Ion separation device

Abstract

Ions are separated according to their mass-to-charge ratio. A separation region receives the ions and extends in a first direction and a second direction that differs from the first. An electrode array confines the ions within the separation region. The electrode array is configured to apply a time-dependent potential within the separation region to cause movement of the ions in the first direction and to apply a potential gradient within the separation region, with the potential gradient opposing the time-dependent potential, so that the ions are separated at different positions in the first direction according to their mass-to-charge ratio. A force is applied to the ions in the second direction to cause movement of the ions in the second direction.

Description

FIELD OF THE INVENTION

[0001] The present disclosure relates to a device for separating ions according to mass-to-charge ratio. STATE OF THE ART

[0002] Ion separation devices are widely used in mass spectrometry. Most tandem mass spectrometers use a quadrupole mass filter (US2939952A) to isolate target ions prior to fragmentation and downstream mass analysis. A disadvantage of this established technology is that unselected ions impinge on the rods, leading to the loss of analyte ions (which may be in short supply) and simultaneously contaminating and ultimately damaging the electrodes. Depending on the isolation windows used, the loss of theoretical sensitivity can exceed 99%.

[0003] One attempt to overcome these problems was to accumulate and roughly separate ions in front of the quadrupole, so that the mass-to-charge ratio (m / z) of the ions delivered to the device roughly corresponds to the range of the isolation window, thus reducing or minimizing ion losses to the accuracy of the pre-separation. Some losses remain unavoidable unless the pre-separator is so good that it renders the quadrupole redundant.

[0004] This method was proposed in GB2442638A, in which ions were first loaded into an ion trap. An RF pseudopotential barrier prevents the release of higher m / z ions unless overcome by a direct current (DC) or traveling wave ("T-wave"), which pushes the ions toward the exit, where they would be released for quadrupole selection / fragmentation, etc. Fig. 3 of GB2442638A shows capture and sequential release via a pseudopotential.

[0005] Previously, a system was proposed in US6794641B2 in which ions in an ion guide could separate under the influence of a traveling wave depending on m / z or mobility and appear in a manner that could be linked to the mass range of an orthogonal ToF analyzer, thereby improving its duty cycle.

[0006] Many methods have been considered to achieve similar goals, similarly in US 10665441B2, and the most successful was the method of parallel accumulation and serial fragmentation from a trapped ion mobility spectrometry (TIMS) device (Meier, F. et al. Parallel Accumulation-Serial Fragmentation (PASEF): Multiplying Sequencing Speed ​​and Sensitivity by Synchronized Scans in a Trapped Ion Mobility Device. Journal of Proteome Research 2015, 12, 5378-5387, US20170122906A1 and US 10794861B2). Further variations include accumulation in multiple traps, either orthogonally via an RF pseudopotential (US10199208B2) or via ion mobility (US20170076928A1).

[0007] Traveling waves are a well-known method for propelling ions through ion guides. Either a series of phase-shifted RF potentials (US7375344B2) or switched DC pulses (Giles et al., Applications of a traveling wave-based radio-frequency-only stacked ring ion guide, Rapid Commun. Mass Spectrom. 2004; 18: 2401-2414) can be applied to successive axial segments of an ion guide. This creates a potential front that moves downward over time in the center of the guide, pulling ions along with it.

[0008] The interaction between a traveling wave and an opposing linear DC gradient has been previously described. US8841608B2 describes the use of an opposing DC gradient to increase the residence time of ions in a T-wave-driven mobility separator, thereby improving resolution and also proposing bandpass filters to remove unwanted ions. Fig. 3 of US8841608B2 shows a combination of a T-wave and a decelerating DC force.

[0009] Some ion guide technologies may be suitable for applying traveling waves and / or DC gradients. Typically, axial segmentation is required; thus, stacked ring ion guides are most commonly used. Printed circuit board-printed ion guides such as SLIM (Structures for Lossless Ion Mobility) enable a cost-effective method for applying segmentation and have been demonstrated with DC and RF traveling waves (Hamid et al., Characterization of Traveling Wave Ion Mobility Separations in Structures for Lossless Ion Manipulations, Anal. Chem. 2015, 87, 22, 11301-11308). RF carpets that combine an RF surface with a DC counter electrode are suitable for use with traveling waves (G. Bollen, “Ion surfing” with radiofrequency carpets, Int. J. Mass. Spectrom., 2011, 299, 131-138).

[0010] US6914241B2 and US6838662B2 describe methods for using an opposing traveling wave and a DC gradient, including nonlinear direct current, to cause ion separation within a guide. The ions reach equilibrium positions and can then be released in a time-dependent manner by a quadrupole, increasing efficiency. US6914241B2 indicates that ion mobility in a static gas field plays a role in the ion equilibrium positions.

[0011] Although the above-mentioned systems perform adequately in some respects, there is still a need for improved ion separation methods and equipment. SUMMARY

[0012] Against this background, the present disclosure relates to a device according to claim 1.

[0013] The present disclosure relates to ion separation devices (e.g., ion guides) in which time-dependent potentials (e.g., T-waves) push ions against a potential gradient (e.g., a DC gradient). The ions are separated and assume static positions along the ion guide according to their m / z, and can then be released in m / z order to a downstream device (or devices). The ion guides described herein may have two- or three-dimensional structures, with forces orthogonal to the m / z separation direction being applied to the ions to cause two- or three-dimensional ion motion. Such orthogonal forces may be provided by DC gradients, time-dependent potentials (e.g., RF potentials or T-waves), or gas flows.

[0014] Generally speaking, the present disclosure therefore provides a device for separating ions according to the mass-to-charge ratios of the ions. The device can be described as an ion guide that causes ions with different m / z values ​​to pass through at different velocities depending on their m / z values.

[0015] Embodiments of the present disclosure include a separation region configured to receive the ions. This separation region can receive the ions from any upstream ion source (e.g., an external ion source) via any type of ion guide, conduit, or channel. The separation region extends in a first direction and in a second direction (e.g., in an orthogonal direction) that is different from the first direction.

[0016] Embodiments of the present disclosure include an electrode assembly configured to confine the ions in the separation region (e.g., trap them for an extended period of time). The electrode assemblies of the present disclosure may include any number of individual electrodes or electrode segments. Each electrode of the electrode assemblies may be controlled by a controller coupled to all of the electrodes and configured to individually vary the voltages applied to the electrodes. The controller may be provided at one or a plurality of power sources for applying such voltages.

[0017] The electrode assemblies described herein are configured to apply a time-dependent potential in the separation region to cause the ions to move in the first direction. The electrode assemblies are configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential, such that a combination of the potential gradient and the time-dependent potential results in ions separating into different positions according to their mass-to-charge ratio in the first direction. That is, different ions settle into different positions according to their m / z values. The ions are confined within the device and separated under the combined influence of these applied, overlapping, potentials.

[0018] The devices described herein are further configured to exert a force on the ions in the second direction to cause the ions to move in the second direction. This could, for example, cause ions to move perpendicular to their separation direction, thereby increasing the volume available for the ions and thus reducing the impact of space charge effects.

[0019] Methods are also provided. For example, a method for separating ions according to their mass-to-charge ratio is provided, comprising: introducing the ions into a separation region extending in a first direction and a second direction different from the first direction; applying a potential in the separation region to confine the ions in the separation region; applying a time-dependent potential in the separation region to cause movement of the ions in the first direction; applying a potential gradient in the separation region, the potential gradient being opposite to the time-dependent potential, to separate the ions in different positions in the first direction according to the mass-to-charge ratios of the ions; and exerting a force in the second direction on the ions to cause movement of the ions in the second direction.

[0020] While existing approaches such as US6914241B2 and US6838662B2 illustrate basic ion separation, some embodiments described herein provide two-dimensional (e.g., planar) structures with additional DC or T-wave forces (or other time-dependent potential forces) or gas forces (e.g., due to gas jets or additional gas flows) orthogonal to the m / z separation direction.

[0021] Some embodiments provide multiple capture regions in different positions in the first direction, while some embodiments provide switchable accumulation / transmission regions that run parallel to the separation regions.

[0022] Embodiments of the disclosure provide various advantages. One advantage of the devices described herein over more conventional axial ion traps, where only one exit region is defined, is that the ions can be distributed over a wide plane, and space charge effects from dominant species can be localized and reduced. In an accumulation device that is set up prior to isolation, space charge effects can cause severe problems. Thus, the disclosure can support very large devices, since the ions to be released would always be located near the exit. The devices described herein can also be integrated into vacuum interface ion guides of mass spectrometers that use atmospheric pressure ion sources, such as ESI (electrospray ionization) ion sources.

[0023] A further advantage over existing devices is that tightly controlled gas flows are not necessarily required (although these could be provided in some embodiments as needed), which greatly simplifies the design.

[0024] These and other advantages will become apparent from the following disclosure. LIST OF CHARACTERS

[0025] The present disclosure will now be described by way of example with reference to the accompanying figures, in which: Fig. 1 shows potentials that can be used in embodiments of the disclosure; Fig. 2 shows a device according to an embodiment of the disclosure; Fig. 3 shows a flowchart illustrating a method of operating embodiments of the disclosure; Fig. 4 shows a mass spectrometry system incorporating embodiments of the disclosure; Fig. 5A and Fig. 5B shows an embodiment of the disclosure and an applied traveling wave; Fig. Figure 6 shows the potential incorporated in one embodiment of the disclosure; Fig. Figure 7 shows the simulated movement of ions in one embodiment of the disclosure; Fig. Figure 8 shows the simulated movement of ions in one embodiment of the disclosure; Fig. 9 shows the simulated movement of ions in one embodiment of the disclosure; Fig. 10 shows the simulated movement of ions in one embodiment of the disclosure; Fig. 11 shows potentials applied in one embodiment of the disclosure; Fig. 12 shows electrode arrangements for use in embodiments of the disclosure; Fig. 13 shows an apparatus for separating ions according to embodiments of the disclosure; Fig. 14 shows an apparatus for separating ions according to an embodiment of the disclosure; Fig. 15 shows an apparatus for separating ions according to an embodiment of the disclosure; Fig. 16 shows the simulated movement of ions in one embodiment of the disclosure; Fig. 17 shows electrode arrangements for use in embodiments of the disclosure; and Fig. Figure 18 shows a device incorporating embodiments of the disclosure. DETAILED DESCRIPTION

[0026] Some embodiments of the present disclosure address issues related to the loss of unselected ions, for example, during quadrupole isolation. While the associated problem of rod contamination can be largely resolved by more tolerant prefilter quadrupole segments (USRE45553E), the loss of sensitivity can be avoided or at least reduced by using some degree of preaccumulation and separation.

