Ion mobility separator

Abstract

An ion mobility separation apparatus, the ion mobility separation apparatus comprising: a plurality of ion mobility separator (IMS) devices (12, 13) arranged in parallel; an entrance gate (25) configured to direct ions into one or more of the IMS devices at any given time; and a control circuit configured to operate each of the IMS devices in a separate mode in which a first voltage is applied to the electrodes of the IMS device to provide a static DC electric field that urges ions along the IMS device in one direction and also to apply a second voltage to the electrodes of the IMS device to provide a static DC electric field that urges ions along the IMS device in one direction. The IMS device is configured to provide DC potentials that travel repeatedly along the IMS device in opposite directions such that ions are separated as a function of their mobility within the IMS device.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of UK Patent Application No. 2207395.1 filed on May 20, 2022. The entire contents of this application are incorporated herein by reference. Technical Field

[0003] The present invention relates generally to mass spectrometry and, more particularly, to techniques for separating ions based on their physicochemical properties such as ion mobility or mass-to-charge ratio. Background Art

[0004] An ion mobility separator (IMS) is a known device for separating ions according to their mobility through a gas. An example of such an IMS device is a drift tube IMS device. These devices have an ion trap that pulses ion packets into a drift tube with a background gas therein. A static direct current (DC) gradient is maintained along the drift tube to push the ions through the gas from the upstream end near the ion trap to the downstream end. Ions of different mobilities will have different transit times through the gas to the drift tube outlet and are therefore separated according to their mobility.

[0005] Traveling wave IMS devices are also known. In these devices, a DC potential is repeatedly traveled along the drift tube to push the ions in the downstream direction toward the exit of the drift tube, rather than providing a static DC gradient along the drift tube to push the ions. Each time ions with different mobilities pass through the traveling DC potential, they are pushed downstream by different amounts. Thus, the traveling DC potential causes the ions to separate and leave the IMS device at different times based on their mobilities.

[0006] However, because such conventional IMS devices trap all ions before pulsing them into a drift tube for separation, these devices suffer from space charge effects because ions are trapped at a relatively high charge concentration in the ion trap. This space charge effect reduces the mobility resolution of the IMS device and can also result in ion loss.

[0007] Other types of IMS devices are known that separate ions according to their mobility within an ion trap and then release the ions from the ion trap in order of mobility. These devices capture ions and then provide opposing forces on the ions so that they are separated along a capture region according to their mobility. For example, a gas flow can push the ions in a first direction and a static DC gradient can push the ions in an opposite second direction so that the ions are separated according to their mobility within the ion capture region. The gradient of the static DC gradient can then be gradually reduced so that the ions are eluted from the capture region in order of their ion mobility, i.e., ions with relatively low mobility elute first, and ions with gradually increasing mobility elute later as the DC gradient is gradually reduced. Summary of the invention

[0008] A first aspect of the present invention provides an ion mobility separation apparatus, which includes: a plurality of ion mobility separator (IMS) devices arranged in parallel; an entrance gate configured to direct ions into one or more of the IMS devices at any given time; and a control circuit configured to operate each of the IMS devices in a separation mode, in which a first voltage is applied to electrodes of the IMS device to provide a static DC electric field that pushes ions along the IMS device in one direction, and a second voltage is also applied to the electrodes of the IMS device to provide a DC potential that repeatedly travels along the IMS device in an opposite direction, so that the ions are separated according to their mobility within the IMS device.

[0009] The present inventors have recognised that by providing multiple IMS devices in parallel, where the IMS devices use voltage to apply electrostatic forces to ions in two directions (e.g., instead of using gas flow to push the ions), a relatively high space charge capacity ion separation apparatus is provided which can operate with relatively low vacuum pump requirements.

[0010] Many conventional IMS devices force the ions into a relatively small volume before pulsing them into the drift region, where the ions are separated according to mobility, because it is desirable to pulse all ions into the drift region substantially simultaneously in order for the IMS device to provide a high mobility resolution. Thus, even with a relatively small population of ions, and even if multiple such IMS devices are provided in parallel, these devices may be affected by space charge effects.

[0011] In contrast, embodiments of the present invention do not pulse ions through a drift region to separate them by mobility. Instead, the ions are separated by opposing forces in the capture region. Thus, the ions do not need to be confined or focused in a small volume, and space charge effects are therefore less prevalent. Furthermore, the present invention enables ions to be directed into multiple IMS devices, and thus a relatively large number of ions can be processed by the device before space charge effects within any given one IMS device become a problem.

[0012] The static DC electric field of the present invention may have a gradient such that the amplitude of the electric field increases with increasing distance in the opposite direction, for example the amplitude of the DC potential may increase quadratically with increasing distance in the opposite direction.

[0013] Each time the DC potential travels along the IMS device it may decrease in amplitude (and / or increase in speed).

[0014] Whenever a DC potential as described herein travels along the device, ions with different mobilities are pushed by it by different amounts. Thus, the traveling DC potential causes the ions to separate based on their mobilities.

[0015] The apparatus may be configured to operate each IMS device in an elution mode after operating in a separation mode, during which elution mode: (i) a first voltage is gradually varied such that a gradient of a static DC electric field also changes, thereby causing ions to elute from the IMS device over time in the order of mobility or in the reverse order of mobility; and / or (ii) a second voltage is gradually varied such that at least one property of a DC potential repeatedly traveling along the IMS device also gradually changes, thereby causing ions to elute from the IMS device over time in the order of mobility or in the reverse order of mobility.

[0016] For example, the amplitude of the DC potential may be gradually decreased or increased over time to cause ions to elute from the IMS device in order of mobility or in reverse order of mobility over time.Alternatively or additionally, the speed of the DC potential may be gradually increased or decreased over time.

[0017] Each IMS device is arranged to receive ions from an entrance gate at its upstream end, operate in a separation mode to separate the ions according to mobility, and then operate in an elution mode to cause ions of different mobilities to elute from the IMS device at different respective times. The ions are preferably eluted from a downstream end of the IMS device, which is located at the end of the IMS device opposite to the upstream end.

[0018] The separation mode separates the ions in the capture region.A region of substantially constant DC electric field may be provided immediately downstream of the capture region, which further separates the ions according to mobility once they elute from the capture region.

[0019] The separated ions are eluted from the IMS device, for example, ions with increasing mobility are allowed to leave the IMS device over time, or ions with decreasing mobility are allowed to leave the IMS device over time.

[0020] The IMS devices are arranged in parallel, rather than in series, ie, so that each IMS device can receive ions from an entrance gate without the ions being sent through a different IMS device.

[0021] The apparatus may include control circuitry configured to control elution of ions from the plurality of IMS devices such that ions exiting all of the IMS devices at any given time have substantially the same mobility.

[0022] The device may include a control circuit configured to control the ion mobility separation device so that during a first time period, the entrance gate causes ions to be supplied to a first IMS device in the IMS devices so as to accumulate and separate the ions in the first IMS device, and causes a second IMS device in the IMS devices to elute the ions in the order of ion mobility or in the reverse order of ion mobility while the ions are accumulated and separated. Optionally, the control circuit is configured to control the ion mobility separation device so that during a subsequent second time period, the entrance gate causes ions to be supplied to a second IMS device in the IMS devices so as to accumulate and separate the ions in the second IMS device, and causes the first IMS device to elute the ions in the order of mobility or in the reverse order of ion mobility while the ions are accumulated and separated in the second IMS device.

[0023] Each IMS device may include an ion guide, such as an elongated ion guide, having electrodes and an RF voltage applied thereto such that ions are radially confined within the ion guide. The ion guide may be, for example, an ion tunnel ion guide formed by apertured electrodes such as ring electrodes, or any other type of ion guide such as a multipole rod set ion guide.

[0024] The apparatus may further include an upstream ion guide for directing the ion beam to an entrance gate, wherein the entrance gate is configured to: (i) split the ion beam into a plurality of ion beams that are directed simultaneously to a corresponding plurality of IMS devices; or (ii) direct the ion beam to different IMS devices at different times.

[0025] The entrance gate may be arranged to receive ions along a first axis and include opposing arrays of electrodes spaced apart from one another and at least one voltage source for applying at least one RF voltage to the electrodes of the arrays to confine the ions in an ion guide region between the arrays.

[0026] Each electrode array may include a plurality of rows of electrodes and / or a plurality of columns of electrodes. The electrode columns may be substantially parallel to the first axis, and the electrode rows may be substantially perpendicular to the first axis.

[0027] The same phase RF potential may be applied to all electrodes in the same column of electrodes, while any given adjacent pair of electrode columns may be maintained at different RF phases, preferably opposite RF phases. However, it is alternatively conceivable that the same phase RF potential may be applied to all electrodes in the same row, and any given adjacent pair of electrode rows may be maintained at different RF phases, preferably opposite RF phases. If the array has rows and columns of electrodes, adjacent electrodes in each row may be at opposite RF phases, and adjacent electrodes in each column may be at opposite RF phases.

