Skip to main content
Log in

IR-MALDESI Mass Spectrometry Imaging of Biological Tissue Sections Using Ice as a Matrix

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

Abstract

Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging of biological tissue sections using a layer of deposited ice as an energy-absorbing matrix was investigated. Dynamics of plume ablation were first explored using a nanosecond exposure shadowgraphy system designed to simultaneously collect pictures of the plume with a camera and collect the Fourier transform ion cyclotron resonance FT-ICR mass spectrum corresponding to that same ablation event. Ablation of fresh tissue analyzed with and without using ice as a matrix were compared using this technique. Effect of spot-to-spot distance, number of laser shots per pixel, and tissue condition (matrix) on ion abundance were also investigated for 50 μm-thick tissue sections. Finally, the statistical method called design of experiments was used to compare source parameters and determine the optimal conditions for IR-MALDESI of tissue sections using deposited ice as a matrix. With a better understanding of the fundamentals of ablation dynamics and a systematic approach to explore the experimental space, it was possible to improve ion abundance by nearly one order of magnitude.

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.

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

Similar content being viewed by others

References

  1. 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 

  2. Tanaka, K., Waki, H., Ido, Y., Akita, S., Yoshida, Y., Yoshida, T., Matsuo, 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)

    Article  CAS  Google Scholar 

  3. Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F., Whitehouse, C.M.: Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989)

    Article  CAS  Google Scholar 

  4. Shiea, J., Huang, M.Z., Hsu, H.J., Lee, C.Y., Yuan, C.H., Beech, I., Sunner, J.: Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids Rapid Commun. Mass Spectrom. 19, 3701–3704 (2005)

    CAS  Google Scholar 

  5. Huang, M.Z., Hsu, H.J., Lee, L.Y., Jeng, J.Y., Shiea, J.T.: Direct protein detection from biological media through electrospray-assisted laser desorption ionization/mass spectrometry. J. Proteome Res. 5, 1107–1116 (2006)

    Article  CAS  Google Scholar 

  6. Brady, J.J., Judge, E.J., Levis, R.J.: Mass spectrometry of intact neutral macromolecules using intense non-resonant femtosecond laser vaporization with electrospray post-ionization. Rapid Commun. Mass Spectrom. 23, 3151–3157 (2009)

    Article  CAS  Google Scholar 

  7. Jorabchi, K., Smith, L.M.: Single droplet separations and surface partition coefficient measurements using laser ablation mass spectrometry. Anal. Chem. 81, 9682–9688 (2009)

    Article  CAS  Google Scholar 

  8. Liu, J., Qiu, B., Luo, H.: Fingerprinting of yogurt products by laser desorption spray post-ionization mass spectrometry. Rapid Commun. Mass Spectrom. 24, 1365–1370 (2010)

    Article  CAS  Google Scholar 

  9. Sampson, J.S., Hawkridge, A.M., Muddiman, D.C.: Direct characterization of intact polypeptides by matrix-assisted laser desorption electrospray ionization quadrupole Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun. Mass Spectrom. 21, 1150–1154 (2007)

    Article  CAS  Google Scholar 

  10. Sampson, J.S., Hawkridge, A.M., Muddiman, D.C.: 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, 1712–1716 (2006)

    Article  CAS  Google Scholar 

  11. Nemes, P., Vertes, A.: Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal. Chem. 79, 8098–8106 (2007)

    Article  CAS  Google Scholar 

  12. Rezenom, Y.H., Dong, J., Murray, K.K.: Infrared laser-assisted desorption electrospray ionization mass spectrometry. Analyst 133, 226–232 (2008)

    Article  CAS  Google Scholar 

  13. Sampson, J.S., Murray, K.K., Muddiman, D.C.: Intact and top-down characterization of biomolecules and direct analysis using infrared matrix-assisted laser desorption electrospray ionization coupled to FT-ICR mass spectrometry. J. Am. Soc. Mass Spectrom. 20, 667–673 (2009)

    Article  CAS  Google Scholar 

  14. Barry, J.A., Muddiman, D.C.: Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments. Rapid Commun. Mass Spectrom. 25, 3527–3536 (2011)

    Article  CAS  Google Scholar 

  15. Cochran, K.H., Barry, J.A., Muddiman, D.C., Hinks, D.: Direct analysis of textile fabrics and dyes using infrared matrix-assisted laser desorption electrospray ionization mass spectrometry. Anal. Chem. 85, 831–836 (2012)

