根據衛生福利部國民健康署 103年統計資料顯示，肝癌為台灣癌症死亡率第二名。而初期肝癌診斷常利用各種體積較大(> 40×30×10 cm3)之商用檢測儀器進行血液甲型胚胎蛋白(Alpha-fetoprotein, AFP)之篩檢以作為初期診斷之依據。近年來本實驗室研究團隊致力於微型甲型胚胎蛋白彎曲平板波(Flexural Plate-wave, FPW)生物感測元件之研發，進而結合其他研究團隊共同開發一種體積只有25×10×5 cm3之可攜式多種癌症感測微系統；然而根據前期研究結果顯示，具平行式指叉電極結構之傳統微型FPW感測元件其質量感測靈敏度高(86.03 cm2/g)但元件插入損耗卻較高(-44.87 dB)，改良型之圓形指叉式電極結構雖可降低FPW元件之插入損耗(-40.20 dB)但同時也會降低元件感測靈敏度(11.54 cm2/g)。另一方面，傳統的FPW元件都有製程良率很低(< 10%)的問題，這將嚴重影響元件之製造成本與商用化的可能性。
為了大幅改善以上傳統FPW元件的缺點，本論文縮小圓形指叉式電極尺寸及元件懸浮平板的面積，並且透過兩段式非等向性蝕刻(Anisotropic etching)及高優質氧化鋅壓電薄膜沉積等微機電系統技術(MEMS)，以精準控制懸浮平板之蝕刻速率並縮減懸浮平板尺寸及厚度，進而大幅提升製程良率、降低插入損耗與操作頻率以及提升質量感測靈敏度。本論文所開發高性能FPW元件之製程步驟包含七次薄膜沉積與五次黃光微影製程，其固態質量感測靈敏度與線性度可透過背部沉積精準厚度/質量之鋁薄膜前後之元件中心頻率飄移而測得；另一方面，所開發之FPW元件背部透過胱胺酸(Cystamine)自我組裝單分子層(Self-assembly monolayer, SAM)技術，可分別沉積0、5、25、50、100、300 ng/mL等六種不同濃度之AFP抗體，並進而量出該AFP-FPW生物感測元件之偵測極限(Detection limit)及生物質量感測線性度。
根據量測結果顯示，本論文所開發之圓形FPW元件相較於前期研究其元件面積(1.1×0.9 cm2)、懸浮平板厚度(50 μm)、插入損耗(-40.20 dB)、操作頻率(33.95 MHz)、製程良率(39.51%)、固態質量感測靈敏(11.54cm2/g)與固態質量感測線性度(0.9669)，具有較小之元件面積(0.7×0.9 cm2)、較薄之懸浮平板厚度(20 μm)、較低之插入損耗(-36.04 dB)、較低之操作頻率(17.11 MHz)、較高之製程良率(64.81%)、較高之固態質量感測靈敏度(70.06 cm2/g)與較高之固態質量感測線性度(0.9958)。最後本論文所開發之圓形AFP-FPW生物感測元件具有相當低之偵測極限(5 ng/mL)及相當高之生物質量感測線性度(0.9304)。綜合以上之性能表現可知，本論文所開發之高性能及高製程良率之甲型胚胎蛋白彎曲平板波生物感測器元件具有相當高之研究進步性與商業化潛力。

According to the 2014 annual report of Health Promotion Administration (Ministry of Health and Welfare, Taiwan), the hepatocellular carcinoma (HCC) has become the second major cancer killer in Taiwan. Usually, the concentration of alpha fetoprotein (AFP) in human serum can be detected by various commercial sensing equipment (> 40×30×10 cm3) and be used for the initial stage diagnosis of HCC. Various flexural plate-wave (FPW) micro biosensors and related bio-sensing microsystems (25×10×5 cm3) have been developed for POCT (Point-of-Care Testing) applications in our previous researches. However, the conventional FPW devices have two major disadvantages of high insertion loss (> 40 dB) and low fabrication yield (< 10%) which will limited their commercialization.
To improve effectively the insertion loss and fabrication yield of FPW device, a small-size interdigital transducer with circular-arc geometry design, two different rate of silicon anisotropic etching process and a high C-axis ZnO piezoelectric thin-film deposition process are developed in this thesis. The main fabrication steps of the proposed FPW based on AFP-biosensor including seven thin-film depositions and five photolithography processes. Two major technologies used in this work are micro-electro-mechanical systems (MEMS) technology and cystamine based self-assembly monolayer (SAM) nanotechnology.
The implemented FPW device with dimension only about 0.7×0.9 cm2 and the thickness of suspended silicon plate can be accurately controlled to 20 μm. Under the optimized conditions, a very low insertion loss (-36.04 dB), very high fabrication yield (64.81%) and high mass sensitivity (70.06 cm2/g) can be obtained. Furthermore, the proposed FPW based AFP-biosensor demonstrated a very low detection limit (5 ng/mL) and high mass-sensing linearity (0.9304).

