Photoelectrochemical highly efficient detection of β-amyloid 1-42 based on in-situ grown donor-acceptor covalent organic frameworks combined with dual-aptamer sandwich amplification strategy.

A highly sensitive dual-aptamer sandwich-type photoelectrochemical (PEC) sensor was developed for detecting β-amyloid 1-42 (Aβ42), whose abnormal accumulation in the brain has been considered as the molecular driver of Alzheimer's (AD) pathogenesis and progression. The sensor was constructed based on in-situ grown covalent organic frameworks (COFs) films. Using a simple room-temperature in-situ synthesis method, TAPB-TFPA COFs (TAPB: 1,3,5-tris(4-aminophenyl)benzene, TFPA: tris(4-formylphenyl)amine) films were successfully fabricated on indium tin oxide (ITO) electrodes. By exploiting the specific recognition between two aptamers and Aβ42, a sandwich complex was formed on the electrode surface. This architecture induces pronounced steric hindrance that impedes interfacial charge transfer, resulting in substantial attenuation of the photocurrent response and enabling highly specific detection of Aβ42. The PEC sensing platform exhibited a good linear response to Aβ42 in the concentration range of 1 pM to 1 μM, with a detection limit of 0.86 pM. Meanwhile, the sensor possessed excellent selectivity, reproducibility, and stability, and showed satisfactory detection accuracy in real human serum samples. This work provides a novel method for the detection of Aβ42 in the early diagnosis of AD, and also sheds light on the construction of high-performance PEC sensors and the application expansion of COF materials.