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Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators

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Science  23 Nov 2018:
Vol. 362, Issue 6417, pp. 918-922
DOI: 10.1126/science.aat6457

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Bridging the mass gap

Viruses and many large biomolecule complexes are in a mass range that is challenging to measure with conventional mass spectrometry methods. Nanomechanical resonators can determine masses of impacting molecules, but separation methods often lose too much of the sample to be efficient. Dominguez-Medina et al. used an aerodynamic lens that improved separation and focusing of nebulized molecules with increasing mass. The mass of both filled and empty viral capsids was determined with an array of 20 nanoresonators.

Science, this issue p. 918

Abstract

Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a 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-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100.

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