HIGH-THROUGH MULTIRE-REFLECTIVE MASS SPECTROMETER

Abstract

An array of identical linear quadrupole ion traps, each trap comprising the following: at least four main electrodes (32, 33, 34, 35) extending in a Z-direction to form a quadrupolar field at least in the midline region aligned along the Z-axis, wherein the Z-axis is either straight or curved with a radius that is substantially larger than the distance between the said main electrodes (32, 33, 34, 35); an ion ejection slot (36) in at least one of the main electrodes (32, 33, 34, 35); wherein the slot (36) is oriented in the Z direction; a pair of electrostatic end plugs (37, 38) arranged at the Z-edges of the quadrupole ion trap; wherein the pair of end plugs (37, 38) are a segment of the main electrodes (32, 33, 34, 35) or ring electrodes; an RF generator that provides RF signals with opposite phases, to form a quadrupolar RF field at least in the midline region of the main electrodes (32, 33, 34, 35); a variable DC supply for supplying DC signals to at least two rods in order to form a quadrupolar DC field with a weaker dipolar DC field at least in the midline region of main electrodes (32, 33, 34, 35); a DC, RF or AC supply connected to the aforementioned pair of end plugs (37, 38) to provide axial Z-capture; a gas supply or pumping means for providing a gas pressure in the range of 1 to 100 mTorr [0.133 to 13.332 Pascal], wherein the variable DC supply has means for ramping up the said quadrupolar potential, whereby a sequential ion ejection via the slot (36) occurs in the inverse relationship to the ion m / z, wherein the array further comprises a wide-diameter RF channel (25) with a DC gradient for collecting, transferring and spatially confining ions behind the slots (36) of the quadrupole ion traps; wherein the dimension of said RF channel (25) is defined by the trap sizes of the quadrupole ion traps and the topology of the array and the gas pressure in the quadrupole ion traps, and wherein the individual quadrupole ion traps are oriented such that an ion emission surface is formed which is either planar or at least partially cylindrical or partially spherical for more efficient collection and transfer of ions in the wide diameter RF channel (25).

Description

[0001] The present disclosure relates to the field of mass spectroscopic analysis, multi-reflecting mass spectrometers, ion traps and tandem mass spectrometers for comprehensive all-mass MS-MS analysis. BACKGROUND MR-TOF with frequent pulsing

[0002] US 5017780 A, incorporated herein by reference, discloses multi-reflecting time-of-flight mass spectrometers with a folded ion trajectory (MRTOF). Ion confinement is improved with a set of periodic lenses. MR-TOF achieves resolutions in the range of 100,000. MR-TOF, in combination with an orthogonal accelerator (OA), exhibits a low duty cycle, typically below 1%. In combination with a trap converter, the space charge of ion packets influences the MR-TOF resolution, with the number of ions per packet per shot exceeding 1*10 3ions. This corresponds, considering a time of flight of 1 ms in MR-TOF, to a generally maximum signal below 1*10 6 per peak per second.

[0003] To improve both the duty cycle and the space charge throughput, WO 2011107836 A1, incorporated herein by reference, discloses an open-trap electrostatic analyzer in which ion packets are no longer confined in the drift direction, so that each mass species is represented by multiple signals corresponding to a range of different ion reflectance numbers. This method solves the problem of the duty cycle of OAs and the problem of space charge limitation in the MRTOF analyzer. However, spectral decoding fails for ion fluxes above 1*10 8 ions per second.

[0004] WO 2011135477 A1, incorporated herein by reference, discloses a coded frequent pulsing (EFP) method for solving the same problem in a generally more controlled manner and enabling extremely fast profiling of each previous separation, down to resolution times as low as 10 µs. The spectral decoding step is well suited for recording fragment spectra in tandem MS, as the spectral population is below 0.1%. However, when EFP MR-TOF is applied as a single mass spectrometer, spectral decoding limits the dynamic range to below 1*10 4 due to a densely populated chemical background.

[0005] Modern ion sources can provide mass spectrometers with up to 1*10 10 ions / sec (1.6 nA). The spectral population before any decoding approaches 30-50% when signals in the dynamic range of 1*10 5must be taken into account. State-of-the-art EFP methods are unsuitable for detecting large ion fluxes in the full dynamic range.

[0006] The present disclosure proposes an improvement of EFP-MR-TOF by: (a) using a prior lossless and coarse temporal mass separation; gas damping of the mass-separated ion flux; frequently pulsing an orthogonal accelerator with a time between ejection pulses that is far shorter than the flight time of the heaviest ions in MR-TOF; and using a detector with an extended dynamic range and lifetime to handle ion fluxes up to 1*10 10ions / sec. The lossless first cascade separator can be a trap array followed by a wide-bore ion transfer channel or a trap array with a pulsed converter with a wide-open crude TOF separator followed by a soft damping cell, primarily a surface-induced separation (SID) cell operating at low collision energies below 10–20 eV. Comprehensive MS-MS (C-MS-MS)

[0007] For reliable and specific analyte identification, tandem mass spectrometers operate as follows: Parent ions are selected in a first mass spectrometer and fragmented in a fragmentation cell, such as a collision-induced separation (CID) cell; then, fragment ion spectra are recorded in a second mass spectrometer. Conventional tandem instruments, such as quadrupole TOF (Q-TOF), filter a narrow mass range and reject all others. When analyzing complex mixtures, sequential separation of multiple m / z ranges slows acquisition and affects sensitivity. To improve the speed and sensitivity of MS-MS analysis, so-called “comprehensive”, “parallel” or “all-mass” tandems have been described: Trap-TOF in US 6504148 B1 and WO 01 / 15201 A2, TOF-TOF in WO 2004008481 A1 and LT-TOF in US 7507953 B2, all of which are incorporated herein by reference.

[0008] However, none of the state-of-the-art comprehensive MS-MS can solve the task of tandem MS improvement over filtering tandems, which contradicts the purpose of parallel MS-MS. Several limitations do not allow operation where the total ion flux of up to 1*10 10 ions / sec from ion sources. Thus, the gain of parallel analysis in the first MS is lost due to ion losses at the MS1 input, and the overall sensitivity and speed (primarily limited by signal intensity for smaller components) do not exceed those of conventional filtering Q-TOF.

[0009] Brief estimates are provided to support this statement. In Q-TOF, the duty cycle of MS1 is 1% to enable a standard resolution of R1=100 for parent mass selection. The duty cycle of TOF is on the order of 10–20% with a resolution of R2~50,000. Recent trends in MS-MS analysis demonstrate that such an R2 level offers a significant advantage in terms of MS-MS data reliability. Therefore, the lower R2 value should not be considered for MS-MS, so the lower limit for the TOF period is set at 300 µs. Thus, the overall advantages for the comparison are as follows: DC=0.1% and R=50,000, with an incoming ion flux of 1*10 10Ions / sec. In an exemplary MS-MS as described in US Pat. No. 7,507,953 B2, the time required to record fragment spectra of a single parent ion fraction is at least 1 ms (3 TOF spectra per parent mass fraction). To achieve R1=100 of parent mass separation, the scan time is not less than 100 ms. Considering a space charge capacity of a single linear ion trap of N=3*10 5 ions / cycle, the total charge throughput is 3*10 6 Ions / sec. Considering an input flow of 1*10 10At ions / sec, the total duty cycle of LT-TOF in US 7507953 B2 is 0.03%, which is lower than the Q-TOF tandem estimated above. Since the purpose and objective of parallel MS-MS are not met, the tandem of US 7507953 B2 is simply a combination of previously known solutions: LT to expand the space-charge capacity, an RF channel to transfer ion flux after the trap, TOF for parallel recording of all masses, and a trap-TOF tandem for parallel operation. Added to this is a new component: an RF channel to collect ions behind the linear trap.

[0010] The present disclosure proposes a solution to the task of comprehensive MS-MS analysis with an efficiency that far exceeds that of filtering tandems such as Q-TOF. The same tandem proposed above (lossless mass separator and EFP MR-TOF) further comprises a fragmentation cell between the mass spectrometric cascades. In a trap array, the attenuating wide-bore transfer channel is followed by a converging RF channel, such as an ion funnel, and the ions are introduced into a CID cell, consisting, for example, of an ohmic multipole for fast ion transfer. In the case of a coarse TOF separator, the SID cell with delayed pulsed extraction is used.

[0011] The proposed MS-EFP-MRTOF and MS-CID / SID-EFP-MRTOF tandems would suffer from the same problem (which defeats the purpose) if one of the tandem components fails, which controls the ion flux over 1*10 10Ions / sec during separation and 1*10 9 ions / sec during detection. Apparently, none of the state-of-the-art trap mass spectrometers, neither crude TOF separators, nor TOF detectors, nor data systems, can handle ion fluxes of 1*10 9 up to 1*10 10 ions / sec. New instruments become practical only with the introduction of several new components in the present invention. Parallel mass separators:

[0012] Analytical quadrupole mass analyzers (Q-MS) operate as a mass filter, passing one m / z species and removing all others. To improve the duty cycle, ion trap mass spectrometers (ITMS) operate in cycles – ions of all m / z are injected into the trap and then released sequentially by mass. Mass-dependent ion ejection is achieved by ramping the RF amplitude and with the assistance of the additional AC signal, which promotes the ejection of specific species by resonantly exciting their secular motion. The disadvantages of ITMS are a low scanning rate (100–1000 ms per scan) and a low space charge capacity – less than 3*10 3 in 3D traps and less than 3*10 5 in linear ion traps. Taking into account 0.1-1 sec per scan, the maximum throughput is less than 3*10 6 Ions / sec limited.

[0013] Q-trap mass spectrometers operate with mass-selective ejection via the repulsive trap edge. To eject ions across the edge barrier, a radial secular motion of ions with a specific m / z is selectively excited in a linear quadrupole. Due to the slow scanning (0.3–1 sec per scan), the throughput of Q-traps is below 3*10 6 ions / sec. The MSAE traps operate with a vacuum of 1*10 -5 Torr (0.00133322 Pa), which complicates downstream ion collection and damping.

[0014] The present disclosure proposes a novel mass separator comprising an array of radio frequency (RF) traps operating at elevated gas pressures of 10 to 100 mTorr (1.33 to 13.33 Pa) helium to trap ions emitted from a large area (e.g., 10 x 10 cm) within about 1 ms. In one embodiment, an individual trap is a new type of mass analyzer comprising a quadrupole radio frequency (RF) trap with radial ion ejection by a quadrupolar DC field. In one embodiment, the array can preferably be arranged on the cylinder centerline so that ions are injected into the cylinder. Alternatively, ion-emitting surfaces can be either planar or partially cylindrical or spherical.

[0015] In another embodiment, the TA (radio frequency trap array) comprises an array of linear ion traps with resonant and radial ion ejection. The array can preferably be arranged either on a cylindrical centerline, with the ejected ions trapped radially and driven axially in a cylindrical wide-bore gas damping cell. Alternatively, the array is arranged in a plane, with the ejected ions collected by a wide-bore ion funnel or an ion tunnel. The trap array can preferably be filled with helium at a gas pressure of 10-30 mTorr (1.33 to 4 Pa).

[0016] In one group of embodiments, a fragmentation cell, such as a CID cell, is proposed between said trap array and the EFP-MR-TOF for comprehensive all-mass MS-MS analysis.

