Enzyme-Mediated Quantum Material Phase Transition Enables Proton-Driven Neurotransmitter-Specific Signal Amplification

In medical diagnostics, current biosensors often struggle with sensitivity and selectivity due to molecular interference, especially when analyzing easily obtainable patient specimens. To address these challenges, we developed a novel approach for the real-time detection of biomarkers with exceptional selectivity and sensitivity. We synergistically integrated an enzyme, which produces protons by specifically recognizing ultra-low concentration biomarkers, with a phase-transition oxide capable of generating a one-million-fold resistance change upon proton penetration. Our innovative design enhances the biosensor's performance, offering highly efficient and artifact-less detection of neurotransmitters. As a proof-of-concept, we systematically integrated the neurotransmitter-specific enzyme for selective proton production with the quantum dioxide for proton-driven insulator-to-metal phase transition. The miniaturized enzyme-oxide heterojunction device actualized a novel target-selective proton-driven electric signal amplification mechanism. Our device outperformed all types of previously reported biosensors, demonstrating an extremely low limit of detection (~ 10^-17 M), an ultra-fast response time (50 msec), and a significantly high amplification ratio (> 100), along with the exceptionally high specificity even with one droplet of solution. Moreover, we actualize real-time monitoring of targets at live mouse neurons.