新穎背向閘極奈米帶場效電晶體結合自組裝單分子層於即時偵測肝癌生物標記感測器之應用與探討

Abstract

場效電晶體元件與生物分子偵測的連結應用在未來的疾病診斷與防治是個重要且具發展淺力的新興科技。在此篇論文中，我們選擇血液酸鹼值，B型肝炎病毒X 基因的去氧核醣核酸(DNA)片段序列與甲型胎兒蛋白(alpha feto-protein)抗原來當作偵測肝炎，肝硬化，與肝腫瘤的指標。我們以奈米米帶場效電晶體(nanobelt field effect transsitor)為元件基礎的裝置，做為即時偵測、不需外加標定、高靈敏度以及高特異性結合的生物感測器，可偵測的生物分子或是化學物種包括有低濃度化學成分離子、小分子、抗原抗體反應、去氧核醣核酸片段與檢測蛋白質。在我們的研究裡，使用了互補式金氧半場效電晶體的技術來製作新穎背向閘極奈米帶場效電晶體生物感測器。利用矽的局部氧化製程(LOCOS)來製作內縮線寬的奈米帶，而此奈米帶可以達到優異的高比表面積比以及獲得背向閘極控制，此兩項主要特色對於目前感測元件整合於微流道組件上有極大優勢及應用面潛力。我們量測血液酸鹼值、B型肝炎病毒X 基因的去氧核醣核酸片段序列以及癌症指標物甲型胎兒蛋白抗原對於場效奈米帶元件的電性變化影響，另外還利用了原子力顯微鏡、螢光顯微鏡以及電子顯微鏡量測儀確認表面自組裝固定化的技術以及生物分子實驗條件的確立。 最後總結出我們利用矽的局部氧化製程製作出的奈米帶通道可使其線寬內縮到150奈米以下的線寬，此條件提供元件電性達到優異的105倍的開關電流比。利用此靈敏度高的元件我們可以偵測到接近濃度1fM的標的突變DNA以及濃度為3ng/mL(? 最靈敏應可作到很低)的癌症標誌物抗原分子。結果顯示此新穎的背向閘極奈米線感測元件可以用作未來的免標定、即時偵測、高靈敏度以及優異專一性結合的場效奈米帶電晶體生物感測器。另外，此元件具有控制背向閘極的能力更提供了未來感測元件與微流道技術整合上的一大優勢。

The application of high-sensitive field-effect transistor devices in detecting the bio-molecules is an important and developing thchnology. The development of biological sensors could impact significantly the areas of genomics, proteomics, biomedical di-agnostics, and drug discovery in the future. In our thesis, the serum pH value, HBV X gene DNA fragments, and α-fetoprotein cancer marker were chosen as the target molecules to detect the hepatocellular carcinoma. The devices based on semiconducter nanobelt exhibited highly sensitive and selective characteristics for the real-time, label-free, and excellent specificity detection of biomolecules and chemical species. A novel back-gate silicon nanobelt field effect transistor (SiNB-FET) was fabricated by using the complementary metal oxide semiconductor (CMOS) compatible technology. The shrank nanobelt with high surface-to-volume ratio and individual back-gate were achieved by the local-oxidation of silicon (LOCOS) process. Because of the above advantages, the devices have potential to integrate with microfluidic system for bio-detection application. Therefore, the detection of hepatocellular carcinoma was investigated by measuring the characteristics of electrical signals. The atomic force microscopy (AFM)、fluorescence microscopy and scanning electron microscopy (SEM) were also examined to check out the self-assembly efficiency and appropriate experimental parameter for bio-sensing. In conclusion, the width of nanobelt by LOCOS process can be shrank down to 150 nm. The drain current versus gate voltage (Id-Vg) characteristic of the SiNB-FET exhibited about five orders of magnitude of Ion/Ioff current ratio, and the threshold voltage shifts positively after hybridization of 1fM concentrations of HBV X gene DNA fragments and 3ng/mL concentrations of the cancer marker, antigen-α-AFP, respectively. The results show that the back-gated nanobelt device has the capability of acting as a real-time, label-free, highly sensitivity and excellent selectivity SiNB-FET biosensor in detecting biomolecules. Our approach offers the possibility of highly potential to integrate microfluidic-channel system for future parallel real-time detection of multiple chemical and biological species with controlling the individual back-gate in a single integrated chip.