Enzyme-mimicking metal-organic framework-enabled microsensor for specific electrochemical monitoring in vivo

The pursuit of specific and stable electrochemical sensing techniques is vital for probing physiological and pathological processes in the living brain. Although the widespread adoption of natural enzymes is the cornerstone of current neurochemical recognition strategies, their sensing capabilities are susceptible to failure in complex biological environments. Herein, we have synthesized an ascorbate (AA) oxidase mimic, specifically a copper metal-organic framework functionalized with histidine and tryptophan (CuMOF-HT), using a chelation-assisted selective etching method. The simulant exhibits ultrafast AA sensing properties, with a response time of 0.1 seconds, along with exceptional selectivity and reliability. This is attributed to its robust Cu catalytic centers, specific amino acid recognition sites, and water-stable MOF architectures. Furthermore, the enzyme-like CuMOF-HT is integrated onto the tip of a minimally invasive acupuncture needle, forming a microelectrode that demonstrates superior electron transfer rates, enzymatic reactivity, and monitoring stability, making it ideal for subsequent in vivo AA sensing. As a demonstration, the microsensor can keenly track fluctuations in AA concentrations in mouse brain models such as epileptic seizures and cytotoxic edema. More importantly, the specific recognition strategy, which mimics the function of natural enzymes, holds broad applicability for analyzing a wide range of analytes in the field of brain science.