TIME OF FLIGHT MASS ANALYSER WITH SPATIAL FOCUSSING
20220238320 · 2022-07-28
Assignee
Inventors
Cpc classification
H01J49/004
ELECTRICITY
H01J49/408
ELECTRICITY
H01J49/401
ELECTRICITY
International classification
Abstract
A Time of Flight mass analyser is disclosed comprising: at least one ion mirror 34 for reflecting ions; an ion detector 36 arranged for detecting the reflected ions; a first pulsed ion accelerator 30 for accelerating an ion packet in a first dimension (Y-dimension) towards the ion detector 36 so that the ion packet spatially converges in the first dimension as it travels to the detector 36; and a pulsed orthogonal accelerator 32 for orthogonally accelerating the ion packet in a second, orthogonal dimension (X-dimension) into one of said at least one ion mirrors 34.
Claims
1. A Time of Flight mass analyser comprising: at least one ion mirror for reflecting ions; an ion detector arranged for detecting the reflected ions; a first pulsed ion accelerator for accelerating an ion packet in a first dimension (Y-dimension) towards the ion detector so that the ion packet spatially converges in the first dimension as it travels to the detector; and a pulsed orthogonal accelerator for orthogonally accelerating the ion packet in a second, orthogonal dimension (X-dimension) into one of said at least one ion mirrors; wherein the first ion accelerator is configured to pulse the ion packet out having a first length in the first dimension (Y-dimension), wherein the orthogonal accelerator is configured to pulse the ion packet out having a second length in the first dimension (Y-dimension), and wherein the detector is arranged such that the ion packet has a third length in the first dimension (Y-dimension) when it impacts the detector, wherein the third length is shorter than or substantially the same as the first length and/or second length.
2. The mass analyser of claim 1, wherein the first ion accelerator is configured to pulse the ion packet out having a first length in the first dimension (Y-dimension), wherein the orthogonal accelerator is configured to pulse the ion packet out having a second length in the first dimension (Y-dimension), and wherein the detector is arranged such that the ion packet has a third length in the first dimension (Y-dimension) when it impacts the detector, wherein the third length is shorter than the first length and second length.
3. The mass analyser of claim 1, wherein the first ion accelerator comprises a voltage supply for applying a voltage pulse that accelerates the ion packet in the first dimension (Y-dimension) such that the ion packet is spatially focused in the first dimension to a spatial focal point that is downstream of the first ion accelerator, and wherein the detector is arranged in the first dimension at the spatial focal point.
4. The mass analyser of claim 1, comprising electrodes defining a further ion acceleration region downstream of the first ion accelerator and a voltage supply for applying a potential difference across the further ion acceleration region so as to accelerate ions that have been pulsed out of the first ion accelerator in the first dimension (Y-dimension).
5. The mass analyser of claim 4, wherein the voltage supply is configured to generate an electric field within the further ion acceleration region that has a magnitude in the first dimension (Y-dimension) that is greater than the magnitude of the pulsed electric field in the first dimension within the first ion accelerator.
6. The mass analyser of claim 1, wherein the at least one ion mirror comprises a first ion mirror spaced apart from a second ion mirror, wherein the ion mirrors and detector are arranged and configured such that ions pulsed out of the orthogonal accelerator pass into the first ion mirror and are reflected between the ion mirrors and then onto the detector.
7. The mass analyser of claim 6, wherein the first ion accelerator is configured to pulse the ion packet in the first dimension (Y-dimension) so that the ions have sufficient energy in this dimension that they do not impact upon the orthogonal accelerator after they have been reflected from the first ion mirror.
8. The mass analyser of claim 6, wherein the mass analyser is configured to reflect the ion packet a total of n times in the ion mirrors; wherein a first distance, in the first dimension (Y-dimension), is provided between the centre of the ion extraction region of the orthogonal accelerator and the centre of the detector; and wherein the length of the extraction region of the orthogonal accelerator, in the first dimension (Y-dimension), is at least n times shorter than said first distance.
9. The mass analyser of claim 1, comprising a mesh electrode at the exit of the ion accelerator and/or between the first ion accelerator and orthogonal accelerator.
