MASS SPECTROMETER AND METHOD FOR TIME-OF-FLIGHT MASS SPECTROMETRY

Abstract

A mass spectrometer comprising: a pulsed ion source for generating pulses of ions having a range of masses; a time-of-flight mass analyzer for receiving and mass analyzing the pulses of ions from the ion source; and an energy controlling electrode assembly located between the pulsed ion source and the time-of-flight mass analyzer configured to receive the pulses of ions from the pulsed ion source and apply a time-dependent potential to the ions thereby to control the energy of the ions depending on their m/z before they reach the time-of-flight mass analyzer. Mass dependent differences in average energy of ions can be reduced for injection into a time-of-flight mass analyzer, which can improve ion transmission and/or instrument resolving power.

Claims

1. A mass spectrometer comprising: a pulsed ion source for generating pulses of ions having a range of masses; a time-of-flight mass analyzer for receiving and mass analyzing the pulses of ions generated by the ion source; and an energy controlling electrode assembly, located between the pulsed ion source and the time-of-flight mass analyzer, positioned to receive the pulses of ions from the pulsed ion source and configured to apply a time-dependent potential to the ions, wherein the application of the time-dependent potential changes the energies of at least a portion of the ions to reduce the variation of ion energy with mass-to-charge ratio (m/z).

2. The mass spectrometer of claim 1, wherein the time-dependent potential is synchronised to the arrival times of ions whose energy is to be changed.

3. The mass spectrometer of claim 2, wherein the ions whose energy is to be changed are ions at the low mass end of the range of masses.

4. The mass spectrometer of claim 3, wherein the time-dependent potential lifts the energy of the ions at the low mass end of the range of masses.

5. The mass spectrometer of claim 1, wherein the pulsed ion source comprises an RF ion trap.

6. The mass spectrometer of claim 1, wherein the time-of-flight mass analyzer is a multi-reflection time-of-flight mass analyzer having a mass resolving power of at least 30,000.

7. The mass spectrometer of claim 6, wherein a total flight path length of the ions is at least 10 metres.

8. The mass spectrometer of claim 1, wherein the time-of-flight mass analyzer comprises two ion mirrors opposing each other in a direction X and both mirrors are generally elongated in a drift direction Y, orthogonal to direction X, wherein ions injected into the spectrometer are repeatedly reflected back and forth in the X direction between the mirrors whilst they drift down the Y direction of mirror elongation, the mirrors having a convergence with increasing Y, thereby creating a pseudo-potential gradient along the Y axis that acts as an ion mirror to reverse the ion drift velocity along Y.

9. The mass spectrometer of claim 1, wherein the energy controlling electrode assembly comprises a planar electrode oriented in a plane that is substantially orthogonal to the direction of travel of the ions and having an aperture therein through which the ions pass.

10. The mass spectrometer of claim 1, further comprising an electrode of lower potential than the pulsed ion source downstream of the energy controlling electrode assembly through which the ions pass.

11. The mass spectrometer of claim 10, wherein the electrode of lower potential through which the ions pass is a ground electrode.

12. The mass spectrometer of claim 1, wherein the time-dependent potential is a substantially linear voltage ramp.

13. The mass spectrometer of claim 1, wherein the time-dependent potential is a non-linear voltage ramp.

14. A method of time-of-flight mass spectrometry comprising: generating a pulse of ions from a pulsed ion source; mass analyzing the pulse of ions in a time-of-flight mass analyzer; and using an energy controlling electrode assembly located between the pulsed ion source and the time-of-flight mass analyzer to receive the pulses of ions from the pulsed ion source and apply a time-dependent potential to the ions, wherein the application of the time-dependent potential changes the energies of at least a portion of the ions to reduce the variation of ion energy with mass-to-charge ratio (m/z).

15. The method of claim 14, wherein the time-dependent potential is synchronised to the arrival times of ions whose energy is to be changed.

16. The method of claim 15, wherein the ions whose energy is to be changed are ions at the low mass end of the range of masses.

17. The method of claim 15, wherein the time-dependent potential lifts the energy of the ions at the low mass end of the range of masses.

18. The method of claim 14, wherein the time-of-flight mass analyzer is a multi-reflection time-of-flight mass analyzer having a total flight path length of the ions of at least 10 meters.

19. The method of claim 14, wherein the energy controlling electrode assembly comprises a planar electrode oriented in a plane that is substantially orthogonal to the direction of travel of the ions and having an aperture therein through which the ions pass.

20. The method of claim 14, wherein the time-dependent potential is a substantially linear voltage ramp.

Description

DESCRIPTION OF THE FIGURES

[0055] FIG. 1 shows schematically a plan view of an embodiment of a time of fight mass analyzer.

