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研究生:陳崇仁
研究生(外文):Chung-Jen Chen
論文名稱:在微流通道系統中測量人類紅血球之奈米機械特性
論文名稱(外文):Nanomeasurements of red blood cells in microfluidic systems
指導教授:何孟書
指導教授(外文):Mon-Shu Ho
學位類別:碩士
校院名稱:國立中興大學
系所名稱:物理學系所
學門:自然科學學門
學類:物理學類
論文種類:學術論文
畢業學年度:97
語文別:中文
論文頁數:122
中文關鍵詞:原子力顯微鏡半開放式微流通道系統紅血球聚二甲基矽氧烷
外文關鍵詞:AFMsemi-open microfluidic systemsRBCPDMS
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在此我們利用原子力顯微鏡 (Atomic Force Microscope , AFM) 對人類紅血球 (Red Blood Cells , RBCs)作直接性之量測,借此了解紅血球細胞膜與膜骨架之奈米機械性質的差異;首先於液態環境下量測紅血球置於各基板上之表面形貌以及隨時間衰變情形,接著並對不同的紅血球作應力量測及分析,本實驗主要目的是對本實驗室已建立之開放式微流通道幫浦系統做持續改良,以作為整合之生物感測晶片平台,並以紅血球作為測試生物樣品,並觀測在不同pH值下紅血球細胞膜的黏滯力變化。
第一部分首先於各基板下量測紅血球之表面形貌以其奈米機械特性並作簡單的分析,發現PDMS與紅血球相容性相當恰和,並對PDMS作氧電將改質,發現此作用能使紅血球緊密貼附於基板,此發現對於微流通道改良為一重點。
第二部分先取得新鮮紅血球置於等張溶液的生理食鹽水中作稀釋,於室溫下作量測分析,利用AFM測量在沒有養分供應下紅血球隨時間的變化情形,藉此直接性了解紅血球最真實的衰變情形,以及奈米機械特性變化。
在第三部分成功改良開放式微流道幫浦系統,並設計不同型態的微流道,第四部分以正常紅血球為實驗之生物樣品,並利用AFM測得即時影像,其結果發現紅血球類似子彈形狀通過微流道,與過去研究文獻相似,並測得其擠壓應變之奈米機械特性是如何變化。
由於以往研究發現許多疾病伴隨著心血管疾病,而會引發溶血的情形,而溶血的發生與紅血球的性質改變有關,造成血球的彈性變差而容易破碎,因此本實驗在最後部分將紅血球配置於不同酸鹼值為微調之溶液,藉此模擬酸鹼體質變化,以了解紅血球之性質變異為何。
建立相關參數資料後,除了可更直接了解紅血球,以便日後進一步發展為整合微流體致動器、感測器之快速檢測紅血球形變的多功能生醫平台晶片,判斷出紅血球的彈性是否在正常值範圍之內。
In this work, Atomic Force Microscope(AFM) was employed to test the mechanical properties of Red Blood Cell(RBC) membrances in nano scale.The surface stress and morphology of RBC membrances were studied as time goes by.The decay mechanisms for RBCs through different processes were discussed.Moreover,the adhesion force of RBC membrances were measured in a semi-open microfluidic systems by AFM.
Finally,the characteristics of RBCs in different pH values were investigated .
PART one:
Surface topography and the mechanical properties of RBCs were observed in nano scale. The most important thing for microfluidic system’s improvement is that plasma treating on PDMS.
PART two:
We measured the surface stress and morphology of RBC membrances by AFM. The characteristic of RBCs’membrane were studied as time goes by. The stability of plasma membrane crashed after 5days because many diverse proteins, like ankyrin and Band 4.1, cannot to attach each other. The adhesion forces of cell membranes increase to 3~4 times comparing with the normal ones.
PRAT three:
The semi-open microfluidic pumping systems we fabricated is 1~8µm, 4µm deep, through soft lithography technology.
PART four:
The adhesion force of RBCs in microfluidic system was measured between 0.52~1.01nN.RBCs have to deform into bullet-like shapes to pass through capillaries by increasing the area of the RBC surface in contact with the capillary endothelium.
RBCs are prematurely broken at pH value down to 6.5. The destruction of RBCs membrane causes hemolysis and leads to hemolysis anemia.
After building the normal RBC experimental databases, we attempt to develop a microfluidic chip system of distinguishing RBC healthy or not.
致謝Ⅰ
中文摘要Ⅱ
英文摘要Ⅳ
目錄Ⅵ
圖表目錄IX
第一章 緒論
1.1 前言 1
1.2 研究動機2
1.3 微機電系統4
1.4 生醫微流體晶片6
1.5 微流體晶片之相關文獻8
1.6 人類紅血球11
1.7 雲母 16
1.8 聚二甲基矽氧烷20
1.8.1 微晶片材料21
1.8.2 矽氧烷高分子的發展23
1.8.3 PDMS表面親水性改質 24
1.8.4 軟式微影26
1.9 SU-8厚膜負光阻28
1.9.1 SU-8光阻的基本特性30
1.9.2 SU-8光阻的結構 32
1.10 章節概述 36
第二章 儀器介紹
2.1 原子力顯微鏡儀器由來 38
2.2 原子力顯微鏡基本原理 41
2.3 原子力顯微鏡儀器架構48
2.4 作用力-距離曲線圖55
第三章 實驗設計與製程步驟
3.1 實驗規劃與設計 58
3.2 實驗製備60
3.2.1 Mica基板製備60
3.2.2 SU-8基板製備64
3.2.3 PDMS基板製備66
3.2.4 生物樣品人類紅血球的製備68
3.3 開放式微流幫浦系統製備70
3.3.1 母膜製作70
3.3.2 微流體晶片製作76
3.3.3 微幫浦系統79
3.4 溶液pH值微調製備81
第四章 研究結果與討論
4.1 紅血球在各基板上之基本特性82
4.2 紅血球隨時間衰變的外型與奈米機械特性之探討90
4.3 開放式微流道幫浦系統製程結果討論98
4.4 紅血球在微流通道系統中外型與奈米機械特性之探討 101
4.5 紅血球在不同酸鹼值溶液中外型與奈米機械特性之探 107
第五章 結論與未來方向
結論112
未來方向114
參考文獻115
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