【作者】 张彬；

【导师】 赵远锦；

【作者基本信息】 东南大学 ， 生物医学工程， 2016， 硕士

【摘要】 随着生命科学等相关产业的迅猛发展,出现了大批新型的生物医学制品,为了更好地研究生物系统中各成分的功能及生物分子之间的相互作用,高效易行的生物分析技术是必不可少的。生物分析技术是研究和发展生命科学的本质性工具,也是生物制品能否市场化应用的检验标准,除了已广泛应用的荧光标记分析,电化学分析以及酶联免疫分析技术等,新开发的纳米粒、纳米线和光子晶体等材料,在生物分析领域也具有极大的应用前景。其中反蛋白石结构的光子晶体因其编码稳定性、折射率易调节、三维互相贯穿的孔隙结构、较低的弯曲度以及较大的比表面积等优点,逐渐被广泛的应用到生物分析领域。但目前开发的大多数反蛋白石材料功能单只能实现简单的多元生物分子检测,或者细胞在其表面和内部的培养,而对于其在生物分子的控制释放及细胞尺度的生物检测等方面的应用仍有待探索,因此制备具有多功能且适用于生物医学检测的反蛋白石材料仍然面临极大的挑战。本论文的研究工作主要就是利用功能性水凝胶为材料,通过模版复制技术制备具有不同功能的反蛋白石微载体,并将它们应用到药物释放和细胞检测中。具体工作如下：(1)反蛋白石结构水凝胶微载体的制备：利用玻璃微流控装置,搭建液滴模版发生装置,制备出尺寸可控,单分散性高的光子晶体微球。再以微球做为模版,在纳米粒子孔隙之间填充功能性水凝胶,利用氢氟酸溶液全部或者部分除去模版,分别得到反蛋白石结构的微载体和核壳型结构的微载体。(2)基于反蛋白石结构水凝胶微载体的药物释放与监控：以光子晶体微球为模版,N-异丙基丙烯酰胺(NIPAM)水凝胶为填充材料,制备了一种具有温度响应性能的反蛋白石结构的药物载体,利用微载体随温度变化发生体积相变化的特征实现药物的控制释放。当温度高于其最低临界温度时,水凝胶剧烈收缩,药物分子会被挤压释放出来,并且根据反蛋白石材料的光学特性,可以通过观测反射峰的变化,实现对药物释放过程的实时监控。(3)基于反蛋白石结构水凝胶微载体的血液细胞捕获及检测：制备了一种基于反蛋白石水凝胶微载体的悬浮阵列用于血液细胞的多元捕获与分离。这种反蛋白石微载体由丙烯酰胺水凝胶组成,反蛋白石的周期性结构作为编码元素实现多元检测的目标,通过在微载体上修饰不同的功能蛋白能够实现对血液中细胞的选择特异性无损捕获。更多还原

【Abstract】 With the rapid development of bioscience related industries, a large number of new biomedical products appeared, in order to study the function of each component and their interaction in biological systems, efficient and feasible bioanalytical techniques is indispensable. Bioassay is not only an essential tool for the investigation of bioscience, but also required by regulatory authorities in setting product specifications. In addition to the established fluorescence, electrochemistry and enzymatic amplification technology, newly developed materials, such as nanoparticles, nanowires, and photonic crystals (PCs), have also shown great promise in bioassays. Among these, inverse opal photonic crystals have attracted increasing interests in this field, because of its wonderful characteristic including stability of coding information, easier adjusting of material refractive index, three dimensional interconnected pore system, lower bending and larger specific surface area. However, most of the developed inverse opal materials could only implement simple multivariate biological molecular detection, or cell culture on the surface and internal macropores, while their applications in controlled release of bioactive molecular and bioassays at cell level remains to be explored. Thus there is still great chanllenge to prepare multifunctional and extensive inverse opal materials which are suitable for biomedical assays. Herein, we chose stimuli-responsive hydrogel as framework material to fabricate several kinds of inverse opal microcarriers with different function by template relication technology, and investigated their applications in controlled drug release and cell evaluating. The detailed content of the work are as follows:(1) Fabrication of inverse opal hydrogel microcarriers:perapared glass capillary micofluidic devices to fabricate photonic crystal particles with uniform size and high monodispersity. Then the photenic crystal particles were used as template to produce inverse opal microcarrier and core-shell inverse opal microcarrier by completely and partly removing the slilica template, respectively.(2) Inverse opal hydrogel microcarrier for drug delivery and monitor:the thermo-responsive inverse opal microcarrier was composed of N-isopropylacrylamide (NIPAM) hydrogel. Since the shrink and swell of the microcarrier under different temperature triggers, the encapsulated drug could be extruede from the nanopores of the particle. Therefore, this release can be controlled by adjusting the temperature. With release of the drugs, the characteristic reflection peak of the inverse opal particles blue shifted correspondingly. Thus, the process of drug release from the particles could be monitored in real time.(3) Inverse opal hydrogel microcarrier for the capture and detection of blood cells: we present a new type of suspension array that can simultaneously capture and detect multiple types of blood cells. The barcode particles are polyacrylamide (PAAm) hydrogel inverse opal microcarriers with characteristic reflection peak codes that remain stable during cell capture on their surfaces. The hydrophilic PAAm hydrogel scaffolds of the barcode particles can entrap various plasma proteins to capture different cells in the blood.更多还原