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系統識別號 U0026-1111201311222500
論文名稱(中文) 三維水力聚焦微管道與葡萄糖濃度偵測晶片之研究
論文名稱(英文) Hydrodynamic Focusing in 3-D Microchannel and Glucose Concentration Detection Chip
校院名稱 成功大學
系所名稱(中) 工程科學系
系所名稱(英) Department of Engineering Science
學年度 102
學期 1
出版年 102
研究生(中文) 侯輝雄
研究生(英文) Hui-Hsiung Hou
學號 N98971239
學位類別 博士
語文別 英文
論文頁數 120頁
口試委員 指導教授-楊瑞珍
口試委員-黃吉川
口試委員-傅龍明
口試委員-蔡建雄
口試委員-王耀男
口試委員-林哲信
中文關鍵字 微流體細胞計數器  微擋流結構  數值模擬  水力聚焦  螢光聚苯乙烯珠  Saffman剪升力  微混合器  二氧化碳雷射  葡萄糖濃度  DNS方法 
英文關鍵字 Microflow cytometer  Micro-weir structure  Numerical simulations  Hydrodynamic focusing  fluorescent polystyrene beads  Saffman shear lift force  Micromixer  CO2 laser  Glucose concentration  DNS method 
學科別分類
中文摘要 本篇論文設計且估算三種新式微流體細胞計數儀。在第一個裝置中,樣品流被藉由兩組邊鞘流體水平和垂直地聚焦在微管道的中心處且之後流通過單一微擋流結構處,接著細胞/粒子則一顆一顆流通過下游的偵測區。第二個裝置中,樣品流被水平地聚焦藉由單一組邊鞘流體且通過逐漸降低高度的微擋流結構組。而在第三個裝置中,樣品被直接注射進入具有一連串微擋流結構的微管道中且不需要水力邊鞘流體而是藉由微擋流結構所產生的升力來聚焦。除了這三種細胞計數儀外,本篇論文也發展了低價格且可拋棄式的葡萄糖濃度偵測微流體晶片,文中所提的微流體晶片的偵測效果將會與傳統大型裝置來做比較。
第一章回顧了微流體、細胞計數儀和葡萄糖偵測領域的基本原理,另外,論文的研究動機介紹以及討論。第二章敘述在本論文中微流體裝置的製做過程,此外,實驗和數值程序用來估算效果也在這章節做介紹。第三章說明第一種細胞計數裝置將樣品流先在垂直方向做聚焦接著在水平方向藉由兩組邊鞘流體,之後細胞/粒子一顆接著一顆流過單一微擋流結構通過下游偵測區。微管道圖型與操作參數藉由數值模擬達最佳化,論文所提的細胞計數儀使用直徑5 μm 和 10 μm混合式螢光粒子來驗證。
第四章介紹第二種微流式細胞計數儀,樣品流在水平方向藉由一組邊鞘流體被聚焦且之後流通過一連串逐漸降低高度的微擋流結構區。所提出裝置的效果藉由數值和實驗使用直徑7 μm 和 15 μm的螢光粒子來估算。第五章說明了第三種微流式細胞計數儀,粒子藉由在微管道中微擋流結構所產生的升力而被聚焦在水平和垂直方向。所提出裝置的效果藉由數值和實驗使用直徑5 μm 和 10 μm的螢光粒子來估算。第六章說明了一種低價格且可拋棄式的葡萄糖濃度偵測目的合併雙並聯式微混合器和T型出口微管道,數值模擬被用來分析在混合室裡面的渦流流線分佈和所相對應的混合效率,所提出的裝置被實際的應用在估算葡萄糖濃度為 100 到 500 ppm範圍內。最後,第七章提供具體的結論。
在本論文的結果說明所提出的細胞計數儀和葡萄糖濃度偵測晶片與傳統大型儀器的效果做比較,如結果所示,所提出的裝置提供一個低價、可拋棄式隨身照護應用的理想方案。
英文摘要 This thesis designs and evaluates three novel microflow cytometers. In the first device, the sample stream is focused horizontally and vertically in the center of the microchannel by means of two sets of sheath flows and is then passed over a single micro-weir structure such that the cells / particles within the sample stream flow through the downstream detection region in a one-by-one fashion. In the second device, the sample is focused horizontally by a single set of sheath flows and is then passed over a staggered series of micro-weir structures with a gradually reducing height. In the third device, the sample is injected directly into a microchannel containing a sequential arrangement of micro-weirs and is focused without the need for hydrodynamic sheath flows by means of the Saffman lift force generated by the micro-weir geometry. In addition to the three cytometer devices, this thesis also develops and characterizes a low-cost, disposable microfluidic chip for glucose concentration detection purposes. It is shown that the detection performance of the proposed microchip is comparable with that of a conventional large-scale device. The remainder of this thesis is organized as follows.
