Abstract
Mass spectrometry has emerged as a powerful tool for the bioanalytical sciences because of its ability to characterize small and large biomolecules in vanishingly small amounts. A recurring motif in mass spectrometry aims to decipher the chemical composition of biological samples at the molecular level, requiring drastic improvements in the ability to interrogate well defined and highly spatially resolved areas of a sample surface. With the growth of novel ionization methods, numerous advances have been made in sampling biological tissue surfaces. Here, current advancements in ambient, inlet, and vacuum ionization methods are discussed with respect to the potential improvements in the goal of achieving high spatial resolution and/or fast surface analysis. Of similar importance is the need for improvements in applicable characterization strategies using high performance fragmentation technologies such as electron transfer dissociation and electron capture dissociation directly from surfaces, and gas-phase separation through ion mobility spectrometry and high resolution mass spectrometry.
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Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T (1988) Protein and polymer analysis up to m/z 100,000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2:151–153
Karas M, Hillenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10,000 Daltons. Anal Chem 60:2299–2301
Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64–71
Venter AR, Douglass KA, Shelley JT, Hasman G, Honarvar E (2014) Mechanisms of real-time, proximal sample processing during ambient ionization mass spectrometry. Anal Chem 86:233–249
Fletcher JS, Lockyer NP, Vaidyanathan S, Vickerman JC (2007) TOF-SIMS 3D biomolecular imaging of Xenopus laevis oocytes using Buckminsterfullerene (C60) primary ions. Anal Chem 79:2199–2206
Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF-MS. Anal Chem 69:4751–4760
Nemes P, Vertes A (2007) Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal Chem 79:8098–8106
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 Proteom 10(2) doi:10.1074/mcp.M110.000760
Venter A, Nefliu M, Cooks RG (2008) Ambient desorption ionization mass spectrometry. Trends Anal Chem 27:284–290
Trimpin S, Wang B, Lietz CB, Marshall DD, Richards AL, Inutan ED (2013) New ionization processes and applications for use in mass spectrometry. Crit Rev Biochem Mol Biol 48:409–429
Coon JJ (2009) Collisions or electrons? Protein sequence analysis in the 21st century. Anal Chem 81:3208–3215
Clemmer DE, Jarrold MF (1997) Ion mobility measurements and their applications to clusters and biomolecules. J Mass Spectrom 32:577–592
Brown A, Vickerman JC (1984) Static SIMS for applied surface-analysis. Surf Interface Anal 6:1–14
Piehowski PD, Kurczy ME, Willingham D, Parry S, Heien ML, Winograd N, Ewing AG (2008) Freeze-etching and vapor matrix deposition for ToF-SIMS imaging of single cells. Langmuir 24:7906–7911
Aoyagi S, Fletcher JS, Sheraz S, Kawashima T, Raso IB, Henderson A, Lockyer NP, Vickerman JC (2013) Peptide structural analysis using continuous Ar cluster and C60 ion beams. Anal Bioanal Chem 405:6621–6628
Barber M, Bordoli RS, Sedgewick RD, Tyler AN (1981) Fast atom bombardment of solids as an ion-source in mass-spectrometry. Nature 293:270–275
Barber M, Green BN (1987) The analysis of small proteins in the molecular weight range 10–24 kDa by magnetic sector mass spectrometry. Rapid Commun Mass Spectrom 1(5):80–83
Vertes A, Balazs L, Gijbels R (1990) Matrix-assisted laser desorption of peptides in transmission geometry. Rapid Commun Mass Spectrom 4:263–266
Kaufmann R, Hillenkamp F, Wechsung R (1979) Laser microprobe mass analyzer (LAMMA)—new instrument for biomedical microprobe analysis. Med Prog Technol 6:109–121
Norris JL, Caprioli RM (2013) Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem Rev 113:2309–2342
Zavalin A, Todd EM, Rawhouser PD, Yang J, Norris JL, Caprioli RM (2012) Direct imaging of single cells and tissue at subcellular spatial resolution using transmission geometry MALDI MS. J Mass Spectrom 47:1473–1481
Schober Y, Guenther S, Spengler B, Roempp A (2012) Single cell matrix-assisted laser desorption/ionization mass spectrometry imaging. Anal Chem 84:6293–6297