[0056] FIG. 2 shows schematically a perspective view of another embodiment of a time of fight mass analyzer.

[0057] FIG. 3 shows schematically a rectilinear trap pulsed ion source together with an ion optical arrangement comprising an energy controlling electrode assembly in accordance with the present invention.

[0058] FIG. 4 shows the simulated energy deviation of ions relative to a reference ion, caffeine (m/z=195), from the ion source shown in FIG. 3.

[0059] FIG. 5 shows the energy correction for ions using the energy controlling electrode assembly in accordance with the present invention shown in FIG. 3.

[0060] FIG. 6 shows the simulated relative ion transmission in a time-of-flight mass analyzer, with and without ion energy correction in accordance with the invention.

[0061] FIG. 7 shows the simulated relative resolving power of a time-of-flight mass analyzer, with and without ion energy correction in accordance with the invention.

DETAILED DESCRIPTION

[0062] The present invention will now be described in more detail by way of the following embodiments and with reference to the accompanying figures.

[0063] FIGS. 1 and 2 show schematically embodiments of multi-reflection time of flight mass spectrometers. The designs are described in detail in US 2015/028197 A (the contents of which is hereby incorporated by reference in its entirety).

[0064] As the designs are similar they will be described together for simplicity. The multi-reflection time-of-flight (mr-ToF) analyzers are constructed around two opposing ion mirrors, 71 and 72, generally elongated in a drift direction Y. A pulsed ion source 73 such as an extraction trap having quadrupole rods 111-1 and 111-2, injects ions into the first mirror 72 and the ions then oscillate between the mirrors. The ion beam is shaped by lenses (not shown) after leaving the extraction trap before being deflected by first and second deflectors 114 and 115 respectively. The angle of the extraction trap and additional deflectors, 114 and 115, allow control of the energy of the ions in the drift direction Y, such that ions are directed down the length of the mirrors as they oscillate, producing a zig-zag trajectory. The mirrors themselves are tilted relative to one another, producing a potential gradient that retards the ions' drift velocity (in the Y direction) and causes them to be reflected backwards in the drift direction and focused onto a detector 74, 117. The tilting of the opposing mirrors 71, 72 would normally have the negative side-effect of changing the time period of ion oscillations as they travel down the drift dimension. This is corrected with compensation electrodes 95, 96, 97, located in the space between the mirrors above and below the ion beam, that alter the flight potential for a portion of the inter-mirror space, varying down the length of the opposing mirrors. The combination of the varying width of the compensation electrodes and variation of the distance between the mirrors allows the reflection and spatial focusing of ions onto the detector 74, 117 as well as maintaining a good time focus. The design is advantageous in providing a high mass resolution by virtue of having a long, folded ion path, which may be over 25 m in length (distance travelled by ions from ion source to detector).

[0065] Generally, the only part of the mr-ToF analyzer that requires to be dynamically controlled is the pulsed ion source, i.e. the extraction trap in these embodiments, as it has dynamic voltages to trap ions and subsequently to inject them into the analyzer. All other voltages are static during normal instrument operation.

[0066] Although, a specific mr-ToF design is shown in FIGS. 1 and 2, it will be understood that the invention is applicable to other designs of time of flight mass analyzer.

[0067] The pulsed ion source shown is an RF linear ion trap containing some buffer gas, such as argon for example, at pressures typically of 510.sup.4 to 110.sup.2 mbar. The trap has the ability to quickly switch off RF and apply voltages to extract the trapped ions. The so-called C-Trap, a curved linear ion trap, is one example of a suitable extraction trap for a pulsed ion source.

[0068] An extraction trap, in the form of either a linear or 3D ion trap, is not the only possible ion source for the mr-ToF. In principle, a more traditional orthogonal accelerator as found in standard commercial ToF instruments may be used, or a MALDI ion source may be used.

[0069] A preferred ion source for the mr-ToF embodiments shown is a similar linear trap but constructed of flat plates (a so-called rectilinear trap or R-Trap). There is description of the R-trap and extraction method in U.S. Pat. No. 9,548,195 (B2) (the contents of which is hereby incorporated by reference in its entirety).

[0070] Referring to FIG. 3, there is shown more detail of a rectilinear trap pulsed ion source together with an ion optical arrangement comprising an energy controlling electrode assembly in accordance with the present invention.

[0071] Ions are extracted from a rectilinear ion trap 2 having a 2 mm inscribed radius, with a 4 KV applied DC potential. A trapping RF voltage (1 KV peak-to-peak) is applied, which is quenched before extraction and 750V (relative to the 4 KV) is applied to push and pull electrodes 4 and 6 above and below the centre of the trap (in the ion flight direction), thereby creating a strong field gradient and accelerating ions out of a 0.6 mm8 mm slot 8 in the pull electrode 6, the slot being elongated in the direction of the trap length. In this example the extraction potential has a 100 ns (nanosecond) rise time.

