Polypyrrole-Coated Microneedle Platform for Offline Electrochemical Detection of Interferon-Alpha in Interstitial...

Monitoring cytokines, such as interferon-alpha (IFN-α), is essential for assessing immune responses during viral infections and in immunotherapies. Here, we report the development of a microneedle-based electrochemical biosensor for detecting IFN-α in interstitial fluid (ISF), which combines minimally invasive sampling with label-free, offline analysis. The device comprises polycaprolactone (PCL) microneedles fabricated via 3D-printed molds and thermocompression, coated with polypyrrole (PPy) to enable conductivity and biomolecule immobilization. A range of PPy concentrations (10-200 mmol·L^-1) was evaluated to optimize performance. Structural and physicochemical analyses revealed that intermediate PPy content (50 mmol·L^-1) ensured optimal surface roughness, porosity (29.7%), and electroactive area, while preserving mechanical integrity and biocompatibility. Electrochemical impedance spectroscopy and cyclic voltammetry demonstrated a sensitive and specific response to IFN-α, with a limit of detection of 8.6 pg/mL and a linear range of up to 1000 pg/mL. Selectivity studies in gelatin matrices and cytotoxicity assays confirmed the robust performance and safety of the system. The biosensor operates via skin insertion, immunocapture, and analyte quantification after removal, enabling offline detection without complex instrumentation. These results demonstrate the potential of PPy-coated microneedles as cost-effective, scalable, and minimally invasive platforms for cytokine monitoring in point-of-care diagnostics.