Single-Virion SARS-CoV-2 Mass Spectrometry in Air by On-Chip Focusing NEMS

The COVID-19 pandemic highlighted the necessity to develop rapid in situ viral detection techniques to isolate infection breakouts. Current biochemical detection techniques, such as polymerase chain reaction (PCR), remain inadequate for initial response due to the delay associated with sequencing the viral genome and reagent development. Alternatively, physical properties of the virus such as mass and size can be quickly profiled and utilized for rapid detection using mass spectrometry (MS). The recent developments in Nanoelectromechanical Systems (NEMS) have made it possible to measure the mass of single particulates with high accuracy; however, significant challenges still exist in adapting NEMS-MS for real biological samples. Sample delivery to the sensing element generally requires the use of delicate vacuum systems and the sensing element suffers from low capture efficiency due to its miniscule size. Here, we develop a NEMS-MS device with an integrated polymeric electrostatic lens to enhance the capture efficiency by several orders-of-magnitude compared to the state-of-the-art, while allowing for operation under atmospheric conditions. After benchmarking and validating device performance with nanoparticles, we successfully detected the mass of single inactivated SARS-CoV-2 virions from cell lysates with minimum sample preparation. The results establish NEMS technology as an effective approach for the label-free detection of emerging viruses.