Device for separating ions

Abstract

The ions are separated according to their mass-to-charge ratio. A separation region receives the ions, the separation region extending in a first direction and a second direction different from the first direction. An electrode arrangement confines the ions in the separation region. And an electrode arrangement configured to apply a time-varying potential in the separation region such that the ions move in the first direction, and configured to apply a potential gradient in the separation region opposite the time-varying potential, the ions are separated at different positions in the first direction according to the mass-to-charge ratio of the ions. A force is applied to the ions in the second direction to cause the ions to move in the second direction.

Description

Technical Field

[0001] The present disclosure relates to apparatus for separating ions according to their mass-to-charge ratio. Background Art

[0002] Devices for separating ions are widely used in the field of mass spectrometry. Most tandem mass spectrometers use quadrupole mass filters (US2939952A) to separate target ions before fragmentation and further downstream mass analysis. The disadvantage of this long-standing technology is that unselected ions hit the rods, resulting in the loss of analyte ions (which may be rare), while also contaminating and eventually damaging the electrodes. Depending on the isolation window used, the loss of theoretical sensitivity can exceed 99%.

[0003] One attempt to address these problems is to accumulate and coarsely separate the ions before the quadrupole so that the mass-to-charge ratio (m / z) of the ions delivered to the device approximately matches the range of the isolation window, and ion losses are thus reduced or minimized to the accuracy of the pre-separation. Some losses are still unavoidable unless the pre-separator is so good as to make the quadrupole redundant.

[0004] This method is proposed in GB2442638A, where ions are first loaded into an ion trap. The RF pseudopotential barrier prevents the release of higher m / z ions unless overcome by a direct current (DC) or traveling wave that pushes the ions toward the outlet, where they will be released for quadrupole selection / fragmentation, etc. Figure 3 Trapping and sequential release on a pseudopotential are shown.

[0005] Prior to this, US6794641B2 proposed a system in which ions were allowed to separate in an m / z or mobility dependent manner in an ion guide under the influence of a travelling wave and presented in a manner that could be linked to the mass range of an orthogonal ToF analyser, thereby improving its duty cycle.

[0006] Many methods have been considered to achieve similar goals, similarly in US10665441B2, and the most successful is the parallel accumulation serial fragmentation method from trapped ion mobility spectrometry (TIMS) equipment (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 US10794861B2). Other variations include accumulation into multiple traps, or orthogonally passing through RF pseudopotentials (US10199208B2) or via ion mobility (US20170076928A1).

[0007] Traveling waves are a known method of propelling ions through an ion guide. A series of out-of-phase RF potentials (US7375344B2) or switched DC pulses (Giles et al., Applications of a travelling 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 the ion guide. This creates a potential front that moves down the center of the guide over time, thereby using it to drag ions.

[0008] The interaction of traveling waves and opposing linear DC gradients has been described previously. US8841608B2 describes the use of opposing DC gradients to increase the residence time of ions in a T-wave driven mobility separator, improving resolution and also proposes a bandpass filter to remove unwanted ions. Figure 3 The combination of T wave and blocking DC force is shown.

[0009] Several ion guiding techniques may be suitable for the application of traveling waves and / or DC gradients. Axial segmentation is usually required, and therefore stacked ring ion guides are most commonly used. PCB printed ion guides such as SLIM (Structures for Lossless Ion Mobility) allow a cost-effective method of applying segmentation and have been demonstrated using DC and RF traveling waves (Hamamid 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 can be used with traveling waves (G. Bollen, "Ion surfing" with radiofrequency carpets, Int. J. Mass. Spectrom., 2011, 299, 131-138).

[0010] US6914241B2 and US6838662B2 describe methods of using opposing traveling waves and DC gradients (including nonlinear DC) to cause ion separation in a guide. The ions reach an equilibrium position and can then be released in a time-dependent manner by a quadrupole, thereby improving efficiency. US6914241B2 indicates that ion migration in a static gas field plays a role in the equilibrium position of the ions.

[0011]

[0011] While the above-described systems perform adequately in certain respects, a need remains for improved methods and apparatus for separating ions. Summary of the invention

[0012] In this context, the present disclosure provides an apparatus according to claim 1 .

[0013] The present disclosure relates to an apparatus (e.g., an ion guide) for separating ions, wherein a time-varying potential (e.g., a T wave) pushes the ions against a potential gradient (e.g., a DC gradient). The ions are caused to separate and take static positions along the ion guide according to their m / z, and can then be released to a downstream device (or multiple downstream devices) in order of m / z. The ion guides described herein may have a two-dimensional or three-dimensional structure, wherein forces orthogonal to the m / z separation direction are applied to the ions to cause two-dimensional or three-dimensional ion motion. Such orthogonal forces may be provided by a DC gradient, a time-varying potential (e.g., an RF potential or a T wave), or a gas flow.

[0014] Thus, in summary, the present disclosure provides an apparatus for separating ions according to their mass-to-charge ratio. The apparatus can be described as an ion guide that causes ions of different m / z values ​​to pass through at different velocities related to their m / z values.

[0015] Embodiments of the present disclosure include a separation region configured to receive ions. The separation region can receive 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 a second direction different from the first direction (e.g., an orthogonal direction).

[0016] Embodiments of the present disclosure include electrode arrangements that are configured to confine ions (e.g., to trap for a considerable period of time) in a separation region. Electrode arrangements of the present disclosure may include any number of separate electrodes or electrode segments. Each electrode of the electrode arrangement may be controlled by a controller that is coupled to all electrodes and is configured to individually change the voltage applied to the electrode. The controller may be provided to one or more power supplies to apply such voltage.

[0017] The electrode arrangement described herein is configured to apply a time-varying potential in the separation region so that the ions move in a first direction. The electrode arrangement is configured to apply a potential gradient in the separation region, the potential gradient being opposite to the time-varying potential, so that the combination of the potential gradient and the time-varying potential causes the ions to separate at different positions in the first direction according to the mass-to-charge ratio of the ions. That is, different ions are deposited at different positions according to their m / z values. The ions are confined in the device and separated under the combined influence of these applied potentials of the superposition.

[0018] The apparatus described herein is further configured to exert a force in a second direction on the ions so that the ions move in the second direction. For example, this can allow the ions to move perpendicular to the direction in which they were separated, which can increase the volume available for the ions and thus reduce 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, the method comprising: introducing ions into a separation region extending in a first direction and in 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-varying potential in the separation region to cause the ions to move in the first direction; applying a potential gradient in the separation region, the potential gradient being opposite to the time-varying potential, to separate the ions at different positions in the first direction according to their mass-to-charge ratio; and applying a force in a second direction to the ions to cause the ions to move in the second direction.

[0020] Although existing methods such as US6914241B2 and US6838662B2 show basic ion separation, some embodiments described herein provide two-dimensional (e.g., planar) structures with additional DC or T-wave (or other time-varying 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 trapping regions at different locations in the first direction, while some embodiments provide switchable accumulation / transmission regions extending parallel to the separation regions.

[0022] Embodiments of the present disclosure provide a variety of benefits. The advantage of the device described herein over more conventional axial ion traps in which only the exit region is defined is that the ions can be spread across a wide plane and the space charge effects from the primary species can be localized and reduced. For any accumulation device set up before isolation, space charge effects can cause serious problems. Therefore, the present disclosure can support very large devices because the ions expected to be released will always be close to the exit. The device described herein can also be integrated into a vacuum interface ion guide having a mass spectrometer that utilizes an atmospheric pressure ion source, such as an ESI (electrospray ionization) ion source.

[0023] Another advantage over existing devices is that highly controlled gas flows are not necessarily required (although in some embodiments these can be provided as required), thereby greatly simplifying engineering.

[0024] These and other advantages will become apparent from the following disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present disclosure will now be described by way of example with reference to the accompanying drawings, in which:

[0026] Figure 1 shows potentials that may be used in embodiments of the present disclosure;

[0027] Figure 2 An apparatus according to one embodiment of the present disclosure is shown;

[0028] Figure 3 A flow chart illustrating a method of operating an embodiment of the present disclosure is shown;

[0029] Figure 4 A mass spectrometry system incorporating an embodiment of the present disclosure is shown;

[0030] Figure 5A and Figure 5B An embodiment of the present disclosure and an applied traveling wave are shown;

[0031] Figure 6shows the potential applied in one embodiment of the present disclosure;

[0032] Figure 7 shows the simulated motion of ions in one embodiment of the present disclosure;

[0033] Figure 8 shows the simulated motion of ions in one embodiment of the present disclosure;

[0034] Fig. 9 shows the simulated motion of ions in one embodiment of the present disclosure;

[0035] Fig.10 shows the simulated motion of ions in one embodiment of the present disclosure;

[0036] Fig.11 shows the potential applied in one embodiment of the present disclosure;

[0037] Fig.12 shows an electrode arrangement for use in embodiments of the present disclosure;

[0038] Fig.13 An apparatus for separating ions according to an embodiment of the present disclosure is shown;

[0039] Fig.14 shows an apparatus for separating ions according to one embodiment of the present disclosure;

[0040] Fig.15 shows an apparatus for separating ions according to one embodiment of the present disclosure;

[0041] Fig.16 shows the simulated motion of ions in one embodiment of the present disclosure;

[0042] Fig.17 shows an electrode arrangement for use in embodiments of the present disclosure; and

[0043] Fig.18 An apparatus incorporating an embodiment of the present disclosure is shown. DETAILED DESCRIPTION

[0044] Some embodiments of the present disclosure address problems associated with ion loss of unselected ions, for example, during quadrupole isolation. Although problems associated with rod contamination can be substantially addressed by more forgiving pre-filtering quadrupole segments (USRE45553E), sensitivity loss can be avoided or at least reduced by using a certain level of pre-accumulation and separation.

[0045] A known process to achieve this is pre-accumulation in TIMS devices, which can increase the sensitivity of TIMS-ToF instruments by an order of magnitude. The disadvantages of such devices are limited space charge capacity and the need for laminar flow to provide opposing gas forces. Separation by drift rather than properly matching m / z to the quadrupole presents certain limitations in terms of achievable performance, as well as the effect of different charge states being filtered. The latter part is beneficial for peptide identification applications, as singly charged ions that may not be generated by digested peptides can be distinguished.

