臺灣博碩士論文加值系統

本研究以有限元素的數值模擬方式分析微晶片聚合脢連鎖反應器(Polymerase Chain Reaction Chip, PCR Chip)模型，在接觸式加熱及非接觸式加熱兩種機制中晶片模型的溫度場分佈及影響溫昇、降速率之相關因素進行分析與探討。
在接觸式加熱分析中，可得知在DNA整體溫度分佈十分均勻且其溫度極小。有限元素的模擬結果以一維理論加以驗證後亦獲得相同結果。將經模擬改良後的快速溫程曲線，實際應用在C型肝炎病毒的DNA複製過程，獲得極佳之DNA複製結果，由此可見以模擬結果來改善溫程曲線時間是確實可行。
由非接觸式加熱分析中知，在相同能量之下影響其溫程速率最大的因素為深度變化及加熱光源的波長。故以四種不同波長的加熱光源配合三種不同的反應腔深度，分別代入工程分析軟體分析。對部分波長而言，其對光源主要吸收層在矽。對另一部分波長而言，其對光源主要吸收層在矽和DNA，但其矽和DNA的個別吸收率會隨深度變化而有所不同，但整體的吸收率均維持一定值。

This study used the finite element method (FEM) to simulate and analyze the transient temperature distributions in the micro polymerase chain reaction (PCR) chip. The contact and non-contact heating mechanisms were considered and the temperature uniformity, distribution, heating and cooling rates were investigated herein.
When the contact heating mechanism was considered, the distribution temperature of the reaction chamber is uniform. The numerical results were also confirmed by one-dimensional theoretic analysis. The improved thermal cycle of the rapid micro-PCR system were verified using serum sample form patients with chronic hepatitis C. The simulated results were used to improve the thermal cycles time of a rapid mPCR system.
As the non-contact heating mechanism was considered, the size of the reaction chamber and the wavelength of the optical source influenced the heating/cooling rate under the same amount of the incidence energy. Four different wavelengths of the optical sources and three different sizes of the reaction chamber were employed in the present study. For several wavelengths of the optical sources, the energy deposited only in the silicon layer. For the other wavelength, energy deposited in both silicon and reaction chamber. The temperature distributions under contact and non-contact heating mechanisms have been simulated and discussed in the present work.

目 錄
摘 要 I
英文摘要 III
誌 謝 IV
目 錄 V
表 目 錄 VIII
圖 目 錄 IX
第一章 序論 1
1-1前言 1
1-2文獻回顧 10
1-3研究動機與目的 13
第二章 理論與模型 14
2-1簡介及原理 14
2-2理論模型 18
2-3光學加熱理論 20
2-4有限元素分析 22
第三章 接觸式加熱 24
3-1分析模型 24
3-2穩態分析 26
3-3暫態分析 28
3-4結果與驗證 29
3-4.1一維理論分析 29
3-4.2實驗的驗證 30
3-5結果與討論 32
第四章 非接觸式加熱 35
4-1分析模型 35
4-2自然對流 39
4-3強制對流 49
4-4結果與討論 57
第五章 加熱光源之波長效應 61
5-1分析模型 61
5-2波長效應 64
5-3反應腔尺寸分析 73
5-4結果與討論 79
第六章 結論與建議 93
6-1結論 93
6-2建議 95
參考文獻 96

