博碩士論文 91521072 詳細資訊




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姓名 梁柏榮(Bo-Rong Liang)  查詢紙本館藏   畢業系所 電機工程學系
論文名稱 電子式基因序列偵測晶片之原型
(A prototype of gene-chip based on electrical detection)
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摘要(中) 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。
摘要(英) 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.
關鍵字(中) ★ 改質
★ 阻抗
★ 導納
★ 奈米粒子
★ 生物晶片
關鍵字(英) ★ biochip
★ modification
★ DNA
★ impedance
★ nanoparticle
論文目次 論文摘要------------------------------------------------------------------I
Abstract-------------------------------------------------------------------II
目錄----------------------------------------------------------------------III
圖目錄--------------------------------------------------------------------V
表目錄-------------------------------------------------------------------IX
第一章 緒論--------------------------------------------------------1
1.1 前言----------------------------------------------------------------1
1.2 動機和目標-------------------------------------------------------4
1.3 文獻回顧----------------------------------------------------------5
1.3.1 國內外有關本研究之研究情況-------------------------5
1.3.2 參考文獻探討---------------------------------------------6
1.4 論文架構----------------------------------------------------------8
第二章 研究方法與原理----------------------------------------10
2.1 DNA 分子簡介-------------------------------------------------10
2.2 基因晶片的檢測原理------------------------------------------17
2.3 基因晶片的檢測流程------------------------------------------27
第三章 實驗方法與步驟----------------------------------------29
3.1 基因晶片之微電極設計與製程---------------------------------------29
3.1.1 微電極圖案設計與製程規劃--------------------------------29
3.1.2 實驗儀器設備--------------------------------------------------32
3.1.3 微電極製程步驟-----------------------------------------------36
3.2 DNA之固定化與雜交反應實驗---------------------------------------40
3.2.1 實驗藥品與寡核苷酸序列----------------------------------------40
3.2.2 儀器儀器設備----------------------------------------------------49
3.2.3 實驗目的---------------------------------------------------------50
3.2.4 實驗方法---------------------------------------------------------53
3.3 電性量測與SEM觀測---------------------------------------------------60
3.3.1 量測之儀器設備------------------------------------------------60
3.3.2 電性量測實驗---------------------------------------------------63
3.3.3 SEM觀測實驗--------------------------------------------------64
3.4 量測電路與基因晶片之整合-------------------------------------------64
3.5 非相等長度電極的實驗-------------------------------------------------68
第四章 結果與討論------------------------------------------------------72
4.1 電性量測結果與討論-------------------------------------------------72
4.2 奈米金粒子之分佈情形-------------------------------------------------76
4.3 量測電路與基因晶片之整合的結果與討論-------------------------82
4.4 非相等長度電極的實驗之結果與討論--------------------------------83
第五章 結論與未來展望-------------------------------------------85
參考文獻------------------------------------------------------------88
參考文獻 [1] 林志生、袁俊傑、吳東昆、林玉娟,生物感測技術與應用(II),中北區 ( 交通大學 ) 奈米科技人才培育中心,民國93年
[2] 楊裕雄、徐文祥、黃遠東,生物感測技術與應用(I),中北區 ( 交通大學 ) 奈米科技人才培育中心,民國93年
[3] Joon Sung Lee, et al., Nanogap capacitor for label free DNA analysis, Journal of Materials Research, Mat. Res. Soc. Symp. Proc. Vol. 729, Materials Research Society, 2002
[4] So-Jung Park, et al., Array-Based Electrical Detection of DNA with Nanoparticle Probes, Science, vol 295, pp. 1503-1506, 2002
[5] 彭敬欽,陳炳煇教授指導,以電訊號檢測DNA之CMOS微陣列生物晶片系統,民國九十二年,國立台灣大學機械研究所碩士論文
[6] 蔡宜樺,陳炳煇教授指導,應用奈米電極檢測之單一核酸多型性生物晶片,民國九十二年,國立台灣大學機械研究所碩士論文
[7] Zhen Guoet al, Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports, Nucleic Acids research, Vol. 22, No. 24, 1994
[8] Sverre Grimnes, Orjan Grottem Martinsen, Bioimpedance and Bioelectricity Basics, Academic Press, USA, 2000
[9] David Halliday, Robert Resnick, and Jearl Walker, Fundamentals of Physics, Extended, John Wiley & Sons, New York, April 2002
[10] C.B. Whan, Full capacitance matrix of coupled quantum dot arrays: static and dynamical effects , Massachusetts Institute of Technology, Cambridge, MA 02139, 6 May 2002
[11] Daniel L. et al., Electron transfer in self-assembled inorganic polyelectrolyte/metal nanoparticle heterostructures, J. Am. Chem. Soc,Vol. 118, pp. 7640-7641, 1996
