Intra-cochlear detection of Interleukin-6 using nanoMIPs embedded in a biodegradable matrix

A major challenge in cochlear implant (CI) therapy is postoperative inflammation, which can compromise long-term electrode function. Conventional interleukin-6 (IL-6) detection is challenging due to factors such as its inherent instability. In this study, we present a cost-effective detection strategy using epitope-specific molecularly imprinted polymer nanoparticles (nanoMIPs). These nanoMIPs enable sensitive detection of both IL-6 and its epitope, representing a scalable and economical alternative for inflammation monitoring. NanoMIPs were embedded in a biodegradable chitosan matrix and sprayed onto electrodes. To detect the biomarker, electrochemical impedance spectroscopy was used, a functionality which is already embedded in CI circuits. The sensors enabled reliable detection of IL-6 down to 29 pg/mL, which represents the lowest concentration investigated in this study, with improved sensitivity to the small epitope, as the larger protein causes higher impedance changes due to steric hindrance. Additionally, the sensors enabled concentration-dependent IL-6 detection in human perilymph samples down to 2 pg/mL, with higher signal responses for IL-6 relative to other perilymph components. Comparison with an immunoassay supported analytical accuracy and diagnostic relevance. The sensors were subsequently tested weekly for functionality over four weeks under physiological conditions, with nanoMIP:chitosan ratios of 1:6 and 1:8 being optimal for long-term monitoring. Moreover, the nanoMIPs have a diameter of 56 nm (a parameter that can influence physiological excretion) and cytotoxicity tests demonstrated their biocompatibility. This work presents an epitope-based nanoMIP sensor platform that overcomes economic and biochemical limitations of protein-based biosensors, enabling advanced, real-time self-monitoring CI systems for in-vivo inflammation tracking to reduce implant failure. • Detection of IL-6 at a minimal used concentration of 29 pg/mL. • Selectivity with 10:1 suppression of other perilymph signals. • Concentration-dependent IL-6 detection in human perilymph. • Continuous monitoring stable over 4 weeks under physiological conditions. • NanoMIPs (56 nm) show excellent biocompatibility and safety.