Dual-Probe Strategy-Enabled Multiplex Photoelectrochemical Sensor for Highly Sensitive Screening of Diabetes and Related Complications

Photoelectrochemical (PEC) biosensing has emerged as a vital tool in disease surveillance and therapeutic monitoring. However, most current PEC platforms are constrained to single biomarker detection, limiting their utility in comprehensive disease management. In this study, we report the development of a dual-target PEC biosensor by integrating silane molecules and β-cyclodextrin (β-CD) with carbon nitride materials, specifically designed for monitoring diabetes and its associated complication, uremia. The silane molecules enhance the photocurrent through an in situ sensitization effect triggered by α-glucosidase (α-Glu)-catalyzed hydrolysis products, while the complexation between β-CD and l-histidine (l-His) results in a contrasting photocurrent suppression due to steric hindrance. This dual-response mechanism enables precise and selective detection of both biomarkers. The developed biosensing platform displays remarkable detection capability for α-Glu, achieving a linear photocurrent response across the concentration range of 5-100 mU/mL, with the method demonstrating exceptional sensitivity down to 0.62 mU/mL. Simultaneously, l-His detection is achieved over a range of 0.01-1 mM, with a detection limit down to 7.2 μM. In addition to high sensitivity, the resultant sensing platform demonstrates excellent stability, reproducibility, and resistance to interference. By integrating in situ sensitization and host-guest complexation effects, this work presents a novel and robust strategy for multifunctional PEC biosensor design, offering new opportunities for efficient and comprehensive disease monitoring.