[0027] One known method for achieving this is pre-accumulation in a TIMS device, which can improve the sensitivity of TIMS-ToF instruments by an order of magnitude. Disadvantages of such devices include the limited space-charge capacity and the need to provide laminar flow with opposing gas force. Separation by drift, rather than proper m / z matching to the quadrupole, imposes certain limitations on the achievable performance and results in the filtering out of different charge states. This latter part is advantageous for peptide identification applications, as it allows for the discrimination of singly charged ions that are unlikely to originate from digested peptides.

[0028] A process in which the ions are not distributed over a wide space is severely affected by space charge effects, including TIMS, but also all respective trapping modes (including the device described in GB2442638A). While methods enabling flow-based separation and arrayed traps, such as those described in US 10199208B2 and US20170076928A1, are significantly more robust to space charge effects, they suffer from considerable complexity. US6914241B2 and US6838662B2 provide examples for ions distributed over a long channel. Some embodiments described herein propose ion trapping methods that separate ions within a relatively large trap volume (e.g., a two-dimensional planar region or a large three-dimensional volume), thus reducing space charge effects.

[0029] Methods that separate by ion drift times tend to require accumulation in a small space, leading to space charge limitations, or require large separation devices to achieve useful results. In general, a small-footprint device is desirable. Large ion guides may require a PCB-based design (such as SLIM), which introduces risks from charging the exposed insulating material or the use of more exotic structures such as helical shapes.

[0030] By extending the isolation window of a quadrupole (or other mass filter), sensitivity can be improved, and for applications with very low ion loading, the m / z window can advantageously even be enlarged to extreme widths (such as 100), compared to a more regular single m / z target width of 1 or 2. However, the high complexity of spectra from multiple precursor fragments can pose problems for deconvolution and identification software, although rapid progress is being made in this area (Frejno et al., CHIMERYS: An AI-Driven Leap Forward in Peptide Identification, Proceedings of the 69th ASMS Conference on Mass Spectrometry and Allied Topic, Philadelphia PA, 2021 and Demichev et al., (2020). DIA-NN: Neural networks and interference correction enable deep proteome coverage in high throughput. Nature Methods, 17(1), 41-44.).

[0031] Some non-destructive selection techniques can eliminate the need for a quadrupole. For example, high-resolution ion mobility using ion guides suitable for very long drift paths (US8835839B1, GB2574796A) can provide sufficient separation quality and slow ion release, allowing their output to be directly coupled to a fragmentation device and a primary analyzer. While quadrupole RF ion trap isolation with axial ion collection can provide sufficient resolution, it is, in principle, too severely compromised by space charge and ion capacitance for fine isolation.

[0032] Therefore, there is still a need for improvements in the way ions are separated and processed. For example, it is desirable to mitigate the effects of space charge while ensuring good ion separation.

[0033] Fig. 1 shows the potentials used in certain embodiments of the present disclosure. The potentials in Fig. 1 can be used in a device for separating ions according to the mass-to-charge ratio of the ions. Generally speaking, such a device may comprise a separation region configured to receive the ions (e.g., from an upstream ion source), the separation region extending in a first direction and a second direction different from the first direction.

[0034] The potentials for implementing Fig. 1 may comprise an electrode arrangement configured to confine the ions in the separation region (e.g., to trap them at least for some time under the influence of the different potentials applied by the electrode arrangement). The electrode arrangement is configured to apply a confinement potential and thereby confine the ions within the separation region. The electrode arrangement is configured to apply a time-dependent potential in the separation region to cause the ions to move in the first direction. The electrode arrangement is configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential to separate the ions in different positions in the first direction according to their mass-to-charge ratio (i.e.Due to the different effects of the time-dependent potential and the potential gradient on ions with different m / z, different ions may deposit in different locations. The different potentials (e.g., time-dependent potentials, potential gradients, and confinement potentials) applied in the separation region may overlap. For example, a time-dependent potential (e.g., T-wave) and a potential gradient (e.g., DC gradient) may be superimposed on a confining potential (e.g., a confining RF potential).

[0035] The electrodes of the electrode array can be controlled by a controller coupled to all electrodes, and all electrodes can be connected to a current source to apply potentials. Some or all electrodes can be individually and independently controllable.

[0036] Fig. Figure 1 shows a nonlinear DC gradient (an opposing potential gradient) and a traveling wave (a time-dependent potential) causing separation of ions over a length. Fig. Figure 1 shows the traveling wave at a single point in time; in practice, the traveling wave is caused to propagate continuously in the first direction. The opposing direct current and pseudopotential forces cause ions with different m / z to deposit in different positions.

[0037] To achieve the m / z-dependent separation of Fig. 1, ions can be separated by opposing a potential gradient (e.g., a static field) with a pseudopotential force generated by a dynamic (time-dependent) potential. In some embodiments of the present disclosure, an axial pseudopotential generated by a traveling wave (T-wave) opposes an increasing DC gradient. Such a T-wave could be a multiphase (e.g., 4- or higher-phase) traveling wave. The pseudopotential force pushes the ions until they reach a region where the DC force is equal to or greater than the pseudopotential force; at this point, the ions are trapped (or, if the DC gradient is insufficient, the ions are pushed out of the device). Since the pseudopotential force is m / z dependent, the trapping position of the ions also depends on their m / z.Therefore, ions can be trapped in different positions in the separation direction (first direction).

[0038] Separated ions can be released from the device by scanning / step-changing the applied DC potential or the amplitude / frequency of the traveling wave (or the duty cycle / pulse rate for digital waveforms) in an m / z-dependent manner. Alternatively, many other methods can be used to extract ions from the guide: the DC gradient and T-wave can be removed and ions released over time based on their spatial separation / drift time, or a very slow traveling wave can be applied to expel ions in slow bunches, etc. Accumulated ions can then be released, for example, to a quadrupole (or other mass filter) matching their m / z, thus mitigating losses at the quadrupole.

[0039] Since the application of a traveling wave potential typically requires axial segmentation of the electrodes, the arrangement in Fig. 1 for a stacked ring ion guide and similar structures. Fig. Figure 2 shows an example of an ion guide structure, which is an ion separation device using the approach of Fig. 1 can be implemented. The device includes a separation region 201, a pre-accumulation region 202, a funnel / initial detection region 203, and an ion outlet 204.

[0040] In this particular example, the separation device has a stacked ring structure that also includes optional sections for ion capture from an inlet capillary and a pre-accumulation region 202 to maximize the duty cycle. In addition to a separation region 201 where a T-wave and a DC gradient are applied, the device is shown to include a similar pre-accumulation region 202 for pre-accumulating ions while the separator 201 is operating. An ion funnel 203 receives ions from an inlet capillary, and a small, funnel-shaped region compresses the extracted ions as the ions pass out of the device into a region of higher vacuum (lower pressure). Separate DC offsets and gradients may be imposed on the funnel region 203 and the pre-accumulation region 202, and a controllable (ievariable) DC barrier may be provided. Potentials (e.g., from auxiliary electrodes not shown) may be applied within the guide to cause lateral movement of the ions (i.e., perpendicular to the axis of the ion guide) to enable the distribution of large amounts of charge over a wider surface and thus reduce space charge effects. After passing through the separation region 201, the ions exit the device through the ion outlet 204, for example, to an ion guide of higher vacuum (lower pressure). Therefore, the separation regions and / or accumulation regions described herein may generally be one or more vacuum regions. The separation region and / or accumulation regions may have a lower pressure than an upstream region (i.e.,A region upstream of the separation region and / or the accumulation region of the device and / or may have a higher pressure than a downstream region (i.e., a region downstream of the separation region and / or the accumulation region) of the device. To ensure the formation of a vacuum, various gas-tight enclosures and a pumping function may be provided.

[0041] The properties of the traveling wave are preferably adjusted so that ions pass over the waves, so that the ions feel the influence of a pseudopotential force rather than being completely entrained in the waves. To achieve this, for example, the frequency and / or voltage amplitude of the traveling wave can be varied. In principle, a sufficiently high traveling wave potential will simply carry the ions away, and no separation will occur unless an opposing direct current is set high enough to counteract this effect. Therefore, the opposing potential and the time-dependent potential can be fine-tuned to optimize separation performance. Implementation in practice

[0042] Fig. Figure 3 shows a flow diagram for the operation of a combined accumulator / separator device of the type described with respect to Fig. 2. First, an accumulated packet of mixed m / z ions is transferred from an accumulation region to a separation region; this can be achieved by applying a DC gradient / offset across the accumulator or by using a traveling wave to push the ions forward. Once the accumulator is emptied of ions, it closes with respect to the separator and begins accumulating additional ions as they enter. In parallel, the separation process begins in the separator. The amplitude of the DC gradient (which is preferably curved) is reduced to the level (or alternatively, an increase in the traveling wave amplitude is provided, or both) required to exit the first, lowest m / z target region.After a short delay (typically on the order of 0.25 to 5 ms), the target ions exit the system and migrate to the downstream quadrupole (or other mass filter) for finer isolation. The TLC gradient can then be further reduced to the next target m / z in the sequence, and so on until the m / z range is exhausted, at which point the accumulation region can be emptied again and the cycle repeated.

[0043] Thus, in each cycle of the separation device, several different mass ranges are released sequentially from the separation device.

[0044] Fig. Figure 4 shows a suitable instrument layout incorporating embodiments of the present disclosure. The instrument includes a separation region 401, a pre-accumulation region 402, an ion funnel 403, an ion source 405 (which in this example is an electrospray ion source), an ion inlet 406 (illustrated as an inlet capillary), a foreline pump 407, an intermediate ion guide 408, turbopumps 409, a resolving quadrupole 410, a collision cell 411, and a mass analyzer 412 (illustrated as an orthogonal time-of-flight mass analyzer).

[0045] In use, electrospray ions are introduced into the vacuum system via capillary 406 and collected by ion funnel 403, which directs the ions to accumulation and separation devices 402 and 401. Ions ejected from separator 401, pressurized to ~ 1 mbar, are guided through at least one intermediate ion guide 408 (~ 5 × 10 -2mbar) for fine insulation to the quadrupole 410 (~ 1 × 10 -4 mbar) to allow sufficient differential pumping. Selected ions are then fragmented in the collision cell 411, and the fragments are measured by a suitable mass analyzer 412; this may be a time-of-flight analyzer, as shown, or any other suitable mass analyzer, for example, one or more of a quadrupole, ion trap, or orbital trap mass analyzer.

