Multi-reflecting time of flight mass analyser

Abstract

A mass spectrometer comprising: an ion energy filter 14 arranged and configured to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; and a multi-reflecting time of flight mass analyser or mass separator 1 having an ion accelerator 6, and two gridless ion mirrors 2 that are elongated in the first dimension (z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (x-dimension), wherein the ion accelerator 6 is arranged to receive ions from the energy filter 14 and accelerate the ions into one of the ion mirrors 2.

Claims

1. A mass spectrometer comprising: an ion energy filter arranged and configured to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; and a multi-reflecting time of flight mass analyser or mass separator having an ion accelerator, and two gridless ion mirrors that are elongated in the first dimension (z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (x-dimension), wherein the ion accelerator is arranged to receive ions from the energy filter and accelerate the ions into one of the ion mirrors; wherein the energy filter is configured to only transmit ions having a kinetic energy spread, in the first dimension (z-dimension), of ≤5 eV.

2. The spectrometer of claim 1, comprising a controller for controlling the energy filter so as to only onwardly transmit ions having said component of kinetic energy in the first dimension (z-dimension) within the selected range such that substantially all of these transmitted ions are reflected the same number of times, N, between the ion mirrors.

3. The spectrometer of claim 2, wherein N is: ≥8; ≥9; ≥10; ≥11; ≥12; ≥13; ≥14; ≥15; ≥16; ≥17; ≥18; ≥19; or ≥20.

4. The spectrometer of claim 2, wherein substantially all ions having a component of kinetic energy in a first dimension (z-dimension) that is outside of the selected range would be reflected between the mirrors a number of times other than N, were they to be transmitted into the mass analyser or mass separator.

5. The spectrometer of claim 1, wherein the energy filter is configured to only transmit ions having a kinetic energy in the first dimension (z-dimension) that is above a first threshold value; and/or wherein the energy filter is configured to only transmit ions having a kinetic energy in the first dimension (z-dimension) that is below a second threshold value.

6. The spectrometer of claim 1, wherein the energy filter is configured to only transmit ions having a kinetic energy spread, in the first dimension (z-dimension), that is selected from: ≤4 eV; ≤3 eV; ≤2 eV; ≤1 eV; ≤0.9 eV; ≤0.8 eV; ≤0.7 eV; ≤0.6 eV; ≤0.5 eV; ≤0.4 eV; ≤0.3 eV; ≤0.2 eV; or ≤0.1 eV.

7. The spectrometer of claim 1, wherein the energy filter comprises at least one electrostatic sector for filtering ions according to their kinetic energy.

8. The spectrometer of claim 1, wherein the mass analyser or separator comprises a deflection module configured to deflect the average trajectory of the ions leaving the ion accelerator towards the second dimension (x-dimension) so as to reduce the velocity component of these accelerated ions in the first dimension (z-dimension).

9. The spectrometer of claim 1, comprising an ion cooling device upstream of the energy filter for reducing the average energy of the ions received by the energy filter.

10. The spectrometer of claim 9, wherein the ion cooling device is a collisional cooling cell configured to be maintained at a gas pressure such that ions collide with gas in the cell to reduce their energy.

11. The spectrometer of claim 1, wherein the mass analyser or separator is configured such that ions are substantially not spatially focussed and/or collimated in the first dimension (z-dimension) as the ions travel between the ion mirrors; or wherein the mass analyser or separator is configured such that there are substantially no aberrations due to spatial focusing in the first dimension (z-dimension) as the ions travel between the ion mirrors.

12. The spectrometer of claim 1, wherein the two ions mirrors are configured to reflect ions over substantially the same length in the first dimension (z-dimension).

13. The spectrometer of claim 1, wherein the mass analyser or mass separator comprises an ion accelerator for accelerating ions into one of the ion mirrors and that is arranged between the ion mirrors; and/or comprising an ion detector for detecting ions after having been reflected by the ion mirrors and that is arranged between the ion mirrors.

14. The spectrometer of claim 1, wherein the mass analyser or separator is housed in a housing and the spectrometer further comprises an ion source, and/or at least one ion manipulation device, mounted to or arranged adjacent a wall of the housing; wherein the spectrometer is configured to transmit ions from the ion source, and/or through the at least one ion manipulation device, in a first direction and then turn the ions in a second, opposite direction and into the mass analyser or separator.