[0028] The entrance gate may include side electrodes on each side of the first axis and at least one power supply for applying voltage to the side electrodes to push ions orthogonal to the first axis.

[0029] Each IMS device may have a longitudinal axis passing therethrough along which ions are received; wherein at least one of the IMS devices or each of at least some of the IMS devices has its longitudinal axis displaced from a first axis; and wherein the entrance gate has a control circuit configured to apply different DC voltages to different electrodes in the array and / or to different side electrodes so as to deflect ions received along the first axis onto one or more longitudinal axes of one or more IMS devices so that the ions enter the one or more IMS devices.

[0030] The ion mobility separation assembly may include a mobility filter for filtering ions according to their mobility, such that only ions within a selected mobility range are sent to one or more IMS devices, while other ions are filtered out. This helps to further avoid space charge effects in the IMS device, for example by filtering out relatively abundant low mobility ions that are of less interest for research.

[0031] The different DC voltages can provide a static DC electric field that pushes the ions in a first direction orthogonal to the first axis, and the control circuit can be configured to also apply a voltage to an electrode of the entrance gate so as to provide a DC potential that repeatedly travels along the entrance gate in a second direction opposite to the first direction, so that the ions separate according to their mobility along the first direction and therefore have different trajectories through the entrance gate.

[0032] Therefore, ions leave the entrance gate at different locations depending on their mobility.

[0033] The control circuitry may control the values ​​of the various DC voltages and the parameters of the DC travel potential so that ions having a selected mobility range exit the entrance gate at a certain location so as to be able to enter one or more IMS devices.

[0034] Different DC potentials may be applied to different electrodes in the array in order to push ions from the entrance of the entrance gate toward its exit along a first axis.

[0035] However, it is contemplated that the entrance gate may take other forms. For example, the entrance gate may include a first transition portion having electrodes positioned to receive ions along a first axial path, a second portion having electrodes configured to direct ions along the axial path to a first IMS device in the IMS device, and a third portion having electrodes configured to direct ions along the axial path to a second IMS device in the IMS device, wherein the electrodes receiving ions along the first axial path are arranged to provide at least one gap at a circumferential position around the first axial path, and wherein the entrance gate includes a power source for applying a DC voltage to the electrodes of the entrance gate such that ions are pushed orthogonally from the first axial path, through the at least one gap, and onto the axial path of the first IMS device and / or the second IMS device.

[0036] The first axial path, the axial path of the first IMS device, and the axial path of the second IMS device may all be displaced from one another. Alternatively, the first axial path may be displaced from the axial path of the first IMS device, but may coincide with the axial path of the second IMS device. In other words, ions may be pushed orthogonally from the first axial path to the axial path leading to the first IMS device, but may not be pushed orthogonally when they continue to the second IMS device.

[0037] The entrance gate may include at least one plate-like electrode stack arranged between a first electrode and a second electrode to define a first ion guide path for guiding ions from an ion entrance region of the entrance gate to a first IMS device in the IMS device, and a second ion guide path for guiding ions from the ion entrance region to a second IMS device in the IMS device.

[0038] Where a plurality of electrode stacks are provided, the different stacks may be spaced apart (in a direction orthogonal to the direction between the first electrode and the second electrode) so as to define ion guiding paths between the stacks.

[0039] The electrodes in at least one stack and optionally the top and bottom electrodes may be maintained at an RF voltage such that ions are repelled from these electrodes. Adjacent electrodes may be maintained at different phases of the RF voltage, such as opposite phases, in the direction between the top and bottom electrodes. Electrodes in different stacks but within the same layer may be maintained at the same RF phase. In addition to or as an alternative to applying an RF voltage, a DC voltage may be applied to the top and bottom electrodes to repel ions.

[0040] The apparatus may further include a downstream ion guide and an exit gate between the IMS device and the downstream ion guide, wherein the exit gate is configured to receive ions from the plurality of IMS devices and direct the ions into the downstream ion guide.

[0041] Ions may be eluted from multiple IMS devices simultaneously, and these multiple ion streams from multiple IMS devices may be combined by an exit gate to form a single ion beam.

[0042] Although the preferred embodiment employs DC voltages within each IMS device to push the ions in opposite directions and separate them by mobility, it is contemplated that the ions may be pushed in one or both directions by another force such as, for example, gas flow.

[0043] Therefore, a second aspect of the present invention provides an ion mobility separation apparatus, which comprises: a plurality of ion mobility separator (IMS) devices arranged in parallel; an entrance gate configured to direct ions into one or more of the IMS devices at any given time; and a control circuit configured to operate each of the IMS devices in a separation mode, in which a voltage is applied to electrodes of the IMS devices so as to push ions along the IMS devices in one direction, and wherein the apparatus is configured to provide a gas flow in an opposite direction so that the ions are separated according to their mobility within the IMS device.

[0044] The gas flow may be provided in a downstream direction (ie in a direction away from the ion source), but less preferably the gas flow may be provided in an upstream direction.

[0045] The control circuit may be configured to apply the voltage to the electrodes of the IMS device so as to provide a static DC electric field that pushes the ions in the one direction. For example, the electric field may have a gradient such that the magnitude of the electric field increases with increasing distance in the opposite direction, for example the amplitude of the DC potential may increase quadratically with increasing distance in the opposite direction.

[0046] Alternatively, the control circuit may be configured to apply said voltage to the electrodes of the IMS device so as to provide a DC potential that travels repeatedly along the IMS device in said one direction.The amplitude of the DC potential may decrease each time it travels in said one direction.

[0047] The apparatus according to the second aspect of the invention may have any of the features described in relation to the first aspect of the invention except that the gas flow is used to propel the ions in one direction.

[0048] For example, the device may have an entry gate as described herein that can filter ions by mobility.

[0049] It is conceivable that ions can be separated by physicochemical properties (such as mass-to-charge ratio) different from mobility or in addition to mobility. For example, it is known that in IMS equipment, wherein DC potential is repeatedly advanced along equipment to separate ions by mobility, and there is mass-to-charge ratio dependence in ion separation, such as K.Richardson, D.Langridge, K.Giles, "Traveling Wave Ion Mobility Foundation Re-exploration: I. Waves Moving Steadily", "International Journal of Mass Spectrometry", Vol. 428, 2018, described in pages 71-80. The operating parameters of the separator can be selected, such as the speed of the DC potential of pressure and / or travel, so that it is mainly separated by mobility, so that it is mainly separated by mass-to-charge ratio, or so that it is significantly dependent on the mode operation of both mobility and mass-to-charge ratio with ion separation. It is also conceivable that the separator can be switched between two or more modes in these modes by changing one or more operating parameters in its operating parameters. For example, it is envisioned that such an embodiment, wherein the pressure in the separator is reduced to reduce the mobility dependence of separation and increase the mass-to-charge ratio dependence of separation. This embodiment can switch from a mode where ions are separated primarily by mobility to a mode where ions are separated primarily by mass-to-charge ratio by reducing the pressure in the separator.

[0050] In a mode where ions are separated primarily according to mobility, the separated ions can be allowed to elute from the separator in an order of increasing or decreasing mobility. The calibration of the elution times of the ions to their mobility values ​​can take into account the mass-to-charge ratio dependence of the ion separation. Similarly, in a mode where ions are separated primarily according to mass-to-charge ratio, the separated ions can be allowed to elute from the separator in an order of increasing or decreasing mass-to-charge ratio. The calibration of the elution times of the ions to their mass-to-charge ratio values ​​can take into account the mobility dependence of the ion separation.

[0051] Therefore, the third aspect of the present invention also provides an ion separation device, which includes: a plurality of separator devices arranged in parallel, each separator device being used to separate ions according to physicochemical properties; an entrance gate, which is configured to guide ions into one or more separator devices among the separator devices at any given time; and a control circuit, which is configured to operate each separator device in the separator device in a separation mode, in which a first voltage is applied to the electrodes of the separator device so as to provide a static DC electric field that pushes the ions along the separator device in one direction, and a second voltage is also applied to the electrodes of the separator device so as to provide a DC potential that repeatedly travels along the separator device in the opposite direction, so that the ions are separated according to the physicochemical properties within the separator device.

[0052] The apparatus according to the third aspect of the invention may have any of the features described in relation to the first aspect of the invention, except that the ions are separated according to a physicochemical property other than mobility.

[0053] For example, the device may have an access door as described above.

[0054] For example, a physicochemical property may be the mass-to-charge ratio.

[0055] The present invention also provides a mass spectrometer and / or ion mobility spectrometer, the mass spectrometer and / or ion mobility spectrometer comprising a device for separating ions by mobility or said physicochemical properties as described herein. The spectrometer may include a mass analyzer and a detector for mass analysis and / or detection of these ions or ions derived therefrom.

