Patent Application
20200168447
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 electrostatic trap mass spectrometers and is particularly concerned with pulsed converters.
Time-of-flight mass spectrometers (TOF MS) are widely used for combination of sensitivity and speed, and lately with the introduction of ion mirrors and multi-reflecting schemes, for their high resolution and mass accuracy.
In last two decades, the resolution of TOF MS has been substantially improved by using multi-pass TOFMS (MPTOF), employing either ion mirrors for multiple ion reflections in a multi-reflecting TOFMS (MRTOF), 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) as described in U.S. Pat. Nos. 7,504,620, 7,755,036, and M. Toyoda, et. al, J. Mass Spectrom. 38 (2003) 1125, incorporated herein by reference. The term “pass” generalizes ion mirror reflection in MRTOF and ion turn in MTTOF.
Electrostatic traps (E-traps) with image current detection is an emerging technology. With success of compact Orbitrap electrostatic analyzers, alternative approaches were proposed for higher space charge capacity and throughput of E-traps. Historically ion traps were used for accumulation and pulsed ejection of large size ion clouds into E-traps. However, elongated pulsed converters are equally feasible. Open traps is another intermediate hybrid of TOF MS and E-trap.
Operation of TOF MS starts with pulsed injection of ion packets. Pulsed sources are used 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 become more and more popular for mass spectral surface imaging, where relatively large surface area is analyzed simultaneously while using mapping properties of TOF MS.
Even more popular are TOF MS, where pulsed converters are used to form pulsed ion packets out of continuous ion beams produced by ion sources like Electron Impact (EI),
Electrospray (ESI), Atmospheric pressure ionization (APPI), atmospheric Pressure Chemical Ionization (APCI), Inductively couple Plasma (ICP) and gaseous (MALDI). Most common pulsed converters are orthogonal accelerators as exampled in WO9103071, and radiofrequency ion traps with pulsed radial ejection, lately used for ion injection into Orbitraps.
Elongated orthogonal accelerators have been recently proposed in WO2016174462 and co-pending application by the inventor for higher duty cycle and sensitivity. This raises a question of ion beam retaining in the elongated OA. U.S. Pat. Nos. 5,763,878 or 8,373,120 propose using RF fields for transverse ion confinement, which limits the retained mass range and produces multiple mass dependent and RF phase dependent effects at ion pulsed ejection. RU2013149761 proposed using static quadrupolar field for moderate elongation of OA, which allows moderate elongation of the OA, since the quadrupole field defocuses the ion beam in the second direction.
From a first aspect the present invention provides a pulsed ion accelerator for a mass spectrometer comprising: an ion guide portion having electrodes arranged to receive ions travelling along a first direction (Z-dimension), including a plurality of DC electrodes spaced along the first direction; DC voltage supplies configured to apply different DC potentials to different ones of said DC electrodes such that when ions travel through the ion guide portion along the first direction they experience an ion confining force, generated by the DC potentials, in at least one dimension (X- or Y-dimension) orthogonal to the first direction; and a pulsed voltage supply configured to apply a pulsed voltage to at least one electrode of the ion accelerator for pulsing ions out of the ion accelerator in a second direction (X-dimension) substantially orthogonal to the first direction (Z-dimension).
The DC electrodes and DC voltage supplies generate an electrostatic field that spatially varies along the first direction. As such, the ions travelling along the first direction experience different forces at different distances along the first direction. This enables the ions to be confined by the DC potentials in an effective potential well that may be independent of the mass to charge ratios of the ions.
The ion confining force generated by the DC potentials desirably confines ions in the second dimension (X-dimension). This may improve the initial spatial distribution of the ions for pulsing in the second dimension (X-dimension).
The DC voltage supplies may be configured to apply different DC potentials to different ones of said DC electrodes such that when ions travel through the ion guide portion along the first direction they experience an ion confining force generated by the DC potentials in both dimensions (X- and Y-dimensions) orthogonal to the first direction.
Embodiments of the ion guide portion enable the pulsed ion accelerator to be relatively long in the first direction, whilst having relatively low ion losses, ion beam spreading and surface charging of the electrodes of the ion accelerator.
The ion confinement may be performed without the use of resonant RF circuits, and can be readily switched on and off. More specifically, the use of DC potentials to confine the ions in the ion guide portion enables embodiments to switch off the confining potentials relatively quickly (as opposed to RF confinement voltages), e.g. just before the pulsed ion ejection. Also, the pulsed voltage for ejecting ions does not excite the DC ion confinement electrodes in the detrimental manner that it would with RF confinement electrodes.
