A Plasmonic Nanopore Sensor for Dual-Gating Optoelectronic Detection of Cysteine

Cysteine (Cys) is a crucial biomarker and a significant analyte in physiological and pathological processes; however, achieving its accurate detection with high spatiotemporal resolution in complex biological environments remains challenging. Herein, we address this by developing a dual-mode optoelectronic sensing platform. A self-designed Cys fluorescent probe was integrated into a plasmonic nanopore via a site-selective functionalization strategy. This platform synergistically combines plasmon-enhanced fluorescence with nanopore-based electrochemical detection, providing complementary optical and electrical signals that enable high spatio-temporal resolution for accurate analyte quantification. The confined geometry of the nanopore enhances sensitivity by concentrating electromagnetic fields into sub-diffraction volumes and restricting molecular motion within the nanospace. The developed Cys sensor achieves high sensitivity, along with excellent selectivity and strong anti-interference capability, as validated through an "AND" logic gate operation. Importantly, the practical utility of the sensor is demonstrated by successful quantification of exogenous Cys in living MDA-MB-231 cells, confirming its capability for in situ cellular analysis. Furthermore, this versatile plasmonic nanopore platform can be readily adapted for the detection of various small molecules by simply substituting the probe molecule, offering a simple, stable, and generalizable sensing approach in small molecules detection.