Electrochemical/pH Dual-Responsive Smart MOF-Based Gated Sensor for Fluorescence Detection of Acetylcholinesterase Activity.

It is still difficult for conventional gated sensors to be applied in practical scenarios because of formidable challenges, including complex preparation, premature leakage, protracted response, and low sensitivity and accuracy. Herein, we present a novel design strategy to construct smart MOF-based gated sensors by well-integrating the stimuli responsiveness of the support and the target responsiveness of the gatekeeper in a single MOF-based gated sensing platform. Specifically, an electroresponsive Zr-MOF, UiO-67-EE, served as the support to adaptively encapsulate the fluorescent reporter via dynamic host-guest charge-transfer interaction. It enabled controlled release of the loaded reporter by electrochemical stimuli, which, on the one hand, lowered the background signal to ensure sensitivity and accuracy and, on the other hand, shortened the response time because the release was effectively transformed from a passive to an on-command format. Additionally, pH-sensitive cDNA was easily modified onto the MOF surface, whose reversible conformational transition under alternate pH conditions modulated the opening/closing of the MOF pores the reporter traversed, thus constituting a straightforward basis for pH-relevant biosensing applications. Taking advantage of the excellent dual-responsive feature of the presented gated sensing platform, it was exploited for sensitive detection of acetylcholinesterase activity and accurate evaluation of its inhibitor efficiency based on pH changes during acetylcholine hydrolysis by quantitatively monitoring the fluorescence of the released reporter. This study provides new insights for tackling key issues in the development of high-performance gated sensors that would advance their practical applications.