Multiple reflection TOF mass analysis

Abstract

The mass spectrometer includes a storage device and an analyzer. The analyzer includes a mirror, an accelerator that receives ions from the storage device and pulses them onto one of the mirrors, causing the ions to reflect back and forth in a first dimension between the mirrors as the ions drift in the drift dimension, a reflector that reflects the ions in the drift dimension, a detector, and control circuitry that activates the reflector to make multiple passes along the drift dimension and deactivates one of the reflectors so that the ions pass to the detector and can be detected, the timing of the reflector activation and deactivation being such that only ions within a first range of mass-to-charge ratios undergo the same number of passes in the drift dimension at any one time that they are detected by the detector. The control circuitry synchronizes the time of pulses from the storage device with the time of pulses from the ion accelerator so that only ions having a mass-to-charge ratio within the first range are pulsed onto one of the mirrors by the accelerator.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of UK Patent Application No. 2301462.4 filed on 1 February 2023, the entire contents of which are incorporated herein by reference.

[0003] The present invention relates generally to mass spectrometers, and more particularly to time-of-flight mass spectrometers, such as multi-reflecting time-of-flight (MRTOF) mass spectrometers, and methods for their use. [Background technology]

[0004] Time-of-flight (TOF) mass analyzers are well-known devices that use an ion accelerator to pulse packets of ions into a field-free region toward an ion detector. As the pulsed ions travel toward the detector, they separate according to their mass-to-charge ratio, with ions of different mass-to-charge ratios arriving at and being detected by the detector at different times. The mass analyzer can then determine the mass-to-charge ratios of the detected ions based on the duration between the ions being pulsed and their respective times of detection.

[0005] It is known to be advantageous in TOF mass analyzers to provide a relatively long ion flight path from the ion accelerator to the detector, as this allows ions having different mass-to-charge ratios to be separated to a relatively high degree, and therefore the mass analyzer can have a relatively high mass resolution and mass measurement accuracy. Alternatively, providing such a relatively long ion flight path allows a target mass resolution or mass measurement accuracy to be achieved with less stringent parameters, along with other parameters associated with the mass analyzer, such as detector peak width and mechanical tolerances.

[0006] Multi-reflection time-of-flight (MRTOF) mass analyzers are known that provide the above-mentioned relatively long ion flight path lengths by repeatedly reflecting ions between two ion mirrors as the ions drift in the drift dimension from the ion accelerator to the ion detector. Such an arrangement allows for relatively long ion flight paths in an instrument with a relatively small volume. It is also known to reflect ions in the drift dimension, causing the ions to make multiple passes along the mass analyzer in the drift dimension, with the ions being reflected back and forth between mirrors during each pass. This increases the number of mirror reflections that ions make, and therefore the ion flight path length, without increasing the size of the mass analyzer. This mode of operation is referred to in the art as a "zoom" mode or a "multi-pass" mode.

[0007] However, it can be difficult to operate a mass analyzer in the above-mentioned mode without the ions experiencing different ion flight path lengths to the detector, because lower mass-to-charge ratios move faster in the drift dimension than higher mass-to-charge ratios and therefore may undergo more passes along the mass analyzer, and therefore more mirror reflections, than ions of higher mass-to-charge ratios. Such a mode can also limit the mass analyzer to having relatively low sensitivity, as the relatively long ion flight times limit the duty cycle of the instrument. Summary of the Invention

[0008] From a first aspect, the present invention provides a mass spectrometer comprising an ion storage device for accumulating and pulsing ions and a time-of-flight mass analyzer, the mass analyzer comprising a plurality of ion mirrors for reflecting ions, an ion accelerator positioned and configured to receive ions from the ion storage device and pulse them to one of the ion mirrors so that the ions are reflected back and forth in a first dimension between the mirrors as they drift in the drift dimension, a reflector for reflecting ions in the drift dimension, an ion detector for detecting the ions, and control circuitry configured to activate the reflector to make multiple passes along the drift dimension and then deactivate one of the reflectors to allow the ions to pass to the ion detector and be detected, wherein the timing of the activation and deactivation of the reflector is such that only ions within a first range of mass-to-charge ratios undergo the same number of passes in the drift dimension at any time that they are detected by the ion detector. The mass spectrometer has control circuitry that synchronizes the time at which ions are pulsed from the ion storage device with the time at which ions are pulsed by the ion accelerator so that only ions having a mass-to-charge ratio within the first range are pulsed by the ion accelerator into one of the ion mirrors.

[0009] The spectrometer is configured such that the ion storage device pulses ions having a range of mass to charge ratios to the ion accelerator, the first range being smaller than but within the range, In other words, the control circuit synchronizes the time at which ions are pulsed from the ion storage device with the time at which ions are pulsed by the ion accelerator, such that ions having a mass to charge ratio within the first range are pulsed by the ion accelerator, and ions having a mass to charge ratio outside the first range are transmitted from the ion storage device to the ion accelerator but are not pulsed by the ion accelerator.

[0010] It has been recognised that synchronising the ion storage device with the ion accelerator is a particularly useful technique for restricting the range of mass-to-charge ratios that are mass analysed so that only ions that have made the same number of passes along the mass analyser reach the detector, whilst also providing the mass analyser with a relatively high sampling duty cycle and sensitivity.

[0011] The mass analyzer may be configured to determine the mass-to-charge ratio of the detected ions based on the duration between the ions being pulsed by the ion accelerator and the respective times at which they are detected.

[0012] The mass spectrometer may be configured such that ions pulsed out of the ion storage device separate according to mass to charge ratio as they travel to the ion accelerator, with ions of different mass to charge ratios entering the ion accelerator at different times.

[0013] For example, the region between the exit of the ion storage device and the ion accelerator may be substantially free of an electric field (in the mean direction of ion motion), and this region may also have a length and be at a pressure such that collisions between ions and background gas molecules are relatively few or substantially absent.

[0014] The times at which ions are pulsed out of the ion storage device and the ions are pulsed out of the ion accelerator are synchronized so that at the time the ions are pulsed out of the ion accelerator, only ions having mass to charge ratios in the first range (or a narrower range within the first range) are in the ion accelerator, and ions having mass to charge ratios outside of this first range have either already passed through the ion accelerator or have not yet entered the ion accelerator at the time the ions are pulsed out of the ion accelerator.

[0015] The ion storage device may comprise an ion guide having a trapping electrode at its downstream exit.

[0016] The ion guide may be an RF ion guide, ie an RF voltage is applied to the electrodes of the ion guide to confine ions therein.

[0017] The ion storage device may be configured to store ions and periodically pulse packets of ions toward the MRTOF mass analyzer. The ion accelerator may be synchronized with the ion storage device in the manner described herein for each pulse from the ion storage device. The ion accelerator may be configured to repeatedly pulse packets of ions toward the ion accelerator during a single experimental run, and the ion accelerator may be synchronized with the ion storage device for each pulse from the ion storage device.

