Stiff to Soft: A Protein‐Based Buffer Layer for Improving the Long‐Term Performance of Microneedle Sensors

ABSTRACT Long‐term monitoring of electrolyte dynamics is essential for managing chronic diseases. Conventional diagnostic tests are steadily evolving toward greater convenience, personalization, and accuracy, while wearable microneedle sensors offer a compelling alternative. However, their long‐term biocompatibility is hampered by the mechanical stiffness required to penetrate the skin. Here we report a crosslinking–recombination bovine serum albumin (CR‐BSA) coating that undergoes a unique stiff‐to‐soft transition, reconciling insertion capability with tissue compatibility. For Na + sensing, CR‐BSA serves as a functional buffer layer, delivering high sensitivity (70.6 µA/decade) and stability for more than 14 days, while significantly reducing inflammation and fibrosis compared with commercial Nafion coatings. CR‐BSA–coated microneedle sensors achieve reliable continuous monitoring of both acute and chronic hyponatremia and hypernatremia for over five days. This stiff‐to‐soft coating strategy overcomes a central barrier to microneedle sensor integration, advancing the prospects of long‐term, minimally invasive electrolyte monitoring for chronic disease management.