Advertisement

Metabolomics

, Volume 9, Supplement 1, pp 102–109 | Cite as

Imaging of metabolites using secondary ion mass spectrometry

  • Emily G. Armitage
  • Helen L. Kotze
  • Nicholas P. Lockyer
Original Article

Abstract

This article provides an overview of the technique of secondary ion mass spectrometry imaging and highlights some current and future areas of application relevant to the field of metabolomics. The approach benefits from label-free analysis of molecular species up to ~1500 Da with minimal sample preparation. Offering the highest spatial resolution of current mass spectrometry imaging methodologies, the technique is well-suited to metabolite imaging in both biological tissue and cells, in both 2D and 3D.

Keywords

Mass spectrometry imaging Secondary ion mass spectrometry SIMS Metabolic profiling Metabolites 

Notes

Acknowledgments

E.G.A and H.L.K are supported by studentships from the Biological Sciences Research and Engineering and Physical Sciences Research Councils under the Systems Biology Doctoral Training Centre, University of Manchester. Kaye Williams and John Vickerman are acknowledged for provision of samples and facilities access, and for stimulating discussions. John Fletcher and Alex Henderson are acknowledged for assistance with ToF–SIMS analysis and data processing respectively. ToF–SIMS instrumentation is funded through Engineering and Physical Sciences Research Council, EPSRC, UK under grants EP/C008251 and EP/G045623/1.

