Method and apparatus for ion fragmentation in mass spectrometry
| Title: | Method and apparatus for ion fragmentation in mass spectrometry |
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| Patent Number: | 8,188,423 |
| Publication Date: | May 29, 2012 |
| Appl. No: | 12/784532 |
| Application Filed: | May 21, 2010 |
| Abstract: | A method for fragmentation of analyte ions for mass spectroscopy and a system for mass spectroscopy. The method produces gas-phase analyte ions, produces gas-phase odd-electron containing species separately from the analyte ions, and mixes the gas-phase analyte ions and the odd-electron containing species at substantially atmospheric pressure conditions to produce fragment ions prior to introduction into a mass spectrometer. The system includes a gas-phase analyte ion source, a gas-phase odd-electron containing species source separate from the gas-phase analyte ion source, a mixing region where the gas-phase analyte ions and the odd-electron containing species are mixed at substantially atmospheric pressure to produce fragment ions of the analyte ions, a mass spectrometer having an entrance where at least a portion of the fragment ions are introduced into a vacuum of the mass spectrometer, and a detector in the mass spectrometer which determines a mass to charge ratio analysis of the fragment ions. |
| Inventors: | Doroshenko, Vladimir M. (Sykesville, MD, US); Berkout, Vadym D. (Rockville, MD, US); Vilkov, Andrey (Tustin, CA, US) |
| Assignees: | Science & Engineering Services, Inc. (Columbia, MD, US) |
| Claim: | 1. A method for fragmentation of analyte ions for mass spectroscopy, comprising: producing gas-phase analyte ions; producing gas-phase odd-electron containing species separately from the analyte ions; and mixing said gas-phase analyte ions and said odd-electron containing species at substantially atmospheric pressure conditions to produce fragment ions prior to introduction into a mass spectrometer. |
| Claim: | 2. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing the analyte ions by electrospray ionization. |
| Claim: | 3. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing the analyte ions by atmospheric pressure chemical ionization. |
| Claim: | 4. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing the analyte ions by photoionization. |
| Claim: | 5. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing the analyte ions by atmospheric pressure matrix-assisted laser desorption ionization. |
| Claim: | 6. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing analyte ions of a positive polarity. |
| Claim: | 7. The method according to claim 1 , wherein producing gas-phase analyte ions comprises producing analyte ions of a negative polarity. |
| Claim: | 8. The method according to claim 1 , wherein producing gas-phase analyte ions comprises providing as a source of the gas-phase analyte ions at least one of proteins, peptides, DNA, RNA, lipids, polysaccharides, and metabolite products. |
| Claim: | 9. The method according to claim 1 , wherein producing gas-phase odd-electron containing species comprises generating the odd-electron containing particles by electrical discharge. |
| Claim: | 10. The method according to claim 9 , further comprising: producing final or intermediate products of chemical reactions caused by the electrical discharge. |
| Claim: | 11. The method according to claim 9 , wherein generating the odd-electron containing particles by electrical discharge comprises generating the odd-electron containing particles from at least one of a pulsed electrical discharge, a microwave discharge, an inductively-coupled RF discharge, a capacitively-coupled RF discharge, a glow discharge, and a corona discharge. |
| Claim: | 12. The method according to claim 1 , wherein producing gas-phase odd-electron containing species comprises generating the odd-electron containing particles by photoionization. |
| Claim: | 13. The method according to claim 1 , wherein producing gas-phase odd-electron containing species comprises producing neutral odd-electron containing species. |
| Claim: | 14. The method according to claim 1 , wherein producing gas-phase odd-electron containing species comprises producing ionic odd-electron containing species. |
| Claim: | 15. The method according to claim 1 , wherein producing gas-phase odd-electron containing species comprises producing free electrons. |
| Claim: | 16. The method according to claim 1 , wherein mixing the analyte ions and the odd-electron containing species comprises mixing at pressures between 0.1 Torr and 10 Torr. |
| Claim: | 17. The method according to claim 1 , wherein mixing the analyte ions and the odd-electron containing species comprises mixing at pressures between 10 Torr and 100 Torr. |
