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.

doi:10.64898/2026.02.02.703204

bioRxiv · 10.64898/2026.02.02.703204

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.

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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.

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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. Continuous mass photometry by single molecule trapping. https://doi.org/10.64898/2026.02.02.703204

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