IP Library › Granted Patent US 12,205,813
Granted Patent B2
US 12,205,813 · App. 17/440,998 · Granted Jan 21, 2025

Multiplexed time of flight mass spectrometer

Inventors: Jason Lee Wildgoose (Stockport, GB); John Brian Hoyes (Stockport, GB); Richard Denny (Newcaste-under-Lyme, GB)
Assignee: Micromass UK Limited
H01J49/40H01J49/0036
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Quick Facts
Patent No.
US 12,205,813
App. No.
17/440,998
Granted
Jan 21, 2025
Kind
B2
Abstract

A method of time of flight (ToF) mass spectrometry comprising: pushing ions into a ToF mass analyser in a plurality of pushes, wherein the time spacing between adjacent pushes is shorter than either the longest flight time, or the range of flight times, of the ions; detecting the ions so as to obtain spectral data; decoding the spectral data to determine first mass spectral data relating to ions pushed into the ToF mass analyser by a first plurality of the pushes (P 1 -P 4 ), and allocating this first mass spectral data to a first time stamp (t 1 ); and decoding the spectral data to determine second mass spectral data relating to ions pushed into the ToF mass analyser by a second plurality of the pushes (P 5 -P 8 ), and allocating this second mass spectral data to a second time-stamp (t 2 ); wherein the first and second time-stamps have a time difference therebetween that is shorter than said longest flight time, or said range of flight times ( 4 ), in the ToF mass analyser.

Claims (33)

1. A method of time of flight (ToF) mass spectrometry comprising:

pushing ions into a ToF mass analyser in a plurality of pushes, wherein the time spacing between adjacent pushes is shorter than either the longest flight time, or the range of flight times, of the ions in the ToF mass analyser from any given one of the pushes;

detecting the ions with a ToF detector so as to obtain spectral data;

decoding the spectral data to determine first mass spectral data relating to ions pushed into the ToF mass analyser by a first plurality of the pushes, and allocating this first mass spectral data to a first time-stamp, wherein said allocating the first mass spectral data to the first time-stamp comprises summing the first mass spectral data together and associating it with the first time-stamp; and

decoding the spectral data to determine second mass spectral data relating to ions pushed into the ToF mass analyser by a second plurality of the pushes, and allocating this second mass spectral data to a second time-stamp, wherein said allocating the second mass spectral data to the second time-stamp comprises summing the second mass spectral data together and associating it with the second time-stamp;

wherein the first time-stamp and the second time-stamps have a time difference therebetween that is shorter than said longest flight time, or said range of flight times, in the ToF mass analyser.

2. The method of claim 1 , comprising performing the first plurality of the pushes before the second plurality of the pushes.

3. The method of claim 1 , comprising separating ions according to their ion mobility and/or mass to charge ratio in one or more ion separator and transmitting the separated ions, or ions derived therefrom, to the ToF mass analyser whilst performing said plurality of pushes.

4. The method of claim 3 , wherein ions elute from the one or more ion separator over time as one or more ion peak, and wherein the first and second time-stamps have a time difference therebetween that is shorter than the width of each of the one or more ion peaks.

5. The method of claim 3 , wherein the ion separator performs a plurality of ion separation cycles and ions from the ion separator, or ions derived therefrom, are pushed into the ToF mass analyser a plurality of times during each cycle.

6. The method of claim 3 , comprising providing two dimensional nested data sets, wherein one dimension is the mass to charge ratio determined by the ToF mass analyser and the other dimension is the separation time from the one or more ion separator.

7. The method of claim 1 , comprising transmitting ions in a CID fragmentation device and pushing ions from the CID fragmentation device, or ions derived therefrom, into the ToF mass analyser in said plurality of pushes,

varying an operational parameter of a spectrometer that performs said method such that the ion signal at the ToF detector varies with time, and performing said step of pushing ions into the ToF mass analyser from the CID fragmentation device in a plurality of pushes whilst varying said operational parameter, wherein the operational parameter is the collision energy with which ions are subjected to in the CID fragmentation device.

