This application is a U.S. national phase filing under 35 U.S.C. § 371 claiming the benefit of and priority to International Patent Application No. PCT/GB2018/052104, filed on Jul. 26, 2018, which claims priority from and the benefit of United Kingdom patent application No. 1712612.9, United Kingdom patent application No. 1712613.7, United Kingdom patent application No. 1712614.5, United Kingdom patent application No. 1712616.0, United Kingdom patent application No. 1712617.8, United Kingdom patent application No. 1712618.6 and United Kingdom patent application No. 1712619.4, each of which was filed on Aug. 6, 2017. The entire content of these applications is incorporated herein by reference.
The invention relates to the area of multi-pass time-of-flight mass spectrometers (MPTOF MS) [e.g. multi-turn (MT) and multi-reflecting (MR) TOF MS with orthogonal pulsed converters, and electrostatic ion trap mass spectrometers E-Trap MS], and is particularly concerned with improved injection mechanism and control over drift ion motion in MPTOF analyzers.
Orthogonal accelerators are widely used in time-of-flight mass spectrometers (TOF MS) to form ion packets from intrinsically continuous ion sources, like Electron Impact (EI), Electrospray (ESI), Inductively couple Plasma (ICP) and gaseous Matrix Assisted Laser Desorption and Ionization (MALDI) sources. Initially, the orthogonal acceleration (OA) method has been introduced by Bendix corporation in 1964. Dodonov et. al. in SU1681340 and WO9103071 improved the OA injection method by using an ion mirror to compensate for multiple inherent OA aberrations. The beam propagates in the drift Z-direction through a storage gap between plate electrodes. Periodically, an electrical pulse is applied between plates. A portion of continuous ion beam, in the storage gap, is accelerated in an orthogonal X-direction, thus forming ribbon-shaped ion packets. Due to conservation of initial Z-velocity, ion packets drift slowly in the Z-direction, thus traveling within the TOF MS along an inclined mean ion trajectory, get reflected by an ion mirror and finally reach a detector.
The resolution of a Time of Flight mass spectrometer (TOFMS) has recently been improved by using multi-pass TOFMS (MPTOF), employing either ion mirrors for multiple ion reflections in a multi-reflecting TOFMS (MRTOF mass spectrometer), e.g. as described in SU1725289, U.S. Pat. Nos. 6,107,625, 6,570,152, GB2403063, U.S. Pat. No. 6,717,132, or employing electrostatic sectors for multiple ion turns in a multi-turn TOFMS (MTTOF mass spectrometer), e.g. as described in U.S. Pat. Nos. 7,504,620 and 7,755,036, incorporated herein by reference. The term “pass” generalizes ion mirror reflection in MRTOFs and ion turns in MTTOFs. The resolution of MPTOF mass spectrometers grows with increasing numbers of passes N, by reducing the effect of the initial time spread of ion packets and of the detector time spread. MPTOF analyzers are arranged to fold ion trajectories for substantial extension of ion flight path (e.g. over 10-50 m) within commercially reasonable size (e.g. 0.5-1 m) instruments.
By nature, the electrostatic 2D-fields of MPTOF mass analysers have zero electric field component (EZ=0) in the drift Z-direction, i.e. they have no effect on the ion packet's free propagation and its expansion in the drift Z-direction. Most of MPTOF mass analysers employ orthogonal accelerators (OA). Specific energy per charge (controlled by source bias) KZ of continuous ion beam is preserved by ion packets within the MPTOF mass analyser, thus, defining the inclination angle α of ion packets for a certain energy KX of accelerated ion packets, so as the energy spread ΔKZ then defines the initial angular spread Δα:
α=(KZ/KX)0.5; Δα=α*ΔKZ/(2KZ) (eq. 1)
To fit multiple turns (for the purpose of higher resolution), the ion beam energy KZ shall be reduced, usually under 10V, diminishing efficiency of ion beam injection into OA. Denser folding of the ion paths results in a problem of bypassing the rims of the OA and ion detector. The inevitable ion packets angular divergence Δα of a few mrad at low KZ converts into tens of mm spatial spread at the detector, causing ion losses if using skimming slits.
As understood by the inventor and not yet recognized in the field, a major problem with the performance of MPTOF mass analysers using OA injection is caused by minor misalignments of ion mirrors or sectors. Those misalignments affect free ion propagation in the drift Z-direction, and what is much more important, cause time fronts of ion packets to become tilted, affecting MPTOF isochronicity. Those effects are aggregated by mixing of ion packets at multiple reflections or turns, since time front tilting is different for initially wide parallel ion packets and for initially diverging ion packets.
The prior art proposes complex methods to define the ion drift motion and to confine the angular divergence of ion packets. For example, U.S. Pat. No. 7,385,187 proposed a periodic lens and edge deflectors for MRTOF instruments; U.S. Pat. No. 7,504,620 proposed laminated sectors for MTTOF instruments; WO2010008386 and then US2011168880 proposed quasi-planar ion mirrors having weak (but sufficient) spatial modulation of mirror fields; U.S. Pat. No. 7,982,184 proposed splitting mirror electrodes into multiple segments for arranging EZ field; U.S. Pat. No. 8,237,111 and GB2485825 proposed electrostatic traps with three-dimensional fields, though without sufficient isochronicity in all three dimensions and without non-distorted regions for ion injection; WO2011086430 proposed first order isochronous Z-edge reflections by tilting ion mirror edge combined with reflector fields; U.S. Pat. No. 9,136,101 proposed bent ion MRTOF ion mirrors with isochronicity recovered by trans-axial lens. However, those solutions have limited power and no methods were developed for compensating analyzer misalignments.
Various embodiments of the present invention provide an efficient mechanism of ion injection into MPTOF mass analyser, improve control over ion drift motion in the analyser; and provide mechanisms and methods of compensating minor analyzer misalignments to improve analyzer isochronicity. Various embodiments provide an MPTOF instrument with a resolution of R>80,000 at an ion flight path length of over 10 m for separating major isobaric interferences. This may be achieved in a compact and low cost instrument with a size of about 0.5 m or under, and without stressing requirements of the detection system and affecting peak fidelity.
From a first aspect the present invention provides a mass spectrometer comprising: a multi-pass time-of-flight mass analyzer or electrostatic ion trap having an orthogonal accelerator and electrodes arranged and configured so as to provide an ion drift region that is elongated in a drift direction (z-dimension) and to reflect or turn ions multiple times in an oscillating dimension (x-dimension) that is orthogonal to the drift direction; and an ion deflector located downstream of said orthogonal accelerator, and that is configured to back-steer the average ion trajectory of the ions, in the drift direction, and to generate a quadrupolar field for controlling the spatial focusing of the ions in the drift direction.
The ion deflector is configured to back-steer the average ion trajectory of the ions, in the drift direction. The average ion trajectory of the ions travelling through the ion deflector may have a major velocity component in the oscillation dimension (x-dimension) and a minor velocity component in the drift direction. The ion deflector back-steers the average ion trajectory of the ions passing therethrough by reducing the velocity component of the ions in the drift direction. The ions may therefore continue to travel in the same drift direction upon entering and leaving the ion deflector, but with the ions leaving the ion deflector having a reduced velocity in the drift direction. This enables the ions to oscillate a relatively high number of times in the oscillation dimension, for a given length in the drift direction, thus providing a relatively high resolution.
However, it has been recognised that a conventional ion deflector inherently has a relatively high focusing effect on the ions, hence undesirably increasing the angular spread of the ion trajectories exiting the deflector, as compared to the angular spread of the ion trajectories entering the ion deflector. This may cause excessive spatial defocusing of the ions downstream of the focal point, resulting in ion losses and/or causing ions to undergo different numbers of oscillations in the spectrometer before they reach the detector. This may cause spectral overlap due to ions from different ion packets being detected at the same time. The mass resolution of the spectrometer may also be adversely affected. Such conventional ion deflectors are therefore particularly problematic in multi-pass time-of-flight mass analysers or multi-pass electrostatic ion traps, since a large angular spread of the ions will cause any given ion packet to diverge a relatively large amount over the relatively long flight path through the device. Embodiments of the present invention provide an ion deflector configured to generate a quadrupolar field that controls the spatial focusing of the ions in the drift direction, e.g. so as to maintain substantially the same angular spread of the ions passing therethrough, or to allow only the desired amount of spatial focusing of the ions in the z-direction.
The quadrupolar field for in the drift direction may generate the opposite ion focusing or defocusing effect in the dimension orthogonal to the drift direction and oscillation dimension. However, it has been recognised that the focal properties of MPTOF mass analyser (e.g. MRTOF mirrors) or electrostatic trap are sufficient to compensate for this.
The multi-pass time-of-flight mass analyser may be a multi-reflecting time of flight mass analyser having two ion mirrors that are elongated in the drift direction (z-dimension) and configured to reflect ions multiple times in the oscillation dimension (x-dimension), wherein the orthogonal accelerator is arranged to receive ions and accelerate them into one of the ion mirrors; or the multi-pass time-of-flight mass analyser may be a multi-turn time of flight mass analyser having at least two electric sectors configured to turn ions multiple times in the oscillation dimension (x-dimension), wherein the orthogonal accelerator is arranged to receive ions and accelerate them into one of the sectors.
Where the mass analyser is a multi-reflecting time of flight mass analyser, the mirrors may be gridless mirrors.
Each mirror may be elongated in the drift direction and may be parallel to the drift dimension.
It is alternatively contemplated that the multi-pass time-of-flight mass analyser or electrostatic trap may have one or more ion mirror and one or more sector arranged such that ions are reflected multiple times by the one or more ion mirror and turned multiple times by the one or more sector, in the oscillation dimension.
The mass analyser or electrostatic trap may be an isochronous and/or gridless mass analyser or an electrostatic trap.
The mass analyser or electrostatic trap may be configured to form an electrostatic field in a plane defined by the oscillation dimension and the dimension orthogonal to both the oscillation dimension and drift direction (i.e. the XY-plane).
This two-dimensional field may have a zero or negligible electric field component in the drift direction (in the ion passage region). This two-dimensional field may provide isochronous repetitive multi-pass ion motion along a mean ion trajectory within the XY plane.
