Ion transport between ion optical devices under different gas pressures

Abstract

A mass spectrometer includes: a first ion optical device in a relatively low-pressure region; a second ion optical device in a relatively high-pressure region, the first and second ion optical devices receiving corresponding RF voltages from corresponding RF power sources to generate corresponding RF fields that confine ions to corresponding trapping regions of the ion optical devices; and a gas conduction limiting member that restricts gas flow from the relatively high-pressure region to the relatively low-pressure region, the gas conduction limiting member having an aperture allowing ions to pass from the second ion optical device to the first ion optical device. The first and second RF power sources are independent to allow the RF voltage used to generate the first RF field to have a different amplitude than the RF voltage used to generate the second RF field.

Description

Technical Field

[0001] This disclosure relates to a mass spectrometer that includes ion optical devices, such as multipolar ion optical devices. Background Technology

[0002] Extraction ion traps serve as ion accumulation and preparation devices for paired mass analyzers. They receive a continuous beam of light from an ion source and pulse a cooled ion packet with spatial and energy properties typically matched to the analyzer's acceptability. Such devices are often paired with time-of-flight (ToF) and orbital capture mass analyzers. US9312114 B2 describes an extraction trap well-suited for ToF analyzers. US7425699 B2 describes an instrument for an extraction trap used in conjunction with an orbital capture mass analyzer.

[0003] First refer to Figure 1a This shows a longitudinal cross-sectional view of an existing example extraction ion trap, and references... Figure 1b , showed Figure 1a A cross-sectional view of the extraction ion trap is shown. This includes: axial inlet and outlet orifices 10; and orthogonal extraction orifices 15 for extracting ions to the mass analyzer 20. The RF and DC voltages used for extraction are also shown.

[0004] Such traps are typically quadrupole assemblies of four parallel rod electrodes, where each pair of opposing rods is applied with an RF waveform of opposite polarity to provide radial trapping pseudopotential. The rod electrodes can be employed as follows: Figure 1a and 1b The diagram shows the form of a planar electrode. The rod assembly terminates at an electrode to which a DC voltage is applied to prevent ion axial escape. Holes in these electrodes allow ions to enter from adjacent ion optics.

[0005] Another common structure is the 3D or Paul trap, which includes a ring electrode with an applied RF voltage located between a pair of DC end cap electrodes that together generate a quadrupole trapping field (REMarch et al., "Quadrupole Storage Mass Spectrometry", John Wiley & Sons, pp. 31-110, 1989).

[0006] Upon entering the trap, the ions are cooled by collisions with a buffer gas (typically nitrogen or helium), forming a compressed pack at the center of the trap. This compressed pack can be further compressed by increasing the repulsive DC voltage at the inlet and outlet orifices. The ion pack is extracted by applying a pulsed DC voltage to one or more electrodes in the rod electrode. Figure 1a and 1bThe "push" and "pull" actions in the trap generate a strong DC field orthogonal to the trap axis, through which ions are ejected via a groove cut into a rod. Prior to extraction, an RF voltage is typically applied at optimal phase quench as described in US7250600 B2 and US9312114 B2 to optimize ion spatial and / or energy distribution and minimize RF interference during extraction.

[0007] Axial trapping of ions does not necessarily require termination electrodes or orifices. If the RF rod itself is segmented, different DC voltages can be applied to each segment to form an axial trapping trap to hold ions, or to form a DC gradient to guide ions to the extraction region (described in US8981287 B2). Another alternative is to provide axial DC via auxiliary DC trapping electrodes mounted in the space between the RF rods and elongating only a portion of the entire rod length (GB2570435A and Stewart et al., 'Axial Pulsed-Extraction Ion Trap with Auxiliary Axial DC Trapping Electrodes', American Society for Mass Spectrometry Conference, San Antonio, 2018). Other methods for generating superimposed axial gradients or traps using auxiliary DC electrodes are well known, including those using wedge electrodes (US20140353491 A1), segmented rods (US20140353491 A1), and chains of PCB-based electrodes (US9396919 B2).

[0008] A major challenge in extraction traps is the efficient capture and rapid thermalization of injected ions from energies of a few eV. This is advantageous when the buffer gas is at a relatively high pressure, typically greater than 2 x 10⁻⁶. -3 mbar (0.2 Pa). However, effective pulse extraction requires minimal collisions between thermal ions and the buffer gas, especially for high-quality ions. Time-of-flight, multiple-reflection flight time, and orbital capture mass analyzers require very low pressures to minimize gas leakage from the trap to the analyzer. A simple solution is to use pulse gas valves, as described in GB2439107 B, but these valves operate slowly, thus limiting the analyzer repeatability to approximately 10 Hz when higher frequencies than 100 Hz are required.

[0009] Another solution involves rapidly pre-cooling the ions in the high-pressure trapping region and then transferring the lower-energy ions to the low-pressure extraction region (Stewart et al., 'A Robust C-Trap Ion Injection Method Incorporating Electrodynamic Squeeze', American Society for Mass Spectrometry Conference, 2020). See now for reference. Figure 2 The illustration schematically depicts an example dual-pressure region extraction arrangement and an exemplary applied DC axial potential. The extraction arrangement includes a quadrupole extraction trap (C-Trap) 100 with bent electrodes, which is coupled to a pressurized area (e.g., 1x10⁻⁶) with an auxiliary DC gradient. -2 A quadrupole ion director (referred to as "ion routing multipole" or "IRM") 200 (mbar or 1Pa). The C-trap 100 has an inlet lens 110 and an outlet lens 120.

[0010] Ions first travel from the ion source through C-Trap 100 to IRM 200, where they are rapidly cooled. This is achieved by using an accelerating lens potential 101 applied to the inlet lens 110 and an IRM injection potential 201 to inject ions into IRM 200. The ions are then cooled in IRM 200. After a few milliseconds, the cooled ions are then swept back into the much lower-pressure C-Trap 100 using a trapping potential 102 applied to the inlet lens 101 and a purge potential 202. Furthermore, a small dynamic DC ramp potential 203 is applied to IRM 200 and the exit lens 120 of C-Trap 100 to prevent reflected ions from returning and impacting the lens or leaving the trap before being properly cooled. Figure 2 The intermediate DC offset step is not shown.

[0011] One limitation of this approach is that ions still must pass through a pinhole lens (exit lens 120 of the C-Trap 100), which hinders ion transfer and requires several eV of ion energy to avoid significant losses. An aperture is needed to maintain the pressure difference between the two regions and to eliminate edge field effects caused by the interaction of individual RF fields. Ideally, low-energy ion transfer between regions is required, necessitating a barrier-free interface that sufficiently restricts gas conduction.

[0012] US20190103263 A1 describes a segmented trap that combines two pressure regions separated by gas conduction-confined segments. (See the document...) Figure 3As shown in (a), the gas conduction-containment segment is a segment with a small inscribed radius surrounded by a potential barrier. An AC (RF) voltage power supply provides the voltage to induce radial confinement or extraction. By applying a suitable DC voltage, ions can be axially confined or transferred between two regions at different pressures. However, practical implementations of such traps have not yet been realized. Summary of the Invention

[0013] In this context, a mass spectrometer is provided. Additional optional and / or advantageous features are defined in the dependent claims.

[0014] The design shown in US20190103263 A1 (comprising two multipolar ion optics, typically quadrupoles, one in a high-pressure region and the other in a low-pressure region, with a gas conduction confinement element between them) may offer advantageous benefits. For example, by appropriately segmenting the AC voltage across the low-radius segments to match the capture parameter q, ions pre-cooled and pre-accumulated in the high-pressure region can, in principle, be transferred segmentally through the interface with energies essentially no greater than 1 eV. Therefore, much lower pressures (not exceeding 5 x 10⁻⁶) can be used in the extraction region. -4 (mbar or 0.05Pa) without causing significant ion loss or excessively long cooling time.

[0015] However, it is now recognized that the edge fields where the RF fields from the high-pressure and low-pressure regions overlap can create large potential barriers, requiring higher ion energies to penetrate and negating most of the advantages of the device. It has been determined that this can occur even if the capture parameter q is matched, but the phase, frequency, and / or amplitude are mismatched. Additional problems arise when different ion swarms are provided, which can result in significant differences in mass-to-charge ratio (m / z) because the RF on each side may not be optimized when using a single RF power supply. This effect can be mitigated by providing independent RF power supplies to the ion optics (multipolar) devices in two different pressure regions, specifically by allowing independent control of the RF amplitude. This problem may also apply even if one or both of the ion optics are not multipolar ion optics but are configured to confine ions using RF potentials. Other examples of such ion optics include stacked ion directors, ion tunneling devices, and ion optics comprising one or more ion blankets. For example, an ion optics device may include cross ion blankets (one or more downstream ion blankets oriented perpendicularly or orthogonally to one or more upstream ion blankets).

