Biosensors that use biological molecules to detect substances hold great potential for diagnosing diseases, monitoring biological processes, and detecting environmental toxins. Traditional fluorescent biosensors are among the most common and are limited by the low-contrast reagents needed. Their probes are always active, requiring complex processes to identify accurate signals.
Researchers recently developed high-contrast “binding-activated fluorescent biosensors,” or nanosensors, which light up only when bound to a target molecule. Despite their promise, creating such nanosensors has been challenging. Effective target-binding and fluorescence on-switch must be combined in a small molecular package that can be efficiently delivered to various samples and cost-efficiently manufactured at scale.
A team of researchers has developed a synthetic biology platform that streamlines the discovery, molecular evolution, and manufacturing of nanosensors. This platform utilizes new fluorogenic amino acids (FgAAs) they can encode into protein sequences, enabling the rapid creation of nanosensors with up to 100-fold increased fluorescence upon target binding. This new system significantly improves high-throughput sensor screening, validation, and evolution, offering a powerful tool for medical diagnostics, environmental monitoring, and augmented therapeutics.
The researchers demonstrated the potential of their platform by developing nanosensors targeting various molecules, including the SARS-CoV-2 Spike protein, cancer-related growth factor receptors, and the stress hormone cortisol. Their platform allows for the rapid synthesis and testing of millions of nanosensor variants, drastically reducing the time required for development and enabling real-time disease monitoring. They further optimized their nanosensors through directed evolution, achieving highly specific sensors for newer Omicron variants of the virus.
This advancement could lead to low-cost, real-time diagnostic tools with enormous potential in precision medicine and disease monitoring. The platform also opens the door to creating new therapeutics by incorporating synthetic amino acids with additional functionalities into various proteins.