[0017] Trap arrays with about 100 channels of 10 cm length can be 1*10 8ions per cycle. The EFP method allows rapid temporal profiling of the incoming ion flux with a temporal resolution of 10 µs, which in turn allows the TA cycle time to be reduced to 10 ms, thus increasing the throughput of the trap array to 1*10 10 ions / sec can be brought. Resistive ion guides

[0018] Fast ion transfer can be effectively achieved in RF ion guides with a superimposed axial DC gradient. State-of-the-art resistive ion guides suffer from practical limitations, such as the instability of thin resistive films or RF suppression in bulk ferrites. The present invention proposes an improved resistive ion guide employing bulk carbon-filled resistors made of SiC or B4C materials, improved RF coupling with DC-isolated traces, and a standard RF circuit with DC supply via central taps from secondary RF coils. TOF detectors:

[0019] Most current time-of-flight detectors, such as dual microchannel plates (MCPs) and secondary electron multipliers (SEMs), have a lifetime measurement of 1 coulomb of output charge. Considering a detector gain of 1*10 6The detector can operate for less than 1000 seconds at an ion flux of 1*10 10 A Daly detector has long been known, in which ions impinge on a metal converter and secondary electrons are collected by an electrostatic field onto a scintillator, followed by a photomultiplier tube (PMT). The lifetime of a closed PMT can be up to 300 °C. However, the detector introduces a significant delay (dozens of nanoseconds) and, due to the formation of negative secondary ions, spurious signals.

[0020] An alternative hybrid TOF detector comprises a sequentially connected microchannel plate (MCP), a scintillator, and a PMT. However, both the MCP and the scintillator fail below 1°C. Scintillators degrade due to the destruction of the submicron metal coating. Considering the lower gain of a single-stage MCP (1*10 3) the lifetime is extended to 1*10 6 Seconds (one month) at 1*10 10 Ions / sec flux.

[0021] To overcome the limitations of the prior art, the present disclosure proposes an isochronous Daly detector with an improved scintillator. Secondary electrons are guided by a magnetic field and directed onto a scintillator. The scintillator is covered with a metal grid to ensure charge removal. Two photomultipliers collect secondary photons at different solid angles, thus improving the dynamic range of the detector. At least one high-gain PMT has a conventional circuit for limiting the electron impact discharge current. The lifetime of the new detector is estimated to be over 1*10 7 Seconds (1 year) at 1*10 10 Ions / sec flux is estimated, making the tandems described above practical. Data system:

[0022] Conventional TOF MS operates with an integrating ADC, where the signal is integrated across multiple waveforms, synchronized with TOF start pulses. The data flow is proportionally reduced to a number of waveforms per spectrum that matches the speed of the signal transfer bus in a PC. Such a data system naturally meets TOF MS requirements, since weak ion signals require waveform integration to detect small species.

[0023] EFP-MRTOF requires the storage of time-history information of the rapidly changing waveform during the tandem cycle and the recording of long waveforms (up to 100 ms). Long waveforms can be summed during the integration time, which is still shorter than the time required for a chromatographic separation. When using gas chromatography (GC) with 1-second peaks, the integration time should be significantly shorter, for example, 0.1–0.3 seconds. This allows a limited number of waveforms (3–30) to be integrated. To reduce data flow over the bus, the signal can preferably be zero-filtered. Alternatively, a zero-filtered signal can be transferred to a PC in data logging mode, where non-zero data strings are recorded along with the laboratory timestamp.The signal is preferably analyzed on-the-fly and compressed either with a multi-core PC or with multi-core processors, such as video cards. Conclusion:

[0024] The proposed MS-only and C-MS-MS solution set is expected to achieve a high resolution of R2=100,000 and a high (~10%) duty cycle of MR-TOF for an ion flux of 1*10 10ions / sec, thus significantly improving a range of different mass spectrometric devices compared to the state of the art. DE 11 2010 005 323 T5 discloses a mass spectrometer with an open electrostatic trap for operation with extended and diverging ion packets. Furthermore, US 2013 / 0 048 852 A1 discloses a method for operating an open electrostatic trap (E-Trap) or a multi-pass TOF mass spectrometer with an extended trajectory. Finally, CN 101320016 A belongs to the field of quality analysis and relates in particular to a method for using a plurality of ion traps for tandem mass spectrometric analysis. SUMMARY

[0025] The invention is defined by independent claim 1. The proposed methods and devices are designed to overcome charge throughput limitations of state-of-the-art mass spectrometers and comprehensive tandem MS, thereby achieving an ion flux of up to 1*10 10 ions / sec and provide high-resolution (R>100,000) mass spectral analysis with a temporal resolution comparable to a chromatographic timescale of 0.1–1 sec. New methods and devices are proposed, along with several improved components, to achieve the same goal.

[0026] In one embodiment, a method for high charge throughput mass spectral analysis is proposed, comprising the following steps: (a) generating ions with a broad m / z range in an ion source; (b), in a first mass separator, crude temporal separation of an ion flow according to ionic m / z with a resolution between 10 and 100; and (c) mass spectral analysis with high resolution of R2>50,000 in a time-of-flight mass analyzer, triggered with a period much shorter than the ion flight time in the same time-of-flight separator to minimize or avoid spectral overlaps between signals, which is achieved by generating individual starts at an injection of ions with a narrower m / z window due to a temporal separation in the first separator.

[0027] The method may preferably further comprise an ion fragmentation step between said mass separation and mass analysis stages, wherein trigger pulses of said time-of-flight analyzer are time-coded for unique time intervals between each pair of trigger pulses within a time-of-flight period. Said coarse mass separation step may advantageously comprise temporal separation in a multi-channel ion trap or in a wide-bore spatially focused time-of-flight separator preceded by a multi-channel trap pulse converter.The method may preferably further comprise a step of bypassing said first separator for a period of time and admitting a portion of ion flow from said ion source into said high-resolution mass analyzer so that the most abundant ion species are analyzed without saturating the space charge of said TOF analyzer or avoiding saturation of a detector.

[0028] In another embodiment, a detailed method for high charge throughput mass spectral analysis is provided, comprising the steps of: (a) generating, for a chromatographically separated analyte flow, in an ion source, a plurality of ions in a wide ion m / z range and directing said ion flow at up to 1E+10 ions / sec into a radio frequency ion guide having an intermediate gas pressure; (b) splitting said ion flow between a plurality of channels of a radio frequency confinement ion buffer; (c) accumulating said flow in said ion buffer and periodically ejecting at least a portion of the accumulated ion ensemble into a multi-channel trap; (d) dampening ions in said multi-channel trap in collisions with helium gas at a gas pressure between 10 and 100 mTorr in a plurality of RF and DC trap channels;the number of said trapping channels N>10 and the length of individual channels L are chosen such that the product L*N>1m; (e) sequentially ejecting ions from said multi-channel trap progressively with ion m / z either in direct or reverse order, such that ions of different m / z are temporally separated with a resolution R1 between 10 and 100; (f) accepting the ejected and temporally separated ion flow from said multi-channel trap into a wide-open RF ion channel and driving ions with a DC gradient for rapid transmission with a temporal spread of less than 0.1-1 ms; (g) spatially confining said ion flow by RF fields, while maintaining the previously achieved temporal separation with a temporal spread of less than 0.1-1 ms;(h) forming a narrow ion beam with an ion energy between 10 and 100 eV, a beam diameter of less than 3 mm, and an angular divergence of less than 3 degrees at the entrance of an orthogonal accelerator; (i) forming ion packets with the orthogonal accelerator at a frequency between 10 and 100 kHz with a uniform pulse period or a pulse period encoded to form unique time intervals between said pulses; due to the coarse separation in step (e), the packets comprise ions with a mass range at least 10 times narrower than the initial m / z range generated in the ion source; (j) analyzing the ion flight time of the ion packets with an instantaneously narrow m / z range in multi-reflecting electrostatic fields of a multi-reflecting time-of-flight mass analyzer with an ion flight time for 1000 Th ions of at least 300 µs and a mass resolution above 50,000;and (k) recording signals after time-of-flight separation by a detector with sufficient lifetime to accept more than 0.0001 coulombs at the detector input.;

[0029] The method may preferably further comprise an ion fragmentation step between said sequential mass ejection steps and said high-resolution time-of-flight mass analysis step. The method may preferably further comprise a step of admitting and analyzing at least a portion of the original broad m / z range ion flow with said high-resolution TOF MS to extend the dynamic range and analyze large analyte species.Said step of coarse mass separation in the trap array (step of sequentially ejecting ions from said multi-channel trap) preferably comprises one step from the following list: (i) radial ion ejection from a linear RF quadrupole array through a quadrupolar DC field; (ii) resonant radial ion ejection from a linear RF quadrupole array; (iii) mass-selective axial ion ejection from an RF quadrupole array; (iv) mass-selective axial transmission in an array of RF channels with radial RF confinement, an axial RF barrier, and an axial DC gradient for ion propulsion, all formed by distributing DC voltage, RF amplitudes, and phases between a plurality of ring electrodes; and (v) ion ejection by a DC field from multiple quadrupolar traps fed by ions through an orthogonal RF channel.Said mass separator can preferably be arranged either on a planar or at least partially cylindrical or spherical surface, wherein said separator can be geometrically matched with ion buffers and ion collection channels of the appropriate topology. Said coarse mass separation step can preferably be carried out in helium at a gas pressure of 10 to 100 mTorr (1.33 to 13.33 Pa) to accelerate ion collection and transfer the ions past said coarse mass separation step.The method may preferably further comprise a step of additional mass separation between said step of sequential ion exchange and the step of orthogonal ion acceleration into a multi-reflecting analyzer, wherein said step of additional mass separation comprises one step selected from the following list: (i) mass-dependent sequential ion ejection from an ion trap or trap array; (ii) mass filtering in a mass spectrometer, wherein said mass filtering is mass-synchronized with said first mass-dependent ejection.

[0030] In yet another embodiment, a tandem mass spectrometer device is provided, comprising: (a) a comprehensive multi-channel trap array for sequential ion exchange according to their m / z in T1=1 to 100 ms time with a resolution R1 between 10 and 100; (b) an RF ion channel with a sufficiently wide entrance bore for collecting, quenching, and spatially confining most of said ejected ions at 10 to 100 mTorr gas pressure; wherein said RF ion channel has an axial DC gradient for a sufficiently short temporal spread ΔT <T1 / R1 aufweist, um die zeitliche Auflösung des ersten umfassenden Massenseparators zu unterstützen; (c) einen multireflektierenden Flugzeit-(MR-TOF)-Masseanalysator; (d) einen Orthogonalbeschleuniger mit häufig codierter gepulster Beschleunigung, platziert zwischen der genannten Mehrkanalfalle und dem genannten MR-TOF-Analysator;(e) a clock generator for generating start pulses for said orthogonal accelerator, wherein the period between said pulses is at least 10 times shorter than the time of flight of the heaviest m / z ions in said MR-TOF analyzer, and wherein the time intervals between said pulses are the same or coded for unique intervals between any pair of pulses in the time of flight period; and (f) a time-of-flight detector with a lifetime of more than 0.0001 coulombs of the input ion flux.

[0031] Said apparatus may preferably further comprise a fragmentation cell between said multi-channel trap array and said orthogonal accelerator. Preferably, said multi-channel trap array comprises a plurality of traps of a group: (i) a linear RF quadrupole with a quadrupolar DC field for radial ion ejection; (ii) a linear RF quadrupole for resonant radial ion ejection; (iii) an RF quadrupole with an axial DC plug for mass-selective axial ion ejection; (iv) ring electrodes with distributed DC voltages, RF amplitudes, and phases between electrodes for forming an RF channel with radial RF confinement, an axial RF barrier, and an axial DC gradient for ion propulsion; and (v) a quadrupolar linear trap fed by ions through an orthogonal RF channel for ion ejection by a DC field through an RF barrier.Said mass separator array may preferably be arranged either on a planar or at least partially cylindrical or spherical surface, wherein said separator is geometrically matched to ion buffers and ion collection channels of the appropriate topology.

