| Title: |
Tandem Time-Of-Flight Mass Spectrometry With Simultaneous Space And Velocity Focusing |
| Document Number: |
20120168618 |
| Publication Date: |
July 5, 2012 |
| Appl. No: |
13/415802 |
| Application Filed: |
March 08, 2012 |
| Abstract: |
A tandem TOF mass spectrometer includes a first TOF mass analyzer that generates an ion beam comprising a plurality of ions and that selects a group of precursor ions from the plurality of ions. A pulsed ion accelerator accelerates and refocuses the selected group of precursor ions. An ion fragmentation chamber is positioned to receive the selected group of precursor ions that is refocused by the pulsed ion accelerator. At least some of the selected group of precursor ions is fragmented in the ion fragmentation chamber. A second TOF mass analyzer receives the selected group of precursor ions and ion fragments thereof from the ion fragmentation chamber and separates the ion fragments and then detects a fragment ion mass spectrum. |
| Inventors: |
Vestal, Marvin L. (Framingham, MA, US) |
| Assignees: |
VIRGIN INSTRUMENTS CORPORATION (Sudbury, MA, US) |
| Claim: |
1. A tandem time-of-flight mass spectrometer comprising: a. a first time-of-flight mass analyzer that performs a first TOF mass analysis by generating an ion beam comprising a plurality of ions and then selecting a group of precursor ions with predetermined mass-to-charge ratios from the plurality of ions, wherein an ion flight time of the selected group of precursor ions through the first time-of-flight mass analyzer is substantially independent to first order of both an initial position and an initial velocity; b. an ion fragmentation chamber positioned in the ion flight path of the selected group of precursor ions, the ion fragmentation chamber fragmenting at least one of the selected group of precursor ions accelerated by the ion accelerator; and c. a second time-of-flight mass analyzer positioned in the ion flight path of the selected group of precursor ions, the second time-of-flight mass analyzer performing a second TOF mass analysis by separating the ion fragments and then detecting a fragment ion mass spectrum with a detector, wherein a flight time of precursor ions and fragments thereof to the ion detector is dependent on a mass-to-charge ratio of the selected precursor ions and fragments thereof and is nearly independent of a velocity distribution of the selected precursor ions and fragments thereof. |
| Claim: |
2. The tandem time-of-flight mass spectrometer of claim 1 wherein the first time-of-flight mass analyzer comprises: a. an ion source that generates a pulse of ions; b. a two-field ion accelerator having an input that receives the ions generated by the ion source, the two-field ion accelerator generating an electric field that accelerates the ions generated by the ion source through the ion flight path and causes the ion flight time to a first focal plane in the ion flight path to be independent of an initial position of the ions; c. a pulsed ion accelerator positioned in the ion flight path after the two-field ion accelerator, the pulsed ion accelerator generating an accelerating electric field that focuses ions of a predetermined mass-to-charge to a second focal plane wherein the ion flight time to the second focal plane is substantially independent to first order of an initial velocity and an initial position of the ions prior to acceleration; and d. a timed ion selector positioned at the focal plane to select and transmit ions of the predetermined mass-to-charge ratio. |
| Claim: |
3. The tandem time-of-flight mass spectrometer of claim 2 wherein the timed ion selector comprises a pair of Bradbury-Nielson ion gates configured to provide high resolution selection of precursor ions with minimal perturbations of transmitted ions. |
| Claim: |
4. The tandem time-of-flight mass spectrometer of claim 2 wherein the ion source comprises a MALDI ion source. |
| Claim: |
5. The tandem time-of-flight mass spectrometer of claim 2 wherein the fragmentation chamber is positioned in a field-free region between the pulsed ion accelerator and the timed ion selector. |
| Claim: |
6. The tandem time-of-flight mass spectrometer of claim 2 wherein the ion fragmentation chamber is positioned in a field-free region between the timed ion selector and the second time-of-flight mass analyzer. |
| Claim: |
7. The tandem time-of-flight mass spectrometer of claim 1 wherein the second time-of-flight mass analyzer comprises a second pulsed ion accelerator and an ion detector positioned at a predetermined position in a field-free region adjacent to the second pulsed ion accelerator, the selected precursor ions and fragments thereof from the fragmentation chamber being accelerated by the second pulsed ion accelerator and being directed to the ion detector. |
| Claim: |
8. The tandem time-of-flight mass spectrometer of claim 7 wherein the second time-of-flight mass analyzer further comprises an ion mirror that is positioned in a path of the selected precursor ions and fragments thereof accelerated by the second pulsed ion accelerator, the ion mirror generating a reflected ion beam that is directed to the ion detector. |
