Amyloid-like nanofilm-decorated antifouling field effect transistor biosensor array for enhancing Alzheimer's disease diagnosis.

Alzheimer's disease (AD) is a common neurodegenerative disorder. Compared to the limited specificity of single-biomarker detection, the combined detection of multiple biomarkers can significantly improve the accuracy of AD diagnosis. In this study, a field-effect transistor (FET) biosensor array integrating four independently functionalized regions was fabricated by modifying carbon nanotube (CNT) surfaces with amyloid bovine serum albumin (AL-BSA) nanofilm as an antifouling layer, enabling the simultaneous detection of multiple tau proteins. The proposed FET biosensor exhibited excellent anti-fouling performance while maintaining high sensitivity, with detection limits as low as 3.3 fg/mL, 0.17 fg/mL, 0.02 fg/mL, and 2.5 fg/mL for p-tau181, p-tau217, p-tau231, and t-tau, respectively. Evaluation of 35 clinical serum samples indicated that p-tau181 outperformed the other three tau proteins as an AD diagnostic biomarker. By further incorporating a support vector machine (SVM)-based machine learning algorithm and employing multi-biomarker co-detection, the accuracy of AD diagnosis can be improved to nearly 100%. This study provides a novel strategy for array FET biosensors with high clinical application potential for the precise detection of AD.