[0056] The present invention also provides a method for separating ions by ion mobility, the method comprising: providing an ion mobility separation apparatus according to any preceding claim; providing ions to an entrance gate and controlling the entrance gate so as to direct the ions into one or more of the IMS devices in the IMS device at any given time; and operating the IMS device so as to operate in a separation mode simultaneously or sequentially so as to separate ions according to the mobility of the ions.

[0057] The present invention also provides a method for separating ions according to physicochemical properties, the method comprising: providing an ion separation device as described above in this document; providing ions to an entrance gate and controlling the entrance gate so as to direct the ions into one or more separation devices in the separation device at any given time; and operating the separation device so as to operate in a separation mode simultaneously or sequentially so as to separate ions according to physicochemical properties.

[0058] The present invention also provides a method of mass spectrometry and / or ion mobility spectrometry, which method comprises separating ions by mobility or said physicochemical properties as described herein, and then mass analyzing and / or detecting these ions or ions derived therefrom. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Various embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings, in which:

[0060] Figure 1 A schematic diagram of a known IMS device is shown;

[0061] Figure 2 An embodiment of the present invention is shown;

[0062] Figure 3A-3C An embodiment of an ion separator using a traveling DC potential to separate ions is shown;

[0063] Figure 4 Shows something like Figure 2 Another embodiment of;

[0064] Figure 5 An embodiment illustrating an entrance gate for deflecting ions into different IMS devices is shown;

[0065] Figure 6A-6B An embodiment of an entry gate including an electrode array is shown;

[0066] Figure 7A-7B An embodiment of an exit gate including an electrode array is shown;

[0067] Figure 8 Shows the corresponding Fig. 6A Another embodiment of an entrance door of the entrance door shown in , except having a plurality of side electrodes on each side;

[0068] Figure 9A-9C An embodiment of an inlet gate when operating as an ion mobility filter is shown;

[0069] Figure 10A-10B Another embodiment of an entry door is shown; and

[0070] Figure 11A-11BAnother embodiment of an access gate formed by stacked plate electrodes is shown. DETAILED DESCRIPTION

[0071] Figure 1 A schematic diagram of a known IMS device is shown. The IMS device comprises an ion guide 2 in which ions are radially confined. Ions are received at an upstream end, as indicated by arrow 3, and are radially confined within the ion guide 2. A gas flow in a downstream direction provides a driving force on the ions in the downstream direction, as illustrated by arrow 4. A DC electric field is applied along the ion guide to provide a driving force on the ions in the upstream direction, as illustrated by arrow 5.

[0072] The two opposing forces acting on the ions caused by the gas flow 4 and the electric field 5 cause the ions to separate along the ion guide according to their ion mobility. More specifically, for ions of different mobilities, the two opposing forces acting on the ions are balanced at different positions along the ion guide. Therefore, ions of different mobilities are trapped at different axial positions along the capture region of the ion guide 2. Figure 1 ion 6 represents an ion with low mobility, ion 7 represents an ion with high mobility, and ion 8 represents an ion with even higher mobility.

[0073] When it is desired to release ions from the ion trapping region, the gradient of the DC electric field 5 is gradually reduced so that the gas flow 4 can force the ions to elute from the trapping region gradually in the order of ion mobility. The gas flow forces the ions to elute from the downstream end of the trapping region, such as Figure 1 As illustrated by arrow 9 in FIG. 1 , when the electric field gradient is reduced, the lowest mobile ions 6 elute first, then when the gradient is reduced further, the high mobile ions 7 elute, then when the gradient is reduced still further, the still higher mobile ions 8 elute.

[0074] Figure 2 An embodiment of the invention is shown. In this embodiment, the spectrometer has two IMS devices 12, 13, each of which is arranged to receive ions at its upstream end, separate the ions according to mobility, and elute the ions from its downstream end. Each IMS device may be about Figure 1 The type described, or may be a different type of IMS device, as described in more detail below. Figure 2 Only two IMS devices are depicted in FIG. 1 , but it should be understood that one or more further such IMS devices may be provided in parallel with the depicted IMS devices.

[0075] The ions can be directed toward multiple IMS devices as a single ion beam 3. The single ion beam can then be split into multiple ion beams 10, 11 so that the ions enter the upstream ends of multiple IMS devices simultaneously while they all simultaneously operate in an ion accumulation mode that traps the ions in a capture region. Alternatively, the single ion beam 3 can be deflected so that all ions in the single ion beam enter only a single IMS device in the IMS device at any given time while the IMS device operates in an ion accumulation mode to trap the ions in a capture region. In this embodiment, ions from a single ion beam 3 are directed to different IMS devices at different times.

[0076] Because multiple IMS devices are provided in parallel, embodiments of the present invention provide for relatively high space charge capacity because, at any given time, ions may be distributed across multiple trapping regions of multiple IMS devices.

[0077] During or after ion accumulation in the capture region of any given IMS device, the IMS device separates the ions according to their mobility. The separated ions are then eluted from a downstream outlet of the IMS device, such as causing ions with increasing mobility to leave the IMS device over time, or causing ions with decreasing mobility to leave the IMS device over time.

[0078] Ions may be eluted from the outlets of multiple IMS devices simultaneously, and these multiple ion streams from multiple IMS devices may be combined to form a single ion beam 9, such as Figure 2 In such an embodiment, the multiple IMS devices are preferably synchronized so that the ions leaving all IMS devices at any given time have the same mobility. This enables the ions to remain separated according to mobility in the combined ion beam 9. This may be preferred in embodiments where a single ion beam 3 received by an IMS device is split so that the ions enter multiple IMS devices simultaneously.

[0079] In embodiments where individual ion beams 3 are directed into different IMS devices at different times, the multiple IMS devices can still be synchronized so that ions leaving all IMS devices at any given time have the same mobility so that ions in a combined ion beam can be separated according to mobility.

[0080] Alternatively, at any given time, ions eluted from different IMS devices may have different mobilities. For example, an IMS device that is first filled by a single ion beam at a first fill time may begin eluting ions with a first mobility at the first elution time, while an IMS device that is filled by a single ion beam at a second fill time later than the first fill time may begin eluting ions with the first mobility at the second elution time later than the first elution time. The spectrometer may still be configured to combine ions from multiple IMS devices into a single ion beam such that ions remain separated according to mobility in the single ion beam.

[0081] Ions eluted from multiple IMS devices may be combined into a single ion beam in a substantially continuous manner. Alternatively, ions eluted from multiple IMS devices may be combined into a single ion beam discontinuously, for example, ions with a range of mobilities may be eluted from a first IMS device, and only ions with a smaller range of mobilities from a second IMS device may be combined with them.

[0082] Each of the IMS devices may be related to Figure 1 An IMS device of the type described. Thus, the IMS device may include an ion guide 2, such as an elongated ion guide, having electrodes and an RF voltage applied thereto so that ions are radially confined within the ion guide. The ion guide 2 may be, for example, an ion tunnel ion guide formed by a perforated electrode such as an annular electrode, or any other type of ion guide such as a multipole group ion guide. At least during the ion accumulation period, ions are received at the upstream end of the ion guide and enter the ion guide. The ions are radially confined within the ion guide and are prevented from leaving the downstream end of the ion guide during the ion accumulation period. Thus, the ions are trapped in a capture region of the ion guide, which may be an axially elongated volume.

[0083] As will be further described below, ions are separated in an axial direction along the ion trapping region by applying forces to the ions in opposite axial directions. Ions can be prevented from entering or leaving the trapping region while separating the ions according to mobility. After the ions have been separated by mobility, the IMS device can be made to elute the ions in ascending or descending order of mobility.

[0084] Each IMS device 12, 13 can separate ions according to mobility by providing a gas flow 4 that pushes the ions in a first axial direction and applying a voltage to the electrodes of the ion guide so as to push the ions in an opposite second axial direction. The gas flow can be provided in the downstream direction (i.e., towards the ion outlet of the IMS device), which is generally easier to achieve because the pressure in the spectrometer tends to decrease in the downstream direction. However, it is envisioned that the gas flow can alternatively be in the second axial direction (i.e., the upstream direction) and the voltage can push the ions in the opposite direction.

[0085] As described above, a voltage may be applied to the ion guide 2 so as to push ions against the gas flow in the second axial direction. The voltage is selected so that the gas flow 4 can push ions of different mobilities (i.e., mobilities through the gas) to different axial positions along the ion guide. More specifically, the gas flow will push ions with relatively low mobility against the opposing force attributed to the voltage until these ions reach a relatively far position along the ion guide in the first direction, while the gas flow will only be able to push ions with higher mobility along the ion guide in the first direction for a shorter distance. The voltage may be arranged to provide a static DC electric field 5 that pushes ions in the second direction. The electric field may have a gradient so that the amplitude of the electric field increases with increasing distance in the first direction, for example, the amplitude of the DC potential may increase quadratically with increasing distance in the first direction. Alternatively, the DC potential may be repeatedly advanced along the ion guide in the second axial direction so as to push ions against the gas flow. When the DC potential advances in the second axial direction, its amplitude may decrease.

