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The potential for clinical applications using a new ionization method combined with ion mobility spectrometry-mass spectrometry

  • Original Research
  • Published:
International Journal for Ion Mobility Spectrometry

Abstract

Recently discovered ionization methods for use in mass spectrometry (MS), are widely applicable to biological materials, robust, and easy to automate. Among these, matrix assisted ionization vacuum (MAIV) is astonishing in that ionization of low and high-mass compounds are converted to gas-phase ions with charge states similar to electrospray ionization simply by exposing a matrix:analyte mixture to the vacuum of a mass spectrometer. Using the matrix compound, 3-nitrobenzonitrile, abundant ions are produced at room temperature without the need of high voltage or a laser. Here we discuss chemical analyses advances using MAIV combined with ion mobility spectrometry (IMS) real time separation, high resolution MS, and mass selected and non-mass selected MS/MS providing rapid analyte characterization. Drugs, their metabolites, lipids, peptides, and proteins can be ionized simultaneously from a variety of different biological matrixes such as urine, plasma, whole blood, and tissue. These complex mixtures are best characterized using a separation step, which is obtained nearly instantaneously with IMS, and together with direct ionization and MS or MS/MS provides a fast analysis method that has considerable potential for non-targeted clinical analyses.

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References

  1. Pieper R, Su Q, Gatlin CL, Huang ST, Anderson NL, Steiner S (2003) Multi-component immunoaffinity subtraction chromatography: an innovative step towards a comprehensive survey of the human plasma proteome. Proteomics 3:422–432

    Article  CAS  Google Scholar 

  2. Pieper R, Gatlin CL, McGrath AM, Makusky AJ, Mondal M, Seonarain M, Field E, Schatz CR, Estock MA, Ahmed N, Anderson NG, Steiner S (2004) Characterization of the human urinary proteome: a method for high-resolution display of urinary proteins on two-dimensional electrophoresis gels with a yield of nearly 1400 distinct protein spots. Proteomics 4:1159–1174

    Article  CAS  Google Scholar 

  3. Wang H, Hanash S (2003) Multi-dimensional liquid phase based separations in proteomics. J Chromatog B 787:11–18

    Article  CAS  Google Scholar 

  4. Shushan B (2010) A review of clinical diagnostic applications of liquid chromatography–tandem mass spectrometry. Mass Spectrom Rev 29:930–944

    Article  CAS  Google Scholar 

  5. Kasper DC, Herman J, De Jesus VR, Mechtler TP, Metz TF, Shushan B (2010) The application of multiplexed, multi-dimensional ultra-high-performance liquid chromatography/tandem mass spectrometry to the high-throughput screening of lysosomal storage disorders in newborn dried bloodspots. Rapid Commun Mass Spectrom 24:986–994

    Article  CAS  Google Scholar 

  6. Ang CS, Rothacker J, Patsiouras H, Gibbs P, Burgess AW, Nice EC (2011) Use of multiple reaction monitoring for multiplex analysis of colorectal cancer-associated proteins in human feces. Electrophoresis 32:1926–1938

    Article  CAS  Google Scholar 

  7. Zhang X, Fang A, Riley CP, Wang M, Regnier FE, Buck C (2010) Multi-dimensional liquid chromatography in proteomics. Anal Chim Acta 664:101–113

    Article  CAS  Google Scholar 

  8. Issaq HJ (2001) The role of separation science in proteomics research. Electrophoresis 22:3629–3638

    Article  CAS  Google Scholar 

  9. Zhang J, Xu X, Gao M, Yang P, Zhang X (2007) Comparison of 2-D LC and 3-D LC with post-and pre-tryptic-digestion SEC fractionation for proteome analysis of normal human liver tissue. Proteomics 7:500–512

    Article  CAS  Google Scholar 

  10. Dixon SP, Pitfield ID, Perrett D (2006) Comprehensive multi-dimensional liquid chromatographic separation in biomedical and pharmaceutical analysis: a review. Biomedical Chromatog 20:508–529

