本研究利用微機電製程技術，設計並製作出一個利用電動力操控的微流體生醫晶片。首先研究出電動式微流體進樣1×N（1：檢測液注射端、N：檢測液出口端）和M×N（M：檢測液注射端、N：檢測液出口端）兩組微流體晶片。這個新式的微流體晶片整合了兩種重要的輸送微流體現象，即是電動集中效應和無閥式開關切換之功能。實驗的結果顯示，樣品流可以被預先集中成一個範圍較小的帶寬，然後連續地被引導入預期的出口端。
流式細胞/顆粒計數器及分類器已廣泛地應用在生醫研究等相關領域。微流體生醫晶片整合光纖元件可作為細胞即時之偵測，利用電動力去集中樣品流的帶寬與操控其導入位置，可以使整個微流體系統更微小化。本微流體系統整合了幾個關鍵的模組，包含電動集中裝置、控制電極的建立、光學偵測裝置及電動開關切換裝置。實驗結果顯示，可以成功地計數及收集細胞和顆粒。

A novel microfluidic device for cell/particle counting and sorting is designed and fabricated. The chip is fabricated on soda-line glass substrates using MEMS technologies. The numerical and experimental investigation into electrokinetic focusing flow injection for bio-analytical applications on 1´N (i.e. 1 sample inlet port and N outlet ports) and M´N (i.e. M sample inlet ports and N outlet ports) microfluidic chips are performed. The device integrates two important microfluidic phenomena, namely electrokinetic focusing and valve-less flow switching within multi-ported microchannels. Experimental results show the samples may be pre-focused electro-kinetically into a narrow stream prior to being injected continuously into specified outlet ports.
The microfluidic device is then used as a flow cytometer, which is a general method for analyzing micro-particles such as cell, bacteria and even euglena with high efficiency. The microfluidic chip is integrated with buried optical fibers for on-line cell/particle detection. Instead of using hydrodynamic forces, the device uses electrokinetic forces for flow focusing and sample switching, resulting in a compact microfluidic system and easier integration process. Several critical modules have been integrated to form the device, including electrokinetic focusing devices, built-in control electrodes, buried optical fibers for on-line detection, and electrokinetic flow switches for bio-particles collection. Experimental data show that successful cell counting and sorting could be achieved.

1. Probstein, R. F., Physicochemical Hydrodynamics: An Introduction, 2nd ed.; Wiley and Sons: New York, 1994.
2. Gravesen, P., Branebjerg, O. J. and Jensen, S. “Microfluidics – a Review,” Journal of Micromechanics And Microengineering, Vol. 3, 168-182, 1993.
3. Shoji, S., “Microfabrication Technologies and Micro-flow Devices for Chemical and Bio-chemical Micro Flow Systems, ”Microprocesses and Nanotechnology '99, 72 –73, 1999.
4. Harrison, D. J. and Berg, A., “Micro Total Analysis Systems ’98,” Kluwer Academic Publishers, Netherlands 1998.
5. Manzs, A., Graber, N., Widmer, H. M., Sens. Actuators B1, 244-248, 1990.
6. Lee, G. B., Lin, C. H. Chang, G. L., "Micro Flow Cytometers With Buried Su-8/Sog Optical Waveguides," accepted for publishing, Sensors and Actuators A, 2002.
7. Heller, C., “Principles of DNA separation with capillary electrophoresis ,” Electrophoresis, 22, 629-643, 2001.
8. Varpoorte, E., “Microfluidic chips for clinical and forensic analysis,” Electrophoresis, 23, 677-712, 2002.
9. Rochu, D., Masson, P., “Multiple advantages of capillary zone electrophoresis for exploring protein conformational stability, ” Electrophoresis, 23, 189-202, 2002.
10. Rossier, J., Reymond, F., Michel, P. E., “Polymer microfluidic chips for electrochemical and biochemical analyses, ” Electrophoresis, 23, 858-867, 2002.
11. Mistry, K., Krull, I., Grinberg, N., “Capillary electrochromatography: An alternative to HPLC and CE ,” J. of Separation Science, 25, 935-958, 2002.
12. Russel, W. B., Saville, D. A., Schowalter, W. R., Colloidal Dispersion, New York, 1989.
13. Yang, R. J., Fu, L. M., Lin, Y. C., “Electroosmotic Flow in Microchannels,” J. of Colloid and Interface Science, 239, 98-105, 2001.
14. Yang, R. J., Fu, L. M., Hwang, C. -C., “Electroosmotic Entry Flow in a Microchannel” J. of Colloid and Interface Science, 244, 173-179, 2001.
15. Patankar, N. A., Hu, H. H., “Numerical Simulation of Electroosmotic Flow” Analytical Chemistry, 70, 1870-1881, 1998.
16. Erickson, D., Li, D., “Influence of Surface Heterogeneity on Electrokinetically Driven Microfluidic Mixing” Langmuir, 18, 1883-1892, 2002.
