本文關(guān)鍵詞： 單光子熒光 雙光子熒光 光學(xué)非線性效應(yīng) 量子點(diǎn) AIE染料 納米金棒 光學(xué)生物成像 深層組織成像　出處：《浙江大學(xué)》2015年博士論文　論文類型：學(xué)位論文

【摘要】：隨著社會(huì)的進(jìn)步,健康問題愈受重視。生物成像為醫(yī)學(xué)研究與臨床的診斷治療提供了很好的輔助,是現(xiàn)代醫(yī)學(xué)的重要組成部分。相較于廣泛使用的X射線,B超,磁共振等成像手段,光學(xué)生物成像具有分辨率高,無輻射污染,適用范圍廣等優(yōu)點(diǎn),而倍受人們關(guān)注。本文介紹了以幾種光學(xué)效應(yīng)為核心,采用納米顆粒作為輔助顯色劑的生物成像方面的許多研究工作。主要的研究內(nèi)容包括：1、采用高量子產(chǎn)率的量子點(diǎn)來做單光子熒光成像。疏水的CdSe/Zn S量子點(diǎn)通過SiO2包覆與羧基修飾,轉(zhuǎn)化為親水性,以與生物環(huán)境相匹配。包覆后它們具有良好的均一性,穩(wěn)定性,與分散性。將它們與轉(zhuǎn)鐵蛋白連接后,用于對HeLa細(xì)胞的單光子熒光成像,實(shí)現(xiàn)了對癌細(xì)胞的特異性標(biāo)記,這在腫瘤的識(shí)別與治療中具有重要意義。2、采用具有高熒光亮度的AIE染料來做雙光子熒光成像。對有機(jī)染料BT3的AIE特性進(jìn)行了表征,并將它們包覆成納米顆粒。BT3納米顆粒發(fā)紅光,并且有很大的Stokes頻移,有利于生物成像。通過雙光子誘導(dǎo)熒光法測得BT3納米顆粒在1040 nm處的雙光子吸收(2PA)截面達(dá)到了2.9×106GM,比770-860 nm范圍內(nèi)的值都要高,也比許多商用染料(如若丹明B)的2PA截面要大很多。采用蒙特卡洛仿真發(fā)現(xiàn)了1040 nm比800 nm激光束在生物組織中有更好的穿透能力。觀察了BT3納米顆粒在小鼠體內(nèi)的分布與代謝情況,發(fā)現(xiàn)它們主要集中在肝臟,并且可以通過代謝排出體外。采用1040 nm的飛秒光源激發(fā),用BT3納米顆粒注射小鼠,實(shí)現(xiàn)了鼠腦活體的雙光子熒光成像,可以清晰地看到各種血管,成像中深度達(dá)到了700 μm。這種合適的激發(fā)光源與大2PA截面的AIE納米顆粒的結(jié)合對提高成像濃度非常有效。3、采用具有豐富非線性信號(hào)的納米金棒來實(shí)現(xiàn)非線性光學(xué)效應(yīng)成像。制備了多種納米金棒,并對它們分別進(jìn)行了高分子聚合電解質(zhì)包覆,SiO2包覆,與PEG包覆以適應(yīng)不同的需求。利用離散偶極子近似(DDA)對納米金棒的吸收、散射與表面電場特性進(jìn)行了模擬。采用自搭建的系統(tǒng)測量了納米金棒在近紅外飛秒光激發(fā)下的非線性信號(hào)。用納米金棒來標(biāo)記細(xì)胞,分別以1260 nm與1580 nm飛秒光作為激發(fā)光源,利用納米金棒的二次諧波、三次諧波等信號(hào)實(shí)現(xiàn)了細(xì)胞的多通道非線性成像,這對于今后將納米金棒應(yīng)用于活體的第二與第三光學(xué)組織窗口非線性成像提供了很好的基礎(chǔ)。
[Abstract]:With the progress of society, the health problems are paid more and more attention. Biomedical imaging provides a good aid for medical research and clinical diagnosis and treatment, is an important part of modern medicine. Compared with the widely used X-ray, B-ultrasound, Magnetic resonance imaging and other imaging methods, optical biological imaging has the advantages of high resolution, no radiation pollution, wide range of application, and has attracted much attention. This paper introduces several optical effects as the core. Many research work on biological imaging using nanoparticles as auxiliary chromogenic agent. The main research contents include: 1, single photon fluorescence imaging using quantum dots with high quantum yield. Hydrophobic CdSe/Zn s quantum dots pass through SiO2. Coating with carboxyl group, They were transformed into hydrophilic to match the biological environment. They were coated with good uniformity, stability, and dispersion. They were connected with transferrin and used for single photon fluorescence imaging of HeLa cells. The specific labeling of cancer cells was realized, which is of great significance in the recognition and treatment of cancer cells. Two-photon fluorescence imaging was performed with AIE dyes with high fluorescence brightness. The AIE characteristics of organic dyes BT3 were characterized. They are coated into nanoparticles. BT3 nanoparticles glow red and have a large Stokes shift. The two-photon absorption 2PA cross-section of BT3 nanoparticles at 1040nm is 2.9 脳 106GM, which is higher than that in the range of 770-860 nm. The cross section of 2PA was also much larger than that of many commercial dyes (such as Rhodamine B). Monte Carlo simulation showed that 1040nm laser beam had better penetration ability in biological tissue than 800nm laser beam. The BT3 nanoparticles were observed in mice. Distribution and metabolism, It is found that they are mainly concentrated in the liver and can be excreted from the body by metabolism. By using 1040nm femtosecond light source and injecting mice with BT3 nanoparticles, two-photon fluorescence imaging of the brain is realized, and various blood vessels can be clearly seen. The depth of the imaging is 700 渭 m. The combination of the suitable excitation source and the AIE nanoparticles with large 2PA cross-section is very effective to increase the imaging concentration. The gold nanorods with abundant nonlinear signals are used to realize the nonlinear optical effect. A variety of nanocrystalline gold rods have been prepared. They were coated with polyelectrolyte and PEG respectively to meet different requirements. The absorption of nanocrystalline gold rods was obtained by using discrete dipole approximation (DDAA). The characteristics of scattering and surface electric field were simulated. The nonlinear signals of nanocrystalline gold rods excited by near-infrared femtosecond light were measured by a self-built system. The cells were labeled with nanocrystalline gold rods, using 1260nm and 1580nm femtosecond light sources, respectively. The second harmonic and third harmonic signals of gold nanorods are used to realize the multichannel nonlinear imaging of cells, which provides a good basis for the application of nanocrystalline gold bars to the nonlinear imaging of the second and third optical tissue windows in vivo in the future.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：Q-33

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本文編號(hào)：1505654