15. A method of mass spectrometry comprising: providing a spectrometer as claimed in claim 1; controlling the ion energy filter to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; accelerating the transmitted ions into one of the ion mirrors using the ion accelerator; and reflecting the ions between the ion mirrors multiple times.

16. A mass spectrometer comprising: an ion energy filter arranged and configured to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; and a multi-reflecting time of flight mass analyser or mass separator having an ion accelerator, and two gridless ion mirrors that are elongated in the first dimension (z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (x-dimension), wherein the ion accelerator is arranged to receive ions from the energy filter and accelerate the ions into one of the ion mirrors; wherein the energy filter comprises an ion entrance, an ion exit, and at least two axially spaced electrodes arranged therebetween, wherein the energy filter is configured to arrange a potential difference between the electrodes that urges ions in a direction from the ion exit to the ion entrance for filtering the ions according to their kinetic energy.

17. The spectrometer of claim 16, wherein the energy filter is configured such that ions travel therethrough along a central axis, and wherein the electrodes are arranged and configured such when the potential difference is arranged between them it provides an axial potential barrier that increases as a function of radial distance from the central axis.

18. The spectrometer of claim 16, wherein said electrodes comprise a first electrode arranged towards the ion entrance, a second electrode arranged towards the ion exit, and a third electrode arranged between the first and second electrodes; wherein the energy filter is configured to maintain the first and second electrodes at the same potential and the third electrode at a different potential.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1 shows a prior art MRTOF mass analyser;

(3) FIG. 2 shows examples of energy distributions of ions of three mass to charge ratios accelerated by a 30 V voltage after cooling in a collision cell;

(4) FIG. 3 shows a schematic of part of an MRTOF mass spectrometer according to an embodiment of the present invention having an electrostatic sector energy filter;

(5) FIGS. 4A-4B show an MRTOF mass spectrometer according to another embodiment of the present invention wherein ion manipulation devices are mounted to the MRTOF mass analyser housing;

(6) FIGS. 5A-5B show an energy filter according to an embodiment of the present invention; and

(7) FIG. 6 shows a schematic of part of an MRTOF mass spectrometer according to an embodiment of the present invention in which the orthogonal accelerator is inclined.

DETAILED DESCRIPTION

(8) FIG. 1 shows a known Multi-Reflecting TOF (MRTOF) mass spectrometer. The instrument comprises two ion mirrors 2 that are separated in the x-dimension by a field-free region. Each ion mirror 2 comprises multiple electrodes for reflecting ions in the x-dimension, and is elongated in the z-dimension. An array of periodic lenses 4 is arranged in the field-free region between the ion mirrors 2. An orthogonal ion accelerator 6 is arranged at one end of the analyser and an ion detector 8 is arranged at the other end of the analyser (in the z-dimension).

(9) In use, an ion source delivers ions to the orthogonal ion accelerator 6, which accelerates packets of ions 10 into a first of the ion mirrors at an inclination angle to the x-axis. The ions therefore have a velocity in the x-dimension and also a drift velocity in the z-dimension. The ions enter into the first ion mirror and are reflected back towards the second of the ion mirrors. The ions then enter the second mirror and are reflected back to the first ion mirror. The first ion mirror then reflects the ions back to the second ion mirror. This continues and the ions are continually reflected between the two ion mirrors as they drift along the device in the z-dimension until the ions impact upon ion detector 8. The ions therefore follow a substantially sinusoidal mean trajectory within the x-z plane between the ion source and the ion detector 8.

(10) The periodic lens array 4 is arranged such that the ion packets 10 pass through them as they are reflected between the ion mirrors 2. Voltages are applied to the electrodes of the periodic lens array 4 so as to spatially focus the ion packets in the z-dimension. This prevents the ion packets from diverging excessively in the z-dimension, which would otherwise result in some ions reaching the detector 8 having only been reflected a certain number of times and other ions reaching the detector having been reflected a larger number of times. The periodic lens array 4 therefore prevents ions have significantly different flight path lengths through the mass analyser on the way to the detector 8.

(11) The inventors have recognised that ions may be prevented from performing different numbers of reflections between the ion mirrors by other means and without necessarily using a periodic lens between the ion mirrors, the use of which may cause aberrations in the ion flight time.

