Abstract:Molecular blotting technology mimics the antigen-antibody specific recognition mechanism of the organism's immune system, and designs and synthesises functional polymers with pre-assembled recognition sites to achieve highly selective recognition and capture of target molecules. In recent years, this technology has demonstrated its potential application in biomedical detection through cross-fertilisation with electrochemical sensing technology, and has attracted much attention for its excellent detection sensitivity, selectivity and stability. In this paper, we systematically review the construction elements of molecularly imprinted electrochemical sensors, focusing on the categories of functional monomers and their selection strategies, as well as the preparation of highly efficient imprinted membranes, and review the progress of the application of such sensors in biomedical detection fields such as biological and clinical marker detection and pathogen identification, and discuss the challenges of the development of sensors in the areas of sensitivity, precision, reproducibility, and suitability for complex biological samples. It also discusses the challenges of sensor development, such as sensitivity, precision, repeatability, and adaptation of complex biological samples, and looks forward to the future development of this field in the application of new smart materials, multimodal sensing integration and standardised detection platform construction, which will provide an important reference to promote the application of molecularly imprinted electrochemical sensors in the field of precision medicine.
师帆, 张国军, 李玉桃, 唐丽娜. 分子印迹电化学传感器的生物医学检测应用:研究进展与挑战[J]. 中国生物医学工程学报, 2025, 44(4): 502-512.
Shi Fan, Zhang Guojun, Li Yutao, Tang Lina. Research Progress on Application of Molecularly Imprinted Electrochemical Sensors in BiomedicalField. Chinese Journal of Biomedical Engineering, 2025, 44(4): 502-512.
[1] Belbruno JJ. Molecularly imprinted polymers [J]. Chem Rev, 2019, 119(1): 94-119.
[2] Komiyama M, Mori T, Ariga K. Molecular imprinting: materials nanoarchitectonics with molecular information [J]. B Chem Soc Jpn, 2018, 91(7): 1075-1111.
[3] Xing Rongrong, Wang Shuangshou, Bie Zijun, et al. Preparation of molecularly imprinted polymers specific to glycoproteins, glycans and monosaccharides via boronate affinity controllable-oriented surface imprinting [J]. Nat Protoc, 2017, 12(5): 964-987.
[4] Culver HR, Peppas NA. Protein-imprinted polymers: the shape of things to come? [J]. Chem Mater, 2017, 29(14): 5753-5761.
[5] Jafari MT, Rezaei B, Zaker B. Ion mobility spectrometry as a detector for molecular imprinted polymer separation and metronidazole determination in pharmaceutical and human serum samples [J]. Anal Chem, 2009, 81(9): 3585-3591.
[6] Maeda M, Bartsch RA. Molecular and ionic recognition with imprinted polymers: a brief overview [J]. ACS Symp Ser Am Chem Soc, 1998, 703(1): 1-8.
[7] Arabi M, Ostovan A, Wang Y, et al. Chiral molecular imprinting-based sers detection strategy for absolute enantiomeric discrimination [J]. Nat Commun, 2022, 13(1): 5757.
[8] Li Xiaowei, Milad Z, Zhao Yan. Molecularly imprinted synthetic glucosidase for the hydrolysis of cellulose in aqueous and nonaqueous solutions [J]. Am Chem Soc, 2021, 143(13): 5172-5181.
[9] Wu Dan, Baaziz W, Gu B, et al. Surface molecular imprinting over supported metal catalysts for size-dependent selective hydrogenation reactions [J]. Nat Cataly, 2021, 4(7): 595-606.
[10] Gu Zikuan, Dong Yueru, Xu Shuxin, et al. Molecularly imprinted polymer-based smart prodrug delivery system for specific Targeting, prolonged retention, and tumor microenvironment-triggered release [J]. Angew Chem Int Ed, 2020, 133(5): 2695-2699.
