本文選題：DNA　切入點(diǎn)：分子機(jī)器　出處：《中國科學(xué)技術(shù)大學(xué)》2015年博士論文　論文類型：學(xué)位論文

【摘要】：從二十世紀(jì)九十年代中期,兩個(gè)具有開拓性的實(shí)驗(yàn)組同時(shí)提出DNA可以用來調(diào)控金納米粒子的組裝以后,該技術(shù)后續(xù)有著非常廣泛的應(yīng)用。然而,該組裝技術(shù)中可控的參數(shù)單一,在實(shí)際的應(yīng)用中具有一定的限制。為此,我們提出了一種利用動(dòng)態(tài)的DNA分子機(jī)器推動(dòng)金納米粒子組裝的策略。在這種新型的組裝技術(shù)中,金納米粒子的組裝需要經(jīng)過一系列的DNA鏈替換反應(yīng)才能完成。經(jīng)過-我們的實(shí)驗(yàn)的認(rèn)證,發(fā)現(xiàn)具有催化鏈效果的DNA鏈的濃度會(huì)影響金納米粒子的的組裝速率。讓我們更加震驚的是：該技術(shù)能夠非常靈活的應(yīng)用到構(gòu)建雙組份的“與”“或”邏輯們。我們相信這種這種新技術(shù)的提出可以說是動(dòng)態(tài)的DNA技術(shù)與無機(jī)納米技術(shù)的“橋梁”,后續(xù)將有廣闊的應(yīng)用背景。 為了進(jìn)一步的驗(yàn)證我們利用DNA驅(qū)動(dòng)的金納米粒子組裝技術(shù)的實(shí)用性,我們先專注于它在調(diào)控金納米粒子組裝速率上于傳統(tǒng)技術(shù)的差異。因?yàn)椴煌膽?yīng)用領(lǐng)域都體現(xiàn)出納米粒子組裝速率的重要性。經(jīng)過反復(fù)的實(shí)驗(yàn),我們發(fā)現(xiàn)我們的新型組裝技術(shù)無論是否經(jīng)過“預(yù)先雜交”的處理都能夠使得金納米粒子具有相對更快的組裝速率。而且在我們的組裝技術(shù)中存在多個(gè)可控參數(shù),例如：復(fù)合鏈的濃度還有催化鏈的濃度。這些都將為我們在設(shè)計(jì)DNA診斷以及構(gòu)建復(fù)雜的納米器件提供了基礎(chǔ)。 緊接著,我們將DNA驅(qū)動(dòng)的金納米粒子組裝技術(shù)應(yīng)用到單堿基突變(SNP)的檢測。結(jié)合理論的分析與實(shí)驗(yàn)的驗(yàn)證,我們確定了最優(yōu)的單堿基突變的檢測條件。我們的這種檢測方法相對于其他的檢測技術(shù)具有高效,無溫度依賴性,以及易于操作的特點(diǎn)。而且我們發(fā)現(xiàn)我們這種新型的檢測技術(shù)不僅僅能夠高效率的實(shí)現(xiàn)任意位置上的單堿基突變檢測,同時(shí)可以用于各種類型的單堿基突變檢測,例如：堿基的突變,插入或缺失的檢測。在完成了所有條件的優(yōu)化以后,我們將該技術(shù)用到與乳腺癌相關(guān)的BRCA1基因的突變檢測。 盡管我們實(shí)現(xiàn)了在不同策略下DNA調(diào)控金納米粒子的組裝并且探索了一些可能的應(yīng)用,但是上述的所有工作的基礎(chǔ)是在金納米粒子合成結(jié)束以后將DNA修飾上去。很顯然,這里并不涉及對金納米粒子的形貌的改變。據(jù)我們所知,調(diào)控納米粒子的生長(特別是金納米棒的生長)對其后續(xù)的很多應(yīng)用都具有極大的影響。我們發(fā)現(xiàn)編碼DNA的序列能夠高效的調(diào)控金納米棒的再生長以后的形貌,最終的形狀包括啞鈴狀,正八面體,以及對應(yīng)的中間結(jié)構(gòu)。通過動(dòng)力學(xué)的研究發(fā)現(xiàn)兩種不同的生長路徑會(huì)得到截然不同的結(jié)構(gòu)。最后我們發(fā)現(xiàn)充分利用DNA的可編程能力,例如：序列的共混以及特定的巰代磷酸化(PS)修飾,都能有效的調(diào)節(jié)最終的納米粒子形狀以及光學(xué)特性。如果PS修飾數(shù)目達(dá)到一定數(shù)量,最終納米粒子的表面等離子體共振吸收峰的位置會(huì)紅移到1000nm以外,進(jìn)入第二紅外區(qū)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.
【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：TB383.1;O614.123

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

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