Li Y, Shrestha B, Vertes A (2008) Atmospheric pressure infrared MALDI imaging mass spectrometry of plant metabolomics. Anal Chem 80:407–420
Vestal ML (2009) Modern MALDI time-of-flight mass spectrometry. J Mass Spectrom 44:303–317
Angel TE, Aryal UK, Hengel SM, Baker ES, Kelly RT, Robinson EW, Smith RD (2012) Mass spectrometry-based proteomics: existing capabilities and future directions. Chem Soc Rev 41:3912–3928
Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473
Eberlin LS, Norton I, Dill AL, Golby AJ, Ligon KL, Santagata S, Cooks RG, Agar NYR (2012) Classifying human brain tumors by lipid imaging with mass spectrometry. Cancer Res 72:645–654
Kertesz V, Van Berkel GJ, Vavrek M, Koeplinger KA, Schneider BB, Covey TR (2008) Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography. Anal Chem 80:5168–5177
Campbell DI, Ferreira CR, Eberlin LS, Cooks RG (2012) Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization. Anal Bioanal Chem 404:389–398
Wu CP, Dill AL, Eberlin LS, Cooks RG, Ifa DR (2013) Mass spectrometry imaging under ambient conditions. Mass Spectrom Rev 32:218–243
Lanekoff I, Heath BS, Liyu A, Thomas M, Carson JP, Laskin J (2012) Automated platform for high-resolution tissue imaging using nanospray desorption electrospray ionization mass spectrometry. Anal Chem 84:8351–8356
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
Huang MZ, Chang SC, Jhang SS, Chou CC, Cheng CN, Shiea J, Popov IA, Nikolaev EN (2012) Ambient molecular imaging of dry fungus surface by electrospray laser desorption ionization mass spectrometry. Int J Mass Spectrom 325(327):172–182
Sampson JS, Hawkridge AM, Muddiman DC (2006) Generation and detection of multiply-charged peptide and proteins by matrix-assisted laser desorption electrospray ionization Fourier Transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 17:1712–1716
Robichaud G, Barry JA, Garrard KP, Muddimann DC (2013) Infrared matrix-assisted laser-desorption electrospray ionization (IR-MALDESI) imaging source coupled to a FT-ICR mass spectrometer. J Am Soc Mass Spectrom 24:92–100
Shrestha B, Javonillo R, Burns JR, Pirger Z, Vertes A (2013) Comparative local analysis of metabolites, lipids, and proteins in intact fish tissues by LAESI mass spectrometry. Analyst 138:3444–3449
Shrestha B, Vertes A (2010) Direct analysis of single cells by mass spectrometry at atmospheric pressure. J Vis Exp 43:1–4
Smith JW, Siegel EE, Maze JT, Jarrold MF (2011) Image charge detection mass spectrometry: pushing the envelope with sensitivity and accuracy. Anal Chem 83:950–956
Contino NC, Pierson EE, Keifer DZ, Jarrold MF (2013) Charge detection mass spectrometry with resolved charge states. J Am Soc Mass Spectrom 24:101–108
Park J, Qin H, Scalf M, Hilger RT, Westphall MS, Smith LM, Blick RH (2011) A mechanical nanomembrane detector for time-of-flight mass spectrometry. Nano Lett 11:3681–3684
Jungmann J, Smith DF, MacAleese L, Klinkert I, Visser J, Heeren RMA (2012) Biological tissue imaging with a position and time sensitive pixelated detector. J Am Soc Mass Spectrom 23:1679–1688
Spraggins JM, Caprioli RM (2011) High-speed MALDI-TOF imaging mass spectrometry: rapid ion image acquisition and considerations for next generation instrumentation. J Am Soc Mass Spectrom 22:1022–1031
Tsai MT, Lee S, Lu IC, Chu KY, Liang CW, Lee CH, Lee YT, Ni CK (2013) Ion-to-neutral ratio of 2,5-dihydroxybenzoic acid in matrix assisted laser desorption/ionization. Rapid Commun Mass Spectrom 27:955–963
Trimpin S, Herath TN, Inutan ED, Wager-Miller J, Kowalski P, Claude E, Walker JM, Mackie J (2010) Automated solvent-free matrix deposition for tissue imaging by mass spectrometry. Anal Chem 82:359–367
Trimpin S, Inutan ED, Herath TN, 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 Proteom 9:362–367
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
Inutan ED, Wang B, Trimpin S (2011) Commercial intermediate pressure MALDI ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions. Anal Chem 83:678–684
Inutan ED, Wager-Miller J, Narayan SB, Mackie K, Trimpin S (2013) The potential for clinical applications using a new ionization method combined with ion mobility spectrometry-mass spectrometry. Int J Ion Mobil Spectrom 16:145–159
Trimpin S, Wang B, Inutan B, Li J, Lietz CB, Harron A, Pagnotti VS, 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
