在現今半導體產業的發展，電路設計已經是非常成熟的產業，使得跨領域的研究越發興起，而將電路與微機電系統整合於一片晶片上，可以製作出高感測度的生醫感測晶片就是其中之一，再藉由不同的表面修飾方法，可以感測不同的細胞或生物分子，以利於進行多方面研究及利用。
本論文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，而在電路設計方面，我們設計了不同的操作頻率，運用高頻操作來進行Debye length 效應探討，並且運用高頻操作下達到能夠在高離子濃度的緩衝溶液下，感測到低濃度的DNA分子。
最後整合讀出電路，量測8×8陣列式感測器，ISFET當電容使用，在pH值感測上，不同設計分別得到56.7 mV/pH、52.8 mV/pH及72.8 mV/pH的感測度。由於DNA帶負電荷，因此當target DNA與表面probe DNA進行雜交反應後，ISFET MOS電容會上升，得到的實驗結果為輸出頻率變化呈現下降趨勢，且高頻設計中在PBS 1X的緩衝溶液下量測，感測target DNA其頻率有3 %的變化。

Nowadays, the development of the semiconductor industry, circuit design is already a very mature industry, making cross-domain research more and more popular; for example, integrating circuits and MEMS into a single chip can produce high-sensitivity biomedical sensors. Different surface modification methods can be used to sense biological cells or biomolecules for various applications.
In this paper, ion-sensitive field-effect transistors (ISFETs) are used to detect hepatitis B virus DNA molecules at low concentration (fM level). We have designed circuits with different operating frequencies in the aim to study the Debye length effect. The high-frequency operation is able to achieve detection of low DNA concentration upon hybridization in buffer solution with high ionic strength.
With the ISFET operated as a MOS capacitor, an 8 × 8 ISFET array demonstrated pH sensitivity of 56.7 mV/pH, 52.8 mV/pH and 72.8 mV/pH, respectively. Since the DNA is negatively charged, the ISFET MOS capacitance increases when the target DNA hybridizes with the surface probe DNA. The experimental results show that the output frequency decreases upon hybridization. One of the designs shows a frequency shift up to 3% when tested in 1X PBS buffer.

致謝 III
摘要 IV
Abstract V
目錄 VI
圖目錄 VIII
表目錄 XIII
第1章 緒論 1
1-1 前言 1
1-2 文獻回顧 2
1-3 研究動機 5
第2章 設計與模擬 7
2-1 ISFET等效電路模型 7
2-2 電路架構 9
2-3 電路模擬 16
第3章 生醫實驗介紹 26
3-1 介紹生物分子 — DNA 26
3-2 表面修飾鍵結步驟 27
第4章 量測結果與分析 31
4-1 量測設備介紹 31
4-2 晶片結構檢視與PCB板封裝 33
4-3 量測結果 34
4-3-1 pH值標準液環境量測 34
4-3-2 PBS緩衝溶液中量測 40
4-3-3 DNA分子感測實驗 46
第5章 結論與未來工作 69
參考文獻 70
附錄 77

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