Patent Application
20210134582
This application claims priority from and the benefit of United Kingdom patent application No. 1807626.5 filed on 10 May 2018. The entire content of this application is incorporated herein by reference.
The present invention relates generally to Multi-Reflecting Time of Flight (MRTOF) mass analysers or mass separators, and in particular to techniques for controlling the number of ion reflections between the ion mirrors.
Time of Flight (TOF) mass analysers pulse ions into a time of flight region towards a detector. The duration of time between an ion being pulsed and being detected at the detector is used to determine the mass to charge ratio of that ion. In order to increase the resolving power of a time-of-flight mass analyser it is necessary to increase the flight path length of the ions.
Multi-reflecting TOF mass analysers are known in which ions are reflected multiple times between ion mirrors in a time of flight region, so as to provide a relatively long ion flight path to the detector. A periodic lens it provided between the ion mirrors so as to control the trajectories of the ions through the analyser so as to ensure that all ions are reflected the same number of times between the ion mirrors and hence travel the same flight path length. However, the periodic lens introduces aberrations to the ion flight times, which restricts the resolving power of the instrument. For example, positive aberrations to the ion flight time may be introduced for ions that travel close to the elements of the periodic lens (“orthogonal aberrations”), since it normally takes these ions longer to travel through the lens system. Negative orthogonal aberrations may also occur if so called immersion lens elements are used. Such immersion lens elements may be arranged in acceleration or deceleration elements of ion optics, and particularly, in ion mirrors. It is difficult to compensate for these aberrations due multiple interfering parameters.
From a first aspect the present invention provides a mass spectrometer comprising: an ion energy filter arranged and configured to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; and a multi-reflecting time of flight mass analyser or mass separator having an ion accelerator, and two gridless ion mirrors that are elongated in the first dimension (z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (x-dimension), wherein the ion accelerator is arranged to receive ions from the energy filter and accelerate the ions into one of the ion mirrors.
The ion accelerator may pulse the ions into the first ion mirror as a series of ion packets and towards a detector. Ions in the different packets may be received over the same area of the detector.
The ion accelerator in a multi-reflecting time of flight (MRTOF) mass analyser or mass separator is arranged and configured for accelerating ions into a first of the ion mirrors at an angle to the second dimension (x-dimension) such that the ions are repeatedly reflected between the ion mirrors in the second dimension (x-dimension) as they drift through the mass analyser or separator in the first dimension (z-dimension). The energy filter filters out ions having kinetic energies in the first dimension that are outside of the selected/desired range. This reduces the spread of ion velocities, in the first dimension, of the ions that are received in the mass analyser or mass separator. As such, this reduces the expansion of the ion beam in the first dimension, within the mass analyser or separator, so that the ions are reflected the same number of times between the ion mirrors. This ensures that the flight path lengths that the ions travel through the mass analyser or separator are substantially the same. In the mass analyser embodiments, this may prevent ions being assigned the wrong mass to charge ratio and improves the mass resolution.
It has previously been contemplated to introduce ions into the space between the ion mirrors in an MRTOF mass spectrometer by using various ion optical devices, such as an electric sector. It is also known to perform some energy filtering of the ions. However, previously, the energy filtering has been performed to filter the ion energy in the direction between the ion mirrors (x-dimension), after the ions have already been accelerated to their time of flight energy. In contrast, the embodiments of the present invention energy filter the ions before the ions are accelerated to their time of flight energies. The energy filtered ions may therefore have a relatively low energy spread in the first dimension (z-dimension) before being accelerated to their time of flight energies by the ion accelerator, e.g. an energy spread of 0.1-1 eV. The embodiments form ions having a desired phase-volume (i.e. spread of velocities and spatial distributions) for introduction into the mass analyser or separator.
As far as the inventors are aware, it is not known to control the drift velocity/energy of the ions entering the mass analyser to be within a range such that the ions perform the same number of ion reflections between the ion mirrors.
For the avoidance of doubt, a gridless ion mirror as used herein is an ion mirror that does not have any grid electrodes arranged in the ion path within the ion mirror. The use of gridless ion mirrors enables ions to be reflected multiple times within the ion mirrors without the mirrors attenuating or scattering the ion beam, which may be particularly problematic in MRTOF instruments.
The spectrometer of the present invention may comprise a controller for controlling the energy filter so as to only onwardly transmit ions having said component of kinetic energy in the first dimension (z-dimension) within the selected range such that substantially all of these transmitted ions are reflected the same number of times, N, between the ion mirrors. The controller may control the voltages applied to electrodes of the energy filter to achieve this.
Said same number of reflections, N, may be: ≥8; ≥9; ≥10; ≥11; ≥12; ≥13; ≥14; ≥15; ≥16; ≥17; ≥18; ≥19; or ≥20.
