Skip to main content
Log in

Matrix Assisted Ionization in Vacuum, a Sensitive and Widely Applicable Ionization Method for Mass Spectrometry

  • Research Article
  • Published:
Journal of The American Society for Mass Spectrometry

Abstract

An astonishingly simple new method to produce gas-phase ions of small molecules as well as proteins from the solid state under cold vacuum conditions is described. This matrix assisted ionization vacuum (MAIV) mass spectrometry (MS) method produces multiply charged ions similar to those that typify electrospray ionization (ESI) and uses sample preparation methods that are nearly identical to matrix-assisted laser desorption/ionization (MALDI). Unlike these established methods, MAIV does not require a laser or voltage for ionization, and unlike the recently introduced matrix assisted ionization inlet method, does not require added heat. MAIV-MS requires only introduction of a crystalline mixture of the analyte incorporated with a suitable small molecule matrix compound such as 3-nitrobenzonitrile directly to the vacuum of the mass spectrometer. Vacuum intermediate pressure MALDI sources and modified ESI sources successfully produce ions for analysis by MS with this method. As in ESI-MS, ion formation is continuous and, without a laser, little chemical background is observed. MAIV, operating from a surface offers the possibility of significantly improved sensitivity relative to atmospheric pressure ionization because ions are produced in the vacuum region of the mass spectrometer eliminating losses associated with ion transfer from atmospheric pressure to vacuum. Mechanistic aspects and potential applications for this new ionization method are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Vestal, M.L.: Modern MALDI Time-of-flight mass spectrometry. J. Mass Spectrom. 44, 303–317 (2009)

    CAS  Google Scholar 

  2. Tanaka, K., Waki, H., Ido, Y., Akita, S., Yoshida, Y., Yoshida, T.: 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 (1988)

    CAS  Google Scholar 

  3. Karas, M., Hillenkamp, F.: Laser desorption ionization of proteins with molecular masses exceeding 10,000 Daltons. Anal. Chem. 60, 2299–2301 (1988)

    CAS  Google Scholar 

  4. Garrett, T.J., Yost, R.A.: Analysis of intact tissue by intermediate-pressure MALDI on a linear ion trap mass spectrometer. Anal. Chem. 78, 2465–2469 (2006)

    CAS  Google Scholar 

  5. Landgraf, R.R., Garrett, T.J., Calcutt, N.A., Stacpoole, P.W., Yost, R.A.: MALDI-linear ion trap microprobe MS/MS studies of the effects of dichloroacetate on lipid content of nerve tissue. Anal. Chem. 79, 8170–8175 (2007)

    CAS  Google Scholar 

  6. Trimpin, S., Rouhanipour, A., Az, R., Räder, H.J., Müllen, K.: New aspects in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: A universal solvent-free sample preparation. Rapid Commun. Mass Spectrom. 15, 1364–1373 (2001)

    CAS  Google Scholar 

  7. Trimpin, S.: A perspective on MALDI alternatives - total solvent-free analysis and electron transfer dissociation of highly charged ions by laserspray ionization. J. Mass Spectrom. 45, 471–485 (2010)

    CAS  Google Scholar 

  8. Merchant, M., Weinberger, S.R.: Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis 21, 1164–1177 (2000)

    CAS  Google Scholar 

  9. Caldwell, R.L., Caprioli, R.M.: Tissue profiling by mass spectrometry—a review of methodology and applications. Mol. Cell. Proteom. 4, 394–401 (2005)

    CAS  Google Scholar 

  10. McDonnell, L.A., Heeren, M.A.: Imaging mass spectrometry. Mass Spectrom. Rev. 26, 606–643 (2007)

    CAS  Google Scholar 

  11. Sunner, J., Dratz, E., Chen, Y.C.: Graphite surface-assisted laser desorption/ionization time-of-flight mass spectrometry of peptides and proteins from liquid solutions. Anal. Chem. 67, 4335–4342 (1995)