The provision of the DC electrodes spaced along the first direction enables the strength and shape of the DC confining field to be set up to vary along the first direction of the ion guide portion, e.g. to provide an axial gradient, a slight wedge or curvature of the confining field, without constructing complex RF circuits.
The pulsed ion accelerator may be an orthogonal accelerator.
The ions may enter into the pulsed ion accelerator along the first direction.
The ion guide portion may comprise a first pair of opposing rows of said DC electrodes on opposing sides of the ion guide portion, wherein each row extends in the first direction (Z-dimension).
The rows may be spaced apart in a third direction (Y-dimension), that is orthogonal to the first and second directions, by a gap. The pulsed ion accelerator may be configured such that when the pulsed voltage is applied to the at least one electrode, the ions are pulsed in the second direction (X-dimension) through the gap between the rows of electrodes and out of the ion guide portion. The ions may therefore be pulsed out of the ion guide without impacting on the rows of electrodes.
The DC voltage supplies may be configured to maintain at least some of the adjacent DC electrodes in each row at potentials having opposite polarities.
Each electrode in a given row may be maintained at an opposite polarity to the opposing electrode in the other row, i.e. each electrode in a given row may be maintained at an opposite polarity to the electrode having the same location (in the first direction) in the opposing row.
The ion guide portion may comprise a second pair of opposing rows of said DC electrodes on opposing sides of the ion guide portion, wherein each row extends in the first direction (Z-dimension). These rows may be spaced apart in the third direction (Y-dimension), that is orthogonal to the first and second directions, by a gap. The DC voltage supplies maybe configured to maintain at least some of the adjacent DC electrodes in each row at potentials having opposite polarities.
Each electrode in a given row of the second pair may be maintained at an opposite polarity to the opposing electrode in the other row of the second pair, i.e. each electrode in a given row of the second pair may be maintained at an opposite polarity to the electrode having the same location (in the first direction) in the opposing row of the second pair.
Ions may be received in the ion guide portion in the region radially inward of (and defined by) the first and second pairs of rows.
The DC voltage supplies may be configured to maintain the DC electrodes at potentials so as to form an electrostatic quadrupolar field in the plane orthogonal to the first direction, wherein the polarity of the quadrupolar field alternates as a function of distance along the first direction.
The DC electrodes may be arranged to form a quadrupole ion guide that is axially segmented in the first direction, and wherein the DC voltage supplies are configured to maintain DC electrodes that are axially adjacent in the first direction at opposite polarities, and DC electrodes that are adjacent in a direction orthogonal to the first direction at opposite polarities.
The DC quadrupolar field may spatially oscillate in the first direction.
The DC electrodes may have the same lengths in the first direction and may be periodically spaced along the first direction.
The DC electrodes may be arranged on one or more printed circuit board (PCB), insulating substrate, or insulating film.
For example, each of the rows of DC electrodes may be arranged on a respective printed circuit board, insulating substrate, or insulating film. Alternatively, two of the rows of DC electrodes may be arranged on two opposing sides of a PCB, insulating substrate, or insulating film. Alternatively, two of the rows of DC electrodes may be arranged on different layers of a multi-layer PCB or insulating substrate.
The PCB(s), insulating substrate(s), or insulating film(s) may comprise a conductive coating (e.g. in the regions that the electrodes do not contact) to prevent charge build up due to ion strikes. For example, a resistive layer may be provide between the electrodes, so as to avoid the insulating material becoming electrically charged.
PCB as used herein may refer to a component containing conductive tracks, pads and other features etched from, printed on, or deposited on one or more sheet layers of material laminated onto and/or between sheet layers of a non-conductive substrate.
It may be desired to increase the ion confining force as a function of distance in the first direction, e.g. so that the amplitude of oscillation of the ions (e.g. micro-motion) orthogonal to the first direction is (gradually) reduced as a function of distance along the ion guide portion.
For example, the DC voltage supplies may be configured to apply different DC voltages to the DC electrodes so as to form a voltage gradient in the first direction that increases the ion confining force as a function of distance in the first direction.
This may be achieved by connecting the DC electrodes aligned in the first direction using resistive dividers.
For the avoidance of doubt, said function of distance in the first direction is the distance away from the ion entrance to the ion guide portion.
The DC electrodes may be arranged in rows that are spaced apart in at least one dimension orthogonal to the first direction for confining the ions between the rows, and the DC electrodes may be spaced apart in said at least one dimension by an amount that decreases as a function of distance in the first direction.
