▎ 摘　　要

Opioid neuropeptides play a significant role in pain perception, appetite regulation, sleep, memory, and learning. Advances in understanding of opioid peptide physiology are held back by the lack of methodologies for real-time quantification of affinities and kinetics of the opioid neuropeptide receptor interaction at levels typical of endogenous secretion (<50 pM) in biosolutions with physiological ionic strength. To address this challenge, we developed all electronic opioid neuropeptide biosensors based on graphene microelectrodes functionalized with a computationally redesigned water-soluble mu-opioid receptor. We used the functionalized microelectrode in a bias-free charge measurement configuration to measure the binding kinetics and equilibrium binding properties of the engineered receptor with [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin and beta-endorphin at picomolar levels in real time.