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Introduction to Modern Techniques in Mass Spectrometry

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Part of the book series: Handbook of Modern Biophysics ((HBBT,volume 3))

Abstract

Mass spectrometry has emerged as an invaluable technique with a wide array of applications ranging from clinical to biodefense. With the development of different ionization techniques and mass analyzers, even challenging samples can be analyzed, thereby making mass spectrometry an important analytical tool in the field of biophysics. Mass spectrometry is the only technique that offers the combination of high sensitivity (attomole) with structural information. While other analytical techniques may provide higher sensitivity, these techniques do not provide structural information. Conversely, other techniques may provide more complete structures but have significantly less sensitivity. The different ionization techniques allow for the examination of analytes ranging from small metabolites to large macromolecular assemblies. In this chapter the major components are described rather than the possible applications, which would require volumes. With the major concepts in hand, the student is encouraged to read specific reviews regarding the kinds of applications of interest to the researcher.

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Further Study

  • Cotter RJ. 1997. Time-of-flight mass spectrometry. Washington, DC: American Chemical Society.

    Google Scholar 

  • Ekman R, Silberring J, Westman-Brinkmalm A, Kraj A. 2009. Mass spectrometry instrumentation, interpretation, and applications. Hoboken, NJ: John Wiley & Sons.

    Google Scholar 

  • Hillenkamp F, Peter-Katalinic J, eds. 2007. MALDI MS: A practical guide to instrumentation, methods and applications. Weinheim: Wiley-VCH.

    Book  Google Scholar 

  • McIver RT, McIver JR. 2006. Fourier transform mass spectrometry: principles and applications. Lake Forest, IL: IonSpec.

    Google Scholar 

References

  1. Dempster AJ. 1921. Positive ray analysis of lithium and magnesium. Phys Rev 18:415-422.

    Article  CAS  Google Scholar 

  2. Watson JT, Sparkman OD. 2007. Introduction to mass spectrometry. Chichester: John Wiley & Sons.

    Book  Google Scholar 

  3. Ekman R, Silberring J, Westman-Brinkmalm A, Kraj A. 2009. Mass spectrometry instrumentation, interpretation, and applications. Hoboken, NJ: John Wiley & Sons.

    Google Scholar 

  4. Munson MSB, Field FH. 1966. Chemical ionization mass spectrometry, I: general introduction. J Am Chem Soc 88:2621-2630.

    Article  CAS  Google Scholar 

  5. Fenn JB. 2003. Electrospray wings for molecular elephants (Nobel lecture). Angew Chem, Int Ed 42:3871-3894.

    Article  CAS  Google Scholar 

  6. Dole ML, Mack LL, Hines RL, Mobley RC, Ferguson LD, Alice MB. 1968. Molecular beams of macroions. J Chem Phys 49:2240-2249.

    Article  CAS  Google Scholar 

  7. Iribarne JV, Thomson BA. 1976. On the evaporation of small ions from charged droplets. J Chem Phys 64:2287.

    Article  CAS  Google Scholar 

  8. Karas M, Hillenkamp F. 1988. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60:2299-2301.

    Article  CAS  PubMed  Google Scholar 

  9. Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T. 1988. Protein and Polymer Analyses up to m/z 100000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2:151-153.

    Article  CAS  Google Scholar 

  10. Hillenkamp F, Peter-Katalinic J. 2007. MALDI MS: a practical guide to instrumentation, methods and applica- tions. Weinheim: Wiley-VCH Verlag.

    Book  Google Scholar 

  11. Zenobi R, Knochenmuss R. 1998. Ion formation in MALDI mass spectrometry. Mass Spectrom Rev 17:337- 366.

    Article  CAS  Google Scholar 

  12. Comisarow MB, Marshall AG. 1974. Fourier transform ion cyclotron resonance spectroscopy. Chem Phys Lett 25:282-283.

    Article  CAS  Google Scholar 

  13. Comisarow MB, Marshall AG. 1996. The early development of Fourier transform ion cyclotron resonance (FT-ICR) spectroscopy. J Mass Spectrom 31:581-585.

    Article  CAS  PubMed  Google Scholar 

  14. Lawrence EO, Livingston MS. 1932. The production of high speed light ions without the use of high voltages. Phys Rev 40:19-35.

    Article  CAS  Google Scholar 

  15. Marshall AG, Grosshans PB. 1991. Fourier transform ion cyclotron resonance mass spectrometry: the teenage years. Anal Chem 63:215A-229A.