[0016] Specifically, the edge field can be configured such that the RF frequencies and phases of the RF fields in two different pressure regions are the same. This particularly mitigates the edge field where the RF fields overlap, thus preventing the formation of a substantial potential barrier.

[0017] The gas conduction limiting element may include a diaphragm and / or may have an aperture larger than the inscribed radius (r0) of the ion optics. Alternatively or additionally, there may be nothing with a radius smaller than r0 between the high-pressure and low-pressure ion optics (e.g., no ion optics). The RF electrodes of one or two ion optics (specifically, multipole) may have lips extending toward the electrodes of other ion optics (e.g., multipole) (and may enter the gas conduction limiting element). Small lips may allow quadrupoles to reach or enter the aperture (e.g., the aperture of the diaphragm) and approach each other to further reduce edge field effects. In addition to radial limiting, a bridge between the RF electrodes at the end of the low-pressure ion optics (multipole) away from the high-pressure ion optics (multipole) can provide an RF pseudopotential for axial limiting of ions. Axial limiting may alternatively be achieved via a DC electrode at the distal end of the low-pressure ion optics (multipole).

[0018] Therefore, an advantageous operating mode is one in which the low-pressure or extraction region is operated by a separate RF power supply to the high-pressure region, allowing one ion cluster to be extracted into the analyzer in parallel (e.g., via quench RF), while another ion cluster is accumulated and cooled in the high-pressure region. This allows for rapid parallel processing and lower pressure within the extraction trap.

[0019] A highly parallel filling sequence with three capture regions (e.g., using an upstream mass filter and / or collision cell), comprising a downstream low-pressure region and at least one upstream high-pressure region, advantageously allows for rapid instrument operation. One or two ion packets may accumulate in one or more upstream devices, while another ion packet is accumulating in the high-pressure (multipolar) region of the extraction trap, and yet another ion packet is being extracted from the low-pressure (multipolar) region of the extraction trap. Optionally, another ion packet can be analyzed simultaneously in the downstream mass analyzer. This is significantly different from existing methods, which use only two capture stages in parallel upstream (downstream). In the proposed method, three, four, or five ion packets can be processed simultaneously, with high reproducibility (200 Hz or higher). The method is preferably implemented in conjunction with the aforementioned mass spectrometer design or independently.

[0020] One or both of the ion optical devices (multipolar) can be formed by a stack of electrodes (separated by insulating pads). A first (low-pressure) ion optical device (multipolar) can be formed by a first pair of opposing electrodes and orthogonally segmented opposing electrodes, the first pair of opposing electrodes being applied with a first-phase RF voltage and a DC voltage of opposite polarity. The segmented opposing electrodes are applied with a second-phase RF voltage opposite to the first phase and a DC voltage of opposite polarity. A second (high-pressure) ion optical device (multipolar) can be formed by a first pair of opposing electrodes with an applied first-phase RF voltage and a second pair of opposing electrodes (orthogonally oriented from the first pair) with an applied second-phase RF voltage opposite to the first phase.

[0021] Combining two different quadrupole cells has a particular advantage: one cell with a (diagonally mounted) auxiliary DC electrode that facilitates ion trapping transitions into another quadrupole with a split RF trapping electrode and an (equatorial mounted) auxiliary DC electrode best suited for efficient ion extraction. The auxiliary DC electrodes can taper gradually along the axis of the ion optics device (multipole) and / or they can be spaced approximately equally around their radius (e.g., for a quadrupole ion trap, there may be four auxiliary DC electrodes).

[0022] Two independent RF power supplies can share a core RF generator. The two RF power supplies can be arranged using separate coils (transformers). A phase adjuster can be used to acquire the RF generated by either the core RF generator or one of the power supplies and use it to provide RF to the second RF power supply (in this case, a sampler can be used to sample one of the generated RF voltages). Attached Figure Description

[0023] This invention can be embodied in various ways, and preferred embodiments will now be described by way of example only and with reference to the accompanying drawings, in which:

[0024] Figure 1a A longitudinal cross-sectional view of an existing example extraction ion trap is shown;

[0025] Figure 1b It shows Figure 1a A cross-sectional view of the extraction ion trap;

[0026] Figure 2 An example dual-pressure region extraction arrangement and an exemplary applied DC axial potential are schematically illustrated.

[0027] Figure 3 The illustration shows an example schematic layout of an embodiment of a combined ion trap configuration according to the present disclosure;

[0028] Figure 4 against Figure 3The embodiment depicts a graph of the axial DC potential versus the distance along the longitudinal axis;

[0029] Figure 5a An end view of an example electrode structure for a multipolar ion optical device in a low-pressure region is shown.

[0030] Figure 5b It shows Figure 5a A perspective view of the electrode structure;

[0031] Figure 6a An end view of an example electrode structure for a multipolar ion optical device in a high-voltage region is shown.

[0032] Figure 6b It shows Figure 6a A perspective view of the electrode structure;

[0033] Figure 7 A block diagram of the first possible power supply arrangement is schematically illustrated.

[0034] Figure 8 A block diagram illustrating the second possible power supply arrangement is shown schematically.

[0035] Figure 9 The relationship between simulated pressure and distance along the longitudinal axis of the combined ion trap was plotted based on the embodiments in Figures 5 and 6.

[0036] Figure 10 A simulated velocity-time trajectory of an ion mass passing through the interface between two quadrupoles is shown according to the embodiments of Figures 5 and 6.

[0037] Figure 11 The relationship between the normalized signal area of ​​1022 m / z ions and the high-pressure to low-pressure transition time was plotted under two different pressures.

[0038] Figure 12 The signal area of ​​the 202 m / z ion and the pressure estimate in the low-pressure region are shown, with three different high-pressure to low-pressure transition times.

[0039] Figure 13 The relationship between the signal area and the relative voltage offset between the high-voltage and low-voltage regions was plotted when RF was applied to two regions in phase or 180 degrees out of phase.

[0040] Figure 14 A schematic diagram of a mass spectrometer incorporating the disclosed extraction trap is shown;

[0041] Figure 15 schematically depicted Figure 14 An improved processing sequence for the mass spectrometer;

[0042] Figure 16AA top view schematically depicts an example configuration of two ion optical devices according to this disclosure, each ion optical device including a corresponding ion blanket; and

[0043] Figure 16B schematically illustrated Figure 16A The front view of the instance.

[0044] The use of the same reference numerals across different figures is intended to show the same features. Unless otherwise stated, the drawings should be considered schematic diagrams. Detailed Implementation

[0045] As previously understood, a combined ion trap can be used to provide efficient capture and rapid thermalization of injected ions from energies of several eV. This combines a high-pressure cooling region, a low-pressure extraction region, and minimal barriers at the interfaces between the regions to allow ions to transfer between the regions at reduced energies, thereby minimizing cooling time and ion loss. To achieve the benefits of this configuration, ions are ideally transferred to the extraction region without requiring excessive buffer gas pressure or excessive transfer and cooling time within the extraction region.

[0046] The method disclosed herein provides an extraction RF trap that can operate with high reproducibility by efficiently accumulating and extracting different implanted ions in parallel. Specifically, this can be achieved through barrier-free low-energy transfer across the pressure interface, allowing for rapid ion thermalization within the low-pressure extraction region.

[0047] In other words, the combined extraction trap integrates a high-pressure cooling (and / or fragmentation) region and a parallel low-pressure extraction region, separated by conductive confinement elements but without a substantial barrier to ion transport. Different multipole ion optics are arranged in each region. Advantageously, RF is supplied to the multipole on both sides of the interface via two independent RF generators. Advantageously, the outputs of the two independent RF generators are phase- and frequency-locked, for example, by sharing a core frequency generator.

[0048] Now for reference Figure 3 The illustration shows an example schematic layout of an embodiment of the combined ion trap configuration according to the present disclosure. This includes a low-pressure region 300 and a high-pressure region 400. A first trapping electrode 310 having a first RF voltage (RF1) is disposed in the low-pressure region 300, and a second trapping electrode 410 having a second RF voltage (RF2) is disposed in the high-pressure region 400. A vertical (x) axis is also shown to understand the movement of ions.

[0049] In the low-pressure region 300, a vacuum pump 320 is provided at a rate of approximately 20 liters per second. In the high-pressure region 400, N2 buffer gas 420 is provided through a capillary tube 425. A diaphragm 350 is provided between the low-pressure region 300 and the high-pressure region 400.

[0050] Auxiliary DC electrodes are provided in both the low-pressure region 300 and the high-pressure region 400. The outlines of the low-pressure auxiliary DC electrode 330 and the high-pressure auxiliary DC electrode 430 are schematically shown above the trap to illustrate their shapes.

