過去，在醫生治療腫瘤的手段中，一直以來都是以切除手術為主，而除了依靠外科醫師的肉眼判斷腫瘤區域外，常使用外源的訊號分子來進行腫瘤區域的識別，輔助手術中的來源多為螢光分子例如5-ALA，螢光分子具有極高的亮度，但是受到光照容易造成光漂白(Photobleaching)，使得螢光失去發光能力，產生觀測上的困難，另一個缺點在於生物體本身有許多也會有螢光訊號產生的物質，因此在接收螢光訊號時，容易因為接收到背景的假陽性訊號導致對比下降無法準確的觀察患部。
為解決這個問題，本實驗室已開發的拉曼標記以核心-衛星金粒子叢集結構為基底，其位於內部間隙處會產生熱點效應，透過表面增強拉曼散射技術(Surface Enhance Raman Scattering, SERS)將Cyanine5(Cy5)螢光分子的拉曼訊號有效增強約108倍，在叢集結構外部包覆二氧化矽保護殼並在表面修飾對Epidermal growth factor receptor (EGFR)有專一性的抗體透過抗體與抗原的專一性連結，將叢集結構定位於Glioblastoma (GBM)癌細胞上，之後粒子利用633 nm雷射照射核衛星結構透過表面電漿共振增強吸收光能後轉換的熱能，執行定位在GBM細胞上的光熱治療實驗[1]。
如果將治療層級移到組織的光熱治療，此時就要考慮組織間物質的吸收、散射，以光熱治療實驗使用的雷射波段為例，633 nm的雷射其穿透深度就有限，而生物體在650-1350 nm這個波段對光具有較高的穿透率，稱為生物的組織光學窗口(tissue optical window)利用近紅外光波長的光源，透過生物的組織光學窗口我們可以將光源入射到較深層的人體組織，之後藉由非線性光學的倍頻轉換過程讓核心-衛星金粒子叢集結構產生二倍頻(Second-harmonic generation, SHG)、三倍頻(Third-harmonic generation, THG)的訊號，最後利用表面增強技術將所獲得的非線性訊號增強，達到在較深層組織的光學影像檢測。
本論文主要貢獻為整合本實驗室製作的核心-衛星金粒子叢集結構目前已知的光學訊號，並解釋非線性訊號其產生的機制以及相關的原理，之後透過定性與定量的分析，驗證核心-衛星金粒子叢集結構作為一個多功能的光學標記的潛力。
最後，希望透過本研究，能夠提供一個實現多重光學標記的可能性，提高癌症切除手術的準確性。

In the past, resection is always the main method in the treatment of tumors. In addition to identify tumor cell by the eyes, doctors usually use extrinsic source, likes fluorescent material or chromophore.
However, photobleaching is a serious problem in almost every fluorescent material. Another problem is hard to detect in human body which also offers some fluorescent background.
To solve this problem, a robust and brilliant Raman tag called core-satellite-assemblies (CSA) which could enhance the Raman signal of Cyanine5 to 108 times at the 1-2 nm intra-nanogap hot spot theoretically is presented in our previous works.
And we also use CSA to perform a photothermal therapy at cell level. But, if we want to operate at tissue, we need to solve the high optical absorption in the tissue.
In the range about 650-1350 nm, called tissue optical window, the optical absorption become relatively low. So, this is a good idea about optical harmonic generation effect. If we use second harmonic generation technique, we could convert wavelength from 1280 nm to 640 nm to avoid the high absorption at fundamental wavelength in human tissue.
In this work, we want verify CSA which show several optical properties likes SHG, THG and Raman scattering could be a multi-function optical tag theoretically and experimentally.

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