臺灣博碩士論文加值系統

　　拉曼標記是一項新穎的科技應用於生物影像技術，其主要的功能是可以標定各種細胞、分子，而因為拉曼訊號一般較螢光強度弱，所以需要金屬叢集結構來使訊號增強，而核心－衛星奈米金屬叢集結構是其中常用的一種結構，在本論文中提供以靜電力相吸合成核心－衛星奈米金屬叢集結構的方法，而不用DNA連結等較複雜的方式，可以較快速且簡易地合成此叢集結構。合成後的奈米金屬叢集結構穩定度與分散性是現今拉曼標記主要的議題之一，原因是此結構的穩定度與分散性會影響到拉曼標記訊號的穩定度與是否能定量分析，在本論文中，主要在製程方面提供幾種方法去提升奈米金屬叢集結構的穩定度與分散性，以及合成之後提供純化方法分離出所需要的奈米金屬叢集結構。
　　以靜電力合成核心－衛星奈米金屬叢集結構中，訊號增強的地方主要在核心與衛星粒子連結的間隙處，所以衛星粒子的吸附率會影響單一個拉曼標記的訊號強度，衛星粒子吸附率越高則單一個拉曼標記的訊號強度越強，在本論文中嘗試數種連結化學物質與調配不同濃度去提升衛星粒子的吸附率，並且藉由調整核心粒子與衛星粒子的粒子數比、混合方式等方法控制合成叢集結構後的分散性。
　　由於合成後的奈米金屬叢集結構會因為環境改變而遭受破壞，所以需要包覆保護層，在本論文中以二氧化矽作為保護層，合成二氧化矽殼製程中對分散性、穩定度有影響的因素，在本論文中都有做改善與討論。
　　此外，在合成完叢集結構與附上保護層後有量測其拉曼訊號，在石英基板上可以量測到單一複合粒子的拉曼訊號，對於之後細胞的標定量測可能會有所幫助。

The core-satellite nanostructures are applied to enhance electric field in SERS (Surface enhanced Raman scattering) tags. The method using electrostatic induction to produce core-satellite nanostructures is offered in this research. This method is simpler than those using DNA. The stability of Raman signal and whether the signal can be quantitative analysed depends on the stability and dispersion of nanostructures. There are several methods for improving the stability and dispersion of nanostructures in this research. Also, the purification of core-satellite nanostructures are provided in this research. The Raman signal’s intensity of a SERS tag depends on the number of satellites per core. The more satellites it has, the stronger Raman signal’s intensity it has. In this research, several chemicals were experimented for improving the number of satellites per core. Furthermore, the dispersion of the core-satellite nanostructures was improved by adjusting the satellites concentration and the method of mixture. The core-satellite nanostructures would be destroyed by the change of environment. Therefore, the core-satellite nanostructures was coated by silica chell in this research. The factors which would influence the dispersion or stability of the nanostructures were discussed in this research. In addition, the Raman signal of the core-satellite nanostructures with silica shell was measured in this research. The Raman signal of the single core-satellite nanostructure was measured successfully which could be applied to quantitative analysis.

目錄
摘要 I
Abstract II
誌謝 X
目錄 XI
第一章 序論 1
1-1 前言 1
1-2 研究目的 5
1-3 研究動機 5
1-4 文獻回顧 6
第二章 研究方法 12
2-1表面增強拉曼散射基本原理 12
2-1-1 表面電漿共振原理 12
2-1-2 拉曼光譜學 14
2-1-3 表面增強效應 17
2-2 二氧化矽殼包覆複合奈米金粒子製程原理 18
2-2-1 Zeta 電位原理 19
2-2-2 PAH與金粒子反應 20
2-2-3 APTMS水解與吸附 21
2-2-4 矽酸鹽類(Silicate)水解與聚合 22
2-3 實驗儀器原理 22
2-3-1 穿透式電子顯微鏡(TEM) 23
2-3-2 動態光散射儀(Dynamic light scattering，DLS)量測 24
2-3-3 紫外－可見光吸收光譜儀(UV-Vis Spectroscopy) 26
2-3-4 拉曼光譜儀 28
2-3-5 彈性散射光譜儀 31
2-4 複合奈米金粒子包覆二氧化矽殼結構製備 34
2-4-1 複合粒子製程 36
2-4-2 複合粒子包覆二氧化矽殼製程步驟 36
第三章 實驗結果與討論 37
3-1 比較不同連結化學物質製備複合粒子之反應 37
3-1-1 DMcT 37
3-1-2 AMT 40
3-1-3 BDT 43
3-1-4 BDA 45
3-1-5 PAH 48
3-1-6 比較不同連結化學物質製備複合粒子的結論 51
3-2 PAH濃度與複合粒子結構之關係 54
3-3 50 nm金粒子與20 nm金粒子比例對複合粒子合成之影響 56
3-4 附上PAH後的50 nm金粒子濃度對複合粒子聚集之影響 58
3-5 20 nm與50 nm金粒子混合方式的影響 60
3-6 離心轉速對去除20 nm金粒子、複合粒子聚集之影響 62
3-7 合成二氧化矽殼時化學藥品濃度影響 64
3-8 合成二氧化矽殼震盪轉速、震盪時間對粒子損失率、聚集之影響 66
3-9 合成二氧化矽殼(以APTMS與矽酸鈉為反應化學物質) 70
3-9-1 APTMS濃度影響 71
3-9-2 APTMS-pH值之影響 72
3-9-3 稀釋APTMS方法不同對金粒子的影響 73
3-9-4 pH值對矽酸鈉合成二氧化矽殼之影響 76
3-9-5 矽酸鈉加鹽酸對pH值的變化 77
3-10 純化單顆複合粒子 78
3-10-1 多重離心分離法 78
3-10-2 多相溶液分離法 81
3-11 光學量測 82
3-12 實驗總成果 87
第四章 討論 91
4-1 複合粒子分散性改進方向 91
4-1-1 製程上改進 91
4-1-2 分離法純化 91
4-2 衛星粒子吸附率改進方向 92
4-2-1 連結化學物質的選擇 92
4-2-2 化學物質濃度控制Zeta電位 93
4-3 拉曼訊號增強改進方向 93
4-3-1 提高雷射光源強度 93
4-3-2 加上拉曼訊號明顯的分子 93
4-3-3 降低背景干擾 94
參考文獻 95

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