(12) Ions may be conditioned upstream of MRTOF mass analysers by being collided with background gas in a gas-filled RF ion guide so as to collisionally cool them. The phase volume of the ion beam may be reduced to tens of milli-electron volts, including the axial movement of ions. This is five orders of magnitude lower than the typical drift energy of ions in TOF mass analysers (which is in the keV range). If this energy spread could be maintained it would be possible, for example, to provide only 6 mm of ion beam expansion for 10 m of travel in the drift direction. However, the inventors have recognised that the axial velocity spread of the ions is increased, during acceleration of the ions, by ion collisions at the exit of the collisional cooling ion guide and that this results in an increased energy spread of the ions that causes the above-described problem of ions diverging in the MRTOF mass analyser.

(13) FIG. 2 shows examples of energy distributions of ions of three mass to charge ratios (100, 200 and 1000) after having been collisionally cooled and accelerated by a potential difference (that would result in ions having an energy of 30 eV if there was no background gas). It can be seen that the ions have been decelerated by collisions with gas so has to have different energies spanning significant ranges, and also that ions of different mass to charge ratio have different energy distributions.

(14) The inventors have recognised that the ion beam may be conditioned prior to entering the mass analyser such that the ions can be reflected between the ions mirrors a reasonably high number of times without different ions performing different numbers of reflections in the time of flight region. More specifically, this may be achieved by decreasing the energy spread, or decreasing the velocity spread, of the ions prior to the ions entering the mass analyser. Referring to FIG. 2 as an example, this may be achieved by preventing ions in the low energy tail of the energy distributions from entering the mass analyser. Any type of energy filter may be used for this purpose, although a number of examples will be discussed below.

(15) FIG. 3 shows a schematic of part of an MRTOF mass spectrometer according to an embodiment of the present invention. The instrument comprises two ion mirrors 2 that are separated in the x-dimension by a field-free region 3. Each ion mirror 2 comprises multiple electrodes so that different voltages may be applied to the electrodes to cause the ions to be reflected in the x-dimension. The electrodes are elongated in the z-dimension, which allows the ions to be reflected multiple times by each mirror 2 as they pass through the device, as will be described in more detail below. Each ion mirror 2 may form a two-dimensional electrostatic field in the X-Y plane. The drift space 3 arranged between the ion mirrors 2 may be substantially electric field-free such that when the ions are reflected and travel in the space between the ion mirrors 2 they travel through a substantially field-free region 3. An orthogonal ion accelerator 6 is arranged at one end of the mass analyser and an ion detector 8 is arranged at the other end of the analyser (in the z-dimension). The instrument also comprises a collisional cooling cell 12 and an energy filter 14 upstream of the MRTOF mass analyser. In the depicted embodiment the energy filter 14 is in the form of an electrostatic sector having an entrance for receiving ions and a slotted exit for transmitting ions of the desired energy. The collisional cooling cell 12 may comprise an ion guide 13 for radially confining ions and optionally for urging ions through the collisional cooling cell 12.

(16) In use, the collisional cooling cell 12 is supplied with gas and ions are supplied to the collisional cooling cell 12. The ions collide with the gas in the cell 12 so as to transfer their kinetic energy to the gas molecules, thus reducing the energy of the ions and reducing their energy spread. The ions are then transferred from the collisional cooling cell 12 into the electrostatic sector energy filter 14. The ions may be supplied to the entrance of the energy filter 14 in an intermittent or pulsed manner, or continuously. The ions may be accelerated from the collisional cooling cell 12 to the electrostatic sector energy filter 14. As described above, the energy distribution range that the ions have may broaden during this transfer process. Voltages are applied to the electrodes of the electrostatic sector energy filter 14 such that only ions having axial energies in the desired energy range are capable of being transmitted from the entrance to the exit slot. The ions pass into the entrance and experience a force orthogonal to their direction of travel, due to the voltages applied to the electrostatic sector 14. The flight paths of ions having energies within the desired range of energies are bent such that these ions travel through the electrostatic sector 14 and out of the slotted exit so as to be onwardly transmitted to the MRTOF mass analyser. The flight paths of ions having energies outside of the desired range of energies are bent such that these ions impact on the internal walls of the electrostatic sector 14 and do not pass out of the exit, and are therefore not onwardly transmitted to the MRTOF mass analyser.

(17) Ions that are transmitted by the energy filter 14 are received in the MRTOF mass analyser and pass into the orthogonal accelerator 6 along a first axis (e.g. extending in the z-dimension). This allows the duty cycle of the instrument to remain high. The orthogonal accelerator 6 pulses the ions (e.g. periodically) orthogonally to the first axis (i.e. pulsed in the x-dimension) such that packets of ions travel in the x-dimension towards and into a first of the ion mirrors 2. The ions retain a component of velocity in the z-dimension from that which they had when passing into the orthogonal accelerator 6. As such, ions are injected into the time of flight region 3 of the instrument at a small angle of inclination to the x-dimension, with a major velocity component in the x-dimension towards the first ion mirror 2 and a minor velocity component in the z-dimension towards the detector 8.

