MASS SPECTROMETER

Abstract

A time-of-flight, TOF, mass spectrometer, MS, comprising: an ion source for supplying a group of ions, including a first ion having a first mass-to-charge ratio m.sub.1/z.sub.1, a second ion having a second mass-to-charge ratio m.sub.2/z.sub.2 and a third ion having a third mass-to-charge ratio m.sub.3/z.sub.3 wherein m.sub.3/z.sub.3>m.sub.2/z.sub.2>at a time t.sub.0; a first set of electrodes, including a first electrode, and a second set of electrodes, including a first electrode and an Nth electrode, wherein the first set of electrodes and the second set of electrodes are mutually spaced apart by a gap therebetween; an ion detector for detecting the ions; a set of power supplies, including a first power supply, electrically coupled to the first set of electrodes and to the second set of electrodes; and a controller configured to control the set of power supplies to apply respective potentials to the first set of electrodes and the second set of electrodes; wherein the controller is configured to control the set of power supplies to: provide a first substantially field-free region between the ion source and the first set of electrodes to allow the group of ions to expand theretowards and/or therein, at the time t0; apply an extraction potential V.sub.extraction to the first set of electrodes at a time t.sub.extraction>t.sub.0, to extract the expanded group of ions, while maintaining a second substantially field-free region beyond the first set of electrodes, in the gap between the first set of electrodes and the second set of electrodes; and optionally, change an acceleration potential V.sub.acceleration applied to the second set of electrodes during a time period Δt=t.sub.off−t.sub.on, wherein ton>t.sub.extraction, to vary acceleration of the extracted group of ions based, at least in part, on respective mass-to-charge ratios.

Claims

1. A time-of-flight, TOF, mass spectrometer, MS, comprising: an ion source for supplying a group of ions, including a first ion having a first mass-to-charge ratio m.sub.1/z.sub.1, a second ion having a second mass-to-charge ratio m.sub.2/z.sub.2 and a third ion having a third mass-to-charge ratio m.sub.3/z.sub.3 wherein m.sub.3/z.sub.3>m.sub.2/z.sub.2>m.sub.1/z.sub.1, at a time t.sub.0; a first set of electrodes, including a first electrode, and a second set of electrodes, including a first electrode and an Nth electrode, wherein the first set of electrodes and the second set of electrodes are mutually spaced apart by a gap therebetween; an ion detector for detecting the ions; a set of power supplies, including a first power supply, electrically coupled to the first set of electrodes and to the second set of electrodes; and a controller configured to control the set of power supplies to apply respective potentials to the first set of electrodes and the second set of electrodes; wherein the controller is configured to control the set of power supplies to: provide a first substantially field-free region between the ion source and the first set of electrodes to allow the group of ions to expand theretowards and/or therein, at the time t.sub.0; apply an extraction potential V.sub.extraction to the first set of electrodes at a time t.sub.extraction>t.sub.0, to extract the expanded group of ions, while maintaining a second substantially field-free region beyond the first set of electrodes, in the gap between the first set of electrodes and the second set of electrodes; and change an acceleration potential V.sub.acceleration applied to the second set of electrodes during a time period Δt=t.sub.off−t.sub.on, wherein t.sub.on>t.sub.extraction, to vary acceleration of the extracted group of ions based, at least in part, on respective mass-to-charge ratios.

2. The TOF MS according to claim 1, wherein the controller is configured to control the set of power supplies to provide the first substantially field-free region between the ion source and the first set of electrodes by applying a static voltage V.sub.B to the first set of electrodes.

3. The TOF MS according to any previous claim, wherein the controller is configured to control the set of power supplies to provide the first substantially field-free region between the ion source and the first set of electrodes for a time period t.sub.delay=t.sub.extraction−t.sub.0.

4. The TOF MS according to any previous claim, wherein the controller is configured to control the set of power supplies to provide a substantially linear field in the second set of electrodes while providing the first substantially field-free region between the ion source and the first set of electrodes.

5. The TOF MS according to any previous claim, wherein the controller is configured to control the set of power supplies to maintain the second substantially field-free region beyond the first set of electrodes, in the gap between the first set of electrodes and the second set of electrodes, to at most 1% of the extraction potential V.sub.extraction/mm.

6. The TOF MS according to any previous claim, wherein a length of the gap between the first set of electrodes and the second set of electrodes is at least a diameter of an ion aperture in the first set of electrodes or the second set of electrodes.

7. The TOF MS according to any previous claim, wherein the controller is configured to control the set of power supplies to change a magnitude of the acceleration potential V.sub.acceleration applied to the second set of electrodes monotonically during the time period Δt=t.sub.off−t.sub.on.

8. The TOF MS according to any previous claim, wherein the controller is configured to control the set of power supplies to quasi-linearly or linearly change the acceleration potential V.sub.acceleration applied to the second set of electrodes during the time period Δt=t.sub.off−t.sub.on.

9. The TOF MS according to any previous claim, wherein the first set of electrodes consists of the first electrode.

10. The TOF MS according to any previous claim, wherein the set of power supplies includes the first power supply electrically coupled to the first set of electrodes and a second power supply electrically coupled to the second set of electrodes.

11. A method of controlling a time-of-flight, TOF, mass spectrometer, MS, the method comprising: supplying a group of ions, including a first ion having a first mass-to-charge ratio m.sub.1/z.sub.1, a second ion having a second mass-to-charge ratio m.sub.2/z.sub.2 and a third ion having a third mass-to-charge ratio m.sub.3/z.sub.3 wherein m.sub.3/z.sub.3>m.sub.2/z.sub.2>m.sub.1/z.sub.1, from an ion source at a time t.sub.0 and allowing the group of ions to expand towards and/or into a first substantially field-free region between the ion source and a first set of electrodes, including a first electrode; applying an extraction potential V.sub.extraction to the first set of electrodes at a time t.sub.extraction>t.sub.0, to extract the expanded group of ions, while maintaining a second substantially field-free region beyond the first set of electrodes, in a gap between the first set of electrodes and a second set of electrodes, including a first electrode and an Nth electrode, wherein the first set of electrodes and the second set of electrodes are mutually spaced apart by the gap; changing an acceleration potential V.sub.acceleration applied to the second set of electrodes during a time period Δt=t.sub.off−t.sub.on, wherein t.sub.on>t.sub.extraction, to vary acceleration of the extracted group of ions based, at least in part, on respective mass-to-charge ratios; and detecting the ions.

12. The method according to claim 11, comprising providing the first substantially field-free region between the ion source and the first set of electrodes by applying a static voltage V.sub.B to the first set of electrodes.

13. The method according to any of claims 11 to 12, comprising providing the first substantially field-free region between the ion source and the first set of electrodes during a time period t.sub.delay=t.sub.extraction−t.sub.0.