[0046] Any method that does not diffuse ions out in a wide space will be severely affected by the space charge effect, including TIMS and all single trapping modes (including the device described in GB2442638A). Methods such as those allowing flow separation and arrayed traps in US10199208B2 and US20170076928A1 will be more resistant to the space charge effect, but there is considerable complexity. US6914241B2 and US6838662B2 provide examples of ion diffusion in long channels. Some embodiments described herein propose an ion trapping method that separates ions in a relatively large trapping volume (e.g., a 2D planar area or a large 3D volume) to reduce the space charge effect.

[0047] Methods that separate based on ion drift time often require accumulation in a small space and are therefore space-charge limited, or require large separation equipment to achieve viable results. Generally speaking, low footprint equipment is desired. Large ion guides may require PCB-based constructions (such as SLIM), which introduce risks of charging from exposed insulating materials or by using more exotic structures (such as spirals).

[0048] Widening the quadrupole (or other mass filter) isolation window can enhance sensitivity, and for very low ion load applications, the m / z window can even be beneficially increased to extreme widths (such as 100) compared to more regular single m / z target widths of 1 or 2. However, the enormous complexity of multi-precursor fragmentation spectra can cause problems for deconvolution and identification software, although the field is rapidly developing (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 enabled eep proteome coverage in high throughput. Nature methods, 17 (1), 41-44.).

[0049] Some non-destructive selection methods can eliminate the need for quadrupoles. For example, high-resolution ion migration using ion guides suitable for very long drift paths (US8835839B1, GB2574796A) can produce sufficient separation quality and slow ion release so that their output can be directly coupled to fragmentation equipment and primary analyzers. Quadrupole RF ion trap isolation with axial collection of ions can have sufficient resolution, but in principle will suffer from too large a space charge and ion capacity for fine isolation.

[0050] 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 providing good ion separation.

[0051] Figure 1 The potentials used in certain embodiments of the present disclosure are shown. Figure 1 The potential in can be used in a device for separating ions according to their mass-to-charge ratio. In general, such a device may include a separation region configured to receive ions (e.g., from an upstream ion source), the separation region extending in a first direction and in a second direction different from the first direction.

[0052] To achieve Figure 1The device for applying a potential in the separation region may include an electrode arrangement configured to confine (e.g., trap for at least a period of time under the influence of various potentials applied by the electrode arrangement) ions in a separation region. The electrode arrangement is configured to apply a confining potential to confine the ions in the separation region. The electrode arrangement is configured to apply a time-varying potential in the separation region to cause the ions to move in a first direction. The electrode arrangement is configured to apply a potential gradient in the separation region, which is opposite to the time-varying potential, to separate the ions at different positions in the first direction according to the mass-to-charge ratio of the ions (i.e., different ions may settle at different positions due to the different effects of the time-varying potential and the potential gradient on ions of different m / z). The various potentials applied in the separation region (e.g., time-varying potential, potential gradient, and confining potential) may be superimposed; for example, a time-varying potential (e.g., a T wave) and a potential gradient (e.g., a DC gradient) may be superimposed on a confining potential (e.g., a confining RF potential).

[0053] The electrodes of the electrode arrangement may be controlled by a controller coupled to all electrodes, and all electrodes may be connected to a power supply to apply an electrical potential.Some or all of the electrodes may be individually and independently controllable.

[0054] Figure 1 The nonlinear DC gradient (opposite potential gradient) and the traveling wave (time-varying potential) that cause the separation of ions over a certain length are shown. Figure 1 The traveling wave at a single instant is shown; in practice, the traveling wave is made to travel continuously in the first direction. Opposing DC and pseudoforces cause ions of different m / z to settle at different locations.

[0055] To achieve Figure 1 m / z-dependent separation can be performed by opposing the potential gradient (e.g., static field) to the pseudoforce generated by the dynamic (time-varying) potential to separate ions. In some embodiments of the present disclosure, the axial pseudopotential generated by a traveling wave (T wave) is opposite to the rising DC gradient. Such a T wave can be a multi-phase (e.g., 4-phase or higher) traveling wave. The pseudoforce pushes the ions until they reach a region where the DC force is equal to or greater than the pseudoforce, at which point the ions are trapped (or pushed out of the device if the DC gradient is insufficient). Since the pseudoforce depends on m / z, the trapping position of the ions also depends on their m / z. Therefore, ions can be trapped at various different positions in the separation (first) direction.

[0056] By scanning / stepping the applied DC potential or the traveling wave amplitude / frequency (or duty cycle / pulse speed for a digital waveform), separated ions can be released from the device in an m / z-dependent manner. Alternatively, many other ways of extracting ions from the guide can be applied: the DC gradient and T wave can be removed and the ions released over time based on their spatial separation / drift time, or a very slow traveling wave can be applied to drive out ions in a slow beam, etc. The accumulated ions can then be released, for example, to a quadrupole (or other mass filter) matched to their m / z, and losses at the quadrupole can thus be mitigated.

[0057] Because the application of traveling wave potential usually requires axial segmentation of the electrodes, Figure 1 The arrangement in is suitable for stacked ring ion guides and related structures. Figure 2 An example of an ion guide structure is shown, which is a device for separating ions in which a Figure 1 The device comprises a separator region 201, a pre-accumulation region 202, a funnel / initial capture region 203 and an ion outlet 204.

[0058] In this particular example, the separation device has a stacked ring structure, also includes an optional section for ion capture from the inlet capillary and a pre-accumulation region 202 to maximize the duty cycle. In addition to the separation region 201 in which T waves and DC gradients are applied, the device is shown to include a similar pre-accumulation region 202 for pre-accumulating ions when the separator 201 is in operation. The ion funnel 203 receives ions from the inlet capillary, and when the ions leave the device to reach a higher vacuum (lower pressure) region, the small funnel-shaped region compresses the extracted ions. The funnel-shaped region 203 and the pre-accumulation region 202 may have their own applied DC offsets and gradients, and a controllable (i.e., variable) DC barrier may be provided between the accumulator 202 and the separator 201. A potential may be applied in the guide (e.g., from an auxiliary electrode, which is not shown) to cause the ions to move laterally (i.e., perpendicular to the axis of the ion guide) to allow a large amount of charge to be spread over a wider area to reduce space charge effects. After the ions have passed through the separation region 201, they exit the device through the ion outlet 204, for example to reach an ion guide of higher vacuum (lower pressure). Thus, in summary, the separation region and / or accumulation region described herein may be a vacuum region. The separation region and / or accumulation region may be at a lower pressure than an upstream region of the device (i.e., a region upstream of the separation region and / or accumulation region) and / or may be at a higher pressure than a downstream region of the device (i.e., a region downstream of the separation region and / or accumulation region). Various airtight enclosures and pumping may be provided to ensure that a vacuum is formed.

[0059] The properties of the traveling wave are preferably set so that the ions pass on the wave so that they feel the influence of the pseudo force rather than being completely entrained in the wave. For example, the frequency and / or voltage amplitude of the traveling wave can be varied to achieve this. In principle, a sufficiently high traveling wave potential will simply carry away the ions and there will be no separation unless the opposing DC is set high enough to balance the effect. Thus, the opposing potential and the time-varying potential can be fine-tuned to optimize separation performance.

[0060] Practical implementation

[0061] Figure 3 Shown for reference Figure 2 Flow chart of the operation of the accumulator / separator combination device of the type described. First, the accumulation grouping of the ions of mixed m / z is transferred from the accumulation region to the separation region, which can be realized via applying a DC gradient / offset across the accumulator or a traveling wave that pushes the ions to move forward. Once the ions are emptied, the accumulator is then closed to the separator, and other ions begin to accumulate when the ions enter. At the same time, the separation process is started in the separator. The amplitude of the DC gradient (which is preferably curved) is reduced (or alternatively an increase in the traveling wave amplitude is provided, or both) to the first lowest target m / z range to leave the required level. After a short delay (usually about 0.25ms to 5ms), the target ion leaves the system and travels to the downstream quadrupole (or other mass filter) for more refined isolation. The DC 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, so the accumulation region can be emptied again, and the cycle is repeated.

[0062] Thus, in each cycle of the separation device, a plurality of different mass ranges are sequentially released from the separation device.

[0063] Figure 4 A suitable instrument layout incorporating embodiments of the present disclosure is shown. The instrument includes a separation region 401, a pre-accumulation region 402, an ion funnel 403, an ion source 405 (which is an electrospray ion source in this example), an ion inlet 406 (which is shown as an inlet capillary), a forepump 407, an intermediate ion guide 408, a turbo pump 409, a decomposition quadrupole 410, a collision cell 411, and a mass analyzer 412 (which is shown as an orthogonal time-of-flight mass analyzer).

[0064] In use, the electrosprayed ions enter the vacuum system via capillary 406 and are collected by ion funnel 403, which delivers the ions to accumulation device 402 and separation device 401. The ions discharged from the approximately 1 mbar pressurized separator 401 are passed through at least one intermediate ion guide 408 (approximately 5×10 -2 mbar) is transmitted to the quadrupole 410 (about 1×10-4 mbar) for fine isolation, thereby allowing appropriate differential pressure pumping. The selected ions are then fragmented in the collision cell 411, and the fragments are measured by a suitable mass analyzer 412, which can be a time-of-flight analyzer as shown, or any other suitable mass analyzer, such as one or more of a quadrupole, an ion trap, or an orbital trap mass analyzer.

[0065] Figure 4 The arrangement in can be optimized in some way. Carefully aligning the mass range of quadrupole 410 and extraction can be advantageous. If it is desired to align the quadrupole isolation window with the ions released by the separator, then the resolution of both can be considered. For example, if the separator resolution allows the m / z window to be only 100, and the trapping range is 100-1000, then releasing m / z 100 will also substantially release more than m / z 150, at which point, making the quadrupole inject m / z 100 and then inject 110 (because m / z 110 ions will have left) may be almost no benefit. Therefore, it is advantageous to stagger (that is, space) the quadrupole isolation range to match the quadrupole isolation range not yet released from the separator, and then return to fill the gap with the next separator cycle. That is, when the separator has a resolution lower than the quadrupole, the separator will release a wider range of ions than the quadrupole transmission, and then these ions are lost on the rod, and therefore in this case, it is useless to try to isolate these ions without first refilling the separator.