The energy of the ions received at the orthogonal accelerator and the average back steering angle of the ion deflector may be configured so as to direct to an ion detector after a pre-selected number of ion passes (i.e. reflections or turns).
The spectrometer may comprise an ion source. The ion source may generate an substantially continuous ion beam or ion packets.
The orthogonal accelerator may be a gridless orthogonal accelerator.
The orthogonal accelerator has a region for receiving ions (a storage gap) and may be configured to pulse ions orthogonally to the direction along which it receives ions. The orthogonal accelerator may receive a substantially continuous ion beam or packets of ions, and may pulse out ion packets.
The drift direction may be linear (i.e. a dimension) or it may be curved, e.g. to form a cylindrical or elliptical drift region.
The mass analyser or ion trap may have a dimension in the drift direction of: ≤1 m; ≤0.9 m; ≤0.8 m; ≤0.7 m; ≤0.6 m; or ≤0.5 m. The mass analyser or trap may have the same or smaller size in the oscillation dimension and/or the dimension orthogonal to the drift direction and oscillation dimension.
The mass analyser or ion trap may provide an ion flight path length of: between 5 and 15 m; between 6 and 14 m; between and 13 m; or between 8 and 12 m.
The mass analyser or ion trap may provide an ion flight path length of: ≤20 m; ≤15 m; ≤14 m; ≤13 m; ≤12 m; or ≤11 m. Additionally, or alternatively, the mass analyser or ion trap may provide an ion flight path length of: ≥5 m; ≥6 m; ≥7 m; ≥8 m; ≥9 m; or ≥10 m. Any ranges from the above two lists may be combined where not mutually exclusive.
The mass analyser or ion trap may be configured to reflect or turn the ions N times in the oscillation dimension, wherein N is: ≥5; ≥6; ≥7; ≥8; ≥9; ≥10; ≥11; ≥12; ≥13; ≥14; ≥15; ≥16; ≥17; ≥18; ≥19; or ≥20. The mass analyser or ion trap may be configured to reflect or turn the ions N times in the oscillation dimension, wherein N is: ≤20; ≤19; ≤18; ≤17; ≤16; ≤15; ≤14; ≤13; ≤12; or ≤11. Any ranges from the above two lists may be combined where not mutually exclusive.
The spectrometer may have a resolution of: ≥30,000; ≥40,000; ≥50,000; ≥60,000; ≥70,000; or ≥80,000.
The spectrometer may be configured such that the orthogonal accelerator received ions having a kinetic energy of: ≥20 eV; ≥30 eV; ≥40 eV; ≥50 eV; ≥60 eV; between 20 and 60 eV; or between 30 and 50 eV. Such ion energies may reduce angular spread of the ions and cause the ions to bypass the rims of the orthogonal accelerator.
The spectrometer may comprise an ion detector.
The detector may be an image current detector configured such that ions passing near to it induce an electrical current in it. For example, the spectrometer may be configured to oscillate ions in the oscillation dimension proximate to the detector, inducing a current in the detector, and the spectrometer may be configured to determine the mass to charge ratios of these ions from the frequencies of their oscillations (e.g. using Fourier transform technology). Such techniques may be used in the electrostatic ion trap embodiments.
Alternatively, the ion detector may be an impact ion detector that detects ions impacting on a detector surface. The detector surface may be parallel to the drift dimension.
The ion detector may be arranged between the ion mirrors or sectors, e.g. midway between (in the oscillation dimension) opposing ion mirrors or sectors.
The ion deflector may be configured to generate a substantially quadratic potential profile in the drift direction.
The ion deflector may back steers all ions passing therethrough by the same angle; and/or may control the spatial focusing of the ion packet in the drift direction such that the ion packet has substantially the same size in the drift dimension when it reaches an ion detector in the spectrometer as it did when it enters the ion deflector.
The ion deflector may the spatial focusing of the ion packet in the drift direction such that the ion packet has a smaller size in the drift dimension when it reaches a detector in the spectrometer than it did when it entered the ion deflector.
The spectrometer may comprise at least one voltage supply configured to apply one or more first voltage to one or more electrode of the ion deflector for performing said back-steer and one or more second voltage to one or more electrode of the ion deflector for generating said quadrupolar field for said spatial focusing, wherein the one or more first voltage is decoupled from the one or more second voltage.
The ion deflector may comprise at least one plate electrode arranged substantially in the plane defined by the oscillation dimension and the dimension orthogonal to both the oscillation dimension and the drift direction (X-Y plane), wherein the plate electrode is configured back-steer the ions; and wherein the ion deflector comprises side plate electrodes arranged substantially orthogonal to the opposing electrodes and that are maintained at a different potential to the opposing electrodes for controlling the spatial focusing of the ions in the drift direction.
The side plates may be Matsuda plates.
The at least one plate electrode may comprise two electrodes and a voltage supply for applying a potential difference between the electrodes so as to back-steer the average ion trajectory of the ions, in the drift direction.
The two electrodes may be a pair of opposing electrodes that are spaced apart in the drift direction.
However, it is contemplated that only the upstream electrode (in the drift direction) may be provided, so as to avoid ions hitting the downstream electrode.
The ion deflector may be configured to provide said quadrupolar field by comprising one or more of: (i) a trans-axial lens/wedge; (iii) a deflector with aspect ratio between deflecting plates and side walls of less than 2; (iv) a gate shaped deflector; or (v) a toroidal deflector such as a toroidal sector.
The ion deflector may focus the ions in a y-dimension that is orthogonal to the drift direction and the oscillation dimension, and wherein the orthogonal accelerator and/or mass analyser or electrostatic ion trap is configured to compensate for this focusing.
For example, the orthogonal accelerator and/or mass analyser or electrostatic ion trap may defocus the ions in the y-dimension.
In embodiments where the multi-pass time-of-flight mass analyser is a multi-reflecting time of flight mass analyser having ion mirrors, the ion mirrors may compensate for the y-focusing caused by the ion deflector. In embodiments where the multi-pass time-of-flight mass analyser is a multi-turn time of flight mass analyser having sectors, the sectors may compensate for the y-focusing caused by the ion deflector.
The ion deflector may be arranged such that it receives ions that have already been reflected or turned in the oscillation dimension by the multi-pass time-of-flight mass analyser or electrostatic ion trap; optionally after the ions have been reflected or turned only a single time in the oscillation dimension by the multi-pass time-of-flight mass analyzer or electrostatic ion trap.
The location of the deflector directly after the first ion mirror reflection allows yet denser ray folding.
The orthogonal accelerator may be arranged and configured to receive ions along an ion receiving axis that is tilted at an angle to the drift direction, in a plane defined by the drift direction and the oscillation dimension (XZ-plane), and to pulse the ions orthogonally to the ion receiving axis such that the time front of the ions exiting the orthogonal accelerator is parallel to the ion receiving axis. The ion deflector may be configured to back-steer the ions, in the drift direction, such that the time front of the ions becomes parallel, or more parallel, to the drift dimension and/or an impact surface of an ion detector after the ions exit the ion deflector.
For the avoidance of doubt, the time front of the ions may be considered to be a leading edge/area of ions in the ion packet having the same mass (and optionally the mean average energy).
The ion receiving axis may be tilted at an acute tilt angle β to the drift direction; wherein the ion deflector back steers ions passing therethrough by a back-steer angle ψ, and wherein the tilt angle and back-steer angle are the same.
It is believed that it had not previously been recognised that the combination of the tilting of the orthogonal accelerator and the ion deflector back steering may compensate for the chromatic angular spread of the ions by the ion deflector at exactly the same condition.
Ion injection may be improved by tilting the orthogonal accelerators as described above, since it allows the ion beam energy at the entrance to the orthogonal accelerator to be increased, thereby reducing angular spread of the ions and causing the ions to bypass the rims of the orthogonal accelerator. The orthogonal accelerator may be tilted to the drift direction by an acute angle, e.g. several degrees.
The spectrometer may comprise an ion optical lens for spatially focusing or compressing the ion packet in the drift direction, wherein the ion deflector is configured to defocus the ion packet in the drift direction, and wherein the combination of the ion optical lens and ion deflector are configured to provide telescopic compression of the ion beam.
The ion optical lens may be located between the orthogonal accelerator and the ion deflector.
The ion optical lens may be a trans-axial lens, and may be combined with trans-axial wedge for both focusing and deflection.
The wedge lens referred to herein may generate equipotential field lines that diverge, converge or curve as a function of position along the drift direction (Z-direction). For example, this may be achieved by two electrodes that are spaced apart by an elongated gap that is curved along the longitudinal axis of the gap. Alternatively, this may be achieved by two electrodes that are spaced apart by a wedge-shaped gap.
The spectrometer may comprise an ion optical lens for compressing the ion packet in the drift direction by a factor C; wherein said orthogonal accelerator is arranged and configured to receive ions along an ion receiving axis that is tilted at an angle β to the drift direction, in a plane defined by the drift direction and the oscillation dimension (XZ-plane); wherein the ion deflector is configured to back-steer the ions, in the drift direction, by angle ψ, and wherein β=ψ/C.
The inventor has discovered that this relationship compensates for the tilted time front caused by the orthogonal ion accelerator.
The combination of the ion optical lens and ion deflector may be configured to provide telescopic compression of the ion beam.
The spectrometer may comprise a further ion deflector proximate an ion detector in the spectrometer for deflecting the average ion trajectory such that ions are guided onto a detecting surface of the detector.
This avoids ions impacting on inactive regions of the detector, such as its rims.
The further deflector may deflect ions after the final and/or penultimate reflection or turn in the oscillation dimension.
An intermediate ion optical lens (e.g. Einzel lens or trans-axial lens) may be arranged between the orthogonal accelerator and ion detector for providing additional focusing and/or steering of the ions. This lens may be arranged to have a relatively long focal length (e.g. 5-10 m or more).
The ions may pass through the intermediate ion optical lens at least four times as they are reflected in the mirrors or turned in the sectors.
