A review of binding properties of molecularly imprinted materials and strategies to suppress nonspecific recognition in complex matrices

Abstract

Molecularly imprinted polymers (MIPs) are tailor-made antibody mimics fabricated by moulding the three-dimensional shape and functional groups of a target molecule within a polymer network. The resulting imprinted cavities exhibit exquisite molecular recognition in both gas and liquid phases, in aqueous and nonaqueous media, and even under extreme pH conditions, where antibodies often fail to perform effectively. In some cases, the affinity and selectivity of MIPs are comparable to, or even surpass, those of antibodies. An ideal MIP should recognize a single target exclusively, exhibiting both high specificity and selectivity, and remain unoccupied in the absence of that target. In practice, however, this ideal behavior is rarely achieved due to nonspecific binding and the presence of multiple binding sites with varying affinities. In complex matrices, these nonspecific interactions may become pronounced, so requiring additional strategies to mitigate matrix effects prior to molecular recognition. This review summarizes the techniques employed to study the binding properties of MIPs, including batch-binding assays, spectroscopy/microscopy, and isothermal titration calorimetry (ITC). It also highlights the limitations of MIPs in developing analytical methods with real-world impact and discusses advanced strategies to suppress nonspecific recognition, including anti-fouling modifications (e.g., hydrophilic hairy MIPs, cladded MIPs) and emerging detection mechanisms. To the best of our knowledge, this is the first review to systematically investigate the binding properties of MIPs, instrumental approaches to evaluate the binding performance of MIPs, and the strategies developed to overcome nonspecific recognition.