[0032] In another embodiment, an array of identical, linearly extending quadrupolar ion traps is provided, each trap comprising: (a) at least four main electrodes extending in a Z-direction to form a quadrupolar field at least in the centerline region oriented along the Z-axis; (b) said Z-axis being either straight or curved with a radius much greater than the distance between said electrodes; (c) an ion ejection slit in at least one of said main electrodes; said slit being oriented in said Z-direction; (d) Z-edge electrodes located at Z-edges of said quadrupolar trap to form electrostatic ion plugging at said Z-edges; said Z-edge electrodes being a segment of the main electrodes or ring electrodes;(e) an RF generator producing RF signals of opposite phases to form a quadrupolar RF field at least in the centerline region of main electrodes; (f) a variable DC supply providing DC signals to at least two rods to form a quadrupolar DC field with a weaker dipolar DC field at least in the centerline region of main electrodes; (g) a DC, RF, or AC supply connected to said Z-edge electrodes to achieve axial Z-trapping; (h) a gas supply or pumping means for providing gas pressure in the range of 1 to 100 mTorr (1.33 to 13.33 Pa); (i) wherein said variable DC supply comprises means for ramping said quadrupolar potential to thereby cause sequential ion ejection across said slit in inverse relationship to the ion m / z;and (j) wherein said trap array further comprises a wide-bore DC gradient RF channel for collection / detection, transfer, and spatial confinement of ions behind said quadrupolar trap slits; wherein the dimension of said RF channel is defined by trap sizes and topology and gas pressure.

[0033] Said individual traps may preferably be aligned to form an ion emission surface that is either planar or at least partially cylindrical or partially spherical for more efficient collection / capture and transfer of ions in said wide bore RF channel.

[0034] In another embodiment, an ionic conductor is proposed comprising: (a) electrodes extending in a Z-direction; said Z-axis is either straight or curved with a radius much greater than the distance between said electrodes; (b) said electrodes being made of either carbon-filled ceramic resistors or silicon carbide or boron carbide to form a bulk resistor with a resistivity between 1 and 1000 ohm*cm; (c) conductive Z-edges on each electrode; (d) an insulating coating on one side of each rod; said coatings being oriented away from the interior region of the conductor surrounded by said electrodes; (e) at least one conductive track per electrode, attached to the top of said insulating coating; said conductive track being connected to a conductive electrode edge;(f) an RF generator having at least two sets of secondary coils, with DC supplies connected to central taps of said sets of secondary coils; so as to provide at least four separate signals DC1+sin(wt), DC2+sin(wt), DC1-sin(wt), and DC2-sin(wt); said signals being connected to electrode ends to produce an alternating RF phase between adjacent electrodes and an axial DC gradient along the electrodes;

[0035] Said DC voltages can preferably be pulsed or rapidly adjusted, with a time constant equal to or longer than the period of said RF signal. Said electrodes are preferably either circular rods or plates.

[0036] In another embodiment, a long lifetime time-of-flight detector is provided, comprising: (a) a conductive converter surface exposed parallel to the time front of detected ion packets and generating secondary electrons; (b) at least one electrode with a side window; (c) said converter being negatively floated compared to surrounding electrodes, with a voltage difference between 100 and 10,000 V; (d) at least two magnets with magnetic field strengths between 10 and 1,000 Gauss for bending electron trajectories; (e) a scintillator positively floated with respect to said converter surface at 1 kV to 20 kV and located behind said electrode window at 45 to 180 degrees relative to said converter; and (f) a closed photomultiplier tube behind the scintillator.

[0037] Said scintillator is preferably made of antistatic material or said scintillator is covered with a grid to remove charge from the scintillator surface.

[0038] All the above aspects of the invention appear necessary to provide the general and detailed method and apparatus without loss of target performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Various embodiments of the present invention, together with an arrangement given for illustrative purposes only, will now be described by way of example and with reference to the accompanying drawings, in which: Fig. Figure 1 is a schematic diagram of a preferred embodiment in a very general form, which is also used to illustrate two general methods of the invention - the dual-cascade MS and the comprehensive MS-MS method; Fig. Figure 2 shows a schematic diagram of a preferred embodiment with the trap array separator and the multi-reflecting TOF (MR-TOF) mass spectrometer operating with coded frequent pulses (EFP); two particular embodiments with planar and cylindrical trap array arrangements are shown. Fig. 3 a schematic of a new quadrupolar trap with sequential ion ejection by a quadrupolar DC field; Fig. 4A a stability diagram in quadrupolar traps to illustrate the operation procedure of the trap of Fig. 3; Fig. 4B Results of an optical ion simulation of the Fig. 3 shown trap during ion ejection with a quadrupolar field at elevated gas pressures; Fig. 4C Results of an optical ion simulation of the Fig. 3 shown trap with a resonant ion ejection at elevated gas pressures; Fig. 5 a scheme of a trap separator with an axial RF barrier, also accompanied by axial distributions of RF and DC fields; Fig. Figure 6 is a schematic of a new linear RF trap with a lateral ion supply via an RF channel; Fig. Figure 7 is a schematic of a synchronized double trap array, optionally followed by a synchronized mass separator; Fig. 8 an exemplary mechanical design of the cylindrical trap array; Fig. 9 shows an exemplary design for components that support the cylindrical trap array of Fig. 8 surrounded; Fig. 10 an electrical scheme for an improved ohmic ion conductor; and Fig. 11 a schematic of a new TOF detector with extended lifetime.

[0040] The same reference symbols indicate similar elements in the different drawings. DETAILED DESCRIPTIONGeneral procedure and design

[0041] With reference to Fig. 1, which shows a block diagram, a mass spectrometer 11 of the present invention comprises: an ion source 12; a high-throughput coarse and comprehensive mass separator 13; a time separator flow conditioner 14; a frequently coded pulse (EFP) accelerator 16; a multi-reflecting time-of-flight (MR-TOF) mass spectrometer 17; and an extended-lifetime ion detector 18. Optionally, a fragmentation cell 15, such as a CID or SID cell, is inserted between said conditioner 14 and said pulsed accelerator 16. The mass spectrometer 11 further includes several standard components (not shown), such as a vacuum chamber, pumps and walls for differential pumping, RF conductors for coupling between stages, DC, RF power supplies, pulse generators, etc. The mass spectrometer also includes components not yet shown that are specific to each particular embodiment.

[0042] It is understood that the high-throughput mass spectrometer of the invention is primarily designed for combination with a chromatographic pre-separation, such as liquid chromatography (LC), capillary electrophoresis (CE), single- or double-stage gas chromatography (GC and GCxGC). Furthermore, it is understood that a variety of different ion sources can be used, such as electrospray (ESI), atmospheric pressure chemical ionization (APCI), atmospheric and intermediate pressure photochemical ionization (APPI), matrix-assisted laser desorption (MALDI), electron impact (EI), chemical ionization (CI), or a conditioned glow discharge ion source, as described in WO 2012024570 A2.

[0043] In a preferred method, referred to herein as “dual cascade MS”, an ion source 12 generates an ion flow comprising several species of the analyzed compounds within a broad m / z range, such as a rich chemical background forming several thousand species, with a level of 1*10- 3 up to 1*10 -5 compared to major species. The m / z multiplicity is represented by m1, m2, m3, shown below Source Box 12. Typical ion currents of 1-2 nA (ie 1*10 10Ions / sec) are introduced into the radio frequency (RF) ion guide at intermediate gas pressures of 10–1000 mTorr (1.33 Pa to 133.32 Pa) of air or helium (for GC separation). The continuous ion flow is admitted to a crude and comprehensive separator 13, which converts the entire ion flow into a time-separated sequence aligned by ion m / z. "Comprehensive" means that most m / z species are not rejected but are instead separated temporally over a period of 1 to 100 ms, as depicted by a symbolic icon below box 14. Certain comprehensive separators (C-MS), such as various trap array separators, are described below, while certain TOF separators are described in a separate co-dependent application.To reduce space charge limitations, the C-MS separator preferably comprises multiple channels, as indicated by several arrows connecting boxes 12, 13, and 14. The temporally separated flow enters the conditioner 14, which slows the ion flow and reduces its phase space, symbolized by a triangle in box 14. The conditioner is designed to have a minor to negligible effect on the temporal separation. Various conditioners are described below, such as wide-bore RF channels followed by a converging RF channel. A pulsed accelerator 16 operates at a high frequency of approximately 100 kHz, optionally with coded pulse intervals, as shown in the icon below box 16. The accelerator 16 frequently injects ion packets into the MR-TOF analyzer 17.Since the instantaneous ion flux is represented by a relatively narrow m / z range, corresponding to a narrow time-of-flight interval in MR-TOF, frequent ion injection without spectral overlaps can be provided on the MR-TOF detector 18, as shown in signal field 19. The fast operation of the accelerator can be either periodic or, preferably, EFP-encoded, e.g., to avoid systemic signal overlaps with pick-up signals from the accelerator. The direct ejection sequence (heavy ions arrive later) of the separator 13 is preferred, as overlaps are avoided even at maximum separation speed. If the separator speed is not a priority, the reverse ejection sequence (heavy m / z arrive first) is possible.

[0044] Due to the coarse temporal separation in the first MS cascade, the MR-TOF of the second cascade can be operated at high frequency (~100 kHz) and a high duty cycle (20-30%) without overloading the space-charge capacity of the MR-TOF analyzer and without saturating the detector. Thus, the described dual-stage MS, i.e., the tandem of coarse separator 13 and high-resolution MR-TOF 17, results in mass analysis with a high overall duty cycle (dozens of percent), at a high MR-TOF resolution (50,000-100,000), with an extended space-charge throughput of the MR-TOF, and without stress requirements on the dynamic range of detector 18.

[0045] In a numerical example, the first mass spectrometer 13 separates an ion flow with a resolution of R1=100 in a time of 10 ms, i.e., a single m / z fraction arrives at an accelerator 16 during 100 µs; the time of flight for the heaviest m / z in MR-TOF is 1 ms; the accelerator operates with a pulse period of 10 µs. Then, a single m / z fraction would correspond to 10 pulsed accelerations, and each pulse would generate a signal corresponding to a signal train of 5 µs. Obviously, the signals from neighboring pulses (duration of approximately 10 µs) do not overlap at the detector 18. An ion flow of 1*10 10 Ions / sec is between 1*10 5 pulses per second, which is 1*10 4ions per pulse into the MR-TOF, which represents a realistic accelerator efficiency (described below). Fast pulsing lowers the analyzer's space charge limitations and prevents saturation of the detector's dynamic range. The sampling rate of the first cascade can be accelerated to 1 ms (e.g., when using a TOF separator) or slowed to 100 ms (e.g., for implementing double-stage trap separators), which still does not affect the described principle, as long as the first separator has sufficient charge capacity per sampling period to achieve the desired charge flow of 1*10 10 ions / sec, which will be analyzed in the following description of certain separator designs.

[0046] The dynamic range of dual-stage MS 11 can be further improved by switching between dual-MS and single-MS modes. At one time, at least a portion of the original ion flux can be injected directly into the MR-TOF analyzer operating in either the EFP or standard accelerator mode to record signals for larger ionic components, albeit at a low duty cycle, while still generating sufficiently strong signals for large components.

