Biosensors have achieved a significant feat in bioanalytical chemistry and translational science: high-frequency, real-time and quantitative measurements of clinically relevant molecules in vitro and in vivo. Despite their advantages, our ability to precisely control and regulate the binding activity of their bioreceptors (i.e. the recognition element) still represents a highly relevant bioengineering challenge and limitation. Indeed, complete control of the binding properties of bioreceptors would allow the design of new biosensors with improved and predictable analytical performance. These improvements in bioreceptor properties have a direct impact and benefit on any biosensing technology, not only the newly developed but also the already established techniques. In fact, this will allow the development of innovative, high performance and programmable biosensors capable of achieving personalized medicine. For example, the high precision of the measurements could allow the tailoring of dietary or drug therapy, improving the clinical treatment of cancer, diabetes and metabolic disorders. In the MSCA action (Entropic DNA Sensors), the experienced researcher (Dr. Andrea Idili) proposed a multidisciplinary, innovative and versatile approach that allowed to fine-tune the activity and the response of synthetic bioreceptors. Specifically, the work has focused on the exploration and characterization of various naturally inspired mechanisms, such as entropic allostery and sequestration, as a novel signal transduction mechanism to improve measurement precision. This has allowed the development of a general bioengineering approach to precisely tune biosensor performance through the rational introduction of intrinsically disordered moieties. Finally, the senior researcher demonstrated the application of these mechanisms in representative biosensors (electrochemical and optical) and their use for real-time, high-precision measurements of clinically relevant molecules to achieve the detection of clinically relevant molecules (i.e. doxorubicin, ATP, vancomycin, and NGAL) directly in complex biological fluids in vitro. To achieve these project goals, Dott. Idili's previous experience in in vivo biosensing and point-of-care (PoC) testing technologies was synergistically combined with the recognized expertise in functional DNA nanotechnology and synthetic biology of Prof. Francesco Ricci at the University of Rome Tor Vergata (UNITOV-Rome, Italy).
