ring stack arrangement. The RF ring stack preferably comprises an input electrode 1, a series of intermediate ring electrodes 2, and an output electrode 3. Opposite phases of an alternating voltage oscillating at an RF frequency are preferably applied to alternating ring electrodes 2 to generate a radial RF containment force or a pseudopotential. The ring stack preferably comprises multiple electrodes, each having an opening through which ions are allowed to pass during use.Alternative embodiments are also being considered in which the ion mobility separator or other separation device comprises a segmented multipole rod assembly or several planar electrodes, generally arranged in a plane parallel to the plane in which ions move through the device.

[0168] Fig. Figure 1A shows the preferred device in the y,z dimension and Fig. Figure 1B shows a single ring electrode 2 in the x,y dimension.

[0169] During operation, ions are preferably forced from the inlet end 1 to the outlet end 3 of the device by applying a traveling DC voltage wave or several transient DC voltages or DC potentials 4 to the ring electrodes 2, which form the ion mobility separator or the other separation device. A countercurrent of gas 5 is preferably provided in the opposite direction to the direction of movement of the traveling DC voltage wave or to the direction in which the several transient DC voltages or DC potentials 4 propagate along the length of the ion mobility separator or other separation device.As will be understood, although the separation device is preferably operated in a mode in which ions are separated over time according to their ion mobility or collision cross-section, an advantageous aspect of the present invention is that the separation device can also be easily operated in a mode in which ions are separated over time according to their mass or mass-to-charge ratio. A particularly preferred aspect of the present invention is that the separation device can be easily switched between a first operating mode in which ions are separated over time according to their ion mobility or collision cross-section and a second operating mode in which ions are separated over time according to their mass or mass-to-charge ratio.

[0170] A SIMION-8 model (RTM model) of a traveling-wave ion mobility device comprising multiple ring electrodes was constructed to model the behavior of the preferred device. The inner diameter of the ring electrodes was modeled as 5 mm. The ring plates or ring electrodes were modeled as 0.5 mm thick and spaced 1 mm apart. In the model, the ring electrodes were supplied with an alternating current potential oscillating at 2.7 MHz with a peak-to-peak amplitude of 250 V. It was modeled that opposite phases of the RF are applied to adjacent plates or electrodes.

[0171] It was modeled that transient DC voltages or potentials are applied to two pairs of plate electrodes in a six-plate-pair repeating pattern. For each group of six plate pairs, the transient DC voltage or potential was applied to the same plate pair at a given time in a sequence of 67 pairs. A DC traveling wave was established by applying a transient DC voltage or potential to each plate pair sequentially. Therefore, the potential advances by one plate pair, i.e., 3 mm, in one time step.

[0172] The speed of the traveling DC wave can be controlled by changing the time between switching the DC voltage or potential between each pair of plates. For example, switching the DC voltage or potential between adjacent pairs of plates every 10 µs in the sequence results in a traveling wave speed of 300 m / s.

[0173] The trajectory of the ensemble of singly and doubly charged ions with a range of mass-to-charge ratios and collision cross-sections was modeled starting at the entrance end of the ion guide. The exit time of ions exiting the ion guide was recorded. The total length along which the ions were modeled during motion was 185 mm. The mean drift times and the standard deviation of the mean drift times were recorded.

[0174] The collision cross section CCS of the ions was estimated as follows: CCS=π∗[Dion2+Dgas2]2 where D ion the hard sphere radius of the ions is and was estimated from the following: Dion = 1.436 * Mion³ where M ion the ion mass is and where: Dgas=1.436∗Mgas3 where M gas the mass of the IMS buffer gas.

[0175] In all cases, helium was modeled as a buffer gas.

[0176] To simulate the movement of ions in a gas-filled device, a hard-sphere gas collision model was used.

[0177] A detailed list of the masses and cross-sectional areas used for each ion ensemble is given below in Tables 1 and 2. Table 1 describes the mass and collision cross-section of singly charged ions that were modeled, and Table 2 describes the mass and collision cross-section of doubly charged ions that were modeled.

[0178] In addition, the orbits of a third ensemble of singly charged ions with different collision cross sections were also investigated. These ion ensembles differed from those in Table 1 in that they had twice the mass and their collision cross section values ​​were scaled by a factor of 0.75. A list of the masses and collision cross sections of the third ion group is shown below in Table 3.

