Fast pushing time of flight mass spectrometer combined with restricted mass to charge ratio range delivery

Abstract

Ions having a restricted range of mass to charge ratios are transmitted to the acceleration region of a Time of Flight mass analyser. A control system applies a first extraction pulse to an acceleration electrode in order to accelerate a first group of ions into the time of flight region at a first time T1, wherein ions having the lowest mass to charge ratio in the first group of ions have a time of flight ΔT1.sub.min through the time of flight region and ions having the highest mass to charge ratio in the first group of ions have a time of flight ΔT1.sub.max through the time of flight region. The control system applies a second extraction pulse to the acceleration electrode at a subsequent second time T2, wherein ΔT1.sub.max−ΔT1.sub.min≦T2−T1<ΔT1.sub.max.

Claims

1. A mass spectrometer comprising: a Time of Flight mass analyser comprising an acceleration electrode, a time of flight region and an ion detector; a control system arranged and adapted to apply a first extraction pulse to said acceleration electrode in order to accelerate a first group of ions into said time of flight region at a first time T1, wherein ions having the lowest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.min through said time of flight region and ions having the highest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.max through said time of flight region and wherein said control system is arranged and adapted to apply a second extraction pulse to said acceleration electrode at a subsequent second time T2, wherein T2−T1<ΔT1.sub.max; and a restriction device arranged upstream of said acceleration electrode, wherein said restriction device is arranged and adapted to restrict the upper and lower mass to charge ratios and hence the mass to charge ratio range of ions which are present in an acceleration region adjacent said acceleration electrode when an extraction pulse is applied to said acceleration electrode so that the mass to charge ratio range of ions which are subsequently accelerated into said time of flight region is restricted; wherein the period between extraction pulses is set based upon said restricted mass to charge ratio range of ions, and wherein the period between extraction pulses is varied as a function of time; wherein said restriction device is selected from the group consisting of: (i) a quadrupole mass filter; (ii) a magnetic sector mass filter; (iii) an ion mobility separator; (iv) a travelling wave device; and (v) a Time of Flight mass analyser.

2. A mass spectrometer as claimed in claim 1, wherein said second extraction pulse is applied at said subsequent second time T2, wherein ΔT1.sub.max−ΔT1.sub.min<T2−T1.

3. A mass spectrometer as claimed in claim 1, wherein said control system is arranged and adapted to apply said second extraction pulse to said acceleration electrode in order to accelerate a second group of ions into said time of flight region at said second time T2, wherein ions having the lowest mass to charge ratio in said second group of ions have a time of flight ΔT2.sub.min through said time of flight region and ions having the highest mass to charge ratio in said second group of ions have a time of flight ΔT2.sub.max through said time of flight region, wherein said control system is arranged and adapted to apply a third extraction pulse to said acceleration electrode at a subsequent third time T3, wherein ΔT2.sub.max−ΔT2.sub.min <T3−T2 <ΔT2.sub.max.

4. A mass spectrometer as claimed in claim 1, wherein said Time of Flight mass analyser comprises an orthogonal acceleration Time of Flight mass analyser.

5. A mass spectrometer as claimed in claim 1, wherein said control system determines the mass to charge ratio or time of flight of ions detected by said ion detector by post processing summed or combined data or mass spectral data.

6. A mass spectrometer as claimed in claim 1, wherein the restricted mass to charge ratio range of ions entering said Time of Flight mass analyser is varied as function of time by a device selected from the group consisting of: (i) a further mass spectrometer or mass analyser; (ii) an ion trap; (iii) a Time of Flight mass analyser; (iv) an ion trap having one or more pseudo-potential barriers wherein ions are scanned out of said ion trap via said one or more pseudo-potential barriers; (v) a mass filter; (vi) a quadrupole mass filter; (vii) a magnetic sector mass filter; (viii) an ion mobility separator.

7. A mass spectrometer as claimed in claim 3, wherein said control system is arranged and adapted to apply said third extraction pulse to said acceleration electrode in order to accelerate a third group of ions into said time of flight region at said third time T3, wherein ions having the lowest mass to charge ratio in said third group of ions have a time of flight ΔT3.sub.min through said time of flight region and ions having the highest mass to charge ratio in said third group of ions have a time of flight ΔT3.sub.max through said time of flight region, wherein said control system is arranged and adapted to apply a fourth extraction pulse to said acceleration electrode at a subsequent fourth time T4, wherein ΔT3.sub.max−ΔT3.sub.min<T4−T3 <ΔT3.sub.max.

