Hydrogen-bond mediated pre-enrichment in antioxidant nano-confined 3D flexible cellulose fibers for ultrasensitive 10-19 M level SERS detection.

To address key limitations of traditional surface-enhanced Raman scattering (SERS) substrates (Ag oxidation, poor enrichment, impractical in-situ detection) restricting real-world application, we propose a "hydrophilic 3D network for hydrogen-bond enrichment" strategy. Hydroxypropyl methylcellulose (HPMC)/Ag composite nanofibrous membranes (3D-AH-NFMs) were fabricated via green water-ethanol electrospinning, with AgNPs in-situ encapsulated into a biomimetic "nacre-shell" structure. HPMC's hydroxyl groups enable dual "reduction-anchoring" (reducing Ag + to Ag0, anchoring via O-Ag coordination), forming dense 3D SERS "hotspots" and an antioxidant barrier (≤4% signal decay after 6 months). Abandoning reliance on superhydrophobicity, the 3D network enriches polar analytes via hydrogen bonding (≈25 kJ/mol), capillary action, and Ag-S anchoring (≈200 kJ/mol), achieving an analytical enhancement factor (AEF) of ≈1.46 × 108 and an ultralow limit of detection (LOD) of 10-19 M for 4-ATP, outperforming most reported noble-metal substrates by 3-10 orders of magnitude. It also exhibits high selectivity for benzaldehyde (lung cancer biomarker) without acetone/methanol interference. Integrated into a smart-mask platform and coupled with a support vector machine (SVM) algorithm, the system performs non-invasive breath analysis with 99% accuracy and a 3-s response. This work establishes a new paradigm for designing green, stable, and ultrasensitive SERS substrates, paving the way for practical, early-stage disease diagnostics and personalized home-healthcare monitoring.