[0179] To compare the calculated data sets under different conditions, two quality factors were used.

[0180] Firstly, a measure of the average separation RMob between ions with the same mass-to-charge ratio but different collision cross sections (CCS) can be used, where: RMob=∑n[DTx(n)−DTy(n)]22.35∗0.5(SDx(n)+SDy(n))∗1n where DTx and Dty are pairs of the calculated drift time values ​​for ions with the same mass-to-charge ratio from Tables 1 and 2 or Tables 1 and 3.

[0181] A higher RMob value indicates a separation with a stronger ion mobility dependency.

[0182] The second quality factor is a measure of the average separation RMass between drift times, calculated for successive mass-to-charge ratio values ​​in Table 1 for singly charged ions: RMass=∑n=0n−1[DTz(n+1)−DTz(n)]2.35∗0.5(SDx(n)+SDy(n))∗1n where DTz is the drift time calculated for the impact cross-section and the mass-to-charge ratio values ​​from Table 1.

[0183] RMass is a measure of the mass-to-charge ratio separation efficiency. A higher RMass value indicates a higher mass separation efficiency.

[0184] The relative changes in these two quality factors indicate the extent to which ions are separated due to differences in their ion mobility or due to differences in their mass-to-charge ratio. Table 1 Masse CCS (A 2 ) Ladungszustand 100.0 62.83969 1+ 290.0 109.0725 1+ 480.0 143.6271 1+ 670.0 173.0813 1+ 860.0 199.442 1+ 1050.0 223.6533 1+ 1240.0 246.2517 1+ 1430.0 267.5781 1+ 1620.0 287.8655 1+ 1810.0 307.2821 1+ 2000.0 325.9539 1+ Table 2 Masse CCS (A 2 ) Ladungszustand 200 89.53889 2+ 580 159.5992 2+ 960 212.4126 2+ 1340 257.618 2+ 1720 298.1845 2+ 2100 335.5159 2+ 2480 370.4129 2+ 2860 403.386 2+ 3240 434.7848 2+ 3620 464.8619 2+ 4000 493.8072 2+ Table 3 Masse CCS (A 2 ) Ladungszustand 200 47.12977 1+ 580 81.80441 1+ 960 107.7203 1+ 1340 129.811 1+ 1720 149.5815 1+ 2100 167.74 1+ 2480 184.6888 1+ 2860 200.6836 1+ 3240 215.8991 1+ 3620 230.4615 1+ 4000 244.4654 1+

[0185] Fig. Figure 2 shows a graph plotting a mass-to-charge ratio against a drift time for ions detailed above using standard traveling-wave ion mobility conditions. The error bars represent the standard deviation of the drift times for each ensemble of ions and provide an indication of the separation performance of the preferred device at half-widths.

[0186] The data that is in Fig. The results shown in Figure 2 were obtained when the gas was static and helium at a pressure of 1 Torr. The traveling wave velocity was modeled as 300 m / s, and the amplitude of the transient DC voltage was ramped up from 2 V at a rate of 0.2 V / ms.

[0187] The two trend lines show the separation of doubly and singly charged ions at the same mass-to-charge ratio due to differences in their ion mobility. For these data, RMob was determined to be 3.8 and RMass to be 1.9.

[0188] This reflects the relatively large difference in ion mobility between ions of the same mass-to-charge ratio and different charge states compared with the smaller difference in mobility between successive singly charged ions in Table 1.

[0189] Fig. Figure 3 shows a graph plotting a mass-to-charge ratio against a drift time for the same ions found in Fig. Two models were created under the same pressure of 1 Torr helium, but according to a preferred embodiment of the present invention, wherein a gas was modeled as flowing at a velocity of 20 m / s in a direction opposite to the movement of the ions. The gas was modeled as helium at a pressure of 1 Torr. The traveling wave velocity was modeled as 300 m / s, and the amplitude of the transient DC voltage was ramped up from 2 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 8.1 and RMass to be 3.8.

[0190] It is derived from the various drift time scales in Fig. 2 and Fig. 3. It is clear that the separation between ions of the same mass-to-charge ratio and different charge states, and between ions of the same charge state and different masses, was increased by essentially the same factor (2x) due to the application of the low-velocity countercurrent gas. This shows that the preferred device benefits from an increased ion mobility resolution. The total drift time (DT) increased from 22 ms to 37 ms.

