本研究旨在發展一種新型的蛋白質微陣列(protein microarray)方法，包含使用微機電技術製作壓印晶片，並將蛋白質平行蓋印至生物檢測晶片上以形成蛋白質微陣列。本研究完成兩代壓印晶片之研發，第一代的壓印晶片為沾印式。沾印式壓印晶片利用微印章陣列以及微印台所構成之微印章-微印台壓印系統，可將不同之蛋白質平行轉印至生物檢測晶片之表面上。本研究之微印章係以彈性材料(polydimethylsiloxane：PDMS)製作而得，因此，微印章具有足夠之柔軟性可與粗糙平面做良好完整之接觸。實驗證明，本研究之沾印式壓印晶片可成功地將蛋白質溶液轉印至可結合蛋白質之表面，壓印出的蛋白質印之間的尺寸差異小於10%。但因表面張力作用關係，所能打印之尺寸難以小於350μm，因此無法達到高密度微陣列之需求。
為解決以上問題，本研究研發的第二代壓印晶片為背後填充式，填充式壓印晶片包含三個部分：上層為儲液區、中層是垂直微通道陣列區、下層是微印章陣列區。單一微印章之中心包含一微通道，生醫溶液注入儲液區，藉由表面張力驅動而流經中層微通道及微印章的微通道，最後來到微印章之壓印面，再與生物檢測晶片接觸，將生醫溶液傳送到生物檢測晶片上。為了製作出能產生功能之微印章，本研究同時進行數值模擬計算以求最佳的設計成果。由於驅動液體流動的總表面張力取決於液體-氣體界面之形狀，因此，數值模式必須具備能夠精確地追蹤液體-氣體界面的功能。本研究之數值模式採用流體體積法(Volume of Fluid, VOF)。第二代填充式壓印晶片的壓印實驗證明，蛋白質溶液可成功地轉印至生物檢測晶片上，且壓印出的蛋白質印亮度及面積之標準差可小於3%。此外，所能成功轉印之蛋白質印的尺寸可小至100μm。

Arenkov, P., Kukhtin, A., Gemmell, A., Voloshchhuk, S., Chupeeva, V., and Mirzabekov, A., “Protein Microchips: Use for Immunoassay and Enzymatic Reactions,” Analytical Biochemistry, Vol. 278, pp. 123-131, 2000.
Bernard, A., Michel, B., and Delamarche, E., “Micromosaic Immunoassays,” Analytical Chemistry, Vol. 73, pp. 8-12, 2001.
Blanchard, A. P., Kaiser, R. J., and Hood, L. E., “High-Density Oligonucleotide Arrays,” Biosensors and Bioelectronics, Vol. 11, pp. 687-690, 1996.
Blawas, A. S., and Reichert, W. M., “Review Protein Patterning,” Biomaterials, Vol. 19, pp. 595-609, 1998.
Brackbill, J. U., Kothe, D. B., and Zemach, C., “A Continuum Method for Modeling Surface Tension,” Journal of Computational Physixs, Vol. 100, pp. 335-354, 1992.
Britland, S., Perez-Arnaud, E., Clark, P., McGinn, B., Connolly, P., and Moores, G., “Micropatterning Protein and Synthetic Peptides on Solid Supports: A Novel Application for Microelectronics Fabrication Technology,” Biotechnology Progress, Vol. 8, pp. 155-160, 1992.
Cohen, C. B., Chin-Dixon, E., Jeong, S., and Nikiforov, T. T., “A Microchip-Based Enzyme Assay for Protein Kinase A,” Analytical Biochemistry, Vol. 273, pp. 89-97, 1999.
Delamarche, E., Bernard, A., Schmid, H., Michel, B., and Biebuyck, H., “Patterned Delivery of Immunoglobulins to Surfaces Using Microfluidic Networks,” Science, Vol. 276, pp. 779-781, 1997.
Demers, L.M., Ginger, D.S., Park, S.J., Li, Z., Chung, S.W., and Mirkin, C.A., “Direct Patterning of Modified Oligonucleotides on Metals and Insulators by Dip-Pen Nanolithography,” Science, Vol. 296, pp. 1836-1838, 2002.
Dontha, N., Nowall, W. B., and Kuhr, W. G., “Generation of Biotin/Avidin/Enzyme Nanostructures with Maskless Photolithography,” Analytical Chemistry, Vol. 69, No. 14, pp. 2619-2625, 1997.
Folch, A., and Schmidt, M. A., “Wafer-Level In-Registry Microstamping,” IEEE Journal of Microelectromechanical Systems, Vol. 8, No. 1, pp. 85-89, 1999.
Guschin, D., Yershov, G., Zaslavsky, A., Gemmell, A., Shick, V., Proudnikov, D., Arenkov, P., and Mirzabekov, A., “Mannual Manufacturing of Oligonucleotide, DNA, and Protein Microchips,” Analytical Biochemistry, Vol. 250, pp. 203-211, 1997.
Kane, R. S., Takayama, S., Ostuni, E., Ingber, D. E., and Whitesides, G. M., “Patterning Proteins and Cells using soft lithography,” Biomaterials, Vol. 20, pp. 2363-2376, 1999.
