Recent advances of molecular imprinting technology for the separation and recognition of complex biological sample systems

Given continuous improvements in industrial production and living standards, the analysis and detection of complex biological sample systems has become increasingly important. Common complex biological samples include blood, serum, saliva, and urine. At present, the main methods used to separate and recognize target analytes in complex biological systems are electrophoresis, spectroscopy, and chromatography. However, because biological samples consist of complex components, they suffer from the matrix effect, which seriously affects the accuracy, sensitivity, and reliability of the selected separation analysis technique. In addition to the matrix effect, the detection of trace components is challenging because the content of the analyte in the sample is usually very low. Moreover, reasonable strategies for sample enrichment and signal amplification for easy analysis are lacking. In response to the various issues described above, researchers have focused their attention on immuno-affinity technology with the aim of achieving efficient sample separation based on the specific recognition effect between antigens and antibodies. Following a long period of development, this technology is now widely used in fields such as disease diagnosis, bioimaging, food testing, and recombinant protein purification. Common immuno-affinity technologies include solid-phase extraction (SPE) magnetic beads, affinity chromatography columns, and enzyme linked immunosorbent assay (ELISA) kits. Immuno-affinity techniques can successfully reduce or eliminate the matrix effect; however, their applications are limited by a number of disadvantages, such as high costs, tedious fabrication procedures, harsh operating conditions, and ligand leakage. Thus, developing an effective and reliable method that can address the matrix effect remains a challenging endeavor. Similar to the interactions between antigens and antibodies as well as enzymes and substrates, biomimetic molecularly imprinted polymers (MIPs) exhibit high specificity and affinity. Furthermore, compared with many other biomacromolecules such as antigens and aptamers, MIPs demonstrate higher stability, lower cost, and easier fabrication strategies, all of which are advantageous to their application. Therefore, molecular imprinting technology (MIT) is frequently used in SPE, chromatographic separation, and many other fields. With the development of MIT, researchers have engineered different types of imprinting strategies that can specifically extract the target analyte in complex biological samples while simultaneously avoiding the matrix effect. Some traditional separation technologies based on MIP technology have also been studied in depth; the most common of these technologies include stationary phases used for chromatography and adsorbents for SPE. Analytical methods that combine MIT with highly sensitive detection technologies have received wide interest in fields such as disease diagnosis and bioimaging. In this review, we highlight the new MIP strategies developed in recent years, and describe the applications of MIT-based separation analysis methods in fields including chromatographic separation, SPE, diagnosis, bioimaging, and proteomics. The drawbacks of these techniques as well as their future development prospects are also discussed.