8. A mass spectrometer as claimed in claim 1, wherein the intensity of ions as a function of mass to charge ratio is determined directly by said ion detector without requiring spectral de-convolution or the comparison of two mass spectral data sets.

9. A mass spectrometer as claimed in claim 5, where said control system determines the mass to charge ratio or time of flight of ions detected by said ion detector based upon knowledge of the period between extraction pulses.

10. A mass spectrometer as claimed in claim 1, wherein the period between extraction pulses is varied on a push by push basis.

11. A mass spectrometer comprising: a Time of Flight mass analyser comprising an acceleration electrode, a time of flight region and an ion detector; a control system arranged and adapted to apply a first extraction pulse to said acceleration electrode in order to accelerate a first group of ions into said time of flight region at a first time T1, wherein ions having the lowest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.min through said time of flight region and ions having the highest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.max through said time of flight region and wherein said control system is arranged and adapted to apply a second extraction pulse to said acceleration electrode at a subsequent second time T2, wherein T2−T1<ΔT1.sub.max; and a separation device arranged upstream of said acceleration electrode, wherein said separation device is arranged and adapted to cause ions to undergo a mass or mass to charge ratio correlated separation so that the upper and lower mass to charge ratios and hence mass to charge ratio range of ions present in an acceleration region adjacent said acceleration electrode when an extraction pulse is applied to said acceleration electrode is restricted so that the mass to charge ratio range of ions which are subsequently accelerated into said time of flight region is restricted; wherein the period between extraction pulses is set based upon said restricted mass to charge ratio range of ions, and wherein the period between extraction pulses is varied as a function of time; wherein said separation device comprises: (i) an ion mobility separator; or (ii) a travelling wave device.

12. A mass spectrometer as claimed in claim 11, wherein the period between extraction pulses is set in synchronisation with or based upon said separation.

13. A mass spectrometer as claimed in claim 11, wherein said second extraction pulse is applied at said subsequent second time T2, wherein ΔT1 .sub.max−ΔT1.sub.min<T2−T1.

14. A mass spectrometer as claimed in claim 11, wherein the period between extraction pulses is set in synchronisation with or based upon said separation in real time.

15. A mass spectrometer comprising: a Time of Flight mass analyser comprising an acceleration electrode, a time of flight region and an ion detector; a control system arranged and adapted to apply a first extraction pulse to said acceleration electrode in order to accelerate a first group of ions into said time of flight region at a first time T1, wherein ions having the lowest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.min through said time of flight region and ions having the highest mass to charge ratio in said first group of ions have a time of flight ΔT1.sub.max through said time of flight region and wherein said control system is arranged and adapted to apply a second extraction pulse to said acceleration electrode at a subsequent second time T2, wherein T2−T1 <ΔT1 .sub.max; and a restriction device arranged upstream of said acceleration electrode, wherein said restriction device is arranged and adapted to restrict the upper and lower mass to charge ratios and hence the mass to charge ratio range of ions which are present in an acceleration region adjacent said acceleration electrode when an extraction pulse is applied to said acceleration electrode so that the mass to charge ratio range of ions which are subsequently accelerated into said time of flight region is restricted; wherein the period between extraction pulses is set based upon said restricted mass to charge ratio range of ions, and wherein the period between extraction pulses is varied as a function of time; wherein said restriction device is selected from the group consisting of: (i) a travelling wave device; and (ii) a Time of Flight mass analyser.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments of the present invention together with other arrangements given for illustrative purposes only will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1A shows a travelling wave device arranged upstream of a Time of Flight mass analyser, FIG. 1B shows how the release of a packet of ions from a travelling wave device can result in mass to charge ratio separation of the ions as they travel towards the acceleration region of the Time of Flight mass analyser, FIG. 1C shows how the application of an extraction pulse may be synchronised with the arrival of ions having desired mass to charge ratios at an acceleration region adjacent an acceleration electrode and FIG. 1D shows how a restricted mass to charge ratio range of ions may be transmitted or pulsed into the drift region of the Time of Flight mass analyser;

