Combined ion mobility spectrometer - mass spectrometer and separation method

Abstract

A method of mass and / or mobility spectrometry comprising: performing a first, survey acquisition that comprises separating ions in an ion separation device and determining a first duration of elution from the ion separation device of a first ion species; selecting a threshold duration for an ion species to elute from the ion separation device; and performing a second acquisition in which the ion separation device is controlled, based on the first duration of elution determined in the first, survey acquisition, such that it causes said first ion species to elute from the ion separation device over a second duration that is different to said first duration and that is less than or equal to said selected threshold duration.

Description

[0001] COMBINED ION MOBILITY SPECTROMETER - MASS SPECTROMETER AND SEPARATION METHOD

[0002] CROSS-REFERENCE TO RELATED APPLICATION

[0003] This application claims priority from and the benefit of United Kingdom patent application No. 2411416.7 filed on 2 August 2024. The entire content of this application is incorporated herein by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention relates generally to techniques for separating ions according to a physicochemical property such as ion mobility or mass to charge ratio.

[0006] BACKGROUND

[0007] 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 a packet of ions into a drift tube that has a background gas therein. A static DC electric field is maintained along the drift tube so as to urge the ions through the gas from the upstream end, near the ion trap, to a downstream end. Ions of different mobility will have different transit times through the gas to the exit of the drift tube and hence are separated according to their mobility.

[0008] Travelling wave IMS devices are also known. In these devices a DC potential is repeatedly travelled along the drift tube so as to urge the ions in the downstream direction towards the exit of the drift tube, rather than providing a static DC electric field along the drift tube for urging the ions. Ions having different mobilities are urged downstream by different amounts each time that they are passed by a travelling DC potential. As such, the travelling DC potentials cause the ions to become separated and exit the IMS device at different times based on their mobility.

[0009] Other types of IMS devices are known that separate ions according to ion mobility within an ion trap and then release the ions from the ion trap in order of mobility. These devices trap the ions and then provide opposing forces on the ions such that they separate out along the trapping region according to their mobility. One of the forces may then be progressively reduced such that ions elute from the trapping region in order of ion mobility.

[0010] However, problems exist in how the elution of ions from such devices are interfaced with downstream devices, such as mass filters. SUMMARY

[0011] From a first aspect the present invention provides a method of mass and / or mobility spectrometry comprising: performing a first, survey acquisition that comprises separating ions in an ion separation device and determining a first duration of elution from the ion separation device of a first ion species; selecting a threshold duration for an ion species to elute from the ion separation device; and performing a second acquisition in which the ion separation device is controlled, based on the first duration of elution determined in the first, survey acquisition, such that it causes said first ion species to elute from the ion separation device over a second duration that is different to said first duration and that is less than or equal to said selected threshold duration.

[0012] As the present invention controls the ion separation device in the second acquisition so as to elute the ion species over a duration that is less than or equal to a selected threshold duration, the overall length of time of the second acquisition can be maintained relatively low.

[0013] The method may perform the second acquisition described herein periodically, where ions are accumulated in an ion trap upstream of the ion separation device whilst each instance of the second acquisition is being performed. After that instance of the second acquisition has been performed the ions in the ion trap may be transferred to the ion separation device so as to perform the next instance of the second acquisition. As the overall length of time of the second acquisition is able to be maintained relatively low, the time over which ions are accumulated in the ion trap is relatively low and hence so is the amount of charge that the ion trap is required to accommodate.

[0014] The first, survey acquisition may comprise determining a duration of elution from the ion separation device for each of a plurality of ion species, wherein in the second acquisition the ion separation device is controlled, based on the durations of elution determined for the plurality of ion species in the first, survey acquisition, such that it causes each of said plurality of ion species to elute from the ion separation device over a duration that is less than or equal to the selected threshold duration.

[0015] During the second acquisition, the method may control the ion separation device, based on the durations of elution determined for the plurality of ion species in the first, survey acquisition, such that only some of the ion species detected in the survey acquisition are caused to elute from the ion separation device over a duration that is less than or equal to the selected threshold duration. These ions may be ions of interest that have been selected, e.g. based on having mass to charge ratios in certain ranges.

[0016] The method may comprise determining in the first, survey acquisition that the first ion species elutes from the ion separation device with a first elution duration that is longer than the selected threshold duration; and in the second acquisition the ion separation device may be controlled so as to elute the first ion species at a faster rate than in the first, survey acquisition such that the first ion species elutes from the ion separation device with an elution duration that is less than or equal to the selected threshold duration.

[0017] The method may comprise determining in the first, survey acquisition that a second ion species elutes from the ion separation device with a further elution duration that is shorter than the selected threshold duration; and in the second acquisition the ion separation device may be controlled so as to elute the second ion species at a slower rate than in the first, survey acquisition such that the second ion species elutes from the ion separation device with an elution duration that is longer than said further second elution duration, but less than or equal to the selected threshold duration.

[0018] The method may comprise controlling the ion separation device, in the second acquisition, so as to elute the ions over an elution period; and mass filtering the eluting ions by scanning or stepping a mass transmission window of a mass filter in synchronism with the elution period of the ion separation device so that at least said first ion species is, and optionally said plurality of ion species are, transmitted by the mass filter.

[0019] Ions passing into the mass filter that have mass to charge ratios within the range of mass to charge ratios that the mass transmission window is set at, at that time, are transmitted by the mass filter. In contrast, ions passing into the mass filter that have mass to charge ratios outside of the range of mass to charge ratios that the mass transmission window is set at, at that time, are not transmitted by the mass filter and are filtered out.

[0020] The mass filter may be controlled such that it only transmits some of the ion species detected in the survey acquisition, i.e. the ions of interest.

[0021] During the elution period the mass transmission window of the mass filter may be stepped between different ranges of mass to charge ratios, being paused at each range for a dwell time, wherein the length of said threshold duration is selected based on the duration of the dwell time.

[0022] The mass transmission window of the mass filter may be stepped between different ranges of mass to charge ratio in a manner such that each time the mass transmission window is stepped the mass to charge ratio range of the mass transmission window partially overlaps with the mass to charge ratio range of the mass transmission window in the preceding step. Alternatively, the mass transmission window of the mass filter may be stepped between different mass to charge ratio ranges in a manner such that each time the mass transmission window is stepped the mass to charge ratio range of the mass transmission window does not overlap with the mass to charge ratio range of the mass transmission window in the preceding step.

[0023] The mass filter may be paused at all of the ranges of mass to charge ratio for the same dwell time.

[0024] The threshold duration may be equal to or less than the dwell time. This enables ion species of interest to be transmitted by the mass filter without significantly attenuating ions of interest.

[0025] Embodiments are contemplated in which, during the elution period, the mass transmission window of the mass filter is substantially continuously and progressively scanned across a range of mass to charge ratios. The length of the threshold duration may be selected based on the rate that the mass filter is scanned across said range of mass to charge ratios.

[0026] The rate that the mass filter is scanned is the number of mass to charge ratio units that the mass window moves per unit time. For example, if the spectrometer is selected to use a relatively high scan rate then the spectrometer may automatically select a threshold duration that is relatively short, whereas if the spectrometer is selected to use a lower scan rate then the spectrometer may automatically select a threshold duration that is longer.

[0027] The method may comprise mass analysing the ions that have been transmitted by the mass filter, or ions derived therefrom, so as to determine their mass to charge ratio.

[0028] The mass analyser may be a time of flight mass analyser.

