WO2017042665A1 - Séparateur de masse par résonance - Google Patents

Séparateur de masse par résonance Download PDF

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Publication number
WO2017042665A1
WO2017042665A1 PCT/IB2016/055201 IB2016055201W WO2017042665A1 WO 2017042665 A1 WO2017042665 A1 WO 2017042665A1 IB 2016055201 W IB2016055201 W IB 2016055201W WO 2017042665 A1 WO2017042665 A1 WO 2017042665A1
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Prior art keywords
ion
mass
excitation
ions
trap
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PCT/IB2016/055201
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English (en)
Inventor
Alexander VEDENIN
Anatoly Verenchikov
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Q-Tek D.O.O.
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Application filed by Q-Tek D.O.O. filed Critical Q-Tek D.O.O.
Priority to GB1804549.2A priority Critical patent/GB2556830A/en
Publication of WO2017042665A1 publication Critical patent/WO2017042665A1/fr

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
    • H01J49/4205—Device types
    • H01J49/421—Mass filters, i.e. deviating unwanted ions without trapping

Definitions

  • the invention relates to the field of mass spectrometry and in particular to resonant mass spectrometers and tandem mass spectrometers, and methods of mass separation for use therewith.
  • tandem mass spectrometers are widely used for routine trace analyses within complex mixtures and matrices, like food and biological extracts.
  • triple quadrupoles (3Q) are most popular for their sensitivity and speed.
  • Triple quadrupoles operate as follows. Ion source, say, Electrospray (ESI) or electron impact (EI) ion source, generates continuous ion beams of parent ions of different compositions and of different m/z ratios.
  • First analytical quadrupole (called Ql or MSI) is used to select parent ions, i.e.
  • m/z target m/z
  • M2 target m/z
  • Both quadrupole analyzers do filter and pass one m/z specie in a time.
  • Both parent and characteristic fragment ion masses are determined in prior calibration experiments when injecting standards.
  • the target pair of Ml and M2 is called “reaction” or "channel”. Since detected compounds generate multiple fragment species, the M1-M2 pair is selected to minimize interference with M1-M2 channels of the matrix. The reliability of compound detection may be improved by detecting several fragment ions at proper intensity ratio.
  • SRM single reaction monitoring
  • M1-M2 pair remains constant during the analysis time.
  • SRM signal profile at chromatographic (LC or GC) separation provides selective detection within complex matrices (food extracts, blood, urine) at part per billion (ppb) levels.
  • MRM Multiple Reaction Monitoring
  • the M1-M2 channels are mapped per chromatographic retention time RT. Rapid development and continuous additions of new libraries extend the area of 3Q application.
  • Magnetic sector mass spectrometers are capable of providing high resolution in excess of 30,000 and large dynamic range of the analysis, but they are bulky, slow, expensive and introduce significant ion losses. To obtain resolution above 10,000, magnetic sectors operate with narrow (tens of microns) slits while accepting about one percent of ion beams.
  • Linear ion traps mass spectrometers are capable of MS-MS analysis at higher resolutions up to 10,000-30,000, but at a cost of very slow analysis and at significant compromises in the dynamic range, primarily caused by space charge effects at prolonged ion trapping.
  • resonant mass spectrometers exampled by Omegatrons of US2958774, radio-frequency (RF) signals are used for resonant excitation of ion orbital motion within magnetic fields, this way bringing ions of selected m/z to higher orbits. Resolution of those analyzers is low.
  • RF radio-frequency
  • radiofrequency mass spectrometers the RF signals are used to excite oscillations of ions of interest between mesh electrodes.
  • resonant mass spectrometers were never implemented into mass product for their low mass resolution and poor transmission.
  • Time-of-flight mass spectrometers and in particularly multi-reflecting MR- TOF MS do provide high resolving power but they are not yet adopted for parent ion selection out of continuous ion beams at high ion currents in nA range.
  • tandem MS-MS for enhancing specificity of routinely used tandem MS-MS, it is desirable improving mass resolution of mass selectors, while operating with continuous ion beams at high nA range currents, without dramatic losses of ion transmission and at moderate instrument cost. It is also desirable providing parallel detection of fragment ions for (a) yet higher sensitivity and speed and for (b) simplifying MRM method development for new applications.
  • the resonant mass separator (RMS) of the present invention employs open isochronous ion traps with two-dimensional electric field in the X-Y-plane, substantially extended in the third orthogonal Z-direction.
  • isochronous open traps an RF quadrupole with local dipole field; a multi-turn electrostatic sector analyzer; and a multi- reflecting electrostatic analyzer built of ion mirrors.
  • Multiple ion species in a range of ion m/z are injected into one of such open traps to induce multiple ionic oscillations in the X-Y plane.
  • the exemplar open traps are known to provide for isochronous ion oscillations, with oscillation period independent on ion spatial and energy spreads at least to the first order of aberrations, while the oscillation period is m/z dependent.
  • Two-dimensional electric field of open traps does not have Z-component, which allows ion propagation through the open trap in the third, drift Z-direction.
  • the ion propagation in the Z-direction may be controlled by either local spatial modulation of X-Y field of the open trap along the Z- direction, or by a set of periodic einzel lens, or by a set of quadrupolar lens.
  • the mean ion trajectory become spiral (in case sectors) or zigzag (in case of ion mirrors), characterized by a fixed z-advance per turn and a fixed number of ion oscillations through the open trap.
  • excitation electrode Inducing excitation electric field within at least one spatially local excitation region, whereto ions get periodically in time.
  • excitation regions lying spatially periodic along the mean ion path.
  • isochronously oscillating ions get into the excitation region/regions periodically in time.
  • a time periodic excitation signal is then applied to said at lest one excitation electrode.
  • Excitation signal may be either harmonic or pulsed or of an arbitrary shape.
  • the excitation field may be deflecting ions off the mean path, focusing/defocusing ion beams or accelerating/decelerating ions along the mean ion path.
  • Novel principle of resonant stabilization is strong departure from conventionally used principle of resonant excitation of target m/z species, commonly employed in RF ion traps.
  • the invention proposes another two novel features, not typical for ion traps: (a) spatially local excitation fields and (b) high harmonics of the excitation signal.
  • the combination of the two allow for substantial acceleration of ion separation in fewer oscillation cycles.
  • the resonant separator now can be constructed within an open trap of reasonably compact size, which has been unthinkable before.
  • analytical quadrupole with 1000 RF cycles shall be several meters long, which would ruin the required micron precision of electrodes.
  • Single desired mass band can be selected by a crude mass filter (such as quadrupole mass analyzer) placed upstream or downstream of the RMS, or by applying a second excitation signal of a second frequency, e.g. two signals corresponding to N and N-l, N and N+l, N-l and N+l harmonics, etc.
