Self-Extracting Dextran-Based Hydrogel Microneedle Arrays with an Interpenetrating Bioelectroenzymatic Sensor for Transdermal Monitoring with Matrix Protection.

Abstract

Continuous glucose monitors have revolutionized diabetes management, yet such devices are limited by their cost, invasiveness, and stability. Microneedle (MN) arrays could offer improved comfort compared to invasive implanted or mm-sized needle devices, but such arrays are hampered by complex fabrication processes, limited mechanical and sensor stability, and/or cytotoxicity concerns. This work demonstrates the first crosslinked hydrogel microneedle-bioelectroenzymatic sensor arrays capable of biomarker extraction and robust transdermal continuous monitoring in artificial interstitial fluid for 10 days. The fabrication process via micromolding of dextran-methacrylate (Dex-MA) and dry-state visible light crosslinking is simple and permits the robust fixation of diverse prefabricated electrodes in a single array. Dry-state crosslinking minimized material shrinkage to enable the formation of resistant Dex-MA microneedles with shape control and reproducibility. The polymer substitution level (9-62%) and mass content (10-30 wt%) affect the mechanical, swelling, and bioelectrocatalytic properties of the integrated sensors. Crosslinked Dex-MA hydrogel matrices provide beneficial cytotoxicity protection and flux-limiting membrane properties to the integrated second generation dehydrogenase-based nanostructured buckypaper biosensor and Ag/AgCl reference electrodes. Polysaccharide-based microneedle technology with encapsulated porous bioelectrodes promise to be a valuable alternative to more invasive devices for safer and longer-term biomarker monitoring.