基于纳米复合材料的生物传感器的研制及性能分析
发布时间：2018-12-06 20:06
【摘要】：电致化学发光生物传感器具有很高的灵敏度,并且具有仪器设备简单、操作方便、快捷、线性响应范围宽和易于实现自动化等显著优点,因此该新型传感器越来越受到研究者们的广泛关注。本文开展了针对三种不同纳米复合材料的生物传感器的优化、制备和组装,并且分别应用于人体肝癌细胞的检测之中,实现了对癌细胞的灵敏检测,为生物医学领域中的临床检测提供了新的平台。本文开展了如下几个方面的工作:利用CFD方法,通过Fluent软件进行模拟计算并优化结构设计,以光刻法为基础,以PDMS为原料,成功地设计和制备出具有不同结构的微流控芯片。基于模拟数据得到的最优条件,其中最优条件包括芯片的最优结构(直通道,入射角度为120°),以及流速为50μL/min等。利用氨水和硝酸铈溶液之间的化学反应,基于软件模拟计算的最优条件,本文将以上两种溶液分别注入到微流控芯片中,开展二氧化铈纳米材料的合成,以及二氧化铈纳米材料形貌的控制。通过条件温度,流速等外界参数,实现了对产物二氧化铈纳米材料形貌的均匀可控。并基于此,利用离子层吸附法制备出硫化镉包覆的二氧化铈纳米粒子,用于组装电致化学发光传感器。该组装中,利用铂丝电极为基底,利用层层组装法实现了电致化学发光传感器的制备,并应用于人体肝癌细胞的检测之中。其检测范围是1000-5000细胞每毫升,检测限为1210个细胞。鉴于基于二氧化铈-硫化镉纳米复合材料的生物传感器的检测范围较窄,难以实现在临床检测中应用的难题,所以,亟需制备新型纳米复合材料的生物传感器。鉴于二氧化硅的无毒性,以及良好的供电子能力,本文展开了合成纳米二氧化硅材料的实验。首先,利用溶液法和微流控方法分别制备出二氧化硅纳米粒子,筛选出具有均一形貌的纳米粒子,并利用离子层吸附法制备出二氧化硅-硫化镉纳米复合材料。紫外可见光谱、能谱,以及扫描电子显微镜等仪器被用来确认该材料成功的被制备出来。通过利用铂丝电极为基底,利用层层组装法再次实现了电致化学发光传感器的制备,并应用于癌细胞的检测之中。其检测范围是300-14000细胞每毫升。通过评估该传感器的性能,发现该新式传感器具有良好的稳定性,选择性和重现性。能够用于癌症早期临床检测的需要,是一种理想的新型检测平台。鉴于上述工作中制备的新型传感器都需要进行封装工序,而不能够直接进行检测,本文开发出一种利用泡沫镍为基底的无需封装的新型生物传感器,并应用于人体肝癌细胞的检测之中。首先,通过对泡沫镍表面的化学修饰改性,实现了泡沫镍的亲疏水性改变,紫外可见光谱,能谱,以及扫描电子显微镜等仪器被用来确认该材料成功的被制备出来。然后利用层层组装法制备出电致化学发光传感器,并应用于肝癌细胞的检测之中。其检测范围是200-10000细胞每毫升,检测限位78个细胞。通过评估该传感器的性能,发现其具有良好的选择性和重现性。但是通过多次检测发现,由于未经过封装,其稳定性相比于封装过的二氧化硅-硫化镉纳米复合材料的生物传感器要略差。
[Abstract]:The electro-chemiluminescence biosensor has a high sensitivity, and has the remarkable advantages of simple instrument, convenient operation, rapidness, wide linear response range and easy realization of automation, so that the novel sensor is more and more widely concerned by the researchers. The invention has carried out the optimization, preparation and assembly of the biosensor for three different nano-composite materials, and is respectively applied to the detection of human liver cancer cells, and the sensitive detection of the cancer cells is realized, and a new platform is provided for clinical detection in the field of biomedicine. This paper has carried out the work of the following aspects: using the CFD method, the Fluent software is used to simulate and design the structure, based on the photolithography method, PDMS is used as the raw material, and the micro-flow control chip with different structure is successfully designed and prepared. The optimal conditions are obtained based on the simulation data, wherein the optimal conditions include the optimal structure of the wafer (straight pass, incident angle of 120 deg.), and flow rate of 50. m u.L/ min, etc. By means of the chemical reaction between the ammonia and the nitric acid solution, based on the optimal conditions of the software simulation, the above two solutions are respectively injected into the micro-flow control chip to carry out the synthesis of the double-oxidized nano-material and the control of the morphology of the two-oxidation-type nano-material. Through the external parameters such as the condition temperature, the flow rate and the like, the uniform and controllable morphology of the product binary oxide nano-material is realized. and based on the method, an ion-layer adsorption method is utilized to prepare the copper sulfide-coated dioxide nano-particles, and is used for assembling an electric-induced chemiluminescence sensor. in the assembly, a platinum wire electrode is used as a substrate, and the preparation of the electro-induced chemiluminescence sensor is realized by a layer-by-layer assembly method, and is applied to the detection of human liver cancer cells. The detection range is 1000-5000 cells per milliliter and the detection limit is 1210 cells. In view of the narrow detection range of the biosensor based on the dioxide-sulfide-sulfide nanocomposite, it is difficult to realize the problem of the application in clinical detection, and therefore, there is an urgent need to prepare a biosensor for a novel nanocomposite. In view of the non-toxicity of the silicon dioxide and the good electron supply capacity, the experiment of the synthesis of the nano-silica material is carried out. firstly, the silicon dioxide nano-particles are prepared by the solution method and the micro-flow control method, and the nano-particles with uniform morphology are screened out, and the silicon dioxide-copper sulfide nano composite material is prepared by the ion layer adsorption method. An instrument such as an ultraviolet visible spectrum, an energy spectrum, and a scanning electron microscope was used to confirm that the material was successfully prepared. By using the platinum wire electrode as the substrate, the preparation of the electro-induced chemiluminescence sensor is realized again by the layer-by-layer assembly method, and the method is applied to the detection of cancer cells. The range of detection is 300-14000 cells per milliliter. By evaluating the performance of the sensor, it is found that the new type of sensor has good stability, selectivity and reproducibility. can be used for early clinical detection of cancer, and is an ideal novel detection platform. In view of the fact that the new type of sensors prepared in the above-mentioned work need to be packaged, and the detection can not be carried out directly, a new type of biosensor based on foamed nickel as a substrate is developed and is applied to the detection of human liver cancer cells. First, by modifying the chemical modification of the surface of the foam nickel, the hydrophobic property change of the foam nickel, the ultraviolet visible spectrum, the energy spectrum, and the scanning electron microscope are used to confirm that the material is successfully prepared. and then the electro-induced chemiluminescence sensor is prepared by a layer-by-layer assembly method, and is applied to the detection of the liver cancer cells. The detection range is 200-10000 cells per milliliter, and the detection limit of 78 cells is detected. By evaluating the performance of the sensor, it was found to have good selectivity and reproducibility. but by multiple tests it is found that the stability is slightly less than that of the encapsulated silica-sulphide nanocomposite due to the fact that the package is not packaged.
