Abstract
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is potentially well placed to contribute to metabolomic analysis while bringing the added benefit of high resolution, label free imaging. The focused ion beams used to desorb species from the sample can be focused below 1 μm allowing chemical imaging on a sub-cellular scale. In this study we test the capability of ToF-SIMS to generate mass spectrometry and MSMS spectra from a set of standard metabolites that can be compared with open access metabolite databases containing ESI-CID MSMS spectra. The influence of the chemical environment, the matrix effect, on the observed mass spectra is assessed using a mixed metabolite sample and the data discussed in terms of compound identification and quantification. Radical ions and small fragment ions seem to be less sensitive to ion suppression or enhancement and may provide a route to quantification. Understanding such parameters will be key for the successful application of the technique for in situ metabolomics with ToF-SIMS.
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References
Armitage, E. G., 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.
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, 1249–1256. doi:10.1002/anie.200604468.
Brison, J., Benoit, D. S. W., Muramoto, S., Robinson, M., Stayton, P. S., & Castner, D. G. (2011). ToF-SIMS imaging and depth profiling of HeLa cells treated with bromodeoxyuridine. Surface and Interface Analysis, 43, 354–357. doi:10.1002/sia.3415.
Brunelle, A., Touboul, D., & Laprévote, O. (2005). Biological tissue imaging with time-of-flight secondary ion mass spectrometry and cluster ion sources. Journal of Mass Spectrometry, 40, 985–999. doi:10.1002/jms.902.
Cappiello, A., Famiglini, G., Palma, P., Pierini, E., Termopoli, V., & Trufelli, H. (2010). Direct-EI in LC–MS: Towards a universal detector for small-molecule applications. Mass Spectrometry Reviews, 30, 1242–1255. doi:10.1002/mas.20329.
Caprioli, R. M., Farmer, T. B., & Gile, J. (1997). Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS. Analytical Chemistry, 69, 4751–4760. doi:10.1021/ac970888i.
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, 7921–7929. doi:10.1021/ac801712s.
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. doi:10.1016/S0169-4332(02)00631-1.
Fiehn, O., et al. (2007). The metabolomics standards initiative (MSI). Metabolomics, 3, 175–178. doi:10.1007/s11306-007-0070-6.
Fletcher, J. S. (2009). Cellular imaging with secondary ion mass spectrometry. Analyst, 134, 2204–2215. doi:10.1039/b913575h.
Fletcher, J. S., Henderson, A., Biddulph, G. X., Vaidyanathan, S., Lockyer, N. P., & Vickerman, J. C. (2008a). Uncovering new challenges in bio-analysis with ToF-SIMS. Applied Surface Science, 255, 1264–1270. doi:10.1016/j.apsusc.2008.05.253.
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, 2199–2206. doi:10.1021/ac061370u.
Fletcher, J. S., Lockyer, N. P., & Vickerman, J. C. (2011). Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions. Mass Spectrometry Reviews, 30, 142–174. doi:10.1002/mas.20275.
Fletcher, J. S., et al. (2008b). A new dynamic in mass spectral imaging of single biological cells. Analytical Chemistry, 80, 9058–9064. doi:10.1021/ac8015278.
Garrison, B. J., & Postawa, Z. (2008). Computational view of surface based organic mass spectrometry. Mass Spectrometry Reviews, 27, 289–315. doi:10.1002/mas.20165.
Goodacre, R., Vaidyanathan, S., Dunn, W. B., Harrigan, G. G., & Kell, D. B. (2004). Metabolomics by numbers: Acquiring and understanding global metabolite data. Trends in Biotechnology, 22, 245–252. doi:10.1016/j.tibtech.2004.03.007.
Heinemann, M., & Zenobi, R. (2011). Single cell metabolomics. Current Opinion in Biotechnology, 22, 26–31. doi:10.1016/j.copbio.2010.09.008.
Horai, H., et al. (2010). MassBank: A public repository for sharing mass spectral data for life sciences. Journal of Mass Spectrometry, 45, 703–714. doi:10.1002/jms.1777.
Jones, E. A., Lockyer, N. P., & Vickerman, J. C. (2006). Suppression and enhancement of non-native molecules within biological systems. Applied Surface Science, 252, 6727–6730. doi:10.1016/j.apsusc.2006.02.158.
Knochenmuss, R., & Zenobi, R. (2003). MALDI ionization: The role of in-plume processes. Chemical Reviews, 103, 441–452. doi:10.1021/cr0103773.
Kollmer, F. (2004). Cluster primary ion bombardment of organic materials. Applied Surface Science, 231, 153–158. doi:10.1016/j.apsusc.2004.03.101.