14. The method according to any of claims 11 to 13, comprising providing a substantially linear field in the second set of electrodes while providing the first substantially field-free region between the ion source and the first set of electrodes.

15. The method according to any of claims 11 to 14, wherein maintaining the second substantially field-free region beyond the first set of electrodes, in the gap between the first set of electrodes and the second set of electrodes, comprises maintaining the second substantially field-free region beyond the first set of electrodes, in the gap between the first set of electrodes and the second set of electrodes, to at most 1% of the extraction potential V.sub.extraction/mm.

16. The method according to any of claims 11 to 15, wherein a length of the gap between the first set of electrodes and the second set of electrodes is at least a diameter of an ion aperture in the first set of electrodes or the second set of electrodes.

17. The method according to any of claims 11 to 16, wherein changing the acceleration potential V.sub.acceleration applied to the second set of electrodes during the time period Δt=t.sub.off−t.sub.on comprises changing a magnitude of the acceleration potential V.sub.acceleration applied to the second set of electrodes monotonically during the time period Δt=t.sub.off−t.sub.on.

18. The method according to any of claims 11 to 17, wherein changing the acceleration potential V.sub.acceleration applied to the second set of electrodes during the time period Δt=t.sub.off−t.sub.on comprises quasi-linearly or linearly changing the acceleration potential V.sub.acceleration applied to the second set of electrodes during the time period Δt=t.sub.off−t.sub.on.

19. The method according to any of claims 11 to 18, wherein the first set of electrodes consists of the first electrode.

20. The method according to any of claims 11 to 19, comprising independently applying respective voltages to the first set of electrodes and to the second set of electrodes.

21. A computer comprising a processor and a memory configured to implement, at least in part, a method according to any of claims 11 to 20, a computer program comprising instructions which, when executed by a computer comprising a processor and a memory, cause the computer to perform, at least in part, a method according to any of claims 11 to 20 or a non-transient computer-readable storage medium comprising instructions which, when executed by a computer comprising a processor and a memory, cause the computer to perform, at least in part, a method according to any of claims 11 to 20.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0147] For a better understanding of the invention, and to show how exemplary embodiments of the same may be brought into effect, reference will be made, by way of example only, to the accompanying diagrammatic Figures, in which:

[0148] FIG. 1(a) schematically depicts a TOF MS according to an exemplary embodiment; FIG. 1(b) schematically depicts a potential diagram for the TOF MS at a time t.sub.0; FIG. 1(c) schematically depicts a potential diagram for the TOF MS at a time t.sub.extraction>t.sub.0; FIG. 1(d) schematically depicts a potential diagram for the TOF MS at a time t.sub.on>t.sub.extraction; and FIG. 1(e) schematically depicts a potential diagram for the TOF MS at a time t.sub.off>t.sub.on;

[0149] FIG. 2 schematically depicts the TOF MS of FIG. 1(a), in more detail;

[0150] FIG. 3 schematically depicts an extraction potential V.sub.extraction applied to the first set of electrodes of the TOF MS of FIG. 1(a) at a time t.sub.extraction>t.sub.0;

[0151] FIG. 4 schematically depicts an acceleration potential V.sub.acceleration applied to the second set of electrodes of the TOF MS of FIG. 1(a) during a time period Δt=t.sub.off−t.sub.on, wherein t.sub.on>t.sub.extraction;

[0152] FIG. 5 schematically depicts a simulation of the TOF MS of FIG. 1(a);

[0153] FIG. 6 schematically depicts results of the simulation of FIG. 5;

[0154] FIG. 7 schematically depicts results of the simulation of FIG. 5;

[0155] FIG. 8(a) shows a mass spectrum acquired using a conventional TOF MS; and FIG. 8(b) shows a mass spectrum acquired using a TOF MS according to an exemplary embodiment;

[0156] FIG. 9 schematically depicts a method of controlling a TOF MS according to an exemplary embodiment;

[0157] FIGS. 10(a) to 10(i) schematically depict a simulation of the TOF MS of FIG. 1(a);

[0158] FIGS. 11(a) to 11(d) shows the simulation of FIGS. 10(a) to 10(i), in more detail; and

[0159] FIG. 12 schematically depicts a method of controlling a TOF MS according to an exemplary embodiment, in more detail.

DETAILED DESCRIPTION OF THE DRAWINGS

[0160] FIG. 1(a) schematically depicts a TOF MS 10 according to an exemplary embodiment; FIG. 1(b) schematically depicts a potential diagram for the TOF MS 10 at a time t.sub.0; FIG. 1(c) schematically depicts a potential diagram for the TOF MS 10 at a time t.sub.extraction>t.sub.0; FIG. 1(d) schematically depicts a potential diagram for the TOF MS 10 at a time t.sub.on>t.sub.extraction; and FIG. 1(e) schematically depicts a potential diagram for the TOF MS 10 at a time t.sub.off>t.sub.on. Particularly, FIGS. 1(a)-(e) show a schematic diagram of a linear TOF MS 10 incorporating a multiple-stage acceleration configuration according to an exemplary embodiment and related potential diagrams.

[0161] In this example, the TOF MS comprises:

[0162] an ion source 109, 110 for supplying a group of ions, including a first ion m.sub.1 having a first mass-to-charge ratio m.sub.1/z.sub.1, a second ion m.sub.2 having a second mass-to-charge ratio m.sub.2/z.sub.2 and a third ion m.sub.3 having a third mass-to-charge ratio m.sub.3/z.sub.3 wherein m.sub.3/z.sub.3>m.sub.2/z.sub.2>m.sub.1/z.sub.1, at a time t.sub.0 (time=0);

[0163] a first set of electrodes SE1, including a first electrode 103, and a second set of electrodes SE2, including a first electrode 105 and an Nth electrode 107, wherein the first set of electrodes SE1 and the second set of electrodes SE2 are mutually spaced apart by a gap g therebetween;

[0164] an ion detector 111 for detecting the ions;

[0165] a set of power supplies (not shown), including a first power supply (not shown), electrically coupled to the first set of electrodes SE1 and to the second set of electrodes SE2; and

[0166] a controller (not shown) configured to control the set of power supplies to apply respective potentials to the first set of electrodes SE1 and the second set of electrodes SE2;

[0167] wherein the controller is configured to control the set of power supplies to:

[0168] provide a first substantially field-free region between the ion source and the first set of electrodes to allow the group of ions to expand theretowards and/or therein, at the time t.sub.0;

[0169] apply an extraction potential V.sub.extraction (V.sub.PE−V.sub.B) to the first set of electrodes SE1 at a time t.sub.extraction>t.sub.0 (time=t_ext), to extract the expanded group of ions, while maintaining a second substantially field-free region 104 beyond the first set of electrodes SE1, in the gap g between the first set of electrodes SE1 and the second set of electrodes SE2; and

[0170] change an acceleration potential V.sub.acceleration (V.sub.R) applied to the second set of electrodes during a time period Δt=t.sub.off−t.sub.on=t.sub.off−t_on, wherein t.sub.on>t.sub.extraction, to vary acceleration of the extracted group of ions based, at least in part, on respective mass-to-charge ratios.

