Crosstalk-free dual-mode biosensing in a single MOF for α-glucosidase activity monitoring and inhibitor screening

This study presents a novel crosstalk-free dual-mode biosensing platform based on a single cerium-incorporated metal-organic framework (UiO-66-NH₂(Ce)) for sensitive detection of α-glucosidase activity and inhibitor screening. Unlike traditional dual-mode systems affected by signal interference, this monolithic MOF platform intrinsically produces orthogonal colorimetric and fluorescent responses. Upon α-glucosidase-mediated generation of hydroquinone, simultaneous signal transduction occurs through independent pathways: colorimetric attenuation via suppression of the oxidase-like catalytic process, and fluorescence recovery due to ligand-to-metal charge transfer modulation. Rigorously optimized for clinical application, the platform achieves ultra-low detection limits of 0.0166 U/L in colorimetric mode and 0.0094 U/L in fluorescent mode, surpassing existing methods. The platform demonstrates selectivity against potential interferents and successfully quantifies α-glucosidase in human serum with satisfactory recovery rates. Furthermore, the system facilitates precise inhibitor screening with IC₅₀ values of 8.13 μM for fluorescence-based detection and 10.06 μM for colorimetric detection of acarbose. By integrating self-validating detection and drug evaluation within a single-material architecture, this work establishes a paradigm for designing robust MOF-based biosensors equipped with built-in cross-validation capabilities.