  • multiple ion beam signals can be acquired at AC frequency scan (steps), or multiple parent mass bands could be admitted into a fragmentation cell, and MS or MS-MS spectra may be recovered by spectral decoding after frequency AC scan, smooth or stepped.
  • the method of admitting multiple bands is expected to improve the MS and MS-MS throughput.
  • a method of mass separation comprising the following steps:
  • said excitation frequency may substantially exceed the ion oscillation frequency corresponding to N»l . This improves the resolution of mass separation per ion path, space charge throughput, and the transmission of continuous ion beams.
  • said ion beam may be time modulated to provide temporary and spatially compressed ion packets in said regions of spatially local AC excitation field.
  • said step of arranging electric fields for isochronous oscillating motion may comprise one step of the group: (i) arranging an RF dipolar trap with substantially quadrupolar RF fields; (ii) arranging electrostatic field of multi-turn sector analyzers with spiral ion trajectories; and (iii) arranging electrostatic fields of mirror based multi-reflecting TOF mass analyzers with zigzag ion trajectories.
  • said ion drift motion in the Z-direction may be one of the group: (i) free propagation at variable number of oscillation cycles; (ii) a controlled Z-motion defined by spatially-periodic electric fields in the Z-direction to provide fixed number of oscillations through the open trap; and (iii) temporal ion entrapment in the Z-direction with subsequent release of mass separated species.
  • the method may be applied to tandem mass spectrometry analysis, where said resonance separation is employed in at least one stage of mass selection.
  • the method may further comprise a step of transmitting a set of multiple mass windows and a step of scanning the frequency of said AC excitation for scanning said set of multiple mass windows.
  • said two dimensional electric field of open trap may be either of planar or cylindrical topology with corresponding straight or bent at constant radius axes Z.
  • a resonant mass separator comprising:
  • An isochronous multi-pass open trap built of gridless electrodes, extended along a Z- axis to form two-dimensional electric fields in X-Y plane being orthogonal to said Z-axis; shape and potentials of said open trap are arranged to provide periodic and isochronous ion oscillations (turns or reflections) along a mean ion path P in said X-Y plane; wherein the oscillation period along said ion path and between spatially periodic focusing points is at least first-order independent on ion spatial and energy spreads, but is dependent on ion mass to charge ratio m/z;
  • At least one AC excitation electrode arranged for providing multiple substantially local regions of excitation electric field around said focal points, deviating said ion beam off the mean ion path;
  • a generator of a periodic AC excitation signal, applied to said at least one electrode at excitation period being substantially shorter compared to said oscillation period;
  • said excitation frequency substantially exceeds the ion oscillation frequency.
  • said open trap may be one of the group: (a) an RF dipolar trap with substantially quadrupolar RF fields; (b) a multi-turn electrostatic sector analyzer with spiral ion trajectories; and (c) a mirror based electrostatic multi-reflecting TOF mass analyzers with zigzag ion trajectories.
  • said open trap may further comprise one set of means for spatial ion confinement in the drift Z-direction of the group: (i) local spatial modulation in the Z-direction of electrodes of said open trap; (ii) a set of spatially periodic einzel lens in a field free region of said open trap; (iii) a set of quadrupolar lens in field free region of said open trap; and (iv) an Z- end deflector for trapping ions for a fixed time period.
  • the mass separator may further comprise a pulsed accelerating modulator after said ion source for temporary ion packet compression in said AC excitation regions.
  • the mass separator may further comprise an additional crude mass selector between said ion source and said ion receiver.
  • said at least one AC excitation electrode may comprise one of the group: (i) a pair of deflecting electrodes extended along said Z-axis; (ii) a set of deflectors; (iii) a set of periodic einzel lens; (iv) a set of quadrupolar lens.
  • the method and apparatus may be applied within a tandem mass spectrometer for at least one stage of mass selection.
  • the proposed resonant mass selectors are expected to provide an improved combination of resolution and sensitivity compared to prior art continuous beam separators, like quadrupoles and magnet sectors, and are expected to provide much higher dynamic range compared to prior art ion trap mass spectrometers and TOF MS.
  • the RMS may be used as a single stage mass spectrometer or may be used in tandem MS-MS, like RMS-RMS, Q-RMS; RMS-Q and RMS-TOF.
  • the excitation frequency may substantially exceed the ion oscillation frequency in order to increase the separation per ion path and this way reducing the vacuum requirements.
  • the continuous ion beams may be time modulated to provide temporary and spatially compressed ion packet in the region of spatially local AC deflection field.
  • the said step of arranging electric fields for isochronous oscillating motion may comprise one step of the group: (a) arranging an RF dipolar trap with substantially quadrupolar RF fields; (b) arranging electrostatic field of multi-turn sector analyzers with spiral ion trajectories; and (c) arranging electrostatic fields of mirror based multi-reflecting TOF mass analyzers with zigzag ion trajectories.
  • Ion motion in the drift Z-direction may in some embodiments be either free propagation at variable number of oscillation cycles, or a controlled Z-motion defined by spatially-periodic electric fields in the drift direction to provide fixed number of oscillations through the open trap; or a trap is arranged for temporal ion entrapment in the Z-direction with subsequent release of mass separated species.
  • the method of mass separation may be used for at least one stage of mass selection in a tandem mass spectrometry analysis.
  • the method of mass separation may further comprise a step of transmitting a set of multiple mass windows and a step of scanning the frequency of said AC excitation for scanning said set of multiple mass windows.
  • the method may comprise a step of crude mass selection with resolution to distinguish between multiple transmitted mass window at high AC harmonics for the purpose of selecting a single m/z specie.
  • a resonant mass separator comprising:
  • said open trap is arranged for ion confinement in the second orthogonal Y-direction
  • said open trap is arranged for ion propagation through the trap in the third orthogonal Z-direction;
  • At least one electrode of said trap is arranged for providing a substantially local region of deflecting electric field, being substantially orthogonal to the X-direction;
  • the open trap may be selected from one of the group: (a) an RF dipolar trap with substantially quadrupolar RF fields; (b) a multi-turn electrostatic sector analyzer with spiral ion trajectories; and (c) a mirror based electrostatic multi-reflecting TOF mass analyzers with zigzag ion trajectories.
  • the mass spectrometer may have an open trap comprising means for spatial modulation of electric fields to provide the spatial confining of the ion Z-motion in the drift direction, thus, providing a fixed number of oscillations per ion passage through said open trap.
  • the mass spectrometer may comprise a pulsed accelerating modulator after said ion source for temporary ion packet compression in said AC deflection zone.
  • the mass spectrometer may comprise an additional crude mass selector between said open trap and said ion receiver.
