運用局部焦耳熱進行矽奈米帶元件選擇性修飾於生醫檢測偵測靈敏度研究

Abstract

本篇論文利用矽奈米帶元件進行聚乙二醇矽烷 (mPEG-sil)的選擇性修飾，進而提升檢測速率及檢測極限。聚乙二醇矽烷主要被應用於減少蛋白質的非專一性吸附。選擇性修飾是利用在矽奈米帶元件本身的局部焦耳加熱移除在矽奈米帶上的聚乙二醇矽烷來達成。矽奈米帶元件則是利用傳統半導體製程技術製造，總共有兩種矽奈米帶元件被應用於此研究，一種是電阻式(RNBD)，另一種是電晶體式(TNBD)。局部焦耳加熱是利用在矽奈米帶元件中製造出一個局部高電阻區來實現，而局部高電阻區則是靠離子佈值來定義。電阻式元件的高電阻區的產生是靠參雜劑量的高低來達成(n+/n-/n+)；而電晶體式元件則是靠不同類型的參雜來達成(n+/p-/n+)。電阻式和電晶體式元件的熱分布行為則由COMSOL和TCAD軟體來分析。模擬結果顯示兩種元件都呈現出局部加熱的現象，而讓電阻式和電晶體式元件達到移除自組裝單分子層的最低溫度，分別需要施加40伏和15伏的脈衝電壓。原子力顯微鏡被用來檢查聚乙二醇矽烷的移除狀況，結果顯示在電阻式元件中的焦耳加熱是均勻分布在高電阻區；由於衝擊游離效應(Impact ionization effect)造成在電晶體式元件中的焦耳加熱是不均勻分布的且集中在汲極端。此外，我們也在真空和大氣的環境下檢視局部焦耳加熱的行為，在真空中進行加熱可以移除更大範圍的聚乙二醇矽烷。為了瞭解選擇性修飾和聚乙二醇矽烷抵擋非專一性蛋白質的狀況，我們將進行局部焦耳加熱後的移除區經過胺丙基三甲氧矽烷 (APTMS)，N-羥基琥珀酰亞胺生物素酯 (NHS-biotin)，和螢光標記的卵白素(dye-labeled streptavidin)修飾後進行螢光偵測。結果顯示只有在移除區內才會出現螢光訊號且訊號，出現的位置也和原子力顯微鏡的調查的結果對應；而在移除區外的螢光訊號則是非常微弱。曠時螢光偵測(time-lapse fluorescence detection)和即時檢測方式(real-time detection)則分別被利用在電阻式和電晶體式元件針對偵測速率和偵測極限提升的驗證。結果顯示，經過選擇性修飾的元件不論是在曠時螢光偵測和即時量測方式中都具有較快的偵測速率(兩倍快)和較低的偵測極限(低一個數量級)。由此可知，我們提出的方法具有相當優異的選擇性修飾效果且針對未來的生醫領域的應用具有極高的發展潛力。

In this dissertation, a self-assembled monolayer (SAM) of methoxy poly (ethylene glycol) silane (mPEG-sil) was selectively modified on the surface of nanobelt devices (NBDs) to act as a passivation layer that inhibits non-specific binding of proteins, thus increasing the sensing rate and improving the limit of detection (LOD). The template for selective modification was achieved by localized Joule heating of NBDs, with the mPEG-sil on localized heating region being ablated. Two different characteristic NBDs, resistor-type (RNBD) and transistor-type (TNBD), were fabricated by a CMOS-compatible process. Localized Joule heating was achieved by producing a local high resistance in NBDs through an implantation process. The RNBD is designed as n+/n-/n+ structure, whereas the TNBD is designed as n+/p-/n+. The thermal distribution was simulated prior to experiments using COMSOL and TCAD for RNBD and TNBD, respectively. The results show that both NBDs exhibited localized heating phenomena in our design, and can reach the minimum temperature for removing SAM (673 K) by 40-V and 15-V pulse voltages in the RNBD and TNBD, respectively. AFM was used to investigate the removal of mPEG-sil, with the results demonstrating that the localized Joule heating is uniform in the n- region in RNBD and non-uniform in the p- region for TNBD due to the impact ionization mechanism. In addition, localized Joule heating was examined in both vacuum and ambient, and indicated that the removal region was longer in vacuum for the same pulse bias. The 3-aminopropyltrimethoxysilane (APTMS), NHS-biotin and dye-labeled streptavidin which were deposited selectively in the removal regions were characterized by fluorescence detection to substantiate the selective modification and the resistivity of mPEG-sil to the non-specific binding. The results showed that fluorescence is only apparent in the removal regions, which is consistent to the surface analysis via AFM. Moreover, the enhancements of sensing rate and LOD were demonstrated by time-lapse fluorescence detection of dye-labeled streptavidin for RNBD and real-time detection of streptavidin for TNBD. Both the results of time-lapse fluorescence detection and real-time detection showed the same trend, that of NBDs with selective modification exhibiting a higher sensing rate (>2x enhancement) and lower LOD (1-order improvement) when compared with NBDs with non-selective modification.