Continuous mass photometry by single-molecule trapping

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