[0046] The arrangement in Fig. 4 can be optimized in several ways. Careful alignment of the quadrupole 410 and the extracted mass range can be advantageous. If a quadrupole isolation window is to be aligned with the ions released by the separator, it may be possible to consider the resolution of both. For example, if the separator resolution allows an m / z window of only 100 and the trapped range is 100-1000, then as m / z 100 is released, it will also release considerably above m / z 150, at which point there is little benefit to injecting m / z 100 and then 110 through the quadrupole (since the m / z 110 ions will already be gone). Therefore, it may be advantageous to stagger (i.e., space) the quadrupole isolation ranges to match what has not yet been released from the separator, and then return to fill in the gaps with the next separator cycle.This means that if the separator has a lower resolution than the quadrupole, the separator will release a wider range of ions than the quadrupole transmits, which are then lost to the rods; therefore, in this case, it is pointless to try to isolate these ions without first refilling the separator.

[0047] The number of mass ranges per cycle depends on the separator resolution and the balance between ion current and space charge. For example, if the mass resolution power of the separator is 401 ~ 10% and the trapped range is 10x, a maximum of 10 separate mass ranges can be extracted in one cycle. The quadrupole, meanwhile, can be operated in a DIA (Data Independent Acquisition) procedure, which scans through much smaller mass windows, which could therefore be interleaved with the larger separator extractions. For example, a range of 100–1000 is considered with stepwise separator extractions of 100–200, 200–300, and 900–1000. A quadrupole scanning through an isolation window of 10 m / z cannot scan in the regular sequence 100–110, 110–120, etc.run, but can instead potentially collect a single sample from each extracted area per separator cycle: 100-110, 200-210...900-910, then 110-120, 210-220...910-920, and so on. If each extraction cycle can be completed in ~100 ms, similar to a TIMS device, the full DIA cycle would take about one second.

[0048] For DDA (Data Dependent Acquisition), a precursor list can be generated from unfragmented MS1 data. This can be either a true full mass scan or a combination of both, with separately extracted mass ranges for low-abundance regions of the spectrum, resulting in a Boxcar / Orbitrap™ HDR-like spectrum, but obtained much more efficiently. Target species from the precursor list can be extracted in an optimized order, one per extracted mass range per separator cycle. These ranges can be dynamically adjusted up to the limit of the separator's resolving power based on ion current / number of targets, etc.

[0049] In the flowchart of Fig. 3 it is not shown that the entire accumulator / separator device 401 / 402 of Fig. 4 can be opened and the entire ion range can pass through as in a regular mass spectrometer. This can be useful for occasionally acquiring spectra across the entire range or for measuring very intense peaks that might exceed the dynamic range of the instrument (such a segment could easily be specified in a data-dependent precursor list, or specific isolation windows could otherwise be marked and removed from the accumulator DIA sequence based on AGC data (i.e., from MS1 scans or prescans). The strong ion pulse from the accumulator, which initially appears when the device is put into streaming mode, can either be ignored or otherwise used in a full MS scan with very high load.

[0050] Generally speaking, embodiments of the present disclosure may be integrated into a mass spectrometry system comprising: one of the ion separation devices described herein; and a mass filter (e.g., a quadrupole) downstream of the device, wherein the mass filter is configured to receive the ions from the device. The isolation window of the mass filter may correspond to the mass-to-charge ratio of the ions extracted from the separation region. A mass analyzer may be provided and configured to receive the ions from the mass filter or ions derived from those ions (e.g., fragment ions) and to perform mass analysis on the received ions. Simulations of embodiments of the disclosure

[0051] The effectiveness of embodiments of the present disclosure can be demonstrated using simulations. The simulations described herein are performed using the MASIM3D software suite, which was developed to test and optimize device performance.

[0052] Fig. Figure 5A shows a 10 or 15 cm long, two-dimensional ion guide made of stacked plates with a 6 mm envelope. A 4-phase traveling RF and a 2-phase trapping RF were applied. Each plate was 0.5 mm thick and had a 1 mm air gap between the plates, which is practical for such a design without the need for printed or etched electrodes. A trapping RF of 2 MHz, 200 V was used. 0-Peakapplied, with each electrode 180 degrees out of phase with its nearest neighbors. The traveling wave was then generated from a superimposed 200 kHz RF applied to each subsequent electrode with a 90-degree phase shift. Additionally, an opposing DC gradient was generated and superimposed as an analytical function to simplify calculations, rather than labeling each electrode individually.

[0053] Fig. Figure 5B also shows the structure of the traveling wave generated in the center of the channel by the four-phase 50 V, 200 kHz RF. Furthermore, the phase motion in 1 microsecond is shown, as well as the wave-influenced ion travel. A separate plot is also presented showing the traveling wave superimposed on a 50 V DC curve following a 4-function. The gradient can be any nonlinear function, but power functions of 2-4 were used in these simulations. This is similar in some respects to US8841608B2, except that a nonlinear DC gradient is provided; a linear gradient with only a single retarding force would be unable to separate ions except as a filter or by drift velocity as a mobility device.A linear DC gradient would counteract the T-wave-induced ion motion, for example, by slowing the ions; in US8841608B2, it is therefore used to increase residence time in a mobility separator, but separation occurs via ion mobility. The T-wave pushes ions up a linear gradient until they exit, or for high m / z ions without sufficient T-wave force, the DC current pushes them out in the other direction (filtering them in the process), but there is no deposition of ions with different axial positions. Therefore, in embodiments of the present disclosure, the potential gradient is preferably non-linear to enable separation. However, as will be described below with reference to FIG. Fig. As explained in Figure 17, separation can be achieved with an axially varied pseudopotential force in conjunction with a linear potential gradient.

[0054] Generally speaking, the arrangement in Fig. 5, as shown, has a separation region extending in a third direction (z) that is different from the first (x-direction, also referred to as the separation direction) and the second (y-) direction. A length of the separation region in the third direction is less than a length of the separation region in the first direction and / or the second direction. For example, the device of the present disclosure may be relatively thin in the z-direction and relatively large in the x- and / or y-direction. Such devices may include opposing parallel, planar surfaces with a relatively thin, planar separation region between them. The width of the separation region in the z-direction could be less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the length of the separation region in the x- and / or y-direction. A planar carpet structure could be provided.A planar or substantially planar electrode assembly could be provided with a separation region adjacent to and defined by the electrodes of the electrode assembly.

[0055] In Fig. In Figure 5, the first direction is shown as perpendicular to the second direction, and the first and second directions are shown as perpendicular to a third direction. There is no requirement that the x, y, and z directions be orthogonal to each other. Instead, a non-orthogonal geometry could be used.

[0056] Fig. Figure 5 shows an embodiment that separates ions in the x-direction by combining a traveling wave with an opposing curved DC gradient. Ions can propagate in the y-direction because this structure does not restrict them. However, the ions are relatively confined in the z-direction because they are restricted by a confining RF potential. The height of the system in the z-direction can therefore be relatively low to allow the traveling waves to penetrate to the center. The embodiment of Fig. 5 can be adjusted with additional forces to demonstrate the orthogonal manipulation of ion motion in the y-direction.

[0057] Fig. Figure 6 shows the instantaneous potential across the central axis generated by a traveling wave of 50 V, 200 kHz and a superimposed DC curve (in the form 50 V*length^3).

[0058] Fig. Figure 7 shows the movement of bunches of ions with different m / z values ​​through a 150 mm long separation device after they were generated near the entrance, illustrating the simulated ion trajectories and the deposition of the ions in different regions of the device. It can be seen that the ions with different m / z values ​​reach equilibrium at different axial positions, with the ions with the lowest m / z value being most strongly affected by the traveling wave and therefore migrating closest to the exit. Ions with a higher m / z value are less affected by the traveling wave and therefore stop further from the exit. In this simulation, both the traveling wave (T-wave) and DC gradient amplitudes were set to 40 V, with the applied T-wave being 40 V at 200 kHz and the trend being DC: 40 V ^4. The pressure was set to 1 mbar.Even at these strong fields, it can be seen that the ions adopt a relatively broad axial spread, so the device could function both crudely as a mass analyzer and perform well as a low-resolution pre-separator. For example, a resolution of at least 5 or at least 10 can be achieved. In some embodiments, the resolution can be over 50 or even up to 100.

[0059] Fig. Figure 8 shows the influence of different DC power functions on the ion deposition points, highlighting the shift in ion equilibrium toward the trap exit. The applied T-wave was 40 V at 200 kHz, DC: 40 V, and the pressure was 1 mbar. Higher power functions create a stronger gradient near the exit and thus better prevent ions from escaping at the same applied DC current; this occurs at the expense of a wider low-field region where ions with different m / z are less well separated. Since in a physical device, the DC current amplitude can reach approximately ~200 V without major problems, a less sharp function can be used. However, there is also some advantage in that higher functions push the ions closer to the exit, thus reducing the delay with which released ions leave the system.It should be noted that for a real DC gradient derived from a resistor chain, the DC function may not necessarily be a smooth polynomial, but may instead look step-like (e.g., a piecewise function roughly approximating a curve) and may be limited in accuracy by the quality and range of available resistors.

[0060] In Fig. 9, the length of the device was reduced to 10 cm, and the amplitudes of the traveling wave and the DC gradient were scanned. Subsequently, the movements of ions with m / z 500 were tracked from a central starting point until the equilibrium point (or ion escape) was reached. As expected, a high DC gradient amplitude shifts the equilibrium point backward in the device, while a high T-wave amplitude shifts it forward, until finally the gradient is overcome and ions are ejected from the device. Although in Fig. While not shown in Figure 9, it is possible that the DC gradient pushes ions out of the rear part of the device in simulations. A real system could simply be sealed off by a DC barrier provided by any suitable electrode of an electrode array.

[0061] One method for sequentially releasing ions from a separation region is to scan down the DC gradient. Alternatively, however, the T wave could be increased. In some embodiments, both could be performed together to maximize the applied fields without incurring radial ion losses.

[0062] In Fig. 10, ions with different m / z and charge states generated in the center of the device are tracked while the DC gradient decreases linearly from 40 V to mass over 10 ms. This is faster than the preferred actual cycle time, which depends on the separator resolution, but is at least 50–100 ms to allow a fast mass analyzer to acquire 10–20 spectra at different mass positions. Nevertheless, the illustrated timescales are sufficient to demonstrate the operating principles of the setup. It was recorded that m / z 200 appears very quickly in the m / z range 200–1000, followed by a large gap until m / z 330, which occurs after 5 ms, while m / z 500–1000 appears in the last 3 ms of the scan. To compensate for this nonlinearity of ion emergence, a nonlinear decay of the DC gradient could be provided (iethe opposite potential gradient can be time-dependent), and / or the exit potential can be calibrated and adjusted for each mass window.

[0063] The emergence time of the ions appears to be largely independent of the charge state in the simulation. This means that the reduced ion mobility of a heavier doubly or triply charged ion had no influence on the emergence time. This can be advantageous because little information is required to avoid the inadvertent omission of different charge states. One consequence of this is that distinguishing unwanted charge states, such as singly charged background ions, is difficult. Therefore, if discrimination of unwanted charge states is desired, further filtering can be performed.

