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.

[1] Song, Sha, et al. "Asymmetric hetero-assembly of colloidal nanoparticles through “crash reaction” in a centrifugal field." Dalton Transactions 43.16 (2014): 5994-5997.
[2] Chang, Hyejin, et al. "Ag Shell–Au Satellite Hetero-Nanostructure for Ultra-Sensitive, Reproducible, and Homogeneous NIR SERS Activity." ACS applied materials & interfaces 6.15 (2014): 11859-11863.
[3] Yoon, Jun Hee, Jonghui Lim, and Sangwoon Yoon. "Controlled Assembly and Plasmonic Properties of Asymmetric Core–Satellite Nanoassemblies." ACS nano 6.8 (2012): 7199-7208.
[4] Ge, Jianping, et al. "Core–satellite nanocomposite catalysts protected by a porous silica shell: controllable reactivity, high stability, and magnetic recyclability." Angewandte Chemie 120.46 (2008): 9056-9060.
[5] Dey, Priyanka, et al. "Self assembly of plasmonic core–satellite nano-assemblies mediated by hyperbranched polymer linkers." Journal of Materials Chemistry B 2.19 (2014): 2827-2837.
[6] Liu, Zhen, et al. "Highly Sensitive, Uniform, and Reproducible Surface‐Enhanced Raman Spectroscopy from Hollow Au‐Ag Alloy Nanourchins."Advanced Materials 26.15 (2014): 2431-2439.
[7] Rossner, Christian, and Philipp Vana. "Planet–Satellite Nanostructures Made To Order by RAFT Star Polymers." Angewandte Chemie International Edition53.46 (2014): 12639-12642.
[8] He, Ru, et al. "Plasmonic Core/Satellite Heterostructure with Hierarchical Nanogaps for Raman Spectroscopy Enhanced by Shell‐Isolated Nanoparticles." Advanced Optical Materials 2.8 (2014): 788-793.
[9] Gandra, Naveen, et al. "Plasmonic planet–satellite analogues: hierarchical self-assembly of gold nanostructures." Nano letters 12.5 (2012): 2645-2651.
[10] Sebba, David S., et al. "Reconfigurable Core− Satellite Nanoassemblies as Molecularly-Driven Plasmonic Switches." Nano letters 8.7 (2008): 1803-1808.
[11] Chen, Shiuan-Yeh, and Anne A. Lazarides. "Quantitative amplification of Cy5 SERS in ‘Warm Spots’ created by plasmonic coupling in nanoparticle assemblies of controlled structure†." The Journal of Physical Chemistry C113.28 (2009): 12167-12175.
[12] Wang, Siying, et al. "Collective fluorescence enhancement in nanoparticle clusters." Nature communications 2 (2011): 364.
[13] Urban, Alexander S., et al. "Three-dimensional plasmonic nanoclusters." Nano letters 13.9 (2013): 4399-4403.
[14] Wang, Yan-Qin, et al. "A novel core-satellite CdTe/Silica/Au NCs hybrid sphere as dual-emission ratiometric fluorescent probe for Cu 2+." Biosensors and Bioelectronics 51 (2014): 40-46.
[15] Wang, Xuesi, et al. "Hierarchical AgNR@ Cys@ AuNPs Helical Core–Satellite Nanostructure: Shape-Dependent Assembly and Chiroptical Response." The Journal of Physical Chemistry C 118.11 (2014): 5782-5788.
[16] Jia, Lei, et al. "Unconventional Assembly of Bimetallic Au–Ni Janus Nanoparticles on Chemically Modified Silica Spheres." Chemistry-A European Journal 20.7 (2014): 2065-2070.
[17] Wu, Yiping, et al. "Individual SERS substrate with core–satellite structure decorated in shrinkable hydrogel template for pesticide detection." Journal of Raman Spectroscopy 45.1 (2014): 68-74.
[18] Yoon, Jun Hee, and Sangwoon Yoon. "Probing Interfacial Interactions Using Core–Satellite Plasmon Rulers." Langmuir 29.48 (2013): 14772-14778.
[19] Weng, Ziqing, et al. "Self-assembly of core-satellite gold nanoparticles for colorimetric detection of copper ions." Analytica chimica acta 803 (2013): 128-134.
[20] Xiao, Qingfeng, et al. "A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy." Journal of the American Chemical Society 135.35 (2013): 13041-13048.