[0086] After the ions have been separated according to mobility, within the capture region, the ions may be caused to elute from the outlet of the IMS device 12, 13 by gradually changing the voltage so that the gas flow 4 pushes the ions of increasing mobility to elute from the IMS device in a first direction over time. For example, the gradient of the electric field 5 may decrease over time so that this is achieved by gradually decreasing the gradient over time or by scanning the gradient downward over time in a substantially continuous manner. Alternatively, if the gas flow 4 is in an upstream direction and the electric field 5 pushes the ions in a downstream direction, the ions may be caused to elute from the outlet of the IMS device by gradually changing the voltage so that the force from the DC voltage 5 pushes the ions of decreasing mobility to elute from the IMS device in a first direction over time. For example, the gradient of the electric field may increase over time so that this is achieved by gradually increasing the gradient over time or by scanning the gradient upward over time in a substantially continuous manner.

[0087] A constant electric field region can be provided immediately downstream of the capture region, which further separates the ions according to mobility once they elute from the capture region. At any given time, the amplitude of the electric field in the constant electric field region is substantially constant along the constant electric field region. The amplitude of the electric field is substantially the same as the amplitude of the electric field at the downstream end of the capture region. Therefore, when the electric field in the capture region varies with time to cause ions of different mobilities to elute, the electric field in the constant electric field region will vary with time in a corresponding manner.

[0088] As described below, rather than using a static axial electric field to push ions against the gas flow, one or more DC potentials may be repeatedly passed along the ion guide in a direction opposite to the direction of the gas flow. Each time the one or more DC potentials pass along the ion guide, they may decrease in amplitude (and / or increase in speed) as they pass.

[0089] When the ions have been separated according to mobility within the capture region, the ions can be eluted from the outlet of the IMS device by gradually changing at least one property of one or more DC potentials that are repeatedly traveling along the ion guide, so that the gas flow pushes the ions of gradually increasing mobility to elute from the IMS device in a first direction over time. For example, when the gas flow is in a first direction and the DC potential is traveling in a second direction, the amplitude of the one or more DC potentials can be gradually reduced (smaller at any given point along the ion guide in elution mode than when operating in capture mode before ion elution). Alternatively or in addition, the speed of the one or more DC potentials in the second direction can be gradually increased (higher at any given point along the ion guide in elution mode than when operating in capture mode before ion elution).

[0090] Alternatively, when the gas flow is in the second (upstream) direction and the DC barrier is traveling in the first (downstream) direction, ions can be eluted from the outlet of the IMS device by gradually changing at least one property of one or more DC barriers that are repeatedly traveling along the ion guide, so that one or more DC potentials promote ions with gradually decreasing mobility to elute from the IMS device in the first direction over time. For example, the amplitude of one or more DC potentials can be gradually increased (greater at any given point along the ion guide in elution mode than when operating in capture mode prior to ion elution). Alternatively or in addition, the speed of one or more DC potentials in the first direction can be gradually reduced (lower at any given point along the ion guide in elution mode than when operating in capture mode prior to ion elution).

[0091] Although embodiments have been described in which the axial electric field or DC potential is varied to cause ion elution, it is contemplated that, in addition or alternatively, the gas flow rate may be varied to cause ion elution. For example, in any of the above embodiments, the gas flow rate may be gradually increased or decreased so that ions of different mobilities are eluted from the IMS device at different times.

[0092] The inventors have recognized that, although it is desirable to use a gas flow to push ions against opposing forces in order to separate ions when using a single IMS device, this is difficult to do when using multiple IMS devices. Providing multiple IMS devices that each use a gas flow to separate ions results in a relatively high combined gas flow rate through and out of the IMS device. The IMS device is located within a vacuum enclosure of the spectrometer, and therefore, the high gas flow rate increases the work that must be done by the vacuum pump of the spectrometer. This can also limit the gas flow rate that can be used to separate ions and / or the number of such IMS devices that can be used. Therefore, when using such a gas flow IMS device, the maximum space charge capacity is limited.

[0093] To overcome this, embodiments are contemplated in which at least some of the plurality of IMS devices do not rely on gas flow to separate ions by mobility. For example, one or more of the plurality of IMS devices may use voltage to exert a force on the ions in both a first direction and a second direction. Figure 3A A schematic diagram of an IMS device according to this embodiment is shown.

[0094] Figure 3A An IMS device is shown having an ion tunnel ion guide 2 comprising a plurality of electrodes spaced apart along the longitudinal axis of the IMS device, although alternative types of ion guides may be used as described above. The IMS device comprises an entrance electrode 15, a series of intermediate electrodes 16 and an exit electrode 17. Opposite phases 18a, 18b of an RF voltage may be applied to different (e.g. alternating) electrodes 16 in order to generate a pseudo potential which confines ions radially within the ion guide.

[0095] A voltage may be applied to the ion guide 2 in each of the one or more IMS devices 12, 13 to provide a static DC electric field that propels ions in a first (downstream) direction. The axial electric field may be substantially constant, i.e., due to a linear DC potential gradient. The one or more DC potentials 20 may be repeatedly passed along the ion guide in a second (upstream) direction to propel ions in the second direction. Each time the one or more DC potentials pass along the ion guide 2 in the second direction, they may decrease in amplitude (and / or increase in velocity) as they pass in the second direction, e.g., as Figure 3BAs shown in , the forces due to the axial electric field and due to the forces due to one or more DC potentials 20 cause the ions to separate axially along the trapping region and according to mobility.

[0096] When ions have been separated according to mobility within the capture region, the ions can be eluted from the outlet of the IMS device by gradually changing at least one property of one or more DC potentials 20 that are repeatedly traveling along the ion guide, so that the axial electric field in the first direction pushes the ions to elute from the IMS device in the first direction in the order of mobility (for example, in the order of increasing mobility) over time. For example, the amplitude of one or more DC potentials 20 can be gradually reduced (smaller at any given point along the ion guide in the elution mode than when operating in the capture mode before ion elution). Alternatively or in addition, the speed of one or more DC potentials in the second direction can be gradually increased (higher at any given point along the ion guide in the elution mode than when operating in the capture mode before ion elution).

[0097] Alternatively, the static DC electric field may be arranged to push the ions in the second (upstream) direction, and the DC potential 20 may be repeatedly passed along the ion guide in the first (downstream) direction to push the ions in the first direction. Each time the one or more DC potentials pass along the ion guide 2 in the first direction, they may decrease in amplitude (and / or increase in speed) as they pass in the first direction, e.g. Figure 3C As shown in . The forces generated by the axial electric field and the forces generated by one or more DC potentials 20 cause the ions to separate axially along the capture region and according to mobility. In these embodiments, the ions can be eluted from the outlet of the IMS device by gradually changing at least one property of one or more DC potentials that are repeatedly traveling along the ion guide, so that the one or more DC potentials push the ions to elute from the IMS device in a first direction in an order of mobility (for example, in an order of gradually decreasing mobility) over time. For example, the amplitude of one or more DC potentials can be gradually increased (greater at any given point along the ion guide in the elution mode than when operating in the capture mode before ion elution). Alternatively or in addition, the speed of one or more DC potentials in the first direction can be gradually reduced (lower at any given point along the ion guide in the elution mode than when operating in the capture mode before ion elution).

[0098] Embodiments have been described in which, during the separation mode, the axial electric field is substantially constant and the DC potential varies as it travels along the ion guide. However, it is alternatively contemplated that, in the separation mode, the amplitude of the axial electric field may vary with distance along the ion guide. For example, as the DC potential travels in the second direction, the amplitude of the axial electric field may decrease as distance in the first direction increases. Alternatively, as the DC potential travels in the first direction, the amplitude of the axial electric field may increase as distance in the first direction increases. In embodiments in which the axial electric field varies with distance along the ion guide, the amplitude and / or velocity of the DC potential 20 may not vary with distance along the ion guide, for example as Figure 3A as shown in .

[0099] For the avoidance of doubt, the first direction is the direction in which ions are eluted from each IMS device, which corresponds to the direction from the ion source to the ion detector in the spectrometer.

[0100] As about Figure 2 As depicted, ions are directed from a single ion beam 3 into the upstream ends of the IMS devices 12 , 13 .

[0101] Figure 4 Shown with Figure 2 1, except that it illustrates a single upstream ion guide 22 directing a single ion beam 3 into the upstream ends of the multiple IMS devices 12, 13, and also shows a single downstream ion guide 23 receiving ions eluted from the multiple IMS devices to form a single ion beam 9. The path of the ions through the first IMS device 12 is shown as a dashed line.

