Transforming spatial and structural biology: Native ambient mass spectrometry

A new mass spectrometry technique lets scientists identify and map individual proteins directly from human tissue, without needing to label them first. Current methods for studying proteins in tissue—like immunohistochemistry—require researchers to know in advance which proteins they are looking for, and they cannot easily show how those proteins are folded or interacting with other molecules. This technique, called native ambient mass spectrometry (NAMS), captures proteins in their natural, folded state and records their spatial location simultaneously. It can detect protein-drug complexes and protein assemblies that other methods miss entirely. If NAMS becomes the gold standard, it could transform two areas. In molecular pathology, it would allow pathologists to see not just which proteins are present in a diseased tissue sample, but how they are behaving—whether they are misfolded, aggregated, or bound to a drug. In drug discovery, it could reveal where a candidate drug actually lands in tissue and which proteins it touches, without needing fluorescent tags or prior assumptions. The research is engineering-focused: it aims to boost the technique’s sensitivity and protein-identification confidence to make it reliable enough for routine clinical and pharmaceutical use.