[0171] In this example, the TOF MS comprises and/or is a linear TOF MS, for example having a linear flight tube arranged between the second set of electrodes and the detector.

[0172] In this example, the ion source is a MALDI ion source (pulsed laser energy 110 shown, passing through apertures in electrodes 103 and 105). In this example, the ion source comprises, in use, a MALDI sample plate 101, having a sample 109 thereon. In this example, the first electrode 103 of the first set of electrodes SE1 comprises a plate, having an ion aperture therethrough. In this example, the first set of electrodes consists of the first electrode 103. In this example, a diameter D of the first electrode and/or of the Mth electrode of the first set of electrodes is at least twice a length g of the gap. In this example, the second set of electrodes SE2 includes N electrodes 105, 108, 108 and 107, including the first electrode 105 and the Nth electrode 107, wherein N is a equal to 4, wherein the N electrodes are mutually spaced apart, preferably mutually equispaced apart. In this example, a diameter D of the first electrode 105 of the second set of electrodes SE2 is at least twice a length g of the gap. In this example, a length g (also known as axial extent) of the gap between the first set of electrodes SE1 and the second set of electrodes SE2 is at least a diameter d of an ion aperture 100 in the first set of electrodes SE1, for example in the first electrode 103, and the second set of electrodes, for example in the first electrode 105 thereof. In this example, the ion detector 111 is a microchannel plate, MCP, detector.

[0173] In more detail, FIG. 1(a) is a schematic diagram of the TOF MS 10 showing a set of parallel electrodes (i.e. the first set of electrodes SE1 and the second set of electrodes SE2) with apertures 100, positioned at a distance ‘s’ from, and parallel to, a solid sample plate 101, that together form a multiple-stage acceleration configuration 120. The ion detector 111 is located at a distance ‘l’ from the multiple-stage acceleration configuration 120, between which is a field free region 112.

[0174] The first substantially field-free region, of length ‘s’, is provided between the sample plate 101 and the first electrode 103 of the first set of electrodes SE1 of the first set of electrodes SE1, during ablation and ionisation of the sample 109. This first substantially field-free region eliminates the prompt acceleration of ions and distortion of phase space during the time-delay prior to the application of the extraction pulse, due, for example, to the electrical fields therebeyond in the gap 104 of length ‘g’. Elimination of the prompt acceleration effect allows for a more precise correlation between initial ion position and initial velocity to be established at the onset of the extraction voltage pulse, which has a strong effect on mass resolving power. Subsequently, the first acceleration stage 102, of length ‘s’, is formed between the sample plate 101 and the first electrode 103 of the first set of electrodes SE1 of the first set of electrodes SE1 (i.e. the first substantially field-free region becomes the first acceleration stage 102) and simultaneously, the field free gap 104 (i.e. the second substantially field-free region), of length ‘g’, is formed between the first electrode 103 of the first set of electrodes SE1 and the first electrode 105 of the second set of electrodes SE2. This second substantially field-free region eliminates distortion phase space in the first pulsed extraction stage 102, due, for example, to the second acceleration stage 106 of the second set of electrodes SE2, which would otherwise adversely affect mass resolving power. The second acceleration stage 106, of length ‘d’, is formed between the first electrode 105 of the second set of electrodes SE2 and the Nth electrode 107 of the second set of electrodes SE2, with several intermediate electrodes 108 (two shown) distributed evenly through the second acceleration stage 106.

[0175] The voltages applied to the electrodes that form the multiple-stage acceleration configuration are shown in FIG. 1(b-e). V.sub.B, V.sub.PE and V.sub.R are the voltages applied to the sample plate 101, the first electrode 103 of the first set of electrodes SE1 and the first electrode 105 of the second set of electrodes SE2 respectively. The Nth electrode 107 of the second set of electrodes SE2 is connected to ground potential, with the intermediate electrodes 108 connected in series between the first electrode 105 of the second set of electrodes SE2 and the Nth electrode 107 of the second set of electrodes SE2 by a chain of resistors and capacitors that maintain a linear potential gradient across the second acceleration stage 106. The actual number of intermediate electrodes 108 required in the second acceleration stage 106 depends on the specific geometry with a larger number required for smaller diameter electrodes to prevent significant radial field penetration into the relatively long second acceleration stage 106.

[0176] FIG. 1(b) shows the potential distribution across the multiple-stage acceleration configuration 120 when the pulsed laser energy 110 is incident on the sample 109 located on the sample plate 101 (time=0): [0177] 1. A static voltage V.sub.B is supplied to the sample plate 101; [0178] 2. A static voltage V.sub.PE is initially supplied to the first electrode 103 of the first set of electrodes SE1, equal to the voltage on the sample plate 101, V.sub.PE=V.sub.B, thus initially establishing a field free region across the first acceleration stage 102 into which the desorbed ion plume can expand prior to the application of the time-delayed extraction pulse; and [0179] 3. A static voltage V.sub.R, ‘ramp bias’ is initially supplied to the first electrode 105 of the second set of electrodes SE2 and, with the Nth electrode 107 of the second set of electrodes SE2 grounded, forms a linear static field (V.sub.R/d) across the second acceleration stage 106.

[0180] FIG. 1(c) shows the potential distribution across the multiple-stage acceleration configuration 120, after a time-delay (t.sub.extraction), of typically a few hundred ns, following the irradiation of the sample plate 101 by the laser radiation 110, when an extraction field is pulsed across the first acceleration stage 102: [0181] 1. The voltage V.sub.PE supplied to the first electrode 103 is pulsed, from a voltage equal to that supplied to the sample plate 101 (V.sub.PE=V.sub.B), to a voltage equal to that on the first electrode 105 of the second set of electrodes SE2 (V.sub.PE=V.sub.R), thus establishing an extraction acceleration field between the sample plate 101 and the first electrode 103 of the first set of electrodes SE1 (V.sub.B−V.sub.PE/s) and a field free gap between the first electrode 103 and the first electrode 105 of the second set of electrodes SE2 (V.sub.PE=V.sub.R); and [0182] 2. The field free gap 104 is an important advantage of this invention, eliminating electric field penetration from the second accelerating stage 106 into the first pulsed extraction stage 102, thereby eliminating distortion phase space in the first pulsed extraction stage 102, which would otherwise adversely affect mass resolving power.

