臺灣博碩士論文加值系統

本研究利用半導體微機械加工製程技術製備植入型微電極陣列感測探針，其中包含光罩設計與半導體加工製程兩大重點方向，在光罩設計方面，我們以繪圖軟體Auto CAD設計繪製光罩上元件圖樣，本製程包含三道光罩，分別用以電極金屬沉積、絕緣層蝕刻及探針形狀定義，每片4吋晶圓上共設有164隻探針，其中有(1)四極式、(2)四+二長極式和(3)六極式共3種探針設計，分別占有53隻、74隻與37隻，每根探針由電極端(electrode sites)、導線端(channels)、封裝端(bonding pads)組成，四+二長極式與六極式微電極陣列探針為同一尺寸，全長18 mm (針軸部長11 mm)、寬度3 mm、探針尖端寬度150 μm、厚度200 μm，電極大小為200 μm × 50 μm；而四極式全長13 mm (針軸部長9 mm)、寬度3 mm，探針尖端寬132 μm，電極大小為140 μm × 30 μm，尺寸較小。可根據未來的應用選擇所需之探針；在製程方面，我們於微影、擴散、蝕刻、薄膜等加工製程中，將製程參數進行最佳化試驗，製作出精確、高產量、低成本的微型電極陣列探針，良率高達95%。不同於傳統的三極式電化學感測系統，我們所設計的探針具有多效合一的概念，以本研究為例，將銀/氯化銀(Ag/AgCl)沉積於探針上所設置的長型微電極後，可形成自身參考電極，再選擇另一長型微電極作為輔助電極，而探針上的微工作電極陣列於修飾後則可用以感測不同待測分析物質，形成工作電極、輔助電極、參考電極三極合一的生物感測器，可應用於植入型生物感測以及大幅提升其使用上與商品化的可行性及便利性。
另一方面，為驗證所製備之微電極陣列探針的感測效能，我們將經過封裝、表面修飾與酵素塗佈後製備而成穀氨酸感測探針，進行一系列的效能測試，包含靈敏度(190±7.5 nA·μM-1·cm-2)、感測極限(1.15±0.01 μM)、感測範圍(20-500 μM)、響應時間(3±2 s)，以及干擾物測試，驗證結果顯示所製備的微電極陣列探針具有良好的感測能力。未來可於所製備的探針上進行不同酵素的修飾，以應用在不同研究領域進行分析量測，包含植入型的動物實驗。

In this research, we used the semiconductor manufacturing technique to fabricate implantable multi-electrode array microprobes and AutoCAD software to design masks. The process to prepare microprobes was divided into three parts, including formation of the specific pattern of platinum metal layer on the silicon wafer, etching of the specific insulation layer and defining the outline of microprobes. We have three kinds of microprobes designed on a 4-inch wafer, including 53 probes with 4 microelectrodes, 74 probes with 4 microelectrodes and 2 long electrodes, 37 probes with 6 microelectrodes. Each probe consists of electrode sites, channels, bonding pads. Additionally, the 4-electrode microprobes were smaller than the others with full length 13 mm, width 3 mm, probe tip width 132 μm, and platinum area size 140 μm × 30 μm; while the others were of the same size with full length 18 mm, width 3 mm, thickness 200 μm, probe tip width 150 μm, and platinum area size 200 μm × 50 μm. The appropriate pattern can be selected according to future applications.
Moreover, we optimized parameters in each processing step (i.e. thermal oxidation, photolithography, thin film deposition, and etching) to miniaturize the size, reduce cost, and improve the production rate of multi-electrode array microprobes. Different from the traditional three-electrode system, we designed our microprobes as all-in-one biosensor probes. For example, silver/silver chloride can be deposited onto one of electrode sites to make a self-reference electrode, while others are responsible for the counter and working electrode. An all-in-one biosensor can be applied in implantable biological sensing and greatly enhance its applications, feasibility, and convenience.
In the second part of this thesis, sensors abilities were tested. In detail, we modified the electrode surface with permselective polymer layers and glutamate oxidase layers to construct glutamate biosensors. For this study, our glutamate sensors have fast response time 3±2 s, wider linear detection range 20-500 μM, low detection limit 1.15±0.01 μM, and high sensitivity 190±7.5 nA·μM-1·cm-2. We have proposed a multi-electrode array glutmate biosensor probe with good sensing ability. The proposed all-in-one glutmate sensor microprobes could be applied for different kinds in vivo experiment in live rodents in the future.

