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    题名: 電子式基因序列偵測晶片之原型;A prototype of gene-chip based on electrical detection
    作者: 梁柏榮;Bo-Rong Liang
    贡献者: 電機工程研究所
    关键词: 改質;阻抗;導納;奈米粒子;生物晶片;biochip;modification;DNA;impedance;nanoparticle
    日期: 2004-07-07
    上传时间: 2009-09-22 11:56:21 (UTC+8)
    出版者: 國立中央大學圖書館
    摘要: 本研究的目的是研討電性偵測用於微米等級的基因晶片之檢測。使用半導體製程技術,在晶片上製作梳狀微電極,此微電極類似超大型積體電路的電容器構造,兩個電極為一組,每一組電極中間的間距為數微米,使用表面化學改質技術改質電極中間的區域,先將單股的寡核苷酸序列固定上去,之後進行雜交反應。雜交反應完成後,再將奈米金粒子與寡核苷酸分子的最頂端的端點的硫鍵結,於是奈米金粒子可當成雜交反應的標記。利用此程序可避免複雜的化學處理步驟,而且不需要奈米級製程,只需用到微米級製程就可以做到夠小的電極間距,達到有效偵測。 傳統的 DNA 雜交偵測方法有一些缺點,如螢光標記的信號會隨時間衰減,放射線標記傷害人體,而且偵測這些信號必須使用昂貴的偵測裝置。本研究使用直流電與交流電量測微電極,發現雜交反應的發生 ( 奈米金粒子鍵結 ) 會使量測到的信號與沒有雜交反應的信號有差異,進而利用這些信號達到檢測的目標,便可避開傳統的偵測法的缺點。實驗成功後研製一組簡單的量測電路,在量測時不必使用昂貴的儀器,可降低成本,還可以大量偵測且偵測自動化。 雜交反應的偵測是基因晶片的重點技術,本研究的偵測技術可應用在基因晶片的基因表達、篩檢、及比對等研究,也可以應用在病原體基因檢測、基因表現比較、基因突變分析、基因序列分析等領域。 In this research, we make comb-shape electrodes using semiconductor process. One pair of electrodes is two electrodes, and the distance between them is several micro-meter. Electrodes are like capacitance structure of VLSI. The surface was treated by surface chemical modification and was immobilized with single strand oligonuceotide, then carry out hybridization. After the hybridization, the top-end of DNA was bond with gold nanoparticle. The silver-enhancer and gold muiltilayer deposition can be avoided if the process was used. Furthermore, the good detection was discovered and only use of UV exposure without E-beam lithography. There are some disadvantages of tradition detection methods, for example, fluorescence signal decay with time, and human body was hurt by radioactive labeling. The research avoid disadvantages of traditional detection methods, the detection was implemented by DC measurement and AC measurement on micro-electrodes. After the binding of gold nanoparticle, the change of admittance value was discovered. The detection of hybridization can be represented by the admittance value. Hybridization detection is the key technique of gene chip, the detection method of the research can be applied on gene expression, and quantification of expressed genes, differentistion of expression genes, mutations, identification of sequence, evaluation of specific DNA-binding proteins or molecules.
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