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  • 學位論文

矽奈米線場效電晶體在生化研究上的應用: 1.利用選擇性表面修飾法減低偵測所需樣品量及時間 2.結合生物脂雙層膜與矽奈米線場效電晶體作為偵測平台

Applications of silicon nanowire field-effect transistors on biochemistry study: 1. Minimizing sample volume and detection time via selective surface modification 2. Coupling supported lipid bilayer to a silicon nanowire transistor as a biosensing platform

指導教授 : 陳逸聰
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摘要


矽奈米線場效電晶體 (silicon nanowire field-effect transistor, SiNW-FET) 生物感測器,具有高靈敏度 (sensitivity)、專一選擇性 (selectivity)、即時回應 (real-time response)、及無標記偵測 (label-free detection) 等優異特性,在近年來的生醫檢測應用上,引起相當廣大的關注與期待。本論文致力於矽奈米線場效電晶體製備之改良,與發展其在生物膜蛋白研究領域上的應用。 傳統上矽奈米線場效電晶體的表面化學修飾,並非僅在矽奈米線的表面,而 是全基材表面的修飾 (all area modified, AAM)。而在本研究裡,我們成功地以“bottom-up”(由上而下) 的方法製作出具選擇性表面修飾(selective surface modification, SSM) 之矽奈米線場效電晶體。在此實驗中,首先以 3-胺丙基三甲氧基矽烷 (3-aminopropyltrimethoxysilane, APTMS) 修飾於矽奈米線的表面上,再以光刻法 (photolithography) 進行SSM SiNW-FET元件的製備。而透過一系列的實驗,我們確認了 APTMS 在經過製程技術的操作過後,依然存在並不受破壞。這種僅修飾矽奈米線感測表面之場效電晶體,仍然保持優異的電學性質 (具有歐姆接觸 (ohmic contact) 和高跨導 (high transconductance))。我們亦將 SSM SiNW-FET與傳統修飾方法製作 AAM SiNW-FET相互比較,實驗結果顯示 SSM SiNW-FET 於電訊號偵測時,具有 (1) 反應所需時間短和 (2) 所需樣品量少的優點。此實驗證明了:限制修飾區域,可以改善 SiNW-FET的靈敏度,提供一個具高靈敏度的生物感測平台。此外,我們亦致力於 SiNW-FET的表面上,鋪上生物脂雙層膜 (lipid bilayer) 以取代一般的化學修飾法。這種仿細胞膜的表面修飾,讓矽奈米線場效電晶體生物感測器,成為全新的生物膜相關研究之平台。在此實驗中,我們使用 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) 中性磷脂質分 子以微胞融合 (vesicle fusion) 的方式,於矽奈米線場效電晶體的表面鋪成生物脂雙層膜,並以螢光顯微鏡觀察脂雙層膜的覆蓋情形,以 AFM 確認脂雙層膜的 厚度,且透過一系列的電性實驗觀察脂雙層膜修飾後的性質。實驗結果顯示,矽奈米線場效電晶體的表面在形成脂雙層膜後,因其遮蔽了矽奈米線的表面,造成 電訊號強度的下降,對此我們設計出網絡式 (multiple-parallel-connection, MPC) 矽奈米線場效電晶體的系統,以增強訊號強度與偵測極限。結合脂雙層膜與 MPC的優點,我們將可在仿生物所處環境中,利用 SiNW-FET進行相關主題的研究。

並列摘要


Silicon nanowire field-effect transistors (SiNW-FETs) have drawn great attention because of their potential as a label-free, real-time, and ultra-sensitive sensor for biomolecular detections. As a biological sensor, the surface of a SiNW-FET device was conventionally all area modified (AAM) with receptors, covering not only the minute SiNW surface area but also the relatively massive surrounding substrate area. However, target molecules could be captured on the upstream substrate area before reaching the SiNW surface in sensing measurements, thus jeopardizing the detection sensitivity. In this study, we have successfully fabricated SiNW-FETs with the selective surface modification (SSM) of receptors only on the SiNW sensing surface via gas-phase premodification and a bottom-up fabrication technique. Our results show that a SSM SiNW-FET, exhibiting desirable electrical characteristics with regard to ohmic contact and high transconductance, has the merits of faster response time, less sample requirements, and much improved detection sensitivity. Besides, we integrated SiNW-FET with a lipid bilayer to mimic the cell membrane for biological research, especially for the membrane protein studies. Our results show that a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayer membrane with single or double lipid bilayers could be homogeneously formed on the SiNW-FET surface via a vesicle fusion method. However, because the shielding of the lipid bilayers on the underlying SiNW, signals were reduced in electrical measurement. To improve the signal acquisition from a lipid bilayer membrane covered SiNW-FET, we demonstrated that the electrical signals and the detection limit can be enhanced by utilizing a multiple-parallel-connection (MPC) SiNW-FET system.

參考文獻


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