It would not be desirable to reflect ions this many times in instruments having gridded mirrors, since the ion losses would be very large. It is known to reflect ions between gridless mirrors in an MRTOF mass analyser many times in order to provide long ion flight path lengths. However, in order to ensure that all ions undergo the same, high number of reflections, it has been necessary to provide periodic focusing of the ions in the dimension that the mirrors are elongated. In contrast, embodiments herein use the ion energy filter to ensure that the transmitted ions perform the same number of reflections.
It is contemplated that the number of reflections N may be numbers other than those described above, such as N≥5, N≥6 or N≥7.
Optionally, substantially all ions having a component of kinetic energy in a first dimension (z-dimension) that is outside of the selected range would be reflected between the mirrors a number of times other than N, were they to be transmitted into the mass analyser or mass separator.
The selected energy range that is transmitted by the energy filter into the mass analyser or mass separator is therefore as broad as possible, whilst ensuring that all transmitted ions undergo the same number of N reflections. The energy filter is therefore optimised for the configuration of the mass analyser or mass separator, whilst maintaining relatively high transmission/sensitivity.
The energy filter may be configured to only transmit ions having a kinetic energy in the first dimension (z-dimension) that is above a first threshold value; and/or the energy filter may be configured to only transmit ions having a kinetic energy in the first dimension (z-dimension) that is below a second threshold value.
The energy filter may be configured to only transmit ions having a kinetic energy spread, in the first dimension (z-dimension), that is selected from: ≤5 eV; ≤4 eV; ≤3 eV; ≤2 eV; ≤1 eV; ≤0.9 eV; ≤0.8 eV; ≤0.7 eV; ≤0.6 eV; ≤0.5 eV; ≤0.4 eV; ≤0.3 eV; ≤0.2 eV; or ≤0.1 eV.
The energy filter may comprise at least one electrostatic sector for filtering ions according to their kinetic energy. The electrostatic sector may comprise a cylindrical, spherical or toroidal shaped sector.
The energy filter may comprise an ion entrance, an ion exit, and at least two axially spaced electrodes arranged therebetween, and the energy filter may be configured to arrange a potential difference between the electrodes that urges ions in a direction from the ion exit to the ion entrance for filtering the ions according to their kinetic energy.
This allows relatively high energy ions to pass through the energy filter but not relatively low energy ions, thereby reducing the range of energies that are onwardly transmitted by the energy filter. The electrodes may be grid or mesh electrodes arranged such that the ions pass through the holes in the grid or mesh. The diameter of the ion beam received at the grid or mesh electrodes may be larger than the holes in the grid or mesh electrodes. Alternatively, the electrodes may be apertured electrodes having apertures through which the ions pass, wherein the apertures are larger than the ion beam. Other electrode arrangements are also contemplated, such as axially segmented multipole rod sets or plate electrodes, wherein different voltages are applied to the different axial segments so as to provide the potential difference.
The energy filter may be configured such that ions travel therethrough along a central axis, and the electrodes may be arranged and configured such when the potential difference is arranged between them it provides an axial potential barrier that increases as a function of radial distance from the central axis.
Alternatively, or additionally, the electrodes may be are arranged and configured such when the potential difference is arranged between them it results in curved equipotential field lines that allow ions having a first kinetic energy and travelling along a central axis of the energy filter to be onwardly transmitted by the energy filter, but deflect ions having the first kinetic energy and travelling radially outward of the central axis so as not to be onwardly transmitted by the energy filter. This arrangement helps to skim off peripheral ions and form a narrow ion beam without using diaphragms. As a result, contamination and charging of the electrode surfaces may be avoided, providing robust beam parameters.
Said electrodes may comprise a first electrode arranged towards the ion entrance, a second electrode arranged towards the ion exit, and a third electrode arranged between the first and second electrodes. The energy filter may be configured to maintain the first and second electrodes at the same potential and the third electrode at a different potential.
The energy filter herein may be configured to receive ions along an ion entrance axis that is coaxial with, parallel to, or angled to the ion exit axis of the energy filter. The ions may travel in the same direction when entering and exiting the energy filter. Alternatively, the ions may travel in different or opposite directions when entering and exiting the energy filter (e.g. in a sector energy filter).
The ion accelerator may pulse the ions into the first ion mirror as ion packets.
The ion accelerator may be an orthogonal accelerator.
The ion accelerator may be an orthogonal accelerator configured to receive ions along an ion receiving axis and accelerate those ions orthogonally to the ion receiving axis; and wherein either: (i) the ion receiving axis is parallel to the first dimension (z-dimension) and the energy filter ion exit axis is parallel to the first dimension (z-dimension); or (ii) the ion receiving axis is at an acute angle to the first dimension (z-dimension) and the energy filter ion exit axis is at an acute angle to the first dimension (z-dimension). In both cases, the ion exit axis of the energy filter may be coaxial with the ion receiving axis of the orthogonal accelerator.
The mass analyser or separator may comprise a deflection module configured to deflect the average trajectory of the ions leaving the ion accelerator towards the second dimension (x-dimension) so as to reduce the velocity component of these accelerated ions in the first dimension (z-dimension).