目錄
研究動機 I
中文摘要 II
Abstract IV
致謝 VI
目錄 VII
圖目錄 X
表目錄 XIV
第一章 緒論 1
1.1 生物感測器簡介 1
1.2 電化學分析裝置與原理 3
1.3 半導體加工技術 6
1.3.1 晶圓生產 7
1.3.2 濕式清洗製程 8
1.3.3 擴散製程 9
1.3.4 微影製程 10
1.3.5 蝕刻製程 16
1.3.6 薄膜製程 19
1.4 穀氨酸生物感應器 20
1.4.1 穀氨酸生物感測器簡介與文獻回顧 21
第二章 光罩設計與介紹 24
2.1 第一道微影製程光罩－定義金屬層圖形 25
2.2 第二道微影製程光罩－定義探針封裝端與電極端 29
2.3 第三道微影製程光罩－定義探針邊界輪廓 32
第三章 微電極陣列探針製程 36
3.1 晶圓預處理 36
3.1.1 爐管前清洗 36
3.1.2 爐管濕式熱氧化 37
3.2 第一道微影製程－定義金屬層圖形 37
3.2.1 第一道微影製程 38
3.2.2 金屬層沉積 41
3.2.3 探針表面絕緣-介電層沉積 43
3.3 第二道微影製程－定義封裝端與電極端 44
3.3.1 探針封裝端與電極端蝕刻 45
3.4 第三道微影製程－定義探針邊界輪廓 46
3.4.1 RIE探針邊界輪廓介電層蝕刻 48
3.4.2 ICP探針邊界輪廓深蝕刻 50
第四章 微電極陣列穀氨酸感測器製備 52
4.1 實驗設備 52
4.2 實驗藥品 54
4.2.1 藥品配置 55
4.3 穀氨酸感測探針之製備 56
4.3.1 探針清洗 56
4.3.2 探針封裝 57
4.3.3 電化學量測組態 58
4.3.4 電極表面修飾 59
4.3.5 手動塗佈酵素 60
4.4 實驗測量方法 61
4.4.1 分析量測組態 61
4.4.2 實驗量測方法 62
第五章 結果與討論 64
5.1 第一道微影製程-金屬沉積 64
5.1.1 第一道微影製程結果分析 64
5.1.2 金屬層沉積圖型結果與分析 66
5.2 第二道微影製程－探針絕緣 68
5.2.1 晶圓表面絕緣 68
5.2.2 第二道微影製程結果分析 68
5.2.3 介電層蝕刻結果分析 69
5.3 第三道微影製程－探針輪廓定義 70
5.3.1 第三道微影製程結果分析 71
5.3.2 RIE介電層蝕刻結果分析 73
5.3.3 ICP矽的深蝕刻結果分析 74
5.4 探針基本測試 77
5.4.1 過氧化氫訊號測試 77
5.4.2 探針導線區域絕緣測試 78
5.5 利用微電極陣列探針製備穀氨酸感測器之效能評估 79
5.5.1 最佳酵素塗佈厚度測試 79
5.5.2 干擾物測試 80
5.5.3 穀氨酸感應器線性範圍與靈敏度測試 81
5.5.4 穀氨酸感測器穩定度測試 82
5.5.5 感測極限與響應時間測試 83
5.5.6 感測探針應用於無線裝置之初步實驗設置 85
結論 87
參考文獻 88
附錄A微電極陣列探針製備流程表 93
附錄B代工廠商資訊 99
附錄C微電極陣列製程耗材廠商資訊 99
附錄D恆電位儀使用注意事項 99
附錄E微電極封裝流程 100
附錄F榖胺酸氧化酵素(250 U/ml)配製方法 100
附錄G穀氨酸氧化酵素的固定方法 101

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