Ultrasensitive and Label-Free Detection of Phosphorylated Tau-217 Protein in Alzheimer's Disease Using Carbon Nanotube Field-Effect Transistor (CNT-FET) Biosensor.

Early diagnosis of Alzheimer's disease (AD) remains challenging due to the extremely low concentration of relevant biomarkers and the limited sensitivity of conventional detection techniques. In this study, we present a carbon nanotube field-effect transistor (CNT-FET) immunosensor for label-free detection of phosphorylated tau at threonine 217 (p-tau217). The device employs a Y2O3/HfO2 dielectric layer and gold nanoparticles (AuNPs) to improve biofunctionalization, with anti-p-tau217 antibodies immobilized on the CNT channels. In phosphate-buffered saline (PBS), the sensor exhibited a linear response over a concentration range of 3 fM to 30 pM (R2 = 0.973) and achieved a limit of detection (LOD) of 1.66 fM. The device demonstrated high selectivity, with a normalized signal response (NSR) for p-tau217 that was 5-6 times higher than for human serum albumin (HSA) and p-tau231, even at 1000-fold higher concentrations of these interferents. The sensor exhibited reproducibility with a relative standard deviation (RSD) of 4.8% (n = 9) and storage stability with only a 10% decrease in signal after 7 days at 4 °C. Mechanistic analysis indicated that the net positive charge and structural flexibility of the p-tau217 peptide led to a reduction in drain current upon binding, consistent with electrostatic gating effects in p-type CNT-FETs. Current limitations include the absence of standardized p-tau217 reference materials. Future work will focus on validation with clinical samples. This CNT-FET platform enables rapid, minimally invasive detection of p-tau217 and holds strong potential for integration into clinical workflows to facilitate early AD diagnosis.