Multi-layer Ag-embedded Silica Nanostructure as SERS-based Chemical Sensor with Dual-Function Internal Standards.

Surface-enhanced Raman scattering (SERS) spectroscopy is attractive in various bioanalysis fields owing to its extraordinarily high sensitivity enough for the detection of a single molecule. The key issues in developing quantitative analysis methods by using SERS spectroscopy are the fabrication of reliable SERS-active materials such as nanoparticle-based structures and the acquisition of SERS signal without any disturbance that may change the SERS signal intensity and frequency. Here, the fabrication of seamless multi-layered core-shell nanoparticles with an embedded Raman label compound as an internal standard (ML dots) for quantitative SERS analysis is reported. The embedded Raman label compound in the nanostructure provides a reference value for calibrating the SERS signals. By using the ML dots, it is possible to gain target analyte signals of different concentrations while retaining the Raman signal of the internal standard. The ML dots, containing 4-bromobenzenethiol (4-BBT) as an internal standard, are successfully applied in the quantitative analysis of 4-fluorobenzenethiol (4-FBT) and thiram, a model pesticide. Additionally, ratiometric analysis was proved practical through normalization of the relative SERS intensity. The ratiometric strategy could be applied to various SERS substrates for quantitative detection of a wide variety of targets.