Acoustic droplet generation and opto-mechanical nano-resonators mass spectrometry for fast analysis of viral particles. – AERONEMS

Viruses are biological entities that infect all life forms. They occur in a broad variety of samples, and their small size (<400 nm) makes them particularly elusive. Assessing the presence of viruses in the environment or in biological specimen is a key requirement to identify viral threats, improve our understanding of transmission routes, and make better-informed decisions on protective measures. Virus confirmation commonly relies on genome sequencing or immuno-assays to detect specific nucleic acids sequences or viral proteins. These methods are very sensitive yet time-consuming, and unable to discriminate between infectious viral particles and harmless virus fragments.
Viral particles result from tightly regulated auto-assembly processes yielding structures of definite molecular composition. Therefore, their molecular mass constitutes a specific attribute. Yet, characterizing the mass of supramolecular assemblies like viruses, composed of several millions of atoms, is an intractable challenge for conventional mass spectrometry (MS). IRIG and LETI at CEA Grenoble (France) recently established the proof of concept of a unique mass spectrometer based on nano-electro-mechanical resonators, and operating in a mass range beyond the reach of conventional MS systems. Using this system, we demonstrated the detection of viral capsids with a mass in excess of 100 MDa [Dominguez-Medina et al. Science, 2018]. Although this technology holds great promises for the detection and characterization of viruses, limitations in terms of sensitivity and analytical throughput do not currently allow virus detection in biologically relevant samples (<10e7 particle/ml) within a reasonable timeframe (minutes).
In AERONEMS, we propose to address issues limiting the efficiency of nanoresonator-MS technology to achieve 300 times faster and more sensitive viral particles characterization. For this purpose, we will investigate surface acoustic wave approaches to generate a controlled viral aerosol in order to boost particle sampling efficiency by a factor of 20. In addition, a breakthrough sensing technology will be established, with the inception of 100-plexed optomechanical resonators arrays for simultaneous single-mode mass sensing, yielding 15 times better particle capture efficiency and speed compared to current electromechanical device arrays.
To reach its objectives, AERONEMS will rely on the combined expertise of renowned specialists in acoustofluidics at IFW (Dresden, Germany), recognized leaders in the fundamentals and engineering of nanomechanical resonators at LETI (CEA Grenoble, France), and an established biological MS team at IRIG (CEA Grenoble, France). They will have access to state of the art facilities at IFW, the only VLSI optomechanical platform worldwide available at LETI, and a unique nanoresonator MS demonstrator developed at IRIG.
Tackling fundamental challenges associated with particle supply, intake and capture, and ‘lighting up’ the particle detection scheme, AERONEMS will establish the first optomechanical MS system able to weigh individual viral particles in a matter of minutes, providing virologists, epidemiologists and decision makers with a new tool for real time virus detection.