本研究之目的，就是結合微機電技術設計及製作一種腫瘤檢驗晶片，在此晶片上進行酵素免疫分析法，作為危機評估、篩檢，進而評估病情，以期達到早期發現早期治療，減少癌症的死亡率。
研究的內容，主要分為兩方面：一方面是反應區晶片的設計及製作，包括比較不同晶片材質如：聚甲基丙烯酸甲酯、聚碳酸酯、聚苯乙烯及聚二甲基矽氧烷，反應區晶片表面之結構設計及反應區晶片之表面活化處理部分，探討上述之變因，進而設計出一個適合進行酵素免疫分析法之反應區晶片，並使用準分子雷射加工方式作為本研究中製作晶片之製程。
另一方面，則是設計一光學偵測系統，偵測因酵素免疫分析法所產生之化學冷光，主要架構是由光電倍增管將光源吸收並轉換成電壓訊號，透過鎖頻放大器作訊號處理，進而判斷在晶片上進行酵素免疫分析法之結果。
本研究之結果可證明在晶片上進行酵素免疫分析法是可行的，且晶片上反應具有良好之線性關係，在整個免疫分析處理的時間，相較於傳統方式縮短了許多，確實可以達到快速及準確的效果。

The goal of the study is to design and fabricate a tumor marker chip by using the techniques of MEMS. Apply enzyme-linked immunosorbent assay (ELISA) on the chip for the analysis of tumor marker in biological fluids. There are many advantages, including low reagent consumption, lowsample volume and waste production, faster response time, and feasibility to operate as a point-of-care testing.
The contents of the study have two parts. One is to design and fabricate the reaction area of the chip. The optimization of the chip was performed analyzing the parameters, including the materials that included PMMA, PC, PS and PDMS, the surface structures and the activation of chip’s surfaces.
The other is to develop a detection device for the chemiluminescence signal of ELISA reaction on chips. The signal is detection by an photomultiplier tube and processed by a lock-in amplifier.
The chip surface was activated for better reactivity and reproducibility after the surface coated with poly-L-lysine. Higher signal intensities were found on poly-L-lysine-treated chips. The results of the study show excellent sensitivity and linearity using the microchips for the immunobiochemical reaction.

[1] K. Seiler, D.J. Harrison, A. Manz, “Planar Chips Technology for Miniaturization and Integration of Separation Techniques into Monitoring Systems,” J. Chromato., 593, pp. 253-258, 1992.
[2] J.S. Schultz, “Biotechnology-Based Recognition Elements,” IEEE Engineering in Medicine and Biology, pp. 210-216, March 1995.
[3] M. Washizu, T. Yamamoto, O. Kurosawa, N. Shimamoto, “Moleclar Surgery Based on Microsystems,” Conference on Solid-State Sensors and Actuators, pp. 473-476, June 1997.
[4] J. Stafford, J. Brignac, R. Gangadharan, M. McMahon, J. Denman, “Engineering in Genomics,” IEEE Engineering in Medicine and Biology, pp. 120-122, March 1999.
[5] B. LePioufle, P. Surbled, H. Nagia, K.S. Chun, Y. Murakami, E. Tamiya, H. Fujita, “Attachment of Cells on Microsystems:Application to the Gene Transfection,” Conference on Solid-State Sensors and Actuators, pp. 18-25, 1999.
[6] M.T. Cronin, R.V. Fucini, S.M. Kim, R.S. Masino, R.M. Wespi, C.G. Miyada, “Cystic Fibrosis Mutation Detection by Hybridization to Light-generated DNA Probe Arrays,” Hum. Mutat., pp. 244-255,1996.
[7] J. Michanel, D. Heller, “An Integrated Microelectronic Multiplex Hybridzation Systems : Design and Microfabrication,” IBC BioChip Technology, 1998.
[8] M.I. Song, K. Iwata, M. Yamada, K. Yokoyama, T. Takeuchi, “Multisample Analysis Using an Array of Microreactors for an Alternating-current Field-enhanced Latex Immunoassay,” Anal. Chem., 66, pp. 778-781, 1994.
[9] J. Briggs, P.R. Fanfili, “Quantitation of DNA and Protein Impurities in Biopharmaceuticals,” Anal. Chem., 63, pp. 850-859, 1991.
[10] A. Manz, D.J. Harrison, E. Verpoorte, H.M. Wildmer, “Planer Chips Technology for Miniaturization of Separation Systems : A Developing Perspective in Chemical Monitoring [Review]. In : P.R. Brown, E. Grushka, eds. Advances in Chromatography,” New York: Marcel Dekker, pp. 1-66, 1993.
[11] L.B. Koutny, D. Schmaizing, T.A. Tayor, M. Fuchs, “MicroChip Electrophoretic Immunoassay for Serum Cortisol,” Anal. Chem., 68, pp. 18-22, 1996.
[12] L.J. Kricka, O. Nozaki, S.Heyner, W.T. Garside, P. Wilding, “Applications of A Microfabricated Device for Evaluating Sperm Function,” Clin. Chem., 39, pp. 1944-1947, 1993.
[13] http://www.biochipmaster.com
[14] http://www.affymetrix.com
[15] http://www.nanogen.com
[16] http://www.hyseq.com
[17] http://www.biacore.com
[18] 國科會精密儀器中心儀器訓練手冊，2001。
[19] 準分子雷射微細加工機一般使用者訓練教材，2000/9。
[20] S.A. Berson, R.S. Yalow, “Assay of plasma insulin in human subjects by immunological methods,” Nature, 184, pp. 1648-1649, 1959.
[21] Roitt, Brostoff, Male原著，王聖予等人編譯，“免疫學”，藝軒出版社，中華民國八十五年十月第四版。
[22] D.S. Hage, “Immunoassay,” Anal. Chem., 71, pp. 294-304, 1999.
[23] J.P. Gosling, “A Decade of Development in Immunoassay Methodology,” Clin. Chem., 36, pp. 1408-1427, 1990.
[24] T.T. Ngo, “Developments in Immunoassay Technology,” Methods- ImmunoMethods, 22, pp. 1-3, 2000.
[25] M. Aizawa, “Immunosensor for Clinical Analysis,” Adv. Clin. Chem., 31, pp. 247-275, 1994.
[26] “Photomultiplier Tube Principle to Application,” HAMAMATSU, 1994.
[27] http://www.srsys.com
[28] “SR810 DSP Lock-in Amplifier Operating Manual and Programming Reference,” Stanford Research System Inc., 1993.