[0029] The ions that are transmitted by the mass filter may be fragmented or reacted to produce fragment or other product ions that are then mass analysed.

[0030] The mass analyser may associate mobilities with the ions that it detects based on their time of detection by the mass analyser, e.g. relative to the start of the elution period from the ion separation device.

[0031] In each of the first and second acquisitions the ion separation device may separate the ions by ion mobility and causes the ions to elute in an order according to their mobilities; or in each of the first and second acquisitions the ion separation device may separate the ions by mass to charge ratio and causes the ions to elute in an order according to their mass to charge ratios.

[0032] The ion separation device may comprise a plurality of electrodes and the method may comprise applying voltages to the electrodes so that in each of the first and second acquisitions the ion separation device causes ions to be separated and eluted according to their mobilities or mass to charge ratios.

[0033] In each of the first and second acquisitions the method may comprise: applying voltages to electrodes of the ion separation device such that an electrical potential repeatedly travels along the ion separation device so as to urge ions in a first direction along the ion separation device, and applying different voltages to electrodes at different respective positions along the ion separation device so as to provide an electric field for urging ions in a second, opposite direction to said first direction, so as to cause ions to be separated according to mass to charge ratio or mobility.

[0034] In each of the first and second acquisitions the ion separation device may cause ions to elute in an order according to mobility or mass to charge ratio by: (i) varying the speed and / or amplitude of the electrical potential that repeatedly travels along the ion separation device; and / or (ii) varying the electric field maintained along the ion separation device.

[0035] The first direction is preferably the downstream direction through the ion separation device and the second direction may be the upstream direction through the ion separation device.

[0036] The method may comprise determining from the first, survey acquisition that the first ion species elutes from the ion separation device with a first elution duration that is longer than the selected threshold duration; and in response to this controlling the ion separation device in the second acquisition so as to: (i) increase the rate at which the amplitude and / or speed of the electrical potential is varied, relative to the rate that it was varied in the first acquisition, so that the first ion species elutes at a faster rate in the second acquisition than in the first acquisition; and / or (ii) increase the rate at which the electric field is varied, relative to the rate that it was varied in the first acquisition, so that the first ion species elutes at a faster rate in the second acquisition than in the first acquisition.

[0037] The method may comprise determining from the first, survey acquisition that a second ion species elutes from the ion separation device with a further elution duration that is shorter than the selected threshold duration; and in response to this controlling the ion separation device in the second acquisition so as to: (i) decrease the rate at which the amplitude and / or speed of the electrical potential is varied, relative to the rate that it was varied in the first acquisition, so that the second ion species elutes at a slower rate in the second acquisition than in the first acquisition; and / or (ii) decrease the rate at which the electric field is varied, relative to the rate that it was varied in the first acquisition, so that the second ion species elutes at a slower rate in the second acquisition than in the first acquisition.

[0038] The first aspect of the present invention also provides a mass and / or mobility spectrometer that is set up and configured to perform any of the methods described in relation to the first aspect of the present invention.

[0039] Accordingly, the present invention provides a mass and / or mobility spectrometer comprising: an ion separation device; an ion detector; and control circuitry configured to control the spectrometer to: select a threshold duration for an ion species to elute from the ion separation device; perform a first, survey acquisition in which ions are separated in the ion separation device and detected at the ion detector so as to determine a first duration of elution from the ion separation device of a first ion species; and perform a second acquisition in which the ion separation device is controlled, based on the first duration of elution determined in the first, survey acquisition, such that it causes said first ion species to elute from the ion separation device over a second duration that is different to said first duration and that is less than or equal to said selected threshold duration.

[0040] From a second aspect the present invention provides a method of mass spectrometry comprising: performing a first, survey acquisition that comprises separating ions in an ion separation device and determining a duration over which each of a plurality of ion species elute from the ion separation device; determining from said first, survey acquisition that a first ion species elutes from the ion separation device over a first elution duration and that a second ion species elutes from the ion separation device over a second, shorter elution duration; performing a second acquisition that comprises separating ions in the ion separation device such that a plurality of ion species elute over an elution period, and mass filtering ions eluting from the ion separation device by scanning or stepping a mass transmission window of a mass filter in synchronism with the elution period; wherein the method comprises: determining the period of time over which the first ion species elutes and reaches the mass filter during the second acquisition based on said first elution duration determined from the first, survey acquisition, and controlling the mass filter so that during this period of time the mass transmission window is scanned or stepped at a first rate; and determining the period of time over which the second ion species elutes and reaches the mass filter during the second acquisition based on said second elution duration determined from the first, survey acquisition, and controlling the mass filter so that during this period of time the mass transmission window is scanned or stepped at a second rate that is faster than the first rate.

[0041] The ion separation device may be operated in the same manner during the first and second acquisitions, e.g. such that each ion species elutes at the same rate in both the first and second acquisitions.

[0042] During the second acquisition, the method may control the mass filter, based on data obtained in the first, survey acquisition, such that only some of the ion species detected in the survey acquisition are transmitted by the mass filter. These ions may be ions of interest that have been selected, e.g. based on having mass to charge ratios in certain ranges.

[0043] Ions passing into the mass filter that have mass to charge ratios within the range of mass to charge ratios that the mass transmission window is set at, at that time, are transmitted by the mass filter. In contrast, ions passing into the mass filter that have mass to charge ratios outside of the range of mass to charge ratios that the mass transmission window is set at, at that time, are not transmitted by the mass filter and are filtered out.

[0044] The first ion species may have a different mass to charge ratio to the second ion species and so may be transmitted by the mass filter at different times.

[0045] The mass filter may be a quadrupole mass filter.

[0046] The mass transmission window may be scanned or stepped at said first rate for a duration that is substantially the same as, or shorter than, or longer than the period of time over which the first ion species reaches the mass filter; and / or the mass transmission window may be scanned or stepped at said second rate for a duration that is substantially the same as, or shorter than, or longer than the period of time over which the second ion species reaches the mass filter.

[0047] For example, the mass transmission window may be scanned or stepped at said first rate for the entire period of time that the first ion species arrives at the mass filter; and / or the mass transmission window may be scanned or stepped at said second rate for the entire period of time that the second ion species arrives at the mass filter.

[0048] The mass transmission window of the mass filter may be stepped between different ranges of mass to charge ratios, being paused at each range for a dwell time. The mass transmission window of the mass filter may be stepped between different ranges of mass to charge ratio in a manner such that each time the mass transmission window is stepped the mass to charge ratio range of the mass transmission window partially overlaps with the mass to charge ratio range of the mass transmission window in the preceding step. Alternatively, the mass transmission window of the mass filter may be stepped between different mass to charge ratio ranges in a manner such that each time the mass transmission window is stepped the mass to charge ratio range of the mass transmission window does not overlap with the mass to charge ratio range of the mass transmission window in the preceding step.

[0049] Alternatively, during the elution period the mass transmission window of the mass filter may be substantially continuously and progressively scanned across a range of mass to charge ratios. The rate that the mass filter is scanned is the number of mass to charge ratio units that the mass window moves per unit time.

[0050] The method may comprise mass analysing the ions that have been transmitted by the mass filter, or ions derived therefrom, so as to determine their mass to charge ratio.

[0051] The mass analyser may be a time of flight mass analyser.

[0052] The ions that are transmitted by the mass filter may be fragmented or reacted to produce fragment ions or other product ions that are then mass analysed.