[11] Xu Jingjing, Miao Haohan, Wang Jixiang, et al. Molecularly imprinted synthetic antibodies: from chemical design to biomedical applications [J]. Small, 2020, 16(27): e1906644.
[12] Carballido L, Karbowiak T, Cayot P, et al. Applications of molecularly imprinted polymers and perspectives for their use as food quality trackers [J]. Chem, 2022, 8(9): 2330-2341.
[13] Chen Lingxin, Xu Shoufang, Li Jinhua. Recent advances in molecular imprinting technology: current status,challenges and highlighted applications [J]. Chem Soc Rev, 2011, 40(5): 2922-2942.
[14] Wulff G. Molecular imprinting in cross-linked materials with the aid of molecular templates: a way towards artificial antibodies [J]. Angew Chem Int Ed, 1995, 34(17): 1812-1832.
[15] Hall AJ, Lanza-Sellergren F, Manesiotis P, et al. Non-covalent imprinting of phosphorous esters [J]. Anal Chim Acta, 2005, 538(1-2): 9-14.
[16] Del Sole R, Lazzoi MR, Arnone M, et al. Experimental and computational studies on non-covalent imprinted microspheres as recognition system for nicotinamide molecules [J]. Molecules, 2009, 14(7): 2632-2649.
[17] Ikegami T, Mukawa T, Nariai H, et al. Bisphenol a-recognition polymers prepared by covalent molecular imprinting [J]. Anal Chim Acta, 2004, 504(1): 131-135.
[18] Limthin D, Leepheng P, Tunhoo B, et al. Preparation of surface-modified electrode of copper(ii) oxide mixed with the molecularly imprinted polymer for enhancement of melamine detection with photoelectrochemical technique [J]. Rsc Advances, 2023, 13(21): 14729-14736.
[19] Cetinkaya A, Unal MA, Nazir H, et al. Two different molecularly imprinted polymeric coating techniques for creating sensitive and selective electrochemical sensors for the detection of ribavirin [J]. Sensors Actuat B-Chem, 2023, 389: 133914.
[20] Zhou Binbin, Xie Hao, Zhou Sisi, et al. Construction of aunps/reduced graphene nanoribbons co-modified molecularly imprinted electrochemical sensor for the detection of zearalenone [J]. Food Chem, 2023, 423: 136294.
[21] Zhang Jin,Wang Chaoying,Niu Yanhui,et al. Electrochemical sensor based on molecularly imprinted composite membrane of poly (o-aminothiophenol) with gold nanoparticles for sensitive determination of herbicide simazine in environmental samples [J]. Sensors Actuat B-Chem, 2017,249:747-755.
[22] Guo Wei, Pi Fuwei, Zhang Hongxia, et al. A novel molecularly imprinted electrochemical sensor modified with carbon dots, chitosan, gold nanoparticles for the determination of patulin [J]. Biosens Bioelectron, 2017, 98: 299-304.
[23] Zhou Yanqiang, Abdurexit A, Jamal R, et al. Highly sensitive electrochemical sensing of norfloxacin by molecularly imprinted composite hollow spheres [J]. Biosens Bioelectron, 2024, 251: 116119.
[24] Shao Yanming, Zhu Ying, Zheng Rui, et al. Highly sensitive and selective surface molecularly imprinted polymer electrochemical sensor prepared by Au and MXene modified glassy carbon electrode for efficient detection of tetrabromobisphenol A in water [J]. Adv Compos hybrid Mater, 2022, 5(4): 3104-3116.
[25] Lofgreen JE, Ozin GA. Controlling morphology and porosity to improve performance of molecularly imprinted sol-gel silica [J]. Chem Soc Rev, 2014, 43(3): 911-933.
[26] Karadurmus L, Corman ME, Uzun L, et al. Enantioselective recognition of esomeprazole with a molecularly imprinted sol-gel-based electrochemical sensor [J]. Microchim Acta, 2022, 189(6): 225.