[0018] The mass analyzer may be configured to pulse ions into the MRTOF mass analyzer such that ions in different ion packets are detected at the detector during separate, non-overlapping time periods, i.e., ions injected into the MRTOF in one ion packet are not detected at the detector before all of the ions in the preceding ion packet are detected at the detector, i.e., the MRTOF mass analyzer does not have to be operated in a coded high frequency pulse mode.

[0019] Ion optics may be disposed between the ion storage device and the ion accelerator to transfer ions from the ion storage device to the ion accelerator, and may comprise, for example, at least one of an ion lens, one or more ion beam collimator plates, or an ion guide.

[0020] The ion accelerator may be configured to pulse ions in a direction substantially orthogonal to the drift dimension, eg the first dimension is orthogonal to the drift dimension.

[0021] The ion accelerator may receive ions as they are traveling in a first direction and pulse the ions so that they are accelerated into one of the ion mirrors in a substantially orthogonal direction. Ions received by the ion accelerator from the ion storage device may be traveling substantially in the drift dimension.

[0022] Alternatively, ions received by the ion accelerator may be moving in a dimension substantially orthogonal to the drift dimension. In these embodiments, the ion accelerator may be configured such that when pulsing ions, ions are propelled into the ion mirror in the drift dimension as well as the first dimension.

[0023] The plurality of ion mirrors may comprise two mirrors spaced apart in the first dimension, although it is contemplated that more than two ion mirrors may be provided.

[0024] The mass spectrometer may be configured to allow a user to select what the first range of mass to charge ratios is, and the control circuit may be configured to control, in response to the user selection, when the reflector is activated and deactivated, and the time at which ions are pulsed out of the ion storage device relative to the time at which ions are pulsed out by the ion accelerator.

[0025] The mass spectrometer may be configured to allow a user to select the number of passes ions should make before detection, and the control circuit may be configured to control, in response to the user selection, when the reflector is activated and deactivated, and the time at which ions are pulsed out of the ion storage device relative to the time at which ions are pulsed out by the ion accelerator, so that ions having a first range of mass-to-charge ratios undergo the selected number of passes before detection.

[0026] Thus, the mass spectrometer has an interface for use in selecting a first range of mass to charge ratios and / or for selecting the number of passes that ions should make before detection.

[0027] The mass spectrometer may comprise a mass filter upstream of the ion storage device for mass filtering ions passing to the ion storage device.

[0028] The mass spectrometer may comprise control circuitry configured to control the mass filter such that the mass filter transmits only ions having a mass to charge ratio within a second range to the ion storage device, the first range being narrower than and within the second range.

[0029] The provision of such a mass filter reduces the ion current entering the ion storage device, thereby reducing the amount of charge per push of the ion accelerator (for a given storage time), thereby reducing space charge effects in the ion storage device and / or mass analyzer and improving the dynamic range. This may improve the mass accuracy and mass resolution of the instrument. The provision of a mass filter also allows a greater proportion of ions entering the ion storage device to have a mass-to-charge ratio corresponding to those pulsed out by the ion accelerator. This is particularly beneficial in MRTOF mass analyzers, which traditionally have relatively poor sensitivity.

[0030] It is contemplated that devices other than a mass filter may be used to selectively transmit ions having a mass to charge ratio within the second range into the ion storage device, for example a mass selective ion trap may be provided upstream of the ion storage device and the mass selective ion trap may be controlled to transmit only ions having a mass to charge ratio within the second range into the ion storage device.

[0031] A first one of the reflectors may be located at a first end of the mass analyzer in the drift dimension. The ion accelerator and ion detector may be located at a second, opposite end of the mass analyzer in the drift dimension, and a second one of the reflectors may be located in the drift dimension between the first reflector and the ion detector. The timing for activating and deactivating the reflectors is such that ions within a first range of mass-to-charge ratios undergo an even number of passages in the drift dimension by the time they are detected by the ion detector.

[0032] Ions passing through the mass analyzer will have different velocities in the drift dimension depending on their mass-to-charge ratio, i.e. ions with lower mass-to-charge ratios will have higher velocities in the drift dimension than ions with higher mass-to-charge ratios.

[0033] The control circuitry may be configured to maintain the first reflector active to reflect ions for a duration that begins when ions having the lowest mass-to-charge ratio within the first range first reach the first reflector, and that continues at least until ions having the highest mass-to-charge ratio within the first range have been reflected by the first reflector and made their final pass in the drift dimension.

[0034] The control circuitry may be configured to activate the second reflector starting when an ion having the highest mass-to-charge ratio within the first range passes through the second reflector for the first time after being injected into the mirror by the ion accelerator.

[0035] The control circuit may be configured to (i) keep the second reflector active until ions having the highest mass-to-charge ratio in the first range are reflected by the second reflector to begin their penultimate pass in the drift dimension, and (ii) deactivate the second reflector before ions having the lowest mass-to-charge ratio in the first range reach the second reflector during their final pass in the drift dimension, allowing the ions to reach the ion detector.

[0036] Ions may be made to pass, for example, 4, 6, 8, 10, or 12 (or any even number greater than 12) times along the drift dimension before being detected by the ion detector.

[0037] Alternatively, the ion detector may be located at a first end in the drift dimension of the mass analyzer, and the ion accelerator may be located at a second, opposite end in the drift dimension of the mass analyzer, and a first and second of the reflectors may be positioned between the ion accelerator and the ion detector in the drift dimension such that the first reflector is closer to the ion detector than the second reflector, and the timing at which the reflectors are activated and deactivated is such that ions within a first range of mass-to-charge ratios undergo an odd number of passages in the drift dimension in the time it takes for them to be detected by the ion detector.

[0038] Ions with lower mass to charge ratios will have higher velocities in the drift dimension than ions with higher mass to charge ratios.

[0039] The control circuit may be configured to (i) activate the first reflector to reflect ions at a time before the time when ions having the lowest mass-to-charge ratio in the first range first arrive at the first reflector, (ii) keep the first reflector active until ions having the highest mass-to-charge ratio in the first range are reflected by the first reflector to make their penultimate pass in the drift dimension, and (iii) deactivate the first reflector before ions having the lowest mass-to-charge ratio in the first range arrive at the first reflector during their final pass in the drift dimension, allowing the ions to reach the ion detector.

[0040] The control circuit may be configured to (i) activate the second reflector starting when ions having the highest mass-to-charge ratio in the first range pass through the second reflector for the first time after being injected into the mirror by the ion accelerator, and (ii) maintain the second reflector active until ions having the highest mass-to-charge ratio in the first range are reflected by the second reflector to make their final pass in the drift dimension.

[0041] It will be appreciated that the mass spectrometer may control the timing at which the first reflector is activated and deactivated so that ions undergo any odd number of passes along the drift dimension at which they are detected. For example, ions may be made to pass 3, 5, 7, 9, or 11 (or any odd number greater than 11) times along the drift dimension before they are detected at the ion detector.

