臺灣博碩士論文加值系統

本研究提出了一種具有三維水力聚焦技術的微流體細胞計數儀，利用3D的流體動力聚焦現象迫使樣品流固定於管道中的偵測位置上，一開始樣品流會先受到水平方向邊鞘流的壓縮因此會固定於微管道的中間位置，接著樣品流會在垂直方向受到第二對邊鞘流的擠壓而產生垂直方向的聚焦現象，之後樣品流緊接著通過微擋流結構處，並在此處利用光偵測系統擷取細胞/粒子的螢光訊號。
此三維水力聚焦細胞計數儀的幾何形狀以及操作參數的最佳化定義是利用數值模擬的方式，針對垂直和水平聚焦比、第二對邊鞘流管道入口處的夾角以及第二對邊鞘流管道的寬度和深度對樣品流分佈的影響進行數值分析，接著利用數值模擬的參數，經由微機電製程技術以及等向性濕式蝕刻的方式，製作出微流體細胞計數儀，分析的結果為樣品流成功的被水平和垂直方向的邊鞘流夾擠成一狹窄的樣品流體，接著利用微擋流結構在垂直方向對細胞/粒子產生分離的效應，並有效的使細胞/粒子各別連續的通過微管道的偵測區並有效的計數細胞/粒子。

This study presents a novel three-dimensional hydrodynamic focusing technique for micro-flow cytometers. To employ hydrodynamic focusing phenomenon to press sample stream constrain in the microchannel positioned directly beneath an detection system. The sample stream is initially compressed in the horizontal direction by sheath flows such that it is constrained in the central region of the microchannel. The sample stream is then focused in the vertical direction by a second pair of sheath flows and to produce vertical direction of focusing phenomenon. After that the sample stream subsequently passes over a micro-weir structure and to employ optical detection system to capture cells/particles fluorescent signal.
The microchannel configuration and operational parameters are optimized by performing a series of numerical simulations to examine the effects on the sample stream distribution of the vertical and horizontal focusing ratios, the entrance angle of the second set of sheath flow channels, and the width and depth of the second set of sheath flow channels. And to employ numerical simulation parameters via MEMS fabrication technique and isotropic wet etch method to fabricate micro-flow cytometer. The results indicate that the horizontal and vertical sheath flows successfully constrain the sample stream within a narrow,well-defined region of the microchannel. Furthermore, the micro-weir structure results in the separation of the cells/particles in the vertical direction and ensures that they flow in a sequential fashion through the detection region of the microchannel and can therefore be reliably counted.

摘要......................................................I
Abstract…...…………………………………………………………..…. II
謝誌………………………………………………………………….………IV
目錄……………………………………………………………………...….. V
圖目錄…………………………………………………………………IX
符號說明………………………………...………………………………XVII
第1章 緒論………………………...……………………...………………...1
1.1 前言…………………………………………………..…..…………...1
1.2 微機電系統…………………………………………..……...…...…2
1.3 微流體………………….……………………………………..…...…4
1.4微流體生醫晶片……………………………………………...……...5
1.5文獻回顧……............……………………………….………….7
1.6 研究動機與目的……………………………………………………..17
第2章 數學模型與數值方法........……………...…….……...……..20
2.1 數學模型………..……………………………………..………..……21
2.1.1 克努森數(Knudsen Number) ………..………………..…………21
2.1.2 基本假設……..………………………..………………………….21
2.1.3 描述流場之Navier-Stokes方程式……………………………….22
2.1.4 邊界條件………………………………………………………….22
2.2 數值方法……………………………………………………………..24
2.2.1 離散化(Discretization)………………………………………24
2.2.2 一階上風法（first-order upwind scheme）……….……..25
2.2.3 壓力與速度(pressure-velocity coupling)之耦合算法……26
2.2.4 格點系統………………………………………………………….28
2.2.5 收斂標準………………………………………………………….30
第3章 晶片製作與實驗方法………………...…………..…..….……..31
3.1 晶片基材……………………………..…..……………….………….31
3.2 光罩的設計………………………………..……..…....……….…32
3.3 微流體晶片製作……………………………………….…………….34
3.3.1 退火(Annealing)………………………………………...…...34
3.3.2 晶片清洗(Cleaning)………………………………………………34
3.3.3 HMDS塗佈……………..….…………………………………..35
3.3.4 塗佈光阻及軟烤(Spin Coating and Soft-bake)………..35
3.3.5 曝光(Exposure)………………………………………………...36
3.3.6 顯影(Developing)…………………………………………………37
3.3.7 硬烤(Hard-bake)………………………………..…………...37
3.3.8 蝕刻及去光阻(Etching and PR stripping)…………………38
3.3.9 鑽孔、清洗、對位及高溫熔融接合……………………………….39
3.3.10 晶片封裝(Package)………………………………………….….42
3.4 實驗理論………………………………………………………..……43
3.5 實驗方法……………………………………………………………..43
3.6 實驗步驟……………………………………………………………..47
第4章 結果與討論…………..…………………………………...…..…...49
4.1 細胞計數晶片的內部微結構………...………………….…………..49
4.2 第一對邊鞘流水平聚焦比的影響…………………………………..52
4.3 第二對邊鞘流管道夾角θ的影響…………………………….…….55
4.4 第二對邊鞘流管道寬度W1的影響……………………………….…60
4.5 第二對邊鞘流管道深度d的影響……………………………..……..62
4.6 第二對邊鞘流管道位置P的影響……………………………………66
4.7 第二對邊鞘流幾何形狀最佳化設計結果…………………………..68
4.8 最佳化幾何圖形實驗結果…………………………………..………72
4.9 微擋流結構的影響…………………………………………………..74
第5章 結論與未來展望……………………………………………………79
5.1 結論 …………………………………………………………………..79
5.2 未來展望……………………………………………………………. 80
參考文獻 ……………………………………………………………………..81
作者簡介 ……………………………………………………………………..85

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