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研究生： SEPTILA RENATA
SEPTILA - RENATA
論文名稱： SILVER and Ag@Au CORE SHELL SERS NANOTAGS for BREAST CANCER DETECTION
SILVER and Ag@Au CORE SHELL SERS NANOTAGS for BREAST CANCER DETECTION
指導教授： 黃炳照
Bing-Joe Hwang
口試委員: 蘇威年
Wei-Nien Su
周宏隆
Hung-Lung Chou
張君照
Chun-Chao Chang
學位類別： 碩士
Master
系所名稱： 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年： 2013
畢業學年度： 101
語文別： 英文
論文頁數： 83
中文關鍵詞： 銀奈米粒子 、Ag@Au 奈米粒子 、表面增強拉曼散射奈米標靶 、HER2抗體 、乳癌
外文關鍵詞： Ag NPs, Ag@Au NPs, SERS nanotags, HER2 antibody, breast cancer
相關次數： 點閱：397  下載：5 
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    • 表面增強拉曼散射光譜為對生化與化學分析具有極佳靈敏性與選擇性之工具。奈米標靶可增強目標物的拉曼散射訊號，因為拉曼標籤產生的拉曼光譜可用來鑑定生化分子間的作用。而金屬表面可用來增強拉曼散射訊號於超靈敏偵測上之應用。
    在本研究中，吾人使用R6G染料分子當拉曼標籤，以Ag 與Ag@Au為拉曼基材，接著以二氧化矽將其包覆。銀奈米粒子以晶種成長法來合成，其粒徑約為30-40奈米之間；而Ag核Au殼之Ag@Au奈米粒子藉由金屬置換反應來合成，其Au殼層非常均勻地包覆住Ag核。將R6G拉曼標籤置於合成之奈米金屬表面上，接著利用修飾stober 法將二氧化矽均勻包覆於有R6G吸附之奈米金屬粒子上。二氧化矽之厚度約為1.5奈米。二氧化矽表面首先接上胺基與羧基，然後再以EDC 和 NHS活化其表面。 SERS奈米標靶與HER抗體結合可應用於乳癌細胞之檢測上。
    表面增強拉曼散射光譜顯示Au奈米粒子的增強效應比Ag@Au更佳。二氧化矽的包覆會減弱拉曼表面增強的效應。SERS奈米標靶表面修飾之目的為使HER2抗體的吸附更加穩定。此SERS奈米標靶與HER2抗體的結合目的在於檢測乳癌細胞之HER2狀態。HER2抗體可用來捕抓於乳癌細胞表面之HER2受體。

    Surface-enhanced Raman Scattering (SERS) spectroscopy is a highly sensitive and selective tool for the identification of biological and chemical analytes based on the SERS effect of nanostructured metal surfaces. SERS nanotags introducing Raman label compounds onto noble metal (Ag NPs and Ag@Au NPs). SERS nanotags can enhance the Raman scattering signal of targets because Raman label generates the Raman spectral signature used to identify a biomolecular interaction (chemical enhancement), whereas the metal nanostructure is used to amplify the Raman scattering signal for ultrasensitive detection (electromagnetic enhancement).
    In this research synthesis of SERS nanotags consist of rhodamine 6G as Raman label, Ag and Ag@Au as Raman substrate, then encapsulated with silica. Silver nanoparticles were synthesis using seed-growth method and produced particle size 30 - 40 nm, while Ag@Au nanoparticles were synthesis using galvanic replacement reaction, resulted very thin and uniform gold shell around silver core. SERS nanotags were synthesized by placing rhodamine 6G as Raman label to nanoparticles (Ag and Ag@Au). The encapsulation SERS nanotags with silica were performed by the modified Stober method, and resulted in a silica shell of 1.5 nm thickness. The surface of silica was first anchored by amine and carboxyl groups and then activated by EDC and NHS molecules. SERS Nanotags, which had been conjugated with HER2 antibody, applied to the detection of breast cancer cell.
    SERS spectroscopy shows that Ag NPs give higher enhancement than Ag@Au NPs. Nevertheless, encapsulation also decreases the enhancement effect of SERS, especially in Ag SERS nanotags because part of laser excitation is scattered before they arrive to the surface of silver. The aim of SERS nanotags surface modification is to yield stable amine bond which can be well bioconjugated with HER2 antibody.
    HER2 antibody is used to capture HER2 receptor on the surface of breast cancer cells, so that an early and precise detection of HER2 status of breast cancer calls can be realized in near future.