    Article  CAS  Google Scholar 

  11. Han H, Miyoshi Y, Ueno K, Okamura C, Tojo Y, Mita M, Lindner W, Zaitsu K, Hamase K (2011) Simultaneous determination of d-aspartic acid and d-glutamic acid in rat tissues and physiological fluids using a multi-loop two-dimensional HPLC procedure. J Chromatog B 879:3196–3202

    Article  CAS  Google Scholar 

  12. Zerefos PG, Aivaliotis M, Baumann M, Vlahou A (2012) Analysis of the urine proteome via a combination of multi-dimensional approaches. Proteomics 12:391–400

    Article  CAS  Google Scholar 

  13. Liu W, Liu B, Cai Q, Li J, Chen X, Zhu Z (2012) Proteomic identification of serum biomarkers for gastric cancer using multi-dimensional liquid chromatography and 2D differential gel electrophoresis. Clinica Chim Acta 413:1098–1106

    Article  CAS  Google Scholar 

  14. Gray TR, Shakleya DM, Huestis MA (2009) A liquid chromatography tandem mass spectrometry method for the simultaneous quantification of 20 drugs of abuse and metabolites in human meconium. Anal Bioanal Chem 393:1977–1990

    Article  CAS  Google Scholar 

  15. Liu XY, Valentine SJ, Plasencia MD, Trimpin S, Naylor S, Clemmer DE (2007) Mapping the human plasma proteome by SCX-LC-IMS-MS. J Am Soc Mass Spectrom 18:1249–1264

    Article  CAS  Google Scholar 

  16. Isailovic D, Plasencia MD, Gaye MM, Stokes ST, Kurulugama RT, Pungpapong V, Zhang M, Kyselova Z, Goldman R, Mechref Y, Novotny MV, Clemmer DE (2012) Delineating diseases by IMS-MS profiling of serum N-linked glycans. J Proteome Res 11:576–585

    Article  CAS  Google Scholar 

  17. Trimpin S, Tan B, O’Dell DK, Bohrer BC, Merenbloom SI, Pazos MX, Clemmer DE, Walker JM (2009) Profiling of phospholipids and related lipid structures using multidimensional ion mobility spectrometry-mass spectrometry. Int J Mass Spectrom 287:58–69

    Article  CAS  Google Scholar 

  18. Wyttenbach T, von Helden G, Bowers MT (1996) Gas-phase conformation of biological molecules: bradykinin. J Am Chem Soc 118:8355–8364

    Article  CAS  Google Scholar 

  19. Kanu AB, Dwivedi P, Tam M, Matz L, Hill HH Jr (2008) Ion mobility-mass spectrometry. J Mass Spectrom 43:1–22

    Article  CAS  Google Scholar 

  20. Baumketner A, Bernstein SL, Wyttenbach T, Bitan G, Teplow DB, Bowers MT, Shea JE (2006) Amyloid beta-protein monomer structure: a computational and experimental study. Protein Sci 15:420–428

    Article  CAS  Google Scholar 

  21. Wu C, Siems WF, Klasmeier J, Hill HH (2000) Separation of isomeric peptides using electrospray ionization/high-resolution ion mobility spectrometry. Anal Chem 72:391–395

    Article  CAS  Google Scholar 

  22. Ruotolo BT, Verbeck GF, Thomson LM, Woods AS, Gillig KJ, Russell DH (2002) Distinguishing between phosphorylated and nonphosphorylated peptides with ion mobility−mass spectrometry. J Proteome Res 1:303–306

    Article  CAS  Google Scholar 

  23. Hoaglund CS, Valentine SJ, Sporleder CR, Reilly JP, Clemmer DE (1998) Three-dimensional ion mobility/TOFMS analysis of electrosprayed biomolecules. Anal Chem 70:2236–2242

    Article  CAS  Google Scholar 

  24. Thalassinos K, Slade SE, Jennings KR, Scrivens JH, Giles K, Wildgoose J, Hoyes J, Bateman RH, Bowers MT (2004) Ion mobility mass spectrometry of proteins in a modified commercial mass spectrometer. Int J Mass Spectrom 236:55–63