[0047] In another preferred method, the coarse C-MS separator 13 generates a temporally separated ion flux aligned by ion m / z. The flux is directed directly or via a conditioner 14 into a fragmentation cell 15. The cell 15 induces ion fragmentation for parent ions within a relatively narrow momentarily m / z window. The flux of fragment ions is preferably conditioned to reduce the flux phase space and then pulsed into the MR-TOF 17 by the accelerator 16, which operates at a fast average rate of 100 kHz. The pulse intervals of the accelerator 16 are preferably encoded to establish unique time intervals between each pulse pair. For example, the time of the current pulse numbered j is defined as T(j) = j*T1 + j(j-1)*T2, where T1 = 10 µs and T2 = 5 ns.The coded frequent pulsing (EFP) method is described in WO 2011135477 A1, which is incorporated herein by reference. The signal at the MR-TOF detector has spectral overlaps because fragment ions are formed in a wide m / z range. The exemplary detector signal segment is shown in panel 20, where two series of signals for ion fragments of different m / z are shown and labeled F1 and F2. However, efficient spectral decoding is expected because the instantaneous spectral population is significantly reduced compared to standard EFP-MR-TOF.

[0048] Note that the parent mass resolution can be further increased using the so-called time deconvolution procedure. Indeed, extremely fast OA pulsing and recording long spectra with a duration matching the cycle time of separator 13 allow the time profiles of individual mass components to be reconstructed with a temporal resolution of 10 µs. Fragment and parent peaks can then be temporally correlated, allowing neighboring fragment mass spectra to be separated with a temporal resolution lower than the temporal width of the parent ion ejection profile downstream of separator 13. The deconvolution principles were developed for GC-MS in the late 1960s by Klaus Bieman.

[0049] In a numerical example, the first separator forms a time-separated m / z sequence with a resolution of R1=100 and a duration of 10–100 ms. An MR-TOF with a 1 ms time-of-flight operates with EFP pulsing at an average repetition rate of 100 kHz. Long spectra are acquired corresponding to the entire MS-MS cycle, which can be summed for several cycles if chromatographic timing allows. The fragment spectrum per m / z fraction of parent ions lasts 0.1–1 ms and corresponds to 10–100 accelerator pulses, which should be sufficient for spectral decoding. The method is well suited for the analysis of several small analyte components. However, for large analyte components, the instantaneous flux can be concentrated up to 100 times. Even taking into account signal partitioning between multiple fragment peaks, the instantaneous maximum number of ions per shot can be as high as 1*10 4 up to 1*10 5Ions on the detector are greater than both the space charge capacity of the MR-TOF analyzer and the dynamic range of the detector. To increase the dynamic range, the C-MS-MS Tandem 11 can be operated in alternating mode, where the signal intensity is either suppressed or temporally dispersed for a period of time. Alternatively, automatic space charge suppression can be incorporated into the MR-TOF analyzer so that intense ion packets are spatially dispersed and transmitted with lower transmission. The advantages of Tandem 11 in terms of charge throughput and speed are demonstrated in the following description. Main effects of the procedure 1. In a dual-cascade MS procedure, a coarse upstream mass separation allows pulsing of MR-TOF at a high repetition rate without spectral overlap, allowing large ion fluxes up to 1*10 10ions / sec with a high duty cycle (20-30%), a high overall resolution of R2=100,000, and without stressing the instrument's space charge and detector limits. For clarity, we refer to this operating mode as "Dual-MS." 2. In a comprehensive MS-MS (C-MS-MS) procedure, tandem mass spectra can be obtained for all parent ions at an ion flux of up to 1*10 10 Ions / sec with a duty cycle of approximately 10%, a parent ion resolution of R1=100 and a fragment spectral resolution of R2=100,000 without stressing the space charge limits of the MR-TOF analyzer and without stressing the dynamic range of the detector. 3. In C-MS-MS mode, the resolution of parent mass separation can be further improved by temporal deconvolution of fragment spectra, similar to deconvolution in GC-MS. Two-dimensional deconvolution would also take chromatographic separation profiles into account. 4. Both methods, dual-MS and C-MS-MS, can be performed in the same device 11 simply by adjusting ion energy at the entrance of the fragmentation cell and / or by switching between low and high duty cycle modes of accelerator operation. 5. Tandem operation and the EFP method are used to detect multiple small analyte components on a chromatographic timescale. For a period of time, the same device can be used in the conventional mode to detect signals from large components, thus further improving the dynamic range. Example with a trap array

[0050] With reference to Fig. 2, which shows a block diagram, a mass spectrometer 21 of the present invention comprises an ion source 22, a multi-channel accumulating ion buffer 23, an array of parallel ion traps 24, a wide-bore dampening RF ion channel 25, an RF ion guide 26, an orthogonal frequently coded pulse (EFP) accelerator 27, a multi-reflecting mass spectrometer 28, and an extended-lifetime ion detector 29. Optionally, the ion guide 25 can serve as a fragmentation cell such as the CID cell. The mass spectrometer 21 further includes several standard components (not shown) such as a vacuum chamber, pumps and walls for differential pumping, RF guides for coupling between stages, DC and RF power supplies, pulse generators, etc.

[0051] Two configurations, 21 and 21C, are shown, which differ in the topology of the buffer and trap array, corresponding to planar 23, 24 and cylindrical 23C, 24C arrangements. A planar emission surface of the trap array 24 can also be curved to partially form a cylindrical or spherical surface. In the cylindrical arrangement 21C, the trap 24C ejects ions inward, and the inner part of the cylinder serves as a wide-bore ion channel, equipped with resistive RF rods to accelerate ion transfer through an axial DC field. Otherwise, both configurations 21 and 21C operate similarly.

[0052] During operation, ions are formed in the ion source 22, which is usually preceded by a suitable chromatographic separator. The continuous and slowly varying (time constant is 1 second for GC and 3-10 seconds for LC) ion flow comprises several species of the analyzed components, such as a rich chemical background containing several thousand species at a level of 1*10 -3 up to 1*10 -5 compared to the main species. Typical ion currents of 1-2 nA (ie 1*10 10 Ions / sec) are fed into high-frequency ion guides at intermediate gas pressures of 10-100 mTorr (1.33 Pa to 13.33 Pa) of air or helium (GC case).

[0053] The continuous ion flow is distributed between multiple channels by the ion buffer 23 with radio frequency (RF) ion confinement operating at intermediate gas pressures of 10 mTorr to 100 Torr (1.33 Pa to 13332.2 Pa). Helium gas is preferably used to tolerate higher ion energies in the mass ejection step. The buffer 23 continuously accumulates ions and periodically (every 10-100 ms) transfers most of the ion content to the trap array 24. The ion buffer 23 can comprise various RF devices, such as an array of RF-only multipoles, an ion channel, or an ion funnel, etc. To support an ion flow of 1*10 10 ions / sec the buffer must be filled every 100 ms up to 1*10 9 ions. For example, a single RF quadrupole of 100 mm length can capture up to 1*10 7 up to 1*10 8Accommodate ions. Thus, the ion buffer should comprise tens to tens of individual quadrupole ion guides. Preferably, quadrupole rods are aligned on two coaxial centerline surfaces. Preferably, quadrupole rods are resistive (ohmic) to enable controlled ion ejection via an axial DC field. It may be more practical to use coaxial ion channels, ion tunnels, or ion funnels. Such devices preferably include means for generating an axial DC field for controlled ion ejection. An improved resistive multipole is described below.

[0054] The trap array 24 periodically admits ions from the ion buffer 23. Ions are expected to be distributed between multiple channels and along the channels by self-space charge on timescales of 1-10 ms. When the trap array 24 is full, the trap potentials are ramped to achieve mass-dependent ion ejection, thereby forming an ion flow in which ions are ejected sequentially according to their m / z ratio. In one embodiment, the trap channels are aligned on a cylinder centerline. Ions are injected into the cylinder into a wide-bore channel 25 with RF ion confinement and an axial DC field for rapid ion evacuation on a timescale of 0.1-1 ms. The RF channel 25 has a converging cross-section. Several embodiments of trap arrays 24 and RF channels 25 are described below.To discuss the operating principles of the entire set, assume that the trap array allows temporal separation of ion flux with a mass resolution of 100 within 10-100 ms cycles, i.e., each separated fraction has a time duration of 0.1-1 ms.

[0055] From a converging cross-section of the RF channel 25, ions enter the ion guide 26, which is typically configured as a differentially pumped chamber and operates at gas pressures of 10-20 mTorr (1.33 Pa to 2.66 Pa). The ion guide 26 preferably comprises a resistive quadrupole or a multipole. Exemplary ion guides are described below. The guide continuously transfers ions with a time delay of approximately 0.1-0.2 ms and a temporal duration of substantially less than 0.1 ms. For example, a 10 cm multipole guide operating at 5 V DC at 10 mTorr (1.33 Pa) helium would transfer ions in approximately 1 ms and yet induce no fragmentation. The temporal duration for ions with a narrow m / z range is expected to be 10-20 µs.The guide is followed by a standard (for MR-TOF) ion optic (not shown), which allows for gas pressure reduction and forms a substantially parallel ion beam with an ion energy of 30 to 100 eV (depending on the MR-TOF design). The parallel ion beam enters an orthogonal accelerator 27.

[0056] The accelerator 27 is preferably an orthogonal accelerator (OA) oriented substantially orthogonal to the plane of the ion path in the MR-TOF 28, allowing the use of a longer OA, as described in US 20070176090 A1, which is incorporated herein by reference. An MR-TOF analyzer is preferably a planar multi-reflecting time-of-flight mass spectrometer with a set of periodic lenses, as described in WO 2005001878 A2. With a typical OA length of 6-9 mm (depending on the MR-TOF mirror design) and a typical ion energy of 50 eV, ions of m / z=1000 have a velocity of 3 mm / µs and pass through the OA within 2-3 microseconds. With current technology, high-voltage pulse generators can be pulsed at up to 100 kHz (pulse period 10 µs), which brings the duty cycle of the OA to 20-30%. If ion separation in the trap array 24 is excluded, the time-of-flight spectra can overlap significantly.Taking into account the trap separation, the incoming ion beam has a narrow mass fraction, i.e. from 1000 to 1010 amu (1.66054*10. -15 up to 1.67714*10 -15 micrograms). A typical time-of-flight in MR-TOF 28 is 1 ms, so each individual OA pulse would generate signals between 1 and 1.005 ms. Thus, the OA can be pulsed with a 10 µs period without generating ion spectral overlaps. Thus, the pre-mass separation in the first MS cascade allows MR-TOF to be pulsed at a high repetition rate without spectral overlaps, while achieving an overall duty cycle of approximately 10%, considering an OA duty cycle of 20-30% and 2-3 times the beam collimation losses before the OA. The instrument then records spectra of an input flux of 1*10 10 ions / sec and an ion flux of 1*10 9ions / sec at the MR-TOF detector 29 at 10% total duty cycle and at R2=100,000 resolution, supporting the detection of small analyte components with chromatographic timing.

[0057] A high (10%) duty cycle of the instrument 22 places a strain on the dynamic range at the upper end. In dual-cascade MS mode, the strongest ion packets (assuming a high concentration of a single analyte) can be up to 1*10 6ions per shot, taking into account a 100-fold temporal concentration in separator 22, 100 kHz OA frequency, and 10% efficiency of OA operation. Such packets would definitely overload the MR-TOF space charge capacity and the dynamic range of the MR-TOF detector. The invention proposes a solution: The instrument 22 supports two modes – double-cascade MS mode for recording weak analyte components and a standard operating mode, where an ion flow is injected directly from the ion buffer 23 into the RF channel 25, e.g., during the loading time of the trap 24. In the standard operating mode, the maximum ion packet would be approximately 1*10 4Ions, i.e., at the edge of the MR-TOF space charge capacity. For completely safe operation, the detector should have overload protection, e.g., through limiting circuits in the final PMT stages. An additional layer of protection is preferably provided by space charge repulsion in the MR-TOF analyzer 28, controlled by the strength of the periodic lens in the analyzer.