[0072] An energy controlling electrode 10, which may also be termed an energy correcting electrode, comprising a metal plate 1 mm thick provided with a 4 mm high slot, is located 2 mm downstream from the 2 mm thick pull electrode (the thickness of the plate and height of the slot being shown in the plane of the page). The slot width in the dimension perpendicular to the page is greater than its height and accommodates substantially the full width of the ion beam. Alternatively to a metal plate, a non-metallic plate having a metallic coating may be used as the energy controlling electrode. The plate electrode is planar and oriented in a plane that is substantially orthogonal to the direction of travel of the ions as shown by the arrow.

[0073] In use, for energy correction, a voltage ramp can be applied to the electrode 10, which starts with +690 V applied at the point of extraction and ramps linearly to +1240V after 245 nanoseconds. After this 245 ns rise period a constant +1240 V is applied. The correcting electrode 10 serves an additional purpose of shaping the extracted ion beam, with +1240V being the optimum value. Ions extracted from the pull electrode accelerate through the voltage gradient between the two electrodes, and then further accelerate to their full 4 KV flight potential as they enter a 1 mm to 2 mm slot of a grounded electrode 12 located a further 8 mm downstream from the correcting electrode 10. The grounded electrode enables bringing the ions up to their flight energy of 4 KV. Thereafter, the ions enter the time of flight mass analyzer (optionally after one or more stages of deflection to align the ion beam). The grounded electrode may be a thin plate with an entrance slot, preferably followed by a deflector region. The entrance slot is preferably relatively small (e.g. 2 mm high12 mm wide), typically smaller in cross sectional area than the aperture in the energy correcting electrode, to reduce gas leakage into the time of flight mass analyzer which lies downstream. The deflector region preferably includes at least one ion deflector to provide a desired injection angle for the ions into the ToF analyzer.

[0074] FIG. 4 shows the simulated energy deviation of ions relative to a reference ion, caffeine (m/z=195), from the ion trap source with 2 mm inscribed radius and 100 ns rise time on a 375 V/mm extraction field. The invention provides the solution of applying a voltage gradient (vs time) to the correcting electrode located down the ion flight path from the ion source. A simulation based on the above described electrode assembly and voltages was made and ion energies (relative to m/z=195) at different masses measured with and without the applied voltage gradient on the energy correcting electrode 10. The 550V voltage ramp with 245 ns rise time applied to the energy correcting electrode was demonstrated to remove much of the energy perturbation from ions m/z=50-150 as shown in FIG. 5. Further simulation of a full time of flight mass analyzer incorporating the above described ion source and ion optical arrangement showed a substantial reduction in mass related transmission losses (see FIG. 6) together with an improvement in resolving power (see FIG. 7). Correspondingly, the mass range of the instrument can also be extended.

[0075] It will be appreciated that the invention may be implemented in numerous variants of the above described embodiments. The example above uses a single energy controlling electrode positioned immediately after, i.e. in front of, the pulsed ion trap so that the energy controlling electrode assembly also serves as a spatial focusing device or lens, but the energy controlling electrode assembly could be incorporated somewhere further down the ion path where there is space to include the ion optical arrangement for the purpose of energy adjustment. More preferably, the energy correcting electrode should be located at or near an isochronous plane, and most preferably at the first time focus or focal plane (which lies before the ToF analyzer), as otherwise ions at different m/z will be poorly separated in space, giving ions with the same m/z an additional energy dispersion, shifting and distorting the subsequent ToF focii. In a preferred embodiment, therefore, the energy correcting electrode assembly is located at or near an isochronous focal plane upstream of the ToF analyzer, especially the first isochronous focal plane. The assembly may even be included within the time-of-flight analyzer itself, although this is disadvantageous compared to locating it at or near the first time focus or focal plane, upstream of the ToF analyzer.

[0076] The energy controlling electrode assembly need not be provided or activated in one stage, i.e. a plurality of energy adjusting stages may be provided. The plurality of energy adjusting stages may be provided at different times (e.g. one energy controlling electrode assembly operated at different times) and/or at different locations, i.e. at different energy controlling electrode assemblies.

[0077] The applied potential lift, i.e. voltage ramp, need not be linear with respect to time. In fact, a non-linear voltage lift wherein a voltage gradient diminishes with time would typically be better to match the initial mass related energy perturbation of the ions. It is, however, much simpler to implement a linear or an approximately linear voltage ramp, which can be achieved by using a single electronic switch between two voltage levels (e.g. one of which may be ground) and an RC circuit with an appropriate RC time constant to control the rate of change of voltage on an electrode. The most preferable practical embodiment would be to have a single correction electrode, with a linear voltage ramp. The voltage ramp may be either between two high voltages and starting at the point of time of ion extraction from the ion source (e.g. when the extraction pulse is applied), or between ground and a high voltage with a suitable delay between the start of the voltage ramp and the point of extraction (i.e. the correction ramp starts before the ion extraction).