This enables the ions to perform a greater number of ion mirror reflections as they drift through the mass analyser or separator in the first dimension than would otherwise occur if the ion trajectory was not altered.
The deflection module may comprise two electrodes that are axially spaced in the first dimension, through which the ions pass in use, and voltage supplies connected to these electrodes so as to deflect the ions as described herein.
The ion accelerator may be an orthogonal accelerator configured to receive ions along an ion receiving axis that is arranged at an acute angle to the first dimension (z-dimension), wherein the deflection module is configured to deflect the average trajectory of the ions leaving the ion accelerator towards the second dimension (x-dimension) by said acute angle.
The may comprise an ion cooling device upstream of the energy filter for reducing the average energy of the ions received by the energy filter.
This enables the phase-volume of the ion beam to be reduced and a relatively large concentration of ions to be transmitted through the energy filter towards the mass analyser/separator, potentially increasing the duty cycle of the instrument.
The ion cooling device may be a collisional cooling cell configured to be maintained at a gas pressure such that ions collide with gas in the cell to reduce their energy.
The cooling cell may be maintained at a higher pressure than directly adjacent upstream and/or downstream regions. The cooling cell may have a dedicated gas supply of collisional gas. The cooling cell may comprise an ion guide.
Alternatively, other forms of ion cooling device may be used, such as laser cooling.
The spectrometer may be configured to accelerate ions from the ion cooling cell to the energy filter and/or from the ion cooling cell to the ion accelerator.
The mass analyser or separator may be configured such that ions are substantially not spatially focused and/or collimated in the first dimension (z-dimension) as the ions travel between the ion mirrors. Alternatively, or additionally, the mass analyser or separator may be configured such that there are substantially no aberrations due to spatial focusing in the first dimension (z-dimension) as the ions travel between the ion mirrors
For example, the spectrometer may be configured such that ions are substantially not spatially focused and/or collimated in the first dimension (z-dimension) within the mass analyser or separator; or are substantially not spatially focused and/or collimated in the first dimension (z-dimension) within the mass analyser or separator after the first ion-mirror reflection.
This is in contrast to conventional MRTOF mass analysers, which include a periodic lens array between the ions mirrors for focusing ions in the first dimension (z-dimension). Embodiments of the present invention therefore avoid the time of flight aberrations associated with periodic lens arrays.
The ion accelerator may be configured to pulse ions in a series of pulses, wherein the timings of the pulses are determined by an encoding sequence that varies the duration of the time interval between adjacent pulses as the series of pulses progresses; and wherein the spectrometer comprises a processor configured to use the timings of the pulses in the encoding sequence to determine which ion data detected at a detector relate to which ion accelerator pulse so as to resolve spectral data obtained from the different ion accelerator pulses.
The ion accelerator may be configured to pulse ions towards the detector at a rate such that some of the ions pulsed towards the detector in any given pulse arrive at the detector after some of the ions that are pulsed towards the detector in a subsequent pulse.
The two ions mirrors may be configured to reflect ions over substantially the same length in the first dimension (z-dimension). This enables a relatively high number of reflections, and simplifies construction and operation of the instrument.
The mass analyser or mass separator may comprise an ion accelerator for accelerating ions into one of the ion mirrors and that is arranged between the ion mirrors; and/or may comprise an ion detector for detecting ions after having been reflected by the ion mirrors and that is arranged between the ion mirrors.
The arrangement of the ion accelerator and/or detector between the ion mirrors enables the effect of the fringe fields of the ion mirrors on the ions to be avoided.
The ion accelerator and/or detector may be arranged substantially midway, in the second dimension (x-dimension) between the ion mirrors. This may facilitate the use of simple ion mirrors. For example, the ions mirrors may be substantially symmetrical about a plane defined by the first dimension and a third dimension that is orthogonal to the first and second dimensions (i.e. the y-z plane).
To minimize aberrations due to the spread of ions in the first dimension (z-dimension), the gridless mirrors may not vary in size or electrical potential along the first dimension, except for at the edges of the mirror (in the first dimension).
The means for directing the ions into the mirror (e.g. the ion accelerator) may be arranged so that the first point of ion entry into either ion mirror is spaced from the leading edge of that ion mirror, in the first dimension, such that all ions travelling through the mirror have the same conditions independent of their coordinate in the first dimension.
Alternatively, or additionally, the means for receiving the ions from the mirrors (e.g. the detector) may be arranged so that the final point of ion exit from either ion mirror is spaced from the trailing edge of that ion mirror, in the first dimension, such that all ions travelling through the mirror have the same conditions independent of their coordinate in the first dimension.
For example, the mass analyser or mass separator may be configured such that the first point of ion entry into either ion mirror is at a distance from both ends of that ion mirror, in the first dimension (z-dimension), that is greater than 2H, where H is the largest internal dimension of the ion mirror in a third dimension (y-dimension) that is orthogonal to the first and second dimensions. The final point that the ions exit either mirror may also be a distance from both ends of that ion mirror, in the first dimension (z-dimension), that is greater than 2H.
