以微流技術製作高分子細胞支架

Polymer cell scaffold fabricated by microfluidic technology

陳亦新

指導教授 ： 衛榮漢

國立清華大學/工學院/動力機械工程學系/碩士(2012年)

摘要

本文主要的貢獻為成功將微流體技術應用於生醫組織工程中細胞的圖型化，分成兩個部份，第一，是運用磁流體在磁場下因磁水力不穩定而分散的特性，產生均勻排列的磁液滴陣列以製作高分子材料母模，再利用另一高分子材料進行翻模，形成陣列式的凹凸結構，以其凹處的平坦面做為細胞圖型化之區域。第二是使用微流道系統製作微形細胞支架，方法是使兩種不互溶的流體在T字微流道中產生黏滯剪斷現象，並透過流率的控制產生出各種大小的高光敏聚合物液滴，其尺寸誤差最小可達1.7 %。接著，再藉由壁面的處理及高光敏聚合物液滴曝照UV光的參數控制，成功使固化後的聚合物堆疊在一起而形成陣列結構，有圓球堆積陣列及長形堆積陣列兩種，而結構中的低窪縫隙處即為欲使細胞排列之處。在第一部份的實驗結果中，因高分子結構中凹凸之間高低差很大，因此可使細胞均排列在凹處的平坦面；而在第二部份我們成功將細胞排成蜂窩狀圖形，細胞佔有率可高達94.8 %，並使貼附式細胞成功貼附生長，此結果將可對細胞圖形化及細胞組織工程的研究有相當的助益。

關鍵字

磁流體 ； 黏滯剪斷 ； 細胞圖形化 ； 組織工程

並列摘要

This thesis contributes to apply microfluidic technique on cell patterning of tissue engineering. We fabricate two kinds of cell scaffolds in different ways. The first scaffold is fabricated by polymer molding. We induce the magnetic hydrodynamic instability and fission of ferrofluid droplets to generate ordered droplet arrays to be the masters for polymeric mother mold fabrication. Then we use the fabricated mother molds to molding PDMS scaffolds in shape of cones stand on a flat surface, and the bottom flats are the cell patterning regions. Due to the height difference between cone top and bottom flat is very large and the cone side is very steep, we can easily obtain high cell patterning rate (approximately 100%) by using this kind of cell scaffold.
The second kind of cell scaffold is fabricated by using microchannel systems. We use T-shaped microchannels to induce the break of viscous shear between UV-light curable agent and immiscible background fluid to generating UV-light curable droplets, and cure the collection of these droplets to fabricate polymeric cell scaffolds. In this way we can generate numerous sized UV-light curable droplets by controlling the flow rate of fluids, and the droplet size is pretty uniform at each selected fluid flow rate. The minimal deviation of the droplet diameter is found as small as 1.7%. In addition to controlling the fluid flow rate, adjusting the UV curing parameter is another way to fabricate types of cell scaffolds. Including honeycomb- and bamboo-like shaped scaffolds are fabricated. In our experiment results, we successfully pattern and culture cells on honeycomb scaffolds, and the best patterning rate is as high as 94.8%. We believe our proposed methods will benefit the research of cell patterning and tissue engineering.

並列關鍵字

ferrofluid ； break of viscous shear ； cell patterning ； tissue engineering

參考文獻

[1] H. Andersson and A. van den Berg, “Microfluidic devices for cellomics: a review,” Sensors and Actuators B, vol. 92, pp. 315-325, 2003.

[2] U. Bilitewski, M. Genrich, S. Kadow, and G. Mersal, “Biochemical analysis with microfluidic systems,” Analytical and Bioanalytical Chemistry, vol. 377, pp. 556-569, 2003.

[3] Y. Sun and Y. C. Kwok, “Polymeric microfluidic system for DNA analysis,” Analytica Chimica Acta, vol. 556, pp. 80-96, 2006.

[4] D. N. Breslauer, P. J. Lee, and L. P. Lee, “Microfluidics-based systems biology,” Molecular BioSystems, vol. 2, pp. 97-112, 2006.

[6] G. M. Whitesides, “The origins and the future of microfluidics,” Nature, vol. 442, pp. 368-373, 2006.