[0058] Again with reference to Fig. 2, the same tandem 21 can be operated as a comprehensive MS-MS by activating ion fragmentation, e.g., by inducing ions with sufficiently high (20-50 eV) ion energy into the resistive ion conductor 26, thus effectively converting it into a CID cell. During operation, the time-separated flow of parent ions occurs in a narrow m / z range (e.g., 5 amu (8.3027*10 -18 micrograms) for net 500 amu (8.3027*10 -16 micrograms) and 10 amu (1.6605*10 -17 micrograms) for net 1000 amu (1.6605*10 -15micrograms) enters the CID cell 26 within approximately 0.1-1 ms. The mass window is slightly wider than the width of isotopic groups. The group enters a fragmentation cell and forms fragment ions, e.g., by collisional dissociation. The fragments continuously enter the OA 26. The OA is operated in EFP mode, as described in WO 2011135477 A1. Briefly, the pulse intervals are encoded with a non-uniform time sequence, e.g., as Ti = i*T1 + i(i+1) / 2*T2 with typical T1=10 µs and T2=10 ns. Although fragment spectra overlap, the overlap of any peak pair is not systematically repeated. Standard-type TOF spectra are recovered in the spectral decoding step, taking into account pulse intervals and analyzing overlaps between peak series. Due to the limited spectral population characteristic of fragment spectra, EFP spectral decoding is effective.Consequently, fragment spectra are obtained for all parent species with a parent resolution power of R1~100, a fragment resolution power of R2~100,000, with about 10% total duty cycle and handling ion fluxes up to 1*10. 10 ions / sec recorded.

[0059] Let us estimate the dynamic range of the C-MS 2 The maximum ion packet can be up to 1*10 4 ions, taking into account a total ion flux of 1*10 10 ions / sec, a maximum of 10% signal content in the large analyte component (there is no need for C-MS-MS when considering large components), a 100-fold temporal compression in separator 23, a 10% total duty cycle of the OA 27 (also taking into account spatial ion losses upstream of the OA), and a 100 kHz pulse rate of the OA. Such strong ion packets would be recorded at lower resolution in MR-TOF. However, the mass accuracy in MR-TOF is known to be 1*104 ions per packet. Additional protection can be achieved by lowering the periodic lens voltage for automatic suppression of strong signals through self-space charge repulsion in the MR-TOF analyzer. To detect strong signals, the resolution (and thus the temporal signal concentration) of the first separator 23 can be periodically lowered. This allows maximum signals to be recorded for compounds subject to an input ion flux of 1*10 9 ions / sec. To estimate minimal signals, consider that competitive Q-TOF instruments acquire informative MS-MS spectra when the total fragment ion signal exceeds 1*10 3 per log at the detector. Thus, the dynamic range per second is DR=1*10 5 estimated, ie a ratio of large detected signal per second of 1*10 8 and small recorded spectrum of 1*10 3ions. The integral dynamic range, ie the ratio of total signal per smallest identified species, is Int-DR=1*10 6 per second, which is about two orders of magnitude higher than filtering tandems such as Q-TOF, where additional ion losses are induced by selecting only single parent ions at a time.

[0060] The above description assumes the ability of the trap array to capture flows of 1*10 10 ions / sec. Existing ion traps cannot handle ion fluxes above 1*10 6 up to 1*10 7 ions / sec. To increase the ion flux while maintaining a resolution of approximately 100, the invention proposes several new trapping solutions, which will be described before considering trap arrays. RF trap with quadrupole DC output

[0061] It is with reference to Fig. 3, a new trap 31 with quadrupolar DC output for coarse mass separation with a resolution of R1~100 is proposed. The trap comprises a linear quadrupole with parallel electrodes 32, 33, 34, 35 extending in a Z-direction; and end plugs 37, 38 for electrostatic ion trapping in the Z-direction. Electrode 32 includes a slit 36 ​​aligned with the trap axis Z. End plugs 37, 38 are preferably segments of electrodes 32-35, biased by a few volts DC, as shown by the axial DC distribution in icon 39. Alternatively, the end plugs are DC-biased ring electrodes. The trap is filled with helium at a pressure between 10 and 100 mTorr (1.33 to 13.33 Pa).

[0062] Both RF and DC signals are applied, as shown in icon 40, to form quadrupole RF and DC fields, i.e., one phase (+RF) and +DC are applied to one pair of electrodes 33 and 35, and the opposite phase (-RF) and -DC are applied to another pair of electrodes 32 and 34. Optionally, a dipolar bias voltage VB is applied between electrodes of a pair, namely between electrodes 32 and 34. It should be understood that to generate an RF and DC difference between electrode pairs, each signal type can be applied separately. For example, the RF signal can be applied to electrodes 33 and 35 with DC=0, while -DC signals can be applied to the pair 32 and 34.

[0063] In one embodiment, the electrodes are parabolic. In another embodiment, the electrodes are round rods with a radius R relative to the plotted trap radius R0, such that R / R0 = 1.16. In alternative embodiments, the ratio R / R0 varies between 1.0 and 1.3. Such a ratio results in a weak octupole component in both the RF and DC fields. In yet another embodiment, the trap is stretched in one direction, i.e., the distances between rods in the X and Y directions differ, to introduce weaker dipolar and sextupole field components.

[0064] The electrode arrangement of the trap 31 device is reminiscent of a conventional linear resonant ejection mass spectrometer (LTMS), described, for example, in US Pat. No. 5,420,425 A, which is incorporated herein by reference. The device difference lies primarily in the use of a quadrupolar DC field for ion ejection and, due to a lower resolution requirement (R=100 versus 1000-10,000 in LTMS), a parameter difference with respect to length (100-200 mm versus 10 mm in LTMS), an unusually high helium pressure of 10 to 100 mTorr (1.33 to 13.33 Pa) versus 1 mTorr (0.133 Pa) in LTMS. The method differs in the ion ejection mechanism employed, the scanning direction, and the operating modes.While LTMS samples an RF amplitude and applies an AC voltage to excite secular motion, the new Trap 21 provides mass-dependent ejection through a quadrupolar DC field that opposes the mass-dependent radial RF confinement. In one sense, the operating mode is similar to that of a quadrupole mass spectrometer, with the upper mass limit of the transmitted mass window defined by a balance between the DC quadrupole field and an effective RF potential. However, quadrupoles operate in deep vacuum, separating a flow of ions passing through, and operation is based on the development of a secular motion instability. In contrast, the new Trap 21 operates with trapped ions and with the elevated gas pressure small enough to suppress RF micromotions, but large enough to partially dampen the secular motion and thus suppress resonance effects.The increased pressure is primarily chosen to accelerate ion attenuation as ions are admitted into the trap in order to accelerate the capture, attenuation and transfer of the ejected ions.

[0065] With reference to Fig. 4A shows the operating modes of quadrupoles and various traps in the conventional stability diagram 41, shown on the axes U DC and V RF , where U DC is the DC potential between electrode pairs and V RF is the peak-to-peak amplitude of the RF signal. Ion stability regions 42, 43, and 44 are shown for three ion m / z: minimum m / z in ensemble M min , exemplary intermediate m / z in M ​​and maximum m / z of the ensemble M maxThe operating line 45 corresponds to the operation of quadrupole filters. The line intersects the peaks of stability diagrams 42-44, thus providing transmission of individual m / z species and rejection of others. Line 46 corresponds to the operation of LTMS considering resonant excitation of secular ion motion by AC excitation at a certain fixed q = 4Vze / ω 2 R0 2 M. The excited q-value is defined by the ratio of RF and AC frequencies. As a result of a linear ramp-up of the RF signal, the trap ejects small ions first and heavy ions later, which is referred to as "direct scanning."

[0066] The effective potential well of the quadrupole field is known to be D = Vq / 4 = 0.9V RFM0 / 4M, where M0 is the lowest stable mass at q~0.9. The equation shows that the effective barrier is mass-dependent and decreases inversely proportional to mass. Thus, for small U DC , the heavier ions would be ejected by the quadrupole DC field, while small ions would remain. When ramping up the DC potential, ions would be ejected sequentially in a so-called reverse scan, the heavier ions first. The principle of trapping operation can be understood by considering the total barrier D comprising DC and RF barriers with D = 0.9V RF M0 / 4M - U DC considered, which at any given U DC positive for ions with M < M*=4U DC / (0.9V RFM0) and negative for M>M*. In quadrupoles, RF and DC field components increase proportionally with radius, therefore the boundary between stable (lower mass) and unstable (higher mass) trapped ions remains at the same M*. For an exemplary scan rate corresponding to 0.1 ms per mass fraction, the stable ions with total barrier D > 10 kT / e ~ 0.25 V would not be ejected, since the ion ejection rate is approximately (1 / F)*exp(-D e / 2 kT), where F is the RF field frequency, kT is the thermal energy, and e is the electron charge. The equation takes into account that ion kinetic energies are doubled in RF fields compared to static fields. Thus, the trapping resolution can be expressed in volts. For a DC barrier of 25 V, the estimated resolution is R1=100. At the same time, the kinetic energy of ions passing through the DC barrier is comparable to the height of the DC barrier.To avoid ion fragmentation, the trap operates with helium gas, with the mass energy center reduced by a factor of M. He / M deeper. The model allows a simple estimation of space charge effects. The trap resolution is expected to decrease proportionally to the ratio of thermal energy to space charge potential 2kT / Usc. The effective spatial resolution at large space charge can be expressed as R ~ U DC / (U SC +2kT / e) can be estimated.

[0067] The final part of the description presents the results of optical ion simulations when the DC voltage is ramped up at a rate of 1 to 5 V / ms. The time profiles are well separated for ions with m / z = 100 and 98 and at a DC voltage of 20 V. The HWFM resolution is on the order of 100, confirming a very simple separation model.

[0068] With reference to Fig. 4A, the new trap 41 operates along scan lines 47 or 48 or 49. In the simplest (although not optimal) scan 49, the RF signal is fixed (constant V RF ), while the DC signal is ramped up. The RF amplitude is chosen so that the lowest mass has a q below 0.3-0.5 for adiabatic ion motion in RF fields. To avoid excessive energies and ion fragmentation during ejection, it is preferred that the RF amplitude be kept at constant U DC is reduced, as shown by scan line 49. For the highest mass resolution, both RF and DC signals should be scanned along line 48. Such a scan can be selected if the tandem is used in C-MS-MS mode and ion fragmentation is desired anyway.

[0069] With reference to Fig. 4B, and describing the results of optical ion simulations, the quadrupolar trap with a diameter of 6 mm is operated with the following parameters: U DC [V] = 0.025*t[µs]; V RF (op)[V] = 1200 - 1*t[µs]; dipolar voltage of +0.2 and -0.2 V. The operating gas pressure of helium varies from 0 to 25 mTorr (0 to 3.33 Pa).

[0070] The top row shows time profiles for ions with m / z = 1000 and 950 (left) and m / z = 100 and 95 (right). The typical profile width is 0.2–0.3 ms and can be obtained in a 20 ms scan. The mass resolution of 20 corresponds to a mass range selection of 1 / 40 of the total flight time. The ion ejection efficiency is close to unity. Ions are ejected with a mass-dependent angular range that varies from 5 to 20 degrees (graphs in the middle row). The kinetic energy can be up to 60 eV for 1000 amu (1.6605*10 -15micrograms) ions, while it is 30 eV for 100 amu (1.6605*10 -16 micrograms) of ions. Such an energy is still safe for soft ion transfer in helium.