The spacing between the DC electrodes in said at least one dimension may decrease as a function of distance in the first direction from the ion entrance at a first end of the ion guide portion to a downstream portion.
The spacing between the DC electrodes in said at least one dimension may be maintained constant from the downstream portion at least part of the distance to a second end of the ion guide portion.
The at least one dimension may be the dimension (Y-dimension) orthogonal to both the first direction (Z-dimension) and the second direction (X-dimension).
The pulsed ion accelerator may be configured to control the DC voltage supplies to switch off at least some of said DC potentials applied to the DC electrodes and then subsequently control the pulsed voltage supply to apply the pulsed voltage for pulsing ions out of the ion accelerator; and/or the pulsed ion accelerator may be configured to control the DC voltage supplies to progressively reduce the amplitudes of the DC potentials applied to the DC electrodes with time, and then subsequently control the pulsed voltage supply to apply the pulsed voltage for pulsing ions out of the ion accelerator.
The ion accelerator may repeatedly (and optionally periodically) pulse ions out, and prior to each pulse may switch off the DC potentials applied to the DC electrodes. Alternatively, or additionally, the ion accelerator may repeatedly (and optionally periodically) pulse ions out, and prior to each pulse may progressively reduce the amplitudes of the DC potentials applied to the DC electrodes with time.
The above embodiments may reduce the micro-motion of the ions within the confined ion beam before pulsed ejection.
The pulsed ion accelerator may comprise pulsed electrodes spaced apart in the second direction (X-dimension) on opposite sides of the ion guide portion, at least one of which is connected to the pulsed voltage supply for pulsing ions in the second direction (X-dimension).
The pair of pulses electrodes may comprise at least one push electrode connected to the pulsed voltage supply for pulsing ions away from the at least one push electrode, out of the ion guide portion, and out of the ion accelerator; and/or at least one puller electrode connected to the pulsed voltage supply for pulsing ions towards the at least one puller electrode, out of the ion guide portion, and out of the ion accelerator.
The at least one puller electrode may have a slit therein, or may be formed from spaced apart electrodes, so as to allow the pulsed ions to pass therethrough.
The pulsed ion accelerator may comprise electrodes spaced apart in the second direction (X-dimension) on opposite sides of the ion guide portion; wherein these electrodes are spaced apart in said second direction (X-dimension) by an amount that decreases as a function of distance in the first direction.
These electrodes may be the pulsed electrodes described above.
The spacing between the electrodes in said second direction (X-dimension) may decrease as a function of distance in the first direction from the ion entrance at a first end of the ion guide portion to a downstream portion. The spacing between the electrodes in said second direction (X-dimension) may be maintained constant from the downstream portion at least part of the distance to a second end of the ion guide portion.
The pulsed ion accelerator may comprise electrodes spaced apart in the second direction (X-dimension) on opposite sides of the ion guide portion; wherein the average DC potential of said DC potentials may be negative relative to said electrodes spaced apart in the second direction so as to form a quadrupolar field that compresses the ions in the second direction (X-dimension).
Said electrodes spaced apart in the second direction may be the pulsed electrodes described above.
The pulsed ion accelerator may comprise electrodes and voltage supplies forming a DC ion acceleration field arranged downstream of the ion guide portion, in the second direction (X-dimension).
The present invention also provides a mass spectrometer comprising: a time-of-flight mass analyser or electrostatic ion trap having the pulsed ion accelerator as described hereinabove, and electrodes arranged and configured to reflect or turn ions.
The mass spectrometer may comprise: a multi-pass time-of-flight mass analyser or electrostatic ion trap having the pulsed ion accelerator as described hereinabove, 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.
The drift direction (z-dimension) may corresponds to said first direction and/or the oscillating dimension (x-dimension) may correspond to said second direction; or said first direction may be tilted at an acute angle to the drift direction (z-dimension).
The first direction and drift direction (z-dimension) may be arranged at a small angle to each other for isochronous steering of ion packets. The steering angles may be adjusted for aligning the ion packets time front with the drift direction (z-dimension).
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).
The spectrometer may be configured to spatially focus the ion packets in the drift direction (z-dimension) downstream of the pulsed ion accelerator.
The spatial focusing may comprise: (i) spatial focusing or steering of the ions by a field of a trans-axial lens/wedge, optionally complimented with curved electrodes in the pulsed extraction region of the pulsed ion accelerator; (ii) spatial focusing and/or steering of the ions by multiple segments of deflecting fields, e.g. forming a Fresnel lens/deflector; (iii) by arranging a negative spatial-temporal correlation of the ion beam within said ion guide portion at ion beam injection into said ion guide portion; (iv) by arranging a first direction dependent deceleration of the ion beam within said ion guide portion.
