| 研究生: |
黃朝均 Huang, Chao-June |
|---|---|
| 論文名稱: |
整合微流體之葡萄糖檢測及自動化胰島素注射系統 Integrated Microfluidic Systems for Glucose Sensing and Automatic Insulin Injection |
| 指導教授: |
李國賓
Lee, Gwo-Bin |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 微機電系統工程研究所 Institute of Micro-Electro-Mechancial-System Engineering |
| 論文出版年: | 2006 |
| 畢業學年度: | 94 |
| 語文別: | 中文 |
| 論文頁數: | 100 |
| 中文關鍵詞: | 微流體 、微機電系統 、胰島素注射 、微幫浦 、微閥門 、葡萄糖感測器 |
| 外文關鍵詞: | micropump, microfluidics, MEMS, glucose sensor, microvalve, insulin injection |
| 相關次數: | 點閱:116 下載:7 |
| 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 |
摘 要
本研究成功地利用微機電系統製程技術,發展可即時血糖監控並自動化胰島素注射的微流體系統,此微流體系統包含一微流體晶片(Microfluidic Chip)和可攜式的微流體控制器,其中包含空氣壓縮機、幫浦可程式控制系統和電磁閥。微流體晶片由上板微流體操控元件和下板感測電極兩個部分封裝完成,上板微流體操控元件包含微流管道、氣動式微幫浦與微閥門,係以聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)材料製作,利用微流體控制器將壓縮空氣注入PDMS薄膜中,使PDMS薄膜產生幫浦和閥門的效果,下板感測電極包含葡萄糖感測電極和流速感測電極,葡萄糖電極是定電流的方式,利用導電性高分子材料,將葡萄糖氧化酵素(GOD)電聚合在鉑電極上以進行電化學檢測,再將測得的葡萄糖值換算成血糖的濃度,以進行血糖的監控。
和傳統的血糖檢測儀器比較,本系統除了能夠連續地檢測血糖濃度之外,搭配本晶片中商用的留滯針、新型微幫浦和微閥門等微流體控制元件和流速感測器,可以自動精準的進行胰島素注射,以保持血液中的葡萄糖濃度在正常的範圍。
本研究希望能藉由此系統的發展,省去過去糖尿病病患使用血糖計測量完之後仍須自行進行胰島素注射的種種不便,改善眾多糖尿病病患其生活品質。
Abstract
This paper presents a new microfluidic system capable of real-time measurement of glucose concentration and automatic insulin injection. The microfluidic system is composed of a microfluidic chip, a measurement and control circuit system, a compressed air source, and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using microfluidic techniques comprising of glucose sensing electrodes, a flow sensor, and polydimethylsiloxane (PDMS)-based microfluidic structures such as micropumps, microvalves, and microchannels. Commercially available needles are incorporated for continuous glucose monitoring and long-term insulin injection. The microfluidic system performs a variety of processes including blood sample collection, glucose concentration detection, and injection of insulin. Micropumps and microvalves are used to perform the whole process automatically. The valve switching and pumping effects are generated utilizing compressed air to deform thin PDMS membranes. Compared with traditional glucose monitoring platforms, the developed system can be used for on-line monitoring of glucose concentration and precise injection of proper doses of insulin, in order to maintain a stable glucose concentration in human blood. The developed microfluidic system could become a crucial tool for diabetes patients in the future.
參考文獻
1.R. Feynman, “There’s Plenty of Room at the Bottom”, Journal of Micro Electro Systems, Vol. 1, pp. 60-66, 1992.
2.R. Feynman, “Infinitesimal Machinery”, Journal of Micro Electro Mechanical Systems, Vol. 2, pp. 4-14, 1993.
3.C. B. Epstein and R. A. Butow, “Microarray Technology - Enhanced Versatility, Persistent Challenge”, Current Opinion in Biotechnology, Vol. 11, pp. 36-41, 2000.
4.G. H. W. Sanders and A. Manz, “Chip-based Microsystems for Genomic and Proteomic Analysis”, Trends in Analytical Chemistry, Vol. 19, pp. 364-378, 2000.
5.K. Sato, A. Hibara, M. Tokeshi, H. Hisamoto and T. Kitamori, “Microchip-based Clinical and Biochemical Analysis System”, Journal of Chromatography A, Vol. 987, pp. 197-204, 2003.
6.A. C. R. Grayson, R. S. Shawgo, Y. Li, and M. J. Cima, “Electronic MEMS for Triggered Delivery”, Advanced Drug Delivery Reviews, Vol. 56, pp. 173-814, 2004.
