Patent Application
20200168448
This application 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 6 Aug. 2017. The entire content of these applications is incorporated herein by reference
The invention relates to the area of time of flight and multi-reflecting time-of-flight mass spectrometers (MRTOF) with pulsed sources orthogonal pulsed converters, and is particularly concerned with improved control over drift motion in OA-MRTOF.
Time-of-flight mass spectrometers (TOF MS) are widely used for their combination of sensitivity and speed, and lately with the introduction of multiple ion mirrors and multi-reflecting schemes, for their high resolution and mass accuracy.
Pulsed ion sources are used in TOF MS for intrinsically pulsed ionization methods, such as Matrix Assisted Laser Desorption and Ionization (MALDI), Secondary Ionization (SIMS), and pulsed EI. The first two ion sources have become more and more popular for mass spectral surface imaging, where a relatively large surface area is analyzed simultaneously while using mapping properties of TOF MS. Pulsed converters are used to form pulsed ion packets out of ion beams produced by intrinsically continuous ion sources, like Electron Impact (EI), Electrospray (ESI), Atmospheric pressure ionization (APPI), atmospheric Pressure Chemical Ionization (APCI), and Inductively coupled Plasma (ICP).
Most common pulsed converters are orthogonal accelerators (WO9103071) and radiofrequency ion traps with pulsed radial ejection, lately used for ion injection into Orbitraps. Two aspects of prior art ion sources and converters for TOFMS are relevant: (a) they employ pulsed accelerating fields; (b) they are spatially wide which complicates their bypassing.
Resolution of TOF MS instruments has been substantially improved in multi-reflecting TOFMS (MRTOF) instruments. MRTOF instruments have parallel gridless ion mirrors, separated by a drift space, e.g. as described in SU1725289, U.S. Pat. Nos. 6,107,625, 6,570,152, GB2403063, U.S. Pat. No. 6,717,132, incorporated herein by reference. Most of MRTOF employ two dimensional (2D) electrostatic fields in the XY-plane between mirror electrodes, substantially elongated in the drift Z-direction. The 2D-fields of ion mirrors are carefully engineered to provide for isochronous ion motion and for spatial ion packet confinement in the transverse XY-plane. Ion packets are injected at a small inclination angle to the X-axis to produce multiple reflections in the X-direction combined with slow ion drift in the drift Z-direction, thus producing zigzag ion path. The resolving power (also referred as resolution) of MR-TOF grows at larger number of reflections N by reducing effect of the initial time spread and of the detector time spread.
By nature, the electrostatic 2D-fields have zero component EZ=0 in the orthogonal drift Z-direction, i.e. have no effect on the ion packets free propagation and its expansion in the drift Z-direction. In OA-MRTOF, the inclination angle α of zigzag ion trajectory is controlled by ion beam energy UZ and by MRTOF acceleration voltage UX, and the angular divergence Δα by the beam energy spread ΔUZ:
α=(UZ/UX)0.5; Δα=α*ΔUZ/2UZ=ΔUZ/2(UZUX)0.5 (eq. 1)
In attempts to increase MRTOF resolution by denser folding of the ion trajectory, the injection angle α (to axis X) of ion packets shall be reduced, thus, requiring much lower UZ of the injected continuous ion beam, in turn, increasing the spread of injection angles Δα. Ion packets start hitting rims of the orthogonal accelerator (OA) and detector, and may produce trajectories that overlap, thus confusing spectra. For trap converters, similar problems occur at bypassing of the trap and of the detector rims. Most importantly, the scheme appears highly sensitive to unintentional misalignments of MRTOF components, either ruining MRTOF isochronicity or requiring extremely tight precision requirements.
To address those problems, multiple complex solutions have been proposed to define the ion drift advance per reflection, to prevent or compensate the angular divergence of ion packets, and to withstand various distortions, such as stray fields and mechanical distortions of analyzer electrodes: U.S. Pat. No. 7,385,187 proposed periodic lens and edge deflectors for MRTOF; U.S. Pat. No. 7,504,620 proposed laminated sectors for MTTOF; 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. Though prior art solutions do solve the problem of controlling Z-motion, however, they have several drawbacks, comprising: (i) technical complexity; (ii) additional time aberrations, affecting resolution; (iii) limited length of ion packets and limited duty cycle and charge capacity of pulsed converters; and most importantly, (iv) fixed arrangement with low tolerance to manufacturing faults. Those drawbacks become devastating when trying to construct a compact and low cost MRTOF instruments for higher resolutions.
Making larger analyzers raises the manufacturing cost close to the cubic power of the instrument size. It is desirable to keep instrument size at about 0.5 m, which becomes a limiting factor on the flight time TOF and mass resolution R TOF/2DET, where the practical limit for DET=1.5-2 ns if using non-stressed data systems. On the other hand, to resolve isobaric interferences, R=80-100,000 are desired, thus triggering the search for MRTOF schemes with yet denser trajectory folding, longer flight times TOF and longer flight paths L.