The spectrometer may be configured to pulse the ion packets so as to be displaced in the dimension (Y-dimension) orthogonal to the drift direction (Z-dimension) and the oscillating dimension (X-dimension).
This may enable the ions to be displaced onto an isochronous surface of mean ion trajectory within the fields of the isochronous electrostatic analyzer.
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 pulsed ion accelerator is arranged to receive ions and accelerate them into one of the ion mirrors. Alternatively, 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 pulsed ion 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 spectrometer may comprise an ion deflector located downstream of said pulsed ion accelerator, and that is configured to back-steer the average ion trajectory of the ions, in the drift direction, thereby tilting the angle of the time front of the ions received by the ion deflector.
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.
The ion deflector may be configured to generate a substantially quadratic potential profile in the drift direction.
The pulsed ion accelerator and ion deflector may tilt the time front so that it is aligned with the ion receiving surface of the ion detector and/or to be parallel to the drift direction (z-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 pulsed ion accelerator and the average back steering angle of the ion deflector may be configured so as to direct ions 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 pulsed ion accelerator may receive a substantially continuous ion beam or packets of ions, and may pulse out ion packets.
The pulsed ion accelerator may be a gridless orthogonal accelerator.
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 55 and 15 m; between 6 and 14 m; between 7 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 pulsed ion accelerator receives 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 spectrometer may comprise an ion source and a lens system between the ion source and pulsed ion accelerator for telescopically expanding the ion beam from the ion source.
The lens system may form a substantially parallel ion beam along the first direction (Z-direction). The telescopic expansion may be used to optimise phase balancing of the ion beam within the ion guide portion, e.g. where the initial angular divergence and width of the ion beam provide for about equal impact onto the thickness of the confined ion beam.
The spectrometer may comprise an ion source in a first vacuum chamber and the pulsed ion accelerator in a second vacuum chamber, wherein the vacuum chambers are separated by a wall and are configured to be differentially pumped, and wherein the ion guide portion protrudes from the second vacuum chamber through an aperture in the wall and into the first vacuum chamber.
The present invention also provides a method of mass spectrometry comprising: providing a pulsed ion accelerator or mass spectrometer as described hereinabove; receiving ions in said ion guide portion of the pulsed ion accelerator; applying different DC potentials to different ones of said DC electrodes such ions travelling through the ion guide portion along said first direction experience an ion confining force in at least one dimension (X- or Y-dimension) orthogonal to the first direction; and then applying a pulsed voltage to at least one of the electrodes of the pulsed ion accelerator so as to pulse ions out of the ion accelerator in the second direction (X-dimension).
Proposed herein is a spatially alternated DC quadrupolar field within a pulsed accelerator or converter for indefinite confinement of an ion beam without limits on ion mass to charge ratio and enabling for instant switching off of the confining fields. The accelerator may be further improved with “balancing” of ion beam spatial and angular spreads by entrance ion optics for minimizing the phase space of the confined ion beam. The accelerator may further be improved by forming “adiabatic” spatial entrance and temporal exit conditions.
Embodiments comprise PCB variants for implementing the guide, gently curved guides and guides protruding through differentially pumped walls.
The coupling of elongated pulsed converters to MPTOF and E-traps may be enhanced by introducing embodiments for bypassing the converter and by introducing multiple embodiments for isochronous spatial focusing of elongated ion packets.
Embodiments of the present invention provide a method of mass spectrometric analysis within isochronous electrostatic fields, comprising the following steps:
Preferably, the method may further comprise a step of forming a constant per Z-direction quadrupolar electrostatic field in said XY-plane to produce an additional ion beam confinement in the X-direction.
Preferably, the step of pulsed orthogonal acceleration in the X-direction may further comprise a step of switching off of said quadrupolar confining fields to a different field being uniform in the Z-direction for minimizing time, and/or angular aberrations, and/or energy spread of said extracted ion packets.
Preferably, the method may further comprise a step of arranging adiabatic conditions at ion beam entrance and the ion packet exit into and from said quadrupolar fields comprising at least one step of the group: (i) arranging spatial gradual in space rise of said quadrupolar confining field; and (ii) arranging gradual in time switching of said quadrupolar field; wherein gradual means that the moving ions sense the quadrupolar field rise and fall within several cycles of the quadrupolar field alternations.
Preferably, said Z-axis is generally curved.
Preferably, said quadrupolar confining field is arranged to protrude through walls separating differentially pumped stages of an ion source generating said ion beam.
