Dual-polarity SALDI FT-ICR MS imaging and Kendrick mass defect data filtering for lipid analysis

Abstract

Lipids are biomolecules of crucial importance involved in critical biological functions. Yet, lipid content determination using mass spectrometry is still challenging due to their rich structural diversity. Preferential ionisation of the different lipid species in the positive or negative polarity is common, especially when using soft ionisation mass spectrometry techniques. Here, we demonstrate the potency of a dual-polarity approach using surface-assisted laser desorption/ionisation coupled to Fourier transform-ion cyclotron resonance (SALDI FT-ICR) mass spectrometry imaging (MSI) combined with Kendrick mass defect data filtering to (i) identify the lipids detected in both polarities from the same tissue section and (ii) show the complementarity of the dual-polarity data, both regarding the lipid coverage and the spatial distributions of the various lipids. For this purpose, we imaged the same mouse brain section in the positive and negative ionisation modes, on alternate pixels, in a SALDI FT-ICR MS imaging approach using gold nanoparticles (AuNPs) as dual-polarity nanosubstrates. Our study demonstrates, for the first time, the feasibility of (i) a dual-polarity SALDI-MSI approach on the same tissue section, (ii) using AuNPs as nanosubstrates combined with a FT-ICR mass analyser and (iii) the Kendrick mass defect data filtering applied to SALDI-MSI data. In particular, we show the complementarity in the lipids detected both in a given ionisation mode and in the two different ionisation modes.

Graphical abstract

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Ageta H, Asai S, Sugiura Y, Goto-Inoue N, Zaima N, Setou M. Layer-specific sulfatide localization in rat hippocampus middle molecular layer is revealed by nanoparticle-assisted laser desorption/ionization imaging mass spectrometry. Med Mol Morphol. 2009;42:16–23.

    CAS  PubMed  Google Scholar 

  2. 2.

    Dufresne M, Masson J-F, Chaurand P. Sodium-doped gold-assisted laser desorption ionization for enhanced imaging mass spectrometry of triacylglycerols from thin tissue sections. Anal Chem. 2016;88:6018–25.

    CAS  PubMed  Google Scholar 

  3. 3.

    Berry KAZ, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Murphy RC. MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev. 2011;111:6491–512.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Thomas A, Charbonneau JL, Fournaise E, Chaurand P. Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-diaminonapthalene deposition. Anal Chem. 2012;84:2048–54.

    CAS  PubMed  Google Scholar 

  5. 5.

    Huang P, Huang C-Y, Lin T-C, Lin L-E, Yang E, Lee C, et al. Toward the rational design of universal dual polarity matrix for MALDI mass spectrometry. Anal Chem. 2020;92(10):7139–45.

    CAS  PubMed  Google Scholar 

  6. 6.

    Jackson SN, Woods AS. Direct profiling of tissue lipids by MALDI-TOFMS. J Chromatogr B. 2009;877:2822–9.

    CAS  Google Scholar 

  7. 7.

    Li M, Yang L, Bai Y, Liu H. Analytical methods in lipidomics and their applications. Anal Chem. 2014;86:161–75.

    CAS  PubMed  Google Scholar 

  8. 8.

    Goto-Inoue N, Hayasaka T, Zaima N, Setou M. Imaging mass spectrometry for lipidomics. Biochim Biophys Acta. 1811;2011:961–9.

    Google Scholar 

  9. 9.

    Murphy RC, Hankin JA, Barkley RM. Imaging of lipid species by MALDI mass spectrometry. J Lipid Res. 2009;April Supplement:317–22.

    Google Scholar 

  10. 10.

    Gode D, Volmer DA. Lipid imaging by mass spectrometry - a review. Analyst. 2013;138:1289–315.

    CAS  PubMed  Google Scholar 

  11. 11.

    Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CRH, Shimizu T, et al. Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res. 2009;50(April Supplement):S9–14.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Ellis SR, Cappell J, Potocnil NO, Balluff B, Hamaide J, Van der Linden A, et al. More from less: high-throughput dual polarity lipid imaging of biological tissues. Analyst. 2016;141(12):3832–41.

    CAS  PubMed  Google Scholar 

  13. 13.

