Photoelectrochemical biosensor with single atom sites for norepinephrine sensing and brain region synergy in epilepsy

Norepinephrine (NE), a pivotal neurotransmitter in the central and sympathetic nervous systems, is crucial for numerous physiological and pathophysiological processes. Distinguishing NE from structurally similar dopamine and epinephrine in complex in vivo environments is a significant challenge. Herein, we propose a molecular docking strategy for selective, sensitive, and ultrafast detection of NE in vivo. Leveraging the molecular structure of NE, we design a Zn single-atom-modified TiO₂ substrate (Zn₁/TiO₂) as a photoelectrochemical (PEC) biosensor, providing synergistic atomic anchoring sites to “lock” NE molecules and enabling real-time NE detection in the brain of living male mice with a response time of 60 ms. The high specificity and rapid detection capabilities of this biosensor have unveiled a regulatory mechanism of the noradrenergic system across multiple brain regions, including the locus coeruleus, cortex, and hippocampus, highlighting a synergistic effect during epilepsy. This rationally designed single-atomic PEC biosensor for in situ monitoring of neurotransmitter dynamics holds promise for future brain science research.