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

TL;DR

This paper introduces a novel nanomechanical resonator-based mass spectrometry system capable of accurately measuring the mass of individual virus capsids above 100 MDa with high efficiency and resolution, overcoming limitations of previous methods.

Contribution

The authors develop a new system architecture that combines solution nebulization, efficient analyte transfer, and nanomechanical resonator arrays for high-mass particle analysis, achieving unprecedented detection efficiency and mass measurement of large viral particles.

Findings

Measured ~30 MDa polystyrene nanoparticles with 10^6 times higher efficiency.

Performed the highest molecular mass measurement to date at 105 MDa for bacteriophage T5 capsids.

Achieved detection with less than 1 picomole of sample.

Abstract

Most technologies, including conventional mass spectrometry, struggle to measure the mass of particles in the MDa to GDa range. Although this mass range appears optimal for nanomechanical resonators, early nanomechanical-MS systems suffered from prohibitive sample loss, extended analysis time or inadequate resolution. Here, we report on a novel system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of ~30 MDa polystyrene nanoparticles with a detection efficiency 6 orders of magnitude higher than previous nanomechanical-MS systems with ion guides, and successfully performed the highest molecular mass measurement to date with less than 1 picomole of bacteriophage T5 105 MDa viral capsids.