基于微流控技术的生物载体的制备及应用

发布时间：2018-01-02 07:16

本文关键词：基于微流控技术的生物载体的制备及应用　出处：《东南大学》2016年博士论文　论文类型：学位论文

【摘要】：微流控技术是一门在物理、化学、工程学、微加工与生物技术等基础上发展起来的在微米级结构中操控微尺度液体的科学与技术,在微混合、微分离、微反应和微检测等领域迅猛发展。由于其对微尺度流体精确的操纵、处理与控制特性,近年来微流控技术在制备功能化和结构化的微载体材料方面,突显了传统制备技术无法比拟的优越性。所制备的微载体材料有望在基因测序、液相芯片、药物筛选和缓释以及细胞培养等领域有着重要应用,并推动生物医学技术的发展。因此,本论文以微流控技术为技术手段,设计并制备功能性生物载体,开发其在生物医学中的应用,具体研究内容如下：(1)设计并搭建协流式单乳液玻璃毛细管微流控装置,利用该装置生成单分散的二氧化硅乳液液滴,通过固化、清洗和煅烧,将乳液液滴转化为二氧化硅胶体晶体微球；通过水凝胶将量子点均匀地固定在微球内部,以胶体晶体微球的反射光谱和量子点的荧光光谱作为双重编码元素,从而制备了量子点胶体晶体复合编码微球载体；通过引入多种发射波长及荧光强度的量子点,增大了编码载体的编码量；探讨了复合微球作为生物分子的编码载体在生物检测中应用的可行性以及检测结果的可靠性。(2)利用二氧化硅胶体纳米粒子之间的静电排斥作用,将其分散在水凝胶单体溶液中,使其自主装成非密堆积型胶体晶体前聚体溶液；改变协流式单乳液玻璃毛细管微流控装置中出口通道的形貌和尺寸,调节合适的流速,前聚体溶液在出口通道中被挤压成具有一定形貌的非球型液滴；紫外光在线聚合,固定了液滴的形貌,进而得到了一系列具有结构色的棒状、饼状和立方体状凝胶微粒；通过煅烧非密堆积的非球型凝胶微粒,实现了密堆积非球型胶体晶体微粒的制备；研究了不同形貌微粒的光学特性；以胶体晶体微粒的形貌和反射光谱作为双重编码元素,提高了编码的稳定性和准确性,检验了其在多元分析中应用的可行性。(3)设计并搭建了具有可扩展微流通道结构的玻璃毛细管微流控装置,利用海藻酸钠溶液和氯化钙溶液在协流通道口处快速的海藻酸钙微纤维凝胶化反应,实现了一系列仿生多组分微纤维的制备,包括多组分微纤维、多通道中空微纤维、多核壳中空微纤维和多组分中空微纤维；研究了流速、通道尺寸和溶液的浓度对纤维结构和尺寸的影响；将细胞混合在海藻酸钠溶液中,制备了仿生血管状细胞负载纤维,研究了细胞在纤维中的生长情况和生理活性,证明了该纤维在细胞三维共培养和仿生血管构建系统中应用的可行性,实现了人造血管模型的初步构建,为今后开展血管等组织或者器官的体外模拟和研究奠定了基础。
[Abstract]:Microfluidic technology is a physical, chemical, and biological engineering, development of micro processing technology based on the control of science and technology of micro scale liquid in micron structure, micro mixing, differential from the field of micro and micro reaction detection rapidly. Due to its precise manipulation of micro fluid, and control characteristics, micro carrier material microfluidic technology to prepare functional and structural aspects of the system in recent years, highlights the superiority of the traditional preparation technology is unable to compare. The prepared micro carrier material is expected in the liquid phase chip, gene sequencing, drug screening and field release and cell culture have important the application, and promote the development of biomedical technology. Therefore, the microfluidic technology, design and preparation of functional biological carrier, its development and application in biomedicine, the specific contents are as follows: (1). Design and build co flow type single emulsion glass capillary microfluidic device, the device generates monodisperse silica emulsion droplets, through curing, cleaning and calcination, the emulsion droplets into silica colloidal crystal beads; quantum dots are uniformly fixed on the microspheres through hydrogels by fluorescence spectra and reflectance spectra of quantum dots colloidal crystal microspheres as double encoding elements, thus making quantum dot colloidal crystal composite microspheres were prepared by encoding; introducing multiple quantum dot emission wavelength and fluorescence intensity, increasing the amount of vector encoding encoding; discusses the feasibility of the application of reliability of composite microspheres as carrier encoding of biological molecules in biological detection and detection results. (2) the use of electrostatic repulsion between the colloidal silica nanoparticles, the hydrogel dispersed in the monomer solution, making it independent Loaded into non close packed colloidal crystal type precursor solution; the morphology and size change co export channel microfluidic device in glass capillary flow single emulsion, adjust the appropriate flow rate, precursor solution in the export channel is squeezed into a certain shape of non spherical droplets; ultraviolet light online polymerization. Fixed the morphology of droplets, and then got a series of structural color bar, pie and cubic gel particles by calcination; non spherical gel particles closely packed, realize the close packing of non spherical colloidal crystal particle preparation; optical properties of particles with different morphologies and morphology; reflectance spectra of colloidal crystal particles as double encoding elements, improves the stability and accuracy of encoding, to test its feasibility in multivariate analysis. (3) to design and build scalable microfluidic channel structure. Glass capillary microfluidic device, using sodium alginate and calcium chloride solution in the co flow channel at the mouth of the fast calcium alginate fiber gel reaction, to achieve a series of biomimetic multicomponent micro fiber preparation, including multi-component micro fiber, multi channel micro hollow fiber, multi-core fiber and micro hollow shell hollow fiber micro components; study the influence of channel size and velocity, concentration of solution on the fiber structure and size; the cells mixed in sodium alginate solution, preparation of fiber biomimetic vessel shaped cells on the cell load in the fiber growth and physiological activity, proved that the fiber in three-dimensional cell co culture and the feasibility of constructing biomimetic vascular system, realize the preliminary construction of artificial blood vessel model, laid the foundation for future research and development in vitro vascular tissue or organ.

【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TQ427.26;R318

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