10. The mass analyser of claim 1, comprising a first voltage supply for applying a voltage to the first ion accelerator to pulse out the ion packet in the first dimension, a second voltage supply for applying a voltage to the orthogonal accelerator to pulse out the ion packet in the second dimension, and a controller for delaying the start time of the second pulse relative to the first pulse and/or the duration of the second pulse so that at least some of the ions pulsed out of the first ion accelerator are pulsed out of the orthogonal accelerator to the detector.
11. The mass analyser of claim 10, wherein the controller is configured to delay the timing of the second pulse relative to the first pulse based on a pre-set or selected upper and/or lower threshold mass to charge ratio desired to be analysed so that the ions reaching the detector have masses below the upper threshold mass to charge ratio and/or above the lower threshold mass to charge ratio.
12. The mass analyser of claim 11, comprising an input interface for inputting into the mass analyser the upper and/or lower threshold mass to charge ratio desired to be analysed.
13. The mass analyser of claim 1, comprising one or more vacuum pump and vacuum chamber for maintaining the first ion accelerator and/or orthogonal accelerator at a pressure of either: ≤10.sup.−3 mbar; ≤0.5×10.sup.−4 mbar; ≤10.sup.−4 mbar; ≤0.5×10.sup.−5 mbar; ≤10.sup.−5 mbar; ≤0.5×10.sup.−6 mbar; ≤10.sup.−6 mbar; ≤0.5×10.sup.−7 mbar; or ≤10.sup.−7 mbar.
14. A mass spectrometer comprising the mass analyser of claim 1 and an ion source for supplying ions to the mass analyser.
15. The mass spectrometer of claim 14, wherein the ion source is a continuous ion source.
16. The mass spectrometer of claim 14, wherein the mass spectrometer is configured to supply ions to the first ion accelerator in the first dimension (Y-dimension).
17. The mass spectrometer of claim 14, comprising either: an ionisation source inside the first ion accelerator; or an ionisation source configured to emit photons, charged particles or molecules into the first ion accelerator for ionising analyte therein.
18. The mass analyser of claim 1, wherein the ion packet is not reflected in the first dimension (Y-dimension) as it travels from the pulsed orthogonal accelerator to the ion detector.
19. A method of Time of Flight mass analysis comprising: providing a mass analyser as claimed in claim 1; pulsing an ion packet out of the first pulsed ion accelerator so that the ion packet spatially converges in the first dimension (Y-dimension) as it travels to the detector; orthogonally accelerating the ion packet in a second dimension (X-dimension) in the orthogonal accelerator so that the ions travel into one of said at least one ion mirror; reflecting the ions in the at least one ion mirror such that the ions are reflected onto the detector; and determining the mass to charge ratio of the detected ions.
20. A method of mass spectrometry comprising a method as claimed in claim 19.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0065] Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:
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DETAILED DESCRIPTION
[0073]
[0074] In operation, ions 8 are transmitted along an ion entrance axis (Y-dimension) into the orthogonal accelerator 2 to the space between the pusher and mesh electrodes. Voltage pulses are applied between the pusher and mesh electrodes so as to orthogonally accelerate the ions (in the X-dimension). The ions therefore maintain their component of velocity along the ion entrance axis (Y-dimension) but also gain an orthogonal component of velocity (in the X-dimension). The ions pass through the mesh electrode 2b and travel into an electric-field free region 10 between the orthogonal accelerator 2 and the ion mirror 4. The ions begin to separate (in the X-dimension) according to their mass to charge ratios as they travel towards the ion mirror 4. Voltages are applied to the electrodes of the ion mirror 4 so as to generate an electric field in the ion mirror that causes the ions to be reflected (in the X-dimension) and to be spatially focused (in the X-dimension) when they reach the detector 6. The reflected ions then leave the ion mirror 4 and pass back into the field-free region 10 and travel onwards to the ion detector 6. As described above, the ions separate in the dimension of orthogonal acceleration (X-dimension) as they pass from the orthogonal accelerator 2 to the ion detector 6. As such, for any given ion, the duration of time between the ion being pulsed by the orthogonal accelerator 2 to the time that it is detected at the ion detector 6 can be used to determine its mass to charge ratio.
