Higher Sensitivity Secondary Ion Mass Spectrometry of Biological Molecules for High Resolution, Chemically Specific Imaging

To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided ≈15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield ≈3.8 and ≈8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.