(18) The ions pass into a first of the ion mirrors and are reflected back towards the second of the ion mirrors. The ions pass through the field-free region 3 between the mirrors 2 as they travel towards the second ion mirror and they separate according to their mass to charge ratios in the known manner that occurs in field-free regions. The ions then enter the second mirror and are reflected back to the first ion mirror, again passing through the field-free region 3 between the mirrors as they travel towards the first ion mirror. The first ion mirror then reflects the ions back to the second ion mirror. This continues and the ions are continually reflected between the two ion mirrors 2 as they drift along the device in the z-dimension until the ions impact upon ion detector 8. The ions therefore follow a substantially sinusoidal mean trajectory within the x-z plane between the ion source and the ion detector 8. The time that has elapsed between a given ion being pulsed from the orthogonal accelerator 6 to the time that the ion is detected may be determined and used, along with the knowledge of the flight path length, to calculate the mass to charge ratio of that ion.

(19) The desired range of ion energies capable of being transmitted by the energy filter 14 is selected such that all ions received in the MRTOF mass analyser perform the same number of ion mirror reflections when pulsed from the orthogonal accelerator 6 to the detector 8. Although eight ion mirror reflections are shown in FIG. 3, the MRTOF mass analyser and energy filter 14 may be set so as to cause ions to undergo a different numbers of ion reflections.

(20) Embodiments of the present invention relate to an MRTOF mass analyser having substantially no focusing of the ions, in the z-dimension, between the ion mirrors 2 (e.g. there is no periodic lens 4 for focusing the ions in the z-dimension). Rather, the expansion of each packet of ions 10 in the z-dimension as it travels from the orthogonal accelerator 6 to the detector 8 is limited by the range of energies that the ions have when they enter the mass analyser. In contrast, MR-TOF mass spectrometers have conventionally sought to obtain a very high resolution and hence require a high number of reflections between the ion mirrors 2. Therefore, conventionally it has been considered necessary to provide z-dimensional focusing using an array of periodic lenses arranged between the ion mirrors 2 to prevent the width of the ion packet diverging.

(21) In the embodiment depicted in FIG. 3, one particular electrostatic sector energy-filter 14 is shown. However, other forms of electrostatic energy filter may be used (e.g. of cylindrical, spherical or toroidal shape).

(22) FIG. 4A shows a top-down view of an MRTOF mass spectrometer according to another embodiment of the present invention, and FIG. 4B shows a perspective view. This embodiment comprises one or more devices and/or vacuum chambers for forming and/or manipulating an ion beam 16, an energy filter 14, and an MRTOF mass analyser 1. The MRTOF mass analyser 1 is of the same form and operates in the same manner as described in relation to FIG. 3, i.e. the ions are reflected between ion mirrors 2 in the x-z plane. The MRTOF mass analyser is housed in a vacuum chamber 18 having side walls arranged substantially in the x-z plane. The one or more devices and/or vacuum chambers for forming and/or manipulating the ions 16 are located on and/or adjacent a side wall of the MRTOF mass analyser housing 18. The one or more devices and/or vacuum chambers for forming and/or manipulating the ion beam 16 may comprise an atmospheric pressure ion source, an atmospheric pressure interface 20, a first vacuum chamber 22, a second vacuum chamber 23 in which a mass filter 24 (such as a quadrupole mass filter) may be arranged, a collisional cooling cell 25 and ion optics 26. FIG. 4B shows vacuum pumps (cylinders) for pumping the vacuum chambers.

(23) In operation, ions are formed in the atmospheric pressure ion source, such as by an ESI ion source. The ions then enter the atmospheric pressure interface 20 (which may be a tube or ion guide) and pass into the first vacuum chamber 22, which is pumped to a lower pressure than the atmospheric pressure region. The ions then pass into the second vacuum chamber 23, which may be pumped to a lower pressure than the first vacuum chamber 22 (or maintained at the same pressure). The second vacuum chamber 23 may comprise one or more devices for manipulating the ions. For example, the second vacuum chamber 23 may comprise a mass filter 24 that transmits only ions of a selected mass to charge ratio, or a selected range of mass to charge ratios. The selected mass to charge ratio(s) that is transmitted by the mass filter 24 may be controllably varied with time. Alternatively, or additionally, an ion mobility separator may be provided that separates the ions by mobility. Alternatively, or additionally, a fragmentation device (e.g. CID fragmentation cell) may be provided for fragmenting ions. For example, a mass filter and fragmentation device may be provided, wherein the mass filter selects precursor ions to fragment in the fragmentation device, and wherein the resulting fragment ions are then onwardly transmitted for analysis.