    Article  Google Scholar 

  16. Robichaud, G., Barry, J.A., Garrard, K.P., Muddiman, D.C.: 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 (2013)

    Article  CAS  Google Scholar 

  17. Stoeckli, M., Chaurand, P., Hallahan, D.E., Caprioli, R.M.: Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat. Med. 7, 493–496 (2001)

    Article  CAS  Google Scholar 

  18. Caprioli, R.M., Farmer, T.B., Gile, J.: Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal. Chem. 69, 4751–4760 (1997)

    Article  CAS  Google Scholar 

  19. Norris, J.L., Caprioli, R.M.: Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem. Rev. 113, 2309–2342 (2013)

    Article  CAS  Google Scholar 

  20. Chaurand, P.: Imaging mass spectrometry of thin tissue sections: a decade of collective efforts. J. Proteom. (2012). doi:10.1016/j.jprot.2012.04.005

  21. van Hove, E.R.A., Smith, D.F., Heeren, R.M.A.: A concise review of mass spectrometry imaging. J. Chromatogr. A 1217, 3946–3954 (2010)

    Article  Google Scholar 

  22. Baltz-Knorr, M., Schriver, K., Haglund, R.: Infrared laser ablation and ionization of water clusters and biomolecules from ice. Appl. Surf. Sci. 197, 11–16 (2002)

    Article  Google Scholar 

  23. Kraft, P., Alimpiev, S., Dratz, E., Sunner, J.: Infrared surface-assisted laser desorption ionization mass spectrometry on frozen aqueous solutions of proteins and peptides using suspensions of organic solids. J. Am. Soc. Mass Spectrom. 9, 912–924 (1998)

    Article  CAS  Google Scholar 

  24. Berkenkamp, S., Karas, M., Hillenkamp, F.: Ice as a matrix for IR-matrix-assisted laser desorption/ionization: mass spectra from a protein single crystal. Proc. Natl. Acad. Sci. U. S. A. 93, 7003–7007 (1996)

    Article  CAS  Google Scholar 

  25. Oraevsky, A.A., Jacques, S.L.: Mechanism of laser ablation for aqueous media irradiated under confined‐stress conditions. J. Appl. Phys. 78, 1281–1290 (1995)

    Article  CAS  Google Scholar 

  26. Belov, M.E., Alimpiev, S.S., Mlynsky, V.V., Nikiforov, S.M., Derrick, P.J.: Laser ablation of organic molecules from frozen matrices. Rapid Commun. Mass Spectrom. 9, 1431–1436 (1995)

    Article  CAS  Google Scholar 

  27. Williams, P.: Time of flight mass spectrometry of DNA laser-ablated from frozen aqueous solutions: applications to the Human Genome Project. Int. J. Mass Spectrom. Ion Processes 131, 335–344 (1994)

    Article  CAS  Google Scholar 

  28. Von Seggern, C.E., Gardner, B.D., Cotter, R.J.: Infrared atmospheric pressure MALDI ion trap mass spectrometry of frozen samples using a Peltier-cooled sample stage. Anal. Chem. 76, 5887–5893 (2004)

    Article  Google Scholar 

  29. Römpp, A., Schäfer, K.C., Guenther, S., Wang, Z., Köstler, M., Leisner, A., Paschke, C., Schramm, T., Spengler, B.: High-resolution atmospheric pressure infrared laser desorption/ionization mass spectrometry imaging of biological tissue. Anal. Bioanal. Chem. 1–10 (2013)

  30. Pirkl, A., Soltwisch, J., Draude, F., Dreisewerd, K.: Infrared matrix-assisted laser desorption/ionization orthogonal-time-of-flight mass spectrometry employing a cooling stage and water ice as a matrix. Anal. Chem. 84, 5669–5676 (2012)

    Article  CAS  Google Scholar 

  31. Dreisewerd, K., Berkenkamp, S., Leisner, A., Rohlfing, A., Menzel, C.: Fundamentals of matrix-assisted laser desorption/ionization mass spectrometry with pulsed infrared lasers. Int. J. Mass Spectrom. 226, 189–209 (2003)

    Article  CAS  Google Scholar 

  32. Menzel, C., Dreisewerd, K., Berkenkamp, S., Hillenkamp, F.: Mechanisms of energy deposition in infrared matrix-assisted laser desorption/ionization mass spectrometry. Int. J. Mass Spectrom. 207, 73–96 (2001)