    CAS  Google Scholar 

  12. Wei, J., Buriak, J.M., Siuzdak, G.: Desorption-ionization mass spectrometry on porous silicon. Nature 399, 243–246 (1999)

    CAS  Google Scholar 

  13. Hutchens, T.W., Yip, T.T.: New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun. Mass Spectrom. 7, 576–580 (1993)

    CAS  Google Scholar 

  14. Gebhardt, C.R., Tomsic, A., Schruder, H., Durr, M., Kompa, K.L.: Matrix-free formation of gas-phase biomolecular ions by soft cluster-induced desorption. Angew. Chem. Int. Ed. 48, 4162–4165 (2009)

    CAS  Google Scholar 

  15. Yamada, I., Matsou, J., Toyoda, N., Kirkpatrick, A.: Materials processing by gas cluster ion beams. Mater. Sci. Eng. R 34, 231–295 (2001)

    Google Scholar 

  16. Cheng, J., Wucher, A., Winograd, N.: Molecular depth profiling with cluster ion beams. J. Phys. Chem. B 110, 8329–8336 (2006)

    CAS  Google Scholar 

  17. Weibel, D., Wong, S., Lockyer, N., Blenkinsopp, P., Hill, R., Vickerman, J.C.: A C60 primary ion beam system for time of flight secondary ion mass spectrometry: Its development and secondary ion yield characteristics. Anal. Chem. 75, 1754–1764 (2003)

    CAS  Google Scholar 

  18. Karas, M., Bahr, U., Strupat, K., Hillenkamp, F., Tsarbopoulos, A., Pramanik, B.N.: Matrix dependence of metastable fragmentation of glycoproteins in MALDI TOF mass spectrometry. Anal. Chem. 67, 675–679 (1995)

    Google Scholar 

  19. Sheehan, E.W., Willoughby, R.C.: Ion enrichment aperture arrays. U.S. Patent 7,060,976; June 12 (2006)

  20. Page, J.S., Tang, K., Kelly, R.T., Smith, R.D.: Subambient pressure ionization with nanoelectrospray source and interface for improved sensitivity in mass spectrometry. Anal. Chem. 80, 1800–1805 (2008)

    CAS  Google Scholar 

  21. Hakansson, K., Zubarev, R.A., Coorey, R.V., Talrose, V.L., Hakansson, P.: Interaction between explosive and analyte layers in explosive matrix-assisted plasma desorption mass spectrometry. Rapid Commun. Mass Spectrom. 13, 1169–1174 (1999)

    CAS  Google Scholar 

  22. Zubarev, R.A., Hakansson, P., Sundqvist, N., Talrose, V.L.: Enhancement of the molecular ion yield in plasma desorption mass spectrometry using explosive matrices. Rapid Commun. Mass Spectrom. 11, 63–70 (1997)

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  24. Trimpin, S., Inutan, E.D., Herath, T.N., McEwen, C.N.: 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 (2010)

    CAS  Google Scholar 

  25. McEwen, C.N., Pagnotti, V.S., Inutan, E.D., Trimpin, S.: New paradigm in ionization: Multiply charged ion formation from a solid matrix without a laser or voltage. Anal. Chem. 82, 9164–9168 (2010)

    CAS  Google Scholar 

  26. Lietz, C.B., Richards, A.L., Ren, Y., Trimpin, S.: 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 (2011)

    Google Scholar 

  27. Pagnotti, V.S., Chubatyi, N.D., McEwen, C.N.: Solvent assisted inlet ionization: An ultrasensitive new liquid introduction ionization method for mass spectrometry. Anal. Chem. 83, 3981–3985 (2011)

    CAS  Google Scholar 

  28. Wang, B., Inutan, E.D., Trimpin, S.: 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 (2012)

    CAS  Google Scholar 

  29. Inutan, E.D., Wang, B., Trimpin, S.: Commercial intermediate pressure MALDI ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions. Anal. Chem. 83, 678–684 (2011)