    Article  CAS  Google Scholar 

  16. McIver RT, McIver JR. 2006. Fourier transform mass spectrometry principles and applications. Lake Forest, IL: IonSpec.

    Google Scholar 

  17. An HJ, Miyamoto S, Lancaster KS, Kirmiz C, Li B, Lam KS, Leiserowitz GS, Lebrilla CB. 2006. Profiling of glycans in serum for the discovery of potential biomarkers for ovarian cancer. J Proteome Res 5:1626-1635.

    Article  CAS  PubMed  Google Scholar 

  18. de Leoz ML, An HJ, Kronewitter S, Kim J, Beecroft S, Vinall R, Miyamoto S, de Vere White R, Lam KS, Leb- rilla C. 2008. Glycomic approach for potential biomarkers on prostate cancer: profiling of N-linked glycans in human sera and pRNS cell lines. Dis Markers 25:243-258.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kirmiz C, Li B, An HJ, Clowers BH, Chew HK, Lam KS, Ferrige A, Alecio R, Borowsky AD, Sulaimon S, Lebrilla CB, Miyamoto S. 2007. A serum glycomics approach to breast cancer biomarkers. Mol Cell Proteomics 6:43-55.

    Article  CAS  PubMed  Google Scholar 

  20. Li B, An HJ, Kirmiz C, Lebrilla CB, Lam KS, Miyamoto S. 2008. Glycoproteomic analyses of ovarian cancer cell lines and sera from ovarian cancer patients show distinct glycosylation changes in individual proteins. J Proteome Res 7:3776-88.

    Article  CAS  PubMed  Google Scholar 

  21. Niñonuevo MR, Ward RE, LoCascio RG, German JB, Freeman SL, Barboza M, Mills DA, Lebrilla CB. 2007. Methods for the quantitation of human milk oligosaccharides in bacterial fermentation by mass spectrometry. Anal Biochem 361:15-23.

    Article  PubMed  Google Scholar 

  22. Seipert RR, Barboza M, Niñonuevo MR, LoCascio RG, Mills DA, Freeman SL, German JB, Lebrilla CB. 2008. Analysis and quantitation of fructooligosaccharides using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem 80:159-165.

    Article  CAS  PubMed  Google Scholar 

  23. Seipert RR, Dodds ED, Clowers BH, Beecroft SM, German JB, Lebrilla CB. 2008. Factors that influence fragmentation behavior of N-linked glycopeptide ions. Anal Chem 80:3684-3692.

    Article  CAS  PubMed  Google Scholar 

  24. Seipert RR, Dodds ED, Lebrilla CB. 2009. Exploiting differential dissociation chemistries of O-linked glycopeptide ions for the localization of mucin-type protein glycosylation. J Proteome Res 8:493-501.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Clowers BH, Dodds ED, Seipert RR, Lebrilla CB. 2007. Site determination of protein glycosylation based on digestion with immobilized nonspecific proteases and Fourier transform ion cyclotron resonance mass spec- trometry. J Proteome Res 6:4032-4040.

    Article  CAS  PubMed  Google Scholar 

  26. Dodds ED, Clowers BH, Hagerman PJ, Lebrilla CB. 2008. Systematic characterization of high mass accuracy influence on false discovery and probability scoring in peptide mass fingerprinting. Anal Biochem 372:156-166.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Dodds ED, German JB, Lebrilla CB. 2007. Enabling MALDI-FTICR-MS/MS for high-performance proteomics through combination of infrared and collisional activation. Anal Chem 79:9547-9556.

    Article  CAS  PubMed  Google Scholar 

  28. Dodds ED, Hagerman PJ, Lebrilla CB. 2006. Fragmentation of singly protonated peptides via a combination of infrared and collisional activation. Anal Chem 78:8506-8511.

    Article  CAS  PubMed  Google Scholar 

  29. Marshall AG, Rodgers RP. 2004. Petroleomics: the next grand challenge for chemical analysis. Acc Chem Res 37:53-59.

    Article  CAS  PubMed  Google Scholar 

  30. Marshall AG, Rodgers RP. 2008. Petroleomics: chemistry of the underworld. Proc Natl Acad Sci USA 105:18090-1805.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Park Y, Lebrilla CB. 2005. Application of Fourier transform ion cyclotron resonance mass spectrometry to oligosaccharides. Mass Spectrom Rev 24:232-264.