    Article  CAS  Google Scholar 

  33. Venugopalan, V., Nishioka, N., Mikić, B.: Thermodynamic response of soft biological tissues to pulsed infrared-laser irradiation. Biophys. J. 70, 2981–2993 (1996)

    Article  CAS  Google Scholar 

  34. Nemes, P., Vertes, A.: Ambient mass spectrometry for in vivo local analysis and in situ molecular tissue imaging. Trac-Trend Anal. Chem. 34, 22–34 (2012)

    Article  CAS  Google Scholar 

  35. Shrestha, B., Nemes, P., Nazarian, J., Hathout, Y., Hoffman, E.P.: Vertes, A.:Direct analysis of lipids and small metabolites in mouse brain tissue by AP IR-MALDI and reactive LAESI mass spectrometry. Analyst 135, 751–758 (2010)

    Article  CAS  Google Scholar 

  36. Nemes, P., Woods, A.S., Vertes, A.: Simultaneous imaging of small metabolites and lipids in rat brain tissues at atmospheric pressure by laser ablation electrospray ionization mass spectrometry. Anal. Chem. 82, 982–988 (2010)

    Article  CAS  Google Scholar 

  37. Chen, Z., Vertes, A.: Early plume expansion in atmospheric pressure midinfrared laser ablation of water-rich targets. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 77, 036316 (2008)

    Google Scholar 

  38. Apitz, I., Vogel, A.: Material ejection in nanosecond Er: YAG laser ablation of water, liver, and skin. Appl. Phys. A 81, 329–338 (2005)

    Article  CAS  Google Scholar 

  39. Kokai, F., Takahashi, K., Shimizu, K., Yudasaka, M., Iijima, S.: Shadowgraphic and emission imaging spectroscopic studies of the laser ablation of graphite in an Ar gas atmosphere. Appl. Phys. A 69, S223–S227 (1999)

    Article  CAS  Google Scholar 

  40. Thoroddsen, S.T., Takehara, K., Etoh, T.G., Ohl, C.D.: Spray and microjets produced by focusing a laser pulse into a hemispherical drop. Phys. Fluids 21, (2009). doi:10.1063/1.3253394

  41. Robichaud, G., Dixon, R.B., Potturi, A.S., Cassidy, D., Edwards, J.R., Sohn, A., Dow, T.A., Muddiman, D.C.: Design, modeling, fabrication, and evaluation of the air amplifier for improved detection of biomolecules by electrospray ionization mass spectrometry. Int. J. Mass Spectrom. 300, 99–107 (2011)

    Article  CAS  Google Scholar 

  42. Riter, L.S., Vitek, O., Gooding, K.M., Hodge, B.D., Julian, R.K.: Statistical design of experiments as a tool in mass spectrometry. J. Mass Spectrom. 40, 565–579 (2005)

    Article  CAS  Google Scholar 

  43. Robichaud, G., Garrard, K., Barry, J., Muddiman, D.: MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on matlab platform. J. Am. Soc. Mass Spectrom. 24, 718–721 (2013)

    Article  CAS  Google Scholar 

  44. Vogel, A., Venugopalan, V.: Mechanisms of pulsed laser ablation of biological tissues. Chem. Rev. 103, 577–644 (2003)

    Article  CAS  Google Scholar 

  45. Jurchen, J.C., Rubakhin, S.S., Sweedler, J.V.: MALDI-MS imaging of features smaller than the size of the laser beam. J. Am. Soc. Mass Spectrom. 16, 1654–1659 (2005)

    Article  CAS  Google Scholar 

  46. Todd, P.J., Schaaff, T.G., Chaurand, P., Caprioli, R.M.: Organic ion imaging of biological tissue with secondary ion mass spectrometry and matrix-assisted laser desorption/ionization. J. Mass Spectrom. 36, 355–369 (2001)

    Article  CAS  Google Scholar 

  47. Kebarle, P., Tang, L.: From ions in solution to ions in the gas phase-the mechanism of electrospray mass spectrometry. Anal. Chem. 65, 972A–986A (1993)

    CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support received from the National Institutes of Health (R01GM087964) and North Carolina State University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David C. Muddiman.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 11811 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robichaud, G., Barry, J.A. & Muddiman, D.C. IR-MALDESI Mass Spectrometry Imaging of Biological Tissue Sections Using Ice as a Matrix. J. Am. Soc. Mass Spectrom. 25, 319–328 (2014). https://doi.org/10.1007/s13361-013-0787-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13361-013-0787-6

Key words

Navigation