[0102] Figure 5 Shows something like Figure 4 Schematic diagram of an embodiment of the embodiment shown. The embodiment includes a single upstream ion guide 22 for guiding ions toward the upstream end of the IMS device 12, 13 and a single downstream ion guide 23 for receiving ions from the IMS device. An entrance gate 25 is disposed between the upstream ion guide 22 and the IMS device 12, 13 for guiding ions into the IMS device. A deflection electrode 27 may be disposed between the upstream ion guide 22 and the entrance gate 25. One or more blocking electrodes 29 may be disposed between the entrance gate 25 and the IMS device for preventing ions from entering the one or more IMS devices when the one or more IMS devices are operated in an elution mode. An exit gate 30 is disposed between the IMS device 12, 13 and the downstream ion guide 23 for guiding ions into the downstream ion guide. A steering electrode 32 may be disposed between the exit gate 30 and the downstream ion guide 23 to help deflect ions into the downstream ion guide.

[0103] Figure 5 Also shown is a graph of a DC potential profile that may be provided along the instrument to push ions in the downstream direction.

[0104] In operation, ions are pushed along the upstream ion guide 22. The ion guide may be an axially segmented ion guide, and different voltages may be provided to different axial segments in order to push ions through the ion guide and towards the IMS devices 12, 13. Figure 5 At the illustrated point in time, ions from the upstream ion guide 22 are directed into a first IMS device in the IMS device 12, which is operating in an ion accumulation mode. In this mode, a voltage is applied to the entrance gate 25 so that ions are pushed only into the first IMS device 12 and not into the second IMS device 13. In the depicted embodiment, the longitudinal axis through the first IMS device 12 is spaced apart from the longitudinal axis through the upstream ion guide 22, and thus the entrance gate 25 pushes the ions orthogonally (to the axis through the upstream ion guide) to allow the ions to enter the first IMS device. If one or more deflection electrodes 27 are provided, voltages may be applied to these electrodes so as to push the ions in an orthogonal direction. However, it should be understood that in embodiments not illustrated, the longitudinal axis through the first IMS device 12 may alternatively be aligned with the longitudinal axis through the upstream ion guide 22.

[0105] At this point, the blocking electrode 29 between the entry gate array 25 and the first IMS device 12 is maintained at a potential that enables ions to enter the capture region inside the first IMS device. A potential may be applied to the first IMS device and / or other electrodes to prevent ions from leaving the first IMS device. The first IMS device is thus operated in the ion accumulation mode described above.

[0106] exist Figure 5Prior to the illustrated point in time, the instrument has been operating in a mode corresponding to the above-described mode in order to fill the second IMS device 13 during the ion accumulation mode. That is, a voltage has been applied to the entrance gate 25 so that ions are pushed only into the second IMS device 13 and not into the first IMS device 12. Since the longitudinal axis through the second IMS device 13 is spaced apart from the longitudinal axis through the upstream ion guide 22, the entrance gate 25 pushes the ions orthogonally (to the axis through the upstream ion guide) so that the ions enter the second IMS device 13. If one or more deflection electrodes 27 are provided, voltages may be applied to these electrodes in order to push the ions in an orthogonal direction. In this process, the blocking electrode 31 between the entrance gate array 25 and the second IMS device 13 is maintained at a potential that enables the ions to enter the capture region inside the second IMS device. A potential is applied to the second IMS device 13 and / or other electrodes to prevent the ions from leaving the second IMS device. The ions are then separated in one of the above-described ways according to mobility within the capture region of the second IMS device.

[0107] exist Figure 5 At the illustrated point in time, the second IMS device 13 has been switched to an elution mode in which ions are eluted from the second IMS device 13 in order of increasing or decreasing mobility, depending on which of the elution modes described herein is used. A voltage is applied to the exit gate 30 so that the eluted ions are pushed into the downstream ion guide 23. In the depicted embodiment, the longitudinal axis through the downstream ion guide 23 is spaced from the longitudinal axis through the first and second IMS devices 12, 13, and thus the exit gate 30 pushes the ions orthogonally (to the axis through the second IMS device) so as to cause the ions to enter the downstream ion guide. If one or more steering electrodes 32 are provided, voltages may be applied to these electrodes so as to push the ions in an orthogonal direction. However, it will be appreciated that in embodiments not illustrated, the longitudinal axis through the downstream ion guide 23 may alternatively be aligned with the longitudinal axis through one of the first or second IMS devices 12, 13.

[0108] The downstream ion guide 23 may be an axially segmented ion guide, and different voltages may be provided to different axial segments in order to push ions through the ion guide and in the downstream direction.

[0109] Thus, it will be appreciated that ions may be accumulated and / or separated in the first IMS device 12 while ions are separated and / or eluted from the second IMS device 13 .

[0110] Once the ions in the first IMS device 12 have been separated, the first IMS device may be switched to an elution mode so that the ions are eluted from the downstream end of the first IMS device in ascending or descending order of mobility. The voltage applied to the exit gate 30 (and optional steering electrode 32) may then be switched to direct the ions eluted from the first IMS device 12 into the downstream ion guide 23 in a manner corresponding to that described above with respect to directing the ions from the second IMS device 13 into the downstream ion guide.

[0111] When ions are eluted from the first IMS device 12, the second IMS device 13 can be operated in an ion accumulation mode, which corresponds to the mode described above for accumulating ions in the first IMS device. That is, by applying a voltage to the entrance gate 25, ions from the upstream ion guide 22 are guided into the second IMS device 13 so that the ions are only pushed into the second IMS device 13 and not into the first IMS device 12. In the depicted embodiment, the longitudinal axis through the second IMS device 13 is spaced apart from the longitudinal axis through the upstream ion guide 22, and thus the entrance gate array 25 (with the axis through the upstream ion guide) pushes the ions orthogonally to allow the ions to enter the second IMS device. If one or more deflection electrodes 27 are provided, voltages can be applied to these electrodes to push the ions in an orthogonal direction. At this time, the blocking electrode 31 between the entrance gate 25 and the second IMS device 13 is maintained at an electrical potential that enables the ions to enter the capture region inside the second IMS device 13. A potential may be applied to the second IMS device 13 and / or other electrodes in order to prevent ions from leaving the second IMS device.The second IMS device may then be operated in one of the ion separation modes described above.

[0112] Thus, it will be appreciated that ions may be accumulated and / or separated in the second IMS device 13 while ions are separated and / or eluted from the first IMS device 12 .

[0113] The above process may be repeated such that the IMS devices 12, 13 are alternately filled with ions and such that ions are eluted from alternating ions.

[0114] Fig. 6AA schematic perspective view of an embodiment of the entrance gate 25 is shown. The entrance gate 25 includes two electrode arrays 35, 36 spaced apart from each other so as to define an ion guiding region therebetween. Each electrode array includes a plurality of electrodes arranged in rows and columns. Various potentials are applied to these electrodes to manipulate ions, as will be described in more detail below. Each array can be square or rectangular, but other shapes can also be envisioned. The arrays can be parallel to each other, or can be angled to each other, such as diverging in the downstream direction to drive ions to move downstream. The entrance gate 25 can have two side electrodes 37, 38 extending between the arrays 35, 36 on two opposite sides of the array. The other two sides of the entrance gate 25 extending between the two arrays form an ion entrance into the entrance gate and an ion exit from the exit gate. Each of these sides can be completely open or can have a wall with holes therein for allowing ions to enter or leave the entrance gate 25.

[0115] An RF potential is applied to the electrodes in the electrode arrays 35, 36 so as to confine the ions in the direction between the arrays. An RF potential of the same phase may be applied to all electrodes in the same column of electrodes (where the column extends in the direction from the ion inlet side to the ion outlet side), and any given adjacent pair of electrode columns may be maintained at different RF phases, preferably opposite RF phases. However, it is alternatively conceivable that an RF potential of the same phase may be applied to all electrodes in the same row (where the row extends in the direction between the side electrodes 37, 38), and any given pair of adjacent electrode rows may be maintained at different RF phases, preferably opposite RF phases. A DC voltage may be applied to the electrodes in the electrode arrays 35, 36 and / or to the side electrodes 37, 38 so as to push the ions in the direction in which the electrode rows are arranged, as will be described in more detail below.

[0116] In operation, ions exit the upstream ion guide 22 along a first axis, enter the entrance gate 25 along that axis, and are confined between the electrode arrays 35, 36 by RF voltages applied thereto. Initially, different DC voltages may be applied to different electrodes in each electrode array, and optionally different DC voltages may be applied to opposing side electrodes 37, 38, such that the ions are pushed orthogonally to the first axis (i.e., orthogonal to the columns), such that the ions exit the entrance gate 25 and enter the first IMS device 12 along a second axis displaced from the first axis.