    Article  CAS  PubMed  Google Scholar 

  32. Stephens WE. 1946. A pulsed mass spectrometer with time dispersion. Phys Rev 69:691.

    CAS  Google Scholar 

  33. Mamyrin BA, Karataev VI, Shmikk DV, Zagulin VA. 1973. Mass reflection: a new nonmagnetic time-of-flight high resolution mass-spectrometer. Soviet Phys JETP 37:45-48.

    Google Scholar 

  34. Yin H, Killeen K. 2007. The fundamental aspects and applications of Agilent HPLC-Chip. J Sep Sci 30:1427-1434.

    Article  CAS  PubMed  Google Scholar 

  35. Yin H, Killeen K, Brennen R, Sobek D, Werlich M, van de Goor T. 2005. Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospray tip. Anal Chem 77:527-533.

    Article  CAS  PubMed  Google Scholar 

  36. Mohammed S, Kraiczek K, Pinkse MW, Lemeer S, Benschop JJ, Heck AJ. 2008. Chip-based enrichment and NanoLC-MS/MS analysis of phosphopeptides from whole lysates. J Proteome Res 7:1565-1571.

    Article  CAS  PubMed  Google Scholar 

  37. Chu CS, Niñonuevo MR, Clowers BH, Perkins PD, An HJ, Yin H, Killeen K, Miyamoto S, Grimm R, Lebrilla CB. 2009. Profile of native N-linked glycan structures from human serum using high performance liquid chro- matography on a microfluidic chip and time-of-flight mass spectrometry. Proteomics 9:1939-1951.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Niñonuevo M, An H, Yin H, Killeen K, Grimm R, Ward R, German B, Lebrilla C. 2005. Nanoliquid chromatog- raphy-mass spectrometry of oligosaccharides employing graphitized carbon chromatography on microchip with a high-accuracy mass analyzer. Electrophoresis 26:3641-3649.

    Article  PubMed  Google Scholar 

  39. Niñonuevo MR, Perkins PD, Francis J, Lamotte LM, LoCascio RG, Freeman SL, Mills DA, German JB, Grimm R, Lebrilla CB. 2008. Daily variations in oligosaccharides of human milk determined by microfluidic chips and mass spectrometry. J Agric Food Chem 56:618-626.

    Article  PubMed  Google Scholar 

  40. Tao N, DePeters EJ, Freeman S, German JB, Grimm R, Lebrilla CB. 2008. Bovine milk glycome. J Dairy Sci 91:3768-3778.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang J, Xie Y, Hedrick JL, Lebrilla CB. 2004. Profiling the morphological distribution of O-linked oligosaccharides. Anal Biochem 334:20-35.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang J, Lindsay LL, Hedrick JL, Lebrilla CB. 2004. Strategy for profiling and structure elucidation of mucintype oligosaccharides by mass spectrometry. Anal Chem 76:5990-6001.

    Article  CAS  PubMed  Google Scholar 

  43. Li B, An HJ, Hedrick JL, Lebrilla CB. 2009. Collision-induced dissociation tandem mass spectrometry for structural elucidation of glycans. Methods Mol Biol 534:1-13.

    Google Scholar 

  44. Penn SG, Cancilla MT, Lebrilla CB. 1996. Collision-induced dissociation of branched oligosaccharide ions with analysis and calculation of relative dissociation thresholds. Anal Chem 68:2331-2339.

    Article  CAS  PubMed  Google Scholar 

  45. Xie Y, Lebrilla CB. 2003. Infrared multiphoton dissociation of alkali metal-coordinated oligosaccharides. Anal Chem 75:1590-1598.

    Article  CAS  PubMed  Google Scholar 

  46. Xie Y, Schubothe KM, Lebrilla CB. 2003. Infrared laser isolation of ions in Fourier transform mass spectrometry. Anal Chem 75:160-164.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang J, Schubothe K, Li B, Russell S, Lebrilla CB. 2005. Infrared multiphoton dissociation of O-linked mucintype oligosaccharides. Anal Chem 77:208-214.

    Article  CAS  PubMed  Google Scholar 

  48. Lancaster KS, An HJ, Li B, Lebrilla CB. 2006. Interrogation of N-Linked oligosaccharides using infrared multiphoton dissociation in FT-ICR mass spectrometry. Anal Chem 78:4990-4997.

    Article  CAS  PubMed  Google Scholar 

  49. Li B, An HJ, Hedrick JL, Lebrilla CB. 2009. Infrared multiphoton dissociation mass spectrometry for structural elucidation of oligosaccharides. Methods Mol Biol 534:1-13.

