A joint research team led by the Institute of Nanoscience of the National Research Council (CNR-Nano) and the University of Pisa (Department of Pharmacy), in collaboration with the University of Modena and Reggio Emilia and the Scuola Normale Superiore, has developed a next-generation biosensor capable of detecting viral proteins—including the Spike protein of SARS-CoV-2—in biological fluids with high precision.
The findings, recently published in the journal Nanoscale, mark a breakthrough in biosensor design. The new sensor is based on a modular, Lego-like structure that can be easily adapted to detect a variety of molecular targets.
At the core of the sensor is a genetically engineered protein that combines three distinct functions in a single sequence. One segment acts as the detection target, built using fragments of the Spike protein. The central portion, inspired by the human ACE2 receptor, is designed to bind to the viral protein if it is present. The third segment contains green fluorescent protein (GFP), which functions like a light bulb—emitting a fluorescent signal upon contact with the virus, allowing for fast and accurate detection.
“The biosensor was created using both traditional recombinant protein engineering and innovative technologies such as click chemistry,” explains Eleonora Da Pozzo from the University of Pisa. “This interdisciplinary approach enabled us to develop a sensor with extremely high sensitivity, capable of detecting sub-nanomolar concentrations of viral protein.”
“What truly sets this prototype apart is its modularity,” adds Giorgia Brancolini from CNR-Nano. “By combining experimental research with molecular modeling and computer simulations, we were able to fine-tune each component and design a flexible, reprogrammable architecture. By altering specific sequences, the sensor can be adapted to identify other viruses or biomolecules, paving the way for new, customizable diagnostic tools.”
To protect the innovation and support its potential applications, a national patent application has been filed: Development of a FRET sensor for coronavirus detection (Application No. 102022000025416, filed on 13/12/2022).
The project received funding from Spark Global, through the Proof-of-Concept project SPARK PISA 2020–2022 (“FRET sensor for the Assessment of Coronavirus Titre – FACT”), and from the national PRIN2020 project “Early Phase Preclinical Development of PACECOR, a Mutation-Independent Anti-SARS-CoV-2 Therapeutic Strategy.”