[0117] Figure 6BAn example of a DC voltage that may be applied to the side electrodes 37, 38 and the electrode arrays 35, 36 in a mode in which ions are sent into the first IMS device 12 is shown. The first side electrode 38 is maintained at a higher DC potential than the second side electrode 37 for pushing ions in a direction toward the second side electrode 37. The DC potential applied to a first subset of the electrode columns near the first side electrode 38 may gradually decrease with distance in a direction away from the first side electrode 38 so as to push ions in a direction away from the first side electrode. The DC potential applied to a second subset of the electrode columns near the second side electrode 37 may gradually decrease with distance in a direction away from the second side electrode 37 so as to push ions in a direction away from the second side electrode and prevent ions from striking the second side electrode. The electrodes in a third subset of the electrode columns adjacent to the second subset may be maintained at the same DC potential. Similarly, the electrodes in a fourth subset of the electrode columns adjacent to the first subset may be maintained at the same DC potential, where the DC potential may be higher than the DC potential applied to the third subset. It should be understood that the same DC voltage may be applied to all electrodes in any given electrode column. The described DC potential provides a DC potential distribution 40 in a region remote from the electrode, which serves to direct ions from the first axis onto the second axis, wherein the second axis corresponds to the location of a minimum of the potential distribution 40 .

[0118] In a mode where the entrance gate 25 directs ions into the second IMS device 13 rather than the first IMS device 12, the potential applied to the electrode of the entrance gate may be Figure 6B , so that ions are directed from the first axis to a third axis corresponding to the axis of the second IMS device.

[0119] Fig. 7A A schematic perspective view of an embodiment of an exit gate 30 is shown. The exit gate may be identical to the entry gate 25, except that a different potential is applied to its electrodes, e.g. Figure 7B shown.

[0120] Figure 7BExamples of DC voltages that may be applied to the side electrodes 42, 43 and the electrode arrays 44, 45 of the exit gate array 30 are shown. The first and second side electrodes 42, 43 are maintained at a first DC potential and a second DC potential, which may be the same DC potential. The DC potential applied to the first subset of the electrode columns near the first side electrode 42 may gradually decrease with the distance in the direction away from the first side electrode so as to push ions in the direction away from the first side electrode. The DC potential applied to the second subset of the electrode columns near the second side electrode 43 may gradually decrease with the distance in the direction away from the second side electrode so as to push ions in the direction away from the second side electrode and prevent ions from hitting the second side electrode. The third subset of the electrode columns between the first subset and the second subset may be maintained at the same DC potential. The described DC potential provides a DC potential distribution 46 in a region away from the electrodes, which is used to guide ions from the exit axis of the first IMS device 12 or the exit axis of the second IMS device 13 to a third axis corresponding to the position of the minimum value of the potential distribution 46. The third axis may correspond to the axis of the downstream ion guide 23 .

[0121] although Figure 7B The potential distribution in has been illustrated as being symmetric about the minimum because the exit gate 30 in the embodiment shown in Figure 6 is centrally located between the two IMS devices 12, 13 and the downstream ion guide 23 is centrally located relative to the exit gate 30. If this were not the case, the exit gate 30 could apply an asymmetric potential distribution in order to push the ions to the desired axial path.

[0122] Although an embodiment has been described in which two IMS devices 12, 13 are provided for receiving ions from the upstream ion guide 22, as mentioned above, more than two IMS devices may receive ions from the upstream ion guide. In such an embodiment, the entrance gate 25 has an electrode configuration and a power supply so that the entrance gate can be applied with a voltage to selectively guide ions into any one of the plurality of IMS devices. Similarly, the exit gate 30 is configured to receive ions from any one of the plurality of IMS devices and guide them into the downstream ion guide.

[0123] Figure 8 Shows the corresponding Fig. 6A The example of an entrance door 25 of the entrance door shown in FIG. 1 is shown in FIG. 2 , except that instead of having a single side electrode on each of the opposing sides, there is an upper side electrode 37, 38 and a lower side electrode 47, 48 on each side. This embodiment is similar to that of FIG. Figure 6A-6BHowever, this embodiment also selectively directs ions toward one of the electrode arrays 35, 36 by applying a different DC potential to the upper electrodes 37, 38 than to the lower electrodes 47, 48, and / or by applying a different DC potential to the upper array 35 than to the lower array 36. The exit gate 30 may be connected to Figure 7B The same as shown in , except that it may be larger to accommodate additional IMS equipment.

[0124] It is contemplated that the entrance gate 25 may process ions in additional ways, rather than just selectively directing them into selected IMS devices. For example, the entrance gate may perform ion mobility filtering. This is particularly beneficial in reducing the amount of charge entering each IMS device, which has been identified as an important issue in IMS devices of the type described herein. For example, relatively low mobility ions may be filtered out so that they do not enter the IMS device.

[0125] Figure 9A-9C An embodiment of an inlet gate 25 operating as an ion mobility filter is shown. The inlet gate 25 may be provided in a manner similar to that described with respect to Figure 6A-6B (or Figure 8 ) in the same manner as described above, i.e. where a static DC potential is applied to the electrodes of the entrance gate such that it pushes the ions orthogonally from the first axis towards one of the sides 37, 38. However, in addition, the DC potential is repeatedly run in the opposite direction 50 so as to push the ions towards the opposite side. This can be performed by sequentially applying the DC potential to a sequential column of electrodes such that the DC potential runs towards said opposite side 50.

[0126] Fig. 9B An example of a static DC potential that may be applied to the entrance gate 25 to push ions toward the first side 37 is shown. In the depicted embodiment, the potential is Figure 6B The potential in the first side electrode 38 is the same, except that the potential applied to the second side electrode 37 can be removed and / or the potential applied to the second subset of electrodes decreases with increasing distance away from the third subset of electrodes. This is possible because the traveling DC potential prevents the ions of interest from impacting the second side electrode 37. The static DC potential gradient can provide an electric field with an amplitude that increases with distance toward the first side electrode 38, for example, the DC potential amplitude can increase substantially quadratically with distance toward the first side electrode 38.

[0127] The gas pressure within the entrance gate is such that the opposing forces acting on the ions due to the DC travel potential 50 and the DC static gradient cause the ions to separate according to their mobility until they reach their equilibrium position where the time-averaged force acting on any given ion due to the DC travel potential 50 is equal to and opposite to the force acting on the ion due to the DC static gradient. Fig. 9B It can be seen that the relatively high mobility ions 51 are orthogonally pushed to an equilibrium position relatively close to the first side electrode 38 , while the relatively low mobility ions 53 are orthogonally pushed to an equilibrium position relatively close to the second side electrode 37 .

[0128] Fig. 9C A plan view of the ion entrance gate 25 is shown and different ion trajectories of ions of different mobilities are illustrated. As described above, ions of relatively low mobility are pushed relatively far toward the first side electrode 38, while ions of relatively high mobility are pushed relatively far toward the second side electrode 37. Therefore, ions leave the entrance gate 25 at different positions according to their mobility. The parameters (e.g., amplitude and / or speed, etc.) of the static DC gradient and / or DC travel potential 50 can be selected so that ions with desired mobility leave the entrance gate 25 at a certain position so as to be able to enter the desired IMS device. The ion blocking plates 29, 31 can be arranged between the entrance gate 25 and the IMS devices 12, 13, wherein the ion blocking plates have an orifice positioned at the entrance of each IMS device. Then, ions with desired mobility are guided through one of the orifices into the desired IMS device, while ions with other mobilities will impact the ion blocking plates.

[0129] Although an embodiment has been described in which a static DC gradient pushes ions toward the second side electrode 37 and the DC travel potential 50 pushes ions toward the first side electrode 38, it is contemplated that alternatively the static DC gradient may push ions toward the first side electrode 38 and the DC travel potential 50 may push ions toward the second side electrode 37.

[0130] Different DC potentials may be applied to different rows of electrodes in order to push ions downstream from the entrance to the exit of the entrance gate 25. In embodiments where it is not desired to perform this function, each column of electrodes may be replaced by an elongated continuous electrode, such as Fig. 9C shown.

[0131] The entry gate 25 has been described as operating in a mode as an ion mobility filter while filling a first IMS device 12. However, the entry gate 25 may be operated in a corresponding manner so as to mobility filter ions when it fills another IMS device 13. The entry gate 25 may operate as an ion mobility filter, allowing the same range of mobilities to enter each IMS device, or allowing different ranges of mobilities to enter different IMS devices.

[0132] Although an embodiment has been described in which the entrance gate 25 directs ions into a single IMS device 12, 13 at any one time, it will be appreciated that voltages may be applied to the electrodes of the entrance gate 25 so that it receives a single ion beam 3 from the upstream ion guide 22 and splits the ion beam so that ions are directed simultaneously into multiple IMS devices 12, 13. For example, voltages may be applied so that the potential distribution 40 does not have a Figure 6B Rather than a single potential minimum as shown, the potential profile has multiple minima at locations used to direct ions into multiple IMS devices.