From a first aspect the present invention provides a multi-reflecting time-of-flight mass spectrometer comprising:
(a) a pulsed ion emitter having a pulsed acceleration region and a static acceleration region to accelerate ions substantially along an X-direction; said pulsed ion emitter configured to emit ion packets at an inclination angle α0 to said X-direction;
(b) a pair of parallel gridless ion mirrors separated by a drift space; wherein electrodes of said ion mirrors are substantially elongated in a Z-direction that is orthogonal to said X-direction so as to form a substantially two-dimensional electrostatic field in the XY-plane orthogonal to said Z-direction;
(c) a time-of-flight detector;
(d) at least one electrostatic ion deflector arranged for deflecting ion trajectories by angle ψ in the XZ plane; and
(e) at least one electrode structure configured to form a local wedge electrostatic field having equipotential field lines that are tilted with respect to the Z-direction, arranged either in said pulsed accelerating region and/or in an ion retarding region of one or both of said ion mirrors, followed by an electrostatic acceleration field having equipotential field lines that are parallel to the Z-direction; said at least one electrode structure being arranged to adjust the time front tilt angle γ of said ion packets in the XZ plane, and to steer the ion trajectories by inclination angle ϕ in the XZ plane;
(f) wherein said angles ψ and ϕ are arranged for: (i) denser folding of the ion trajectories at inclination angle α to the X-direction that is smaller than said angle α0, (ii) and/or for causing ions to bypass rims of said pulsed ion emitter or ion deflector, (iii) and/or for reversing ion drift motion in said Z-direction;
(g) wherein said time front tilt angle γ and said ion deflecting angle ψ are set for compensation of the ion packets time front tilt angle induced by the ion deflector
In step (g), the time front tilt angle γ and ion steering angles ψ may be electrically adjusted or selected for local mutual compensation of the ion packets time front tilt angle induced by the ion deflector. The local compensation may be performed within at most a pair of ion mirror reflections.
Electrodes of the electrode structure may be connected to an adjustable voltage supply for adjusting the voltages applied to these electrodes so as alter said wedge electrostatic field and hence the angle of the time front tilt caused by said electrode structure.
One or more electrodes of the ion deflector may be connected to an adjustable voltage supply for adjusting the voltage(s) applied to these electrodes so as alter the ion deflecting angles ψ. The ion deflector introduces a time front tilt angle to the ion packets. The adjustable voltages may be adjusted to alter the time front tilt caused by the electrode structure and the deflecting angle of the ion deflector so that the time front tilt caused by the ion deflector is at least partially compensated for.
The time front tilt angle and ion steering angle ψ may be electrically adjusted or set for the global mutual compensation at the detector face of the ion packets time front tilt angle induced by misalignments of an ion source, and/or of said ion mirrors and/or of said detector.
The ion emitter may comprise a continuous ion source, generating an ion beam at mean specific energy UZ in the Z-direction and an orthogonal accelerator in the form of said pulsed ion emitter for pulsed ion acceleration substantially along the X-direction to specific energy UX, thus forming ion packets emitted at said inclination angle α0=(UZ/UX)0.5 to said X-direction.
The ion emitter may comprise a transverse ion confinement device selected from the group of: (i) a radiofrequency rectilinear multipolar ion guide; (ii) an electrostatic quadrupolar ion guide with ion beam compression and/or confinement in the X-direction; (iii) an electrostatic periodic lens; and (iv) an electrostatic ion guide having a quadrupolar field that is spatially alternated along the Z-direction.
A quadrupolar field may be formed within said at least one ion deflector along the Z-direction, optionally by at least one electrode structure of the group of: (i) Matsuda plates; (ii) a gate shaped deflecting electrode; (iii) side shields of the deflector with an aspect ratio under 2; (iv) toroidal sector deflection electrodes; and (v) an electrode curvature within a trans-axial wedge deflector.
Said quadrupolar field may be adjustable for at least one purpose selected from the group of: (i) controlling the spatial focusing or defocusing of ion packets; (ii) arranging telescopic compression of the ion packets; (ii) compensating the second order time aberrations per Z-width in ion packets T|ZZ=0, either locally and/or globally.
The wedge field may be located within said pulsed accelerating region and may be arranged by an electrode structure selected from the group of: (i) a tilted pull, ground or push plate electrode; (ii) a tilted ion guide for spatial confinement of the ion beam within an ion storage region of the pulsed ion emitter; (iii) an auxiliary electrode around electrodes forming an ion storage region of the pulsed ion emitter for forming a non-equally penetrating fringing field through a window, or a mesh, or a gap into the ion storage region.
Said wedge field may be located within said ion retarding region of at least one of the ion mirrors and may be arranged by an electrode structure selected from the group comprising: (i) a wedge-shaped slit oriented in the ZY-plane and located between mirror electrodes; (ii) at least one printed circuit board with discrete electrodes aligned in the Z-direction, connected via a resistive divider and located between mirror electrodes; (iii) a locally tilted portion of at least one electrode of said ion mirror; and (iv) at least one split portion of at least one electrode of said ion mirror, connected to a separate potential.
At least one of the following may be provided: (i) said at least one deflector may be located to receive ions after a first ion mirror reflection and optionally before a second ion mirror reflection; (ii) a lens or a trans-axial lens may be provided at the exit of said pulsed ion emitter and at least one ion deflector may be provided that is configured for ion packet defocusing, so as to provide telescopic compression of said ion packets; (iii) a lens may be located proximate one of said ion mirrors and arranged to receive ions reflected by that ion mirror in one mirror reflection and also after a second subsequent reflection from that ion mirror; (iv) a dual ion deflector may be arranged proximate said detector for causing the ions to bypass the detector's rim; and (v) a dual ion deflector with a spatially focusing quadrupolar field may be provided for reversing the ion drift motion in the Z-direction and compensating a tilt of the ion packet time front.
The spectrometer may further comprise at least one printed circuit board, located between electrodes of at least one of said mirrors; said board having discrete electrodes, connected to each other via a resistive chain and to a voltage supply for forming a wedge or arc shaped electrostatic field within the ion retarding region of the ion mirror for altering the ion packet time-front tilt.