The ion mirrors may have translation symmetry along first dimension (z-dimension), i.e. no changes in size between the points at which the ions first enter and finally exit the ion mirror. This helps avoid perturbations in first-dimension.
The mass analyser or separator may be housed in a housing and the spectrometer may further comprise an ion source, and/or at least one ion manipulation device, mounted to or arranged adjacent a wall of the housing. The spectrometer may be configured to transmit ions from the ion source, and/or through the at least one ion manipulation device, in a first direction and then turn the ions in a second, opposite direction and into the mass analyser or separator.
This arrangement allows the spectrometer to have a compact design.
The housing may be a vacuum chamber in which the mass analyser or separator is arranged.
The wall may be arranged in a plane defined by the first and second dimensions (X-Z plane).
The first and second opposite directions may be in the z-dimension and/or in a plane defined by the first and second dimensions (X-Z plane).
The at least one ion manipulation device may be any at least one, or any number, of the following devices: an ion guide; a mass filter, such as a quadrupole mass filter; an ion mobility separator; an ion trap; a fragmentation device, such as a CID collision cell; a/the cooling cell for reducing the energy spread of the ions; an ion lens; or an ion acceleration device.
The at least one ion manipulation device may comprise one or more vacuum chamber that is mounted to or arranged adjacent the wall of the housing.
The energy filter may perform the function of turning the ions in the second, opposite direction and into the mass analyser or separator. For example, an energy filter comprising one or more electrostatic sector may be used to do perform this. However, it is contemplated that any other means may be used, such as one or more curved multipoles, one or more curved collision cell, or one or more sets of deflection means (with and without energy-filtering properties).
The mass analyser described herein may comprise a time of flight ion detector.
The above-described compact arrangement of the mass spectrometer is considered to be novel in its own right.
Accordingly, from a second aspect the present invention provides a mass spectrometer comprising: a multi-reflecting time of flight mass analyser or mass separator having an ion accelerator, and two ion mirrors that are elongated in a first dimension (z-dimension) and configured to reflect ions multiple times in a second orthogonal dimension (x-dimension), wherein the mass analyser or separator is housed in a housing; and an ion source, and/or at least one ion manipulation device, mounted to or arranged adjacent a wall of the housing; wherein the spectrometer is configured to transmit ions from the ion source, and/or through the at least one ion manipulation device, in a first direction and then turn the ions in a second, opposite direction and into the mass analyser or separator.
The spectrometer of the second aspect may have any of the features described in relation to the first aspect of the invention, except that the spectrometer need not necessarily include the energy filter.
For example, the housing may be a vacuum chamber in which the mass analyser or separator is arranged.
The wall may be arranged in a plane defined by the first and second dimensions (X-Z plane).
The first and second opposite directions may be in the z-dimension and/or in a plane defined by the first and second dimensions (X-Z plane).
The at least one ion manipulation device may be any at least one, or any number, of the following devices: an ion guide; a mass filter, such as a quadrupole mass filter; an ion mobility separator; an ion trap; a fragmentation device, such as a CID collision cell; a/the cooling cell for reducing the energy spread of the ions; an ion lens; or an ion acceleration device.
The at least one ion manipulation device may comprise one or more vacuum chamber that is mounted to or arranged adjacent the wall of the housing.
Any means may be used to turn the ions in said second, opposite direction and into the mass analyser or separator. For example, one or more curved multipoles, one or more curved collision cell, or one or more sets of deflection means (with and without energy-filtering properties) may be used.
It is contemplated that the time of flight mass analyser or mass separator need not necessarily be a multi-reflecting time of flight mass analyser or mass separator and that the mass analyser or separator may have a single ion mirror, whilst still providing the above-described compact arrangement.
The first aspect of the present invention also provides a method of mass spectrometry comprising: providing a spectrometer as described herein above; controlling the ion energy filter to filter ions according to their kinetic energy and so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that is within a selected range; accelerating the transmitted ions into one of the ion mirrors using the ion accelerator; and reflecting the ions between the ion mirrors multiple times.
The method may comprise selecting a desired number of reflections of the ions between the ion mirrors, and then controlling the ion energy filter to filter ions so as to only transmit ions having a component of kinetic energy in a first dimension (z-dimension) that provides the selected number of reflections.
The second aspect of the present invention also provides a method of mass spectrometry comprising: providing a spectrometer as described above; and transmitting ions from the ion source, and/or through the at least one ion manipulation device, in a first direction and then turning the ions in a second, opposite direction and into the mass analyser or separator.
The method may comprise accelerating the transmitted ions into one of the ion mirrors using the ion accelerator, and reflecting the ions between the ion mirrors multiple times.
Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:
In use, an ion source delivers ions to the orthogonal ion accelerator 6, which accelerates packets of ions 10 into a first of the ion mirrors at an inclination angle to the x-axis. The ions therefore have a velocity in the x-dimension and also a drift velocity in the z-dimension. The ions enter into the first ion mirror and are reflected back towards the second of the ion mirrors. The ions then enter the second mirror and are reflected back to the first ion mirror. The first ion mirror then reflects the ions back to the second ion mirror. This continues and the ions are continually reflected between the two ion mirrors as they drift along the device in the z-dimension until the ions impact upon ion detector 8. The ions therefore follow a substantially sinusoidal mean trajectory within the x-z plane between the ion source and the ion detector 8.
The periodic lens array 4 is arranged such that the ion packets 10 pass through them as they are reflected between the ion mirrors 2. Voltages are applied to the electrodes of the periodic lens array 4 so as to spatially focus the ion packets in the z-dimension. This prevents the ion packets from diverging excessively in the z-dimension, which would otherwise result in some ions reaching the detector 8 having only been reflected a certain number of times and other ions reaching the detector having been reflected a larger number of times. The periodic lens array 4 therefore prevents ions have significantly different flight path lengths through the mass analyser on the way to the detector 8.
The inventors have recognised that ions may be prevented from performing different numbers of reflections between the ion mirrors by other means and without necessarily using a periodic lens between the ion mirrors, the use of which may cause aberrations in the ion flight time.
Ions may be conditioned upstream of MRTOF mass analysers by being collided with background gas in a gas-filled RF ion guide so as to collisionally cool them. The phase volume of the ion beam may be reduced to tens of milli-electron volts, including the axial movement of ions. This is five orders of magnitude lower than the typical drift energy of ions in TOF mass analysers (which is in the keV range). If this energy spread could be maintained it would be possible, for example, to provide only 6 mm of ion beam expansion for 10 m of travel in the drift direction. However, the inventors have recognised that the axial velocity spread of the ions is increased, during acceleration of the ions, by ion collisions at the exit of the collisional cooling ion guide and that this results in an increased energy spread of the ions that causes the above-described problem of ions diverging in the MRTOF mass analyser.
The inventors have recognised that the ion beam may be conditioned prior to entering the mass analyser such that the ions can be reflected between the ions mirrors a reasonably high number of times without different ions performing different numbers of reflections in the time of flight region. More specifically, this may be achieved by decreasing the energy spread, or decreasing the velocity spread, of the ions prior to the ions entering the mass analyser. Referring to
In use, the collisional cooling cell 12 is supplied with gas and ions are supplied to the collisional cooling cell 12. The ions collide with the gas in the cell 12 so as to transfer their kinetic energy to the gas molecules, thus reducing the energy of the ions and reducing their energy spread. The ions are then transferred from the collisional cooling cell 12 into the electrostatic sector energy filter 14. The ions may be supplied to the entrance of the energy filter 14 in an intermittent or pulsed manner, or continuously. The ions may be accelerated from the collisional cooling cell 12 to the electrostatic sector energy filter 14. As described above, the energy distribution range that the ions have may broaden during this transfer process. Voltages are applied to the electrodes of the electrostatic sector energy filter 14 such that only ions having axial energies in the desired energy range are capable of being transmitted from the entrance to the exit slot. The ions pass into the entrance and experience a force orthogonal to their direction of travel, due to the voltages applied to the electrostatic sector 14. The flight paths of ions having energies within the desired range of energies are bent such that these ions travel through the electrostatic sector 14 and out of the slotted exit so as to be onwardly transmitted to the MRTOF mass analyser. The flight paths of ions having energies outside of the desired range of energies are bent such that these ions impact on the internal walls of the electrostatic sector 14 and do not pass out of the exit, and are therefore not onwardly transmitted to the MRTOF mass analyser.
Ions that are transmitted by the energy filter 14 are received in the MRTOF mass analyser and pass into the orthogonal accelerator 6 along a first axis (e.g. extending in the z-dimension). This allows the duty cycle of the instrument to remain high. The orthogonal accelerator 6 pulses the ions (e.g. periodically) orthogonally to the first axis (i.e. pulsed in the x-dimension) such that packets of ions travel in the x-dimension towards and into a first of the ion mirrors 2. The ions retain a component of velocity in the z-dimension from that which they had when passing into the orthogonal accelerator 6. As such, ions are injected into the time of flight region 3 of the instrument at a small angle of inclination to the x-dimension, with a major velocity component in the x-dimension towards the first ion mirror 2 and a minor velocity component in the z-dimension towards the detector 8.
The ions pass into a first of the ion mirrors and are reflected back towards the second of the ion mirrors. The ions pass through the field-free region 3 between the mirrors 2 as they travel towards the second ion mirror and they separate according to their mass to charge ratios in the known manner that occurs in field-free regions. The ions then enter the second mirror and are reflected back to the first ion mirror, again passing through the field-free region 3 between the mirrors as they travel towards the first ion mirror. The first ion mirror then reflects the ions back to the second ion mirror. This continues and the ions are continually reflected between the two ion mirrors 2 as they drift along the device in the z-dimension until the ions impact upon ion detector 8. The ions therefore follow a substantially sinusoidal mean trajectory within the x-z plane between the ion source and the ion detector 8. The time that has elapsed between a given ion being pulsed from the orthogonal accelerator 6 to the time that the ion is detected may be determined and used, along with the knowledge of the flight path length, to calculate the mass to charge ratio of that ion.
