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

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

Weighing synthetic polymers of ultra‐high molar mass and polymeric nanomaterials: What can we learn from charge detection mass spectrometry?

“…94 Recently, Masselon, Hentz, and coworkers combined nano-ESI with an aerodynamic lens to ionize and efficiently focus a particle beam which hits a detector composed of an array of 20 nanomechanical resonators etched into a silicon chip. 95,96 thank Laurence Charles for her constant support, encouragement and fruitful discussions and valuable feedback.…”

A century of research on bacteriophages

“…Les très petits phages à ARNsb de la famille des Leviviridae comme MS2 and Q␤, utilisent une protéine de maturation de la capside qui se fixe au pilus et induit le transfert de l'ARN dans le cytoplasme [64]. Les études structurales des bactériophages nous éclairent sur les propriétés fascinantes de ces « nanomachines » dont le programme d'assemblage, codé par un nombre de gènes restreint, contrôle avec une très grande fidélité la construction de particules formées de plusieurs centaines de protéines et dont la masse moléculaire peut dépasser 100 MDa [67]. L'intérêt de comprendre ces mécanismes est multiple, en particulier en biotechnologie.…”

Optomechanical mass spectrometry

“…Eventually, the realization that nanomechanical resonators were ideally suited for analysis of masses in the MDa to GDa range opened the way for MS of species irrespective of charge 8 . Arrays of nanoresonators were demonstrated to circumvent the cross-section issue 9 , 10 and 100 MDa bacteriophage virus capsids were recently analyzed with a neutral nanomechanical MS system displaying high efficiency and resolution without the requirement for ionization 11 .…”

“…In some cases, particle stiffness 12 , size, and shape 13 have to be accounted for. This has deleterious consequences: complex readout schemes must be used for simultaneous monitoring of multiple vibration modes; mass resolution dependence on landing position leads to a degradation of the average resolution by close to an order of magnitude compared with the optimum 11 , forcing a drastic compromise on capture area. Most importantly, the use of such one-dimensional resonators impedes the analysis of many crucial particles of biomedical interest having large aspect ratio, such as tailed viruses or fibrils, in particular when their length is similar to or exceeds the resonator's width.…”