References

  1. Altelaar, A. F. M., Klinkert, I., Jalink, K., de Lange, R. P. J., Adan, R. A. H., Heeren, R. M. A., et al. (2006). Gold-enhanced biomolecular surface imaging of cells and tissue by SIMS and MALDI mass spectrometry. Analytical Chemistry, 78(3), 734–742. doi: 10.1021/ac0513111.PubMedCrossRefGoogle Scholar
  2. Altelaar, A. F. M., Luxembourg, S. L., McDonnell, L. A., Piersma, S. R., & Heeren, R. M. A. (2007). Imaging mass spectrometry at cellular length scales. Nature Protocols, 2(5), 1185–1196. doi: 10.1038/nprot.2007.117.PubMedCrossRefGoogle Scholar
  3. Amantonico, A., Urban, P. L., & Zenobi, R. (2010). Analytical techniques for single-cell metabolomics: state of the art and trends. Analytical and Bioanalytical Chemistry, 398(6), 2493–2504. doi: 10.1007/s00216-010-3850-1.PubMedCrossRefGoogle Scholar
  4. Armitage, E. G., Kotze, H. L., Fletcher, J. S., Henderson, A., Williams, K. J., Lockyer, N. P., et al. (2012). Time-of-flight SIMS as a novel approach to unlocking the hypoxic properties of cancer. Surface and Interface Analysis,. doi: 10.1002/sia.5050.Google Scholar
  5. Baker, M. J., Brown, M. D., Gazi, E., Clarke, N. W., Vickerman, J. C., & Lockyer, N. P. (2008). Discrimination of prostate cancer cells and non-malignant cells using secondary ion mass spectrometry. Analyst, 133(2), 175–179. doi: 10.1039/b712853c.PubMedCrossRefGoogle Scholar
  6. Benabdellah, F., Seyer, A., Quinton, L., Touboul, D., Brunelle, A., & Laprevote, O. (2010). Mass spectrometry imaging of rat brain sections: nanomolar sensitivity with MALDI versus nanometer resolution by TOF–SIMS. Analytical and Bioanalytical Chemistry, 396(1), 151–162. doi: 10.1007/s00216-009-3031-2.PubMedCrossRefGoogle Scholar
  7. Berman, E. S. F., Fortson, S. L., Checchi, K. D., Wu, L., Felton, J. S., Wu, K. J. J., et al. (2008). Preparation of single cells for imaging/profiling mass spectrometry. Journal of the American Society for Mass Spectrometry, 19(8), 1230–1236. doi: 10.1016/j.jasms.2008.05.006.PubMedCrossRefGoogle Scholar
  8. Boxer, S. G., Kraft, M. L., & Weber, P. K. (2009). Advances in imaging secondary ion mass spectrometry for biological samples. Annual Review of Biophysics, 38, 53–74.PubMedCrossRefGoogle Scholar
  9. Breitenstein, D., Rommel, C. E., Stolwijk, J., Wegener, J., & Hagenhoff, B. (2008). The chemical composition of animal cells reconstructed from 2D and 3D ToF–SIMS analysis. Applied Surface Science, 255(4), 1249–1256.CrossRefGoogle Scholar
  10. Carado, A., Passarelli, M. K., Kozole, J., Wingate, J. E., Winograd, N., & Loboda, A. V. (2008). C60 Secondary ion mass spectrometry with a hybrid-quadrupole orthogonal time-of-flight mass spectrometer. Analytical Chemistry, 80(21), 7921–7929. doi: 10.1021/ac801712s.PubMedCrossRefGoogle Scholar
  11. Chandra, S., & Morrison, G. H. (1992). Sample preparation of animal-tissues and cell-cultures for secondary ion mass-spectrometry (SIMS) microscopy. Biology of the Cell, 74(1), 31–42. doi: 10.1016/0248-4900(92)90006-m.PubMedCrossRefGoogle Scholar
  12. Chaurand, P., Cornett, D.S., Angel, P.M. & Caprioli, R.M. (2011). From Whole-body Sections Down to Cellular Level, Multiscale Imaging of Phospholipids by MALDI Mass Spectrometry. Molecular & Cellular Proteomics 10, doi: 10.1074/mcp.O110.004259.
  13. Chughtai, K., & Heeren, R. M. A. (2010). Mass spectrometric imaging for biomedical tissue analysis. Chemical Reviews, 110(5), 3237–3277. doi: 10.1021/cr100012c.PubMedCrossRefGoogle Scholar
  14. Cornett, D. S., Frappier, S. L., & Caprioli, R. M. (2008). MALDI–FTICR imaging mass spectrometry of drugs and metabolites in tissue. Analytical Chemistry, 80, 5648–5653.PubMedCrossRefGoogle Scholar