8. The method of claim 1 , wherein said step of decoding the spectral data to determine the first mass spectral data comprises decoding spectral data obtained by the ToF detector in a first decoding time range, wherein all of the ions that reach the ToF detector in the first decoding time range come from a first set of ToF pushes, wherein every possible pair of ToF pushes in the first set of ToF that are separated from each other by a temporal spacing that is less than said longest flight time, or within said range of flight times, has a unique temporal spacing therebetween; and/or

wherein said step of decoding the spectral data to determine the second mass spectral data comprises decoding spectral data obtained by the ToF detector in a second decoding time range, wherein all of the ions that reach the ToF detector in the second decoding time range come from a second set of ToF pushes, wherein every possible pair of ToF pushes in the second set of ToF pushes that are separated from each other by a temporal spacing that is less than said longest flight time, or within said range of flight times, has a unique temporal spacing therebetween.

9. The method of claim 8 , wherein the first decoding time range corresponds to the duration of time defined by the first plurality of pushes plus either said longest flight time, or said range of flight times, of the ions in the ToF mass analyser for any given one of the pushes; and/or

wherein the second decoding time range corresponds to the duration of time defined by the second plurality of pushes plus either said longest flight time, or said range of flight times, of the ions in the ToF mass analyser for any given one of the pushes.

10. The method of claim 8 , wherein the step of decoding the spectral data to determine first mass spectral data comprises summing the spectral data obtained over the first decoding time range with one or more time shifted version of itself and determining which spectral data in the summed data is coherent; and/or

wherein the step of decoding the spectral data to determine second mass spectral data comprises summing the spectral data obtained over the second decoding time range with one or more time shifted version of itself and determining which spectral data in the summed data is coherent.

11. The method of claim 1 , wherein pushes that occur at least in the duration corresponding to the first plurality of pushes plus said longest flight time, or said range of flight times, have unique temporal spacings therebetween.

12. The method of claim 1 , wherein each of the first and/or second plurality of pushes is a number of pushes selected from: ≥3; ≥4; ≥5; ≥6; ≥7; ≥8; ≥9; or ≥10.

13. The method of claim 1 , wherein the number of pushes in the first plurality of pushes is the same as the number of pushes in the second plurality of pushes.

14. The method of claim 1 , comprising decoding the spectral data to determine third mass spectral data relating to ions pushed into the ToF mass analyser by a third plurality of the pushes, and allocating this third mass spectral data to a third-time-stamp; wherein the second time-stamp and the third time-stamps have a time difference therebetween that is shorter than said longest flight time, or the range of flight times, in the ToF mass analyser;

wherein the mean time of the first plurality of pushes is separated by the mean time of the second plurality of pushes by a first duration, and the mean time of the second plurality of pushes is separated from the mean time of a third plurality of pushes by substantially the same first duration.

15. The method of claim 1 , wherein the ToF mass analyser is a multi-reflecting time of flight mass analyser.

16. The method of claim 1 , comprising using the first mass spectral data at the first time-stamp and/or the time of the first time-stamp to identify the ions pushed into the ToF mass analyser in the first plurality of pushes, or to identify ions from which they are derived; and/or

comprising using the second mass spectral data at the second time-stamp and/or the time of the second time-stamp to identify the ions pushed into the ToF mass analyser in the second plurality of pushes, or to identify ions from which they are derived.

17. A ToF mass spectrometer comprising:

a ToF mass analyser having a pusher configured to push ions into the ToF mass analyser in a plurality of pushes, wherein the time spacing between adjacent pushes is shorter than either the longest flight time, or the range of flight times, of the ions in the ToF mass analyser from any given one of the pushes;

an ion detector for detecting the ions so as to obtain spectral data;

one or more processor configured to decode the spectral data to determine first mass spectral data relating to ions pushed into the ToF mass analyser by a first plurality of the pushes and to store the first mass spectral data associated with a first time-stamp in a memory, wherein said storing the first mass spectral data associated with the first time-stamp in a memory comprises summing the first mass spectral data together and associating it with the first time-stamp; and

one or more processor configured to decode the spectral data to determine second mass spectral data relating to ions pushed into the ToF mass analyser by a second plurality of the pushes and to store the second mass spectral data associated with a second time-stamp in a memory, wherein said storing the second mass spectral data associated with a second time-stamp in the memory comprises summing the second mass spectral data together and associating it with the second time-stamp;

wherein the first time-stamp and second time-stamps have a time difference therebetween that is shorter than said longest flight time, or said range of flight times, in the ToF mass analyser.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2024
From: WILDGOOSE, JASON LEE; HOYES, JOHN BRIAN; DENNY, RICHARD
To: MICROMASS UK LIMITED
Reel/Frame 067560/0402 →
Priority Claims (1)
GB 1903779 · Mar 20, 2019 · national
Continuity (1)
Related Publication 20220165560A1 · May 26, 2022
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