7.A. Manz, N. Graber and H. M. Widmer, “Miniaturized Total Chemical Analysis System: A Novell Concept for Chemical Sensing”, Sensors and Actuators B, Vol. 1, pp. 244-248, 1990.
8.J. H. Tsai and L. Lin, “A Thermal Bubble Actuated Micro Nozzle-Diffuser Pump”, IEEE MEMS-2001 Conference, Interlaken, Switzerland, 409, Vol. 11, pp. 665-671, 2001.
9.J. Lopez, M. Puig-Vidal, M. Carmona, C. Stamopoulos, T. Laopoulos, and S. Siskos, “Temperature Control Configurations for a Thermopneumatic Micropump”, IEEE MEMS’99, Orland, FL, USA, pp. 827-830, 1999.
10.R. Linnemann, P. Woias, C. D. Senfft, and J. A. Ditterich, “A Self-priming and Bubble-tolerant Piezoelectric Silicon Micropump for Liquids and Gases”, IEEE MEMS, Heidelberg, Germany, pp. 532-537, 1998.
11.R. Zengerle, J. Ulrich, S. Kluge, M. Richter and A. Richter, “A bidirectional silicon micropump,” Sensors and Actuators A: Physical, Vol. 50, pp. 81-86, 1995.
12.M. A. Unger, H. P. Chou and T. Thorsen, A. Scherer and S. R. Quake, “Monolithic Microfabricated Valve and Pumps by Multilayer Soft Lithography”, Science, Vol. 288, pp. 113-116, 2000.
13.A. Richter, A. Plettner, K. A. Hofmann, H. Sandmaier: “A micromachined electrohydrodynamic (EHD) pump”, Sensors and Actuators A, Vol. 29, pp. 159-168, 1991.
14.A. Manz, C. S. Effenhauser, N. Burggraf, D. J. Harrison, K. Seiler, and K. Flurri, “Electroosmotic pumping and electrophoretic separations for miniaturized chemical analysis system”, Journal of Micromechanics and Microengineering, Vol. 4, pp. 257-265, 1994.
15.L. Smiht and B. Hok, “A Silicon Self-Aligned Non-Reverse Valve”, Transducers ’91, San Franscisco, CA, USA, pp. 1049-1051, 1991.
16.C. Vieider, O. Ohman, and H.elderstig, “A Pneumatically Actuated Micro Valve with a Silicone Rubber Membrane for Integration with Fluid-handling Systems”, Proc. of Transducers ’95, Stockholm, Swede, pp. 284-286, 1995.
17.M. A. Huff, J. Gilbert, and M. Schmidt, “Flow characteristics of a pressure balanced microvalve”, Proc. The lnternational Conference on Solid state Actuators (Transducers), Yokohama, Japan, June, pp. 98-101, 1993.
18.L. C. Clark, Jr., and C. Lyons, “Electrode System for Continuous Monitoring in Cardiovascular Surgery”, Ann. NY Acad. Sci., 148, pp.133-135, 1962.
19.S. J. Updick, and G. P. Hicks, “The Enzyme Electrode, a Miniature Chemical Transducer Using Immobilized Activity”, Nature vol. 214, pp. 986-988 (1967).
20.L. C. Clark, “Jr. Membrane Polarographic Electrode System and Method with Electrochemical Compensation”, U. S. Patent (1970) No. 3, 539455.
21.A. H. Clemens, P. H. Chang, R. W. Myers, “The Development of Biosensor, a Glucose Controller Insulin Infusion System (GCIIS), Horm. Metab”, Res. Suppl., Vol. 7, pp. 22-23, 1977.
22.J. I. Peterson and S. R. Goldstein, “A miniature fiberoptic pH sensor potentially suitable for glucose measurements”, Diabetes Care Vol. 5, pp. 272-274, 1982.
23.N. C. Foulds and C. R. Lowe, J. Chem. Soc. Faraday Trans., 1, 82, 1259, 1986.
24.J. Michael, O’Brien Π, Brueck S. R. J. Victor H. Perez-Luna, Leonard M. Tender, Gabriel P. Lopez, “SPR Biosensor: Simultaneously Removing Thermal and Bulk-Composition Effects”, Biosensors & Bioelectronics Vol. 14, pp. 145-154, 1999.
25.W. Jian, J. Suls, W. Sansen, “The Glucose Sensor Integra Table in the Microchannel”, Sensors and Actuators B, Vol. 78, pp. 221-227, 2001.
