離子敏感場效電晶體陣列應用於DNA偵測

A CMOS-Based ISFET Array for DNA Detection

孫于涵(Yu-Han Sun)

指導教授 ： 林致廷

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201601190

摘要

生物分子感測分析為現今臨床診斷步驟中重要的一環,即對人體中特定的生 物分子含量進行偵測,作為生物標記。許多 DNA 片段為各種遺傳性疾病、傳染 性疾病及癌症之生物標記,而隨著個人化醫療及重點照護檢驗系統之演進,高靈 敏度與流程簡化成為生物分子感測分析技術著重發展之目標。利用以 CMOS 為 基底之離子敏感場效電晶體,整合傳統上需經數量放大後再取之量測的兩段式 DNA 偵測技術,應能滿足簡化與高靈敏之目標,未來搭配其他微機電相關技術, 可望發展成可攜式之實驗室晶片。
本論文以台積電 0.18 微米 SOI-CMOS 標準製程製作之離子敏感場效電晶體 作為生物感測器,進行其穩定度與偵測 DNA 放大之測試,並研究其對特定 DNA 的感測效能。由實驗結果得知,該感測器在各式環境條件下皆具有高穩定 度,且能成功以電性偵測 DNA 放大的表現。而在量測方面,先執行固定化之優 化,以較佳流程進行感測器表面的固定化,再用來感測 B 型肝炎病毒 DNA。根 據研究結果,我們得知陣列感測器以取得整體平均表現的方式,相較於單一感測 器大幅降低固定化後表面不均所造成的電性差異,將能有效偵測特定 DNA 之含 量及區分不同種類之 DNA。

關鍵字

生物分子感測 ； 生物標記 ； 離子敏感場效電晶體

並列摘要

Biomolecular sensing and analysis play a pivotal role in modern clinical diagnosis. That is to detect the quantity of specific biomolecules, as biomarkers, in human body. Many DNA sequences are the biomarkers of various hereditary diseases, infectious diseases, and cancer. With the progress of personal health care and point-of- care testing system, high sensitivity and simplified procedure have become the focused development goals. Take the advantage of CMOS-based ion-sensitive field-effect transistor (ISFET), the goals shall be satisfied by integrating the conventional two- stage DNA detection technique, which requires amplification before sensing. Combining with other MEMS technology, it is expected to become a portable lab-on-a- chip in the near future.
In this thesis, we apply ISFETs, fabricated by standard TSMC 0.18μm silicon- on-insulator (SOI) CMOS process, to the DNA diagnosis technologies. To test the ISFET, both stability and quantity analysis for DNA amplification are examined. The sensitivity and selectivity to specific DNA are measured as well. According to the experiment results, ISFET performs well under various conditions with high stability. It is capable of detecting the states after DNA amplifications by the electrical property. On the other hand, we improve the immobilization procedure at first hand and detect the sequence of hepatitis B virus DNA afterwards. As a result, array sensor, relative to single sensor, lowers the electrical sensing difference caused by inhomogeneous surface after immobilization.It will effectively detect the quantity of specific DNA and distinguish different kinds of DNA.

並列關鍵字

Biomolecular sensing ； biomarkers ； ISFET

參考文獻

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