The present invention also provides a method of mass spectrometry comprising: providing the spectrometer described herein; transmitting ions into the orthogonal accelerator along an ion receiving axis; accelerating the ions orthogonally to the ion receiving axis in the orthogonal accelerator; and deflecting the ions downstream of said orthogonal accelerator so as to back-steer the average ion trajectory of the ions, in the drift direction, and controlling the spatial focusing of the ions in the drift direction with the quadrupolar field; wherein the ions are oscillated multiple times in the oscillation dimension by the multi-pass time-of-flight mass analyser or electrostatic ion trap as the ions drift through the drift region in the drift direction.
The present invention also provides a mass spectrometer comprising: a multi-pass time-of-flight mass analyzer or electrostatic ion trap having an orthogonal accelerator and electrodes arranged and configured so as to provide an ion drift region that is elongated in a drift direction (z-dimension) and to reflect or turn ions multiple times in an oscillating dimension (x-dimension) that is orthogonal to the drift direction; and an ion deflector located downstream of said orthogonal accelerator, and that is configured to back-steer the average ion trajectory of the ions, in the drift direction, and to compensate for changes in the angular spread of the ions that would be caused by the back-steering.
This aspect may have any of the features described above in relation to the first aspect. For example the compensating for the changes in the angular spread of the ions may be performed by configuring the ion deflector to generate a quadrupolar field for controlling the spatial focusing of the ions in the drift direction.
A range of improvements is proposed for ion injection mechanism into MPTOF MS analyzers, either MRTOF or MPTOF, with two dimensional electrostatic fields and free ion drift in the Z-direction. The improvements are also applicable to other isochronous electrostatic ion analyzers, such as electrostatic traps and open traps, so as to electrostatic analyzers with generally curved drift axis, such as cylindrical trap, or elliptical TOF MS.
Problems of conventional MPTOF instruments have been recognized, which are created by low injection energy of continuous ion beam, by insufficient folding of ion packets caused by the necessity of bypassing rims of OA and detector, by the ion packet divergence and, which is most important, by parasitic effects of components misalignments. It was recognized that those problems can be solved with an improved ion injection mechanism, combining the OA tilting with the beam steering by compensated deflectors, and then adjusting parameters of the injection for compensating the misalignments.
An embodiment of the present invention provides a time-of-flight mass spectrometer comprising:
Preferably, the spectrometer may further comprise means for introducing quadrupolar field within said at least one deflector for compensating the over-focusing of said deflector and for controlling the focal distance of the deflector in the Z-direction; wherein ion packet focusing by said means in the transverse Y-direction is compensated by tuning of said analyzer or of said gridless accelerator.
Preferably, means for introducing quadrupolar field may comprise one of the group: (i) trans-axial lens/wedge; (ii) Matsuda plate or torroidal deflector; (iii) deflector with aspect ratio between deflecting plates and side walls of less than 2; (iv) gate shaped deflector; or (v) torroidal deflector.
Preferably, the spectrometer may further comprise a dual deflector arranged for ion packet displacement at mutual compensation of the time-front tilt; wherein said dual deflector may be used either for ion bypassing the accelerator or detector rim, or for improved transmission between said accelerator and said at least one deflector; or for telescopic compression of ion packets, or for ion reversing in the drift Z-direction; or for the tuning of ion packets time-front tilt T|Z or for compensating ion packets time-front bend T|ZZ.
Preferably, said isochronous gridless analyzer may be part of one of the group: (i) multi-reflecting or multi-turn time-of-flight mass spectrometer; (ii) multi-reflecting or multi-turn open trap; and (iii) multi-reflecting or multi-turn ion trap. Preferably, said drift Z-axis is generally curved to form cylindrical or elliptical analyzers and alike.
An embodiment of the present invention provides a method of mass spectrometric analysis comprising the following steps:
Preferably, the method may further comprise a step of introducing quadrupolar field within said at least one deflector for compensating the over-focusing of said deflector and for controlling the focal distance of the deflector in the Z-direction; wherein ion packet focusing by said quadrupolar field in the Y-direction may be compensated by tuning of said analyzer or of spatial focusing in said gridless accelerator.
Preferably, the method may further comprise a step of ion packet dual steering within adjacent ion passes in a dual deflector, tuned for mutual compensation of the time-front tilt; wherein said dual steering may be used either for ion bypassing the accelerator or detector rim, or for improved transmission between said accelerator and said at least one deflector; or for telescopic compression of ion packets; or for ion reversing in the drift Z-direction; or for the tuning of ion packets time-front tilt T|Z or for compensating ion packets time-front bend T|ZZ.
Preferably, said ion motion within said isochronous two dimensional electric field of said analyzer may be arranged for ion single pass in said drift direction, or for multiple back and forth passes; or for ion trapping by trapping in the drift direction.
Preferably, said drift Z-axis may be generally curved to form cylindrical or elliptical two-dimensional fields.
Preferably, said energy of ion beam and said steering angles are adjusted to compensate for misalignments and imperfection of said pulsed acceleration field, or said isochronous field of analyzer, or of the detector.
Preferably, the method may further comprise a step of ion packet steering and a step of ion packet focusing or defocusing in quadrupolar field, both arranged in-front of the detector, to compensate for components and fields misalignments.
Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:
Referring to
In operation, ion source 11 generates continuous ion beam. Commonly, ion sources 11 comprise gas-filled radio-frequency (RF) ion guides (not shown) for gaseous dampening of ion beams. Lens 12 forms a substantially parallel continuous ion beam 13, entering OA 14 along the Z-direction. Electrical pulse in OA 14 ejects ion packets 15. Packets 15 travel in the MRTOF analyser at a small inclination angle α to the x-axis, which is controlled by the ion source bias UZ. After multiple mirror reflections, ion packets hit detector 17. Specific energy of continuous ion beam 13 controls the inclination angle α and number of mirror reflections.
Referring to
Similarly to the arrangement in
The laminated sectors 27 provide three dimensional electrostatic fields for ion packet 25 confinement in the drift Z-direction along the mean spiral trajectory 24. The fields of the four electrostatic sectors 27 also provide for isochronous ion oscillation along the—figure-of-eight shaped central curved ion trajectory 24 in the XY-plane (also denoted as s). If departing from technically complex lamination, the spiral trajectory may be arranged within two dimensional sectors. However, some means of controlling ion Z-motion are then required, very similar to MRTOF instruments.
The improvements of the embodiments of the present invention are equally applicable to both MRTOF and MTTOF instruments.
Referring to
In example 30, to fit 14 ion reflections (i.e. L=7 m ion flight path) the source bias is set to UZ=9V. Parallel ion rays with an initial ion packet length in the z-dimension of Z0=10 mm and no angular spread (Δα=0) start hitting rims of OA 14 and of detector 17. In example 31, the top ion mirror is tilted by λ=1 mrad, representing a realistic overall effective angle of mirror tilt considering built up faults of stack assemblies, standard accuracy of machining and moderate electrode bend by internal stress at machining. Every “hard” ion reflection in the top ion mirror then changes the inclination angle α by 2 mrad. The inclination angle α grows from α1=27 mrad to α2=41 mard, gradually expanding central trajectory. To hit the detector after N=14 reflections, the source bias has to be reduced to UZ=6V. The angular divergence is amplified by the mirror tilt and increases the ion packets width to ΔZ=18 mm, inducing ion losses on the rims. Obviously, slits in the drift space may be used to avoid trajectory overlaps, however, at a cost of additional ionic losses.
In example 31, the inclination of ion mirror introduces yet another and much more serious problem. The time-front 15 of the ion packet becomes tilted by angle γ=14 mrad in-front of the detector. The total ion packet spreading in the time-of-flight X-direction ΔX=ΔZ*γ=0.3 mm does limit mass resolution to R<L/2ΔX=11,000 at L=7 m flight path, being low even for a regular TOF instrument and too low for MRTOF instruments. To avoid the limitation, the electrode precision has to be brought to a non-realistic level: λ<0.1 mrad, translated to better than 10 um accuracy and straightness of individual electrodes.
Thus, attempts of increasing flight path length enforce much lower specific energies UZ of continuous ion beam and larger angular divergences Δα of ion packets, which induce ion losses and may produce spectral overlaps. Small mechanical imperfections also affect MRTOF resolution and require unreasonably high precision.
Various embodiments of the present invention will now be described.
It is desirable to keep instrument size relatively small, e.g. at about 0.5 m, or under. Using larger analyzers raises manufacturing cost close to the cubic power of the instrument size.
Preferably, data system and detector time spreading (at peak base) shall not be pushed under DET=1.5-2 ns. This will avoid expensive ultra-fast detectors with strong signal ringing. It will also avoid artificial sharpening of resolution by “centroid detection” algorithms, ruining mass accuracy and merging mass isobars.
To resolve practically important isobars at mass resolution RTOF/2DET, the peak width shall be less than isobaric mass difference, hence requiring longer flight time TOF and longer flight path L (calculated for 5 kV acceleration), all shown in the Table 1.
The table presents the most relevant and most frequent isobaric interferences of first isotopes. In case of LC-MS, the required resolution may be over 80,000. In case of GC-MS, where most of ions are under 500 amu, the required resolution may be over 40K.
Thus, various embodiments of the present invention provide an ion flight path over 10 m in length. The mass analyser may also have a size of ≤0.5 m in any one (e.g. horizontal) dimension. The mass analyser may provide N passes (e.g. reflections or turns), where N>20. The analyser may be minimise the effect of aberrations of the ion optical scheme on resolution. Embodiments are able to operate at reasonably high ion beam energy (>30-50 eV) for improved ion beam admission into the orthogonal accelerator.
Embodiments of the invention provide the instrument with sufficient resolution (e.g. R>80,000) and a flight path over 10 m for separating major isobaric interferences, achieved in compact and low cost instrument (e.g. having a size of about 0.5 m or under), without stressing the requirements of the detection system and not affecting peak fidelity.
The below described embodiments are described in relation to particularly compact MRTOF analysers having a size (e.g. in the horizontal dimensions) of 450×250 mm, and operating at 8 kV acceleration voltage. However, other sized instruments and other acceleration voltages are contemplated.