[12] Mathias Brust et al., Self-assembled Gold nanoparticle thin-film with nonmetallic optical and electronic properties, Lanmuir, vol. 14, pp5425-5429, 1998
[13] 王崇人,神奇的奈米科學,科學發展,354期,pp.48-51,2002年6月
[14] T. Andrew Taton, Chad A. Mirkin, and Robert L. Letsinger, Scanometric DNA Array Detection with Nanoparticle Probes, Science, vol. 289, no. 5485, pp. 1757-1760, 2000
[15] James J. Storhoff et al, One-Pot Colorimetric Differentiation of Polynucleotides with Single Base Imperfections Using Nanoparticle Probes, J. Am. Chem. Soc., vol. 120, pp.1959-1964, 1998
[16] Linda A Chrisey et al., Covalent attachment of synthetic DNA to self-assembled monolayer films, Nucleic Acids Reaseach, Vol. 24, no. 15, pp. 3031-3039, 1996
[17] Alice J. Chnningham, Introduction to Bioanalytical Sensors ( Techniques in Analytical Chemistry ), Wiley-Interscience, ISBN: 0471118613, April 17, 1998
[18] James D. Plummer, Michael D. Deal, Peter B. Griffin, Silicon VLSI Technology: Fundamentals, Practice and Modeling, first edition, ISBN: 0130850373, Prentice Hall Inc, 2002
[19] 大眾醫葯網
http://www.windrug.com/pic/30/11/27/018.htm
[20] Chad A. Mirkin, Invited Contribution from recipient ACS Award in Pure Chemistry, Programming the assembly of Two-and Three Dimensional Architecture with DNA and nanoscale Inorganic building blocks , Inorg. Chem, 39, pp.2258-2272, 2000
[21] Christine Berggren, Per Stålhandske, Jan Brundell, Gillis Johansson, A Feasibility Study of a Capacitive Biosensor for Direct Detection of DNA Hybridization, Electroanalysis, Vol. 11, no. 3 , pp. 156–160, 1999.
[22] C. D. Bain, J. Evall, and G. M. Whitesides, Formation of monolayers
by the coadsorption of thiols on gold: variation in the head group, tail
group, and solvent”, J. Am. Chem. Soc., Vol. 111, pp. 7155-7164, 1989
[23] C. D. Bain, and G. M. Whitesides, Formation of monolayers by the
coadsorption of thiols on gold: variation in the length of the alkyl
chain, J. Am. Chem. Soc., Vol. 111, pp. 7164-7175, 1989
[24] Douglas Ruben Call, Darrell P. Chandler and Fred Brockman, Fabrication of DNA Microarrays Using Ummodified Oligonucleotide Probes, Biotechniques, Vol. 30,pp. 368-379, February 2001
[25] Shaowei Chen and Fengjun Deng, Rectified quantized charging of gold nanoparticle self-assembled monolayers by arenedithiol linkages, SPIE , 2002
[26] Robert Elghanian et al. Selective Colorimetric Detecion of
Polynucleotide Based on the Distance-Dependent Optical Properties of Gold Nanoparticles, Science ,Vol. 277, pp. 1078-1081, 22 August 1997
[27] Lisa R. Hilliard, Immobilization of oligonucleotides onto silica nanoparticles for DNA hybridization studies, Analytica Chimica Acta , Vol. 470, pp. 51-56, 2002
[28] Anil Kumar et al. Silanized nucleic acids: a general platform for DNA immobilization, Nucleic Acids Research, Vol. 28, No.15, 2000
[29] Z. Li, R. Jin, C. A. Mirkin, and R. L. Letsinger, “Multiple thiol-anchor
capped DNA-gold nanoparticle conjugates”, Nucleic Acids Research,
Vol. 30, No. 7, 1558-1562 , 2002
[30] Robert C. Mucic et al., DNA-Directed synthesis of Binary Nanoparticle Network Materials, J. Am. Chem. Soc .vol. 120 , pp.12674-12675,1998
[31] Dustin J. Maxwell et al. Self-Assembled nanoparticle probes for recognition and detection of biomolecules, J. Am. Chem. Soc., vol. 124, pp. 9606-9612, 2002
[32] Robert Penchovsky, End-specific covalent photo-dependent immobilization of synthetic DNA to paramagnetic beads, Nucleic Acids research,Vol.28, No.22, 2000
[33] protocols of Microarray http://cmgm.stanford.edu/pbrown/protocols/index.html
[34] Robert M. Umek, Electronic Detection of Nucleic Acids, A versatile Platform for Molecular Diagostics, Journal of Molecular diagnostics. Vol 3, No 2, May 2001
[35] L.L. Wu et al. Preparing of matrix DNA chip and labeling of DNA hybridization by Electrochemical method, state key laboratory for chemistry of the solid surface . Department of chemistry , Xiamen University, Xiamen, 361005, P.R. China
[36] Ning Wang et al. The immobilization of DNA on carboxyl-terminal silane self-assembled monolayers surface, Aug. 1 , 2003 Vol.5 No 9, pp. 70, CJI
[37] 許景翔,陳文逸教授指導,金奈米粒子合成及表面化學改質與其應用於DNA 分子雜交動力學之探討,國立中央大學化學工程與材料工程研究所碩士論文,中華民國九十二年七月
指導教授 蔡章仁、辛裕明
(Jang-Zern Tsai、Yue-ming Hsin)
審核日期 2004-7-14
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