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.

Key words: molecularly imprinted polymers (MIPs), fragment imprinting, dummy template imprinting, preparation, application, review