[0042] A mass spectrometer disclosed herein may include a plurality of electrodes disposed between ion mirrors and spaced apart in a drift dimension such that ions pass between adjacent ones of the electrodes as they move between the mirrors, a first of the electrodes may be a first reflector, and the mass spectrometer may be configured to apply a first voltage to the first electrode when the first reflector is activated to reflect ions in the drift dimension, and to apply a different voltage to the first electrode when the first reflector is deactivated such that the first electrode and an adjacent one of the electrodes focus ions passing between them in the drift dimension. Alternatively or additionally, a second of the electrodes may be a second reflector, and the mass spectrometer may be configured to apply a second voltage to the second electrode when the second reflector is activated to reflect ions in the drift dimension, and to apply another voltage to the second electrode when the second reflector is deactivated, such that the second electrode and an adjacent one of the electrodes focus ions passing between them in the drift dimension.

[0043] A less preferred embodiment is also contemplated in which the time at which ions are pulsed out of the ion storage device is not synchronized with the time at which the ion accelerator pulses ions to select the range of mass to charge ratios to be mass analyzed.

[0044] Thus from a second aspect, the present invention provides a mass spectrometer comprising a first device for transmitting ions and a time-of-flight mass analyser, the mass analyser comprising a plurality of ion mirrors for reflecting ions, an ion accelerator positioned and configured to receive ions from the first device and pulse them to one of the ion mirrors so that the ions are reflected back and forth in the first dimension between the mirrors as they drift in the drift dimension, a reflector for reflecting ions in the drift dimension, an ion detector for detecting the ions, and control circuitry configured to activate the reflector to make multiple passes along the drift dimension and then deactivate one of the reflectors to allow the ions to pass to the ion detector and be detected, wherein the timing of the activation and deactivation of the reflector is such that only ions within a first range of mass to charge ratios undergo the same number of passes in the drift dimension at any time to be detected by the ion detector. The first device is configured to supply ions to the ion accelerator such that when the ion accelerator pulses ions into the one of the ion mirrors, only ions having mass-to-charge ratios within the first range are present in the ion accelerator.

[0045] A mass spectrometer according to the second aspect of the invention may have any of the features described in relation to the first aspect of the invention, but where there is no ion accelerator synchronized with the ion storage device, but instead the first device is provided to supply ions to the ion accelerator.

[0046] For example, the spectrometer may be configured such that a first device supplies ions having a range of mass-to-charge ratios to the ion accelerator, the first range being smaller than and within the range.

[0047] The first device may be a mass selective ion trap, and the mass spectrometer is configured to eject ions from the mass selective ion trap into an ion accelerator.

[0048] The operation of the mass selective ion trap may be synchronized with the time that ions are pulsed out of the ion storage device, so that only ions having a mass to charge ratio within the first range are pulsed into that one of the ion mirrors by the ion accelerator.

[0049] Alternatively, the first device may be a mass filter configured to transmit only ions having a mass to charge ratio within a range and filter out other ions, the first range being smaller than and within the first range.

[0050] The present invention provides a multi-reflecting time-of-flight mass spectrometer configured to reflect ions multiple times between ion mirrors in a first dimension, the ions also being reflected back and forth in the drift dimension by the reflector, the spectrometer being configured to activate and deactivate the reflector at times such that ions having a mass to charge ratio within a first range have undergone the same number of reflections in the drift dimension at the time they are detected, and the mass spectrometer is configured to allow only ions having a mass to charge ratio within the first range to enter the ion mirror.

[0051] The mass spectrometer may have any of the features described herein.

[0052] The present invention provides methods of mass spectrometry using the mass spectrometers described herein.

[0053] The present invention therefore provides a method of mass spectrometry comprising providing a mass spectrometer as described herein, supplying ions from an ion storage device, or a first device, to an ion accelerator, applying voltage pulses to electrodes of the ion accelerator to pulse ions to one of the ion mirrors so that the ions are reflected back and forth between the mirrors in the first dimension as the ions drift in the drift dimension, activating the reflector to make multiple passes along the drift dimension and then deactivating one of the reflectors to allow the ions to pass to an ion detector and be detected, wherein the timing of the activation and deactivation of the reflectors is such that only ions within a first range of mass to charge ratios undergo the same number of passes in the drift dimension at the time they are detected by the ion detector, [Brief explanation of the drawings]

[0054] Various embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0055] [Figure 1] 1 is a schematic diagram of a MRTOF mass analyzer operating in a known mode of operation. [Figure 2] 1 shows an MRTOF mass analyzer configured to operate in a multipass or zoom mode of operation. [Figure 3] FIG. 1 shows a schematic diagram of a portion of a mass spectrometer according to an embodiment of the present invention, in which ions undergo an even number of passes in the drift dimension before being detected. [Figure 4] FIG. 1 shows a schematic diagram of a portion of a mass spectrometer according to an embodiment of the present invention, in which ions undergo an odd number of passes in the drift dimension before being detected. [Figure 5]In the embodiment shown in FIG. 3, a timing diagram is shown illustrating an example of how the components of the spectrometer may be operated relative to one another. [Figure 6A] 1 shows the mass spectra obtained for the third isotope of leucine enkephalin using an embodiment of the present invention and using a conventional approach. [Figure 6B] 1 shows the mass spectra obtained for the third isotope of leucine enkephalin using an embodiment of the present invention and using a conventional approach. [Figure 6C] 1 shows a computer simulation of mass spectral data for the third isotope of leucine enkephalin. [Figure 7] 5 shows an embodiment that is substantially the same as the embodiment of FIG. 4, except that the drift dimension reflector is in a different position. DETAILED DESCRIPTION OF THE INVENTION

[0056] Figure 1 is a schematic diagram of an MRTOF mass analyser operating in a known mode of operation. The instrument comprises two ion mirrors 2 elongated in the drift dimension (i.e., the z dimension) for reflecting ions, an ion accelerator 4 for pulsing ions onto one of the mirrors, and a detector 6 for detecting ions at the end of their flight path through the mass analyser.

[0057] In use, an ion beam 8 enters the mass analyzer while traveling along the drift dimension and enters the ion accelerator 4. Voltages are applied to the electrodes of the ion accelerator to orthogonally accelerate packets of ions in the x dimension toward one of the ion mirrors 2. Thus, the ions have a velocity component in the x dimension and also maintain a velocity component in the drift dimension. Thus, the ions are injected toward the first of the ion mirrors at an angle to the x dimension. The ions pass through the first ion mirror and are reflected toward the second ion mirror. The ions then enter the second ion 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, with the ions continually being reflected between the two ion mirrors as they drift along the device in the drift dimension until they strike the ion detector 6. Thus, the ions follow a substantially sinusoidal average trajectory in the xz plane.

[0058] A series of ion lenses 10 are provided between the ion mirrors 2. Ions pass through these lenses as they travel between the ion mirrors, and the lenses are configured to provide an electric field that prevents the ion packets from expanding in the drift dimension to such an extent that the ion packets have a width in the drift dimension that is greater than the detection area of ​​the ion detector.