(24) The ions are subsequently transmitted into the collisional cooling cell 25, which operates as described above in relation to FIG. 3 so as to reduce the energy spread of the ions. The collisional cooling cell 25 may comprise an axially segmented rod set, and different voltages may be applied to the different segments so that ions move through the collisional cooling cell 25 and into ion optics 26 that guide the ions into the energy filter 14. The energy filter 14 guides ions having the desired range of ion axial energies into the MRTOF mass analyser 1, as described in relation to FIG. 3, except that in the embodiment of FIG. 4 the energy filter 14 may be a cylindrical energy filter that defines an ion path between a radially inner part-cylinder electrode 14a and a radially outer part-cylinder electrode 14b. The ions then pass into the MRTOF mass analyser 1 and are analysed in the same manner as described above in relation to FIG. 3. The ions therefore travel from the ion source to the energy filter 14 along a first direction in the z-dimension, and are guided by the energy filter 14 so as to have an average direction of travel in the MRTOF analyser 1 (i.e. the drift direction) that is in a second direction opposite to the first direction. This arrangement allows the MRTOF mass analyser 1 to be mounted parallel and aside the chambers of the upstream stages 16, resulting in a relatively compact instrument.

(25) Although an atmospheric pressure region and an atmospheric pressure ion source have been described, the region and ion source may be operated at other pressures.

(26) Although a single sector energy filter 14 has been described that bends the ion path by 180 degrees (for ions of desired energies), other forms of energy filter may be provided. For example, the energy filter may bend the ion path (for ions of desired energies) by angles other than 180 degrees. Alternatively, or additionally, the energy filter may be formed by multiple electrostatic sectors, such as two 90 degree sectors that may have a slit arranged between them for transmitting ions of the desired energies. It is also contemplated that other forms of electrostatic energy filters may be used, as are known in the art.

(27) Although the energy filter 14 has been described for turning the ions into the MRTOF mass analyser 1, other ion optical components may perform this function instead. For example, a curved RF ion guide such as a multipole (e.g. quadrupole) ion guide may be provided for this function. Alternatively, the ion beam may be deflected into the MRTOF mass analyser by deflection electrodes, e.g. by a two stage beam deflection device. In these embodiments, if the ion optical components for turning the ions into the MRTOF mass analyser is not configured to perform the energy filtering described herein, then a separate energy filter may be provided upstream or downstream of the ion optical components for turning the ions.

(28) As described above, the energy filter 14 may take a form other than an electrostatic sector. Other exemplary embodiments of the energy filter will now be described below.

(29) For example, the energy filter 14 may comprise electrodes that arrange an ion retarding potential difference (e.g. DC potential difference) that urges the ions in the opposite direction to that in which they are travelling. This may be achieved, for example, by applying different voltages to an axially spaced pair of grid/mesh electrodes, wherein the ions are arranged to travel through the holes in the grid/mesh electrodes. The ion retarding potential difference is easy to adjust and is set so as to allow relatively high energy ions to pass therethough, but to reflect or deflect relatively low energy ions so that they are not onwardly transmitted by the energy filter. Referring back to FIG. 2 as an example, this ensures that the onwardly transmitted ions have a relatively small energy distribution.

(30) Although grid/mesh electrodes through which the ions pass have been described, other electrode arrangements may be provided, e.g. in order to reduce or avoid contamination or charging of these electrodes due ions impacting on them.

(31) FIGS. 5A-5B show another embodiment of the energy filter. FIG. 5A shows a schematic of a cross-sectional side view of the energy filter, whereas FIG. 5B shows a Simion plot showing the ion trajectories through the energy filter. The energy filter comprises a first apertured electrode 30 disposed towards the entrance of the energy filter, a second apertured electrode 31 disposed towards the exit of the energy filter, and a third apertured electrode 32 arranged between the first and second electrodes.

