矽奈米電子元件於生醫感測研究

Abstract

本計畫擬建立一即時、靈敏與準確的癌症早期快篩系統。奈米線場效應電晶體雖具有高 靈敏度、即時偵測、多樣性標記分子量測、可攜式等多項優點。但由於奈米線偵測時其 元件通道(device active channel)裸露於檢體之中，非常容易受檢體中帶電物質干擾，而奈 米線表面未充分遮蔽或修飾的部分也極易與檢體中的物質作用或受其干擾，造成電性擾 動，降低極低濃度應用的偵測靈敏度(Sensitivity)與準確性(Selectivity)。本計畫第一年將 運用標準半導體製程，開發延伸式環繞閘極矽奈米線電晶體，元件結構是將奈米線的偵 測閘極外移，形成延伸閘極結構(extended gate, EG)，使檢體與奈米線元件通道分開，降 低analye 的直接干擾。另外延伸閘極以環繞式(Gate-all-around)閘極包覆奈米線，使奈米 線通道四周均受閘極電位改變的影響，以提升其靈敏度。元件完成後以Biotin-Steptavidin 先驗證偵測之可行，之後再分別檢測攝護腺特異抗原(Prostate Specific Antigen, PSA)與 攝護腺酸性磷酸灯(Prostatic acid phosphatase, PAP)兩個癌症標誌分子，驗證元件之工作 特性。本計畫第二年將研製延伸式環繞閘極矽奈米線二極體，主要因是二極體電流對表 面電位的改變呈指數放大關係；奈米線二極體除了本身具有奈米線的優點外，因蕭特基 能障的調變，使得生醫檢測目標因固定或吸覆於元件延伸閘極表面時，電性有更明顯的 變化。另外、計畫第二年也將設計交流電滲流(AC ElectroOsmosis, ACEO)電極，並製作 於延伸閘極附近，用以集中並擾動待測溶液中之生物標記，在極低濃度偵測時提升target molecules 與延伸閘極表面probe molecules 之碰撞與作用，降低偵測濃度極限與偵測所 需的時間。根據目前臨床研究資料顯示，單一癌症標記分子檢測對相關疾病檢出的準確 度相當有限，本研究第三年中將整合前兩年研究結果，建立並驗證多工早期癌症快篩系 統，即時偵測攝護腺特異抗原(Prostate Specific Antigen, PSA)與攝護腺酸性磷酸灯 (Prostatic acid phosphatase, PAP)兩個癌症標誌分子，達成即時且同時分析multiple 癌症 標記分子偵測的目的。

The early diagnosis of cancer is crucial for patient survival and prognosis; therefore, a real-time, highly sensitive and specific biosensor system is required for early cancer diagnosis. In spite that silicon nanowire (SiNW) FETs own many properties in biomedical sensing applications, interferences from the unblocked surface of SiNWs and exposure of device active channel in the analyte undermine its deploy in very low concentration detection. In the first year of this proposal, a gate-all-around (GAA) SiNW-FET with an extended-gate structure is proposed for biosensing. Due to the sensing area is replaced by the extended gate in stead of the active channel of SiNW, the interferences is expected to be reduced. Also, in the proposed device, the SiNW is surrounded by gate so that field-effect resulted from binding on the surface of extended gate is expected to be significant compared to its SiNW counterpart. In the second year of this study, a nanowire Schottky diode with an extended gate will be investigated. The active channel now is replaced by a metal/Si Schottky barrier such that the change of surface potential, resulted from biding of specific bindings on the extended gate, will be amplified exponentially. Two prostatic cancer markers prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) will be investigated respectively on these nanowire devices in the first two years. To increase the binding efficiency and probability of collision between probes (antibody) and target molecules, AC ElectroOsmosis (ACEO) electrodes will also be fabricated near the extended gate for very low-concentration detection application. In the third year, array of GAA SiNW FETs with extended gate and array of nanowire diodes with extended gate with be investigated for simultaneous detection of PSA and PAP with a home-made multi-channel data acquisition system for prostate cancer in control buffer environment.