[0064] The simulations described above were all performed with a collision model corresponding to 1 mbar of nitrogen. This high pressure dampens the ion energy and minimizes dispersion and ion losses. At high traveling wave amplitudes and lower pressures, some losses of lower m / z ions were observed, which may be due to the radial field perturbation caused by the traveling wave. It will be appreciated that various pressures may be used in embodiments of the disclosure, with a vacuum being maintained in the separation regions of some embodiments.

[0065] Fig. Figure 11 shows a radial transient DC potential in the most unfavorable axial position, where a 40 VT wave exerts a pull of 2 V on the ions. In this simulation, this is sufficient to overcome the trapping pseudopotential and remove ions from the device unless an appropriate gas pressure is present to dampen the radial motion (so that the mean free path length is < < 3 mm). In the upper part of Fig. 11, a radial field perturbation is induced by a traveling wave that pulls ions from the center of the device. In the lower part of Fig. Figure 11 shows a decrease in radial disturbance normalized to the axial T-wave amplitude, where the same T-wave phase is applied to 2 or 3 consecutive plates to improve field penetration.

[0066] It is possible to reduce this radial disturbance, which is caused by smoothing the strong field between the electrodes towards the central axis. A method that is also used in Fig. 11, is to increase the number of consecutive electrodes with the same applied T-wave phase, thereby increasing the penetration to the center without proportionally increasing the interference. Another method is to reduce the field steps between the electrodes by giving the traveling wave significantly more than 4 phases, for example 8, 12, or 24. The time-dependent potentials described herein can be multiphase potentials. It is also possible to increase the frequency of the traveling wave (HF), but this also reduces the axial pseudopotential force. The amplitudes of the T-wave and the DC gradient can be reduced to a level such that a low m / z value is always maintained, but the separation performance may suffer.

[0067] It is known that strong DC gradients and traveling waves can cause ion fragmentation, especially at low pressure. Especially for fragile, multiply charged ions, the field amplitudes can be reduced to protect the fragile ions. Planar 2D devices

[0068] Since many of the devices described here operate in a rough vacuum region, the devices can be combined with the same device, which first collects ions from an inlet capillary.

[0069] While the embodiments described above are described as having a stacked ring ion guide geometry, auxiliary or segmented electrodes may be used to cause ion propagation in directions perpendicular to the axis of the stacked rings (e.g., to cause ions to occupy a planar region within the stacked rings or to occupy a substantially cylindrical volume within the stacked rings). Nevertheless, moving away from stacked rings toward a more planar design may enable larger volumes and thus higher ion capacities. Such planar structures, including RF carpets that either face each other or utilize a DC counter electrode to confine ions to an RF pseudopotential plane, are described, along with application to initial ion capture and focusing, in GB 2209555.8, GB 2213536.2, and GB 2217040.1, the disclosures of which are hereby incorporated by reference.

[0070] Fig. Figure 12 shows examples of RF carpet device layouts suitable for applying both traveling waves and opposing direct current. In some embodiments, T-waves are applied to trapping RF electrodes because, although it is possible to apply a traveling wave to a counter electrode (with appropriate segmentation), the ions are generally closer to the RF electrodes, and a top-to-bottom traveling wave is greatly smoothed. However, the opposing axial direct current can be provided by other electrodes on the same surface of the separation device as the RF electrodes, but can also originate from the counter electrode, either by changing the electrode's distance from the RF carpet or by segmenting and applying an appropriately divided DC potential.

[0071] The different electrode arrangements of Fig. 12 include a counter electrode 1221 and RF electrodes 1222. In Fig. 12, each of the counter electrodes 1221 is opposite the RF electrodes 1222. In the electrode arrangements of Fig. 12 are ion carpet-like structures for applying both traveling waves (applied to RF electrodes 1222) and opposing axial direct current originating from (a) a shaped counter electrode 1221, (b) segmented RF electrodes 1222, and (c) a segmented counter electrode 1221. Combinations of these three options can be provided.

[0072] In Fig. 12(a), an axial direct current provided by the shaped counter electrode counteracts the T-waves provided by the RF electrodes 1222. RF potentials can provide up / down confinement. In Fig. 12(b), RF, T-waves, and a DC gradient are applied to the RF electrodes 1222. In Fig. 12(c), the counter electrode 1221 is provided on a PCB (printed circuit board) 1223 and comprises printed electrodes with a resistive DC gradient, while the RF electrodes 1222 are printed RF PCB electrodes that apply a T-wave.

[0073] Fig. 12 shows only cross-sections of the electrode arrangement in a single plane. The electrode arrangements of Fig. 12 can be configured so that ions can move in a direction perpendicular to the plane of the cross sections.

[0074] Fig. 13 and Fig. 14 show top views of structures in which such electrode arrangements can be integrated. Fig. Figure 13 shows the integration of the concepts described above into a first vacuum region of a mass spectrometer, showing different capillary / nozzle orientations with respect to the ion guide. Fig. Figure 14 shows an additional implementation of separation and accumulation regions by separating DC offsets applied to RF electrodes.

[0075] Fig. Figure 13 shows several ion separation devices, each including an inlet capillary 1306, a pumping function 1314 for a gas jet 1315, a guard electrode 1316 (sometimes referred to as a wall), an ion outlet 1317 (exit aperture), and RF electrodes 1322. Example ion paths 1399 are also shown.

[0076] In Fig. 13(a), the ions enter the separation region 1301 from the inlet 1306 in the first direction (vertical). The electrode arrangement applies potentials that cause the ions to move in the second direction (horizontal) and separate in the first direction (vertical) before exiting in the first direction via the ion outlet 1317.

[0077] In Fig. In Figure 13(b), the m / z separation direction is again vertical. Due to the gas flow, an orthogonal (horizontal) force is applied to the ions. To further control the movement of the ions in the second direction, a horizontal DC gradient or a T-wave can also be applied. The ions enter the separation region 1301 in the second direction, are then separated in the first direction, and exit the separation region in the first direction.

[0078] Returning to the generalized terms used previously, the separation region may be configured to contain a gas, and the force on the ions in the second direction may be exerted by a gas flow through the separation region. In some cases, however, the gas force alone may cause ion movement in the second direction. This orthogonal force may be provided by the gas jet from the ion inlet (e.g., inlet 1316) or could be provided by an additional gas flow. The separation region may be configured to contain a gas (e.g., by having a closed enclosure), and the separation region may be configured so that the gas flows through the separation region in the first direction (e.g., the gas flow may have at least some component of motion in the first direction for at least part of the ion path).The device may comprise a gas inlet and a gas outlet (which may be different from the one or more ion inlets and outlets) arranged such that the gas flows through the separation region in the first direction and / or the second direction. The gas inlet and / or outlet may occur at the separation itself, in the accumulation region, or elsewhere.

[0079] In Fig. 13(c), the ions are caused to move in the second (horizontal) direction by potentials applied by the electrode array. The electrode array then separates the ions in the first (vertical) direction, and the ions leave the separation region 1301 in the first direction.

[0080] Generally speaking, the embodiments of Fig. 13 can be described as having separation regions including an ion outlet that allows the ions to leave the separation region (e.g., when a valve is opened, or when a gate / guard voltage is changed, or when a guiding potential guides the ions). The ion outlet can be positioned at one end of the separation region in the first direction, and the electrode assembly can be configured to cause the ions to leave the separation region in the first direction. For example, the ions can move in the first direction and separate in the first direction, with the outlet located at an extreme position in the first direction.

[0081] Fig. 14 shows an embodiment that is comparable to the embodiment of Fig. 13(a), but with clearly differentiated separation and accumulation regions within the RF electrode array.

[0082] The Fig. The device shown in Figure 14 includes a separation region 1401, an accumulation region 1402, an ion inlet 1406 (in the form of a capillary), a pump function 1414 for the beam 1415, a guard electrode 1416, an exit aperture 1417, and RF electrodes 1422. An example ion path 1499 is shown.

[0083] In the embodiments of Fig. 13 and Fig. 14, the electrode assemblies are configured to apply time-dependent potentials in the separation regions 1301, 1401 to cause the ions to move in a first direction, which is depicted as a vertical direction in the drawings. The electrode assemblies are also configured to apply potential gradients in the separation regions 1301, 1401. These potential gradients counteract the time-dependent potentials to separate the ions at different positions in the first direction according to the mass-to-charge ratio of the ions.

[0084] The RF electrodes 1322, 1422 are preferably (but not necessarily) elongated, so that one electrode line forms a plane. There are either two facing RF planes or one RF plane and a DC counter electrode, which may be shaped or have separate electrodes integrated into it (e.g., printed on a PCB) to generate DC gradients in both directions or to apply auxiliary AC current for the traveling wave (as described above with respect to Fig. 12). Ions are drawn from the postcapillary beam and into the ion guide by an orthogonal DC gradient or a T-wave. The optional guard electrodes 1316, 1416 provide DC (or RF) barriers at the edges of the device to prevent ion escape except through the exit aperture 1316, 1417.

[0085] If an accumulation region 1402 is provided, ions are initially accumulated there before being transferred to the separation region 1401. Optionally, the separation process may begin in the accumulation region 1402 when an appropriately aligned pseudopotential force is applied to the electrode assembly in the accumulation region 1402. Ions may be separated and released from the separation region 1401 as described above. In some embodiments, the separation region 1401 may be a combined accumulation / separation region, while in some embodiments, they may be distinct regions (e.g., separated by gas restrictions or other walls separating the regions).

[0086] Returning to the general terminology used previously, embodiments of the disclosure may include an accumulation region configured to accumulate the ions. The electrode assembly may be configured to: transfer the ions from the accumulation region to the separation region; and separate the ions in the separation region according to the mass-to-charge ratios of the ions; wherein the device is configured to replenish the accumulation region while separating the ions in the separation region. Thus, ions may be accumulated and separated simultaneously, which may reduce the downtime required to refill the device.

[0087] This accumulation region may be located within the boundaries of the same electrode arrangement that defines the separation region, or it may be defined by a separate electrode arrangement. The electrode arrangement(s) of the device may be configured to transfer the accumulated ions between the accumulation region and the separation region, e.g., to transfer ions from the accumulation region to the separation region, or vice versa. The accumulation region may comprise an ion inlet for receiving the ions and / or an ion outlet for providing the ions to the separation region, and the accumulation region may comprise a gas inlet and / or a gas outlet. The ion inlet / outlet and the gas inlet / outlet may be separate outlets of the device, i.e., ions may enter and exit the gas via a different outlet.The ion outlet(s) may comprise one or more exit apertures and / or one or more ion traps, or the outlets may include guides or conduits for transporting ions to these traps.

