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High mass accuracy and high mass resolving power FT-ICR secondary ion mass spectrometry for biological tissue imaging

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Abstract

Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the sub-micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for elemental formula assignment based on exact mass measurement. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy, and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 μm spatial resolution (75 μm primary ion spot size) with mass resolving power (m/Δm 50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/Δm 50% > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 μm. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.

C60 secondary ion FT-ICR MS provides unprecedented mass resolving power and mass accuracy for SIMS imaging of biological tissue sections. Overlaid selected ion images from rat brain (left) and high spatial resolution imaging of organic dye underneath a TEM grid (right).

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Acknowledgments

This work is part of the research program of the Foundation for Fundamental Research on Matter (FOM), which is part of The Netherlands Organization for Scientific Research (NWO). This publication was supported by the Dutch national program COMMIT. Portions of this research were supported by the American Reinvestment and Recovery Act of 2009 and the U.S. Department of Energy (DOE) Office of Biological and Environmental Research. The research described in this article was performed at the W. R. Wiley Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the U.S. Department of Energy under Contract DE-AC05-76RLO 1830. D.F.S. would like to acknowledge the Alternate Sponsored Fellowship program at PNNL and R.M.A.H. the EMSL Wiley Visiting Scientist Fellowship program for support of portions of this work. We thank Jordan Smith and Chuck Timchalk (PNNL) for supplying the rat brain section and Julia Jungmann (AMOLF) for preparing the TEM grid sample.

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Authors and Affiliations

  1. FOM Institute AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands

    Donald F. Smith, Andras Kiss & Ron M. A. Heeren

  2. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99352, USA

    Franklin E. Leach III, Errol W. Robinson & Ljiljana Paša-Tolić

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  1. Donald F. Smith
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  2. Andras Kiss
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  3. Franklin E. Leach III
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  6. Ron M. A. Heeren
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Correspondence to Ron M. A. Heeren.

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Smith, D.F., Kiss, A., Leach, F.E. et al. High mass accuracy and high mass resolving power FT-ICR secondary ion mass spectrometry for biological tissue imaging. Anal Bioanal Chem 405, 6069–6076 (2013). https://doi.org/10.1007/s00216-013-7048-1

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