Synergistic effect of a “stellate” mesoporous SiO2@Au nanoprobe and coffee-ring-free hydrophilic–hydrophobic substrate assembly in an ultrasensitive SERS-based immunoassay for a tumor marker†
In the field of surface-enhanced Raman scattering (SERS)-based immunoassays utilizing a sandwich structure, one of the main barriers to overcome is the development of an immunoprobe and substrate with ultrahigh sensitivity and relatively good reproducibility. In this work, a novel gold (Au)-coated “stellate” mesoporous SiO2 (SMSiO2) hybrid structure was proposed and applied as an immunoprobe. It was noticed that the SMSiO2 matrix with an appropriate coating amount of Au nanoparticles (NPs) demonstrated a much higher SERS intensity than solid SiO2 (SSiO2)@Au NPs with an enhancement ratio of 2.6. Electromagnetic “hot spots” existed around the sharp edges and ultrasmall nanogaps of the multibranched SiO2 matrix were verified to be the main reason responsible for the conspicuous enhancement given by the simulation results. Meanwhile, a hydrophilic–hydrophobic SERS-active immunosubstrate was prepared by linking antibodies onto the hydrophilic Ag-deposited sandpaper assembled with hydrophobic-treated filter paper. Such a novel substrate maintained excellent SERS homogeneity with quite a low relative standard deviation (RSD) of 12.85% arising from the elimination of the coffee-ring effect. The constructed sandwich immunoassay structure using the developed immunoprobe and the substrate was successfully employed in a specific assay for the ferritin (FER) antigen and exhibited an extensive dynamic linear range from 1 × 10−5 to 3 × 10−13 g mL−1 with an ultralow limit of detection (LOD) of 3.16 × 10−14 g mL−1. The simplicity and versatility of this strategy demonstrated its superior sensitivity for tumor markers and it can be expected to have potential practical application in the clinical diagnoses of cancer.