[0075] However, the ions have a spread of speeds along the dimension of the entrance axis (Y-dimension) at the orthogonal accelerator 2. As such, each packet of ions that is pulsed out of the orthogonal accelerator 2 becomes longer in this dimension by the time it reaches the ion detector 6, thus requiring a relatively large ion detector 6 in order to detect a significant proportion of the ions in the ion packet.
[0076] It is desired to focus the ions in the dimension of the ion entrance axis so as to minimise, prevent or reduce the spreading of the ion packet in this dimension between the orthogonal accelerator 2 and the ion detector 6. Embodiments of the present invention provide spatial focusing of the ions in the direction from the orthogonal accelerator to the ion detector (Y-dimension) that is independent of the time of flight focusing (in the X-dimension), without mixing ion motion in the two dimensions (i.e. X and Y dimensions).
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[0079] The inventors have recognised that such spatial focusing techniques may be used in TOF mass analysers in order to spatially focus the ions in a dimension orthogonal to the dimension in which the ions are reflected by the ion mirror(s), i.e. in a dimension orthogonal to the X-dimension. Embodiments described herein enable such spatial focusing to be independent of the parameters in the other dimension(s), i.e. independent of the X-dimension and/or Z-dimension.
[0080]
[0081] In operation, ions 38 are transmitted along an ion entrance axis (Y-dimension) into the first ion accelerator 30. A voltage pulse is then applied to one or more electrodes of the first ion accelerator 30 so as to generate a first electric field that accelerates ions in a direction towards the detector 36 (i.e. in the Y-dimension). In a corresponding manner to that described in relation to
[0082] The ions ejected from the first ion accelerator 30 are received in the orthogonal accelerator 32. At least one voltage pulse is then applied to at least one of the electrodes in the orthogonal accelerator 30 so as to orthogonally accelerate the ions towards the ion mirror 34 (in the X-dimension). It will be appreciated that a delay is provided between pulsing the ions out of the first ion accelerator 30 and pulsing the ions out of the orthogonal ion accelerator 32 such that the same ions may be pulsed by both devices, i.e. the first ion accelerator and orthogonal accelerator are synchronised. The ions maintain their component of velocity along the direction that they were ejected from the first ion accelerator 30 (Y-dimension) but also gain an orthogonal component of velocity (in the X-dimension). The ions travel from the orthogonal accelerator 32 into an electric-field free region 40 between the orthogonal accelerator 32 and the ion mirror 34. The ions begin to separate according to their mass to charge ratios as they travel towards the ion mirror 34. Voltages are applied to the electrodes of the ion mirror 34 so as to generate an electric field in the ion mirror that causes the ions to be reflected and spatially focused at the position of detector (in the X-dimension). The reflected ions then leave the ion mirror 34 and pass back into the field-free region 40 and travel onwards to the ion detector 36. As described above, the ions separate in the dimension of orthogonal acceleration (X-dimension) as they pass from the orthogonal accelerator 32 to the ion detector 36. As such, for any given ion, the duration of time between the ion being pulsed by the orthogonal accelerator 32 to the time that it is detected at the ion detector 36 can be used to determine its mass to charge ratio.
[0083] As the first ion accelerator 30 pulses the ions in the direction towards the ion detector 36 (Y-dimension), the packet of ions pulsed out of the first ion accelerator 30 (and subsequently pulsed out of the orthogonal accelerator 32) will become progressively spatially focused in the direction of pulsing out from the first ion accelerator 30 (Y-dimension) up until a focal point, after which the ions may spatially diverge (in the Y-dimension). The ion detector 36 may be arranged at this focal point. This is illustrated in
[0084] The embodiments described above enable the ion detector 36 to be relatively small in the dimension of ejection from the first ion accelerator 30 (Y-dimension), whilst still receiving a significant proportion or substantially all of the ions in each ion packet. Similarly, the embodiments also enable a relatively large packet of ions (in the dimension of ejection from the first ion accelerator, i.e. Y-dimension) to be ejected from the orthogonal accelerator 32 and received at the ion detector 36.
