[Recent advances in applications of fragment/dummy molecularly imprinted polymers]

Se Pu. 2021 Feb;39(2):134-141. doi: 10.3724/SP.J.1123.2020.08008.
[Article in Chinese]

Abstract

Molecularly imprinted polymers (MIPs) are designed to mimic the specific binding principle of enzymes to substrates or antigens to antibodies, while holding several advantages such as structure predictability, recognition specificity, easy preparation, low cost, high physical robustness, and thermal stability. Therefore, they have been widely applied in many fields including sample preparation (pretreatment), sensing analysis (chemo/biosensors), biomedicine, and environment/food analysis. To date, several strategies were developed for MIPs preparation, aiming to simplify the preparation process and/or improve the properties of the polymers, greatly broadening its usability. The exploration in various advanced imprinting strategies and their combinational use has become a research hotspot in MIPs preparation, among which the fragment imprinting strategy and the dummy template imprinting strategy are especially favored. Fragment imprinting, also called segment imprinting, uses a partial structure of the target molecule as a pseudo-template to prepare MIPs. This strategy is useful to target molecules that are not easy to obtain or that are too large to be used as templates, providing a feasible method for imprinting target analytes that are easy to inactivate or infect, as well as macromolecules that are difficult to imprint. In turn, dummy template imprinting uses molecules with structure, shape, and size similar to the target analytes as templates for imprinting. Because the target is not directly used as a template, this strategy can overcome problems of template leakage, as well as solve target molecule-related difficulties as they can be expensive, infectious, flammable, explosive, or chemically instable. This mini-review compiles information of several articles published in the last four years across ACS, Elsevier, RSC, and other databases, summarizing the most recent advances in the application of fragment/dummy template MIPs (FMIPs/DMIPs). Herein, the biomedical application of FMIPs is mainly addressed as a strategy for the detection of proteins and microorganisms, and the application of FMIPs in the field of food analysis is also explored. In recent years, the imprinting of mammalian cells has made some progress in the application of FMIPs. Mammalian cells, especially cancer cells, overexpress some proteins and sugars, which are good fragment templates. Consequently, the fragment imprinting strategy is widely used in cancer cell imaging, localization, and treatment. Moreover, due to the complicated structure and easy inactivation of some proteins, their MIPs are often prepared by fragment imprinting (also called epitope imprinting). As some microorganisms are infectious, imprinting microorganisms directly can pose a risk; therefore it is safer to also use the fragment imprinting strategy in such cases. The recent application of fragment imprinting strategy in other areas remains scarce. Nonetheless, three studies in the food analysis have explored this possibility. DMIPs are widely used in sample pretreatment and sensing analysis, and they are mainly used as SPE adsorbents for packed SPE, dispersive SPE (DSPE), magnetic SPE (MSPE), and matrix solid phase dispersion (MSPD) extraction. In addition, DMIPs are employed as molecularly imprinted membrane materials. As a result, by virtue of DMIPs, selective extraction and enrichment of target analytes from complicated samples can be achieved. MIP-based sensors can either recognize or transduce, meaning that they can specifically recognize and bind target analytes as well as generate output signals for detection. Because of the high selectivity of MIPs, the use of a dummy template imprinting strategy solves the problem of template leakage in the process of recognition and adsorption, further improving the detection accuracy and sensitivity of the sensor. These features expand the application range of MIP-based sensors. This review briefly overviews the construction and application of chemiluminescence and fluorescence sensors based on DMIPs. Lastly, the advantages and disadvantages, differences, and relationships among the two strategies are summarized. Despite of their potential, four main challenges still remain as major setbacks for the application of FMIPs and DMIPs: (i) the difficulty to select or prepare appropriate fragment templates and dummy templates; (ii) how to ensure that there is almost no difference in the recognition adsorption selectivity between the fragment/dummy template and the original template, so as to ensure optimal recognition specificity; (iii) the use of, environment-friendly reagents to reduce pollution during FMIPs/DMIPs preparation and use to conform with green chemistry requirements; (iv) how to strengthen the industrial and commercial applications of FMIPs and DMIPs. Therefore, significant efforts should be made to develop new imprinting strategies and techniques, as well as to adopt combinational imprinting approaches for FMIPs/DMIPs preparation to expedite the sustainable development and efficient application of FMIPs and DMIPs.

分子印迹聚合物(MIPs)是通过模拟酶与底物或抗原抗体特异性结合原理而制备的高分子聚合物,以其结构预定性、识别特异性、制备简便、成本低、耐受性强等优点而被广泛用于样品前处理、传感分析、生物医药、环境/食品分析等多个领域。目前已发展多种策略用于MIPs制备,达到简化制备过程或提高聚合物性能等目的,极大拓宽了MIPs的应用范围。对各种先进印迹策略及其组合使用的探索已成为MIPs制备的研究热点之一。其中,片段印迹策略和虚拟模板印迹策略备受青睐。片段印迹策略是选择目标分子中含有特定官能团的一部分(片段结构)作为模板进行印迹,通过对片段的识别达到对整个分子的识别,能够克服某些目标物不易获得或体积较大不适合作为模板的问题,为印迹易失活、易传染的目标物及整体印迹困难的大分子提供可行的方法。虚拟模板印迹策略是选用与目标物特异性结构相似或相同的其他物质代替目标物作为模板制备MIPs,可在很大程度上解决模板不易获得或较昂贵等问题,以及避免模板可能泄漏对结果造成的影响,尤其适用于目标物造价高、具有感染性、易燃易爆、易降解等不适合作为模板分子的情况。该文选取了最近4年发表在ACS、Elsevier、RSC等数据库约20篇相关文献,综述了片段/虚拟MIPs(FMIPs/DMIPs)的应用新进展。首先,针对蛋白质和微生物检测以及哺乳动物细胞印迹,介绍了FMIPs在生物医药领域的应用,另外介绍了FMIPs在食品分析领域的研究进展。随后,介绍了DMIPs在样品前处理和传感分析领域的应用。在样品前处理中,DMIPs主要作为固相萃取吸附剂进行装柱固相萃取、分散固相萃取、磁固相萃取、基质固相分散萃取等,或作为分子印迹膜材料,用于选择性萃取和富集分离样品中的目标分析物。在传感分析领域,DMIPs主要作为传感器的传感和转导元件,提高化学发光或荧光检测等方法的灵敏度和准确度。最后,对片段印迹和虚拟模板印迹策略的优缺点、区别与联系进行了总结,并展望了这两种策略的发展与应用前景。

Keywords: application; dummy template imprinting; fragment imprinting; molecularly imprinted polymers (MIPs); preparation; review.

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