  • the open trap may employ RF fields and wherein said open trap is wrapped into a circle or a spiral.
  • the mass spectrometer may be used for at least at least one stage of mass selection in a tandem mass spectrometer.
  • Fig.l schematically depicts a resonant mass separator based on radio-frequency dipole
  • Fig.2 schematically depicts a radio-frequency mass separator with extended separation paths and times
  • Fig.3 schematically depicts a tandem mass spectrometer employing the resonant mass separator of Fig.1;
  • Fig.4 schematically depicts an electrostatic resonant mass separator using multi-turn isochronous analyzer based on electric sectors
  • Fig.5 schematically depicts an electrostatic resonant mass separator using multi- reflecting isochronous analyzer based on gridless ion mirrors
  • Fig.6 schematically depicts an electrostatic resonant mass separator with axial bunching of continuous ion beams
  • Fig.7 depicts a model of resonant separator used for subsequent numerical simulations
  • Fig.10 presents a simulated graph of ion transmission Vs square root of m/z for soft bunched ion beam at shown simulation parameters; the graph illustrates that RMS normally provides multiplicity of transmitted mass bands; the graph also illustrates the principle of resonant stabilization for narrow mass band;
  • Fig.ll shows the peak shape for simulations of Fig.10; peak shape has narrow wings and mass resolving power is over 10,000 at 92% transmission, which exceeds resolution of convention quadrupole separators by factor of 100;
  • Fig.13 shows a SINION model and spiral ion trajectories in a resonance mass separator, constructed of cylindrical sectors and sets of periodic einzel and quadrupolar lens;
  • Figure illustrates two cases - of pulsed ion packets in graph 141 and of continuous ion beams in graph 144;
  • Fig.15 illustrates the principle of parallel MS-MS analysis employing RMS of the present invention for parent separator; AC frequency is scanned to admit multiple m/z species simultaneously, from which normal MS-MS spectra may be recovered after data decoding while improving the MS-MS throughput.
  • Multi-pass open traps are defined as analyzers, trapping ions within a two-dimensional electric (DC or RF) field in an X-Y plane, while passing ions in the third Z-direction.
  • Ion trapping in the X-Y plane is arranged by moving ions along a generally curved mean ion path P, composed of multiple oscillations (turns or reflections), while passing ions through the trap in the generally curved third - drift direction Z, being locally orthogonal to the X-Y plane.
  • the invention proposes using either electrostatic open traps, trapping moving ions within DC electric fields, or electro-dynamic open traps, trapping ions in radiofrequency RF fields.
  • Exemplar multipass traps comprise: (a) RF dipolar trap with substantially quadrupolar RF fields; (b) multi-turn electrostatic sector analyzers with spiral ion trajectories; and (c) mirror based multi-reflecting TOF mass analyzers with zigzag ion trajectories. It is of principal importance that the invention employs open traps passing ion beams through in 0.1-lms time scale without prolonged ion trapping, thus avoiding space charge effects which are present in ion traps of prior art.
  • X and Y axes define the plane of the two-dimensional electric field in planar or cylindrical topologies.
  • curved Z axis is defined being locally orthogonal to X-Y plane, which accounts for examples of cylindrical topology, shown in Fig.2.
  • Two-dimensional electric field does not induce any field in the Z-direction and allows free ion propagation (drift) in the Z-direction, also called as drift direction.
  • axes To keep general annotation of axes, we define a separate set of axes, where P axis corresponds to projection of isochronous mean ion path onto the X-Y plane and N-axis is defined being locally orthogonal to the P-axis within the X-Y plane. In some cases, the P-axis is arranged along the X-direction, as shown in Figs. 1-3, 5, 6 and 13. In case of sector based analyzers, the mean ion trajectory is curved and a set of P and N axis rotate in the X-Y plane to follow the curvature of the mean ion trajectory.
  • the ion motion in the drift Z-direction may be either free or controlled. Free ion propagation at non determined number of oscillations through the trap occurs at zero field in the Z-direction.
  • the ion motion may be confined along a mean ion trajectory by electric fields, thus, providing fixed number of oscillations per ion passage through the open trap.
  • ions may be temporarily trapped in the Z-direction for fixed (though limited to 0.1-lms) trapping time.
  • the period T of ion oscillations (turns or reflections) in the X-Y plane and between time-focal points stays independent on spatial angular and energy spreads of ion beams or packets at least to the first order of corresponding time aberrations.
  • Quadrupolar RF fields are parabolic and thus provide isochronicity for a wide range of ion beam spreads.
  • Multi-turn sector open traps are known to be first-order isochronous relative to spatial, angular and energy spreads.
  • Multi-reflecting ion mirror analyzers are known to be isochronous to high (second and third) order of aberration limits.
  • the proposed resonant mass separators use the same method of ion selection.
  • Continuous, or time modulated ion beam propagates through a multi-pass open trap analyzer.
  • a periodic excitation signal is applied to at least one AC excitation electrode for side deflecting, focusing or defocusing, arranged spatially periodic, say, at symmetry plane of the analyzer.
  • Multiple examples are provided for various AC excitation set of electrodes, like deflectors, periodic einzel lens, or periodic quadrupolar lens.
  • the excitation signal appears in resonance with periodic oscillation for ions of some particular m/z, thus providing an opportunity for various schemes of resonance ion selection, either by removal of unwanted resonant ions or by stabilizing motion of wanted resonant ion species.
  • deflectors the choice between N and N+0.5 depends on ion trajectory inversions in the transverse direction and thus, depends on spatial focusing of a chosen analyzer.
  • the proposed methods and apparatuses employ local regions of excitation AC field and high harmonics (N»l) of the excitation frequency compared to ion oscillation frequency. Both means allow much higher resolution of mass selection at limited ion passage time and ion path.
  • the method would work similarly to gated TOF with rarely pulsed ion packets, but at a cost of very limited duty cycle, space charge effects at higher ion currents, and dynamic range limitations.
  • the proposed method is suitable and employs either continuous ion beams or quasi-continuous beams, e.g. gently modulated with frequent axial bunching usually at MHz frequency range.
  • one preferred embodiment of resonant mass selector 10 comprises a pair of back to back monopoles 11, each monopole 11 being composed of circular rod placed against the 90 corner electrodes, having slits for ion passage between monopoles.
  • the improved embodiment 12 may be a dipole with purely quadrupolar field, composed by two pairs of hyperbolic electrodes 14 and 15, where electrodes 14 have much larger distance to the center relative to one of electrodes 15.
  • the hyperbolic rods of the embodiment 12 may be reasonably approximated with wedge electrodes having circular tips, as shown in the drawing.
  • the electrode system may be energized by RF and DC signals to form quadrupolar fields.
