簡易檢索 / 詳目顯示

研究生: 吳文豪
Wu, Wen-Hao
論文名稱: 仿微血管組織之內皮細胞培養微流體晶片用於趨化反應研究
A Capillary-Endothelium-Mimetic Microfluidic Chip for the study of Chemotactic Response
指導教授: 劉承賢
Liu, Cheng-Hsien
口試委員:
學位類別: 碩士
Master
系所名稱: 工學院 - 動力機械工程學系
Department of Power Mechanical Engineering
論文出版年: 2010
畢業學年度: 98
語文別: 中文
論文頁數: 71
中文關鍵詞: 流場趨化行為仿生晶片表面受器
外文關鍵詞: fluid field, chemotaxis, mimetic chip, surface receptor
相關次數: 點閱:2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
  • 動脈粥樣硬化為現今心絞痛、冠心病主要原因,由於膽固醇堆積在血管分歧處或轉彎處而改變動脈血管內流場的變化,研究發現血液中的白血球因流場混亂處容易堆積而行免疫反應,久而久之使得管壁管徑縮小而導致血液中流量減少而所帶的養份無法充分的提供給心肌細胞,因心肌細胞的受損而增加心臟上的負擔。
    現今生物學家為了能了解其中血液循環疾病的形成,在體外建立複雜流場的晶片研究其中致病的原因,特別針對白血球細胞黏附在循環系統的內皮細胞上投入許多心血與努力。血液中複雜的流場往往伴隨者免疫反應發生,其中分兩派研究方向,其一研究白血球受到趨化因子的吸引而往受傷組織移動的趨化現象,另者探討內皮細胞上表面受器與白血球上表面受器互相關系,其中這兩者的行為是互相影響有關聯性的。
    本研究著重在微血管循環系統下,創造出一複雜流場的微流體晶片研究白血球趨化的行為,仿生晶片可提供趨化因子的環境亦可提供不同流場區域變化的能力,可讓生物學家因流場上的變化進而觀察白血球滲透作用與內皮細胞表面受器的互相關係而得知循環系統疾病上致病的主要原因


    Atherosclerosis is the major cause behind Coronary Artery Disease and Angina Pectoris. Cholesterol deposits on the inner surface of the artery leading to change in the arterial fluid field, especially near the arterial branches and curvatures. Leukocytes are likely to adhere on the surface where the fluid field is disturbed, leading to gradual decrease in the arterial diameter. This leads to insufficient supply of blood i.e. nutrients to the cardiac muscles, leading to increased load on the heart due to injury of cardiac muscles.
    Scientists have gained insight in vascular function and dysfunction but still lot of work has to be done. Recently, microfluidic technology is gaining interest in vascular research due to its ability to mimic the 3D vascular microenvironment. Immunological research is focused on adhesion of leucocytes on endothelial cells during blood circulation and the complex fluid dynamics present there in. The immunological research is divided into two parts. Some scientists believe that the leukocyte migration to the injured tissue is due to the chemotactic stimulus and some are trying to study the relation between the leucocytes and the surface receptors on endothelial cells. However, both the phenomena are linked to each other.
    We have designed a complex and reusable microfluidic chip which mimics the capillary endothelial lining, imitating the hemodynamic factor to study the extravasation behavior of neutrophils. We believe that our unique microfluidic device will help scientists to gain insight in vascular research.

    第一章 緒論 -1- 1-1背景與動機 -1- 1-2文獻回顧 -3- 1-2-1細胞培養晶片 - 3- 1-2-2趨化作用 -10- 1-2-3流體剪應力 -18- 第二章晶片構想與模擬-24- 2-1晶片設計概念 -24- 2-2數值模擬 -28- 第三章晶片製作 -32- 3-1製程流程 -32- 3-2製程結果 -34- 第四章實驗架設與結果-36- 4-1實驗設備的架設 -36- 4-2材料的準備 -37- 4-2-1 纖維蛋白、固化膠原蛋白、細胞激素及趨化因子-37- 4-2-2 內皮細胞 -37- 4-2-3 嗜中性白血球-38- 4-3實驗量測結果 -38- 4-3-1蓋內皮細胞不同流速之趨化量測-40- 4-3-2無覆蓋內皮細胞不同流速之趨化量測-46- 4-3-3覆蓋內皮細胞無趨化因子之趨化量測-52- 4-3-4無覆蓋內皮細胞無趨化因子之趨化量測-58- 4-3-5定量圖表-64- 第五章結論與未來展望.-68- 5-1 結論-68- 5-2 未來展望-69- 參考資料 -70-