[0051] The first capture electrode 310 and the second capture electrode 410 form a corresponding capture RF multipole assembly having a length of 100 mm and an inscribed radius r0 of 2 mm, separated by a conductive confinement element (in this case, a diaphragm 350). The diaphragm 350 is a thin-walled structure with pores much larger than the multipole r0 to avoid interfering with the ion capture region. The two capture RF multipole assemblies should have the same inscribed radius to match the quadrupole field structure. While some degree of tolerance for variation is possible, any variation is generally negligible. The diaphragm 350 has the added benefit of minimizing the capacitance between the multipole assemblies, thereby making the RF power supply design more feasible.

[0052] The first capture electrode 310 has a small lip 315 cut into it, and similarly, the second capture electrode 410 has a small lip 415 cut into it. These lips allow critical edges to be as close as possible (even possibly within the diaphragm) without damaging the diaphragm 350. Ideally, the multi-electrode electrodes are as close as possible to each other without causing electrical breakdown. A gap of about 0.5 mm is typically preferred. The diaphragm 350 can extend this distance by another 0.5 mm, so the presence of the lips 315, 415 can reduce this distance by 0.5 mm or more.

[0053] The captured RF is supplied from two power sources (not shown) to two multipole assemblies, each with independent amplitude control (for parallel processing of two different ion packets) but identical frequency and phase. This mitigates the formation of an RF barrier and the heating process at the interface between the regions. The DC offset of each multipole assembly is preferably independently controllable. Edge field problems in segmented multipole directors are reported in US7034292B1, and mitigation measures such as maximizing ion cooling before transfer are cited.

[0054] Nitrogen buffer gas 420 is fed into the second capture electrode 410 or the high-voltage region 400 through capillary tube 425, so that it reaches 5 x 10 -3 Pressure in the mbar (0.5 Pa) range, despite 1 to 20 x 10 -3mbar (0.1 Pa to 2 Pa) is normal, depending on the analyte ions. A combination of gas conduction limiting devices and a pumping rate of approximately 20 L / s in the low-pressure zone 300 should ensure a pressure drop of 5 to 10 times at the ion extraction point.

[0055] The auxiliary DC electrodes 330 and 430 are wedge-shaped (i.e., tapering gradually along their length) and are coupled between the RF trapping electrodes 310 and 410 to generate superimposed axial DC gradients along the length of the trap. These are desirable for rapidly guiding ions through the gas-filled trapping region and accumulating ions at the extraction point. Alternatively, the axial DC gradient could be provided by heavy segmentation of the RF trapping electrodes 310 and 410, but this is expected to be much more complex to implement mechanically and electronically. Ions 360 enter the high-voltage region 400 via the inlet lens 440. The polarity of the DC voltage applied to the auxiliary electrodes, as shown in the figure, is suitable for the trapping and transport of positively charged ions. It can be understood that by switching the polarity of the voltage, negatively charged ions can also be trapped and transported in this manner.

[0056] Optionally, a bridge 340 may be provided on the back side to bridge the first RF trapping electrode 310 in the low-pressure region 300. This can generate an additional RF delay pseudopotential to prevent ions from axially escaping the trap. Alternatively, the same effect can be achieved by providing an additional DC electrode.

[0057] Next, refer to Figure 4 Among them, targeting Figure 3 The embodiment depicts a graph of an axial DC potential of 500 versus a distance along the longitudinal axis (x) to explain the process of ion implantation, transfer, and extraction to a (time-of-flight or ToF) mass analyzer. When using with... Figure 3 The same reference markers indicate the same features.

[0058] In the first step 510, ions from the source are injected into the high-pressure region 400 through an inlet lens, which is preferably positioned at a higher DC offset than the high-pressure region 400. The high-pressure region 400 at this point should also have a lower DC offset than the low-pressure extraction region 300 to prevent ion escape. It can also be configured to induce fragmentation of the injected ions and / or collision energy can be used for fragmentation. The ions are then cooled and moved along a superimposed DC gradient to the region interface at the distal end of the high-pressure region 400 (the distal end of the inlet lens 440).

[0059] After a reasonable cooling time (approximately 1 ms), the second step 520 is performed. The potential of the DC auxiliary electrode applied to the high-pressure region 400 is slightly increased (+10V) to just above the potential of the DC auxiliary electrode applied to the low-pressure region 300. As a result, ions 525 drift into the low-pressure region 300 and cool at the center of the trap in this region because the axial DC field is configured to create a potential trap at the center of the trap, as shown in the figure. The DC offset applied to the high-pressure region 400 is increased to just above the level of the offset applied to the low-pressure region 300 (approximately 0.25V), thereby injecting ions into the low-pressure region with minimal energy and cooling them into the extraction point (in this case, the center of the trap).

[0060] After a cooling time of 0.5 ms to 20 ms, a third step 530 is optionally performed, in which the offset of the DC auxiliary electrode applied to the low-voltage region 300 is increased, for example, to 4 kV. Thus, ions are still trapped and ready for implantation (ToF) mass analyzer. During this period, the potentials applied to the DC and RF electrodes in the high-voltage region 400 are not limited by the field in the low-voltage region 300. Therefore, new ions (new ion packs) can then be implanted into the ion trap in the high-voltage region 400, for example, from an ion source.

[0061] Finally, in the fourth step 540, a quench is applied to the RF of the electrode in the low-pressure region 300, and an extraction DC pulse voltage is applied. This causes ions to be ejected into the mass analyzer.

[0062] Understandably, segmentation of the RF trapping electrode between the two pressure regions is largely unnecessary, as an auxiliary DC electrode can be used to trap ions in the high-pressure region and guide them to the low-pressure region. However, this would preclude parallel processing of different ions in the two regions, as the high-pressure region would see an electronic signal ejecting ions from the extraction region, thus significantly slowing down trap operation.

[0063] Generally, a mass spectrometer can be considered, comprising: a first ion optical device in a relatively low-pressure region; a second ion optical device in a relatively high-pressure region; and a gas conduction restrictor configured to restrict gas flow from the relatively high-pressure region to the relatively low-pressure region. The first ion optical device is configured to receive an RF voltage from a first RF power source for generating a first RF field that confines ions within a capture region of the first ion optical device. The second ion optical device is configured to receive an RF voltage from a second RF power source for generating a second RF field that confines ions within a capture region of the second ion optical device. The gas conduction restrictor has an aperture that allows ions to pass from the second ion optical device to the first ion optical device. Advantageously, the first and second RF power sources are independent, specifically, to allow the RF voltage used to generate the first RF field to have a different amplitude than the RF voltage used to generate the second RF field.

[0064] While one aspect of this disclosure can be considered as a form of arrangement of an ion optical device or mass spectrometer, it can also be considered as a method of processing ions. This method may include steps of providing and / or operating structural components of said arrangement or mass spectrometer according to their functionality. All structural features discussed herein can be equivalently considered as process steps in a method of providing or operating a mass spectrometer.

[0065] In the embodiments, each of the first and second ion optical devices is a corresponding multipole ion optical device. The benefits of this disclosure are applicable to ion optical devices (e.g., ion guides) that use an RF field for confinement, specifically, multipole ion optical devices (which may include, for example, quadrupole, hexapole, octapole, decapole, etc.).

[0066] Advantageously, the first and second RF power supplies are configured to provide RF voltages for generating a first RF field and RF voltages for generating a second RF field having the same frequency and aligned phase.

[0067] Preferably, the first and second RF power supplies are configured to provide RF voltages to generate a second RF field to capture ions in the second ion optical device, and simultaneously configured to generate RF voltages for ejecting or extracting ions from the first ion optical device (the amplitude of the ejected or extracted RF voltage can be zero, i.e., the first RF field can be quenched).

[0068] In some embodiments, the gas conduction limiting element includes a diaphragm. Additionally or alternatively, the orifice of the gas conduction limiting element (which may be an orifice in the diaphragm) is larger than the inscribed radius r0 of the first and / or second ion optical devices. Preferably, there is no ion optical device between the first and second ion optical devices with a radius smaller than that of the first and second ion optical devices.

[0069] Advantageously, at least one multipole or RF electrode (optionally more than one multipole or RF electrode and having a lip extending toward an electrode of the other ion optical device) is present in one or both of the first and second ion optical devices. The lip may enter a gas conduction restrictor.

[0070] Optionally, a buffer gas is introduced through a capillary tube into a relatively high-pressure region to achieve the desired pressure. Alternatively, a pumping rate in a relatively low-pressure region is selected to achieve the desired pressure in the relatively high-pressure region. Preferably, the buffer gas and / or pumping rate can be set to achieve a pressure drop of 5 to 10 times in the ion extraction region (in the second ion optics device or multipolar region).

[0071] In some embodiments, the multipole or RF electrode of the first ion optics may further include a bridge, such that the second RF field provides radial and axial confinement, specifically, due to the bridge resulting in an RF pseudopotential for axial confinement.

[0072] Further details of the invention will be discussed again in general below. First, details of other specific embodiments will be introduced.

