Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

MALDI imaging mass spectrometry: molecular snapshots of biochemical systems

Nature Methods volume 4, pages 828–833 (2007)Cite this article

Abstract

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is emerging as a powerful tool for investigating the distribution of molecules within biological systems through the direct analysis of thin tissue sections. Unique among imaging methods, MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement. We discuss the current state of the art of MALDI-IMS along with some recent applications and technological developments that illustrate not only its current capabilities but also the future potential of the technique to provide a better understanding of the underlying molecular mechanisms of biological processes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: General overview of MALDI-IMS.
Figure 2: Workflow for histology-directed profiling.
Figure 3: MALDI-IMS analysis of 12-μm section of mouse epididymis.

Similar content being viewed by others

References

  1. Claydon, M.A., Davey, S.N., Edwards-Jones, V. & Gordon, D.B. The rapid identification of intact microorganisms using mass spectrometry. Nat. Biotechnol. 14, 1584–1586 (1996).

    Article  CAS  Google Scholar 

  2. Holland, R.D. et al. Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 10, 1227–1232 (1996).

    Article  CAS  Google Scholar 

  3. Krishnamurthy, T., Ross, P.L. & Rajamani, U. Detection of pathogenic and non-pathogenic bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 10, 883–888 (1996).

    Article  CAS  Google Scholar 

  4. 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 

  5. 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 

  6. Stauber, J. et al. New developments in MALDI imaging mass spectrometry for pathological proteomic studies; introduction to a novel concept, the specific MALDI imaging. Mol. Cell. Proteomics 5, S247–S247 (2006).

    Google Scholar 

  7. Skold, K. et al. Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. J. Proteome Res. 5, 262–269 (2006).

    Article  Google Scholar 

  8. Chaurand, P., Norris, J.L., Cornett, D.S., Mobley, J.A. & Caprioli, R.M. New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J. Proteome Res. 5, 2889–2900 (2006).

    Article  CAS  Google Scholar 

  9. Stoeckli, M., Staab, D. & Schweitzer, A. Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections. Int. J. Mass Spectrom. 260, 195–202 (2007).

    Article  CAS  Google Scholar 

  10. Meistermann, H. et al. Biomarker discovery by imaging mass spectrometry — Transthyretin is a biomarker for gentamicin-induced nephrotoxicity in rat. Mol. Cell. Proteomics 5, 1876–1886 (2006).

    Article  CAS  Google Scholar 

  11. Kulkarni, M.J., Vinod, V.P., Umasankar, P.K., Patole, M.S. & Rao, M. Intact cell matrix-assisted laser desorption/ionization mass spectrometry as a tool to screen drugs in vivo for regulation of protein expression. Rapid Commun. Mass Spectrom. 20, 2769–2772 (2006).

    Article  CAS  Google Scholar 

  12. Khatib-Shahidi, S., Andersson, M., Herman, J.L., Gillespie, T.A. & Caprioli, R.M. Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal. Chem. 78, 6448–6456 (2006).

    Article  CAS  Google Scholar 

  13. Lemaire, R. et al. Direct analysis and MALDI imaging of formalin-fixed, paraffin-embedded tissue sections. J. Proteome Res. 6, 1295–1305 (2007).

    Article  CAS  Google Scholar 

  14. Norris, J.L. et al. Processing MALDI mass spectra to improve mass spectral direct tissue analysis. Int. J. Mass Spectrom. 260, 212–221 (2007).

    Article  CAS  Google Scholar 

  15. Shimma, S., Furuta, M., Ichimura, K., Yoshida, Y. & Setou, M. Direct MS/MS analysis in mammalian tissue sections using MALDI-QIT-TOFMS and chemical inkjet technology. Surf. Interface Anal. 38, 1712–1714 (2006).

    Article  CAS  Google Scholar 

  16. Aerni, H.R., Cornett, D.S. & Caprioli, R.M. Automated acoustic matrix deposition for MALDI sample preparation. Anal. Chem. 78, 827–834 (2006).

    Article  CAS  Google Scholar 

  17. Reyzer, M.L. & Caprioli, R.M. MALDI-MS-based imaging of small molecules and proteins in tissues. Curr. Opin. Chem. Biol. 11, 29–35 (2007).

    Article  CAS  Google Scholar 

  18. Pevsner, P.H. et al. Direct identification of proteins from T47D cells and murine brain tissue by matrix-assisted laser desorption/ionization post-source decay/collision-induced dissociation. Rapid Commun. Mass Spectrom. 21, 429–436 (2007).

    Article  CAS  Google Scholar 

  19. Hsieh, Y. et al. Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue. Rapid Commun. Mass Spectrom. 20, 965–972 (2006).

    Article  CAS  Google Scholar 

  20. Atkinson, S.J., Loadman, P.M., Sutton, C., Patterson, L.H. & Clench, M.R. Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun. Mass Spectrom. 21, 1271–1276 (2007).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

  22. Woods, A.S. & Jackson, S.N. Brain tissue lipidomics: direct probing using matrix-assisted laser desorption/ionization mass spectrometry. AAPS J. 8, E391–E395 (2006).

    Article  Google Scholar 

  23. Spengler, B. & Hubert, M. Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: instrumentation for sub-micrometer resolved LDI and MALDI surface analysis. J. Am. Soc. Mass Spectrom. 13, 735–748 (2002).

    Article  CAS  Google Scholar 

  24. Chaurand, P., Schriver, K.E. & Caprioli, R.M. Instrument design and characterization for high resolution MALDI-MS imaging of tissue sections. J. Mass Spectrom. 42, 476–489 (2007).

    Article  CAS  Google Scholar 

  25. Altelaar, A.F.M. et al. High-resolution MALDI imaging mass spectrometry allows localization of peptide distributions at cellular length scales in pituitary tissue sections. Int. J. Mass Spectrom. 260, 203–211 (2007).

