基于新型金属有机配位聚合物的肿瘤标志物及小分子的电化学检测

发布时间：2018-10-12 11:56

【摘要】：近年来,对恶性肿瘤的早期检测成为研究的热门问题,传统的技术在恶性肿瘤早期检测上存在一定的困难。核酸适配体是一种能够靶向结合各种肿瘤标志物,其不仅具有高的特异性识别的能力,还具有高的亲和力以及修饰简单、靶目标物丰富、易于合成等诸多优点,从而提供了一种理想的肿瘤靶向识别分子。与此同时,金属-有机骨架(Metal-Organic Frameworks, MOFs)配合物是通过金属离子或者金属簇与有机配体之间通过配位键连接形成周期性的、无限网络的聚合物多孔结构。由于MOFs材料具有多孔结构、孔隙易于调节、易于功能化、以及特殊的光磁电性能等诸多优点,使得其显示出比传统的纯无机材料和纯有机物质更加丰富和优异的物化性能,使其在气体的储存与分离、光电化学传感器、催化剂等方面都具有很可观的前景。基于此,本论文以发展新型恶性肿瘤早期检测方法为目标,通过金属有机聚合物结合核酸适配体作为新型肿瘤靶向识别分子,并过电化学生物传感器来放大信号,达到检测肿瘤标志物效果。并将合成的功能性MOFs应用于过氧化氢(H202),抗坏血酸(AA)等小分子的检测,具体包括以下几个部分的内容。(1)以硫堇类有机物硫堇(Thi)和1,8蒽二羧酸二甲酯(Dada)为配体,以过渡金属铜和钴为配位中心,合成两种新型的金属有机聚合物Cu-Dada以及Co-Thi。并确定分子式。并将Cu-Dada以及Co-Thi和Sgc8c结合生成Cu-Dada-Sgc8c以及Co-Thi-Sgc8c。(2) Cu-Dada-Sgc8c以及Co-Thi-Sgc8c构建电化学生物传感器检测肿瘤标志物蛋白络氨酸激酶(PTK7K),实验结果表明Cu-Dada-Sgc8c检测PTK7K的线性范围为6.25×10-7-3.75×10-6mg mL-1,检出限为 1.5×10-8 mgmL-1,灵敏度为 3.87mAmL mg-1 cm-2。Co-Thi-Sgc8c 检测 PTK7K 线性范围 1.25 ×10-5-2×10-4 mg mL-1,检出限为 1.67×10-6mg mL-1,灵敏度为 1.66mA mL mg-1 cm-2。(3) Cu-Dada构建电化学传感器催化过氧化氢、抗坏血酸、亚硝酸盐。实验结果表明,Cu-Dada/GCE检测过氧化氢的线性范围为5×10-7-2.6×10-3 M,灵敏度为199.6 mA mol-1 L cm-2,最低检出限为2.6×10-7 M。利用碳纳米管改性后,制成Cu-Dada/MWCNTs/GCE,该传感器的线性范围为5×10-7-1.8×10-1M,该传感器的灵敏度为424.3 mA mol-1 L cm-2,最低检出限为2.4×10-8M。Cu-Dada/GCE检测抗坏血酸的线性范围为 1.6×10-5-2.2×10-3M (R=0.997),灵敏度为 37.5 mAmol-1 Lcm-2,最低检出限为1.37×10-6M。Cu-Dada/GCE检测亚硝酸钠的线性范围为5×10-5-1.2×10-1M,该传感器的灵敏度为2.1mAmol-1 Lcm-2,最低检出限为1.6×10-5M。当我们掺杂碳纳米管改性制成Cu-Dada/MWCNTs/GCE后,性能有所提高,线性范围为5×10-5-9.8×10-3 M,该传感器的灵敏度为76 mA mol-1 Lcm-2,最低检出限为7.3×10-6M。
[Abstract]:In recent years, the early detection of malignant tumors has become a hot issue, and the traditional technology has some difficulties in the early detection of malignant tumors. The aptamer of nucleic acid is a kind of target binding tumor marker, which not only has the ability of high specificity recognition, but also has many advantages, such as high affinity, simple modification, rich target material, easy synthesis and so on. This provides an ideal tumor target recognition molecule. At the same time, the metal-organic skeleton (Metal-Organic Frameworks, MOFs) complexes form periodic, infinite network polymer porous structures through the bonding of coordination bonds between metal ions or metal clusters and organic ligands. Due to its porous structure, easy adjustment of pores, easy functionalization, and special optomagnetoelectric properties, MOFs materials exhibit more abundant and excellent physical and chemical properties than traditional pure inorganic materials and pure organic materials. It has a promising future in gas storage and separation, photochemical sensors, catalysts and so on. Based on this, the aim of this paper is to develop a new method for early detection of malignant tumor, which uses organometallic polymer and nucleic acid aptamer as novel tumor target recognition molecules and over-electrochemical biosensor to amplify the signal. The effect of detecting tumor markers was achieved. The synthesized functional MOFs was applied to the detection of hydrogen peroxide (H202), ascorbic acid (AA) and other small molecules, including the following parts. (1) the ligand of thionine (Thi) and 1,8-anthracene dicarboxylate (Dada) were used as ligands. Two novel organometallic polymers, Cu-Dada and Co-Thi., were synthesized by using transition metal copper and cobalt as coordination centers. And determine the formula. Cu-Dada, Co-Thi and Sgc8c were combined to form Cu-Dada-Sgc8c, Co-Thi-Sgc8c. (2) Cu-Dada-Sgc8c and Co-Thi-Sgc8c to construct an electrochemical biosensor for the detection of tumor marker protein complex aminokinase (PTK7K). The linear range of Cu-Dada-Sgc8c for PTK7K detection was 6.25 脳 10-7-3.75 脳 10-6mg mL-1, and the detection limit was 1.5 脳 10-8 mgmL-1,. The linear range of 3.87mAmL mg-1 cm-2.Co-Thi-Sgc8c detection for PTK7K was 1.25 脳 10-5-2 脳 10-4 mg mL-1,. The detection limit was 1.67 脳 10-6mg mL-1,. The sensitivity was 1.66mA mL mg-1 cm-2. (3) Cu-Dada to construct electrochemical sensor to catalyze hydrogen peroxide. Ascorbic acid, nitrite. The experimental results show that the linear range of Cu-Dada/GCE is 5 脳 10-7-2.6 脳 10-3 Mand the minimum detection limit of 199.6 mA mol-1 L cm-2, is 2.6 脳 10-7 M. Modified by carbon nanotubes, The linear range of the sensor is 5 脳 10-7-1.8 脳 10-1M, the sensitivity of the sensor is 424.3 mA mol-1 L cm-2, the minimum detection limit of ascorbic acid is 2.4 脳 10-8M.Cu-Dada/GCE, the linear range is 1.6 脳 10-5-2.2 脳 10-3M (RV 0.997), the sensitivity is 37.5 mAmol-1 Lcm-2, minimum detection limit of nitrite is 1.37 脳 10-6M.Cu-Dada/GCE. The linear range of sodium is 5 脳 10 ~ (-5) to 1.2 脳 10 ~ (-1) M, and the sensitivity of the sensor is 1.6 脳 10 ~ (-5) M. the sensitivity of the sensor is 1.6 脳 10 ~ (-5) M. When we modified Cu-Dada/MWCNTs/GCE with carbon nanotubes, the linear range was 5 脳 10-5-9.8 脳 10-3 M.The sensitivity of the sensor was 76 mA mol-1 Lcm-2, and the minimum detection limit was 7.3 脳 10-6 M.The linear range of the sensor was 5 脳 10-5-9.8 脳 10-3 M.The sensitivity of the sensor was 7.3 脳 10-6M.
【学位授予单位】：南京师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O657.1;O641.4

