Multi-engineered Graphene Extended-Gate Field-Effect Transistor for Peroxynitrite Sensing in Alzheimer's Disease

The expression of β-amyloid peptides (Aβ), a pathological indicator of Alzheimer's disease (AD), was reported to be inapparent in the early stage of AD. While peroxynitrite (ONOO^-) is produced excessively and emerges earlier than Aβ plaques in the progression of AD, it is thus significant to sensitively detect ONOO^- for early diagnosis of AD and its pathological research. Herein, we unveiled an integrated sensor for monitoring ONOO^-, which consisted of a commercially available field-effect transistor (FET) and a high-performance multi-engineered graphene extended-gate (EG) electrode. In the configuration of the presented EG electrode, laser-induced graphene (LIG) intercalated with MnO₂ nanoparticles (MnO₂/LIG) can improve the electrical properties of LIG and the sensitivity of the sensor, and graphene oxide (GO)-MnO₂/Hemin nanozyme with ONOO^- isomerase activity can selectively trigger the isomerization of ONOO^- to NO₃^-. With this synergistic effect, our EG-FET sensor can respond to the ONOO^- with high sensitivity and selectivity. Moreover, taking advantage of our EG-FET sensor, we modularly assembled a portable sensing platform for wireless tracking ONOO^- levels in the brain tissue of AD transgenic mice at earlier stages before massive Aβ plaques appeared, and we systematically explored the complex role of ONOO^- in the occurrence and development of AD.