[0073] More details are now provided regarding specific embodiments of the RF electrode used in a combined ion trap. See below for further details. Figure 5a An end view of an example electrode structure for a multipolar ion optical device (ion trap) (generally a first multipolar ion optical device) used in a low-pressure region is shown. Also referenced... Figure 5b , showed Figure 5a A perspective view of the electrode structure. This structure follows a similar scheme of applied potential as shown in the following literature: GB2570435A and Stewart et al., 'Linear Pulse Extraction Ion Trap with Auxiliary Axial DC Capture Electrode', American Society for Mass Spectrometry Meeting, San Antonio, 2018.

[0074] The trap is formed by a stack of elongated electrodes separated by insulating pads. The electrode structure includes (applied RF and DC potentials are shown in parentheses): pull electrode 610 (+RF1, -DC) PP ); Push electrode 620 (+RF1, +DC) PP ); Split-type pull electrode 630 (-RF1, -DC) PP); Segmented push electrode 640 (-RF1, +DC) PP ); auxiliary DC electrode 650; gasket 660; insulating rod 670; and ejector slot 680.

[0075] Therefore, applying one phase of the RF to the top and bottom electrodes (pull electrode 610 and push electrode 620), and applying a 180-degree phase-shifted RF to the four electrodes offset from the equatorial plane (segmented pull electrode 630 and segmented push electrode 640), generates a trapping pseudopotential. For a 2mm r0 well, the applied 4MHz RF has an amplitude range of 200-2000V. 峰-峰 It is suitable for common analyte ions.

[0076] Auxiliary DC electrode 650 (which is wedge-shaped, such as...) Figure 3 (As shown) A small voltage is applied along the equatorial plane to generate a weak axial potential gradient, such as a potential well at a point extracted from the well. Optionally, an insulating rod 670 may be inserted between electrodes that extend from the inlet to approximately half the length of the well to further improve conduction confinement between regions.

[0077] As ions are captured and sufficiently cooled at the ejection (or extraction) tank 680, the potential across the entire extraction region can optionally be increased, followed by quenching of the RF potential, preferably first at the pull electrode 610 and push electrode 620, and then at the split push electrode 630 / pull electrode 640 after half a cycle (as discussed in similar schemes mentioned above). A negative extraction (or push / pull) DC (relative to ion polarity) is applied to the pull electrode 610 and split pull electrode 630, while a positive DC is applied to the push electrode 620 and split push electrode 640, thereby ejecting ions through the extraction tank 680. This relatively complex voltage application produces a strong and uniform field at the center of the trap, but simpler methods also work, such as applying the extraction DC only to the pull electrode 610 or push electrode 620 alone, or both. An extraction field of 250–500 V / mm is considered suitable for ejection into a time-of-flight analyzer. Since the auxiliary DC electrodes 650 are located at the zero potential line where the DC gradient is extracted, they do not need to apply any additional potential at the extraction point.

[0078] Segmented RF electrodes can offer two distinct advantages. First, their use can enhance the pulse extraction field at the center of the trap; second, they can create space to introduce auxiliary DC electrodes 650. Alternatively, non-equatorial auxiliary DC electrodes could be positioned (i.e., entering from the four corners), but the extracted DC would then have to be applied to these electrodes, which can be quite complex electronically.

[0079] Now for reference Figure 6aAn end view of an example electrode structure for a multipolar ion optics device (ion trap) (a second multipolar ion optics device in a general sense) used in a high-voltage region is shown. Also referenced... Figure 6b , showed Figure 6a A perspective view of the electrode structure. The inlet hole (lens) is not shown in this figure.

[0080] The electrode structure includes: an external capture electrode (RF potential +RF2 applied thereto) 710; an internal capture electrode 720 (RF potential -RF2 applied thereto); a pad 730; and an auxiliary DC electrode 740. This electrode stack is simpler than the corresponding stack used for the extraction region because only four capture electrodes have alternating in-phase and 180-degree out-of-phase RF applied from a frequency-locked second RF power supply.

[0081] In this configuration, four auxiliary DC electrodes 740 are mounted protruding to the corners of the capture region's circumference (alternating between RF electrodes 710 and 720) and wedged in to reduce the length of the protrusions along the region. The reverse approach is also possible, but it might make determining the absolute DC potential at the interface slightly more difficult, as it becomes the sum of the rod potential and the perturbation from the auxiliary DC electrodes 740. The use of four auxiliary DC electrodes 740 is preferred for this region because the radial capture pseudopotential is perturbed by the superimposed octet DC field much less than the quadrupole perturbation caused by the equatorial DC electrode 650 in the extraction region.

[0082] The switching between a quadrupole configuration of a multipolar ion optics device with auxiliary electrodes suitable for capture or transport in high-pressure regions and a configuration suitable for extraction in low-pressure regions is highly advantageous. It is readily apparent how this electrode configuration is surrounded by an insulating cap to control airflow.

[0083] Returning to the general meaning of this disclosure discussed above, further optional and / or preferred details may be considered. For example, the first and / or second (multipolar) ion optical devices may be formed by a stack of elongated electrodes spaced apart by insulating pads. Advantageously, the first ion optical device may be configured to receive ions from the second ion optical device along the common axis of the first and second ion optical devices, and to allow the received ions to be extracted in a direction orthogonal to the axis.

[0084] Advantageously, the first and / or second ion optical devices include auxiliary DC electrodes arranged to receive a DC potential to generate an axial DC gradient superimposed on the corresponding RF field. The auxiliary DC electrodes may taper gradually along the axis of the corresponding ion optical device. In some embodiments, the auxiliary DC electrodes are spaced approximately equally around the radius of the corresponding (multipolar) ion optical device. The first (multipolar) ion optical device may include an electrode stack with the auxiliary DC electrode located at the center of the electrode stack. Alternatively or additionally, the second (multipolar) ion optical device may include equally spaced RF electrodes for generating the RF field, and the auxiliary DC electrodes may be staggered between the RF electrodes.

[0085] In an embodiment where the first ion optical device is a first multipolar ion optical device, the first multipolar ion optical device includes: a first pair of opposing electrodes applied with the same RF voltage of the same amplitude and first phase, and a DC voltage of opposite polarity at a DC voltage level; and a second pair of opposing electrode arrangements. Each of the opposing electrode arrangements includes: a split RF electrode comprising two separate electrode components applied with the same RF voltage of the same amplitude and second phase opposite to the first phase, and a DC voltage of opposite polarity at a DC voltage level. An auxiliary DC electrode may then be disposed between the two separate electrode components of the split RF electrode. Optionally, the first multipolar ion optical device further includes a bridge located between the first pair of opposing electrodes of the first multipolar ion optical device, such that the first RF field provides radial and axial confinement. Alternatively or additionally, the second ion optical device is a second multipolar ion optical device, and the second multipolar ion optical device includes: a first pair of opposing electrodes applied with the same RF voltage of the same amplitude and first phase; and a second pair of opposing electrodes applied with the same RF voltage of the same amplitude and second phase opposite to the first phase. The auxiliary DC electrode can be positioned between each electrode in the first pair of opposing electrodes and the corresponding electrode in the second pair of opposing electrodes.

[0086] The first and / or second multipolar ion optics may include an insulating rod located between the multipolar electrodes of the ion optics. The insulating rod may then extend from the inlet of the ion optics to approximately half the length of the ion optics.

[0087] Further specific details of this disclosure will now be discussed. A more detailed description, in a general sense, will follow.

[0088] Now consider possible embodiments of RF power supplies for (multipolar) ion optics devices in high-pressure and low-pressure regions. It is highly desirable that the RF power supplies for both pressure regions share the same frequency, as this mitigates the generation of strong edge field effects at the region interface. However, the RF power supplies are advantageously configured as separate power supplies, for example, such that the RF field applied in the high-pressure region is able to withstand the quenching of the RF field in the low-pressure region and the high-pressure offset used for extraction.

[0089] Even a small frequency error can result in completely different fields in each region over a short period of time, thus the two power supplies are advantageously frequency-locked. One way to achieve this is to drive the primary coils of each power supply from the same frequency generator, which may also be combined with a device that generates a phase shift on one power supply to allow the output RF phase to be aligned.

[0090] Next reference Figure 7 A block diagram schematically illustrates a first possible power supply arrangement. This includes: a frequency generator 800; an RF1 coil arrangement 810, which includes a primary winding 811 and secondary windings 815, 816, 817, and 818; V 推压 DC power supply 821V; 拉动 DC power supply 822; RF2 coil arrangement 830, which includes primary winding 831 and secondary windings 835, 836; and phase adjustment block 840. Thus, by incorporating secondary coils in each power supply, each output RF phase can be driven, and push-pull extraction DC potentials can be added. This provides push electrode potential 825; pull electrode potential 826; segmented push electrode potential 827; segmented pull electrode potential 828; +RF 838 for high-voltage regions; and -RF 839 for high-voltage regions. This is similar to the method used in US6340814B1, where adjacent RF power supplies are frequency-locked by sharing a common frequency generator or clock.