    Article  CAS  Google Scholar 

  25. Ruotolo BT, Giles K, Campuzano I, Sandercock AM, Bateman RH, Robinson CV (2005) Evidence for macromolecular protein rings in the absence of bulk water. Science 310:1658–1661

    Article  CAS  Google Scholar 

  26. Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G, Teplow DB, Shea JE, Ruotolo BT, Robinson CV, Bowers MT (2009) Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer’s disease. Nat Chem 1:326–331

    Article  CAS  Google Scholar 

  27. Benesch JL, Ruotolo BT, Simmons DA, Robinson CV (2007) Protein complexes in the gas phase: technology for structural genomics and proteomics. Chemical Reviews-Columbus 107:3544–3567

    Article  CAS  Google Scholar 

  28. Seo Y, Andaya A, Leary JA (2012) Preparation, separation, and conformational analysis of differentially sulfated heparin octasaccharide isomers using ion mobility mass spectrometry. Anal Chem 84:2416–2423

    Article  CAS  Google Scholar 

  29. Niñonuevo MR, Leary JA (2012) Ion mobility mass spectrometry coupled with rapid protein threading predictor structure prediction and collision-induced dissociation for probing chemokine conformation and stability. Anal Chem 84:3208–3214

    Article  CAS  Google Scholar 

  30. Giles K, Williams JP, Campuzano I (2011) Enhancements in travelling wave ion mobility resolution. Rapid Commun Mass Spectrom 25:1559–1566

    Article  CAS  Google Scholar 

  31. Li H, Giles K, Bendiak B, Kaplan K, Siems WF, Hill HH Jr (2012) Resolving structural isomers of monosaccharide methyl glycosides using drift tube and traveling wave ion mobility mass spectrometry. Anal Chem 84:3231–3239

    Article  CAS  Google Scholar 

  32. Chawner R, McCullough B, Giles K, Barran PE, Gaskell SJ, Eyers CE (2012) A QconCAT standard for calibration of ion mobility mass spectrometry systems. J Proteome Res 11:5564–5572

    Article  CAS  Google Scholar 

  33. Jungmann JH, Heeren RMA (2012) Emerging technologies in mass spectrometry imaging. J Proteomics 75:5077–5092

    Article  CAS  Google Scholar 

  34. Syka JEP, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF (2004) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci 101:9528–9533

    Article  CAS  Google Scholar 

  35. Reid GE, McLuckey SA (2002) Top down protein characterization via tandem mass spectrometry. J Mass Spectrom 37:663–675

    Article  CAS  Google Scholar 

  36. Mikesh LM, Ueberheide B, Chi A, Coon JJ, Syka JEP, Shabanowitz J, Hunt DF (2006) The utility of ETD mass spectrometry in proteomic analysis. Biochimica et Biophysica Acta-Proteins and Proteomics 1764:1811–1822

    Article  CAS  Google Scholar 

  37. Moss CL, Chamot-Rooke J, Nicol E, Brown J, Campuzano I, Richardson K, Williams JP, Bush MF, Bythell B, Paizs B, Turecek F (2012) Assigning structures to gas-phase peptide cations and cation-radicals. An infrared multiphoton dissociation, ion mobility, electron transfer, and computational study of a histidine peptide ion. The Journal of Physical Chemistry B 116:3445–3456

    Article  CAS  Google Scholar 

  38. Rand KD, Pringle SD, Morris M, Engen JR, Brown JM (2011) ETD in a traveling wave ion guide at tuned Z-spray ion source conditions allows for site-specific hydrogen/deuterium exchange measurements. J Am Soc Mass Spectrom 22:1784–1793

    Article  CAS  Google Scholar 

  39. Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473

    Article  CAS  Google Scholar 

  40. Cody RB, Laramee JA, Durst HD (2005) Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal Chem 77:2297–2302

    Article  CAS  Google Scholar 

  41. McEwen CN, McKay RG, Larsen BS (2005) Analysis of Solids Liquids and Biological Tissues using Solid Probe Introduction at Atmospheric Pressure on Commercial LC/MS Instruments. Anal Chem 77:7826–7831

    Article  CAS  Google Scholar 

  42. Shiea J, Huang MZ, Hsu HJ, Lee CY, Yuan CH, Beech I, Sunner J (2005) Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids. Rapid Commun Mass Spectrom 19:3701–3704

