Octadecylamine-Modified CuO NPs Enabling Highly Selective In Vivo Ascorbic Acid Potentiometric Detection with Enhanced Sulfide Tolerance

Although currently reported in vivo ascorbic acid (AA) sensors based on galvanic redox potentiometry (GRP) feature good selectivity toward biological molecules, the interference from sulfides (e.g., H 2 S) is still a great challenge. Herein, we demonstrate a novel shielding strategy for highly selective AA assay without the interference from H 2 S. The electrode was constructed by confinement of octadecylamine (ODA)-modified CuO nanoparticles (NPs) on a carbon fiber electrode (CFE), in which CuO NPs rapidly convert H 2 S into CuS, minimizing its electrochemical redox contribution, while the ODA layer shields against potential fluctuations arising from electrical double-layer (EDL) changes. Using this sensor, we achieved synchronous tracking of neuronal activity and H 2 S interference-free AA release dynamics during cortical spreading depression (CSD) in the rat cortex. AA release was temporally coincident with neuronal suppression, and higher KCl concentrations prolonged both AA elevation and neuronal silencing. Repeated induction of CSD resulted in a cumulative effect, characterized by a progressive decrease in the induction threshold and gradual increases in both the magnitude of AA elevation and its recovery time. These findings suggest that AA can serve as a real-time marker of CSD, reflecting the degree of injury burden imposed by CSD events.