生物耦聯金奈米環的製作與應用

在本論文中，我們展示高濃度金奈米環水溶液的製備方法及其應用。由於金奈米粒子具有良好的生物相容性，因此廣泛地應用於生物醫學領域，包括增強光學同調斷層掃描的影像對比、光熱治療、藥物傳遞等。常見的金奈米粒子主要經由化學合成的方式製作，這些奈米粒子的侷域表面電漿子共振波長一般位於1000奈米以內的紅外光範圍。由於波長在1300奈米的光源對生物組織擁有較大之穿透深度，因此侷域表面電漿子共振波長位於1300奈米的金奈米環較適用於較深組織的診斷與治療。在本論文中，我們首先使用奈米球微影術以及金的二次濺鍍製程，在藍寶石基板上製作金奈米環，隨後再將其轉移到水溶液內。經估計金奈米環在其共振波長的消散截面積大約為10-10-10-9 cm2。藉由控制金奈米環的幾何形狀，我們可以製作侷域表面電漿子在生物組織內共振波長為1300奈米之金奈米環。接下來，我們使金奈米環擴散入豬脂肪組織中，經由其表面電漿子共振的加強散射與吸收特性，我們可以觀察到光學同調斷層掃描影像對比明顯提升，此外，金奈米環之侷域表面電漿子共振所產生的光熱效應造成豬脂肪細胞在光學同調斷層掃描影像中因溫度上升而變為透明。接下來，為縮短金奈米環侷域表面電漿子之共振波長，我們施展兩種製程方法使金奈米環水溶液之侷域表面電漿子共振波長可短於900奈米。我們也提出將金奈米環製作在氮化矽奈米柱結構上，以便在基板上進行金奈米環生物耦聯。然後，我們展示使用奈米壓印技術以及金的二次濺鍍製程在高分子基板上製作生物耦聯之金奈米環，並轉移到水溶液。在基板上進行奈米環的生物耦聯具有許多優點，包括可以有效避免奈米環在離心過程中的損失，進而提升其產率。接下來，我們將生物耦聯之金奈米環施加在人類肝癌細胞中，在波長為1315奈米的雷射照射下，展示金奈米環的光熱治療效果。經由量測不同強度之雷射對細胞的殺傷範圍，我們可以推算出造成細胞損傷的臨界雷射強度。

關鍵字

奈米環；表面電漿子；奈米粒子；生物耦聯；光熱療法；光學同調斷層掃描

並列摘要

In this dissertation, we first demonstrate the preparation of a high-concentration Au nanoring (NRI) water solution and its applications to the enhancement of image contrast in optical coherence tomography (OCT) and the generation of photothermal effect in a bio-sample through localized surface plasmon (LSP) resonance. Au NRIs are first fabricated on a sapphire substrate with colloidal lithography and secondary sputtering of Au, and then transferred into water solution through a liftoff process. By controlling the NRI geometry, the LSP dipole resonance wavelength in tissue can cover the spectral range of 1300 nm for OCT scanning of deep tissue penetration. The extinction cross sections of the fabricated Au NRIs in water are estimated to give the levels of 10-10-10-9 cm2 near their LSP resonance wavelengths. The fabricated Au NRIs are then delivered into pig adipose samples for OCT scanning. It is observed that when resonant Au NRIs are delivered into such a sample, LSP resonance-induced Au NRI absorption results in a photothermal effect, making the opaque pig adipose cells transparent. Also, the delivered Au NRIs in the intercellular substance enhance the image contrast of OCT scanning through LSP resonance-enhanced scattering. By continuously OCT scanning a sample, both photothermal and image contrast enhancement effects are observed. However, by continually scanning a sample with a low scan frequency, only the image contrast enhancement effect is observed. We also demonstrate two fabrication methods to produce Au NRI solution with LSP resonance wavelength below 900 nm. Then, the structure of Au NRIs on SiN nanopilars are demonstrated, which can be used for on-substrate bio-conjugation of Au NRIs. Next, The on-substrate fabrication of bio-conjugated Au NRI solution with the LSP resonance wavelength in the 1200-1300 nm range is demonstrated. Also, the effects of photothermal therapy through LSP resonance-induced absorption enhancement are illustrated by applying the bio-conjugated Au NRIs to human liver cancer cells and illuminating the cells with laser of 1315 nm in wavelength. The Au NRI fabrication is based on the techniques of nano-imprint lithography and metal secondary sputtering. The procedure for on-substrate surface modification of Au NRI leads to a high production yield of bio-conjugated NRI. The threshold levels of the local laser intensity for injuring cancer cells based on the LSP resonances of Au NRIs of two different samples are determined.

並列關鍵字

nanoring ； nanoparticle ； surface ； plasmon ； bioconjugation ； photothermal ； contrast agent ； optical coherence tomography

參考文獻

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[1.11] J. Z. Zhang, J. Phys. Chem. Lett. 1, 686 (2010).

[1.15] M. E. Brezinski, G. J. Tearney, B. E. Bouma, J. A. Izatt, M. R. Hee, E. A. Swanson, J. F. Southern, and J. G. Fujimoto, Circulation 93, 1206 (1996).

國際替代計量

生物耦聯金奈米環的製作與應用

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