Kebarle, P., and Tang, L., “From Ions in Solution to Ions in the Gas Phase,” Analytical Chemistry, Vol. 65, pp. 972-986, 1993.
Kothe, D. B., Rider, W. J., Mosso, S. J., and Brock, J. S., “Volume Tracking of Interfaces Having Surface Tension in Two and Three Dimensions,” 34th Aerospace Science Meeting and Exhibit, AIAA-96-0859, 1996.
Kumar, A., and Whitesides, G. M., “Features of Gold Having Micrometer to Centimeter Dimensions Can Be Formed through a Combination of Stamping with an Elastomeric Stamp and an Alkanethiol ‘Ink’ Followed by Chemical Etching," Applied Physical Letters, Vol. 63, No. 14, pp. 2002-2004, 1993.
Kumar, A., Biebuyck, H., and Whitesides, G. M., “Patterning Self-Assembled Monolayers: Applications in Materials Science,” Langmuir, Vol. 10, pp. 1498-1511, 1994.
Lee, K.B., Park, S.J., Mirkin, C.A., Smith, J.C., and Mrksich, M., “Protein Nanoarrays Generated by Dip-Pen Nanolithography,” Science, Vol. 295, pp. 1702-1705, 2002.
Libioulle, L., Bietsch, A., Schmid, H., Michel, B., and Delamarche, E., “Contact-Inking Stamps for Microcontact Printing of Alkanethiol on Gold,” Langmuir, Vol. 15, pp. 300-304, 1999.
Lin, S.C., Tseng, F.G., Huang, H.M., Huang, C.Y., and Chieng, C.C., “Microsized 2D Protein Arrays Immobilized by Micro-Stamps And Micro-Wells for Disease Diagnosis And Drug Screening,” Fresenius J. of Analytical Chemistry, Vol. 371, pp. 202-208, 2001.
Lueking, A., Horn, M., Eickhoff, H., B ssow, K., Lehrach, H., and Walter, G., “Protein Microarrays for Gene Expression and Antibody Screening,” Analytical Biochemistry, Vol. 270, pp. 103-111, 1999.
Martin, B. D., Gaber, B. P., Patterson, C. H., and Turner, D. C., “Direct Protein Microarray Fabrication Using a Hydrogel ‘Stamper’,” Langmuir, Vol. 14, No. 15, pp. 3971-3975, 1998.
Mendoza, L. G., McQuary, P., Mongan, A., Gangadharan, R., Brignac, S., and Eggers, M., “High-Throughput Microarray-Based Enzyme-Linked Immunosorbent Assay (ELISA),” BioTechniques, Vol. 27, No. 4, pp. 778-788, 1999.
Morozov, V. N., and Morozova, T. Ya., “Electrospray Deposition as a Method to Fabricate Functionally Active Protein Films,” Analytical Chemistry, Vol. 71, pp. 1415-1420, 1999.
Morozov, V. N., and Morozova, T. Ya., “Electrospray Deposition as a Method for Mass Fabrication of Mono- and Multicomponent Microarrays of Biological and Biologically Active Substances,” Analytical Chemistry, Vol. 71, pp. 3110-3117, 1999.
Mooney, J. F., Hunt, A. J., Mcintosh, J. R., Liberko, C. A., Walba, D. M., and Rogers, C. T., “Patterning of Functional Antibodies and Other proteins by Photolithography of Silane Monolayers,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, pp. 12287-12291, 1996.
Nilsson, S., Lager, C., Laurell, T., and Birnbaum, S., “Thin-Layer Immunoaffinity Chromatography with Bar Code Quantitation of C-Reactive Protein,” Analytical Chemistry, Vol. 67, pp. 3051-3056, 1995.
Piner, R.D., Zhu, J., Xu, F., Hong, S., and Mirkin, C.A., “Dip-Pen Nanolithography,” Science, Vol. 283, pp. 661-663, 1999.
Rider, W. J., and Kothe, D. B., “Stretching and Tearing Interface Tracking Methods,” 33rd Aerospace Science Meeting and Exhibit, AIAA-95-1717, 1995.
Spellman, P. T., Sherlock, G., Zhang, M. Q., Iyer, V. R., Anders, K., Eisen, M. B., Brown, P. O., Botstein, D., and Futcher, B., “Comprehensive Identification of Cell Cycle-Regulated Genes of the Yeast Saccharomyces Cerevisiae by Microarray Hybridization,” Molecular Biology of the Cell, Vol. 9, pp. 3273-3297, 1998.
Tseng, F.G., Lin, S.C., Huang, H.M., Huang, C.Y., and Chieng, C.C., “Protein Micro Arrays Immobilized by μ-Stamps And -Protein Wells on PhastGel® pad,” Sensors and Actuators B, Vol. 83, pp. 22-29, 2002.
Xia, Y., Tien, J., Qin, D., and Whitesides, G. M., “Non-Photolithographic Methods for Fabrication of Elastomeric Stamps for Use in Microcontact Printing,” Langmuir, Vol. 12, pp. 4033-4038, 1996.
黃朝裕， ”壓印式蛋白質微陣列晶片之印台研發，” 清華大學工程與系統科學所碩士論文，2001。