Dual‐Interface Nanopipette Sensor for Electrochemical Interferent Shielding

Enzyme‐based sensors have been widely utilized for their superior selectivity. However, they cannot distinguish the same kind of redox mediators from different sources. Typically, both the H₂O₂ produced in glucose (analyte) oxidation by glucose oxidase (GOD) and the endogenous H₂O₂ (interferent) existing in the detection system can be simultaneously measured, causing inaccurate results in glucose detection. To address this long‐standing and inevitable obstacle, we proposed a new sensor design strategy, a dual‐interface nanopipette sensor (DINS), to shield against the interferent electrochemically. The DINS comprised an anti‐interference interface at the orifice of the nanopipette, and a sensing interface located at the inner wall with a certain distance from the orifice. Anti‐interference interface, functioning as an “electrochemical Faraday cage”, electrochemically eliminated the interferents with high efficiency while allowed the target species to pass through and be detected at the sensing interface. With the synergy of these two independent interfaces, the GOD‐modified DINS (GOD‐DINS) allowed the accurate detection of intracellular glucose with effectively eliminating endogenous H₂O₂, facilitating the quantitative study on the glucose metabolism inside single cells. Furthermore, this DINS configuration is expected to accurately quantify more substances, and reveal complex crosstalk interactions between multiple species in the physiological, pathological and pharmacological research.