Electrodes of at least one of said ion mirror may be made of one or more printed circuit boards having conductive pads; optionally having a rib mounted thereto for maintaining the flatness thereof.
The present invention also provides a method of multi-reflecting time-of-flight mass spectrometry comprising:
providing a spectrometer as described hereinabove;
pulsing ions along the X-direction with the pulsed ion emitter so as to emit ion packets at said inclination angle α0;
oscillating ions in the X-direction between the mirrors as the ions drift in the Z-direction; and
deflecting the ion trajectories by angle ψ in the XZ plane using the ion deflector;
wherein the time front tilt angle γ of the ion packets is adjusted, and the steering angle of the ion trajectories is adjusted by inclination angle ϕ, in the XZ plane, using said wedge electrostatic field and electrostatic acceleration field so as to (i) more densely fold the ion trajectories at inclination angle α to the X-direction that is smaller than said angle α0, (ii) and/or to cause ions to bypass a rim of said pulsed ion emitter or ion deflector, (iii) and/or to reverse ion drift motion in said Z-direction.
The method may comprise adjusting one or more voltages applied to the ion deflector and/or pulsed ion emitter so as to adjust the ion deflecting angle ψ and/or time front tilt angle γ so as to at least partially compensate for a time front tilt angle induced by the ion deflector.
The wedge field may be arranged in at least one of said ion mirrors and so as to extend in the Z-direction by a distance such that ions reflected by that mirror between 2 and 4 times pass through the wedge field.
The method may comprise forming a wedge-shaped or curved electric field within the reflecting region of at least one ion mirror and along substantially the entire ion path in the Z-direction, optionally for compensating the isochronicity of ion motion related to the ion packet Z-width.
The method may comprise adjusting voltages applied to the spectrometer so as to spatially vary the wedge-shaped or curved electric field.
Said compensating of the tilt angle of the ion packets time front may comprise monitoring the resolution of the spectrometer whilst adjusting said deflecting angle and/or steering angle and/or ion beam energy at the entrance of said pulsed ion emitter.
The deflecting angle and/or steering angle and/or ion beam energy may be varied until the resolution is optimised, and then these parameters may then be fixed.
This technique may account for mechanical inaccuracies or misalignments of said ion emitter, of said ion mirrors, of said wedge field structures, or of said ion detector.
The method may comprise at least one step of the following group: (i) providing said at least one ion deflector downstream of the first ion mirror reflection; (ii) telescopically compressing said ion packets using a lens or a trans-axial lens at the exit of said pulsed ion emitter and setting said at least one deflector to an ion defocusing state; (iii) focusing ion packets using a lens located in proximate one of said ion mirrors and arranged to receive ions reflected by that ion mirror in one mirror reflection and also after a second subsequent reflection from that ion mirror; (iv) displacing the ion trajectory using a dual ion deflector arranged in proximate said detector so that ions bypass the detector's rim; and (v) reversing of the ion drift motion in the Z-direction at compensated tilt of the ion packet time front with a dual deflector having a spatially focusing quadrupolar field.
There are proposed herein several ion optical elements and solutions which are novel at least for MRTOF field:
I. A combination of wedge reflecting fields or wedge accelerating fields with “flat” post-acceleration. Such optical element, further referred as “amplifying wedge field” appears a powerful, flexible and electrically adjustable tool for tilting time fronts of ion packets while introducing very minor ion ray steering;
II. An electrically controlled wedge field near retarding equipotential of ion mirrors for compensation of time-front parasitic tilts introduced by mechanical unintentional misalignments of accelerators, ion mirror electrodes and detector;
III. A compensated deflector, incorporating quadrupolar field, in most simple example produced by Matsuda plates. The compensated deflector overcomes the over-focusing of conventional deflectors in MRTOF, so as provides an opportunity for controlled ion packet focusing and defocusing;
IV. A set of compensated deflectors for flexible controlling of both time-front tilt angle and ion ray steering angle.
Further, it has been realized that applying a combination of compensated deflectors with amplifying wedge fields to MRTOF allows reaching the desired combination of: (a) elevated energies of ion beams at the entrance of orthogonal accelerators for improved sensitivity and for reduced angular divergence Δα of ion packets; (b) dense folding of ion rays at small inclination angles for higher resolution of MPTOF; (c) spatial ion packet focusing Z|Z=0 onto detector; and (d) mutual compensation of multiple aberrations, including (i) first order time-front tilt T|Z, (ii) chromatic angular spread α|β and, accounting analyzer properties, most of Y-related time-of-flight aberrations.
Most of the proposed schemes and embodiments were tested and are presented herein in ion optical simulations, which have verified the stated ion optical properties, including flexible tuning and compensation of misalignments; so as confirmed an ability of reaching substantially improved combination of resolution and sensitivity within compact MPTOF systems. As an example,
Embodiments of the present invention provide a multi-reflecting time-of-flight mass spectrometer comprising:
Preferably, said ion emitter may comprise a continuous ion source, generating an ion beam at mean specific energy UZ in the Z-direction and an orthogonal accelerator for pulsed ion acceleration substantially along a second orthogonal X-direction to specific energy UX, thus forming ion packets emitted at an inclination angle α0=(UZ/UX)0.5 to said X-axis;
Preferably, said ion emitter may comprise one mean of transverse ion confinement of the group: (i) a radiofrequency rectilinear multipolar ion guide; (ii) an electrostatic quadrupolar ion guide with ion beam compression in the X-direction; (iii) an electrostatic periodic lens; and (iv) an electrostatic ion guide with quadrupolar field being spatially alternated along the Z-axis.