[0191] Fig. Figure 4 shows a graph plotting a mass-to-charge ratio against a drift time for the same ions found in Fig. Two models were created under the same pressure of 1 Torr helium. In this case, the gas was static and at a pressure of 1 Torr helium. The traveling wave velocity was modeled as increased to 600 m / s, and the amplitude of the transient DC voltage was ramped up from 2 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 2.4 and RMass to be 1.7.

[0192] The maximum drift time is similar to that which is in Fig. Figure 3 shows a counterflow of gas at 20 m / s. Compared to Fig. However, in step 2, the separation between the different charge states is reduced, indicating a lower mobility separation. In contrast, the separation between different masses of the same charge state is reduced by a smaller factor. This shows that applying a countercurrent of gas does not have the same effect as increasing the traveling wave velocity, although both methods result in a similar increase in drift time.

[0193] Fig. Figure 5 shows a graph plotting a mass-to-charge ratio against a drift time for the ions, which is shown above in relation to Fig. Two models were simulated under the same pressure of 1 Torr helium. In this case, the gas was again static and at a pressure of 1 Torr helium. The traveling wave velocity was further increased to 1500 m / s, and the amplitude of the transient DC voltage was ramped up from 8 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 1.3 countercurrent of gas, and RMass to be 2.3.

[0194] When a faster traveling wave was applied, the drift time increased to a maximum of 80 ms. It is also clear that the two trend lines corresponding to singly and doubly charged ions show reduced separation. This is reflected by the low RMob value. However, the separation between singly charged ions of different mass-to-charge ratios is increased, as indicated by an RMass value of 2.3 compared to an RMass value of 1.9 for the Fig. The arrangement shown in Figure 2 indicates that the separation is no longer dominated by the mobility of the ions and now depends essentially on the mass-to-charge ratio of the ions.

[0195] To confirm that at higher traveling wave velocities a separation is dominated by the mass-to-charge ratio rather than the ion mobility, ions of the same mass-to-charge ratio but with different collision cross sections were investigated.

[0196] Fig. Figure 6 shows a graph plotting a mass-to-charge ratio against a drift time for the ions listed in Tables 1 and 3. In this case, the gas was static and helium at a pressure of 1 Torr. The traveling wave velocity was 300 m / s, and the amplitude of the transient DC voltage was ramped up from 2 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 3.4 and RMass to be 1.9.

[0197] This is very similar to the data in Fig. 2. However, the ions are now all singly charged ions with the same mass-to-charge ratio and differ only in the collision cross-section (“CCS”).

[0198] Fig. Figure 7 shows a graph plotting a mass-to-charge ratio against a drift time for the ions, which are in Fig. The following are modeled: In this case, the gas was static and helium at a pressure of 1 Torr. The traveling wave velocity was increased to 1500 m / s, and the amplitude of the transient DC voltage was ramped up from 8 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 1.3 and RMass to be 2.3.

[0199] This is very similar to the data found in Fig. Figure 5 shows that separation at this higher wave velocity is dominated by the mass-to-charge ratio and not by ion mobility or collision cross-section (“CCS”).

[0200] Fig. Figure 8 shows a graph plotting a mass-to-charge ratio against a drift time for the ions, which are in Fig. The following scenarios are modeled: In this case, the gas flowed at a velocity of 20 m / s in a direction opposite to the motion of the ions and at a pressure of 1 Torr helium. The traveling wave velocity was 1500 m / s, and the amplitude of the transient DC voltage was ramped up from 8 V at a rate of 0.2 V / ms. For these data, RMob was determined to be 2.4 and RMass to be 6.6.

[0201] It is clear from the increase in RMass that the mass-to-charge ratio separation efficiency of this device is nearly 3 times higher than that of the device mentioned above, due to the application of a counterflow of gas. Fig. The separation due to ion mobility is increased by a factor of 1.04 in the arrangement described in section 5. The maximum drift time is also increased by a factor of 3.

[0202] This shows that applying a countercurrent of gas to a traveling wave ion separation device operating in a mass or mass-to-charge ratio separation mode with a fast traveling wave velocity advantageously increases the mass or mass-to-charge ratio separation performance of the device.

[0203] Fig. Figures 9A to 9C show a further embodiment of the present invention, wherein the countercurrent of gas may not be completely opposite to the direction in which the ions are pushed by the traveling wave.

