A wash-free and direct SERS platform for non-invasive kidney health monitoring via multiplexed urinary biomarker detection.

Routine monitoring of urinary biomarkers is critical for the early diagnosis of chronic kidney disease (CKD), yet conventional surface-enhanced Raman scattering (SERS) methods often require tedious washing steps to remove unbound reporters. Herein, we report a wash-free, multiplexed SERS chip designed for the spatially resolved profiling of albumin, uric acid (UA), creatinine, and urea. The chip features a micro-structured bowl-shaped PDMS substrate assembled with silver nanoparticles (AgNPs), providing high-density hotspots for sensitive detection. To achieve multiplexed urinalysis, we developed a hybrid sensing strategy tailored to the analytes' properties. For macromolecules (albumin) and specific metabolites (UA), hairpin aptamers labeled with Raman reporters undergo a conformational switch upon binding, separating the reporter from the Ag surface and resulting in a quantitative "signal-off" response without washing. Simultaneously, high-abundance small molecules (urea and creatinine) are quantified via their characteristic label-free vibrational fingerprints. This "dip-and-read" platform demonstrates excellent linearity across clinically relevant ranges and successfully analyzes simulated patient samples. By integrating aptamer modulation with intrinsic signal detection, this work provides a rapid, low-cost, and non-invasive tool for personal kidney health management.