DNA调控金纳米粒子的组装,生长及其应用
发布时间:2018-03-13 23:08
本文选题:DNA 切入点:分子机器 出处:《中国科学技术大学》2015年博士论文 论文类型:学位论文
【摘要】:从二十世纪九十年代中期,两个具有开拓性的实验组同时提出DNA可以用来调控金纳米粒子的组装以后,该技术后续有着非常广泛的应用。然而,该组装技术中可控的参数单一,在实际的应用中具有一定的限制。为此,我们提出了一种利用动态的DNA分子机器推动金纳米粒子组装的策略。在这种新型的组装技术中,金纳米粒子的组装需要经过一系列的DNA链替换反应才能完成。经过-我们的实验的认证,发现具有催化链效果的DNA链的浓度会影响金纳米粒子的的组装速率。让我们更加震惊的是:该技术能够非常灵活的应用到构建双组份的“与”“或”逻辑们。我们相信这种这种新技术的提出可以说是动态的DNA技术与无机纳米技术的“桥梁”,后续将有广阔的应用背景。 为了进一步的验证我们利用DNA驱动的金纳米粒子组装技术的实用性,我们先专注于它在调控金纳米粒子组装速率上于传统技术的差异。因为不同的应用领域都体现出纳米粒子组装速率的重要性。经过反复的实验,我们发现我们的新型组装技术无论是否经过“预先杂交”的处理都能够使得金纳米粒子具有相对更快的组装速率。而且在我们的组装技术中存在多个可控参数,例如:复合链的浓度还有催化链的浓度。这些都将为我们在设计DNA诊断以及构建复杂的纳米器件提供了基础。 紧接着,我们将DNA驱动的金纳米粒子组装技术应用到单碱基突变(SNP)的检测。结合理论的分析与实验的验证,我们确定了最优的单碱基突变的检测条件。我们的这种检测方法相对于其他的检测技术具有高效,无温度依赖性,以及易于操作的特点。而且我们发现我们这种新型的检测技术不仅仅能够高效率的实现任意位置上的单碱基突变检测,同时可以用于各种类型的单碱基突变检测,例如:碱基的突变,插入或缺失的检测。在完成了所有条件的优化以后,我们将该技术用到与乳腺癌相关的BRCA1基因的突变检测。 尽管我们实现了在不同策略下DNA调控金纳米粒子的组装并且探索了一些可能的应用,但是上述的所有工作的基础是在金纳米粒子合成结束以后将DNA修饰上去。很显然,这里并不涉及对金纳米粒子的形貌的改变。据我们所知,调控纳米粒子的生长(特别是金纳米棒的生长)对其后续的很多应用都具有极大的影响。我们发现编码DNA的序列能够高效的调控金纳米棒的再生长以后的形貌,最终的形状包括哑铃状,正八面体,以及对应的中间结构。通过动力学的研究发现两种不同的生长路径会得到截然不同的结构。最后我们发现充分利用DNA的可编程能力,例如:序列的共混以及特定的巯代磷酸化(PS)修饰,都能有效的调节最终的纳米粒子形状以及光学特性。如果PS修饰数目达到一定数量,最终纳米粒子的表面等离子体共振吸收峰的位置会红移到1000nm以外,进入第二红外区域。
[Abstract]:Since the middle of 1990s, two pioneering experimental groups have simultaneously proposed that DNA can be used to regulate the assembly of gold nanoparticles. There are some limitations in practical application. Therefore, we propose a strategy of using dynamic DNA molecular machine to promote the assembly of gold nanoparticles. The assembly of gold nanoparticles takes a series of DNA chain substitution reactions to complete. It has been found that the concentration of DNA chains with catalytic effect affects the assembly rate of gold nanoparticles. What is more shocking to us is that the technology can be applied to the construction of two-component "and" or "logic" very flexibly. It is believed that this new technology can be said to be a bridge between dynamic DNA technology and inorganic nanotechnology, and will have a broad application background in the future. In order to further verify the practicability of the gold nanoparticles assembly technology driven by DNA, We're going to focus on the difference in the traditional technology in regulating the assembly rate of gold nanoparticles, because different applications have shown the importance of the rate of assembly of gold nanoparticles, and it's been experimented with over and over again. We found that our new assembly technology, whether pre-hybridized or not, allows gold nanoparticles to assemble at a relatively faster rate, and there are many controllable parameters in our assembly technology. For example, the concentration of the composite chain and the concentration of the catalytic chain will provide the basis for the design of DNA diagnostics and the construction of complex nanodevices. Then, we apply the gold nanoparticles assembly technology driven by DNA to the detection of single base mutation. We have determined the optimal conditions for detection of single base mutation. Our method is more efficient and temperature independent than other detection techniques. And easy to operate. And we find that our new detection technology can not only efficiently detect single base mutation at any location, but also can be used for all kinds of single base mutation detection. For example, base mutation, insertion or deletion detection. After all the conditions have been optimized, we use this technique to detect mutations in BRCA1 genes associated with breast cancer. Although we have achieved DNA regulation of the assembly of gold nanoparticles under different strategies and explored some possible applications, all this work has been based on the modification of DNA after the gold nanoparticles have been synthesized. This does not involve changes in the morphology of gold nanoparticles. As far as we know, The regulation of the growth of nanoparticles (especially the growth of gold nanorods) has great influence on many subsequent applications. We found that the sequence encoding DNA can efficiently regulate the morphology of gold nanorods after growth. The final shapes include dumbbells, octahedrons, and corresponding intermediate structures. Kinetic studies show that two different growth paths lead to very different structures. Finally, we find that we can take full advantage of the programmable capabilities of DNA. For example, the blending of sequences and the modification of specific PSs can effectively regulate the shape and optical properties of the final nanoparticles, if the number of PS modifications reaches a certain number, Finally, the position of the surface plasmon resonance absorption peak of the nanoparticles will move red beyond 1000 nm into the second infrared region.
【学位授予单位】:中国科学技术大学
【学位级别】:博士
【学位授予年份】:2015
【分类号】:TB383.1;O614.123
【共引文献】
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