[0085] The embodiments enable the mass analyser to have a relatively high duty cycle. More specifically, the duty cycle is related to the ratio of length of the ion packet in the Y-dimension, when it is accelerated by the orthogonal accelerator 32, to the distance from the centre of the orthogonal accelerator 32 to the centre of the ion detector 36. For any given ion detector 36, the embodiments enable a relatively long ion packet (in the Y-dimension) to be ejected from the orthogonal accelerator 32 and hence enable a relatively high duty cycle.
[0086] It will be appreciated that multiple ion packets may be sequentially pulsed from the first ion accelerator to the detector.
[0087] The spectrometer may comprise an ion source for supplying ions to the first ion accelerator 30, wherein the ion source is arranged such that said first ion accelerator 30 receives ions from the ion source travelling in the Y-dimension. This enables the beam to pulsed out of the first ion accelerator to be elongated in the Y-dimension (e.g. for increased duty cycle) whilst being small in the X-dimension and Z-dimension.
[0088] Although a single reflection TOF mass analyser has been described above, the invention may be applied to other TOF mass analysers, such as a multi-reflecting TOF mass analyser (also known as a folded flight path mass analyser).
[0089]
[0090] The mass analyser may be configured such that all ions that reach the detector 36 have performed the same number of reflections between the mirrors 34,35, so that the ions have the same flight path length. The first ion accelerator 30 may be controlled so as to eject the ions with velocities that achieve this.
[0091] It is also necessary, in this embodiment, for the first ion accelerator 30 to provide the ions with sufficient energy in the Y-dimension such that after they are first reflected by an ion mirror 34, the reflected ions have travelled a sufficient distance in the Y-dimension such that they do not strike the orthogonal accelerator 32 as they travel towards the next ion mirror 35. In order to achieve this for n reflections between the ion mirrors, the length in the in Y-direction of the push-out region of the orthogonal accelerator 32 is configured to be at least n times shorter than the distance in the Y-direction between the push-out region of the orthogonal accelerator 32 and the detector 36.
[0092] It is desired that the first ion accelerator 30 accelerates ions in the Y-dimension (with the ion mirror and ion detector planes in the Y-Z plane) and the longitudinal axis of the orthogonal accelerator is aligned in the Y-dimension. This avoids cross-aberrations caused by mixing of X and Y dimension parameters. However, other arrangements such as that in
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[0094] The first ion accelerator 30 described herein may receive the ions in the same direction that it pulses ions out. This enables the ion beam to be maintained relatively small in one or both of the dimensions (e.g. X-dimension) perpendicular to the dimension along which ions are pulsed out of the first ion accelerator 30. For example, the ion beam may be maintained relatively small in the dimension that they are pulsed out of the orthogonal accelerator (X-dimension) and as parallel as possible. The ions may be received, for example, as a substantially continuous ion beam, e.g. from a continuous ion source.
[0095] The ion acceleration region in the first ion accelerator 30 may be relatively long in the direction of ion acceleration, so as to provide the mass analyser with a relatively high duty cycle. The electric field for accelerating the ions is desired to be strongly homogeneous, so as to avoid introducing orthogonal (X and Z dimension) ion beam deviations. This acceleration region may therefore be relatively large in the dimensions (e.g. X and Z dimensions) orthogonal to the dimension in which ions are accelerated and/or a plurality of electrodes and voltage supplies may be provided to support a homogenous ion acceleration field.
[0096] In the MRTOF embodiments, it is desired to provide a relatively high number n of ion mirror reflections and so the spatial focal distance provided by the first ion accelerator 30 is desired to be relatively long. The kinetic energy of the ions after being accelerated by the first ion accelerator is desired to be much higher (e.g. ˜n/2 times higher) than the additional energy acquired during the pulse of the accelerating field in the ion acceleration region of the first ion accelerator.