    Google Scholar 

  50. Adamson JT, Hakansson K. 2006. Infrared multiphoton dissociation and electron capture dissociation of high-mannose type glycopeptides. J Proteome Res 5:493-501.

    Article  CAS  PubMed  Google Scholar 

  51. Adamson JT, Hakansson K. 2007. Electron capture dissociation of oligosaccharides ionized with alkali, alkaline earth, and transition metals. Anal Chem 79:2901-2910.

    Article  CAS  PubMed  Google Scholar 

  52. Hakansson K, Chalmers MJ, Quinn JP, McFarland MA, Hendrickson CL, Marshall AG. 2003. Combined electron capture and infrared multiphoton dissociation for multistage MS/MS in a Fourier transform ion cyclotron resonance mass spectrometer. Anal Chem 75:3256-3262.

    Article  CAS  PubMed  Google Scholar 

  53. Hakansson K, Cooper HJ, Emmett MR, Costello CE, Marshall AG, Nilsson CL. 2001. Electron capture disso- ciation and infrared multiphoton dissociation MS/MS of an N-glycosylated tryptic peptic to yield complemen- tary sequence information. Anal Chem 73:4530-4536.

    Article  CAS  PubMed  Google Scholar 

  54. Hakansson K, Hudgins RR, Marshall AG, O'Hair RA. 2003. Electron capture dissociation and infrared mul- tiphoton dissociation of oligodeoxynucleotide dications. J Am Soc Mass Spectrom 14:23-41.

    Article  CAS  PubMed  Google Scholar 

  55. Zubarev RA, Kelleher NL, McLafferty FW. 1998. Electron capture dissociation of multiply charged protein cations: a nonergodic process. J Am Chem Soc 120:3265-3266.

    Article  CAS  Google Scholar 

  56. Cooper HJ, Hakansson K, Marshall AG. 2005. The role of electron capture dissociation in biomolecular analysis. Mass Spectrom Rev 24:201-222.

    Article  CAS  PubMed  Google Scholar 

  57. Zubarev RA. 2004. Electron-capture dissociation tandem mass spectrometry. Curr Opin Biotechnol 15:12-16.

    Article  CAS  PubMed  Google Scholar 

  58. Zubarev RA, Zubarev AR, Savitski MM. 2008. Electron capture/transfer versus collisionally activated/induced dissociations: solo or duet? J Am Soc Mass Spectrom 19:753-761.

    Article  CAS  PubMed  Google Scholar 

  59. Baba T, Hashimoto Y, Hasegawa H, Hirabayashi A, Waki I. 2004. Electron capture dissociation in a radio frequency ion trap. Anal Chem 76:4263-4266.

    Article  CAS  PubMed  Google Scholar 

  60. Coon JJ, Syka JE, Schwartz JC, Shabanowitz J, Hunt DF. 2004. Anion dependence in the partitioning between proton and electron transfer in ion/ion reactions. Int J Mass Spectrom 236:33-42.

    Article  CAS  Google Scholar 

  61. Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF. 2004. Peptide and protein sequence analysis by elec- tron transfer dissociation mass spectrometry. Proc Natl Acad Sci USA 101:9528-9533.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Mikesh LM, Ueberheide B, Chi A, Coon JJ, Syka JE, Shabanowitz J, Hunt DF. 2006. The utility of ETD mass spectrometry in proteomic analysis. Biochim Biophys Acta 1764:1811-1822.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Coon JJ, Syka JE, Shabanowitz J, Hunt DF. 2005. Tandem mass spectrometry for peptide and protein sequence analysis. Biotechniques 38:519, 21, 23.

    Google Scholar 

  64. Coon JJ, Ueberheide B, Syka JE, Dryhurst DD, Ausio J, Shabanowitz J, Hunt DF. 2005. Protein identification using sequential ion/ion reactions and tandem mass spectrometry. Proc Natl Acad Sci USA 102:9463-9468.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Coon JJ. 2009. Collisions or electrons? Protein sequence analysis in the 21st century. Anal Chem 81:3208-3215.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Correspondence to Carlito B. Lebrilla .

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Chu, C.S., Lebrilla, C.B. (2010). Introduction to Modern Techniques in Mass Spectrometry. In: Jue, T. (eds) Biomedical Applications of Biophysics. Handbook of Modern Biophysics, vol 3. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-233-9_6

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