[0066] 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 resolving power of separator 401 is about 10% and the trapping range is 10x, up to 10 separated mass ranges can be extracted in one cycle. At the same time, the quadrupole can be operated in a DIA (data independent acquisition) method that scans through a much smaller mass window, so it can be interleaved with larger separator extractions. For example, consider a range of 100-1000, with a separator extraction of 100-200, 200-300, ..., 900-1000 steps. A quadrupole running through a 10 m / z isolation window cannot be run in a regular sequence 100-110, 110-120, etc., but can instead perform a single emission from each extracted range in each separator cycle: 100-110, 200-210, ..., 900-910 then 110-120, 210-220, ..., 910-920, etc. If each extraction cycle can be completed in about 100 ms, similar to a TIMS device, the entire DIA cycle will take about one second.

[0067] For DDA (data dependent acquisition), a precursor list can be generated from the uncleaved MS1 data, which can be a true full mass scan or some combination thereof with a mass range of low abundance regions of the spectrum extracted by the skimmer, for Boxcar / Orbitrap TM HDR-like spectra, only acquired significantly more efficiently. Target species from the precursor list can be removed in an optimized order; one target species per extracted mass range per separator cycle. These ranges can be set dynamically to the limits of the separator's resolving power based on ion current / number of targets etc.

[0068] exist Figure 3 Not shown in the flowchart is this understanding: Figure 4 The entire accumulator / separator device 401 / 402 can be turned on and the full range of ions can be allowed to pass, as in a conventional mass spectrometer. This can be used to occasionally acquire a full range spectrum, or to measure very strong peaks that may exceed the dynamic range of the instrument (such segments can be easily specified in the data-dependent precursor list, or based on automatic gain control AGC data (i.e., from MS1 scans or prescans) and certain isolation windows taken out of the accumulator DIA sequence). The large pulse of ions from the accumulator that initially appears when the device is set to flow mode can be ignored or otherwise used in ultra-high load full MS scans.

[0069] In general, embodiments of the present disclosure may be incorporated into a mass spectrometry system comprising: any of the devices described herein for separating ions; and a mass filter (e.g., a quadrupole) downstream of the device, the mass filter being configured to receive 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 the mass analyzer is configured to receive ions from the mass filter or ions derived from those ions (e.g., fragmentation ions) and perform mass analysis on the received ions.

[0070] Simulation of the embodiments of the present disclosure

[0071] Simulations can be used to demonstrate the efficacy of embodiments of the present disclosure.The simulations described herein were performed using the MASIM3D software suite, which is designed to detect and optimize device performance.

[0072] Figure 5A A 10 cm or 15 cm long 2D stacked plate ion guide constructed with a 6 mm envelope is shown. 4 phases of traveling RF plus 2 phases of trapping RF are applied. Each plate is 0.5 mm thick with 1 mm of air space between the plates, which is practical for such a construction without resorting to printed or etched electrodes. 2 MHz, 200 V are applied. 0-峰The RF is captured with each electrode 180 degrees out of phase with its nearest neighbor. A traveling wave is then generated from the superimposed 200KHz RF which is applied to each subsequent electrode with a 90 degree phase shift. An opposing DC gradient is also generated as an analysis function and superimposed to simplify calculations rather than labeling each electrode individually.

[0073] Figure 5B Also shown is the structure of the traveling wave generated by 4-phase 50V, 200KHz RF down along the center of the channel. Also shown is the movement of the phase within 1 microsecond, and the movement of the ion travel affected by the wave. Also presented is a separate drawing showing the traveling wave superimposed on the 50V DC curve following the ^4 function. The gradient can be any nonlinear function, although a power function of 2-4 is used in these simulations. This is similar to US8841608B2 in some aspects, except that a nonlinear DC gradient is provided; a linear gradient with only a single blocking force will not be able to separate ions, except as a filter, or as a migration device through drift velocity. The linear DC gradient will counteract the ion movement caused by the T wave, such as slowing down the ions, and is therefore used in US8841608B2 to increase the residence time in the migration separator, but the separation is carried out via ion migration. The T wave will push the ions upward with a linear gradient until they leave, or for ions of high m / z without enough T wave force, DC will push them out (filter them) in other ways, but there is no sedimentation of ions in different axial positions. Therefore, in embodiments of the present disclosure, the potential gradient is preferably nonlinear to provide separation. However, as will be described later with reference to Fig.17 As discussed, the separation can be achieved by utilizing an axially varying pseudo-force combined with a linear potential gradient.

[0074] In general, the arrangement in Figure 5 can be described as having a separation region extending in a third direction (z) that is different from the first (x-direction, also described as the separation direction) and the second (y) direction. The length of the separation region in the third direction is less than the 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 directions. Such a device may have relatively parallel planar surfaces defining a relatively thin planar separation region therebetween. The width of the separation region in the z-direction may 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 directions. A planar carpet structure may be provided. A planar or substantially planar electrode arrangement may be provided with a separation region adjacent to and defined by electrodes of the electrode arrangement.

[0075] In Figure 5, the first direction is shown as being perpendicular to the second direction, and the first and second directions are shown as being perpendicular to the third direction. It is not required that the x, y and z directions be orthogonal. Non-orthogonal geometries may alternatively be used.

[0076] FIG. 5 shows an embodiment of separating ions in the x-direction by a combination of opposing traveling waves and curved DC gradients. Although ions can diffuse in the y-direction, this structure does not restrict them. However, ions are relatively confined in the z-direction because the confined RF potential constrains the ions. Therefore, the height of the system in the z-direction can be relatively small to allow the traveling wave to penetrate to the middle. The embodiment of FIG. 5 can be adapted to have additional forces to demonstrate orthogonal manipulation of ion motion in the y-direction.

[0077] Figure 6 The instantaneous potential across the central axis generated by a 50V, 200KHz travelling wave and a superimposed DC curve (of the form 50V*length^3) is shown.

[0078] Figure 7 The movement of ion beams of various m / z through a 150 mm long separation device after being generated near the entrance is shown, showing simulated ion trajectories and the sedimentation of ions in different areas of the device. It can be seen that ions of different m / z reach equilibrium at different axial positions, where the ions of the lowest m / z are most affected by the traveling wave, and therefore travel closest to the outlet. Ions of higher m / z are less affected by the traveling wave, and therefore stay further away from the outlet. In this simulation, both the traveling wave (T wave) and the DC gradient amplitude are set to 40V, where the applied T wave is 40V and 200KHZ, and DC: 40V^4 trend. The pressure is set to 1mbar. Even with these strong fields, it can be seen that the ions occupy a relatively wide axial diffusion, so that the device can be roughly used as a mass analyzer and provide good performance in the role of a low-resolution pre-separator. For example, a resolution of at least 5 or at least 10 can be obtained. In some embodiments, the resolution can exceed 50 or can be as high as 100.

[0079] Figure 8 The effect of different DC power functions on the ion settling point is shown, showing the shift of the ion equilibrium towards the exit of the trap. The applied T wave is 40V and 200KHZ, DC: 40V, and the pressure is 1mbar. Higher power functions produce stronger gradients near the exit and therefore better constrain ions leaving the same applied DC, at the expense of leaving a wider low field region where ions of different m / z are separated more poorly. Since in physical devices the DC amplitude can reach about 200V without major problems, less sharp functions can be used. However, there are also some advantages, namely that higher functions push ions closer to the exit and therefore reduce the delay of released ions leaving the system. It should be noted that for a true DC gradient derived from a resistor chain, the DC function does not have to be a smooth polynomial, but can be stepped in appearance (e.g., a piecewise function that loosely approximates a curve) and is limited in accuracy by the quality and range of available resistors.

[0080] exist Fig. 9 In the experiment, the device length was reduced to 10 cm and the amplitudes of the traveling wave and DC gradient were scanned. The movement of the m / z 500 ion from the central starting point was then tracked until the equilibrium point (or ion escape) was reached. As expected, the high DC gradient amplitude pushed the equilibrium point back down the device while the high T wave amplitude pushed it forward, eventually overcoming the gradient and ejecting the ion from the device. Although Fig. 9 Not shown in the diagram, but in the simulations, the DC gradient is likely to push ions out the back of the device. A practical system could easily be terminated by a DC barrier provided by any suitable electrodes of the electrode arrangement.

[0081] One way to sequentially release ions from the separation region is to scan down the DC gradient. Alternatively, however, a T wave may be added. In some embodiments, both may be performed together to maximize the applied field without incurring radial ion losses.

[0082] exist Fig.10 In the embodiment of the present invention, as the DC gradient is linearly reduced from 40V to ground in 10ms, the ions of various m / z and charge states generated in the middle of the device are tracked. This is faster than the preferred actual cycle time, which depends on the separator resolution, but will be at least 50ms to 100ms to allow the fast mass analyzer to take 10 to 20 spectra at different mass positions. However, the time scale shown is sufficient to demonstrate the working principle of the device. Recorded in the range of m / z 200-1000, m / z 200 appears very quickly, then appears at 5ms to a large gap of m / z 330, and m / z 500-1000 appears in the last 3ms of the scan. A nonlinear decline of the DC gradient (that is, the opposite potential gradient can be time-varying) can be provided to balance the nonlinearity of the ion appearance, and / or the departure potential can be calibrated and set for each mass window.

[0083] The appearance time of the ions is shown in the simulation to be substantially independent of the charge state. That is, the reduced ion migration and departure time of heavier doubly or triply charged ions are no different. This may be advantageous because less information is needed to avoid accidentally missing different charge states. A corollary is that it is difficult to distinguish unwanted charge states, such as singly charged background ions. Therefore, if it is desired to distinguish unwanted charge states, further filtering may be performed.

[0084] The simulations described above were all performed using a collision model equivalent to 1 mbar nitrogen. This high pressure suppresses ion energy and minimizes dispersion and ion loss. Some losses of lower m / z ions were observed at high traveling wave amplitudes and lower pressures, which can be attributed to the radial field disturbances generated by the traveling waves. It should be appreciated that various pressures may be used in embodiments of the present disclosure, with vacuum being maintained in the separation region of some embodiments.

[0085] Fig.11 The radial transient DC potential is shown at the worst possible axial position, where for a 40VT wave there is a 2V pull on the ion. In this simulation, this is sufficient to overwhelm the trapping pseudopotential and remove the ion from the device unless there is appropriate gas pressure to suppress radial motion (so that the mean free path is << 3mm). Fig.11 In the top of the device, radial field disturbances are caused by traveling waves that pull ions out from the center of the device. Fig.11 In the bottom panel, the reduction of radial perturbations, normalized to the axial T-wave amplitude, is shown, where the same T-wave phase is applied to 2 or 3 consecutive plates to enhance field penetration.