論文審定書 ....................................................................................................................... i
誌謝 ................................................................................................................................. iii
摘要 ................................................................................................................................. iv
Abstract............................................................................................................................ vi
目錄 ............................................................................................................................... viii
圖目錄 .............................................................................................................................. x
表目錄 ........................................................................................................................... xiii
第一章 緒論 .................................................................................................................. 1
1.1 前言 ..................................................................................................................... 1
1.2 研究動機與論文架構 ......................................................................................... 3
1.3 文獻回顧 ............................................................................................................. 4
1.3.1 生物感測器簡介及分類 ............................................................................ 4
1.3.2 聲波感測器種類與比較 ............................................................................ 6
第二章 FPW 元件材料分析與理論 ........................................................................... 14
2.1 金屬指叉轉換器 ............................................................................................... 14
2.2 反射閘極結構理論 ........................................................................................... 14
2.2.1 反射閘極與 IDT 之間距離之關係 ......................................................... 16
2.2.2 反射閘極週期 .......................................................................................... 18
2.2.3 反射閘極對數之原理 .............................................................................. 18
2.3 壓電效應簡介與壓電薄膜選擇 ....................................................................... 18
2.3.1 壓電效應 .................................................................................................. 18
2.3.2 氧化鋅壓電薄膜晶格結構與特性 .......................................................... 20
2.4 氧化鋅壓電薄膜沉積方法與特性分析 ........................................................... 22
2.4.1 氧化鋅壓電薄膜沉積方法 ...................................................................... 22
ix
2.4.2 氧化鋅壓電薄膜沉積原理 ...................................................................... 23
2.4.3 反應性射頻磁控濺鍍原理 ...................................................................... 24
2.5 FPW 質量感測之理論推導 ............................................................................... 25
2.6 FPW 生物感測元件 ........................................................................................... 26
2.6.1 自我組裝單分子層 .................................................................................. 26
2.6.2 胱胺酸-戊二醛鍵結法 ............................................................................. 26
第三章 小尺寸圓形 IDT 設計之 FPW 元件設計與製作 ......................................... 28
3.1 小尺寸圓形 IDT 設計之 FPW 元件光罩佈局設計 ........................................ 28
3.2 小尺寸圓形式 IDT 設計之 FPW 元件製作 .................................................... 34
3.3 生物感測方法及步驟 ....................................................................................... 40
第四章 實驗結果與討論 ............................................................................................ 45
4.1 氧化鋅壓電薄膜之材料特性 ........................................................................... 45
4.2 FPW 元件特性量測結果與分析 ....................................................................... 48
4.2.1 反射閘極結構對數對 FPW 元件特性之影響 ........................................ 48
4.2.2 指叉式 IDT 結構對數對 FPW 元件特性之影響 ................................... 49
4.2.3 矽基板之 KOH 蝕刻時間對 FPW 元件中心頻率的影響 ..................... 50
4.2.4 KOH 矽基板蝕刻之良率討論 ................................................................. 52
4.3 具聚焦式反射閘極結構之 FPW 固態質量感測器特性分析 ......................... 53
4.4 FPW 元件生物質量感測結果與分析 ............................................................... 54
第五章 結論與未來展望 ............................................................................................ 55
5.1 結論 ................................................................................................................... 55
5.2 未來展望 ........................................................................................................... 58
參考文獻 ........................................................................................................................ 59

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