    Article  CAS  Google Scholar 

  43. Sampson JS, Hawkridge AM, Muddiman DC (2006) Generation and detection of multiply-charged peptides and proteins by Matrix-Assisted Laser Desorption Electrospray Ionization (MALDESI) fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 17:712–1716

    Article  CAS  Google Scholar 

  44. Trimpin S, Inutan ED, Herath T, McEwen CN (2010) Laserspray ionization—a new atmospheric pressure MALDI method for producing highly charged gas-phase ions of peptides and proteins directly from solid solutions. Mol Cell Proteomics 9:362–367

    Article  CAS  Google Scholar 

  45. McEwen CN, Trimpin S (2011) An alternative ionization paradigm for atmospheric pressure mass spectrometry: flying elephants from Trojan Horses. Int J Mass Spectrom 300:167–172

    Article  CAS  Google Scholar 

  46. Li J, Inutan ED, Wang B, Lietz CB, Green DR, Manly CD, Richards AL, Marshall DD, Lingenfelter S, Ren Y, Trimpin S (2012) Matrix assisted ionization: new aromatic and non aromatic matrix compounds producing multiply charged lipid peptide and protein ions in the positive and negative mode observed directly from surfaces. J Am Soc Mass Spectrom 23:1625–1643

    Article  CAS  Google Scholar 

  47. Trimpin S, Wang B, Inutan ED, Li J, Lietz CB, Pagnotti VS, Harron A, Sardelis D, McEwen CN (2012) A mechanism for ionization of nonvolatile compounds in mass spectrometry: considerations from MALDI and inlet ionization. J Am Soc Mass Spectrom 23:1644–1660

    Article  CAS  Google Scholar 

  48. Frankevich V, Nieckarz RJ, Sagulenko PN, Barylyuk K, Zenobi R, Levitsky LI, Yu Agapov A, Perlova TY, Gorshkov MV, Tarasova IA (2012) Probing the mechanisms of ambient ionization by laser-induced fluorescence spectroscopy. Rapid Commun Mass Spectrom 26:1567–1572

    Article  CAS  Google Scholar 

  49. Trimpin S, Inutan ED, Herath T, McEwen CN (2010) Matrix-assisted laser desorption/ionization mass spectrometry method for selectively producing either singly or multiply charged molecular ions. Anal Chem 82:11–15

    Article  CAS  Google Scholar 

  50. Inutan ED, Trimpin S (2010) Laserspray ionization (LSI) ion mobility spectrometry (IMS) mass spectrometry. J Am Soc Mass Spectrom 21:1260–1264

    Google Scholar 

  51. Inutan ED, Trimpin S (2010) Laserspray ionization-ion mobility spectrometry-mass spectrometry: baseline separation of isomeric amyloids without the use of solvents desorbed and ionized directly from a surface. J Proteome Res 9:6077–6081

    Article  CAS  Google Scholar 

  52. McEwen CN, Pagnotti V, Inutan ED, Trimpin S (2010) A new paradigm in ionization: multiply charged ion formation from a solid matrix without a laser or voltage. Anal Chem 82:9164–9168

    Article  CAS  Google Scholar 

  53. Lietz CB, Richards AL, Ren Y, Trimpin S (2011) Inlet ionization: protein analyses from the solid state without the use of a voltage or a laser producing up to 67 charges on the 66 kDa BSA protein. Rapid Commun Mass Spectrom 25:3453–3456

    Article  CAS  Google Scholar 

  54. Pagnotti VS, Chubatyi ND, McEwen CN (2011) Solvent assisted inlet ionization: an ultrasensitive new liquid introduction ionization method for mass spectrometry. Anal Chem 83:3981–3985

    Article  CAS  Google Scholar 

  55. Pagnotti VS, Inutan ED, Marshall DD, McEwen CN, Trimpin S (2011) Inlet ionization: a new highly sensitive approach for liquid chromatography-mass spectrometry of small and large molecules. Anal Chem 83:7591–7594

