Creation of a Self-Powered, Real-Time Sensor for Therapeutics in Blood: from Protein Engineering to Electronic Integration

Abstract Precision medicine is expected to revolutionize healthcare by prioritizing accuracy and efficacy over the traditional "one-fits-all" approach. Point-of-care (POC) sensors, which are low-cost and user-friendly, play a crucial role in driving this trend by providing quick results for individuals. Modeled after the 5G network, we conceptualized an innovative approach for transmitting biomolecular signals - encoding biomolecular binding by modulating the electrical signal from glucose oxidation. We implement this concept by engineering a hybrid protein that incorporates a biomarker binding domain within a glucose oxidoreductase. By constructing an effective bioelectrochemical interface, we could detect 4-hydroxytamoxifen, an estrogen antagonist, in human blood samples, as real-time changes in the electrical signal. Moreover, our design uses blood glucose to power this real-time sensor and an additional transistor, which yields a self-powered prototype with high signal-to-noise. We foresee this novel approach transforming the conventional glucometer into a therapeutic biosensor with add-in functions.