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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.

acs nano

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