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研究生: 曾逸銘
論文名稱: 多功能隨機存取式微液滴反應器陣列晶片之開發
A Random-Access Microarray for Programmable Droplet Storing, Retrieval and Manipulation
指導教授: 蘇育全
Su, Yu-Chuan
曾繁根
Tseng, Fan-Gang
口試委員: 范士岡
黃士豪
蘇育全
曾繁根
學位類別: 碩士
Master
系所名稱: 原子科學院 - 工程與系統科學系
Department of Engineering and System Science
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 74
中文關鍵詞: 數位微流體微陣列微液珠儲存篩檢
外文關鍵詞: Random-Access Microarray, 2-D Multiplexing, Microfluidic, Droplet, Storing, Retrieval, Screening
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  • 數位微流體系統為在近年來越來越受注目的研究領域之一,由於它擁有快速、精準、大量且自動化的優點,使得在化學、生物及醫學領域的應用上有著極大的潛力。利用數位微流體系統的特性,可把不同反應的實驗,置入在各自獨立且微小的微液珠中進行,同時在微小化與平行化的系統晶片中,做出各種實驗所需功能動作,在完成各種生化反應實驗後的微液珠可視為一組實驗樣本,再透過本研究所提供的定址存取系統晶片平台,加以儲存,透過此晶片平台進行長期觀察、篩選,甚至在日後樣品取樣,皆為本實驗研究的目標成果。希望透過此多功能隨機存取式晶片所具有微量檢測、精準定量、快速平行處理及自動化操控的優點,加快和便利在各種生物、化學和醫學研究實驗上的突破與發展。在本研究論文提出一種可依實驗需求而達到任意存入取出微液珠的多功能陣列式晶片,此晶片為多層PDMS微結構元件,利用氣動式薄膜來控制兩層微流道結構,在數位微流道控制的概念下,透過特殊設計的微流道暫存單元(microwell)陣列,來達到指定微液珠定址在微流道陣列晶片中的特定暫存單元,並達成微液珠在微流道晶片中展現任意定址存入取出的功能。在實驗原型晶片中,可依實驗需求製作所需要成份與定量的微液珠,並選擇性地存入4×4的目標暫存單元內或從中取出,並且現階段可達到微量合成、長期觀察、選擇指定樣品目標的功能,進階的在原型晶片陣列(4×4)只須要4 個(=2×log24)控制訊號即可。隨著此控制訊號與晶片設計發展,能實現更大數量級的陣列晶片,未來可應用在生化分析領域上,尤其可應用在快速合成藥物與成份檢體篩檢(screening)的領域上。


    This thesis presented a multi-function microfluidic array that is capable of programmably metering, entrapping, coalescing, addressably storing and retrieving droplets, which could potentially serve as reactors for continuous tracking and multi-step processing. A PDMS multi-layer chip with specially designed fluidic-channels dynamically re-configured by pneumatically-actuated diaphragms is utilized to realize various droplet manipulation schemes. We have fabricated the prototype demonstration that droplets with desired volumes and compositions are generated. Once droplets are formed, their motions are coordinated by a 2-D multiplexing scheme, which exploits the bi-directional movement of diaphragms to implement a random-access microarray, which means our microarray chip could be selectively stored, and retrieved from a 4×4 array, which employs just 4 (=2×log24) control inputs for the operation. With droplets functioning as micro-reactors, have the advantages such as low sample consumption and high reaction that the proposed random-access storage array could potentially serve as a chip for high throughput and multi-step reaction control. The chip is expected to significantly accelerate the progress in drug discovery, and various chemical and biological screening and synthesis. There are three accomplishments have been achieved in this thesis paper : (1) 2-D multiplexing can be largely facilitated using bi-directional diaphragm valves, (2) N×N multiplexing of droplets could be realized utilizing only 2×log2N control inputs and (3) a fully addressable, random-access array can be accomplished employing multi-layer microarray PDMS chip.

    目錄: 摘要 I ABSTRACT II 致謝 III 目錄: IV 圖目錄: VI 表目錄: VIII 第1章 緒論 1 1.1 背景 1 1.2 微流體技術介紹 2 1.3 研究動機與目標 4 第2章 文獻回顧 6 2.1 微液珠型成 6 2.2 微液珠混合 7 2.3 微流道數位控制 9 2.4 微液珠導向定控制系統 10 第3章 晶片系統原理與設計 16 3.1 實驗晶片微氣閥設計 16 3.2 微氣閥工作原理 19 3.3 微液珠混合元件 21 3.4 微液珠導向定位原理 22 3.5 微流道數位控制原理(多工器MULTIPLEXER) 26 3.6 元件設計 28 3.6.1 微液珠混合震盪元件 28 3.6.1.1 混合震盪元件工作機制 28 3.6.1.2 微流道形狀與震盪速度關係 31 3.6.2 微液珠定址存取陣列元件 35 3.6.2.1 Y與X方向多工器 35 3.6.2.2 自動化設計 38 3.6.2.3 四層結構設計 40 第4章 晶片系統製作與實驗設置 44 4.1 微機電製程 44 4.1.1 光罩設計 44 4.1.2 黃光製程步驟 44 4.1.3 母模抗沾黏機制 48 4.1.4 PDMS微鑄模製程(Micro-molding process) 48 4.1.5 PDMS晶片元件接合原理 53 4.2 實驗系統設置 54 第5章 實驗結果與結論 56 5.1 微液珠混合震盪元件 56 5.2 微液珠定址存取元件 58 5.3 討論 63 5.3.1 各代晶片比較 63 5.3.2 多功能元件介紹 64 5.3.3 串聯式與並聯式工作型態 68 第6章 結論與未來工作 71 6.1 結論 71 6.2 未來工作 72 REFERENCE: 73

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