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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 宋孔彬(Kung-Bin Sung) | |
dc.contributor.author | Cheng-Chu Wu | en |
dc.contributor.author | 吳政舉 | zh_TW |
dc.date.accessioned | 2021-05-20T20:02:12Z | - |
dc.date.available | 2010-02-01 | |
dc.date.available | 2021-05-20T20:02:12Z | - |
dc.date.copyright | 2009-08-21 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-08-20 | |
dc.identifier.citation | 參考文獻
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8832 | - |
dc.description.abstract | 目前在微陣列晶片( microarray )分析中,對於基因表現( gene expression )的測量與定量越來越為重要,目前最常使用的便是螢光表現量的偵測方式為架構,然而使用螢光標記時我們需要將目標物放大( target amplification )以期得到較為足夠的信號源,再者螢光偵測所需的儀器系統也較為複雜,而偵測上容易受到螢光本身及螢光背景值的影響,因此我們希望可以發展一套更為簡單、低成本且快速的偵測方式。
本研究目標主要為發展金屬奈米粒子 DNA 檢測平台,利用各種不同金屬奈米粒子散射光譜的不同來達到多樣信號源的目的。在本論文中主要著重在金奈米粒子於 DNA 晶片的應用,由金奈米粒子區域表面電漿共振的特性,我們可以得到其散射光譜及粒子影像。論文中提出了金奈米粒子應用於 DNA 晶片的製備流程:包括晶片表面修飾、金奈米粒子與 DNA 的三明治雜交反應流程、估算金奈米粒子表面 DNA 分子數、金奈米粒子應用的偵測極限以及不同奈米粒子的初步實驗結果。 與 Cy3 螢光標記方法互相比較,本論文提出的金屬奈米粒子光學標記方法,大約有 1000 倍靈敏度的增加。利用本實驗室所發展的傅立葉光譜儀系統掃描,可達到大面積的散射光譜掃描,與商用的微陣列晶片掃描儀器比較,也較為簡便且成本為低。 本研究所發展的金屬奈米粒子 DNA 檢測平台,利用實驗室所建構的傅立葉光譜儀光譜掃描,可以讓我們達到低成本、快速掃描且高靈敏的偵測方式。 | zh_TW |
dc.description.abstract | DNA microarray is a powerful tool allowing simultaneous detection of many different target molecules present in a sample. By using these techniques, large-scale parallel analyses can be performed in short time periods. Fluorescence technology has been the gold standard for detection of DNA on microarrays due to its high sensitivity, dynamic range, and multiplexing capabilities. Despite these attributes, fluorescence labeling typically requires target amplification to obtain sufficient amounts of target and complex instrumentation is needed for detection, ultimately limiting its utility in the applications described above.
The development of a metal nanoparticle-based detection methodology for sensitive and specific DNA microarray is described. The technology utilizes gold and silver nanoparticles derivatives with thiol modified oligonucleotides that are designed to bind complementary DNA targets. Scattered light from nanoparticle-tagged biomolecules can be imaged and quantified extremely sensitively. It allows for detection and quantization by measuring evanescent wave induced light scatter with low-cost optical detection systems. Compared to Cy3-based fluorescence, gold nanoparticle probes provide for a 1000-fold increase in sensitivity. | en |
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dc.description.tableofcontents | 目錄 I
圖目錄 IV 表目錄 VI 中文摘要 VII Abstract VIII 第壹章 緒論 1 第貳章 研究背景與動機 3 2.1 DNA 分子簡介 3 2.2 生物晶片簡介 5 2.2.1 微陣列晶片 ( Microarray ) 6 2.2.2 實驗室晶片 ( Lab-on-a-chip ) 10 2.3 金屬奈米粒子簡介 12 2.4 研究動機 15 第參章 文獻回顧 17 3.1 金奈米粒子應用領域 17 3.1.1 標記 ( Labeling ) 與成像 ( Visualizing ) 17 3.1.2 輸送媒介 ( A vehicle for delivery ) 17 3.1.3 生醫感測 ( Biosensor ) 18 3.2 奈米粒子的光學效應 19 3.2.1 區域性表面電漿共振效應 ( Localized Surface Plasmon Resonance) 19 3.2.2 尺度對於 LSPR 的影響 20 3.2.3 形狀對於 LSPR 的影響 20 3.3 金奈米粒子於 DNA 之應用 21 3.4 奈米粒子標記技術 23 3.4.1 量子點 ( Quantum dots ) 23 3.4.2 金奈米粒子 ( Gold nanoparticles ) 24 第肆章 實驗設計與材料方法 26 4.1 實驗設計 26 4.1.1 一對一單股 DNA 於微陣列晶片上雜交反應 26 4.1.2 微陣列晶片上 DNA 三明治雜交反應 27 4.1.3 系統偵測方式: 28 4.2 材料與方法 29 4.2.1 微陣列晶片製作 29 4.2.2 奈米粒子合成 37 4.2.3 探針 DNA 修飾於金奈米粒子表面 39 4.2.4 DNA 雜交反應 42 4.2.5 微陣列晶片掃描 47 第伍章 實驗結果與討論 49 5.1 探針 DNA 修飾於金奈米粒子表面 49 5.1.1 BSA 應用於金奈米粒子表面修飾 49 5.1.2 金奈米粒子上 DNA 數量 53 5.2 金屬奈米粒子散射光譜 56 5.2.1 奈米粒子散射光譜 56 5.2.2 DNA 修飾奈米粒子散射光譜 60 5.3 DNA 三明治雜交反應 ( DNA sandwich hybridization ) 72 5.3.1 DNA 三明治雜交反應初步測試 72 5.3.2 傅立葉光譜儀掃描系統應用於晶片掃描 74 5.3.3 樣本濃度於系統的極限偵測 78 5.4 金屬奈米粒子與螢光分子比較 79 5.5 混合兩種奈米粒子光譜系統初步測試 80 第陸章 結論與未來建議 83 參考文獻 84 圖目錄 圖 1:四種不同的核酸鹼基。 4 圖 2:A 與 T、C 與 G 之間彼此以氫鍵相連。 4 圖 3:UV-vis extinction spectra of Ag nanoparticle arrays on mica substrates. 14 圖 4:不同大小尺寸的量子點有不同的螢光波長。 23 圖 5:不同大小的金奈米粒子溶液。 24 圖 6:capture- DNA 與 probe-DNA 雜交反應 26 圖 7:三明治雜交反應流程圖示。 27 圖 8:以醛基修飾表面為基礎之微陣列晶片製作流程圖。 29 圖 9:基材矽烷化改質:矽烷化反應流程圖。 32 圖 10:胺基基材表面進行醛基化修飾反應流程圖。 34 圖 11:暗視野顯微鏡示意圖與顯微鏡及掃描的晶片實照。 47 圖 12:傅立葉轉換光譜儀 (FTS) 示意圖 (77)。 48 圖 13:thiol- DNA (probe-DNA) 修飾於金奈米粒子表面流程圖。 50 圖 14:經BSA修飾及未修飾的金奈米粒子吸收光譜。 51 圖 15:時間對 Au-probe DNA 的影響。 51 圖 16:單顆金奈米粒子上的 DNA 數量。 53 圖 17:估計單顆金奈米粒子表面所含 DNA 數量流程圖。 54 圖 18:不同金屬奈米粒子散射光譜圖。 56 圖 19:晶片表面上 32 nm 金奈米粒子與雜質散射光譜。 58 圖 20: 32 nm 金奈米粒子與雜質散射光譜強度。 58 圖 21:40 nm 銀奈米粒子與金奈米粒子的原始散射光譜信號強度差異。 59 圖 22:32 nm 金奈米粒子與 DNA 修飾金奈米粒子表面散射光譜圖。 61 圖 23:在暗視野顯微鏡下所得 32 nm 金奈米粒子影像。 61 圖 24:40 nm 金奈米粒子平均光譜。 64 圖 25:40 nm 銀奈米粒子平均光譜。 64 圖 26:一對一單股 DNA 雜交反應示意圖。 66 圖 27:一對一單股 DNA 雜交反應於暗視野顯微鏡下所得影像。 67 圖 28:不同區域所得的32nm金奈米粒子光譜圖。 68 圖 29:低濃度 Au-probe-DNA 雜交反應光譜圖。 69 圖 30:不同濃度的 Au-probe DNA 於晶片上進行一對一單股 DNA 雜交反應 CCD 影像。 70 圖 31:不同濃度 Au- DNA 於晶片上的一對一的單股 DNA 雜交反應。 71 圖 32:三明治雜交反應實驗控制組與對照組示意圖。 72 圖 33:三明治雜交反應實驗控制組與對照組於暗視野顯微鏡下所得影像。 72 圖 34:不同Au-probe/target DNA 濃度下,散射光譜影像與測量光譜圖。 73 圖 35:利用傅立葉光譜儀的操作介面圖。 74 圖 36:商用光譜儀與傅立葉光譜儀針對單點的光譜比較。 75 圖 37:傅立葉光譜儀於大範圍的晶片表面金奈米粒子掃描。 75 圖 38:不同濃度下Au-probe/target DNA 進行三明治雜交反應強度。 76 圖 39:不同 target DNA 濃度進行雜交反應所得的光譜強度。 78 圖 40:螢光系統在不同濃度下的信號強度值。 79 圖 41:40 nm 金奈米粒子與 40 nm 銀奈米混合之 CCD 影像。 80 圖 42:40 nm 金奈米粒子與 40 nm 銀奈米之混合光譜 81 圖 43:暗視野顯微鏡下金、銀奈米粒子影像。 82 圖 44:40 nm 金奈米粒子與 40 nm 銀奈米混合光譜與原始單粒子光譜比較。 82 表目錄 表 貳 1:基因晶片研究上相關的廠商與機構。 8 表 貳 2:不同型式的蛋白質晶片。 9 表 參 1:Mirkin 團隊對於金奈米粒子應用 DNA 領域的研究 21 表 伍 1:Thiol-DNA 序列及相關資訊。 52 表 伍 2:單顆金奈米粒子紅移實驗所用之 DNA 序列 60 表 伍 3:金奈米粒子平均光譜紅移實驗所用之 DNA 序列 63 表 伍 4:Au-probe DNA 稀釋濃度。 69 表 伍 5:Au-probe/target DNA 的濃度序列稀釋。 76 表 伍 6:由傅立葉光譜儀在不同濃度下所得的光譜圖。 77 表 伍 7:進行雜交反應時,不同濃度的target DNA 。 78 | |
dc.language.iso | zh-TW | |
dc.title | 金屬奈米粒子標記於 DNA 微陣列晶片應用 | zh_TW |
dc.title | Application of Metal Nanoparticles (MNPs) Labeling to DNA Microarray | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊曜宇(Eric Yao-Yu Chuang),林乃君(Nai-Chun Lin),黃志清(Chih-Ching Huang) | |
dc.subject.keyword | 微陣列晶片,金奈米,DNA,散射光譜, | zh_TW |
dc.subject.keyword | microarray,gold nanoparticle,DNA,scattering spectra, | en |
dc.relation.page | 98 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2009-08-20 | |
dc.contributor.author-college | 電機資訊學院 | zh_TW |
dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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