| 研究生: |
李政庭 Li, Cheng-Ting |
|---|---|
| 論文名稱: |
毛細力微流體晶片的製作與在血液凝固檢測的應用 A study on the fabrication of capillary microfluidic chip and it’s application to blood coagulation inspection |
| 指導教授: |
鍾震桂
Chung, Cheng-Kuei |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 機械工程學系 Department of Mechanical Engineering |
| 論文出版年: | 2011 |
| 畢業學年度: | 99 |
| 語文別: | 中文 |
| 論文頁數: | 93 |
| 中文關鍵詞: | 毛細力晶片 、電容 、血液凝固 |
| 外文關鍵詞: | capillary pump chip, capacitance, blood coagulation |
| 相關次數: | 點閱:117 下載:0 |
| 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 |
微流體實驗室晶片(Lab on a chip)的主要應用為生醫檢測或混合器(mixer)等,其中微流體晶片運用在生醫檢測的最主要的目的是將傳統複雜的檢測步驟給簡化,並透過微流道與電極的設計使檢體在晶片內混合、反應而最終即可得到所需的結果。大部分微流體的驅動均需額外輸入能量,如針筒式幫浦(Syringe pump)等等。本文實驗所使用皆為不需額外輸入能量之毛細驅動晶片,利用材料親水的特性產生之毛細力,讓流體在微流道中達到自驅動。本研究將微流體晶片應用於血液凝固時間的量測並做探討,在本文的微流體晶片製作上,使用玻璃當作基材,因為玻璃有良好的親水特性將可得到長時效毛細驅動晶片。晶片電極的設計則採用上下電極並與微流道整合成電容式(Capacitive)微流體晶片。優點在於樣本不須與電極直接接觸,其量測原理利用微流體在晶片內流動使晶片的電容值隨流體的流動而產生變化,並搭配使用HP 4194A阻抗分析儀與LabVIEW介面來觀測電容變化,並再使用MATLAB做訊號處理判斷出血液凝固的時間。
由實驗結果得知使用長時效毛細晶片所量測的全血凝固時間約為8分36秒~9分28秒,此時間符合內路徑到共同路徑所需的5-12分鐘。之後加入高嶺土量測血液凝固時間得到的結果明顯的縮短,由於高嶺土有加速凝血內路徑反應的作用,所以此現象非常合理。最後則加入肝素量測,因為肝素會阻止血液凝固反應,而量測的血液凝固時間也延長數倍之久。這些結果驗證毛細力晶片量測血液凝固時間是可行的。而使用電容式毛細晶片所量測全血凝固時間約9分5秒,加入高嶺土之後也有縮短凝固時間的趨勢。這些結果都符合血液凝固的特性。實驗中驗證了藉著電容訊號可以清楚判斷每個階段反應所造成的訊號變化,證明了電容式晶片量測血液凝固時間的可行性,最後若能將此電容晶片整合其它應用則將可使此晶片有更好的發展。
The major application for microfluidic Lab on a chip has been focused on the biomedical test and fluid mixing. It aimed to simplify the traditional complicated fabrication and test procedures on the Lab on a chip, and design the microchannels together with electrodes so as to make the chip work on the fluid mixing, reactions and obtaining the results. Most microfluidic flow requires external pump for fluid transportation e.g., syringe pump. This thesis focuses on the capillary-driven chip which does not need any external power to push the flow. In addition, we adopt the hydrophilicity of the material in making the chip in order to get the self-driven mechanism of flow in microchannels. We study on the coagulation time of blood in the chip. In this thesis, we also propose the fabrication procedures of chip by using glass as the substrate. Glass materials play an important role in possessing good property of hydrophilicity and making a long-term self-driven capillary chip. The electrodes are placed on top and bottom of glasses and integrated in a capacitive microfluidic chip. The advantages of the capacitive chip are to measure the variations of capacitance against the flows in the channels and avoid the contact of samples with the electrodes. Using HP 4194A and LabVIEW are able to observe the variations of capacitances, and with the aid of Matlab, we can perform the signal process method to calculate the coagulation time of blood in the chip.
