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  • 學位論文

利用氧化鋅奈米柱發光二極體發展腫瘤偵測技術

Tumor detection for cancers by using ZnO light emitting nanorods

指導教授 : 黃建璋

摘要


近年來由於氧化鋅獨特的光學特性,氧化鋅奈米結構得到高度的重視,包括在室溫下3.37 eV的高能隙和60 meV的激子束縛能(exciton binding energy)。而在眾多的奈米結構中,一維氧化鋅奈米柱更是被廣泛的使用在不同的應用領域之中,如短波長發光二極體(light emitters),場發射器(field emitters),發光元件,紫外光雷射以及太陽能電池。 而在眾多的應用領域中,一維氧化鋅奈米柱在生醫科技中更是相當具有潛力的一種材料。由於一維氧化鋅奈米柱在各種生物分子中有著相當穩定的性質,不容易與生物分子產生化學作用,以及相當高的生物相容性,這都使得一維氧化鋅奈米柱成為當今的熱門研究材料。除此之外,一維氧化鋅奈米柱可以藉由各種成長方式來製備,包含金屬有機化學氣相沉積(MOCVD)、脈衝雷射蒸鍍技術(pulse laser deposition)以及射頻磁控濺鍍(RF magnetron sputtering)等。而在本篇論文當中,我們則利用水熱法的方式將一維氧化鋅奈米柱成長於藍寶石基板和矽基板。 本文提出了具高光指向性之紫外光氧化鋅奈米柱發光二極體。藉由低溫的水熱法成長氧化鋅奈米柱於p型氮化鎵上,並在其介面加入一氧化鎂電子阻擋層,透過此結構之設計,電子能夠有效的被阻擋於氧化鋅側並與電洞結合,成功做出具有398nm近紫外光波段放光之奈米柱發光二極體。同時更進一步量測奈米柱在低溫之下之電激發光光譜,並對元件發光強度隨溫度下降而減弱以及波長峰值隨溫度變化而藍移之效應提出載子穿隧模型與溫度對能隙關係加以解釋。 接著,我們利用氧化鋅奈米柱獨特的發光性質應用在癌症細胞的偵測。在現今的癌症偵測技術中,螢光染色法是最為普遍的其中一種檢測法。然而,螢光染色法存在許多的缺點,例如螢光衰退、螢光顯色的限制與細胞自體螢光分辨上的困難,這些都使得在手術過程中難以達成癌症細胞的即時檢測。 有許多團隊利用量子點並藉由表面改質的方式來解決這些困難,然而量子點在製備以及表面改質都的過程不僅會改變本半導體特姓,並且製程昂貴。為了克服這些困難,我們利用半導體光源來替代有機螢光物質。藉著利用氧化鋅奈米柱作為細胞標記,將氧化鋅奈米柱接合上抗體之後,用此標記接合上癌症細胞。我們先行利用IgG 抗體作為對照測試,在不同的條件以及抗體濃度下完成氧化鋅奈米柱與IgG抗體之接合,並藉由間接染色法來確認抗體的連結特性,並且發現氧化鋅奈米柱對抗體之特殊接合能力。由於氧化鋅奈米柱有很高的親和力(Affinity),並且更大的表面積對體積之比值可以提供更多的抗體接合位,故抗體與之有相當強的接合力。在確認氧化鋅奈米柱與IgG抗體的接合能力後,我們便使用EGFR (epidermal growth factor receptor) antibody 取代IgG抗體,EGFR antibody是近年來研究癌症細胞的重要議題,多數的癌症細胞對EGFR有很高的表現,因此利用EGFR antibody 可以容易的對癌症細胞做檢測。藉由結合EGFR antibody 的氧化鋅奈米柱作為癌細胞偵測標記,當此標記自動結合癌細胞上的EGF receptor,我們再利用氧化鋅的光學性質特性來檢測帶有此標記的癌症細胞,藉以達成高偵測性的癌症檢測。

並列摘要


ZnO nanostructures have received great attention due to their desirable optical properties, which include a wide bandgap of 3.37 eV and a large exciton binding energy of 60 meV at room temperature. 1-D ZnO nanorod has been previously demonstrated as a candidate material for use in a broad range of technological applications, such as short-wavelength light emitters, field emitters, luminescence devices, UV lasers, and solar cells. 1-D ZnO nanorod also has very good potential for aiding optical detection of target bioconstituents, as ZnO nanomaterials are stable in typical biomolecular detection environments, have attractive optical properties, and can be easily processed. There are numerous vapor-phase methods for the growth of ZnO nanorods such as metal organic chemical vapor deposition, pulse laser deposition, radio frequency magnetron sputtering and deposition within anodized aluminum oxide membrane. In this study, we used hydrothermal method to grow nanorods on sapphire and Si substrates. Then we demonstrate ZnO nanorod/p-GaN LEDs fabricated using hydrothermal method for the single crystal ZnO nanorod arrays growth. MgO blocking layer between ZnO nanorod and p-GaN are inserted to enhance the UV emission from ZnO nanowires. After that, we utilized the special optical properties of ZnO nanorod for tumor detection. Generally, to visually observe cancer cells, fluorescence cancer detection is one of the most common methods. However, there are many disadvantages for fluorescence cancer detection such as the phototoxicity, the limited number of available fluorescent channels, and the overlap of the excitation and emission spectra of the stains. Furthermore, under a constant light illumination, it possesses the issue of photobleaching, making real time surgery difficult. Many groups has reported that QDs can conquer these problems, however, the QDs method requires surface modification and the surface state induced by modification changes the property of semiconductor material. Moreover, all the processes cost high. To overcome these issues, the semiconductor light sources are alternative choices. In this work, ZnO nanorods are proposed as biomarkers. The ZnO nanorods were synthesized and bonded to antibodies. In the beginning, we conduct the IgG binding to ZnO nanorods for different concentration. The binding ability was verified by indirect fluorescence method. IgG was then replaced by EGFR (epidermal growth factor receptor) antibody. In previous studies, many types of cancer cells have greatly express in EGFR. Therefore, the biomarker made from binding the EGFR antibody to ZnO nanorods can easily mark the targeted cancer cells. By measuring optical properties of the biomarker, the detection of cancer cells will be monitored and analyzed.

並列關鍵字

ZnO nanorod nanorod EGFR antibody cancer cell

參考文獻


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