在醫學治療中，如何快速且精準地檢測出患者所得到的疾病是一個十分重要的課題。
根據統計，有三分之一的人口曾經被B型肝炎病毒傳染，其中全世界肝炎患病率最高的地區在台灣。如果能夠有一種快速與簡易的方式來檢測出血清中較低濃度的B型肝炎病毒載量的話，它有助於B型肝炎病毒感染的早期診斷和預防進一步傳播。
本研究提出以離子感測場效電晶體(ion-sensitive field-effect transistor)來進行低濃度(fM等級)下即時檢測B型肝炎病毒DNA分子，離子感測場效電晶體是使用TSMC 0.35μm CMOS製程來製作，之後藉由自組單層膜固定法將表面官能基與DNA分子修飾在感測器上的絕緣層；在電路設計方面，我們設計不同尺寸的ISFET搭配指叉式電極與平版式電極，來進行感測器特性的探討，其中最好的設計之感測度為32mV/pH。
最後整合讀出電路，用於同時量測多個感測器，且將ISFET電流轉成數位輸出訊號，由於DNA帶負電荷，因此當target DNA與表面probe DNA進行雜和反應後，得到的實驗結果為輸出頻率變化呈現上升趨勢。

How to detect the disease of a patient is a very important issue in medical treatment.
According to statistics, one third of people has been infected with hepatitis B virus, and the region of the highest hepatitis prevalence in the world occurs in Taiwan. If there is a rapid and simple method to detect a lower concentration of hepatitis B viral load in serum, it facilitates early diagnosis of hepatitis B virus infection and prevention of further transmission.
Ion-sensitive field-effect transistors are presented in this case to get a real-time detection of a lower concentration DNA molecules (fM level). Ion-sensing field-effect transistors are fabricated using TSMC 0.35μm CMOS process. And then surface functionalization and DNA molecules are modified on the passivation of sensors by Self-assembled monolayers. In terms of circuit design, we design different sizes of ISFETs with interdigitated electrodes or planar electrodes to explore the characteristics of the sensors. The best sensitivity of the designs in this case is 32mV/pH.
In the end, this scheme can be combined with the readout circuit for the measurement of several sensors and convert the ISFET current to a digital output signal. Due to DNA molecules have the negatively electrical property, the output frequency will be increased when target DNAs hybridize with probe DNAs.

摘要 I
Abstract II
目錄 III
圖目錄 V
表目錄 IX
第1章 緒論 1
1-1 研究動機 1
1-2 文獻回顧 4
第2章 電路設計與模擬 7
2-1 ISFET設計 7
2-2 感測電路設計 10
2-2-1 電路架構 10
2-2-2 放大器 11
2-2-3 電壓緩衝器 12
2-2-4 比較器 13
2-2-5 解碼器與多工器 14
2-3 電路模擬 16
第3章 生醫實驗介紹 21
3-1 介紹生物分子 — DNA 21
3-2 表面修飾步驟 22
3-3 液態環境中電容效應 24
第4章 量測結果與分析 25
4-1 量測設備介紹 25
4-2 晶片結構檢視與PCB板封裝 27
4-3 量測結果 29
4-3-1 pH值標準液環境量測 29
4-3-2 DNA分子感測實驗 38
第5章 結論與未來工作 47
參考文獻 48
附錄 52

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