| 研究生: |
李慶良 Ching-Liang Lee |
|---|---|
| 論文名稱: |
生物晶片螢光分析之微光學模組 |
| 指導教授: |
楊宗勳
Tsung-Hsun Yang |
| 口試委員: | |
| 學位類別: |
碩士 Master |
| 系所名稱: |
理學院 - 光電科學與工程學系 Department of Optics and Photonics |
| 畢業學年度: | 94 |
| 語文別: | 中文 |
| 論文頁數: | 80 |
| 中文關鍵詞: | 微光柵 、微透鏡 、消逝波 |
| 外文關鍵詞: | micro-grating, micro-lens, evanescent wave |
| 相關次數: | 點閱:12 下載:0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
近幾年來,由於生物科技一日千里,並且搭配成熟的微系統加工技術,使得生物晶片的研究蔚為風潮。目前應用在生物晶片上的訊號偵測方法有許多種,例如:螢光檢測法和電位量測法等,本文主要探討的是螢光檢測法,利用消逝波的激發方式激發螢光,進而整合微透鏡和微光柵成一微光學系統,用來調制螢光光源,而促成整個生物晶片檢測系統。
本文模擬主要針對微光學元件設計和混光分析做討論,微透鏡設計概念為先定義系統所需照度分佈結果,再藉由結果反推透鏡形式,本文所設計的非球面平凸透鏡發散角為0.5、規一化照度分佈為0.92以上。微光柵結構設計成循環比為50﹪、相位深度為π,目的讓有分光效果的一階繞射效率提升為40.5﹪。混光分析利用混合頻譜訊號,反推算出組成此混合頻譜訊號的不同頻譜訊號所佔的總能量比。
本文製程主要利用壓模方式製作微透鏡,文中將針對模具製作、灌模和量測系統做詳細介紹,本文所製作的非球面平凸透鏡發散角為7.1、規一化照度分佈為近似高斯分佈。
Recently, according to the great progress in biotechnology and the miniaturization techniques in engineering, the development on the technology of lab on a chip becomes one of the most important subjects for the multi-discipline integration. There are many signal detection methods applied on the biochip, such as the fluorescence detection method and the potentiometric detection method etc. Here, this study focus on the fluorescence detection method and utilize the evanescent wave to excite the fluorescence, then use micro-lens and micro-grating to modulate the fluorescent light source and promote the detective system of the biochip.
The lens design focuses on the planoaspherical lens. This lens can be used to generate a homogenous irradiance on the target in the grating, which uses the fluorescent light as light source.
The grating design focuses on the binary phase grating. As the binary structures are based on π-phase depth and 50﹪-duty cycle, diffraction efficiency of the binary approximation is only 40.5﹪in the +1 diffraction order.
Templates with inverse images of the planoaspherical lens using casting techniques. The image of microstructures are then transferred from templates to quartz.
[1] J. Craig Venter, “The Sequence of the Human Genome”, Science, vol. 291, pp.1304-1351, 2001.
[2] T. Strachan, “Human Molecular Genetics, 3th ED”, 2004.
[3] H. Lodish, “Molecular Cell Biology, 5th ED”, 2004.
[4] K. K. Jain, “Biochips for Gene Spotting”, Science, vol. 294, pp. 621-623, 2001.
[5] J. Khan, “Expression profiling in cancer using cDNA”, Electrophoresis, vol. 20, pp. 223-229, 1999.
[6] G. Macbeath, S. L. Schreiber, “Printing Proteins as Microarrays for High- Throughput Function Determination”, Science, vol. 289, pp. 1760-1763, 2000.
[7] D. Erickson, “Integrated microfluidic devices”, Analytica Chimica Acta, vol. 507, pp. 11-26, 2004.
[8] A. Manz, “Miniaturized Total Chemical Analysis System: A Novel Concept for Chemical Sensing”, Sensors and Actuators, B1, pp. 244-248, 1990.
[9] M. Schena, “Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray”, Science, vol. 270, pp. 467-470, 1995.
[10] 張玉瓏,“生物技術”, 新文京開發出版有限公司, 2003。
[11] R. J. Lipshutz, “High density synthetic oligonucleotide arrays”, Nature genetics, vol. 21, pp. 20-24, 1999.
[12] A. Gorg, “The current stage of two dimensional electrophoresis with immobilized pH gradients”, Electrophoresis, vol. 21, pp. 1037-1053, 2000.
[13] A. Gorg, Postel, W., Gunther, s., “Nuclear integrations of mitochondrial DNA in primates: Inference of associated mutational events”, Electrophoresis, vol. 9, pp.531-546, 1988.
[14] M. Koch, “The dynamic micropump driven with a screen printed PZT actuator,” Journal of Micromechanics and Microengineering, vol. 8, pp. 119-122, 1998.