[0086] It is possible to reduce the radial disturbances that are caused by the strong field between the electrodes being smoothed out toward the central axis. Fig.11 One approach shown in is to increase the number of consecutive electrodes with the same T wave phase applied, which increases penetration to the center with a disproportionate increase in perturbations. Another approach is to reduce the field step between electrodes by having the traveling wave have more phases than 4 (e.g. 8, 12 or 24). The time-varying potentials described herein may be multiphase potentials. It is also possible to increase the frequency of the traveling wave RF, although this also reduces the axial artifact force. The amplitude of the T wave and the DC gradient can be reduced to a level such that the low m / z will always be present, but the separation performance may be impaired.

[0087] It is known that strong DC gradients and traveling waves can cause fragmentation of ions, especially at low pressures. Especially for fragile multiply charged ions, the field amplitude can be reduced to preserve the fragile ions.

[0088] 2D flat device

[0089] Because many of the devices described herein operate in the rough vacuum region, the device can be incorporated with the same device that initially collects ions from the inlet capillary.

[0090] Although the above embodiments are described as having a stacked ring ion guide geometry, auxiliary electrodes or segmented electrodes may be used to cause ions to diffuse in a direction perpendicular to the axis of the stacked ring (e.g., to cause ions to occupy a planar area within the stacked ring or to occupy a substantially cylindrical volume within the stacked ring). However, moving away from the stacked ring to a more planar configuration may allow for a larger volume and therefore a higher ion capacity. Such planar structures (including RF carpets that face each other or use a DC counter electrode to pin ions to the RF pseudopotential plane, and applications for initial ion trapping and focusing) are described in GB 2209555.8, GB 2213536.2, and GB 2217040.1, the disclosures of which are incorporated herein by reference.

[0091] Fig.12 An example of an RF carpet device layout suitable for application of both traveling waves and opposing DC is shown. In some embodiments, the T wave is applied on the trapping RF electrode because, although it is possible to apply a traveling wave to the counter electrode (if appropriately segmented), the ions are generally closer to the RF electrode and the top-down traveling wave will be greatly smoothed out. However, the opposing axial DC can be provided by other electrodes on the same separation device surface as the RF electrode, but can also be derived from the counter electrode by varying the distance of the electrode from the RF carpet or by segmentation and application of an appropriately divided DC potential.

[0092] Fig.12 The various electrode arrangements include a counter electrode 1221 and an RF electrode 1222. Fig.12 In the embodiment, each of the counter electrodes 1221 is opposite to the RF electrode 1222. Fig.12 The electrode arrangement is an ion carpet structure for applying both a traveling wave (applied to RF electrode 1222) and relative axial DC originating from (a) shaped counter electrode 1221, (b) segmented RF electrode 1222 and (c) segmented counter electrode 1221. A combination of these three options can be provided.

[0093] exist Fig.12 In (a), the axial DC provided by the shaped counter electrode is opposite to the T wave provided by the RF electrode 1222. The RF potential can provide confinement in the upward / downward direction. Fig.12 In (b), the RF electrode 1222 has applied RF, T waves, and DC gradients. Fig.12 In (c), the counter electrode 1221 is disposed on a PCB 1223 and comprises a printed electrode having a resistive DC gradient, while the RF electrode 1222 is an RF PCB printed electrode to which a T wave is applied.

[0094] Fig.12 Only a cross section of the electrode arrangement in a single plane is shown. Fig.12The electrode arrangement can be configured to enable ions to move in a direction perpendicular to the plane of the cross section.

[0095] Fig.13 and Fig.14 A plan view of a structure that may incorporate such an electrode arrangement is shown. Fig.13 The integration of the above concept into the first vacuum region of a mass spectrometer is shown, showing different capillary / jet orientations relative to the ion guide. Fig.14 An additional implementation is shown by separating the separation and accumulation regions of the DC offset applied to the RF electrodes.

[0096] Fig.13 Several devices for separating ions are shown, each including an inlet capillary 1306, a pump 1314 for a gas jet 1315, a guard electrode 1316 (sometimes called a wall), an ion outlet 1317 (exit aperture), and an RF electrode 1322. An exemplary ion path 1399 is also shown.

[0097] exist Fig.13 In (a), ions enter the separation region 1301 in a first direction (vertically) from the inlet 1306. The electrode arrangement applies a potential that causes the ions to move in a second direction (horizontally) and separate in the first direction (vertically) before exiting via the ion outlet 1317 in the first direction.

[0098] exist Fig.13 In (b), the m / z separation direction is again vertical. An orthogonal (horizontal) force is provided to the ions by means of gas flow. A horizontal DC gradient or T wave may also be provided to further control the motion of the ions in the second direction. The ions enter the separation region 1301 in the second direction, and then separate in the first direction and leave the separation region in the first direction.

[0099] Returning to the general term used previously, the separation region can be configured to keep gas, and the force on the ion in the second direction can be applied by the flow of the gas through the separation region. However, in some cases, only gas force can produce the movement of the ions in the second direction. This normal force can be provided by the gas jet from the ion inlet (for example, inlet 1316) or can be provided by additional gas flow. The separation region can be configured to keep gas (for example, by having a closed shell), and the separation region can be configured to make gas flow through the separation region in a first direction (for example, for at least a portion of the ion path, gas flow can have at least some motion components in the first direction). The device can have a gas inlet and a gas outlet (which can be different from the ion inlet and outlet), and the gas inlet and the gas outlet are arranged to make gas flow through the separation region in the first direction and / or the second direction. Gas inlet and / or outlet can be in the separation itself or in the accumulation region, or elsewhere.

[0100] exist Fig.13 In (c), the ions are caused to move in the second (horizontal) direction by a potential applied by the electrode arrangement. The electrode arrangement then separates the ions in the first (vertical) direction, and the ions leave the separation region 1301 in the first direction.

[0101] In summary, Fig.13 Embodiments may be described as having a separation region including an ion outlet for allowing ions to leave the separation region (e.g., when a valve is opened or when a gate / protection voltage is changed or when a guide potential guides ions). The ion outlet may be positioned at an end of the separation region in a first direction, and the electrode arrangement may be configured such that ions leave the separation region in the first direction. For example, ions may move in a first direction and separate in the first direction, with the outlet at an extreme position in the first direction.

[0102] Fig.14 Shown with Fig.13 A related embodiment to that of (a), but with clearly distinguished separation and accumulation areas within the RF electrode arrangement.

[0103] Fig.14 The device shown includes a separation region 1401, an accumulation region 1402, an ion inlet 1406 (in the form of a capillary), a pump 1414 for a jet 1415, a guard electrode 1416, an exit aperture 1417, and an RF electrode 1422. An exemplary ion path 1499 is shown.

[0104] exist Fig.13 and Fig.14 In an embodiment of the present invention, the electrode arrangement is configured to apply a time-varying potential in the separation region 1301, 1401 to cause the ions to move in a first direction, which is shown as a vertical direction in the figure. The electrode arrangement is also configured to apply potential gradients in the separation region 1301, 1401. These potential gradients are opposite to the time-varying potential to separate the ions at different positions in the first direction according to the mass-to-charge ratio of the ions.

[0105] The RF electrodes 1322, 1422 are preferably (but not necessarily) elongated so that the electrode lines form a plane. There are two facing RF planes, or an RF plane and a DC counter electrode, which can be shaped or incorporated into separate electrodes (e.g., printed PCBs) to generate a DC gradient in either direction or to apply auxiliary AC to the traveling wave (as described above with respect to Fig.121316, 1417). Ions are dragged out of the post-capillary jet by an orthogonal DC gradient or T wave and into the ion guide. Optional guard electrodes 1316, 1416 provide a DC (or RF) barrier at the edge of the device to prevent ions from escaping except through exit apertures 1316, 1417.

[0106] When an accumulation region 1402 is provided, the ions are first accumulated there before being transferred to the separation region 1401. Optionally, if a properly aligned pseudo force is applied to the electrode arrangement in the accumulation region 1402, the separation process can be initiated in the accumulation region 1402. As previously described, the ions can be separated and released from the separation region 1401. In some embodiments, the separation region 1401 can be a combined accumulation / separation region, while in some embodiments, these regions can be distinct regions (e.g., separated by a gas confinement or other wall to separate the regions).

[0107] Returning to the general terminology used previously, embodiments of the present disclosure may include an accumulation region configured to accumulate ions. The electrode arrangement may be configured to: transfer ions from the accumulation region to a separation region; and separate ions in the separation region according to the mass-to-charge ratio of the ions; wherein the device is configured to refill the accumulation region when the ions are separated in the separation region. Thus, ions can be accumulated while the ions are being separated, which can reduce the downtime required when refilling the device.

[0108] The accumulation region may be within the range of the same electrode arrangement that defines the separation region, or may be defined by a separate electrode arrangement. The electrode arrangement of the device may be configured to transfer accumulated ions between the accumulation region and the separation region, for example to transfer ions from the accumulation region to the separation region, or vice versa. The accumulation region may include an ion inlet for receiving ions and / or an ion outlet for providing ions to the separation region, and the accumulation region may include 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 leave the gas from different outlets. The ion outlet may include one or more exit holes and / or one or more ion traps, or the outlet may include a guide or conduit for transporting ions to such traps.

[0109] The ion inlets 1306, 1406 (which are shown as capillaries, but other ion inlets may be provided) and the resulting jets 1315, 1415 may be aligned with the ion guide in a wide variety of orientations, as also shown. Fig.13As shown. Preferably, the jets 1315, 1415 are oriented so that they do not contribute to the m / z separation, at least near the final axis of ion equilibrium and transfer, because the jet forces may exceed the electric field. However, in some embodiments, gas forces may be expected to be a component of the separation force, similar to trapped ion migration. Therefore, in various different embodiments described herein, the ion inlet 1406, 1306 can direct ions parallel to the separation (first) direction, perpendicular to the separation direction, or at some other angle to the separation direction.

[0110] Fig.13 and Fig.14 A common theme among the embodiments is that each of these embodiments provides an additional force normal to the jet to pull ions out of the jet and move them to the far side of the separation region. Fig.13 and Fig.14 In the apparatus, ions are separated according to m / z in a first direction while being moved in a second direction due to gas forces in the device or due to a potential applied to the electrode arrangement. As previously noted, there are many ways to achieve this, such as by applying a DC gradient to the auxiliary electrode from a top counter electrode (shaped electrode or multi-electrode chain), a wedge-shaped or segmented RF trapping electrode, a gas inlet and / or outlet, etc. In any case, Fig.13 and Fig.14 The apparatus shown is configured to apply a force to the ions in a second direction (horizontally in these figures) so that the ions move in the second direction.