From the results, we obtain the coagulation time of whole blood in the capillary chip to be around 8’ 36” ~ 9’ 28”, which is in accordance with the results of 5-12 mins from intrinsic pathway to common pathway. We also perform the experiment by adding kaolin in the blood samples in order to measure the coagulation time. The result shows the coagulation time has been significantly shortened up. This is because kaolin will speed up the reaction mechanism of coagulation intrinsic pathway. Such a phenomenon has been well-known in the literature. For the purpose of comparisons, we measure the coagulation time by adding heparin in the blood samples. The final coagulation time has been reached to show that it is feasible to use the capillary chip in measuring the coagulation of blood in the chip.The whole blood coagulation time has been reported to be 9’ 05” by using our capacitive capillary chip. Moreover, the addition of kaolin also shows the significant blood coagulation time in the chip. Our experiments show the characteristic of blood coagulation in the capacitive capillary chip. By analyzing the signals of capacity, we are able to judge the reaction of blood in the channels on every time point. It not only shows the feasibility of the capacitive capillary chip in measuring the coagulation time but also the potentials in a wide application to the biomedicine.
1. Dong Sung Kim, Se Hwan Lee, Chong H. Ahn, Jae Y. Lee and Tai Hun Kwon, “Disposable integrated microfluidic biochip for blood typing by plastic microinjection moulding”, Lab on a Chip, 6 794-802, 2006.
2. Ronald R. Lamonte and Donal McNally, “Cyclic olefin copolymers”, Advanced materials & Processes, 2001.
3. Lidong Qin, Ophir Vermesh, Qihui Shi and James R. Heath, “Self-powered microfluidic chips for multiplexed protein assays from whole blood”, Lab on a Chip, 9 2016-2020, 2009.
4. Y.C Fung, “Stochastic flow in capillary blood-vessels”, Microvascular Research, 5 34-38, 1973.
5. E. Engvall and P. Perlmann, “Enzyme-Linked Immunosorbent Assay (ELISA) Quantitative Assay of Immunoglbulin-g”, Immunochemistry, 8 871-874, 1971.
6. Helen Song, Hung-Wing Li, Matthew S. Munson, Thuong G. Van Ha and Rustem F. Ismagilov, “On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System”, Analytical Chemistry, 78 4839-4849, 2006.
7. Yan-You Lin, Randall D. Evans, Erin Welch, Bang-Ning Hsu, Andrew C. Madison and Richard B. Fair, “Low voltage electrowetting-on-dielectric platform using multi-layer insulators”, Sensors and Actuators B, 150 465-470, 2010.
8. A. A. Kornyshev, A. R. Kucernak, M. Marinescu, C. W. Monroe, A. E. S. Sleightholme and M. Urbakh, “Ultra-Low-Voltage Electrowetting”, J. Phys. Chem. C, 114 14885–14890, 2010.
9. Zhaowei Zhang, Xiaojun Feng, Qingming Luo and Bi-Feng Liu, “Environmentally friendly surface modification of PDMS using PEG polymer brush”, Electrophoresis, 30 3174–3180, 2009.
10. Salim Bouaidat, Ole Hansen, Henrik Bruus, Christian Berendsen, Niels Kristian Bau-Madsen, Peter Thomsen, Anders Wolff and Jacques Jonsmann, “Surface-directed capillary system; theory, experiments and applications”, Lab on a Chip, 5 827-836, 2005.
11. Hyejin Moon, Sung Kwon Cho, Robin L. Garrell and Chang-Jin Kim “Low voltage electrowetting-on-dielectric”, Journal of applied physics, 92 4080-4087, 2002.
12. C. Channy Wong, Douglas R. Adkins and Dahwey Chu, “Development of a micropump for microelectronic cooling”, Microelectromechanical System, 59, 1996.
13. Si-Hong Ahn and Yong-Kweon Kim “Fabrication and experiment of a planar micro ion drag pump”, Sensors and Actuators A, 70 1-5, 1998.
14. Jeff Darabi, Member, IEEE, Mihai Rada, Michael Ohadi, and John Lawler “Design, Fabrication, and Testing of an Electrohydrodynamic Ion-Drag Micropump”, Journal of Microelectromechanical System, 11 684-690, 2002.
15. Akinori Furuya, Fusao Shimokawa, Tohru Matsuura and Renshi Sawada, “Fabrication of fluorinated polyimide microgrids using magnetically controlled reactive ion etching (MC-RIE) and their applications to an ion drag integrated micropump”, Journal of Micromechanics and Microengineering, 6 310-319, 1996.
16. D J Laser and J G Santiago, “A review of micropumps”, Journal of Micromechanics and Microengineering, 14 R35-R64, 2004.
17. W. Huang, Q. Liu and Y. Li, “Capillary filling flows inside patterned-surface microchannels”, Chemical Engineering and Technology, 29 827-836, 2006.
