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系統識別號 U0026-0812200911413062
論文名稱(中文) 整合型分子模版微流體晶片應用於表面電漿共振生物感測器之檢測
論文名稱(英文) A Microfluidic Chip Integrated with Molecular Imprinting Polymers for Surface Plasmon Resonance Detection
校院名稱 成功大學
系所名稱(中) 工程科學系碩博士班
系所名稱(英) Department of Engineering Science
學年度 93
學期 2
出版年 94
研究生(中文) 黃仕強
研究生(英文) Shih-Chiang Huang
學號 n9692161
學位類別 碩士
語文別 中文
論文頁數 116頁
口試委員 口試委員-陳顯禎
口試委員-楊瑞珍
指導教授-李國賓
中文關鍵字 微流體  生物晶片  表面電漿共振  微幫浦  微機電系統  分子模版  區域性分子模版 
英文關鍵字 Localized MIP  Biochip  Surface Plasmon Resonance  Microfluidics  Micropumps  Molecular Imprinting Polymer  MEMS 
學科別分類
中文摘要   本研究成功地整合分子模版(Molecular Imprinting Polymers, MIP)於一創新之微流體生物晶片,並且運用表面電漿共振(Surface Plasmon Resonance, SPR)生物感測技術檢測生物檢體。當微量生物檢體進樣後,經由微流體晶片中的“蜘蛛網型蠕動式微氣動幫浦”與微氣動閥門驅動至高靈敏度及高專一性之區域性分子模版(Localized MIP)反應區域,並且同時運用表面電漿共振生物感測儀器進行即時性分析。

  本研究在微流體生物晶片製作方面,利用微機電製程技術將為流體元件及微型溫度控制元件製作於玻璃(BK-7)與聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)等基材之上。其中,流速感測器能校正微氣動幫浦流率之誤差,以達到精確地控制檢體進樣之流率;微型溫度控制晶片精準地控制檢測環境溫度之穩定,使其能精準地使環境溫度維持在37℃,且誤差範圍可控制在0.1℃以內,藉此降低背景雜訊並提高分析訊號之噪訊比。

  最後,本研究成功地在1×3分子模版/表面電漿共振整合型生物晶片上,同時針對三種不同分子模版(黃體激素、睪酮、膽固醇)進行生物分子吸附檢測,更結合表面電漿共振生物感測器的高靈敏度、高解析度、動態分析及不須事先標定生物分子之特性,使得本研究能偵測到達人體生理濃度之極限。相信此成果可對未來分子模版及生醫疾病檢測分析提供了一種便利且穩定之研究工具。
英文摘要   This study reports a novel microfluidic system integrated with localized molecular imprinting polymers (MIP) for surface plasmon resonance (SPR) detection of specific label-free bio-samples. The innovative microfluidic biochip is capable of transporting a specific amount of bio-samples inside multiple microchannels using micro pneumatic micropumps and micro pneumatic valves to sensing regions where multiple MIP films are locally spin-coated such that highly-sensitive, highly-specific bio-sensing could be achieved.

  The innovative microfluidic biochip is fabricated by using MEMS (Micro-Electro-Mechanical System) technology on glass (BK-7) and PDMS (Polydimethylsiloxane) substrates. The flow sensor can be certain calibrated the error of pumping rate and realized the accurate sample transfer. In addition, since SPR detection could be very sensitive to temperature variation, a micromachine-based temperature control module comprised of micro-heaters and a temperature sensor was used to maintain a uniform temperature with a variation less than 0.1℃ during measurement.

  The microfluidic MIP/SPR biochips have the potential to be widely used for bio-sensing applications. While compared to large-scale SPR techniques, the developed microfluidic system has several advantages, including labeling-free, high sensitivity, capability of quantitative analysis of nano-scale bio-molecules in real-time fashion.
論文目次 摘 要 i
Astract iii
誌 謝 v
目 錄 vii
表 目 錄 x
圖 目 錄 xi
符 號 說 明 xv

第一章 緒論
1-1 前言 1
1-2 生醫微機電系統 2
1-3 表面電漿共振感測技術簡介 4
1-4 分子模版感測技術簡介 7
1-5 研究動機及目的 10
1-6 研究架構 12
1-7 文獻回顧 14
1-7-1 表面電漿共振感測技術文獻回顧 15
1-7-2 分子模版感測技術文獻回顧 16
1-7-3 微閥門及微幫浦文獻回顧 18

第二章 基礎理論
2-1 晶片設計原理 25
2-1-1 表面電漿子感測元件設計原理 26
2-1-2 微型溫度控制元件設計原理 28
2-1-3 微氣動幫浦與微氣動閥門設計原理 31
2-2 分子模版感測技術 37
2-2-1 分子模版合成原理 38
2-2-2 分子模版溶液之製備 40
2-2-3 分子模版之聚合 41

第三章 分子模版/表面電漿共振整合型生物晶片之設計及製作
3-1 整合型生物晶片設計 43
3-1-1 微流體晶片設計 44
3-1-2 微型溫度控制晶片設計 46
3-1-3 1×3分子模版/表面電漿共振整合型生物晶片設計 48
3-2 光罩製作 50
3-3 製程技術 51
3-3-1 晶片表面清洗 51
3-3-2 標準微影製程 53
3-3-3 金屬濺鍍與蒸鍍 56
3-3-4 SU-8母模與剝離製程 59
3-3-5 PDMS微注模技術 64
3-3-6 多樣區域性分子模版技術 67
3-4 晶片接合與封裝 69

第四章 結果與討論
4-1 微流體晶片測試 72
4-1-1 微流體晶片實驗裝置 72
4-1-2 微流體晶片測試與分析 74
4-2 微型溫度控制晶片測試 78
4-2-1 微型溫度控制晶片實驗裝置 79
4-2-2 微型溫度控制晶片測試與分析 80
4-3 分子模版感測 82
4-4 1×3分子模版/表面電漿共振整合型生物晶片測試 88

第五章 結論與未來展望
5-1 結論 99
5-2 未來展望 100

參 考 資 料 102
自 述 114
著 作 115
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