  • RF and DC signals Preferably, high amplitude RF signal is applied to large electrodes 14, while a dipolar excitation AC signal and an optional positive DC are applied to smaller electrodes 15.
  • Frequency F is independent on oscillation amplitudes, on ion beam spatial (dX, dY) and energy (dK) spreads, or in other words, the proposed asymmetric quadupolar open trap 10, 12 and 13 are highly isochronous in regard to secular oscillations in both X and Y-directions.
  • the oscillation period T l/f is proportional to square root of ion m/q, which is used here for resonant mass separation.
  • the shown embodiment employs purely two dimensional RF and (optionally) DC fields in X-Y plane and has no electric field in the drift Z-direction.
  • the ion motion in the drift Z- direction is free propagation with number of oscillation cycles depending on an ion injection angle, an energy and their spreads.
  • an end electrodes of the open trap may be set to temporary retarding RF or DC potentials for temporary ion entrapment in the Z-direction with subsequent release of the already mass separated species.
  • the latter method allows more precise control over the separation time, being less dependent on ion beam parameters, however adds the complexity of the cyclic operation.
  • the side view of the embodiment 12 illustrates the operation principle.
  • a continuous beam of ions is introduced via an aperture 17 at an angle to axis X and ions follow trajectories 19, composed of major secular oscillations 19X in the X-direction and of secular oscillations 19Y in the Y direction, the latter having much smaller amplitude because of the ion injection scheme.
  • the P direction is chosen along the X-axis
  • N-direction is chosen along the Y-axis.
  • Ion motion is composed of (a) ion oscillations along the P-axis; (b) transverse oscillations in the N-direction at relatively smaller velocities and amplitudes; and (c) relatively slower ion drift in the Z-direction.
  • the RF field retards ions to the axis along the X direction, while both RF and DC field do confine ions in the Y-direction.
  • ions experience so-called secular oscillations, being independent in both- X and Y directions, while propagating along the axis Z.
  • Period T(m/z) of secular oscillations is longer than RF signal period 1/ ⁇ and it depends on m/z.
  • T(m/z) the frequencies of oscillations in Y and X directions are equal.
  • ion trajectories 19Y in the Y direction the AC excitation provides side kick, adds ion velocity from the axis and throws ions from dash line trajectory to solid line trajectory with larger oscillation amplitude.
  • the dipolar excitation field is arranged spatially local, as shown in the embodiment 13, where the AC signal is applied to narrow electrode inserts 16.
  • Resonant mass selection depends on secular frequencies of target m/z, which in turn depend on quadrupolar field a and q parameters for target mass ions in the quadrupole.
  • Switching between target m/z values may include adjustment of (a) RF signal amplitude and/or frequency; (b) DC voltage; (c) ion beam energy; and (d) AC signal frequency and amplitude.
  • the combination of RF and DC quadrupolar signals may be chosen to transmit a relatively wide - several a.m.u. or several tens of a.m.u. - mass range, similar to operation of conventional analytical quadrupoles, while the AC signal amplitude and frequency may be used to select a sharp band within the transmitted mass range, this way selecting single m/z specie at much higher resolving power compared to conventional analytical quadrupoles.
  • multiple narrow mass windows can be filtered out, for example, mass windows corresponding to purely hydrocarbon chemical background and matrix background, while passing through hetero-atomic compounds, like nitrogen, oxygen or halogen containing molecules in GC-MS analyses.
  • the AC frequency is scanned in a wide range so that the same narrow mass window is transmitted several times during the frequency scan, though in combination with new intermixed windows, and then the normal type mass spectrum is recovered by a decoding algorithm. Details of the decoding algorithm are not described in this application.
  • the continuous ion beam 17 is soft bunched in the axial direction by axial pulsed electric field to compress the ion beam 17 into bunches 19B.
  • the axial bunching is arranged for temporal bunch compression in the P-direction with the focal plane, matching the plane of AC deflector 16.
  • the period of axial bunching matches the frequency of either the secular frequency of target ions or the frequency of the AC excitation.
  • the time shift between the axial bunching pulses and the excitation AC signal may be optimized individually per the selected m/z. Such scheme is likely to remove at least some of the unwanted m/z species.
  • the axial energy spread, introduced at axial bunching is kept low enough to entrap target ions within the RF effective potential well.
  • the energy spread, introduced at axial bunching is maintained less than 10-20eV, in order to precisely define the ions energy at the subsequent CID cell past the RMS selector, as described below for embodiment 30 of tandem MS-MS.
  • the limit to usefully highest AC frequencies is set by the degree of the electrodes asymmetry. It is understood that RF separator may have only limited asymmetry. Setting electrodes 15 too narrow would be trimming ion beams, and setting electrodes 15 too wide would require non practical RF amplitudes. Accounting the limit on harmonics, it is also expected that the separation improves with number of secular cycles, the latter being proportional to the separation times and ion paths within the separator.
  • RF mass separator 21-24 in order to improve the resolution of mass separation, several embodiments of RF mass separator 21-24 are setup for longer separation times and ion paths.
  • the embodiment 21 employs temporarily DC biased segments 25 and 26 of the RF resonant separator.
  • pulsed DC bias from generators 28 may be applied to entrance and exit slits 27. Both means can be arranged in ensemble.
  • the pulsed DC bias is expected to lock a portion of continuous ion beam for extending the separation time, thus improving mass resolution.
  • the DC bias is removed and separated ions are released at the exit side.
  • the described cycled operation does sacrifice sensitivity and dynamic range, but improves mass resolution of the RF resonant separator 21.
  • the option of "extended separation time" may be switched on and off, either according to the preset scenario in the target analyses, or may be triggered by data in the so-called data dependent analysis strategies.
  • the embodiment 22 is arranged within an RF separator which is folded into a ring, this way extending the separation path, while providing (a) stability of electrodes with larger perimeter (controlled by precise isolating spacers) and (b) extending the separation path within a compact packaging.
  • the ring may be split for ion injection at the entrance and for ion sampling at the exit.
  • Further extension of the ion path may be arranged within the embodiment 23 with spiral electrodes.
  • One possible way of making such electrodes precise is splitting ring electrodes and precise spacers and gently distorting the ring to segment of a spiral as shown in the sketch 24.
  • a preferred embodiment 30 of the invention comprises a tandem MS, where both MS stages are employing the RF dipolar resonant separator RMS 33 of the earlier described embodiment 10.
  • the embodiment 30 further comprises an ion source 31, either EI, or CI or conditioned glow discharge source for GC-MS analysis, or ICP for elemental analysis, or ESI, APCI, APPI for LC-MS analysis, all set-up for either MS-only or MS-MS analyses.
