Three-Dimensional Hierarchical Plasmonic Nano-Architecture Enhanced Surface-Enhanced Raman Scattering Immunosensor for Cancer Biomarker Detection in Blood Plasma

A three-dimensional (3D) hierarchical plasmonic nano-architecture has been designed for a sensitive surface-enhanced Raman scattering (SERS) immunosensor for protein biomarker detection. The capture antibody molecules are immobilized on a plasmonic gold triangle nanoarray pattern. On the other hand, the detection antibody molecules are linked to the gold nanostar@Raman reporter@silica sandwich nanoparticles. When protein biomarkers are present, the sandwich nanoparticles are captured over the gold triangle nanoarray, forming a confined 3D plasmonic field, leading to the enhanced electromagnetic field in intensity and in 3D space. As a result, the Raman reporter molecules are exposed to a high density of "hot spots", which amplifies the Raman signal remarkably, improving the sensitivity of the SERS immunosensor. This SERS immunosensor exhibits a wide linear range (0.1 pg/mL to 10 ng/mL) and a low limit of detection (7 fg/mL) toward human immunoglobulin G protein in the buffer solution. This biosensor has been successfully used for detection of the vascular endothelial growth factor in the human blood plasma from clinical breast cancer patient samples.