Single-Virus Stochastic Biosensing: Proof of Concept for SARS-CoV-2 Detection in Complex Medium Using CMOS-Based Nanocapacitor Arrays

Abstract

Stochastic detection opens a promising window toward improved biosensing assays, despite the challenges posed by the unpredictable behavior of nanoscale entities as well as interference from the target medium. This study presents a novel proof of concept for label-free detection of single virus particles in complex media at physiological salt concentrations using stochastic electrochemical impedance. SARS-CoV-2 particles are successfully detected in cell culture medium using thiolated aptamers that selectively bind to the virus's spike S1 proteins, enabling the identification of individual viral particles. Stochastic biosensing, which relies on large datasets, is powered here by CMOS-based nanocapacitor arrays with 65536 individually addressable electrodes serving as electrochemical transducers. This configuration allows for high-frequency impedance measurements under physiological conditions, demonstrating the potential for scalable, real-time, label-free virus detection.