超高解析度表面電漿共振生物感測器之研製

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姓名

簡汎清(Fan-Ching Chien) 查詢紙本館藏

畢業系所

機械工程學系

論文名稱

超高解析度表面電漿共振生物感測器之研製
(Design and fabrication of ultrahigh-resolution surface plasmon resonance biosensors)

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摘要(中)

藉由對各種模態的表面電漿共振(surface plasmon resonance，SPR)生物感測器之靈敏度加以分析比對。目前，不論何種組態之SPR生物感測器其偵測極限大約為1 pg/mm2的生物分子表面覆蓋度，難以偵測低濃度之微小生物分子的交互作用情形。因此，本論文提出一種含有金奈米粒子強化(Au nanoparticle-enhanced)之SPR生物感測器光學量測系統，經實驗證實其偵測解析度有機會降低至100 fg/mm2。此嶄新式奈米粒子強化之超高解析度SPR生物感測器透過Maxwell-Garnett模態理論及Fresnel方程式來分析設計，並經由RF co-sputter鍍膜技術製作。將可應用到新藥研發、基因定序、醫療診斷等領域上，並且此奈米粒子強化之超高解析度SPR生物感測器事先不須經額外標記(label-free)，即可直接分析微量生物分子間交互作用分析(biomolecular interaction analysis，BIA)，將成為生物醫學領域上最重要的篩檢感測器。
在生物分子交互作用分析的應用上，分別對於去氧核糖核酸分子雜交(DNA hybridization)反應動力學之研究，並利用外加電場效應降低雜交反應時間，加速生物晶片檢測的速率。以及探討蛋白質分子的吸附動力學。並將SPR技術應用到新興的分子拓印高分子(molecular imprinted polymer，MIP)晶片篩檢上。經由上述的動力學研究，將可建立一完整生物分子行為之作用機制技術平台，將提昇藥物設計與蛋白質體學(proteomics)研究之能力。

摘要(英)

Theoretically, simulate and compare the sensitivity of any mode of the existing thin film surface plasmon resonance (SPR) biosensors. No matter which mode of the existing thin film SPR biosensors such as convential SPR biosesor, couple plasmon-waveguide resonance (CPWR) biosesor, and long-range surface plasmon resonance (LRSPR) biosesor, the detection resolution is limited to approximately 1 pg/mm2 of biomolecular surface coverage. Under this constrain, small biomolecular interactions in low concentration are hard to be analyzed.
Hence, by increasing the enhancement factor of SPR through metal nanoparticles and eliminating sensing noise with the optical differential metrology system, we demonstrate the resolution of Nanoparticle-enhanced SPR biosensors for detecting the surface coverage of biomaterial down to 100 fg/mm2. The novel nanoparticle-enhanced ultrahigh-resolution SPR biosensors are designed based on the Maxwell-Garnett model and Fresnel equations, and are fabricated by using the RF co-sputter deposition. Therefore, the nanoparticle-enhanced ultrahigh-resolution SPR biosensors can directly analyze tiny biomolecular interactions without adding labels and they will likely become the most important sensing device in the field of biomolecular diagnosis.
About biomolecular interaction analysis (BIA), focus on the kinetics of DNA hybridization, then also utilize electric field to reduce time of hybridization and will be able to speed up the rate of detection of biochip greatly, the fundamental study of adsorption kinetics of protein molecules. Furthermore, apply this technology to detection of novel molecular imprinted polymer (MIP) chip. Provide systematical information of interaction mechanism and kinetics of processes of biomolecules and advance the ability of drug design, proteomics study.

關鍵字(中)

★ 耦合電漿波導共振
★ 表面電漿共振
★ 生物分子交互作用分析
★ 分子拓印高分子
★ 波導耦合表面電漿共振
★ 長距離表面電漿共振
★ 奈米粒子強化
★ 生物感測器
★ 靈敏度
★ 超高解析度

關鍵字(英)

★ biosensor
★ sensitivity
★ ultrahigh-resolution
★ nanoparticle-enhanced
★ waveguide-coupled surface plasmon resonance
★ long-range surface plasmon resonance
★ coupled plasmon-waveguide resonance
★ surface plasmon resonance
★ biomolecular interaction analysis
★ molecular im

論文目次

第一章緒論 1
1-1前言 1
1-2研究動機與目的 2
1-3文獻回顧 4
1-3-1光波耦合方式 6
1-3-2表面電漿共振現象的量測方式 8
1-3-3表面電漿共振生物感測器之靈敏度提昇 10
1-4 論文架構 12
第二章表面電漿共振與衰逝全反射生物感測儀 13
2-1表面電漿共振現象 13
2-1-1表面電漿波 13
2-1-2單一界面組態之Fresnel方程式及色散關係式及其共振條件 14
2-1-3二層界面組態之Fresnel方程式及色散關係式 20
2-1-4三層界面組態之Fresnel方程式及色散關係式 23
2-2表面電漿共振生物感測器之研製 26
2-3衰逝全反射生物感測儀 28
2-3-1光學系統 29
2-3-2旋轉平台操控 31
2-3-3溫度控制系統 31
2-3-4系統程式設計 32
第三章各式模態表面電漿共振生物感測器與其靈敏度之比較 34
3-1傳統表面電漿共振生物感測器 34
3-1-1靈敏度推導 34
3-1-2靈敏度模擬分析 39
3-2耦合電漿波導共振生物感測器 42
3-2-1耦合電漿波導共振生物感測器之推導 42
3-2-2靈敏度模擬分析 46
3-3長距離表面電漿共振生物感測器 50
3-3-1長距離表面電漿共振生物感測器之推導 50
3-3-2靈敏度模擬分析 54
第四章超高解析度表面電漿共振生物感測器 60
4-1奈米粒子強化表面電漿共振之理論分析 61
4-2奈米粒子表面電漿共振生物感測器之製作 64
4-3奈米粒子表面電漿共振生物感測器之強化效應 66
4-3-1強化效應之分析 66
4-3-2超高解析度之測試 69
4-4波導耦合表面電漿共振生物感測器 76
4-4-1理論分析 76
4-4-2設計與靈敏度比較 79
第五章生物分子間交互作用動力學之研究 82
5-1去氧核糖核酸雜交之動力學 83
5-1-1去氧核糖核酸探針固定化試驗 87
5-1-2去氧核糖核酸晶片雜交反應試驗 90
5-1-3專一性雜交反應試驗 96
5-2外加電場於DNA雜交反應動力學之研究 99
5-2-1短鏈DNA於流速50 l/min之試驗 99
5-2-2長鏈DNA於流速靜止之試驗 103
5-3蛋白質分子吸附動力學 106
5-3-1晶片表面改質硫醇化合物之試驗 108
5-3-2 HSA蛋白質吸附於羧基改質之晶片表面之試驗 110
5-3-3 HSA蛋白質吸附於胺基改質之晶片表面之試驗 112
5-4分子拓印高分子晶片檢測 114
第六章結論 118
參考文獻 120

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指導教授

陳顯禎、吳漢雄
(Shean-Jen Chen、John H. Wu)

審核日期

2003-7-7

推文