[27] Zhi Keke, Wang Lulu, Zhang Yagang, et al. Influence of size and shape of silica supports on the sol-gel surface molecularly imprinted polymers for selective adsorption of gossypol [J]. Materials, 2018, 11(5): 777.
[28] Oghli AH, Soleymanpour A. Ultrasensitive electrochemical sensor for simultaneous determination of sumatriptan and paroxetine using molecular imprinted polymer/sol-gel/polyoxometalate/rGO modified pencil graphite electrode [J]. Sensors Actuat B-Chem, 2021, 344: 130215.
[29] Fu Donglei, Deng Junjie, Zhang Bowei, et al. Bioenzyme-induced molecularly imprinted polymers using optimal design of computational chemistry for enhanced specific electrochemical sensing of protocatechuic acid in medicines [J]. Sensors Actuat B-Chem, 2023, 393: 134153.
[30] 谭学才,吴佳雯,胡琪,等. 基于石墨烯的毒死蜱分子印迹电化学传感器的制备及对毒死蜱的测定 [J]. 分析化学, 2015, 43(3): 387-393.
[31] Deng Fei, Goldys EM, Liu Guozhen. Molecularly imprinted polymer-based reusable biosensing device on stainless steel for spatially localized detection of cytokine il-1β [J]. Sensors Actuat B-Chem, 2019, 292: 277-283.
[32] Asl AZ, Rafati AA, Khazalpour S. Highly sensitive molecularly imprinted polymer-based electrochemical sensor for voltammetric determination of adenine and guanine in real samples using gold screen-printed electrode [J]. J Mol Liq, 2023, 369: 120942.
[33] You Min, Yang Shuai, F Jiao, et al. Label-free electrochemical multi-sites recognition of g-rich DNA using multi-walled carbon nanotubes-supported molecularly imprinted polymer with guanine sites of DNA [J]. Electrochim Acta, 2016, 199: 133-141.
[34] Campagnol D, Karimian N, Paladin D, et al. Molecularly imprinted electrochemical sensor for the ultrasensitive detection of cytochrome c [J]. Bioelectrochem, 2022, 148: 108269.
[35] Karami P, Bagheri H, Johari-Ahar M, et al. Dual-modality impedimetric immunosensor for early detection of prostate-specific antigen and myoglobin markers based on antibody-molecularly imprinted polymer [J]. Talanta, 2019, 202: 111-122.
[36] He Shuang, Zhang Pei, Sun Jing, et al. Integrating potential-resolved electrochemiluminescence with molecularly imprinting immunoassay for simultaneous detection of dual acute myocardial infarction markers [J]. Biosens Bioelectron, 2022, 201: 113962.
[37] Li Qianjin, Shinde S, Grasso G, et al. Selective detection of phospholipids using molecularly imprinted fluorescent sensory core-shell particles [J]. Sci Rep 2020, 10(1): 9924.
[38] Feng Dongwei, Huang Peng, Miao Yunfei, et al. Novel photoelectrochemical sensor for cholesterol based on CH3NH3PbBr3 perovskite /TiO2 inverse opal heterojunction coated with molecularly imprinted polymers [J]. Sensors Actuat B-Chem, 2022, 368: 132121.
[39] Duan Dingding, Lu Huan, Li Yaping, et al. A molecularly imprinted electrochemical sensors based on bamboo-like carbon nanotubes loaded with nickel nanoclusters for highly selective detection of cortisol [J]. Microchem J, 2022, 175: 107231.
[40] Goyal A, Sakata T. Development of a redox-label-doped molecularly imprinted polymer on β-cyclodextrin/reduced graphene oxide for electrochemical detection of a stress biomarker [J]. ACS Omega, 2022, 7(37): 33491-33499.
[41] Yeasmin S, Wu Bo, Liu Ye, et al. Nano gold-doped molecularly imprinted electrochemical sensor for rapid and ultrasensitive cortisol detection [J]. Biosens Bioelectron, 2022, 206: 114142.
