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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68590
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dc.contributor.advisor林啟萬(Chii-Wann Lin)
dc.contributor.authorYi-Ming Chenen
dc.contributor.author陳一銘zh_TW
dc.date.accessioned2021-06-17T02:26:32Z-
dc.date.available2020-10-19
dc.date.copyright2017-08-28
dc.date.issued2017
dc.date.submitted2017-08-18
dc.identifier.citation[1] Eggins, B.R., 'Chemical sensors and biosensors'. Vol. 28. John Wiley & Sons. 2008
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[35] Pollack, K.A., et al., 'Hyperbranched fluoropolymer-polydimethylsiloxane-poly(ethylene glycol) cross-linked terpolymer networks designed for marine and biomedical applications: heterogeneous nontoxic antibiofouling surfaces', ACS Applied Materials & Interfaces, 2014. 6(21): p. 19265-74.
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[39] Fernandez, F., et al., 'A label-free and portable multichannel surface plasmon resonance immunosensor for on site analysis of antibiotics in milk samples', Biosensors and Bioelectronics, 2010. 26(4): p. 1231-8.
[40] 'Introduction to Digital Micromirror Device (DMD) Technology'. Texas Instruments.
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[45] Choi, Y.H., et al., 'Development of SPR biosensor for the detection of human hepatitis B virus using plasma-treated parylene-N film', Biosensors and Bioelectronics, 2014. 56: p. 286-94.
[46] Gao, Y., et al., 'Secondary structure effects on DNA hybridization kinetics: a solution versus surface comparison', Nucleic Acids Research, 2006. 34(11): p. 3370-7.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68590-
dc.description.abstract傳統上,表面電漿子共振生物感測器(Surface Plasmon Resonance biosensor, SPR biosensor)之表面修飾法(Surface functionalization)以硫金單層自組裝膜(Thiol- gold based Self-Assembled Monolayer, Thiol-gold based SAM)以及其衍生之相關技術為主流。在整個領域的大方向上,除了葡聚醣(Dextran)相關研究與應用外,以高分子層作為修飾方法之基材的研究並不多。由於以高分子層作為修飾層具有許多偵測應用上的優勢,本論文希望提出一套以聚對二甲苯(Parylene)作為基底之修飾方法學。本方法以針對硫醇基之探針分子,以紫外光觸發點擊反應來進行表面固定化。結合數位光源處理技術(Digital Light Process, DLP)系統來控制紫外光之曝光樣式,本修飾方法可以在晶片表面進行指定位置之「定址修飾」。
晶片製作部分,我們透過特殊化學氣相沉積系統來進行聚對二甲苯之鍍膜,並透過表面電漿共振角之偏移以及橢圓儀量測來計算膜厚。根據模擬結果,25 nm之膜厚為最佳化之參數。為進行紫外光曝光,我們以DLP4500 0.45 WXGA DMD為核心建構了一套紫外光曝光系統。此系統的曝光面積大小為10×15 mm2,單位面積之紫外光功率為1×10-4 W/ mm2,每個畫面最小切換週期為235 μs,並結合實驗室之表面電漿共振量測裝置進行即時監測。
為驗證修飾之效能,我們選擇了25-mer 核糖核酸探針分子作為修飾之模型。實驗結果顯示,我們可以在反應濃度1 μM 的probe DNA與5 mM的光啟始劑甲醇溶液,體積比例1:1之條件下,在1000秒內,修飾0.00902 RIU之核糖核酸探針分子。相對於,條件最佳化之硫-金修飾反應,反應速度約快8.9倍。我們透過開啟一半的DMD進行曝光修飾,驗證了定址修飾之效果。實驗結果顯示,UV光照射之區域,產生了1°的角度偏移。
論文最後一章,我們也針對未來技術之潛在議題與未來之發展方向,如在同濃度probe DNA條件下較傳統晶片具有更高的修飾量,進行探討。
zh_TW
dc.description.abstractSurface functionalization of Surface Plasmon Resonance Biosensor (SPR biosensor) is characterized by thiol-gold based self-assembled monolayer. In addition, there is not so many research and application of polymer layer, dextran for example, as a modified method of the substrate. In this study, we propose a method of surface functionalization using parylene as a linker layer, due to its advantages in the detection of applications. We use a probe molecule with thiol group to immobilize the sensing surface by a UV-triggered click reaction and import a digital light processing (DLP) system to control the exposure pattern of ultraviolet light. The modification method can be ‘‘Spatially Selective’’ on the sensing surface.