    Schuhmann K, Almeida R, Baumert M, Herzog R, Bornstein SR, Shevchenko A. Shotgun lipidomics on a LTQ Orbitrap mass spectrometer by successive switching between acquisition polarity modes. J Mass Spectrom. 2012;47:96–104.

    CAS  PubMed  Google Scholar 

  14. 14.

    Hsiao C, Hong C, Liu B, Chen CW, Wu C, Wang Y. Comprehensive molecular imaging of photolabile surface samples with synchronized dual-polarity time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 2011;25:834–42.

    CAS  PubMed  Google Scholar 

  15. 15.

    Feenstra AD, Hansen RL, Lee YJ. Multi-matrix, dual polarity, tandem mass spectrometry imaging strategy applied to a germinated maize seed: toward mass spectrometry imaging of an untargeted metabolome. Analyst. 2015;140(21):7293–304.

    CAS  PubMed  Google Scholar 

  16. 16.

    Guo S, Wang Y, Zhou D, Li Z. Significantly increased monounsaturated lipids relative to polyunsaturated lipids in six types of cancer microenvironment are observed by mass spectrometry imaging. Sci Rep. 2014;4(5959):1–9.

    Google Scholar 

  17. 17.

    Kaya I, Jennische E, Langer S, Malmberg P. Dual polarity MALDI imaging mass spectrometry on the same pixel points reveals spatial lipid localizations at high-spatial resolutions in rat small intestine. Anal Methods. 2018;10:2428–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Li B, Sun R, Gordon A, Ge J, Zhang Y, Li P, et al. 3-Aminophthalhydrazide (luminol) as a matrix for dual-polarity MALDI MS imaging. Anal Chem. 2019;91:8221–8.

    CAS  PubMed  Google Scholar 

  19. 19.

    Tsai S, Chen CW, Huang LCL, Huang M, Chen C, Wang Y. Simultaneous mass analysis of positive and negative ions using a dual-polarity time-of-flight mass spectrometer. Anal Chem. 2006;78:7729–34.

    CAS  PubMed  Google Scholar 

  20. 20.

    Schnapp A, Niehoff A, Koch A, Dreisewerd K. Laser desorption/ionization mass spectrometry of lipids using etched silver substrates. Methods. 2016;104:194–203.

    CAS  PubMed  Google Scholar 

  21. 21.

    Ellis SR, Brown SH, in het Panhuis M, Blanksby SJ, Mitchell TW. Surface analysis of lipids by mass spectrometry: more than just imaging. Prog Lipid Res. 2013;52:329–53.

    CAS  PubMed  Google Scholar 

  22. 22.

    Shanta SR, Zhou L-H, Park YS, Kim YH, Kim Y, Kim KP. Binary matrix for MALDI imaging mass spectrometry of phospholipids in both ion modes. Anal Chem. 2011;83:1252–9.

    CAS  PubMed  Google Scholar 

  23. 23.

    Jackson SN, Baldwin K, Muller L, Womack VM, Schultz JA, Balaban C, et al. Imaging of lipids in rat heart by MALDI-MS with silver nanoparticles. Anal Bioanal Chem. 2014;406:1377–86.

    CAS  PubMed  Google Scholar 

  24. 24.

    Muller L, Kailas A, Jackson SN, Roux A, Barbacci DC, Schultz JA, et al. Lipid imaging within the normal rat kidney using silver nanoparticles by matrix-assisted laser desorption/ionization mass spectrometry. Kidney Int. 2015;88(1):186–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Muller L, Baldwin K, Barbacci DC, Jackson SN, Roux A, Balaban CD, et al. Laser desorption/ionization mass spectrometric imaging of endogenous lipids from rat brain tissue implanted with silver nanoparticles. J Am Soc Mass Spectrom. 2017;28:1716–28.

    CAS  PubMed  Google Scholar 

  26. 26.

    Guan M, Zhang Z, Li S, Liu J, Liu L, Yang H, et al. Silver nanoparticles as matrix for MALDI FTICR MS profiling and imaging of diverse lipids in brain. Talanta. 2018;179:624–31.

    CAS  PubMed  Google Scholar 

  27. 27.

