運用矽奈米元件陣列之生醫感測系統研發

Abstract

據衛生署的統計，『癌症』是目前國內十大死亡原因之首。若能提高癌症初期篩 檢機率，將有助其治癒的機率與生活品質！所以，初期檢測技術，於癌症的防治工 作上，便成了很重要的一環 。本計畫擬運用奈米半導體元件，建立一“簡易”、“即 時”、與“精準”的癌症初期快篩系統並與傳統ELISA 檢測交叉驗證其可行性。 當場效應電晶體通道的厚度小於德拜長度(Debye length)，元件本身即具有高靈 敏的表面電位偵測特性。本計畫第一年將運用半導體製程，於Silicon-on-Insulator (SOI)基材上，開發“超薄(5~10 奈米)通道場效應電晶體陣列”與製作訊號放大電 路，單獨驗證胎兒球蛋白(α-fetoprotein, AFP)，磷脂肌醇蛋白聚-3 (Glypican-3, GPC3) 和血管內皮生長因子(vascular endothelial growth factor, VEGF)等個別癌症標誌 (Marker)之早期診斷特性，並與傳統ELISA 方式交叉驗證比較。 本計畫第二年將研製奈米線二極體(直徑10~30 奈米)作為極靈敏感測元件；這 主要因奈米線二極體的電流-電壓特性，對表面電位的改變有指數放大效應；奈米 線二極體除了本身具有奈米線的優點外，還具有內建電位或蕭特基能障，使生醫檢 體分子固定或吸覆於元件表面時，具有更明顯的變化，因此更適合用於低濃度生物 標記的偵測。第二年將驗證奈米線二極體於胎兒球蛋白(α-fetoprotein, AFP)，磷脂 肌醇蛋白聚-3 (Glypican-3, GPC3)和血管內皮生長因子(vascular endothelial growth factor, VEGF)等個別癌症標誌(Marker)之早期診斷特性，並與傳統ELISA 方式交 叉驗證比較。 由於單一癌症標於初期檢測篩檢準確度不高，本研究於第三年將建立一套“可 攜式多工分析癌症快篩系統”，將不同抗體分別固定於奈米元件陣列晶片表面，同 時偵測胎兒球蛋白，磷脂肌醇蛋白聚-3 和血管內皮生長因子等癌症標誌，祈即時 分析與提供多種癌症標誌資訊，提高初期檢測篩檢準確度，以作為肝癌診斷篩選與 治療追蹤的依據。

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is one of the most important diseases with high lethality in Taiwan. The early diagnosis of cancer is crucial for patient survival and successful prognosis of the disease; therefore, highly sensitive and specific biosensors are urgently required. The ultra-thin-body structures will be fabricated with simple thermal oxidation and wet etching technologies. The thickness of the ultra-thin-body channel is expected to be scaled down to 10 nm or less. The UTB-FETs biosensor shows highly sensitive to the binding of charged molecules due to the channel thickness smaller than the Debye screening length. In the first year, this project focuses on fabrication and measurement of ultra-thin body filed effect transistors (UTB-FETs) biosensor on (100) silicon-on-insulator wafer. Detection of α-fetoprotein (AFP), Glypican-3, (GPC3) and vascular endothelial growth factor (VEGF) will be demonstrated respectively for the feasibility of the proposed platform. Results will be compared with those resulted from ELISA. In the second year, silicon nanowire diodes will be studied as the biosensors. The nanowire diode owns a larger sensitivity than that of nanowire-FET because of the barrier lowering, which results from the binding of charge biomolecules on the surface of device. Again, detection of AFP, GPC3 and VEGF will be demonstrated respectively for the feasibility of the proposed nanodevice. Results will be compared again with those resulted from ELISA. In the third year, a multiple markers detection platform based on the detection of AFP, GPC3 and VEGF using nanowire diode array as biosensors will be demonstrated. Results will be compared again with those resulted from ELISA.