Microfluidic sol-gel coating of ultrathin silica shells on Au NPs for thiol-free LSPR biosensing

Localized surface plasmon resonance (LSPR) biosensors offer high sensitivity, potential for miniaturization, and compatibility with microfluidic platforms. But their broader application is limited by the instability and cost of conventional thiol-based biofunctionalization strategies. In this work, we report a robust microfluidic-based biofunctionalization approach that uses an ultrathin silica coating of Au NPs, followed by epoxy-silane modification. An LSPR microfluidic sol-gel process was used to deposit an ultrathin silica shell (4.5 nm) on immobilized 80 nm Au NPs, enabling thickness control while preserving plasmonic performance. The impact of the silica layer on both the bulk and surface refractive-index sensitivities was systematically evaluated using ethylene glycol solutions and layer-by-layer polyelectrolyte deposition, respectively. The ultrathin coating resulted in only a minor reduction in bulk sensitivity (1.88 nm RIU^-1) while retaining 75-77% of the surface refractive-index sensitivity. Subsequent epoxy-silane functionalization enabled stable covalent attachment of amino-terminated DNA probes, as verified by LSPR and Raman spectroscopy. A proof-of-concept DNA hybridization assay demonstrated specific binding of complementary targets under microfluidic conditions. The presented approach overcomes key limitations of thiol chemistry and provides a stable, versatile, and microfluidics-compatible platform for LSPR bioanalytics.