[0204] Fig. Figure 9A shows the device in the (y,z) plane. The device is constructed from two planar arrangements of plate-like electrodes 6, which are preferably inclined or angled with respect to the direction of the gas flow 5. Ions are preferably confined in the y-direction by applying alternating phases of an RF frequency AC voltage potential to the plate electrodes. This forms a pseudopotential confinement force in the y-direction. If necessary, ions can be confined in the x-direction by electrodes extending along the z-length of the device in the z-direction, to which a DC confinement potential is applied. Fig. Figure 9B shows the device in the (x,y) direction and shows the planar electrodes 6 and the DC electrodes 7. Fig. Figure 9C shows the device in the (x,z) plane. During operation, a DC traveling wave is preferably applied to the planar electrodes 6.

[0205] Fig. Figure 10A shows the same device in the (y,z) plane and shows the path that ions preferably take through the device in the absence of a countercurrent of gas. Ions can be introduced continuously or as a pulse. All ions preferably follow the same path.

[0206] When ions are introduced as a packet or pulse, the ions are preferably separated according to ion mobility or mass-to-charge ratio depending on the speed of the traveling wave and will leave the device as shown or strike one of the electrodes.

[0207] Fig. Figure 10B shows the path of ions in the presence of a countercurrent of gas 5. Ions with a specific ion mobility or mass-to-charge ratio can be designed to exit the device at an outlet opening 10 and strike an ion detector or to be allowed to pass forward to a further device. Ions with lower mobility or with a higher mass-to-charge ratio 11 will not migrate as far through the device. These ions can be discarded by design. Ions with higher mobility or with a lower mass-to-charge ratio 8,9 preferably migrate further through the device and can also be discarded.

[0208] The device, as described above, can be designed to provide high-resolution ion mobility filtering or mass-to-charge ratio filtering, depending on the speed of the traveling wave. The device can be used with either a pulsed or a continuous beam of ions.

[0209] By varying the amplitude or speed of the traveling wave or the speed of the gas flow, ions with different properties can be designed to leave the device.

[0210] Fig. Figure 11 shows another embodiment of the device. This embodiment is identical to the one in Fig.Figure 1 shows the device 3, except that in this case the gas flow 5 runs in one direction from the inlet 1 to the outlet of the device 3. A traveling wave voltage is preferably applied to the electrodes, preferably to counteract the gas flow 4, which drives ions from the outlet 3 to the inlet of the device 1. In operation, the amplitude and velocity of the traveling wave are such that ions of interest cannot be overtaken by the traveling wave and are therefore driven towards the inlet of the device. Ions are effectively trapped near the inlet of the device by a combination of the gas flow and the opposing traveling wave, essentially without separation.Preferably, ions migrate from this capture region to the device's output by increasing the speed of the traveling wave or the rate at which transient DC voltages or potentials are applied to the electrodes, such that ions with low mobility begin to be overtaken by the traveling wave or the transient DC voltages or potentials. By scanning or grading the speed of the traveling wave or the transient DC voltages or potentials from low to high speed, ions preferably exit the device in ascending order of ion mobility or collision cross-section. Complete high-resolution ion mobility separation spectra can be generated.Less preferably, the amplitude of the traveling wave or the transient DC voltages or DC potentials can be reduced to allow ions to leave the device, or a combination of amplitude and velocity can be used.

[0211] Using a continuously introduced ion beam, this approach can be used to provide an operating mode with a mobility limit.

[0212] This embodiment can be implemented in the intermediate pressure pass-through region between an atmospheric ion source and a downstream analytical device or mass spectrometer. In this region, the gas flow direction is from high pressure at the ion source or ion inlet to low pressure at the outlet of the device. Ions can be trapped using a traveling wave or transient DC voltages or potentials and sequentially sampled in order of their ion mobility within this region of the mass spectrometer.

[0213] In some cases it may be advantageous to operate the device in an intermediate separation mode in which the separation includes a component of ion mobility as well as a component of mass-to-charge ratio, rather than in a situation in which the separation is predominantly dependent on ion mobility, collision cross-section or predominantly dependent on mass-to-charge ratio.

[0214] The device can be operated in discrete steps or continuously between mass-charge ratio separation and ion mobility separation, depending on the desired operating mode.