[0111] Thus, in general, the electrode arrangements described herein may be configured to apply a guide potential in the separation region to guide ions toward an ion outlet (optionally under the combined influence of any gas flow). Additionally or alternatively, the devices described herein may be configured to use gas flow through the separation region to guide ions toward an ion outlet (optionally under the combined influence of the potential applied by the electrode arrangements). These arrangements may provide a large volume for ions to occupy and alleviate space charge confinement.

[0112] One or more guide electrodes may apply such a guide potential. The one or more guide electrodes may include any one or more of the following: one or more direct current DC plate electrodes (e.g., applied to a DC top plate PCB only), wherein the guide potential comprises a DC gradient; a shaped (e.g., wedge-shaped or curved, with different distances between electrode groups) 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 a first direction and / or a second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposing DC potential in a separation region.

[0113] The electrode arrangement may be configured to apply a guiding potential so that ions leave the separation region in the order of the mass-to-charge ratio of the ions. For example, ions may be allowed to leave the separation region at different times through a single outlet in the order of their m / z. Alternatively, ions may be spatially ordered and leave the separation region in the order of m / z at different spatial positions. The electrode arrangement may be configured to release at least a portion of ions from the separation region by adjusting one or both of the time-varying potential and the potential gradient and allow ions to leave the separation region through the ion outlet. This may occur by sequentially adjusting one or both of the time-varying potential and the potential gradient. For example, ions may be released sequentially in the following manner: the voltage magnitude of the opposite potential is reduced over time, or the force applied by the time-varying potential is increased, or both are performed. Both of these potentials may vary linearly or nonlinearly. The electrode arrangement may be configured to apply a guiding, time-varying potential and / or potential gradient so that ions are separated in the first direction in the order of mass-to-charge ratio (under their combined influence).

[0114] Auxiliary electrodes may also be used to provide travelling waves (including low frequency RF based as in US10317364B2, although this example is not for pseudopotential generation as it gives an example at 4KHz).

[0115] exist Fig.13 and Fig.14 In one embodiment, one or more operating parameters of the device may be sequentially changed (e.g., stepped) over time so that ions in different m / z ranges are sequentially released from the separation region. The electrode arrangement may be configured to sequentially adjust one or both of the time-varying potential and the potential gradient. For example, at a first time point, ions in a first m / z range may settle at a first position closer to the ion outlet than a second position at which ions in a second m / z range settle. The magnitude of the opposite potential gradient may then be reduced so that ions in the first m / z range (i.e., those closest to the outlet) pass through the outlet, and ions in the second m / z range move closer toward the outlet and then settle at a new position (the new position being defined by the new operating parameters after undergoing the step change); this may be repeated until ions in the second m / z range pass through the ion outlet. This may be repeated for any number of m / z ranges.

[0116] In addition to or in lieu of this reduction in the magnitude of the opposing potential gradient, the time-varying potential may be altered, for example by adjusting its frequency (note that increasing the frequency of the traveling wave reduces the axial pseudoforce) and / or by adjusting its magnitude. These properties of the time-varying potential may thus be altered so that the force exerted by the time-varying potential on the ions increases and thus begins to overcome the opposing potential gradient. Thus, the time-varying potential may be altered (i.e., its magnitude or frequency is altered) so that ions in a first m / z range pass through the exit and ions in a second m / z range move closer to the exit and settle at a new location; this may also be repeated until ions in the second m / z range pass through the ion exit. These processes may be supplemented by additional gating or guiding potentials to cause the ions to pass through the exit. Furthermore, this process of altering the potential in the separation may be repeated for any number of m / z ranges.

[0117] Orthogonal extraction

[0118] Fig.15 A slightly different device incorporating the separation concept is shown in FIG. Instead of extracting m / z separated ions from a single ion outlet 1317, 1417 over time as previously described, Fig.15 The separated ions are shown to be 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 instead. In this case, the separation is ideally by m / z only. Ions of different m / z take different paths through the separation region and are therefore directed to different outlets 1517. The inlet capillary 1506 is shown as exceeding the limitations of the device, but a suitable DC offset may be sufficient to attract ions, and this side of the device may optionally be funneled to provide additional acceptance. The ion outlet 1517 can be a trap for trapping ions of different m / z, or it can be a conduit or funnel that guides ions toward a downstream trap.

[0119] In summary, the separation region described herein may include multiple ion outlets for allowing ions to leave the separation region. There may be two, three, four or more ion outlets, each of which is used to allow ions of a corresponding m / z to leave the separation region. The m / z passing through each ion outlet may be adjusted and regulated, for example, by appropriately selecting a voltage applied by an electrode arrangement and / or by adjusting the gas flow in the separation region. Therefore, ions of a given m / z may be directed to a certain outlet in the multiple outlets under certain conditions, but may be directed to different outlets under other conditions.

[0120] A plurality of ion outlets (which may be holes or any type of channel / conduit to transport ions to downstream processing, such as a trap) are preferably spaced apart in a first direction. Thus, ions separated in a first direction are divided into ion groups with corresponding m / z. A 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 ions to leave the separation region in a second direction, for example, by an appropriately applied potential.

[0121] Pull the ions toward the exit (i.e., Fig.15 An additional potential (e.g., a DC force) in the horizontal direction (in the middle) may be desirable to supplement (or replace) the gas force, which can be generated in the manner described in GB2209555.8 (which is incorporated by reference): the DC gradient can be applied to the DC-only top plate PCB, or to a shaped counter electrode (if it is an RF blanket type), or to an additional DC electrode mounted between the RF electrodes, or by shaping of the RF electrodes. In this example, each RF electrode 1522 extends horizontally, that is, the electrode extends toward the outlet 1517, or equivalently orthogonal to the direction in which the multiple outlets 1517 are spaced apart. Therefore, the RF electrode 1522 may have a traveling wave / opposite DC applied directly thereto. Alternatively, the traveling wave / opposite DC may be applied to one or more electrodes (e.g., an auxiliary electrode) of the electrode arrangement or the top plate counter electrode to provide a force in the first direction. In the case where the device includes multiple ion outlets, a guiding potential may be applied to guide ions to the corresponding outlets in the manner previously described.

[0122] Fig.13 , Fig.14 and Fig.15 The devices share a number of common features. For example, the embodiments show related electrode structures that apply related or similar potentials.

[0123] In some embodiments, the time-varying potential includes any one or more of the following: an oscillating potential; an RF potential; a pseudopotential that varies in a first direction (e.g., the time-varying potential can be an axially varying pseudopotential); a traveling wave; and a DC traveling wave. Various combinations of these potentials can be used to drive ions against an opposing potential and thereby achieve separation.

[0124] The potential gradient described herein and / or the time-varying potential described herein may vary nonlinearly. For example, the potential gradient may vary as a nonlinear function (e.g., a polynomial) of spatial position. The potential gradient may be defined by a piecewise linear approximation to a nonlinear function. For example, a segmented electrode may apply a local potential that varies 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 some AC component may be present. The magnitude of the time-varying potential may additionally or alternatively vary nonlinearly with spatial position.

[0125] The electrode arrangement described herein may include a plurality of electrodes, and these electrodes may be classified according to the functions they perform. For example, the electrode arrangement may include a first group of one or more electrodes (e.g., counter electrodes) configured to apply a potential gradient and a second group of one or more electrodes (e.g., RF electrodes) configured to apply a time-varying potential. The first group of one or more electrodes and / or the second group of one or more electrodes may each include a plurality of electrodes.

[0126] The first set of one or more electrodes and the second set of one or more electrodes may be on opposite sides of the separation region. The separation region may be defined as the area directly between the electrode sets. The electrode sets may be mounted on a wall of the housing of the device.

[0127] In some embodiments, the first group of one or more electrodes is connected in parallel with the second group of one or more electrodes. For example, both groups can be arranged on a planar surface. Thus, the first group of one or more electrodes can be planar or substantially planar and / or the second group of one or more electrodes can be planar or substantially planar.

[0128] The first set of one or more electrodes and / or the second set of one or more electrodes may comprise a plurality of electrode segments. Additionally or alternatively, the first set of one or more electrodes and / or the second set of one or more electrodes may be on a printed circuit board (PCB).

[0129] The first set of one or more electrodes may include 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 customize the spatial form of the applied potential.

[0130] The distance between the first group of one or more electrodes and the second group of one or more electrodes can vary along the length of the separation region. For example, one or two groups of electrodes can be curved, with the spatial form of the electric potential applied to customize. The shaped counter electrode will be closer to the ion at some point and therefore can apply stronger force to the ion. The distance between the electrode groups on the third direction can be different at different positions on the first and / or second direction.

[0131] In some embodiments, the first set of one or more electrodes and the second set of one or more electrodes can be arranged on a common surface or substrate. For example, the two sets can be coplanar.

[0132] The first set of one or more electrodes and / or the second set of one or more electrodes may include any one or more of the following: one or more direct current DC plate electrodes, wherein the guided potential comprises a DC gradient; a shaped counter electrode, wherein the guided 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 a first direction and / or a second direction; and a plurality of RF electrodes configured to apply a traveling wave and / or an opposite DC potential in a separation region. These may be as previously described.

[0133] One or more guard electrodes may form part of the electrode arrangement. Such guard electrodes may be positioned along at least one edge of the separation region. This may ensure that the ions are confined. Where an accumulation region is provided, the guard electrodes may additionally or alternatively be along the edge of the accumulation region.

[0134] Ion transmitter

[0135] Methods have been proposed to allow operation at lower pressures such as 0.1 mbar and 0.01 mbar. This would allow the device to operate in a collision cell, or in a differentially pumped region immediately before a quadrupole. The apparatus described herein may operate at pressures of at most 1 mbar, at most 0.5 mbar, at most 0.1 mbar, at most 0.05 mbar, or at most 0.01 mbar. Consider a combined trapping and traveling wave RF similar to an ion transporter (US7375344B2), which is essentially the same 4-phase traveling wave as before, but operates at MHz frequencies and higher voltages for the trapping RF. Fig.16 Shown with Fig.10 A similar simulation, whereby the DC gradient was ramped down in 10 ms, and at only 0.1 mbar pressure and using an ion transmitter type travelling wave allowed the separated ions to appear sequentially. Fig.16 In, a combined trapped RF and traveling wave ion transmitter (US7375344B2) type is provided, DC: 15V^3 trend with 10ms ramp to ground, RF: 750V and 2MHz.