    Article  CAS  Google Scholar 

  56. Wang B, Inutan ED, Trimpin S (2012) A new approach to high sensitivity liquid chromatography-mass spectrometry of peptides using nanoflow solvent assisted inlet ionization. J Am Soc Mass Spectrom 23:442–445

    Article  CAS  Google Scholar 

  57. Chubatyi ND, Pagnotti VS, Bentzley CM, McEwen CN (2012) High sensitivity steroid analysis using liquid chromatography/solvent-assisted inlet ionization mass spectrometry. Rapid Commun Mass Spectrom 26:887–892

    Article  CAS  Google Scholar 

  58. Inutan ED, Wang B, Trimpin S (2010) Commercial intermediate pressure MALDI Ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions. Anal Chem 83:678–684

    Article  CAS  Google Scholar 

  59. Trimpin S, Ren Y, Wang B, Lietz CB, Richards AL, Marshall DD, Inutan ED (2011) Extending the laserspray ionization concept to produce highly charged ions at high vacuum on a time-of-flight mass analyzer. Anal Chem 83:5469–5475

    Article  CAS  Google Scholar 

  60. Inutan ED, Wager-Miller J, Mackie K, Trimpin S (2012) Laserspray ionization imaging of multiply charged ions using a commercial vacuum MALDI ion source. Anal Chem 84:9079–9084

    CAS  Google Scholar 

  61. Inutan ED, Li J, Manly CM, Wang B, Trimpin S (2012) Laserspray ionization and solvent assisted inlet ionization developments and ion mobility spectrometry mass spectrometry applications. 60th ASMS Conference on Mass Spectrometry and Allied Topics, May 20–24 2012, Vancouver, Canada, WP30-slot 627.

  62. Inutan ED, Trimpin S (2013) Matrix assisted ionization vacuum, a new ionization method for biological materials analysis using mass spectrometry. Mol Cell Proteomics 12:792–796

    Google Scholar 

  63. Trimpin S, Inutan ED (2013) Matrix assisted ionization in vacuum, a sensitive and widely applicable ionization method for mass spectrometry. J Am Soc Mass Spectrom. doi:10.1007/s13361-012-0571-z

  64. Inutan ED, Richards AL, Wager-Miller J, Mackie K, McEwen CN, Trimpin S (2011) Laserspray ionization, a new method for protein analysis directly from tissue at atmospheric pressure with ultrahigh mass resolution and electron transfer dissociation. Mol Cell Proteomics 10:1–8

    Google Scholar 

  65. Richards AL, Lietz CB, Wager-Miller JB, Mackie K, Trimpin S (2011) Imaging mass spectrometry in transmission geometry. Rapid Commun Mass Spectrom 25:815–820

    Article  CAS  Google Scholar 

  66. Hoaglund-Hyzer CS, Lee YJ, Counterman AE, Clemmer DE (2002) Coupling ion mobility separations, collisional activation techniques, and multiple stages of MS for analysis of complex peptide mixtures. Anal Chem 74:992–1006

    Article  CAS  Google Scholar 

  67. Ferrige AG, Seddon MJ, Green BN, Jarvis SA, Skilling J, Staunton J (1992) Disentangling electrospray spectra with maximum entropy. Rapid Commun Mass Spectrom 6:707–711

    Article  CAS  Google Scholar 

  68. Krutchinsky AN, Chait BT (2002) On the nature of the chemical noise in MALDI mass spectra. J Am Soc Mass Spectrom 13:129–134

    Article  CAS  Google Scholar 

  69. Eibisch M, Zellmer S, Gebhardt R, Suss R, Fuchs B, Schiller J (2011) Phosphatidylcholine dimers can be easily misinterpreted as cardiolipins in complex lipid mixtures: a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric study of lipids from hepatocytes. Rapid Commun Mass Spectrom pp 2619–2626

  70. James PF, Perugini MA, O’Hair RAJ (2006) Sources of artefacts in the electrospray ionization mass spectra of saturated diacylglycerophosphocholines: From condensed phase hydrolysis reactions through to gas phase intercluster reactions. J Am Soc Mass Spectrom 17:384–394