[0071] The same trap can be operated in a resonant ion ejection mode, similar to LTMS, but differs from standard LTMS by: using trap arrays that operate with much higher spatial charge loadings, operating at much larger gas pressures (10-100 mTorr (1.33 to 13.33 Pa) compared to 0.5-1 mTorr (0.07 to 0.13 Pa) helium in LTMS), and running faster despite lower mass resolution.

[0072] With reference to Fig. Figure 4C, describing the results of optical ion simulations, uses a linear trap with a slightly elongated geometry, where the separation between one pair of electrodes is 6.9 mm and between others 5.1 mm, corresponding to approximately an octupolar field of 10%. Applied signals are labeled as follows in the drawing: (a) a 1 MHz, 450 Vo-p RF signal is applied to vertically spaced rods, the RF amplitude is scanned down to a rate of 10 V / ms; (b) a dipolar DC signal of +1 VDC and -1 VDC is applied between horizontally spaced electrodes; (c) a dipolar AC signal with a frequency of 70 kHz and an amplitude of 1 V is applied between horizontally spaced rods. The upper trace shows two time profiles for resonant ejection of ions with 1000 and 1010 amu (1.66054*10 -15 and 1.67714*10 -15micrograms). The reverse mass scan corresponds to a mass resolution of approximately 300, while the total RF ramp-down time is approximately 30–40 ms. As can be seen from the lower curves, ions are ejected at an angle of 20 degrees and their kinetic energy is spread between 0 and 30 eV, which still allows for soft ion capture / collection in helium gas. Trap with axial RF barrier

[0073] With reference to Fig. 5, an axial RF barrier trap 51 comprises a set of plates 52 with multiple aligned sets of apertures or slots 53, an RF supply 54 with multiple intermediate outputs from the secondary RF coil, where phase and amplitude are denoted by k*RF, a DC supply 55 with multiple adjustable outputs U1...Un, and a resistive divider 56. The RF signals of both phases taken from intermediate and end points of the secondary coils are applied to plates 52 to form alternating amplitude or alternating phase RF between the adjacent plates 52 to form a steep radial RF barrier, thereby creating an effective axial RF trap, as can be seen by an exemplary RF distribution on plates in icon 57. The trap is surrounded by input and output barriers, whereby the input RF barrier 58 can be lower than the output barrier 59.The DC potentials from the resistive divider are connected to plates 52 via resistors in the megohm range to create a combination of an axially driving DC gradient with a nearly square axial DC field in the region of the RF trap 57. Thus, the axial RF and DC barriers mimic those formed in quadrupoles, at least near the point of origin. The trap is filled with gas in the 10-100 mTorr (1.33 to 13.33 Pa) gas pressure range.

[0074] During operation, ions flow along the RF channel with alternating RF phases and with an axial DC drive voltage applied to plates 52. To fill the trap, the DC voltage 54a is lowered. Then, the potential 54a is raised above the potential 54c to create a slight dipolar field in the trap region 57. Next, the potential 54b is ramped up to induce sequential mass ejection in the axial direction. The portion of the resistive divider between points 54a, 54b, and 54c is chosen to achieve a nearly quadratic potential distribution. The mass-dependent ion ejection then occurs using a similar mechanism as for the quadrupolar trap in Fig. 4 described.

[0075] A subsequent similar trap can be placed downstream of a sufficiently gaseous attenuation segment of the RF signal. Multiple traps can be arranged sequentially along the RF channel. Multiple sequential traps are expected to reduce space charge effects. Indeed, after filtering a narrower m / z range, the next trap would operate with a smaller space charge load, thus improving trap resolution. Multiple traps can be placed to "sharpen" trap resolution, similar to peak shape sharpening in gas chromatography, where multiple sorption events with broad time distributions form time profiles with narrow relative temporal durations dT / T. Hybrid trap with side ion supply

[0076] With reference to Fig. 6, yet another new trap is proposed, a hybrid trap 61, applying the same principle of equilibrium opposition of near-quadrupolar RF and DC fields with an intergas pressure of 10-100 mTorr (1.33 to 13.33 Pa). The trap 61 comprises an RF channel 62; quadrupolar rods 63-65; rod 65 having an ejection slot 66. The RF channel 62 is oriented orthogonally to the set of rods 63-65; said RF channel is formed of resistive rods supplied with alternating RF signals (o and +RF) and electrostatic potentials U1 and U2 to the array ends. The effective RF at the axis of the channel is RF / 2. The RF signal is also applied to rods 63 and 64. An adjustable DC bias voltage U3 is applied to the rod 62 to control ion ejection, ramping, and mass-dependent ejection via the slot 66.

[0077] During operation, ions flow through RF channel 62. The channel maintains the ion flow radially due to changing RF. Optionally, the channel is formed from resistive rods for controlled axial movement by an axial DC gradient U1-U2. Channel 62 communicates with trap region 67, formed by rods 63-64 and a channel acting as a fourth "open rod." The net RF on the axis of channel 62 is RF / 2. Since the RF signal on rod 65 is zero and the RF is applied to rods 63 and 64, there appears to be an RF trap near the origin, which is highly distorted on one side, the input side (connected to channel 62), but maintains a nearly quadrupolar field near the trap origin. Ions are injected into the trap 61 by arranging a trapping DC field by setting U3 sufficiently high.After ion damping in gas collisions (at approximately 1-10 ms at 10 mTorr (1.33 Pa) helium), the DC barrier is adjusted to be higher on the entrance side, i.e., U2>U3, while reduced on the exit side. Then, the quadrupolar DC potential comprising U2+U3 is ramped up by rods 63 and 64 to create a dipolar DC gradient that pushes ions toward the entrance. Since the RF barrier is larger for small ions, the heavy ions would leave the trap first, thus forming a time-separated flux aligned by ion m / z in the reverse order. Compared to RF / DC traps 31 and 51, trap 61 has the advantage of faster trap filling, although one would expect a somewhat lower resolution of trap 61 due to stronger distortions of the quadrupolar field. Space charge capacity and throughput of traps

[0078] Let us consider a trap that encloses a cylinder of ions with length L and radius r at a charge concentration n. The space charge field Esc grows in a cylinder as Esc = nr / 2ε0 and thus forms a space charge potential on the ion cylinder surface equal to U SC =q / 4πε0L. To minimize the effects of space charge on trap resolution, the space charge potential Usc should be below 2 kT / e. Then, the ion ribbon length (LL) must be LL>N / (8πε0KT), where N is the number of stored elementary charges. Assuming a median trap scan time of 10 ms to achieve a throughput of 1*10 10 ions / sec, the trap must be up to N=1*10 8Collect charges, and the ion band length must be L>3m. One proposed solution is to provide a parallel trap array. Another proposed solution is to provide a multi-stage (at least two-stage) trap, with the first trap operating with a total charge and low resolution to pass a relatively narrow mass range into the second stage trap, which operates with a fraction of space charge to enable higher resolution of the sequential mass ejection. Two-stage traps

[0079] With reference to Fig. 7, a two-stage trap array 71 comprises a sequentially communicating ion buffer 72, a first trap array 73, a gaseous RF guide 74 for ion energy attenuation; a second trap array 75, a spatially confining RF channel 76, and an optional mass filter 77 for the synchronized passage of an even narrower mass range.

[0080] During operation, currently selected mass ranges are as shown in diagram 78. An ion buffer injects ions in a wide m / z range, either continuously or in a pulsed mode. Both traps 73 and 75 are arranged for synchronized mass-dependent ion ejection, so that an ion flow is separated in time with a direct or reverse m / z sequence. The first trap 73 operates with a lower resolution of the mass-selective ejection, primarily caused by a higher space charge of the ion content. The trap cycle is set between 10 and 100 ms. Considering an ion flow up to 1*10 10 ions / sec from the ion source (not shown), the first trap array 73 is filled with approximately 1*10 8 up to 1*10 9ions. To reduce the total electrical capacity of the trap, the trap has about 10 channels of 100 mm length. The space charge potential is set at 1.5 V for a 100 ms cycle at 1*10 10 Ions / sec estimated, corresponding to 1*10 9 ions per 1 m of total ion band. For a 15-50 V DC barrier, the resolution of the first trap is expected to be between 10 and 30. Consequently, the trap rejects 73 ions in the 30-100 amu (4.9816*10 -17 up to 1.6605*10 -16microgram) m / z window. The ejected ions are attenuated in gas collisions and then injected into the second trap array 75 for additional and finer separation. The space charge of the second trap is expected to be 10–30 times lower. The space charge potential will be 0.05 to 0.15 V, i.e., would allow a mass ejection at higher resolution of approximately 100. The dual-trap arrangement helps reduce the overall electrical capacitance of the trap, as the same effect is achieved with 20 individual trap channels compared to a single-stage trap, which would require 100 channels and thus have a larger capacity. An optional mass filter 75, like an analytical quadrupole, can be used in addition to or instead of the second trap array when ions are spatially confined and attenuated in a confining RF channel 76.The transmitted mass range of the mass filter 77 is synchronized to the mass range transmitted by a downstream trap or by two traps.

[0081] Even with double trap arrangements, a high charge throughput of up to 1*10 10 Ions / sec can only be achieved in multi-channel trap arrays. Trap arrays

[0082] To improve charge throughput, several trap array designs are proposed. These designs were designed with the following key considerations in mind: ease of fabrication; achievable accuracy and reproducibility between individual trap channels; limiting the overall electrical capacitance of the trap; simplicity and speed of ion injection and ejection; efficiency of trap coupling with ion transfer devices; and limitations of the differential pumping system.

[0083] The trap array can consist of several traps, as in Fig. 3 - Fig. 7, as well as conventional traps with sequential ion ejection, such as LTMS with resonant ion ejection, described by Syka et al. in US 5420425 A, or traps with axial ion ejection by resonant radial ion excitation, as described by Hager et al. in US 6504148 B1. The conventional traps can be modified to operate at higher ~10 mTorr (1.33 Pa) gas pressure, albeit with a modest decrease in their resolving power.

[0084] For efficient and fast ion detection of ions behind the trap array, several geometric configurations are proposed:

[0085] A planar array of axially ejecting ion traps with the outlets located on a plane, or a gently curved cylindrical or spherical surface; the planar array is followed by a wide-bore RF ion channel, then an RF ion funnel; a DC gradient is applied across the RF channel and funnel to accelerate ion transfer past the trap array.

[0086] A planar array of radially ejecting traps with outlet slots aligned on a plane or a gently curved cylindrical or spherical surface. The planar array is followed by a wide-bore RF ion channel, then an RF ion funnel; a DC gradient is applied to the RF channel and funnel to accelerate ion transfer past the trap array.

[0087] A planar array located on the cylindrical surface with ejection slots directed inward into the cylinder. Ions are collected, attenuated, and transferred into a wide-bore cylindrical channel. Mechanical construction of new components

[0088] According to Fig. 8 shows an exemplary trap array 81 (in Fig. 2 (denoted by 24C) is formed by a plurality of identical linear quadrupole traps aligned on the cylindrical centerline. The electrode shape is achieved by electrical discharge machining from a single workpiece to form an outer cylinder 82 with incorporated curved electrodes 82C, a plurality of inner electrodes 83, and an inner cylinder 84 with a plurality of incorporated curved electrodes 84C. The assembly is held together by tubular or rod-shaped ceramic spacers 85. The incorporated electrodes 82C and 84C can have parabolic, circular, or rectangular shapes. The inner cylinder 84 has a plurality of slots 86 alternating with structural ribs 86R, which are formed when a plurality of machined grooves 86 are matched with EDM full-length slots 87. Characteristic dimensions are: registered radius 3 mm, centerline diameter 120 mm to form 24 traps, ie one trap every 15 degrees, and length 100 mm.The inner region is lined with ohmic or resistive rods 88 to form a multipole with axial DC field with a total potential drop of a few volts to a few dozen volts depending on the gas pressure of the helium, which is in the range 10-100 mTorr (1.33 to 13.33 Pa).