The desired range of ion energies capable of being transmitted by the energy filter 14 is selected such that all ions received in the MRTOF mass analyser perform the same number of ion mirror reflections when pulsed from the orthogonal accelerator 6 to the detector 8. Although eight ion mirror reflections are shown in
Embodiments of the present invention relate to an MRTOF mass analyser having substantially no focusing of the ions, in the z-dimension, between the ion mirrors 2 (e.g. there is no periodic lens 4 for focusing the ions in the z-dimension). Rather, the expansion of each packet of ions 10 in the z-dimension as it travels from the orthogonal accelerator 6 to the detector 8 is limited by the range of energies that the ions have when they enter the mass analyser. In contrast, MR-TOF mass spectrometers have conventionally sought to obtain a very high resolution and hence require a high number of reflections between the ion mirrors 2. Therefore, conventionally it has been considered necessary to provide z-dimensional focusing using an array of periodic lenses arranged between the ion mirrors 2 to prevent the width of the ion packet diverging.
In the embodiment depicted in
In operation, ions are formed in the atmospheric pressure ion source, such as by an ESI ion source. The ions then enter the atmospheric pressure interface 20 (which may be a tube or ion guide) and pass into the first vacuum chamber 22, which is pumped to a lower pressure than the atmospheric pressure region. The ions then pass into the second vacuum chamber 23, which may be pumped to a lower pressure than the first vacuum chamber 22 (or maintained at the same pressure). The second vacuum chamber 23 may comprise one or more devices for manipulating the ions. For example, the second vacuum chamber 23 may comprise a mass filter 24 that transmits only ions of a selected mass to charge ratio, or a selected range of mass to charge ratios. The selected mass to charge ratio(s) that is transmitted by the mass filter 24 may be controllably varied with time. Alternatively, or additionally, an ion mobility separator may be provided that separates the ions by mobility. Alternatively, or additionally, a fragmentation device (e.g. CID fragmentation cell) may be provided for fragmenting ions. For example, a mass filter and fragmentation device may be provided, wherein the mass filter selects precursor ions to fragment in the fragmentation device, and wherein the resulting fragment ions are then onwardly transmitted for analysis.
The ions are subsequently transmitted into the collisional cooling cell 25, which operates as described above in relation to
Although an atmospheric pressure region and an atmospheric pressure ion source have been described, the region and ion source may be operated at other pressures.
Although a single sector energy filter 14 has been described that bends the ion path by 180 degrees (for ions of desired energies), other forms of energy filter may be provided. For example, the energy filter may bend the ion path (for ions of desired energies) by angles other than 180 degrees. Alternatively, or additionally, the energy filter may be formed by multiple electrostatic sectors, such as two 90 degree sectors that may have a slit arranged between them for transmitting ions of the desired energies. It is also contemplated that other forms of electrostatic energy filters may be used, as are known in the art.
Although the energy filter 14 has been described for turning the ions into the MRTOF mass analyser 1, other ion optical components may perform this function instead. For example, a curved RF ion guide such as a multipole (e.g. quadrupole) ion guide may be provided for this function. Alternatively, the ion beam may be deflected into the MRTOF mass analyser by deflection electrodes, e.g. by a two stage beam deflection device. In these embodiments, if the ion optical components for turning the ions into the MRTOF mass analyser is not configured to perform the energy filtering described herein, then a separate energy filter may be provided upstream or downstream of the ion optical components for turning the ions.
As described above, the energy filter 14 may take a form other than an electrostatic sector. Other exemplary embodiments of the energy filter will now be described below.
For example, the energy filter 14 may comprise electrodes that arrange an ion retarding potential difference (e.g. DC potential difference) that urges the ions in the opposite direction to that in which they are travelling. This may be achieved, for example, by applying different voltages to an axially spaced pair of grid/mesh electrodes, wherein the ions are arranged to travel through the holes in the grid/mesh electrodes. The ion retarding potential difference is easy to adjust and is set so as to allow relatively high energy ions to pass therethough, but to reflect or deflect relatively low energy ions so that they are not onwardly transmitted by the energy filter. Referring back to
Although grid/mesh electrodes through which the ions pass have been described, other electrode arrangements may be provided, e.g. in order to reduce or avoid contamination or charging of these electrodes due ions impacting on them.