Claims

[1] Method for separating ions, comprising: Providing a separation device comprising multiple electrodes; Applying one or more transient DC voltages to at least some of the electrodes to drive ions through the separation device in a first direction; Providing a gas flow in a second direction that is inclined or opposite to the first direction; Performing a first operating mode in which one or more transient DC voltages are traversed along at least a part of the axial length of the separation device at a first speed to cause ions to be separated according to their ion mobilities; and Performing a second mode of operation in which one or more transient DC voltages are traversed along at least a part of the axial length of the separation device at a second speed higher than the first speed in order to cause ions to be separated according to their mass-to-charge ratios; the gas flow is provided during the first and second operating modes. [2] The method of claim 1, wherein the second operating mode causes ions to leave the separation device in order of increasing or decreasing mass-to-charge ratio; wherein the second operating mode further comprises: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer. [3] Method according to claim 2, wherein the ion analyzer comprises an ion filter which only allows ions to pass through which have a certain value or range of values ​​of a physicochemical property at a given time, and wherein the value or range of values ​​which passes through the ion filter is varied over time in the second operating mode based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer. [4] The method of claim 2, wherein the ion analyzer is a batch ion analyzer which receives ions from the separation device and repeatedly pulses ions into an analysis area; and wherein the duration of the time between the pulses is varied as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer; or wherein the duration of the time between the exit of a given ion from the separation device and the pulse into the analysis area is varied as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer. [5] Method according to claim 4, wherein the ion analyzer is a time-of-flight mass analyzer and the analysis range is a time-of-flight range. [6] Method according to any one of claims 2-5, wherein the ion analyzer is a mass analyzer and / or the physicochemical property is a mass-to-charge ratio. [7] A method according to any of the preceding claims, wherein the first operating mode causes ions to leave the separation device in order of increasing or decreasing ion mobility; wherein the first operating mode further comprises: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronously with the ion mobilities of the ions leaving the separation device and received at the ion analyzer. [8] Method according to claim 7, wherein the ion analyzer in the first operating mode comprises an ion filter which only allows ions to pass through which have a certain value or range of values ​​of a physicochemical property at a given time, and wherein the value or range of values ​​which passes through the ion filter is varied over time in the first operating mode based on and synchronously with the ion mobilities of the ions leaving the separation device and being received at the ion analyzer. [9] Method according to claim 7 or 8, wherein the ion analyzer operating in the first mode is a mass analyzer and / or the physicochemical property is a mass-to-charge ratio. [10] Method according to claim 9, wherein the one or more mass-to-charge ratios of the ions passed through the ion filter in the first operating mode are varied over time and as a function of the ion mobilities received at the ion filter from the separation device in order to allow only ions of a selected charge state to pass through. [11] Method according to one of the preceding claims, comprising determining the mass-to-charge ratios of the separated ions in the second operating mode. [12] Method according to any one of the preceding claims, wherein the speed of one or more transient DC voltages in the first operating mode is ≤ x % of the speed of one or more transient DC voltages in the second operating mode, wherein X is selected from the following group: 90; 80; 70; 60; 50; 40; 30; 20; 10; or 5. [13] Method according to one of the preceding claims, wherein in the first operating mode the one or more transient DC voltages and the counter-gas current cause the ions to reach their final velocities; and in the second operating mode the one or more transient DC voltages and the counter-gas current do not cause the ions to reach their final velocities. [14] A method according to any of the preceding claims, comprising varying the amplitude of one or more transient DC voltages as a function of time during the first operating mode and / or the second operating mode; and / or wherein the one or more transient DC voltages have different amplitudes during the first and during the second operating mode. [15] The method of claim 14, comprising increasing and / or decreasing the amplitude of one or more transient DC voltages as a function of time during the first operating mode and / or the second operating mode; and / or wherein the one or more transient DC voltages have a higher amplitude during the first operating mode than during the second operating mode or a lower amplitude during the first operating mode than during the second operating mode. [16] Method according to any one of the preceding claims, wherein in the first and / or the second operating mode ions are separated in a separation zone which is maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; (ix)> 1000 mbar; (x) ≤ 5 mbar; and (xi) ≤ 10 mbar. [17] Method according to any of the preceding claims, wherein the method switches between the first and second operating modes while the same sample is analyzed in a single test run. [18] Methods for separating ions, comprising: Providing a separation device comprising multiple electrodes; Applying multiphase alternating or RF voltages to at least some of the electrodes, switching the phase of the voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction through the separating