Wang Yixiao, Li Jinhua, Wang Liyan, Qi Ji, Chen Lingxin
Chinese Academy of Sciences Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.
School of Source and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Se Pu. 2021 Feb;39(2):134-141. doi: 10.3724/SP.J.1123.2020.08008.
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)旨在模拟酶与底物或抗原与抗体的特异性结合原理,同时具有结构可预测性、识别特异性、易于制备、成本低、物理稳定性高和热稳定性等优点。因此,它们已广泛应用于许多领域,包括样品制备(预处理)、传感分析(化学/生物传感器)、生物医学以及环境/食品分析。迄今为止,已开发出多种制备MIPs的策略,旨在简化制备过程和/或改善聚合物的性能,极大地拓宽了其适用性。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,其中片段印迹策略和虚拟模板印迹策略尤其受到青睐。片段印迹,也称为区段印迹,使用目标分子的部分结构作为假模板来制备MIPs。该策略对于难以获得或太大而无法用作模板的目标分子很有用,为印迹易于失活或感染的目标分析物以及难以印迹的大分子提供了一种可行的方法。反过来,虚拟模板印迹使用结构、形状和大小与目标分析物相似的分子作为印迹模板。由于目标不直接用作模板,该策略可以克服模板泄漏问题,以及解决与目标分子相关的困难,因为它们可能昂贵、具有传染性、易燃、易爆或化学不稳定。本综述汇编了过去四年在ACS、爱思唯尔、皇家化学学会等数据库上发表的几篇文章的信息,总结了片段/虚拟模板MIPs(FMIPs/DMIPs)应用的最新进展。在此,主要探讨FMIPs在生物医学领域作为检测蛋白质和微生物的策略的应用,并探索FMIPs在食品分析领域的应用。近年来,哺乳动物细胞的印迹在FMIPs的应用方面取得了一些进展。哺乳动物细胞,尤其是癌细胞,过度表达一些蛋白质和糖类,它们是很好的片段模板。因此,片段印迹策略广泛应用于癌细胞成像、定位和治疗。此外,由于一些蛋白质结构复杂且易于失活,它们的MIPs通常通过片段印迹(也称为表位印迹)制备。由于一些微生物具有传染性,直接印迹微生物可能会带来风险;因此在这种情况下使用片段印迹策略也更安全。片段印迹策略在其他领域的近期应用仍然很少。尽管如此,但食品分析中的三项研究已经探索了这种可能性。DMIPs广泛应用于样品预处理和传感分析,它们主要用作填充固相萃取(SPE)、分散固相萃取(DSPE)、磁性固相萃取(MSPE)和基质固相分散(MSPD)萃取的SPE吸附剂。此外,DMIPs还用作分子印迹膜材料。因此,借助DMIPs,可以从复杂样品中选择性提取和富集目标分析物。基于MIP的传感器既可以识别也可以转换,这意味着它们可以特异性识别并结合目标分析物,还可以生成用于检测的输出信号。由于MIPs具有高选择性,使用虚拟模板印迹策略解决了识别和吸附过程中的模板泄漏问题,进一步提高了传感器的检测准确性和灵敏度。这些特性扩大了基于MIP的传感器的应用范围。本综述简要概述了基于DMIPs的化学发光和荧光传感器的构建及应用。最后,总结了两种策略的优缺点、差异和关系。尽管它们具有潜力,但四个主要挑战仍然是FMIPs和DMIPs应用的重大障碍:(i)难以选择或制备合适的片段模板和虚拟模板;(ii)如何确保片段/虚拟模板与原始模板之间的识别吸附选择性几乎没有差异从而确保最佳识别特异性;(iii)使用环境友好型试剂以减少FMIPs/DMIPs制备和使用过程中的污染以符合绿色化学要求;(iv)如何加强FMIPs和DMIPs的工业和商业应用。因此,应大力开发新的印迹策略和技术,以及采用组合印迹方法制备FMIPs/DMIPs,以加快FMIPs和DMIPs的可持续发展和高效应用。