Synthesis and characterization of perm-selective SERS-active silica-coated gold nanospheres for the direct detection of small molecules

Noble metal nanomaterials have numerous uses in plasmonic and surface enhanced Raman scattering (SERS) detection applications; however, upon the addition of analytes, nanomaterials often undergo uncontrolled aggregation which leads to inconsistent signal intensities. To overcome this limitation, the effect of gold nanosphere concentration, column purification, and surface chemistry functionalization using internally etched silica stabilization methods was investigated on SERS assays for small molecule detection. Nanostructure composition, size, shape, stability, surface chemistry, optical properties, and SERS-activity were monitored using localized surface plasmon resonance (LSPR or extinction) spectroscopy, transmission electron microscopy (TEM), and Raman spectroscopy. First, the behavior of citrate-stabilized gold nanospheres was monitored as a function of molecular surface coverage. Both extinction and SERS spectral intensities increased linearly below monolayer functionalization. Above this value, however, uncontrolled nanoparticle aggregation occurred and large but irreproducible SERS signal intensities were monitored. Next, gold nanoparticles were encapsulated with varying silica shell thicknesses and purified using traditional centrifugation steps and/or column chromatography. Relative to the traditionally purified (i.e. centrifuged) samples, the SERS responses from small molecules using the column purified nanoparticle samples followed a well-known SERS distance-dependence model. Thus, surface chemistry cannot form more than a 2 nm thick layer on gold nanospheres if SERS applications were targeted. To overcome these challenges, gold nanospheres encapsulated with a thick silica shell were made SERS-active by etching the internal silica layer near the metal surface. During the synthesis of these internally etched silica-coated gold nanospheres, the LSPR wavelength shift, a parameter related to the effective local refractive index near the gold core, was monitored instead of etching time, in order to produce nanostructures with more uniform internal silica etching from sample to sample. The SERS-activity of a target molecule using these nanostructures was measured as a function of LSPR wavelength shift. SERS signal intensity increased, which suggested that more analyte molecules were able to bind to the gold surface because of the larger pore size in the silica layer near the metal core. Further exploration of these findings should increase the integration of solution-phase nanoparticles in more predictable functions in future applications, resulting in more quantitative and reproducible molecular detection in complex sample matrices, including biological and environmental samples.