device; and Providing a gas flow in a second direction that is inclined or opposite to the first direction; Performing a first operating mode in which one or more alternating or RF voltages are applied along at least a part of the axial length of the separation device such that the pseudo-potential barrier moves along the device at a first velocity to cause ions to be separated according to their ion mobilities; and Performing a second mode of operation in which one or more alternating or RF voltages are applied along at least a part of the axial length of the separation device such that the pseudo-potential barrier moves along the device at a second speed higher than the first speed in order to cause ions to be separated according to their mass-to-charge ratios; the gas flow is provided during the first and second operating modes. [19] Method for separating ions according to mass-charge ratio, comprising: Providing a separation device comprising multiple electrodes; Applying one or more transient DC voltages to at least some of the electrodes to drive ions through the separation device in a first direction; Providing a gas flow in a second direction that is inclined or opposite to the first direction; where ions are separated according to their mass-to-charge ratios by one or more transient DC voltages and the counter-current gas flow. [20] The method of claim 19, wherein ions are caused to leave the separation device in order of increasing or decreasing mass-to-charge ratio; wherein the method further comprises: sending the ions, while separated, from the separation device to a downstream ion analyzer; and varying the operation of the ion analyzer as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer. [21] Method according to claim 20, wherein the ion analyzer comprises an ion filter which allows only ions to pass through which have a certain value or range of values ​​of a physicochemical property at a given time, and wherein the value or range of values ​​which passes through the ion filter is varied over time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and being received at the ion analyzer. [22] The method of claim 20, wherein the ion analyzer is a batch ion analyzer which receives ions from the separation device and repeatedly pulses ions into an analysis area; and wherein the duration of the time between the pulses is varied as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer; or wherein the duration of the time between the exit of a given ion from the separation device and the pulse into the analysis area is varied as a function of time based on and synchronously with the mass-to-charge ratios of the ions leaving the separation device and received at the ion analyzer. [23] Method according to claim 22, wherein the ion analyzer is a time-of-flight mass analyzer and the analysis range can be a time-of-flight range. [24] Method according to one of claims 20-23, wherein the ion analyzer is a mass analyzer and / or the physicochemical property is a mass-to-charge ratio. [25] Method according to one of claims 19-24, comprising determining the mass-to-charge ratios of the separated ions. [26] Method according to one of claims 19-25, wherein ions having the same mass-charge ratio but different ion mobilities are separated by the device. [27] Method according to one of claims 19-26, comprising varying the amplitude of one or more transient DC voltages as a function of time. [28] Method according to claim 27, wherein the ions are separated with higher mass-to-charge ratio resolution when one or more transient DC voltages have a higher velocity, and are separated with lower mass-to-charge ratio resolution when one or more transient DC voltages have a lower velocity. [29] Methods for separating ions according to mass-charge ratio or ion mobility, comprising: Providing a separation device comprising multiple electrodes; Applying multiphase alternating or RF voltages to at least some of the electrodes, switching the phase of the Voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction through the separation device; and Providing a gas flow in a second direction that is inclined or opposite to the first direction; the ions are separated according to their mass-to-charge ratios or ion mobilities by the pseudo-potential barrier and the counter-gas flow. [30] Method for mass spectrometry or ion mobility spectrometry comprising a method according to any of the preceding claims. [31] Separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages to at least some of the electrodes in order to drive ions through the separation device in a first direction; a second device designed and adapted to provide a gas flow in a second direction that is inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices for the following: Performing a first operating mode in which one or more transient DC voltages are traversed along at least a part of the axial length of the separation device at a first speed to cause ions to be separated according to their ion mobilities; Performing a second mode of operation in which one or more transient DC voltages are traversed along at least a portion of the axial length of the separation device at a second speed higher than the first speed, in order to cause ions to be separated according to their mass-to-charge ratios; and Providing the gas flow during the first and second operating modes. [32] Separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply multiphase alternating or RF voltages to at least some of the electrodes and to switch the phase of the voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction through the separating device; a second device designed and adapted to provide a gas flow in a second direction that is inclined or opposite to the first direction; a controller designed and adapted to control the first and second devices for the following: Performing a first operating mode in which one or more alternating or RF voltages are applied along at least a part of the axial length of the separation device such that the pseudo-potential barrier moves along the device at a first velocity to cause ions to be separated according to their ion mobilities; Performing