臺灣博碩士論文加值系統

本研究提出無酵素葡萄糖感測器，首先，以半導體黃光微影製程於6吋再生矽晶圓上製作規則排列之微米半球陣列結構，再於其上濺鍍一層金薄膜，最後，以溶膠凝膠方法製作奈米金顆粒，並均勻沉積於金薄膜表面，形成奈、微米複合結構之感測電極，進行電化學量測。由量測結果顯示此電極感測區域為平面結構之金電極的10.2倍，實際進行葡萄糖量測，此感測器可檢測葡萄糖濃度之線性範圍為55.6 µM到13.89 mM，靈敏度達749.2 µA·mM-1·cm-2，檢測極限為9 µM，顯示此無酵素葡萄感測器有極佳之檢測效能。此外；本感測器可有效檢測葡萄糖變化，精確度達±0.18 mg/dL，遠優於FDA規範之±20 mg/dL與ISO 15197規範之±15 mg/dL。本研究所提出之無酵素葡萄糖感測器有製程簡單、成本低廉、高靈敏度且無酵素活性降解之問題等優點，有極佳之商品化可行性。

This study proposes a non-enzymatic glucose sensor fabricated by utilizing photolithography commonly used in the semiconductor industry. First, an ordered array of microhemispherical features was formed on a 6-inch regenerated silicon wafer through photolithography. Next, a thin gold layer was sputtered onto the hemispheres and then gold nanoparticles were uniformly deposited via sol-gel to form a microstructural composite sensing electrode substrate for electrochemistry. It was observed from the results that the effective sensing area of the proposed glucose sensor was 10.2 times greater than a planar gold electrode. Further investigation revealed that the sensor’s linear detection range for glucose was from 55.6 µM to 13.89 mM, with a sensitivity of 749.2 µA·mM-1·cm-2 and a detection limit of 9 µM. In addition, the proposed sensor can also effectively detect changes in glucose levels to an accuracy of ±0.18 mg/dL; far greater than the FDA specification of ±20 mg/dL and ISO15197 specification of ±15 mg/dL. The simple and low-cost manufacturing combined with a high sensitivity, enzyme-free and excellent sensing performace indicates that the proposed non-enzymatic glucose sensor is commercially feasible.

目錄
誌謝 i
摘要 ii
Abstract iii
目錄 iv
圖目錄 vii
表目錄 ix
第一章 緒論 1
1.1研究動機 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1糖尿病概述 3
2.1.1糖尿病類型 3
2.1.2糖尿病判定標準 4
2.2血糖檢測方式 5
2.3葡萄糖感測器之發展 6
2.3.1酵素葡萄糖生物感測器 7
2.3.2無酵素葡萄糖生物感測器 10
2.4葡萄糖生物感測器於抗干擾之方法 12
第三章 實驗材料與方法 14
3.1實驗藥品 14
3.2溶液配置 15
3.3實驗設備與分析儀器 16
3.4實驗原理 17
3.4.1黃光微影製程 18
3.4.2電化學分析法 22
3.5實驗方法與步驟 27
3.5.1矽基微米半球陣列結構晶片製備 27
3.5.2沉積奈米金顆粒 30
3.5.3抗干擾層建立 31
3.5.4電化學量測分析 31
第四章 實驗結果與討論 32
4.1無酵素葡萄糖感測電極 32
4.1.1微米結構製備結果 32
4.1.2奈米金顆粒沉積結果 32
4.1.3平面金電極與奈米金電極之探討 34
4.2奈米金電極偵測葡萄糖之電化學分析 35
4.2.1電子擴散速率 35
4.2.2葡萄糖濃度檢測 36
4.2.3葡萄糖與電流響應之關係 37
4.2.4偵測葡萄糖之操作電位的探討 38
4.2.5無酵素葡萄糖感測器之干擾物試驗 39
4.2.6探討奈米金電極的穩定性 40
第五章 結論與未來展望 43
參考文獻 45

圖目錄
圖2.1、葡萄糖氧化酵素電極偵測葡萄糖反應機制圖[5] 8
圖2.2、無酵素葡萄糖感測器之反應機制示意圖[23] 11
圖3.1、無酵素葡萄糖感測電極製作流程圖 18
圖3.2、板狀光阻結構之熱成型質量傳遞機制[36] 21
圖3.3、熱成型之光阻輪廓變化過程 21
圖3.4、光阻熱熔前與熱熔後體積示意圖 21
圖3.5、三電極系統配置圖 23
圖3.6、循環伏安法的電位變化示意圖[37] 24
圖3.7、典型的可逆氧化還原反應循環伏安圖。R為還原；O為氧化[38]。 24
圖3.8、計時安培法示意圖。(a)電位-時間之關係圖 (b)時間-濃度之關係圖 (c)電流-時間之關係圖[39] 26
圖3.9、黃光微影搭配熱熔法製作半球陣列晶片。(A)晶圓清洗及塗佈光阻；(B)本研究之光罩圖案；(C)黃光微影製程；(D)熱熔處理 27
圖3.10、(A)以黃光微影製作完成之 6 吋晶圓電極陣列(B)封裝示意圖 30
圖4.1、無酵素葡萄糖感測電極在不同製造階段之SEM圖。(A)微米半球陣列結構濺鍍金薄膜；(B)為(A)之放大圖；(C)溶膠凝膠法沉積奈米金顆粒；(D)為(C)之放大圖；(E)微米半球結構之剖面圖；(F)溶膠凝膠法所製作之奈米金顆粒 33
圖4.2、無酵素葡萄糖感測電極之EDS元素分析圖 34
圖4.3、表面積檢測結果。(A)電位與電流(E-I)之關係圖；(B)時間與電流(I-T)之關係圖 35
圖4.4、(A) 溶膠凝膠法無酵素葡萄糖感測器於不同掃速的CV圖；(B)溶膠凝膠法奈米金電極與平面金電極之Randles－Sevcik氧化曲線圖 36
圖4.5、溶膠凝膠法無酵素葡萄糖感測器(A)檢測不同葡萄糖濃度之CV圖；(B)峰值電流與濃度關係的校準曲線 37
圖4.6、溶膠凝膠法無酵素葡萄糖感測器(A)偵測葡萄糖的電流響應圖；(B)葡萄糖電流響應的校準曲線 38
圖4.7、溶膠凝膠法無酵素葡萄糖感測器於不同電位下之葡萄糖電流響應 39
圖4.8、溶膠凝膠法無酵素葡萄糖感測器之葡萄糖與干擾物的影響測試 40
圖4.9、溶膠凝膠法無酵素葡萄糖感測器測試電極的穩定性 41

表目錄
表4.1、基於奈米結構的溶膠凝膠法無酵素葡萄糖感測器之特性比較 42

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