[0183] FIG. 1(d) and FIG. 1(e) show the potential distribution through the multiple-stage acceleration configuration 120 at times t.sub.on and t.sub.off respectively. At t.sub.on, the ions in the m/z range of interest (say m.sub.1 to m.sub.3), must have passed through the field free gap 104 and into the second acceleration stage 106 (FIG. 1(d)). The faster (m.sub.1), lower m/z, ions of interest will be at the Nth electrode 107 of the second set of electrodes SE2, the exit of the second acceleration stage 106, and the slower (m.sub.3), higher m/z, ions of interest will be at the first electrode 105 of the second set of electrodes SE2, the entry to the second acceleration stage 106.

[0184] During the period t.sub.on to t.sub.off the potential distribution across the second acceleration stage 106 is modified by a time-dependent voltage ramp ΔV(t) of duration Δt=t.sub.off−t.sub.on, applied to the first electrode 105 of the second set of electrodes SE2, whereby heavier ions traversing this stage 106 at later times experience a linear, most preferably a quasi-linear, increase in the magnitude of the accelerating field thus enhancing mass resolving power over the extended m/z range of interest.

[0185] All the ion over the m/z range of interest (m.sub.1 to m.sub.3) must be within this second acceleration stage 106 at the onset (t.sub.on) of the dynamic ramp (FIG. 1(d)) and the highest m/z of interest (m.sub.3) must be at, or beyond, the exit of the second acceleration stage 106 at t.sub.off (FIG. 1(d)) for time focusing to be achieved over this extended m/z range.

[0186] FIG. 2 schematically depicts the TOF MS 10 of FIG. 1(a), in more detail. Particularly, FIG. 2 shows a schematic diagram of the multiple-stage acceleration configuration and associated HV electronics.

[0187] FIG. 3 schematically depicts an extraction potential V.sub.extraction applied to the first set of electrodes of the TOF MS 10 of FIG. 1(a) at a time t.sub.extraction>t.sub.0. Particularly, FIG. 3 shows a potential plot for an extraction pulse applied across the first acceleration stage.

[0188] FIG. 4 schematically depicts an acceleration potential V.sub.acceleration applied to the second set of electrodes of the TOF MS 10 of FIG. 1(a) during a time period Δt=t.sub.off−t.sub.on, wherein t.sub.on>t.sub.extraction Particularly, FIG. 4 shows a potential plot for a quasi-linear ‘dynamic ramp’ applied across the second acceleration stage.

[0189] FIG. 2 is a schematic of the preferred electronic configuration. As previously stated, this invention overcomes several limitations of other approaches to the utilization of multiple time varying potentials. The introduction of the short intermediate field-free gap 104, created between two consecutive electrodes, decouples the application of the extraction voltage pulse across the first extraction stage 102 and the application of the high voltage dynamic ramp across the second acceleration stage 106, which would otherwise complicate the analogue electronics design considerably. For example, HV pulsing induces different DC offsets (depending on duty cycle and amplitude of the pulse) on the first (extraction) electrode 103 and third (ramp) electrode 105 that can only be effectively tuned out by adjusting the bias PSUs independently, which can only be done by decoupling the application of the extraction and ramp pulses as revealed in this invention.

[0190] In this example, the set of power supplies SPS includes the first power supply 202 electrically coupled, for example only electrically coupled, to the first set of electrodes SE1, a second power supply 204 electrically coupled, for example only electrically coupled, to the second set of electrodes SE2 and a third power supply 201 electrically coupled, for example only electrically coupled, in use to the sample plate 101. In this example, the set of power supplies SPS includes a fourth power supply 207 electrically coupled, for example only electrically coupled, to the second set of electrodes SE2. [0191] 1. A static voltage V.sub.B is supplied to the sample plate 101 by a high voltage power supply 201, which also provides a voltage bias to the first electrode 103 via resistor R1, thus ensuring an initial field free region 102 between the sample plate 101 and the first electrode 103 of the first set of electrodes SE1 before the time-delayed extraction pulse is applied to the first electrode 103 at a time t.sub.extraction after irradiation of sample plate 101 by laser energy 110. [0192] 2. The extraction pulse 301, applied to the first electrode 103, is derived from a high voltage power supply 202 and high voltage ‘Extraction Pulser’ unit 203 coupled to the first electrode 103 via capacitor C1. The extraction pulse 301 drops the potential V.sub.PE on the first electrode 103 from the sample plate potential, V.sub.PE=V.sub.B, to the ramp bias potential, V.sub.PE=V.sub.R, on the first electrode 105 of the second set of electrodes SE2, thus establishing the pulsed extraction field across the first acceleration stage 102 and the field free gap 104 that ensures no field penetration from second acceleration stage 106 into the first acceleration stage 102 during the extraction phase. [0193] 3. A static voltage V.sub.R, ‘ramp bias’, is supplied to the first electrode 105 of the second set of electrodes SE2, start of second acceleration stage 106, by a high voltage power supply 207, biasing this electrode to the same voltage as the potential on the first electrode (V.sub.R=V.sub.PE) after the extraction pulse has been applied to the first electrode 103. The time-dependent ‘dynamic ramp’ is formed by high voltage power supply 204 and high voltage ‘Ramp Pulser’ 205 driving the ‘RC network’ 206, coupled to the first electrode 105 of the second set of electrodes SE2 by capacitor C2, to derive the quasi-linear change in the field across the second acceleration stage 106. [0194] 4. The HV pulse applied across the RC network 206 gives rise to an exponential ramp 401 (FIG. 4) that deviates significantly from the ‘ideal’ linear ramp 402. However, by applying a much higher potential 403 across the RC network than the amplitude required for the actual ‘dynamic ramp’ 404, it is possible to achieve a quasi-linear ramp 405 over the required ‘dynamic ramp’ duration Δt=t.sub.off−t.sub.on. The pulser 205, designed for this invention, is of a ‘push-pull’ configuration; driving the RC ramp ‘on’ at time t.sub.on in a positive direction and driving the ramp ‘off’ in negative direction at a time t.sub.off. Thus, a quasi-linear ramp 405 of amplitude ΔV is generated over a time period Δt=t.sub.off−t.sub.on. The exponential decay of the quasi-linear ramp 405 (i.e. after the time t.sub.off) is not important and is due to the HV switch supplying the pulse to the RC network being of a ‘push-pull’ type. So, a positive going pulse is applied across the network and you would get the profile 401 if you waited for ‘natural’ rise of the ramp; it would rise to amplitude close to that of the ramp PSU (10 kV). That's the ‘push’ part, but the ‘pull’ part actively pulls the supply back to ground at the time t.sub.off (and we get the exponential decay because connected across same RC network). This has the advantage of not having the full potential of the PSU being applied to an electrode and also driving the ramp back to zero, ready for next pulse. The latter only really being important for higher repetition rate systems. So, whilst the system would work fine with a pulse like 401, we chose to use ‘push-pull’ configuration for our implementation for the reasons give. [0195] 5. Since all of the ions in m/z range of interest must be within the second acceleration stage 106 at the onset (t.sub.on) of the dynamic ramp 405, the second acceleration stage 106 must be somewhat longer than in a traditional two-stage ion source. To ensure the field along the axis of the second acceleration stage 106 is not distorted by radial field penetration, additional electrodes 108 are evenly distributed along the length of this stage 106, connected by a series of resistors (R3, R4, R5) to evenly distribute the ‘ramp bias’ between the electrodes and a series of capacitors (C3, C4, C5) to evenly distribute the ‘dynamic ramp’ potential between the electrodes. [0196] 6. Capacitors C6 and C7 protect the extraction HV power supply 201 and ramp bias power supply 207 from overvoltage and instability during extraction and ramp pulsing operation.

