Biological mass spectrometry enables spatiotemporal 'omics: From tissues to cells to organelles

Biological processes unfold across broad spatial and temporal dimensions, and measurement of the underlying molecular world is essential to their understanding. Interdisciplinary efforts advanced mass spectrometry (MS) into a tour de force for assessing virtually all levels of the molecular architecture, some in exquisite detection sensitivity and scalability in space-time. In this review, we offer vignettes of milestones in technology innovations that ushered sample collection and processing, chemical separation, ionization, and 'omics analyses to progressively finer resolutions in the realms of tissue biopsies and limited cell populations, single cells, and subcellular organelles. Also highlighted are methodologies that empowered the acquisition and analysis of multidimensional MS data sets to reveal proteomes, peptidomes, and metabolomes in ever-deepening coverage in these limited and dynamic specimens. In pursuit of richer knowledge of biological processes, we discuss efforts pioneering the integration of orthogonal approaches from molecular and functional studies, both within and beyond MS. With established and emerging community-wide efforts ensuring scientific rigor and reproducibility, spatiotemporal MS emerged as an exciting and powerful resource to study biological systems in space-time.

Automated summary

Biological processes unfold across broad spatial and temporal dimensions, and measurement of the underlying molecular world is essential to their understanding. Mass spectrometry (MS) has advanced significantly, allowing for precise analysis of molecular architecture at various levels, with high detection sensitivity and scalability. This review highlights technology innovations that have improved sample collection and processing, chemical separation, ionization, and 'omics analyses, enabling deeper study of limited and dynamic specimens. The integration of orthogonal approaches from molecular and functional studies, combined with spatiotemporal MS, has become an exciting and powerful resource in the study of biological systems.