可功能化編碼之表面增強拉曼光譜標籤探針於高靈敏與多重生醫分子檢測

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姓名

廖子瑜(Zi-Yu Liao) 查詢紙本館藏

畢業系所

生物醫學工程研究所

論文名稱

可功能化編碼之表面增強拉曼光譜標籤探針於高靈敏與多重生醫分子檢測
(Encodable Functional SERS Tag for Highly Sensitive and Multiplex Biomolecule Detection)

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摘要(中)

在生化與臨床醫學等項目，透過標識分子進行檢測與分析是很重要的一種方式，而可實行於多重與高通量檢測中之標識分子可有效的提高檢測分析之功能性與量能。其中，使用編碼粒子做為光譜標記之檢測方法擔任十分重要之角色。為此，本研究論文發展出具功能化編碼之表面增強拉曼光譜標籤探針並將其於生化與臨床醫學中應用。
本研究利用拉曼散射中所展現的材料光譜獨特性，結合表面增強拉曼光譜機制，研發具有功能化編碼與可定量之標籤探針。此新型光學奈米標識分子探針，是採用特定的標記分子與貴金屬奈米粒子結合，可產生強烈的特徵拉曼光譜訊號，並藉由此獨特的光譜訊號完成編碼特性，使其具有高靈敏度、多重分析能力與可定量等獨特優點與特性。
本研究已成功完成一系列功能化之表面增強拉曼光譜標籤的合成與分析，包含合成多種編碼標籤分子以及利用不同型態之奈米材料製備出光譜增強奈米粒子，並以生物分子免疫反應之測試為例，驗證了本研究所提出之方法與系統的可行性。此研究成果提供未來在多重與高通量檢測方式之選擇外，也拓展了使用編碼粒子做為光譜標記之相關應用層面，可望在生物化學分析與臨床醫學上有更好、更廣泛的應用。

摘要(英)

Encoded particles are one of the most powerful approaches for multiplex and high-throughput detection. The sensitive and specific analysis of biomolecules from complex mixtures is essential in the field of clinical diagnostics. The presence and progression of disease generally involve a multitude of different biomolecules. Thus detecting multiple events in tandem can reduce time and cost and obtain significantly more information from a small clinical sample.
In this study, we report a universal, inexpensive, high sensitivity, and encodable synthetic protocol for fabricating a series of SERS-encoded nanoparticles. As a newly emerging optical nanoprobe, SERS-encoded nanoparticles synthesize through attaching intrinsically strong Raman scattering molecules to the surface of plasmon-resonant gold nanoparticles. It can provide strongly enhanced spectroscopic signals due to the enhancement of local optical fields at metal surfaces. With these distinctive spectroscopic signals, it is of great use in biochemical detection and analysis. The advantage including high sensitivity, easily quantitative analysis, great multiplexing capacity, and so on.
Until now, our study has successfully fabricated a series of encodable functional SERS-active nanoprobes, including SERS-encoded nanoparticle, nanoaggregated, nanostars. Furthermore, through the proof-of-concept with biomolecule immune testing, the encodable functional SERS-active nanoprobes can be used for multiplex biomolecule detection. We anticipate that this novel optical nanoprobes method may expand the application of encoded particles in optical encoding systems, which is promising in biochemical multiplex and high-throughput detection.

關鍵字(中)

★ 表面增強拉曼光譜
★ 編碼粒子
★ 新型光學奈米探針
★ 多重與高通量檢測

關鍵字(英)

★ Surface-enhanced Raman spectroscopy
★ Encoded Particles
★ Novel Optical Nanoprobes
★ Multiplex and High-throughput Detection

論文目次

中文摘要 i
Abstract ii
誌謝 iii
目錄 iv
圖目錄 vii
表目錄 ix
專有名詞縮寫對照表 x
符號說明 xi
第一章緒論 1
1-1 前言 1
1-2 研究動機與目的 2
1-3 論文架構 2
第二章文獻回顧 3
2-1 拉曼散射 3
2-1-1 拉曼散射歷史 3
2-1-2 拉曼散射原理 4
2-2 表面增強拉曼散射(Surface-Enhanced Raman Scattering, SERS) 8
2-2-1 表面增強拉曼散射歷史 8
2-2-2 表面增強拉曼散射原理 9
2-3 表面增強拉曼光譜標籤探針 11
2-3-1 背景 11
2-3-2 表面增強拉曼光譜標籤探針之組成 13
2-3-3 表面增強拉曼光譜標籤探針用於生物醫學相關之檢測 14
第三章研究材料與方法 17
3-1 實驗方法與架構 17
3-2 實驗儀器與藥品 19
3-2-1 藥品 19
3-2-2 儀器 20
3-3 系統性、功能化編碼方式 21
3-4 水相金奈米粒子 (Gold nanoparticles) 23
3-4-1 實驗原理 23
3-4-2 水相金奈米合成步驟 24
3-5 單顆SERS標籤探針 25
3-5-1 SERS標籤合成原理 25
3-5-2 SERS標籤表面生化修飾原理 27
3-5-3 單顆SERS標籤合成步驟 30
3-5-4 單顆SERS標籤表面生化修飾步驟 32
3-6 多顆聚集型SERS標籤探針 33
3-6-1 實驗原理 33
3-6-2 多顆聚集型SERS標籤合成步驟 34
3-7 星形SERS標籤 36
3-7-1 實驗原理 36
3-7-2 星形金奈米粒子(Gold Nanostars)合成步驟 38
3-7-3 星形SERS標籤合成步驟 39
3-8 SERS標籤探針免疫反應之測試 40
3-8-1 實驗原理 40
3-8-2 Polystyrene microspheres (PS球)表面修飾步驟 41
3-8-3 SERS標籤探針和PS球反應步驟 42
3-9 實驗檢測系統 43
3-9-1 顯微拉曼光譜儀 43
第四章研究結果分析與討論 44
4-1 水相金奈米粒子之鑑定 44
4-1-1 可見光吸收光譜及TEM影像圖 44
4-1-2 粒徑分析結果 46
4-2 單顆SERS標籤編碼粒子之鑑定 47
4-2-1 可見光吸收光譜 47
4-2-2 TEM影像圖及粒徑分析結果 47
4-2-3 SERS光譜圖 51
4-3 多顆SERS標籤之鑑定 53
4-3-1 可見光吸收光譜 53
4-3-2 TEM影像圖及粒徑分析結果 53
4-3-3 SERS光譜圖 56
4-4 星形SERS標籤之鑑定 58
4-4-1 可見光吸收光譜 58
4-4-2 TEM影像圖及粒徑分析結果 59
4-4-3 SERS光譜圖 60
4-5 SERS標籤探針免疫反應測試之鑑定 61
4-5-1 PS球之鑑定 62
4-5-2 10μm PS- AuNP@TP@SiO2之鑑定 63
4-5-3 6μm PS- AuNP@4-ATP@SiO2之鑑定 64
4-5-4 2μm PS- AuNP@4-FlTP@SiO2之鑑定 65
第五章結論 66
第六章未來展望 66
參考文獻 Reference 67

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指導教授

黃貞翰(Chen-Han Huang)

審核日期

2022-7-26

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