A SERS-Based Sandwich Assay for Ultrasensitive and Selective Detection of Alzheimer's Tau Protein

In this study, a simple and highly selective homogeneous sandwich assay was developed for fast and ultrasensitive detection of the tau protein using a combination of monoclonal antitau functionalized hybrid magnetic nanoparticles and polyclonal antitau immobilized gold nanoparticles as the recognition and surface-enhanced Raman scattering (SERS) component, respectively. The magnetic silica particles were first coated with poly(2-hydroxyethyl methacrylate) via surface-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization and then biofunctionalized with monoclonal antitau, which are both specific for tau and can be collected via a simple magnet. After separating tau from the sample matrix, they were sandwiched with the SERS substrate composed of polyclonal antitau and 5,5-dithiobis(2-dinitrobenzoic acid); on gold nanoparticles. The correlation between the tau concentration and SEAS signal was found to be linear within the range of 25 EM to 500 nM. The limit of detection for the sandwich assay is less than 25 fM. Moreover, the sandwich assay was also evaluated for investigating the tau specificity on bovine serum albumin and immunoglobulin G.