3D Hydrogel SERS Substrate for Enantioselective Sensing

Enantioselective sensing is crucial for distinguishing between chiral molecules, which can have vastly different biological activities, thus ensuring drug safety and efficacy. Additionally, it plays a significant role in environmental monitoring and food safety by detecting trace amounts of chiral pollutants and additives. The surface-enhanced Raman scattering-chiral anisotropy (SERS-ChA) effect, derived from opposite chiral plasmonic nanostructures, has emerged as a promising enantioselective sensing approach. However, developing highly selective and sensitive enantioselective sensors using the SERS-ChA effect is technically demanding, requiring a sophisticated manufacturing process and often posing challenges related to stability and reproducibility. Moreover, due to the inherent weakness of the Raman signal, achieving quantitative analysis of enantiomers with this technique remains difficult. In this work, we report the facile fabrication of a hydrogel SERS substrate for an enantioselective sensor with high reusability and reproducibility. Our polyethylene glycol diacrylate (PEGDA) hydrogel-based SERS-ChA substrate can be rapidly polymerized and customized, providing a flexible and tunable matrix with high water content for use as a biosensing platform. This platform effectively discriminates between different amino acid enantiomers. The 3D hydrogel SERS-ChA substrate can immobilize chiral gold nanoparticles (AuNPs), enhancing their density and interaction with target analytes. This improvement leads to increased stability, reproducibility, and sensitivity of SERS-based detection, facilitating both qualitative and quantitative analyses with superior detection limits. This 3D hydrogel SERS-ChA substrate-mediated biosensor platform shows promise for adaptation to larger biomolecules in various media, potentially enabling its use in complex diagnostic applications.