[0059] The mass analyzer determines the mass-to-charge ratio of the ions based on the duration between the time they are pulsed by the ion accelerator and their respective detection time at the ion detector.

[0060] It will be appreciated that as ions are reflected back and forth between the ion mirrors, this provides a relatively long ion flight path between the ion accelerator and the detector, whilst allowing the instrument to have a relatively small volume.

[0061] It is known to further increase the ion flight path length within a mass analyzer by reflecting ions in the drift dimension such that the ions make multiple passes along the mass analyzer in the drift dimension while being reflected multiple times between ion mirrors during each pass in the drift dimension, this mode being known in the art as a "multi-pass" or "zoom" mode of operation.

[0062] FIG. 2 shows an MRTOF mass analyzer configured to operate in a multi-pass or zoom mode of operation. The mass analyzer has the same configuration as described with respect to FIG. 1, except that an ion detector 6 is located at the same end (in the drift dimension) of the mass analyzer as the ion accelerator 4, and a drift dimension reflector 12 is located at the other end of the mass analyzer. In use, the ion accelerator 4 pulses ions onto one of the mirrors 2, and the ions are reflected back and forth between the mirrors in the same manner as described with respect to FIG. 1 until they reach the drift dimension reflector 12. The ions are then reflected in the drift dimension by reflector 12 to travel back toward the detector 6, and as they do so, are reflected back and forth between mirrors 2. The ions may then impinge on the ion detector 6. It will be appreciated that the use of the drift dimension reflector 12 doubles the flight path length of the ions.

[0063] 3 shows a schematic diagram of a portion of a mass spectrometer according to one embodiment of the present invention. The spectrometer includes an MRTOF mass analyzer and an ion storage device 14 configured to store ions and then periodically pulse ion packets 8 toward the MRTOF mass analyzer. Ion optics 16 may be positioned between the ion storage device 14 and the ion accelerator 4 of the MRTOF mass analyzer to transfer ions from the ion storage device to the MRTOF mass analyzer. The ion optics 16 may include, for example, at least one of an ion lens, one or more ion beam collimator plates, or an ion guide.

[0064] The MRTOF mass analyzer comprises two ion mirrors 2a, 2b extending along the drift dimension (z dimension) for reflecting ions, an ion accelerator 4 arranged to receive ions from a storage device 14 and pulse them onto one of the ion mirrors 2a, a first drift dimension reflector 12a at a first end of the mass analyzer for reflecting ions in the drift dimension, a second drift dimension reflector 12b at a second, opposite end of the mass analyzer for reflecting ions in the drift dimension, and an ion detector 6 for detecting ions.

[0065] In use, ions are accumulated in the ion storage device 14 and periodically pulsed out of the ion storage device in the drift dimension toward the MRTOF mass analyzer. These ions are received by the ion accelerator 4 of the MRTOF mass analyzer. As the ions pass through the ion accelerator, voltage pulses are applied to one or more electrodes of the ion accelerator, orthogonally accelerating packets of ions in the x dimension toward one of the ion mirrors 2a. As ions enter the mass analyzer in the drift dimension, they retain a velocity component in this direction and therefore exit the ion accelerator with an average ion trajectory that is tilted relative to the x dimension. Thus, ions have a dominant velocity component in the x dimension and also a velocity component in the drift dimension. Ions enter the first ion mirror 2a and are reflected toward the second ion mirror 2b. They then enter the second mirror 2b and are reflected back to the first ion mirror 2a. The first ion mirror then reflects the ions back to the second ion mirror. This continues, with the ions continually being reflected between the two ion mirrors as they drift along the mass analyzer in the z dimension until they reach the first drift dimension reflector 12a, located at the first end of the mass analyzer. At this point, the ions have undergone their first pass along the mass analyzer in the drift dimension. A static DC voltage can be applied to reflector 12a to reflect the ions in the drift dimension back towards the ion accelerator 4. The ions continue to be reflected between the two ion mirrors 2a, 2b as they drift back along the mass analyzer in the drift dimension until they strike the ion detector 6 at the second end of the mass analyzer. At this point, the ions have undergone two passes along the mass analyzer in the drift dimension. As is conventional in TOF mass analyzers, the mass analyzer determines the mass-to-charge ratio of the ions based on the duration between the time they are pulsed out by the ion accelerator 4 and their respective detection time at the ion detector 6.

[0066] It is contemplated that ions may make more than two passes along the mass analyzer in the drift dimension before being detected. Thus, instead of being allowed to strike the detector 6 in time for the ions to complete two passes along the mass analyzer, the ions may be reflected again in the drift dimension by the second drift dimension reflector 12b so that they make one or more additional passes along the mass analyzer in the drift dimension before striking the detector 6, with the ions being continually reflected between the two ion mirrors 2a, 2b as they make each pass.

[0067] In such an embodiment, ions can be made to undergo an even number of passes before being detected. In such an embodiment, the second drift dimension reflector 12b can be first activated after the ions first pass through the second drift dimension reflector 12b, i.e., after being injected into the mirror by the ion accelerator 4. The first drift dimension reflector 12a remains activated at least until all of the ions to be detected have been reflected by it to make their final pass in the drift dimension along the mass analyzer. After being activated, the second drift dimension reflector 12b must remain activated until all of the ions to be detected have been reflected by it to make their penultimate pass along the mass analyzer. The second reflector 12b must then be deactivated before the ions to be detected reach the second reflector during their final pass along the mass analyzer. This is necessary to allow the ions to reach the ion detector 6.

[0068] It will be appreciated that the mass spectrometer may control when the second reflector 12b is activated and deactivated so that an ion undergoes any even number of passages along the drift dimension at which it is detected, for example, an ion may undergo 4, 6, 8, 10, or 12 (or any even number greater than 12) passages along the drift dimension before being detected by the ion detector.

[0069] Alternatively, ions can be made to undergo an odd number of passes in the drift dimension by the time they are detected. FIG. 4 shows an example of such an embodiment. In these embodiments, the ion detector 6 is positioned at the first end of the mass analyzer, farther from the ion accelerator 4 than the first drift dimension reflector 12a. In these embodiments, the second drift dimension reflector 12b can be activated first after the ions have first passed through the second drift dimension reflector, i.e., after being injected by the ion accelerator 4 onto mirror 2a. The second drift dimension reflector 12b remains activated at least until all of the ions to be detected have been reflected by it to make their final pass along the mass analyzer. The first drift dimension reflector 12a must be activated before the ions to be detected first reach it. The first reflector 12a must remain activated until all of the ions to be detected have been reflected by it to make their penultimate pass along the mass analyzer in the drift dimension. The first reflector 12a must then be deactivated before the ions to be detected reach it during their final pass along the mass analyzer.

[0070] It will be appreciated that the mass spectrometer may control the timing at which the first reflector 12a is activated and deactivated so that an ion undergoes any odd number of passes along the drift dimension at which point it is detected. For example, an ion may be made to pass 3, 5, 7, 9, or 11 (or any odd number greater than 11) times along the drift dimension before it is detected by the ion detector 6.