  15. Davies, N., Weibel, D. E., Blenkinsopp, P., Lockyer, N., Hill, R., & Vickerman, J. C. (2003). Development and experimental application of a gold liquid metal ion source. Applied Surface Science, 203–204, 223–227.CrossRefGoogle Scholar
  16. Drexler, D. M., Garrett, T. J., Cantone, J. L., Diters, R. W., Mitroka, J. G., Prieto Conaway, M. C., et al. (2007). Utility of imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) on an ion trap mass spectrometer in the analysis of drugs and metabolites in biological tissues. Journal of Pharmacological and Toxicological Methods, 55, 279–288.PubMedCrossRefGoogle Scholar
  17. Fletcher, J. S., Conlan, X. A., Lockyer, N. P., & Vickerman, J. C. (2006). Molecular depth profiling of organic and biological materials. Applied Surface Science, 252(19), 6513–6516. doi: 10.1016/j.apsusc.2006.02.213.CrossRefGoogle Scholar
  18. Fletcher, J. S., Kotze, H. L., Armitage, E. G., Lockyer, N. P., & Vickerman, J. C. (2012). Time-of-Fight Secondary Ion Mass Spectrometry for Metabolomics—Challenges for In Situ Metabolite Identification and Quantification. Journal of Metabolomics (submitted).Google Scholar
  19. Fletcher, J. S., Lockyer, N. P., Vaidyanathan, S., & Vickerman, J. C. (2007). TOF–SIMS 3D biomolecular imaging of Xenopus laevis oocytes using buckminsterfullerene (C60) primary ions. Analytical Chemistry, 79(6), 2199–2206. doi: 10.1021/ac061370u.PubMedCrossRefGoogle Scholar
  20. Fletcher, J. S., Lockyer, N. P., & Vickerman, J. C. (2010). Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions. Mass Spectrometry Reviews, 30(1), 142–174. doi: 10.1002/mas.20275.CrossRefGoogle Scholar
  21. Fletcher, J. S., Lockyer, N. P., & Vickerman, J. C. (2011a). Molecular SIMS imaging; spatial resolution and molecular sensitivity: have we reached the end of the road? Is there light at the end of the tunnel? Surface and Interface Analysis, 43(1–2), 253–256. doi: 10.1002/sia.3488.CrossRefGoogle Scholar
  22. Fletcher, J. S., Rabbani, S., Henderson, A., Blenkinsopp, P., Thompson, S. P., Lockyer, N. P., et al. (2008). A new dynamic in mass spectral imaging of single biological cells. Analytical Chemistry, 80(23), 9058–9064. doi: 10.1021/ac8015278.PubMedCrossRefGoogle Scholar
  23. Fletcher, J. S., Rabbani, S., Henderson, A., Lockyer, N. P., & Vickerman, J. C. (2011b). Three-dimensional mass spectral imaging of HeLa-M cells - sample preparation, data interpretation and visualisation. Rapid Communications in Mass Spectrometry, 25(7), 925–932. doi: 10.1002/rcm.4944.PubMedCrossRefGoogle Scholar
  24. Frisz, J. F., Choi, J. S., Wilson, R. L., Harley, B. A. C., & Kraft, M. L. (2012). Identifying differentiation stage of individual primary hematopoietic cells from mouse bone marrow by multivariate analysis of TOF–Secondary ion mass spectrometry data. Analytical Chemistry, 84(10), 4307–4313. doi: 10.1021/ac203329j.PubMedCrossRefGoogle Scholar
  25. Gazi, E., Lockyer, N. P., Vickerman, J. C., Gardner, P., Dwyer, J., Hart, C. A., et al. (2004). Imaging ToF–SIMS and synchrotron-based FT-IR microspectroscopic studies of prostate cancer cell lines. Applied Surface Science, 231–232, 452–456.CrossRefGoogle Scholar
  26. Guerquin-Kern, J. L., Wu, T. D., Quintana, C., & Croisy, A. (2005). Progress in analytical imaging of the cell by dynamic secondary ion mass spectrometry (SIMS microscopy). Biochimica Et Biophysica Acta-General Subjects, 1724(3), 228–238. doi: 10.1016/j.bbagen.2005.05.013.CrossRefGoogle Scholar
  27. Henderson, A., Fletcher, J. S., & Vickerman, J. C. (2009). A comparison of PCA and MAF for ToF–SIMS image interpretation. Surface and Interface Analysis, 41, 666–674.CrossRefGoogle Scholar