[0133] The ion entrance gate may be in a form other than that shown and described above.

[0134] Figure 10A-10B Another embodiment of an ion entrance gate is shown. The ion entrance gate includes a first transition portion 60 positioned to receive ions from the upstream ion guide 22 along a first axial path; a second portion 61 configured to direct ions along a different second axial path to the first IMS device 12; and a third portion 62 configured to direct ions along a different third axial path to the second IMS device 13. The entrance gate can be configured so that the first axial path is substantially parallel to and displaced from the second axial path and the third axial path.

[0135] Each of the transition portion 60, the first portion 61 and the second portion 62 may comprise a plurality of axially spaced apart electrodes, wherein each electrode is an electrode having an aperture through which ions are sent in use.

[0136] Fig. 10B1 shows a cross-sectional view of the ion entrance gate at a position near the upstream end in the downstream direction. It can be seen that the transition portion 60 includes an upper electrode and a lower electrode 63, 64 arranged on opposite sides of the first axial path. The upper electrode and the lower electrode are separated by a gap on opposite sides of the first axial path so that ions can be pushed orthogonally from the first axial path to the second axial path or the third axial path, as will be further described below. The transition portion 60 also includes a C-shaped electrode 65, which only partially surrounds the second axial path and has a gap in its circumference, which faces one of the gaps between the upper electrode 63 and the lower electrode 64. The transition portion 60 includes another C-shaped electrode 66, which only partially surrounds the third axial path and has a gap in its circumference, which faces another gap between the upper electrode 63 and the lower electrode 64 of the transition portion. Fig. 10B The illustrated electrode arrangement shows the electrodes at one axial position along the transition portion 60 , but stacking of such electrode arrangements may be repeated along the axis of at least a portion of the transition portion 60 .

[0137] The second portion 61 may include an ion tunnel ion guide, such as a stacked annular ion guide, arranged to receive ions along a second axial path from the transition portion 60. Similarly, the third portion 62 may include an ion tunnel ion guide, such as a stacked annular ion guide, arranged to receive ions along a third axial path from the transition portion 60.

[0138] RF voltage is applied to the upper electrode 63, the lower electrode 64 and the C-shaped electrodes 65, 66 of the transition section 60, and also to the electrodes of the first and second sections 61, 62, for radially confining ions therein. In each of these sections, the electrodes arranged adjacent to each other in the axial direction may be in different RF phases, such as opposite RF phases. In contrast, the electrodes of the transition section 60 adjacent to each other in the transverse direction (e.g., Fig. 10B All electrodes in the axial direction may be in the same RF phase. Different DC voltages may be applied to different electrodes in the axial direction to push ions downstream through the transition portion and / or through the first portion and the second portion.

[0139] In use, ions enter the transition portion 60 between the upper electrode 63 and the lower electrode 64 and travel along the first axial path. When it is desired to send ions into the first IMS device 12, a DC potential difference is applied between the upper / lower electrodes 63, 64 and at least some of the C-shaped electrodes 65 surrounding the second axial path to push the ions radially from the first axial path through the gap 67 and onto the second axial path. The RF voltage applied to these C-shaped electrodes 65 directs the ions along the second axial path into the second portion 61 of the entrance gate 25, which then directs the ions into the first IMS device 12. Similarly, when it is desired to send ions into the second IMS device 13, a DC potential difference is applied between the upper / lower electrodes 63, 64 and at least some of the C-shaped electrodes 66 surrounding the third axial path to push the ions radially from the first axial path through the gap 68 onto the third axial path. The RF voltage applied to the C-shaped electrodes 66 directs the ions along a third axial path into the third portion 62 of the entrance gate, which then directs the ions into the second IMS device 13 .

[0140] In addition, the transition section 60 can be configured to send ions to a third IMS device or another IMS device. For example, in this arrangement, a second series of upper and lower electrodes corresponding to those electrodes described above but surrounding a fourth axial path can be provided between the upper / lower electrodes 63, 64 surrounding the first axial path and the C-shaped electrode 65 surrounding the second axial path. The entrance gate can have a fourth portion, such as an ion tunnel ion guide that receives ions from the second series of electrodes and guides them to the third IMS device. In use, different DC potentials can be applied to different electrodes of the transition region 60, so that ions are pushed from the first axial path to the fourth axial path and thereby pushed to the third IMS device. Alternatively, different DC potentials can be applied to different electrodes of the transition region 60, so that ions are pushed from the first axial path through the fourth axial path and to the second axial path, and thereby sent to the first IMS device 12.

[0141] Although the transition portion 60, first portion 61, and second portion 62 of the entrance gate 25 have been described as radially segmented ion guides, it is alternatively contemplated that one, both, or all of these portions may be formed by a multipole having continuously extending electrodes having circumferential gaps such that ions may be propelled from the first axial path to the second and third axial paths.

[0142] The exit door 30 may have the same Figure 10A-10BThe configuration described above may be a configuration corresponding to that described above, but operating in reverse. For example, the second portion 61 may receive ions from the first IMS device 12 and direct those ions to the transition portion 60. Different DC potentials may be applied to different electrodes of the transition portion to push ions from the second axis of the second portion to the first axis. The ions may then be directed along the first axis into the downstream ion guide 23. Similarly, the third portion 62 may receive ions from the second IMS device 13 and direct those ions to the transition portion. Different DC potentials may be applied to different electrodes of the transition portion to push ions from the third axis of the third portion to the first axis. The ions may then be directed along the first axis into the downstream ion guide 23.

[0143] Figure 11A-11B Another embodiment of an ion entrance gate is shown. Fig.11A shows an end view of the entrance gate when looking towards the ion entrance, and Fig. 11B A plan view of the entry door is shown (with the top panel removed for ease of viewing).

[0144] like Fig.11A As shown, the entrance gate comprises a stack of plate electrodes 70,71,72 arranged between a top plate electrode 73 and a bottom plate electrode 74. The electrode stack is arranged to define an ion guiding path for guiding ions from a first entrance port 75 towards second and third exit ports 76,77. Fig. 11B A plan view is shown in which the top plate 73 is not illustrated, and thus a layer of electrodes in the stack 70-72 of electrodes is shown. It should be understood that a plurality of such electrode layers are stacked between the top plate electrode 73 and the bottom plate electrode 74. The electrodes in the stack and the optional top and bottom electrodes can be maintained at an RF voltage so that ions are repelled from these electrodes. In the direction between the top electrode and the bottom electrode, adjacent electrodes can be maintained at different phases of the RF voltage, such as opposite phases. Electrodes in different stacks but in the same layer (i.e., electrodes adjacent horizontally) can be maintained at the same RF phase. In addition to or as an alternative to applying an RF voltage, a DC voltage can be applied to the top and bottom electrodes to repel ions.

[0145] In use, ions are received at the first port 75 and directed through the entrance region of the entrance gate. Different DC voltages may be applied to the electrodes in different stacks 70-72 of electrodes to control the path of the ions through the entrance gate. For example, different DC voltages may be applied to different stacks 70-72 so that ions are directed only along the first path to the second port 76 and into the first IMS device 12. Similarly, when desired, different DC voltages may be applied to different stacks so that ions are directed only along the second path to the third port 77 and into the second IMS device 13. Alternatively, different DC voltages may be applied to different stacks so that ions are directed to the second and third ports 76, 77 along both the first and second paths and into both the first IMS device and the second IMS device 12, 13.

[0146] The top and bottom plate electrodes 73, 74 and / or the stack of electrodes 70-72 may be segmented in the direction between the inlet 75 and outlets 76, 77, and different DC voltages may be applied to different segments to push ions in the downstream direction.

[0147] The exit door 30 may have the same Figure 11A-11B 1, 2, 4, 6, 8, 9, 10, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 90, 91, 97, 98, 99, 91, 98, 99, 90, 91, 92, 93, 94, 95

[0148] While the present invention has been described with reference to various embodiments, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the scope of the present invention as set forth in the following claims.

[0149] For example, while ions eluted from multiple IMS devices have been described as being combined into a single ion beam, it is alternatively contemplated that ions eluted from multiple IMS devices may be processed (eg, mass analyzed and / or detected) independently of one another.

[0150] The IMS devices may be controlled to capture and separate the same range of mobilities. Alternatively, different IMS devices may be controlled to capture, separate and elute different respective ranges of mobilities.

[0151] The ions in a single beam may be split simultaneously between IMS devices, or directed sequentially to different IMS devices at different times such that the different IMS devices capture ions having substantially the same charge (at the end of the ion accumulation mode). For example, if a single ion beam is split simultaneously between IMS devices, the ions may be split such that each IMS device receives the same proportion of the single ion beam at the same time. If a single ion beam is directed sequentially to different IMS devices at different times, the single ion beam may be directed to each IMS device for the same duration.

