光學式生化反應即時偵測系統

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：20

、訪客IP：3.136.154.103

姓名

吳建宏(Jian-Hung Wu) 查詢紙本館藏

畢業系所

光電科學與工程學系

論文名稱

光學式生化反應即時偵測系統

相關論文

★ 新型光電生化感測器之分析與研究	★ 薄膜電晶體液晶顯示器中視角色偏之優化補償方法
★ 特定色度背光模組零組件之光學特性評估	★ 電子紙增亮分析與模擬設計
★ 生物晶片螢光檢測之光源模型探討	★ 介電電濕式數位微流體驅動系統之探討
★ 發光二極體照明系統之色彩特性優化設計	★ 以EWOD為基礎的長鏈高分子原位合成器
★ 色盲量化測試系統之研究	★ 可調式自然日光模擬光源之製作
★ 演色性評估之相關性指標	★ 亞精胺影響下DNA構形與DNA碎片分佈之研究
★ 生物晶片之螢光光學檢測	★ 生物晶片螢光分析之微光學模組
★ 微液滴驅動之研究與探討	★ LED光源新式應用之研究

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

本文研製一新型光學生物感測器：導模共振(guided mode resonance, GMR)光學生物感測器。本元件利用半導體技術，製作一次波長光柵結構，並利用其產生的窄帶高反射率之效果，及其光柵表面區域之高敏感度，應用於共種生化反應，本元件具有以下優點：免標定、微小化、可高產量、即時偵測、易與其它半導體元件接合之優點。
本研究已將GMR元件組裝至流體系統內，形成GMR流體晶片。除了方便將整個生化實驗於晶片內進行外，所使用到的檢體量也相對的減少，並發展出一套即時檢測平台，縮短了檢測所需時間。目前於晶片本身已能檢測出折射率變化量小於0.001，且偵側去氧核醣核酸之雜交行為，除了可即時觀察出有無雜交反應外，其有無雜交差異量更達9倍之多。對於胜肽合成，能成功偵測出每段長度約0.3nm之胺基酸接合反應及其反應之分子動力學行為。

摘要(英)

We report a novel method for detecting biomolecular interaction which utilizes the guided-mode resonance (GMR) phenomenon with narrow-band high reflection efficiency characteristics. The structure of GMR device generally consists of two stages — upper grating layer and waveguide layer. GMR device and flow cell are combined to from a GMR flow cell system. The system has several advantages such as label-free, minimizing, real time monitoring, high throughput, low cost, and the potential to become portable. We show the system experimentally with the ability to detect the refractive index variations <0.001,the amino acid thickness variations <0.3nm. It also can detect DNA hybridization and measure molecular interaction.

關鍵字(中)

★ 光學感測器
★ 導膜共振

關鍵字(英)