[0197] In this example, the first (extraction pulse) power supply 202 is a 2.5 kV power supply unit (PSU), having a stability of <1000 ppm, for example an Applied Kilovolts HP2.5×AA025. In this example, the second (ramp pulse) power supply 204 is a 10 kV PSU having a stability of <100 ppm, for example an Applied Kilovolts HPO10×AA025. In this example, the third (source) power supply 201 is a 10 kV PSU having a stability of <100 ppm, for example an Applied Kilovolts HPO10×AA025. In this example, the fourth (ramp bias) power supply 207 is a 10 kV PSU having a stability of <100 ppm, for example an Applied Kilovolts HPO10×AA025. Reversible versions of these power supplier may be employed to enable switching between the analysis of positive and negative ions.

[0198] Ion Optics Simulation

[0199] FIG. 5 schematically depicts a simulation of the TOF MS of FIG. 1(a). Particularly, FIG. 5 shows a schematic of ion optics geometry and potentials applied across acceleration stages for ion optical simulations using SIMION and SIMAX programs. The multiple-stage acceleration configuration described here, developed using the new set of analytical equations, was verified using software modelling tools SIMION and SIMAX. The parameters used for modelling purposes, shown in FIG. 5, are the preferred embodiment of the present invention. FIG. 5 shows the multiple-stage acceleration configuration geometry 120, the ‘extraction bias’ and ‘extraction pulse’ waveform 602 applied to the first electrode 103 and the ‘ramp bias’ and ‘dynamic ramp’ waveform 603 applied to the first electrode 105 of the second set of electrodes SE2.

[0200] The multiple-stage configuration 120 is shown with ion groups over a m/z range from 2 kDa 611 to 17 kDa 612 at time t.sub.on=6.3 μs 610, the start of the application of the ‘dynamic ramp’ across the second acceleration stage 106. Only the m/z range of ions, 2 kDa to 17 kDa, within the second acceleration stage 106 at this time (t.sub.on=6.3 μs) will be time focused at the detector. In this example, the length of first acceleration stage 102 s=6.4 mm, field free gap 104 g=3 mm, second acceleration stage 106 d=70 mm and field free distance 112, from exit of second acceleration stage 107 to detector 111, I=500 mm. Sample plate 101 has static potential of 9.5 kV applied, first electrode 103 is pulsed from initial potential of 9.5 kV 604 to 8 kV 605 after time delay t.sub.extraction=800 ns 606, and the second electrode ramped from static ‘ramp bias’ potential of 8 kV 607 to 13 kV 608 over 10 μs window 609 after initial time-delay of 6.3 μs 610. Four intermediate electrodes 108 ensure a linear field is maintained across second acceleration stage 106 with no significant radial field penetration.

[0201] FIG. 6 schematically depicts results of the simulation of FIG. 5. Particularly, FIG. 6 shows SIMAX simulation results of resolution achieved over an extended m/z range of interest. FIG. 6 shows plot of resolution [=time_of_flight/(2*peak width (FWHM)] over m/z range of interest, here 2 kDa to 17 kDa, being the m/z range over which ions are present in the second acceleration stage 106 at the time the ‘dynamic ramp’ 603 is applied across the second acceleration stage 106 at t.sub.on=6.3 μs 610.

[0202] Plot (1) 620 shows result of simulation with amplitude of ‘dynamic ramp’, across the second acceleration stage 106, set to zero (ΔV=0 kV), that is, a static potential across the second acceleration stage 106, which is equivalent to traditional two-stage acceleration configuration. Results in sharp peak in resolution of 1800 at m/z of 2 kDa 623 (actual m/z position of peak resolution determined by delayed-extraction pulse time, here t.sub.extraction=800 ns). Resolution rapidly fall away from peak value 623 with increasing m/z, as would be expected in the absence of any time-dependent acceleration scheme.

[0203] Plot (2) 621 shows the resolution obtained with application of an ‘ideal’ linear 402 ‘dynamic ramp’ (ΔV=5 kV, Δt=10 μs) applied across the second acceleration stage 106. Enhanced resolution is now obtained over the entire m/z range of interest, resolution of 2000 at 2 kDa 624 to 2200 at 17 kDa 625, demonstrating a significant improvement in resolution over this extended m/z range with respect to resolution achieved 620 in the absence of any time-dependent acceleration scheme.

[0204] Plot (3) 622 shows resolution obtained with application of practical quasi-linear ‘dynamic ramp’ 603, equivalent to 8 kV pulsed across and RC network (R=132 kΩ, C=65 pF) in 10 μs window, creating exponential ramp of amplitude ΔV=5 kV 626 over Δt=10 μs 609. Resolution 622 is reduced slightly, compared to that achieved with ‘ideal’ linear ‘dynamic ramp’ 621 at the higher end of the m/z range of interest, but resolution is still significantly enhanced with respect to the resolution obtained 620 with the ‘static ramp’ configuration, over the whole extended mass range.

[0205] FIG. 7 schematically depicts results of the simulation of FIG. 5. Particularly, FIG. 7 shows peak shape and peak width simulation results achieved within the extended m/z range of interest.

[0206] FIG. 7 shows the peak shapes achieved, from SIMAX simulations using 3 kDa, 6 kDa and 12 kDa ions, under conditions with ‘static ramp’, equivalent to traditional two-stage source, and quasi-linear ‘dynamic ramp’ 603 applied across second acceleration stage 106. FIG. 7 (a) and (b) show peak widths (FWHM) achieved with 3 kDa ions for static and dynamic ramps to be 14 ns and 6 ns respectively. FIG. 7 (c) and (d) show peak widths (FWHM) achieved with 6 kDa ions for static and dynamic ramps to be 52 ns and 6 ns respectively. FIG. 7 (e) and (f) show peak widths (FWHM) achieved with 12 kDa ions for static and dynamic ramps to be 142 ns and 13.5 ns respectively. The peak widths are significantly reduced by the implementation of the dynamic ramp over this extended m/z range.

