Molecularly imprinted polymers for biomarker detection: Advances in design, modeling, and sensing strategies
M. M. Abdelhamied, Soumya Rajpal, Prashant Mishra, Christine Kranz, Boris Mizaikoff
Abstract
Molecularly imprinted polymers (MIPs) are highly attractive for biomarker detection by offering highly stable, selective, and tailorable synthetic receptors that overcome key limitations of traditional biorecognition elements. As the demand for rapid, sensitive, and multiplexed diagnostic tools intensifies, MIPs have gained considerable attention for their ability to recognize structurally diverse and low-abundance biomarkers. We critically evaluate next-generation imprinting techniques, such as solid-phase synthesis for the development of high-affinity nanoMIPs, electrospinning for producing high-surface-area fibrous MIPs, and 3D-imprinting for creating structured MIPs with improved kinetic properties. Special attention is given to innovative strategies that significantly enhance MIP functionality: multi-template imprinting for the simultaneous detection of multiple analytes, snapshot imprinting for capturing complex epitopes, hybrid systems that integrate MIPs with aptamers or antibodies for synergistic effects, and boronate-affinity imprinting methods for selective glycoprotein recognition. Additionally, we discuss how these cutting-edge design strategies are being further empowered by computational modeling and seamlessly integrated into novel transducer platforms, bridging the gap between materials innovation and functional device performance. We also address the remaining challenges that must be overcome to enable widespread clinical translation and real-world deployment of MIP-based biosensors.