結合光操控及水膠直寫模組之自動化微流體系統於雞尾酒藥物之應用

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研究生：	鍾克勤 Chung, Ko-Chin
論文名稱：	結合光操控及水膠直寫模組之自動化微流體系統於雞尾酒藥物之應用 DEMONSTRATION OF DIGITAL DRUG COCKTAILS BY USING A COMBINATION OF OPTICAL MANIPULATION OF PARTICLES AND PATTERNING OF HYDROGELS
指導教授：	李國賓 Lee, Gwo-Bin
口試委員:	陳致真 Chen, Chih-Chen 何宗易 Ho, Tsung-Yi
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：	2017
畢業學年度：	105
語文別：	英文
論文頁數：	54
中文關鍵詞：	雞尾酒療法、聚（乙二醇）二丙烯酸酯、水膠、微鏡陣列晶片、微流體、光誘發電場驅動力
外文關鍵詞：	Drug cocktail, PEGDA, Hydrogel, Digital micromirror device, Microfluidics, Optically-induced-dielectrophoresis
相關次數：	點閱：4 下載：0
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此研究裡使用的整合型微流體系統包含兩個技術，分別是光誘發電場驅動力模組，用以操控微粒子以實行藥物的比例操控，以及紫外光微鏡陣列晶片直寫模組，用以藥物的成型封裝。此系統設計能夠實行全自動及客製化的雞尾酒療法製藥方式。藉由光誘發電場驅動力模組，微粒子可以依照設計的不同被挑選、分類及聚集成特定組合。再者，一種水膠溶液poly (ethylene glycol) diacrylate (PEGDA)　其可以配合光起始劑及紫外光，產生特定大小圖形的固化產物，以用來固化水膠內特定數量的藥物，並使經過操控後的微粒子得以被固定，因此首次被用來當作光誘發電場驅動力模組的流體，初期結果顯示PEGDA具有良好的光誘發電場表現 (最高粒子移動速度356 μm/s和最大力量335 pN)，使得微粒子比例控制及圖形固化封裝得以並行，並且，在直寫模組中的微鏡陣列晶片使得不同形狀紫外光圖形設計變得容易，圖形轉換也更加快速，使得不同比例不同圖形的製藥流程都能在60秒內完成。藉由此機台，將可以首次自動化及客製化的製作雞尾酒療法藥物，對客製化研發或製作雞尾酒藥物將有很大的助力。

This study presents an integrated microfluidic system combining two techniques, namely, an optically-induced-dielectrophoresis (ODEP) module for manipulation of drug-containing particles and a UV-direct-writing module capable of patterning hydrogel for application in the formulation of digital drug cocktails. This system is capable of providing an automatic and customized production of drug cocktails. Using the ODEP module, the drug-contained particles could be selected and assembled. Moreover, , poly (ethylene glycol) diacrylate (PEGDA), a kind of hydrogel, was used for the first time as a medium in the ODEP module such that the manipulated particles could be UV-cured to specific sizes and patterns such that they could accommodate drug combinations subsequently. In addition, drug in PEGDA could also be quantified by the size of the cured PEGDA. The results showed better performance of ODEP in 15% PEGDA aqueous solution (with highest bead movement velocity of 356 μm/s and maximum ODEP force of 335 pN) which made it possible to control and UV-cure the drug-contained particles. Also, with the digital micromirror device (DMD) inside the UV-direct-writing module, different UV patterns could be easily designed and projected, thereby allowing the formation of drug cocktails patterned as different shapes less than 60 seconds. It is for the first time that an automatic digital drug cocktail fabrication could be demonstrated with this approach, which shows immense promise for personalized medicine.

Table of content
摘要    I
Abstract    II
致謝    IV
Table of content    V
List of figures    VII
Abbreviations and nomenclature    XIII
Chapter 1  Introduction    1
1-1 Microfluidic technology    1
1-2 Drug cocktails    2
1-3 Background and literature survey    3
1-3-1 Fine-tuning process for drug cocktails    3
1-3-2 Microfluidic applications    4
1-4 Motivation and novelty    5
1-4-1 Optically-induced-dielectrophoresis (ODEP)    5
1-4-2 UV-curable hydrogel and Digital Micromirror Device (DMD)    8
Chapter 2  Materials and methods    11
2-1 Hydrogel sample preparation    11
2-2 Setup of optically induced dielectrophoresis module    12
2-3 Setup of UV direct writing module    13
2-3-1 Digital micromirror device    13
2-3-2 UV beam separation design    14
2-4 Chip design    16
2-5 Chip fabrication and packaging    18
2-5-1 Polydimethylsiloxane casting and bonding process with glass    18
2-5-2 Double-sided tape channel fabrication    20
2-6 Setup of integrated microfluidic system    20
2-7 Experimental procedure    22
2-8 The original ODEP system used to investigate PEGDA feasibility    24
Chapter 3  Results and discussion    26
3-1 PEGDA application on UV-curing    26
3-1-1 Lowest PEGDA concentration for curing in channel    26
3-1-2 UV-light pattern on chip    28
3-1-3 Optimization of curing resolution    30
3-1-4 UV-light intensity versus exposure time    32
3-2 ODEP operation in PEGDA solution    34
3-2-1 Maximum particle velocity and ODEP force    34
3-2-2 Influence of the addition of photo initiator    36
3-2-3 Demonstration of ODEP on PEGDA    38
3-2-4 Feasibility of patterned hydrogels after ODEP manipulation    39
3-3 Demonstration of selecting and embedding targets by using the integrated system    40
3-3-1 Light patterns exposed from two different modules    40
3-3-2 Beads selection using the integrated system    42
3-3-3 Drug cocktails by using the integrated system    43
3-3-4 Drug cocktails by using the integrated system    48
Chapter 4  Conclusion and future perspective    49
4-1 Conclusion    49
4-2 Future perspective    50
References    51
Publication    54
































                                

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