Chapter 1 reviews the basic principles of the microfluidics, cytometry and glucose detection fields. In addition, the motivations and scope of the thesis are introduced and discussed. Chapter 2 describes the fabrication processes used to realize the microfluidic devices proposed in this thesis. Moreover, the experimental and numerical procedures used to evaluate their performance are briefly introduced. Chapter 3 presents the first cytometer device, in which the sample stream is focused first in the vertical direction and then in the horizontal direction by two sets of sheath flows and is then flowed over a single micro-weir structure such that the cells / particles within the sample pass through the downstream detection region in a one-by-one fashion. The microchannel configuration and operational parameters are optimized by means of numerical simulations. The validity of the proposed cytometer is demonstrated using a mixed sample comprising 5 μm and 10 μm fluorescent polystyrene beads.
Chapter 4 introduces the second microflow cytometer, in which the sample stream is focused in the horizontal direction only by a set of sheath flows and is then flowed over a sequential micro-weir structure comprising three staggered sets of micro-weirs with a gradually reducing height. The performance of the proposed device is evaluated both numerically and experimentally using fluorescent polystyrene beads with diameters of 7 μm and 15 μm, respectively. Chapter 5 presents the third microflow cytometer, in which the particles are focused in the horizontal and vertical directions by means of the Saffman shear lift force generated within a microchannel incorporating three micro-weir structures. The proposed device is characterized both numerically and experimentally using fluorescent polystyrene beads with diameters of 5 μm and 10 μm, respectively. Chapter 6 presents a low-cost, disposable microfluidic chip for glucose concentration detection purposes incorporating a Double Parallel Connection Micromixer (DPCM) and a T-type outlet microchannel. The vortex streamline distributions within the mixing chambers of the DPCM and the corresponding mixing performance are analyzed by means of numerical simulations. The practical applicability of the proposed device is then evaluated using glucose samples with concentrations ranging from 100 to 500 ppm. Finally, Section 7 provides a series of brief concluding remarks.
In general, the results presented in this thesis show that the performance of the proposed cytometers and glucose concentration detection chip is comparable with that of existing large-scale instruments. As a result, the proposed devices provide an ideal solution for low-cost, disposable point-of-care applications.
論文目次 Abstract...........I
中文摘要..............IV
誌謝...........VI
Table of Contents..........VII
List of Tables...........X
List of Figures............XI
Abbreviation.........XVII
Nomenclature........... XIX
Chapter 1 Introduction ........1
1.1 Microfluidic Devices.......1
1.2 Poiseuille Flow........2
1.3 Flow Cytometer.........5
1.4 Glucose Assay........9
1.5 Motivation and Objectives of Thesis......11
Chapter 2 Materials and Methods......13
2.1 Fabrication of Microfluidic Chips......13
2.1.1 Glass-based microchips......13
2.1.2 PMMA-based microchips......15
2.2 Observation and Measurement Equipment....18
2.3 Simulation Method........19
Chapter 3 Microflow Cytometer Incorporating Single Micro-weir Structure.20
3.1 Introduction........20
3.2 Experimental Section.......24
3.2.1 Experimental setup.......24
3.2.2 Sample preparation.......26
3.3 Simulation Model........27
3.4 Results and Discussion.......29
3.4.1 Effect of horizontal focusing ration on stream width..29
3.4.2 Effect of depth of second set of sheath flow channels...32
3.4.3 Optimal design of 3-D focusing microflow cytometer..34
3.4.4 Experimental focusing results.....37
Chapter 4 Microflow Cytometer Incorporating Sequential Micro-weir
Structure.........42
4.1 Introduction........42
4.2 Experimental Section.......45
4.2.1 Experimental setup.......45
4.2.2 Sample preparation.......48
4.3 Simulation Model .........49
4.4 Results and Discussion.......49
Chapter 5 Microcytometer Incorporating Sequential Micro-weir Structure with Saffman Lift Force.......57
5.1 Introduction........57
5.2 Experimental Section.......60
5.2.1 Experimental setup.......60
5.2.2 Sample preparation.......63
5.3 Simulation Model ........63
5.3.1 Governing equations and numerical method...63
5.3.2 Particle trajectory model.......64
5.3.3 Saffman lift effect acting on single particle in shear flow..66
5.4 Results and Discussion.......68
Chapter 6 Integrated Microfluidic Chip for Glucose Concentration Detection........74
6.1 Introduction........74
6.2 Experimental Section.......78
6.2.1 Chemical reaction and sample preparation....78
6.2.2 Chip configuration and design.....79
6.2.3 Experimental setup.......81
6.3 Simulation Model.......83
6.4 Results and Discussion.......84
Chapter 7 Concluding Remarks.......91
7.1 Microflow Cytometers........91
7.2 Glucose Concentration Detection Microchip.....93
References...........95
Appendix A Beer’s Law........112
Appendix B Interpretation of Coefficient of Determination (R2) in Regression
Analysis.........114
Curriculum Vitae..........116
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