[0071] It is contemplated that ion detectors may be located at both the first and second ends of the mass analyzer such that the mass analyzer can operate in a first mode in which ions have undergone an even number of passes at the time of their detection, and such that the mass analyzer can also operate in a second mode (at a different time than the first mode) in which ions have undergone an odd number of passes (greater than one) at the time of their detection.

[0072] It is also contemplated that in another mode, the mass analyzer may be controlled so that ions make only one pass along the mass analyzer before being detected. To implement such a mode, the ion detector is located at a first end of the mass analyzer, and the first and second deflectors are not activated.

[0073] One or more ion lenses 10 may be positioned between the ion mirrors 2a, 2b such that ions pass through one or more lenses as they move between the mirrors. The one or more lenses may be positioned such that ions pass through them during each pass in the drift dimension, i.e., when moving from the first end of the mass analyzer to the second end, and also when moving from the second end of the mass analyzer to the first end. To prevent each ion packet pulsed into the mass analyzer from diverging excessively in the drift dimension by the time the ions are detected, one or more voltages may be applied to one or more electrodes of the ion lenses to focus the ions passing therethrough in the drift dimension. For example, the one or more lenses may be configured to focus ions such that, by the time the ions impact the detector, the width of the ion packet in the drift dimension is smaller than the width of the detector's detection region. Additionally or alternatively, the one or more lenses may focus ions in the drift dimension to ensure that substantially all ions have experienced the same total number of mirror reflections during each pass along the drift dimension.

[0074] In embodiments including one or more ion lenses 10, the electrodes of the ion lenses may be controlled to perform the function of a first and / or second drift dimension reflector. For example, with reference to Figures 3 and 4, each ion lens may comprise two adjacent electrodes spaced apart in the drift dimension such that ions pass between the two electrodes as they are reflected from one mirror to another. The two electrodes may be maintained at substantially the same potential to focus ions in the drift dimension. However, if it is desirable to reflect ions in the drift dimension, the two electrodes may be maintained at different potentials to cause reflection of ions in the drift dimension.

[0075] However, it is contemplated that the mass analyser need not include one or more ion lenses 10 between the mirrors 2a, 2b.

[0076] By making multiple passes along the drift dimension before detection, the ion flight path length can be significantly increased, thus improving mass resolution and mass accuracy. This can be seen in the example shown in FIG. 3. For example, if an ion makes only one pass in the drift dimension before detection, the ion will undergo 14 mirror reflections before detection. If an ion makes only two passes in the drift dimension before detection, the ion will undergo 28 mirror reflections before detection. If an ion makes N passes in the drift dimension before detection, where N≧3, the ion will undergo [(N×13)+14] reflections. This is because the ion flight path is primarily composed of the distance ions travel when passing between ion mirrors, and this distance is much greater than the total distance ions travel in the drift dimension. Thus, in the illustrated example, the ion flight path is increased by approximately 1.9 times when ions make two passes compared to one pass before detection (i.e., 27 reflections divided by 14 reflections). Similarly, when N passes are made, the ion flight path increases by a factor of approximately [13(N-13)+14] / 14 compared to a single pass.

[0077] While allowing ions to make multiple passes along the drift dimension before detection is beneficial for increasing flight path length, it has been recognized that unless certain precautions are taken, this technique can result in different ions from the same ion packet arriving at the detector after traveling flight paths of different lengths. This is problematic because mass analyzers are configured to determine the mass-to-charge ratio of ions based on the duration between the time the ions are pulsed out by the ion accelerator and their respective detection times at the ion detector, assuming that the ions all travel the same flight path length. In other words, mass analyzers determine the mass-to-charge ratios of detected ions under the assumption that ions arrive at the detector in order of their mass-to-charge ratios and have arrival times at the detector related to their mass-to-charge ratios. However, if ions with relatively high mass-to-charge ratios travel shorter flight paths to the detector than ions with lower mass-to-charge ratios, these higher mass-to-charge ratio ions may be detected before the lower mass-to-charge ratios and therefore may be assigned too low a mass-to-charge ratio.

[0078] It can be difficult to control when a drift dimension reflector should be activated and deactivated so that all ions in an ion packet undergo the same number of passes (i.e., the same flight path length) upon detection. For example, a drift dimension reflector needs to be deactivated so that ions can reach the detector just before completing the desired number of passes. However, ions with higher mass-to-charge ratios move slower in the drift dimension than ions with lower mass-to-charge ratios. Therefore, just before a relatively low mass-to-charge ratio ion has completed the desired number of passes and the reflector needs to be deactivated, some higher mass-to-charge ratio ions may still need to be reflected by the reflector to ensure that they make the same desired number of passes as the relatively low mass-to-charge ratio ions. Therefore, in this situation, when a drift dimension reflector is deactivated to allow detection of lower mass-to-charge ratio ions, some higher mass-to-charge ratio ions will reach the detector through fewer passes than the relatively low mass-to-charge ratio ions. On the other hand, if the deactivation of the reflector is delayed to allow ions of higher mass to charge ratio to make the desired number of passes, the drift dimension reflector may reflect ions of lower mass to charge ratio to make more passes than desired.

[0079] As an example, referring to FIG. 3 , it may be desired that all of the ions undergo four passes in the drift dimension by the time they are detected. In other words, it may be desirable for the ions to travel from the ion accelerator 4 to the first drift dimension reflector 12a, be reflected back to the second drift dimension reflector 12b, be reflected back to the first drift dimension reflector 12a, and then be reflected back to the detector 6. In this example, the first drift dimension reflector 12a may remain activated the entire time the ions are in the mass analyzer, but the second drift dimension reflector 12b must be activated and deactivated as the ions pass through the mass analyzer. The second drift dimension reflector 12b may be deactivated at the time the ions are pulsed onto the first mirror 2a by the ion accelerator 4. The second drift dimension reflector 12b may remain deactivated until all of the ions have made their first pass through the second drift dimension reflector 12b (after being pulsed onto the mirror by the ion accelerator). The second drift dimension reflector 12b then on ions to the detector 6 at time T off It may remain activated until it is deactivated in

[0080] In this example, time T off is the mass-to-charge ratio M Low The time is selected so that an ion having a mass-to-charge ratio M Low ions with time T off Since they later reach the second drift dimension reflector, they proceed to the detector and are detected, just like ions with higher mass-to-charge ratios. Low Ions with lower mass-to-charge ratios are those with mass-to-charge ratios M Low ions have a higher velocity in the drift dimension than the ions of off, and while still activated. These lower mass-to-charge ratio ions are therefore reflected by the second drift dimension reflector 12b such that they are forced to make more than four passes in the drift dimension before being detected. By the time they are detected, these ions have reached a mass-to-charge ratio M Low This is undesirable as it will travel a longer flight path than ions with

[0081] M Low Ions with a mass-to-charge ratio higher than Low have a lower velocity in the drift dimension than the ions of M Low Ions with a mass-to-charge ratio substantially higher than off Therefore, these higher mass-to-charge ratio ions travel to the detector after only two passes in the drift dimension. At the time of detection, these ions have a mass-to-charge ratio M Low This is undesirable because it will travel a shorter flight path length than ions with

[0082] Therefore, the time T at which the second drift dimension deflector 12b is deactivated off In this case, the mass-to-charge ratio M High It will be appreciated that an ion having M has just made two passes in the drift dimension and has just been reflected in the drift dimension by the second drift dimension deflector. Low and M High Only ions having a mass-to-charge ratio between 0 and 1 undergo the same number of passes in the drift dimension, and therefore travel the same flight path length, when detected by the detector 6. It is therefore desirable to limit the range of mass-to-charge ratios that are pulsed by the ion accelerator 4 to the mass analyzer, to avoid the problems mentioned above.

