Regenerable, closed-loop, nonenzymatic continuous glucose monitoring enabled by in situ electrochemical interfacial alkalinization

Continuous glucose monitoring in interstitial fluid (ISF) is important for diabetes management, but enzyme-based sensors can lose activity, while many nonenzymatic alternatives show optimal activity in alkaline media. Here we present a regenerable wrist-worn hollow microneedle platform for closed-loop nonenzymatic ISF glucose monitoring. Negative pressure extracts ISF into a detachable sensor cartridge that separates the tissue interface from the electrochemical sensing chamber and enables rinsing and reuse. A brief cathodic step triggers the hydrogen evolution reaction (HER) at an Au–Pt/Ni foam electrode, electrochemically generating a local alkaline interface for the subsequent glucose oxidation reaction (GOR). Integrated pH feedback regulates the HER–GOR sequence. In vitro and in vivo studies demonstrate rapid ISF extraction and quasi-continuous glucose monitoring in rats, with preliminary feasibility in one human participant. This work illustrates local microenvironment regulation as a strategy for enabling alkaline-dependent glucose electrocatalysis in near-neutral ISF. Continuous glucose monitoring is central to diabetes management, yet conventional testing provides only intermittent snapshots and may miss clinically important glycaemic fluctuations. Here, the authors present a wrist-worn hollow microneedle platform that combines active interstitial fluid extraction with nonenzymatic electrochemical glucose sensing in a wearable format. Its detachable microneedle cartridge enables independent cleaning or replacement, supporting quasi-continuous monitoring while improving practicality and long-term usability for wearable glucose tracking.