焦耳熱進行矽奈米元件選擇性修飾與鏈抗生物素蛋白偵測研究

Abstract

本論文成功利用焦耳熱技術將生物素(biotin)選擇性修飾在矽奈米元件上，並利用生物素與蛋白質(streptavidin)的專一性，即時量測不同濃度蛋白質(streptavidin)；本論文首先控制矽奈米元件參雜濃度不同，製做出矽奈米元件通道中間為低濃度參雜之矽奈米元件結構；結合低濃度參雜區域電阻集中與元件通道低載子濃度區域對表面電位變化靈敏等特性，將焦耳熱技術與生醫感測連結。研究顯示在矽奈米元件上施加5微秒短脈衝電壓，利用焦耳熱將覆蓋在矽奈米元件場效電晶體低濃度參雜區域(感測區)上PMMA去除，此局部焦耳熱技術也可以用來將金薄膜退火成金奈米粒子，退火時間只要50微秒，比起一般快速退火所需時間來的短許多。此項技術成功的在線寬500奈米的奈米帶狀元件與線寬100奈米元件進行，並觀察研究奈米元件表面溫度分布情形，本實驗更進一步利用COMSOL多重物理偶合模擬矽奈米線場效電晶體在低濃度參雜區域經由焦耳熱表面升溫至780K，與PMMA被燒除所需條件符合(>400℃)。利用矽奈米線上被燒除之PMMA區域修飾APTES後，進行選擇性修飾biotin分子做為即時偵測streptavidin，經由焦耳熱選擇性修飾之矽奈米線場效電晶體，成功增加偵測低濃度streptavidin時的靈敏度，並將streptavidin偵測極限推至150 fM。

In this research, we report the experimental results of selective modification of biotin on silicon nanodevices for streptavidin real-time detection. First, we used localized Joule heating to ablate poly(methyl methacrylate) (PMMA) and generate a template at the lightly doped region (sensing region) on silicon nanodevice channel. The rapid and self-aligned ablation of PMMA via a single electrical pulse (ca. 5 µs) can be achieved. This localized Joule heating was also demonstrated to anneal gold film and converted it into gold nanoparticles in 50µs. On the other hand, COMSOL simulations showed that a temperature larger than 780 K can be generated at the lightly doped region, which was confirmed by the experimental results that the temperature is larger than 400 ℃ for the ablation of PMMA. Finally, we immobilized APTES selectively within the template and followed by selective modification of biotin for the detection of streptavidin. The selective modification on sensing area of silicon nanodevice increases sensitivity in low-level concentration of streptavidin and pushes the detection limit down to 150 fM.