  • the embodiment 30 further comprises an optional gaseous RF ion guide 32, a collision induced dissociation (CID) cell 34, preferably made as a slit channel ion funnel.
  • Alternative tandems 35, 36 and 39 comprise at least one RMS analyzer 33, a CID cell 34 and either quadrupole analytical quadrupole 36 or TOF MS 38.
  • ion source 31 In operation, ion source 31 generates a mixture of m/z ion species.
  • the ion beam is dampened in the gaseous RF ion guide 32 to reduce the ion beam spatial and energy spreads. Ions are injected either at an angle to Z axis or at X-displacement from the middle plane to induce the secular ion oscillations along trajectories 19.
  • a target parent m/z ions are selected in the first RF dipolar RMS1 by applying a resonant AC deflecting signal to electrodes 16, as described in the embodiment 10.
  • the transmitted ions are spread in Z-direction between multiple trajectories 19, thus forming an ion flow occupying a ribbon zone, extended along the X-axis.
  • the transmitted m/z band enters the CID cell 34, preferably made as an RF channel - a set of slits with alternated RF potential, said slits being extended in the X-direction in order to maximize the ion beam acceptance.
  • the ion beam acceptance into the CID cell 34 may be enhanced by a focusing RF or electrostatic ion optics (not shown).
  • the initial injection energy and the potential bias between the RMS1 33 and the CID cell 34 do control the ion energy at the CID entrance.
  • the voltage bias is setup for either soft ion transmission (MS-only regime) or to induce the fragmentation of the selected ions in the CID cell.
  • the CID cell is set up for sufficient length and gas pressure for ion collisional dampening.
  • the dampened beam of fragment ions then enters the RMS2 33 for selecting a target fragment mass.
  • the MS-MS tandem 30 employs the method of multiple reaction monitoring MRM for target MS-MS analysis compatible with the upfront chromatographic separation.
  • the continuous ion beam is soft bunched in the axial direction, to form ion packets with the energy spread of less than 10-20eV, so that to precisely define the ions energy at subsequent CID cell 34.
  • the ion energy spread in the RMS may be selected higher, as soon as the beam energy does not exceed the height of the RF potential well.
  • the proposed RMS are expected to provide unprecedented combination of resolution and transmission, thus improving sensitivity and specificity of tandem target analysis.
  • Transmission of RMS is expected to strongly bypass about 1% transmission of costly magnet sector instruments.
  • the improved resolution allows much higher selectivity at either MSI, or MS2, or both MS stages, this way strongly improving selectivity of tandem MS-MS analysis.
  • both mass separators shall pass a single mass specie without scanning, thus avoiding duty cycle losses.
  • the tandem may employ RMS for at least one stage, while using either lower cost quadrupole or high throughput TOF for other MS stages.
  • another preferred embodiment 40 of the invention comprises electrostatic sectors 41 (here, shown as cylindrical sectors, though torroidal topology remains an option), separated by a field-free space 42, and a set of deflectors 43.
  • the RMS is preceded or followed by a secondary mass filter, here presented by lens/decelerator 47, analytical quadrupole 48, and collisional cell 49.
  • sectors 41 have curvature in the X-Y plane and are extended in the Z- direction to form an open trap, i.e. ions are trapped and focused in the X-Y plane along the mean ion path 45, thus defining curved P-axis as projection of the ion path 45 onto the X-Y plane.
  • Electrostatic sector fields are known to spatially confine ions in the transverse N direction.
  • the two-dimensional field of electrostatic sectors have zero field component in the Z-direction, so ions freely propagate in the Z-direction.
  • Continuous or soft modulated ion beam is passed along the mean path 45 at small angle to the axis P. Ions have Z-component of ion velocity 46, thus making the mean path spiral.
  • ions are spatially focused along the mean path 45 in the Z direction by a set of auxiliary electrodes 44, or by a lens field, arranged by electrical biasing of the middle section of deflectors 43, or by a set of periodic einzel or a set of quadrupolar lens (shown for other systems below) thus, defining the number of spiral turns.
  • the deflection scheme is arranged for primary deflection in the Z direction for retaining the isochronicity of ion motion in the X-Y plane, along the curved P-axis.
  • the ion motion in the X-Y plane and along P-axis remains substantially isochronous, i.e. the ion oscillation between adjacent time focal points (here located at middle plane) occurs at a period T, wherein the period T remains proportional to the square root of ion m/z and stays independent on moderate excitation and on the moderate ion spatial, angular and energy spreads.
  • the open trap passes through all the ionic species towards the downstream detector (not shown) or towards the downstream CID cell, similar to arrangement 30.
  • an AC signal is applied to deflector set 43.
  • the deflection is arranged in the Z-direction, though may be arranged in the Y-direction as well.
  • the excitation is provided by a set of periodic quadrupolar lens.
  • Ionic species with target mass m/z experience resonant compensation of the deflection between the adjacent revolutions, and do pass through the RMS. Ions with the adjacent m/z appear off the resonance, they get excited in the Z-direction (or N direction) and hit the deflector 43.
  • the RMS passes through a multiplicity of other ion species, having masses (m/z)*K*/N, where K and N are integer numbers.
  • the secondary crude mass separator AQ 48 is then followed by a fragmentation cell CID 49, as part of MS-MS strategy in the embodiments 30, 35, 37 or 39 of Fig.3.
  • the continuous ion beam is soft bunched in the axial direction, to form ion packets with the energy spread of less than 10-30eV, so that to precisely define the ions energy at subsequent CID cell and in order to maintain isochronicity of ion revolutions along the trajectory 45.
  • another preferred embodiment 50 of the invention comprises two- dimensional gridless ion mirrors 51, separated by a field free space 52, and a set of spatially periodic quadrupolar lenses 53 (optionally being a set of deflectors.
  • the RMS 50 is followed by a secondary mass filter, here presented by lens/decelerator 57, analytical quadrupole 58 and CID collisional cell 59.
  • Two dimensional ion mirrors 51 may be of either planar or cylindrical topology with corresponding drift axis Z being either straight or curved at constant radius, similarly to those described in WO2011086430 and WO2011107836.
  • the two gridless ion mirrors 51 do form two regions of electrostatic field in the X-Y plane, being substantially extended in the Z-direction.
  • Ion mirror fields are known to isochronously reflect ions in the X-direction, to provide spatial ion focusing in the Y direction and to generate no field in the Z-direction, thus forming an isochronous open electrostatic trap.
  • Continuous or weakly modulated ion beam is passed along the mean trajectory 55, having Z- component of ion velocity 56, thus forming zigzag ion trajectory 55 within the RMS analyzer 50.
  • P-axis of isochronous oscillations coincides with X-axis.
  • Normal axis N does coincide with Y- axis or Z-axis.