★ Biosensor
★ Guide-mode resonance
★ DNA hybridization

論文目次

第一章緒論......................................................................1
1.1 生物晶片簡介..............................................................3
1.1.1 微陣列晶片...............................................................4
1.1.2 實驗室晶片...............................................................5
1.2 生物反應訊號之光學檢測方法..................................6
1.2.1 螢光共振能量轉移法...............................................7
1.2.2 表面電漿共振儀.......................................................9
1.2.3 MACH-ZEHNDER干涉儀生物感測法......................10
1.2.4全內反射螢光法......................................................11
1.3 研究動機.... ............................................................ 14
1.3.1 GMR發展................................................................15
1.3.2 GMR生物檢測流體晶片....................................... 17
第二章 GMR流體晶片之設計與模擬.............................19
2.1 GMR理論...................................................................19
2.1.1 GMR簡介................................................................19
2.1.2 GMR嚴格耦合波概論............................................20
2.2 GMR流體晶片之設計...............................................26
2.2.1 GMR元件設計........................................................26
2.2.2 GMR流道系統之設計............................................29
2.3 GMR流體晶片之模擬...............................................39
2.3.1 GMR元件之模擬....................................................40
2.3.2 GMR流體晶片之模擬............................................44
第三章 GMR流體晶片之製作與量測.............................48
3.1 GMR流體晶片之製作...............................................48
3.1.1 GMR元件之製作....................................................48
3.1.2 GMR流道之製作....................................................51
3.2 GMR流體晶片之特性量測.......................................54
3.2.1量測系統..................................................................54
3.2.2 GMR流體晶片之特性量測...................................55
3.3 即時監測軟體之開發............................................... 57
3.3.1多項式的曲線擬合..................................................59
3.3.2 系統操作說明.........................................................61
第四章 GMR即時生物檢測流體晶片.............................63
4.1 靈敏度之分析……………………………………….63
4.1.1不同溶液之偵測…………………………………...63
4.1.2 不同濃度已醇溶液偵測..................................................65
4.2 去氧核醣核酸之雜交偵測.................................................67
4.2.1 去氧核醣核酸之雜交......................................................70
4.2.2 DNA雜交實驗流程..........................................................71
4.2.3 去氧核醣核酸偵測訊號分析..........................................76
4.2.4 DNA雜交之重複性偵測..................................................77
4.3 胜肽合成.............................................................................81
4.3.1 胺基酸接合......................................................................82
4.3.2 胜肽合成實驗流程..........................................................86
4.3.3去氧核醣核酸偵測訊.......................................................88
4.3.4胜肽合成之反應動力曲線分析.......................................91
第五章結論與未來展望............................................................. 93
參考文獻........................................................................... 96