In the fabrication section, we use a special chemical vapor deposition system to coat parylene and calculate the film thickness through the angle shift of SPR. According to the simulation results, the optimized thickness of the film is 25 nm. For UV exposure, we built a UV exposure system with DLP4500 0.45 WXGA DMD. The exposure area is 10×15 mm2, the UV power per unit area is 1×10-4 W/ mm2, and the minimum frame period is 235 μs. For real-time measurement, we use a SPR device of our laboratory.
To verify, we selected a 25-mer probe DNA as a modified model. The results show that we can modify the probe DNA, and create 0.00902 RIU shift in 1000 seconds. The volume ratio of 1 μM probe DNA and 5 mM DMPA methanol solution is 1:1. Our reaction rate is about 8.9 times faster than sulfur-gold reaction and produces 1° angular offset in UV-exposure. In the last chapter of the thesis, we discuss the potential issues of future technology and development, such as in the same concentration of probe DNA conditions, our chips have high performance than the traditional chips.
en
dc.description.provenanceMade available in DSpace on 2021-06-17T02:26:32Z (GMT). No. of bitstreams: 1
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Previous issue date: 2017
en
dc.description.tableofcontents口試委員會審定書 i
誌謝 ii
摘要 iii
Abstract iv
目錄 v
圖目錄 vii
表目錄 ix
第一章 緒論 1
1.1 研究背景 1
1.2 研究動機與貢獻 2
1.2.1 生物感測表面修飾之發展現況 2
1.2.2 多通道生物感測之優勢與限制 4
1.2.3 新型修飾方法之提出 4
1.3 章節架構 6
第二章 基本原理與文獻回顧 7
2.1 表面電漿子共振 7
2.1.1 表面電漿子共振原理與激發方式 7
2.1.2 表面電漿子共振生物感測器 11
2.1.3 表面電漿子共振量測方式 12
2.1.4 生物感測表面修飾方式 15
2.1.5 非特異性吸附 19
2.2 數位光源處理技術 22
2.2.1 數位微型反射鏡特性 22
2.3 點擊反應 23
2.3.1 硫醇-烯反應 23
第三章 研究材料與方法 25
3.1 表面電漿子共振模擬 25
3.1.1 公式推導 25
3.1.2 模擬軟體 27
3.2 晶片製程 28
3.2.1 基材清洗 29
3.2.2 物理氣相蒸鍍 29
3.2.3 化學氣相蒸鍍 31
3.2.4 硫醇-烯化學改質 34
3.3 系統建構 36
3.3.1 光學系統 36
3.3.2 流體通道設計與種類 40
3.3.3 曝光圖案設計與數位微型反射鏡之控制 42
3.3.4 系統邊界參數測量方式 45
3.3.5 量測軟體 48
3.4 量測與數據分析方法 49
3.4.1 角度調變量測方式 49
3.4.2 強度調變量測方式 50
3.4.3 反射光強度的歸一化 50
3.4.4 折射率的歸一化 51
第四章 研究結果與討論 52
4.1 DMD曝光性能與角度極限測試 52
4.2 緩衝液之水對甲醇比例測試 54
4.3 聚對二甲苯厚度對SPR反應之影響 55
4.4 靈敏度與偵測極限 56
4.5 修飾核酸適體 58
4.6 空間選擇性修飾法驗證 60
4.7 聚對二甲苯之蛋白質吸附測試 63
第五章 結論與未來展望 65
參考文獻 66
附錄一 SPR模擬之MATLAB程式碼 70
附錄二 繪製點陣列圖之Python程式碼 72
dc.language.isozh-TW
dc.subject數位微型反射鏡zh_TW
dc.subject硫醇-烯反應zh_TW
dc.subject表面電漿子共振zh_TW
dc.subjectThiol-ene reactionen
dc.subjectDigital Micromirror deviceen
dc.subjectSurface plasmon resonanceen
dc.title以數位微型反射鏡定址硫醇-烯化學改質之適體探針陣列電漿子晶片zh_TW
dc.titleSpatially Selective Thiol-ene Functionalization of Plasmonic Apta-sensor Array by Digital Micromirror Deviceen
dc.typeThesis
dc.date.schoolyear105-2
dc.description.degree碩士
dc.contributor.oralexamcommittee陳賢燁(Hsien-Yeh Chen),彭盛裕(Sheng-Yu Peng),楊家銘(Chia-Ming Yang)
dc.subject.keyword表面電漿子共振,硫醇-烯反應,數位微型反射鏡,zh_TW
dc.subject.keywordSurface plasmon resonance,Thiol-ene reaction,Digital Micromirror device,en
dc.relation.page75
dc.identifier.doi10.6342/NTU201700786
dc.rights.note有償授權
dc.date.accepted2017-08-19
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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