Vacancy-Regulated Prussian Blue-Based Hollow Microneedle Biosensor for Interface Protective Glucose Monitoring in Interstitial Fluid

Although continuous glucose monitoring (CGM) is essential for precise and personalized diabetes management, conventional approaches rely on invasive finger-prick blood sampling. Furthermore, existing CGM systems suffer from major limitations, including user discomfort, biofouling of implanted sensors, and unstable sensing components. To address these challenges, we present a hollow microneedle-based (MN) biosensor that minimally invasively accesses the interstitial fluid (ISF) for in-situ glucose monitoring. The MN biosensor integrates a miniaturized three-electrode system within the lumen of MNs filled with synthesized vacancy-regulated Prussian blue intercalated thermoplastic graphite composite (GP@PB). The GP@PB composite, prepared through a precipitation-conversion strategy, exhibits hierarchical and hollow morphology that provides a large active surface area and mitigates structural degradation. The sensing interface is further protected by an external MN body and a poly(methyl methacrylate) (PMMA) substrate, both of which greatly improve mechanical robustness and electrochemical stability. The MN biosensor enables real-time and continuous glucose monitoring in ISF with great sensitivity, selectivity, biocompatibility, and long-term reliability. In vivo studies in rat models validate the real-world feasibility of the biosensor by providing dynamic analysis of ISF glucose in response to metabolic variations, showing a strong correlation with gold-standard results measured using commercial devices. This work facilitates the clinical translation of minimally invasive CGM in personalized diabetes management, highlighting the potential of wearable electronics toward chronic disease healthcare.