17. Cui, L., Holmes, D., Morgan, H., “The dielectrophoretic levitation and separation of latex beads in microchips” Electrophoresis, 22, 3893-3901, 2001.
18. Cui, L., Morgan, H., “Design and fabrication of travelling wave dielectrophoresis structures” J. Micromech. Microeng., 10, 72-79, 2000.
19. Woolley, A. T., Hadley, D., Landre, P., de Mello, A. J., Mathies, R. A., Northrup, M. A., “Functional Integration of PCR Amplification and Capillary Electrophoresis in a Microfabricated DNA Analysis Device” Analytical Chemistry, 68, 4081-4086, 1996.
20. Hong, J. W., Fujii, T., Seki, M., Yamamoto, T., Endo, I., Integration of gene amplification and capillary gel electrophoresis on a polydimethylsiloxane-glass hybrid microchip Electrophoresis, 22, 328-333, 2001.
21. Lin, C. H., Chang, Lee, G. B., Li, C. H., Chang, G. L., J. “A fast prototyping for fabrication of microfluidic systems on soda-lime glass “ Micromech. Microeng. 11, 726-732. 2001.
22. Fort, F., Krivankova, L., Bocek, P., Capillary zonw Electrophoresis; VCH Verlagsgesellschaft mbH; weinheim, 1993.
23. Harrison, D. J., Manz, A., Ludi, Z. H., “capillary electrophoresis and sample injection systems integrated on a planar glass chip”, Anal. Chem., 64, 1926-1932, 1992.
24 Seiler, K., Harrison, D. J., Manz, A., “Planar Glass Chip for Capillary Electrophoresis : Repetitive Sample Injection, Quantitation, Separation Efficiecy”, Anal. Chem., 65, 1481-1488, 1993.
25 Fan, Z. H., Harrison, D. J., “Micromachining of Capillary Electrophoresis Injectors and Separators on Glass Chips and Evaluation of Flow at Capillary Intersections”, Anal. Chem., 66, 177-184, 1994.
26 Effenhauser, C. S., Manz, A., “Manipulation of Sample Fraction on a Capillary Electrophoresis Chip”, Anal. Chem., 67, 2284-2287, 1995.
27 Freyer, J. P., Wilder, M. E., Schor, P. L., Coulter, J., M. R., “A Simple Electronic Volume Cell Sorter for Clonogenicity Assays,” Cytometry 10 273-281, 1989.
28 Coulter, W. H., “High speed automatic blood cell counter and size analyzer,” Proc. Natl. El. Conf. 12, 1034-1040, 1956.
29 Lee, G. B., Hung, C. I., Ke, B. J., Huang, G. R., Hwei, B. H, “Micromachined pre-focused 1×N flow switches for continuous sample injection”, J. Micromech. Microeng. 11, 567-573, 2001.
30 Lee, G. B., Hwei, B. H., Huang, G. R., “Micromachined pre-focused M×N flow switches for continuous sample injection”, J. Micromech. Microeng. 11, 654-661, 2001.
31 黃冠瑞, 高效能微流體晶片之設計製作與其在生物醫學之應用, 國立成功大學工程科學系, 2001.
32 Larsen, U. D., Blankenstein, G., Brangebjerg, J., “A Novel Design in Chemical and Biochemical Liquid Analysis System”, proc. 2nd Int. Symp. μTAS96, 113-115, 1996.
33 Blankenstein, G., Scampavia L, Branebjerg, J., Larsen, U. D., Ruzicka J “Flow switch for analyte injection and cell/particle sorting”, proc. 2nd Int. Symp. μTAS96, 82-84, 1996.
34 Lin, C. H., Lee, G. B., Hwei, B. H., “A Novel Micro Flow Cytometer with 3-Dimensional Focusing Utilizing Dielectrophoresis and Hydrodynamic Forces”, accepted for publishing, IEEE MEMS 2003.
35 Schrum, D. P., Culbertson, C. T., Jacobson, S. T., Ramsey, J. M., “Microchip Flow Cytometry Using Electrokinetic Focusing”, Anal Chem., 71, 4173-4177, 1999.
36 Lemoff, A. V., Lee, A. P., “An ac magnetohydrodynamic microfluidic switch”, proc. Total Analysis Systems 2000.
37 Fu, L. M., Yang, R. J., Gwo-Bin Lee, G. B., Pan, Y. J., “Multiple Injection Techniques for Microfluidic Sample Handling”, Electrophoresis.
38 Döring, C., Grauer, T., Marek, J., Mettner, M., Trah, H. P., Willman, M., “Micromachined thermoelectrically driven cantilever beams for fluid deflection”, proc. IEEE Micro Electro Machanical Systems Workshop, MEMS, 12-18, 1992.