    摘要 I ABSTRACT II ACKNOWLEDGEMENT IV TABLE OF CONTENTS VI LIST OF FIGURES X LIST OF SCHEME XIII LIST OF TABLE XIV CHAPTER I INTRODUCTION 1 I.1 BACKGROUND 1 I.2 MOTIVATION 5 I.3 RESEARCH PURPOSES 6 CHAPTER II LITERATURE REVIEW 7 II.1 NANOPARTICLES 7 II.1.1 DEFINITION OF NANOPARTICLE 7 II.1.2 APPROACH OF NANOPARTICLES SYNTHESIS 8 II.1.3 NANOPARTICLES SYNTHESIS STRATEGIES 9 II.1.4 PROPERTIES OF NANOPARTICLES 18 II.1.4.1 OPTICAL PROPERTIES 18 II.1.4.2 MECHANICAL PROPERTIES 19 II.1.4.3 THERMAL PROPERTIES 19 II.1.4.4 MAGNETIC PROPERTIES 20 II.1.5 APPLICATION OF NANOPARTICLES 20 II.2 SILVER NANOPARTICLES 21 II.3 SERS PROBE 23 II.4 CORE SHELL NANOPARTICLES 25 II.4.1 AG@AU CORE SHELL NANOPARTICLE 26 II.4.2 SILICA COATED NANOPARTICLES 27 II.5 SURFACE-ENHANCED RAMAN SCATTERING (SERS) SPECTROSCOPY 28 II.6 BIOCONJUGATION 32 II.6.1 PHYSISORPTION 33 II.6.2 CHEMISORPTION 33 II.6.2.1 MODIFICATION OF AMINE WITH SILANE COMPOUND 34 II.6.2.2 MODIFICATION OF CARBOXYLATE WITH SUCCINIC ANHYDRIDE 35 II.6.2.3 EDC AND NHS AS ZERO LENGTH CROSSLINKERS 36 II.7 BREAST CANCER CELL 38 II.7.1 DEFINITION OF BREAST CANCER 38 II.7.2 HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2) 41 CHAPTER III RESEARCH METHODOLOGY 45 III.1 RESEARCH DESIGN 45 III.2 MATERIALS 48 III.3 EQUIPMENTS 49 III.4 EXPERIMENTAL PROCEDURE 49 III.4.1 SYNTHESIS SILVER NANOPARTICLES 49 III.4.2 SYNTHESIS SILVER GOLD CORE SHELL NANOPARTICLES 51 III.4.3 SYNTHESIS SERS NANOTAGS 52 III.4.4 ENCAPSULATING AG AND AG@AU SERS NANOTAGS 53 III.4.5 FUNCTIONALIZATION OF SERS NANOTAG@SIO2 SURFACE 54 III.4.6 ANTIBODY CONJUGATION 56 III.5 SAMPLE CHARACTERIZATION 56 III.5.1 UV –VIS SPECTROSCOPY 56 III.5.2 TRANSMISSION ELECTRON MICROSCOPY (TEM) 57 III.5.3 RAMAN SPECTROSCOPY 57 CHAPTER IV RESULT AND DISCUSSION 59 IV.1 SYNTHESIS OF NANOPARTICLES 59 IV.1.1 SYNTHESIS SILVER NANOPARTICLES 59 IV.1.2 GOLD COATED SILVER NANOPARTICLES 62 IV.2 SERS NANOTAGS 68 IV.3 ENCAPSULATION SERS NANOTAGS 69 IV.4 SURFACE FUNCTIONALIZATION OF SERS NANOTAGS 75 CHAPTER V CONCLUSION 79 BIBLIOGRAPHY 81

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