各向异性微球的微流控制备及其在生物分析中的应用

发布时间：2018-03-14 00:54

本文选题：微流控　切入点：微球　出处：《东南大学》2017年博士论文　论文类型：学位论文

【摘要】：多元分析技术在生物医学领域具有重要的应用价值。基于流动载体的多元生物分析技术具有明显的优越性,其关键环节是开发合适的编码载体。传统的高分子微球其表面化学组成是均匀(各向同性)的,随着研究的深入,理论和实验结果表明各向异性微球在控制分子识别和自组装过程中拥有普通微球所没有的特殊性质。此外,如果可以制备出具有多种化学组成和功能分区的微球,则可以赋予编码载体更加丰富的功能,从而大大拓展其灵活性和应用价值。微流控技术是指在微观尺度下将不同的流体按照特定的方式整合于一个体系内,并对其行为进行系统地控制和操作的技术。经过近几十年来的发展,微流控技术为许多科技领域提供了新的方法,包括化学合成、生化分析、即时诊断、药物开发以及环境监测等等。尤其是在材料制备方面,微流控技术可以对所制备的材料结构进行精确的控制。因此,本论文以微流控为技术手段,设计并制备各向异性功能性生物载体,开发其在生物分析中的应用,具体研究内容如下:(1)基于单乳液体系,设计构建了两组分Janus乳液生成装置,由此通过溶剂蒸发诱导单分散的二氧化硅纳米粒子自组装成胶体晶体密堆积结构,同时使磁性纳米粒子在磁场的作用下进行沉积,从而制备具有各向异性Janus结构的磁响应性可控运动的胶体晶体微球,并将其应用于生物分析。(2)基于双乳液体系,设计并构建了基于七孔毛细管阵列的一步法生成双乳液的玻璃毛细管微流控芯片。毛细管阵列中最内部的一个毛细管和环绕在外部的六根毛细管形成精确的中心对称结构,从而避免了传统的芯片构建过程中的人工对中操作,使得制备工艺得到简化。利用此芯片,可以实现单核及多核双乳液的可控制备。(3)基于双乳液体系,制备了具有胶体晶体微气泡结构的可悬浮编码载体,并用于生物分析。首先利用微流控技术制备壳层为选择透过性膜,内核为水溶液的微胶囊,通过高渗溶液诱导,使微胶囊发生空化现象,并在胶囊内部产生气泡。此方法操作简单,过程可控。以此为基础,制备内核为胶体纳米粒子分散液的微胶囊;通过诱导胶囊内部发生空化现象,引导纳米粒子在固液气三相界面组装成密堆积的球形胶体晶体层。最终得到的双壳层微气泡结构解决了传统载体在检测液中迅速沉降的缺点,并具有稳定性高、编码量可扩增,以及多功能等优点,在免疫分析、细胞培养及生物材料相容性评价方面具有重要应用价值。(4)基于单乳液双乳液复合体系,同时制备液滴和纤维,并使单分散的液滴被纤维串起而形成微载体阵列结构,通过实验参数的控制使得载体在纤维上可以具有固定和自由滑动两种模式。这种微载体阵列在细胞培养方面具有很高的灵活性。另一方面,液滴在剪切力和界面张力的共同作用下沿着纤维生成的方向发生形变,由球形变成纺锤状。因此,所制备的微载体阵列还具有仿天然蜘蛛丝的结构,并具有水分收集、温度响应、非球形胶体晶体组装等多重功能。
[Abstract]:Multivariate analysis technique has important application value in the biomedical field. Multiple biological carrier flow analysis technology has obvious superiority on the key is to develop appropriate vector encoding. The surface of polymer microspheres of traditional chemical composition is uniform (isotropic), with further research, theoretical and experimental results show that the special nature of anisotropic microspheres in the control of molecular recognition and self-assembly process with ordinary microspheres have not. In addition, if can be prepared with a variety of chemical composition and function partition of the microspheres can be endowed with more abundant function vector encoding, thereby greatly expanding the flexibility and application value. Microfluidic technology refers to the micro scale the different fluid in a specific manner and integrated into a system, and system control and operation technology of its behavior. After recent Ten years of development, provides a new method of microfluidic technology for many scientific and technological fields, including chemical synthesis, biochemical analysis, real-time diagnosis, drug development, environmental monitoring and so on. Especially in the fabrication of materials, microfluidic technology can control on the structure of the material prepared for accurate. Therefore, this based on the micro fluidic technology, design and preparation of anisotropic functional bio carrier, the development of its application in biological analysis, the specific contents are as follows: (1) single emulsion system based on the design of two components of Janus emulsion forming device by solvent evaporation induced self monodisperse silica nanoparticles assemble the colloidal crystal close packed structure, while the magnetic nanoparticles were deposited in the magnetic field, so as to prepare the Janus structure with anisotropic magnetic response of colloidal crystal microspheres controlled movement, and Its application in biological analysis. (2) double emulsion system based on the design and construction of glass capillary generated double emulsion one-step seven capillary array based on microfluidic chip. The capillary array in a capillary inside and around the outside of the six capillary formation center symmetrical structure accurately, so as to avoid the construction process of traditional chip in artificial to operate, the preparation process is simplified. By using this chip, can realize the mononuclear and polynuclear double emulsion can be controlled. (3) double emulsion has been prepared based on colloidal crystal micro bubble structure of the suspended carrier and encoding for biological analysis. First. Using microfluidic technology for preparation of shell for selectively permeable membrane, the kernel for the microcapsule aqueous solution, hypertonic solution induced by the micro capsule, cavitation phenomenon, and bubbles in the internal capsule. This method of operation The process is simple, controllable. On this basis, the preparation of microcapsule core colloidal nanoparticles dispersion induced by the internal capsule; cavitation phenomenon, guide the nanoparticles in the solid liquid gas interface assembly into a spherical colloidal crystal layer of closely packed structure. The micro bubble Double Shell finally solve the traditional carrier settlement quickly in the test solution the shortcomings, and has high stability, the amount of amplification and encoding, etc., in immune analysis, has important application value in evaluation of compatible cell culture and biological material. (4) single emulsion double emulsion composite system based on simultaneous preparation of droplets and fibers, and monodisperse droplets by forming a micro fiber string vector array structure, controlled by the experimental parameters of the carrier can be fixed and free to slide two modes in the fiber. The micro carrier training in cell array It possesses high flexibility. On the other hand, the interaction of droplet on shear stress and interfacial tension along the fiber direction generated by the spherical deformation into spindle. Therefore, micro structure array carrier prepared with imitation of natural spider silk, and has the water collection, temperature response, multiple functions non spherical assembly of colloidal crystals.

【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q5-3

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