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Continuous mass photometry by single molecule trapping

Loewenthal, D.; Asor, R.; Thorpe, S.; Peters, J. S.; Zouboulis, K. C.; Kaplan, M.; Thiele, J. C.; Bardzil, J.; Helmi, S.; Burnap, S. A.; Tan, T. K.; Struwe, W. B.; Benesch, J. L.; Kukura, P.

2026-02-03 biophysics
10.64898/2026.02.02.703204 bioRxiv
Show 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.

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