Synthesis-free swellable hydrogel microneedles for rapid interstitial fluid extraction and on-site glucose detection via an electrochemical biosensor system

Current methods to detect biomarkers often involve lengthy turnaround times due to the need for blood extraction and subsequent laboratory analysis. Microneedles (MNs) offer a minimally invasive solution to access the interstitial fluid (ISF); however, they are limited by challenges such as hazardous material synthesis, insertion techniques, small ISF volumes (2–5 μL), and lengthy extraction time. This study presents a novel swellable MN patch combined with a biosensing platform to enable on-site glucose detection through an optimized applicator-assisted insertion method. The highly efficient MN patch extracts up to 7.06 ± 0.44 μL of ISF in 5 min without the typical post-processing instruments such as vacuum or suction. The extracted ISF is applied to the modified electrodes, which detect the target biomarker (glucose) with high sensitivity (9.68 μA mM −1 cm −2 ) and a low detection limit (0.08 mM) under optimized conditions. In addition to effectively recovering glucose molecules, the MN patch demonstrates enhanced efficiency and penetration depth, with a critical correlation established between the volume of extracted ISF and the glucose recovery rate, as validated through comprehensive in-vitro and ex-vivo tests. This MN-based biosensing approach could offer a viable alternative to traditional blood tests, glucometers, finger-prick methods, or continuous monitoring devices. • Microneedle patch rapidly extracted 7.06 μL of interstitial fluid in 5 min. • The applicator improved microneedle penetration and fluid extraction. • The volume of fluid extracted impacts biomarker recovery, such as glucose. • On-site glucose detection with high sensitivity and low detection limit was achieved. • Microneedle-based biosensors are a promising substitute for blood tests, finger pricks, and wearables.