(3) FIG. 2A shows a standard duty cycle (solid curve) and an enhanced duty cycle (dashed curve) obtained by restricting the mass to charge ratio of ions transmitted to the Time of Flight mass analyser and FIG. 2B shows a time of flight dependent duty cycle and illustrates time of flight regions which are not utilised conventionally;

(4) FIG. 3A shows a reduced extraction period with duty cycle enhancement and restricted mass to charge ratio range according to an embodiment of the present invention and FIG. 3B shows a resultant reduced extraction period with duty cycle enhancement and restricted mass to charge ratio range; and

(5) FIG. 4 shows a two dimensional plot showing pre-Time of Flight mass to charge ratio separation.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

(6) A preferred embodiment of the present invention will now be described. According to the preferred embodiment the duty cycle of a Time of Flight mass analyser is preferably enhanced by restricting the mass to charge ratio of ions transmitted to the Time of Flight mass analyser at any instance in time. The sensitivity of the Time of Flight mass analyser is preferably improved over a reduced mass range in a manner similar to that illustrated in FIG. 2A.

(7) FIG. 2B shows the effect of converting the x-axis of the enhanced profile from mass to charge ratio to time of flight and highlights the extent to which portions of the time of flight axis of separation are not used in conventional methods of Time of Flight mass analysis involving enhanced duty cycle. The preferred embodiment seeks to exploit the unused time of flight periods to increase the duty cycle yet further.

(8) FIGS. 3A and 3B illustrate how a sequence of profiles as shown in FIG. 2B can be arranged according to the preferred embodiment so as to increase the utilisation of the time of flight axis of separation. According to the preferred embodiment the delay between orthogonal acceleration pulses being applied to the orthogonal acceleration region is preferably reduced.

(9) In FIG. 3A the subsequent extraction pulses (pushes) are illustrated along a different axis in order to illustrate how mass spectral overlap is preferably prevented or avoided according to the preferred embodiment but nonetheless better utilisation is made of the time of flight axis as shown in FIG. 3B. As a result, the approach according to the preferred embodiment results in improved duty cycle and dynamic range.

(10) According to a further unillustrated and less preferred embodiment, some useful data may still be obtained if the mass to charge ratio range of interest is smaller than that bounded by the duty cycle enhancement profile. In this case the period between pushes can be reduced still further allowing the tails of adjacent profiles to overlap whilst preventing the tails overlapping the mass to charge ratio range of interest. According to this embodiment although there is some overlap of adjacent profiles along the time axis, the central portion of each profile is preferably not distorted by the tail of an adjacent profile. As a result, the time of flight data in the central portions of each profile can yield some useful data which does not need to be deconvoluted in any manner.

(11) In another embodiment the ions may be arranged to undergo a mass to charge ratio correlated pre-separation prior to the arrival at the orthogonal acceleration region. The ions are preferably separated on a significantly longer time scale than that of the orthogonal acceleration Time of Flight separation.

(12) For example, ions may be separated by Ion Mobility Separation (“IMS”). According to another embodiment ions may be separated using an ion trap in conjunction with a relatively poor resolution mass to charge ratio separator such as a scanwave device wherein ions are scanned out of an ion trap which has a variable height pseudo-potential barrier located, for example, at the exit of the device.

(13) The longer timescales allow multiple Time of Flight separations per pre-separation cycle resulting in two dimensional data sets as shown in FIG. 4. The x-axis (mass to charge ratio) in FIG. 4 can be considered a function of time or push number. As a result, even given modest resolution pre-separation (ten for FIG. 4), the Time of Flight range at any given push number is significantly restricted as indicated by the δm value for the push number associated with mass to charge ratio of 1000.

(14) In this type of geometry the period between pushes may be increased in synchronisation with the pre-separation on a push to push basis or in more discrete jumps after multiple pushes to again improve the duty cycle and dynamic range as well a sensitivity in this case.

(15) Knowledge of the fast or slow pre-separations and the Time of Flight characteristics preferably allow accurate measurement of the data in real time or post acquisition.

(16) Although the present invention has been described with reference to the 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.