Preferably, an additional quadrupolar field may be formed within said at least one deflector by at least one electrode structure of the group: (i) Matsuda plates; (ii) gate shaped deflecting electrode; (iii) side shields of the deflector with the aspect ratio under 2; (iv) toroidal sector deflection electrodes; and (v) additional electrode curvature within a trans-axial wedge deflector.
Preferably, said additional quadrupolar field may be adjusted for the at least one purpose of the group: (i) controlling spatial focusing or defocusing of ion packets; (ii) arranging telescopic compression of ion packets; (ii) compensating second order time aberrations per Z-width in ion packets T|ZZ=0, either locally and/or globally.
Preferably, said accelerating wedge field within said emitter may be arranged with one electrode structure of the group: (i) a tilted pull, ground or push plate; (ii) a tilted ion guide for spatial confinement of said ion beam within said ion storage region; (iii) an auxiliary electrode around electrodes of said accelerator forming a non equally penetrating fringing field through a window, or a mesh, or a gap.
Preferably, said reflecting wedge field within ion retarding region of at least one ion mirror may be arranged with one electrode structure of the group: (i) a wedge slit oriented in the ZY-plane and located between mirror electrodes; (ii) at least one printed circuit board with discrete electrodes aligned in the Z-direction, connected via resistive divider and located between mirror electrodes; (iii) a locally tilted portion of at least one electrode of said ion mirror; and (iv) at least one split portion of at least one electrode of said ion mirror, connected to a separate potential.
Preferably, said spectrometer may further comprise at least one means of the group: (i) said at least one deflector is located after first ion mirror reflection or first ion turn; (ii) a lens or a trans-axial lens at the exit of said emitter in combination with setting of at least one deflector for ion packet defocusing, this way providing for telescopic compression of said ion packets; (iii) a lens located in close vicinity of said ion mirror and arranged to surround two adjacent ion trajectories; (iv) a dual deflector arranged in close vicinity of said detector for improved bypassing of the detector's rim; and (v) a dual deflector with spatially focusing quadrupolar field for reversing of the ion drift motion at compensated tilt of the ion packet time front.
Preferably, for the purpose of electrically compensating the ion packet time front tilting by unintentional minor inaccuracy of misalignments of said ion mirrors, said spectrometer may further comprise at least one printed circuit board, located between said mirror electrodes; said board forms discrete electrodes, connected via resistive chain to form a wedge or an arc shaped electrostatic wedge field within the ion retarding region of at least one ion mirror; said compensation is arranged both locally (within one or two adjacent ion mirror reflections) and/or globally for the entire ion path.
Preferably, said ion mirror electrodes may be made of printed circuit boards with conductive pads; wherein the flatness of said electrodes is improved by at least one attached orthogonal rib; and wherein the straightness and flatness of the electrode assembly is improved by milling slots in said electrodes for compensating the uneven thickness of the boards.
Embodiments of the present invention provide a method of multi-reflecting time-of-flight mass spectrometry comprising the following steps:
Preferably, said step of emitting ion packets may comprise a step of generating a continuous ion beam at mean specific energy UZ in the Z-direction and a step of pulsed ion acceleration substantially along a second orthogonal X-direction to specific energy UX, thus forming ion packets emitted at an inclination angle α0=(UZ/UX)0.5 to said X-axis; Preferably, said step of ion emitting may further comprise a step of transverse ion confinement by one field of the group: (i) a quadrupolar radiofrequency field; (ii) an electrostatic quadrupolar field with ion beam compression in the X-direction; (iii) an electrostatic periodic focusing field of periodic lens; and (iv) an electrostatic quadrupolar field, spatially alternated along the Z-axis.
Preferably, at the step of ion packet steering may further comprise a step of forming an additional quadrupolar field for the at least one purpose of the group: (i) controlling spatial focusing or defocusing of ion packets; (ii) arranging telescopic compression of ion packets; (ii) compensating second order time aberrations per Z-width in ion packets T|ZZ=0, either locally and/or globally.
Preferably, said step of forming an electrically adjustable reflecting wedge field in at least one ion mirror field may comprise a step of spreading said wedge field within a region extended in the Z-direction for several but few (between 2 and 4) ion reflections; said region being located either in the region of ion injection past said orthogonal accelerator, or in the region of ion reverting their drift motion.
Preferably, for the purpose of globally compensating isochronicity of ion motion related to the ion packet Z-width, affected by unintentional minor inaccuracy of misalignments of said ion mirror fields, said accelerator field, or with non parallel installation of said detector, the method may further comprise a step of forming electrically adjustable global (on the entire Z-width of ion path) wedge and/or arc field within reflecting region of at least one ion mirror.
Preferably, said step of global compensating of the tilt angle γ of ion packets time-front on the detector may further comprise a step of linked adjustments of said steering angles, and of ion beam energy at the entrance of said ion emitter while monitoring resolution of said method, this way accounting a given and occurred mechanical inaccuracy or misalignment of said ion emitter, of said ion mirrors, of said wedge field structures, or of said ion detector.
Preferably, the method may further comprise at least one step of the group: (i) improving the deflector bypassing by locating at least one deflector after first ion mirror reflection or after first ion turn; (ii) telescopically compressing said ion packets by a lens or a trans-axial lens at the exit of said orthogonal accelerator combined with setting of said at least one deflector to a defocusing state; (iii) focusing of ion packets by a lens located in close vicinity of said ion mirror and arranged to surround two adjacent ion trajectories; (iv) displacing ion trajectory with a dual deflector arranged in close vicinity of said detector for improved bypassing of the detector's rim; and (v) reversing of the ion drift motion at compensated tilt of the ion packet time front with a dual deflector with spatially focusing quadrupolar field.
