Sybodies as novel bioreceptors toward field-effect transistor-based detection of SARS-CoV-2 antigens

The SARS-CoV-2 pandemic has increased the demand for low-cost, portable and rapid biosensors, driving huge research efforts toward new nanomaterial-based approaches with high sensitivity. Many of them employ antibodies as bioreceptors, which have a costly development process requiring animal facilities. Recently, sybodies emerged as an alternative new class of synthetic binders/receptors with high antigen binding efficiency, improved chemical stability, and lower production costs via animal-free methods. Their smaller size is an important asset to consider in combination with ultrasensitive field-effect transistors (FETs) as transducers, which respond more intensely when the biorecognition occurs in close proximity to their surface. This work demonstrates the immobilization of sybodies against the spike protein of the virus on silicon surfaces, which are often the integral part of the semiconducting channel of FETs. Immobilized sybodies maintain the capability to capture antigens even at low concentrations in the femtomolar range, as observed by fluorescence microscopy. Finally, the first proof-of-concept of sybody-modified FET sensing is provided, using a nanoscopic silicon net as the sensitive area where the sybodies are immobilized. The future development of further sybodies against other biomarkers and their generalization in biosensors could be critical to decrease the cost of biodetection platforms in future pandemics.