A Novel Method in Identifying Pyroptosis and Apoptosis Based on the Double Resonator Piezoelectric Cytometry Technology

In this study, a double resonator piezoelectric cytometry (DRPC) technology based on quartz crystal microbalance (QCM) was first employed to identify HeLa cell pyroptosis and apoptosis by monitoring cells' mechanical properties in a real-time and non-invasive manner. AT and BT cut quartz crystals with the same frequency and surface conditions were used concurrently to quantify the cells-exerted surface stress (Δ ). It is the first time that cells-exerted surface stress (Δ ) and cell viscoelasticity have been monitored simultaneously during pyroptosis and apoptosis. The results showed that HeLa pyroptotic cells exerted a tensile stress on quartz crystal along with an increase in the elastic modulus ( '), viscous modulus ( ″), and a decrease of the loss tangent ( ″/ '), whereas apoptotic cells exerted increasing compressive stress on quartz crystal along with a decrease in ', ″ and an increase in ″/ '. Furthermore, engineered GSDMD -DEVD- HeLa cells were used to investigate drug-induced disturbance and testify the mechanical responses during the processes of pyroptosis and non-pyroptosis. These findings demonstrated that the DRPC technology can serve as a precise cytomechanical sensor capable of identifying pyroptosis and apoptosis, providing a novel method in cell death detection and paving the road for pyroptosis and apoptosis related drug evaluation and screening.