Detection of Aβ40 in cerebrospinal fluid and plasma of Alzheimer's disease patients using photoelectrochemical biosensors

An ultra-sensitive photoelectrochemical (PEC) biosensor for amyloid-beta 40 (A beta 40), a biomarker for Alzheimer's disease (AD), was developed using g-C3N4 modified with gold nanoparticles (Au NPs) to form Au-C3N4. This was further combined with TiO2 to create a tightly bonded TiO2/Au-C3N4 heterojunction, leading to a highly responsive photocatalytic process. Furthermore, the incorporation of noble metal Au NPs not only enhances photocurrent generation but also securely immobilizes the aptamer through Au-S bonds, providing additional surface binding sites. This significantly increases the sensor's capture efficiency. The sensor exhibited excellent performance, featuring a linear detection range from 10(-15) to 10(-11) g/mL and a remarkably low detection limit (LOD) of 0.33 fg/mL. Moreover, the validation in clinical settings demonstrated the successful detection in real cerebrospinal fluid (CSF) and plasma, from AD patients and non-AD controls. These results strongly suggest that PEC biosensors possess significant potential as cost-effective and highly sensitive tools for detecting ultra-trace substances in human body fluids, which offers promising opportunities for the early screening of high-risk populations for AD.