    [1] http://www.gluegrant.org/chemotaxis.htm
    [2] Natanel Korin, Avishay Bransky, Uri Dinnar and Shulamit Levenberg “A parametric study of human fibroblasts culture in a microchannel bioreactor” Lab. Chip, 2007,7, 611-617
    [3] Philip Lee, Rob Lin, James Moon, Luke P. LeeBiomed“Microfluidic alignment of collagen fibers for in vitro cell culture”Biomed Microdevices , 2006,8, 35-41
    [4] Bonnie L. Gray, Deborah K. Lieu, Scott D. Collins, Rosemary L. Smith and Abdul I. Barakat “Microchannel platform for the study of endothelial cell shape and function” Biomedical Microdevices , 2002,4, 9-16
    [5] Anna Tourovskaia, Xavier Figueroa-Masot and Albert Fol“Differentiation-on-a-chip: A microfluidic platform for long-term cell culture studies” Lab. Chip, 2004,5, 14-19
    [6] Wei Gu, Xiaoyue Zhu, Nobuyuki Futai , Brenda S. Cho and Shuichi Takayama “Computerized microfluidic cell culture using elastomeric channels and Braille displays”PNAS, 2004,101, 15861-15866
    [7] Seog Woo Rhee, Anne M. Taylor, Christina H. Tu, David H. Cribbs, Carl W. Cotman and Noo Li Jeon“Patterned cell culture inside microfluidic devices” Lab. Chip, 2005,5, 102-107
    [8] Hongmei Yu, Caroline M. Alexander and David J. Beebe. “Understanding microchannel culture: parameters involved in soluble factor signaling” Lab. Chip, 2007,7, 726-730
    [9] Yo TANAKA, Yuji KIKUKAWA, Kae SATO, Yasuhiko SUGII, and Takehiko KITAMORI “Culture and Leukocyte Adhesion Assay of Human Arterial Endothelial Cells in a Glass Microchip” Analytical sciencess ,2007,23, 261-266
    [10] Glenn M. Walker, Jiqing Sai, Ann Richmond, Mark Stremler, Chang Y. Chung and John P. Wikswo“Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator”Lab Chip, 2005, 5, 611-618
    [11] Francis Lin and Eugene C. Butcher“T cell chemotaxis in a simple microfluidic device”Lab. Chip, 2006, 6, 1462-1469
    [12] Noo Li Jeon, Harihara Baskaran, Stephan K.W. Dertinger, George M. Whitesides. Livingston Van De Water, and Mehmet Toner“Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device”Nature, 2002,20, 826-830
    [13] Wajeeh Saadi, Shur-Jen Wang, Francis Lin, Noo Li Jeon “A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis” Biomedical Microdevices ,2006,8, 109-118
    [14] Nitin Agrawal, Mehmet Toner and Daniel Irimia“Neutrophil migration assay from a drop of blood” Lab. Chip, 2008, 8, 2054–2061
    [15] G.M. Walker, M.S. Ozers and D.J. Beebe “Cell infection within a microfluidic device using virus gradients” Sensors and Actuators, 2004,98, 347-355
    [16] Sachiko Koyama, Dragos Amarie, Helena A. Soini, Milos V. Novotny and Stephen C. Jacobson“Chemotaxis Assays of Mouse Sperm on Microfluidic Devices” Anal. Chem, 2006,78, 3354-3359
    [17] PETER F. DAVIES, ANDREA REMUZZItt, ETHEL J. GORDON, C. FORBES DEWEY, JR. AND MICHAEL A. GIMBRONE, JR“Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro” Cell Biology, 1986,83, 2114-2117
    [18] H. Tani, K. Maehana, T. Kamidate. “Chip-based bioassay using bacterial sensor strains immobilized in three-dimensional microfluidic network” Anal. Chem., 2004,76, 6693-6697
    [19] Cheng-Nan Chen, Shun-Fu Chang, Pei-Ling Lee, Kyle Chang, Li-Jing Chen, Shunichi Usami, Shu Chien and Jeng-Jiann Chiu “Neutrophils, lymphocytes, and monocytes exhibit diverse behaviors in transendothelial and subendothelial migrations under coculture with smooth muscle cells in disturbed flow” Blood, 2006,107, 1933-1942
    [20] Sabrena Noria, Feng Xu, Shannon McCue Mara Jones, Avrum I. Gotlieb and B. Lowell Langille“Assembly and Reorientation of Stress Fibers Drives Morphological Changes to Endothelial Cells Exposed to Shear Stress” American Journal of Pathology, 2004,164, 1211-1223
    [21] Sabrena Noria, Douglas B. Cowan, Avrum I. Gotlieb and B. Lowell Langille“Transient and Steady-State Effects of Shear Stress on Endothelial Cell Adherens Junctions” American Heart Association, 1999,85, 504-514
    [22] Jonathan T. Butcher, Andrea M. Penrod, Andrés J. García and Robert M. Nerem “Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments” American Heart Association, 2004,24, 1429-1434
    [23] 國家衛生研究院電子報 第 69 期 2004-10-20
    [24] David H. Cormack著,陳金山譯:《簡明組織學》(合記圖書出版社)

    無法下載圖示 全文公開日期 本全文未授權公開 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)

    QR CODE