| 摘要: | 近代，微流體裝置逐漸廣泛地研究，不論是紙基微流體裝置、微流體晶片、生物反應器，皆朝著以外部致動件搭配自動化控制的方向邁進，而這些致動件也增加了其在主動式控制及相關領域上的應用，例如:紙基微流體裝置中以主動式控制的方式控制流體在濾紙上的流速、微流體晶片及生物反應器中影響細胞成長的外部物理刺激等等，因此本研究將嘗試依據不同微流體裝置的需求來開發外部致動之微流體平台。
在紙基微流體裝置中，目前許多裝置仍以被動式閥門控制作為主要流體傳輸控制的依據，卻捨棄控制流體在濾紙上流速的機會，在本論文第一部份中將嘗試結合紙基微流體裝置與自動化運作概念，並試著以主動式閥門控制的方式來解決以往裝置在做細胞培養或檢測時濾紙上液體流速無法控制的問題，同時藉由平台開發的概念來應用在不同孔徑的濾紙以達到多方應用的能力，並藉由實驗結果來評估未來紙基微流體平台的發展性。
有鑑於許多研究指出，外部物理刺激擁有促進細胞成長、分化的作用，例如:機械拉伸、電刺激、剪應力等，然而許多研究仍無法以多種外部物理刺激的方式對細胞刺激。本論文第二部分中將嘗試結合微流體晶片及生物反應器設計概念與優勢，進行外部致動之微流體機電控制平台的開發及製程設計。微流體晶片和生物反應器是體外細胞培養的裝置並作為代替動物實驗的仿生環境，但它們仍分別存在一些限制如:重複使用性、細胞脫附等問題。雖然生物反應器能解決上述問題，但當微觀設備近一步放大時，先前未顯現的問題也相對被放大如:漏氣、漏液、細胞外部刺激數將隨裝置設計而成為有限制的發展。同時，在多種生物實驗下，電路控制將是影響生物實驗結果的關鍵，也造成實驗者在裝置製備與控制方面受到一定程度的負擔。因此本論文將嘗試以聚甲基丙烯酸甲酯(PMMA)製作結合微流體晶片及生物反應器概念的生物晶片，並以已沉積聚吡咯(PPy)的聚二甲基矽氧烷(PDMS)薄膜作為細胞培養的依據，生物晶片設計會以固定深度微流道抽真空的方式對薄膜進行機械拉伸並放置導電裝置來對細胞電刺激，同時確保裝置對細胞的生物的相容性及影響性，最後將改良機電控制端以達到最佳化控制並將生物晶片整合應用於可升降式微流道(可調式機械拉伸量)的外部致動之微流體機電控制平台。
為了提高細胞分化率我們評估了細胞培養所需的空間，同時兼顧裝置的重複使用性及可拆卸性，最終將達到以外部致動的方式提供細胞外部刺激，透過7天的細胞培養，我們證明了細胞在裝置上透過多重刺激下增加了排列及分化結果，藉此開拓外部致動之微流體機電控制平台未來持續開發的可能性。
;In recent year, the microfluidic devices have been widely developed. Whether the paper based microfluidic device, microfluidic chip or bioreactor, they are developed toward the direction of automatic control with external actuators. And these actuators are also increase their applications in active control. For example: in the paper-based microfluidic device, the active control of fluid flow rate on the filter paper. or external physical stimulation that affect the cells growth in the microfluidic chip and bioreactor, etc. Therefore, we target to develop an external actuated microfluidic platform according different microfluidic device.
In paper-based microfluidic devices, many devices still use passive valve control, but didn’t develop the active valve control to change the flow rate on the filter paper. In the first part of this thesis, we will combine the concepts of paper-based microfluidic devices and automated operation to design a microfluidic electromechanical control platform. And we use active control to solve the liquid transmission problem and promote the multiple drug testing needs in the future.
In many studies, external physical stimulation can promote cells growth and differentiation, such us mechanical stretching, electrical stimulation, shear stress, etc. However, they can’t affect cells by multi external physical stimulation in many researches. In second part of thesis, we combine the design concept and advantages of microfluidic chip and bioreactors, to develop and design the external actuated microfluidic electromechanical control platform. Microfluidic chip and bioreactor are in vitro cell culture device as a biomimic environment to replace animal experiments. Although microfluidic chip have some limitation of unreplaceable, reusability etc. Although the bioreactor can solve the problems, but the problems will happen while the device or equipment redesign to be bigger, such as air leakage, liquid leakage, development of external stimulations. At the same time, system control will be a crucial factor to affect the various biological experiments. It also causes operator spent more time to setup the device and control.
Therefore, we target use PMMA to fabricate a biochip and PPy-PDMS film for cell culture. the function of biochip will have mechanical stretching and electrical stimulation, and we will ensure the biochip biocompatibility for cells. Finally, we will improved the electromechanical control and integrated the biochip into an externally actuated microfluidic electromechanical control platform.
To promote cell differentiation rate, we evaluate the cells need to design the function and development of external actuated microfluidic electromechanical control platform that synchronous applied the electrical pulse and mechanical stimulation. By 7 days culture, we verify the cell increased the differentiation and alignment result by multi-stimulation. And develop the possibility of modular device in the future. |
