Enhancement of Lipid Signals in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry with Ammonium Fluoride as a Matrix Additive

Lipids are essential macromolecules that play a crucial role in numerous biological events. Lipids are structurally diverse which allows them to fulfill multiple functional roles. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful tool to understand the spatial localization of lipids within biological systems. Herein, we report the use of ammonium fluoride (NH4F) as a comatrix additive to enhance lipid detection in biological samples, with signal increase up to 200%. Emphasis was placed on anionic lipid enhancement with negative polarity measurements, with some preliminary work on cationic lipids detailed. We observed lipid signal enhancement of [M-H]- ions with the addition of 500 uM NH4F additive attributed to a proton transfer reaction in several different lipid classes. Overall, our study demon-strates that the use of NH4F comatrix additive substantially improves sensitivity for lipid detection in a MALDI system.