The below described embodiments of the present invention may employ ion deflectors, and optionally, improved deflectors with compensated over-focusing.
Referring to
Referring back to
γ(z)=−ψ(z)=U/K*D/2H+ε(z),
ε(z)=ψ*U/K*z/H; F=2D/ψ2
The inevitable focusing of such conventional deflectors makes them a poor choice for controlling ion drift motion in MPTOF instruments. However, the inventor has recognised that an ion deflector may be used in an advantageous manner.
Again referring to
EZU/H−2UQ*z/H2,
γ=−ψ=−D/2H*U/K
F=D/(ψ2/2−K/UQ)
The quadrupolar fields allows controlling spatial focusing (at negative UQ) and defocusing (at negative UQ) of the ions by the deflector 40.
The quadrupolar field in the Z direction inevitably generates an opposite focusing or defocusing field in the transverse Y-direction. However, it has been recognised that the focal properties of MPTOF mass analyser (e.g. MRTOF mirrors) are sufficient to compensate for the Y-focusing of the quadrupolar deflectors 40, even without adjustments of ion mirror potentials and without any significant time-of-flight aberrations.
Similar compensated deflectors are proposed to be constructed out of trans-axial (TA) deflectors, formed by wedge electrodes. Similarly to embodiment 40, an embodiment of the invention proposes using a first order correction, produced by an additional curvature of TA-wedge. Third, yet simpler compensated deflector can be arranged with a single potential while selecting the size of Matsuda plates, suitable for a narrower range of deflection angles. The asymmetric deflector is then formed with a deflecting electrode having gate shape, surrounded by shield, set at the drift potential. Forth, similarly (though more complex), the compensated deflector can be arranged with torroidal sector.
As described above, various embodiments provide improved compensated ion deflectors to overcome the over-focusing problem of conventional ion deflectors, so as to control the focal distance of the deflectors, including defocusing by quadrupolar fields. Transverse effects of the quadrupolar field may be well compensated by the spatial and isochronous properties of MPTOF mass analyser.
In operation, ion source 11 generates continuous ion beam at specific energy UZ (e.g. defined by source 11 bias). Preferably, ion source 11 comprise gas-filled radio-frequency (RF) ion guide (not shown) for gaseous dampening of ion beam 13. Lens 12 forms a substantially parallel continuous ion beam 13. Ion beam 13 may enter OA 54 directly, while tilting at least the exit part of ion optics 12. It is more convenient and preferred to arrange the source along the Z-axis while steering the beam 13 by a deflector 51, followed by collimation of steered beam 53 with a slit 52 and yet preferably by a pair of heated slits for limiting both—the width and the divergence of beam 53.
Beam 53 enters tilted OA 54. An electrical pulse in OA 54 ejects ion packets 55 along a mean ion ray inclined by angle α1=α0−β, where β is the OA tilt angle and α0 is natural inclination angle past OA, which is defined by the ion source bias and the ion energy in the z-dimension Ux: α0 (UZ/UX)0.5. The time front of ion packets 55 stay parallel to the OA 54 and at an angle to the z-dimension of γ=β. In order to increase the number N of mirror reflections (and hence ion path length and resolution), the ion ray inclination angle α2 may be reduced by back steering ion packets in the deflector 40 by angle ψ. This is preferably performed after a single ion mirror reflection (which allows yet denser ray folding). The ion energy UZ, the OA tilt angle β and the back steering angle ψ of deflector 40 may be chosen and tuned so that the back steering angle ψ equals the time-front tilt angle γ: ψ=γ. As a result, the time-fronts of ion packets 56 becomes aligned and parallel with the Z-axis. After multiple mirror reflections, ion packets 59 hit detector 17 with time-fronts being parallel to the detector face. Mutual compensation of tilt and steering may occur at the following compensation conditions:
β=ψ=(α0−α1)/2 where α0=(UZ/UX)0.5 and α1=DZ/DXN
where DZ is the distance in the z-dimension from the midpoint of the OA 54 to the midpoint of the detector 17, and DX is the cap-to-cap distance between the ion mirrors.
It is believed that it had not previously been recognised that the combination of OA tilt and deflector steering does in fact compensate for the chromatic angular spread by the deflector at exactly the same condition:
α|K=0 and T|Z=0 at β=ψ
A numerical example of an embodiment will now be described, again referring to
To enhance the ion beam admission into the OA and to reduce the angular divergence of ion packets Δα=ΔUZ/2(UZ*UX)0.5, the ion beam specific energy is chosen UZ=80V, which corresponds to α0=100 mrad at UX=8 kV. The ray inclination angle is chosen to be α1=22 mrad to fit N=20 reflections into the compact MRTOF mass analyser, where the ion advance per reflection is LZ=10 mm, i.e. slightly smaller than the ion packets initial width Z0=10 mm. Note that such a small advance LZ becomes possible because of the optimal location of deflector 40, and because of the improved design of the deflector 40 arranged without the right deflection plate. Then the OA tilt and back steering angles are: β=ψ=(α0−α1)/2=39 mrad to provide for compensated steering while bringing the tilt angle of ion packets 56 to zero.
Choosing higher energy UZ helps reducing ion packets angular divergence to as low as Δα=0.6 mrad. After N=20 reflections and L=10 m flight path, ion packets expand by 6 mm only. The potentials of the Matsuda plates in the deflector 40 may be chosen to focus initially parallel and Z0=10 mm wide ion packets into a point. Since chromatic angular spread by the deflector is compensated (α|K=0), the final width ΔZ of the ion packet 56 in-front of the detector is expected to be as low as 6 mm, i.e. allows the shown dense folding of ion trajectory.
Increased the flight path to L=9 m corresponds to a flight time T=225 us for 1000 amu ions at UX=8 kV, thus setting a resolution limit of R=T/2ΔT>50,000 when using non stressed detectors with ΔT=2 ns time spread with smaller detector ringing.
As described in relation to
If pushing the compact MRTOF mass analyser for higher resolutions, yet denser folding of the ion trajectory may become limited in the embodiment 50 by the ion packet interference with the deflector right wall and with the detector rim.
Referring to
Similar to mass analyser 50 of
The combination of TA-lens/wedge 66 with the compensated deflector 40 allow arranging telescopic compression of the ion packet width, here from 10 mm to 5 mm. While TA lens 66 focuses ion packets to achieve two-fold compression, the potential of the Matsuda plate in the deflector 40 may be adjusted for moderate packet defocusing, so that initially parallel rays with ion packet width Z0=10 mm were spatially focused onto the detector. It is a new finding that with the ion packet spatial compression by factor C between OA 64 and deflector 40 (in this example C=2) there appears newly formulated condition for compensating of the time front tilt γ=0 (i.e. overall T|Z=0), occurring at β=ψ/C. Thus, the OA tilt angle becomes:
β=ψ/C=(α0−α1)/(1+C)
where α0=(UZ/UX)0.5 is defined by ion source bias UZ, and α1 is chosen from trajectory folding in MRTOF.
When TA-wedge 67 is used for steering, still γ=0 may be recovered and relations for angles can be figured out with regular geometric considerations.
To bypass the detector 17 rim, ion packets are preferably displaced by dual deflector 68, preferably also equipped with Matsuda plates. The dual symmetric deflector may compensate for time-front tilt. Slight asymmetry between deflector legs may be used for adjusting the scheme imperfections and misalignments.
Optionally, an intermediate lens 67 (either Einzel or TA) may be arranged to surround two adjacent ion trajectories. The arrangement allows minor additional focusing and/or steering of ion rays, preferably set at long focal distance (say above 5-10 m).
The tuning steps of the mass analyser will now be described.
(1) At start, OA tilt angle β may be preliminary chosen from optimal ion beam energy and for the desired number of ion reflections N. The dual deflector 68 and TA-lens 67 may be set up at simulated voltages, while lens 67 may be either omitted or not energized;
(2) The pair of tilted OA 64 and deflector 40 may be tuned for reaching both time-front recovery for γ=0, and adjusting angle α1 (for N reflections) by adjusting source bias UZ and steering angle ψ, Such tuning also compensates for some instrumental misalignments;
(3) Spatial focusing of ion packets onto the detector 17 may be achieved by independent tuning of Matsuda plate potential in deflector 40 at negligible shifts of step (2) tuning;
(4) Further optimizing tuning of the optional lens 69, or of the slight imbalance of the dual deflector 68 may be figured out experimentally.
A numerical example will now be described again referring to
Various embodiments of the present invention therefore include a novel injection mechanism that has a built-in and not before fully appreciated virtue—an ability to compensate for mechanical imperfections of MPTOF mass analysers by electrical tuning of the instrument by adjusting of ion beam energies UZ, and deflector 40 steering angle.
As described in relation to
Telescopic spatial focusing is also arranged by a pair of compensated deflectors, where at least one deflector may be a transaxial (TA) lens/wedge, mutually optimized with the exit lens of gridless OA. A new method is discovered for mutual compensation of the time front tilt in pair of deflectors at spatial focusing/defocusing between them.
Referring to
An important improvement is provided with the novel method of global compensation of parasitic time-front tilts, produced by unintentional instrumental misalignments. Additional compensating tilt is produced by first deflector (in pair with adjustments of ion beam energy) and by tuning the imbalance of the exit dual deflector.
Referring back to
Yet another improvement in compact trajectory folding is arranged with the novel mechanism and method of rear-edge Z-reflection, illustrated on the example of a sector MTTOF mass analyser, though being equally applicable to MRTOF mass analysers.
Similar to
Deflectors 82 and 83 are arranged for spatial focusing by 82 and defocusing by 83 with quadrupolar fields. The pair produces a telescopic packet compression and then expansion of ion packets Z-width by factor C: Z2/Z3C. Deflector 83 produces forward steering for angle ψ2 and deflector 84—reverse steering for angle ψ3. To return ion packet's 87 alignment with the Z-axis, i.e. T|Z=0 and γ2=0, the compression factor and the steering angles are chosen as: ψ2=−ψ3*C. Thus, here is introduced yet another novel method of compensated reversal of ion drift motion in MRTOF and MTTOF.