| Claim: | 18. The method according to claim 1 , wherein mixing the analyte ions and the odd-electron containing species comprises mixing at pressures between 100 Torr and 1 atmosphere. |
| Claim: | 19. The method according to claim 1 , wherein mixing the analyte ions and the odd-electron containing species comprises mixing at pressure above 1 atmosphere. |
| Claim: | 20. The method of claim 1 , further comprising: supplying additional activation energy to the analyte ions. |
| Claim: | 21. The method according to claim 20 , wherein supplying additional activation energy occurs after a mixing with gas-phase odd-electron containing species. |
| Claim: | 22. The method according to claim 20 , wherein supplying additional activation energy precedes a mixing with gas-phase odd-electron containing species. |
| Claim: | 23. The method according to claim 20 , wherein supplying additional activation energy comprises supplying the activation energy in the form of photoactivation. |
| Claim: | 24. The method according to claim 20 , wherein supplying additional activation energy comprises supplying the activation energy in collisions with background gas having an elevated temperature. |
| Claim: | 25. The method according to claim 20 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures less than 100° C. |
| Claim: | 26. The method according to claim 20 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures between 100° C. and 300° C. |
| Claim: | 27. The method according to claim 20 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures above 300° C. |
| Claim: | 28. The method of claim 1 , further comprising: supplying additional activation energy to intermediate products formed in the interaction of the analyte ions with the odd-electron containing species. |
| Claim: | 29. The method according to claim 28 , wherein supplying additional activation energy comprises supplying the activation energy in the form of photoactivation. |
| Claim: | 30. The method according to claim 28 , wherein supplying additional activation energy comprises supplying the activation energy in collisions with background gas having an elevated temperature. |
| Claim: | 31. The method according to claim 30 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures less than 100° C. |
| Claim: | 32. The method according to claim 30 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures between 100° C. and 300° C. |
| Claim: | 33. The method according to claim 30 , wherein supplying the activation energy in collisions with background gas comprises supplying the background gas at temperatures above 300° C. |
| Claim: | 34. The method of claim 1 , further comprising: selecting the analyte ions using at least one of gas-phase and liquid-phase chromatography. |
| Claim: | 35. The method of claim 1 , further comprising: selecting the analyte ions using at least on of ion mobility and field-asymmetric ion mobility methods. |
| Claim: | 36. A method for acquiring fragment ion spectra, via fragmentation of analyte ions in reactions with odd-electron containing species, comprising: generating the analyte ions in a gas phase from a first sample; generating the odd-electron containing species in a gas phase from a second sample; mixing the analyte ions and the odd-electron containing species at substantially atmospheric pressure conditions to produce fragment ions; introducing at least part of the fragment ions into a mass spectrometer; and measuring mass to charge ratios of the fragment ions in the mass spectrometer. |
| Claim: | 37. A system for mass spectroscopy, comprising: a gas-phase analyte ion source configured to generate gas-phase analyte ions; a gas-phase odd-electron containing species source separate from the gas-phase analyte ion source and configured to generate gas-phase odd-electron containing species; a mixing region where said gas-phase analyte ions and said odd-electron containing species are mixed at substantially atmospheric pressure to produce fragment ions of said analyte ions; a mass spectrometer having an entrance where at least a portion of said fragment ions are introduced into a vacuum of the mass spectrometer; and a detector in the mass spectrometer which determines a mass to charge ratio analysis of the fragment ions. |
| Claim: | 38. The system according to claim 37 , wherein the gas-phase analyte ion source comprises an electrospray ionization unit. |
| Claim: | 39. The system according to claim 37 , wherein the gas-phase analyte ion source comprises an atmospheric pressure chemical ionization unit. |
| Claim: | 40. The system according to claim 37 , wherein the gas-phase analyte ion source comprises a photoionization unit. |
| Claim: | 41. The system according to claim 37 , wherein the gas-phase analyte ion source comprises an atmospheric pressure matrix-assisted laser desorption ionization unit. |
