Hydrogel-gated silicon nanotransistors for SARS-CoV-2 antigen detection in physiological ionic strength

The recent COVID-19 outbreak has strongly pushed the field of biosensors, resulting in multiple new approaches for quantitative virus detection. Among them, those using nanostructured field-effect transistors (FETs) as transducers provide an ultrasensitive approach requiring simple setups for their miniaturization toward point-of-care diagnostics of the disease. However, this type of biosensors suffer from limited sensitivity when it comes to analyzing biofluids due to their shortened screening length in presence of complex liquids with high ionic strength. In this work we propose a solution to this problem, which consists on the surface modification of the FETs with a hydrogel based on star-shaped polyethylene glycol and loaded with specific antibodies against SARS-CoV-2 spike protein. The hydrogel increases the effective Debye length, allowing to preserve the sensitivity in high ionic strength solutions. We provide the demonstration employing silicon nanonet-based FETs for the detection of viral antigens in buffer and in saliva, as well as cultured viral particles. We finally discriminate positive and negative patient samples (nasopharyngeal swab), and propose the theoretical frame that discusses the mechanism of the sensitivity preservation based on the presence of the pegylated hydrogel.