    Dufresne M, Thomas A, Breault-Turcot J, Masson J-F, Chaurand P. Silver-assisted laser desorption ionization for high spatial resolution imaging mass spectrometry of olefins from thin tissue sections. Anal Chem. 2013;85:3318–24.

    CAS  PubMed  Google Scholar 

  28. 28.

    Goto-Inoue N, Hayasaka T, Zaima N, Kashiwagi Y, Yamamoto M, Nakamoto M, et al. The detection of glycosphingolipids in brain tissue sections by imaging mass spectrometry using gold nanoparticles. J Am Soc Mass Spectrom. 2010;21:1940–3.

    CAS  PubMed  Google Scholar 

  29. 29.

    Phan NTN, Said Mohammadi A, Dowlatshahi Pour M, Ewing AG. Laser desorption ionization mass spectrometry imaging of Drosophila brain using matrix sublimation versus modification with nanoparticles. Anal Chem. 2016;88:1734–41.

    CAS  PubMed  Google Scholar 

  30. 30.

    Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Schultz JA, et al. MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom. 2007;42:1093–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Tempez A, Ugarov M, Egan T, Schultz JA, Novikov A, Della-Negra S, et al. Matrix implanted laser desorption ionization (MILDI) combined with ion mobility-mass spectrometry for bio-surface analysis research articles. J Proteome Res. 2005;4:540–5.

    CAS  PubMed  Google Scholar 

  32. 32.

    Vidova V, Novak P, Strohalm M, Po J, Havlicek V, Volny M. Laser desorption-ionization of lipid transfers: tissue mass spectrometry imaging without MALDI matrix. Anal Chem. 2010;82(12):4994–7.

    CAS  PubMed  Google Scholar 

  33. 33.

    Fincher JA, Dyer JE, Korte AR, Yadavilli S, Morris NJ, Vertes A. Matrix-free mass spectrometry imaging of mouse brain tissue sections on silicon nanopost arrays. J Comp Neurol. 2019;527(13):2101–21.

    CAS  PubMed  Google Scholar 

  34. 34.

    Fincher JA, Korte AR, Dyer JE, Yadavilli S, Morris NJ, Jones DR, et al. Mass spectrometry imaging of triglycerides in biological tissues by laser desorption ionization from silicon nanopost arrays. J Mass Spectrom. 2020;55(4):e4443.

    CAS  PubMed  Google Scholar 

  35. 35.

    Fincher JA, Jones DR, Korte AR, Dyer JE, Parlanti P, Popratiloff A, et al. Mass spectrometry imaging of lipids in human skin disease model hidradenitis suppurativa by laser desorption ionization from silicon nanopost arrays. Sci Rep. 2019;9(1):1–10.

    Google Scholar 

  36. 36.

    Hsu PY, Ge L, Li X, Stark AY, Wesdemiotis C, Niewiarowski PH, et al. Direct evidence of phospholipids in gecko footprints and spatula – substrate contact interface detected using surface-sensitive spectroscopy. J R Soc Interface. 2012;9:657–64.

    CAS  PubMed  Google Scholar 

  37. 37.

    Patti GJ, Shriver LP, Wassif CA, Woo H, Uritboonthai W, Apon J, et al. Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome. Neuroscience. 2010;170:858–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Tata A, Fernandes AMAP, Santos VG, Alberici RM, Araldi D, Parada CA, et al. Nanoassisted laser desorption-ionization-MS imaging of tumors. Anal Chem. 2012;84:6341–5.

    CAS  PubMed  Google Scholar 

  39. 39.

    Cha S, Yeung ES. Colloidal graphite-assisted laser desorption/ionization mass spectrometry and MSn of small molecules. 1. Imaging of cerebrosides directly from rat brain tissue. Anal Chem. 2007;79(6):2373–85.

    CAS  PubMed  Google Scholar 

  40. 40.

    Wu Q, Chu JL, Rubakhin SS, Gillette MU, Sweedler JV. Dopamine-modified TiO2 monolith-assisted LDI MS imaging for simultaneous localization of small metabolites and lipids in mouse brain tissue with enhanced detection selectivity and sensitivity. Chem Sci. 2017;8:3926–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Shrivas K, Hayasaka T, Sugiura Y, Setou M. Method for simultaneous imaging of endogenous low molecular weight metabolites in mouse brain using TiO2 nanoparticles in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry. Anal Chem. 2011;83:7283–9.