[0089] In Fig. 9, the exemplary assembly 91 is also presented for modules surrounding the cylindrical trap 81. The full assembly view is supplemented by icons showing the assembly details. The ion source (not shown) communicates with the assembly 91 either via a multipole 92m or via a heated capillary 92c passing through an inlet 92p. The ion inlet 92p can be placed orthogonal to the trap axis to inject ions into a sealed ion channel 93. Gas can be pumped through a gap 94g between the ion channel 93 and a repulsion electrode 94.Channel 93 is fed with a varying RF signal and a DC voltage divider for ion transfer into a multi-stage ion funnel 95, which is made of thin plates with individual holes that vary from plate to plate to form ion channels with a conical expanding portion 95e, then an optional cylindrical portion 95c that further diverges into several circular channels 95r that are aligned with channels of trap 81. The multi-stage ion funnel 95 preferably also has an axial central RF channel 95a. Connecting ribs can be used to support the inner axial portion 95a of the ion funnel 95. An adjustable DC voltage can be applied to the final multi-hole ring 96 for ion gating. The circular channels 95r of the ion funnel are aligned with and connected to individual channels of the trap 81, as described above. The ion collection channel, orIon capture channel 97 is formed with ohmic rods 88 fed with RF and axial DC signals, and an electrostatic repulsion plate 97p. Ohmic rods 88 can be bonded to a ceramic support 88c with inorganic adhesive. Ions are collected behind ohmic rods 88 by a confining ion funnel 98 and are guided into an ohmic multipole 99. Optionally, ion funnel 98 can be replaced by a set of converging ohmic rods for radial RF confinement in combination with a DC gradient. The presented design demonstrates a possible approach for constructing the trap array using conventional machining.

[0090] According to Fig. 10 comprises an exemplary ohmic multipolar ion conductor 101 (in Fig. 2 with 26, in Fig. 8, designated 88) resistive rods 106 and an RF supply to DC, connected via central taps of 102 from secondary coils 103 and 104. Optionally, the DC signal can be pulsed with a smoothing RC circuit using a switch 105 as shown. The rods 106 include conductive edge terminals 107. The outer (non-ion exposed) side of rods 106 includes an insulating coating 108 with conductive traces 109 on the top for improved RF coupling. The rods are placed so that a multipole is formed due to an alternating RF phase supply between adjacent rods. Since there are two groups of equally excited rods, the electrical schematic of Fig. 10 only two poles.

[0091] The rods 106 are preferably made of carbon-filled bulk ceramic or clay resistors, commercially available from US Resistors Inc. or HVP Resistors Inc. Alternatively, rods are made of silicon carbide or boron carbide, which is known to offer a resistance range of 1-100 ohms*cm depending on the sintering process. The electrical resistance of an individual rod 3 to 6 mm in diameter and 100 m long is chosen between 100 and 1000 ohms for an optimal compromise between (a) power dissipation at approximately 10 VDC drop and (b) RF signal sag due to stray capacitance per rod in the range 10-20 pF, corresponding to a reactance Rc~1 / ωC of approximately 5-10 kOhm.For use with higher rod impedance, RF coupling can be improved by a DC-insulated thick metallized track 109 on the outer (non-ion-exposed) side of electrodes 106, coupled to an (arbitrary) edge terminal 107 and insulated from rod 106 by an insulating layer 108. Such tracks and insulators can be achieved, for example, with insulating and conductive inorganic adhesives and pastes commercially available from Aremco Co. Ohmic rods are fed with RF and DC signals using a well-known RF circuit, with the DC voltage being fed via central taps 102 from several secondary RF coils 103 and 104. When using resistive rods 88 for an ion liner of trap 81, the total capacitance of the ion conductor (0.5-1 nF) becomes a concern in the design of the RF driver.The resonant RF circuit can use powerful RF amplifiers or even vacuum tubes as in ICP spectrometry.

[0092] Prior art ohmic conductors, GB 2412493 B, US 7064322 B2, US 7164125 B2, US 8193489 B2, use either bulk ferrites, which suppress the RF signal along rods and have poor resistance linearity and reproducibility, or thin ohmic films, which can be destroyed by occasional electrostatic discharges from large RF signals at intermediate gas pressures. The present invention proposes a reproducible, robust, and uniform ohmic ionic conductor that is also stable over a wide temperature range.

[0093] The mechanical design of conductor 101 can be based on the use of metal edge clamps for precise alignment of mass- or EDM-machined rods and to avoid thermal expansion conflicts. Alternatively, rods 88 are bonded with an inorganic paste onto ceramic holders 88c as shown in Fig. 8, with one holder fixed and another holder axially aligned but linearly floated to avoid thermal expansion conflicts. Preferably, the rods are centerless ground for precise alignment, allowing the production of accurate rods with diameters down to 3 mm.

[0094] It is understood that assemblies according to the designs in Fig. 8 to Fig. 10 allow the formation of several other specific configurations and combinations of the described elements for forming hybrid ion channels and conductors with planar, curved, conical, or cylindrical ion channels communicating with an array of individual channels. It is expected that the particular configurations will be optimized based on the desired parameters of individual devices, such as space charge capacity, ion transfer rate, assembly accuracy, insulation stability, electrical electrode capacitance, etc. TOF detector with long lifetime

[0095] Existing TOF detectors are characterized by their lifetime, measured as 1 coulomb of output charge. Considering a typical gain of 1*10 6 this corresponds to 1*10 6 C at the entrance. Thus, the detector lifetime is only 1000 seconds (15 min) at an ion flux of 1*10 9Ions / sec. Hybrid detectors are commercially available, comprising a single-stage front MCP followed by a scintillator and then a PMT. In our own experiments, the detector operated about 10 times longer, which is still not long enough. Apparently, the hybrid detector degrades due to the destruction of a 1-micron metal coating at the top of the scintillator. The invention provides an improvement in detector lifetime, achieved by: a) covering a scintillator with a conductive mesh to remove electrostatic charge from a surface; (b) using a metal converter with high ion energy (about 10 kEV) in combination with magnetic steering of secondary electrons; and (c) using dual PMTs with different solid angles to collect / detect signals into channels, while circuits in PMT are tuned for active signal limiting in downstream magnification stages.

[0096] According to Fig. 11, two types of improved TOF detectors 111 and 112 utilize several common components. Both detectors 111 and 112 comprise: a scintillator 118; a grating 117 coating the scintillator; a photon-transparent pad 119 with a reflective coating; and at least one photomultiplier 120, preferably located on the atmospheric side. Preferably, two photomultipliers 120 are used to detect photons with different solid angles. Designs 111 and 112 differ in the type of ion-to-electron conversion: detector 111 utilizes a metal converter surface 114 with a magnet 114M having a magnetic field between 30 and 300 gauss and with magnetic lines oriented along the surface. Detector 112 utilizes a single-stage microchannel plate 115.

[0097] During operation, a packet of ions 113 with 4-8 keV energy approaches the detector 111. The ion beam is driven by several kilovolts difference between U D and more negative Uc potentials, e.g., in a simple three-electrode system shown. Ions with approximately 10 keV energy impact the metal conversion surface 114 and generate secondary electrons, primarily by kinetic emission. High-energy ion bombardment causes little surface contamination. Unlike specially designed conversion surfaces, the flat metal surface (stainless steel, copper, beryllium copper, etc.) does not degrade. Secondary electrons are accelerated by a more negative Uc potential and are guided by a magnetic field between 30 and 300 gauss (preferably 50-100 gauss) of magnets 114M. Secondary electrons are guided into a window along track 116 and impact the scintillator 118.

[0098] The scintillator 118 is preferably a fast scintillator with a response time of 1-2 ns, such as BC418 or BC420 or BC422Q scintillators from St. Gobain (scintillators@Saint-Gobain.com), or a ZnO / Ga (http: / / scintillator.1bl.gov / ED Bourret-Courchesne, SE Derenzo, and MJ Weber. Development of ZnO:Ga as an ultra-fast scintillator. Nuclear Instruments & Methods in Physics Research Section a-Accelerators Spectrometers Detectors and Associated Equipment, 601:358-363, 2009). To avoid electrostatic charge, the scintillator 118 is covered with a conductive grid 117. The front surface of the scintillator is preferably maintained at a positive potential of approximately +3 to +5 kV to avoid slow electrons in the passage and to improve the electron-per-photon gain. The typical scintillator gain is 10 photons per 1 kV of electron energy, meaning that 10 kV of electrons is expected to produce approximately 100 photons.Because photons are emitted isotropically, only 30–50% of them reach the downstream multiplier, which is expected to have a quantum efficiency of about 30% at a typical photon wavelength of 380–400 nm. Consequently, a single secondary electron is expected to generate about 10 electrons in the PMT photocathode. The PMT gain can be estimated at about 1*10. 5 to detect individual ions. Closed PMTs, such as Hamamtsu's R9880, can provide a short response time of 1-2 ns while maintaining a much longer lifetime on the order of 300 °C at the output compared to TOF detectors operating in the technical vacuum of the MR-TOF analyzer. The output charge is 300 °C with a total gain of 1*10 6 corresponds to 0.0003 C ion charge. The lifetime of the detector can be further improved by: (a) using a smaller PMT gain, for example 1*10 4, when operating with a larger resistance in the range 1-10 kOhm, which is possible due to the low capacitance of PMTs, and (b) operating with an even smaller gain, since up to 10 PMT electrons per secondary electron 116 provides a far narrower (factor 2-3) signal height distribution than standard TOF detectors. The lifetime of the detector 111, measured as the total charge at the detector input, is estimated to be between 0.0003 and 0.001 coulomb.

[0099] To extend the detector's dynamic range and lifetime, two PMT channels are preferably used to detect signals with a 10-100x sensitivity difference between PMT1 and PMT2, controlled by the solid angle for collecting (capturing) photons. The channel (e.g., PMT2) with low sensitivity can be used to detect extremely strong signals (1*10 2 up to 1*10 4Ions per ion packet with a duration of 3-5 ns). Even higher intensity from short ion packets would be prevented by spatial self-space charge scattering of intense ion packets in the RF-TOF analyzer. To avoid saturation of the sensitive channel (e.g., PMT1), the PMT-1 preferably includes an active protection circuit to automatically limit the charge pulses per dynode stage. Alternatively, a PMT with a long propagation time and narrow temporal dispersion (or duration) is used (such as the R6350-10 from Hamamtsu), which allows the use of active suppression circuits that detect charge in upstream dynodes. The dynamic range improvement is estimated to be 10-fold, and the lifetime improvement is 10 to 100-fold, depending on the efficiency of the active suppression circuits.

[0100] Again with reference to Fig.11, design 112 is somewhat inferior and more complex than design 111, but avoids additional temporal dispersion (or duration) in the secondary electron path and allows for the suppression of the effects of slow scintillator fluorescence. During operation, the ion packet 113 impinges on the microchannel plate 115, which operates at a gain of 100-1000. Secondary electrons 116 are directed onto the scintillator 118, which is covered with a grid 117 to remove electrostatic charge. Electrons are preferentially accelerated to 5-10 keV energy while maintaining the front MCP surface at the accelerating potential of the MR-TOF (-4 to -8 kV) and by applying 0 to +5 kV potential Usc to the grid 117. Consequently, single ions would generate 1000 to 10,000 electrons on the PMT photocathode.In contrast to strong signals from fast fluorescence, slow fluorescence would generate single electrons on the photocathode, and such slow signals could be suppressed. Otherwise, detector 112 operates in the same way as detector 111 described above. To estimate the lifetime of detector 112, we assume an MCP gain of 100. Then the total MCP output charge is less than 1*10. -6 C and the total input charge is less than 0.001 Coulomb.