Trimpin S, Inutan ED, Herath TN, McEwen CN (2010) A matrix-assisted laser desorption/ionization mass spectrometry method for selectively producing either singly or multiply charged molecular ions. Anal Chem 82:11–15
McEwen CN, Larsen BS, Trimpin S (2010) Laserspray ionization on a commercial atmospheric pressure-MALDI mass spectrometer ion source: selecting singly or multiply charged ions. Anal Chem 82:4998–5001
Richards AL, Lietz CB, Wager-Millar JB, Mackie K, Trimpin S (2011) Imaging mass spectrometry in transmission geometry. Rapid Commun Mass Spectrom 25:815–820
Richards AL, Lietz CB, Wager-Miller J, Mackie K, Trimpin S (2012) Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet. J Lipid Res 53:1390–1398
Inutan ED, Trimpin S (2010) Laserspray ionization-ion mobility spectrometry-mass spectrometry: Baseline separation of isometric amyloids without the use of solvents desorbed and ionized directly from a surface. J Proteome Res 9:6077–61081
Silveira JA, Fort KL, Kim D, Servage KA, Pierson NA, Clemmer DE, Russell DH (2013) From solution to the gas phase: stepwise dehydration and kinetic trapping of substance p reveals the origin of peptide conformations. J Am Chem Soc 135:19147–19153
McEwen CN, Pagnotti VS, Inutan ED, Trimpin S (2010) New paradigm in ionization: multiply charged ion formation from a solid matrix without a laser or voltage. Anal Chem 82:9164–9168
Zenobi R, Knochenmuss R (1998) Ion formation in MALDI mass spectrometry. Mass Spectrom Rev 17:337–366
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 nonaromatic 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
Harron AF, Hoang K, McEwen CN (2013) High mass resolution tissue imaging at atmospheric pressure using laserspray ionization mass spectrometry. Int J Mass Spectrom 352:65–69
Nyadong L, Inutan ED, Wang X, Hendrickson CL, Trimpin S, Marshall AG (2013) Laserspray and matrix-assisted ionization inlet coupled to high-field FT-ICR mass spectrometry for peptide and protein analysis. J Am Soc Mass Spectrom 24:320–328
Inutan ED, Trimpin S (2010) Laserspray ionization (LSI) ion mobility spectrometry (IMS) mass spectrometry. J Am Soc Mass Spectrom 21:1260–1264
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
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
Inutan ED, Trimpin S (2013) Matrix assisted ionization vacuum (MAIV), a new ionization method for biological materials analysis using mass spectrometry. Mol Cell Proteomics 12:792–796
Trimpin S, Inutan ED (2012) Matrix assisted ionization in vacuum, a sensitive and widely applicable ionization method for mass spectrometry. J Am Soc Mass Spectrom 24:722–732
Trimpin S, Inutan ED (2013) New ionization method for analysis on atmospheric pressure ionization mass spectrometers requiring only vacuum and matrix assistance. Anal Chem 85:2005–2009
Mitchell J Jr, Deveraux HD (1978) Determination of traces of organic compounds in the atmosphere: role of detectors in gas chromatography. Anal Chim Acta 100:45–52
Sweeting LM, Cashel ML, Rosenblatt MM (1992) Triboluminescence spectra of organic crystals are sensitive to conditions of acquisition. J Lumin 52:281–291
Sweeting LM (2001) Triboluminescence with and without air. Chem Mater 13:854–870
Trimpin S, Herath TN, Inutan ED, Cernat SA, Miller JB, Mackie K, Walker JM (2009) Field-free transmission geometry atmospheric pressure matrix-assisted laser desorption/ionization for rapid analysis of unadulterated tissue samples. Rapid Commun Mass Spectrom 23:3023–3027
Chakrabarty S, Pagnotti VS, Inutan ED, Trimpin S, McEwen CN (2013) A new matrix assisted ionization method for the analysis of volatile and nonvolatile compounds by atmospheric pressure probe mass spectrometry. J Am Soc Mass Spectrom 24:1102–1107
Acknowledgements
The authors are grateful for funding and support from 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 S.T.), and Wayne State University (Schaap and Rumble Dissertation Fellowships to both B.W. and E.D.I. as well as Schaap Faculty Scholar to S.T.).
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El-Baba, T.J., Lutomski, C.A., Wang, B. et al. Toward high spatial resolution sampling and characterization of biological tissue surfaces using mass spectrometry. Anal Bioanal Chem 406, 4053–4061 (2014). https://doi.org/10.1007/s00216-014-7778-8
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DOI: https://doi.org/10.1007/s00216-014-7778-8