參考文獻

[1] W. Tan, X. Fang, J. Li and X. Liu,“Molecular beacons: a noel DNA probe for nucleic acid and protein studies,”Chem. Eur. J. 6 1107-1111(2000)
[2] E. Ortiz, G. Estrada and P. M. Lizardi,“PNA Molecular Beacons for Rapid Detection of PCR Amplicons,’’ Mol. Cell. Probes 12, 209-216(1998)
[3] B.Liedberg, C. Nylander, and I. Lundsr,“Surface plasmon resonance for gas detection and biosensing,’’ Sensor and Actuators B 4,299-304(1983)
[4] J. Homola, S. Yee and G. Gauglitz, “Surface Plasmon Resonance Sensors: Review,’’ Sensors and Actuators B 54, 3-5(1999)
[5] X. Su and J. Zhang,“Comparison of surface plasmon resonance spectroscopy and quartz crystal microbalance for human IgE quantification,’’ Sensors and Actuators B : Chemical 100 (3),311-316(2004)
[6] L. Thierry, B. Hervé, C. Patrice and R. André,“Electroconducting polymers for the construction of DNA or peptide arrays on silicon chips ,” Biosensors and Bioelectronics 13 (6), 629-634 (1998).
[7] J. Obeid Pierre and K. Christopoulos Theodore,“Continuous-flow DNA and RNA amplification chip combined with laser-induced fluorescence detection,” Analytica Chimica Acta 494 (1-2), 1-9 (2003).
[8] J. Cahill Dolores,“Protein and antibody arrays and their medical applications,” J. of Immunological Methods 205 (1-2), 81-91 (2001).
[9] J. Seo and L. P. Lee,“Disposable integrated microfluidics with self-aligned planar microlenses,” Sensors and Actuators B: Chemical 99(2-3), 615-622 (2004).
[10] David A. Wicks and Paul C.H .Li,“Separation of fluorescent derivatives of hydroxyl-containing small molecules on a microfluidic chip,” Analytica Chimica Acta 507(1), 107-114 (2004).
[11] B. C. Kim, K. S. Park, S. D. Kim and M. B. Gu,“Evaluation of a high throughput toxicity biosensor and comparison with a Daphnia magna bioassay,” Biosensors and Bioelectronics 18(5-6), 821-826 (2003).
[12] D. S. Mehta, C. Y. Lee and A.Chiou,“Multipoint parallel excitation and CCD-based imaging system for high-throughput fluorescence detection of biochip micro-arrays,” Optics Communications 190 (1-6), 59-68 (2001).
[13] Y. Ito and M. Nogawa,“Preparation of a protein micro-array using a photo-reactive polymer for a cell-adhesion assay,” Biomaterials 24(18), 3021-3026 (2003).
[14] Kang, Joo H.; Park, Je-Kyun,“Development of a microplate reader compatible microfluidic device for enzyme assay,” Sensors & Actuators: B. Chemical 107 (2), 980-985 (2005).
[15] Y. Huang and B. Rubinsky,“Flow-through micro-electroporation chip for high efficiency single-cell genetic manipulation,” Sensors and Actuators A: Physical 104(3), 205-212 (2003).
[16] A. Manz,“miniaturized total Chemical Analysis System: A Novel Concept for Chemical Sensing,” Sensors and Actuators, B1, 1990.
[17] K. Zimmermann, T. Eiter and F. Scheiflinger,“Consecutive analysis of bacterial PCR samples on a single electronic microarray ,” J. of Microbiological Methods 55(2), 471-474 (2003).
[18] Y. J. Hun and P. Je-Kyun,“Cytotoxicity test based on electrochemical impedance measurement of HepG2 cultured in microfabricated cell chip,” Analytical Biochemistry 341 (2), 308-315 (2005).
[19] FT Chen, RA Evangelista.,” Feasibility studies for simultaneous immunochemical multianalyte drug assay by capillary electrophoresis with laser-induced fluorescence.,” Clin Chem, 1819-1823 (1994).
[20] M Rahman; X. P. Li; X. D. Zhang; K. H. W. Seah,“A three-dimensional model of chip flow, chip curl and chip breaking under the concept of equivalent parameters,” International J. of Machine Tools and Manufacture 35(7), 1015-1031 (1995).
[21] R. G. Heideman and P. V. Lambeck,“Remote Opto-Chemical Sensing with Extreme Sensitivity: Design, Fabrication and Performance of a Pigtailed Intergrated Optical Phase-Modulated Mach Zehnder Interferometer System ”, Sensors and Actuators B, 100-127 (1999).
[22] Y. Sako, S. Miniguchi and T. Yanagida,“Single-molecule imaging of EGFR signaling on the surface of living cells,” Nature Cell Biol. 2, 168-172 (2000).