[0053] The mass analyser may associate mobilities with the detected ions based on their time of detection by the mass analyser, e.g. relative to the start of the elution period from the ion separation device.

[0054] In each of the first and second acquisitions the ion separation device may separate the ions by ion mobility and cause the ions to elute in an order according to their mobilities; or in each of the first and second acquisitions the ion separation device may separate the ions by mass to charge ratio and cause the ions to elute in an order according to their mass to charge ratios.

[0055] In embodiments in which the ion separation device separates and elutes ions according to mobility in each of the first and second acquisitions, the first ion species that elutes from the ion separation device over the first elution duration may be an ion species having a first mass to charge ratio and a relatively large mobility range, whereas the second ion species that elutes from the ion separation device over the second elution duration is an ion species having a second, different mass to charge ratio and a narrower mobility range.

[0056] Alternatively, in embodiments in which the ion separation device separates and elutes ions according to mass to charge ratio in each of the first and second acquisitions, the first ion species that elutes from the ion separation device over the first elution duration may be an ion species having a first mass to charge ratio and a relatively wide mass peak, whereas the second ion species that elutes from the ion separation device over the second elution duration is an ion species having a second, different mass to charge ratio and a narrower mass peak.

[0057] The ion separation device may comprise a plurality of electrodes and the method may comprise applying voltages to the electrodes so that in each of the first and second acquisitions the ion separation device causes ions to be separated and eluted according to their mobilities or mass to charge ratios.

[0058] In each of the first and second acquisitions the method may comprise: applying voltages to electrodes of the ion separation device such that an electrical potential repeatedly travels along the ion separation device so as to urge ions in a first direction along the ion separation device, and applying different voltages to electrodes at different respective positions along the ion separation device so as to provide an electric field for urging ions in a second, opposite direction to said first direction, so as to cause ions to be separated according to mass to charge ratio or mobility.

[0059] In each of the first and second acquisitions the ion separation device may cause ions to elute in an order according to mobility or mass to charge ratio by: (i) varying the speed and / or amplitude of the electrical potential that repeatedly travels along the ion separation device; and / or (ii) varying the electric field maintained along the ion separation device.

[0060] The first direction is preferably the downstream direction through the ion separation device and the second direction may be the upstream direction through the ion separation device.

[0061] The second aspect of the present invention also provides a mass spectrometer that is set up and configured to perform any of the methods described in relation to the second aspect of the present invention.

[0062] Accordingly, the present invention provides a mass spectrometer comprising: an ion separation device; a mass filter; an ion detector; and control circuitry configured to control the spectrometer to: perform a first, survey acquisition in which ions are separated in the ion separation device and detected at the ion detector so as to determine a duration over which each of a plurality of ion species elute from the ion separation device; determine from said first, survey acquisition that a first ion species elutes from the ion separation device over a first elution duration and that a second ion species elutes from the ion separation device over a second, shorter elution duration; perform a second acquisition in which the ion separation device separates ions such that a plurality of ion species elute over an elution period, and the mass filter mass filters ions eluting from the ion separation device by scanning or stepping a mass transmission window of the mass filter in synchronism with the elution period; wherein the spectrometer has control circuitry configured to: determine the period of time over which the first ion species elutes and reaches the mass filter during the second acquisition based on said first elution duration determined from the first, survey acquisition, and control the mass filter so that during this period of time the mass transmission window is scanned or stepped at a first rate; and determine the period of time over which the second ion species elutes and reaches the mass filter during the second acquisition based on said second elution duration determined from the first, survey acquisition, and control the mass filter so that during this period of time the mass transmission window is scanned or stepped at a second rate that is faster than the first rate.

[0063] BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Various embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings in which:

[0065] Figs. 1A-1C show views of an ion separation device used in embodiments of the present invention;

[0066] Figs. 2A-2B illustrate how the electric field profile along the ion separation device may be varied so as to cause ions to elute;

[0067] Figs. 3A-3B illustrate another way in which ions may be caused to elute from the ion separation device;

[0068] Fig. 4 shows a schematic of a mass spectrometer according to an embodiment of the present invention; and

[0069] Fig. 5 shows how the mass transmission window of a mass filter may be varied with elution time from the ion separation device.

[0070] DETAILED DESCRIPTION

[0071] Figs. 1A-1C show views relating to an ion separation device according to an embodiment of the present invention. The ion separation device 1 has an entrance electrode 2, a series of intermediate electrodes 3 that form an ion guide and an exit electrode 4. The electrodes are apertured such that ions can pass through them and opposite phases 5,8 of an RF voltage supply are applied to axially alternate electrodes of the ion guide in order to produce a pseudo-potential that confines ions radially within the IMS device. DC voltages are transiently applied to axially successive electrodes of the ion guide at successive respective times so as to provide DC potentials 6, as shown in Fig. 1 B, that repeatedly travel along the length of the ion guide in the downstream direction. Ions 7 are transferred into the ion separation device and the travelling DC potentials urge the ions in the downstream direction as they pass the ions. A DC voltage supply applies voltages to electrodes of the ion guide so as to provide a DC electric field that urges the ions along the ion separation device in the upstream direction.

[0072] The magnitude of the DC electric field varies as a function of position along the axial length of the ion separation device such that when the ions are driven against this electric field by the travelling DC potentials the ions separate out along the axis of the ion separation device according to their ion mobility. Ions having different mobilities are axially confined at different respective axial equilibrium positions along the ion separation device where the force on them due to the electric field is counter-balanced with the time- averaged force on them due to the travelling DC potentials. When the ions have been separated according to mobility within the ion separation device, the ions are caused to elute from the exit of the ion separation device in an order according to their mobilities. Alternatively, the ion separation may be configured and controlled to separate and elute ions according to their mass to charge ratios. The ions may be caused to elute from the ion separation device according to mobility or mass to charge ratio in a number of ways, e.g. as described below with reference to Figs. 2A-3B.

[0073] Fig. 2A illustrates an example of the electric field profile along the ion separation device during an ion accumulation phase during which ions are accumulated in the ion separation device. As can be seen, the ion separation device has a trapping region 10 within which the magnitude of the electric field increases as a function of position in the downstream direction. Although the magnitude of the electric field in the trapping region 10 is shown as increasing linearly, the magnitude of the field may increase non-linearly. At the end of the trapping region there is a further region 11 along which the magnitude of the electric field is substantially constant, which will be referred to herein as the analytical region since the separation of the ions increases in this region as they are driven to elute from the ion separation device. The magnitude of the electric field in the analytical region is higher than at any point in the trapping region. Fig. 2A also illustrates the travelling DC potentials 12 that move along the ion separation device in the downstream direction, through the trapping region and the analytical region.

[0074] Fig. 2A also shows that ions 13 of different mobility (or different mass to charge ratio) are trapped at different equilibrium positions along the trapping region, the different mobilities (or mass to charge ratios) being illustrated by the differently sized circles. The ratio of maximum to minimum DC field amplitude in the trapping region dictates the ion mobility (or mass to charge ratio) range trapped in that region. This ratio can be adjusted to accommodate the specific analysis or application being performed such that ions of interest are axially spread over as much of the trapping range as possible, thus maximizing space-charge capacity of the device. Once the ions have been separated according to mobility (or mass to charge ratio) within the ion separation device, the ions may be caused to elute from the exit of the device during an elution period by progressively decreasing the magnitude of the DC electric field, as will be described with reference to Fig. 2B.