[15] A. Manz, “Micromachining a Miniaturized Capillary Electrophoresis -Based Chemical Analysis System on a Chip,” Science, vol. 261, pp. 895-897, 1993.
[16] C. G. J. Schabmueller, “Closed Chamber PCR Chips for DNA Amplification”, Engineering Science and Education Journal, vol.9, pp.259-264, 2000.
[17] J. Chiou, “Performance of a Closed-cycle Capillary Polymerase Chain Reaction Machine”, Micro Total Analysis System 2001, pp. 495-496, 2001.
[18] C. F. Chou, “A miniaturized cyclic PCR device-modeling and experiments”, Microelectronic Engineering, vol. 61, pp. 921-925,2002.
[19] E. Thrusha, “ Monolithically integrated semiconductor fluorescence sensorfor microfluidic applications”, Sensors and Actuators B, vol.105, pp.393–399, 2005.
[20] Der-chang Chen, “Palladium Film Decoupler for Amperometric Detec -tion in Electrophoresis Chips”, Anal. Chem., vol.73, pp.758-762, 2001.
[21] C. S. Effenhauser, “Integrated Capillary Electrophoresis on Flexi -ble Silicone Microdevices: Analysis of DNA Restriction Fragments and Detection of Single DNA Molecules on Microchips” , Anal. Chem., vol.69, pp.3451-3457, 1997.
[22] D.M. Pinto, “An enhanced microfluidic chip coupled to an electro -spray Qstarmass spectrometer for protein indentification”, Electrophoresis, vol.21, pp.181-190, 2000.
[23] P.A. Walker, “Isotachophoretic Separations on a Microchip. Normal Raman Spectroscopy Detection”, Anal. Chem., vol.70, pp.3766-3769, 1998.
[24] Z. Liang, “Microfabrication of a Planar Absorbance and Fluorescence Cell for Integrated Capillary Electrophoresis Devices”, Anal. Chem., vol.68, pp.1040-1046, 1996.
[25] T. Kamei, “Integrated Hydrogenated Amorphous SiPhotodiode Detector for Microfluidic Bioanalytical Devices”, Anal. Chem., vol.75, pp.5300-5305, 2003.
[26] 周虹宇,“生物晶片螢光檢測之光源模型探討”,國立中央大學光電科學研究所,碩士論文,民國九十三年。
[27] X. Deng, X. Liang, Z. Chen, W. Yu, R. Ma, “Uniform illumination of large targets using a lens array”, Appl. Opt. ,vol. 25, pp.377–381, 1986.
[28] D. G. Burkhard , D. L. Shealy, “Specular aspheric surface to obtain a specified irradiance from discrete or continuous line source radiation: design”, Appl. Opt., vol.14, pp.1279–1284, 1975.
[29] D. Shafer, “Gaussian to flat-top intensity distributing lens”, Opt. Laser Technol, vol.14, pp.159–160, 1982.
[30] R. Winston , H. Ries, “Nonimaging reflectors as functionals of the desired irradiance”, SPIE Nonimaging Optics Press, vol.2016, pp.1902–1908,1993.
[31] M. Bass, “Handbook of optics Ⅱ, 2th ED”, McGraw-Hill, New York, 1995.
[32] Virendra N., Mahajan, “ Optical Imaging and Aberrations ”, SPIE Optical Engineering Press, Bellingham, WA, 1998.
[33] W. Tai , R. Schwarte, “Design of an aspherical lens to generate a homogenous irradiance for three-dimensional sensors with a light-emitting-diode source”, Appl. Opt., Vol.39, pp.5801-5805, 2000.
[34] Fluorescence imaging: principles and methods, Technical manual, Amersham Pharmacia biotech.
[35] J. R. Leger, “Laser beam shaping”, a chapter in the book Microoptics, H. P. Herzig, ed., Taylor, Francis, London, pp.223–257, 1996.
[36] 黃淳權,“數值分析”, 全威圖書有限公司, pp. 482-487 , 民國八十九年。
[37] Breault Research Organization: The ASAP™ Primer
(http://www.breault.com/)
[38] M.C. Hutley, “Diffraction Gratings”, Academic Press, London, 1982.
[39] E.G. loewen,“Diffraction Grating and Applications”, Marcel Dekker, New York, 1997.
[40] J.W. Goodman, “Introduction to Fourier Optics, 2th ED”, McGraw-Hill, San Francisco, 1996.
[41] D.C. O’Shea, “Diffractive Optics: design, fabrication, and test”, SPIE Press, Bellingham, WA, 2003.
[42] 葉星輝,“生物晶片之螢光光學檢測”,國立中央大學光電科學研究所,碩士論文,民國九十四年。