  • Ions of interest either freely propagate along the Z-axis, or they are spatially focused along the mean trajectory 55 in the Z direction by the set of spatially periodic and AC excited quadrupolar lens 53 to resist the natural ion beam divergence.
  • Properly designed and tuned ion mirrors are known to provide second to third order of time-of-flight focusing with respect to moderate energy, spatial and angular spreads, which allows occupying 15-20% of ion mirror window at 5-10% relative energy spread without yet violating ion motion isochronicity at a resolution of up to 100,000.
  • the periodically excited quadrupolar lens 53 provides focusing /defocusing action in both Y and Z directions, depending on the AC phase at the time of ion passage.
  • the lens may have a DC bias for continuous confinement of ions in the Z-direction to resist an ion angular divergence.
  • N- harmonics the ion oscillation frequency
  • the RMS passes through a multiplicity of other ion species, having masses (m/z)*(K+l/2)*/(N+l/2), where K and N are integer numbers.
  • the transmission of multiple mass bands is desired for higher throughput.
  • another segment of RMS is employed at different AC frequency.
  • at least two-frequency signal is applied, say with N and N-l harmonics.
  • the lens block 53 may be used for entrapping ions within the separator for several Z-paths.
  • outer electrodes of the block 53 may be setup for small angle deflection of ions, this way returning ions back into the analyzer for another through passage.
  • the outer deflectors may be also used (may also be used) for selecting a narrower mass range by proper setting of the deflection times (by properly setting the deflection times).
  • the entrapping time may controlled for a sequence of injection bunches at 1-lOms time range.
  • the preferred embodiment of RMS with ion bunching 60 comprises an ion source (not shown), followed by an RF dampening guide 32 for reducing ion beam emittance and energy spread.
  • the embodiment further comprises optional spatially focusing lens 62, an axial buncher 63, optional curved inlet and outlet 66, and an RMS 61.
  • the RMS 61 may be of any above described type: 10, 20-24, 40 or 50.
  • Fig.6 shows electrostatic RMS built of electrostatic ion mirrors 51, separated by a drift space 52 with a set of quadrupolar lenses 53, located in the middle plane of the RMS 61.
  • the embodiment 60 may further comprise an exit focusing lens 67, a crude mass filter 68, and a CID cell 69.
  • the crude mass filter 68 may be used upstream of the ion guide 32 to reduce the total ion current of the entire mass range.
  • an ion beam is generated in an ion source of EI, ESI or ICP type (not shown) and is preferably dampened in the gaseous RF ion guide 32 to reduce ion beam diameter to fraction of mm, reduce radial ion energy to nearly thermal and axial energy spread well under leV (dKo ⁇ leV).
  • the expected beam diameter is in the order of 1mm and the expected angular divergence is of few mrad.
  • the axial buncher 63 provides a time-periodic pulsed deceleration (optionally, pulsed acceleration) in order to form ion bunches and to provide temporal ion bunch compression in the middle plane of the RMS.
  • the ion velocity is approximately 30mm/us.
  • the bunching pulse amplitude is kept moderate, say 25 V, to limit the buncher induced ion energy spread dK ⁇ 25eV.
  • the next focal plane is formed past the isochronous curved inlet 66, since the combination of field-free region and sector 66 is known to provide time-of-flight focusing, where field free region is extended by the focal distance FD.
  • Parameters of buncher 63 and of curved inlet 66 are chosen to move the next time-focal plane to match the middle plane of RMS, where the lens 53 is placed.
  • the isochronous analyzer then refocuses ion packets every time they cross the middle plane. In this numerical example, let us assume an effective flight path per ion reflection being 300mm. Ions of lOOamu at 500eV energy and 30mm/us velocity will make single reflection in lOus.
  • the buncher 63 and curved inlet 66 are tuned so that the target m/z species pass the center of lens 53 at zero excitation signal at every ion mirror reflection.
  • the adjacent m/z species will have slightly different reflection period and will hit at least some of lens 53 at an unfavorable time, thus being defocused or over-focused from the mean ion path 65.
  • the ultimate time resolution of the selecting scheme can be estimated as the ratio of total flight time per the time spread of ion packets.
  • the total flight time has to be over 200us, total flight path about 6m, corresponding to approximately 20 ion mirror reflections.
  • the throughput of the suggested RMS 60 is estimated over 1E+9 ion/s at AC frequency (and bunching frequency) in multi-MHz range and assuming tolerance of multi-reflecting analyzer being over 300 ions/packet. If using sector RMS of Fig.4, the analyzer tolerance approaches 1E+4 ions/packet and the RMS throughput is expected being over lE+10 ion/s.
  • the model system 70 comprises two ion mirrors 71, separated by a 2D long drift space 72, and an ideal thin deflector 73.
  • Each ion mirror 71 is approximated by an ultra-thin spatially focusing lens 74 and a dual stage ion mirror 75.
  • Solid line 72 shows an exemplar ion trajectory at full turn (two mirror reflections).
  • the dashed line shows an exemplar ion trajectory after deflection at angle ⁇ within the deflector 73; both Y displacement and deflection angle are inversed after single reflection. If resonant signal is applied in phase, after second deflection the trajectory returns back to parallel trajectory.
  • the example presents very basic explanation for resonant separation: for ions with m/z of interest, getting into time resonance, the adjacent excitations are compensated. Following ion trajectories may be easier if hypothetically straightening the reflected trajectories into a number of repetitive cells 78, as shown in the scheme 77.
  • Isochronous properties of ion mirror 75 are modeled with an ideal dual-stage grid- covered mirror 75, where the first gap is infinitively short and has potential drop of 2/3 vs mean ion energy.
  • Results are presented for odd (A, B) and even (C, D) harmonics.
  • the comparison is made between exact resonant M/Zo ions (A, C) and ions different by 1/10,000 mass defect (B, D), i.e. of 1.0001 * /Z 0 .
  • Model parameters are shown in the icon of Fig.8A.
  • Fig.10 there are presented results of simulating the ion mass separation in the model RMS 70.
  • Ion packets are modeled at 5mm diameter, 2 degree full angular divergence, and 20eV energy spread on the top of IkeV mean energy.
  • the ion packets are assumed to be time compressed (bunched) to 10ns pulsed packets.
  • Results of the simulations are presented in the plot of ion packet transmission Vs square root of ion m/z.
  • Plots 101-104 show the progression of transmitted spectra with growth of excitation amplitude A from 0.1 deg to 3 deg.
  • narrow band in plot 104 is fully transmitted at 100%.
  • the effect of full transmission of narrow mass bands was intuitively unexpected. If assuming RMS mechanism as excitation and rejection of species being off resonance, one can expect significant drop in transmission of narrow bands. As we realized in simulations, there appear a novel unexpected effect of resonant stabilization of narrow mass bands.