(32) In use, a beam of ions passes into the energy filter along the axis extending through the apertured electrodes 30-32. Voltages are applied to the electrodes (e.g. DC voltages) such that ions of relatively high energy are able to be transmitted through the apertures of the electrodes and out of the exit of the energy filter as shown by arrow 34, whereas ions of relatively low energy are reflected or deflected such that they are not transmitted by the energy filter as shown by arrows 35. As described above in relation to FIG. 2, this enables the energy spread of the ions transmitted by the energy filter to be reduced.

(33) The diameter of the apertures in the electrodes 30-32 is larger than that of the ion beam and may be at least twice the diameter. The voltage applied to the third electrode 32 may be set relative to the first electrode 30 such that a decelerating electric field is arranged between the first electrode 30 and third 32 electrode. The potential on the third electrode 32 may be set according to the range of ion energies that are desired to be transmitted by the energy filter. As shown in FIG. 5B, due to penetration of the electric fields, there is a potential saddle in the centre of the aperture in the third electrode 32. As will be described below, ions that have relatively low energy or travel substantially off the central axis cannot pass through the energy filter. This allows the selection of the required phase-space in both the axial (e.g. z-dimension) and orthogonal (e.g. x- and y-dimensions) directions for incoming ion beam.

(34) The second electrode 31 may be maintained at substantially the same voltage as the first electrode 30, such that ions which are transmitted to the exit of the energy filter have the same energy as when they enter the energy filter. In other words, the energy filter may comprise an Einzel lens. In this embodiment the ion retarding voltage applied to the third electrode 32 may be set to be substantially at the same voltage as the final electrode upstream of the energy filter (e.g. the exit of the collisional cooling cell).

(35) The electric field lines between the adjacent apertured electrodes 30-32 are shown schematically in FIG. 5A. The electrodes may be arranged, and voltages applied to them, such that the electrodes provide electric fields that form an ion lens. Ions that have relatively low kinetic energy (i.e. undesirable ions), or that have flight paths that are substantially inclined relative to the longitudinal axis of the energy filter, will be reflected or deflected such that they do not pass through the energy filter. As can be seen from FIG. 5A, ions that pass relatively close to the electrodes 30-32 will pass through significantly curved equipotential field lines and will therefore also be deflected such that they do not pass through the energy filter. This may be used to filter out radially outer ions at the periphery of the ion beam. This may be used so as to only transmit ions at the centre of the ion beam, without necessarily having to use a collimation aperture. This is advantageous, for example, as the collimation of intense low energy ion beams by collimation apertures is known to cause variation of beam parameters due to contamination and charging of these elements by the ions.

(36) Although the energy filter has been described above as comprising three electrodes, it is contemplated that the second 31 electrode may be omitted. Additionally, or alternatively, the electrodes of the energy filter need not be apertured electrodes by may be electrodes of other forms. For example, the energy filter electrodes may be a segmented multipole (e.g. quadrupole) having two, three or more axial segments and wherein different voltages may be applied to the electrodes of the different axial segments so as to perform the above-described energy filtering.

(37) In order reflect the ions multiple times in the MRTOF mass analyser 1 before the ions impact on the detector 8, the velocity of the ions in the z-dimension (i.e. the drift dimension through the mass analyser) is required to be significantly smaller than the velocity of the ions in the direction of ion reflection between the ion mirrors 2 (i.e. in the x-dimension). However, it can be difficult to arrange the ion beam incoming into the MRTOF mass analyser so have sufficiently low velocity (i.e. energy) in the z-dimension. Also, even though the ions may be collisionally cooled upstream of the MRTOF mass analyser in order to reduce their energy spread, the ions may still emerge from the collisional cooling cell 12 having a substantial spread of kinetic energies. It can also be problematic to simply set the energy filter 14 so as to transmit only ions in a narrow energy band, such as those having energies above a relatively high cut-off value, since then relatively few ions will be transmitted by the energy filter and the sensitivity of the instrument will be diminished.

(38) The maximum number of double ion-mirror reflections before ions begin to undergo differing numbers of ion-mirror reflections can be estimated approximately as the ratio of the drift length of the ions through the MRTOF mass analyser in z-dimension to the size of ion packet in z-dimension. Even if the ion packet begins with very small size in the z-dimension, this size will expand as the ions travel through the mass analyser and according to the following relationship:
ΔZ=ΔV.sub.z*L.sub.z/V.sub.z
where ΔZ is the change in size of the ion packet in the z-dimension as it travels through the MRTOF mass analyser, ΔV.sub.z is the spread of ion velocities in the z-dimension that the ions have, L.sub.z is the length that the ions travel in the z-dimension in the MRTOF mass analyser, and V.sub.z is the average ion velocity in the z-dimension within the MRTOF mass analyser.