[0091] A drawback of this system is that the two regions may not be able to be frequency tuned independently. Typically, the frequency is fine-tuned for each power supply to achieve resonance. Another drawback found with this power supply scheme is that the phase may shift with amplitude, so an alternative arrangement has been considered.

[0092] Next reference Figure 8 The diagram schematically illustrates a second possible power supply arrangement. (In conjunction with...) Figure 7The same reference numerals are used in the same boxes. This provides frequency and / or phase locking by using the output of one phase of the first RF power supply (e.g., a split pull electrode potential 828), sampling that output with measurement block 841, and then using it to drive the second power supply (via phase adjustment block 840), thereby protecting the second power supply from phase shifts that occur in the first power supply.

[0093] Referring to the general meaning detailed above, the first and second RF power supplies can form at least part of a power system. Therefore, the power system can include: a core RF generator configured to provide an RF waveform of a specific frequency; a first coil configuration (or transformer) configured to receive the RF waveform and provide an RF voltage to generate a first RF field; and a second coil configuration (or transformer) configured to receive an RF signal derived from the RF waveform and provide an RF voltage to generate a second RF field. The core RF generator and the first coil configuration can define the first RF power supply, and the core RF generator and the second coil configuration can define the second RF power supply.

[0094] Optionally, the power system further includes a phase adjuster configured to receive a signal as an RF waveform or a waveform generated from an RF waveform, and based on the received signal, to provide the RF signal derived from the RF waveform to a second coil configuration (or alternatively, to a first coil configuration) by setting the phase of the RF signal to a desired level.

[0095] In some embodiments, the power supply system further includes a sampler configured to sample one of the RF voltages used to generate a first RF field from a first coil configuration (or alternatively, to sample one of the RF voltages used to generate a second RF field from a second coil configuration), and to provide a waveform generated from the RF waveform to the phase adjuster based on the sampled RF voltage.

[0096] Before returning to the general meaning of the present discussion, we will further describe the performance results and additional details of the specific implementation scheme.

[0097] Simulation results are now presented to illustrate the effects of the described embodiments. Reference is now made to... Figure 9 Based on the embodiments in Figures 5 and 6, the relationship between simulated pressure and distance along the longitudinal axis (Z) of the combined ion trap was plotted. This figure illustrates the results of gas dynamics simulations performed on a combined extraction trap model in the ion optics modeling software package (MASIM 3D), which may or may not be coupled with conductive confinement cylinders between the extraction region electrodes. The trajectories of 10,000 gas particles were calculated, and the pressure gradient across the trap length was inferred.

[0098] Regardless of the additional conduction limiters, a pressure drop of nearly 10-fold was observed from the high-pressure region to the extraction point. However, these cylinders can be used to maintain higher pressures at the interface, thus allowing for slightly better cooling of the ions as they are transported to the extraction point.

[0099] Figure 10 The simulated velocity-time trajectory of the ion mass across the interface between the two quadrupoles according to the embodiments of Figures 5 and 6 is shown. The top two plots show the radial velocity, and the bottom two plots show the axial velocity. The simulation used a 4MHz 400V RF, with the left plot using a locked frequency and 5% phase and amplitude errors, and the right plot using a 10% frequency error (3.8MHz to 4.2MHz).

[0100] It is clear that ion movement is largely unaffected by small phase or amplitude differences that might be readily present in a real power source, as shown by the minute change in axial energy at 900. However, frequency errors cause significant radial heating of the ions at 910 and exhibit such a strong axial barrier (large axial energy change) at 920 that some ions are reflected.

[0101] Further results were obtained by constructing an extraction trap representing the apparatus disclosed in Figures 5 and 6, which was combined with a time-of-flight analyzer and supplied with ions via an electrospray ionization source. The resulting experimental results are now described.

[0102] Now for reference Figure 11 Two different pressures (approximately 4x10) were plotted. -3 mbar or 0.4 Pa and 9x10 -4 A graph showing the relationship between the normalized signal area of ​​1022 m / z ions at mbar (or 0.09 Pa) and the high-to-low pressure transition time. Also referenced... Figure 12 It shows the signal area of ​​202 m / z ions and the pressure estimate in the low-pressure region, with three different high-pressure to low-pressure transition times. Figure 4 The transfer and cooling times during the transition from the high-pressure region to the low-pressure region before the 4KV boost and extraction are shown and discussed. Poorly cooled ions are lost from the extraction region during the 4KV boost and are not detected.

[0103] In approximately 4x10 -3 At a standard extraction zone pressure of mbar (0.4 Pa), ions with m / z 1022 are almost completely retained at any transfer time, even as short as 2 milliseconds. However, transfer times below 1 x 10⁻⁶ are significantly reduced. -3The low pressure of mbar (0.1 Pa) means that a considerable cooling time is required to maximize the signal. For ions with m / z 202, this effect is much smaller when the pressure is below 2 x 10⁻⁶. -3 At mbar (0.2 Pa), the ions suffer some capture loss at a cooling time of 2 milliseconds, but no loss is observed at transfer times of 5 milliseconds or 10 milliseconds.

[0104] This may represent a limitation of this design; for very fast operations (approximately 5 milliseconds total cycle time), it typically requires 1x10. -3 mbar (0.1 Pa) to 2 x 10 -3 A pressure of mbar (0.2 Pa) is used to rapidly cool uniformly injected ions at energies less than 1 eV. If a large number of multiply charged ions are present, lower pressures and longer waiting times appear to be required, as the risk of accidental collisions during extraction or within the analyzer may necessitate minimum gas pressures. It should be noted that some experimental factors, such as a ripple of approximately 0.5 V in the DC offset of the extraction region, may increase ion energy and, to some extent, increase cooling time.

[0105] Now for reference Figure 13 The relationship between the signal area and the relative voltage shift between the high-voltage and low-voltage regions was plotted when RF was applied to two regions in phase or 180 degrees out of phase. This demonstrates the sweep of the injection energy, defined by the offset displacement of the high-voltage and low-voltage regions and their impact on the m / z 524 ion detection signal. It was observed that for out-of-phase RF, ions require a considerable injection energy to overcome the interfacial RF barrier, and there always appears to be signal loss compared to in-phase RF experiments.

[0106] The in-phase RF scan also revealed a high-signal "sweet spot" at low injection energies. This could be due to optimal cooling or because, under conditions of excess energy, some ions are believed to be able to penetrate the relatively weak trapping RF (700V) used and strike the auxiliary DC pin or the end of the trap. This demonstrates the practical benefits of frequency locking between the two RF power supplies and maintaining good phase alignment.

[0107] Next reference Figure 14A schematic diagram of a mass spectrometer incorporating the disclosed extraction trap is shown. This includes: an electrospray ionization (ESI) ion source 1010; an RF lens 1020; an ion director 1030; a mass filter 1040; an ion gate 1050; an additional ion director 1060; a curved ion trap (C-trap) 1070; a Z-lens 1080; an orbital trap mass analyzer 1090; a collision cell 1100; a downstream ion trap 1110; an extraction trap 1120; a tilted ion mirror 1140; a deflector 1150; a calibration strip electrode 1160; and a detector 1170.

[0108] This is a hybrid instrument combining a quadrupole mass filter 1040, an orbital trap mass analyzer 1090, and a multiple reflection time-of-flight (MR-ToF) mass analyzer 1130. The extraction trap assembly 1120 is used in this example to supply the MR-ToF analyzer 1130. For example, this general instrument layout has previously been described in US10699888B2 and US10593525B2. US10699888B2 describes a general data-independent acquisition method in which the complete ion beam from source 1010 is occasionally sampled by a C-Trap 1070 (an extraction trap form) and measured by the orbital trap mass analyzer 1090, but primarily, the ion beam is filtered in a mass sequence manner, broken up in the collision cell 1100, and the debris is analyzed in the MR-ToF analyzer 1130. The MR-ToF analyzer 1130 is described in detail in WO2013110587A2, although it can be replaced by a more conventional time-of-flight analyzer.

[0109] When operating this instrument at high repetition rates, considerable problems can arise. Besides the time required for thermalizing the ions, the ions travel through approximately 10... -2 The time required for a short region of mbar (1 Pa) pressure is approximately 1 millisecond. The time for switching the resolving quadrupole (mass filter 1040) and transferring a new separated ion pack is also around this level. For an instrument operating at a repetition rate of 200 Hz, the time for switching the quadrupole, sending ions to the high-pressure region of the extraction trap 1120, cooling and transferring them to the extraction region of the trap, and then cooling and extracting them to the MR ToF 1130 can easily exceed the 5 milliseconds allowed by the repetition rate.

[0110] As described in US20190103263A1, parallelizing the stages by pre-capturing ions in the high-pressure region of extraction trap 1120 while completing its sequence (ion cooling, 4kV boost, extraction to ToF) in the low-pressure region can buy some time. However, the rate determination step for ion transfer from the high-pressure region to the low-pressure region of extraction trap 1120 may still limit the reproducibility. Worse still, there may not be enough time for the quadrupole itself to transport ions, thus only a small amount of ion beam can be sampled (low duty cycle) unless there is a pre-accumulation step before the mass filter 1040. This is highly undesirable because space charge effects quickly become uncontrollable.

