Abstract:

Molecularly imprinted technology （MIT） represents an advanced synthetic strategy that emulates biological recognition mechanisms， such as antigen-antibody or enzyme-substrate interactions， by creating three-dimensional cavity-like structures through the directional assembly of functional monomers around a template molecule. This process generates spatial and functional complementarity， enabling highly selective recognition of target species. Molecularly imprinted polymers （MIPs）， often described as “synthetic antibodies”， overcome the intrinsic limitations of natural biomolecules by offering superior selectivity， robustness， cost-effectiveness， and structural tunability. These features position MIPs as promising alternatives to natural antibodies in targeted sensing and drug delivery， with broad applications across biomedical， environmental， and pharmaceutical domains， including pollutant detection， and food safety monitoring. Despite substantial progress， key challenges remain， such as uneven imprinting layers， template residue， and limited aqueous compatibility in macromolecular imprinting. Furthermore， issues of industrial scalability， unclear recognition mechanisms， and insufficient integration with emerging fields such as microfluidics and artificial intelligence have hindered large-scale translation. In recent years， our research team has systematically advanced MIT through a tri-dimensional strategy encompassing high-throughput monomer screening， mechanistic elucidation of molecular recognition， and directional assembly of functional units. By establishing a standardized monomer library and integrating molecular dynamics simulations， we achieved precise material design under complex conditions. Through process optimization and material innovation， we developed a highly efficient solid-phase surface imprinting method that enables the fabrication of smart MIPs with stimuli-responsive properties （e.g.， temperature and pH）. These MIPs exhibit markedly enhanced binding affinity， with equilibrium dissociation constant （K_D） reaching 10^-12 mol/L， over four orders of magnitude higher than those of non-imprinted polymers （NIPs）. Building on these advances， we established cross-disciplinary application platforms， including affinity-based protein separation and purification systems capable of efficient dual-enzyme cascade immobilization and inactivated enzyme renaturation. In the biomedical domain， we developed ultrasensitive biosensing methods achieving picogram-level detection of heart failure biomarkers and single-digit （≈5 cells/mL） detection of cancer cells in whole blood， extending these methods toward integrated tumor theranostics and microbial community regulation. This paper comprehensively summarizes our team’s recent innovations in the rational design， functionalized fabrication， and cross-disciplinary applications of MIPs， spanning biosensing， biocatalysis， and biomedical diagnostics/therapeutics， while contextualizing these within the latest global advances in biomedicine and catalysis. Looking forward， we identify three strategic research frontiers for next-generation MIT. （i） Smart responsive material systems： design MIPs capable of multi-stimuli responsiveness （e.g.， magnetic， photothermal， and pH cues） to enable programmable drug release， real-time signal monitoring， and dynamic feedback regulation. （ii） Quantitative modeling of dynamic recognition： establish multi-scale theoretical frameworks to elucidate coupling between cavity flexibility and target conformational dynamics， guiding structure optimization and function-oriented design of adaptive MIPs. （iii） Integrated intelligent theranostic platforms： integrate microfluidics and biomimetic recognition modules into closed-loop systems capable of biomarker detection， targeted delivery， and real-time therapeutic feedback， bridging the gap between in vitro sensing and in vivo precision intervention. Synergistic advancement along these trajectories will empower MIT to transcend its role as a “static recognition material” and evolve into an intelligent， adaptive， and systematic biomedical platform. Such evolution will accelerate the translation of MIT innovations from laboratory to clinic and industry， propelling progress in personalized medicine， point-of-care diagnostics， and synthetic biology， and yielding profound scientific and societal impact.

Key words: molecular imprinting polymers（MIP）, stimuli-responsive materials, biocatalysis, medical diagnosis and therapy, high-throughput screening and specific molecular recognition