Embodiments of the present invention provide a low cost means for controlling drift ion motion in planar MRTOF.
Embodiments provide a means and method for electronically adjusted compensation of unintentional misalignments of MRTOF components.
Embodiments provide a compact (say, 0.5 m) and low cost instrument with sufficiently high resolution R>80,000 for separating major isobaric interferences, yet without stressing requirements of the detection system and not affecting peak fidelity, while operating at reasonably high energy of continuous ion beams for improved ion beam admission into the orthogonal accelerator.
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 to charge ratio (and which may have the mean average energy).
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 a 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. An electrical pulse in OA 14 ejects ion packets 15. Packets 15 travel in MRTOF at a small inclination angle α to the X-axis, controlled by the ion source bias UZ.
Referring to
In the example 20, to fit 14 reflections (i.e. L=7 m flight path) the source bias is set to UZ=9V. Parallel rays with initial ion packet width Z0=10 mm and no angular spread Δα=0 start hitting rims of the OA 14 and detector 17.
In example 21, the top ion mirror is tilted by λ=1 mrad, representing a realistic overall effective angle of mirror tilt, accounting for built up faults of the stack assemblies, standard accuracy of machining and moderate electrode bend due to 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 mrad, gradually expanding the 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 21, the inclination of the ion mirror introduces yet another and much more serious problem—the time-front 15 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 limits mass resolution to R<L/2ΔX=11,000 at L=7 m flight path, which is too low compared to, for example, a desired R=80,000. To avoid the limitation, the electrode precision has to be brought to a non-realistic level: λ<0.1 mrad, which translates to better than 10 um accuracy and straightness of individual electrodes.
Summarizing problems of prior art MRTOFs, attempts of increasing flight path require much lower specific energies UZ of the continuous ion beam and larger angular divergences Δα of ion packets, which induce ion losses on component rims and may produce spectral overlaps. Most important, small mechanical imperfections strongly affect MRTOF resolution and require unreasonably high precision.
With a complex electrode structure and tight requirements on the parallelism of analyzer electrodes in MPTOF, it is desirable to keep instrument size at about 0.5 m. Electrodes stability and vacuum chamber sagging under atmospheric pressure limit the analyzer width to under 300-350 mm. Making larger analyzers raises the manufacturing cost close to the cubic power of the instrument size.
The ideal MPTOF is expected to provide a significant gain in resolution, while not pushing the data system and detector time spreading (at peak base) under DET=2 ns, thus, not requiring ultra-fast detectors with strong signal ringing, or without artificially sharpening resolution by “centroid detection” algorithms, mining mass accuracy and merging mass isobars. To resolve practically important isobars at mass resolution R=TOF/2DET, the peak width shall be less than the isobaric mass difference, hence requiring longer flight time TOF and longer flight path L (calculated for 5 kV acceleration), all shown in Table 1 below.
The table presents the most relevant and most frequent isobaric interferences of first isotopes. In case of LC-MS, the required resolution is over 80,000. In case of GC-MS, where most ions are under 500 amu, the required resolution is over 40K.
Embodiments of the present invention provide the instrument with sufficiently high resolution R>80,000 for separating major isobaric interferences, yet without stressing requirements of the detection system and not affecting peak fidelity.
Referring to
rψ=D/2H*U/K; γ=−ψ=const(z) (Eq. 3)
Alternatively, compensated deflectors may be trans-axial (TA) deflectors, formed by wedge electrodes. Embodiments of the invention propose using a first order correction, produced by an additional curvature of TA-wedge. Controlled focusing/defocusing may be also generated by combination of the TA-wedge and TA-lens, arranged separately or combined into a single TA-device. For a narrower range of deflection angles, the compensated deflector may be arranged with a single potential while selecting the size of Matsuda plates or with a segment of toroidal sector.
Compensated deflectors nicely fit MRTOF. The quadrupolar field in the Z-direction generates an opposite focusing or defocusing field in the transverse Y-direction. Below simulations prove that the focal properties of MRTOF analyzers are sufficient to compensate for the Y-focusing of deflectors 30 without any significant TOF aberrations.
Again referring to
Referring to
Exemplary orthogonal accelerator 40 OA comprises: a region of pulsed wedge field 45, arranged between tilted push electrode 44 and ground plate 47 aligned with the Z-axis; and a straight DC accelerating field 48 formed by electrodes parallel to the Z-axis. Field 48 may have accelerating and decelerating regions for producing low time spread and spatial ion focusing of ion packets in the XY-plane, however, all equipotential lines of field 48 stay parallel to the Z-axis.
In operation, continuous ion beam 41 enters OA along the Z-axis at specific ion energy UZ, e.g. defined by voltage bias of an upstream RF ion guide. Preferably ion beam angular divergence, spatial expansion and beam initial position are controlled by some radial confinement means, e.g. of the group: (i) a radiofrequency rectilinear multipolar ion guide; (ii) an electrostatic quadrupolar ion guide with ion beam compression in the X-direction; (iii) an electrostatic periodic lens; and (iv) proposed in a co-pending application, an electrostatic ion guide with quadrupolar field being spatially alternated along the Z-axis. An electrical pulse is applied periodically to push plate 44, ejecting a portion of the beam 41 through an aperture in electrode 47, thus forming an ion packet with starting time-front 42, which crosses a starting equipotential 46, tilted at the angle λ0. Ions start with zero mean energy in the X-direction K=0. At the exit of wedge field 45 ions gain specific energy K1 and at the exit of the DC field 48 the ions have energy K0. Assuming a small angle λ0 of equipotential 46 (in further examples 0.5 deg), a beam thickness of at least ΔX>1 mm and a moderate ion packet length (examples use Z0=10 mm), the λo tilt of starting equipotential 46 produces negligible corrections on energy spread ΔK of ion packet 49.
