Advances in Protein Biomarker Assay via the Combination of Molecular Imprinting and Surface-enhanced Raman Scattering

doi:10.6023/A20080364

Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (1): 45-57.DOI: 10.6023/A20080364 Previous Articles Next Articles

Review

基于分子印迹与表面增强拉曼散射的蛋白质疾病标志物检测研究进展

贺晖^a, 周玲俐^a, 刘震^a^,^*()

a 南京大学化学化工学院生命分析化学国家重点实验室南京 210023

投稿日期:2020-08-14 发布日期:2020-11-27
通讯作者: 刘震

作者简介:

贺晖, 2012年本科毕业于西北农林科技大学, 2015年硕士毕业于西北农林科技大学, 2019年博士毕业于南京大学化学化工学院, 取得博士学位后留校工作任副研究员. 主要研究方向为等离激元增强效应研究、生物分子质谱分析及单细胞分析.

周玲俐, 2017年本科毕业于郑州大学化学与分子工程学院, 2020年硕士毕业于南京大学化学化工学院, 主要从事基于分子印迹聚合物和表面增强拉曼光谱的蛋白质检测方向的研究.

刘震, 1998年于中国科学院大连化学物理研究所获博士学位. 2000~2002年, 日本兵库大学日本学术振兴会(JSPS)特别研究员; 2002~2005年, 加拿大滑铁卢大学博士后. 2005年获聘南京大学教授, 2006年起任博士生导师, 2011~2014年任加拿大滑铁卢大学工程学院兼职教授, 2014年获国家杰出青年科学基金. 主要研究方向: 以仿生分子识别为核心, 结合纳米技术、先进材料、分离科学、生物质谱和拉曼光谱等手段, 发展生物分离、组学分析、疾病诊断分析、单细胞分析、癌症靶向及免疫治疗新方法和新材料.

* E-mail: zhenliu@nju.edu.cn

基金资助:
国家自然科学基金重大科研仪器研制项目(21627810); 国家自然科学基金重点项目(21834003)

Advances in Protein Biomarker Assay via the Combination of Molecular Imprinting and Surface-enhanced Raman Scattering

Hui He^a, Lingli Zhou^a, Zhen Liu^a^,^*()

a State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

Received:2020-08-14 Published:2020-11-27
Contact: Zhen Liu
Supported by:
the Key Scientific Instrument and Equipment Development Project(21627810); the Key Grant of the National Natural Science Foundation of China.(21834003)

Abnormal protein expression closely correlates with the occurrence and development of diseases. Thus, proteins have been widely used as disease markers for early diagnosis, treatment monitoring and prognosis evaluation of diseases. However, protein biomarkers in clinical samples are usually present in extremely low concentration while the detection often suffers from severe interference by high-abundance sample matrix, which challenges the specificity and sensitivity of protein biomarker assay methods. Currently, the main detection method of protein biomarkers is immunoassay. Nevertheless, immunoassay mainly relies on antibodies for specific recognition, and antibodies are associated with disadvantages such as difficulty in preparation, poor stability, and high-cost. Meanwhile, immunoassay is mainly based on fluorescence and chemiluminescence to achieve high-sensitivity detection, but they have inherent defects such as cumbersome operation, photobleaching and broad spectrum. Molecularly imprinted polymers (MIP) have developed as biomimetic recognition materials with antibody-comparable specificity and affinity, while offering advantages such as ease in preparation, good stability and low cost. On the other hand, surface-enhanced Raman scattering (SERS) has been widely used in chemical or biological assays due to its merits including ultra-high sensitivity, narrow spectrum, speed, non-destructivity, and so on. In recent years, the combination of molecular imprinting and SERS has generated a series of advanced protein detection methods that exhibited unique strengths, which has gained wide attention. This review aims to survey the main advances of this hybrid analytical technique. After introduction of MIP and SERS as well as their separate applications in the detection of protein biomarkers, we mainly focus on the combination of MIP and SERS as well as its application in protein biomarker detection. We finally briefly sketch the future development of this hybrid analytical method.

Key words: molecularly imprinted polymer, surface-enhanced Raman scattering, protein, detection, disease biomarker

Cite this article

Hui He, Lingli Zhou, Zhen Liu. Advances in Protein Biomarker Assay via the Combination of Molecular Imprinting and Surface-enhanced Raman Scattering[J]. Acta Chimica Sinica, 2021, 79(1): 45-57.

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Fig. & Tab. 12

Figure 1. Schematic of the principle of molecular imprinting[47]

Figure 2. Schematic of the principle of photolithographic boronate affinity molecular imprinting[34]

Figure 3. Schematic of the principle of boronate affinity controllable- oriented surface imprinting[72]

Figure 4. Schematic of the principle of controllable oriented surface imprinting of boronate affinity-anchored epitopes[100]

Figure 5. Overview of MIP-based fluorescence sensor applied to Cyt C detection[105]

Figure 6. SERS and its electromagnetic enhancement mechanism[117]

Figure 7. Overview of label-free SERS detection of protein[124]

Figure 8. Schematic representation of the process of SERS-based multiplex detection of liver cancer antigens[131]

Figure 9. Schematic of PISA for the detection of proteins in single cells[140] and complex samples[141]

Figure 10. Schematic of the combination of MIP and antibodies modified (A) Au nanostar[148] and (B) Au@Ag nanostructure[149] for SERS detection

Figure 11. Schematic of the duMIP-based indirect SERS detection of target protein[102]

Figure 12. Overview of (A) molecularly imprinted plasmonic nanosensor for selective SERS detection of transferrin[151] and (B) gold nanorods coated with imprinted layer (MIP@AuNR) SERS sensor[152]

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基于分子印迹与表面增强拉曼散射的蛋白质疾病标志物检测研究进展

Advances in Protein Biomarker Assay via the Combination of Molecular Imprinting and Surface-enhanced Raman Scattering

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