A novel electrochemical biosensor with molecularly imprinted polymers and aptamer-based sandwich assay for determining amyloid-β oligomer

Amyloid-β oligomers (AβOs) are highly toxic species involved in Alzheimer's disease (AD). Hence, a reliable detection method for AβOs, which are promising potential therapeutic targets and biomarkers for AD, is of great significance for improving the diagnosis of AD. Herein, a novel sandwich assay electrochemical biosensor was developed for highly sensitive and selective detection of AβO, using molecularly imprinted polymers (MIPs) and aptamer as the recognition element. Instead of using an antibody to recognize the AβO target molecules, the AβO in the samples were captured by the film of MIPs and the AβO-specific aptamer, forming a MIPs/target/aptamer sandwich assay for the highly selective detection of AβO. The AβO-specific aptamer was immobilized on the surface of core-shell nanoparticles that combined silver nanoparticles with silica nanoparticles (SiO₂@Ag NPs). The highly sensitive electrochemical signal from the sandwich assay was generated by using a small amount of AβO to trigger a large number of electrochemically active Ag NPs. Under the optimized conditions, the developed biosensor showed good linearity in the concentration range of 5 pg mL⁻¹ to 10 ng mL⁻¹ with a limit of detection of 1.22 pg mL⁻¹. The biosensor also showed excellent specificity, reproducibility and stability. In addition, the feasibility of detecting AβO in human serum was successfully verified, demonstrating the promising potential of this approach for clinical research and the early diagnosis of AD.