[0083] The present invention limits the range of mass-to-charge ratios in the ion packets pulsed by the ion accelerator 4 to the mass analyzer so that the ions being mass analyzed undergo the same number of passes in the drift dimension at the time they are detected.

[0084] An embodiment of the present invention accomplishes this as follows: Ions are accumulated in an ion storage device 14 and then pulsed from this device toward an ion accelerator 4. The ions are transmitted from the ion storage device to the ion accelerator, optionally via ion optics 16, in such a way that the ions separate according to their mass-to-charge ratio as they pass toward the ion accelerator 4. For example, the region between the exit of the ion storage device 14 and the ion accelerator 4 may be substantially free of an electric field (in the average direction of ion movement). This region may also have a length and pressure such that collisions between ions and background gas molecules are relatively few or substantially absent. Ions of different mass-to-charge ratios enter the ion accelerator at different times. Therefore, the time at which the ion accelerator pulses ions onto the first mirror determines the range of mass-to-charge ratios that are mass-analyzed.

[0085] An embodiment of the present invention synchronizes the time at which the ion accelerator 4 pulses ions onto the first mirror 2a with the time at which ions are pulsed out of the ion storage device 14, so that only ions having mass to charge ratios within a preselected range are pulsed onto the first ion mirror 2a. This preselected range is the same range of mass to charge ratios as the range of mass to charge ratios that the mass analyzer is configured to perform the same number of passes in the drift dimension during mass analysis, i.e., M in the example above. Low From M High Alternatively, the preselected range may be narrower and lie within the range of mass to charge ratios for which the mass analyzer is configured to perform the same number of passes in the drift dimension during mass analysis.

[0086] Thus, the ion storage device 14 is controlled to help select and limit the range of mass-to-charge ratios that are mass analyzed. Furthermore, the use of an ion storage device to store and then pulse ions to the mass analyzer provides the mass analyzer with a relatively high quadrature sampling duty cycle.

[0087] The ion storage device 14 may comprise an ion guide, such as an RF ion guide, having a trapping electrode 18 at its downstream outlet. The mass analyzer can control the ion storage device 14 to operate in an ion storage mode, during which a voltage is applied to the trapping electrode 18 to prevent ions from exiting through the outlet. However, ions may pass into the upstream entrance of the ion guide during this mode. If it is subsequently desired to mass analyze the ions, the mass analyzer can control the ion storage device to operate in an ion ejection mode, during which the voltage applied to the trapping electrode 18 is changed to allow ions to exit through the outlet and proceed to the ion accelerator. In this mode, the voltage applied to the trapping electrode may extract ions from the ion guide, i.e., the trapping electrode may act as an extraction electrode. Additionally or alternatively, one or more electrodes of the ion guide may be maintained at a voltage to eject ions through the outlet. Ions may or may not be prevented from entering the ion storage device during the ejection mode.

[0088] The ion guide of the ion storage device 14 may be a linear ion guide having an elongated ion confinement volume, or the ion storage device may have other ion confinement structures.

[0089] The ion storage device 14 is -4 mbar~5×10 -2Ions can be accumulated in a region having a pressure in the mbar range. This can be useful for collisional cooling of ions before pulsing them into a mass analyzer. Additionally or alternatively, it is contemplated that the ion storage device may be, or form part of, an ion fragmentation cell. For example, the ion storage device may be, or form part of, a collision-induced dissociation (CID) device, an ion-ion reaction cell, or an electron-triggered dissociation device.

[0090] Figure 5 shows a timing diagram illustrating an example of how the ion storage device 14, ion accelerator 4, and second drift dimension reflector 12b may operate relative to one another in the embodiment shown in Figure 3. The top plot of Figure 5 shows an example of how the potential applied to the trapping electrode 18 of the ion storage device 14 may vary over time. It can be seen that the potential is typically kept high to trap ions in the ion storage device, but is briefly lowered to release the ions into the ion accelerator 4.

[0091] The middle plot in Figure 5 shows an example of how the potential applied to the electrodes of the ion accelerator 4 can vary over time. The potential is generally low so as not to cause the ion mirror 2 to pulse out ions. However, at time T after the potential applied to the trapping electrode 18 of the ion storage device 14 is reduced to eject the ions, pulse At , the potential applied to the electrodes of the ion accelerator 4 is increased for a short duration to pulse ions into the ion mirror 2. As mentioned above, for a duration T pulse is selected so that only ions having a particular range of mass to charge ratios are pulsed into the ion mirror 2. The time it takes for an ion to travel from the exit of the ion storage device 14 to the ion accelerator 4 may be proportional to the square root of the ion's mass to charge ratio. The exact value of this time will depend on the geometry of the ion storage device, ion optics and ion accelerator, but expected values ​​for an ion with a mass to charge ratio of 1000 are in the range of 5-500 μs.

[0092] The bottom plot of Figure 5 shows how the potential applied to the second drift dimension reflector 12b can vary over time in the embodiment shown in Figure 3, i.e., when an even number of passes are performed during detection. The potential applied to the second drift dimension reflector 12b is initially low, so that ions pulsed onto mirror 2 by the ion accelerator can pass through deflector 12b and travel to the first end of the mass analyzer. From the start of the ion accelerator pulse for a duration T on After this, the potential applied to the second drift dimension reflector 12b is increased so that it can reflect ions passing from the first end to the second end of the mass analyzer. on is chosen to be large enough so that ions with the highest mass-to-charge ratio to be detected have time to travel from the ion accelerator 4 through the second reflector 12b before the reflector 12b is activated. The time it takes for ions to travel this distance may be proportional to the square root of their mass-to-charge ratio, and therefore T on may also be proportional to the square root of the maximum mass-to-charge ratio detected.

[0093] Duration T on is also selected to be short enough so that deflector 12b is activated by the time that the ions with the lowest mass-to-charge ratio are reflected in the drift dimension by first drift dimension reflector 12a at the first end of the mass analyzer and first return to second drift dimension reflector 12b. on The exact value of depends on the geometry of the ion storage device, ion optics, and ion accelerator, but expected values ​​for ions with a mass-to-charge ratio of 1000 are in the range of 100-4000 μs (e.g., 750 μs).