After reverse drift in the analyzer 81, ions arrive to deflector 40 (assumed set static), change inclination angle from α2 to α1 and packets 89 have time front tilted for angle γ1. Deflector 88 steers ion packets for ψ=γ1 to bring time front parallel to the detector face. Matsuda plates in the deflector 88 may be adjusted to compensate for residual T|ZZ aberrations, accumulated due to analyzer imperfections or slight shift in the overall tuning.
Back end reflection nearly doubles ion path and allow yet higher resolutions and/or yet more compact analyzers.
As described in relation to
E=E0(x−y)*sin(2πz/H)
Ion source 11, floated to bias UZ forms an ion beam 11 with about the same specific energy. Ion optics 12 forms a nearly parallel ion beam 13 with the beam diameter and divergence being optimized for ion transmission and spread within the guide 91, where the portion of beam 13 within the guide 91 is annotated as 63. Ions moving along the Z-axis, do sense time periodic quadrupolar field, and experience radial confinement. Contrary to RF fields, the effective well D(r) of the novel electrostatic confinement is mass independent:
D(r)=[E02H2/2π2UZ]*(r2/R2)
Electrostatic quadrupolar ion guide 91 may be used for improvement of the OA elongation at higher OA duty cycles, for a more accurate positioning of ion beam 63 within the OA, and for preventing the ion beam contact with OA surfaces.
Thus, improvements proposed for MPTOF MS with straight Z-axis are equally applicable to other isochronous electrostatic ion analyzers, such electrostatic traps and open traps and to other electrostatic analyzers with generally curved drift axis, such as cylindrical trap, exampled in WO2011086430, and or so-called elliptical TOF MS, exampled in US2011180702, as long as the analyzer field remains two-dimensional and the analyzer field has zero field component in the drift Z-direction.
Annotations
Coordinates and Times:
Potentials and Fields:
Angles:
Aberration Coefficients
indexes are defined within the text
Although the present invention has been describing with reference to preferred embodiments, it will be apparent to those skilled in the art that various modifications in form and detail may be made without departing from the scope of the present invention as set forth in the accompanying claims.
Number | Date | Country | Kind |
---|---|---|---|
1712612 | Aug 2017 | GB | national |
1712613 | Aug 2017 | GB | national |
1712614 | Aug 2017 | GB | national |
1712616 | Aug 2017 | GB | national |
1712617 | Aug 2017 | GB | national |
1712618 | Aug 2017 | GB | national |
1712619 | Aug 2017 | GB | national |
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/GB2018/052104 | 7/26/2018 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2019/030476 | 2/14/2019 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
3898452 | Hertel | Aug 1975 | A |
4390784 | Browning et al. | Jun 1983 | A |
4691160 | Ino | Sep 1987 | A |
4731532 | Frey et al. | Mar 1988 | A |
4855595 | Blanchard | Aug 1989 | A |
5017780 | Kutscher | May 1991 | A |
5107109 | Stafford, Jr. et al. | Apr 1992 | A |
5128543 | Reed et al. | Jul 1992 | A |
5202563 | Cotter et al. | Apr 1993 | A |
5331158 | Dowell | Jul 1994 | A |
5367162 | Holland et al. | Nov 1994 | A |
5396065 | Myerholtz et al. | Mar 1995 | A |
5435309 | Thomas et al. | Jul 1995 | A |
5464985 | Cornish et al. | Nov 1995 | A |
5619034 | Reed et al. | Apr 1997 | A |
5654544 | Dresch | Aug 1997 | A |
5689111 | Dresch et al. | Nov 1997 | A |
5696375 | Park et al. | Dec 1997 | A |
5719392 | Franzen | Feb 1998 | A |
5763878 | Franzen | Jun 1998 | A |
5777326 | Rockwood et al. | Jul 1998 | A |
5834771 | Yoon et al. | Nov 1998 | A |
5955730 | Kerley et al. | Sep 1999 | A |
5994695 | Young | Nov 1999 | A |
6002122 | Wolf | Dec 1999 | A |
6013913 | Hanson | Jan 2000 | A |
6020586 | Dresch et al. | Feb 2000 | A |
6080985 | Welkie et al. | Jun 2000 | A |
6107625 | Park | Aug 2000 | A |
6160256 | Ishihara | Dec 2000 | A |
6198096 | Le Cocq | Mar 2001 | B1 |
6229142 | Bateman et al. | May 2001 | B1 |
6271917 | Hagler | Aug 2001 | B1 |
6300626 | Brock et al. | Oct 2001 | B1 |
6316768 | Rockwood et al. | Nov 2001 | B1 |
6337482 | Francke | Jan 2002 | B1 |
6384410 | Kawato | May 2002 | B1 |
6393367 | Tang et al. | May 2002 | B1 |
6437325 | Reilly et al. | Aug 2002 | B1 |
6455845 | Li et al. | Sep 2002 | B1 |
6469295 | Park | Oct 2002 | B1 |
6489610 | Barofsky et al. | Dec 2002 | B1 |
6504148 | Hager | Jan 2003 | B1 |
6504150 | Verentchikov et al. | Jan 2003 | B1 |
6534764 | Verentchikov et al. | Mar 2003 | B1 |
6545268 | Verentchikov et al. | Apr 2003 | B1 |
6570152 | Hoyes | May 2003 | B1 |
6576895 | Park | Jun 2003 | B1 |
6580070 | Cornish et al. | Jun 2003 | B2 |
6591121 | Madarasz et al. | Jul 2003 | B1 |
6614020 | Cornish | Sep 2003 | B2 |
6627877 | Davis et al. | Sep 2003 | B1 |
6646252 | Gonin | Nov 2003 | B1 |
6647347 | Roushall et al. | Nov 2003 | B1 |
6664545 | Kimmel et al. | Dec 2003 | B2 |
6683299 | Fuhrer et al. | Jan 2004 | B2 |
6694284 | Nikoonahad et al. | Feb 2004 | B1 |
6717132 | Franzen | Apr 2004 | B2 |
6734968 | Wang et al. | May 2004 | B1 |
6737642 | Syage et al. | May 2004 | B2 |
6744040 | Park | Jun 2004 | B2 |
6744042 | Zajfman et al. | Jun 2004 | B2 |
6747271 | Gonin et al. | Jun 2004 | B2 |
6770870 | Vestal | Aug 2004 | B2 |
6782342 | LeGore et al. | Aug 2004 | B2 |
6787760 | Belov et al. | Sep 2004 | B2 |
6794643 | Russ, IV et al. | Sep 2004 | B2 |
6804003 | Wang et al. | Oct 2004 | B1 |
6815673 | Plomley et al. | Nov 2004 | B2 |
6833544 | Campbell et al. | Dec 2004 | B1 |
6836742 | Brekenfeld | Dec 2004 | B2 |
6841936 | Keller et al. | Jan 2005 | B2 |
6861645 | Franzen | Mar 2005 | B2 |
6864479 | Davis et al. | Mar 2005 | B1 |
6870156 | Rather | Mar 2005 | B2 |
6870157 | Zare | Mar 2005 | B1 |
6872938 | Makarov et al. | Mar 2005 | B2 |
6888130 | Gonin | May 2005 | B1 |
6900431 | Belov et al. | May 2005 | B2 |
6906320 | Sachs et al. | Jun 2005 | B2 |
6940066 | Makarov et al. | Sep 2005 | B2 |
6949736 | Ishihara | Sep 2005 | B2 |
7034292 | Whitehouse et al. | Apr 2006 | B1 |
7071464 | Reinhold | Jul 2006 | B2 |
7084393 | Fuhrer et al. | Aug 2006 | B2 |
7091479 | Hayek | Aug 2006 | B2 |
7126114 | Chernushevich | Oct 2006 | B2 |
7196324 | Verentchikov | Mar 2007 | B2 |
7217919 | Boyle et al. | May 2007 | B2 |
7221251 | Menegoli et al. | May 2007 | B2 |
7326925 | Verentchikov et al. | Feb 2008 | B2 |
7351958 | Vestal | Apr 2008 | B2 |
7365313 | Fuhrer et al. | Apr 2008 | B2 |
7385187 | Verentchikov et al. | Jun 2008 | B2 |
7388197 | McLean et al. | Jun 2008 | B2 |
7399957 | Parker et al. | Jul 2008 | B2 |
7423259 | Hidalgo et al. | Sep 2008 | B2 |
7498569 | Ding | Mar 2009 | B2 |
7501621 | Willis et al. | Mar 2009 | B2 |
7504620 | Sato et al. | Mar 2009 | B2 |
7521671 | Kirihara et al. | Apr 2009 | B2 |
7541576 | Belov et al. | Jun 2009 | B2 |
7582864 | Verentchikov | Sep 2009 | B2 |
7608817 | Flory | Oct 2009 | B2 |
7663100 | Vestal | Feb 2010 | B2 |
7675031 | Konicek et al. | Mar 2010 | B2 |
7709789 | Vestal et al. | May 2010 | B2 |
7728289 | Naya et al. | Jun 2010 | B2 |
7745780 | McLean et al. | Jun 2010 | B2 |
7755036 | Satoh | Jul 2010 | B2 |
7772547 | Verentchikov | Aug 2010 | B2 |
7800054 | Fuhrer et al. | Sep 2010 | B2 |
7825373 | Willis et al. | Nov 2010 | B2 |
7863557 | Brown | Jan 2011 | B2 |
7884319 | Willis et al. | Feb 2011 | B2 |
7932491 | Vestal | Apr 2011 | B2 |
7982184 | Sudakov | Jul 2011 | B2 |
7985950 | Makarov et al. | Jul 2011 | B2 |
7989759 | Holle | Aug 2011 | B2 |
7999223 | Makarov et al. | Aug 2011 | B2 |
8017907 | Willis et al. | Sep 2011 | B2 |
8017909 | Grinfeld et al. | Sep 2011 | B2 |
8063360 | Willis et al. | Nov 2011 | B2 |