  28. Heeren, R. M. A., Kukrer-Kaletas, B., Taban, I. M., MacAleese, L., & McDonnell, L. A. (2008). Quality of surface: The influence of sample preparation on MS-based biomolecular tissue imaging with MALDI-MS and (ME-)SIMS. Applied Surface Science, 255(4), 1289–1297. doi: 10.1016/j.apsusc.2008.05.243.CrossRefGoogle Scholar
  29. Horai, H., Arita, M., Kanaya, S., Nihei, Y., Ikeda, T., Suwa, K., et al. (2010). MassBank: a public repository for sharing mass spectral data for life sciences. Journal of Mass Spectrometry, 45(7), 703–714. doi: 10.1002/jms.1777.PubMedCrossRefGoogle Scholar
  30. Johansson, B. (2006). ToF–SIMS imaging of lipids in cell membranes. Surface and Interface Analysis, 38(11), 1401–1412. doi: 10.1002/sia.2361.CrossRefGoogle Scholar
  31. Jones, E. A., Lockyer, N. P., & Vickerman, J. C. (2006). Suppression and enhancement of non-native molecules within biological systems. Applied Surface Science, 252(19), 6727–6730.CrossRefGoogle Scholar
  32. Jungnickel, H., Jones, E. A., Lockyer, N. P., Oliver, S. G., Stephens, G. M., & Vickerman, J. C. (2005). Application of TOF–IMS with chemometrics to discriminate between four different yeast strains from the species Candida glabrata and Saccharomyces cerevisiae. Analytical Chemistry, 77(6), 1740–1745. doi: 10.1021/ac048792t.PubMedCrossRefGoogle Scholar
  33. Kaleta, B. K., van der Wiel, I. M., Stauber, J., Güzel, C., Kros, J. M., Luider, T. M., et al. (2009). Sample preparation issues for tissue imaging by imaging MS. Proteomics, 9, 2622–2633.CrossRefGoogle Scholar
  34. Kotze, H. L., Armitage, E. G., Fletcher, J. S., Henderson, A., Williams, K. J., Lockyer, N. P., et al. (2012). ToF–SIMS as a tool for metabolic profiling small biomolecules in cancer systems. Surface and Interface Analysis,. doi: 10.1002/sia.5055.Google Scholar
  35. Kulp, K. S., Berman, E. S. F., Knize, M. G., Shattuck, D. L., Nelson, E. J., Wu, L., et al. (2006). Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry. Analytical Chemistry, 78(11), 3651–3658. doi: 10.1021/ac060054c.PubMedCrossRefGoogle Scholar
  36. Lanekoff, I., Kurczy, M. E., Hill, R., Fletcher, J. S., Vickerman, J. C., Winograd, N., et al. (2010). Time of flight mass spectrometry imaging of samples fractured in situ with a spring-loaded trap system. Analytical Chemistry, 82(15), 6652–6659. doi: 10.1021/ac101243b.PubMedCrossRefGoogle Scholar
  37. Lechene, C., Hillion, F., McMahon, G., Benson, D., Kleinfeld, A. M., Kampf, J. P., et al. (2006). High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry. Journal of biology, 5(6), 20. doi: 10.1186/jbiol42.PubMedCrossRefGoogle Scholar
  38. Lidstrom, M. E., & Konopka, M. C. (2010). The role of physiological heterogeneity in microbial population behavior. Nature Chemical Biology, 6(10), 705–712. doi: 10.1038/nchembio.436.PubMedCrossRefGoogle Scholar
  39. Lin, Y., Trouillon, R., Safina, G., & Ewing, A. G. (2011). Chemical analysis of single cells. Analytical Chemistry, 83(12), 4369–4392. doi: 10.1021/ac2009838.PubMedCrossRefGoogle Scholar
  40. Magnusson, Y., Friberg, P., Malmberg, P., & Chen, Y. (2008). Application of multivariate analysis of TOF–SIMS spectra for studying the effect of high glucose intake on aortic lipid profile. Applied Surface Science, 254(20), 6580–6585. doi: 10.1016/j.apsusc.2008.04.035.CrossRefGoogle Scholar
  41. Mahoney, C. M., Roberson, S. V., & Gillen, G. (2004). Depth profiling of 4-acetamindophenol-doped poly(lactic acid) films using cluster secondary ion mass spectrometry. Analytical Chemistry, 76(11), 3199–3207. doi: 10.1021/ac035532n.PubMedCrossRefGoogle Scholar