    Article  CAS  Google Scholar 

  71. Woods AS, Ugarov M, Egan T, Koomen J, Gillig KJ, Fuhrer K, Gonin M, Schultz JA (2004) Lipid/peptide/nucleotide separation with MALDI-ion mobility-TOF MS. Anal Chem 76:2187–2195

    Article  CAS  Google Scholar 

  72. Fenn LS, Kliman M, Mahsut A, Zhao SR, McLean JA (2009) Characterizing ion mobility-mass spectrometry conformation space for the analysis of complex biological samples. Anal Bioanal Chem 394:235–244

    Article  CAS  Google Scholar 

  73. Vestal ML, Juhasz P, Martin SA (1995) Delayed extraction MALDI TOF MS. Rapid Commun Mass Spectrom 9:1044–1050

    Article  CAS  Google Scholar 

  74. Shariatgorji M, Nilsson A, Goodwin Richard JA, Svenningsson P, Schintu N, Banka Z, Kladni L, Hasko T, Szabo A, Andren PE (2012) Deuterated matrix-assisted laser desorption ionization matrix uncovers masked mass spectrometry imaging signals of small molecules. Anal Chem 84:7152–7157

    Article  CAS  Google Scholar 

  75. Sun J, Baker A, Chen P (2011) Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 25:2591–2602

    CAS  Google Scholar 

  76. Plumb RS, Johnson KA, Rainville P, Smith BW, Wilson ID, Castro-Perez JM, Nicholson JK (2006) UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom 20:1989–1994

    Article  CAS  Google Scholar 

  77. Bateman KP, Castro-Perez J, Wrona M, Shockcor JP, Yu K, Oballa R, Nicoll-Griffith DA (2007) MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun Mass Spectrom 21:1485–1496

    Article  CAS  Google Scholar 

  78. Ronci M, Bonanno E, Colantoni A, Pieroni L, Di Ilio C, Spagnoli LG, Federici G, Urbani A (2008) Protein unlocking procedures of formalin-fixed paraffin-embedded tissues: Application to MALDI-TOF Imaging MS investigations. Proteomics 8:3702–3714

    Article  CAS  Google Scholar 

  79. Cheng FY, Blackburn K, Lin YM, Goshe MB, Williamson JD (2009) Absolute protein quantification by LC/MSE for global analysis of salicylic acid-induced plant protein secretion responses. J Proteome Res 8:82–93

    Article  CAS  Google Scholar 

  80. Castro-Perez JM, Kamphorst J, DeGroot J, Lafeber F, Goshawk J, Yu K, Shockcor JP, Vreeken RJ, Hankemeier T (2010) Comprehensive LC− MSE lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients. J Proteome Res 9:2377–2389

    Article  CAS  Google Scholar 

  81. Finamore F, Pieroni L, Ronci M, Marzano V, Mortera SL, Romano M, Cortese C, Federici G, Urbani A (2010) Proteomics investigation of human platelets by shotgun nUPLC-MSE and 2DE experimental strategies: a comparative study. Blood Transfusion 8:S140–S148

    Google Scholar 

  82. Prasad B, Garg A, Takwani H, Singh S (2011) Metabolite identification by liquid chromatography-mass spectrometry. Trends Anal Chem 30:360–387

    Article  CAS  Google Scholar 

  83. Bijlsma L, Sancho JV, Hernández F, Niessen W (2011) Fragmentation pathways of drugs of abuse and their metabolites based on QTOF MS/MS and MSE accurate-mass spectra. J Mass Spectrom 46:865–875

    Article  CAS  Google Scholar 

  84. Martins-de-Souza D, Guest PC, Guest FL, Bauder C, Rahmoune H, Pietsch S, Roeber S, Kretzschmar H, Mann D, Baborie A, Bahn S (2012) Characterization of the human primary visual cortex and cerebellum proteomes using shotgun mass spectrometry-data-independent analyses. Proteomics 12:500–504

    Article  CAS  Google Scholar 

  85. Cha IS, Kwon J, Park SH, Nho SW, Jang HB, Park SB, del Castillo CS, Hikima J, Aoki T, Jung TS (2012) Kidney proteome responses in the teleost fish Paralichthys olivaceus indicate a putative immune response against Streptococcus parauberis. J Proteomics 75:5166–5175