[0152] Alternatively, ions in a single beam may be split simultaneously between IMS devices, or directed sequentially to different IMS devices at different times, such that different IMS devices capture ions with different charges (at the end of the ion accumulation mode). For example, if a single ion beam is split simultaneously between IMS devices, the ions may be split such that different IMS devices receive different proportions of the single ion beam (e.g., over the same duration). If a single ion beam is directed sequentially to different IMS devices at different times, the single ion beam may be directed to each IMS device for different durations.

[0153] While embodiments have been described in which ions are eluted simultaneously from multiple IMS devices, arrangements of multiple IMS devices may be used to improve the duty cycle of the instrument by accumulating ions in one IMS device while eluting a population of ions from another IMS device.

[0154] An embodiment has been described in which ions enter each IMS device directly into a (first) capture region where they are separated according to mobility and then eluted from the (first) capture region. However, it is conceivable that at least one of the IMS devices or at least some of the IMS devices may have a second capture region upstream of the first capture region. Ions may accumulate in the second capture region (separated or not separated according to mobility) while ions are captured in the first capture region and eluted from the first capture region. Once all ions have been eluted from the first capture region, ions may be transferred from the second capture region to the first capture region where they are then separated by mobility and eluted from the first capture region according to mobility. This process may be repeated, thereby further increasing the duty cycle of the instrument, since ions may be captured in the second capture region, rather than being discarded, while ions are separated and eluted from the first capture region.

[0155] The ion guide of each IMS device may have a circular, annular, elliptical, rectangular or other elongated shaped cross section. The IMS devices may have the same or different cross-sectional shapes.

[0156] The described embodiments may form part of a mass spectrometer.For example, ions eluted from an IMS device, or ions derived therefrom, may be mass analysed (eg in a time-of-flight mass analyser).

[0157] Although the ions have been described as being separated by mobility, it is contemplated that the ions may alternatively be separated by another physicochemical property, such as mass-to-charge ratio. This may be performed, for example, in embodiments where the ions experience opposing forces due to a static axial electric field and a traveling DC potential.

Claims

1. An ion mobility separation device, comprising: multiple ion mobility separator (IMS) devices arranged in parallel; an entry gate configured to direct ions into one or more of the IMS devices at any given time; and and control circuitry configured to operate each of the IMS devices in a separation mode in which a first voltage is applied to electrodes of the IMS device to provide a static DC electric field that pushes ions along the IMS device in one direction, and a second voltage is also applied to the electrodes of the IMS device to provide a DC potential that travels repeatedly along the IMS device in an opposite direction such that ions are separated according to their mobility within the IMS device.

2. The apparatus of claim 1 , wherein the apparatus is configured to operate each of the IMS devices in an elution mode after operating in the separation mode, during which: (i) gradually changing the first voltage so that the gradient of the static DC electric field also gradually changes, thereby causing ions to elute from the IMS device in the order of mobility or in the reverse order of mobility over time; and / or (ii) gradually varying the second voltage so that at least one property of the DC potential repeatedly traveling along the IMS device also gradually varies, thereby causing ions to elute from the IMS device over time in order of mobility or in reverse order of mobility.

3. The apparatus of claim 2, comprising control circuitry configured to control elution of ions from a plurality of IMS devices such that ions exiting all of the IMS devices at any given time have substantially the same mobility.

4. The apparatus according to claim 2, comprising a control circuit, the control circuit being configured to control the ion mobility separation device so that during a first time period, the inlet gate causes ions to be supplied to a first IMS device among the IMS devices so as to accumulate and separate ions in the first IMS device, and causes a second IMS device among the IMS devices to elute ions in the order of ion mobility or in the reverse order of ion mobility while the ions are accumulated and separated; and optionally in, The control circuit is configured to control the ion mobility separation device so that during a subsequent second time period, the entrance gate causes ions to be supplied to the second IMS device in the IMS devices so as to accumulate and separate the ions in the second IMS device, and so that while the ions are accumulated and separated in the second IMS device, the first IMS device elutes the ions in the order of mobility or in the reverse order of ion mobility.

5. An apparatus according to any preceding claim, further comprising an upstream ion guide for directing an ion beam to the entrance gate, wherein The entry gate is configured as: (i) dividing the ion beam into a plurality of ion beams, wherein the plurality of ion beams are simultaneously directed into a corresponding plurality of the IMS devices; or (ii) directing said ion beam into different said IMS devices at different times.

6. An apparatus according to any preceding claim, wherein: The entrance gate is arranged to receive ions along a first axis and comprises arrays of opposing electrodes spaced apart from one another and at least one voltage source for applying at least one RF voltage to the electrodes of the arrays to confine ions in an ion guide region between the arrays.

7. The device according to claim 6, wherein: The entrance gate includes side electrodes on each side of the first axis and at least one power supply for applying voltages to the side electrodes to push the ions orthogonal to the first axis.

8. The device according to claim 6 or 7, wherein: Each of the IMS devices has a longitudinal axis passing therethrough along which ions are received; wherein at least one of the IMS devices or each of at least some of the IMS devices has its longitudinal axis displaced from the first axis; and wherein the entrance gate has a control circuit configured to apply different DC voltages to different electrodes in the array and / or to different side electrodes so as to deflect ions received along the first axis onto one or more longitudinal axes of one or more IMS devices so that the ions enter the one or more IMS devices.

9. The device according to claim 8, wherein: The different DC voltages provide a static DC electric field that pushes the ions in a first direction orthogonal to the first axis, and the control circuit is configured to also apply a voltage to an electrode of the entrance gate to provide a DC potential that repeatedly travels along the entrance gate in a second direction opposite to the first direction, so that the ions separate according to their mobility along the first direction and therefore have different trajectories through the entrance gate.

10. The device according to any one of claims 6 to 9, wherein: Different DC potentials are applied to different electrodes in the array so as to push ions along the first axis from the entrance to the exit of the entrance gate.

11. The device according to any one of claims 1 to 5, wherein: The entrance gate comprises a first transition portion having electrodes positioned to receive ions along a first axial path, a second portion having electrodes configured to direct ions along the axial path to a first IMS device in the IMS devices, and a third portion having electrodes configured to direct ions along the axial path to a second IMS device in the IMS devices, wherein the electrodes receiving ions along the first axial path are arranged to provide at least one gap at a circumferential position around the first axial path, and wherein the entrance gate comprises a power supply for applying a DC voltage to the electrodes of the entrance gate such that ions are pushed orthogonally from the first axial path, through the at least one gap, and onto the axial path of the first IMS device and / or the second IMS device.

12. The device according to any one of claims 1 to 5, wherein: The entrance gate includes at least one plate-like electrode stack arranged between a first electrode and a second electrode to define a first ion guiding path for guiding ions from an ion entrance region of the entrance gate to a first IMS device in the IMS device, and a second ion guiding path for guiding ions from the ion entrance region to a second IMS device in the IMS device.

13. An apparatus according to any preceding claim, further comprising a downstream ion guide and an exit gate between the IMS device and the downstream ion guide, wherein The exit gate is configured to receive ions from the plurality of IMS devices and direct the ions into the downstream ion guide.

14. An ion mobility separation device, comprising: multiple ion mobility separator (IMS) devices arranged in parallel; an entry gate configured to direct ions into one or more of the IMS devices at any given time; and control circuitry configured to operate each of the IMS devices in a separation mode in which voltages are applied to electrodes of the IMS devices to push ions along the IMS devices in one direction, and wherein the apparatus is configured to provide a gas flow in an opposite direction such that ions are separated according to their mobility within the IMS devices.

15. An ion separation device, comprising: a plurality of separator devices arranged in parallel, each separator device being used to separate ions according to physicochemical properties; an entrance gate configured to direct ions into one or more of the separator devices at any given time; and A control circuit configured to operate each of the separator devices in a separation mode in which a first voltage is applied to electrodes of the separator device to provide a static DC electric field that pushes ions along the separator device in one direction, and a second voltage is also applied to the electrodes of the separator device to provide a DC potential that repeatedly travels along the separator device in an opposite direction, so that ions are separated according to physicochemical properties within the separator device.

16. The ion separation device according to claim 15, wherein: The physicochemical property is the mass-to-charge ratio.

17. A method for separating ions by ion mobility, the method comprising: Providing an ion mobility separation device according to any one of claims 1 to 14; providing ions to an entrance gate and controlling the entrance gate to direct ions into one or more of the IMS devices at any given time; as well as The IMS devices are operated to operate in a separation mode, either simultaneously or sequentially, to separate ions according to their mobility.

18. A method for separating ions based on physicochemical properties, the method comprising: Providing an ion separation device according to claim 15 or 16; providing ions to an entrance gate and controlling the entrance gate to direct ions into one or more of the separation devices at any given time; as well as The separation devices are operated to operate in a separation mode, either simultaneously or sequentially, to separate ions according to the physicochemical properties.

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