Novel vacuum stable ketone‐based matrices for high spatial resolution MALDI imaging mass spectrometry

We describe the use of aromatic ketones and cinnamyl ketones that have high vacuum stability for analyzing tissue sections using matrix‐assisted laser desorption/ionization imaging mass spectrometry. Specifically, the matrix, (E)‐4‐(2,5‐dihydroxyphenyl)but‐3‐en‐2‐one (2,5‐cDHA) provides high sensitivity and high vacuum stability while producing small size crystals (1‐2 μm). A high throughput and highly reproducible sample preparation method was developed for these matrices that first involves using an organic spray solution for small matrix crystal seeding followed by spraying of the matrix in a 30% acetonitrile/70% water solution on the tissue surface to obtain a homogeneous coating of small crystals, suitable for high spatial resolution imaging.