In use, a beam of ions passes into the energy filter along the axis extending through the apertured electrodes 30-32. Voltages are applied to the electrodes (e.g. DC voltages) such that ions of relatively high energy are able to be transmitted through the apertures of the electrodes and out of the exit of the energy filter as shown by arrow 34, whereas ions of relatively low energy are reflected or deflected such that they are not transmitted by the energy filter as shown by arrows 35. As described above in relation to
The diameter of the apertures in the electrodes 30-32 is larger than that of the ion beam and may be at least twice the diameter. The voltage applied to the third electrode 32 may be set relative to the first electrode 30 such that a decelerating electric field is arranged between the first electrode 30 and third 32 electrode. The potential on the third electrode 32 may be set according to the range of ion energies that are desired to be transmitted by the energy filter. As shown in
The second electrode 31 may be maintained at substantially the same voltage as the first electrode 30, such that ions which are transmitted to the exit of the energy filter have the same energy as when they enter the energy filter. In other words, the energy filter may comprise an Einzel lens. In this embodiment the ion retarding voltage applied to the third electrode 32 may be set to be substantially at the same voltage as the final electrode upstream of the energy filter (e.g. the exit of the collisional cooling cell).
The electric field lines between the adjacent apertured electrodes 30-32 are shown schematically in
Although the energy filter has been described above as comprising three electrodes, it is contemplated that the second 31 electrode may be omitted. Additionally, or alternatively, the electrodes of the energy filter need not be apertured electrodes by may be electrodes of other forms. For example, the energy filter electrodes may be a segmented multipole (e.g. quadrupole) having two, three or more axial segments and wherein different voltages may be applied to the electrodes of the different axial segments so as to perform the above-described energy filtering.
In order reflect the ions multiple times in the MRTOF mass analyser 1 before the ions impact on the detector 8, the velocity of the ions in the z-dimension (i.e. the drift dimension through the mass analyser) is required to be significantly smaller than the velocity of the ions in the direction of ion reflection between the ion mirrors 2 (i.e. in the x-dimension). However, it can be difficult to arrange the ion beam incoming into the MRTOF mass analyser so have sufficiently low velocity (i.e. energy) in the z-dimension. Also, even though the ions may be collisionally cooled upstream of the MRTOF mass analyser in order to reduce their energy spread, the ions may still emerge from the collisional cooling cell 12 having a substantial spread of kinetic energies. It can also be problematic to simply set the energy filter 14 so as to transmit only ions in a narrow energy band, such as those having energies above a relatively high cut-off value, since then relatively few ions will be transmitted by the energy filter and the sensitivity of the instrument will be diminished.
The maximum number of double ion-mirror reflections before ions begin to undergo differing numbers of ion-mirror reflections can be estimated approximately as the ratio of the drift length of the ions through the MRTOF mass analyser in z-dimension to the size of ion packet in z-dimension. Even if the ion packet begins with very small size in the z-dimension, this size will expand as the ions travel through the mass analyser and according to the following relationship:
ΔZ=ΔVz*Lz/Vz
where ΔZ is the change in size of the ion packet in the z-dimension as it travels through the MRTOF mass analyser, ΔVz is the spread of ion velocities in the z-dimension that the ions have, Lz is the length that the ions travel in the z-dimension in the MRTOF mass analyser, and Vz is the average ion velocity in the z-dimension within the MRTOF mass analyser.
Therefore, the number of reflections between the ion mirrors is restricted by the ratio of Vz to ΔVz, which is approximately equal to 2Ebeam/Ebeam, where Ebeam is the average energy of the ion beam in the z-dimension that enters the MRTOF mass analyser and ΔEbeam is the spread of energies in the z-dimension of ions that enter the mass analyser.
The above does not take into account the original size of the ion packet in the z-dimension (e.g. at the orthogonal accelerator) Z0−ΔZ. Accounting for the original size of the ion beam in the z-dimension may result in an increase in the final size of the ion beam in the z-dimension by the time at the time it reaches the detector, with a corresponding decrease (approximately by a factor of two) in the number of ion mirror reflections that may be performed whilst still maintaining the same number of ion mirror reflections for all ions. Therefore, the number of ion mirror reflections that may be performed whilst maintaining the same number of reflections for all ions, Nmax, may be given by:
N
max
˜E
beam
/ΔE
beam
It therefore follows that it is required to minimize the energy spread of ions entering the MRTOF mass analyser, ΔEbeam, using the collisional cooling cell and energy filter in order to maximise the number of ion mirror reflections Nmax.
In order to increase the number of ion mirror reflections, Nmax, so as to increase the ion flight path length, and hence increase the resolving power of the MRTOF mass analyser, the energy of the original ion beam Ebeam may be increased. The velocity of the ions in the z-dimension through the mass analyser may then be decreased such that the ions have time to perform the desired number of reflections before they reach the detector. This reduction of the ion velocity in the z-dimension may be performed by a deflection module arranged downstream of the orthogonal accelerator that deflects the ion packet leaving the orthogonal accelerator so that its component of velocity in the z-dimension is decreased (and its component of velocity in the x-dimension is increased), as will be described below in relation to
A disadvantages of this approach (and other approaches that increase the number of ion mirror reflections) is that the duty cycle of the mass analyser is reduced, i.e. the proportion of the ions that are transmitted from the entrance of the mass analyser to the detector is reduced. Without the use of a deflection module, the duty cycle (DC) of the mass analyser can be estimated (assuming Z0˜ΔZ) as follows:
DC=Z
0
/L
Z˜½Nmax
If a deflection module is used to decrease the ion trajectory angle (relative to the x-dimension) and increase the number of ion mirror reflections, as described above, then the duty cycle is additionally reduced in proportion to the decrease in the ion trajectory angle.