a second mode of operation in which one or more alternating or RF voltages are applied along at least a portion of the axial length of the separation device such that the pseudo-potential barrier moves along the device at a second velocity higher than the first velocity to cause ions to be separated according to their mass-to-charge ratios; and Providing the gas flow during the first and second operating modes. [33] Separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages to at least some of the electrodes in order to drive ions in a first direction through the separation device; and a second device designed and adapted to provide a gas flow in a second direction inclined or opposite to the first direction; and a controller designed and adapted to control the first and second devices such that the one or more transient DC voltages drive the ions against the gas flow in such a way that the ions are separated according to their mass-to-charge ratios by the one or more transient DC voltages and the counter-gas flow. [34] Separation device for separating ions, comprising: multiple electrodes; a first device designed and adapted to apply multiphase alternating or RF voltages to at least some of the electrodes and to switch the phase of the voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction through the separating device; a second device designed and adapted to provide a gas flow in a second direction inclined or opposite to the first direction; and a controller designed and adapted to control the first and second devices such that the pseudo-potential barrier drives the ions against the gas flow in such a way that the ions are separated by the pseudo-potential barrier and the counter-gas flow according to their mass-to-charge ratios or ion mobilities. [35] Mass spectrometer or ion mobility spectrometer comprising a separation device according to any one of claims 31-34. [36] Method for filtering ions, comprising: Providing an ion filter that includes multiple electrodes; Applying one or more transient DC voltages to the electrodes to drive ions in a first direction along the filter; and Providing a gas flow along the filter in a second direction to counteract the movement of ions in the first direction; wherein the first and second directions are angled relative to each other at a different angle than orthogonal, so that ions with different physicochemical property values ​​migrate along different paths through the filter and so that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path. [37] Method according to claim 36, wherein the physicochemical property is an ion mobility or a mass-to-charge ratio. [38] Method according to claim 36 or 37, wherein the multiple electrodes to which the one or more transient DC voltages are applied are arranged parallel and in a third direction, wherein the first and the third direction are angled relative to each other at an angle other than orthogonal. [39] A method according to claim 36, 37 or 38, comprising varying one or more operating parameters of the filter to select or vary one or more physicochemical property values ​​of the ions leaving the filter along the desired exit path, wherein the one or more operating parameters are: gas flow velocity; gas flow direction; velocity of the transient DC voltage along the filter; amplitude of the transient DC voltage; and direction of motion of the transient DC voltage. [40] Method for filtering ions, comprising: Providing an ion filter that includes multiple electrodes; Applying multiphase alternating or RF voltages to at least some of the electrodes, switching the phase of the voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or modulating the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction along the filter; and Providing a gas flow along the filter in a second direction to counteract the movement of ions in the first direction; wherein the first and second directions are angled relative to each other at a different angle than orthogonal, so that ions with different physicochemical property values ​​migrate along different paths through the filter and so that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path. [41] Ion filters, which include: multiple electrodes; a first device designed and adapted to apply one or more transient DC voltages to the electrodes to drive ions in a first direction along the filter; a second device designed and adapted to provide a gas flow in a second direction to counteract the movement of the ions in the first direction, wherein the first and second directions are angled relative to each other at an angle other than orthogonal; and a controller designed and adapted to control the first and second devices such that one or more transient DC voltages push the ions against the gas flow, so that ions with different physicochemical property values ​​migrate along different paths through the filter and that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path. [42] Ion filters, which include: multiple electrodes; a first device designed or adapted to apply multiphase alternating or RF voltages to the electrodes, to switch the phase of the voltages applied to successive electrodes along the device such that a pseudo-potential barrier moves along the device, or to modulate the amplitude of the voltages successively along the device such that a pseudo-potential barrier moves along the device, the pseudo-potential barrier driving ions in a first direction along the filter; a second device designed or adapted to provide a gas flow in a second direction to counteract the movement of the ions in the first direction, wherein the first and second directions are angled relative to each other at an angle other than orthogonal; and a controller designed or adapted to control the first and second devices such that the pseudo-potential barrier pushes ions against the gas flow, so that ions with different physicochemical property values ​​migrate along different paths through the filter and that only ions of a selected value or range of values ​​of the physicochemical property leave the ion filter along a desired exit path.

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