[0094] The duration T from the start of the ion accelerator pulse off After time T, the potential applied to the second drift dimension reflector 12b is reduced so that the second reflector 12b is deactivated and ions can pass to the detector 6. offmay be selected to be the time just before the ions with the lowest mass to charge ratio arrive back at the second drift dimension reflector 12b after just completing the desired number of passes in the drift dimension. The exact value of this time depends on the geometry of the ion storage device, ion optics, and ion accelerator, but expected values ​​for ions with a mass to charge ratio of 1000 are in the range of 100-5000 μs.

[0095] As discussed above in connection with FIG. 4, embodiments are contemplated in which the ion detector 6 is located at the first end of the mass analyzer and ions have undergone an odd number of passes in the drift dimension when detected. Such embodiments are contemplated in which the second drift dimension reflector 12b is located at the T on The first drift dimension reflector 12a operates in a manner corresponding to that described above, except that it may remain activated afterward and does not need to be deactivated because ions do not proceed to the detector 6 at the second end of the mass analyzer. Rather, ions proceed to the detector at the first end of the mass analyzer, and therefore the first drift dimension reflector 12a must be deactivated at some time. More specifically, the first drift dimension reflector 12a must be activated before the ions having the lowest mass-to-charge ratio to be detected arrive at the first drift dimension reflector 12a, and deactivated just before those ions return to the first drift dimension reflector 12a after completing the desired number of passes in the drift dimension. However, the first drift dimension reflector 12a is not deactivated until the ions having the highest mass-to-charge ratio to be detected have been reflected by the first drift dimension reflector and have performed their penultimate pass in the drift dimension.

[0096] 6A-6B show the results of the synthesis of a third isotope of leucine enkephalin (C) using one embodiment of the type described above and using a conventional approach, respectively. 28 H 386A shows a mass spectrum obtained for NO (NO). FIG. 6A shows the absolute intensity of the ion signal as a function of mass-to-charge ratio. It can be seen that mass spectral data 20 obtained in accordance with an embodiment of the present invention is significantly more intense than mass spectral data 22 obtained in accordance with conventional techniques. The increased sensitivity of embodiments of the present invention is made possible by storing ions in an ion storage device.

[0097] Figure 6B shows the same mass spectral data as shown in Figure 6A, except that the intensities have been normalized. By comparing mass spectral data 20 and 22, it can be seen that embodiments of the present invention provide mass spectral data with higher mass resolution than conventional techniques, enabling, for example, the determination of fine isotopic structures.

[0098] Figure 6C shows the third isotope (C) of leucine enkephalin at a high resolution of 300,000 FWHM. 28 H 38 6A and 6B show computer simulations of mass spectral data for NO (NO). The data was generated using envipat.eawag.ch. By comparing FIG. 6A or FIG. 6B with FIG. 6C, it can be seen that the mass spectral data obtained in accordance with an embodiment of the present invention is in good agreement with the simulated high-resolution mass spectral data of FIG. 6C.

[0099] 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 therein without departing from the scope of the invention as set forth in the appended claims.

[0100] For example, although embodiments have been described in which ions undergo a particular number of mirror reflections and passes in the drift dimension before being detected, it will be appreciated that a different number of mirror reflections and / or passes may be implemented.

[0101] Additionally or alternatively, the locations of the first and / or second drift dimension reflectors within the mass analyzer may differ from those shown and described above. For example, Figure 7 shows an embodiment that is substantially the same as that of Figure 4, except that the first and second drift dimension reflectors 12a, 12b are spaced apart from the detector 6 and ion accelerator 4, respectively.

[0102] In some embodiments, a mass filter is provided upstream of the ion storage device 14 to mass filter the ions entering the storage device 14. The mass filter can be operated to transmit only ions having a mass-to-charge ratio within a specific range into the ion storage device 14. As described above, the mass analyzer of the embodiment can be configured so that only ions within a first range of mass-to-charge ratios undergo the same number of passes in the drift dimension in time as they are detected by the detector 6. Also, as described above, the synchronization between the pulsing of ions from the ion storage device 14 and the pulsing of ions to the mirror 2 using the ion accelerator 4 can be selected so that only ions having a mass-to-charge ratio within the first range are pulsed to the ion mirror 2. By providing a mass filter upstream of the ion storage device 14, the ion current entering the ion storage device 14 and the amount of charge per push of the ion accelerator 4 (for a given storage time) are reduced, thereby reducing space charge effects in the ion storage device and / or mass analyzer and improving the dynamic range. This can improve the mass accuracy and mass resolution of the instrument. The provision of a mass filter also allows a greater proportion of ions entering the ion storage device to have mass-to-charge ratios that correspond to those pulsed out by the ion accelerator.

[0103] The mass filter may be a quadrupole mass filter, although other types of mass filters may alternatively be used.

Claims

1. 1. A mass spectrometer comprising: an ion storage device that stores ions and outputs them in pulses; 1. A time-of-flight mass analyzer comprising: a plurality of ion mirrors that reflect ions; an ion accelerator positioned and configured to receive ions from the ion storage device and pulse them to one of the ion mirrors, such that the ions are reflected back and forth in a first dimension between the mirrors as they drift in a drift dimension; a reflector for reflecting the ions in the drift dimension; an ion detector for detecting ions; a control circuit configured to activate the reflectors to make multiple passes for the ions along the drift dimension and then deactivate one of the reflectors to allow the ions to pass to the ion detector and be detected, the timing at which the reflectors are activated and deactivated is such that only ions within a first range of mass to charge ratios undergo the same number of passes in the drift dimension at any time that they are detected by the ion detector; a control circuit for the mass spectrometer that synchronizes the time at which ions are pulsed from the ion storage device with the time at which ions are pulsed by the ion accelerator such that only ions having a mass to charge ratio within the first range are pulsed by the ion accelerator into the one of the ion mirrors.

2. 10. The mass spectrometer of claim 1, wherein the ions pulsed out of the ion storage device are configured to separate according to mass-to-charge ratio as they travel to the ion accelerator, such that ions of different mass-to-charge ratios enter the ion accelerator at different times.

3. 3. A mass spectrometer as claimed in claim 1 or 2, wherein the ion storage device comprises an ion guide having a trapping electrode at its downstream exit.

4. 4. The mass spectrometer of claim 1, wherein the mass spectrometer is configured to allow a user to select what the first range of mass to charge ratios is, and the control circuitry is configured to control, in response to the user selection, when the reflector is activated and deactivated and the time at which ions are pulsed out of the ion storage device relative to the time at which ions are pulsed out by the ion accelerator.

5. 5. The mass spectrometer of claim 1, wherein the mass spectrometer is configured to allow a user to select a number of passes the ions should make before detection, and the control circuit is configured to, in response to the selection by the user, control when the reflector is activated and deactivated, and the time at which ions are pulsed out of the ion storage device relative to the time at which ions are pulsed out by the ion accelerator, so that ions having the first range of mass to charge ratios undergo the selected number of passes before detection.