18. Shuhuai Yao, David E. Hertzog, Shulin Zeng, James C. Mikkelsen Jr. and Juan G. Santiago, “Porous glass electroosmotic pumps: design and experiments”, Journal of Colloid and Interface Science, 268 143-153, 2003.
19. Andrew Machauf, Yael Nemirovsky and Uri Dinnar, “A membrane micropump electrostatically actuated across the working fluid”, Journal of Micromechanics and Microengineering, 15 2309-2316, 2005.
20. M Elwenspoek, T. S. J. Lammerink, R. Miyakei and J. H. J. Fluitman, “Towards integrated microliquid handling systems”, Journal of Micromechanics and Microengineering, 4 227-245, 1994.
21. T.Y. Ng, T.Y. Jiang, Hua Li, K.Y. Lam and J.N. Reddy, “A coupled field study on the non-linear dynamic characteristics of an electrostatic micropump”, Journal of Sound and Vibration, 273 989-1006, 2004.
22. Olivier Fraqais and Isabelle Dufour, “Dynamic simulation of an electrostatic micropump with pull-in and hysteresis phenomena”, Sensors and Actuators A, 70 56-60, 1998.
23. Sebastian Bohm , Wouter Olthuis and Piet Bergveld, “A plastic micropump constructed with conventional techniques and materials”, Sensors and Actuators A, 77 223-228, 1999.
24. Mir Majid Teymoori and Ebrahim Abbaspour-Sani, “Design and simulation of a novel electrostatic peristaltic micromachined pump for drug delivery applications”, Sensors and Actuators A, 117 222-229, 2005.
25. Dae-Sik Leea, Jong Soo Koa and Youn Tae Kim, “Bidirectional pumping properties of a peristaltic piezoelectric micropump with simple design and chemical resistance”, Thin Solid Films, 117 285-290, 2004.
26. Michael Koch, Nick Harris, Alan G.R. Evans, Neil M. White and Arthur Brunnschweiler, “A novel micromachined pump based on thick-film piezoelectric actuation”, Sensors and Actuators A, 70 98-103, 1998.
27. J. H. Tsai and L. W. Lin, “A Thermal bubble actuated micronozzle-diffuser pump”, Proceedings of the IEEE Micro Electro Mechanical Systems (MEMS), 409-412, 2001.
28. J. H. Tsai and L. W. Lin, “A Thermal-bubble-actuated micronozzle-diffuser pump”, Journal of Microelectromechanical systems, 11 665-671, 2002.
29. Eiji Makino, Takayuki Shibata and Kazuhiro Kato, “Dynamic thermo-mechanical properties of evaporated TiNi shape memory thin film”, Sensors and Actuators A, 78 163-167, 1999.
30. Eiji Makino, Takashi Mitsuya and Takayuki Shibata, “Fabrication of TiNi shape memory micropump”, Sensors and Actuators A, 88 256-262, 2001.
31. Yuta Nakashima, Sakiko Hata and Takashi Yasuda, “Blood plasma separation and extraction from a minute amount of blood using dielectrophoretic and capillary forces”, Sensors and Actuators B, 145 561-569, 2010.
32. Matthew S. Pommer, Yanting Zhang, Nawarathna Keerthi, Dong Chen, James A. Thomson, Carl D. Meinhart and Hyongsok T. Soh, “Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels”, Electrophoresis, 29 1213-1218, 2008.
33. Timothy A. Crowley and Vincent Pizziconi, “Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications”, Lab on a Chip, 5 922-929, 2005.
34. Joon S. Shim, Andrew W. Browne and Chong H. Ahn, “An on-chip whole blood/plasma separator with bead-packed microchannel on COC polymer”, Lab on a Chip, 12 949-957, 2010.
35. Angeles Ivon Rodriguez-Villarreal, Martin Arundell, Manuel Carmonaab and Josep Samitier, “High flow rate microfluidic device for blood plasma separation using a range of temperatures”, Lab on a Chip, 10 211-219, 2010.
36. Lucy A. Norris, “Blood coagulation”, Best Practice & Research Clinical Obstetrics & Gynaecology, 17 369-383, 2003.
37. Rong Fan, Ophir Vermesh, Alok Srivastava, Brian K H Yen, Lidong Qin, Habib Ahmad, Gabriel A Kwong, Chao-Chao Liu, Juliane Gould, Leroy Hood and James R Heath, “Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood”, Nature Biotechnology, 26 1373-1378, 2008.