Preferably, said fields of isochronous electrostatic analyzer may comprise either isochronous fields of gridless ion mirrors or isochronous fields of electrostatic sectors; and wherein said fields may be arranged for either time-of-flight analysis or for ion trapping with measuring frequency of their oscillations within said isochronous electrostatic fields.
Preferably, said field of electrostatic analyzer may be two-dimensional and substantially extended along a tilted Z′-axis; wherein axes Z and Z′ may be arranged as mall angle for isochronous steering of ion packets; wherein said steering angles are adjusted for aligning the ion packets time front with the axis Z′.
Preferably, the method may further comprise a step of ion packet spatial focusing in the Z-direction past said step of ion pulsed ejection; wherein said spatial focusing may comprise one step of the group: (i) spatial focusing or steering by a field of trans-axial lens/wedge, complimented with curved electrodes in the pulsed extraction region; (ii) spatial focusing and/or steering by multiple segments of deflecting fields, forming a Fresnel lens/deflector; (iii) by arranging a negative spatial-temporal correlation of ion beam within said ion storage gap at ion beam injection into said storage gap; (iv) by arranging a Z-dependent deceleration of ion beam within said ion guide.
Preferably, the method may further comprise a step of pulsed displacing of said ion packets in the Y-direction to bring said ion packets onto an isochronous surface of mean ion trajectory within said fields of isochronous electrostatic analyzers.
Preferably, the timing and the duration of said pulsed ion packet displacement in the Y-direction is arranged for reducing the mass range of the ion packet and wherein the period of said pulsed acceleration is arranged shorter compared to flight time of the heaviest ion species in said isochronous analyzer.
Embodiments of the present invention provide a mass spectrometer, comprising:
Preferably, said Z-axis may be generally curved.
Preferably, said ion guide may be arranged extended beyond said storage gap of said orthogonal accelerator.
Preferably, said ion guide may be arranged to protrude through walls of differentially pumped stages.
Preferably, said isochronous electrostatic analyzer may comprise either isochronous gridless ion mirrors or isochronous electrostatic sectors; and wherein said fields may be arranged for either time-of-flight analysis or for ion trapping with measuring frequency of their oscillations within said isochronous electrostatic fields.
Preferably, said electrostatic analyzer may form two-dimensional fields substantially extended along a Z′-axis; wherein axes Z and Z′ may be arranged at small angle for isochronous steering of ion packets; wherein said steering angles may be adjusted for aligning the ion packets time front with the axis Z′.
Preferably, past said orthogonal accelerator, the spectrometer may further comprise one means for ion packet spatial focusing in the Z-direction of the group: (i) a trans-axial lens/wedge, complimented with curved electrodes in the pulsed extraction region; (ii) a Fresnel lens/deflector; (iii) pulsed or time variable signals applied upstream of said orthogonal accelerator for arranging a negative spatial-temporal correlation of ion beam within said ion storage gap; (iv) a Z-dependent voltage gradient within said guide for deceleration of said ion beam.
Preferably, past said orthogonal accelerator, the spectrometer may further comprise at least a pair of deflectors or sectors, placed immediately after said orthogonal accelerator for pulsed displacing of said ion packets in the Y-direction to bring said ion packets onto an isochronous surface of mean ion trajectory.
Embodiments improve the process of ion beam confinement within elongated OA; extend the mass range and remove the mass dependent and RF dependent effects at pulsed ejection; and improve coupling of elongated pulsed converters with MRTOF and E-trap mass spectrometers for higher sensitivities and duty cycles.
Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:
Referring to
Continuous ion beam 11 propagates along the Z-axis and enters the space between push P and mesh G electrodes. Within this space, confining electric field 12 is arranged with the aid of auxiliary electrodes 13, connected to some electric signal U, either RF (in device 15) or DC (in device 17). Periodic pulses are applied to electrodes P and N to extract ion packets 14 out of continuous beam 11 for injection into a TOF MS mass analyser.
OA 15 of prior art U.S. Pat. Nos. _5,763,878 or U.S. Pat. No. 8,373,120, proposes the spatial confinement of the ion beam 11 by radiofrequency RF radial field 16, generated by applying an RF signal to side electrodes 13. Optionally, the RF field is switched off before ion extraction pulses are applied (to P and N). Both the effective potential well of the RF field and the micro-oscillations of the ions depend on ion mass to charge ratio m/z=μ. Parameters of the ion beam 11 and of pulsed ion packets 14 depend on μ, on the RF phase at switching off, and on the time delay to pulses. In addition, OA 15 has two major drawbacks: (a) the RF field limits the transmitted mass range and (b) the extraction pulses induce strong oscillations onto resonant RF generators, thus impeding transmission, resolution and mass accuracy of TOF MS.
