Multiplexed SERS Profiling of Gout Biomarkers in Sweat via Polymer-Mediated Ag Nanoflakes

Personalized management of gout requires profiling multiple metabolites over time. Sweat offers a noninvasive matrix for such profiling. However, simultaneous detection of trace metabolic precursors amidst a complex chemical background remains a major analytical challenge. In this study, a flexible surface-enhanced Raman spectroscopy (SERS) substrate is developed for the multiplexed monitoring of a gout biomarker panel, including uric acid (UA), xanthine, hypoxanthine, and creatinine. The sensor is fabricated via in situ droplet-grown Ag nanostructures on microwell-patterned polydimethylsiloxane (PDMS), ensuring robust mechanical integration. The results demonstrate that polyvinylpyrrolidone (PVP)-mediated synthesis is critical for optimizing SERS performance. PVP drives a morphological transition from spherical nanoparticles to sharp-edged Ag "nanoflakes," while reducing competitive adsorption from abundant sweat interferents. The optimized platform achieves an LOD of 5 μM for UA, a 2-fold improvement over the unmodified substrate, with a linear quantification range of 5-100 μM. Clinical potential was validated by analyzing real human sweat, identifying UA in 16 of 20 samples and capturing diet-induced metabolic fluctuations. Furthermore, the device exhibits exceptional mechanical resilience, retaining signal stability under 50% tensile strain and cyclic fatigue. This work advances a robust, high-sensitivity pathway toward wearable chemical sensing by bridging plasmonic nanofabrication with sweat-based multiplexed monitoring.