    Article  CAS  Google Scholar 

  26. DeKeyser, S.S., Kutz-Naber, K.K., Schmidt, J.J., Barrett-Wilt, G.A. & Li, L.J. Imaging mass spectrometry of neuropeptides in decapod crustacean neuronal tissues. J. Proteome Res. 6, 1782–1791 (2007).

    Article  CAS  Google Scholar 

  27. Taban, I.M. et al. Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry. J. Am. Soc. Mass Spectrom. 18, 145–151 (2007).

    Article  CAS  Google Scholar 

  28. Brand, G.D. et al. Bradykinin-related peptides from Phyllomedusa hypochondrialis. Peptides 27, 2137–2146 (2006).

    Article  CAS  Google Scholar 

  29. Han, J. & Schey, K.L. MALDI tissue imaging of ocular lens alpha-crystallin. Invest. Ophthalmol. Vis. Sci. 47, 2990–2996 (2006).

    Article  Google Scholar 

  30. Verhaert, P.D., Conaway, M.C.P., Pekar, T.M. & Miller, K. Neuropeptide imaging on an LTQ with vMALDI source: The complete 'all-in-one' peptidome analysis. Int. J. Mass Spectrom. 260, 177–184 (2007).

    Article  CAS  Google Scholar 

  31. Cornett, D.S. et al. A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Mol. Cell. Proteomics 5, 1975–1983 (2006).

    Article  CAS  Google Scholar 

  32. Schwartz, S.A. et al. Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. Cancer Res. 65, 7674–7681 (2005).

    Article  CAS  Google Scholar 

  33. Caldwell, R.L., Gonzalez, A., Oppenheimer, S.R., Schwartz, H.S. & Caprioli, R.M. Molecular assessment of the tumor protein microenvironment using imaging mass spectrometry. Cancer Genomics Proteomics 3, 279–288 (2006).

    CAS  Google Scholar 

  34. Suzuki, K. et al. Epididymis-specific promoter-driven gene targeting: a transcription factor which regulates epididymis-specific gene expression. Mol. Cell. Endocrinol. 250, 184–189 (2006).

    Article  CAS  Google Scholar 

  35. Chaurand, P. et al. Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry. Proteomics 3, 2221–2239 (2003).

    Article  CAS  Google Scholar 

  36. Groseclose, M.R., Andersson, M., Hardesty, W.M. & Caprioli, R.M. Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. J. Mass Spectrom. 42, 254–262 (2007).

    Article  CAS  Google Scholar 

  37. Thiery, G. et al. Multiplex target protein imaging in tissue sections by mass spectrometry—TAMSIM. Rapid Commun. Mass Spectrom. 21, 823–829 (2007).

    Article  CAS  Google Scholar 

  38. Lemaire, R. et al. Tag-mass: specific molecular imaging of transcriptome and proteome by mass spectrometry based on photocleavable tag. J. Proteome Res. 6, 2057–2067 (2007).

    Article  CAS  Google Scholar 

  39. Signor, L. et al. Analysis of erlotinib and its metabolites in rat tissue sections by MALDI quadrupole time-of-flight mass spectrometry. J. Mass Spectrom. 42, 900–909 (2007).

    Article  CAS  Google Scholar 

  40. Corr, J.J. et al. Design considerations for high speed quantitative mass spectrometry with MALDI ionization. J. Am. Soc. Mass Spectrom. 17, 1129–1141 (2006).

    Article  CAS  Google Scholar 

  41. Reyzer, M.L. et al. Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics. Cancer Res. 64, 9093–9100 (2004).

    Article  CAS  Google Scholar 

  42. Cha, S.W. & Yeung, E.S. Colloidal graphite-assisted laser desorption/ionization mass spectrometry and MSn of small molecules. 1. Imaging of cerebrosides directly from rat brain tissue. Anal. Chem. 79, 2373–2385 (2007).

    Article  CAS  Google Scholar 

  43. Woods, A.S. et al. IR-MALDI-LDI combined with ion mobility orthogonal time-of-flight mass spectrometry. J. Proteome Res. 5, 1484–1487 (2006).

    Article  CAS  Google Scholar 

  44. Jackson, S.N., Wang, H.Y.J. & Woods, A.S. Direct tissue analysis of phospholipids in rat brain using MALDI-TOFMS and MALDI-ion mobility-TOFMS. J. Am. Soc. Mass Spectrom. 16, 133–138 (2005).

    Article  CAS  Google Scholar 

  45. McLean, J.A., Ridenour, W.B. & Caprioli, R.M. Profiling and imaging of tissues by imaging ion mobility-mass spectrometry. J. Mass Spectrom. 42, 1099–1105 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  47. Heeren, R.M.A. et al. Why don't biologists use SIMS? A critical evaluation of imaging MS. Appl. Surf. Sci. 252, 6827–6835 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank E. Seeley, N. Caprioli, M.-C. Orgebin-Crist and P. Massion for assistance with the figures and have received financial support from the US National Institutes of Health, 5R01-GM058008-08, and Department of Defense, W81XWH-05-1-0179.

Author information

Authors and Affiliations

  1. Mass Spectrometry Research Center, 465 21st Avenue, Vanderbilt University Medical Center, Nashville, 37232, Tennessee, USA

    Dale S Cornett, Michelle L Reyzer, Pierre Chaurand & Richard M Caprioli

Authors
  1. Dale S Cornett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michelle L Reyzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierre Chaurand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard M Caprioli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cornett, D., Reyzer, M., Chaurand, P. et al. MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat Methods 4, 828–833 (2007). https://doi.org/10.1038/nmeth1094

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth1094

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing