An arginine chiral sensor based on walnut-like molecularly imprinted polymers

Enantioselective discrimination of chiral amino acids is critically important across biomedicine, pharmacology, and food science, given the distinct biological roles of D- and L-enantiomers. In this study, a novel chiral sensor based on walnut-shaped molecularly imprinted polymers (w-MIPs) was developed for the highly sensitive and selective recognition of D- and L-arginine (Arg). The unique core–shell w-MIPs architecture, containing targeted binding sites, was synthesized via tailored precipitation polymerization and characterized using transmission electron microscopy (TEM), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FT-IR). The sensing mechanism for Arg detection involves two consecutive steps. First, Arg molecules which diffuse to specific w-MIPs recognition sites are preferentially captured by the specific w-MIPs recognition sites. Subsequently, the Arg molecules captured on the electrode surface underwent oxidation. Electrochemical characterization demonstrated the exceptional performance of the chiral sensor, exhibiting a broad linear range of 0.005–5000 nM and ultra-low detection limits (1.34 pM for L-Arg; 1.20 pM for D-Arg). Importantly, the sensor exhibits high binding affinity for L-Arg, enabling effective chiral discrimination. This capability was validated by accurately determining L-Arg levels in pig serum (recovery: 95.0–103.0%), with results showing excellent agreement with HPLC analysis. This work establishes w-MIPs as a powerful platform for chiral sensing, offering significant potential for applications in drug monitoring, clinical diagnostics, and biochemical analysis.