[0078] The invention allows an improvement in the transmission and resolution of time-of-flight instruments, particularly in advanced time-of-flight designs that may have a more limited acceptance of ion energy ranges, since the invention can ensure that ion energy related losses in transmission and resolution are better controlled. The invention is especially useful for time-of-flight mass spectrometers requiring a range (spread) of ion energies that is less than 5%, or less than 3% of the average energy of the ions (e.g. 200 eV or less, or 100 eV or less, for a 4 kV flight energy of ions).

[0079] As an alternative to the multi-reflection time of flight (mr-TOF) mass analyzer shown in FIGS. 1 and 2, the present invention may comprise another type of time of flight mass analyzer. A linear TOF mass analyzer could be used. A racetrack type of TOF mass analyzer could be used (e.g. with an oval or figure of eight ion beam path). However, a mr-TOF mass analyzer is preferably used. Other types of mr-TOF mass analyzer that could be used may include, for example, one of the following types: [0080] A mr-TOF mass analyzer comprising an arrangement of two parallel opposing mirrors, as described by Nazarenko et. al. in patent SU1725289. In such embodiments, the mirrors are elongated in a drift direction and ions followed a zigzag flight path, reflecting between the mirrors and at the same time drifting relatively slowly along the extended length of the mirrors in the drift direction. Each mirror can be made of parallel bar electrodes. [0081] A mr-TOF mass analyzer comprising parallel opposing gridless ion mirrors, for example as described by Wollnik in GB patent 2080021. Two rows of mirrors in a linear arrangement or two opposing rings of mirrors can be arranged. Some of the mirrors may be tilted to effect beam injection. [0082] A mr-TOF mass analyzer comprising a gridded parallel plate mirror arrangement elongated in a drift direction, as described by Su in International Journal of Mass Spectrometry and Ion Processes, 88 (1989) 21-28. The opposing ion reflectors can be arranged to be parallel to each other and ions follow a zigzag flight path for a number of reflections before reaching a detector. [0083] A mr-TOF mass analyzer comprising periodically spaced lenses located within a field free region between two parallel elongated opposing mirrors as described by Verentchikov in WO2005/001878 and GB2403063. The purpose of the lenses is to control the beam divergence in the drift direction after each reflection, thereby enabling a longer flight path to be obtained. [0084] A mr-TOF mass analyzer comprising a system for beam focusing in the drift direction for a multi-reflection elongated TOF mirror analyzer, as described by Makarov et al in WO2009/081143. In such embodiments, a first gridless elongated mirror is opposed by a set of individual gridless mirrors elongated in a perpendicular direction, set side by side along the drift direction parallel to the first elongated mirror. The individual mirrors provide beam focusing in the drift direction. [0085] A mr-TOF mass analyzer comprising a system for beam focusing in the drift direction comprising elongated parallel opposing mirrors as described by Verentchikov and Yavor in WO2010/008386. In this arrangement, periodic lenses are introduced into one or both the opposing mirrors by periodically modulating the electric field within one or both the mirrors at set spacings along the elongated mirror structures. [0086] A mr-TOF mass analyzer as described by Ristroph et al in US2011/0168880 comprising opposing elongated ion mirrors that comprise mirror unit cells, each having curved sections to provide focusing in the drift direction and to compensate partially or fully for a second order time-of-flight aberration with respect to the drift direction. [0087] A mr-TOF mass analyzer comprising two parallel gridless mirrors and further comprising a third mirror oriented perpendicularly to the opposing mirrors and located at the distal end of the opposing mirrors from the ion injector as described by Sudakov in WO2008/047891.

[0088] As used herein, including in the claims, unless the context indicates otherwise, singular forms of the terms herein are to be construed as including the plural form and vice versa. For instance, unless the context indicates otherwise, a singular reference herein including in the claims, such as a or an means one or more.

[0089] Throughout the description and claims of this specification, the words comprise, including, having and contain and variations of the words, for example comprising and comprises etc, mean including but not limited to and are not intended to (and do not) exclude other components.

[0090] It will be appreciated that variations to the foregoing embodiments of the invention can be made while still falling within the scope of the invention. Each feature disclosed in this specification, unless stated otherwise, may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0091] The use of any and all examples, or exemplary language (for instance, such as, for example and like language) provided herein, is intended merely to better illustrate the invention and does not indicate a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.