參考文獻
1.蘇遠志, “生物技術產業國內外市場發展趨勢”, 生物醫學報導, 第一期, 2000.
2.邱爾德、李政育、黃鈞正、丁君毅, “生物晶片關聯光電系統偵測”, 科學發展月刊, 第29卷, 第10期, pp. 716-723, 2001.
3.行政院國家科學委員會光電小組編著, “雷射醫學：原理及臨床應用”, 行政院國家科學委員會國科會, pp. 203-210, 2001.
4.http://www.ncku.edu.tw/~cbst/biochip.htm
5.張寅, “光學在生物醫學上的應用”, 教育部本土化醫學工程教科書暨醫療器材技術規範編輯委員會, 教育部, pp. 66-91, 1999.
6.M. A. Northrup, C. Gonzalez, D. Hadley, R. F. Hills, P. Landre, S. Lehew, R. Saiki, J. J. Sninsky, R. Watson, and R. Watson, Jr., “A MEMS-based miniature DNA analysis system,” Proceedings of the 8th International Conference on Solid-State Sensors and Actuators, and Eurosensors IX Stockholm, Sweden, pp. 25-29, June 1995.
7.M. U. Kopp, M. B. Luechinger and A. Manz, “Continuous flow PCR on a chip,” Proceedings of the mTAS’98 Workshop, pp. 7-10, 1998.
8.R. P. Oda, M. A. Strausbauch, A. F. R. Huhmer, N. Borson, S. R. Jurrens, J. Craighead, P. J. Wettstein, B. Kline, and J. P. Landers, “Infrared-mediated thermocycling for ultrafast polymerase chain reaction amplification of DNA”, Anal. Chem., pp. 4361-4368, 1998.
9.C. Qijuan, W. Zhipeng and L. Yan, “Intelligent PID control for PCR process,” IEEE International Conference, Vol. 1, pp. 828-831, 1998.
10.T. B. Taylor, S. E. Harvey, M. Albin, L. Lebak, Y. Ning, I. Mowat, T. Schuerlein and E. Principe, “Proceess control for optimal PCR performance in glass microstructures,” Biomedical Microdevices, pp. 65-70, 1998.
11.S. Kondo, K. Kano, and E. Shinohara, “Reaction chamber for PCR made by microfabrication technologies,” Technical Digest of Transducers ‘99, the 10th International Conference on Solid-State Sensors and Actuators, pp. 1718-1721, 1999.
12.Y. C. Lin, M. Y. Hung, K. C. Young, T. T. Chang, C. T. Wu, “A rapid micro-PCR system for hepatitis C virus amplification,” Sens. Actuators B, Vol. 71, pp. 2-8, 2000.
13.Y. C. Lin, C. C. Yang, M. Y. Hung, “Simulation and experimental validation of micro PCR chips,” Sens. Actuators B, Vol. 71, pp. 127-133, 2000.
14.Maxim N. Slyadnev, Yuki Tanaka, Manabu Tokeshi, and Takehiko kitamori, “Photothermal temperature control of a chemical reaction on a microchip using an infrared diode,” Anal. Chem., Vol. 73, No.16, pp. 4037-4044, 2001.
15.Oswald T. Avery, Colin M. MacLeod, and Maclyn McCarty, “Studies on chemical nature of the substance inducing transformation types,” J. Experimental Medicine, Vol. 79, No. 2, pp. 137-158, 1944.
16.R. K. Saiki, S. Scharf, F. Faloona, K. B. Mullis, G. T. Horn, H. A. Erlich and N. Arnheim, “Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia,” Science, Vol. 230, pp. 1350-1354, 1985.
17.謝奉家, 高穗生, “聚合脢連鎖反應(PCR)在農業生物技術上之應用簡介”, 行政院農委會農業藥物毒物試驗所專題報導, 第56期, 2000.
18.T. Jalava, P. Lethovaara, A. Kallio, M. Ranki, H. Soderlund, “Quantification of hepatitis B virus DNA by competitive amplification and hybridization on microplates,” BioTechniques, Vol. 15, No. 1, pp. 134-139, 1993.
19.Yunus A. Çengel, “Heat transfer a practical approach,” McGrawHill 1998.
20.S. Kakac, R. K. Shah, W. Aung, “Handbook of single-phase convective heat transfer,” John Wiley & Sons, pp. 1-11, 1987.
21.H. A. Macleod, “Thin-film optical filters,” McGrawHill, 1989.
22.D. R. Lide, “Handbook of chemistry and physics,” CRC 80TH, pp. 10-220, 1999-2000.
23.“Pyrex 7740 material properties,” Corning glass technology book.
24.P. Schiebener, J. Straub, J. M. H. Levelt Sengers, J. S. Gallagher, “Refractive index of water and steam as function of wavelength, temperature and density,” J. Phys. Chem. Ref. Data. Vol. 19,No. 3, pp. 677-715, 1990.
25.E. D. Palik, “Handbook of optical constants of solids,” Academic Press, pp. 547-569, 1985.
26.E. D. Palik, “Handbook of optical constants of solidsⅡ,” Academic Press, pp. 761-775, 1991.
27.D. R. Lide, “Handbook of chemistry and physics,” CRC 80TH, pp. 6- 3; 12-196; 12-198, 1999-2000.
28.W. M. Rohsenow, J. P. Hartnett “Handbook of heat transfer,” McGraw-Hill, pp. 3-71, 1973.
29.L. A. Abol, R. T. Kiepura, P. Thomas, H. F. Lampman, N. D. Wheaton, “Properties and selection: nonferrous alloys and special purpose materials,” ASM, Vol. 2, pp. 45-103, 1990.
30.http://www.qsl.net/vr2xbp/Spectrum/Spectrum.html
31.www.valleydesign.com/1737.jpg