The SARS-CoV-2 pandemic has increased the demand forlow-cost,portable, and rapid biosensors, driving huge research efforts towardnew nanomaterial-based approaches with high sensitivity. Many of thememploy antibodies as bioreceptors, which have a costly developmentprocess that requires animal facilities. Recently, sybodies emergedas a new alternative class of synthetic binders and receptors withhigh antigen binding efficiency, improved chemical stability, andlower production costs via animal-free methods. Their smaller sizeis an important asset to consider in combination with ultrasensitivefield-effect transistors (FETs) as transducers, which respond moreintensely when biorecognition occurs near their surface. This workdemonstrates the immobilization of sybodies against the spike proteinof the virus on silicon surfaces, which are often integral parts ofthe semiconducting channel of FETs. Immobilized sybodies maintainthe capability to capture antigens, even at low concentrations inthe femtomolar range, as observed by fluorescence microscopy. Finally,the first proof of concept of sybody-modified FET sensing is providedusing a nanoscopic silicon net as the sensitive area where the sybodiesare immobilized. The future development of further sybodies againstother biomarkers and their generalization in biosensors could be criticalto decrease the cost of biodetection platforms in future pandemics.