Single-use microneedle biosensor for detecting clinically relevant glucose in interstitial fluid

Effective diabetes management is increasingly shifting toward minimally invasive technologies that enable frequent and reliable assessment of glucose levels in interstitial fluid (ISF), enabling more informed and patient-centered monitoring. However, current approaches to glucose detection rely heavily on invasive blood-based glucometers or complex wearable devices for continuous monitoring. This study introduces a complete biosensing system using a novel swellable biocompatible microneedle (MN) array combined with chemically modified screen-printed electrodes (SPEs). Optimization of ISF collection was achieved using a customized applicator with variable vibration, which resulted in ISF uptake of 6.55 ± 0.47 μL (0Hz) and 7.06 ± 0.44 μL (100 Hz) within 5 min of application. The Prussian Blue/chitosan-SWCNT/GO_x/Nafion-modified SPE shows excellent sensitivity of 12.26 μA mM^-1 cm^-2, a detection limit of 0.08 mM, and high selectivity against common ISF interferents. In vitro and ex vivo validation across clinically relevant glucose concentrations showed strong linearity (R² = 0.989 and 0.978, respectively), with recovery exceeding 70 % in vitro and 50 % ex vivo compared with a commercial glucometer. This minimally invasive MN SPE platform enables reliable glucose quantification from microliter ISF volumes and shows strong potential for future multi-biomarker, point-of-care monitoring.