在現今半導體產業的發展，積體電路設計與矽晶片製造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。可高感測度的生醫感測晶片就是其中之一，藉由不同的表面修飾方法，可以感測極微量的生物分子(蛋白質、DNA)，以利於進行多方面定性及定量研究。
然而，這些生物分子須保存在含有鹽分的環境中，而高離子強度檢體會因離子遮蔽形成電雙層效應，造成電場只能穿透距離感測電極數個Debye length的距離(~nm)。因此，若欲量測此生物分子的訊號，須提高電場於高離子環境下量測的感測度。
本論文提出使用以高頻訊號的方式，使離子無法形成電雙層聚集於表面，進而提高感測器的感測度。晶片使用TSMC 0.35μm 2P4M CMOS製程，設計不同間距、大小的指叉電容，並以頻譜分析儀，即時分析並偵測B型肝炎病毒DNA分子於高離子強度下隨著頻率的變化，並建立相關於液體量測的電路模型。
最後整合讀取電路，並搭配使用SR445A訊號放大器，用以驅動頻譜分析儀。在不同的離子強度下可以觀測到明顯的增益與相位隨著頻率的變化。由於DNA在溶液中帶負電，因此當target DNA與表面probe DNA進行雜交反應後，將會改變晶片表面的電容值以及介電常數，進而改變其頻率響應。吾人等可藉由此結果量化等效的阻抗及電路模型。

Nowadays, both IC design and semiconductor manufacturing have become mature industries, leading to a research trend toward integrating sensors and IC onto a single silicon chip. Highly sensitive CMOS bio-sensors are great examples of this trend. By modifying different kinds of proteins or ssDNA on detector, we can detect certain proteins or sequences of DNA, and quantify their concentration down to fM level. These proteins and DNA should be kept in buffer solutions in order to prevent bio-molecules from denaturing. However, these ions in buffer solutions can form a double layer in the process of sensing bio-molecules, and the local electric field can only penetrate a few Debye length distance (~nm) thorough the solution. If we want to get a better S/N ratio, we must enhance out sensitivity in such salty condition.
In this work, we developed a solution to solve this problem by measuring these bio-molecules in relatively high frequency. Using this method, ions cannot form double layer on our detector in such short time, this enhanced our sensitivity and S/N ratio. The fabricated bio-MEMs chips were layout by full-custom design flow using TSMC 0.35 2P4M technology. In order to detect small amount of HBV-DNA, various types of interdigitated capacitor with different gap sizes and capacitances were fabricated and analyzed by spectrum analyzer,
Finally, integrated with read-out circuit and SR445A (amplifier, aim to drive spectrum analyzer), our impedance sensor can output frequency response up to 100MHz. With DNA negatively charged, when target DNA hybridized with probe DNA on the surface, we can indirectly build up equivalent circuits and directly quantify the impedance change induced by DNA hybridization.

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