[0075] Fig. 2B shows the same example as in Fig. 2A, except wherein the magnitude of the electric field at each point along the trapping region 10 and analytical region 11 has been reduced. The travelling DC potentials 12 are then able to urge the ions further downstream along the ion separation device and such that first ions 14 of relatively high ion mobility (or low mass to charge ratio) are urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher mass to charge ratio) are retained in the trapping region by the DC electric field. The first ions 14 are able to pass through the analytical region and out of the downstream end of the ion separation device.

[0076] At a later time the magnitude of the electric field at each point along the ion separation device is reduced further such that second ions having a lower mobility (or higher mass to charge ratio) than the first ions are urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher mass to charge ratio) than the second ions are retained in the trapping region by the DC electric field. The second ions are able to pass through the analytical region and out of the downstream end of the ion separation device. The magnitude of the electric field at each point along the ion separation device is progressively reduced such that ions having progressively lower mobilities (or progressively higher mass to charge ratios) elute from the downstream end of the ion separation device.

[0077] As an alternative to, or in addition to, progressively reducing the magnitude of the electric field at each point along the ion separation device in order to cause ions having progressively lower mobilities (or progressively higher mass to charge ratios) to elute, the amplitude of the travelling DC potentials 12 that travel through the trapping and analytical regions may be increased in order to cause ions having progressively lower mobilities (or progressively higher mass to charge ratios) to elute, e.g. as will be described with reference to Figs. 3A-3B.

[0078] Figs. 3A-3B illustrate an example of the electric field profile along an ion separation device according to an embodiment of the present invention. As can be seen from Figs. 3A-3B, the ion separation device has a trapping region 10 within which the magnitude of the electric field increases as a function of position along the ion separation device in the downstream direction. Although the magnitude of the electric field in the trapping region 10 is shown as increasing linearly, the magnitude of the field may increase non-linearly. At the end of the trapping region there is an analytical region 11 , along which the magnitude of the electric field is substantially constant. The magnitude of the electric field in the analytical region may be the same as the magnitude of the electric field in the trapping region. Fig. 3A also illustrates the travelling DC potentials 12 that move along the ion separation device in the downstream direction, through the trapping region and also through the analytical region.

[0079] Fig. 3A also shows that ions 13 of different mobility (or different mass to charge ratio) are trapped at different equilibrium positions along the trapping region, the different mobilities (or mass to charge ratios) being illustrated by the differently sized circles. The ratio of maximum to minimum DC field amplitude in the trapping region dictates the ion mobility (or mass to charge ratio) range trapped in that region. This ratio can be adjusted to accommodate the specific analysis or application being performed such that ions of interest are axially spread over as much of the trapping range as possible, thus maximizing space-charge capacity of the device. Once the ions have been separated according to mobility (or mass to charge ratio) within the ion separation device, the ions may be caused to elute from the exit of the device during an elution period by progressively increasing the amplitude of the travelling DC potentials, as shown in Fig. 3B.

[0080] Fig. 3B shows the same example as in Fig. 3A, except wherein the amplitude of the travelling DC potentials that travel along the ion separation device has been increased. The travelling DC potentials 12 are then able to urge the ions in the trapping region further downstream along the ion separation device and such that first ions 14 of relatively high ion mobility (or relatively low mass to charge ratio) are urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher mass to charge ratio) are retained in the trapping region by the DC electric field. The first ions 14 are able to pass through the analytical region and out of the downstream end of the ion separation device.

[0081] At a later time (not shown) the amplitudes of the travelling DC potentials are increased further. Second ions having a lower mobility (or higher mass to charge ratio) than the first ions are urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher mass to charge ratio) than the second ions are retained in the trapping region by the DC electric field. The second ions are able to pass through the analytical region and out of the downstream end of the ion separation device. The amplitudes of the travelling DC potentials may be progressively increased such that ions having progressively lower mobility (or progressively higher mass to charge ratio) elute from the downstream end of the ion separation device. At any point in time, the maximum amplitudes of the travelling DC potentials that travel along the analytical region 11 may be the same as the maximum amplitudes of the travelling DC potentials that travel along the trapping region 10, as is shown in Figs. 3A-3B.

[0082] In each of Figs. 3A-3B, the magnitude of the DC electric field is shown as a function of position along the ion separation device, whereas the maximum amplitudes of the travelling DC potentials are illustrated (rather than the electric field due to the traveling DC potentials). The magnitude of the DC electric field increases along the trapping region, but the maximum amplitudes of the travelling DC potentials (relative to the potentials of the underlying DC electric field) are the same at all points along the trapping region. Similarly, the magnitude of the electric field is constant along the analytical region, and the maximum amplitudes of the travelling DC potentials (relative to the potentials of the underlying DC electric field) are the same at all points along the analytical region.

[0083] The travelling DC potentials described herein may be travelled along the ion separation device by applying a voltage to each of a plurality of electrodes that are spaced along the ion separation device, where the magnitude of the voltage is varied with time so as to follow a voltage waveform (e.g. such as the waveform shown in Fig. 1B), and wherein the voltages applied to different electrodes at different positions along the ion separation device are at different phases of the voltage waveform. The voltage waveform applied to each electrode may be superimposed on the DC voltage that is applied to that electrode in order to generate the DC electric field, e.g. by capacitive coupling. The voltage waveform has a peak-to-peak amplitude and may be superimposed in a manner so that the waveform is symmetrical about the DC voltage that is applied to that electrode in order to generate the DC electric field, i.e. such that half of the peak-to-peak amplitude is above the DC voltage and half of the peak-to-peak amplitude is below the DC voltage. Alternatively, the voltage waveform may be superimposed in a manner so that the waveform is asymmetrical about the DC voltage that is applied to that electrode in order to generate the DC electric field, e.g. such that a greater proportion of the peak-to-peak amplitude is above the DC voltage than is below the DC voltage. For example, the entire peak-to-peak amplitude may be above the DC voltage that is applied to that electrode in order to generate the DC electric field.

[0084] Embodiments have been described above in which the electric field is reduced and / or the amplitudes of the travelling DC potentials are increased in order to elute ions. Additionally, or alternatively, the speed at which the travelling DC potentials travel along the ion separation device may be decreased in order to elute ions during the elution period. In such embodiments, ions are trapped in the trapping region as has been discussed above, i.e. using the opposing forces due to the travelling DC potentials and the electric field. The speed at which the travelling DC potentials travel along the ion separation device is then decreased. The travelling DC potentials 12 are then able to urge the ions in the trapping region further downstream along the ion separation device and such that first ions 14 of relatively high ion mobility (or relatively low mass to charge ratio) are urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher low mass to charge ratio) are retained in the trapping region by the DC electric field. The first ions 14 are able to pass through the analytical region and out of the downstream end of the ion separation device.

[0085] At a later time the speed at which the travelling DC potentials travel along the ion separation device is decreased further. This causes second ions having a lower mobility (or higher mass to charge ratio) than the first ions to be urged out of the trapping region and into the analytical region, whereas ions of lower mobility (or higher mass to charge ratio) than the second ions are retained in the trapping region by the DC electric field. The second ions are able to pass through the analytical region and out of the downstream end of the ion separation device. The speed of the travelling DC potentials in both the trapping and analytical regions may be progressively decreased such that ions having progressively lower mobility (or progressively higher mass to charge ratio) elute from the downstream end of the ion separation device.