In order to better understand the effect of using a deflection module, a numerical example will now be described. Assuming that an MRTOF mass analyser having no deflection module has been set up so that the number of ion mirror reflections are optimised, and it is desired to improve the resolving power of the mass analyser (i.e. the ion flight path length and hence number of reflections) by a factor Q, then the energy of the incoming ion beam may be increased and a deflection module may be provided after the orthogonal accelerator (whilst retaining the same energy spread in the incoming ion beam and the same drift length Lz through the mass analyser). The increase in ion beam energy and use of the deflection module alters the main parameters of the mass analyser by the factors listed below, where the second column indicates the factors in general terms and the third column indicates the factors for an example in which the resolution is increased by a factor of 2 (i.e. Q=2).
It can be seen that the resolution and number of reflections Nmax are increased, but the required length of the orthogonal accelerator (OA) and the duty cycle are reduced.
If a deflection module is not used then in order to achieve the same increase in resolving power, the main parameters of the mass analyser are required to be varied by the factors listed below, where the second column indicates the factors in general terms and the third column indicates the factors for an example in which the resolution is increased by a factor of 2 (i.e. Q=2).
It can be seen that the required length of the orthogonal accelerator (OA) and the drift length through the mass analyser Lz are required to be increased.
In this embodiment the deflection module 38 comprises two deflection electrodes spaced apart in the z-dimension and arranged so that ions pulsed out of the orthogonal accelerator 6 pass between them. Voltages are applied to these deflection electrodes so as to change the trajectory of the ions such that the ions have a lower velocity component in the z-dimension, thereby increasing the number of reflections between the ion mirrors 2. It is known to use deflection electrodes in order to control the trajectory of the ions after the orthogonal accelerator 6. However, the deflection electrodes may introduce first order aberrations to the time of flight of the ions that is proportional to the size of the ion packet in the z-dimension (due to the angle of trajectory of the ion packet at the exit of the deflection region). Embodiments of the present invention eliminate these aberrations by arranging the orthogonal accelerator 6 so that its ion receiving axis is inclined at an acute angle α to the z-dimension. The ions are then pulsed into the region between the deflection electrodes by the orthogonal accelerator 6 along a first trajectory, and the deflection electrodes deflect the ions by an angle α towards the x-dimension so that they travel more orthogonally to the elongated ion mirrors 2.
In the embodiments that comprise a deflection module 38, second order positive z-dimension aberrations may introduced by a lens-effect. These aberrations may be compensated for by intentionally introduced negative z-dimension aberrations. For example, this may be achieved through the use of a gridless orthogonal accelerator, e.g. having accelerating slots that operate as an immersion lens and provide the compensating negative second-order aberrations.
According to the embodiments described herein, the ions have a relatively long time of flight in the MRTOF mass analyser 1 due to the multiple reflections between the ion mirrors 2. This enables the ions in each pulse to become temporally well separated in the time of flight region, thus providing the instrument with a high resolution. However, due to this high temporal separation of the ions, pulsing the ions into the MRTOF at too high a rate would lead to spectral overlap in which slow ions from a first ion injection pulse are detected after fast ions from a second, later ion injection pulse. This limits the rate at which ions can be pulsed into the MRTOF before spectral overlap occurs, thus limiting the duty cycle of the instrument. Also, as described above, the use of the deflection module 38 may reduce the duty cycle of the instrument. In order to overcome this problem, the instrument may be operated in an encoded frequency pulsing (EFP) mode. In this mode, the orthogonal accelerator 6 pulses ions into the Time of Flight region in a series of pulses, wherein the time delay between pairs of adjacent ion injection pulses is varied in a predetermined manner, as opposed to the conventional method of employing a uniform time delay between all of the pairs of adjacent pulses. The ions may then be pulsed into the ion mirrors at a relatively high rate, in which the ions in a first pulse temporally overlap with the ions in a subsequent pulse. The detector 8 then detects the arrival times of the ions and obtains a signal corresponding to the overlapping spectra. As the variable time delays between ion injection pulses are known in the EFP method, this can be used to unpick overlapping peaks in the TOF spectra so as to obtain non-overlapping spectra. This may be performed by correlating the overlapping spectra with the encoded sequence for injecting ions into the flight region 3. The EFP mode enables ions to be injected into the TOF device at time intervals that are shorter than the TOF separation time and so enables the duty cycle of the spectrometer to be increased.
Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.
For example, although the embodiments have been described in relation to an MRTOF mass analyser having a detector for determining the mass to charge ratios of the ions, it is alternatively contemplated that the ion mirrors may simply provide a mass separation region without a TOF detector.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1807626.5 | May 2018 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2019/051235 | 5/3/2019 | WO | 00 |
