金奈米粒子應用於細胞標定之模擬與分析

Simulation and Analysis of Cellular Labeling with Gold Nanoparticles

蔡宏鑫(Hung-Hsin Tsai)

指導教授 ： 曾雪峰

國立臺灣大學/電機資訊學院/光電工程學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.00867

摘要

金屬表面的自由電子在適當的電磁波激發下，自由電子將會與電磁波耦合產生集體震盪的行為，此即所謂的表面電漿共振（surface plasmon resonance），其發生於金屬與介質交界面。表面電漿共振會因奈米粒子在不同形狀、大小下使金屬具有不同的光學特性。根據文獻記載，許多的癌細胞將會在細胞表面累積大量的表皮細胞生長因子接受體（epidermal growth factor receptor：EGFR），實驗上可利用抗體先與金屬奈米粒子結合，由於抗會體針對EGFR結合，且正常細胞和癌細胞的EGFR數目差異很大，故可標定細胞，而標定後的細胞在光譜或是影像上將會有很大的差異。
本論文使用時域有限差分法（finite-difference time-domain method），探討奈米粒子在細胞中造成的光學現象。本論文分析在不同金粒子大小下，奈米粒子在正常細胞與癌細胞中的光散射現象與對比度的影響；並探討使用OIT法（optical immersion technique）對於對比度的影響；與不同殼層厚度的二氧化矽/金奈米殼層粒子在細胞中所造成光散射現象的差異。金屬奈米粒子具備光學性質穩定、不會有光漂白（photobleaching）的現象，尤其是金（gold）具有對人體無毒性的優點，因此在生物細胞標定上的應用非常具有潛力。

關鍵字

時域有限差分法 ； 表面電漿共振 ； 金 ； 奈米粒子 ； 奈米殼層粒子 ； 細胞標定

並列摘要

Surface plasmon resonance (SPR) is a phenomenon of free electrons on the surface of metal coupled to the electromagnetic excitations exhibiting coherent collective oscillations. The optical properties of SPR of metal are sensitive to particle size, shape and the surrounding medium. The SPR of metal nanoparticles have special optical properties that can be applied for biomedical applications; nanoparticles can be conjugated with anti-epidermal growth factor receptor (anti-EGFR) antibodies that bind specifically to the cells due to the overexpressed EGFR on the cytoplasmic membrane of the cancerous cells. In this research, we build a simple model to describe the nanoparticles’ distribution in cancerous and normal cells. The finite-difference time-domain (FDTD) method and the Drude-CP (Drude-critical point) model are employed to simulate the nanoparticles in the biological cells. The calculation of total scattering cross-section (TSCS) spectrum and intensity contrast of nanoparticles in cancerous and normal cells, respectively, are compared. The optical immersion technique (OIT) effect of contrast is discussed. The silica/gold nanoshells in cells with different thickness of shells are also compared. Metal nanoparticles are in general optically stable, and resistive to photobleaching. In particular, gold nanoparticles are toxic-free, which makes them very suitable for human body. Therefore, metal nanoparticles have potential for labeling of biological cells and other applications.

並列關鍵字

FDTD method ； Drude-CP model ； surface plasmon resonance ； gold ； nanoparticles ； nanoshells ； cellular labeling

參考文獻

[39] 鐘煒竣, "以時域有限差分法模擬二維奈米金屬粒子之表面電漿共振現象," 光電工程學研究所(國立台灣大學, 2007).

[1] C. F. Bohren, and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

[2] C. L. Haynes, and R. P. Van Duyne, "Plasmon-sampled surface-enhanced Raman excitation spectroscopy," Journal of Physical Chemistry B 107, 7426-7433 (2003).

[3] A. Taflove, and S. C. Hagness, Computational Electrodynamics: The Finite-difference Time-Domain Method (Artech House Publishers, 2005).

[5] W. B. Sun, N. G. Loeb, and Q. Fu, "Light scattering by coated sphere immersed in absorbing medium: a comparison between the FDTD and analytic solutions," Journal of Quantitative Spectroscopy & Radiative Transfer 83, 483-492 (2004).