[0086] Other techniques may be used to cause the ions to separate and elute according to mobility or mass to charge ratio. For example, the travelling DC potentials described in the embodiment shown in Figs. 2A-2B may be replaced by a gas flow that urges ions in the downstream direction. It will be appreciated that this will also cause ions to be separated according to mobility or mass to charge ratio in the trapping region 10 and that reducing the electric field as described above will cause ions to elute in order of decreasing mobility or increasing mass to charge ratio. Alternatively, the electric field may not be reduced so as to cause ions to elute, but the gas flow rate may instead be progressively increased in order to cause ions to elute in order of decreasing mobility or increasing mass to charge ratio.

[0087] Less preferably, the electric field described in the embodiment shown in Figs. 2A- 2B may be replaced by a gas flow that urges ions in the upstream direction. In this embodiment the amplitudes and / or speed of the travelling DC potentials vary as they pass along the trapping region, so as to cause ions to be separated according to mobility or mass to charge ratio in the trapping region 10. The gas flow rate may then be progressively reduced in order to cause ions to elute in order of mobility or mass to charge ratio.

[0088] Furthermore, it is contemplated that each of the two opposing forces in all of the above embodiments may act in the opposite direction to that described above and still cause the ions to be separated and eluted according to mobility or mass to charge ratio. For example, referring to Figs. 2A-3B, the magnitude of the electric field may decrease along the trapping region in the downstream direction and the travelling DC potentials may travel in the upstream direction so as to separate ions along the trapping region. The magnitudes of the electric field may be increased, and / or the amplitudes and / or speed of the travelling DC potentials may be decreased, in order to cause ions to elute from the downstream end of the device in an order according to mobility or mass to charge ratio.

[0089] Fig. 4 shows a schematic of a mass spectrometer according to an embodiment of the present invention that includes an ion separation device as described above. The spectrometer comprises an ion source 20 for generating ions, a first ion guide 21 arranged in a first vacuum chamber 22, an ion separation device 1 according to the present invention arranged in a second vacuum chamber 23, a quadrupole mass filter 24 and a fragmentation or reaction cell 25 comprising a quadrupole rod set ion guide 26 arranged in a third vacuum chamber 27. The spectrometer also comprises ion optics 28 arranged in a fourth vacuum chamber 29 for focussing ions into a TOF mass analyser 30 that is arranged in a fifth vacuum chamber 31. Gas is pumped out of the vacuum chambers by one or more vacuum pump so as to reduce the pressure inside them. It will be appreciated that the illustrated spectrometer is exemplary and that the present invention is not limited to this arrangement. For example, the spectrometer may have fewer or more vacuum chambers and / or different or addition ion-optical devices, such as a different type of mass analyser.

[0090] In use, a sample to be analysed is supplied to the ion source 2. The sample may be separated prior to being supplied to the ion source, such as by a liquid or gas chromatography separator. The sample delivered to the ion source is ionised and the resulting ions pass into the first vacuum chamber 22. The ions are guided through the first vacuum chamber 22 by the first ion guide 21 and into the ion separation device 1 located in the second vacuum chamber 23. The ions are separated in, and caused to elute from, the ion separation device 1 according to their mobility or mass to charge ratio during an elution period, as described above. The separated ions then pass into the mass filter 24.

[0091] The mass spectrometer is operated to perform a first, survey acquisition in which the mass filter is operated as an RF ion guide so as to substantially not mass filter ions passing therethrough, or in which the mass filter is operated in a wide-band pass mode having a relatively low mass to charge ratio resolution so as to transmit ions having a relatively broad range of mass to charge ratios. Alternatively, the mass filter may be operated in a bandpass mode so that it only transmits ions having mass to charge ratios within a mass transmission window at any given time, wherein the mass filter is operated so that the mass range of the mass transmission window is scanned or stepped over a range of values and in synchronism with said elution period. The mass spectrometer is also operated such that the ions transmitted by the mass filter are subjected to a relatively low level of fragmentation or reaction in the fragmentation or reaction cell 25, such as substantially no fragmentation or reaction. The ions exit from the fragmentation or reaction cell 25, pass through the ion optics 28 in the fourth vacuum chamber 29 and into the fifth vacuum chamber 31. The ions then arrive at the pusher 32 of the TOF mass analyser 30, and a voltage pulse is applied to the pusher 32 so that the pusher pushes a packet of the ions into the time of flight region 33 towards an ion mirror 34. The ions are reflected back through the time of flight region 33 by the ion mirror 34 and onto the ion detector 35. The ions can therefore be mass analysed by the TOF mass analyser 30 in the known manner, i.e. by determining the mass to charge ratios of the ions based on their flight time from the pusher 32 to the detector 35. The mass spectrometer may also associate elution times from the ion separation device 1 with the detected ions, e.g. based on their time of detection by the mass analyser relative to the start of the elution period of the ion separation device. This data is then interrogated so as to identify ion species that are of interest, such as ion species that have mass to charge ratios in one or more ranges. A second acquisition is then performed on the sample, in which ions are again separated in the ion separation device such that they elute according to mass to charge ratio or mobility during an elution period. The eluting ions pass to the mass filter, which is operated in a bandpass or resolving mode so that it only transmits ions having mass to charge ratios within a mass transmission window at any given time. The mass filter is operated so that the mass range of the mass transmission window is scanned or stepped over a range of values and in synchronism with said elution period so that the ions of interest detected in the survey acquisition are transmitted by the mass filter. More specifically, the mass spectrometer determines from the data obtained during the survey acquisition when each ion species of interest will elute from the ion separation device and arrive at the mass filter, and controls the mass filter in response to this so that when this ion species arrives at the mass filter the mass transmission window of the mass filter encompasses the mass to charge ratio of that ion species of interest.

[0092] The precursor ions that are transmitted by the mass filter are transmitted into the fragmentation or reaction cell 25 and caused to fragment into fragment ions, or react with other ions or molecules so as to form other product ions. Voltages are applied to the ion guide 26 in the fragmentation or reaction cell 25 such that the fragment or product ions are guided out of the exit of the fragmentation or reaction cell. The ions then pass through the ion optics 28 and into the mass analyser, where they are mass analysed in the same manner as described above so as to obtain mass spectral data for the fragment or product ions, and for any remaining unfragmented precursor ions. The mass spectral data for the fragment or product ions may then be associated with the mass spectral data for their precursor ions that was obtained during the survey acquisition, in the known manner.

[0093] During the elution period of the ion separation device, different ion species may take different durations to elute from the ion separation device. For example, if an ion species is present in multiple different conformations, then that species may have a relatively broad range of mobilities and so may elute from the ion separation device over a longer duration than an ion species that is present with fewer conformations, especially if the ion separation device is operated in a mobility separation mode. Although the mass filter is scanned or stepped in synchronism with the elution period of the ion separation device so that the ion species of interest are transmitted by the mass filter, it has been recognised that if the mass filter is scanned or stepped at a constant rate, as is conventional, then ion species that take a relatively long duration to elute from the ion separation device may be undesirably relatively highly attenuated by the mass filter.

[0094] It is known to step the mass filter between transmitting different non-overlapping ranges of mass to charge ratios at different times, where the mass filter is controlled so that its mass transmission window is held at each range of mass to charge ratio for a dwell time. In such a technique it is possible to mitigate the above problem by varying the dwell times based on the ion species that are expected to elute from the ion separation device. For example, if an ion species having a first mass to charge ratio and a relatively wide mobility peak is expected to elute from the ion separation device over a first, relatively long duration then the mass filter may be controlled to transmit ions having the first mass to charge ratio for a first, relatively long dwell time whilst it receives these ions. In contrast, when an ion species having a second mass to charge ratio and a narrower mobility peak is expected to elute from the ion separation device over a second, shorter duration then the mass filter may be controlled to transmit ions having the second mass to charge ratio for a second, shorter dwell time whilst it receives these ions. Although this may help to increase the proportion of ions of interest that are transmitted through the mass filter, it may not be desired to vary the dwell time of the mass filter.

