本文主旨在研發高效能微流體反應器，可應用於增強DNA雜交反應或其它生化反應，並開發新式的微流體診測技術。研究版圖分三大塊，包含：(1)創新元件的設計、分析與驗證、(2)原創量測技術的開發、(3)元件應用測試— 生化流體的反應試驗。研究結果總結如下：
藉由光罩圖樣的設計，實現連續溝槽微混合器(connected-groove micromixer, CGM)，其流道內具有橫跨流道底部與側壁的連續溝槽，可增強流體的橫向運動以及質量導引，進而促進流體混合。實驗結果顯示，當傳統的斜向溝槽微混合器(SGM)在加入側壁溝槽的輔助後，在30 mm內增強流體翻轉能力達10-20 %，證實側壁溝槽增強流體橫向運動的效果。進一步設計具有錯位排列溝槽的微混合器(CGM-2)，讓流場產生兩個同向旋轉的螺旋流，螺旋流之間的交互作用引發流體傳輸、切割、混合，CGM-2的混合效能高於SGM約50%。
為因應生化流體混合之複雜性(流體黏滯度範圍大)，設計出分離與再結合式微反應器(SAR □-reactor)，具有分離與再結合(split-and-recombination, SAR)以及混沌對流(chaotic advection)之混合機制。經由特殊設計之切割結構與匯流流道，讓流場產生大幅度的質量切割與轉移，引起強烈的3D旋轉流來拉扯、扭曲流體介面。經化學反應試驗與黏滯流體混合實驗，證實SAR □-reactor的混合效能是SGM的兩倍，其操作範圍大(雷諾數Re = 0.01-100)，特別適用於黏滯流體(□□= 0.000855-0.1 kg/m˙s)的混合反應，可望應用於化工合成與生醫檢測方面。
在實驗量測技術的開發上，首先發展一套微流體混合/反應定量的技術，此技術結合共軛焦螢光顯微術以及原創的定量方法，可達成流體混合圖樣的定量化，進而客觀估算混合長度，過程中提出一通用指數(universal index)— 混合品質指數(mixing quality index, Mqi)，用來量化圖樣內流體的混合程度。以交疊流道(overlapping channels)元件當作測試對象，結果顯示：本方法估算元件的混合長度，明顯較一般染料混合實驗所估算的混合長度長而且準確，兩種方法的相對誤差為30-40 %。本技術也實現同時監控兩種相異波長的螢光溶液，清楚拍攝兩流體於元件內的交互作用與橫向運動。
本文所提出的另一套原創的量測技術，結合多重螢光微粒子影像測速儀(micro particle image velocimetry, micro-PIV )與自行開發的粒子計數法，可同步診斷物種(粒子)速度以及濃度場。粒子的速度場由micro-PIV求得，而粒子的濃度場分佈由粒子計數法(particle-counting method)所獲得，濃度場可進一步被量化成混合指數。所開發的粒子計數法，以分水嶺法(watershed-segmentation algorithm)與高斯比重函數(Gaussian weighting function)修正過後，不準度約為± 4%。本技術成功觀察流體2D速度與濃度場，進一步結合共軛焦螢光顯微術，成功重建流道內3D的速度與濃度場的影像。以T形流道當測試對象，其實驗結果與模擬結果相互比較，濃度場與速度場的平均誤差約為5%；混合指數的誤差約為10%，而3D流場的速度與濃度場的輪廓也如模擬所預期，具有不錯的一致性。
最後，本文在開發的反應元件內成功執行生化反應試驗，試驗包含：兩互補DNA片段的雜交反應以及DNA與修飾化金奈米粒子的鍵結反應，以共軛焦螢光顯微術搭配螢光共振能量轉移(fluorescence resonance energy transfer, FRET)原理，完整呈現反應過程並將之定量化，研究過程中，逐步驗證本文所提出之移動鍵結(mobile conjugation/hybridization)的概念。本文於元件內執行的生化試驗，僅需數十秒達成反應平衡，遠低於傳統靜態雜交需耗費數小時以上的時間，證實樣品間移動鍵結的功效，透由流道內結構的設計，確實可增強樣品內分子雜交的速率。
本文主要貢獻：研發性能優異且製程簡單的微流體混合/反應器，貼近工程與實務上的應用，再者，在學術上貢獻，所提出的原創量測技術、設計理念、分析方法以及獨到見解可做為後人參考的依據。期望透由本文的研究脈絡，讓讀者概觀了解過去研究的演進，激發未來研究的靈感。

The purpose of this thesis is to research and develop high performance micro-bioreactors applied to enhance DNA hybridization and other biochemical reactions; novel measuring techniques also proposed in this study. There are three major branches in this thesis, including the design, analysis, and verification of the original devices, the invention of measuring techniques as well as the pilot tests concerning biochemical fluidic reactions in the devices. The research results are summarized as follows:
A novel micromixer named connected-groove micromixer, CGM with connected grooves across the bottom and the sidewall of the channel has been realized by microfabrication using the specific design of mask patterns; the connected grooves have ability to promote the lateral motion and mass conduction of fluids so as to improve fluidic mixing. CGM-2 induces two co-helical flows in the flow field; the interaction of the flows involves mechanisms of cutting, transport, and mixing fluids. The CGM-2 hence possesses better mixing performance than a common device, slanted-groove micromixer, SGM.
