Carboxyl-enriched molecularly imprinted interface with enhanced electrostatic binding for ultrasensitive oxytocin detection in a portable electrochemical platform

Innovative application of a monomer for molecularly imprinted polymer (MIP) functionality. • Portable and miniaturized device enable point-of-care testing of oxytocin anytime and anywhere. • Comparison of pyrrole and P2CA as functional monomers of MIP. • The detection results of OT sensor showed a strong correlation with those obtained by ELISA. Oxytocin is a key peptide hormone regulating pregnancy and parturition, yet its accurate quantification remains challenging due to its ultra-low abundance and poor stability. Here, we report a portable electrochemical sensing platform based on an electrostatically engineered molecularly imprinted polymer interface for ultrasensitive OT detection in maternal serum. Pyrrole-2-carboxylic acid (P2CA) was rationally selected as the functional monomer to introduce carboxyl groups that enhance interfacial negative charge density, thereby strengthening electrostatic interactions with OT and improving binding affinity. Compared with conventional pyrrole-based systems, the P2CA-based MIP sensor exhibits a wide linear range of 10 - 1000 pg/mL with a low detection limit of 1.15 pg/mL. Molecular simulations combined with high-ionic-strength experiments reveal that electrostatic adsorption dominates the recognition mechanism and underpins the enhanced sensitivity. Integration of petal-shaped gold nanoparticles further increases surface area and conductivity, which amplify the electrochemical signal. The sensor is incorporated into a compact portable device enabling rapid detection (<15 min) with microliter sample volumes (30 μL). It demonstrates excellent selectivity, stability, and mechanical robustness. This system was validated using clinical serum samples, which show strong agreement with ELISA (r > 0.95). These results highlight its potential for point-of-care diagnostics and maternal health monitoring. Download: Download high-res image (337KB) Download: Download full-size image