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

Lipids are essential macromoleculesthat play a crucialrole innumerous biological events. Lipids are structurally diverse whichallows them to fulfill multiple functional roles. Matrix-assistedlaser desorption/ionization mass spectrometry imaging (MALDI-MSI)is a powerful tool to understand the spatial localization of lipidswithin biological systems. Herein, we report the use of ammonium fluoride(NH4F) as a comatrix additive to enhance lipid detectionin biological samples, with a signal increase of up to 200%. Emphasiswas placed on anionic lipid enhancement with negative polarity measurements,with some preliminary work on cationic lipids detailed. We observedlipid signal enhancement of [M-H](-) ions withthe addition of NH4F additive attributed to a proton transferreaction in several different lipid classes. Overall, our study demonstratesthat the use of the NH4F comatrix additive substantiallyimproves sensitivity for lipid detection in a MALDI system and iscapable of being applied to a variety of different applications.

Automated summary

Lipids are essential macromolecules that play crucial roles in numerous biological events. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful tool for understanding the spatial localization of lipids in biological systems. In this study, the use of ammonium fluoride (NH4F) as a comatrix additive was found to enhance lipid detection in biological samples, with a signal increase of up to 200%. The addition of NH4F was observed to enhance the lipid signal of [M-H](-) ions, attributed to a proton transfer reaction in various lipid classes. Overall, the study shows that the NH4F comatrix additive significantly improves sensitivity for lipid detection in a MALDI system and can be applied to various applications.