Engineered Synthetic Nano-Composite Hydrogels for Biomolecule Detection via SERS

The development of reproducible and sensitive plasmonic materials is essential foradvancing single-molecule detection using surface-enhanced Raman spectroscopy (SERS),specially for label-free biomedical sensing and cancer diagnostics. We fabricated silvernanoparticle–embedded hydrogels that are stable, active SERS substrates enabling highlysensitive, label-free molecular analysis. SERS enhances Raman scattering by placing targetmolecules in close proximity to a roughened metallic surface, generating localized surfaceplasmon resonances that amplify the Raman signal. Silver, which induces strong and consistentplasmonic enhancement compared to other metals, and methylene blue, a model analyte forwell-defined Raman peaks, provide a reliable standard for measuring enhancement performance.Silver nanoparticles were synthesized by chemical reduction of silver nitrate (AgNO3),combination of PVP K90 and L-ascorbic acid and the addition of heat to promote nucleation andgrowth before purification into concentrated pellets. Nanoparticle size will be measured usingdynamic light scattering (DLS),and SERS performance was evaluated using methylene blue,which produced characteristic peaks at 770, 1389, and 1620 cm-1. Comparative analysis showedthat the nanoparticle-embedded hydrogels produced stronger signal than conventional Ramanmeasurements, confirming effective SERS amplification for low-concentration biomoleculardetection.Hydrogel matrices made from poly(ethyleneglycol)diacrylate (PEGDA)provided ahydrated, tunable backbone that uniformly dispersed and stabilized the nanoparticles.Optimization efforts targeted UV curing time, PEGDA concentration, and nanoparticle loadingto maintain structural integrity and maximize signal enhancement. By varying nanoparticle sizeand comparing reducing agents such as L-ascorbic acid and sodium borohydride, we found thathigher particle concentrations did not always improve SERS intensity, underscoring the need tooptimize particle size and distribution for effective plasmonic coupling.In conclusion, the PEGDA–silver composite hydrogels functioned as robust,reproducible, and tunable SERS substrates for label-free molecular sensing with clear potentialfor cancer diagnostics. Optimizing nanoparticle synthesis, reduction chemistry, and hydrogelformulation improved both sensitivity and structural stability. Demonstrating a promisingpotential for future SERS-based chemical and diagnostic applications. Citation Format: Harlie G. Rios, Cason M. Hancock, Swarna Ganesh. Engineered synthetic nano-composite hydrogels as tunable SERS substrates for biomolecule detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 724.