    CAS  Google Scholar 

  30. Trimpin, S., Ren, Y., Wang, B., Lietz, C.B., Richards, A.L., Marshall, D.D., Inutan, E.D.: 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 (2011)

    CAS  Google Scholar 

  31. Inutan, E.D., Li, J., Manly, C., Wang, B., Trimpin, S.: Laserspray ionization and solvent assisted inlet ionization developments and ion mobility spectrometry mass spectrometry applications. Proceedings of the 60th ASMS Conference on Mass Spectrometry and Allied Topics, Vancouver, Canada, May 20–24 (2012)

  32. Li, J., Inutan, E.D., Wang, B., Lietz, C.B., Green, D.R., Manly, C.D., Richards, A.L., Marshall, D.D., Lingenfelter, S., Ren, Y., Trimpin, S.: 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 (2012)

    CAS  Google Scholar 

  33. Trimpin, S., Wang, B., Inutan, E.D., Li, J., Lietz, C.B., Harron, A., Pagnotti, V.S., Sardelis, D., McEwen, C.N.: A mechanism for ionization of nonvolatile compounds in mass spectrometry: Considerations from MALDI and inlet ionization. J. Am. Soc. Mass Spectrom. 23, 1644–1660 (2012)

    CAS  Google Scholar 

  34. Wang, B., Lietz, C.B., Inutan, E.D., Leach, S., Trimpin, S.: Producing highly charged ions without solvent using laserspray ionization: A total solvent-free analysis approach at atmospheric pressure. Anal. Chem. 83, 4076–4084 (2011)

    CAS  Google Scholar 

  35. Inutan, E.D., Trimpin, S.: 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 (2010)

    CAS  Google Scholar 

  36. Inutan, E.D., Trimpin, S.: Laserspray ionization (LSI) ion mobility spectrometry (ims) mass spectrometry. J. Am. Soc. Mass Spectrom. 21, 1260–1264 (2010)

    CAS  Google Scholar 

  37. Mitchell Jr., J., Deveraux, H.D.: Determination of traces of organic compounds in the atmosphere—role of detectors in gas chromatography. Anal. Chim. Acta 100, 45–52 (1978)

    CAS  Google Scholar 

  38. Sroka-Bartnicka, A., Ciesielskl, W., Libiszowski, J., Duda, A., Sochacki, M., Potrzebowski, M.J.: Complementarity of solvent-free MALDI TOF and solid-state NMR spectroscopy in spectral analysis of polylactides. Anal. Chem. 82, 323–328 (2010)

    CAS  Google Scholar 

  39. Saunders, C.: Charge separation mechanisms in clouds. Space Sci. Rev. 137, 335–353 (2008)

    Google Scholar 

  40. Cheng, R.J.: Water drop freezing: Ejection of microdroplets. Science 170, 1395–1396 (1970)

    CAS  Google Scholar 

  41. Latham, J., Stow, C.D.: Mechanism of charge transfer associated with evaporation of ice. J. Atmos. Sci. 23, 245–247 (1968)

    Google Scholar 

  42. Sweeting, L.M., Cashel, M.L., Rosenblatt, M.M.: Triboluminescence spectra of organic crystals are sensitive to conditions of acquisition. J. Lumin. 52, 281–291 (1992)

    CAS  Google Scholar 

  43. Sweeting, L.M.: Triboluminescence with and without air. Chem. Mater. 13, 854–870 (2001)

    CAS  Google Scholar 

  44. Zink, J.I.: Triboluminescence. Accts. Chem. Res. 11, 289–295 (1978)

    CAS  Google Scholar 

  45. Lin, S.H., Wutz, D., Ho, Z.Z., Eyring, H.: Mechanism of triboluminescence. Proc. Natl. Acad. Sci. U.S.A. 77, 1245–1247 (1980)

    CAS  Google Scholar 

  46. Dole, M., Mack, L.L., Hines, R.L., Mobley, R.C., Ferguson, L.D., Alice, M.B.: Molecular beams of macroions. J. Chem. Phys. 49, 2240–2249 (1968)

