| Title: |
Tandem TOF Mass Spectrometer With Pulsed Accelerator To Reduce Velocity Spread |
| Document Number: |
20110049350 |
| Publication Date: |
March 3, 2011 |
| Appl. No: |
12/549076 |
| Application Filed: |
August 27, 2009 |
| Abstract: |
A tandem TOF mass spectrometer includes a pulsed ion source that generates a pulse of precursor ions from a sample to be analyzed. A first pulsed ion accelerator accelerates and refocuses a predetermined group of precursor ions. A first timed ion passes the predetermined group of precursor ions and rejects substantially all other ions. An ion fragmentation chamber fragments at least some of the precursor ions in the predetermined group. A second timed ion selector selects a predetermined range of masses centered on each precursor in the predetermined group and rejects substantially all other ions. A second pulsed ion accelerator accelerates and refocuses the selected precursor ions and fragments thereof. An ion mirror generates a reflected ion beam. An ion detector detects precursor ions and fragments, wherein a flight time from the second pulsed ion accelerator to the ion detector is dependent on a mass-to-charge ratio of the selected precursor ions and fragments thereof and nearly independent of an initial velocity distribution of ions in the pulse of ions. |
| Inventors: |
Vestal, Marvin L. (Framingham, MA, US) |
| Assignees: |
VIRGIN INSTRUMENTS CORPORATION (Sudbury, MA, US) |
| Claim: |
1. A tandem TOF mass spectrometer comprising: a) a pulsed ion source that generates a pulse of precursor ions from a sample to be analyzed; b) a first pulsed ion accelerator positioned to receive the pulse of precursor ions generated by the pulsed ion source, the first pulsed ion accelerator accelerating and refocusing a predetermined group of precursor ions; c) a first timed ion selector positioned to receive the predetermined group of precursor ions accelerated by the first pulsed accelerator, the first timed ion selector passing the predetermined group of precursor ions and rejecting substantially all other ions; d) an ion fragmentation chamber positioned to receive the predetermined group of precursor ions from the first timed ion selector, the ion fragmentation chamber fragmenting at least some of the precursor ions in the predetermined group of precursor ions; e) a second timed ion selector positioned to receive the precursor ions and fragments thereof from the ion fragmentation chamber, the second timed ion selector selecting a predetermined range of masses centered on each precursor in the predetermined group of precursor ions and rejecting substantially all other ions; f) a second pulsed ion accelerator that is positioned to receive selected precursor ions and fragments thereof in the predetermined range of masses from the second timed ion selector, the second pulsed ion accelerator accelerating and refocusing the selected precursor ions and fragments thereof, g) an ion mirror having an input that is positioned in a path of the ions accelerated by the second pulsed ion accelerator, the ion mirror generating a reflected ion beam; and h) an ion detector positioned in a path of the reflected ion beam, the ion detector detecting precursor ions and fragments, wherein a flight time from the second pulsed ion accelerator to the ion detector is dependent on a mass-to-charge ratio of the selected precursor ions and fragments thereof and nearly independent of an initial velocity distribution of ions in the pulse of ions. |
| Claim: |
2. The tandem TOF mass spectrometer of claim 1 wherein the pulsed ion source comprises a MALDI pulsed ion source. |
| Claim: |
3. The tandem TOF mass spectrometer of claim 1 further comprising an ion deflector positioned in a path of the pulse of precursor ions, the ion deflector deflecting the pulse of precursor ions at a predetermined angle to the first pulsed ion accelerator. |
| Claim: |
4. The tandem TOF mass spectrometer of claim 3 wherein the predetermined angle reduces ion trajectory errors that limit mass resolving power. |
| Claim: |
5. The tandem TOF mass spectrometer of claim 3 wherein the predetermined angle is substantially equal to a predetermined angle of the input to the ion mirror relative to a path of precursor ions and fragments. |
| Claim: |
6. The tandem TOF mass spectrometer of claim 1 further comprising: a) a third timed ion selector positioned in a path of the precursor ions and fragments accelerated by the second pulsed ion accelerator, the third timed ion selector selecting a predetermined portion of the fragment ions from each precursor; and b) a field-free drift space positioned between the third timed ion selector and the ion detector, the field free drift space being biased with a static accelerating field that accelerates the fragment ions and corresponding precursor ion, wherein the ion detector comprises an input surface biased at substantially the same potential as the field-free drift space. |
