  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.
