Vacuum-Free Mass Spectrometry of Single Viruses and Nanoparticles by Nano-Electromechanical Systems

Mass spectrometry of intact nanoparticles and viruses can serve as a unique characterization tool for material science and biophysics. Inaccessible by conventional techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by NEMS (Nano-electromechanical Systems) based Mass Spectrometry, where charged and isolated analyte particles are generated by Electrospray Ionization (ESI) in air and transported onto the NEMS surface for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes towards the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ionic lens onto the NEMS chip. The ionic lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes towards an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with record capture efficiencies. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup and the operation capability under ambient conditions, the technique brings NEMS mass spectrometry one step closer towards efficient mass detection of engineered nanoparticles and biological samples.