Continuous mass photometry by single molecule trapping

Dan Loewenthal; Roi Asor; Stephen Austen Thorpe; Jack S. Peters; Konstantin Zouboulis; Merve Kaplan; Jan Christoph Thiele; Jack Bardzil; Seham Helmi; Sean Anthony Burnap; Tiong Kit Tan; Weston B. Struwe; Justin L. P. Benesch; Philipp Kukura

doi:10.1038/s41592-026-03252-1

BiophysicsNature MethodsOct 26, 2026

Peer-reviewed journal article

Continuous mass photometry by single molecule trapping

Dan Loewenthal iD, Roi Asor iD, Stephen Austen Thorpe iD, Jack S. Peters iD, Konstantin Zouboulis iD, Merve Kaplan iD, Jan Christoph Thiele iD, Jack Bardzil iD, Seham Helmi iD, Sean Anthony Burnap iD, Tiong Kit Tan iD, Weston B. Struwe iD, Justin L. P. Benesch iD, Philipp Kukura iD

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Abstract

The dynamic choreography of biomolecular interactions underpins the processes of life, but its direct observation remains challenging. Here, we introduce confined diffusion mass photometry, enabling hour-long, mass-resolved observation of individual biomolecules, their complexes and interactions with up to sub-kDa mass precision and ms temporal resolution. Our approach represents a quantitative time-resolved single-molecule measurement modality for studying complex biomolecular mechanisms in action.