    CAS  Google Scholar 

  47. Iribarne, J.V., Thomson, B.A.: On the evaporation of small ions from charged droplets. J. Chem. Phys. 64, 2287–2294 (1976)

    CAS  Google Scholar 

  48. McEwen, C.N., Trimpin, S.: An alternative paradigm in mass spectrometry: Flying elephants from trojan horses. Int. J. Mass Spectrom. 300, 167–172 (2011)

    CAS  Google Scholar 

  49. Frankevich, V., Nieckarz, R., Sagulenko, P., Barylyuk, K., Levitsky, L., Agapov, A., Perlova, T., Gorshkov, M., Tarasova, I., Zenobi, R.: Probing the mechanisms of ambient ionization by laser-induced fluorescence spectroscopy. Rapid Commun. Mass Spectrom. 26, 1567–1572 (2012)

    CAS  Google Scholar 

  50. Zhigilei, L.V., Garrison, B.J.: Microscopic mechanisms of laser ablation of organic solids in the thermal and stress confinement irradiation regimes. J. Appl. Phys. 88, 1281–1298 (2000)

    CAS  Google Scholar 

  51. Zhigilei, L.V.: Dynamics of the plume formation and parameters of the ejected clusters in short-pulse laser ablation. Appl. Phys. A 76, 339–350 (2003)

    CAS  Google Scholar 

  52. Zink, J.I., Klimt, W.: Triboluminescence of coumarin-fluorescence and dynamic spectral features excited by mechanical-stress. J. Am. Chem. Soc. 96, 4690–4692 (1974)

    CAS  Google Scholar 

  53. Sabbah, R., Elwatik, K.: Thermodynamic study of anthrone, coumarin, and phenazine. J. Thermal Anal. 38, 803–809 (1992)

    CAS  Google Scholar 

  54. Richards, A.L., Marshall, D.D., Inutan, E.D., McEwen, C.N., Trimpin, S.: High-throughput analysis of peptides and proteins by laserspray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 25, 247–250 (2011)

    CAS  Google Scholar 

  55. Krutchinsky, A.N., Chait, B.T.: On the nature of the chemical noise in MALDI mass spectra. J. Am. Soc. Mass Spectrom. 13, 129–134 (2002)

    CAS  Google Scholar 

  56. Smith, R.M.: The mass spectrum of cocaine. J. Forensic Sci. 42(3), 475–480 (1997)

    Google Scholar 

  57. Jagerdeo, E., Abdel-Rehim, M.: Screening of cocaine and its metabolites in human urine samples by direct analysis in real-time source coupled to time-of-flight mass spectrometry after online preconcentration utilizing microextraction by packed sorbent. J. Am. Soc. Mass Spectrom. 20, 891–899 (2009)

    CAS  Google Scholar 

  58. McEwen, C.N., McKay, R.G., Larsen, B.S.: Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments. Anal. Chem. 77, 7826–7831 (2005)

    CAS  Google Scholar 

Download references

Acknowledgments

NSF CAREER 0955975, ASMS Research Award (Waters Co.), DuPont (Young Professor Award), Eli Lilly (Young Investigator Award in Analytical Chemistry), Waters Co. (COI program), and Schaap Faculty Scholar (to S.T.), and Schaap Graduate Fellow (to E.D.I.) are acknowledged. The authors are grateful for Professor Hendrickson (WSU) and Professor McEwen (USP) for valuable feedback on this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah Trimpin.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 2.03 MB)

(AVI 82407 kb)

ESM 3

(AVI 27997 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trimpin, S., Inutan, E.D. Matrix Assisted Ionization in Vacuum, a Sensitive and Widely Applicable Ionization Method for Mass Spectrometry. J. Am. Soc. Mass Spectrom. 24, 722–732 (2013). https://doi.org/10.1007/s13361-012-0571-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13361-012-0571-z

Key words

Navigation