| Claim: |
9. The tandem time-of-flight mass spectrometer of claim 7 wherein the second time-of-flight mass analyzer further comprises: a. a second timed ion selector positioned in a path of the selected precursor ions and fragments thereof accelerated by the second pulsed ion accelerator, the second timed ion selector selecting a predetermined portion of the fragment ions from each precursor; and b. a field-free drift space positioned between the second timed ion selector and the ion detector, the field free drift space being biased with a static accelerating field that accelerates the fragment ions from each precursor ion, wherein the ion detector comprises an input surface that is biased at substantially the same potential as the field-free drift space. |
| Claim: |
10. The tandem time-of-flight mass spectrometer of claim 1 wherein the first time-of-flight mass analyzer comprises: a. an ion source that generates a pulse of ions; b. a two-field ion accelerator having an input that receives the ions generated by the ion source, the two-field ion accelerator generating an electric field that accelerates the ions generated by the ion source through the ion flight path and causes the ion flight time to a first focal plane in the ion flight path to be independent of an initial position of the ions; c. a pulsed ion accelerator positioned in the ion flight path after the two-field ion accelerator, the pulsed ion accelerator generating an accelerating electric field that focuses ions of a predetermined mass-to-charge to a second focal plane wherein the ion flight time to the first focal plane is substantially independent to first order of an initial velocity and an initial position of the ions prior to acceleration; d. an ion reflector positioned in the ion flight path that focuses ions to a third focal plane where the ion flight time to the third focal plane for an ion of predetermined mass-to-charge ratio is substantially independent to first order of an initial velocity of the ions prior to the acceleration; and e. a timed ion selector positioned at the second focal plane to select and transmit ions of the predetermined mass-to-charge ratio. |
| Claim: |
11. The tandem time-of-flight mass spectrometer of claim 10 wherein the timed ion selector comprises a pair of Bradbury-Nielson ion gates configured to provide high resolution selection of precursor ions with minimal perturbations of transmitted ions. |
| Claim: |
12. The tandem time-of-flight mass spectrometer of claim 10 wherein the ion source comprises a MAIDI ion source. |
| Claim: |
13. The tandem time-of-flight mass spectrometer of claim 10 wherein the fragmentation chamber is located in a field-free region between the ion reflector and the timed ion selector. |
| Claim: |
14. The tandem time-of-flight mass spectrometer of claim 10 wherein the fragmentation chamber is located in a field-free region between the timed ion selector and the second time-of-flight mass analyzer. |
| Claim: |
15. The tandem time-of-flight mass spectrometer of claim 10 wherein the second time-of-flight mass analyzer comprises a second pulsed ion accelerator and an ion detector positioned at a predetermined position in a field-free region adjacent to the second pulsed ion accelerator, the selected precursor ions and fragments thereof from the fragmentation chamber being accelerated by the second pulsed ion accelerator and being directed to the ion detector. |
| Claim: |
16. The tandem time-of-flight mass spectrometer of claim 15 wherein the second time-of-flight mass analyzer further comprises a second ion mirror that is positioned in a path of the selected precursor ions and fragments thereof accelerated by the second pulsed ion accelerator, the second ion mirror generating a reflected ion beam that is directed to the ion detector. |
| Claim: |
17. The tandem time-of-flight mass spectrometer of claim 10 wherein the second time-of-flight mass analyzer further comprises: a. a second timed ion selector positioned in a path of the selected precursor ions and fragments thereof accelerated by the second pulsed ion accelerator, the second timed ion selector selecting a predetermined portion of the fragment ions from each precursor; and b. a field-free drift space positioned between the second timed ion selector and the ion detector, the field free drift space being biased with a static accelerating field that accelerates the fragment ions from each precursor ion, wherein the ion detector comprises an input surface that is biased at substantially the same potential as the potential of the field-free drift space. |
| Claim: |