[0088] The ion inlet 1306, 1406 (shown as a capillary, but other ion inlets could be provided) and the resulting beam 1315, 1415 can be directed to the ion guide in a wide variety of orientations, as also shown in Fig. 13. It is preferable to orient the beams 1315, 1415 so that they do not oppose the m / z separation, at least not near the final axis of ion equilibration and transfer, since the beam force could be stronger than the electric fields. However, in some embodiments, the gas force may be desired as a component of the separation force, similar to the mobility of trapped ions. Therefore, in the various embodiments described herein, the ion inlet 1406, 1306 can direct the ions parallel to the (first) separation direction, perpendicular to the separation direction, or at some other angle to the separation direction.

[0089] A common theme at Fig. 13 and Fig. 14 is that these embodiments each provide an additional force orthogonal to the beam to pull ions out of the beam and move them to the other side of the separation region. In addition, the ions are Fig. 13 and Fig. 14 are separated in a first direction according to m / z, while being moved in a second direction either due to the gas forces in the device or due to the potentials applied to the electrode arrays. As already mentioned, there are many ways to achieve this, for example, with DC gradients applied to auxiliary electrodes, from an upper counter electrode (a shaped electrode or a multi-electrode chain), wedge-shaped or segmented RF trapping electrodes, gas inlets and / or outlets, etc. In any case, the Fig. 13 and Fig. 14 is configured to apply a force in the second direction (horizontal in these figures) to the ions to cause the ions to move in the second direction.

[0090] Therefore, the electrode assemblies described herein can generally be configured to apply a guiding potential in the separation region to guide the ions (optionally under the combined influence of a gas flow) toward the ion outlets. Additionally or alternatively, the device described herein can be configured to guide the ions (optionally under the combined influence of potentials applied by the electrode assembly) through the separation region toward the ion outlet(s) using a gas flow. These assemblies can provide the ions with a large volume to occupy and compensate for space charge limitations.

[0091] One or more guide electrodes can apply such a guide potential. The one or more guide electrodes can comprise one or more of the following: one or more DC plate electrodes (e.g., applied to a DC-only top plate PCB), wherein the guide potential comprises a DC gradient; a shaped (e.g., wedge-shaped or curved, with varying spacing between the electrode sets) counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode (e.g.,the strength of the potential varies with the distance between the ions and the electrode); a segmented counter electrode; one or more DC electrodes mounted between a plurality of RF electrodes; a plurality of RF electrodes extending in the first and / or second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in the separation region.

[0092] The electrode array can be configured to apply the guiding potential such that the ions leave the separation region in order of the ions' mass-to-charge ratio. For example, ions could be caused to leave the separation region in order of their m / z at different times through a single outlet. Alternatively, the ions could be spatially ordered and leave the separation region in order of m / z at different spatial positions. The electrode array can be configured to release at least a portion of the ions from the separation region and cause the ions to leave the separation region through the ion outlet(s) by adjusting the time-dependent potential and / or the potential gradient. This could be done by sequentially adjusting the time-dependent potential and / or the potential gradient.For example, ions can be released sequentially by decreasing the magnitude of the opposing potential over time, increasing the force exerted by the time-dependent potential, or both. The magnitudes of these potentials could be varied linearly or nonlinearly. The electrode array can be configured to apply the time-dependent guiding potential and / or the potential gradient such that the ions (under their combined influence) separate in the first direction in order of their mass-to-charge ratio.

[0093] Auxiliary electrodes may also be used to provide the traveling wave (including those based on low frequency RF as in US 10317364B2, although this example does not serve to generate pseudopotentials as examples at 4 kHz are mentioned).

[0094] In Fig. 13 and Fig. 14, one or more operating parameters of the device can be varied sequentially in time (e.g., stepwise) so that ions within different m / z ranges are sequentially released from the separation region. The electrode arrangement can be configured to sequentially adjust the time-dependent potential and / or the potential gradient. For example, at a first time, ions in a first m / z range can deposit in a first position that is closer to the ion exit than a second position in which ions in a second m / z range deposit. Then, the magnitude of the opposing potential gradient can be reduced so that the ions in the first m / z range (i.e.,The first m / z range (i.e., those ions closest to the exit) pass through the exit and the ions in the second m / z range move closer toward the exit and then settle in a new position (where the new position is defined by the new operating parameters after a stepwise change); this can be repeated until the ions in the second m / z range pass through the ion exit. This can be repeated for any number of m / z ranges.

[0095] In addition to or instead of this reduction in the magnitude of the opposing potential gradient, the time-dependent potential could be varied, for example, by adjusting its frequency (note that increasing the frequency of the traveling wave decreases the axial pseudopotential force) and / or by adjusting its magnitude. These properties of the time-dependent potential can therefore be varied such that the force exerted by the time-dependent potential on the ions increases and thus begins to overcome the opposing potential gradient. Thus, the time-dependent potential could be varied (i.e., its magnitude or frequency varied) so that the ions in the first m / z range pass through the exit and the ions in the second m / z range move closer to the exit and deposit in a new position; this can also be repeated until the ions in the second m / z range pass through the ion exit.These processes could be supplemented by additional gating or guiding potentials to induce the ions to pass through the exit. Furthermore, this process of changing the potential during separation can be repeated for any number of m / z ranges. Orthogonal extraction

[0096] Fig. Figure 15 shows a slightly different device in which the separation concept is integrated. Instead of extracting m / z separated ions from a single ion outlet 1317, 1417 over time, as previously described, Fig. 15, how separated ions are instead extracted orthogonally (i.e., orthogonal to the direction in which they are separated by m / z) from the separation region 1501 via a series of ion outlets (apertures) 1517. In this case, the separation is ideally performed solely by m / z. Ions of different m / z take different paths through the separation region and are therefore directed to the different outlets 1517. The inlet capillary 1506 is shown as being outside the device boundaries, but a suitable DC offset may be sufficient to attract ions, and this side of the device can optionally be funnel-shaped to allow additional uptake. The ion outlets 1517 can be traps for capturing ions of different m / z or conduits or funnels for directing ions towards downstream traps.

[0097] Generally speaking, the separation regions described herein may comprise a plurality of ion outlets that allow ions to exit the separation region. There may be two, three, four, or more ion outlets, each serving to allow ions of a particular m / z to exit the separation region. The m / z passing through each ion exit may be adjusted or tuned, for example, by appropriately selecting the voltages applied by the electrode assemblies and / or by adjusting gas flows within the separation region. Thus, ions of a given m / z could be directed to a particular outlet of the plurality of outlets under certain conditions, but to a different outlet under other conditions.

[0098] The plurality of ion outlets (which may be apertures or any type of channel / conduit for transporting ions for downstream processing, such as traps) are preferably spaced apart in the first direction. Thus, the ions separating in the first direction are separated into sets of ions with corresponding m / z. The plurality of ion outlets may be positioned along an edge (e.g., any boundary) of the separation region. The electrode arrangement is configured to cause the ions to exit the separation region in the second direction, for example, by applying appropriate potentials.

[0099] An additional potential (e.g. a DC force) that pulls ions towards the exits (i.e. horizontally in Fig. 15), may be desirable to supplement (or replace) gas forces that can be generated in the manner described in GB2209555.8 (which is incorporated by reference): DC gradients can be applied to a DC-only top plate PCB, or a shaped counter electrode (in the RF carpet type), or additional DC electrodes mounted between the RF electrodes, or by shaping the RF electrodes. In this example, the individual RF electrodes 1522 extend horizontally, i.e., the electrodes extend in the direction of the outputs 1517 or, equivalently, are orthogonal to the direction in which the plurality of outputs 1517 are spaced from each other. Therefore, the traveling wave / opposing DC current can be applied directly to the RF electrodes 1522. Alternatively, a traveling wave / opposing DC current can be applied to one or more electrodes of the electrode array (e.g.,Auxiliary electrodes) or a counter electrode can be applied to the top plate to provide the force in the first direction. If the device comprises a plurality of ion outlets, guiding potentials can be applied to guide ions to the respective outlets in the manner described above.

[0100] The facilities of Fig. 13, Fig. 14 and Fig. 15 share a number of common features. For example, these embodiments show related electrode structures that apply related or similar potentials.

[0101] In some embodiments, the time-dependent potential comprises one or more of: an oscillating potential; an RF potential; a pseudopotential that varies in the first direction (e.g., the time-dependent potential may be an axially varying pseudopotential); a traveling wave; and a DC traveling wave. Various combinations of these potentials can be used to drive ions toward an opposite potential and thus achieve separation.

[0102] The potential gradients described herein and / or the time-dependent potentials described herein may vary nonlinearly. For example, the potential gradients could vary as a nonlinear function (e.g., a polynomial) of spatial position. The potential gradients could be defined by a piecewise linear approximation to a nonlinear function. For example, segmented electrodes could apply local potentials that vary locally linearly, while the overall potential landscape defined by all segments follows a generally nonlinear trend with spatial position. The potential gradient is preferably a DC potential gradient, but an AC component may also be present. The magnitude of the time-dependent potential could additionally or alternatively vary nonlinearly with spatial position.

[0103] The electrode assemblies described herein may comprise a plurality of electrodes, and these electrodes may be classified according to the function they perform. For example, the electrode assemblies may comprise a first set of one or more electrodes (e.g., a counter electrode) configured to apply the potential gradient and a second set of one or more electrodes (e.g., RF electrodes) configured to apply the time-dependent potential. The first and / or second set of one or more electrodes may each comprise a plurality of electrodes.

[0104] The first and second sets of one or more electrodes may be located on opposite sides of the separation region. The separation region may be defined as the region directly between these sets of electrodes. The sets of electrodes may be mounted on walls of a housing of the device.

[0105] In some embodiments, the first set of one or more electrodes is parallel to the second set of one or more electrodes. For example, both sets may be arranged on a planar surface. Thus, the first set of one or more electrodes may be planar or substantially planar, and / or the second set of one or more electrodes may be planar or substantially planar.

[0106] The first and / or second set of one or more electrodes may comprise a plurality of electrode segments. Additionally or alternatively, the first and / or second set of one or more electrodes may be located on a printed circuit board (PCB).

[0107] The first set of one or more electrodes may comprise a counter electrode. The counter electrode may be a shaped (e.g., curved) counter electrode, and the potential gradient may have a shape corresponding to the shaped counter electrode. For example, the counter electrode may be curved to adapt the spatial shape of the applied potential.

[0108] A distance between the first set of one or more electrodes and the second set of one or more electrodes can vary along a length of the separation region. For example, one or both sets of electrodes can be curved to adjust the spatial shape of the applied potentials. Shaped counter electrodes are located closer to the ions at certain locations and can thus exert stronger forces on the ions. A distance between the sets of electrodes in the third direction can vary at different positions in the first and / or second direction.