8080782 | Hidalgo et al. | Dec 2011 | B2 |
8093554 | Makarov | Jan 2012 | B2 |
8237111 | Golikov et al. | Aug 2012 | B2 |
8354634 | Green et al. | Jan 2013 | B2 |
8373120 | Verentchikov et al. | Feb 2013 | B2 |
8395115 | Makarov et al. | Mar 2013 | B2 |
8492710 | Fuhrer et al. | Jul 2013 | B2 |
8513594 | Makarov | Aug 2013 | B2 |
8633436 | Ugarov | Jan 2014 | B2 |
8637815 | Makarov et al. | Jan 2014 | B2 |
8642948 | Makarov et al. | Feb 2014 | B2 |
8642951 | Li | Feb 2014 | B2 |
8648294 | Prather et al. | Feb 2014 | B2 |
8653446 | Mordehai et al. | Feb 2014 | B1 |
8658984 | Makarov et al. | Feb 2014 | B2 |
8680481 | Giannakopulos et al. | Mar 2014 | B2 |
8723108 | Ugarov | May 2014 | B1 |
8735818 | Kovtoun et al. | May 2014 | B2 |
8772708 | Kinugawa et al. | Jul 2014 | B2 |
8785845 | Loboda | Jul 2014 | B2 |
8847155 | Vestal | Sep 2014 | B2 |
8853623 | Verenchikov | Oct 2014 | B2 |
8884220 | Hoyes et al. | Nov 2014 | B2 |
8921772 | Verenchikov | Dec 2014 | B2 |
8952325 | Giles et al. | Feb 2015 | B2 |
8957369 | Makarov | Feb 2015 | B2 |
8975592 | Kobayashi et al. | Mar 2015 | B2 |
9048080 | Verenchikov et al. | Jun 2015 | B2 |
9082597 | Willis et al. | Jul 2015 | B2 |
9082604 | Verenchikov | Jul 2015 | B2 |
9099287 | Giannakopulos | Aug 2015 | B2 |
9136101 | Grinfeld et al. | Sep 2015 | B2 |
9147563 | Makarov | Sep 2015 | B2 |
9196469 | Makarov | Nov 2015 | B2 |
9207206 | Makarov | Dec 2015 | B2 |
9214322 | Kholomeev et al. | Dec 2015 | B2 |
9214328 | Hoyes et al. | Dec 2015 | B2 |
9281175 | Haufler et al. | Mar 2016 | B2 |
9312119 | Verenchikov | Apr 2016 | B2 |
9324544 | Rather | Apr 2016 | B2 |
9373490 | Nishiguchi et al. | Jun 2016 | B1 |
9396922 | Verenchikov et al. | Jul 2016 | B2 |
9417211 | Verenchikov | Aug 2016 | B2 |
9425034 | Verentchikov et al. | Aug 2016 | B2 |
9472390 | Verenchikov et al. | Oct 2016 | B2 |
9514922 | Watanabe et al. | Dec 2016 | B2 |
9576778 | Wang | Feb 2017 | B2 |
9595431 | Verenchikov | Mar 2017 | B2 |
9673033 | Grinfeld et al. | Jun 2017 | B2 |
9679758 | Grinfeld et al. | Jun 2017 | B2 |
9683963 | Verenchikov | Jun 2017 | B2 |
9728384 | Verenchikov | Aug 2017 | B2 |
9779923 | Verenchikov | Oct 2017 | B2 |
9786484 | Willis et al. | Oct 2017 | B2 |
9786485 | Ding et al. | Oct 2017 | B2 |
9865441 | Damoc et al. | Jan 2018 | B2 |
9865445 | Verenchikov et al. | Jan 2018 | B2 |
9870903 | Richardson et al. | Jan 2018 | B2 |
9870906 | Quarmby et al. | Jan 2018 | B1 |
9881780 | Verenchikov et al. | Jan 2018 | B2 |
9899201 | Park | Feb 2018 | B1 |
9922812 | Makarov | Mar 2018 | B2 |
9941107 | Verenchikov | Apr 2018 | B2 |
9972483 | Makarov | May 2018 | B2 |
10006892 | Verenchikov | Jun 2018 | B2 |
10037873 | Wang et al. | Jul 2018 | B2 |
10141175 | Verentchikov et al. | Nov 2018 | B2 |
10141176 | Stewart et al. | Nov 2018 | B2 |
10163616 | Verenchikov et al. | Dec 2018 | B2 |
10186411 | Makarov | Jan 2019 | B2 |
10192723 | Verenchikov et al. | Jan 2019 | B2 |
10290480 | Crowell et al. | May 2019 | B2 |
10373815 | Crowell et al. | Aug 2019 | B2 |
10388503 | Brown et al. | Aug 2019 | B2 |
10593525 | Hock et al. | Mar 2020 | B2 |
10593533 | Hoyes et al. | Mar 2020 | B2 |
10622203 | Veryovkin et al. | Apr 2020 | B2 |
10629425 | Hoyes et al. | Apr 2020 | B2 |
10636646 | Hoyes et al. | Apr 2020 | B2 |
20010011703 | Franzen | Aug 2001 | A1 |
20010030284 | Dresch et al. | Oct 2001 | A1 |
20020030159 | Chernushevich et al. | Mar 2002 | A1 |
20020107660 | Nikoonahad et al. | Aug 2002 | A1 |
20020190199 | Li | Dec 2002 | A1 |
20030010907 | Hayek et al. | Jan 2003 | A1 |
20030111597 | Gonin et al. | Jun 2003 | A1 |
20030232445 | Fulghum | Dec 2003 | A1 |
20040084613 | Bateman et al. | May 2004 | A1 |
20040108453 | Kobayashi et al. | Jun 2004 | A1 |
20040119012 | Vestal | Jun 2004 | A1 |
20040144918 | Zare et al. | Jul 2004 | A1 |
20040155187 | Axelsson | Aug 2004 | A1 |
20040159782 | Park | Aug 2004 | A1 |
20040183007 | Belov et al. | Sep 2004 | A1 |
20050006577 | Fuhrer et al. | Jan 2005 | A1 |
20050040326 | Enke | Feb 2005 | A1 |
20050103992 | Yamaguchi et al. | May 2005 | A1 |
20050133712 | Belov et al. | Jun 2005 | A1 |
20050151075 | Brown et al. | Jul 2005 | A1 |
20050194528 | Yamaguchi et al. | Sep 2005 | A1 |
20050242279 | Verentchikov | Nov 2005 | A1 |
20050258364 | Whitehouse et al. | Nov 2005 | A1 |
20060169882 | Pau et al. | Aug 2006 | A1 |
20060214100 | Verentchikov et al. | Sep 2006 | A1 |
20060289746 | Raznikov et al. | Dec 2006 | A1 |
20070023645 | Chernushevich | Feb 2007 | A1 |
20070029473 | Verentchikov | Feb 2007 | A1 |
20070176090 | Verentchikov | Aug 2007 | A1 |
20070187614 | Schneider et al. | Aug 2007 | A1 |
20070194223 | Sato et al. | Aug 2007 | A1 |
20080049402 | Han et al. | Feb 2008 | A1 |
20080197276 | Nishiguchi et al. | Aug 2008 | A1 |
20080203288 | Makarov et al. | Aug 2008 | A1 |
20080290269 | Saito et al. | Nov 2008 | A1 |
20090090861 | Willis et al. | Apr 2009 | A1 |
20090114808 | Bateman et al. | May 2009 | A1 |
20090206250 | Wollnik | Aug 2009 | A1 |
20090250607 | Staats et al. | Oct 2009 | A1 |
20090272890 | Ogawa et al. | Nov 2009 | A1 |
20090314934 | Brown | Dec 2009 | A1 |
20100001180 | Bateman et al. | Jan 2010 | A1 |
20100044558 | Sudakov | Feb 2010 | A1 |
20100072363 | Giles et al. | Mar 2010 | A1 |
20100078551 | Loboda | Apr 2010 | A1 |
20100140469 | Nishiguchi | Jun 2010 | A1 |
20100193682 | Golikov et al. | Aug 2010 | A1 |
20100207023 | Loboda | Aug 2010 | A1 |
20100301202 | Vestal | Dec 2010 | A1 |
20110133073 | Sato et al. | Jun 2011 | A1 |
20110168880 | Ristroph et al. | Jul 2011 | A1 |
20110180702 | Flory et al. | Jul 2011 | A1 |
20110180705 | Yamaguchi | Jul 2011 | A1 |
20110186729 | Verentchikov et al. | Aug 2011 | A1 |
20120168618 | Vestal | Jul 2012 | A1 |
20120261570 | Shvartsburg et al. | Oct 2012 | A1 |
20130048852 | Verenchikov | Feb 2013 | A1 |
20130056627 | Verenchikov | Mar 2013 | A1 |
20130068942 | Verenchikov | Mar 2013 | A1 |
20130187044 | Ding et al. | Jul 2013 | A1 |
20130240725 | Makarov | Sep 2013 | A1 |
20130248702 | Makarov | Sep 2013 | A1 |
20130256524 | Brown et al. | Oct 2013 | A1 |
20130313424 | Makarov et al. | Nov 2013 | A1 |
20130327935 | Wiedenbeck | Dec 2013 | A1 |
20140054454 | Hoyes | Feb 2014 | A1 |
20140054456 | Kinugawa et al. | Feb 2014 | A1 |
20140084156 | Ristroph et al. | Mar 2014 | A1 |
20140117226 | Giannakopulos | May 2014 | A1 |
20140138538 | Hieftje et al. | May 2014 | A1 |
20140183354 | Moon et al. | Jul 2014 | A1 |
20140191123 | Wildgoose et al. | Jul 2014 | A1 |
20140217275 | Ding | Aug 2014 | A1 |
20140239172 | Makarov | Aug 2014 | A1 |
20140291503 | Shchepunov et al. | Oct 2014 | A1 |
20140312221 | Verenchikov et al. | Oct 2014 | A1 |
20140361162 | Murray et al. | Dec 2014 | A1 |
20150028197 | Grinfeld et al. | Jan 2015 | A1 |
20150028198 | Grinfeld | Jan 2015 | A1 |
20150034814 | Brown et al. | Feb 2015 | A1 |
20150048245 | Vestal et al. | Feb 2015 | A1 |
20150060656 | Ugarov | Mar 2015 | A1 |
20150122986 | Haase | May 2015 | A1 |
20150194296 | Verenchikov et al. | Jul 2015 | A1 |
20150228467 | Grinfeld et al. | Aug 2015 | A1 |
20150279650 | Verenchikov | Oct 2015 | A1 |
20150294849 | Makarov et al. | Oct 2015 | A1 |
20150318156 | Loyd et al. | Nov 2015 | A1 |
20150364309 | Welkie | Dec 2015 | A1 |
20150380233 | Verenchikov | Dec 2015 | A1 |
20160005587 | Verenchikov | Jan 2016 | A1 |
20160035558 | Verenchikov et al. | Feb 2016 | A1 |
20160079052 | Makarov | Mar 2016 | A1 |
20160024036 | Verenchikov | Aug 2016 | A1 |
20160225598 | Ristroph | Aug 2016 | A1 |
20160225602 | Ristroph et al. | Aug 2016 | A1 |
20160240363 | Verenchikov | Aug 2016 | A1 |
20170016863 | Verenchikov | Jan 2017 | A1 |
20170025265 | Verenchikov et al. | Jan 2017 | A1 |
20170032952 | Verenchikov | Feb 2017 | A1 |