[23] R. M. Dickson, D. J. Norris, Y.-L. Tzeng and W. E. Moerner,“Three-dimensional imaging of sibgle molecules solvated in pores of poly gels,” Science 274, 966-969 (1996).
[24] G. Boisde and A. Harmer,“Chemical and biochemical sensing with optical fibers and waveguides,” Artech House, Bosston-London, 1996.
[25] R. W. Wood,“On a remarkable care of uneven distribution of light in a diffraction grating spectrum,” Philos.Mag,4,396 02(1902).
[26] R. W. Wood,“On a remarkable case of uneven distribution of light in a diffraction grating spectrum,” Philos. Mag, 4, 396–402 (1902).
[27] A. Hessel and A. A. Oliner,“A new theory of Wood’s anomalies on optical gratings,”Appl. Opt. 4, 1275–1297 (1965).
[28] S. S. Wang and R. Magnusson,“Guided-mode resonances in planar dielectric-layer diffraction gratings,” J. Opt. Soc. Am. A 7, 1464–1468 (1990).
[29] L. Mashev and E. Popov,“Zero order anomaly of dielectric coated gratings,” Opt. Commun. 55, 377–380 (1985).
[30] L. Mashev and E. Popov,“Zero order anomaly of dielectric coated gratings,”Opt. Commun. 55, 377 (1985).
[31] I. A. Avrutsky and V. A. Sychugov,“Reflection of a beam of finite size from a corrugated waveguide, ”J. Mod. Opt, 36, 1527 (1989).
[32]A. Sharon, D. Rosenblatt, A. A. Friesem, H. G. Weber, H. Engel, and R. Steingrueber, “Light Modulation with Resonant Grating-Waveguide Structures,“ Opt. Lett. 21, 1564-1567 (1996).
[33]S. S. Wang and R. Magnusson,“Theory and applications of guidedmode resonance filters,“Appl. Opt. 32, 2606–2613 (1993).
[34] K. Fu, Z. Wang, Q. Zhang, J. Zhang and Y. Nie,“The resonance peak theory of reflection guided-mode resonance filters,“Chin. J. Lasers B 8, 313–321 (1999).
[35]Z. S. Liu, S. Tibuleac, D. Shin, P. P. Young and R. Magnusson,“ High efficiency guided-mode resonance filter,” Opt. Lett. 23, 1556–1558 (1998).
[36] A. Sharon, D. Rosenblatt and A. A. Friesem,“Resonant grating-waveguide structures for visible and near-infrared radiation,”J. Opt. Soc. Am. A 14 (11), 2985-2993 (1997)
[37] B. Cunningham, P. Li, B. Lin and J. Pepper,“Colorimetric resonant reflection as a direct biochemical assay technique,”Sensors & Actuators: B. Chemical 81, 316–328 (2002).
[38] B. Cunningham, B. Lin, J. Qiu, P. Li, J. Pepper and B. Hugh,“A plastic colorimetric resonant optical biosensor for multiparallel detection of label-free biochemical interactions,”Sensors & Actuators: B. Chemical 85 219–228 (2002).
[39] B. Cunningham, J. Qiu, P. Li and B. Lin,“Enhancing the surface sensitivity of colorimetric resonant optical biosensors,” Sensors & Actuators: B. Chemical 87, 365–370 (2002).
[40] B. Lin, J. Qiu, J. Gerstenmeier, P. Li, H. Pien, J. Pepper and B. Cunningham,“A label-free optical technique for detecting small molecule interactions,”Biosensors and Bioelectronics 17, 827-/834 (2002).
[41] Carlos F. R. Mateusa, Michael C. Y. Huanga, Jonathan Foleyb, P. Robert Beattyc, Peter Lid, Brian T. Cunninghamd and Connie J. Chang-Hasnaina,“Ultra-Compact, High Sensitivity Label-Free Biosensor Using VCSEL,”SPIE Vol.5328 (2004)
[42] M.G. Moharam, Drew A. Pommet, Eric B. Grann, and T. K. Gaylord,“Stable implementation of the rigorous coupled-wave analysis for surface-relief gratings: enhanced transmittance ma trix approach,”Vol. 12, No. 5/May 1995/J.Opt.SOC.Am.A
[43] Zubay G. L., W.W. Parson and D. E. Vance,“Principles of biochemistry,” 美商麥格羅, 希爾國際股份有限公司, 2002
[44] 王志豪, 林誠謙, 李弘謙, “談蛋白質摺疊與氨基酸序列” 物理雙月刊, Vol. 24, pp. 320-324, 2002.
[45] Advanced ChemTech, “Hand book of Combinatorial, Organic & Peptide Chemistry,” pp.46, 2003-2004
[46] Carlos F. R. Mateusa, Michael C. Y. Huanga, Jonathan Foleyb, P. Robert Beattyc, Peter Lid, Brian T. Cunninghamd and Connie J. Chang-Hasnaina,“Ultra-Compact, High Sensitivity Label-Free Biosensor Using VCSEL,”SPIE Vol.5328 (2004)
[47] M. Vallet, M. Vallade, and B.Berge,“Limiting phenomena for the spreading of water on polymer films by electrowetting,” Eur. Phys. J. B 11, pp. 583-591, 19

指導教授

楊宗勳(Tsung-Hsun Yang)

審核日期

2006-7-20

推文