  • a dual frequency excitation signal may be applied to select a single mass band, say at N and N-l, or N and N+l, or N-l and N+l, which may present a challenge when synchronizing pulsed beam with the excitation, but is expected to work at least in case of continuous ion beams, as described below.
  • the plot shows the mass peak profile after a model separator 70.
  • Parameters of the model RMS are shown in the icon.
  • the excitation amplitude corresponds to O. lrad steering (6 degrees).
  • the separator is setup for 20 oscillations before ions leave the open trap of the RMS.
  • the proposed method of periodic ion beam pulsed bunching introduces an additional complication, wherein the bunching period has to be matched with the period of the excitation signal and the phase of two may have to be adjusted per selected m/z, for example, by tuning pulse amplitude of the pulsed buncher as described in Fig.6.
  • the RMS 70 does work for continuous ion beams as well, though at a cost of moderate reduction of the transmission.
  • the AC excitation period was lus, the number of turns within the RMS 60 was equal to 20 (similar to the pulsed bunching case).
  • the excitation amplitude is varied. Higher AC amplitudes do reduce the ion transmission but improve the resolution. There were also observed narrow and wide transmission bands.
  • the right plot show the compromise between resolution and transmission. To achieve 10,000 resolution, the excitation has to be higher and the transmission drops to 20-30%.
  • the left plot shows how the excitation amplitude is linked with the transmission.
  • a model RMS 130 is constructed of cylindrical sectors 131 and 132 with different radii, similar to Sakurai et al (Nucl. Instrum. Meth. A427, 1999, 182-186). Cylindrical sectors generate substantially two-dimensional electrostatic field in the X-Y-plane. Ion path 133 is arranged spiral by injecting ion beam (or gently bunched ion packets) at small angle to the X-Y-plane and by confining ions with a set of periodic einzel lens 134 and with periodic quadrupolar lens 135.
  • Ions follow a spiral ion path 133 which is composed of the curved oval mean ion path projection in the X-Y-plane and of relatively slow ion drift in the drift Z- direction.
  • Periodic lens 134 and 135 do confine ion beam along the spiral ion path in spite of moderate ion packet divergence.
  • ions of lOOOamu do pass through the RMS without losses.
  • the AC excitation is then applied to quadrupolar lens 135, having 4mm aperture and 4mm effective length, accounting fringing fields.
  • FIG.14 there are presented graphs of ion transmission Vs excitation AC frequency for two cases - for pulsed ion packets (graphs 141 and 144) and for continuous ion beam (graph 1445).
  • AC signal is applied to quadrupolar lens 135 of RMS analyzer 130.
  • the transmission band corresponds to non integer N to compensate focusing/defocusing action of adjacent lens cells. To obtain the effect of resonant stabilization, ions have to arrive to adjacent lens cells at opposite phase.
  • the ion packet X-length is 0.35mm corresponding to ion packet duration 10ns.
  • the resolution of RMS does not improve by further shortening of ion packets, since it is primarily limited by spatial resolution of the quadrupolar lens 135.
  • the SIMION model of Fig.13 has clarified one limiting factor onto the resolution: R ⁇ L/2AX, where L - is total flight path and ⁇ - is spatial resolution of exciting quadrupolar lens.
  • L 28m
  • the ion packet X-length is 0.35mm corresponding to ion packet duration 10ns.
  • the continuous beam has been modeled as a sum of ion packets with full range of initial AC phases -90° ⁇ ⁇ 90°.
  • the overall transmission drops to 12% and the resolution drops to 4500, though lower than for bunched ion packets, but still being notably better than results obtained in analytical quadrupoles and magnet sectors.
  • the proposed method of tandem MS-MS analysis capitalizes on higher throughput at setting multiple parent mass transmission window and on the scanning of the window multiplicity by scanning AC frequency of the excitation signal.
  • tandem MS-MS 150 of the present invention comprises an RMS parent mass separator 151, fed by AC excitation signal 152, a fragmentation CID cell 153, a pulsed converter 154 and a time-of-flight mass spectrometer TOF MS 156 for analysis of fragment ions.
  • RMS 151 may be of any above described type, either a dipolar RF RMS 10, 20- 24, or sector based spiral electrostatic open trap 40 or ion mirror based multi-reflecting electrostatic open trap 50.
  • Exemplar TOF MS 156 comprises a pair of gridless ion mirrors 51, separated by a field free space 52, periodic lens 58, and a detector 59.
  • pulsed converter 154 is operated with method of frequent encoded pulsing, as described in US8853623.
  • the main principle of the proposed MS-MS method is visualized on the icon 157, schematically showing a set of transmitted parent ion mass windows.
  • the RMS 151 is arranged for transmission of multiple parent ion windows at moderate to high resolving power in the order from 3,000 to 10,000. Transmission of multiple windows dramatically improves the sensitivity and the throughput of the analysis.
  • any individual parent specie will be transmitted multiple times at predictable times - with a linear AC frequency scan the signal will be repeated at equal time intervals.
  • the set of simultaneously transmitted mass windows are spread non linearly in mass, which reduces number of simultaneously admitted parents and reduces a probability of forming same fragment ion mass by the set of simultaneously transmitted parents.
  • a single MS spectrum may be acquired for multiple transmitted mass bands, where normal mass spectra may be recovered by spectral decoding after AC scan, since through the AC scan, the same parent ion appears multiple times, though every time in combination with other set of transmitted bands.
  • Prior art separators of continuous beam do operate within statically set DC or RF fields, where present invention employs resonant excitation, i.e. different principle of ion separation.
  • Prior art ion traps employ resonant excitation for mass separation. However, they trap ions, which severely restrict the space charge capacity and the charge throughput.
  • Present invention solves the problem of space charge throughput by passing continuous or frequently modulated ion beams through open traps.
  • Prior art RF ion traps employ resonant excitation of narrow bands, where the selected ions are excited.
  • Present invention provides novel method of resonant separation, where resonant excitation is mutually canceled for ions with m/z of interest, or in other words, the present invention employs a novel principle of resonant stabilization for ions of interest, contrary of previously used method of resonant excitation.
  • Prior art RF ion traps employ AC signals of equal or lower frequencies compared to frequency of secular ion motion.
  • Prior art RF ion traps employ the excitation field within the entire volume of the trap.
  • Present invention proposes using spatially local excitation fields and using higher harmonics of the excitation field for dramatic acceleration of ion separation at fewer oscillation cycles.
  • Passing of continuous or frequently modulated ion beams is the second inventive step, since knowledgeable person would not consider isochronicity or time-of-flight synchronization for continuous ion beams.
  • Resonant stabilization of narrow mass band is the major inventive step of the present invention.
