Skip to main content

TOF-SIMS Imaging of Biological Tissue Sections and Structural Determination Using Tandem MS

Part of the Methods in Molecular Biology book series (MIMB,volume 2437)

Abstract

Over the past couple of years, imaging mass spectrometry (IMS) has arisen as a powerful tool to answer research questions in the biomedical field. Imaging mass spectrometry allows for label-free chemical imaging by providing full molecular information. The IMS technique best positioned for cell and tissue analysis is time-of-flight secondary ion mass spectrometry (ToF-SIMS) because it has the best spatial resolution of all the molecular IMS techniques and can detect many biochemical species and especially lipids with high sensitivity. Because one must rely on the mass and isotopic pattern of an ion in combination with positive correlations with lower mass fragments to help identify its structure, one major problem during ToF-SIMS experiments is the ambiguity when assigning a molecule to a certain mass peak. The solution are instruments with tandem MS capabilities as was already the case for many MALDI-ToF instruments more than a decade ago. It has been a few years since instruments with this capability were introduced and a number of interesting publications have been produced highlighting the advantages in biological SIMS work. Here, we present a protocol describing how tandem MS can be used to elucidate the structure of unknown or ambiguous mass peaks in biological tissue samples observed during ToF-SIMS imaging based on our experiences.

Key words

  • SIMS
  • Time-of-flight
  • Orbitrap
  • Tandem MS
  • Imaging mass spectrometry
  • Lipids
  • Fatty acids

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

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-0716-2030-4_5
  • Chapter length: 10 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   169.00
Price excludes VAT (USA)
  • ISBN: 978-1-0716-2030-4
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Hardcover Book
USD   219.99
Price excludes VAT (USA)
Fig. 1

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Vickerman JC, Briggs D (2013) ToF-SIMS: materials analysis by mass spectrometry. SurfaceSpectra, Manchester

    Google Scholar 

  2. Fearn S (2015) An introduction to time-of-flight secondary ion mass spectrometry (ToF-SIMS) and its application to materials science. Morgan & Claypool Publishers, San Rafael

    CrossRef  Google Scholar 

  3. Tuck M, Blanc L, Touti R, Patterson NH, Van Nuffel S, Villette S, Taveau J-C, Römpp A, Brunelle A, Lecomte S, Desbenoit N (2021) Multimodal imaging based on vibrational spectroscopies and mass spectrometry imaging applied to biological tissue: a multiscale and multiomics review. Anal Chem 93:445–477. https://doi.org/10.1021/acs.analchem.0c04595

    CAS  CrossRef  PubMed  Google Scholar 

  4. Fletcher JS, Kotze HL, Armitage EG, Lockyer NP, Vickerman JC (2013) Evaluating the challenges associated with time-of-fight secondary ion mass spectrometry for metabolomics using pure and mixed metabolites. Metabolomics 9:535–544. https://doi.org/10.1007/s11306-012-0487-4

    CAS  CrossRef  Google Scholar 

  5. Wehrli PM, Lindberg E, Angerer TB, Wold AE, Gottfries J, Fletcher JS (2014) Maximising the potential for bacterial phenotyping using time-of-flight secondary ion mass spectrometry with multivariate analysis and tandem mass spectrometry. Surf Interface Anal 46:173–176. https://doi.org/10.1002/sia.5505

    CAS  CrossRef  Google Scholar 

  6. Fisher GL, Hammond JS, Larson PE, Bryan SR, Heeren RMA (2016) Parallel imaging MS/MS TOF-SIMS instrument. J Vac Sci Technol B 34:03H126. https://doi.org/10.1116/1.4943568

    CAS  CrossRef  Google Scholar 

  7. Fisher GL, Bruinen AL, Ogrinc Potočnik N, Hammond JS, Bryan SR, Larson PE, Heeren RMA (2016) A new method and mass spectrometer design for TOF-SIMS parallel imaging MS/MS. Anal Chem 88:6433–6440. https://doi.org/10.1021/acs.analchem.6b01022

    CAS  CrossRef  PubMed  Google Scholar 

  8. Pirkl A, Moellers R, Arlinghaus H, Kollmer F, Niehuis E, Makarov A, Horning S, Passarelli M, Havelund R, Rakowska P, Race A, Shard AG, West A, Marshall P, Newman CF, Alexander M, Dollery C, Gilmore IS (2016) A novel hybrid dual analyzer SIMS instrument for improved surface and 3D-analysis. Microsc Microanal 22:340–341. https://doi.org/10.1017/S1431927616002555

    CrossRef  Google Scholar 

  9. Passarelli MK, Pirkl A, Moellers R, Grinfeld D, Kollmer F, Havelund R, Newman CF, Marshall PS, Arlinghaus H, Alexander MR, West A, Horning S, Niehuis E, Makarov A, Dollery CT, Gilmore IS (2017) The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nat Methods 14:1175–1183. https://doi.org/10.1038/nmeth.4504

    CAS  CrossRef  PubMed  Google Scholar 

  10. Van Nuffel S, Quatredeniers M, Pirkl A, Zakel J, Le Caer J-P, Elie N, Vanbellingen QP, Dumas SJ, Nakhleh MK, Ghigna M-R, Fadel E, Humbert M, Chaurand P, Touboul D, Cohen-Kaminsky S, Brunelle A (2020) Multimodal imaging mass spectrometry to identify markers of pulmonary arterial hypertension in human lung tissue using MALDI-ToF, ToF-SIMS, and hybrid SIMS. Anal Chem 53:19. https://doi.org/10.1021/acs.analchem.0c02815

    CAS  CrossRef  Google Scholar 

  11. Linner JG, Livesey SA, Harrison DS, Steiner AL (1986) A new technique for removal of amorphous phase tissue water without ice crystal damage: a preparative method for ultrastructural analysis and immunoelectron microscopy. J Histochem Cytochem 34:1123–1135. https://doi.org/10.1177/34.9.2426340

    CAS  CrossRef  PubMed  Google Scholar 

  12. Green FM, Gilmore IS, Seah MP (2006) TOF-SIMS: accurate mass scale calibration. J Am Soc Mass Spectrom 17:514–523. https://doi.org/10.1021/jasms.8b02645

    CAS  CrossRef  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alain Brunelle .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Verify currency and authenticity via CrossMark

Cite this protocol

Van Nuffel, S., Brunelle, A. (2022). TOF-SIMS Imaging of Biological Tissue Sections and Structural Determination Using Tandem MS. In: Lee, YJ. (eds) Mass Spectrometry Imaging of Small Molecules. Methods in Molecular Biology, vol 2437. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2030-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2030-4_5

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2029-8

  • Online ISBN: 978-1-0716-2030-4

  • eBook Packages: Springer Protocols