[0136] Axially variable pseudoforce on linear DC

[0137] Some embodiments of the present disclosure include a pseudopotential (traveling wave) that opposes an axially varying DC force (curved DC gradient). However, traveling waves are not the only way to generate an axial pseudopotential. Another way besides using nonlinear DC is to produce an axially varying pseudopotential in the layer, and then the opposing DC can be a fixed force generated by a linear gradient.

[0138] Fig.17Several methods for generating such effects are shown in , where various non-traveling wave components for generating axially varying pseudopotentials and DC gradients are shown. Fig.17 (a) shows an ion funnel-like variation with the hole size of the stacked ring guides (it may also vary the spacing of the electrodes, or single / double / triple spacing of the auxiliary RF). Fig.17 (b) shows a multipole of RF rods with varying r0 to a fixed auxiliary DC electrode (the alternative is vice versa, and auxiliary RF can also be used, even applied to the same auxiliary DC electrode). Fig.17 (c) shows segmentation of a multipole rod electrode with varying DC and RF applied via a resistor / capacitor divider.

[0139] In more detail, Fig.17 (a) shows an ion funnel structure. It is known that conventional ion funnels usually require a DC gradient or gas force to push ions through the final electrode, where the hole size shrinks to a scale similar to the spacing between the ring electrodes. This is because RF penetration increasingly reaches the central axis, forming a pseudopotential barrier that the ions must be driven across. Normally, this is very unfavorable and leads to fragmentation of the ions. However, this effect can be exploited in the separation device described herein. By shrinking the shell / inscribed radius with axial position, it should be possible to generate a broadly consistent or axially varying pseudopotential force (with some fluctuations). Another way to increase RF penetration is to increase the spacing between the plates, similar to the method used in the Exploris TM The S-lens found in the 120 and 240 mass spectrometers.

[0140] In summary, Fig.17 Embodiments of (a) may be described as comprising a plurality of RF electrode segments. The RF electrode segments are arranged along a first direction (the direction in which the ions travel and separate). The RF electrode segments may be substantially circular or annular in shape. The radius of the RF electrode segments may vary (e.g., decrease) along the path of the ions. Therefore, due to the different distances between the electrodes and the ions, the strength of the pseudopotential experienced by the ions may also vary along the first direction, i.e., the RF electrode segments may generate an axially varying pseudopotential. Such pseudopotentials may be opposed to a DC potential (which may be generated by a linear potential (i.e., a constant force), or it may be a bending potential) to separate the ions.

[0141] Fig.17(b) shows a variable r0 multipole. A plurality of linearly extending rod electrodes may also surround the ion optical axis, and each rod electrode is arranged obliquely in a manner that the distance from the ion optical axis increases toward the direction of travel of the ions. That is, the radius r0 of the inscribed circle of the ion guide may also vary along the direction of the ion optical axis. Similar to the collision cell described in US7985951B2, changing the r0 of the multipole group may produce a type of pseudopotential gradient, and nonlinear changes will produce nonlinear gradients. Displacement of a single electrode may be used in the embodiments of the present disclosure. These do not need to be trapping RF rods, but may involve penetration from auxiliary RF electrodes. Auxiliary DC electrodes may also be used, and even if they are fixed r0 (like a cylinder around an open RF rod), due to changes in the RF electrodes, the field penetration to the center will vary, thereby producing a useful relative DC gradient.

[0142] Generally speaking, Fig.17 Embodiments of (b) may be described as comprising a plurality of multipolar electrodes. The multipolar electrodes are arranged around an axis extending in a first direction (the direction in which the ions travel and separate). The multipolar electrodes may be substantially rod-shaped. The distance between the multipolar electrodes may vary (e.g., decrease) along the path of the ions. Therefore, due to the different distances between the multipolar electrodes and the ions, the intensity of the pseudopotential experienced by the ions may also vary along the first direction, i.e., the multipolar electrodes may generate an axially varying pseudopotential. Such pseudopotentials may be opposite to a DC potential (which may be generated by a linear potential (i.e., a constant force), or it may be a bending potential) to separate the ions.

[0143] Fig.17 (c) shows segmentation of an axial electrode (primary or auxiliary electrode). If separated by a capacitive divider network, the RF amplitude may vary with axial position, similar to how a DC gradient may be produced by a resistor chain. A similar arrangement may be used to produce an axially varying traveling wave amplitude. Thus, in summary, Fig.17 (c) may be described as comprising a plurality of RF electrodes to which an RF potential is applied. The RF electrodes are arranged along an axis extending in a first direction (the direction in which the ions travel and separate). The magnitude of the RF potential varies along the first direction. This may be achieved using a potential divider (e.g. using a capacitive divider network). This may also provide an axially varying pseudopotential. Such a pseudopotential may be opposed to a DC potential (which may be generated by a linear potential (i.e. a constant force), or it may be a bending potential) to separate the ions.

[0144] Another possible method of extracting the ions is that after the initial separation and before extraction, the pseudopotential traveling wave is terminated and the ions are trapped in a series of DC traps. In the case of a pulsed DC traveling wave, this is equivalent to reducing the wave speed to zero or close to zero. The separated packets can then be extracted one by one (or two by two, etc.) by sequentially lowering each DC barrier or running a very slow traveling wave that acts like a moving DC force.

[0145] The traveling wave can be applied by a digital waveform, as can the trapping RF (if separate).

[0146] Axial pseudopotential barriers can be used to control the release of ions in an m / z-dependent manner to provide a head start for slow heavy ions heading towards the orthogonal accelerator of a ToF analyzer. This allows light fast ions to catch up with slow heavy ions, spatially focusing ions of different m / z at the extraction point and greatly enhancing the sensitivity of the pulse generator (US7456388B2). The device can provide a suitable head start for heavy ions by separating ions of different m / z in space, even by giving them a shorter flight path. Due to the high pressures and short time differences (<10s us) at which the device has been simulated for optimal operation, this operation can be adapted.

[0147] Switchable ion path

[0148] Fig.18 Additional embodiments of the present disclosure are shown in . Fig.18 The embodiment of the invention comprises 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 can be connected in parallel with the accumulation region 1802 rather than in series (e.g. Figure 2 and Fig.14 As shown). A beam switching device (such as described in UK patent application number GB 2209555.8) can be used to control the direction of ion flow between them. For example, the electrode arrangement can be configured to control the potential applied by the electrode to switch the ion path. The advantage of this arrangement is that such a system can be switched to a beam transmission mode without the need for empty accumulation and separation regions 1801, 1802. The arrangement can be formed by a stacked plate electrode arrangement, in which an orthogonal DC gradient is provided by an auxiliary electrode, or by an ion carpet with a DC gradient provided from a top plate. In an alternative structure, the separation region and the accumulation region can be arranged in series, with a bypass placed in an appropriate position to facilitate easy switching to beam mode.

[0149] like Fig.14 As shown, the accumulation region may be upstream of the separation region. In such an arrangement, both the accumulation region and the separation region are within the scope of the electrode arrangement. Fig.18As shown, this is not necessary.

[0150] Therefore, in some embodiments, the accumulation region is connected in parallel with the separation region. The device may be configured to switch between the accumulation region / separation region, or to provide a bypass. For example, in some embodiments, the electrode arrangement is configured to switch between any one or more of the following: a first configuration, wherein the electrode arrangement is configured to allow ions to enter the accumulation region without passing through the separation region; a second configuration, wherein the electrode arrangement is configured to allow ions to enter the separation region without passing through the accumulation region; and a third configuration, wherein the electrode arrangement is configured to allow ions to enter the accumulation region and accumulate therein, and to allow the accumulated ions to be transferred from the accumulation region to the separation region. The switching between these different operating modes can be controlled using appropriate electrode potentials. For example, the electrode arrangement may include a variable barrier (e.g., a DC barrier) between the accumulation region and the separation region. Various potential gradients may be applied to the electrode arrangement to transfer ions between different regions.

[0151] It will be appreciated that many variations may be made to the above described systems and methods while retaining the advantages mentioned above. For example, where specific components have been described, alternative components providing the same or similar functionality may be provided.

[0152] For example, in some embodiments, it may be beneficial to connect two separation devices / regions in series. One can perform a rough separation, and the other can perform a fine separation. The advantage is that the second separator does not need to suffer from high space charge or need to be suitable for a voltage setting of a wide m / z range, so better resolution is possible, with a lower chance of negative side effects (such as cracking). Therefore, in general, a first separation region can be provided, wherein the device also includes a second separation region connected in series with the first separation region. The first separation region can be configured to perform a relatively rough separation of ions, and the second separation region can be configured to perform a relatively fine separation of ions. Different resolutions can be used for relatively rough and relatively fine separations. For example, the first separation region can have a resolution of about 5, and the second separation region can have a resolution of about 30. Although both are quite rough, the second separation region can have a resolution greater than the resolution of the first separation region by at least 2x or 3x. The second separation region can be downstream of the first separation region.

[0153] Most of the embodiments described herein show a separation region sandwiched between two opposing electrode structures. However, in some embodiments, the first set of electrodes and the second set of electrodes providing the time-varying potential and the opposite potential gradient may be distributed along a single surface (e.g., a two-dimensional planar surface), with some electrodes providing repulsive forces and other electrodes providing attractive forces. The time-varying potential and the opposite gradient may be provided by a series of electrodes on a single surface (e.g., a flat surface). In some embodiments, the first set of electrodes and the second set of electrodes may be on surfaces oriented perpendicular to each other.

[0154] In other embodiments, the present disclosure provides a device that does not necessarily move ions in a second direction orthogonal to the first direction of ion separation. For example, the present disclosure also provides a device comprising:

[0155] a separation region configured to receive ions, the separation region extending in a first direction and adapted to separate ions according to their mass-to-charge ratio;

[0156] An electrode arrangement configured to confine ions in a separation region, wherein:

[0157] The electrode arrangement is configured to apply a time-varying potential in the separation region to cause ions to move in a first direction; and

[0158] the electrode arrangement being configured to apply a potential gradient in the separation region, the potential gradient being opposite to the time-varying potential, so that the ions are separated at different positions in a first direction according to the mass-to-charge ratio of the ions; and

[0159] An accumulation region is configured to accumulate ions, the accumulation region being connected in parallel with the separation region.

[0160] The electrode arrangement may be configured to switch between any one or more of the following:

[0161] a first configuration in which the electrode arrangement is configured such that ions enter the accumulation region without passing through the separation region;

[0162] a second configuration, wherein the electrode arrangement is configured such that ions enter the separation region without passing through the accumulation region; and

[0163] A third configuration, wherein the electrode arrangement is configured to cause ions to enter the accumulation region and accumulate therein, and to cause the accumulated ions to transfer from the accumulation region to the separation region.

[0164] Such a device may function in a similar manner to the other embodiments described herein.

[0165] In addition, it should be understood that some embodiments provide devices that provide an advantageous way to generate electric potentials in various regions of the device. For example, there is also provided: a device comprising:

[0166] a separation region configured to receive ions, the separation region extending in a first direction and adapted to separate ions according to their mass-to-charge ratio;

[0167] An electrode arrangement configured to confine ions in a separation region, wherein:

[0168] The electrode arrangement is configured to apply a time-varying potential in the separation region to cause ions to move in a first direction; and

[0169] The electrode arrangement is configured to apply a potential gradient in the separation region, the potential gradient being opposite to the time-varying potential, so that the ions are separated at different positions in a first direction according to the mass-to-charge ratio of the ions.

[0170] In such embodiments, the electrode arrangement may include Fig.12 and / or Fig.17 Any of the electrode arrangements shown, for example, to generate an appropriate field for manipulating ions (e.g., causing ions to enter a particular region, or causing ions to be transported and / or separated as they move through a particular region, or for causing ions to leave a particular region). Figure 2 , Figure 5A , Fig.13 , Fig.14 and / or Fig.15 The electrode arrangement in .

[0171] Unless otherwise stated, each feature disclosed in this specification can be replaced by an alternative feature for the same, equivalent or similar purpose. Therefore, unless otherwise stated, each feature disclosed is only an example of a series of equivalent or similar property features.

[0172] As used herein (including in the claims), unless the context indicates otherwise, the singular forms of the terms herein are to be understood to include the plural forms, and vice versa when the context permits. For example, unless the context indicates otherwise, the singular forms herein, including in the claims, such as "one / an" (such as an electrode or an electric potential), mean "one or more" (e.g., one or more electrodes, or one or more electric potentials). In the description and claims of the present disclosure, the words "comprises," "comprising," "having," and "containing," as well as variations of the words, such as "consisting of," and "consisting of," or the like, indicate that the described features include the following additional features, and the presence of other components is not intended to (and does not) be excluded.

[0173] The use of any and all examples or exemplary language ("for example," "such as," and similar language) provided herein is intended to better illustrate the present disclosure only and does not indicate a limitation on the scope of the present disclosure unless otherwise required. No language in this specification should be construed as indicating any non-claimed element necessary to practice the present disclosure.

[0174] Unless otherwise specified or the context requires otherwise, any steps described in this specification may be performed in any order or simultaneously. In addition, where a step is described as being performed after a step, this does not exclude intermediate steps being performed.

[0175] All aspects and / or features disclosed in this specification may be combined in any combination, except for combinations in which at least some of such features and / or steps are mutually exclusive. Specifically, preferred features of the present disclosure are applicable to all aspects and embodiments of the present disclosure and may be used in any combination. Similarly, features described in non-essential combinations may be used alone (not in combination).

[0176] Terms :

[0177] 1. A device for separating ions according to their mass-to-charge ratio, the device comprising:

[0178] a separation region configured to receive the ions, the separation region extending in a first direction and in a second direction different from the first direction; and

[0179] an electrode arrangement configured to confine the ions in the separation region, wherein:

[0180] The electrode arrangement is configured to apply a time-varying potential in the separation region to cause the ions to move in the first direction;

[0181] The electrode arrangement is configured to apply a potential gradient in the separation region, the potential gradient being opposite to the time-varying potential so that the ions are separated at different positions in the first direction according to the mass-to-charge ratio of the ions; and

[0182] The device is configured to apply a force in the second direction to the ions so that the ions move in the second direction.

[0183] 2. A device according to claim 1, wherein the separation region extends in a third direction different from the first direction and the second direction, and wherein the length of the separation region in the third direction is less than the length of the separation region in the first direction and / or the second direction.

[0184] 3. An apparatus according to clause 1 or clause 2, wherein the first direction is substantially perpendicular to the second direction, and optionally wherein the first direction and the second direction are substantially perpendicular to a third direction.

[0185] 4. An apparatus according to any preceding clause, wherein the separation region comprises an ion outlet for allowing the ions to leave the separation region.

[0186] 5. The device according to clause 4, wherein the ion outlet is positioned at an end of the separation region in the first direction.

[0187] 6. An apparatus according to clause 4 or clause 5, wherein the electrode arrangement is configured such that the ions leave the separation region in the first direction.

[0188] 7. An apparatus according to any preceding clause, wherein the separation region comprises a plurality of ion outlets for allowing the ions to leave the separation region.

[0189] 8. The apparatus of clause 7, wherein the ion outlets of the plurality of ion outlets are spaced apart in the first direction.

[0190] 9. Apparatus according to clause 7 or clause 8, wherein the electrode arrangement is configured such that the ions leave the separation region in the second direction.

[0191] 10. The device according to any of clauses 7 to 9, wherein the plurality of ion outlets are located along an edge of the separation region.

[0192] 11. The device according to any of clauses 4 to 10, wherein the ion outlet comprises one or more exit apertures and / or one or more ion traps.

[0193] 12. The device according to any one of clauses 4 to 11, wherein:

[0194] The electrode arrangement is configured to apply a guide potential in the separation region to guide the ions towards the ion outlet; and / or

[0195] The apparatus is configured to direct the ions towards the ion outlet using a flow of gas through the separation region.

[0196] 13. The apparatus of clause 12, wherein the electrode arrangement comprises one or more guiding electrodes configured to apply the guiding potential, the one or more guiding electrodes comprising any one or more of the following:

[0197] one or more direct current (DC) plate electrodes, wherein the pilot potential comprises a DC gradient;

[0198] a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode;

[0199] Segmented counter electrode;

[0200] one or more DC electrodes mounted between the plurality of RF electrodes;

[0201] a plurality of RF electrodes extending in the first direction and / or the second direction; and

[0202] A plurality of RF electrodes configured to apply traveling wave and / or opposing DC potentials in the separation region.

[0203] 14. An apparatus according to clause 12 or clause 13, wherein the electrode arrangement is configured to apply the guide potential so that the ions leave the separation region in order of the mass-to-charge ratios of the ions.

[0204] 15. A device according to any one of clauses 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 by adjusting one or both of the time-varying potential and the potential gradient.

[0205] 16. The apparatus of clause 15, wherein the electrode arrangement is configured to sequentially adjust one or both of the time-varying potential and the potential gradient.

[0206] 17. An apparatus according to any preceding clause, wherein the separation region is configured to retain a gas, and wherein the force in the second direction is exerted by a flow of the gas through the separation region.

[0207] 18. An apparatus according to any preceding clause, wherein the separation region is configured to retain a gas, and wherein the separation region is configured such that the gas flows through the separation region in the first direction.

[0208] 19. Apparatus according to clause 17 or clause 18, comprising a gas inlet and a gas outlet arranged such that the gas flows through the separation region in the first direction and / or the second direction.

[0209] 20. An apparatus according to any preceding clause, wherein one or more electrodes of the electrode arrangement are configured to exert the force in the second direction.

[0210] 21. An apparatus according to clause 20, wherein the potential gradient is a first potential gradient of a first potential applied by a first group of one or more electrodes of the electrode arrangement, and wherein a second group of one or more electrodes of the electrode arrangement are configured to apply a second potential in the separation region to apply the force in the second direction.

[0211] 22. The apparatus of clause 21, wherein the second electrical potential comprises a DC gradient in the second direction.

[0212] 23. An apparatus as described in clause 21 or clause 22, wherein the second electrical potential comprises a travelling wave travelling in the second direction.

[0213] 24. An apparatus according to any preceding clause, wherein the time-varying potential comprises an oscillating potential.

[0214] 25. An apparatus according to any preceding clause, wherein the time-varying potential comprises an RF potential.

[0215] 26. An apparatus according to any preceding clause, wherein the time-varying potential comprises a pseudopotential that varies in the first direction.

[0216] 27. An apparatus according to any preceding clause, wherein the time-varying potential comprises a traveling wave.

[0217] 28. An apparatus according to any preceding clause, wherein the time-varying potential comprises a DC travelling wave.

[0218] 29. An apparatus according to any preceding clause, wherein the potential gradient and / or the time-varying potential varies non-linearly.

[0219] 30. An apparatus according to any preceding clause, wherein the potential gradient is a DC potential gradient.

[0220] 31. An apparatus according to any preceding clause, wherein the electrode arrangement comprises a first set of one or more electrodes configured to apply the electric potential gradient and a second set of one or more electrodes configured to apply the time-varying electric potential.

[0221] 32. The device of clause 31, wherein the first set of one or more electrodes and the second set of one or more electrodes are on opposite sides of the separation region.

[0222] 33. An apparatus according to clause 31 or clause 32, wherein the first set of one or more electrodes is substantially connected in parallel with the second set of one or more electrodes.

[0223] 34. A device according to any of clauses 31 to 33, wherein the first set of one or more electrodes are substantially planar and / or wherein the second set of one or more electrodes are substantially planar.

[0224] 35. An apparatus according to any one of clauses 31 to 34, wherein the first set of one or more electrodes and / or the second set of one or more electrodes comprises a plurality of electrodes.

[0225] 36. An apparatus according to any one of clauses 31 to 35, wherein the first set of one or more electrodes and / or the second set of one or more electrodes comprises a plurality of electrode segments.

[0226] 37. A device according to any of clauses 31 to 36, wherein the first set of one or more electrodes and / or the second set of one or more electrodes are on a printed circuit board (PCB).

[0227] 38. A device according to any of clauses 31 to 37, wherein the first set of one or more electrodes includes a counter electrode.

[0228] 39. A device according to clause 38, wherein the counter electrode is a shaped counter electrode, wherein the potential gradient has a shape corresponding to the shaped counter electrode.