  42. Malmberg, P., Jennische, E., Nilsson, D., & Nygren, (2011) H. High-resolution, imaging TOF-SIMS: novel applications in medical research. Analytical and Bioanalytical Chemistry, 399(8), 2711–2718, doi: 10.1007/s00216-010-4155-0.
  43. Mas, S., Touboul, D., Brunelle, A., Aragoncillo, P., Egido, J., Laprevote, O., et al. (2007). Lipid cartography of atherosclerotic plaque by cluster-TOF-SIMS imaging. Analyst, 132(1), 24–26. doi: 10.1039/b614619h.PubMedCrossRefGoogle Scholar
  44. McQuaw, C. M., Sostarecz, A. G., Zheng, L., Ewing, A. G., & Winograd, N. (2006). Investigating lipid interactions and the process of raft formation in cellular membranes using ToF–SIMS. Applied Surface Science, 252(19), 6716–6718. doi: 10.1016/j.apsusc.2006.02.210.PubMedCrossRefGoogle Scholar
  45. Mei, Y., Saha, K., Bogatyrev, S. R., Yang, J., Hook, A. L., Kalcioglu, Z. I., et al. (2010). Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells. Nature Materials, 9(9), 768–778. doi: 10.1038/nmat2812.PubMedCrossRefGoogle Scholar
  46. Miura, D., Fujimura, Y., & Wariishi, H. (2012). In situ metabolomic mass spectrometry imaging: recent advances and difficulties. Journal of Proteomics,. doi: 10.1016/j.prot.2012.02.011.PubMedGoogle Scholar
  47. Monroe, E. B., Jurchen, J. C., Lee, J., Rubakhin, S. S., & Sweedler, J. V. (2005). Vitamin E imaging and localization in the neuronal membrane. Journal of the American Chemical Society, 127(35), 12152–12153. doi: 10.1021/ja051223y.PubMedCrossRefGoogle Scholar
  48. Mony, M.-C., & Larras-Regard, E. (1997). Imaging of subcellular structures by scanning ion microscopy and mass spectrometry. Advantage of cryofixation and freeze substitution procedure over chemical preparation. Biology of the Cell, 89, 199–210.PubMedGoogle Scholar
  49. Ostrowski, S. G., Kurczy, M. E., Roddy, T. P., Winograd, N., & Ewing, A. G. (2007). Secondary ion MS imaging to relatively quantify cholesterol in the membranes of individual cells from differentially treated populations. Analytical Chemistry, 79(10), 3554–3560. doi: 10.1021/ac061825f.PubMedCrossRefGoogle Scholar
  50. Ostrowski, S. G., Van Bell, C. T., Winograd, N., & Ewing, A. G. (2004). Mass spectrometric imaging of highly curved membranes during tetrahymena mating. Science, 305(5680), 71–73. doi: 10.1126/science.1099791.PubMedCrossRefGoogle Scholar
  51. Passarelli, M. K., & Winograd, N. (2011). Lipid imaging with time-of-flight secondary ion mass spectrometry (ToF-SIMS). Biochimica et Biophysica Acta (BBA)–Molecular and Cell Biology of Lipids, 1811(11), 976–990.CrossRefGoogle Scholar
  52. Piehowski, P. D., Davey, A. M., Kurczy, M. E., Sheets, E. D., Winograd, N., Ewing, A. G., et al. (2009). Time-of-flight secondary ion mass spectrometry imaging of subcellular lipid heterogeneity: poisson counting and spatial resolution. Analytical Chemistry, 81(14), 5593–5602. doi: 10.1021/ac901065s.PubMedCrossRefGoogle Scholar
  53. Piwowar, A. M., Lockyer, N. P., & Vickerman, J. C. (2009). Salt effects on ion formation in desorption mass spectrometry: an investigation into the role of alkali chlorides on peak suppression in time-of-flight-secondary ion mass spectrometry. Analytical Chemistry, 81(3), 1040–1048. doi: 10.1021/ac8020888.PubMedCrossRefGoogle Scholar
  54. Pol, J., Strohalm, M., Havlicek, V., & Volny, M. (2010). Molecular mass spectrometry imaging in biomedical and life science research. Histochemistry and Cell Biology, 134(5), 423–443. doi: 10.1007/s00418-010-0753-3.PubMedCrossRefGoogle Scholar
  55. Rabbani, S., Barber, A. M., Fletcher, J. S., Lockyer, N. P., & Vickerman, J. C. (2011). TOF–SIMS with Argon gas cluster ion beams: a comparison with C60 +. Analytical Chemistry, 83(10), 3793–3800. doi: 10.1021/ac200288v.PubMedCrossRefGoogle Scholar