20170098533 | Stewart | Apr 2017 | A1 |
20170168031 | Verenchikov | Jun 2017 | A1 |
20170229297 | Green et al. | Aug 2017 | A1 |
20170338094 | Verenchikov | Nov 2017 | A1 |
20180144921 | Hoyes et al. | May 2018 | A1 |
20180229297 | Funakoshi et al. | Aug 2018 | A1 |
20180315589 | Oshiro | Nov 2018 | A1 |
20180366312 | Hamish et al. | Dec 2018 | A1 |
20190180998 | Stewart | Jun 2019 | A1 |
20190206669 | Verenchikov | Jul 2019 | A1 |
20190237318 | Brown | Aug 2019 | A1 |
20190360981 | Verenchikov | Nov 2019 | A1 |
20200083034 | Hoyes et al. | Mar 2020 | A1 |
20200090919 | Artaev et al. | Mar 2020 | A1 |
20200126781 | Kovtoun | Apr 2020 | A1 |
20200152440 | Hoyes et al. | May 2020 | A1 |
20200168447 | Verenchikov | May 2020 | A1 |
20200168448 | Verenchikov | May 2020 | A1 |
20200243322 | Stewart | Jul 2020 | A1 |
20200373142 | Verenchikov | Nov 2020 | A1 |
20200373143 | Verenchikov | Nov 2020 | A1 |
20200373145 | Verenchikov | Nov 2020 | A1 |
Number | Date | Country |
---|---|---|
2412657 | May 2003 | CA |
101369510 | Feb 2009 | CN |
102131563 | Jul 2011 | CN |
201946564 | Aug 2011 | CN |
4310106 | Oct 1994 | DE |
10116536 | Oct 2002 | DE |
102015121830 | Jun 2017 | DE |
102019129108 | Jun 2020 | DE |
112015001542 | Jul 2020 | DE |
0237259 | Sep 1987 | EP |
1137044 | Sep 2001 | EP |
1566828 | Aug 2005 | EP |
1901332 | Mar 2008 | EP |
2068346 | Jun 2009 | EP |
1665326 | Apr 2010 | EP |
1789987 | Sep 2010 | EP |
1522087 | Mar 2011 | EP |
2599104 | Jun 2013 | EP |
1743354 | Aug 2019 | EP |
3662501 | Jun 2020 | EP |
3662502 | Jun 2020 | EP |
3662503 | Jun 2020 | EP |
2080021 | Jan 1982 | GB |
2217907 | Nov 1989 | GB |
2300296 | Oct 1996 | GB |
2390935 | Jan 2004 | GB |
2396742 | Jun 2004 | GB |
2403063 | Dec 2004 | GB |
2455977 | Jul 2009 | GB |
2476964 | Jul 2011 | GB |
2478300 | Sep 2011 | GB |
2484361 | Apr 2012 | GB |
2484429 | Apr 2012 | GB |
2485825 | May 2012 | GB |
2489094 | Sep 2012 | GB |
2490571 | Nov 2012 | GB |
2495127 | Apr 2013 | GB |
2495221 | Apr 2013 | GB |
2496991 | May 2013 | GB |
2496994 | May 2013 | GB |
2500743 | Oct 2013 | GB |
2501332 | Oct 2013 | GB |
2506362 | Apr 2014 | GB |
2528875 | Feb 2016 | GB |
2555609 | May 2018 | GB |
2556451 | May 2018 | GB |
2556830 | Jun 2018 | GB |
2562990 | Dec 2018 | GB |
2575157 | Jan 2020 | GB |
2575339 | Jan 2020 | GB |
S6229049 | Feb 1987 | JP |
2000036285 | Feb 2000 | JP |
2000048764 | Feb 2000 | JP |
2003031178 | Jan 2003 | JP |
3571546 | Sep 2004 | JP |
2005538346 | Dec 2005 | JP |
2006049273 | Feb 2006 | JP |
2007227042 | Sep 2007 | JP |
2010062152 | Mar 2010 | JP |
4649234 | Mar 2011 | JP |
2011119279 | Jun 2011 | JP |
4806214 | Nov 2011 | JP |
2013539590 | Oct 2013 | JP |
5555582 | Jul 2014 | JP |
2015506567 | Mar 2015 | JP |
2015185306 | Oct 2015 | JP |
2564443 | May 2017 | RU |
2015148627 | May 2017 | RU |
2660655 | Jul 2018 | RU |
198034 | Sep 1991 | SU |
1681340 | Sep 1991 | SU |
1725289 | Apr 1992 | SU |
9103071 | Mar 1991 | WO |
13045428 | Apr 1992 | WO |
1998001218 | Jan 1998 | WO |
98008244 | Feb 1998 | WO |
200077823 | Dec 2000 | WO |
2005001878 | Jan 2005 | WO |
2006014984 | Feb 2006 | WO |
2006049623 | May 2006 | WO |
2006102430 | Sep 2006 | WO |
2006103448 | Oct 2006 | WO |
2007044696 | Apr 2007 | WO |
2007104992 | Sep 2007 | WO |
2007136373 | Nov 2007 | WO |
2008046594 | Apr 2008 | WO |
2008087389 | Jul 2008 | WO |
2010008386 | Jan 2010 | WO |
2010034630 | Apr 2010 | WO |
2010138781 | Dec 2010 | WO |
2011086430 | Jul 2011 | WO |
2011107836 | Sep 2011 | WO |
2011135477 | Nov 2011 | WO |
2012010894 | Jan 2012 | WO |
2012023031 | Feb 2012 | WO |
2012024468 | Feb 2012 | WO |
2012024570 | Feb 2012 | WO |
2012116765 | Sep 2012 | WO |
13063587 | May 2013 | WO |
2013067366 | May 2013 | WO |
13093587 | Jun 2013 | WO |
2013098612 | Jul 2013 | WO |
13110587 | Aug 2013 | WO |
13124207 | Aug 2013 | WO |
2013110588 | Aug 2013 | WO |
2014021960 | Feb 2014 | WO |
2014074822 | May 2014 | WO |
14110697 | Jul 2014 | WO |
2014142897 | Sep 2014 | WO |
2014152902 | Sep 2014 | WO |
2015142897 | Sep 2015 | WO |
2015152968 | Oct 2015 | WO |
2015153622 | Oct 2015 | WO |
2015153630 | Oct 2015 | WO |
2015153644 | Oct 2015 | WO |
2015175988 | Nov 2015 | WO |
2016064398 | Apr 2016 | WO |
2016174462 | Nov 2016 | WO |
2017042665 | Mar 2017 | WO |
2018073589 | Apr 2018 | WO |
2018109920 | Jun 2018 | WO |
2018124861 | Jul 2018 | WO |
2018183201 | Oct 2018 | WO |
2019030472 | Feb 2019 | WO |
2019030474 | Feb 2019 | WO |
2019030475 | Feb 2019 | WO |
2019030476 | Feb 2019 | WO |
2019030477 | Feb 2019 | WO |
2019058226 | Mar 2019 | WO |
2019162687 | Aug 2019 | WO |
2019202338 | Oct 2019 | WO |
2019229599 | Dec 2019 | WO |
2020002940 | Jan 2020 | WO |
2020021255 | Jan 2020 | WO |
2020121167 | Jun 2020 | WO |
2020121168 | Jun 2020 | WO |
Entry |
---|
International Search Report and Written Opinion for International Application No. PCT/US2016/062174 dated Mar. 6, 2017, 8 pages. |
IPRP PCT/US2016/062174 issued May 22, 2018, 6 pages. |
Search Report for GB Application No. GB1520130.4 dated May 25, 2016. |
International Search Report and Written Opinion for International Application No. PCT/US2016/062203 dated Mar. 6, 2017, 8 pages. |
Search Report for GB Application No. GB1520134.6 dated May 26, 2016. |
IPRP PCT/US2016/062203, issued May 22, 2018, 6 pages. |
Search Report Under Section 17(5) for Application No. GB1507363.8 dated Nov. 9, 2015. |
International Search Report and Written Opinion of the International Search Authority for Application No. PCT/GB2016/051238 dated Jul. 12, 2016, 16 pages. |
IPRP for application PCT/GB2016/051238 dated Oct. 31, 2017, 13 pages. |
International Search Report and Written Opinion for International Application No. PCT/US2016/063076 dated Mar. 30, 2017, 9 pages. |
Search Report for GB Application No. 1520540.4 dated May 24, 2016. |
IPRP for application PCT/US2016/063076, dated May 29, 2018, 7 pages. |
IPRP PCT/GB17/51981 dated Jan. 8, 2019, 7 pages. |
International Search Report and Written Opinion for International Application No. PCT/GB2018/051206, dated Jul. 12, 2018, 9 pages. |
N/a: “Electrostatic lens,” Wikipedia, Mar. 31, 2017 (Mar. 31, 2017), XP055518392, Retrieved from the Internet:URL: https://en.wikipedia.org/w/index.phptitle=Electrostatic lens oldid=773161674[retrieved on Oct. 24, 2018]. |
Hussein, O.A. et al., “Study the most favorable shapes of electrostatic quadrupole doublet lenses”, AIP Conference Proceedings, vol. 1815, Feb. 17, 2017 (Feb. 17, 2017), p. 110003. |
Guan S., et al. “Stacked-ring electrostatic ion guide”, Journal of the American Society for Mass Spectrometry, Elsevier Science Inc, 7(1):101-106 (1996). |
International Search Report and Written Opinion for application No. PCT/GB2018/052104, dated Oct. 31, 2018, 14 pages. |
International Search Report and Written Opinion for application No. PCT/GB2018/052105, dated Oct. 15, 2018, 18 pages. |
International Search Report and Written Opinion for application PCT/GB2018/052100, dated Oct. 19, 2018, 19 pages. |
International Search Report and Written Opinion for application PCT/GB2018/052102, dated Oct. 25, 2018, 14 pages. |
International Search Report and Written Opinion for application No. PCT/GB2018/052099, dated Oct. 10, 2018, 16 pages. |
International Search Report and Written Opinion for application No. PCT/GB2018/052101, dated Oct. 19, 2018, 15 pages. |
Combined Search and Examination Report under Sections 17 and 18(3) for application GB1807605.9 dated Oct. 29, 2018, 5 pages. |
Combined Search and Examination Report under Sections 17 and 18(3) for application GB1807626.5, dated Oct. 29, 2018, 7 pages. |
Yavor, M.I., et al., “High performance gridless ion mirrors for multi-reflection time-of-flight and electrostatic trap mass analyzers”, International Journal of Mass Spectrometry, vol. 426, Mar. 2018, pp. 1-11. |
