Imprinted probes achieve highly specific recognition of L-phenylalanine

Molecularly imprinted polymers (MIPs) for amphiphilic small molecules are typically synthesized using a “monolithic imprinting” approach and enable target monolithic recognition, but suffer from non-specific adsorption in complex samples, thereby limiting specificity. To address these limitations, a novel “imprinted probe recognition” mode was proposed for the first time. According to the hydrophilic and hydrophobic structures of molecules as templates respectively, two kinds of MIPs were fabricated, and the “imprinted substrate–target analyte–imprinted probe (with electrochemical signals)” recognition mode was constructed. As a proof of concept, L-phenylalanine was selected as a model analyte for verification. The imprinting factor (evaluating specificity) of “imprinted probe recognition” is increased from 3.63 to 5.47 compared with “monolithic recognition”, and the specificity is improved by more than 50 %. This technology enables effective labeling of amphiphilic small molecules with substantially improved specificity in various environments, providing a general and feasible concept for the accurate recognition of small molecules.