    Article  CAS  Google Scholar 

  86. Dong W, Wang P, Meng X, Sun H, Zhang A, Wang W, Dong H, Wang XJ (2012) Ultra-performance liquid chromatography–high-definition mass spectrometry analysis of constituents in the root of radix stemonae and those absorbed in blood after oral administration of the extract of the crude drug. Phytochemical Analysis 23:657–667

    Article  CAS  Google Scholar 

  87. Barbara JE, Kazmi F, Muranjan S, Toren PC, Parkinson A (2012) High-resolution mass spectrometry elucidates metabonate (False Metabolite) formation from alkylamine drugs during in vitro metabolite profiling. Drug Metabolism Disposition 40:1966–1975

    Article  CAS  Google Scholar 

  88. Bernstein SL, Wyttenbach T, Baumketner A, Shea JE, Bitan G, Teplow DB, Bowers MT (2005) Amyloid β-protein: monomer structure and early aggregation states of Aβ42 and its pro19 alloform. J Am Chem Soc 127:2075–2084

    Article  CAS  Google Scholar 

  89. Aluise CD, Robinson RA, Becket TL, Murphy MP, Cai J, Pierce WM, Markesbery WR, Butterfield DA (2010) Preclinical Alzheimer disease: brain oxidative stress, Aβ peptide and proteomics. Neuro Disease 39:221–228

    Article  CAS  Google Scholar 

  90. Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ (1993) 18-Amyloid-(142) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A 90:10836–10840

    Article  CAS  Google Scholar 

  91. Pan J, Han J, Borchers CH, Konermann L (2011) Conformer-specific hydrogen exchange analysis of a beta(1–42) oligomers by top-down electron capture dissociation mass spectrometry. Anal Chem 83:5386–5393

    Article  CAS  Google Scholar 

  92. Kraus M, Bienert M, Krause E (2003) Hydrogen exchange studies on Alzheimer’s amyloid-beta peptides by mass spectrometry using matrix-assisted laser desorption/ionization and electrospray ionization. Rapid Commun Mass Spectrom 17:222–228

    Article  CAS  Google Scholar 

  93. Seeley EH, Oppenheimer SR, Mi D, Chaurand P, Caprioli RM (2008) Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections. J Am Soc Mass Spectrom 19:1069–1077

    Article  CAS  Google Scholar 

  94. Ceuppens R, Dumont D, Van Brussel L, Van de Plas B, Daniels R, Noben JP, Verhaert P, Van der Gucht E, Robben J, Clerens S, Arckens L (2007) Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry. Int J Mass Spectrom 260:185–194

    Article  CAS  Google Scholar 

  95. Issaq HJ, Nativ O, Waybright T, Luke B, Veenstra TD, Issaq EJ, Kravstov A, Mullerad M (2008) Detection of bladder cancer in human urine by Metabolomic profiling using high performance liquid chromatography/mass spectrometry. The J Urology 179:2422–2426

    Article  CAS  Google Scholar 

  96. Hoke SH (2001) Transformations in pharmaceutical research and development, driven by innovations in multidimensional mass spectrometry-based technologies. Int J Mass Spectrom 212:135–196

    Article  CAS  Google Scholar 

  97. Vogeser M, Seger C (2008) A decade of HPLC–MS/MS in the routine clinical laboratory—Goals for further developments. Clin Biochem 41:649–662

    Article  CAS  Google Scholar 

  98. Gruener BM, Hahne H, Mazur PK, Trajkovic-Arsic M, Maier S, Esposito I, Kalideris E, Michalski CW, Kleeff J, Rauser S, Schmid RM, Kuster B, Walch A, Siveke JT (2012) MALDI imaging mass spectrometry for in situ proteomic analysis of preneoplastic lesions in pancreatic cancer. PLoS One 7:e39424

    Article  CAS  Google Scholar 

  99. Nicolaou N, Xu Y, Goodacre R (2011) MALDI-MS and multivariate analysis for the detection and quantification of different milk species. Anal Bioanal Chem 399:3491–3502