26.J. D. Newman, A. P. F. Turner, “Home Blood Glucose Biosensors: A Commercial Perspective”, Biosensors & Bioelectronics, Vol. 20, pp. 2435-2453, 2005.
27.C. H. Wang, G. B. Lee, “Pneumatic-driven Peristaltic Micropumps Utilizing Serpentine-shape Channels”, Journal of Micromechanics and Microengineering, Vol. 16, Jan. 13, pp. 341-348, 2006.
28.L. H. He, C. W. Lim and B. S. Wu, “A Continuum Model for Size-dependent Deformation of Elastic Films of Nano-scale Thickness”, International Journal of Solids and Structures, 41, pp. 847-857, 2004.
29.S. Timosheko, “Theory of Plate and Shells”, McGraw-Hill, New York, USA, 1970.
30.汪玉銘, “電流聚合導電性高分子流製備葡萄糖生物感測器之研究”, 國立成功大學化學工程研究所博士論文, 2003.
31.A. J. Bard and L. R. Faulkner, “Electrochemical Methods Fundaments and Applications”, Wiley, New York, 1980.
32.J. Parellada, A. Narvaez, E. Dominguez and I. Katakis, “A New Type of Hydrophilic Carbon Paste Electrodes for Biosensor Manufacturing: Binder Paste Electrodes”, Biosensors and Bioelectronics, Vol. 12, No. 4, pp. 267-275, 1997.
33.G. G. Quilbault and J. G. Jr. Montalvo, “A Area-Specific Enzyme Electrode”, J. Am. Chem. Soc., 91 pp. 2164-2165, 1969.
34.S. M. Reddy and P. Vadgama, “Entrapment of GODx in Nonporous PVC”, Analytica. Chimica Acta, 461, pp. 57-64, 2002
35.R. Vaidya and E. Wilkins, “Effect of Interference of Amperometric Glucose Biosensor with Cellulose Acetate Membrane”, Electroanalysis, 6, pp. 677-682, 1994.
36.J. Li, L. S. Chia, N. K. Goh, S. N. Tan, “Renewable Silica Sol-Gel Derived Composite Based Glucose Biosensor”, J. Electroanal. Chem., Vol. 460, pp. 234-241, 1999.
37.M. Umaoa and J. Waller, Anal. Chem., 58, 2979, 1986.
38.Y. M. Uang and T. C. Chou, “Fabrication of the galvanostatic polypyrrole/glucose oxidase biosensor in various pH aqueous solutions”, Biosensors & Bioelectronics, 19, pp. 141-147, 2003.
39.Tamiya E., Siura Y., Akiyama A. and Karube I., “Ultramicro-H2O2 electrode for fabrication of the in vivo biosensor. Ann. NY Acad. Sci., Vol. 613, pp. 396-400, 1990.
40.S. Mu, H. Xuo, “Bioelectrochemical Characteristics of Glucose Oxidase Immobilized in a Polyaniline Film”, Sensor and Actuators B, 31, pp. 155-160, 1996.
41.M. Lemaire, R.Garreau, J. Roncali, D. Delabouglise, H. K. Youssfi and F. Garnier, “Design of Polythiophene Containing Oxyalky Substituents”, New J. Chem., 13, 836, 1989.
42.Panddy P. C., J. Chem. Soc. Faraday Trans., 1, 84,2259, 1998.
43.G. B. Lee, J. H. Hu, and J. J. Miau, “A flexible skin with temperature sensor array,” Journal of the Chinese Institute of Engineers, 2002.
44.李正中,薄膜光學與鍍膜技術,2 版,藝軒圖書出版社,P276-278,90 年元月。
45.Data Sheet for NANOTM SU-8 Negative Tone Photoresists, Formulations 50 & 100, released by MICRO-CHEM. Corp.
46.K. Hosoya, K. Yoshizako, Y. Shirasu, K. Kimata and T. Araki, “Molecularly imprinted uniform-size polymer-based stationary phase for high performance liquid chromatography structural contribution of cross-linked polymer network on specific molecular recognition”, Journal of Chromatography A, 728, pp. 139-147,1996.
47.B. E. Slentz, N. A. Penner and F. E. Regnier, “Capillary Electrochromatography of Peptides on Microfabricated Poly(dimethylsiloxane) Chips Modified by Cerium(IV)-catalyzed Polymerization,” Journal of Chromatography A, Vol. 948, pp. 225–233, 2002.
48.戴健軒, “細胞分離及細胞核萃取之自動化晶片平台”, 國立成功大學工程科學研究所碩士論文, 2005.