| Claim: |
7. The tandem TOF mass spectrometer of claim 1 wherein entrance planes of at least two of the ion mirror, the first timed ion selector, the second timed ion selector, the first ion accelerator, and the ion detector are substantially parallel. |
| Claim: |
8. The tandem TOF mass spectrometer of claim 1 wherein the timed ion selector comprises a pair of Bradbury-Nielson ion gates. |
| Claim: |
9. The tandem TOF mass spectrometer of claim 8 wherein the Bradbury-Nielson ion gates are configured to provide high resolution selection of precursor ions with reduced perturbations of transmitted ions. |
| Claim: |
10. The tandem TOF mass spectrometer of claim 1 wherein the ion mirror comprises a two-stage reflector. |
| Claim: |
11. The tandem TOF mass spectrometer of claim 1 wherein an entrance plane of the ion mirror is inclined at a predetermined angle relative to a direction of ion extraction from the pulsed ion source that is chosen to reduce ion trajectory errors which limit mass resolving power. |
| Claim: |
12. The tandem TOF mass spectrometer of claim 1 wherein the fragmentation chamber comprises a collision cell with an RF-excited octopole that guides the fragment ions. |
| Claim: |
13. The tandem TOF mass spectrometer of claim 1 wherein the ion fragmentation chamber comprises a differential vacuum pumping system that prevent excess collision gas from significantly increasing pressure in the tandem TOF mass spectrometer. |
| Claim: |
14. A method of measuring mass-to-charge ratio, the method comprising: a) performing a first TOF mass analysis by generating an ion beam comprising a plurality of ions, accelerating the ion beam, and selecting a first group of precursor ions from the ion beam that have predetermined mass ranges; b) fragmenting at least some of the selected first group of precursor ions; c) selecting a second group of precursor ions and fragments; and d) performing a second TOF mass analysis by separating the fragments and detecting a fragment ion mass spectrum from at least one of the accelerated ions. |
| Claim: |
15. The method of claim 14 wherein a mass range of the second group of precursor ions is lower than a mass range of the first group of precursor ions. |
| Claim: |
16. The method of claim 14 wherein the generating the ion beam comprises generating an ion beam from a MALDI pulsed ion source. |
| Claim: |
17. The method of claim 14 wherein the performing the first TOF mass analysis further comprises focusing the plurality of ions into an ion beam. |
| Claim: |
18. The method of claim 14 wherein the performing the first TOF mass analysis and the performing the second TOF mass analysis are independently optimized. |
| Claim: |
19. The method of claim 14 wherein the accelerating the ion beam comprises focusing the ion beam. |
| Claim: |
20. The method of claim 14 further comprising reflecting the accelerated precursor ions and fragments thereof. |
| Claim: |
21. The method of claim 20 wherein a flight time of the accelerated precursor ions and fragments is dependent on the mass-to-charge ratio of the precursor ions and fragments and is nearly independent of the velocity distribution of the second group of precursor ions. |
| Claim: |
22. The method of claim 14 further comprising selecting a predetermined portion of the fragment ions for at least one precursor ion. |
| Claim: |
23. The method of claim 14 further comprising biasing a field-free drift space with a static accelerating electric field that accelerates the fragment ions and precursors. |
| Claim: |
24. The method of claim 14 wherein the fragmenting at least some of the selected precursor ions comprises differential vacuum pumping a fragmentation chamber to prevent excess collision gas from significantly increasing pressure. |
| Claim: |
25. The method of claim 14 further comprising deflecting the ion beam at a predetermined angle that reduces ion trajectory errors which limit mass resolving power. |
| Claim: |
26. The method of claim 14 further comprising orienting the ion beam to minimize the first order focusing errors for fragment ions. |
| Claim: |
27. The method of claim 14 wherein a flight time of the accelerated second group of precursor ions is dependent on the mass-to-charge ratio of the precursor ions and is nearly independent of the velocity distribution of the selected ions. |
| Current U.S. Class: |
250/282 |
| Current International Class: |
01 |
| Accession Number: |
edspap.20110049350 |
| Database: |
USPTO Patent Applications |