6. 6. A mass spectrometer according to any preceding claim, comprising a mass filter upstream of the ion storage device for mass filtering ions passing to the ion storage device.

7. 7. A mass spectrometer as claimed in claim 6, comprising control circuitry configured to control the mass filter to transmit only ions having a mass to charge ratio within a second range to the ion storage device, the first range being narrower than and within the second range.

8. 8. The mass spectrometer of claim 1, wherein a first of the reflectors is located at a first end of the mass analyzer in the drift dimension, the ion accelerator and ion detector are located at a second opposite end of the mass analyzer in the drift dimension, and a second of the reflectors is located in the drift dimension between the first reflector and the ion detector, and the timing of activating and deactivating the reflectors is such that ions within the first range of mass to charge ratios undergo an even number of passages in the drift dimension by the time they are detected by the ion detector.

9. 9. The mass spectrometer of claim 8, wherein the control circuitry is configured to maintain the first reflector active to reflect ions for a duration that begins when ions having the lowest mass to charge ratio in the first range first reach the first reflector, the duration lasting at least until ions having the highest mass to charge ratio in the first range are reflected by the first reflector and make their final pass in the drift dimension.

10. 10. The mass spectrometer of claim 8, wherein the control circuitry is configured to activate the second reflector starting when an ion having a highest mass to charge ratio in the first range passes through the second reflector for the first time after being injected into the mirror by the ion accelerator.

11. The control circuit (i) maintaining the second reflector active until ions having the highest mass to charge ratio within the first range are reflected by the second reflector to begin their penultimate pass in the drift dimension; 11. The mass spectrometer of claim 8, 9, or 10, configured to: (ii) deactivate the second reflector before ions having the lowest mass to charge ratio in the first range reach the second reflector during their final pass in the drift dimension to allow ions to reach the ion detector.

12. 8. The mass spectrometer of claim 1, wherein the ion detector is located at a first end of the mass analyzer in the drift dimension, the ion accelerator is located at a second opposite end of the mass analyzer in the drift dimension, a first reflector and a second reflector are located in the drift dimension between the ion accelerator and the ion detector such that the first reflector is closer to the ion detector than the second reflector, and the timing of activating and deactivating the reflectors is such that ions within the first range of mass to charge ratios undergo an odd number of passages in the drift dimension before being detected by the ion detector.

13. The control circuit (i) activating the first reflector to reflect ions at a time before the time at which ions having the lowest mass-to-charge ratio within the first range first arrive at the first reflector; (ii) maintaining the first reflector active until ions having the highest mass to charge ratio within the first range are reflected by the first reflector so as to make their penultimate pass in the drift dimension; 13. The mass spectrometer of claim 12, configured to: (iii) deactivate the first reflector before ions having the lowest mass to charge ratio in the first range reach the first reflector during their final pass in the drift dimension to allow ions to reach the ion detector.

14. The control circuit (1) activating the second reflector starting when an ion having a highest mass-to-charge ratio within the first range passes through the second reflector for the first time after being injected into the mirror by the ion accelerator; 14. A mass spectrometer as claimed in claim 12 or 13, configured to: (i) maintain the second reflector active until ions having the highest mass to charge ratio within the first range are reflected by the second reflector to make their final pass in the drift dimension.

15. a plurality of electrodes disposed between the ion mirrors and spaced apart in the drift dimension such that the ions pass between adjacent ones of the electrodes as they move between the mirrors; (i) a first electrode of the electrodes is the first reflector, and the mass spectrometer is configured to apply a first voltage to the first electrode when the first reflector is activated to reflect ions in the drift dimension, and to apply a different voltage to the first electrode when the first reflector is deactivated, such that the first electrode and an adjacent one of the electrodes focus ions passing therebetween in the drift dimension; 15. The mass spectrometer of claim 1, wherein (ii) a second one of the electrodes is the second reflector, and the mass spectrometer is configured to apply a second voltage to the second electrode when the second reflector is activated to reflect ions in the drift dimension, and to apply another voltage to the second electrode when the second reflector is deactivated, such that the second electrode and an adjacent one of the electrodes focus ions passing between them in the drift dimension.

16. 1. A mass spectrometer comprising: a first device for transmitting ions; 1. A time-of-flight mass analyzer comprising: a plurality of ion mirrors that reflect ions; an ion accelerator positioned and configured to receive ions from the first device and pulse them onto one of the ion mirrors, such that the ions are reflected back and forth in a first dimension between the mirrors as they drift in the drift dimension; a reflector for reflecting the ions in the drift dimension; an ion detector for detecting ions; a control circuit configured to activate the reflectors to make multiple passes for the ions along the drift dimension and then deactivate one of the reflectors to allow the ions to pass to the ion detector and be detected, the timing at which the reflectors are activated and deactivated is such that only ions within a first range of mass to charge ratios undergo the same number of passes in the drift dimension at any time that they are detected by the ion detector; the first device is configured to supply ions to the ion accelerator such that when the ion accelerator pulses ions into the one of the ion mirrors, only ions having a mass-to-charge ratio within the first range are present in the ion accelerator.

17. 17. The mass spectrometer of claim 16, wherein the first device is a mass selective ion trap, and the mass spectrometer is configured to eject ions from the mass selective ion trap into the ion accelerator.

18. 17. A mass spectrometer as claimed in claim 16, wherein the first device is a mass filter configured to transmit only ions having a mass to charge ratio within a range and filter out other ions, the first range being smaller than and within the first range.

19. a multi-reflecting time-of-flight mass spectrometer configured to reflect ions multiple times between ion mirrors in a first dimension, the ions also being reflected back and forth in a drift dimension by a reflector; the analyzer is configured to activate and deactivate the reflector at times such that ions having a mass to charge ratio within a first range have undergone the same number of reflections in the drift dimension at the time they are detected; The mass spectrometer is a multi-reflecting time-of-flight mass spectrometer configured to allow only ions having a mass-to-charge ratio within the first range to enter the ion mirror.

20. 1. A method of mass spectrometry comprising: Providing a mass spectrometer according to any one of claims 1 to 18; providing ions from the ion storage device or a first device to the ion accelerator; applying a voltage pulse to an electrode of the ion accelerator to pulse ions onto one of the ion mirrors such that the ions are reflected back and forth between the mirrors in a first dimension as the ions drift in the drift dimension; activating the reflectors to cause the ions to make multiple passes along the drift dimension and then deactivating one of the reflectors to allow the ions to pass to the ion detector and be detected, the timing of the reflector activation and deactivation being such that only ions within a first range of mass to charge ratios are allowed to undergo the same number of passes in the drift dimension at any time to be detected by the ion detector; wherein the ion storage device or the first device supplies ions to the ion accelerator such that when the ion accelerator pulses ions into the one of the ion mirrors, only ions having mass-to-charge ratios within the first range are present in the ion accelerator.

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