While applying trivial mathematics a non-expected and previously unknown result was arrived at: in accelerator 40 with amplifying wedge accelerating field, the time-front tilt angle relative to the z-axis (γ) and the ion steering angle θ introduced by the wedge field are controlled by the energy factor K0/K1 as:
γ=2λ*(K0/K1)0.5=2λ*u0/u1
ϕ=2λ/3*(K1/K0)0.5=2λ/3*u1/u0
i.e. γ/ϕ=3K0/K1>>1
where K1 and K0 are mean ion kinetic energies at the exit of the wedge field 45 (index 1) and at the exit of flat field 48 (index 0) respectively, and u1 and u0 are the corresponding mean ion velocities.
Thus, novel accelerators with amplifying wedge field allow (i) operating with continuous ion beams introduced along the Z-axis, which allows convenient instrumental arrangements; (ii) tilting ion packets time-front by substantial angles γ, which may then be used for compensation of the time-front tilt in ion deflectors; (iii) controlling the tilt angle electronically, either by adjusting the pulse potential or by minor steering of continuous ion beam between various starting equipotential lines.
Again referring to
Ion injection into MRTOF may be improved by using higher energy continuous ion beams for improving the ion beam admission into an orthogonal accelerator (OA) and for reducing angular divergence of ion packets in the MRTOF. For higher MRTOF resolution, ion trajectories may be compact folded by using back steering of ion packets, achieved with an ion deflector. To compensate for the time-front tilt produced by the deflector, it is proposed to use an amplifying wedge accelerating field in the OA.
Referring to
The operation of embodiment 50 is illustrated by simulation example 51, showing time fronts 54 and 55 crossing ion rays. Continuous ion beam 41 at specific energy UZ=57V propagates along the Z-axis to cross starting (K=0) equipotential 46, which is tilted at the angle λ0=0.5 deg by push plate 44 being tilted by 1 deg to the Z-axis. Pulsed wedge field 45 accelerates ions to mean energy K1=800V, and flat field 48 to K0==8 kV, thus producing an amplifying factor K0/K1≅10. The amplifying wedge tilts the ion packets time front 54 at a large angle γ=2λ0*(K0/K)0.5≈6λ0, while having a small effect on the rays angle α1=α0−ϕ=4.7 deg at ϕ≅0.2 deg, i.e. ion rays are inclined almost at the natural inclination angle α0=(UZ/UX)0.5=4.9 deg. After the first ion mirror reflection, deflector 30 steers ion rays by ψ=−γ=−3.2 deg, thus reducing the inclination angle to α2=α1−ψ1.5 deg, while aligning the ion packets time front 55 with the Z-axis, i.e. γ=0. Much higher specific energies of the ion beam (UZ=57V Vs 9V in to prior art 20) improve the ion admission into the OA and reduce the angular divergence Δα of ion packets for denser folding of ion trajectories at smaller inclination angles, here at α2=α1−ψ=1.5 deg Vs natural inclination angle α0=4.9 deg.
Table 2 below summarizes equations for angles within individual deflector 30 and wedge accelerator 40. Table 3 below presents conditions for compensation of the first order time front tilt and of the chromatic spread of Z-velocity. It is of significant importance that both compensations are achieved simultaneously. This is new finding in the field. The pair of wedge accelerator 40 and deflector 30 work nicely for MRTOF 50—it compensates multiple aberrations, including the first order time front tilt, the chromatic angular spread and, accounting focusing properties of gridless ion mirrors in example 51, the angular and spatial spreads of ion packets in the Y-direction.
Referring back to
Referring to
Example 60 illustrates spatial focusing of ion rays 61 for Z=10 mm long ion packets (the initial length of the ion packet along the Z-axis), while not accounting angular spread of ion packets (Δα=0 at ΔUZ=0) and not accounting relative energy spread of ion packets (δ=ΔK/K=0 at ΔX=0). The chosen position of deflector 30 improves the ion packets bypassing of the deflector 30. The Matsuda plate voltage of the deflector 30 is electrically adjusted for geometrical focusing of ion packets onto the detector, which allows a denser folding of ion rays in MRTOF at α2=1.5 deg.
Example 62 illustrates the angular divergence of ion rays 63 at ΔUZ=0.5V, while not accounting for the ion packets width Z0=0 and energy spread δ=0. Dual compensated deflector 30D (another novel component for MRTOF) helps spreading ion rays in front of the detector 17 for bypassing the detector rims (here 5 mm).
Example 64 illustrates the (predicted by Table 4 below) simultaneous compensation of chromatic angular spread α|δ=0 and first order time front tilt γ=0 at δ=0.05, ΔUZ=0, and Z0=0 (dark intervals show positions of ions of different energies at fixed time steps, in particular demonstrating energy focusing at the detector and after each reflection).
Example 66 illustrates the overall mass resolution RM=47,000 achieved in a compact 450×250 mm analyzer while accounting for all realistic spreads of ion beam and ion packets, so as DET=1.5 ns time spread. The embodiment satisfies the previously set goal R>40,000 for resolving major isobars presented in Table 1 for μ=m/z<500 in GC-MS instruments.
