臺灣博碩士論文加值系統

根據國際癌症研究署(International Agency for Research on Cancer, IARC)在2014年世界癌症報告中指出，罹患大腸癌死亡人數從2008年的123萬人攀升到2012年的140萬人，逐年攀升，且為國人十大癌症死因之第三名。癌胚抗原(Carcinoembryonic antigen, CEA)是常見的腫瘤標記之一，主要經由腫瘤細胞所分泌並釋放至血液中，所以當腫瘤細胞形成時，癌胚抗原在血液中之濃度則會增加，目前癌胚抗原在臨床上主要用於大腸癌術後追蹤檢測。然而傳統癌胚抗原檢測儀器體積龐大、造價昂貴且檢測時間長，僅能在大型醫療中心使用，因此為了有效且快速檢測大腸癌發生機率以提早治療，本論文將開發可應用於大腸癌檢測之癌胚抗原彎曲平板波(Flexural Plate-wave, FPW)生物感測器。
本論文運用微機電系統技術製作彎曲平板波生物感測元件，製程步驟包含了七次薄膜沉積與五次黃光微影蝕刻，其中為了能精準控制彎曲平板波元件感測薄膜的厚度並改善製程良率，本論文採用兩階段非等向性濕式蝕刻來進行背面矽腔體之製作。完成之彎曲平板波元件透過胱胺酸自我組裝單分子層(Self-Assembled Monolayers, SAMs)技術將癌胚抗原之抗體鍵結於彎曲平板波感測區，以完成癌胚抗原彎曲平板波生物感測器之開發。
根據網路分析儀量測結果顯示，本論文之彎曲平板波元件具有低插入損耗(-38.652 dB)、高質量感測靈敏度(126.67 cm2/g)、較小之元件尺寸(0.7×0.84 cm2)、較薄之平板厚度(20 μm)；另一方面，癌胚抗原彎曲平板波生物感測器於五種不同濃度之癌胚抗原(5、10、20、40、80 ng/ml)下進行量測，其生物偵測極限為5 ng/ml、生物感測線性度R-square為0.96，綜合上述之結果，本論文所開發之高靈敏度聚焦式圓形彎曲平板波癌胚抗原生物感測器具有極高之研究進步性與商業化潛力。

According to the World Cancer Report 2014 by the International Agency for Research on Cancer (IARC), the global number of cases of colorectal cancer increased from 1.23 million in 2008 to 1.4 million in 2012. The colorectal cancer has also become the third major cancer killer in Taiwan. Carcinoembryonic Antigen (CEA) is a common tumor markers, which is secreted and released into the blood by the tumor cells. When the tumor cells form, the concentration of CEA will also increase in the blood. Currently, the main purpose of CEA in clinical is to keep tracking and detecting of colorectal cancer. However, the traditional CEA detectors usually have disadvantages of huge size, high cost, long detection time, etc. In order to detect colorectal cancer rapidly, a flexural plate-wave (FPW) biosensor for detecting CEA is developed in this thesis.
A FPW transducer was fabricated using micro-electro-mechanical systems (MEMS) technologies. The main fabrication steps of the proposed FPW devices include seven thin-film depositions and five photolithography processes. To accurately control the thickness of the silicon thin-plate and substantially improve the fabrication yield of FPW transducers, a two-step anisotropic wet etching process was also developed. Furthermore, by using cystamine-based self-assembled monolayer (SAM) nanotechnology, we used the proposed FPW device to develop a novel FPW-based carcinoembryonic antigen (CEA) biosensor for detection of colorectal cancer.
The implemented FPW device with dimension only about 0.56×0.56 cm2 and the thickness of suspended silicon plate can be accurately controlled to 20 μm. Under the optimized conditions, a very low insertion loss (-38.652 dB), very high mass sensitivity (126.67 cm2 /g) and high fabrication yield (60.78%) can be obtained. Furthermore, the proposed FPW based CEA-biosensor demonstrated a very low detection limit (5 ng/mL) and high mass-sensing linearity (0.96).

論文審定書 i
誌謝 iii
摘要 iv
Abstract v
目錄 vii
圖目錄 x
表目錄 xii
第一章 緒論 1
1.1 前言 1
1.2 研究動機與論文架構 2
1.3 文獻回顧 4
1.3.1 生物感測器簡介與分類 4
1.3.2 聲波感測器種類與比較 7
第二章 FPW元件材料分析與理論 15
2.1 壓電效應簡介與壓電薄膜選擇 15
2.1.1 壓電效應 15
2.1.2 氧化鋅壓電薄膜晶格結構與特性 16
2.2 氧化鋅壓電薄膜沉積方法與特性分析 18
2.2.1 氧化鋅壓電薄膜沉積方法 18
2.2.2 氧化鋅壓電薄膜沉積原理 19
2.2.3 反應性射頻電漿磁控濺鍍原理 20
2.3 FPW質量感測之理論推導 21
2.4 金屬指叉轉換器之等效電路分析 22
2.5 反射閘極結構理論 23
2.5.1 反射閘極週期 24
2.5.2 反射閘極對數之原理 25
2.5.3 反射閘極與IDT之間距離之關係 25
2.6單層分子薄膜技術 26
2.6.1 單分子層之製作 26
2.6.2 胱胺酸-戊二醛鍵結法 27
第三章 聚焦式圓形IDT設計之FPW元件設計與製作 29
3.1 聚焦式圓形IDT設計之FPW元件光罩佈局設計 29
3.2 聚焦式圓形IDT設計之FPW元件製作 35
3.3 生物感測材料與步驟 40
第四章 實驗結果與討論 44
4.1 氧化鋅壓電薄膜之材料特性 44
4.2 FPW元件特性量測結果與分析 46
4.2.1 FPW元件量測與平台簡介 46
4.2.2 ..矽基板之KOH蝕刻時間與FPW元件中心頻率的關係 47
4.2.3 .聚焦式圓形反射閘極結構對數與FPW元件特性之影響 50
4.2.4 ..聚焦式圓形IDT結構對數對FPW元件特性之影響 50
4.3 FPW元件固態質量感測器結果與分析 52
4.4 FPW元件生物感測器結果與分析 53
第五章 總結與未來展望 55
5.1 總結 55
5.2 未來展望 56
參考文獻 57

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