Ambient mass spectrometry for in vivo local analysis and in situ molecular tissue imaging

Recent technical innovations in mass spectrometry (MS) have extended the application of this powerful technique to direct chemical analysis at atmospheric pressure. These innovations have created an opportunity to appreciate the chemistry of biological systems in their native state, so tissues and single cells of plant, animal, or human origin can be interrogated in situ and in vivo.Ambient MS also allows label-free detection of compounds and gives unique insights into temporal changes and tissue architecture in two and three dimensions. Compounds studied range from natural products (e.g., neurotransmitters, metabolites, organic acids, polyamines, sugars, lipids, and peptides) to xenobiotics (e.g., pharmaceuticals), dyes, polymers, explosives, and toxins.This critical review covers analytical trends in ambient MS. Our discussions primarily touch on the mechanisms of sampling and the bioanalytical implications for in situ and in vivo experiments. We pay special attention to lateral imaging, depth profiling, and three-dimensional-MS imaging, all while working under atmospheric conditions. Our closing remarks highlight some of the present analytical challenges and developmental opportunities in this field.

► Ambient MS emerges to explore biological systems under native conditions to specimens.
► We use the ambient MS framework to gauge trends in in vivo and in situ applications.
► We probe the organism–organ-tissue–cell–organelle realm on a biochemical level.
► We unveil specimen chemistry in time, and in two and three spatial dimensions.
► We identify analytical challenges and developmental opportunities for biochemistry.