A Simple Sandwich Electrochemical Immunosensor for Rapid Detection of the Alzheimer’s Disease Biomarker Tau Protein

Abstract

As a typical biomarker of Alzheimer’s disease, rapid and specific detection of tau protein can help improve the early diagnosis and prognosis of the disease. In this study, a simple sandwich electrochemical immunosensor was developed for rapid detection of tau protein. Primary monoclonal antibodies (mAb1) against the middle domain of tau protein (amino acids 189–195) were immobilized on the gold electrode surface through a self-assembled monolayer (SAM) of 3,3′-dithiobis (sulfosuccinimidyl propionate) (DTSSP). Then the tau protein was captured through the specific adsorption between the antigen and the antibody, resulting in a change in the impedance. Secondary monoclonal antibodies (mAb2) against the N-terminal region of tau protein were used for further amplification of the binding reaction between mAb1 and tau protein. A linear correlation between the total change in impedance and the logarithm of tau concentration was found from 2 × 10−6 mg mL−1 to 2 × 10−3 mg mL−1, with a detection limit as low as 1 × 10−6 mg mL−1. No significant interference was observed from human serum albumin. Furthermore, the fabricated sandwich immunosensor successfully detected target tau protein in artificial cerebrospinal fluid (aCSF) samples, indicating good potential for clinical applications in the future.