[0095] According to a first set of embodiments of the present invention, the manner in which ions are caused to elute from the ion separation device during at least a portion the elution period of the ion separation device may be varied. In particular, the mass spectrometer obtains the data from the first, survey acquisition, as described above, and controls the ion separation device in the second acquisition based on this data such that each of the ion species of interest is caused to elute from the ion separation device over a duration that is less than or equal to a threshold duration. In embodiments in which the mass transmission window of the mass filter is stepped between different mass to charge ratio ranges, being paused at each range for a dwell time, the threshold duration may be selected based on the value of the dwell time. For example, the threshold duration may be substantially equal to or less than the dwell time. The mass filter may therefore be stepped using a constant dwell time without significantly attenuating ions of interest, rather than having to vary the dwell time so as to avoid significantly attenuating ions of interest. Similarly, in embodiments in which the mass transmission window of the mass filter is continuously scanned along a range of mass to charge ratios, e.g. at a constant rate, the threshold duration may be selected based on the rate that the mass filter is scanned. For example, if the scan rate is relatively high then the threshold duration may be relatively short, whereas if the scan rate is relatively low then the threshold duration may be relatively long.

[0096] These embodiments enable the overall elution period in the second acquisition to be relatively short, e.g. shorter than the first, survey acquisition. Also, embodiments may perform multiple instances of the second acquisition after each survey acquisition, where ions are accumulated in an ion trap upstream of the ion separation device whilst each instance of the second acquisition is being performed. For example, in the different instances of the second acquisition the mass filter may be scanned in synchronism with the elution period in different manners, respectively, so that different ion species of interest that were identified from the survey acquisition are transmitted by the mass filter in the different instances of the second acquisition. After each instance of the second acquisition has been performed, the ions that have meanwhile been accumulated in the ion trap may be transferred to the ion separation device so as to perform the next instance of the second acquisition on those ions, i.e. so that those ions are separated and eluted during the elution period. As the embodiments described above enable a relatively short elution period in each second acquisition, a relatively large number of second acquisitions can be performed during a given time period, which enables are relatively large number of ions to be analysed during that time period. Ion species of interest that were detected in the first, survey acquisition as having different elution durations from the ion separation device, may all be caused to elute from the ion separation device in the second acquisition such that each ion species of interest elutes from the ion separation device over a duration that is less than or equal to the threshold duration by varying how the ion separation device operates during that second acquisition. For example, in embodiments in which the ion separation device separates and causes ions to elute using travelling DC potentials and an opposing DC electric field, a condition of the travelling DC potentials (e.g. amplitude and / or speed) and / or the DC electric field may be varied during the elution period so that the different ion species of interest each elute from the ion separation device over a duration that is less than or equal to the threshold duration.

[0097] A first set of embodiments has been described above in which the ion species of interest detected in the first, survey acquisition as having different elution durations from the ion separation device may all be caused to elute from the ion separation device in the second acquisition such that each of these ion species of interest elutes from the ion separation device over a duration that is less than or equal to a threshold duration by varying how the ion separation device operates during that second acquisition. However, according to a second set of embodiments, the operation of the ion separation device during the second acquisition is not varied in this manner and instead the rate at which the mass filter is scanned or stepped during the elution period is varied based on the data obtained in the survey acquisition.

[0098] For example, it may be determined from the data obtained in the survey acquisition that first ions having a first mass to charge ratio of interest elute from the ion separation device over a relatively long duration, whereas second ions having a second mass to charge ratio of interest elute from the ion separation device over a relatively short duration. For instance, an ion species having the first mass to charge ratio may have a relatively large number of conformers and hence a relatively wide range of mobilities, whereas an ion species having the second mass to charge ratio may have fewer conformers and hence a narrower range of mobilities.

[0099] During the second acquisition the first ion species again elutes from the ion separation device over a longer duration than the duration over which the second ion species elutes. In order to optimise the proportion of the ions of interest that are transmitted by the mass filter, the mass filter may be controlled based on the information from the survey acquisition. As described above, the rate at which the mass transmission window of the mass filter is scanned or stepped may be varied based on the elution times and mass to charge ratios of the ions detected in the survey acquisition. For instance, the spectrometer may control the mass filter such that during the duration that the first ion species having the relatively long elution duration elutes from the ion separation device and reaches the mass filter, the rate at which the mass transmission window of the mass filter is scanned or stepped is maintained at a first, relatively slow rate so that the mass filter transmits the first ion species for a first relatively long period. The first, relatively long period may be substantially the same as, or shorter than, the duration over which the first ion species elutes from the ion separation device. In contrast, the spectrometer may control the mass filter such that during the duration that the second ion species having the relatively short elution duration elutes from the ion separation device and reaches the mass filter, the rate at which the mass transmission window of the mass filter is scanned is maintained at a second, faster rate so that the mass filter is only able to transmit the second ion species for a second, shorter period. The second, shorter period may be substantially the same as, or shorter than, the duration over which the second ion species elutes from the ion separation device.

[0100] Fig. 5 shows an example of the second set of embodiments, in which the ion separation device separates and elutes ions according to their mobility. Fig. 5 shows the rate at which the mass transmission window of the mass filter is varied during the elution period of the ion separation device. More specifically, the y-axis represents mass to charge ratio and the x-axis represents the elution time during the elution period of the ion separation device. The upper dashed line 40 represents the upper bound of the mass transmission window of the mass filter, and the lower dashed line 41 represents the lower bound of the mass transmission window of the mass filter. This example also shows four different ion species of interest 42-44.

[0101] As described above, the rate at which the mass transmission window of the mass filter is scanned may be varied based on the elution times (i.e. mobility ranges in this case) and mass to charge ratios of the ions detected in the survey acquisition. For instance, the spectrometer may control the mass filter such that during the duration that the first ions having the relatively large mobility range (e.g. ions 44 or 45) elute from the ion separation device and reach the mass filter, the rate at which the mass transmission window of the mass filter is scanned is maintained at a first, relatively slow rate so that the mass filter transmits the first ions for a first relatively long period. In contrast, the spectrometer may control the mass filter such that during the duration that the second ions having the relatively small mobility range (e.g. ions 42 or 43) elute from the ion separation device and reach the mass filter, the rate at which the mass transmission window of the mass filter is scanned is maintained at a second, faster rate so that the mass filter is only able to transmit the second ions for a second, shorter period.

[0102] In all of the above embodiments, the second acquisition may be repeated periodically, where ions are accumulated in an ion trap upstream of the ion separation device whilst each instance of the second acquisition is being performed. After that instance of the second acquisition has been performed the ions in the ion trap may be transferred to the ion separation device so as to perform the next instance of the second acquisition, i.e. so that those ions are separated and eluted during the elution period

[0103] In the ion separation devices described herein, ions have been described as being separated and eluting from the device according to mobility or mass to charge ratio. It is known that in devices in which a DC potential is repeatedly travelled along the device in order to separate ions by mobility, there is a mass to charge ratio dependence in the ion separation, e.g. as described in K. Richardson, D. Langridge, K. Giles, Fundamentals of travelling wave ion mobility revisited: I. Smoothly moving waves, International Journal of Mass Spectrometry, Volume 428, 2018, Pages 71-80. Operational parameters of the separator, such as pressure and / or speed of the travelling DC potentials, may be selected such that it predominantly separates ions by mobility, such that it predominantly separates ions by mass to charge ratio, or such that it operates in a mode where the ion separation is significantly dependent on both mobility and mass to charge ratio.

