High-Throughput Surface-Enhanced Raman Spectroscopy Platform for Multiplex Detection of Uremic Metabolites Relevant to Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with the accumulation of chemically diverse uremic metabolites, creating a need for rapid and multiplexed analytical platforms beyond conventional single-analyte assays. This work reports a high-throughput surface-enhanced Raman spectroscopy (SERS) platform for simultaneous analysis of CKD-related metabolites. It comprises a flexible SERS substrate composed of silver nanoparticles (AgNPs) on a polydimethylsiloxane (PDMS) film. AgNPs were synthesized directly on the PDMS surface via solvent-exchange-induced surface droplet reactions, yielding a dense, uniform distribution of plasmonic hot spots. Using adenine as a model analyte at a concentration of 1 × 10-6 M, the substrate showed a batch-to-batch variation of 7.32%, confirming its reproducibility. The AgNPs-PDMS substrate was subsequently integrated into a parallel microvolume plate format to detect five CKD-relevant metabolites, achieving the limit of detection (LOD) ≤ 2.5 × 10-4 M across the panel. To the best of our knowledge, this work presents the first SERS detection of quinaldic acid and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. As a proof-of-concept for clinical translation, the platform was used to quantify selected metabolites in serum from patients with kidney failure. This scalable polymer-based SERS platform provides a practical route toward parallel biochemical screening of CKD-associated metabolites.