The injection mechanism 50 has a built-in and not yet fully appreciated virtue—an ability to compensate for mechanical imperfections of MRTOF by electrical tuning of the instrument, including adjustment of ion beam energies UZ, pulse voltage on push plate 44, deflector 30 steering, or steering of continuous ion beam 41 to fit different equipotential lines 46.
Referring to
Embodiments of the invention propose to arrange wedge fields in the reflection region of parallel ion mirrors for effective and electrically tuned control over the inclination angle of ion packets in the MRTOF. Referring to
Flat field 88 has equipotential lines parallel to the Z-axis within boundaries corresponding to mean energies K0 and K1, where K0>K1. Model wedge field 85 is arranged with uniformly diverging equipotentials in the XZ-plane, where the field strength E(z) is independent of the X-coordinate, and within the ion passage Z-region the field E(z) is inversely proportional to the Z-coordinate: E(z)˜1/z. Wedge field 85 starts at an equipotential corresponding to K=K1 and continues at least to the ion turning equipotential 86 (K=0), which is tilted to the Z-axis at λ0 angle.
While applying standard mathematics a non expected and previously unknown result was arrived at: in ion mirror 80 with wedge field 85, the time-front tilt angle γ and the ion steering angle ϕ are controlled by the energy factor K0/K1 as:
γ=4λ0*(K0/K1)0.5=4λ0*u0/u1
ϕ=4λ0/3*(K1/K0)0.5=4λ0/3*u1/u0
i.e. γ/ϕ=3K0/K1>>1
where K1 and K0 are mean ion kinetic energies at the exit of the wedge field 85 (index 1) and at the exit of flat field 88 (index 0) respectively, and ui and uo are the corresponding mean ion velocities. The angle ratio γ/ϕ=3K0/K1 may in practice reach well over 10 or 30 and is controlled electronically.
At K0/K1=1 (i.e. without acceleration in the field 88), the wedge field already provides a twice larger time front tilt γ compared to fully tilted ion mirrors (γ=4λ0Vs γ=2λ0), while producing a smaller steering angle (ϕ=4/3λ0 Vs ϕ=2λ0). The angles ratio γ/ϕ further grows with the energy factor as K0/K1 because the angles are transformed with ion acceleration in the field 88: both flight time difference dT and z-velocity w are preserved with the flat field 88, where the time-front tilt dT/u grows with ion velocity u and the steering angle dw/u drops with ion velocity u. By arranging larger K0/K1 ratio, the combination of wedge field with post-acceleration becomes a convenient and powerful tool for adjustable steering of time fronts, accompanied by negligibly minor steering of ion rays.
Again referring to
An ion optical model for the wedge electrode W of embodiment 81 is illustrated by icons 82 and 83, where Icon 82 shows the electrode structure (C, W and E1) around the ion reflection region and also shows equipotential lines in the XY-plane at one particular Z-coordinate. Icon 83 illustrates a slight bending of the retarding equipotential 86 in the XZ-middle plane, at strong disproportional compression of the picture in the Z-direction so that the slight curvature of the line 86 can be seen. Dark vertical strips in icon 83 correspond to ion trajectories, arranged at relative energy spread δ=0.05, so that angled tips illustrate the range of ion penetration into the mirror. Icon 83 shows that the wedge field 85 is spread in the Z-direction in the region for several ion reflections, which helps distributing the time-front tilting at yet smaller bend of equipotential 86.
Simulations have shown that: (i) adjustments of the amplifying factor of 4(K0/K1)0.5 allows strong tilting of the time-front at small wedge angles λ0, thus not ruining the structure of electrical fields, which are optimized for reaching overall isochronicity and spatial focusing of ion packets; (ii) the time front tilt angle can be electronically adjusted from 0 to 6 degrees if using wedge W in both opposite ion mirrors; (iii) the compensation of the time front tilting for deflectors is reached simultaneously with compensation of chromatic dependence of the Z-velocity, as illustrated in
Referring to
To produce a desired curvature or bend of the ion retarding equipotential 96, the PCB 91 carries multiple electrode segments, connected via resistive chain 92, preferably surface mounted SMD resistors, energized by at least one additional power supply, or by several power supplies U1 . . . Uj 93. Preferably, absolute voltages of supplies 93 are kept at low, say under 1 kV, which is to be achieved at ion optical optimization of the mirror electrode structure. The net of resistors 92 and power supplies 93 may be used for generating electronically controlled amplifying wedge mirror fields. Exemplary retarding equipotential 96 has wedges at both the near and far Z-ends for the purpose of compensated deflection according to
Realistic instruments may have a slight mechanical inaccuracy in parallelism of the orthogonal accelerator electrodes, ion mirror electrodes and of the detector. One mechanism of compensating misalignments was presented in
Again referring to
Optionally, PCB electrodes 91 may be used at manufacturing tests only for measuring the occurred inaccuracy of ion mirrors when measuring the required PCB compensation at recovered MRTOF resolution, which in turn could be used for calibrated mechanical adjustment of individual ion mirrors. Alternatively, the number of regulating power supplies 93 may be potentially reduced and the strategy of analyzer tuning may be optimized for constant use. It is expected that a pair of auxiliary power supplies may be used for simultaneous reaching of: creating preset wedge fields at far and near Z-edges, compensating electrode faulty tilts, and compensating electrode faulty bends. Indeed, all wedge fields produce the same action—to tilt the time front of ion packets, and it is expected that a generic distribution of PCB potentials may be pre-formed for each mirror, while controlling the overall tilt and bow of wedge fields by a pair of low voltage power supplies 93.