Kopka, J., et al. (2005). GMD@CSB.DB: The Golm Metabolome Database. Bioinformatics, 21, 1635–1638. doi:10.1093/bioinformatics/bti236.
Kotze, H. L., 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.
Leggett, G. J., & Vickerman, J. C. (1992). An empirical-model for ion formation from polymer surfaces during analysis by secondary ion mass-spectrometry. International Journal of Mass Spectrometry and Ion Processes, 122, 281–319. doi:10.1016/0168-1176(92)87021-6.
MacAleese, L., Stauber, J., & Heeren, R. M. A. (2009). Perspectives for imaging mass spectrometry in the proteomics landscape. Proteomics, 9, 819–834. doi:10.1002/pmic.200800363.
McDonnell, L. A., Heeren, R. M. A., de Lange, R. P. J., & Fletcher, I. W. (2006). Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging. Journal of the American Society for Mass Spectrometry, 17, 1195–1202. doi:10.1016/j.jasms.2006.05.003.
Mouhib, T., Delcorte, A., Poleunis, C., & Bertrand, P. (2010). Organic secondary ion mass spectrometry: Signal enhancement by water vapor injection. Journal of the American Society for Mass Spectrometry, 21, 2005–2010. doi:10.1016/j.jasms.2010.08.013.
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, 976–990.
Piwowar, A. M., Fletcher, J. S., Kordys, J., Lockyer, N. P., Winograd, N., & Vickerman, J. C. (2010). Effects of cryogenic sample analysis on molecular depth profiles with TOF-secondary ion mass spectrometry. Analytical Chemistry, 82, 8291–8299. doi:10.1021/ac101746h.
Rubakhin, S. S., Romanova, E. V., Nemes, P., & Sweedler, J. V. (2011). Profiling metabolites and peptides in single cells. Nature Methods, 8, S20–S29. doi:10.1038/nmeth.1549.
Sabatine, M. S., et al. (2005). Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation, 112, 3868–3875. doi:10.1161/circulationaha.105.569137.
Sjovall, P., Lausmaa, J., & Johansson, B. R. (2004). Mass spectrometric imaging of lipids in brain tissue. Analytical Chemistry, 76, 4271–4278. doi:10.1021/ac049389p.
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, 9552–9556. doi:10.1021/ac2023348.
Smith, C. A., et al. (2005). METLIN—A metabolite mass spectral database. Therapeutic Drug Monitoring, 27, 747–751. doi:10.1097/01.ftd.0000179845.53213.39.
Sreekumar, A., et al. (2009). Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature, 457, 910–914. doi:10.1038/nature07762.
Takáts, Z., Wiseman, J. M., Gologan, B., & Cooks, R. G. (2004). Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science, 306, 471–473. doi:10.1126/science.1104404.
Vaidyanathan, S., Fletcher, J. S., Goodacre, R., Lockyer, N. P., Micklefield, J., & Vickerman, J. C. (2008). Subsurface biomolecular imaging of Streptomyces coelicolor using secondary ion mass spectrometry. Analytical Chemistry, 80, 1942–1951. doi:10.1021/ac701921e.
Vickerman, J. C. (2011). Molecular imaging and depth profiling by mass spectrometry-SIMS, MALDI or DESI? Analyst, 136, 2199–2217. doi:10.1039/C1AN00008J.
Vickerman, J. C., Briggs, D., & Henderson, A. (2006). The static SIMS library version 4. Manchester: Surfacespectra Ltd.
Weibel, D., Wong, S., Lockyer, N., Blenkinsopp, P., Hill, R., & Vickerman, J. C. (2003). A C60 primary ion beam system for time of flight secondary ion mass spectrometry: Its development and secondary ion yield characteristics. Analytical Chemistry, 75, 1754–1764. doi:10.1021/ac026338o.
Wishart, D. S., et al. (2007). HMDB: The human metabolome database. Nucleic Acids Research, 35, D521–D526. doi:10.1093/nar/gkl923.
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The authors gratefully acknowledge the financial support of the Engineering and Physical Sciences Research Council, EPSRC, UK under grants EP/C008251 and EP/G045623/1.
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John S. Fletcher, Helen L. Kotze, and Emily G. Armitage contributed equally to this work.
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Fletcher, J.S., Kotze, H.L., Armitage, E.G. et al. Evaluating the challenges associated with time-of-fight secondary ion mass spectrometry for metabolomics using pure and mixed metabolites. Metabolomics 9, 535–544 (2013). https://doi.org/10.1007/s11306-012-0487-4
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DOI: https://doi.org/10.1007/s11306-012-0487-4