    Article  CAS  Google Scholar 

  100. Kjellström S, Jensen N (2003) In situ liquid−liquid extraction as a sample preparation method for matrix-assisted laser desorption/ionization ms analysis of polypeptide mixtures. Anal Chem 75:2362–2369

    Article  CAS  Google Scholar 

  101. Warren ME, Brockman AH, Orlando R (1998) On-probe solid-phase extraction/MALDI-MS using ion-pairing interactions for the clean-up of peptides and proteins. Anal Chem 70:3757–3761

    Article  CAS  Google Scholar 

  102. McCombie G, Staab D, Stoeckli M, Knochenmuss R (2005) Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis. Anal Chem 77:6118–6124

    Article  CAS  Google Scholar 

  103. Schwudke D, Hannich JT, Surendranath V, Grimard V, Moehring T, Burton L, Kurzchalia T, Shevchenko A (2007) Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. Anal Chem 79:4083–4093

    Article  CAS  Google Scholar 

  104. Miura D, Fujimura Y, Tachibana H, Wariishi H (2010) Highly sensitive matrix-assisted laser desorption ionization-mass spectrometry for high-throughput metabolic profiling. Anal Chem 82:498–504

    Article  CAS  Google Scholar 

  105. Waloszczyk P, Janus T, Alchimowicz J, Grodzki T, Borowiak K (2011) Proteomic patterns analysis with multivariate calculations as a promising tool for prompt differentiation of early stage lung tissue with cancer and unchanged tissue material. Diagn Pathol 6:1–7

    Article  Google Scholar 

  106. Broadhurst DI, Kell DB (2006) Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2:171–196

    Article  CAS  Google Scholar 

  107. Gowda GN, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D (2008) Metabolomics-based methods for early disease diagnostics. Expert Rev Mol Diagn 8:617–633

    Article  CAS  Google Scholar 

  108. Carpentier SC, Pani B, Vertommen A, Swennen R, Sergeant K, Renaut J, Laukens K, Witters E, Devreese B (2008) Proteome analysis of non-model plants: a challenging but powerful approach. Mass Spectrom Rev 27:354–377

    Article  CAS  Google Scholar 

  109. Trimpin S, Clemmer DE (2008) Ion mobility spectrometry/mass spectrometry snapshots for assessing the molecular compositions of complex polymeric systems. Anal Chem 80:9073–9083

    Article  CAS  Google Scholar 

  110. Park AY, Robinson CV (2011) Protein–nucleic acid complexes and the role of mass spectrometry in their structure determination. Crit Rev Biochem Mol Biol 46:152–164

    Article  CAS  Google Scholar 

  111. Dhong S, Qin Y, Zhang F (2010) Mathematical tools and statistical techniques for proteomic data mining. Computer Sci 5:123–140

    Google Scholar 

  112. Franck J, Arafah K, Elayed M, Bonnel D, Vergara D, Jacquet A, Vinatier D, Wisztorski M, Day R, Fournier I, Salzet M (2009) MALDI imaging mass spectrometry: state of the art. Tech clinical proteomics. Mol Cell Proteomics 8:2023–2033

    Article  CAS  Google Scholar 

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Acknowledgement

The authors are grateful for funding and support from Wayne State University (Schaap, Summer, and Rumble Dissertation Fellowships to EDI, and Schaap Faculty Scholar to ST), NSF CAREER Award 0955975, ASMS Research Award, DuPont Young Professor Award, Waters Center of Innovation Award, and Eli Lilly Young Investigator Award in Analytical Chemistry (to ST), as well as NIH DA011322 and DA021696 (to KM). The authors are thankful to Keith Richardson from Waters Co. for the data analysis using BayesSpray software.

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Inutan, E.D., Wager-Miller, J., Narayan, S.B. et al. The potential for clinical applications using a new ionization method combined with ion mobility spectrometry-mass spectrometry. Int. J. Ion Mobil. Spec. 16, 145–159 (2013). https://doi.org/10.1007/s12127-013-0131-7

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  • DOI: https://doi.org/10.1007/s12127-013-0131-7

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