OA 17, proposed in RU2013149761 employs a rectilinear electrostatic quadrupolar field 18, formed by applying a negative DC potential to electrodes 13. A weak electrostatic quadrupolar field focuses and confines the ion beam in the critical TOF X-direction (towards the ion mirror), while defocusing the ion beam in the non-critical transverse Y-direction. The method allows moderate elongation of ion packets 14, estimated to a length in the z-direction of about LZ≤50 mm. Longer OAs suffer strong ion losses in the Y-direction.
Referring to
In operation, downstream of ion source 27, lens system 28 may expand the ion beam telescopically and form a nearly parallel ion beam 21 along the Z-axis. The telescopic expansion is preferably used to optimize so-called phase balancing of the ion beam 21 within ion guide 23, where initial angular divergence and width of the ion beam 21 provide for about equal impact onto thickness of the confined ion beam 29.
Ion beam 21 enters the P-N gap and becomes spatially confined in the region 22 by a set of alternating electrodes with distinct DC voltages DC1 and DC2, generating a spatially alternating quadrupolar DC field E(X,Y), approximated at the field axis by a transverse field distribution:
E(X,Y)=E0*(X−Y)/R*sin(2πZ/H) (Eq.1)
where E, Y and Z are the dimensions of the ion guide; H is spatial period of quadrupolar field alternation, and R is the characteristic field radius.
For ions having mass to charge ratio μ=m/z at specific axial (along Z-axis) energy UZ, the axial velocity is VZ=(2UZ/μ)0.5. The spatial alternation of the quadrupolar DC field is sensed by ions moving through the DC field as if a periodic RF signal was being applied, which is known to radially confine ions to the field axis. The frequency of the sensed RF field F=H/VZ is inversely proportional to μ0.5. Then the effective potential well D(r) of the sensed RF field depends on the ion radial position r (where r2=X2+Y2). It is important to note that D(r) is independent of the ion mass to charge ratio μ:
D(r)=E02 *(r2/R2)/μ(2πF)2=[E02H2/2πUZ]*(r2/R2) (Eq. 2)
[For reference: D(r)=E02*(r2/R2)/μ(2πF)2=E02*(r2/R2)/μVZ2(2π/H)2]
Thus, the novel electrostatic ion guide equally confines ions of all mass to charge ratios μ, e.g. assuming they have similar axial and radial energies.
The alternating quadrupolar field indefinitely (per Z) confines ion beam 29 in both transverse directions (i.e. X and Y directions), producing a spatially tight ion beam within substantially elongated orthogonal accelerators or other pulsed converters. Electrical pulses may be applied to electrodes P and N to convert the continuous ion beam 29 into pulsed ion packets 24 by orthogonal pulsed extraction. Preferably, voltages DC1 and DC2 are switched to zero or to different setting U1 and U2 at the time of the pulsed ion ejection so as to improve the electric field distribution at ion ejection.
The novel electrostatic quadrupolar ion guide 23 provides for indefinite ion beam confinement. Relative to the RF confinement of prior art device 15 (see
Referring to
In operation, as best seen in 3D view 31, electrodes 34 and 35 form a local quadrupolar electrostatic field 22 in every XY-cross section. The polarity of the quadrupolar field changes when shifting in the Z-direction. Ion beam 21 at specific mean energy UZ may be formed in an ion source 27, and may be shaped by lens 28. Ion beam 21 enters quadrupolar field 22 along the Z-axis. From this point the ion beam is denoted by number 29. Because of the periodically spatially alternating DC quadrupolar field, ions moving along the Z-axis sense a quadrupolar field that periodically changes with time, which is known to provide radial ion confinement towards the field axis (in a similar manner to an RF field acting on a static ion). The ion beam stays spatially confined in the x-y plane at limited angular divergence, without limits on the Z-length. The beam 29 is refocused multiple times by the quadratic field, eventually mixing ions within a limited phase space.
Preferably, lens 28 reshapes the phase space of the ion beam 21 entering the ion guide 23 for optimal balance between width and divergence of the confined ion beam 29. Preferably, the average potential (DC1+DC2)/2 is slightly negative relative to P and N electrodes to form a combination of the alternating quadrupolar field 22 with a constant per Z quadrupolar field, thus providing stronger compression of the ion beam 29 in the X-direction Vs Y-direction.