[0109] In some embodiments, the first and second sets of one or more electrodes may be arranged on a common surface or substrate. For example, both sets may be coplanar.

[0110] The first set of one or more electrodes and / or the second set of one or more electrodes may comprise one or more of the following: one or more DC plate electrodes, wherein the guiding potential comprises a DC gradient; a shaped counter electrode, wherein the guiding potential has a shape corresponding to the shaped counter electrode; a segmented counter electrode; one or more DC electrodes mounted between a plurality of RF electrodes; a plurality of RF electrodes extending in the first and / or second directions; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in the separation region. These may be as previously described.

[0111] One or more guard electrodes may be part of the electrode arrangement. Such guard electrodes may be positioned along at least one edge of the separation region. This can ensure that the ions are confined. If an accumulation region is provided, the guard electrode(s) may additionally or alternatively be located along an edge of the accumulation region. Ion conveyor

[0112] Methods have been presented that allow operation at lower pressures, for example, 0.1 and 0.01 mbar. This would allow the device to be operated within collision cells or in a differentially pumped region immediately upstream of a quadrupole. The device described here can operate at pressures down to 1 mbar, down to 0.5 mbar, down to 0.1 mbar, down to 0.05 mbar, or down to 0.01 mbar. A combined trapping and traveling-wave RF similar to the ion conveyor (US7375344B2) is considered, which is essentially the same 4-phase traveling wave as before, but operates at the MHz frequency and higher voltage of a trapping RF. Fig. 16 shows a similar simulation as Fig. 10, where a DC gradient is ramped down over 10 ms and separated ions can appear sequentially, but only at a pressure of 0.1 mbar and with a traveling wave of the ion conveyor type. In Fig. 16 is provided a combined trapping RF and traveling wave ion conveyor type (US7375344B2), with a DC current of: 15 V ^3 trend with 10 ms ramp to ground, RF: 750 V at 2 MHz. Axially variable pseudopotential force versus linear direct current

[0113] Some embodiments of the present disclosure include a pseudopotential (traveling wave) counteracted by an axially varying DC force (a curved DC gradient). However, a traveling wave is not the only way to generate an axial pseudopotential. Another possibility, besides using nonlinear DC, is to generate an axially varied pseudopotential force; then the opposing DC can be a fixed force generated by a linear gradient.

[0114] Fig. Figure 17 shows several methods for generating such effects, where different means for generating axially varying pseudopotential and DC gradients with non-traveling waves are illustrated. Fig. Figure 17(a) shows an ion funnel-like variation in aperture size of the stacked ring guide (which can also vary the spacing of electrodes or the single / double / triple spacing of the auxiliary RF).

[0115] Fig. Figure 17(b) shows a multipole with varying r0 of the RF rods versus a fixed DC auxiliary electrode (the alternative is reversed, and auxiliary RF can also be used, even applied to the same DC auxiliary electrode). Fig. Figure 17(c) shows the segmentation of multipole rod electrodes with different DC current and different RF applied via resistive / capacitive dividers.

[0116] Fig. Figure 17(a) shows an ion funnel structure in more detail. Conventional ion funnels are known to require either a DC gradient or a gas force to force the ions through the end electrodes, shrinking the aperture size to a similar extent as the distance between the ring electrodes. This is because RF penetration increasingly reaches the central axis, forming a pseudopotential barrier over which the ions must be forced. This is typically highly undesirable and leads to ion fragmentation. However, this effect can be exploited in the separation devices described here. By decreasing the envelope / inscribed radius with axial position, it should be possible to generate a largely consistent or axially varied pseudopotential force (with some ripple).Another way to increase RF penetration is to increase the distance between the plates, similar to the S-lens in the Exploris™ 120 and 240 mass spectrometers.

[0117] Generally speaking, the embodiment of Fig. 17(a) can be described as comprising a plurality of RF electrode segments. The RF electrode segments are arranged along the first direction (the direction in which ions migrate and separate). The RF electrode segments may be substantially circular or ring-shaped. A radius of the RF electrode segments may vary (e.g., decrease) along the path of the ions. The strength of the pseudopotential experienced by the ions may therefore also vary along the first direction due to the varying distance between the electrodes and the ions, i.e., the RF electrode segments may generate an axially varying pseudopotential. Such a pseudopotential may be opposed by a DC potential (which may arise from a linear potential, i.e., a constant force, or be a curved potential) to separate ions.

[0118] Fig. Figure 17(b) shows multipole rods with different r0 values. A plurality of linearly extending rod electrodes can surround an ion-optical axis, and each rod electrode can be arranged at an inclination such that the distance from the ion-optical axis increases in the direction of ion movement. That is, the radius r0 of the inscribed circle of the ion guide can vary along the direction of the ion-optical axis. Similar to the collision cell described in US7985951B2, varying r0 of a set of multipole rods can generate a pseudopotential gradient, while nonlinear variation generates a nonlinear gradient. In embodiments of the present disclosure, displacement of a single electrode can be used. This need not necessarily involve the capture RF rods, but can also involve penetration of auxiliary RF electrodes.DC auxiliary electrodes can also be used; and even if these have a fixed r0 (like a cylinder around spread RF rods), the field penetration towards the center varies due to the change in the RF electrodes, creating a useful opposing DC gradient.

[0119] Generally speaking, the embodiment of Fig. 17(b) can be described as comprising a plurality of multipole electrodes. The multipole electrodes are arranged around the axis extending in the first direction (the direction in which the ions move and separate). The multipole electrodes may be substantially rod-shaped. A distance between the multipole electrodes may vary (e.g., decrease) along the path of the ions. The strength of the pseudopotential experienced by the ions may therefore also vary along the first direction due to the different distance between the multipole electrodes and the ions, i.e., the multipole electrodes may generate an axially varying pseudopotential. Such a pseudopotential may be opposed by a DC potential (which may arise from a linear potential, i.e., a constant force, or be a curved potential) to separate ions.

[0120] Fig. Figure 17(c) shows the segmentation of the axial electrodes (either main rod or auxiliary rod). When separated by a capacitive divider network, the RF amplitude can vary with axial position, similar to how a DC gradient can be generated by a resistor chain. Similar arrangements can be used to generate an axially varying traveling wave amplitude. Therefore, in general terms, Fig. 17(c) can be described as comprising a plurality of RF electrodes to which RF potentials are applied. The RF electrodes are arranged along the axis running in the first direction (the direction in which ions move and separate). The magnitude of the RF potential varies along the first direction. This can be achieved by using voltage dividers, for example, via a capacitive divider network. This can also provide an axially varying pseudopotential. Such a pseudopotential can be opposed by a DC potential (which can arise from a linear potential, i.e., a constant force, or be a curved potential) to separate ions.

[0121] Another approach to ion extraction is to terminate the pseudopotential traveling wave after the initial separation and before extraction, trapping the ions in a series of DC traps. In the case of a pulsed DC traveling wave, this would be equivalent to reducing the wave velocity to zero or near zero. The separated packets can then be extracted individually (or in pairs, etc.) by either dropping each DC barrier sequentially or by applying a very slow traveling wave that acts like a moving DC force.

[0122] The traveling wave can be applied by a digital waveform, as can the capture RF (if separate).

[0123] Axial pseudopotential barriers can be used to control the release of ions in a m / z-dependent manner, giving slow, heavy ions moving toward the orthogonal accelerator of a ToF analyzer a head start. This allows light, fast ions to catch up with slow, heavy ions, spatially focusing ions of different m / z at the extraction point and significantly improving the pulser's sensitivity (US7456388B2). This device can also give heavy ions a corresponding head start by spatially separating ions of different m / z, allowing them an even shorter trajectory. This process is adjustable due to the high pressure at which optimal operation of the device was simulated and the small time differences (<10 s µs). Switchable ion paths

[0124] Another embodiment of the present disclosure is described in Fig. 18. The embodiment of Fig. 18 includes an ion inlet 1806, an ion outlet 1817, a first switchable path 1801, a second switchable path 1819, and a merging region 1820. Advantageously, the separation region 1801 may be arranged in parallel with the accumulation region 1802 and not in series (as in Fig. 2 and Fig. 14). Using a beam switching device (as described in British Patent Application No. GB ​​2209555.8), the direction of the ion flow between them can be controlled. For example, the electrode array can be configured to control the potentials applied by the electrodes to switch the ion paths. An advantage of this arrangement is that such a system could be switched to a beam transmission mode without the need for both empty accumulation and separation regions 1801, 1802. This arrangement can consist of a stacked plate electrode array with orthogonal DC gradients provided by auxiliary electrodes, or of an ion carpet with DC gradients provided by a top plate.In an alternative structure, the separation and accumulation regions may be connected in series and a bypass may be provided to allow easy switching to beam mode.

[0125] As in Fig. As shown in Figure 14, the accumulation region can be located upstream of the separation region. In such an arrangement, both the accumulation and separation regions lie within the boundaries of the electrode array. However, this is not absolutely necessary, as Fig. 18 shows.

[0126] Therefore, in some embodiments, the accumulation region runs parallel to the separation region. The device may be configured to switch between the accumulation / separation regions or to provide a bypass.For example, in some embodiments, the electrode assembly is configured to switch between one or more of the following: a first configuration in which the electrode assembly is configured to cause the ions to enter the accumulation region without passing through the separation region; a second configuration in which the electrode assembly is configured to cause the ions to enter the separation region without passing through the accumulation region; and a third configuration in which the electrode assembly is configured to cause the ions to enter the accumulation region to be accumulated therein and to cause the accumulated ions to be transferred from the accumulation region to the separation region. Switching between these different modes can be controlled by corresponding electrode potentials.For example, the electrode array may include a variable barrier (e.g., a direct current barrier) between the accumulation region and the separation region. To transfer ions between the different regions, different potential gradients could be applied to the electrode arrays.

[0127] It should be understood that many variations of the above-mentioned systems and methods may be made while retaining the aforementioned advantages. For example, where specific components have been described, alternative components may be provided that provide the same or similar functionality.

[0128] For example, in some embodiments, it may be advantageous to have two separation devices / regions connected in series. One could perform a coarse separation and the other a fine separation. One advantage is that the second separator is not burdened by a high space charge and also does not require voltage settings suitable for a wide m / z range; therefore, better resolution with a lower likelihood of negative side effects such as fragmentation may be possible. Therefore, a first separation region may generally be provided, and the device may further comprise a second separation region connected in series with the first separation region. The first separation region may be configured to perform a relatively coarse separation of the ions, and the second separation region may be configured to perform a relatively fine separation of the ions.Different resolutions could be used for the relatively coarse and relatively fine separations. For example, the first separation region could have a resolution of approximately 5, and the second separation region could have a resolution of approximately 30. Although both are quite coarse, the second separation region can have a resolution at least two or three times higher than the resolution of the first separation region. The second separation region can be downstream of the first separation region.

