研究生: |
陳苡瑋 Chen, Yi-Wei. |
---|---|
論文名稱: |
在高離子濃度下進行DNA感測之CMOS 8 x 8離子感測電晶體陣列 CMOS 8 x 8 ion-sensitive field-effect transistors for DNA detection under high ionic strength |
指導教授: |
盧向成
Lu, Shiang-Cheng |
口試委員: |
邱一
Chiu, Yi 劉承賢 Liu, Cheng-Hsien |
學位類別: |
碩士 Master |
系所名稱: |
電機資訊學院 - 電子工程研究所 Institute of Electronics Engineering |
論文出版年: | 2020 |
畢業學年度: | 109 |
語文別: | 中文 |
論文頁數: | 113 |
中文關鍵詞: | 離子感測場效電晶體 、pH值 、DNA 、Debye length效應 、電雙層效應 、高頻 |
外文關鍵詞: | ion-sensitive field-effect transistor (ISFET), pH, DNA, Debye length effect, double layer effect, high frequency |
相關次數: | 點閱:4 下載:0 |
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在現今半導體產業的發展,電路設計已經是非常成熟,使得跨領域的研究開始興起。生醫感測晶片,也就是將電路與微機電系統整合,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,以利於進行多方面的研究及產出。
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。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, ISFET分為兩種設計,一種是大的感測電極(900μm2),另一種是小的感測電極(225μm2)。電路上使ISFET操作在不同的頻率,改變頻率來進行Debye length 效應的探討。
陣列式8×8感測器在pH值的感測,兩種ISFET設計分別得到41.2 mV/pH及37.9mV/pH的感測度。由於DNA帶負電荷,因此當target DNA與表面的probe DNA進行雜交反應後,ISFET 的電流會上升,得到的實驗結果為輸出電壓變化呈現上升的趨勢,且高頻操作中(10MHz以上)在1X PBS的緩衝溶液下量測,能感測到低濃度的target DNA (pM等級)。另外,在DNA濃度為10-11 M時,量測到DNA的反應時間約為450秒。
Nowadays, the development of the semiconductor industry, circuit design is already very mature, making cross-domain research more and more popular. Biomedical sensors, that is, the integration of circuits and MEMS into a single chip and 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 (pM level). Ion-sensing field-effect transistors are fabricated using the TSMC 0.35μm CMOS process.Surface functionalization is performed to immobilize DNA molecules on the oxide layer on top of the sensors by self-assembled monolayers. In terms of the ISFET designs, large sensing electrode(900m2) and small sensing electrode(225m2) are implemented.
We have designed circuits with different operating frequencies in the aim to study the Debye length effect.
8×8 ISFET array demonstrated pH sensitivity of 41.2 mV/pH, 37.9 mV/pH , respectively. Since the DNA is negatively charged, the ISFET current increases when the target DNA hybridizes with the surface probe DNA. The experimental results show that the output voltage change increases upon hybridization. The high-frequency operation (above 10MHz) is able to achieve detection of low DNA concentration (pM level) upon hybridization in buffer solution with high ionic strength. Additionally , the measured DNA reaction time is about 450 seconds when the DNA concentration is
10-11M.
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