Embodiment 30 is further improved by arranging so-called “adiabatic entrance” 36 and “adiabatic exit” 37 conditions for ion beam 29.
For adiabatic entrance 36, there is arranged a smooth spatial rise of quadrupolar DC field, spread for at least 2-3 spatial periods of the DC field alternation. The smooth rise of the quadrupolar field may be arranged either by the illustrated Y-spreading of ion guide 23 electrodes, and/or by narrowing of the storage gap between electrodes N and P in the X-direction, and/or by arranging a gradient of DC voltages in the Z-direction, e.g. by resistive dividers.
Ions staying on axis of the guide 23 experience zero transverse field and have zero micro-motion, however, radially distant ions do not. For “adiabatic exit” 37 of radially distant ions at pulsed extraction of ion packets, embodiments of the invention initially maintain the DC1 and DC2 amplitudes constant and then switch the amplitudes to gradually decrease with time, e.g. as shown for DC1 in graph 37. The switching time may correspond to the time after the ion has passed through several DC alternations of the ion guide 23, as shown in plot 37 by time variation 38 of sensed quadrupolar field for some probe ion. This adiabatic switching reduces the energy of “micro-motion” of the ions within the confined ion beam 29 before pulsed ejection.
Referring to
One particular embodiment 40 of the static quadrupolar guide 23 comprises a set of four parallel-aligned printed circuit boards (PCB) 47. Conductive pads on each board 47 form a row of alternated electrodes 34 and 35, distinct in the drawing by color coding as described above. Two DC potentials are interconnected with the conductive pads through displaced PCB vias, DC1 to electrodes 35 and DC2 to electrodes 34. Each side (in the Y-direction) of ion guide 40 is formed by a pair of boards 47, separated by an insulating plate, which is preferably also a PCB. Alternatively, the pair may be arranged within a single thick multilayer PCB for better precision. Since boards 47 are set distant from spatially confined ion beam 29, only limited care shall be used to shield insulating surfaces from stray ions. Since DC1 and DC2 potentials are expected to be in the range of several tens of Volts, the insulating ridges may be thin. Still, edge slots and edge conductive coatings are preferred for the ion guide robustness against the charging by stray ions.
Another particular embodiment 41 employs conductive electrodes 34 and 35 attached to both sides of a single PCB support 47. This is equivalent to one pair of boards 47 shown in embodiment 40. Another PCB support 47 with conductive electrodes 34 and 35 attached to both sides thereof would be required to form the ion guide 23 according to embodiment 41.
Yet another particular embodiment 42 comprises a row of alternating electrodes 34 and 35 constructed of two thin electrode plates that are spaced apart by a thin insulator such as a film, say, PTFE or Kapton film. Extending electrode ribs appear mutually displaced in the X-direction by the thickness of the insulator, which is expected to generate only minor Z-modulation of the quadrupolar field on the beam 29 axis. This is equivalent to one pair of boards 47 shown in embodiment 40. Another corresponding structure would be required to form the ion guide 23 according to embodiment 42.
Ion guides 42-44 are preferred for their compatibility with heating to approximately 150-200° C. for robust operation of the guide, for preventing built-up of insulating coatings or deposition of droplets from ESI sources.
Yet another particular embodiment 43 comprises machined (say by EDM) electrodes with bent extending electrode ribs. Optionally, ribs may be slightly bent in embodiment 42 as well.
Yet another particular embodiment 44 may have a curved Z axis, e.g. for reducing gas flux, for removal of charged droplets from ESI ion source, for removal of light and metastable particles from EI source, or for convenience of instrumental packaging. Initially turned electrodes may be machined by EDM.
Again referring to
Again referring to
Referring to
In operation, ion beam 21 is generated by source 27, formed by ion optics 28, and entering OA 51 along the Z-direction. Ion beam is transverse confined with guide 51, as described in
Downstream of OA 51, elongated ion packets 58 are pulsed displaced in the Y direction by deflectors 54 and 55, thus bypassing the Y-displaced OA 52 and returning to the axis of ion mirrors M (best seen in the X-Y plane view). Ions are reflected between ion mirrors M in the X-direction within the s-XZ symmetry plane while drifting towards the detector 59 in the z-direction. Since ion packets are focused by trans-axial lens 53 in the Z-direction, they reach the face of detector 59 without hitting the rims of the detector. The duty cycle of the OA-MPTOF 50 may be improved, e.g. to above 50% from the several percent in conventional MPTOFs. The method becomes possible because of ion beam spatial confinement within the OA by the novel quadrupolar electrostatic ion guides. While embodiment 50 depicts multi-reflecting TOF MS (MR TOF), similar improvements are applicable to sector multi-turn TOF MS (MT TOF) and to singly reflecting TOF MS. The injection scheme of circular embodiment 50C may be useful for ion injection into cylindrical electrostatic traps.
