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研究生:戴澤宇
研究生(外文):Tai, Tse-Yu
論文名稱:以適體功能化之氮化鋁鎵/氮化鎵高電子遷移率電晶體生物感測器在高強度離子溶液中檢測多種心血管疾病
論文名稱(外文):Aptamer-functionalized AlGaN/GaN high electron mobility transistor biosensors for multiple cardiovascular disease biomarker detection in high ionic strength solution
指導教授:王玉麟王玉麟引用關係
指導教授(外文):Wang, Yu-Lin
口試委員:李國賓董國忠
口試委員(外文):Lee, Gwo-BinDong, Guo-Chung
口試日期:2018-07-16
學位類別:碩士
校院名稱:國立清華大學
系所名稱:奈米工程與微系統研究所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:68
中文關鍵詞:適體靈敏度高電子遷移率電晶體
外文關鍵詞:NT-proBNPTroponin IFibrinogenDebye lengthSensitivity
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心血管疾病(CVDs)是當今世界的主要死亡原因,識別和管理心血管疾病風險對於有效的病人護理至關重要,正確的風險評估策略可以為健康以及高風險的個人提供有關如何更好地管理健康的信息,這可以大大降低心血管疾病的死亡率,使用蛋白質的心臟病生物指標進行風險評估可以改善早期診斷並有助於CVDs的預防,基於半導體的電子感測器對於快速和靈敏的蛋白質檢測非常有吸引力且高電子遷移率晶體管(HEMT)的感測器已被用於各種應用,如離子,氣體和生物分子感測器,具有高靈敏度和耐惡劣的化學環境等理想特性。
本研究中分為兩個部分,第一個部分選定NT-proBNP、Troponin I、Fibrinogen這三種不同的心臟病生物指標做為檢測物,並且使用氮化鋁鎵/氮化鎵製成之高電子遷移率電晶體(AlGaN / GaN HEMT)的獨特感測方法,在高鹽濃度環境中直接檢測靶蛋白,使用目標特異性適體進行對柵電極功能化,目標蛋白被捕獲在柵電極的表面上與電晶體通道以非常小的間隙分開,通過形成雙電層(EDL)結構,溶液電容調節FET汲極電流。通過這種方式,可以實現在高離子強度介質如1X PBS和人血清中進行心臟生物指標的高靈敏度測定;第二部分同樣以電雙層結構感測其中一個目標蛋白NT-proBNP,並以透過調整柵電極與電晶體通道之間的距離方式來得到不同的靈敏度。
Cardiovascular diseases (CVDs) are the major causes of death in the world today. Identifying and managing CVDs risk is of primary importance in efficient patient care. Proper risk assessment strategies can provide information to healthy as well as high risk individuals on how to better manage their health. This can greatly reduce the mortality rate of cardiovascular disease. Using protein based cardiac biomarkers for risk assessment can improve early diagnosis and aid in prognosis of CVDs. Semiconductor based electronic sensors are very attractive for rapid and sensitive protein detection. Highly Electron Mobility Transistor (HEMT) based sensors have been used in a variety of applications such as ion, gas and biomolecule sensing and possess desirable features such as high sensitivity and resistance to harsh chemical environment.
This study is divided into two parts. The first part, three different biomarker of heart disease such as Nt-proBNP, Troponin I and Fibrinogen were selected as detection objects. A unique sensing methodology using AlGaN/GaN HEMT has been developed to directly detect target protein in high salt concentration environment. The target protein was captured on the surface of the gate electrode, which is separated from the transistor channel by a small gap, and functionalized with target specific aptamer. By forming an electrical double layer (EDL) structure, the solution capacitance modulates the FET drain current. In this way, highly sensitive determination of cardiac biomarkers in high ionic strength media such as 1X PBS and human serum can be realized. The second part also senses one of the target proteins NT-proBNP with an electric double layer structure, and obtains different sensitivities by adjusting the distance between the gate electrode and the transistor channel.
第一章 導論
1.1研究動機…………………………………………………………………………………6
1.2研究目標…………………………………………………………………………………7
第二章 文獻回顧
2.1心血管疾病(CVDs) ………………………………………………………………………8
2.2心血管疾病生物指標蛋白………………………………………………………………9
2.2.1 NT-proBNP作為CVDs生物標誌物……………………………………………9
2.2.2 Troponin I作為CVDs生物標誌物……………………………………………9
2.2.3 Fibrinogen作為CVDs生物標誌物………………………………………………9
2.3場效應電晶體生物感測器………………………………………………………………11
2.3.1 高電子遷移率電晶體……………………………………………………………11
2.4電雙層結構與德拜長度…………………………………………………………………14
2.5 適體選擇…………………………………………………………………………………16
2.6 感測器靈敏度與通道和柵極之間距……………………………………………………18
第三章 實驗步驟
3.1 高電子遷移率電晶體製程………………………………………………………………19
3.2 適體結合…………………………………………………………………………………21
3.3 量測方式…………………………………………………………………………………23
3.4 感測器陣列製作封裝……………………………………………………………………24
第四章 結果與討論
4.1 感測器機制………………………………………………………………………………26
4.2 纖維蛋白原(Fibrinogen)樣本檢測結果………………………………………………28
4.3 心肌肌鈣蛋白I(Troponin I)樣本檢測結果……………………………………………35
4.4 N端前腦利鈉肽(NT-proBNP)樣本檢測結果…………………………………………42
4.5柵極與通道的間距與靈敏度之關係……………………………………………………49
4.6 N端前腦利鈉肽(NT-proBNP)血清樣本盲測結果……………………………………58
第五章 結論………………………………………………………………………………………61
第六章 未來展望…………………………………………………………………………………62
第七章 參考文獻…………………………………………………………………………………63
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