[0229] 40. An apparatus according to any of clauses 31 to 39, wherein the distance between the first set of one or more electrodes and the second set of one or more electrodes varies along the length of the separation region.

[0230] 41. A device according to any of clauses 31 to 39, wherein the first set of one or more electrodes and the second set of one or more electrodes are substantially coplanar.

[0231] 42. The device of any of clauses 31 to 41, wherein the first set of one or more electrodes and / or the second set of one or more electrodes comprises any one or more of the following:

[0232] one or more direct current (DC) plate electrodes, wherein the pilot potential comprises a DC gradient;

[0233] a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode;

[0234] Segmented counter electrode;

[0235] one or more DC electrodes mounted between the plurality of RF electrodes;

[0236] a plurality of RF electrodes extending in the first direction and / or the second direction; and

[0237] A plurality of RF electrodes configured to apply traveling wave and / or opposing DC potentials in the separation region.

[0238] 43. An apparatus according to any preceding clause, wherein the electrode arrangement comprises one or more guard electrodes positioned along at least one edge of the separation region.

[0239] 44. An apparatus according to any preceding clause, wherein:

[0240] The separation region is a vacuum region; and / or

[0241] The separation zone is at a lower pressure than an upstream zone of the device and / or a downstream zone of the device.

[0242] 45. An apparatus according to any preceding clause, further comprising an accumulation region configured to accumulate the ions.

[0243] 46. ​​The apparatus of clause 45, wherein the electrode arrangement is configured to transfer the accumulated ions from the accumulation region to the separation region.

[0244] 47. The device according to any of clauses 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.

[0245] 48. The device according to any of clauses 45 to 47, wherein the accumulation region comprises a gas inlet and / or a gas outlet.

[0246] 49. Apparatus according to any one of clauses 45 to 48, wherein the accumulation zone is upstream of the separation zone.

[0247] 50. A device according to any one of clauses 45 to 49, wherein the accumulation region is

[0248] Separate regions are connected in parallel.

[0249] 51. The apparatus of clause 50, wherein the electrode arrangement is configured to switch between any one or more of:

[0250] a first configuration, wherein the electrode arrangement is configured such that the ions enter the accumulation region without passing through the separation region;

[0251] a second configuration, wherein the electrode arrangement is configured such that the ions enter the separation region without passing through the accumulation region; and

[0252] A third configuration, wherein the electrode arrangement is configured to cause the ions to enter the accumulation region and accumulate therein, and to cause the accumulated ions to transfer from the accumulation region to the separation region.

[0253] 52. The apparatus of clause 51, wherein the electrode arrangement is configured to apply a variable DC barrier between the accumulation region and the separation region.

[0254] 53. An apparatus according to any of clauses 45 to 52, wherein the electrode arrangement is configured to:

[0255] transferring the ions from the accumulation region to the separation region; and

[0256] separating the ions in the separation region according to the mass-to-charge ratio of the ions;

[0257] wherein the apparatus is configured to refill the accumulation region upon separation of the ions in the separation region.

[0258] 54. An apparatus according to any preceding clause, wherein the separation region is a first separation region, and the apparatus further comprises a second separation region connected in series with the first separation region.

[0259] 55. An apparatus according to clause 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.

[0260] 56. A mass spectrometry system, comprising:

[0261] An apparatus for separating ions according to any preceding clause; and

[0262] A mass filter is provided downstream of the device, the mass filter being configured to receive the ions from the device.

[0263] 57. A mass spectrometry system according to clause 56, further comprising a mass analyzer configured to receive the ions from the mass filter or to receive ions originating from the ions from the mass filter and to perform mass analysis on the received ions.

Claims

1. A device for separating ions according to their mass-to-charge ratio, the device comprising: a separation region configured to receive the ions, the separation region extending in a first direction and in a second direction different from the first direction; and an electrode arrangement configured to confine the ions in the separation region, wherein: The electrode arrangement is configured to apply a time-varying 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, the potential gradient being opposite to the time-varying potential so that the ions are separated at different positions in the first direction according to the mass-to-charge ratio of the ions; and The device is configured to apply a force in the second direction to the ions so that the ions 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 direction and the second direction, and wherein a length of the separation region in the third direction is smaller than a length of the separation region in the first direction and / or the second direction.

3. An apparatus according to claim 1 or claim 2, wherein the first direction is substantially perpendicular to the second direction, and optionally wherein the first direction and the second direction are substantially perpendicular to a third direction.

4. An apparatus according to any preceding claim, wherein the separation region comprises an ion outlet for allowing the ions to leave the separation region, preferably wherein the ion outlet is positioned at an end of the separation region in the first direction, and more preferably wherein the electrode arrangement is configured such that the ions leave the separation region in the first direction.

5. An apparatus according to any preceding claim, wherein the separation region comprises a plurality of ion outlets for allowing the ions to leave the separation region, preferably wherein the ion outlets of the plurality of ion outlets are spaced apart in the first direction.

6. The apparatus of claim 5, wherein the electrode arrangement is configured such that the ions leave the separation region in the second direction.

7. An apparatus according to claim 5 or claim 6, wherein the plurality of ion outlets are located along an edge of the separation region.

8. The device according to any one of claims 4 to 7, wherein: The electrode arrangement is configured to apply a guide potential in the separation region to guide the ions towards the ion outlet; and / or The apparatus is configured to direct the ions towards the ion outlet using a flow of gas through the separation region.

9. The apparatus of claim 8, wherein the electrode arrangement comprises one or more guiding electrodes configured to apply the guiding potential, the one or more guiding electrodes comprising any one or more of the following: one or more direct current (DC) plate electrodes, wherein the pilot potential comprises a DC gradient; a shaped counter electrode, wherein the guide potential has a shape corresponding to the shaped counter electrode; Segmented counter electrode; one or more DC electrodes mounted between the plurality of RF electrodes; a plurality of RF electrodes extending in the first direction and / or the second direction; and A plurality of RF electrodes configured to apply traveling wave and / or opposing DC potentials in the separation region.

10. An apparatus according to claim 8 or claim 9, wherein the electrode arrangement is configured to apply the guide potential so that the ions leave the separation region in order of the mass-to-charge ratios of the ions.

11. A device according to any one of claims 4 to 10, 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 by adjusting one or both of the time-varying potential and the potential gradient.

12. The apparatus of claim 11, wherein the electrode arrangement is configured to sequentially adjust one or both of the time-varying potential and the potential gradient.

13. An apparatus according to any preceding claim, wherein the separation region is configured to retain a gas, and wherein the force in the second direction is exerted by a flow of the gas through the separation region.

14. The device of claim 13, comprising a gas inlet and a gas outlet arranged such that the gas flows through the separation region in the first direction and / or the second direction.

15. An apparatus according to any preceding claim, wherein one or more electrodes of the electrode arrangement are configured to exert the force in the second direction.

16. An apparatus according to claim 15, wherein the potential gradient is a first potential gradient of a first potential applied by a first group of one or more electrodes of the electrode arrangement, and wherein a second group of one or more electrodes of the electrode arrangement are configured to apply a second potential in the separation region to apply the force in the second direction, preferably wherein the second potential comprises a DC gradient in the second direction and / or a traveling wave travelling in the second direction.

17. A device according to any preceding claim, wherein the time-varying potential comprises any one or more of the following: Oscillating potential; RF potential; a pseudopotential varying in said first direction; Traveling waves; and DC traveling wave.

18. An apparatus according to any preceding claim, wherein the potential gradient and / or the time-varying potential varies non-linearly.

19. An apparatus according to any preceding claim, wherein the potential gradient is a DC potential gradient.

20. An apparatus according to any preceding claim, wherein the electrode arrangement comprises a first set of one or more electrodes configured to apply the electrical potential gradient and a second set of one or more electrodes configured to apply the time-varying electrical potential.

21. The apparatus of claim 20, wherein: The first set of one or more electrodes and the second set of one or more electrodes are on opposite sides of the separation region; and / or The first set of one or more electrodes is connected substantially in parallel with the second set of one or more electrodes; and / or The first set of one or more electrodes are substantially planar and / or wherein the second set of one or more electrodes are substantially planar; and / or The first set of one or more electrodes and / or the second set of one or more electrodes comprises a plurality of electrodes; and / or The first set of one or more electrodes and / or the second set of one or more electrodes comprises a plurality of electrode segments; and / or The first set of one or more electrodes and / or the second set of one or more electrodes are on a printed circuit board PCB; and / or The first set of one or more electrodes and the second set of one or more electrodes are substantially coplanar.

22. The device of 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 The distance between the first set of one or more electrodes and the second set of one or more electrodes varies along the length of the separation region.

23. An apparatus according to any preceding claim, wherein: The separation region is a vacuum region; and / or The separation zone is at a lower pressure than an upstream zone of the device and / or a downstream zone of the device.

24. An apparatus according to any preceding claim, further comprising an accumulation region configured to accumulate the ions, preferably wherein the electrode arrangement is configured to transfer the accumulated ions from the accumulation region to the separation region.

25. The device according to claim 24, wherein the accumulation region is upstream of the separation region and / or in parallel with the separation region.

26. The apparatus of claim 25, wherein the accumulation region is connected in parallel with the separation region, and wherein the electrode arrangement is configured to switch between any one or more of: a first configuration, wherein the electrode arrangement is configured such that the ions enter the accumulation region without passing through the separation region; a second configuration, wherein the electrode arrangement is configured such that the ions enter the separation region without passing through the accumulation region; and a third configuration, wherein the electrode arrangement is configured such that the ions enter the accumulation region and accumulate therein, And the accumulated ions are transferred from the accumulation region to the separation region.

27. The apparatus according to any one of claims 24 to 26, wherein the electrode arrangement is configured as: transferring the ions from the accumulation region to the separation region; as well as separating the ions in the separation region according to the mass-to-charge ratio of the ions; wherein the apparatus is configured to refill the accumulation region upon separation of the ions in the separation region.

28. An apparatus according to any preceding claim, wherein the separation region is a first separation region, and the apparatus further comprises a second separation region connected 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. A mass spectrometry system, comprising: Apparatus for separating ions according to any preceding claim; and a mass filter downstream of the device, the mass filter configured to receive the ions from the device; The apparatus optionally further comprises a mass analyser configured to receive the ions from the mass filter or to receive ions derived from the ions from the mass filter and to perform mass analysis on the received ions.

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