[0111] Careful use of the extraction trap according to this disclosure can significantly improve performance. Reference now. Figure 15 It schematically depicts Figure 14 An improved processing sequence for the mass spectrometer. (See illustration) Figure 14 The same reference numerals are used for the characteristic parts. Each operation is indicated by an arrow, ordered chronologically from left to right, and the vertical or horizontal position of the arrow indicates which ion pack occupies it at a given time.

[0112] The process simultaneously includes: a data correlation acquisition (DDA) source switch 1200; a fast quadrupole switching of ion pack 5 1210; filling time and capture in the collision chamber 1100 of ion pack 4 1230; transfer of ion pack 3 from the collision chamber 1100 to the high-pressure region 1121 of the extraction trap 1120 1240 and transfer of ion pack 3 from the high-pressure region 1121 of the extraction trap 1120 to the low-pressure region 1122 of the extraction trap 1120 1250; an extraction process of ion pack 2 via 4kV boost and extraction 1260; and ToF analysis of ion pack 1 1270. The maximum injection time is 4 milliseconds at a repetition rate of 200 Hz.

[0113] This method utilizes an additional capture stage adjacent to the quadrupole mass filter 1040, in this case, a collision cell 1100. Ions from the quadrupole 1040 can then accumulate in parallel with the transfer stage, and the slow transfer from the quadrupole 1040 to the low-pressure region 1122 of the extraction trap is divided into two much faster parallel steps 1230, 1240, and 1250.

[0114] As referenced above Figure 4 As discussed, in the collision cell transfer phase 1240, RF2 (the multipole applied to the high-pressure region 400) should have an amplitude set to accept the incoming ion packets. In contrast, in the low-pressure transfer phase 1250, RF1 (the multipole applied to the low-pressure region 300) and RF2 should have approximately equal amplitudes (although RF2 may be slightly higher than RF1) to facilitate barrier-free ion transfer from the high-pressure region to the low-pressure region.

[0115] exist Figure 15 In this study, a highly parallel phase sequence was used, involving simultaneous capture in five different ion packs and three pressurized regions. In this way, the quadrupole collision cell filling phase 1230 is fully parallel and has a minimum time of only about 1 millisecond, leaving 4 milliseconds available for ion filling at a 5-millisecond 200Hz sequence; the duty cycle is 80%. The remaining 20% ​​is more easily recovered through pre-capture before the mass filter 1040, as such a small amount is not necessarily so restrictive of the space charge, but caution should still be exercised. It should also be noted that the other phases are set to about 2 milliseconds, providing some overhead for more difficult ions or higher resting repetition rates. In principle, the parallelization of the extraction process 1260 (4kV boost) and the ToF analysis 1270 is not necessary at a 200Hz repetition rate, but is negligible compared to the other phases and allows for extended total ion cooling time in the extraction regions.

[0116] It should be emphasized that at 0.25x10 -3 mbar (0.025 Pa) to 2 x 10 -3 At the low pressure of the low-pressure region 1122 (mbar (0.2 Pa), if ions are transferred rapidly at low energy, the transfer phase 1250 can only be set to such a short time period. The ability to achieve this is a key advantage of the disclosed device. Even in the best-case scenario, the ideal implantation energy should still be at least 0.05 eV or higher to allow sufficient ion velocity to cover the distance and overcome well-controlled residual barriers caused by power supply noise and misalignment. Energy of at least 0.1 eV and even 0.5 eV is practical as ion implantation energy; higher energies of 2 eV or higher may work, but may sacrifice the advantages of the device.

[0117] The sequence includes a relatively long phase (3 to 5 milliseconds) for switching the source optics 1200. This is not a factor during data independent acquisition (DIA), provided that the transmitted m / z range is wider than the displacement between m / z values. However, in data correlated acquisition (DDA), where quadrupoles can produce very large m / z jumps between target peaks, this delay can be limiting. Based on the knowledge of the transmission time of the implanted ion m / z or the target range of any fragments, the controller can fix or dynamically modify the allowed time for each phase. It should be noted that there may often be some non-parallel overlap between parallel phases, for example, emptying the collision cell 1100 takes approximately 100 microseconds, and it should be understood that power supplies have their own switching times, which may further introduce some delay.

[0118] It should also be noted that, Figure 15In this figure, parallel processing is applied only along the chain to the MR ToF mass analyzer 1130 (ToF mode). The C-Trap 1070 and ion directors 1060 and 1110 are omitted from this figure because ions rarely pass through them and pass too quickly to be relevant to the timing scheme. When the instrument is running in ToF mode, the C-Trap 1070 may be disabled as a trap, instead becoming a very short ion director. The operation of the orbital trap mass analyzer 1090 is also not shown in this figure, but it breaks the chain and only involves filling the C-Trap 1070 or collision cell 1100, then returning the ions to the C-Trap 1070.

[0119] Referring again to the general meaning of this disclosure, the mass spectrometer can be implemented using additional devices. For example, at least one additional ion optics device can be disposed upstream of the second (multipolar) ion optics device. The at least one additional ion optics device can be configured for one or more of ion capture, ion selection (e.g., mass filtering), and ion processing (e.g., collision cell). The mass spectrometer further includes a mass analyzer located downstream of the first (multipolar) ion optics device. An additional ion extraction trap can be disposed upstream of the second (multipolar) ion optics device. The additional ion extraction trap can then be configured to selectively direct ions to the second (multipolar) ion optics device or to an upstream mass analyzer (e.g., to provide a mixed mass spectrometer, tandem mass spectrometer, or MS). n Configuration).

[0120] In one embodiment, at least one additional ion optical device is disposed upstream of the second (multipolar) ion optical device. The mass spectrometer may then further include a controller simultaneously configured such that: a first ion sample is stored (accumulated) and / or processed in the at least one additional upstream ion optical device; a second ion sample is stored in the second (multipolar) ion optical device; and a third ion sample is stored in or ejected from the first (multipolar) ion optical device. Optionally, the at least one upstream ion optical device may include two ion optical devices. The controller may then be simultaneously configured such that: a first ion sample is stored or processed in the first ion optical device among the two upstream ion optical devices; a second ion sample is stored or processed in the second ion optical device among the two upstream ion optical devices; a third ion sample is stored in the second (multipolar) ion optical device; and a fourth ion sample is stored in or ejected from the first (multipolar) ion optical device. The at least one upstream ion optical device may include a mass filter and / or a collision cell.

[0121] The mass spectrometer may further include a mass analyzer located downstream of a second (multipolar) ion optical device. The controller may then be further configured such that, while ions are stored and / or processed in at least one additional ion optical device upstream, the first (multipolar) ion optical device, and the second (multipolar) ion optical device, a further ion sample is analyzed in the mass analyzer.

[0122] According to another aspect of this disclosure (which may be combined with any other features of the aspects disclosed herein), a method for operating a mass spectrometer can be contemplated. The method includes: during a first time period, extracting a first ion sample from a first ion optical device in a relatively low-pressure region to a downstream ion processing device; during the first time period, processing a second ion sample in a second ion optical device in a relatively high-pressure region, the second ion optical device being located upstream of the first ion optical device and separated from the first ion optical device by a gas conduction region; and during the first time period, processing a third ion sample in a third ion optical device located upstream of the second ion optical device. Then, during a second time period immediately following the first time period, the method may further include transferring the second ion sample from the second ion optical device to the first ion optical device and transferring the third ion sample from the third ion optical device to the second ion optical device. Typically, one, some, or all of the first, second, and third ion optical devices are multipolar ion optical devices. The method can also be implemented as a mass spectrometer with a controller of corresponding configuration. The mass spectrometer may be the same as or may differ from the mass spectrometer disclosed herein (e.g., one or more of the ion optical devices may not be multipolar ion optical devices, and may be, for example, stacked ring ion guides, ion tunneling devices or ion optical devices including ion blankets).

[0123] In this method, at least three ion samples (or packets) are processed in parallel. For example, the processing may include receiving, confining, and transferring one or more of the ions (although it may also include cooling, mass selection, or analysis of the ions). Advantageously, this parallel processing of ions can be particularly advantageous for rapid instrument operation. Specifically, each of the first and second time periods may have a duration of no more than (and preferably less than) 5 milliseconds and may be 4 milliseconds or 3 milliseconds.

[0124] Preferably, the downstream ion processing device is a mass analyzer, which in some embodiments may be a time-of-flight mass analyzer or an orbital capture mass analyzer. For example, during the first time period, a fifth ion sample may be analyzed in the downstream ion processing device.

