Integrated sensor array based on vapor-annealed 2D photonic crystals and multi-responsive hydrogels for urinary biomarkers detection

Urine analysis plays a critical role in clinical diagnostics and chronic disease monitoring, yet existing methods face challenges in achieving multiplexed, quantitative, and point-of-care testing (POCT) with high accuracy. This study reports an integrated sensor array for the simultaneous detection of four key urinary biomarkers (glucose, creatinine, urea, and albumin) by combining vapor-annealed two-dimensional photonic crystals (2DPCs) with multi-responsive hydrogels. Large-area, highly ordered polystyrene 2DPCs were fabricated via gas-liquid interface self-assembly followed by toluene vapor annealing, significantly enhancing their structural regularity and optical properties. The 2DPCs were functionalized with four stimulus-responsive hydrogels designed for the specific recognition of glucose, creatinine, urea, and albumin, based on phenylboronic acid recognition, molecular imprinting, urease-catalyzed reaction, and antibody binding, respectively. The sensors were integrated into a four-channel chip, enabling parallel operation with minimal cross-talk. The array demonstrated high sensitivity and specificity. Validation in artificial urine and real urine showed excellent accuracy, with recovery rates of 97.4–99.4% and RSD < 5%. This work provides a versatile, robust platform for multiplexed biomarker detection, bridging the gap between laboratory-grade accuracy and POCT usability.