[0104] The ion separation devices described herein may separate ions predominantly according to mass to charge ratio by providing ion separation conditions that are such that the ions lose only a relatively small portion of their kinetic energy between being accelerated by subsequent travelling DC potentials. Under such conditions the ions do not reach a mobility-related terminal velocity. Such ion separation conditions include relatively low gas pressures, relatively high speed travelling DC potentials, or the gas in the separation region having relatively low mass molecules (such as helium or hydrogen). Conversely, ions may be separated predominantly according to mobility by providing ion separation conditions that are such that the travelling DC potentials cause the ions to reach a mobility-related terminal velocity due to collisions with the gas inside the device. Such ion separation conditions include relatively high gas pressures, relatively low speed travelling DC potentials, or the gas in the separation region having relatively high mass molecules (such as nitrogen). The ion separation device may be operated to select either mass to charge ratio separation or mobility separation by varying these operating conditions. For example, the device may switch from the mobility separation mode to the mass to charge ratio separation mode by performing at least one of the following: increasing the speed of the travelling DC potentials; increasing the amplitude of the travelling DC potentials; reducing the pressure of the gas in the device; and changing the gas in the device to have a lower collisional cross-sectional area. Conversely, the device may switch from the mass to charge ratio separation mode to the mobility separation mode by performing at least one of the following: decreasing the speed of the travelling DC potentials; decreasing the amplitude of the travelling DC potentials; increasing the pressure of the gas in the device; and changing the gas in the device to have a higher collisional cross-sectional area.

[0105] Although 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 detail may be made without departing from the scope of the invention as set forth in the accompanying claims.

[0106] For example, although the ion separation device has been described as being formed from a stack of apertured electrodes, it is contemplated that one or more different ion guide structures may be used instead, such as a segmented multipole (e.g. quadrupole) ion guide.

[0107] Embodiments have been described in which voltages are applied to electrodes of the ion separation device so that DC potentials travel along the ion separation device and urge ions along it so as to separate ions according to mobility or mass to charge ratio. However, there are several ways to provide potentials that travel along the ion separation device so as to urge ions along it. For instance, a periodic or harmonic voltage waveform having an amplitude that oscillates with time may be applied to the electrodes of the ion separation device, where different phases of the voltage waveform are applied to electrodes that are located at different axial locations along the ion separation device so as to cause ions to be urged along the device. The voltage waveform may be any periodic or harmonic wave including, but not limited to, a sine or cosine wave, a square wave, a trapezoidal wave, a triangular wave or a sawtooth wave. The voltage waveform may be a waveform that has a continuously varying amplitude. For example, a first electrode (or multiple axially adjacent electrodes) may be supplied with a harmonically oscillating voltage waveform with an initial phase shift of 0 degrees. A second electrode (or multiple axially adjacent electrodes) may be supplied with the voltage waveform, but with the initial phase shifted by 90 degrees. A third electrode (or multiple axially adjacent electrodes) may be supplied with the voltage waveform, but with the initial phase shifted by 180 degrees. A fourth electrode (or multiple axially adjacent electrodes) may be supplied with the voltage waveform, but with the initial phase shifted by 270 degrees. This pattern of applying the voltage waveform to electrodes of the ion separation device may then be repeated along the device. The voltage waveform may be applied to the electrodes of the device so as to effectively form a substantially smoothly varying potential that travels along the ion separation device and acts to urge ions axially along the device. The frequency of this four-phase voltage supply and the distance between the electrodes (i.e. pitch of the electrodes) may be selected so as to dictate the velocity of the travelling potential. Such a system is described, for example, in A.W. Colburn et al., Physics Procedia 1 (2008) 51- 60, Colburn et al.

[0108] It will be appreciated that a waveform having more than four phases, or even three phases, may be applied to respective electrodes so as to urge the ions along the device.

[0109] It is contemplated that the amplitude and / or frequency of the voltage waveform may be altered with time. Additionally, or alternatively, the phases of the voltage waveform that are applied to the different electrodes may be altered with time, e.g. so that the potential travels along the ion separation device in the opposite direction.

[0110] In addition to the phase shifted voltage waveform, axially adjacent electrodes may be supplied with opposite phases of a separate RF waveform for radially confining ions within the device. This enables the radially confining potential and the axial travelling potential to be adjusted independently of each other. The confining RF waveform and the phase shifted travelling potential waveforms may be superimposed. These oscillating waveforms may be capacitively coupled to the electrodes, optionally allowing complex DC potentials to be simultaneously applied to the electrodes, for example, using DC resistive divider circuits between the electrodes in the axial direction.

[0111] Although the embodiments of the ion separation device described above separate and elute ions according to mobility or mass to charge ratio by applying opposing forces on the ions, it is contemplated that other types of mobility or mass to charge ratio separators may be used instead. For example, the ion separation device may separate and elute ions by driving the ions through a static background gas. The ions may be driven through the gas by travelling potentials along the device or by a static DC electric field.

Claims

Claims:

1. A method of mass and / or mobility spectrometry comprising: performing a first, survey acquisition that comprises separating ions in an ion separation device and determining a first duration of elution from the ion separation device of a first ion species; selecting a threshold duration for an ion species to elute from the ion separation device; and performing a second acquisition in which the ion separation device is controlled, based on the first duration of elution determined in the first, survey acquisition, such that it causes said first ion species to elute from the ion separation device over a second duration that is different to said first duration and that is less than or equal to said selected threshold duration.

2. The method of claim 1 , wherein the first, survey acquisition comprises determining a duration of elution from the ion separation device for each of a plurality of ion species, and wherein in the second acquisition the ion separation device is controlled, based on the durations of elution determined for the plurality of ion species in the first, survey acquisition, such that it causes each of said plurality of ion species to elute from the ion separation device over a duration that is less than or equal to the selected threshold duration.

3. The method of claim 1 or 2, comprising determining in the first, survey acquisition that the first ion species elutes from the ion separation device with a first elution duration that is longer than the selected threshold duration; and wherein in the second acquisition the ion separation device is controlled so as to elute the first ion species at a faster rate than in the first, survey acquisition such that the first ion species elutes from the ion separation device with an elution duration that is less than or equal to the selected threshold duration.

4. The method of claim 1, 2 or 3, comprising determining in the first, survey acquisition that a second ion species elutes from the ion separation device with a further elution duration that is shorter than the selected threshold duration; and wherein in the second acquisition the ion separation device is controlled so as to elute the second ion species at a slower rate than in the first, survey acquisition such that the second ion species elutes from the ion separation device with an elution duration that is longer than said further second elution duration, but less than or equal to the selected threshold duration.

5. The method of any preceding claim, comprising controlling the ion separation device, in the second acquisition, so as to elute the ions over an elution period; and mass filtering the eluting ions by scanning or stepping a mass transmission window of a massfilter in synchronism with the elution period of the ion separation device so that at least said first ion species is, and optionally said plurality of ion species are, transmitted by the mass filter.

