根據世界衛生組織（World Health Organization）調查，心血管疾病是全球死亡的頭號殺手，在2015年造成全球約1770萬人死亡，佔全球總死亡人數3成。當心肌細胞發生損傷或死亡時，細胞內的心肌鈣蛋白T (cardiac troponin T, cTnT)與心肌鈣蛋白I (cardiac troponin I, cTnI)會釋放至血液中，因此可藉由檢測血液中的心肌鈣蛋白濃度判斷心肌細胞損壞程度。為了能早期診斷並把握黃金治療時間，本論文致力於開發一可快速檢測心肌鈣蛋白之微型感測器，以改善傳統檢測儀器檢測時間長、需高度專業人員操作以及檢測成本高之缺點。
本論文以微機電製程技術開發製作微型心肌鈣蛋白感測晶片其包含銀/氯化銀準參考電極、延伸式閘極場效電晶體與氯化鉀洋菜膠封裝晶片等三部分，其中製程共有八次黃光微影製程及八道薄膜沉積。本論文將延伸閘極電極設計成蜂巢幾何以及平行幾何圖形，並改變四種不同的感測閘極面積，以探討其對電性及感測靈敏度之關係。最後運用交聯法使心肌鈣蛋白抗體固定於延伸式感測閘極上，利用抗體抗原鍵結之電位差異進行檢測。
本論文所開發出微型心肌鈣蛋白感測器尺寸為14.1 mm × 7.5 mm × 10 mm，最佳延伸閘極感測電極為面積2.0 mm× 2.0 mm之蜂巢幾何圖形。根據量測結果顯示於0 ng/mL ~ 0.1 ng/mL濃度量測範圍下，最低偵測極限為0.0125 ng/mL、感測靈敏度為214 mV/dec、線性度為0.974、次臨界擺幅為1.51 V、遲滯電壓為85 mV，反應時間300秒。由上述量測結果檢視，本論文所開發之微型心肌鈣蛋白感測器具有體積小、低偵測極限、感測靈敏度高、線性度高及反應時間快等優點。

According to the report by the World Health Organization (WHO), cardiovascular disease is the number one killer of global deaths. An estimated 17.7 million people died from CVDs in 2015, representing 31% of all global deaths. When cardiomyocytes are damaged or killed, important components in the cell, such as troponin T and troponin I, are released outside the cell and can be detected in the blood. In order to diagnose early, this thesis aim to develop a rapid extended gate field-effect-transistor (EGFET)-based microsensor for cardiac troponin detection.
In this research, the EGFET-based cardiac troponin microsensor is developed by micro-electromechanical process technology, which includes three parts: silver/silver chloride quasi-reference electrode, extended gate field effect transistor and potassium chloride gelatin package wafer. The main processing steps of the implemented microsensor in this study involve eight photolithographic and eight thin-film deposition processes. Honeycomb and parallel geometry patterns of the extended gate electrodes with four different size are designed to investigate their impact on the sensitivity. Finally, the combined method immobilizes the cardiac troponin antibody on the extended gate and detects the potential difference of the antibody antigen bond.
The size of the miniature cardiac troponin sensor developed in this paper is 14.1 mm × 7.5 mm × 10 mm. The optimal extended gate is honeycomb geometry pattern with 2.0 mm × 2.0 mm sensing area. Based on the measurement results, the minimum detection limit, sensitivity, sensing linearity and hysteresis voltage are 0.0125 ng/mL, 214 mV/dec, 0.974 and 1.51 V, respectively, as the concentration of the test solution varies from 0 ng/mL to 0.1 ng/mL. The EGFET-based cardiac troponin microsensor developed in this paper has the advatages of small volume, low detection limit, high sensitivity, high linearity and fast response time.

論文審定書 i
誌謝 ii
摘要 iii
Abstract iv
目錄 vi
表目錄 xi
第一章 緒論 1
研究動機 1
文獻回顧 2
電化學發光免疫感測器 2
表面等離子體共振感測器 3
離子選擇電極 3
離子感測場效電晶體 4
延伸式閘極感測電晶體 5
參考電極 6
實驗方法與論文架構 7
第二章 原理介紹 9
延伸式閘極場效電晶體原理 9
能斯特方程式 9
吸附鍵結模型 9
延伸式閘極感測場效電晶體工作原理 11
次臨界擺幅 13
心肌鈣蛋白感測機制 14
心肌鈣蛋白簡介 14
心肌鈣蛋白感測機制 15
第三章 具積體化氯化銀參考電極之微型心肌鈣蛋白感測晶片設計與製作 16
微型準參考電極與延伸式閘極場效電晶體與氯化鉀洋菜膠元件 16
微型準參考電極與延伸式閘極場效電晶體元件結構與佈局設計 16
微型準參考電極與延伸式閘極場效電晶體元件製程整合 20
封裝延伸式感測閘極電晶體與氯化銀參考電極之設計與製作 32
具積體化氯化銀參考電極之可攜式微型心肌鈣蛋白感測晶片 38
具積體化氯化銀參考電極之延伸式閘極場效電晶體晶片 38
心肌鈣蛋白感測薄膜配製 41
實驗藥品與材料 41
感測薄膜調配 42
第四章 結果與討論 43
延伸式閘極場校電晶體特性與分析 43
具積體化氯化銀參考電極之微型心肌鈣蛋白感測晶片特性量測分析 45
感測靈敏度及線性度分析 46
感測元件之次臨界擺幅 51
感測閘極面積 52
感測遲滯電壓分析 54
心肌鈣蛋白感測器比較 55
第五章 結論與未來展望 56
結論 56
未來展望 57
參考文獻 59

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