[21] Song, Hyeon Don, et al. "On-chip colorimetric detection of Cu2+ ions via density-controlled plasmonic core–satellites nanoassembly." Analytical chemistry 85.16 (2013): 7980-7986.
[22] Chen, Dongyun, et al. "Amphiphilic polymeric nanocarriers with luminescent gold nanoclusters for concurrent bioimaging and controlled drug release."Advanced Functional Materials 23.35 (2013): 4324-4331.
[23] Kang, Jeon Woong, et al. "High Resolution Live Cell Raman Imaging Using Subcellular Organelle-Targeting SERS-Sensitive Gold Nanoparticles with Highly Narrow Intra-Nanogap." Nano letters 15.3 (2015): 1766-1772.
[24] Lim, Dong-Kwon, et al. "Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap."Nature nanotechnology 6.7 (2011): 452-460.
[25] Louis, Catherine, and Olivier Pluchery. Gold nanoparticles for physics, chemistry and biology. London: Imperial College Press, 2012.
[26] Wormeester, Herbert, E. Stefan Kooij, and Bene Poelsema. "Self-Assembled Thin Films: Optical Characterization." (2004): 3361-3371.
[27] Ferraro, John R. Introductory raman spectroscopy. Academic press, 2003.
[28] Skoog, Douglas A., and Donald M. West. Principles of instrumental analysis. Vol. 158. Philadelphia: Saunders College, 1980.
[29] Akbulut, Ozge, et al. "Separation of nanoparticles in aqueous multiphase systems through centrifugation." Nano letters 12.8 (2012): 4060-4064.
[30] Mace, Charles R., et al. "Aqueous multiphase systems of polymers and surfactants provide self-assembling step-gradients in density." Journal of the American Chemical Society 134.22 (2012): 9094-9097.
[31] Jain, Prashant K., et al. "Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine." The Journal of Physical Chemistry B110.14 (2006): 7238-7248.
[32] Smith, Ewen, and Geoffrey Dent. Modern Raman spectroscopy: a practical approach. John Wiley & Sons, 2013.
[33] Khanal, Bishnu P., and Eugene R. Zubarev. "Purification of high aspect ratio gold nanorods: complete removal of platelets." Journal of the American Chemical Society 130.38 (2008): 12634-12635.
[34] Gill, Rajinder S., Ravi F. Saraf, and Subrata Kundu. "Self-Assembly of Gold Nanoparticles on Poly (allylamine Hydrochloride) Nanofiber: A New Route to Fabricate “Necklace” as Single Electron Devices." ACS applied materials & interfaces 5.20 (2013): 9949-9956.
[35] Hanauer, Matthias, et al. "Separation of nanoparticles by gel electrophoresis according to size and shape." Nano letters 7.9 (2007): 2881-2885.
[36] Xiong, Bin, et al. "Separation of nanorods by density gradient centrifugation."Journal of Chromatography A 1218.25 (2011): 3823-3829.
[37] Tognalli, N., et al. "SERS in PAH-Os and gold nanoparticle self-assembled multilayers." The Journal of chemical physics 123.4 (2005): 044707.
[38] Hu, Can, and Yi Chen. "Uniformization of silica particles by theory directed rate-zonal centrifugation to build high quality photonic crystals." Chemical Engineering Journal 271 (2015): 128-134.
[39] Liu, Fu-Ken. "Using Size-Exclusion Chromatography to Monitor Variations in the Sizes of Microwave-Irradiated Gold Nanoparticles." ISRN Chromatography2012 (2012).
[40] Wang, Yunqing, Bing Yan, and Lingxin Chen. "SERS tags: novel optical nanoprobes for bioanalysis." Chemical reviews 113.3 (2012): 1391-1428.
[41] Ichim, Christine V., and Richard A. Wells. "Generation of high-titer viral preparations by concentration using successive rounds of ultracentrifugation."Journal of translational medicine 9.1 (2011): 1-8.
[42] Brinker, C. J. "Hydrolysis and condensation of silicates: effects on structure."Journal of Non-Crystalline Solids 100.1 (1988): 31-50.
[43] Ung, Thearith, Luis M. Liz-Marzán, and Paul Mulvaney. "Controlled method for silica coating of silver colloids. Influence of coating on the rate of chemical reactions." Langmuir 14.14 (1998): 3740-3748.