Referring to
The figures show iso-potential lines and ion trajectories. According to simulations, the trans-axial lens 53 serves for: (a) terminating the electrostatic DC accelerating field; (b) providing for ion spatial focusing in the XZ-plane to focal plane f2, in all cases simulated for F=5 m focal distance; and (c) providing substantial parallel beam in the XY-plane. Graph 63 shows time spreads introduced by spatial ion Z-focusing, simulated for 1000 amu ions. The trans-axial lens 53 alone in the embodiment 60 introduces positive T|ZZ aberration with additional time spread dT(z)=T|ZZ*z2. The long focal distance F=5 m helps keeping the aberration moderate and allows focusing LZ=20 mm long ion packets at dT(z)=0.3 ns amplitude.
Use of curved extraction field 64 in the embodiment 61 allows reverting the sign of the overall T|ZZ aberration, which may be further optimized for complete mutual compensation of T|ZZ aberrations. Without describing exhaustive details of ion optical simulation, the novel quadrupolar electrostatic ion guide 23 was found an important part of the Z-focusing trans-axial system: it retains the ion beam at limited width and diameter; it controls initial starting position at acceleration; it helps forming a T|ZZ compensating curvature of extracting pulsed field; it helps forming spatially focusing in Y-directions, while eliminating multiple time per Y aberrations.
Referring to
Within ion packets 58, ions retain the VZ velocity of ion beam in the z-direction. If forming a negative correlation between VZ and z-coordinate in guide 51, ion packets 58 would be naturally focused onto detector 59.
Focusing condition 71 for a narrow range of mass to charge ratios μ=m/z may be achieved by pulsing of ion source or transfer optics, where VZ(z) is the ion axial velocity in guide 51, VZ0=VZ(z=0), and DZ is the OA-detector distance:
V
Z(z)/VZ0=1−z/Dz@μ=m/z (eq. 3)
For this purpose, the embodiment 70 may comprise one of the following means: an RF ion guide 73 with optional auxiliary electrodes 74 and an exit gate 75; a pulse generator; a time dependent U(t) signal generator.
In one method, an ion extracting pulse is applied to gate 75. The extracting pulse is known to generate an ion bunch with an energy spread in spite of gaseous dampening at about 10 mTorr gas pressures. Deeper starting ions will arrive to the OA 52 at later time, appear at smaller z within the guide 51, but will have larger VZ. This produces ion packet compression 71 (eq. 3) at the detector 59. Though the method looks similar to the known Pulsar method, here ions are Z-compressed at the DZ distance of detector 59, rather than at the OA center of conventional TOF instruments. Note that the correlation 71(eq. 3) occurs for narrow μ range only, controlled by the time delay between extraction and OA pulses. The embodiment is attractive for target analysis, where a narrow mass range is selected intentionally, while TOF data may be acquired at maximal OA frequency and at maximal dynamic range of the MRTOF detector.
In another method, to arrange the correlation 71 (eq. 3), either ion guide 73 and/or extraction electrode 75 and/or lens 28 are arranged into an elevator system, whose reference potential is time variable U(t). The effect of the time variable elevator is very similar to the above described bunching effect, though the elevator exit may be set closer to the OA entrance and may allow somewhat wider μ range. In both above methods, a nearly unity duty cycle of OA is expected for narrow μ range, thanks to the novel confinement means 51, permitting substantial OA elongation.
Yet in another method, to obtain focusing conditions for a wide mass range i.e. for all μ, the z-dependent specific energy U(z) (energy per charge) may be arranged with a resistive divider within confining means 51. For optimal ion packet compression onto detector 59, the U(z) shall satisfy condition 72, where UZ0=U(z=0):
U(z)/UZ0=(1−z/DZ)2 (eq. 4)
Ion beam 29 slows down in a Z-dependent axial potential distribution U(z) of confinement means 51. The desired z-focusing of ion packets is achieved for the entire ionic mass range, i.e. occurs for ions of all μ, while confinement means 51 provide mass independent radial confinement, as has been explained with equation Eq. 2. The method may be particularly attractive when using a “soft and prolonged” Pulsar mode, where open gate forms a prolonged quasi-continuous ion beams.
Again referring to
Referring to
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 |
|---|---|---|---|
| 1712612.9 | 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/GB2018/052099 | 7/26/2018 | WO | 00 |