38. Venkat ram Dukkipati, Ji Hoon Kim, Stella W. Pang, and Ronald G. Larson, Chao-Chao Liu, Juliane Gould, Leroy Hood and James R Heath, “Protein-Assisted Stretching and Immobilization of DNA Molecules in a Microchannel”, Nano Letters, 6 2499-2504, 2006.
39. Maiwenn Kersaudy-Kerhoas, Deirdre M. Kavanagh, Resham S. Dhariwal, Colin J. Campbell and Marc P. Y. Desmulliez, “Validation of a blood plasma separation system by biomarker detection”, Lab on a Chip, 10 1587-1595, 2010.
40. L. Metref, F. Bianchi, V. Vallet, N. Blanc, R. Goetschmann and P. Renaud, “Microfluidic System Based on Thermoexpandable Polymer for on Chip Blood Coagulation Testing”, Micro and Nanosystems, 1 41-45, 2009.
41. Helen Berney and J.J. O'Riordan, “Impedance Measurement Monitors Blood Coagulation”, Analog Dialogue, 2008.
42. Ki-Ho Han and A. Bruno Frazier, “Paramagnetic capture mode magnetophoretic microseparator for high efficiency blood cell separations”, Micro and Nanosystems, 6 265-273, 2006.
43. Bai-Yan Qu, Zhi-Yong Wu, Fang Fang, Zhi-Ming Bai, Dong-Zhi Yang and Shu-Kun Xu, “A glass microfluidic chip for continuous blood cell sorting by a magnetic gradient without labeling”, Analytical and bioanalytical chemistry, 392 1317-1324, 2008.
44. Wolfgang-Andreas C. Bauer, Martin Fischlechner, Chris Abellb and Wilhelm T. S. Huck, “Hydrophilic PDMS microchannels for high-throughput formation of oil-in-water microdroplets and water-in-oil-in-water double emulsions”, Lab on a Chip, 10 1814-1819, 2010.
45. Clarissa Lui, Scott Stelick, Nathaniel Cadyc and Carl Batt, “Low-power microfluidic electro-hydraulic pump (EHP)”, Lab on a Chip, 10 74-79, 2010.
46. Jean-François Dhainaut, S. Betty Yan, Benjamin D. Margolis, Jose A. Lorente, James A. Russell, Ross C. Freebairn, Herbert D. Spapen, Hanno Riess, Bruce Basson, Gerald Johnson III and Gary T. Kinasewitz, “Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis”, Thromb Haemost, 90 642-653, 2003.
47. J. Margolis, “The kaolin clotting time”, J. clin. Path., 11 406-409, 1958.
48. C.K. Chung, Y.C. Sung, G.R. Huang, E.J. Hsiao, W.H. Lin and S.L. Lin, “Crackless linear through-wafer etching of Pyrex glass using liquid-assisted CO2 laser processing”, Applied Physics A, 94 927-932, 2009.
49. Ye Gu and Norihisa Miki, “A microfilter utilizing a polyethersulfone porous membrane with nanopores”, Journal of Micromechanics and Microengineering, 17 2308-2315, 2007.
50. Joo-Hyung Lee, Hong-Seok Lee, Byung-Kee Lee, Won-Seok Choi, Hwan-Young Choi and Jun-Bo Yoon, “Simple liquid crystal display backlight unit comprising only a single-sheet micropatterned polydimethylsiloxane (PDMS) light-guide plate”, Optics Letters, 32 2665-2667, 2007.
51. P. Harder, M. Grunze, R. Dahint, G. M. Whitesides and P. E. Laibinis, “Molecular conformation in Oligo(ethylene glycol)-terminated Self-Assembled Monolayers on gold and silver surfaces determines their ability to resist protein adsorption”, Journal of Physical Chemistry B, 102 426-436, 1998.
52. 陳家成,以電阻抗分析法測量人類全血凝固時間,成功大學碩士論文,2005.
53. 陳育聖,新型菱形混合器與毛細驅動晶片設計與製作,成功大學碩士論文,2009.
54. 張恩旗,毛細力驅動流體晶片的設計和混合應用,成功大學碩士論文,2010.
55. George J. Despotis, Alexander L. Alsoufiev, Edward Spitznagel, Lawrence T. Goodnough and Demetrios G. Lappas, “Response of Kaolin ACT to Heparin: Evaluation With an Automated Assay and Higher Heparin Doses”, Annals of thoracic surgery, 61 795-799, 1996.
校內:2021-12-31公開