[0125] During the first time period, the third ion sample can be processed by impact cooling or mass selection. Optionally, the fourth ion sample can also be processed in a fourth ion optical device located upstream of the third ion optical device, and the processing can include impact cooling or mass selection. Additionally or alternatively, during the second time period, the fourth ion sample can be transferred from upstream (e.g., from the fourth ion optical device or an upstream ion source) to the third ion optical device.

[0126] In one embodiment, the first and second (and optionally, third) ion optics are aligned along a common axis. The extraction step can then include transferring the first ion sample orthogonally to the common axis into a downstream ion processing device.

[0127] Although embodiments of the present disclosure have been described with reference to specific types of apparatus and applications (specifically, mass spectrometers) and said embodiments have particular advantages in this case, as discussed herein, the methods according to the present disclosure can be applied to other types of apparatus and / or applications. The specific structure, arrangement, manufacturing details, and operational details (e.g., potentials) of mass spectrometers and / or ion extraction apparatuses and related uses, while potentially advantageous (especially considering known manufacturing constraints and capabilities), can vary considerably to achieve apparatus or modes of operation with similar or identical operation. Unless otherwise stated, each feature disclosed in this specification is interchangeable with alternative features for the same, equivalent, or similar purposes. Therefore, unless otherwise stated, each disclosed feature is merely one instance of a series of equivalent or similar attribute features.

[0128] As an alternative to wedge-shaped or cone-shaped auxiliary DC electrodes, the auxiliary DC electrode can be positioned at an angle to the axis defined by the length of the RF trapping electrode. Additionally or alternatively, auxiliary DC electrodes in low-pressure regions, which tend to form a potential trap at the extraction point to confine ions, can be provided in other forms, such as defined "needle" forms, as in US-10,734,210. Figure 2 As shown; or the first or second DC electrode form as described in co-pending UK patent application No. 2104522.4.

[0129] Although specific embodiments have been described above with respect to the first and second multipolar ion optical devices, each including a quadrupole, one or both of the multipolar ion optical devices may also include any other type of multipolar ion director, such as, for example, a hexapole, octapole, decapole, etc.

[0130] Furthermore, although embodiments have been described above with reference to the first and second multipolar ion optical devices, one or both multipolar ion optical devices can be replaced by any equivalent ion optical device that uses an RF field for confinement, including, for example, a stacked ring ion director, an ion tunneling device, or an ion optical device that includes an ion blanket.

[0131] A stacked ring ion director (or ion tunnel) device includes a plurality of perforated (e.g., ring) electrodes aligned along a central axis. An opposite phase of an RF voltage can be applied to adjacent perforated electrodes to create an ion-trapping region within the device. Optionally, an axial DC electric field can be formed within the ion-trapping region to propel ions in a direction parallel to the central axis.

[0132] An ion blanket (sometimes called an RF blanket) is a known configuration of electrodes that provides an ion-repelling surface, such that ion optics can be provided by combining it with another electrode or electrode arrangement, specifically, by providing another ion-repelling surface (which may be, for example, another ion blanket). For completeness, this configuration is explained further below.

[0133] The ion blanket of an ion optics device including an ion blanket may comprise a one-dimensional or two-dimensional electrode array. An opposite phase of an RF voltage can be applied to adjacent electrodes to create an ion-repelling surface. An ion-trapping region can be created between the ion blanket and the second ion-repelling surface by providing a second ion-repelling surface parallel to the ion blanket. The second ion-repelling surface may be formed by DC repelling electrodes arranged parallel to the ion blanket. Alternatively, the second ion-repelling surface may be formed by a second ion blanket arranged parallel to the first ion blanket. One or more additional DC and / or RF electrodes may be provided to provide additional ion trapping in other directions.

[0134] Now for reference Figure 16A The diagram schematically depicts a top view of an example configuration of two ion optics devices according to the present disclosure, each ion optics device including a corresponding ion blanket. Reference is also made to... Figure 16B The illustration shows Figure 16A A front view of an example is shown. It illustrates a first ion optical device 1200 under relatively low pressure and a second ion optical device 1250 under relatively high pressure. The first ion optical device 1200 is surrounded by a housing 1240, which acts as a gas conduction confinement, thereby restricting gas flow but providing an aperture that allows ions to pass from the second ion optical device 1250 to the first ion optical device 1200. Ion axis 1230 shows the general direction in which ions travel through the second ion optical device 1250 and into the first ion optical device 1200.

[0135] The first ion optical device (or ion guide) 1200 includes a first (top) ion blanket 1210 and a second (bottom) ion blanket 1220. The first ion blanket 1210 is advantageously formed by a plurality of electrodes arranged in a plane, wherein the plane is parallel to the ion axis 1230. The second ion blanket 1220 is parallel to the first ion blanket 1210 to form a trapping region between the first ion blanket 1210 and the second ion blanket 1220, wherein the ion axis 1230 passes through the trapping region. An aperture 1215 is provided in the first ion blanket 1210 to allow orthogonal jetting of ions from the first ion optical device 1200.

[0136] The second ion optical device (or ion guide) 1250 includes a third ion blanket 1260 and a fourth ion blanket 1270. Each of the third ion blanket 1260 and the fourth ion blanket 1270 includes an electrode arrangement extending into a plane perpendicular to the plane. Figure 16A The top view plane and perpendicular to Figure 16B The front view plane in the diagram. Therefore, the parallel planes of the third ion blanket 1260 and the fourth ion blanket 1270 are perpendicular to the parallel planes of the first ion blanket 1210 and the second ion blanket 1220.

[0137] Essentially, both the first ion optics 1200 and the second ion optics 1250 can be considered as classical planar ion tunnels with alternating RF phases (and a DC distribution for the axial field, not shown), but with the electrodes perpendicular to the ion motion rather than extending along it. The electrodes of both devices do not need to be particularly small. A spatial period of the electrodes that is two or more times smaller than the distance between the electrodes and the ions (e.g., based on ion axis 1230) may suffice. Ion confinement on ion axis 1230 can also be facilitated by an additional transverse DC voltage (not shown).

[0138] For example, to extract ions from the first ion optical device 1200, RF can be turned off and DC applied to emit ions through the electrode system, similar to... Figures 2 to 4 The implementation scheme shown is illustrated.

[0139] By placing the planar electrode assemblies perpendicular to each other, conductivity is limited at their intersections. In this way, housing 1240 can be used as a gas conduction limiting element similar to the previously described embodiments.

[0140] In such implementations, the exact configuration of each ion blanket can be varied. Furthermore, some ion blankets can be replaced by (planar) deflector electrodes, for example, providing a DC potential. For example, the first ion blanket 1210 and / or the third ion blanket 1260 can be replaced with such electrodes. The deflector electrodes can have a configuration similar to those used in the formation of… Figure 16A and 16BThe corresponding ion blankets have electrodes of roughly the same size and shape.

[0141] Therefore, returning to the general meaning of this disclosure discussed above, it is understood that, in certain embodiments, the first (low-pressure) ion optical device can and / or the second (high-pressure) ion optical device can be any of the following: (i) a multi-pole ion optical device (e.g., quadrupole, hexapole, octapole, decapole, etc.); (ii) a stacked ring ion guide (or ion tunnel) device; and (iii) an ion optical device comprising an ion blanket. The two ion optical devices can be of the same type or different types. When the two ion optical devices are of the same type, they can have different (e.g., vertical or orthogonal) orientations, which can include verticality in one dimension. As an example, the first ion optical device can include a first ion blanket oriented in a first plane, and the second ion optical device can include a second ion blanket oriented in a second plane orthogonal (or perpendicular) to the first plane. The first ion optical device can also include an electrode arrangement (which can include a DC electrode or another ion blanket) typically parallel to the first ion blanket. The ion trapping area of ​​the first ion optical device can thus be defined. The second ion optical device may further include an electrode arrangement (which may include a DC electrode or an additional ion blanket) typically parallel to the second ion blanket. The ion trapping region of the second ion optical device may thus be defined such that the ion axis may be defined by the overlap between the respective trapping regions of the first and second ion optical devices. A gas conduction constraint may include a housing surrounding at least a portion of the second ion optical device, thereby advantageously allowing ions to transport between the trapping regions of the first and second ion optical devices.

[0142] Advantageously, and as described above, the first ion optical device is configured to inject ions into a mass analyzer (i.e., the first ion optical device is configured as an extraction trap), while the second ion optical device is configured to accumulate and cool ions, and then transfer the accumulated and cooled ions to the first ion optical device for injection into the mass analyzer.

[0143] This aspect may (and in implementations) be combined with any one or more optional features described herein, including any one or more or each optional feature described above with respect to embodiments comprising first and second multipolar ion optical devices.

[0144] As used herein (included in the claims), unless the context otherwise indicates, the singular form of a term herein shall be construed as including the plural form, and vice versa. For example, unless the context otherwise indicates, a singular reference herein (included in the claims), such as “a / an” (e.g., an ion multipolar device), means “one or more” (e.g., one or more ion multipolar devices). In the description and claims of this disclosure, the words “comprise,” “including,” “having,” and “contain,” as well as variations of these words, such as “comprising” and “comprises,” or similar words, mean “including but not limited to” and are not intended to exclude other components.

