NanoGold-enhanced biomimetic sensor for Tau-441 protein detection in serum for Alzheimer's disease diagnosis

Alzheimer's disease (AD) is the leading cause of dementia, and early identification of molecular biomarkers in blood offers a promising avenue for diagnosis and monitoring treatment. Tau-441 stands out as a particularly promising biomarker among the potential molecular targets. This research describes the development of a highly sensitive and cost-effective biomimetic sensor, capable of selectively detecting Tau-441 at femtomolar concentrations. This is achieved through the synergistic combination of gold nanoparticles (AuNPs) with molecularly imprinted polymer (MIP) technology. The MIP layer was sensitised by electropolymerising phenylenediamine (o-PDA) in the presence of Tau-441 and AuNPs onto a gold screen-printed electrode (Au-SPE) using cyclic voltammetry (CV). After polymerisation, the entrapped proteins were removed by proteolytic digestion, generating well-defined imprinted cavities within the polymer matrix. Scanning electron microscopy (SEM) and Raman analysis were conducted to monitor the surface modification of the Au-SPE working electrode. The device displayed linear responses to Tau-441 protein within the range 2.0 pg mL^-1 to 200 ng mL^-1, with a limit of detection of 1.51 fg mL^-1. The analytical performance of the device was validated in complex matrices, including Cormay serum and cell media from primary cultures of hippocampal neurons, using a competitive assay. The platform showed high sensitivity, good reproducibility, and reliable performance in biologically relevant media, demonstrating strong robustness. Its excellent analytical characteristics, together with the potential for integration into portable electrochemical devices, make this sensor a promising tool for rapid and accurate point-of-care testing, enhancing the detection and monitoring of AD.