[0129] Most embodiments described herein show the separation region being sandwiched between two opposing electrode structures. However, in some embodiments, the first and second sets of electrodes providing the time-dependent potential and the opposing potential gradient could be distributed along a single surface (e.g., a two-dimensional planar surface), with some electrodes providing a repulsive force and other electrodes providing an attractive force. The time-dependent potential and the opposing gradient could be provided by an array of electrodes on a single surface (e.g., a flat surface). In some embodiments, the first and second sets of electrodes could be located on surfaces oriented perpendicular to each other.

[0130] In further embodiments, the present disclosure provides devices that do not necessarily cause ions to move in a second direction orthogonal to the first direction in which the ions separate. For example, the disclosure also provides a device comprising: a separation region configured to receive ions, the separation region extending in a first direction and adapted to separate ions according to the mass-to-charge ratios of the ions; an electrode assembly configured to confine the ions in the separation region, wherein: the electrode arrangement is configured to apply a time-dependent potential in the separation region to cause the ions to move in the first direction; and the electrode arrangement is configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential, so that the ions are separated according to the mass-to-charge ratio of the ions in different positions in the first direction; and an accumulation region configured to accumulate the ions, wherein the accumulation region is parallel to the separation region.

[0131] The electrode assembly may be configured to switch between one or more of the following elements: a first configuration in which the electrode arrangement is configured that it allows the ions to enter the accumulation region without passing through the separation region; a second configuration in which the electrode arrangement is configured to allow the ions to enter the separation region without passing through the accumulation region; and a third configuration in which the electrode arrangement is configured to cause the ions to enter the accumulation region to be accumulated there and to cause the accumulated ions to be transferred from the accumulation region to the separation region.

[0132] Such a device may function in a similar manner to the other embodiments described herein.

[0133] Furthermore, it is apparent that some embodiments provide devices that offer advantageous possibilities for generating potentials within the various regions of the devices. For example, there is also provided: a device comprising: a separation region configured to receive ions, the separation region extending in a first direction and adapted to separate ions according to the mass-to-charge ratios of the ions; an electrode assembly configured to confine the ions in the separation region, wherein: the electrode arrangement is configured to apply a time-dependent potential in the separation region to cause the ions to move in the first direction; and the electrode arrangement is configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential, so that the ions are separated in different positions in the first direction according to the mass-to-charge ratio of the ions.

[0134] In such embodiments, the electrode arrangement could be one of the Fig. 12 and / or Fig. 17, for example, to generate suitable fields for manipulating ions (e.g., to cause ions to enter a particular region, or to cause the transport or separation of ions as they move through a particular region, or to cause ions to leave a particular region). The electrode arrangements in Fig. 2, Fig. 5A, Fig. 13, Fig. 14 and / or 15 could also be used.

[0135] Unless otherwise stated, any feature disclosed in this specification may be replaced by alternative features serving the same, equivalent, or similar purpose. Thus, unless otherwise stated, each disclosed feature represents only one example of a generic set of equivalent or similar features.

[0136] As used herein, including the claims, singular forms of terms should be construed to include the plural form, and vice versa, where the context so permits. For example, herein, and in the claims, a singular reference such as "a" or "an" (e.g., an electrode or potential) means "one or more" (e.g., one or more electrodes or one or more potentials), unless the context indicates otherwise. Throughout the description and claims of this disclosure, the words "comprise," "include," "have," and "contain," and variations of the words, for example, "comprising" and "comprises," or the like, mean that the described feature includes the additional features that follow and are not intended to exclude (and do not exclude) the presence of other components.

[0137] The use of any and all examples or exemplary language provided herein ("for example," "such as," "for example," and the like) is intended only to better illustrate the disclosure and does not imply any limitation on the scope of the disclosure unless otherwise claimed. Language in the description should not be construed as indicating that any unclaimed element is essential to practicing the disclosure.

[0138] All steps described in this patent specification may be performed in any order or concurrently, unless otherwise stated or unless the context requires otherwise. Furthermore, the description of a step as being performed after another step does not preclude the performance of intervening steps.

[0139] All aspects and / or features disclosed in this specification may be combined in any combination, except for combinations where at least some of these features and / or steps are mutually exclusive. In particular, the preferred features of the disclosure apply to all aspects and embodiments of the disclosure and may be used in any combination. Likewise, features described in non-essential combinations may be used separately (not combined with each other). Paragraphs: 1. A device for separating ions according to the mass-to-charge ratios of the ions, comprising: a separation region configured to receive the ions, the separation region extending in a first direction and a second direction different from the first direction; and an electrode assembly configured to confine the ions in the separation region, wherein: the electrode arrangement is configured to apply a time-dependent potential in the separation region to cause movement of the ions in the first direction; the electrode arrangement is configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential, so that the ions are separated according to the mass-to-charge ratio of the ions in different positions in the first direction; and the device is configured to exert a force on the ions in the second direction to cause the ions to move in the second direction. 2. Device according to paragraph 1, wherein the separation region extends in a third direction different from the first and second directions, and wherein a length of the separation region in the third direction is less than a length of the separation region in the first direction and / or the second direction. 3. Device according to paragraph 1 or paragraph 2, wherein the first direction is substantially perpendicular to the second direction and optionally wherein the first and second directions are substantially perpendicular to a third direction. 4. Device according to any one of the preceding paragraphs, wherein the separation region comprises an ion outlet to allow the ions to leave the separation region. 5. Apparatus according to paragraph 4, wherein the ion outlet is positioned at one end of the separation region in the first direction. 6. The device according to paragraph 4 or 5, wherein the electrode arrangement is configured to cause the ions to leave the separation region in the first direction. 7. Device according to any one of the preceding paragraphs, wherein the separation region comprises a plurality of ion outlets that allow the ions to leave the separation region. 8. The device according to paragraph 7, wherein the ion outlets of the plurality of ion outlets are spaced apart from each other in the first direction. 9. The device according to paragraph 7 or paragraph 8, wherein the electrode arrangement is configured to cause the ions to leave the separation region in the second direction. 10. The device of any one of paragraphs 7 to 9, wherein the plurality of ion outlets are positioned along an edge of the separation region. 11. Device according to any one of paragraphs 4 to 10, wherein the ion outlet(s) comprise(s) one or more exit apertures and / or one or more ion traps. 12. An establishment as defined in any of paragraphs 4 to 11, where: the electrode arrangement is configured to apply a guiding potential in the separation region to guide the ions towards the ion outlet(s), and / or the device is configured to guide the ions to the ion outlet(s) using a gas flow through the separation region. 13. The device of paragraph 12, wherein the electrode arrangement comprises one or more guide electrodes configured to apply the guide potential, wherein the one or more guide electrodes comprise one or more of the following: one or more DC plate electrodes, wherein the guiding potential comprises a DC gradient; a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode; a segmented counter electrode; one or more DC electrodes mounted between a plurality of RF electrodes; a plurality of RF electrodes extending in the first and / or second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in the separation region. 14. The device according to paragraph 12 or paragraph 13, wherein the electrode assembly is configured to apply the guiding potential such that the ions leave the separation region in order of the mass-to-charge ratio of the ions. 15. The device according to any one of paragraphs 4 to 14, wherein the electrode arrangement is configured to release at least a portion of the ions from the separation region and cause the ions to leave the separation region through the ion outlet(s) by adjusting the time-dependent potential and / or the potential gradient. 16. The device according to paragraph 15, wherein the electrode arrangement is configured to sequentially adjust the time-dependent potential and / or the potential gradient. 17. The device of any preceding paragraph, wherein the separation region is configured to contain a gas, and wherein the force in the second direction is exerted by a gas flow through the separation region. 18. The device of any preceding paragraph, wherein the separation region is configured to contain a gas, and wherein the separation region is configured such that the gas flows through the separation region in the first direction. 19. Apparatus according to paragraph 17 or paragraph 18, comprising a gas inlet and a gas outlet arranged so that the gas flows through the separation region in the first direction and / or the second direction. 20. Device according to any one of the preceding paragraphs, wherein one or more electrodes of the electrode arrangement are configured to exert the force in the second direction. 21. The device of paragraph 20, wherein the potential gradient is a first potential gradient of a first potential applied by a first set of one or more electrodes of the electrode assembly, and wherein a second set of one or more electrodes of the electrode assembly is configured to apply a second potential in the separation region to exert the force in the second direction. 22. Device according to paragraph 21, wherein the second potential comprises a DC gradient in the second direction. 23. A device according to paragraph 21 or paragraph 22, wherein the second potential comprises a traveling wave traveling in the second direction. 24. Device according to any one of the preceding paragraphs, wherein the time-dependent potential comprises an oscillating potential. 25. Device according to any one of the preceding paragraphs, wherein the time-dependent potential comprises an RF potential. 26. Device according to any one of the preceding paragraphs, wherein the time-dependent potential comprises a pseudopotential varying in the first direction. 27. Device according to any one of the preceding paragraphs, wherein the time-dependent potential comprises a traveling wave. 28. Device according to any one of the preceding paragraphs, wherein the time-dependent potential comprises a DC traveling wave. 29. Device according to any one of the preceding paragraphs, wherein the potential gradient and / or the time-dependent potential varies non-linearly. 30. Device according to any one of the preceding paragraphs, wherein the potential gradient is a DC potential gradient. 31. The device according to any one of the preceding paragraphs, wherein the electrode arrangement comprises a first set of one or more electrodes configured to apply the potential gradient and a second set of one or more electrodes configured to apply the time-dependent potential. 32. Device according to paragraph 31, wherein the first and second sets of one or more electrodes are located on opposite sides of the separation region. 33. A device according to paragraph 31 or paragraph 32, wherein the first set of one or more electrodes is substantially parallel to the second set of one or more electrodes. 34. A device according to any one of paragraphs 31 to 33, wherein the first set of one or more electrodes is substantially planar and / or wherein the second set of one or more electrodes is substantially planar. 35. A device according to any one of paragraphs 31 to 34, wherein the first and / or second set of one or more electrodes comprises a plurality of electrodes. 36. A device according to any one of paragraphs 31 to 35, wherein the first and / or second set of one or more electrodes comprises a plurality of electrode segments. 37. Device according to any one of paragraphs 31 to 36, wherein the first and / or second set of one or more electrodes is located on a printed circuit board (PCB). 38. A device according to any one of paragraphs 31 to 37, wherein the first set of one or more electrodes comprises a counter electrode. 39. The device of paragraph 38, wherein the counter electrode is a shaped counter electrode, the potential gradient having a shape corresponding to the shaped counter electrode. 40. The device of any one of paragraphs 31 to 39, wherein a distance between the first set of one or more electrodes and the second set of one or more electrodes varies along a length of the separation region. 41. A device according to any one of paragraphs 31 to 39, wherein the first and second sets of one or more electrodes are substantially coplanar. 42. A device according to any one of paragraphs 31 to 41, wherein the first set of one or more electrodes and / or the second set of one or more electrodes comprises one or more of the following: one or more DC plate electrodes, wherein the guiding potential comprises a DC gradient; a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode; a segmented counter electrode; one or more DC electrodes mounted between a plurality of RF electrodes; a plurality of RF electrodes extending in the first and / or second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in the separation region. 43. Device according to any one of the preceding paragraphs, wherein the electrode arrangement comprises one or more guard electrodes positioned along at least one edge of the separation region. 44. A facility as defined in any of the preceding paragraphs, wherein: the separation region is a vacuum region; and / or the pressure in the separation region is lower than that in an upstream region of the facility and / or a downstream region of the facility. 45. The device of any preceding paragraph, further comprising an accumulation region configured to accumulate the ions. 46. ​​The device of paragraph 45, wherein the electrode assembly is configured to transfer the accumulated ions from the accumulation region to the separation region. 47. A device according to any one of paragraphs 45 to 46, wherein the accumulation region comprises an ion inlet for receiving the ions and / or an ion outlet for providing the ions to the separation region. 48. A device according to any one of paragraphs 45 to 47, wherein the accumulation region comprises a gas inlet and / or a gas outlet. 49. A facility according to any one of paragraphs 45 to 48, wherein the accumulation region is upstream of the separation region. 50. A facility according to any one of paragraphs 45 to 49, wherein the accumulation region is parallel to the separation region. 51. A device according to paragraph 50, wherein the electrode arrangement is configured to switch between one or more of the following: a first configuration in which the electrode assembly is configured to allow the ions to enter the accumulation region without passing through the separation region; a second configuration in which the electrode arrangement is configured to allow the ions to enter the separation region without passing through the accumulation region; and a third configuration in which the electrode arrangement is configured to cause the ions to enter the accumulation region, to be accumulated there and that it causes the transfer of the accumulated ions from the accumulation region to the separation region. 52. The device of paragraph 51, wherein the electrode assembly is configured to apply a variable direct current barrier between the accumulation region and the separation region. 53. Device according to any one of paragraphs 45 to 52, wherein the electrode arrangement is configured to: Transferring the ions from the accumulation to the separation region; and Separating the ions in the separation region according to the mass-to-charge ratio of the ions; wherein the device is configured to replenish the accumulation region while separating the ions in the separation region. 54. A device according to any one of the preceding paragraphs, wherein the separation region is a first separation region and the device further comprises a second separation region connected in series with the first separation region. 55. Apparatus according to paragraph 54, wherein the first separation region is configured to perform a relatively coarse separation of the ions and the second separation region is configured to perform a relatively fine separation of the ions. 56. Mass spectrometry system comprising: the ion separation device according to one of the preceding paragraphs; and and a mass filter downstream of the device, the mass filter configured to receive the ions from the device. 57. The mass spectrometry system of paragraph 56, further comprising a mass analyzer configured to receive the ions from the mass filter or to receive ions from the ions derived from the mass filter and to perform a mass analysis on the received ions. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] US 2939952A