| Claim: | 42. The system according to claim 37 , wherein the gas-phase analyte ion source is configured to produce analyte ions of a positive polarity. |
| Claim: | 43. The system according to claim 37 , wherein the gas-phase analyte ion source is configured to produce analyte ions of a negative polarity. |
| Claim: | 44. The system according to claim 37 , further comprising: a source supply for the gas-phase analyte ions providing at least one of protein, peptide, DNA, RNA, lipid, polysaccharide, and metabolite product. |
| Claim: | 45. The system according to claim 37 , wherein the gas-phase odd-electron containing species source comprises an electrical discharge unit. |
| Claim: | 46. The system according to claim 45 , wherein the electrical discharge unit comprises at least one of a microwave discharge, an inductively-coupled RF discharge, a capacitively-coupled RF discharge, a glow discharge, and a corona discharge. |
| Claim: | 47. The system according to claim 37 , wherein the gas-phase odd-electron containing species source comprises a photoionization unit. |
| Claim: | 48. The system according to claim 37 , wherein the gas-phase odd-electron containing species source is configured to produce neutral odd-electron containing species. |
| Claim: | 49. The system according to claim 37 , wherein the gas-phase odd-electron containing species source is configured to produce ionic odd-electron containing species. |
| Claim: | 50. The system according to claim 37 , wherein the gas-phase odd-electron containing species source is configured to produce free electrons. |
| Claim: | 51. The system according to claim 37 , wherein the mixing region comprises a pressure region between 0.1 Torr and 10 Torr. |
| Claim: | 52. The system according to claim 37 , wherein the mixing region comprises a pressure region between 10 Torr and 100 Torr. |
| Claim: | 53. The system according to claim 37 , wherein the mixing region comprises a pressure region between 100 Torr and 1 atmosphere. |
| Claim: | 54. The system according to claim 37 , wherein the mixing region comprises a pressure region above 1 atmosphere. |
| Claim: | 55. The system according to claim 37 , further comprising: an additional activation energy source configured to supply additional activation energy to at least one of the analyte ions and intermediate products formed in the interaction of the analyte ions with the odd-electron containing species. |
| Claim: | 56. The system according to claim 55 , wherein the additional activation energy source comprises a light source for photoactivation. |
| Claim: | 57. The system according to claim 55 , wherein the additional activation energy source comprises a background gas heater configured to elevate a temperature of a background gas. |
| Claim: | 58. The system according to claim 57 , wherein the background gas heater is configured to supply the background gas at temperatures less than 100° C. |
| Claim: | 59. The system according to claim 57 , wherein the background gas heater is configured to supply the background gas at temperatures between 100° C. and 300° C. |
| Claim: | 60. The system according to claim 57 , wherein the background gas heater is configured to supply the background gas at temperatures between 300° C. and 500° C. |
| Claim: | 61. The system according to claim 37 , further comprising: at least one of a gas-phase unit and a liquid-phase chromatography unit configured to select the analyte ions. |
| Claim: | 62. The system according to claim 37 , further comprising: at least one of an ion mobility unit and a field-asymmetric ion mobility unit configured to select the analyte ions. |
| Claim: | 63. A method for fragmentation of analyte ions for mass spectroscopy, comprising: producing from a first source gas-phase analyte ions; producing from a second source separate from the first source a species for downstream interaction with the gas-phase analyte ions; and mixing said gas-phase analyte ions and said species at substantially atmospheric pressure conditions to produce fragment ions prior to introduction into a mass spectrometer. |
| Current U.S. Class: | 250/281 |
| Patent References Cited: | 5992244 November 1999 Pui et al. 6649907 November 2003 Ebeling et al. 7442921 October 2008 Franzen 7723676 May 2010 Vilkov et al. 2006/0250138 November 2006 Sparkman et al. 2006/0255261 November 2006 Whitehouse et al. |
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| Primary Examiner: | Wells, Nikita |
| Attorney, Agent or Firm: | Oblon, Spivak, McClelland, Maier & Neustadt, L.L.P. |
| Accession Number: | edspgr.08188423 |
| Database: | USPTO Patent Grants |
| Language: | English |
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