Gold nanorod in silver tetrahedron: Cysteamine mediated synthesis of SERS probes with embedded internal markers for AFP detection

Background: Plasmonic core-shell nanostructures with embedded internal markers used as Raman probes have attracted great attention in surface-enhanced Raman scattering (SERS) immunoassay for cancer biomarkers due to their excellent uniform enhancement. However, current core-shell nanostructures typically exhibit a spherical shape and are coated with a gold shell, resulting in constrained local field enhancement. Results: In this work, we prepared a core-shell AuNR@BDT@Ag structure by depositing silver on the surface of Raman reporter-modified gold nanorods (AuNR). With cysteamine-driven specific deposition of Ag atoms, the internal standard nanoprobes with an ortho-tetrahedral morphology were obtained. Owing to its tetrahedral morphology and the effective plasmon coupling at the Ag–Au interface, this internal standard Raman probe exhibited excellent Raman enhancement. Also, with embedded Raman reporter, the probes of Au nanorod in Ag tetrahedron avoided the desorption of Raman reporter and competitive adsorption of interfering molecule, which greatly improved the stability and reproducibility of SERS signal and addressed the drawbacks of low reproducibility existing in SERS immunoassay. The feasibility of the AuNR@BDT@Ag probe was demonstrated by the sensitive detection of the liver cancer biomarker alpha-fetoprotein (AFP) in Eppendorf (EP) tubes and microfluidic chips. The results in EP tubes revealed a linear range of 1 fg/mL-1 ng/mL and a detection limit of 0.631 fg/mL. When the detection was performed in microfluidic chips, the linear range was 10 pg/mL to 0.1 μg/mL, with a limit detection of 8.29 pg/mL. Significance: The performance of AFP detection in EP tubes and microfluidic chips demonstrates that the tetrahedral core-shell AuNR@BDT@Ag nanostructures used as internal standard Raman probes have the potential to detect biomarkers in blood samples for cancer screening.