Compared to tilted push plate 44 in
As described in a co-pending application, the proposed compensation mechanism of
Referring to
Ion beam 41 propagates along the Z-axis at elevated (compared to
Again referring to
Table 4 below presents formulae for time front tilt angles γ, for ray steering angles θ and for chromatic dependence d(Δw)/dδ of the Z-component of ion velocity w induced by wedge ion mirror and by deflectors.
Table 5 below shows conditions for compensating the time front tilt and the chromatic dependence of the Z-velocity in the combined system, apparently achieved simultaneously.
Referring to
Example 110 illustrates spatial focusing of ion rays 111 for Z0=10 mm long ion packets, while not accounting for angular spread of ion packets Δα=0 at ΔUZ=0 and not accounting for relative energy spread of ion packets δ=ΔK/K=0 at ΔX=0. The chosen position of deflector 30 improves the ion packets bypassing of the deflector 30 and of detector 17 rim. Matsuda plates' voltages of the deflectors 30 and 30R are electrically adjusted for moderate spatial focusing of initially parallel rays onto detector 17, while being balanced for achieving optimal focusing in other examples of
Example 112 illustrates the angular divergence of ion rays 113 at ΔUZ=0.5V, while not accounting for ion packets width Z0=0 and energy spread δ=0. The Matsuda plate of the reversing deflector 30R is adjusted (being the same for all examples of
Example 114 illustrates ion rays at all accounted spreads of ion beam. Though trajectories look like they are filling most of the drift space, apparently, simulated ion losses are within 10%.
Example 116 illustrates the overall mass resolution RM=83,000 achieved in a compact 450×250 mm analyzer while accounting for all realistic spreads of ion beam and ion packets, so as DET=1.5 ns time spread. The embodiment satisfies the previously set goal R>80,000 for resolving major isobars presented in Table 1 for μ=m/z<1000 in LC-MS instruments. N=28 reflections correspond to 14 m flight path and TOF=328 us flight time for μ=1000. Thus, the far-end compensated deflector provides almost twice denser folding of ion trajectory.
Yet higher resolutions are expected at larger size instruments, since the flight path L grows as product of instrument dimensions: L=2DX*DZ/LZ, where LZ is the ion advance per reflection. Embodiments of the invention provide methods of compensated steering, shown in
Referring to
In operation, continuous ion beam 41 propagates along the Z-axis at elevated specific energy UZ (expected from 20 to 50V). A compensated ion injection mechanism is arranged with a wedge accelerator 40 (OA) and compensated deflector 30, similar to injection mechanism 50, described in
Embodiment 120 presents yet another novel ion optical solution—a compensated reversing of ion trajectories. The reversing mechanism is arranged with a pair of focusing and defocusing deflectors 124 and 125, best seen in zoom view 121, expanded in the Z-direction. Ion packets reach far Z-end of the sector analyzer at an inclination angle α2. Deflector 124 with Matsuda plates is set for increasing the inclination angle to α3 while focusing the packet Z-width within deflector 125. Deflector 125 is set to reverse ion trajectory with deflection for −2α3 angle and defocuses the packet from Z3 to Z2 by using Z-defocusing quadrupolar field of Matsuda plates in deflector 125. The focusing factor Z3/Z2 and deflection angles are arranged as 2Z3*α3=Z2(α3−α2) to mutually compensate for the time front tilts, as illustrated with simulated dynamics of the time front 129.
x, y, z—Cartesian coordinates;
X, Y, Z—directions, denoted as: X for time-of-flight, Z for drift, Y for transverse;
Z0—initial width of ion packets in the drift direction;
ΔZ—full width of ion packet on the detector;
DX and DZ—used height (e.g. cap-cap) and usable width of ion mirrors
L—overall flight path
N—number of ion reflections in mirror MRTOF or ion turns in sector MTTOF
u—x-component of ion velocity;
w—z-component of ion velocity;
T—ion flight time through TOF MS from accelerator to the detector;
ΔT—time spread of ion packet at the detector;
U— potentials or specific energy per charge;
UZ and ΔUZ—specific energy of continuous ion beam and its spread;
UX—acceleration potential for ion packets in TOF direction;
K and ΔK—ion energy in ion packets and its spread;
δ=ΔK—relative energy spread of ion packets;
E—x-component of accelerating field in the OA or in ion mirror around “turning” point;
μ=m/z—ions specific mass or mass-to-charge ratio;
α—inclination angle of ion trajectory relative to X-axis;
Δα—angular divergence of ion packets;
γ—tilt angle of time front in ion packets relative to Z-axis
λ—tilt angle of “starting” equipotential to axis Z, where ions either start accelerating or are reflected within wedge fields of ion mirror
θ—tilt angle of the entire ion mirror (usually, unintentional);
φ—steering angle of ion trajectories or rays in various devices;
ψ—steering angle in deflectors
ε—spread in steering angle in conventional deflectors;
T|Z, T|ZZ, T|δ, T|δδ, etc; 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 |
|---|---|---|---|
| 1712612.9 | Aug 2017 | GB | national |
| 1712613.7 | Aug 2017 | GB | national |
| 1712614.5 | Aug 2017 | GB | national |
| 1712616.0 | Aug 2017 | GB | national |
| 1712617.8 | Aug 2017 | GB | national |
| 1712618.6 | Aug 2017 | GB | national |
| 1712619.4 | Aug 2017 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2018/052101 | 7/26/2018 | WO | 00 |