[0097] Two different techniques are contemplated for accelerating ions in the first ion accelerator 30. In a first technique, the ions have a relatively high energy when they arrive in the first ion accelerator (e.g. 50 eV) and the first ion accelerator applies a voltage pulse to the ions to accelerate them (e.g. 10 V). In a second technique the ions have a relatively low energy when they arrive in the first ion accelerator (e.g. 5 eV), the first ion accelerator applies a voltage pulse to the ions to accelerate them (e.g. 18 V) and the ions then pass through a further ion acceleration region across which a potential difference is maintained (e.g. of 37 V). The exemplary energies and voltages described in the first and second techniques provide the ions with about the same energy distribution. In both techniques the spatial focal distance in the dimension of ion acceleration (Y-dimension) is about 11 times longer than the length (in the Y-dimension) of the pulsed ion acceleration region of the first ion accelerator. Accordingly, if an orthogonal accelerator having an orthogonal acceleration region of the same length (in the Y-dimension) is arranged adjacent the first ion accelerator (in the Y-dimension), then there will be a further ten such lengths downstream before the ions are spatially focused in the Y-dimension. This allows ten reflections between the ion mirrors before the spatial focusing occurs, e.g. before the ions hit the detector.
[0098] The first technique enables the ion beam to be maintained smaller in the X-dimension, whereas the second technique may be used to provide the mass analyser with a relatively high duty cycle.
[0099] Specific examples of the first and second techniques will now be described, for illustrative purposes only, for analysing ions having a maximum m/z of 1000 Th and a pulsed ion acceleration region in the first ion accelerator having a length in the Y-dimension of 62 mm.
[0100] In an example according to the first technique, the ions are received in the first ion accelerator having a kinetic energy of 50 eV and a velocity of 3.1 mm/μs (m/z=1000 Th), so as to fill the 62 mm ion acceleration region in 20 μs. A voltage pulse of 10 V is then applied across the 62 mm ion acceleration region such that the ions become spatially focused in the Y-dimension at about 700 mm (after a flight time of −225 μs). After about 20 μs from being pulsed out of the first ion accelerator, the ions fill the adjacent orthogonal accelerator and a voltage pulse is applied in the X-dimension so as to orthogonally accelerate these ions into a first ion mirror. The ion packet is then reflected 10 times in the X-dimension by the ion mirrors (without impacting on the orthogonal accelerator between the first and second reflections) before arriving at the ion detector. It is required to wait about 20 μs for an ion of m/z 1000 to leave the first ion accelerator (keeping the voltage pulse applied), and then another 20 μs for the ions to fill the orthogonal accelerator. Whilst the ions are filling the orthogonal accelerator, a second packet of ions (e.g. having an upper m/z of 1000) may fill the first ion accelerator. The second packet of ions can therefore be accelerated out of the first ion accelerator at a time of 40 μs. However, if each ion packet includes a range of mass to charge ratios, then ions from different pulses may arrive at the detector at times which overlap, since the heaviest and slowest ions in one pulse may reach the detector after the lightest and fastest ions from a subsequent pulse. For any given pulse, the lowest mass registered at the ion detector will be the one moving twice as fast as the highest mass desired to be analysed (1000 Th), i.e. a mass of 250 Th, and will arrive at the detector in 112 μs. The duty cycle of the mass analyser depends on the period of the push-out pulses. For the example wherein the upper limit of the mass range detected is m/z=1000 Th, and taking into account the absence of masses below 250 Th, a cycle time of 112 μs can be provided and the duty cycle is then approximately 20/112, i.e. 18%.
