PEDOT:PSS OECTs as versatile devices for real-time monitoring cytotoxicity and viral infection

Semiconducting polymers are very promising materials for biomedical application, owing to their ability to conduct both ions and electrons, their biocompatibility and their flexible and soft mechanical properties. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has high conductivity, electrochemical and thermal stability in aqueous environment and reversable electrochemical properties that render it suitable as smart, nano-biointerface for biological entities. In our work, we present PEDOT:PSS-based Organic Electrochemical Transistors (OECTs) for monitoring of cell viability, providing an easy, fast and real-time electrical output which overcomes standard optical evaluation techniques and do no need toxic substance staining or highly-specialized operators. Cells are directly grown on transparent, biocompatible, PEDOT:PSS-based thin film OECTs: the presence of a cell monolayer slows down ion flux from the electrolyte into the semiconducting polymer, thus allowing for an electronic readout (transistor temporal response to a square potential switch) of cell layer integrity and health. We demonstrated that the devices can be employed for evaluating cytotoxicity of external agents, viral infection pathway and viral titration of both a cytopathic virus (encephalomyocarditis virus, ECMV) and a non-cytopathic one (bovine coronavirus, B-CoV). Noteworthy, testing Sars-Cov-2 infected cells, we observed that OECTs can automatically perform serum neutralization assays in less than 48h (earlier than the usual 72 hours needed for actual standard screening), quantifying the neutralizing antibodies present in human sera. This work shows that PEDOT:PSS OECTs provide a scalable and versatile biosensor able to monitor several cell cultures and their stress/cytopathic response, paving the way for high throughput and low-cost drug discovery screening, toxicology evaluations, viral titration or serum neutralization assays.