[0207] FIG. 8(a) shows a mass spectrum acquired using a conventional TOF MS (i.e. having a conventional source configuration) and FIG. 8(b) shows a mass spectrum acquired using a TOF MS according to an exemplary embodiment. Particularly, FIG. 8(b) shows experimental results achieved with a linear TOF mass spectrometer, employing multiple acceleration configuration according to an exemplary embodiment. demonstrating an improvement in mass resolution over an extended m/z range of interest, compared with the conventional TOF MS.

[0208] In more detail, FIG. 8(a) shows experimental data for species of Cytochrome C with a ‘static ramp’, equivalent to traditional two-stage configuration, applied across second acceleration stage 106 and FIG. 8(b) shows experimental data for species of Cytochrome C with a quasi-linear ‘dynamic ramp’ (ΔV=5 kV in Δt=t.sub.off−t.sub.on=10 μs) applied across second acceleration stage 106. Mass spectral peaks are labelled with m/z, resolution (r) and signal-to-noise (S:N) ratio (s). Clearly, the implementation of time-dependent acceleration scheme across the second acceleration stage has significantly improved the resolution and signal-noise over an extended m/z range, in this case allowing relatively high resolution to be achieved over the m/z range of interest with a relatively short field free region 112 before the detector 111. Furthermore, the signal-to-noise (S:N) ratio for the data of FIG. 8(b) is also improved, across the whole mass range. Particularly, the improvement in resolution gives rise to much narrower peaks, and therefore higher peaks, such that the peak signal level is increased to such an extent as to dramatically increase the S:N ratio. In this way, ions of interest may be better resolved and at lower limits of detection.

[0209] FIG. 9 schematically depicts a method of controlling a TOF MS according to an exemplary embodiment.

[0210] At S901, the method comprises supplying a group of ions, including a first ion having a first mass-to-charge ratio m.sub.1/z.sub.1, a second ion having a second mass-to-charge ratio m.sub.2/z.sub.2 and a third ion having a third mass-to-charge ratio m.sub.3/z.sub.3 wherein m.sub.3/z.sub.3>m.sub.2/z.sub.2>m.sub.1/z.sub.1, from an ion source at a time t.sub.0 and allowing the group of ions to expand towards and/or into a first substantially field-free region between the ion source and a first set of electrodes, including a first electrode.

[0211] At S902, the method comprises applying an extraction potential V.sub.extraction to the first set of electrodes at a time t.sub.extraction>t.sub.0, to extract the expanded group of ions, while maintaining a second substantially field-free region beyond the first set of electrodes, in a gap between the first set of electrodes and a second set of electrodes, including a first electrode and an Nth electrode, wherein the first set of electrodes and the second set of electrodes are mutually spaced apart by the gap.

[0212] At S903, the method comprises optionally, changing an acceleration potential V.sub.acceleration applied to the second set of electrodes during a time period Δt=t.sub.off−t.sub.on, wherein t.sub.on>t.sub.extraction, to vary acceleration of the extracted group of ions based, at least in part, on respective mass-to-charge ratios.

[0213] At S904, the method comprises detecting the ions.

[0214] The method may include any of the steps described herein.

[0215] FIGS. 10(a) to 10(i) schematically depict a simulation of the TOF MS of FIG. 1(a), particularly showing expansion of 2 kDa, 3 kDa, 6 kDa and 17 kDa ions (in this example, into the first substantially field-free region and extraction of the ions therefrom). In this simulation, the time period t.sub.delay=t.sub.extraction−t.sub.0, prior to the application of the extraction potential V.sub.extraction, is 800 ns and the extraction pulse duration is 10 μs. The acceleration potential V.sub.acceleration is applied from a time t.sub.on of 6.3 μs.

[0216] FIG. 10(a) schematically depicts the TOF MS of FIG. 1(a). For convenience, the first acceleration region, the feel free gap and the second acceleration region may be delimited thus: First acceleration region: extraction region between sample plate 101 and extraction plate 103 (entrance to field free gap)

[0217] Field free gap: region between first and second acceleration regions (i.e. between extraction plate 103 and first ramp electrode 105)

[0218] Second acceleration region: ‘dynamic ramp’ acceleration region from first ramp electrode 105 (exit of field free gap) to ground electrode 107 (entrance to TOF analyser).

[0219] FIGS. 10(b) to 10(i) each schematically depict the TOF MS of FIG. 1(a), including the ions, (above) and the corresponding axial potential (below). For convenience, the parameters are described as shown in Table 1. The applied potentials corresponding to FIGS. 10(b) to 10(i) are summarised in Table 2.

TABLE-US-00001 TABLE 1 Definitions, as defined previously Parameter Description t time t.sub.0 time zero, when ions desorbed from sample t.sub.extraction time extraction pulse applied to accelerate ions across first acceleration region (~800 ns) t.sub.extraction.sub.—.sub.duration duration extraction pulse is applied across first acceleration region (>6 μs) t.sub.on time ‘dynamic ramp’ across second acceleration region starts (6.3 μs) t.sub.off time ‘dynamic ramp’ across second acceleration region ends (16.3 μs)

TABLE-US-00002 TABLE 1 Applied potentials as a function of time Sample Ramp plate Extraction bias 101 plate 103 105 Extraction FIG. Time t (V) (V) (V) pulse Comment 10(b) t.sub.0 < t < t.sub.extraction = 9,000 9,000 8,000 off Field free 800 ns across first acceleration stage 10(c) 800 ns = t.sub.extraction < 9,000 8,000 8,000 on Extraction t < t.sub.on pulse applied 10(d) t = t.sub.on = 6.3 μs 9,000 8,000 8,000 on Start of time varying acceleration across second acceleration stage 10(e) t = t.sub.on + 2 μs 9,000 8,000 9,500 on Step through time varying acceleration across second acceleration stage 10(f) t = t.sub.on + 4 μs 9,000 8,000 10,500 on Step through 10(g) t = t.sub.on + 6 μs 9,000 9,000 11,500 off Step through 10(h) t = t.sub.on + 8 μs 9,000 9,000 12,000 off Step through 10(i) t = t.sub.off 9,000 9,000 12,500 off End of time  = t.sub.on + 10 μs varying  = 16.3 μs acceleration across second acceleration stage

[0220] In more detail, FIG. 10(b) shows a condition before the extraction pulse is applied i.e. t.sub.0<t<t.sub.extraction=800 ns, where the ions can expand in the first few mm into what is a substantially field free region (i.e. the first substantially field free region) between the sample plate 101 and the extraction plate 103, which are both at the same potential of 9,000 V. The field beyond the extraction plate 103 is effectively immaterial due to the first substantially field free region.