【参考文献】

中国期刊全文数据库 前10条

1 李贵贤;张小莉;李红伟;梁亚澜;袁琦罡;董鹏;;MOFs材料吸附存储与分离CO_2的研究进展[J];化工新型材料;2014年12期

2 何燕萍;谭衍曦;张健;;基于尺寸识别和离子交换实现有机染料分离的一例阴离子型MOF[J];化学学报;2014年12期

3 Rong-Mei Wen;Song-De Han;Hao Wang;Ying-Hui Zhang;;Synthesis,structure and magnetic properties of manganese(Ⅱ)coordination polymer with azido and zwitterionic dicarboxylate ligand[J];Chinese Chemical Letters;2014年06期

4 贾江涛;王蕾;赵晴;孙福兴;朱广山;;设计合成nia拓扑的金属有机骨架化合物与CO_2吸附[J];化学学报;2013年11期

5 Jin-An Zhao;Shu-Fang Chen;Dan-Dan Zhao;Yan Guo;Kun Peng;Ji-Yong Hu;;The structure and luminescence properties of three complexes based on bifunctional imidazole-dicarboxylate connector[J];Chinese Chemical Letters;2013年06期

6 刘蓓;唐李兴;廉源会;李智;孙长宇;陈光进;;互穿结构及混合配体对金属-有机骨架材料分离性能的影响[J];化学学报;2013年06期

7 杨绍明;查文玲;李红;孙清;刘斌;郑龙珍;;以聚硫堇为电化学探针的非标记型核酸适配体传感器[J];高等学校化学学报;2013年03期

8 李红梅;熊红波;骆耿耿;戴劲草;;Synthesis, Crystal Structural Characterization and Electrochemical Properties of a 1D Tape-like Polymer of Cobalt Adamantanedicarboxylate: [Co_2(adc)_2(py)_4(H_2O)]_n[J];结构化学;2011年09期

9 ;Porous coordination polymers based on three planar rigid ligands[J];Science China(Chemistry);2011年09期

10 袁涛;刘中原;胡连哲;徐国宝;;电化学和电化学发光核酸适体传感器[J];分析化学;2011年07期

中国硕士学位论文全文数据库 前2条

1 汤进录;基于核酸适配体和量子点的急性淋巴白血病细胞检测研究[D];湖南大学;2013年

2 陶涛;MCM-41介孔分子筛的合成方法及催化性能研究[D];江苏大学;2006年

，

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