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Most technologies, including conventional mass spectrometry, struggle tomeasure the mass of particles in the MDa to GDa range. Although this mass rangeappears optimal for nanomechanical resonators, early nanomechanical-MS systemssuffered from prohibitive sample loss, extended analysis time or inadequateresolution. Here, we report on a novel system architecture combiningnebulization of the analytes from solution, their efficient transfer andfocusing without relying on electromagnetic fields, and the mass measurementsof individual particles using nanomechanical resonator arrays. This systemdetermined the mass distribution of ~30 MDa polystyrene nanoparticles with adetection efficiency 6 orders of magnitude higher than previousnanomechanical-MS systems with ion guides, and successfully performed thehighest molecular mass measurement to date with less than 1 picomole ofbacteriophage T5 105 MDa viral capsids.

Charge-independent mass spectrometry of single virus capsids above 100MDa with nanomechanical resonators