Interlaced 2D cellulose networks with molecular enrichment capability for sensitive SERS detection of sweat biomarkers

Efficient localization of analytes near plasmonic hotspots remains a major challenge for surface-enhanced Raman scattering (SERS) detection in complex liquid-phase systems. Herein, an interlaced cellulose-based porous membrane composed of dissolving pulp fibers (DPFs), mechanically ground nanofibers (MGNFs), sodium alginate (SA), and Ag nanoparticles was developed as a molecular enrichment-assisted SERS platform for sweat biomarker determination. The hierarchical porous architecture provided interconnected transport channels and abundant interfacial adsorption sites, facilitating analyte retention and localized enrichment within the plasmonic region. Benefiting from the synergistic effects of porous confinement and uniformly distributed Ag nanoparticles, the optimized substrate exhibited sensitive and reproducible SERS performance with an enhancement factor of 4.36 × 10⁷, a relative standard deviation of 8.04%, and a detection limit down to 1.0 × 10⁻⁸ mol/L for Rhodamine 6G (R6G). Systematic adsorption experiments using molecules with different charge properties further demonstrated the broad molecular enrichment capability of the structured cellulose network. The developed platform enabled quantitative detection of lactate and urea within physiologically relevant sweat concentration ranges and showed satisfactory analytical performance in spiked sweat samples. More importantly, this work demonstrates a structure-engineered porous membrane strategy for integrating molecular enrichment with plasmonic sensing, providing new insight into cellulose-based SERS platforms for complex bioanalytical applications.