18. The tandem time-of-flight mass spectrometer of claim 2 further comprising: a. a static high voltage generator having an output that is electrically connected to at least one of the first time-of-flight mass analyzer, the ion fragmentation chamber, and the second time-of-flight mass analyzer; b. a pulsed high voltage generator having an output that is electrically connected to the pulsed ion accelerator and an output that is electrically connected to the timed ion selector; c. a multiplexed time delay generator having an output that is electrically connected to at least one pulsed accelerator, the multiplexed time delay generator controlling a timing of the high voltage pulses generated by the at least one pulsed accelerators; and d. a computer having outputs that are coupled to at least one of the static high voltage generator, the pulsed high voltage generator, and the multiplexed time delay generator, the computer controlling at least one of a magnitude of voltages generated by the static high voltage generator, a magnitude and a repetition rate of pulses generated by the pulsed high voltage generator, and time delays generated by the multiplexed time delay generator. |
| Claim: |
19. The tandem time-of-flight mass spectrometer of claim 10 further comprising: a. a static high voltage generator having an output that is electrically connected to the tandem mass spectrometer; b. a pulsed high voltage generator having an output that is electrically connected to the pulsed ion accelerator and an output that is electrically connected to the timed ion selector; c. a multiplexed time delay generator having an output that is electrically connected to at least one pulsed accelerator, the multiplexed time delay generator controlling a timing of the high voltage pulses generated by the at least one pulsed accelerators; and d. a computer having outputs that are coupled to at least one of the static high voltage generator, pulsed high voltage generator, and the multiplexed time delay generator, the computer controlling at least one of a magnitude of voltages generated by the static high voltage generator, a magnitude and a repetition rate of pulses generated by the pulsed high voltage generator, and time delays generated by the multiplexed time delay generator. |
| Claim: |
20. The tandem time-of-flight mass spectrometer of claim 10 further comprising a digitizer for digitizing time-of-flight spectra. |
| Claim: |
21. A method for identifying an unknown sample using a tandem mass spectrometer, the method comprising: a. generating an ion beam comprising a plurality of ions; b. selecting at least one monoisotopic precursor ion from the plurality of ions using a first time-of-flight mass spectrometer configured to perform simultaneous space and velocity focusing; c. fragmenting at least one of the selected monoisotopic precursor ions; d. separating the fragmented selected monoisotopic precursor ions with a second time-of-flight mass analyzer so that a flight time of precursor ions and fragments thereof to a detector is dependent on a mass-to-charge ratio of the selected precursor ions and fragments thereof and is nearly independent of a velocity distribution of the selected precursor ions and fragments thereof; e. detecting the separated fragmented ions with the detector; and f. recording the fragment ion mass spectra for at least one selected precursor ion. |
| Claim: |
22. The method of claim 21 wherein the generating the ion beam comprises generating an ion beam with MALDI. |
| Claim: |
23. The method of claim 21 wherein the unknown sample comprises a biological polymer. |
| Claim: |
24. The method of claim 21 wherein the selecting one or more monoisotopic precursor ions comprises selecting a predetermined portion of the fragment ions from each monoisotopic precursor. |
| Claim: |
25. The method of claim 21 wherein the method comprises elucidating at least one of a structure and a sequence of the unknown sample. |
| Claim: |
26. A method for quantifying an unknown sample using a tandem mass spectrometer, the method comprising: a. generating an ion beam comprising a plurality of ions; b. selecting at least two monoisotopic precursor ion from the plurality of ions using a first time-of-flight mass spectrometer configured to perform simultaneous space and velocity focusing; c. fragmenting at least two of the selected monoisotopic precursor ions; d. separating the fragmented selected monoisotopic precursor ions with a second time-of-flight mass analyzer so that a flight time of precursor ions and fragments thereof to a detector is dependent on a mass-to-charge ratio of the selected precursor ions and fragments thereof and is nearly independent of a velocity distribution of the selected precursor ions and fragments thereof; e. detecting the separated fragmented ions with the detector; and f. recording the fragment ion mass spectra for at least two selected precursor ion. |
| Claim: |
27. The method of claim 26 wherein at least one of the selected precursor ions comprise a molecular ion of a known molecule present at a predetermined concentration in the sample. |
| Claim: |
28. The method of claim 26 further comprising determining a concentration of the molecule corresponding to a selected precursor by comparing intensities of fragment ions from the selected precursor to intensities of predetermined fragment ions from known molecules. |
| Current U.S. Class: |
250/282 |
| Current International Class: |
01; 01 |
| Accession Number: |
edspap.20120168618 |
| Database: |
USPTO Patent Applications |
