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

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.