  • the prior art employs the contrary principle of resonant excitation of ions of interest.
  • Ion traps of prior art employ resonant ejection of single band.
  • Present invention passes multiple m/z bands. Mass separation of multiple m/z bands is novel. This novelty is linked to intrinsic characteristics and regimes of novel RMS.
  • the proposed MS and MS-MS apparatus is the first example, wherein multiple ions or multiple parent ions are transmitted simultaneously while selecting ions or parent ions at high resolving power.
  • proposed RMS are more compact and more economic, provide much higher ion transmission and provide an additional advantage of admitting multiple ionic bands simultaneously.
  • the proposed method is the unique and novel example of admitting multiple parent windows with non-linear combination of parent m/z.

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Abstract

L'invention concerne un séparateur de masse par résonance (RMS) et un procédé de séparation de masse par résonance qui se basent sur le passage de faisceaux d'ions continus ou légèrement modulés à travers un champ électrique d'un piège ouvert isochrone de telle sorte que les ions oscillent de façon isochrone (sont réfléchis ou tournent) dans un plan et progressent lentement dans la direction orthogonale. Le champ électrique d'excitation localisé dans l'espace est alimenté périodiquement en énergie, de préférence à des fréquences nettement plus élevées que l'oscillation des ions. Il a été constaté qu'une excitation à courant alternatif spatialement localisée à l'intérieur des pièges isochrones produit un effet de stabilisation de la résonance et une transmission efficace de bandes de masse étroites sélectionnées, tout en déviant ou en déconcentrant les autres composants ioniques. Le piège ouvert peut utiliser un filtre RF dipolaire ou un analyseur multi-tour à secteur électrostatique ou encore un analyseur à réflexion multiple basé sur des miroirs à ions. Des faisceaux d'ions continus sont de préférence modulés pulsés afin d'atteindre une transmission quasi unitaire à un pouvoir de résolution élevé (pour les séparateurs) de 10 000. La MS-MS en tandem est l'application préférée d'un RMS. Dans un procédé, de multiples fenêtres d'ions parents passent à travers le RMS pour l'analyse en tandem, ce qui permet d'atteindre un débit plus élevé des analyses à MS et MS-MS.
PCT/IB2016/055201 2015-09-10 2016-08-31 Séparateur de masse par résonance WO2017042665A1 (fr)

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WO2019202338A1 (fr) 2018-04-20 2019-10-24 Micromass Uk Limited Miroirs ioniques sans grille à champs lisses
WO2020002940A1 (fr) 2018-06-28 2020-01-02 Micromass Uk Limited Spectromètre de masse à plusieurs passages avec cycle de service élevé
US11081332B2 (en) 2017-08-06 2021-08-03 Micromass Uk Limited Ion guide within pulsed converters
US11205568B2 (en) 2017-08-06 2021-12-21 Micromass Uk Limited Ion injection into multi-pass mass spectrometers
CN113841220A (zh) * 2019-05-21 2021-12-24 塞莫费雪科学（不来梅）有限公司 具有减少节点效应的离子导向器
US11239067B2 (en) 2017-08-06 2022-02-01 Micromass Uk Limited Ion mirror for multi-reflecting mass spectrometers
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US11342175B2 (en) 2018-05-10 2022-05-24 Micromass Uk Limited Multi-reflecting time of flight mass analyser
WO2022214815A1 (fr) 2021-04-07 2022-10-13 HGSG Ltd Spectromètre de masse et procédé
US11621156B2 (en) 2018-05-10 2023-04-04 Micromass Uk Limited Multi-reflecting time of flight mass analyser
US11817303B2 (en) 2017-08-06 2023-11-14 Micromass Uk Limited Accelerator for multi-pass mass spectrometers
US11848185B2 (en) 2019-02-01 2023-12-19 Micromass Uk Limited Electrode assembly for mass spectrometer
US11881387B2 (en) 2018-05-24 2024-01-23 Micromass Uk Limited TOF MS detection system with improved dynamic range
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US12205813B2 (en) 2019-03-20 2025-01-21 Micromass Uk Limited Multiplexed time of flight mass spectrometer

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US11817303B2 (en) 2017-08-06 2023-11-14 Micromass Uk Limited Accelerator for multi-pass mass spectrometers
US11081332B2 (en) 2017-08-06 2021-08-03 Micromass Uk Limited Ion guide within pulsed converters
US11205568B2 (en) 2017-08-06 2021-12-21 Micromass Uk Limited Ion injection into multi-pass mass spectrometers
US11756782B2 (en) 2017-08-06 2023-09-12 Micromass Uk Limited Ion mirror for multi-reflecting mass spectrometers
US11211238B2 (en) 2017-08-06 2021-12-28 Micromass Uk Limited Multi-pass mass spectrometer
US11239067B2 (en) 2017-08-06 2022-02-01 Micromass Uk Limited Ion mirror for multi-reflecting mass spectrometers
US11295944B2 (en) 2017-08-06 2022-04-05 Micromass Uk Limited Printed circuit ion mirror with compensation
WO2019030475A1 (fr) 2017-08-06 2019-02-14 Anatoly Verenchikov Spectromètre de masse à multipassage
US11367608B2 (en) 2018-04-20 2022-06-21 Micromass Uk Limited Gridless ion mirrors with smooth fields
WO2019202338A1 (fr) 2018-04-20 2019-10-24 Micromass Uk Limited Miroirs ioniques sans grille à champs lisses
US11342175B2 (en) 2018-05-10 2022-05-24 Micromass Uk Limited Multi-reflecting time of flight mass analyser
US11621156B2 (en) 2018-05-10 2023-04-04 Micromass Uk Limited Multi-reflecting time of flight mass analyser
US11881387B2 (en) 2018-05-24 2024-01-23 Micromass Uk Limited TOF MS detection system with improved dynamic range
US11587779B2 (en) 2018-06-28 2023-02-21 Micromass Uk Limited Multi-pass mass spectrometer with high duty cycle
WO2020002940A1 (fr) 2018-06-28 2020-01-02 Micromass Uk Limited Spectromètre de masse à plusieurs passages avec cycle de service élevé
US11848185B2 (en) 2019-02-01 2023-12-19 Micromass Uk Limited Electrode assembly for mass spectrometer
US12205813B2 (en) 2019-03-20 2025-01-21 Micromass Uk Limited Multiplexed time of flight mass spectrometer
CN113841220A (zh) * 2019-05-21 2021-12-24 塞莫费雪科学（不来梅）有限公司 具有减少节点效应的离子导向器
CN113841220B (zh) * 2019-05-21 2024-05-14 塞莫费雪科学（不来梅）有限公司 具有减少节点效应的离子导向器
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