Search Report under Section 17(5) for application GB1707208.3, dated Oct. 12, 2017, 5 pages. |
Communication Relating to the Results of the Partial International Search for International Application No. PCT/GB2019/01118, dated Jul. 19, 2019, 25 pages. |
Doroshenko, V.M., and Cotter, R.J., “Ideal velocity focusing in a reflectron time-of-flight mass spectrometer”, American Society for Mass Spectrometry, 10(10):992-999 (1999). |
Kozlov, B. et al. “Enhanced Mass Accuracy in Multi-Reflecting TOF MS” www.waters.com/posters, ASMS Conference (2017). |
Kozlov, B. et al. “Multiplexed Operation of an Orthogonal Multi-Reflecting TOF Instrument to Increase Duty Cycle by Two Orders” ASMS Conference, San Diego, CA, Jun. 6, 2018. |
Kozlov, B. et al. “High accuracy self-calibration method for high resolution mass spectra” ASMS Conference Abstract, 2019. |
Kozlov, B. et al., “Fast Ion Mobility Spectrometry and High Resolution TOF MS” ASMS Conference Poster (2014). |
Verenchicov, A. N. “Parallel MS-MS Analysis in a Time-Flight Tandem. Problem Statement, Method, and Instrucmental Schemes” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2004). |
Yavor, M. I. “Planar Multireflection Time-Of-Flight Mass Analyser with Unlimited Mass Range” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2004). |
Khasin, Y. I. et al. “Initial Experimenatl Studies of a Planar Multireflection Time-Of-Flight Mass Spectrometer” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2004). |
Verenchicov, A. N. et al. “Stability of Ion Motion in Periodic Electrostatic Fields” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2004). |
Verenchicov, A. N. “The Concept of Mutireflecting Mass Spectrometer for Continuous Ion Sources” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
Verenchicov., A. N., et al. “Accurate Mass Measurements for Inerpreting Spectra of atmospheric Pressure Ionization” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
Kozlov, B. N. et al., “Experimental Studies of Space Charge Effects in Multireflecting Time-Of-Flight Mass Spectrometes” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
Kozlov, B. N. et al., “Multireflecting Time-Of-Flight Mass Spectrometer With an Ion Trap Source” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
Hasin, Y. I., et al., “Planar Time-Of-Flight Multireflecting Mass Spectrometer with an Orthogonal Ion Injection Out of Continuous Ion Sources” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
Lutvinsky Y. I. et al., “Estimation of Capacity of High Resolution Mass Spectra for Analysis of Complex Mixtures” Institute for Analytical Instrucmentation RAS, Saint-Petersburg, (2006). |
International Search Report and Written Opinion for International application No. PCT/GB2020/050209, dated Apr. 28, 2020, 12 pages. |
Verenchicov, A. N. et al. “Multiplexing in Multi-Reflecting TOF MS” Journal of Applied Solution Chemistry and Modeling, 6:1-22(2017). |
Supplementary Partial EP Search Report for EP Application No. 16869126.9, dated Jun. 13, 2019. |
Supplementary Partial EP Search Report for EP Application No. 16866997.6, dated Jun. 7, 2019. |
Reflectron—Wikipedia, Oct. 9, 2015, Retrieved from the Internet URL:https://en.wikipedia.org/w/index.phptitle=Reflectron oldid=684843442 [retrieved on May 29, 2019]. |
Scherer, S., et al., “A novel principle for an ion mirror design in time-of-flight mass spectrometry”, International Journal of Mass Spectrometry, Elsevier Science Publishers, Amsterdam, NL, vol. 251, No. 1, Mar. 15, 2006. |
International Search Report and Written Opinion for International Application No. PCT/EP2017/070508 dated Oct. 16, 2017, 17 pages. |
Search Report for United Kingdom Application No. GB1613988.3 dated Jan. 5, 2017, 4 pages. |
Sakurai et al., “A New Multi-Passage Time-of-Flight Mass Spectrometer at JAIST”, Nuclear Instruments Methods in Physics Research, Section A, Elsevier, 427(1-2): 182-186, May 11, 1999. |
Toyoda et al., “Multi-Turn-Time-of-Flight Mass Spectometers with Electrostatic Sectors”, Journal of Mass Spectrometry, 38: 1125-1142, Jan. 1, 2003. |
Wouters et al., “Optical Design of the TOFI (Time-of-Flight Isochronous) Spectrometer for Mass Measurements of Exotic Nuclei”, Nuclear Instruments and Methods in Physics Research, Section A, 240(1): 77-90, Oct. 1, 1985. |
Stresau, D., et al.: “Ion Counting Beyond 10ghz Using a New Detector and Conventional Electronics”, European Winter Conference on Plasma Spectrochemistry, Feb. 4-8, 2001, Lillehammer, Norway, Retrieved from the Internet: URL:https://www.etp-ms.com/file-repository/21 [retrieved on Jul. 31, 2019]. |
Kaufmann, R., et. al., “Sequencing of peptides in a time-of-flight mass spectrometer: evaluation of postsource decay following matrix-assisted laser desorption ionisation (MALDI)”, International Journal of Mass Spectrometry and Ion Processes, Elsevier Scientific Publishing Co. Amsterdam, NL, 131:355-385, Feb. 24, 1994. |
Barry Shaulis et al: “Signal linearity of an extended range pulse counting detector: Applications to accurate and precise U-Pb dating of zircon by laser ablation quadrupole ICP-MS”, G3: Geochemistry, Geophysics, Geosystems, 11(11):1-12, Nov. 20, 2010. |
Search Report for United Kingdom Application No. GB1708430.2 dated Nov. 28, 2017. |
International Search Report and Written Opinion for International Application No. PCT/GB2018/051320 dated Aug. 1, 2018. |
International Search Report and Written Opinion for International Application No. PCT/GB2019/051839 dated Sep. 18, 2019. |
International Search Report and Written Opinion for International Application No. PCT/GB2019/051234 dated Jul. 29, 2019. |
Extended European Search Report for EP Patent Application No. 16866997.6, dated Oct. 16, 2019. |
Search Report under Section 17(5) for GB1916445.8, dated Jun. 15, 2020. |
IPRP for International application No. PCT/GB2018/051206, issued on Nov. 5, 2019, 7 pages. |
Combined Search and Examination Report for United Kingdom Application No. GB1901411.7 dated Jul. 31, 2019. |
Examination Report for United Kingdom Application No. GB1618980.5 dated Jul. 25, 2019. |
Combined Search and Examination Report for GB1906258.7, dated Oct. 25, 2019. |
Combined Search and Examination Report for GB1906253.8, dated Oct. 30, 2019, 5 pages. |
Author unknown, “Einzel Lens”, Wikipedia [online] Nov. 2020 [retrieved on Nov. 3, 2020]. Retrieved from Internet URL: https://en.wikipedia.org/wiki/Einzel_lens, 2 pages. |
International Search Report and Written Opinion for International application No. PCT/GB2019/051235, dated Sep. 25, 2019, 22 pages. |
International Search Report and Written Opinion for International application No. PCT/GB2019/051416, dated Oct. 10, 2019, 22 pages. |
Search and Examination Report under Sections 17 and 18(3) for Application No. GB1906258.7, dated Dec. 11, 2020, 7 pages. |
Carey, D.C., “Why a second-order magnetic optical achromat works”, Nucl. Instrum. Meth., 189(203):365-367 (1981). Abstract. |
Sakurai, T. et al., “Ion optics for time-of-flight mass spectrometers with multiple symmetry”, Int J Mass Spectrom Ion Proc 63(2-3):273-287 (1985). Abstract. |
Wollnik, H., and Casares, A., “An energy-isochronous multi-pass time-of-flight mass spectrometer consisting of two coaxial electrostatic mirrors”, Int J Mass Spectrom 227:217-222 (2003). Abstract. |
Examination Report under Section 18(3) for Application No. GB1906258.7, dated May 5, 2021, 4 pages. |
O'Halloran, G.J., et al., “Determination of Chemical Species Prevalent in a Plasma Jet”, Bendix Corp Report ASD-TDR-62-644, U.S. Air Force (1964). Abstract. |
Number | Date | Country | |
---|---|---|---|
20200373144 A1 | Nov 2020 | US |