(39) Therefore, the number of reflections between the ion mirrors is restricted by the ratio of V.sub.z to ΔV.sub.z, which is approximately equal to 2E.sub.beam/E.sub.beam, where E.sub.beam is the average energy of the ion beam in the z-dimension that enters the MRTOF mass analyser and ΔE.sub.beam is the spread of energies in the z-dimension of ions that enter the mass analyser.

(40) The above does not take into account the original size of the ion packet in the z-dimension (e.g. at the orthogonal accelerator) Z.sub.0−ΔZ. Accounting for the original size of the ion beam in the z-dimension may result in an increase in the final size of the ion beam in the z-dimension by the time at the time it reaches the detector, with a corresponding decrease (approximately by a factor of two) in the number of ion mirror reflections that may be performed whilst still maintaining the same number of ion mirror reflections for all ions. Therefore, the number of ion mirror reflections that may be performed whilst maintaining the same number of reflections for all ions, N.sub.max, may be given by:
N.sub.max˜E.sub.beam/ΔE.sub.beam
It therefore follows that it is required to minimize the energy spread of ions entering the MRTOF mass analyser, ΔE.sub.beam, using the collisional cooling cell and energy filter in order to maximise the number of ion mirror reflections N.sub.max.

(41) In order to increase the number of ion mirror reflections, N.sub.max, so as to increase the ion flight path length, and hence increase the resolving power of the MRTOF mass analyser, the energy of the original ion beam E.sub.beam may be increased. The velocity of the ions in the z-dimension through the mass analyser may then be decreased such that the ions have time to perform the desired number of reflections before they reach the detector. This reduction of the ion velocity in the z-dimension may be performed by a deflection module arranged downstream of the orthogonal accelerator that deflects the ion packet leaving the orthogonal accelerator so that its component of velocity in the z-dimension is decreased (and its component of velocity in the x-dimension is increased), as will be described below in relation to FIG. 6.

(42) A disadvantages of this approach (and other approaches that increase the number of ion mirror reflections) is that the duty cycle of the mass analyser is reduced, i.e. the proportion of the ions that are transmitted from the entrance of the mass analyser to the detector is reduced. Without the use of a deflection module, the duty cycle (DC) of the mass analyser can be estimated (assuming Z.sub.0˜ΔZ) as follows:
DC=Z.sub.0/L.sub.Z˜½N.sub.max
If a deflection module is used to decrease the ion trajectory angle (relative to the x-dimension) and increase the number of ion mirror reflections, as described above, then the duty cycle is additionally reduced in proportion to the decrease in the ion trajectory angle.

(43) In order to better understand the effect of using a deflection module, a numerical example will now be described. Assuming that an MRTOF mass analyser having no deflection module has been set up so that the number of ion mirror reflections are optimised, and it is desired to improve the resolving power of the mass analyser (i.e. the ion flight path length and hence number of reflections) by a factor Q, then the energy of the incoming ion beam may be increased and a deflection module may be provided after the orthogonal accelerator (whilst retaining the same energy spread in the incoming ion beam and the same drift length L.sub.z through the mass analyser). The increase in ion beam energy and use of the deflection module alters the main parameters of the mass analyser by the factors listed below, where the second column indicates the factors in general terms and the third column indicates the factors for an example in which the resolution is increased by a factor of 2 (i.e. Q=2).

(44) TABLE-US-00001 Resolution Q 2 N.sub.max Q 2 ΔV.sub.z 1/Q.sup.2 0.25 V.sub.z Q.sup.2 4 Beam Energy Q.sup.4 16 Time of flight Q 2 OA length 1/Q 0.5 Duty Cycle Q.sup.−4 0.0625 L.sub.Z 1 1

(45) It can be seen that the resolution and number of reflections N.sub.max are increased, but the required length of the orthogonal accelerator (OA) and the duty cycle are reduced.

(46) If a deflection module is not used then in order to achieve the same increase in resolving power, the main parameters of the mass analyser are required to be varied by the factors listed below, where the second column indicates the factors in general terms and the third column indicates the factors for an example in which the resolution is increased by a factor of 2 (i.e. Q=2).