[0101] In an example according to the second technique, the ions are received in the first ion accelerator having a kinetic energy of 5 eV and a velocity 0.98 mm/μs (m/z=1000 Th), so as to fill the 62 mm ion acceleration region in 63 μs. A voltage pulse of about 18 V is then applied across the 62 mm ion acceleration region so as to accelerate ions into a further (short) ion acceleration region across which a potential difference of 37 V is maintained. As with the first technique, this provides the ions with the same maximum energy (60 eV) and causes the ions to become spatially focused in the Y-dimension at about 700 mm. The 18 V pulse increases the energy of the last ions up to 23 eV and a velocity 2.1 mm/μs. These ions therefore leave the pulsed acceleration region after 30 μs and are then accelerated to 60 eV in the downstream further acceleration region. The orthogonal acceleration is delayed by 30 μs. In contrast to the first technique, in the second technique the ion packet stretches to 93 mm at the orthogonal acceleration region, instead of 62 mm. If it is still desired to have the same number of reflections as in the first technique (i.e. n=10), then it is required to sacrifice ⅓ of the ions and still use an orthogonal acceleration region having a length of 62 mm. As such, it is still possible to use a 20 μs delay before pulsing the orthogonal accelerator (i.e. the moment that the first ions reach the far end of the orthogonal acceleration region). In this case, the low-mass cut-off will again be 250 Th and so a cycle time of 112 μs can again be used to analyse ions having a mass range of 250-1000. The duty cycle of the mass analyser in this case is about 0.67×63 μs/112, i.e. 37%. Longer cycle times may be used to analyse ions of higher mass to charge ratios, although this has a corresponding lower efficiency of using the incoming ion beam (i.e. a lower duty-cycle). Also, if a gap is provided between the first ion acceleration region and the orthogonal accelerator then the high mass cut-off of the mass range able to be analysed will be defined by the distance of this gap.
[0102] Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.
[0103] For example, although embodiments have been described in which the ions are received in the first acceleration region 30 as a continuous ion beam, the ions may be received as a non-continuous or pulsed ion beam. The mass spectrometer may therefore comprise either a pulsed ion source or other types of ion sources. For example, the ion source may be an electron ionisation ion source or a laser ablation ionisation source (either as vacuum ion sources or ion sources at ambient gas pressure).
[0104] The ionisation source may be arranged inside the first acceleration region. Alternatively, or additionally, the ionisation source may be configured to emit photons, charged particles (such as electrons or reagent ions) or molecules that interact with analyte so as to ionise it, wherein these photons, particles or molecules are directed into the first ion accelerator 30 for ionising analyte therein. The photons, particles or molecules may be directed along the axis of the first accelerator (Y-dimension). This may increase the sensitivity of the analyser.
[0105] The analyser may be configured such that the final ion energy in the Y-dimension is related to the ion energy provided in the X-dimension such that the ion speeds in these dimensions are proportional to their respective effective flight path lengths along these dimensions. For example, the flight path of the ions from the first ion accelerator 30 to the ion detector 36 in the Y-dimension may be significantly smaller than the flight path of the ions in the X-dimension.
[0106] Although the ions have only been described as being reflected by the ion mirror(s) in the X-dimension, it is contemplated that the ions may also be reflected in the Y-dimension so as to extend the length of the ion flight path. For example, the ions may be pulsed in the Y-dimension by the first ion accelerator, reflected in the X-dimension between two ion mirrors, reflected in the Y-dimension back towards the first ion accelerator, reflected between the ion mirrors in the X-dimension and then onto the detector.
[0107] The voltage pulses applied to the first ion accelerator 30 and/or the orthogonal acceleration region 32 are desirably maintained until all ions of interest have exited the first ion accelerator 30 and/or the orthogonal acceleration region 32, respectively. This provides the all masses of interest with the same energy. In contrast, a shorter pulse would provide the same momentum to all masses, which would spatially focus different masses at different distances in the Y-dimension.
[0108] A wire mesh may be provided between the first ion accelerator 30 and the orthogonal accelerator 32 so as to prevent the pulsed electric field from either device entering the other device.
[0109] Embodiments are also contemplated in which the ions may also be accelerated in the Z-dimension in a corresponding manner to that in which the ions are accelerated in the Y-dimension by the first ion accelerator 30. This enables the ions to be spatially focused in the Z-dimension as well as the Y-dimension. This may be useful for embodiments in which the detector 36 is displaced from the orthogonal accelerator 32 in both the Y-dimension and the Z-dimension.
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[0111] Although planar ion mirror geometries in which ions are reflected in a single plane have been described, other geometries are also contemplated.
[0112]