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[0006] US 10199208B2 [0006, 0028] US 20170076928A1 [0006, 0028] US 7375344B2 [0007, 0112] US 8841608B2 [0008, 0053] US 6914241B2 [0010, 0020, 0028] US 6838662B2 [0010, 0020, 0028] US 8835839B1

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[0123] Zitierte Nicht-Patentliteratur

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[0030]

Claims

[1] Apparatus for separating ions according to the mass-to-charge ratios of the ions, comprising: a separation region configured to receive the ions, the separation region extending in a first direction and a second direction different from the first direction; and an electrode assembly configured to confine the ions in the separation region, wherein: the electrode arrangement is configured to apply a time-dependent potential in the separation region to cause movement of the ions in the first direction; the electrode arrangement is configured to apply a potential gradient in the separation region, wherein the potential gradient is opposite to the time-dependent potential, so that the ions are separated according to the mass-to-charge ratio of the ions in different positions in the first direction; and the device is configured to exert a force on the ions in the second direction to cause the ions to move in the second direction. [2] The device according to claim 1, wherein the separation region extends in a third direction different from the first and second directions, and wherein a length of the separation region in the third direction is less than a length of the separation region in the first direction and / or the second direction. [3] The device of claim 1 or claim 2, wherein the first direction is substantially perpendicular to the second direction, and optionally wherein the first and second directions are substantially perpendicular to a third direction. [4] A device according to any preceding claim, wherein the separation region comprises an ion outlet allowing the ions to leave the separation region, the ion outlet preferably being positioned at one end of the separation region in the first direction, and more preferably the electrode arrangement being configured to cause the ions to leave the separation region in the first direction. [5] A device according to any preceding claim, wherein the separation region comprises a plurality of ion outlets allowing ions to exit the separation region, the ion outlets of the plurality of ion outlets preferably being spaced apart from one another in the first direction. [6] The device of claim 5, wherein the electrode arrangement is configured to cause the ions to leave the separation region in the second direction. [7] A device according to claim 5 or claim 6, wherein the plurality of ion outlets are positioned along an edge of the separation region. [8] Device according to one of claims 4 to 7, wherein the electrode arrangement is configured to apply a guiding potential in the separation region to guide the ions towards the ion outlet(s); and / or the device is configured to guide the ions through the separation region to the ion outlet(s) using a gas flow. [9] The device of claim 8, wherein the electrode arrangement comprises one or more guide electrodes configured to apply the guide potential, the one or more guide electrodes comprising one or more of the following: one or more DC plate electrodes, wherein the guiding potential comprises a DC gradient; a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode; a segmented counter electrode; one or more DC electrodes mounted between a plurality of RF electrodes; a plurality of RF electrodes extending in the first and / or second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in the separation region. [10] The device of claim 8 or claim 9, wherein the electrode assembly is configured to apply the guiding potential such that the ions leave the separation region in order of the mass-to-charge ratio of the ions. [11] The device of any one of claims 4 to 10, wherein the electrode assembly is configured to release at least a portion of the ions from the separation region and cause the ions to leave the separation region through the ion outlet(s) by adjusting the time-dependent potential and / or the potential gradient. [12] The device of claim 11, wherein the electrode arrangement is configured to sequentially adjust the time-dependent potential and / or the potential gradient. [13] A device according to any preceding claim, wherein the separation region is configured to contain a gas, and wherein the force in the second direction is exerted by a gas flow through the separation region. [14] Device according to claim 13, comprising a gas inlet and a gas outlet arranged so that the gas flows in the first direction and / or the second direction through the separation region. [15] Device according to one of the preceding claims, wherein one or more electrodes of the electrode arrangement are configured to exert the force in the second direction. [16] The device of claim 15, wherein the potential gradient is a first potential gradient of a first potential applied by a first set of one or more electrodes of the electrode assembly, and wherein a second set of one or more electrodes of the electrode assembly is configured to apply a second potential in the separation region to exert the force in the second direction, wherein the second potential preferably comprises a DC gradient in the second direction and / or a traveling wave traveling in the second direction. [17] Device according to one of the preceding claims, wherein the time-dependent potential comprises one or more of the following: an oscillating potential; an RF potential; a pseudopotential varying in the first direction; a traveling wave; and a DC traveling wave. [18] Device according to one of the preceding claims, wherein the potential gradient and / or the time-dependent potential varies non-linearly. [19] Device according to one of the preceding claims, wherein the potential gradient is a DC potential gradient. [20] A device according to any preceding claim, wherein the electrode arrangement comprises a first set of one or more electrodes configured to apply the potential gradient and a second set of one or more electrodes configured to apply the time-dependent potential. [21] Device according to claim 20, wherein: the first and second sets of one or more electrodes are located on opposite sides of the separation region; and / or the first set of one or more electrodes is substantially parallel to the second set of one or more electrodes; and / or the first set of one or more electrodes is substantially planar and / or the second set of one or more electrodes is substantially planar; and / or the first and / or second set of one or more electrodes comprises a plurality of electrodes; and / or the first and / or second set of one or more electrodes comprises a plurality of electrode segments; and / or the first and / or second set of one or more electrodes is located on a printed circuit board (PCB); and / or the first and second sets of one or more electrodes are substantially coplanar. [22] A device according to any one of claims 20 to 21, wherein the first set of one or more electrodes comprises a counter electrode, wherein: the counter electrode is a shaped counter electrode, wherein the potential gradient has a shape corresponding to the shaped counter electrode; and / or a distance between the first set of one or more electrodes and the second set of one or more electrodes varies along a length of the separation region. [23] Device according to one of the preceding claims, wherein: the separation region is a vacuum region; and / or the pressure in the separation region is lower than in an upstream region of the facility and / or a downstream region of the facility. [24] A device according to any preceding claim, further comprising an accumulation region configured to accumulate the ions, wherein the electrode arrangement is preferably configured to transfer the accumulated ions from the accumulation region to the separation region. [25] Device according to claim 24, wherein the accumulation region is upstream of the separation region and / or is parallel to the separation region. [26] The device of claim 25, wherein the accumulation region is parallel to the separation region and wherein the electrode arrangement is configured to switch between one or more of the following elements: a first configuration in which the electrode assembly is configured to allow the ions to enter the accumulation region without passing through the separation region; a second configuration in which the electrode arrangement is configured to allow the ions to enter the separation region without passing through the accumulation region; and a third configuration in which the electrode arrangement is configured to cause the ions to enter the accumulation region to be accumulated there and to cause the accumulated ions to be transferred from the accumulation region to the separation region. [27] Device according to one of claims 24 to 26, wherein the electrode arrangement is configured to: Transferring the ions from the accumulation to the separation region; and Separating the ions in the separation region according to the mass-to-charge ratio of the ions; wherein the device is configured to replenish the accumulation region while separating the ions in the separation region. [28] A device according to any preceding claim, wherein the separation region is a first separation region, the device further comprising a second separation region in series with the first separation region, preferably wherein the first separation region is configured to perform a relatively coarse separation of the ions and the second separation region is configured to perform a relatively fine separation of the ions. [29] Mass spectrometry system comprising: the device for separating ions according to any one of the preceding claims; and a mass filter downstream of the device, the mass filter configured to receive the ions from the device; wherein the device optionally further comprises a mass analyzer configured to receive the ions from the mass filter or to receive ions from the ions derived from the mass filter and to perform a mass analysis on the received ions.

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