[44] Iler, Ralph K. The chemistry of silica: solubility, polymerization, colloid and surface pro perties, and biochemistry. Wiley, 1979.
[45] Somasundaran, Ponisseril. Encyclopedia of surface and colloid science. Vol. 1. CRC press, 2006.
[46] Liz-Marzán, Luis M., Michael Giersig, and Paul Mulvaney. "Synthesis of nanosized gold-silica core-shell particles." Langmuir 12.18 (1996): 4329-4335.
[47] Zucolotto, Valtencir, et al. "Unusual interactions binding iron tetrasulfonated phthalocyanine and poly (allylamine hydrochloride) in layer-by-layer films." The Journal of Physical Chemistry B 107.16 (2003): 3733-3737.
[48] De Carvalho, Dhieniffer Ferreira, et al. "Surface-enhanced Raman scattering study of the redox adsorption of p-phenylenediamine on gold or copper surfaces." Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013): 108-113.
[49] Kobayashi, Yoshio, et al. "Control of shell thickness in silica-coating of Au nanoparticles and their X-ray imaging properties." Journal of colloid and interface science 358.2 (2011): 329-333.
[50] Kalimuthu, Palraj, and S. Abraham John. "Studies on ligand exchange reaction of functionalized mercaptothiadiazole compounds onto citrate capped gold nanoparticles." Materials Chemistry and Physics 122.2 (2010): 380-385.
[51] Li, Jian Feng, et al. "Shell-isolated nanoparticle-enhanced Raman spectroscopy." nature 464.7287 (2010): 392-395.
[52] Ferrari, A. C., et al. "Raman spectrum of graphene and graphene layers."Physical review letters 97.18 (2006): 187401.
[53] Schwan, J., et al. "Raman spectroscopy on amorphous carbon films." Journal of Applied Physics 80.1 (1996): 440-447.
[54] 2. Hong, Jinpyo, et al. "Origin of new broad raman d and g peaks in annealed graphene." Scientific reports 3 (2013).
[55] Product Data Sheet of Gold NanoUrchins, cytodiagnostics
[56] Hunter, Robert J. Zeta potential in colloid science: principles and applications. Vol. 2. Academic press, 2013.
[57] Rule, K. L.; Vikesland, P. J. Environ. Sci. Technol. 2009, 43,1147.
[58] Tay, L. L.; Huang, P. J.; Tanha, J.; Ryan, S.; Wu, X.; Hulse, J.;Chau, L. K. Chem. Commun. 2012, 48, 1024.
[59] Kneipp, J.; Kneipp, H.; Wittig, B.; Kneipp, K. J. Phys. Chem. C 2010, 114, 7421.
[60] Chuang, Chi‐Hung, and Yit‐Tsong Chen. "Raman scattering of L‐tryptophan enhanced by surface plasmon of silver nanoparticles: vibrational assignment and structural determination." Journal of Raman Spectroscopy 40.2 (2009): 150-156.
[61] 王翠蓮(2004),表面增強拉曼光譜技術應用於單分子偵測及生物分子定量分析,國立陽明大學醫學工程研究所碩士論文。
[62] 張哲瑋(2010),光催化法製備金奈米粒子的研究,私立東海大學化學研究所碩士論文。
[63] 江宇涵(2010),奈米粒子應用於癌細胞標定的拉曼光學量測,國立交通大學分子科學研究所碩士論文。
[64] 徐榮忠(2008),具奈米結構之電漿子生物感測器,國立成功大學工程科學研究所碩士論文。
[65] 許異凡(2010),奈米金屬球與球殼結構之表面電漿子特性分析研究,國立成功大學光電科學與工程研究所碩士論文。
[66] 陳雅文(2009),表面電漿子增強螢光效應之研究,國立成功大學工程科學研究所碩士論文。
[67] 李鵬霄(2010),表面電漿子應用於光譜濾波器之研究,國立成功大學光電科學與工程研究所博士論文。
[68] 曾重賓(2010),氧電漿輔助奈米球微影術之研究與應用,國立成功大學光電科學與工程研究所碩士論文。
[69] 邱品翔(2009),特殊形狀金屬奈米粒子製備技術及其光電應用,國立成功大學光電科學與工程研究所博士論文。
[70] 陳俊皓(2015),彈性與非彈性散射光譜系統的整合,國立中興大學物理學研究所碩士論文。