Based on the mechanisms involving split-and-recombination (SAR) and chaotic mixing, a novel microreactor named SAR □-reactor was proposed for enhancing biofluidic mixing. The SAR □-reactor with in-plane dividing structure and separated channels enables intensive mass split and transport of fluids occurring in the field so as to induce a strong 3D rotating flow to stretch and distort the material interface. The SAR □-reactor was demonstrated by tests of chemical reactions and of viscous fluidic mixing that has excellent performance superior to that of SGM; the SAR □-reactor could be operated at Reynolds number with a wide range and suitable for viscous fluidic mixing.
The thesis reveals a measuring technique for quantification of microfluidic mixing/reaction by using confocal fluorescence microscopy involving original quantification method. A universal index termed mixing quality index (Mqi) was proposed for quantifying mixing patterns that one can reasonable evaluate a mixing lengths of devices. The mixing lengths of devices estimated by this technique are larger and more precise than that by a common dye-blending test. These techniques also facilitate monitoring the behavior of two fluorescence fluids in the devices. Beside, another original measuring technique encompassing micro particle image velocimetry (micro-PIV) and particle-counting method was proposed to simultaneously diagnose species velocities and concentrations. The velocity field is obtained by micro-PIV; the concentration field is obtained by particle-counting method; a mixing index could be derived from a concentration field. For the particle-counting method, a watershed-segmentation algorithm and Gaussian weight function are utilized to amend counting results so as to reduce uncertainty down to ± 4%. 2D and 3D velocity and concentration fields in a T-shaped channel are successfully observed through this technique by taking advantage of confocal fluorescence microscopy. Comparing to the numerical results, the average errors of concentration field, velocity field and mixing index are around 5, 5, and 10%, respectively. The profiles of velocity and concentration fields derived from the experiments are satisfactorily corresponding with the results of numerical simulation.
Finally, bio-reaction tests including hybridization/conjugation of two complimentary DNA and of DNA and functionalized gold nano-paticles (Au-NPs) were successfully executed in intentional reaction devices. This study thoroughly exhibited reaction and quantification process by using confocal microscopy with fluorescence resonance energy transfer, FRET principle. It requires tens of seconds to fulfill equilibrium for the reactions in the devices; this reaction duration is much shorter than a conventional static hybridization requiring more than several hours. This demonstrates that the efficacy of mobile conjugation of molecules in the devices; the structural design of the devices indeed reinforce the efficiency of bio-reactions.
The main contributions of this thesis comprise realizing novel micromixers/microreactors with high performance and simple fabrication and proffering original measuring techniques, design notions, analytical methods, and insightful viewpoints as significant reference materials for successors and future study. Hopefully, through the content of this thesis, readers could grasp the evolution of this study field and then be inspired to create foresighted research.

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