[0221] In more detail, FIG. 10(c) shows a condition immediately after the extraction pulse is applied i.e. 800 ns=t.sub.extraction<t<t.sub.on and the ions are accelerated by the extraction field across the first acceleration region, without any distortion from the field in second acceleration region due to the presence of the field free gap (the second substantially field region) therebetween. Here, the ions are accelerated through the first acceleration region by the application of the extraction pulse (−1,000 V for 10 μs) across this region—this is to achieve velocity focusing (slower ions gain more energy than faster ions of same m/z). Particularly, the potential applied to the sample plate 101 remains 9,000 V while the extraction plate 103 and the first electrode 105 are both at the same potential of 8,000V. Thus, there is a potential gradient across the first acceleration stage and a substantially feel free gap between the first acceleration stage and the second acceleration stage. Importantly, this field free gap prevents axial penetration of the field from the second acceleration region into the first acceleration region during pulse extraction. It should be understood that the field free gap is only field free when the extraction pulse is on i.e. t.sub.extraction≤t<t.sub.extraction+t.sub.extraction_duration and before the dynamic ramp starts across the second acceleration region i.e. t<t.sub.on. The ‘axial potential plot’ clearly demonstrates the effectiveness of this field free gap. The important point is that the field in the first region is maintained until the highest m/z (17 kDa) ions have passed beyond its influence, here at a time >6 μs, as shown in FIG. 10(d). Note that while the extraction pulse is applied (i.e. the extraction potential V.sub.extraction) in FIG. 10(c), the acceleration potential V.sub.acceleration, across the second region, has not yet been applied.

[0222] In more detail, FIG. 10(d) shows a condition when the dynamic ramp across the second acceleration stage is first applied at t=t.sub.on. Here, the ions of the whole mass range of interest are within the second acceleration region. The relatively larger 17 kDa ions are just after the entrance to the second acceleration region i.e. the first ramp electrode 105 (exit of field free gap) while the relatively lighter 2 kDa ions are just before the exit of the second acceleration region i.e. the ground electrode 107 (entrance to TOF analyser). Particularly, the potential applied to the sample plate 101 remains 9,000 V while the extraction plate 103 and the first electrode 105 are both at the same potential of 8,000V. Thus, there is a potential gradient across the first acceleration stage and a substantially feel free gap between the first acceleration stage and the second acceleration stage. The field free gap is maintained, which now prevents any field penetration from first acceleration region into second acceleration region whilst some of the ions (e.g. the 17 kDa ions) are still close to the entrance to the second acceleration region. The dynamic ramp will now be changed across this second acceleration region, as shown in FIGS. 10(e) to 10 (i).

[0223] In this example, this is probably the earliest time when the extraction potential V.sub.extraction would be switched off since the largest m/z ions have passed beyond its influence. Essentially, the extraction pulse is preferably ‘on’ to maintain the field free gap between the first two acceleration stages. FIG. 10(d) shows that not only does the second substantially field free region prevent the field in the second acceleration region distorting the field in the first acceleration region, but it also prevents the field in the first acceleration region from distorting that in the second acceleration region.

[0224] In more detail, FIG. 10(e) shows a condition after the dynamic ramp across the second acceleration stage has been applied at t=t.sub.on+2 μs, whilst the extraction pulse is still also being applied. Particularly, the potential applied to the sample plate 101 remains 9,000 V, the potential applied to the extraction plate 103 remains 8,000 V but the potential applied to the first electrode 105 is changed to 9,500V. Thus, there the potential gradient across the second acceleration region is increased. The relatively lighted 2 kDa and 3 kDa ions have exited the second acceleration region while the relatively heavier 6 kDa and 17 kDa ions are accelerated therethrough.

[0225] In more detail, FIG. 10(f) shows a condition after the dynamic ramp across the second acceleration stage has been applied at t=t.sub.on+4 μs, whilst the extraction pulse is still also being applied. Particularly, the potential applied to the sample plate 101 remains 9,000 V, the potential applied to the extraction plate 103 remains 8,000 V but the potential applied to the first electrode 105 is changed further to 10,500V. Thus, there the potential gradient across the second acceleration region is further increased. The 6 kDa ions are near the exit of the second acceleration region while the relatively heavier 17 kDa ions are further accelerated therethrough. In more detail, FIG. 10(g) shows a condition after the dynamic ramp across the second acceleration stage has been applied at t=t.sub.on+6 μs, when the extraction pulse is no longer applied. Particularly, the potential applied to the sample plate 101 remains 9,000 V, the potential applied to the extraction plate 103 is now 9,000 V (since the extraction pulse is no longer applied) but the potential applied to the first electrode 105 is changed still further to 11,500V. Thus, there the potential gradient across the second acceleration region is still further increased. The relatively heavier 17 kDa ions are still further accelerated therethrough. Changes to the field in the first acceleration region at this time are clearly not going to have any effect on the higher m/z 17 kDa ions in second acceleration region.

[0226] In more detail, FIG. 10(h) shows a condition after the dynamic ramp across the second acceleration stage has been applied at t=t.sub.on+8 μs, when the extraction pulse is also no longer applied. Particularly, the potential applied to the sample plate 101 remains 9,000 V, the potential applied to the extraction plate 103 remains 9,000 V but the potential applied to the first electrode 105 is changed even still further to 12,000V. Thus, there the potential gradient across the second acceleration region is even still further increased. The relatively heavier 17 kDa ions are even still further accelerated therethrough.

[0227] In more detail, FIG. 10(i) shows a condition just before the dynamic ramp across the second acceleration stage is no longer applied at t=t.sub.on+10 μs=t.sub.off, when the extraction pulse is also no longer applied. Particularly, the potential applied to the sample plate 101 remains 9,000 V, the potential applied to the extraction plate 103 remains 9,000 V but the potential applied to the first electrode 105 is changed yet even still further to 12,500V. Thus, there the potential gradient across the second acceleration region is yet even still further increased. The relatively heavier 17 kDa ions are yet even still further accelerated therethrough and are exiting the second acceleration region.

[0228] FIGS. 11(a) to 11(d) shows the simulation of FIGS. 10(a) to 10(i), in more detail.

[0229] In this example, the extraction delay (t.sub.extraction) is a variable for tuning purposes, but typically ˜800 ns.

[0230] In this example, the ‘Dynamic ramp’ t.sub.on and t.sub.off times, 6.3 μs and 16.3 μs respectively, are fixed values determined by design of the MS.

[0231] At time t.sub.0<t<t.sub.extraction, a field free region (FIG. 11(a)) exists between the sample and extraction electrode (the first acceleration region). The ion plume expands into this space until t=t.sub.extraction.