6. The method of claim 5, wherein during the elution period the mass transmission window of the mass filter is stepped between different ranges of mass to charge ratios, being paused at each range for a dwell time, wherein the length of said threshold duration is selected based on the duration of the dwell time.

7. The method of claim 6, wherein the mass filter is paused at all of the ranges of mass to charge ratio for the same dwell time.

8. The method of claim 6 or 7, wherein the threshold duration is equal to or less than the dwell time.

9. The method of claim 5, wherein during the elution period the mass transmission window of the mass filter is substantially continuously and progressively scanned across a range of mass to charge ratios.

10. The method of claim 9, wherein the length of the threshold duration is selected based on the rate that the mass filter is scanned across said range of mass to charge ratios.

11. The method of any one of claims 5-10, comprising mass analysing the ions that have been transmitted by the mass filter, or ions derived therefrom, so as to determine their mass to charge ratio.

12. The method of any preceding claim, wherein in each of the first and second acquisitions the ion separation device separates the ions by ion mobility and causes the ions to elute in an order according to their mobilities; or wherein in each of the first and second acquisitions the ion separation device separates the ions by mass to charge ratio and causes the ions to elute in an order according to their mass to charge ratios.

13. The method of claim 12, wherein in each of the first and second acquisitions the method comprises: applying voltages to electrodes of the ion separation device such that an electrical potential repeatedly travels along the ion separation device so as to urge ions in a first direction along the ion separation device, and applying different voltages to electrodes at different respective positions along the ion separation device so as to provide an electric field for urging ions in a second, opposite direction to said first direction, so as to cause ions to be separated according to mass to charge ratio or mobility.

14. The method of claim 13, wherein in each of the first and second acquisitions the ion separation device causes ions to elute in an order according to mobility or mass to charge ratio by: (i) varying the speed and / or amplitude of the electrical potential that repeatedly travels along the ion separation device; and / or (ii) varying the electric field maintained along the ion separation device.

15. The method of claim 14, comprising determining from the first, survey acquisition that the first ion species elutes from the ion separation device with a first elution duration that is longer than the selected threshold duration; and in response to this controlling the ion separation device in the second acquisition so as to:(i) increase the rate at which the amplitude and / or speed of the electrical potential is varied, relative to the rate that it was varied in the first acquisition, so that the first ion species elutes at a faster rate in the second acquisition than in the first acquisition; and / or(ii) increase the rate at which the electric field is varied, relative to the rate that it was varied in the first acquisition, so that the first ion species elutes at a faster rate in the second acquisition than in the first acquisition.

16. The method of claim 14 or 15, comprising determining from the first, survey acquisition that a second ion species elutes from the ion separation device with a further elution duration that is shorter than the selected threshold duration; and in response to this controlling the ion separation device in the second acquisition so as to:(i) decrease the rate at which the amplitude and / or speed of the electrical potential is varied, relative to the rate that it was varied in the first acquisition, so that the second ion species elutes at a slower rate in the second acquisition than in the first acquisition; and / or(ii) decrease the rate at which the electric field is varied, relative to the rate that it was varied in the first acquisition, so that the second ion species elutes at a slower rate in the second acquisition than in the first acquisition.

17. A mass and / or mobility spectrometer comprising: an ion separation device; an ion detector; and control circuitry configured to control the spectrometer to: select a threshold duration for an ion species to elute from the ion separation device; perform a first, survey acquisition in which ions are separated in the ion separation device and detected at the ion detector so as to determine a first duration of elution from the ion separation device of a first ion species; and perform a second acquisition in which the ion separation device is controlled, based on the first duration of elution determined in the first, survey acquisition, such that it causes said first ion species to elute from the ion separation device over a second duration that is different to said first duration and that is less than or equal to said selected threshold duration.

18. A method of mass spectrometry comprising: performing a first, survey acquisition that comprises separating ions in an ion separation device and determining a duration over which each of a plurality of ion species elute from the ion separation device; determining from said first, survey acquisition that a first ion species elutes from the ion separation device over a first elution duration and that a second ion species elutes from the ion separation device over a second, shorter elution duration; performing a second acquisition that comprises separating ions in the ion separation device such that a plurality of ion species elute over an elution period, and mass filtering ions eluting from the ion separation device by scanning or stepping a mass transmission window of a mass filter in synchronism with the elution period; wherein the method comprises: determining the period of time over which the first ion species elutes and reaches the mass filter during the second acquisition based on said first elution duration determined from the first, survey acquisition, and controlling the mass filter so that during this period of time the mass transmission window is scanned or stepped at a first rate; and determining the period of time over which the second ion species elutes and reaches the mass filter during the second acquisition based on said second elution duration determined from the first, survey acquisition, and controlling the mass filter so that during this period of time the mass transmission window is scanned or stepped at a second rate that is faster than the first rate.

19. The method of claim 18, wherein the mass transmission window is scanned or stepped at said first rate for the entire period of time that the first ion species arrives at the mass filter; and / or wherein the mass transmission window is scanned or stepped at said second rate for the entire period of time that the second ion species arrives at the mass filter.

20. The method of claim 18 or 19, comprising mass analysing the ions that have been transmitted by the mass filter, or ions derived therefrom, so as to determine their mass to charge ratio.

21. The method of claim 18, 19 or 20, wherein in each of the first and second acquisitions the ion separation device separates the ions by ion mobility and causes the ions to elute in an order according to their mobilities; or wherein in each of the first and second acquisitions the ion separation device separates the ions by mass to charge ratio and causes the ions to elute in an order according to their mass to charge ratios.

22. The method of claim 21 , wherein in each of the first and second acquisitions the method comprises: applying voltages to electrodes of the ion separation device such that an electrical potential repeatedly travels along the ion separation device so as to urge ionsin a first direction along the ion separation device, and applying different voltages to electrodes at different respective positions along the ion separation device so as to provide an electric field for urging ions in a second, opposite direction to said first direction, so as to cause ions to be separated according to mass to charge ratio or mobility.

23. The method of claim 22, wherein in each of the first and second acquisitions the ion separation device causes ions to elute in an order according to mobility or mass to charge ratio by: (i) varying the speed and / or amplitude of the electrical potential that repeatedly travels along the ion separation device; and / or (ii) varying the electric field maintained along the ion separation device.

24. A mass spectrometer comprising: an ion separation device; a mass filter; an ion detector; and control circuitry configured to control the spectrometer to: perform a first, survey acquisition in which ions are separated in the ion separation device and detected at the ion detector so as to determine a duration over which each of a plurality of ion species elute from the ion separation device; determine from said first, survey acquisition that a first ion species elutes from the ion separation device over a first elution duration and that a second ion species elutes from the ion separation device over a second, shorter elution duration; perform a second acquisition in which the ion separation device separates ions such that a plurality of ion species elute over an elution period, and the mass filter mass filters ions eluting from the ion separation device by scanning or stepping a mass transmission window of the mass filter in synchronism with the elution period; wherein the spectrometer has control circuitry configured to: determine the period of time over which the first ion species elutes and reaches the mass filter during the second acquisition based on said first elution duration determined from the first, survey acquisition, and control the mass filter so that during this period of time the mass transmission window is scanned or stepped at a first rate; and determine the period of time over which the second ion species elutes and reaches the mass filter during the second acquisition based on said second elution duration determined from the first, survey acquisition, and control the mass filter so that during this period of time the mass transmission window is scanned or stepped at a second rate that is faster than the first rate.

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