【学位授予单位】：哈尔滨理工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TP212.3;TB383.1
本文编号：2366582
[Abstract]:The electro-chemiluminescence biosensor has a high sensitivity, and has the remarkable advantages of simple instrument, convenient operation, rapidness, wide linear response range and easy realization of automation, so that the novel sensor is more and more widely concerned by the researchers. The invention has carried out the optimization, preparation and assembly of the biosensor for three different nano-composite materials, and is respectively applied to the detection of human liver cancer cells, and the sensitive detection of the cancer cells is realized, and a new platform is provided for clinical detection in the field of biomedicine. This paper has carried out the work of the following aspects: using the CFD method, the Fluent software is used to simulate and design the structure, based on the photolithography method, PDMS is used as the raw material, and the micro-flow control chip with different structure is successfully designed and prepared. The optimal conditions are obtained based on the simulation data, wherein the optimal conditions include the optimal structure of the wafer (straight pass, incident angle of 120 deg.), and flow rate of 50. m u.L/ min, etc. By means of the chemical reaction between the ammonia and the nitric acid solution, based on the optimal conditions of the software simulation, the above two solutions are respectively injected into the micro-flow control chip to carry out the synthesis of the double-oxidized nano-material and the control of the morphology of the two-oxidation-type nano-material. Through the external parameters such as the condition temperature, the flow rate and the like, the uniform and controllable morphology of the product binary oxide nano-material is realized. and based on the method, an ion-layer adsorption method is utilized to prepare the copper sulfide-coated dioxide nano-particles, and is used for assembling an electric-induced chemiluminescence sensor. in the assembly, a platinum wire electrode is used as a substrate, and the preparation of the electro-induced chemiluminescence sensor is realized by a layer-by-layer assembly method, and is applied to the detection of human liver cancer cells. The detection range is 1000-5000 cells per milliliter and the detection limit is 1210 cells. In view of the narrow detection range of the biosensor based on the dioxide-sulfide-sulfide nanocomposite, it is difficult to realize the problem of the application in clinical detection, and therefore, there is an urgent need to prepare a biosensor for a novel nanocomposite. In view of the non-toxicity of the silicon dioxide and the good electron supply capacity, the experiment of the synthesis of the nano-silica material is carried out. firstly, the silicon dioxide nano-particles are prepared by the solution method and the micro-flow control method, and the nano-particles with uniform morphology are screened out, and the silicon dioxide-copper sulfide nano composite material is prepared by the ion layer adsorption method. An instrument such as an ultraviolet visible spectrum, an energy spectrum, and a scanning electron microscope was used to confirm that the material was successfully prepared. By using the platinum wire electrode as the substrate, the preparation of the electro-induced chemiluminescence sensor is realized again by the layer-by-layer assembly method, and the method is applied to the detection of cancer cells. The range of detection is 300-14000 cells per milliliter. By evaluating the performance of the sensor, it is found that the new type of sensor has good stability, selectivity and reproducibility. can be used for early clinical detection of cancer, and is an ideal novel detection platform. In view of the fact that the new type of sensors prepared in the above-mentioned work need to be packaged, and the detection can not be carried out directly, a new type of biosensor based on foamed nickel as a substrate is developed and is applied to the detection of human liver cancer cells. First, by modifying the chemical modification of the surface of the foam nickel, the hydrophobic property change of the foam nickel, the ultraviolet visible spectrum, the energy spectrum, and the scanning electron microscope are used to confirm that the material is successfully prepared. and then the electro-induced chemiluminescence sensor is prepared by a layer-by-layer assembly method, and is applied to the detection of the liver cancer cells. The detection range is 200-10000 cells per milliliter, and the detection limit of 78 cells is detected. By evaluating the performance of the sensor, it was found to have good selectivity and reproducibility. but by multiple tests it is found that the stability is slightly less than that of the encapsulated silica-sulphide nanocomposite due to the fact that the package is not packaged.
【学位授予单位】：哈尔滨理工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TP212.3;TB383.1
【参考文献】
相关博士学位论文 前2条
1 陈章;新型生物传感器的构建及其在环境和生物检测中的应用研究[D];湖南大学;2012年
2 庄俭;微注塑成型充模流动理论与工艺试验研究[D];大连理工大学;2007年
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