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Biological tissue imaging by secondary ion mass spectrometry has seen rapiddevelopment with the commercial availability of polyatomic primary ion sources.Endogenous lipids and other small bio-molecules can now be routinely mapped onthe sub-micrometer scale. Such experiments are typically performed ontime-of-flight mass spectrometers for high sensitivity and high repetition rateimaging. However, such mass analyzers lack the mass resolving power to ensureseparation of isobaric ions and the mass accuracy for elemental formulaassignment based on exact mass measurement. We have recently reported asecondary ion mass spectrometer with the combination of a C60 primary ion gunwith a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS)for high mass resolving power, high mass measurement accuracy and tandem massspectrometry capabilities. In this work, high specificity and high sensitivitysecondary ion FT-ICR MS was applied to chemical imaging of biological tissue.An entire rat brain tissue was measured with 150 um spatial resolution (75 umprimary ion spot size) with mass resolving power (m/{\Delta}m50%) of 67,500 (atm/z 750) and root-mean-square measurement accuracy less than twoparts-per-million for intact phospholipids, small molecules and fragments. Forthe first time, ultra-high mass resolving power SIMS has been demonstrated,with m/{\Delta}m50% > 3,000,000. Higher spatial resolution capabilities of theplatform were tested at a spatial resolution of 20 um. The results representorder of magnitude improvements in mass resolving power and mass measurementaccuracy for SIMS imaging and the promise of the platform for ultra-high massresolving power and high spatial resolution imaging.

High Mass Accuracy and High Mass Resolving Power FT-ICR Secondary Ion Mass Spectrometry for Biological Tissue Imaging