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研究生: 王國權
Guo-Quan Wang
論文名稱: 高螢光量子產率之AgInS2量子點表面化學修飾與功能化於細胞影像應用
Preparation and Surface Functionalization of AgInS2 Quantum Dots with High Fluorescence Quantum Yield and Their Cell Imaging Applications
指導教授: 張家耀
Jia-Yaw Chang
口試委員: 何郡軒
Jinn-Hsuan Ho
黃志清
Chih-Ching Huang
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 99
中文關鍵詞: I-III-VI族量子點兩性高分子腫瘤癌細胞
外文關鍵詞: I-III-VI group Quantum dot, Amphiphilic polymer, Cancer cells
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  • 本論文結合了奈米合成技術與生物醫學應用,將奈米材料應用在細胞體上的顯影標靶。藉由優化銀與銦的前驅物比例、界面活性劑加入量、反應溫度及時間以改善材料缺陷性質,再將核層量子點以無機材料包覆在內形成核殼型量子點(AgInS2/ZnS),可明顯提高AgInS2量子點的螢光量子產率;接著利用馬來酸酐-1-十八烯(PMAO)兩性高分子表面改質技術將殼核型量子點包覆溶於水相中,並進行生物體內螢光標記之應用。接著利用高解析穿透式電子顯微鏡(HR-TEM)探測奈米粒子之晶型、X光繞射儀(XRD)測定合成之奈米材料結構;螢光光譜儀(Fluorescence Spectrophotometer、PL)進行光學性質之量測;共軛焦顯微鏡(Confocal)偵測材料於生物體內之放光情況,檢測結果顯示量子點能夠成功染色於細胞體內,進行螢光標記之應用。
    首先使用高溫注入法,將硬酯酸銦、硝酸銀等金屬前驅物進行熱裂解反應,並溶解在辛烯與硫醇之有機溶劑中,探討前驅物組成比例差異及反應溫度對晶體成核與螢光量子產率之影響,以製作出高品質之奈米粒子AgInS2與AgInS2/ZnS量子點;再以馬來酸酐-1-十八烯(PMAO)分子當作兩性高分子包覆法之材料製作量子點複合粒子,使其具有水相性質,接著我們再加入交聯劑使量子點發生交聯反應,將量子點複合材料表面與葉酸分子鍵結。因癌細胞表面上具有過度表現的葉酸受體,因此當量子點表面具有葉酸分子時,可提高材料進入癌細胞的機率;在生物體應用研究上,將表面接有葉酸分子之量子點複合材料進行HepG2人體肝癌細胞之螢光顯影,顯示HepG2人體肝癌細胞在未含有葉酸之量子點複合材料相較之下,證明具有葉酸分子之量子點確實能提高量子點複合材料進入生物體內之機率。


    In this research, we report the effect of the initial Ag:In stoichiometry, capping ligand concentration, and reaction temperature on the optical properties of AgInS2 quantum dots (QDs). The fabricated QDs exhibit excellent optical characteristics, including PL quantum yields of up to 22 % and the appearance of an excitonic absorption peak. This is the first reported observation of such a well-defined exciton absorption feature in AgInS2 QDs. Its appearance could indicate a relatively narrow size distribution or minimization of nonradiative recombination at the surface sites of the QDs.
    Moreover, we report one-pot two-step synthesis of highly luminescent AgInS2-ZnS QDs by injection of ZnS precursors directly into the same reactor with existing AgInS2 cores without any purification. In addition, to demonstrate their potential biomedical application, the AgInS2-ZnS QDs were coated with poly(maleic
    anhydride-alt-1-octadecene) and further conjugated with folic acid for human liver carcinoma (HepG2) tumor cell labeling. The folate-receptor-mediated cellular uptake of the folic-acid-conjugated AgInS2-ZnS QDs was confirmed by confocal imaging characterization. Additionally, the small dimensions and high solubility of the folic-acid-conjugated AgInS2-ZnS QDs were also exploited in prefixed-cell staining; the QDs entered the complex cellular matrix and stained both the nucleoli and cytoplasm of HepG2 cells.

    總目錄 第一章、緒論 1-1 前言…………………………………………………...........................................1 1-2 研究動機與內容....................................................................................................2 第二章、理論基礎與文獻回顧 2-1 奈米半導體材料之光學特性與理論……………………………….....……......3 2-1-1奈米材料之基礎理論與特性…………..………………………………..3 2-1-2量子點之發展與應用…..…………………………………..……………8 2-1-3量子點之製備與文獻回顧……………………………..………………13 2-2 量子點表面改質與文獻回顧……………………………………….…………21 2-2-1配位體交換法………………………..…................................................21 2-2-2兩性高分子包覆法………………..…………….………………..……23 2-2-3氧化矽包覆法…………………………………………….……………27 2-3 量子點在生物技術上顯影與文獻回顧……………………………….…..…..29 2-3-1量子點奈米材料之非特異性細胞內傳遞機制……………………......29 2-3-2量子點奈米材料靶向性功能化之探討與應用………..………...….…33 第三章、實驗方法 3-1 實驗藥品...............................................................................................................43 3-2 實驗量測儀器…………………………………………………………………...46 3-3 實驗步驟……………………………………………………………...…………48 3-3-1 AgInS2量子點合成……………………………………………………...48 3-3-2 AgInS2/ZnS量子點合成………………………………………………..48 3-3-3 AgInS2/ZnS量子點與十八烯馬來酸酐(PMAO)之表面改質…………49 VI 3-3-4 AgInS2/ZnS/PMAO水相量子點與葉酸鍵結之合成………………….49 3-3-5細胞培養…………………………………………………………………50 3-4 樣品分析……………………………………………………………………….53 第四章、實驗結果與討論 4-1 I-III-VI族AgInS2核層量子點之製備與合成……………………...………...56 4-1-1 AgInS2實驗介紹………….....…………………….……………………56 4-1-2 AgInS2前驅物參數調整之量子產率最佳化探討…………….……….59 4-1-3 AgInS2界面活性劑參數調整之量子產率最佳化探討……………......62 4-1-4 AgInS2反應溫度參數調整之量子產率最佳化探討…………………..67 4-2 I-III-VI族AgInS2/ZnS核層-殼層量子點製備與合成….…………………..71 4-2-1 AgInS2/ZnS實驗設計....…………….………………………………...71 4-2-2 AgInS2/ZnS前驅物參數調整之量子產率最佳化探討……..…….….72 4-2-3 AgInS2/ZnS反應溫度參數調整之量子產率最佳化探討…..…….….73 4-3 I-III-VI族AgInS2/ZnS核層-殼層量子點特性分析........................................76 4-3-1 AgInS2/ZnS量子點之型態與結構分析.………….…………………..76 4-3-2 AgInS2/ZnS量子點之光學特性分析………………………..………..78 4-4 AgInS2/ZnS量子點表面改質與功能化合成之鑑定分析................................81 4-4-1 AgInS2/ZnS核-殼型量子點與十八烯馬來酸酐(PMAO)之表面修飾 與分析……….………………………………………………................81 4-4-2 AgInS2/ZnS水相量子點與葉酸接合之製備與分析…………………83 4-5 AgInS2/ZnS奈米複合物之生物顯影與應用…………………………………87 4-5-1共軛焦顯微鏡之生物影像顯影應用……………………….………….87 第五章、結論與未來展望.………………………………………………………….92 文獻參考……………………………………………………………………………..94

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