Machine Learning-Driven Dual-Recognition Magnetic Imprinted Polymers: Host-Guest/Aptamer Synergy Enabling...

To address the challenges in detecting chloramphenicol (CAP) in complex food matrices, this study developed a magnetic solid-phase microextraction coupled with a high-performance liquid chromatography (MSPME-HPLC) system that integrates machine learning and molecular recognition. The system employs magnetic SiO₂@Fe₃O₄ nanoparticles as the carrier and combines the dual recognition functions of carboxylated pillar[5]arene (CP[5]A) and aptamer (Apt) to create a nanocomposite separation material, Apt-MIP-CP[5]A@SiO₂@Fe₃O₄ (AC-MSF). Bayesian optimization and six machine learning models (e.g., XGBoost, SVM) were utilized to dynamically optimize polymerization and extraction conditions. SHAP interpretability analysis identified aptamer dosage and Mg²⁺ concentration as critical parameters, with ML-recommended conditions reducing cross-linker usage by 22.2% and polymerization time by 57%. Kinetic simulations elucidated the synergistic recognition mechanism: CAP's nitrobenzene group embeds in CP[5]A's cavity via strong nonbonded interactions (total energy: -50 to -250 kJ/mol) and H-bond networks (1-4 bonds), while the aptamer binds CAP specifically at DT-18 via H-bonding (ΔG: -34.64 kcal/mol). Circular dichroism spectroscopy confirmed the independent yet synergistic operation of the dual recognition modes, with a synergy factor of 1.4. The system achieved a detection limit of 0.69 μg/L (linear range: 0.004-0.2 mg/L) and recoveries of 85.0%-96.2% in honey, milk, and egg samples.