摘要
在這個半導體產業蓬勃發展的時代，晶片設計被應用在各種層面，更陸續出現許多跨領域的結合與應用。其中，將電路設計和生醫感測結合便是一個熱門的應用，藉由將CMOS電路製程和微機電系統整合在同一片晶片上，我們可以製作出具有良好感測度的生醫感測晶片。如此一來我們可以應用到先進CMOS製程的優點，將感測單位結合電路設計做成陣列。
這些生醫感測晶片可以藉由特定的修飾步驟，用來感測微量的生物分子，比如蛋白質或DNA等。但是這些生物分子需在具有鹽分的溶液中才能保持活性，進而進行感測，而高離子濃度的檢體溶液會因離子遮蔽而產生電雙層，造成Debye Length效應，因此如何解決Debye Length效應也是此議題中需面對的問題。
本論文提出在高頻中以電容式感測器來檢測DNA分子。晶片是使用TSMC 0.18 M 1P6M CMOS製程，感測器是使用指叉式電極做為感測電容，搭配不同操作頻率的環形震盪器做為感測電路，並整合電路設計做出88的陣列進行感測。我們的設計操作於高頻，試圖藉以解決高離子濃度溶液中的Debye Length效應，以提高感測器的感測度。最後我們再利用整合的讀取電路將訊號輸出並進行分析。

關鍵字: DNA感測、電容式感測晶片、CMOS bio-MEMS、電雙層效應、高頻。

Abstract
In this era of vigorous development of the semiconductor industry, chip designs are applied at various levels, and many cross-disciplinary integration and applications have emerged one after another. Among them, the integration of readout circuits and biomedical sensors becomes popular. By integrating the CMOS circuit process and MEMS on the same chip, we can produce biomedical sensor chips with good sensitivity. In this way, we can take advantages of the advanced CMOS process to conveniently implement an integrated sensor array.
These biomedical sensor chips can be used to sense tiny amounts of biomolecules, such as proteins or DNA, through specific modification and binding steps. However, these biomolecules need to be active in a salty solution for sensing, and the sample solution with high ion concentration produces a strong charge screening effect due to the small Debye length of the electrical double layer on sensor surface. Therefore, this work aims to reduce the Debye screening effect when detecting biomolecules under high ionic strength.
To reduce charge screening, this study proposes the use of capacitive sensors to detect DNA molecules at high frequencies. The chips are fabricated using TSMC 0.18 M CMOS 1P6M process. The sensors consist of the interdigitated electrodes as the sensing capacitor and the ring oscillators operating at different frequencies as the readout circuits. An 88 sensor array has been developed. The high-frequency modulation is effective to reduce charge screening so as to improve the sensitivity of the sensor.
Keywords: DNA measurement, capacitive sensors, CMOS bio-MEMS, Debye length effect, high frequency.

摘要...I
Abstract...II
致謝...III
目錄...IV
圖目錄...VI
表目錄...IX
第一章 緒論...1
1-1前言...1
1-2文獻回顧...3
1-3研究動機...6
第二章 設計與模擬...9
2-1 指叉式電容設計...9
2-1-1 指叉電極感測機制...9
2-1-2高頻下的溶液感測模型...10
2-1-3指叉式電容設計與模擬...12
2-2 電路架構及模擬...15
2-2-1 整體電路架構...15
2-2-2 電路模擬結果...24
第三章 生醫實驗介紹...31
3-1 帶測生物分子介紹 – DNA...31
3-2 DNA表面修飾鍵結流程...32
第四章 量測結果與分析...36
4-1 量測設備介紹...36
4-2 晶片架構和PCB板封裝...39
4-3量測結果...41
4-3-1 PBS緩衝液中的穩定度量測...41
4-3-2 pH值緩衝液中的訊號量測...43
4-3-3不同濃度PBS緩衝液中的訊號量測...51
4-3-4 DNA分子感測實驗的訊號量測...55
第五章 結論與未來工作...68
參考文獻...69
附錄...75

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