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Abstract：
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.
摘要：
鉴于工业生产和生活水平的不断提高，复杂生物样品系统的分析和检测变得越来越重要。常见的复杂生物样本包括血液，血清,唾液,还有尿液.目前,在复杂的生物系统中用于分离和识别目标分析物的主要方法是电泳，光谱学,和色谱。然而,因为生物样本由复杂的成分组成，它们受到基质效应的影响，这严重影响了准确性，灵敏度,以及所选分离分析技术的可靠性。除了矩阵效应，痕量成分的检测是具有挑战性的，因为样品中分析物的含量通常很低。此外，缺乏易于分析的样品富集和信号放大的合理策略。针对上述各种问题，研究人员将注意力集中在免疫亲和技术上，目的是基于抗原和抗体之间的特异性识别作用实现有效的样品分离。经过长期的发展,这项技术现在广泛应用于疾病诊断等领域，生物成像,食品检测,和重组蛋白纯化。常见的免疫亲和技术包括固相萃取（SPE）磁珠，亲和色谱柱，和酶联免疫吸附测定（ELISA）试剂盒。免疫亲和技术可以成功地减少或消除基质效应；然而，它们的应用受到许多缺点的限制，比如高成本，繁琐的制造程序，恶劣的操作条件，和配体泄漏。因此，开发一种有效和可靠的方法来解决基质效应仍然是一项具有挑战性的工作。类似于抗原和抗体以及酶和底物之间的相互作用，仿生分子印迹聚合物（MIP）具有很高的特异性和亲和力。此外，与许多其他生物大分子如抗原和适体相比，MIP表现出更高的稳定性，更低的成本,和更容易的制造策略，所有这些都有利于它们的应用。因此,分子印迹技术(MIT)在SPE中经常使用，色谱分离,和许多其他领域。随着MIT的发展,研究人员设计了不同类型的印迹策略，可以在复杂的生物样品中特异性提取目标分析物，同时避免基质效应。还深入研究了一些基于MIP技术的传统分离技术；这些技术中最常见的包括用于色谱的固定相和用于SPE的吸附剂。将MIT与高灵敏度检测技术相结合的分析方法在疾病诊断和生物成像等领域受到了广泛的关注。在这次审查中,我们强调了近年来发展的新的MIP战略，并描述了基于MIT的分离分析方法在色谱分离等领域的应用，SPE,诊断,生物成像,和蛋白质组学。还讨论了这些技术的缺点以及它们未来的发展前景。
