Development and human samples validation of a plasma pTau‑217 electrochemical sensor for Alzheimer's detection in Vietnamese patients.

A multi-walled carbon nanotube - poly (allylamine hydrochloride acid)/platinum nanoparticle (MWCNT-PAH/PtNP) biosensor for phosphorylated Tau-217 (pTau-217) detection and validated using Alzheimer’s disease (AD) plasma samples is described. Morphological characterization confirmed successful deposition of MWCNT-PAH/PtNP, which enhanced the sensor’s surface height range (bare sensor |∆| = 2.2 μm vs. modified sensor |∆| = 5.7 μm) and electrochemical properties. The sensor achieved a detection limit of 9.85 pg/mL by cyclic voltammetry (CV) and 3.83 pg/mL by chronoamperometry (CA), and could detect pTau-217 in the presence of interfering molecules and in complex protein-rich matrices such as fetal bovine serum (FBS). When validated on clinical samples, the sensor could distinguish AD from cognitive normal (CN ) samples more effectively than ELISA (AUCCV: 90.75%; AUCCA: 87.13%; AUCELISA: 52.52%). Subgroup analysis revealed that sensor output primarily reflected disease status, with minimal confounding effects from demographic or social factors. However, a key limitation is that current intensity cannot be directly converted into plasma pTau-217 concentration, restricting the sensor to qualitative AD screening rather than precise quantification. Taken together, this biosensor holds great potential as a cost-effective tool for distinguishing AD and CN plasma samples, with promising prospects for on-site application.