(47) TABLE-US-00002 Resolution Q 2 N.sub.max Q 2 V.sub.z Q.sup.1/2 1.4 ΔV.sub.z/V.sub.z 1/Q 0.5 Beam energy Q 2 Time of flight Q 2 OA length Q.sup.1/2 1.4 Duty Cycle 1/Q 0.5 L.sub.z Q.sup.3/2 2.8

(48) It can be seen that the required length of the orthogonal accelerator (OA) and the drift length through the mass analyser L.sub.z are required to be increased.

(49) FIG. 6 shows an embodiment of the present invention including an MRTOF mass analyser 1 that is similar to that shown and described in relation to FIG. 3, except that the orthogonal accelerator 6 has its ion receiving axis tilted with respect to the z-dimension and the mass analyser includes a deflection module 38 for reducing the velocity of the ions in the z-dimension after the ions have been orthogonally accelerated by the orthogonal accelerator 6. The energy filter 14 shown in FIG. 6 is also of the type shown and described in relation to FIG. 5 rather than an electric sector as shown in FIGS. 3-4, although an electric sector energy filter or any other energy filter may be used. In this embodiment, the ions may be accelerated to a relatively high energy between the collisional cooling cell 12 and the orthogonal accelerator 6.

(50) In this embodiment the deflection module 38 comprises two deflection electrodes spaced apart in the z-dimension and arranged so that ions pulsed out of the orthogonal accelerator 6 pass between them. Voltages are applied to these deflection electrodes so as to change the trajectory of the ions such that the ions have a lower velocity component in the z-dimension, thereby increasing the number of reflections between the ion mirrors 2. It is known to use deflection electrodes in order to control the trajectory of the ions after the orthogonal accelerator 6. However, the deflection electrodes may introduce first order aberrations to the time of flight of the ions that is proportional to the size of the ion packet in the z-dimension (due to the angle of trajectory of the ion packet at the exit of the deflection region). Embodiments of the present invention eliminate these aberrations by arranging the orthogonal accelerator 6 so that its ion receiving axis is inclined at an acute angle α to the z-dimension. The ions are then pulsed into the region between the deflection electrodes by the orthogonal accelerator 6 along a first trajectory, and the deflection electrodes deflect the ions by an angle α towards the x-dimension so that they travel more orthogonally to the elongated ion mirrors 2.

(51) In the embodiments that comprise a deflection module 38, second order positive z-dimension aberrations may introduced by a lens-effect. These aberrations may be compensated for by intentionally introduced negative z-dimension aberrations. For example, this may be achieved through the use of a gridless orthogonal accelerator, e.g. having accelerating slots that operate as an immersion lens and provide the compensating negative second-order aberrations.

(52) According to the embodiments described herein, the ions have a relatively long time of flight in the MRTOF mass analyser 1 due to the multiple reflections between the ion mirrors 2. This enables the ions in each pulse to become temporally well separated in the time of flight region, thus providing the instrument with a high resolution. However, due to this high temporal separation of the ions, pulsing the ions into the MRTOF at too high a rate would lead to spectral overlap in which slow ions from a first ion injection pulse are detected after fast ions from a second, later ion injection pulse. This limits the rate at which ions can be pulsed into the MRTOF before spectral overlap occurs, thus limiting the duty cycle of the instrument. Also, as described above, the use of the deflection module 38 may reduce the duty cycle of the instrument. In order to overcome this problem, the instrument may be operated in an encoded frequency pulsing (EFP) mode. In this mode, the orthogonal accelerator 6 pulses ions into the Time of Flight region in a series of pulses, wherein the time delay between pairs of adjacent ion injection pulses is varied in a predetermined manner, as opposed to the conventional method of employing a uniform time delay between all of the pairs of adjacent pulses. The ions may then be pulsed into the ion mirrors at a relatively high rate, in which the ions in a first pulse temporally overlap with the ions in a subsequent pulse. The detector 8 then detects the arrival times of the ions and obtains a signal corresponding to the overlapping spectra. As the variable time delays between ion injection pulses are known in the EFP method, this can be used to unpick overlapping peaks in the TOF spectra so as to obtain non-overlapping spectra. This may be performed by correlating the overlapping spectra with the encoded sequence for injecting ions into the flight region 3. The EFP mode enables ions to be injected into the TOF device at time intervals that are shorter than the TOF separation time and so enables the duty cycle of the spectrometer to be increased.

(53) 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.

(54) For example, although the embodiments have been described in relation to an MRTOF mass analyser having a detector for determining the mass to charge ratios of the ions, it is alternatively contemplated that the ion mirrors may simply provide a mass separation region without a TOF detector.