A flexible plasmonic SERS hydrogel patch for metabolite sensing on bio-interfaces

The growing demand for real-time, non-invasive monitoring of biochemical molecules has driven the development of advanced, flexible sensing materials. Surface-enhanced Raman spectroscopy (SERS) offers high molecular specificity and ultralow detection limits. While rigid SERS substrates based on plasmonic nanoparticle arrays provide strong signal enhancements, they lack the mechanical compatibility and conformal adhesion required for dynamic biological surfaces, such as human skin or neural tissues. Here, we present a flexible SERS hydrogel patch for the label-free detection of metabolites at bio-interfaces. The patch integrates a self-assembled silver nanoparticle film with an ultrathin polyvinyl alcohol (PVA) hydrogel layer to achieve good plasmonic enhancement, mechanical durability, conformity and reliable SERS stability. The SERS patch allows the detection of metabolites within 6 min upon analyte exposure, enabling the label-free detection of key metabolites, such as glucose, uric acid and urea with concentrations down to 1 μM, 50 μM and 1 mM, respectively. We demonstrate the versatility of this platform by performing ex vivo experiments on porcine brain and muscle tissues to simulate real-world application scenarios in brain-machine interfaces and implantable sensors. This work demonstrates the feasibility of SERS hydrogel-based flexible platforms for the in situ monitoring of metabolites at bio-interfaces.