[0145] Unless otherwise stated, the use of any and all instances or exemplary language (“for instance”, “such as”, “for example”, and similar language) provided herein is intended only to better illustrate the invention and does not constitute a limitation on the scope of the invention. No language in the specification should be construed as indicating that any unclaimed element is necessary for practicing the invention.

[0146] Unless otherwise stated or the context otherwise requires, any steps described in this specification may be performed in any order or simultaneously.

[0147] All aspects and / or features disclosed in this specification can be combined in any combination, except for at least some mutually exclusive combinations of such features and / or steps. As described herein, specific combinations of aspects may exist that have additional benefits, such as aspects for ion guides used in mass spectrometers and / or ion mobility spectrometers. Specifically, preferred features of the invention apply to all aspects of the invention and can be used in any combination. Similarly, features described in a non-essential combination can be used alone (not in combination).

Claims

1. A mass spectrometer, comprising: A first ion optical device in a relatively low-pressure region, the first ion optical device being configured to receive an RF voltage from a first RF power source for generating a first RF field that confines ions to a capture region of the first ion optical device; A second ion optical device in a relatively high-pressure region, the second ion optical device being configured to receive an RF voltage from a second RF power source for generating a second RF field that confines ions within a capture region of the second ion optical device; and A gas conduction restrictor, configured to restrict gas flow from the relatively high-pressure region to the relatively low-pressure region, the gas conduction restrictor having an aperture allowing ions to pass from the second ion optical device to the first ion optical device, wherein the inscribed radius of the aperture of the gas conduction restrictor is greater than the inscribed radius r0 of the first ion optical device and / or the second ion optical device; and The first RF power supply and the second RF power supply are independent to allow the RF voltage used to generate the first RF field to have a different amplitude than the RF voltage used to generate the second RF field.

2. The mass spectrometer of claim 1, wherein the first and second RF power supplies are configured to provide the RF voltage for generating the first RF field and the RF voltage for generating the second RF field having the same frequency and aligned phase.

3. The mass spectrometer according to claim 1 or claim 2, wherein the first and second RF power supplies are configured to provide the RF voltage to generate the second RF field to capture ions in the second ion optical device, and simultaneously configured to generate the RF voltage for generating the first RF field to eject ions from the first ion optical device.

4. The mass spectrometer according to claim 1 or 2, wherein the first ion optical device is a first multipolar ion optical device, and wherein the second ion optical device is a second multipolar ion optical device.

5. The mass spectrometer of claim 4, wherein at least one multipolar electrode of one or both of the first multipolar ion optical device and the second multipolar ion optical device has a lip extending toward the electrode of the other ion optical device.

6. The mass spectrometer according to claim 4, wherein: The first multipolar ion optical device includes: a first pair of opposing electrodes applied with the same RF voltage of the same amplitude and first phase, and a DC voltage of opposite polarity at a DC voltage level; and a second pair of opposing electrode arrangements, each of the opposing electrode arrangements including: a split RF electrode comprising two separate electrode components, the two separate electrode components being applied with the same RF voltage of the same amplitude and second phase opposite to the first phase, and a DC voltage of opposite polarity at a DC voltage level; and an auxiliary DC electrode located between the two separate electrode components of the split RF electrode; and / or The second multipolar ion optical device includes: a first pair of opposing electrodes to which the same RF voltage with RF amplitude and a first phase is applied; a second pair of opposing electrodes to which the RF amplitude and a second phase opposite to the first phase are applied; and an auxiliary DC electrode located between each of the first pair of opposing electrodes and a corresponding electrode of the second pair of opposing electrodes.

7. The mass spectrometer of claim 6, wherein the first multipolar ion optical device further comprises a bridge located between the first pair of opposing electrodes of the first multipolar ion optical device, such that the first RF field provides radial and axial confinement.

8. The mass spectrometer of claim 4, wherein the first and / or second multipolar ion optical device includes an insulating rod located between the multipolar electrodes of the ion optical device, the insulating rod extending from the inlet of the ion optical device to half the length of the ion optical device.

9. The mass spectrometer according to claim 1 or 2, wherein each of the first and / or second ion optical devices is one of: a multipolar ion optical device; a stacked ring ion guide; an ion tunneling device; and an ion optical device including an ion blanket.

10. The mass spectrometer of claim 9, wherein the first ion optical device includes a first ion blanket oriented in a first plane, and the second ion optical device includes a second ion blanket oriented in a second plane orthogonal to the first plane.

11. The mass spectrometer according to claim 1 or 2, wherein the gas conduction limiting element includes a diaphragm and / or the aperture of the gas conduction limiting element is larger than the first ion optics device.

12. The mass spectrometer according to claim 1 or 2, wherein there is no ion optical device with a radius smaller than that of the first and second ion optical devices between the first and second ion optical devices.

13. The mass spectrometer according to claim 1 or 2, wherein the mass spectrometer is configured to cause one or both of the following to occur: The buffer gas is introduced into the relatively high-pressure region through a capillary tube to achieve the desired pressure; and Select the pumping speed in the relatively low-pressure region to achieve the desired pressure in the relatively high-pressure region.

14. The mass spectrometer according to claim 1 or 2, wherein the first ion optics and / or the second ion optics includes an auxiliary DC electrode arranged to receive a DC potential in order to generate an axial DC gradient superimposed on the corresponding RF field.

15. The mass spectrometer of claim 14, wherein one or more of the following occurs: The auxiliary DC electrode gradually tapers along the axis of the corresponding ion optical device or forms an angle with the axis. The auxiliary DC electrodes are spaced apart by an equal radius around the corresponding ion optical device; The first ion optical device includes an electrode stack, wherein the auxiliary DC electrode is located at the center of the electrode stack; and The second ion optical device includes equally spaced RF electrodes for generating the RF field, and the auxiliary DC electrodes are interleaved between the RF electrodes.

16. The mass spectrometer according to claim 1 or 2, wherein the first and / or second ion optical device is formed by a stack of elongated electrodes separated by insulating pads.

17. The mass spectrometer of claim 1 or 2, wherein the first and second RF power supplies form at least a portion of a power supply system, the power supply system comprising: The core RF generator is configured to provide an RF waveform at a specific frequency; A first coil configuration is configured to receive the RF waveform and provide the RF voltage for generating the first RF field, the core RF generator and the first coil configuration defining the first RF power supply; as well as A second coil configuration is configured to receive an RF signal derived from the RF waveform and provide the RF voltage for generating the second RF field, the core RF generator and the second coil configuration defining the second RF power supply.

18. The mass spectrometer of claim 17, wherein the power supply system further includes a phase adjuster configured to receive a signal as the RF waveform or a waveform generated from the RF waveform, and based on the received signal, to provide the RF signal derived from the RF waveform to the second coil configuration by setting the phase of the RF signal to a desired level.

19. The mass spectrometer of claim 18, wherein the power supply system further includes a sampler configured to sample one of the RF voltages used to generate the first RF field from the first coil configuration, and to provide the waveform generated from the RF waveform to the phase adjuster based on the sampled RF voltage.

20. The mass spectrometer of claim 4, wherein one or more of the following occurs: At least one additional ion optical device, configured for one or more of ion trapping, ion selection and ion processing, is disposed upstream of the second multipolar ion optical device. The first ion optical device is configured to receive ions from the second ion optical device along the common axis of the first and second ion optical devices, and to allow the received ions to be extracted in a direction orthogonal to the axis. The mass spectrometer further includes a mass analyzer located downstream of the first ion optics device.

21. The mass spectrometer according to claim 1 or 2, wherein at least one additional ion optical device is disposed upstream of the second ion optical device, the mass spectrometer further comprising a controller configured such that: a first ion sample is stored and / or processed in at least one additional ion optical device upstream; a second ion sample is stored in the second ion optical device; and a third ion sample is stored in or ejected from the first ion optical device.

22. The mass spectrometer of claim 21, wherein the at least one upstream ion optical device comprises two ion optical devices, and the controller is simultaneously configured such that: the first ion sample is stored or processed in the first ion optical device of the two upstream ion optical devices; The second ion sample is stored or processed in the second ion optical device of the two upstream ion optical devices. The third ion sample is stored in the second ion optical device; Furthermore, the fourth ion sample is either stored in or ejected from the first ion optical device.

23. The mass spectrometer of claim 21, wherein the at least one additional ion optics device comprises a mass filter and / or a collision cell.

24. The mass spectrometer of claim 21, wherein the mass spectrometer further comprises a mass analyzer located downstream of the first ion optical device, and the controller is further configured such that: while ions are stored and / or processed in at least one additional ion optical device, the first ion optical device, and the second ion optical device upstream, an additional ion sample is analyzed in the mass analyzer.

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