  56. Rubakhin, S. S., Romanova, E. V., Nemes, P., & Sweedler, J. V. (2011). Profiling metabolites and peptides in single cells. Nature Methods, 8(4), S20–S29. doi: 10.1038/nmeth.1549.PubMedCrossRefGoogle Scholar
  57. Smith, D. F., Robinson, E. W., Tolmachev, A. V., Heeren, R. M. A., & Pasa-Tolic, L. (2011). C-60 Secondary ion fourier transform ion cyclotron resonance mass spectrometry. Analytical Chemistry, 83(24), 9552–9556. doi: 10.1021/ac2023348.PubMedCrossRefGoogle Scholar
  58. Sugiura, Y., & Setou, M. (2010). Imaging mass spectrometry for visualization of drug and endogenous metabolite distribution: toward in situ pharmacometabolomes. Journal of Neuroimmune Pharmacology, 5, 31–43. doi: 10.1007/s11481-009-9162-6.PubMedCrossRefGoogle Scholar
  59. Tahallah, N., Brunelle, A., De La Porte, S., & Laprevote, O. (2008). Lipid mapping in human dystrophic muscle by cluster-time-of-flight secondary ion mass spectrometry imaging. Journal of Lipid Research, 49(2), 438–454. doi: 10.1194/jlr.M700421-JLR200.PubMedCrossRefGoogle Scholar
  60. Touboul, D., Brunelle, A., & Laprevote, O. (2011). Mass spectrometry imaging: towards a lipid microscope? Biochimie, 93(1), 113–119. doi: 10.1016/j.biochi.2010.05.013.PubMedCrossRefGoogle Scholar
  61. Touboul, D., Kollmer, F., Niehuis, E., Brunelle, A., & Laprévote, O. (2005). Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source. Journal of the American Society for Mass Spectrometry, 16(10), 1608–1618. doi: 10.1016/j.jasms.2005.06.005.PubMedCrossRefGoogle Scholar
  62. Touboul, D., Roy, S., Germain, D. P., Chaminade, P., Brunelle, A., & Laprévote, O. (2007). MALDI–TOF and cluster–TOF–SIMS imaging of Fabry disease biomarkers. International Journal of Mass Spectrometry, 260(2–3), 158–165.CrossRefGoogle Scholar
  63. Tyler, B. J., Rayal, G., & Castner, D. G. (2007). Multivariate analysis strategies for processing ToF–SIMS images of biomaterials. Biomaterials, 28, 2412–2423.PubMedCrossRefGoogle Scholar
  64. Vickerman, J. C. (2011). Molecular imaging and depth profiling by mass spectrometry–SIMS, MALDI or DESI? Analyst, 136, 2199–2217.PubMedCrossRefGoogle Scholar
  65. Wong, S. C. C., Hill, R., Blenkinsopp, P., Lockyer, N. P., Weibel, D. E., & Vickerman, J. C. (2003). Development of a C60 + ion gun for static SIMS and chemical imaging. Applied Surface Science, 203–204, 219–222.CrossRefGoogle Scholar
  66. Wu, K. J., & Odom, R. W. (1996). Matrix-enhanced secondary ion mass spectrometry: a method for molecular analysis of solid surfaces. Analytical Chemistry, 68(5), 873–882. doi: 10.1021/ac950717i.PubMedCrossRefGoogle Scholar
  67. Yamada, H., Ichiki, K., Nakata, Y., Ninomiya, S., Seki, T., Aoki, T., et al. (2010). MeV-energy probe SIMS imaging of major components in animal cells etched using large gas cluster ions. Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms, 268(11–12), 1736–1740. doi: 10.1016/j.nimb.2010.02.038.CrossRefGoogle Scholar
  68. Yang, H.-J., Ishizaki, I., Sanada, N., Zaima, N., Sugiura, Y., Yao, I., et al. (2010). Detection of characteristic distributions of phospholipid head groups and fatty acids on neurite surface by time-of-flight secondary ion mass spectrometry. Medical Molecular Morphology, 43(3), 158–164. doi: 10.1007/s00795-009-0487-2.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Emily G. Armitage
    • 1
  • Helen L. Kotze
    • 1
  • Nicholas P. Lockyer
    • 2
  1. 1.Doctoral Training Centre for Integrative Systems Biology, School of Chemical Engineering and Analytical Science, Manchester Institute of BiotechnologyThe University of ManchesterManchesterUK
  2. 2.School of Chemistry, Manchester Institute of BiotechnologyThe University of ManchesterManchesterUK

Personalised recommendations