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研究生: 張愛花
Sasza - Chyntara Nabilla
論文名稱: 金屬玻璃薄膜對於多種癌細胞的附著之抑制性研究
Inhibitory Effects and Possible Mechanisms of Thin Film Metallic Glass Coating on Adhesion of Various Cancer Cells
指導教授: 朱瑾
Jinn P. Chu
口試委員: 戴龑
Yian Tai
陳俊杉
Chuin-Shan (David) Chen
陳明仁
Ming-Jen Chen
張世幸
Shih-Hsin Chang
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2015
畢業學年度: 103
語文別: 英文
論文頁數: 158
中文關鍵詞: 癌症細胞金屬玻璃薄膜疏水性偽足
外文關鍵詞: Cancer cell, Thin film metallic glass, Hydrophobic property, Filopodia
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癌症是一種具有複雜異質性結構的危險疾病,所以早期癌症細胞篩檢及診斷是非常重要的。一些標準治療程序,例如活體組織穿刺檢查或手術等皆有可能會提高癌細胞增殖及轉移的程度。金屬玻璃薄膜(Thin film metallic glass, TFMG)因其固有的獨特性質如非晶結構、相對高的疏水性、光滑表面、低磨擦係數、高強度、高韌性、優異的耐腐蝕及耐磨耗等,具有潛力成為一種可以有效防止癌症細胞附著的材料。
本研究利用磁控濺鍍,以醫藥級玻璃和手術刀做為基板沉積相應50nm及200nm厚的Zr53Cu33Al9Ta5金屬玻璃薄膜,另製備了具有相同厚度純鈦薄膜的試片用於對比。本實驗於基板上共培養三種不同的癌細胞,分別為SKGT4(食道癌)、MB231(乳腺癌)、WiDr(結腸癌),來進行分析評估。對於不同基板上的觀察顯示,各類癌細胞都在鍍有金屬玻璃薄膜的基板上有最小的吸附面積(~0.4-2.6%)與密度(~105-201 cells/mm2),相對應的最高降低幅度分別達到~86%和~84%。研究的結果顯示,癌細胞在鍍有金屬玻璃薄膜的基板上並沒有發生顯著的增殖與擴散,最重要的原因在於金屬玻璃薄膜擁有低表面能(~29.3mN/m)、優良的疏水性(去離子水的接觸角97.7°)以及降低表面粗糙度(分別將玻璃基板的粗糙度從~0.5降至~0.2 nm 以及將手術刀的粗糙度從~317.7降至~160.4 nm)等優異性質,進而減緩了癌細胞的附著。因此,本研究成功的使用金屬玻璃鍍膜降低了癌細胞的吸附及增殖,同時揭示並探討了癌細胞在已鍍與未鍍金屬玻璃薄膜的玻璃基板上的形態及吸附機制,此外癌細胞於鍍有金屬玻璃的基板之表面形貌僅有微小的板狀偽足及絲狀偽足擴張形成萎縮的細胞狀。


Since cancer is one of dangerous diseases having complex heterogeneous structures, an early diagnosis and cancer screening are critically important. In some cases, standard diagnostic and treatment procedures such as biopsy and surgery could increase the level of proliferation and metastasis of cancer cell. Thin film metallic glass (TFMG) is thought to be one of promising materials to prevent the adhesion of cancer cells due to its unique intrinsic properties such as amorphous structure, relatively high hydrophobicity, smooth surface, small frictions, high strength and toughness, excellent corrosion and abrasion resistance.
Zr53Cu33Al9Ta5 TFMG with different thicknesses of 50 and 200 nm was deposited on substrates of medical-grade glass and scalpel using magnetron sputtering. Pure Ti film was also deposited for comparison. Various types of cancer cells including SKGT4 (esophageal cancer), MB231 (breast cancer), and WiDr (colon cancer) were cultured on the substrates for evaluations. For TFMG-coated glasses, all types of cancer cell are found to have relatively small attachment area (~0.4-3.7%) and low density (~105-261 cells/mm2) among other samples studied. TFMG coating also shows the highest reductions area of cancer cell attachment and density of ~86 and ~84%, respectively. As a result, a cell migration and spreading are found to be not significant in the samples with TFMG coating. The low surface free energy and most hydrophobic nature in TFMG coating with the values of ~29.3 mN/m and 97.7°, respectively, are considered as the foremost factor to inhibit cell attachments. Decreasing glass and scalpel roughness from ~0.5 to 0.2 nm and from ~317.7 to 160.4 nm, respectively, is also important factor to deter cancer cell attachments. Therefore, TFMG coating is shown to successfully minimize the adhesion of cancer cell. In addition, the morphology of cancer cell on TFMG coating shows shrunken-cell morphology with minor spreading of lamellipodia and filopodia.

摘要 i Abstract ii Acknowledgements iii Contents iv List of Figures vii List of Tables xiv Chapter 1 Introduction 1 Chapter 2 Literature Review 3 2.1 Cell cycle and cancer 3 2.1.1 Cell cycle progression 3 2.1.2 Cancer 6 2.2 Adhesion molecules in cancer development 13 2.3 Role of bioadhesion 21 2.4 Biomaterials selection 28 2.5 Medical equipment: scalpel 31 2.6 Inhibition of cell adhesion by surface modification treatments 35 2.7 Thin film metallic glass (TFMG) 38 2.7.1 Unique properties of thin film metallic glass 40 2.7.2 TFMG for biomedical application 48 2.8 Magnetron sputtering techniques 57 Chapter 3 Experimental Procedures 61 3.1 Substrate preparations 61 3.2 Thin film depositions 62 3.2.1 TFMG deposition 63 3.2.2 Pure Ti deposition 64 3.3 Material characterizations 65 3.3.1 Thermal analysis 65 3.3.2 Chemical analysis 66 3.3.3 Microstructural analysis 68 3.3.4 Crystallographic analysis 68 3.3.5 Surface morphology observations 69 3.3.6 Surface roughness measurements 70 3.3.7 Contact angle and surface energy measurements 72 3.4 Cell culture 74 3.5 Morphology of cancer cell 75 3.6 Cell attachment area and density measurements 78 Chapter 4 Results & Discussion 79 4.1 TFMG properties 79 4.1.1 Thermal analysis 79 4.1.2 Chemical analysis 80 4.1.3 Microstructural analysis 80 4.1.4 Crystallographic analysis 81 4.2 Characteristics of surgical scalpel 81 4.2.1 Surface morphology observations 81 4.2.2 Chemical composition 85 4.3 Surface roughness measurements 86 4.3.1 Surface roughness measurements on medical-grade glasses 86 4.3.2 Surface roughness measurements on scalpels 89 4.4 Wettability of films 91 4.4.1 Wettability on medical-grade glasses 91 4.4.2 Wettability on scalpels 96 4.5 Morphology of cancer cell 99 4.6 Cell adhesion 108 Chapter 5 Summaries and Future Works 128 5.1 Summaries 128 5.2 Future works 129 References 130

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