[0101] Both new detectors provide a longevity of up to 0.001 coulomb of the input charge. Considering a maximum ion flux of up to 1*10 9 Ions / sec (1.6*10 -10 A) on the MR-TOF detector, the lifetime of newer detectors is over 6*10 6sec, i.e., 2000 hours, or 1 year of operation. The detectors also allow for rapid replacement of a PMT at moderate cost on the atmospheric side. Thus, new detectors enable the operation of new tandems with unprecedentedly high TOFMS ion fluxes.

[0102] While this specification contains numerous specific details, these are not to be considered limiting the scope of the disclosure or the claims, but rather as descriptions of features specific to particular implementations of the disclosure. Certain features described in this specification in the context of separate implementations may also be implemented in combination in a single implementation. Conversely, various features described in the context of a single implementation may also be implemented in multiple implementations, separately or in any subcombination.Furthermore, while features were described above as operating in certain combinations and were even initially claimed as such, one or more features from a claimed combination may, in some cases, be removed from the combination and the claimed combination may be directed to a subcombination or a variation of a subcombination.

[0103] Likewise, while operations have been illustrated in the drawings in a particular order, this should not be understood to require that such operations be performed in the particular order shown or in a sequential order, or that all of the illustrated operations must be performed to obtain desirable results. Under certain circumstances, multitasking and parallel processing may be advantageous. Furthermore, the separation of various system components in the embodiments described above should not be understood to mean that such separation is necessary in all embodiments, and it should be understood that the described program components and systems may generally be integrated with one another into a single software product or packaged into multiple software products.

[0104] A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. Accordingly, other implementations are within the scope of the following claims. For example, the acts recited in the claims may be performed in a different order while still achieving desirable results.

[0105] The following numbered paragraphs describe features in accordance with embodiments of the disclosure: 1. A method for high throughput mass spectral analysis, comprising the steps of: generating ions in a broad m / z range in an ion source; coarse temporal separation, in a first mass separator, of an ion flow according to ion m / z with a resolution between 10 and 100; and high-resolution (R2>50,000) mass spectral analysis in a time-of-flight mass analyzer, triggered at a period significantly shorter than the ion flight time in said time-of-flight separator, in order to minimize or avoid spectral overlaps between signals generated by individual starts upon injection of ions of a narrower m / z window due to temporal separation in the first separator. 2. The method of paragraph 1, further comprising steps of ion fragmentation between said mass separation and mass analysis stages, wherein trigger pulses of said time-of-flight analyzer are time-coded for unique time intervals between each pair of trigger pulses in a time-of-flight period. 3. A method according to paragraph 1 or 2, wherein the coarse mass separation step comprises a temporal separation within a multi-channel ion trap or in a wide-bore spatially focused time-of-flight separator preceded by a multi-channel trap pulse converter. 4. The method of paragraphs 1 to 3, further comprising a step of bypassing said first separator for a period of time and admitting a portion of the ion flux from said ion source into said high resolution mass analyzer to analyze the richest ion species without saturating the space charge of said TOF analyzer or to avoid saturation of a detector. 5. A method for high charge throughput mass spectral analysis, comprising the following steps: a. generating, for a chromatographically separated analyte flow, in an ion source, a plurality of ions in a wide range of ion m / z and directing said ion flow at up to 1E+10 ions / sec into a radio-frequency ion guide with an intermediate gas pressure; b. splitting said ion flow between a plurality of channels of a radio-frequency confinement ion buffer; c. accumulating said flow in said ion buffer and periodically ejecting at least a portion of the accumulated ion ensemble into a multi-channel trap; d. dampening ions in said multi-channel trap in collisions with helium gas at a gas pressure between 10 and 100 mTorr in a plurality of RF and DC trap channels; where the number of said capture channels N>10 and the length of individual channels L are chosen such that the product L*N>1m; e.sequentially ejecting ions from said multi-channel trap progressively with ion m / z either in direct or reverse order, such that ions of different m / z are separated in time with a resolution R1 between 10 and 100; f. accepting the ejected and time-separated ion flow from said multi-channel trap into a wide-open RF ion channel and driving ions with a DC gradient for fast transfer with a time spread of less than 0.1-1 ms; g. spatially confining said ion flow by RF fields, while maintaining the previously achieved temporal separation with a time spread of less than 0.1-1 ms; h. forming a narrow ion beam with ion energy between 10 and 100 eV, a beam diameter of less than 3 mm and an angular divergence of less than 3 degrees at the entrance of an orthogonal accelerator; i.Forming ion packets with said orthogonal accelerator at a frequency between 10 and 100 kHz with a uniform pulse period or with a pulse period encoded to create unique time intervals between said pulses; due to the coarse separation in step (e), said packets comprise ions with a mass range at least 10 times narrower than the initial m / z range generated in said ion source; j. analyzing the ion flight time of said ion packets with an instantaneously narrow m / z range in multi-reflecting electrostatic fields of a multi-reflecting time-of-flight mass analyzer with an ion flight time for 1000 Th ions of at least 300 µs and with a mass resolution above 50,000; and k. recording signals beyond the time-of-flight separation by a detector with a lifetime sufficient to accept above 0.0001 coulomb at the detector input. 6. A method according to paragraph 5, further comprising an ion fragmentation step between said sequential mass ejection steps and said high-resolution time-of-flight mass analysis step. 7. The method according to paragraphs 5 and 6, for the purposes of extending the dynamic range and analyzing large analyte species, further comprising a step of introducing and analyzing, with said high resolution TOF MS, at least a portion of the original broad m / z range ion flux. 8. The method according to paragraphs 5 to 7, wherein said step of coarse mass separation in the trap array comprises one step selected from the following list: (i) radial ion ejection from a linear RF quadrupole array through a quadrupolar DC field; (ii) resonant radial ion ejection from a linear RF quadrupole array; (iii) mass-selective axial ion ejection from an RF quadrupole array; (iv) mass-selective axial transfer in an array of RF channels with radial RF confinement, an axial RF barrier, and an axial DC gradient for ion propulsion, all formed by distributing DC voltage, RF amplitudes, and phases between a plurality of ring electrodes; and (v) ion ejection through a DC field from a plurality of quadrupolar traps fed with ions through an orthogonal RF channel. 9. The method according to paragraphs 5 to 8, wherein said mass separator array is arranged either on a planar or at least partially cylindrical or spherical surface, said separator being geometrically matched to ion buffers and ion collection channels of the appropriate topology. 10. A process according to paragraphs 5 to 9, wherein said coarse mass separation step is arranged in helium having a gas pressure of 10 to 100 mTorr to accelerate collection and transfer of ions after said coarse mass separation step. 11. The method of paragraphs 5 to 10, further comprising a step of additional mass separation between said step of sequential ion ejection and the step of orthogonal ion acceleration into a multi-reflecting analyzer, wherein said step of additional mass separation comprises one step selected from the following list: (i) mass-dependent sequential ion ejection from an ion trap or trap array; (ii) mass filtering in a mass spectrometer, wherein said mass filter is mass-synchronized to said first mass-dependent ejection. 12. A tandem mass spectrometer comprising: a comprehensive multi-channel trap array for sequentially ejecting ions according to their m / z in T1=1 to 100 ms time with a resolution R1 between 10 and 100; an RF ion channel with a sufficiently wide entrance bore to collect, quench and spatially confine most of said ejected ions at 10 to 100 mTorr gas pressure; wherein said RF ion channel has an axial DC gradient for a sufficiently short time spread ΔT <t1 r1 hat, um die zeitliche auflösung des ersten umfassenden massenseparators auszuhalten; einen multireflektierenden flugzeit-(mr-tof)-massenanalysator; orthogonalbeschleuniger mit häufig codierter gepulster beschleunigung zwischen der genannten mehrkanal-falle und dem mr-tof-analysator; taktgenerator zum erzeugen von startpulsen für den orthogonalbeschleuniger, wobei periode pulsen wenigstens 10 mal kürzer ist als flugzeit schwersten m z-ionen in mr-tof-analysator, zeitintervalle entweder gleich oder einmalige intervalle jedem pulspaar flugzeitperiode codiert sind; flugzeitdetektor einer lebenszeit mehr 0,0001 coulomb eingangsionenflusses.13. Apparatus according to paragraph 12, further comprising a fragmentation cell between said multi-channel trap array and said orthogonal accelerator. 14. Apparatus according to paragraphs 12 and 13, wherein said multi-channel trap array comprises a plurality of traps selected from the group consisting of: (i) a linear RF quadrupole with a quadrupolar DC field for radial ion ejection; (ii) a linear RF quadrupole for resonant radial ion ejection; (iii) an RF quadrupole with an axial DC plug for mass-selective axial ion ejection; (iv) ring electrodes with distributed DC voltages, RF amplitudes, and phases between electrodes to form an RF channel with radial RF confinement, an axial RF barrier, and an axial DC gradient for ion propulsion; and (v) a quadrupolar linear trap fed with ions through an orthogonal RF channel for ion ejection by a DC field through an RF barrier. 15. Apparatus according to paragraphs 12 to 14, wherein said mass separator array is arranged either on a planar or an at least partially cylindrical or spherical surface, said separator being geometrically matched to ion buffers and ion collection channels of the appropriate topology.

Claims

[1] An array of identical linear quadrupole ion traps, each trap comprising: at least four main electrodes (32, 33, 34, 35) extending in a Z-direction to form a quadrupolar field at least in the centerline region aligned along the Z-axis, the Z-axis being either straight or curved with a radius that is substantially larger than the distance between said main electrodes (32, 33, 34, 35); an ion ejection slit (36) in at least one of said main electrodes (32, 33, 34, 35); said slit (36) being oriented in the Z direction; a pair of electrostatic end plugs (37, 38) arranged at the Z edges of the quadrupole ion trap; wherein the pair of end plugs (37, 38) are a segment of the main electrodes (32, 33, 34, 35) or ring electrodes; an RF generator that provides RF signals with opposite phases, to form a quadrupolar RF field at least in the centerline region of the main electrodes (32, 33, 34, 35); a variable DC supply for supplying DC signals to at least two rods to form a quadrupolar DC field with a weaker dipolar DC field at least in the centerline region of main electrodes (32, 33, 34, 35); a DC, RF or AC supply connected to said pair of end plugs (37, 38) for providing axial Z-capture; a gas supply or pumping means for providing a gas pressure in the range of 1 to 100 mTorr [0.133 to 13.332 Pascals], the variable DC supply having means for ramping up said quadrupolar potential, thereby providing sequential ion ejection across the slit (36) in inverse relationship to the ion m / z, wherein the array further comprises a wide-diameter RF channel (25) with a DC gradient for collecting, transferring, and spatially confining ions behind the slits (36) from the quadrupole ion traps; wherein the dimension of said RF channel (25) is defined by trap sizes of the quadrupole ion traps and topology of the array and gas pressure in the quadrupole ion traps, and wherein the individual quadrupole ion traps are aligned to form an ion emission surface that is either planar or at least partially cylindrical or partially spherical for more efficient collection and transfer of ions in the wide diameter RF channel (25).

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