Bioinspired microchannel-based ionic current rectification sensor for sensitive detection of S100-β via interface charge density regulation.

Postoperative delirium (POD) is a severe postoperative neurocognitive complication associated with neuroinflammation and blood-brain barrier dysfunction. As a clinically relevant circulating biomarker for POD, S100-β detection is of great importance for accurate diagnosis and progression evaluation. Traditional approaches generally rely on converting antigen-antibody recognition events into the changes in labeled signal molecules, while neglecting the intrinsic charge properties of S100-β. Herein, a bioinspired microchannel-based ion current rectification (ICR) sensor was developed for sensitive S100-β detection, where S100-β antibodies were immobilized on the microchannel surface to simulate natural molecular recognition processes. The low isoelectric point of S100-β (∼4.7) renders the protein negatively charged under neutral conditions. Specific antigen and antibody recognition increased the interfacial negative charge density of the microchannel, thereby facilitating cation transport and enhancing the rectification response under an applied electric field. This process mimics the biological processes of channel opening and ion influx in living systems. The detected rectification ratio (RR) values was linearly correlated with the logarithm of S100-β concentration in the range of 0.01 ∼ 5.0 ng/mL with a detection limit of 4.0 pg mL-1 (S/N = 3). The sensor also showed good selectivity, as well as high stability with small RSD of 2.45%. The proposed sensor was successfully applied to the clinical serum analysis, showing good agreement with enzyme-linked immunosorbent assay and high recovery rates of 97.8% - 104.0%. This work provides a promising strategy for POD-related biomarker analysis and broadens the application of bioinspired microchannel-based ICR sensors in clinical diagnostics and bioanalytical sensing.