    CAS  PubMed  Google Scholar 

  42. 42.

    Hansen RL, Dueñas ME, Lee YJ. Sputter-coated metal screening for small molecule analysis and high-spatial resolution imaging in laser desorption ionization mass spectrometry. J Am Soc Mass Spectrom. 2019;30:299–308.

    CAS  PubMed  Google Scholar 

  43. 43.

    Kune C, McCann A, La Rocca R, Arguelles Arias A, Tiquet M, Van Kruining D, et al. Rapid visualization of chemically related compounds using Kendrick mass defect as a filter in mass spectrometry imaging. Anal Chem. 2019;91:13112–8.

    CAS  PubMed  Google Scholar 

  44. 44.

    Lerno LA, German JB, Lebrilla CB. Method for the identification of lipid classes based on referenced Kendrick mass analysis. Anal Chem. 2010;82:4236–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Tiquet M, La Rocca R, Van Kruining D, Martinez-Martinez P, Eppe G, De Pauw E, Quinton L, Far J. Mass spectrometry imaging using dynamically harmonized FT-ICR at million resolving power: rationalizing and optimizing sample preparation and instrumental parameters. ChemRxiv. 2020. https://doi.org/10.26434/chemrxiv.13013900.v1.

  46. 46.

    Peck B, Schulze A. Lipid desaturation – the next step in targeting lipogenesis in cancer ? FEBS J. 2016;283:2767–78.

    CAS  Google Scholar 

  47. 47.

    Spasov VA, Shi Y, Ervin KM. Time-resolved photodissociation and threshold collision- induced dissociation of anionic gold clusters. Chem Phys. 2000;262:75–91.

    CAS  Google Scholar 

  48. 48.

    Fincher JA, Korte AR, Yadavilli S, Morris NJ, Vertes A. Multimodal imaging of biological tissues using combined MALDI and NAPA-LDI mass spectrometry for enhanced molecular coverage. Analyst. 2020. https://doi.org/10.1039/D0AN00836B.

  49. 49.

    Li J, Condello S, Thomes-Pepin J, Hurley TD, Matei D, Cheng J-X. Lipid desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell. 2017;20:303–14.

    CAS  PubMed  Google Scholar 

  50. 50.

    Hagen RM, Rodriguez-Cuenca S, Vidal-Puig A. An allostatic control of membrane lipid composition by SREBP1. FEBS Lett. 2010;584:2689–98.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Dr. Virginie Bertrand for her technical support in the preparation of mouse brain sections and Mathieu Tiquet for the development of the MSI acquisition method.

Funding

Wendy H. Müller and Cedric Malherbe acknowledge support from the F.R.S.-FNRS (Fonds de la Recherche Scientifique - FNRS) as Research Fellow and Research Associate fellowship, respectively. The authors also acknowledge financial support from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 731077 (EU FT-ICR MS project, INFRAIA-02-2017) and from the European Union and Wallonia program FEDER BIOMED HUB Technology Support (No. 2.2.1/996) for the funding of the SolariX XR 9.4T. The authors also thank the European Union’s Horizon 2020 program (EURLipids Interreg Eurogio Meuse-Rhine project supported by the European Regional Development Fund (FEDER)) for the funding of the SunChrom sprayer.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gauthier Eppe.

Ethics declarations

Mice were previously euthanised by cervical dislocation with the approval of the Institutional Animal Ethics Committee of the University of Liege.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Published in the topical collection Mass Spectrometry Imaging 2.0 with guest editors Shane R. Ellis and Tiffany Porta Siegel.

Electronic supplementary material

ESM 1

(PDF 2.37 mb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Müller, W.H., Verdin, A., Kune, C. et al. Dual-polarity SALDI FT-ICR MS imaging and Kendrick mass defect data filtering for lipid analysis. Anal Bioanal Chem 413, 2821–2830 (2021). https://doi.org/10.1007/s00216-020-03020-w

Download citation

Keywords

  • SALDI
  • Mass spectrometry imaging
  • Nanoparticles
  • Dual-polarity
  • Lipidomics
  • Kendrick mass defect
  • FT-ICR