[42] Yang Jiao, Hu Yue, Li Yingchun. Molecularly imprinted polymer-decorated signal on-off ratiometric electrochemical sensor for selective and robust dopamine detection [J]. Biosens Bioelectron, 2019, 135: 224-230.
[43] Mugo SM, Robertson SV, Lu Weihao. A molecularly imprinted screen-printed carbon electrode for electrochemical epinephrine, lactate, and cortisol metabolites detection in human sweat [J]. Anal Chim Acta, 2023, 1278: 341714.
[44] Xia Yuanyuan, Wang Yuan, Zhang Meng, et al. A highly selective electrochemical sensor based on surface molecularly imprinted copolymer for the detection of 5-hydroxytryptamine [J]. Microchem J, 2021, 160: 105748.
[45] Zou Kuangyi, Li Qianming, Li Dan, et al. A highly selective implantable electrochemical fiber sensor for real-time monitoring of blood homovanillic acid [J]. ACS Nano, 2024, 18(10): 7485-7495.
[46] Kaur S, Singla P, Dann A J, et al. Sensitive electrochemical and thermal detection of human noroviruses using molecularly imprinted polymer nanoparticles generated against a viral target [J]. ACS Appl. Mater. Interfaces, 2024, 16(38): 51397-51410.
[47] Babamiri B, Salimi A, Hallaj R. A molecularly imprinted electrochemiluminescence sensor for ultrasensitive HIV-1 gene detection using EuS nanocrystals as luminophore [J]. Biosens Bioelectron, 2018, 117: 332-339.
[48] Wang Tao, Zhang Mengge, Lu Yuhao, et al. Metal-organic-framework-confined quantum dots enhance photocurrent signals: a molecularly imprinted photoelectrochemical cathodic sensor for rapid and sensitive tetracycline detection [J]. Anal Chim Acta, 2024, 1293: 342269.
[49] Emam S, Adedoyin A, Geng Xiaohua, et al. A molecularly imprinted electrochemical gas sensor to sense butylated hydroxytoluene in air [J]. J Sens, 2018, 2018(1): 3437149.
[50] Liustrovaite V, Pogorielov M, Boguzaite R, et al. Towards electrochemical sensor based on molecularly imprinted polypyrrole for the detection of bacteria-listeria monocytogenes [J]. Polymers, 2023, 15(7): 1597.
[51] Saeki T, Takano E, Sunayama H, et al. Signalling molecular recognition nanocavities with multiple functional groups prepared by molecular imprinting and sequential post-imprinting modifications for prostate cancer biomarker glycoprotein detection[J]. J Mater Chem B, 2020, 8(35): 7987-7993.
[52] Dai Yin, Jiang Wei, Zheng Yani, et al. Recyclable molecularly imprinted polymers based on Fe3O4@ SiO2 and PAMAM dendrimers for the determination of myosmine in cigarettes[J]. Microchim Acta, 2022, 189(12): 467.
[53] Li Xin, Li Bing, Huang Jie, et al. A molecular imprinting photoelectrochemical sensor modified by polymer brushes and its detection for BSA[J]. Chem Eng J, 2024, 483: 149297.
[54] Daniels E, Mustafa Y L, Herdes C, et al. Optimization of cortisol-selective molecularly imprinted polymers enabled by molecular dynamics simulations[J]. ACS Appl Bio Mater, 2021, 4(9): 7243-7253.
[55] Gao Haifeng, You Junyi, Wu Hongbo, et al. A dual action electrochemical molecular imprinting sensor based on FeCu-MOF and RGO/PDA@ MXene hybrid synergies for trace detection of ribavirin[J]. Food Chem, 2025: 143092.
[56] Jiang Zejun, Luo Kui, Zeng Honghu, et al. Monitoring of medical wastewater by sensitive, convenient, and low-cost determination of small extracellular vesicles using a glycosyl-imprinted sensor[J]. ACS Sens, 2024, 9(3): 1252-1260.