Hydrogel-Gated Silicon Nanotransistors for SARS-CoV-2 Antigen Detection in Physiological Ionic Strength

The recent Coronavirus Disease 2019 (COVID-19) outbreak strongly propels advancements in biosensor technology, leading to the emergence of novel methods for virus detection. Among them, those using nanostructured field-effect transistors (FETs) provide an ultrasensitive approach toward point-of-care diagnostics. However, the application of these biosensors in analyzing biofluids has been limited by their reduced screening length in high ionic strength liquids. To address this challenge, a solution is presented involving the surface modification of FETs with a hydrogel based on star-shaped polyethylene glycol. This hydrogel is loaded with specific antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. By incorporating the hydrogel, the effective Debye length is effectively increased, thereby preserving the sensitivity in biofluids. The efficacy of this approach is demonstrated by employing silicon nanonet-based FETs for the detection of viral antigens in both buffer and saliva, as well as cultured viral particle dispersions. Moreover, positive and negative patient samples are successfully differentiated, showcasing the practical application of this method. Finally, a theoretical frame is proposed to elucidate the underlying mechanism behind the preservation of sensitivity.