[0232] At t=t.sub.extraction, the extraction pulse is applied to the extraction electrode, dropping the potential on this electrode from 9000 V to 8000 V; thus creating a potential difference of 1000V across the first acceleration region (FIG. 11(b)) (i.e. between sample plate and extraction electrode). This ‘delayed extraction’ enables velocity focusing, which may be optimised for a given m/z (determined by actual value of t.sub.extraction.).

[0233] The extraction pulse should remain ‘on’ for the whole time any ions of interest are still in the first acceleration region. If the extraction pulse is switched ‘off’ then the first acceleration region will revert to field free (FIG. 11(a)) state and velocity focusing will be lost for any remaining ions in the first acceleration region.

[0234] So, when can the extraction pulse be switched ‘off’? The quick answer is when the highest m/z ions of interest have passed from the first acceleration region, through the field free gap and into the second acceleration region. However, we also need to be aware that a modification to the field in the first acceleration region may affect the field in the second acceleration region, so we might want to wait a little longer.

[0235] Whilst the extraction pulse is ‘on’, we have a field free region between the two acceleration stages that minimises any influence the field in the first acceleration might have on the field in the second acceleration region.

[0236] The best way to determine the earliest time the extraction can be switched ‘off’ is by plotting the resolution of the highest m/z ions (17 kDa) against extraction duration (FIG. 11(c)).

[0237] FIG. 11(d) shows the extraction can be switch ‘off’ anytime after 6 μs i.e. after the ions have passes beyond the entrance to second acceleration stage.

[0238] The resolution plot below shows the minimum extraction duration to be ˜6 μs. A duration of 5 μs, for example, would be too short and the mass resolution would be degraded.

[0239] For illustration, two potential plots are shown, both at time t=6 μs, but with different extraction durations of 5 μs and 6 μs. The location of the highest m/z ions (17 kDa) at time t=6 μs is marked in each case. Clearly the fields at this location are different, for the two extraction durations, giving rise to the difference in resolution shown in the plot.

[0240] An extraction duration of 6 μs is a minimum value in this example, extraction durations longer than this (e.g. 10 μs or 100 μs) will not degrade the resolution since all the ions of interest will have passed into the second acceleration stage, or beyond, by the time the extraction is switched ‘off’.

[0241] Pulsed extraction duration is not generally a tuning variable. However, it needs to be set such that all ions of interest experience the required acceleration as per the design.

[0242] Turning ‘off’ the extraction potential too soon will compromise the velocity focusing and thus the resolution of the higher m/z ions.

[0243] Thus, there is a minimum extraction potential, for the instrument discussed here −6 μs, but there is no specific maximum value, for example 10 μs and 100 μs would be equally effective as 6 μs in this case.

[0244] Essentially, in this case, extraction duration=>6 μs. 6 μs could be used, as could 10 μs and 100 μs. Sometimes a larger value, such as 100 μs, might be chosen to move any electrical noise, associated with switching ‘off’ the extraction potential, outside the time-of-flight range of the analyser. However, the extraction duration must be <<repetition period for the instrument e.g. for an instrument running at 1 kHz the extraction duration must be <<1 ms to ensure the pulser electronics re-stabilise before next pulse triggered.

[0245] FIG. 12 schematically depicts a method of controlling a TOF MS according to an exemplary embodiment, in more detail.

[0246] At S1201, the controller provides a laser trigger pulse.

[0247] At S1202, a laser light pulse is emitted, ablating and ionising the sample, in response to the laser trigger pulse, as described with respect to S901. The laser light pulse typically has a peak width of about 1 ns (FWHM). The sample plate 101 is maintained at a constant potential of 9 kV.

[0248] At S1203, a laser pulse synchronisation signal is provided by a photodiode illuminated by a fraction of the laser light pulse, that defines the time t.sub.0, which occurs at a fixed time after the laser light pulse.

[0249] At S1204, the extraction potential V.sub.extraction is applied to the extraction plate 103 at a time t.sub.extraction>t.sub.0 i.e. after the time delay t.sub.delay=t.sub.extraction−t.sub.0, which is about 800 ns in this example, as described with respect to S902. The extraction potential V.sub.extraction is a square wave of amplitude −1 kV and a duration t.sub.extraction_duration of 10 μs, superimposed on the otherwise constant potential of 9 kV applied to the extraction plate 103.

[0250] At S1205, the acceleration potential V.sub.acceleration applied to the first electrode 105 during the time period Δt=t.sub.off−t.sub.on is varied, as described with respect to S903. The time period Δt is 10 μs and t.sub.on−t.sub.0 is 6.3 μs. The maximum amplitude of the acceleration potential V.sub.acceleration is +5 kV, superimposed on the otherwise constant potential of 8 kV applied to the first electrode 105. At S1206 (not shown), the ions are detected, as described with respect to S904.

[0251] Steps S1201 to S1206 are repeated, for example at a frequency of 1 kHz.

Alternatives

[0252] Although a preferred embodiment has been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention, as defined in the appended claims and as described above.

Summary

[0253] In summary, the invention provides a novel ion optical acceleration scheme to enhance time-focusing over an extended m/z range. The inventors have arrived at several advantages of the proposed ion optical scheme over prior art acceleration configurations largely by decoupling the first ‘pulsed extraction’ acceleration stage 102 from the second time-dependent acceleration stage 106: [0254] Electric field penetration of the second accelerating stage 106 into the first pulsed extraction stage 102 to eliminate prompt acceleration of ions and distortion of phase space during the time-delay and prior to the application of the extraction pulse is accomplished by introducing a short intermediate field-free gap 104. Elimination of the prompt acceleration effect allows for a more precise correlation between initial ion position and initial velocity to be established at the onset of the extraction voltage pulse, which has a strong effect on mass resolving power. [0255] The short intermediate field-free gap 104 also allows for using electrodes with increased size apertures, enhancing transmission of heavier ions with considerably wider initial kinetic energy spreads, while also minimizing the amount of material deposited on critical surfaces, especially those in the desorption-ionization region, extending the operational lifetime of the system. [0256] More importantly, the short intermediate field-free gap 104 created between two consecutive electrodes decouples the application of the extraction voltage pulse and the application of the high voltage ramp, which would otherwise complicate the analogue electronics design considerably. The extraction pulse is applied to the entrance electrode of the field-free gap 103 while the voltage ramp is applied independently to the electrode defining the exit end of the field-free gap 105 while both signals can be produced with high integrity and stability.

Attention

[0257] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0258] All of the features disclosed in this specification (including any accompanying claims and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at most some of such features and/or steps are mutually exclusive.

[0259] Each feature disclosed in this specification (including any accompanying claims, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0260] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.