研發並利用雷射剝蝕技術製成可吸收微流體

Fabrication of Biodegradable/Biocompatible Microfluidic System Using Laser Ablation

陳筱晨(Chen, Shiau Chen)

指導教授 ： 王潔

國立清華大學/工學院/化學工程學系/碩士(2015年)

摘要

至2014年為止，在美國大約有12萬人正著急得等待著進行器官移植手術。然而需接受器官移植等待人數每年不斷增加，器官再生就成為了備受關注的議題。為了能夠再生一個完整的器官，首先需要解決的是製造出血管網絡來提供養分以及移除細胞代謝廢物讓周遭的細胞生長，並進而生長成所需要的器官。此論文主要著重在於研究及探討新的技術-雷射剝蝕，利用雷射剝蝕來製造仿微血管的圖案，亦即提供一個支架讓細胞生長，將細胞養在支架上，進而獲得微血管網絡。

具分支狀的微流體常被運用在偵測器、感測器及物質分析。此論文利用分支狀的微流體來模仿微血管。所使用的高分子為PDMS、PGS以及APS。PDMS具有良好的生物相容性，但其為不可降解高分子。然而PGS與APS不僅具有極佳的生物相容性、可調整的機械性質，更重要的是其具有生物可降解性。生物可降解高分子的特點為: 當組織再生時，高分子會慢慢被分解，不需要有額外的程序取出高分子。

相對於傳統黃光製程或是軟微影技術來說，利用雷射剝蝕技術來製造微流體是較簡單、較安全的製程。微流體的流道深度可以被精準的控制且所設計的圖案可變性高。利用雷射剝蝕來製造圖案所需考慮的參數為: 能量、直徑大小、剝蝕頻率、剝蝕速度以及重複剝蝕的次數。此論文使用能量6J/cm2和直徑150um來製造微流體。其他的參數像是剝蝕頻率、剝蝕速度和重複剝蝕次數也將詳細的探討。使用這些參數，我們成功的製造出多層微流體為的就是能夠模擬更真實的立體微血管網絡。藉著由下往上組裝的方式來製作多層的微流體，希望能在組織工程這個領域裡提供一個組織再生的新選擇。

關鍵字

生物可降解高分子 ； 雷射剝蝕 ； 微流體

並列摘要

As up to 2014, there were about 123,800 patients in the U.S. waiting for a life saving organ transplant. Organ regeneration is a pressing issue as the waiting list of organ transplant is getting longer and longer year by year. To achieve the ultimate goal, the regeneration of organs, the lack of blood vessel in the regeneration of multi-layered is needed to be solved. In this work, a novel fabrication method, laser ablation, is developed for the fabrication of biodegradable microfluidic devices for the regeneration of vascularized tissue.

Mircorfluidic devices with branched micro-size channels have been applied in detectors, sensors, and analytical separation. To crate biocompatible and biodegradable micorfluidic systems, one biocompatible polymer, poly(dimethylsiloxane) (PDMS), and two biodegradable polymers, poly(glycerol sebacate) (PGS) and poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s (APS), were synthesized for the fabrication of branched microfluidic systems using laser ablation. These branched microfluidic systems aim to mimic complex microvascular systems to provide nutrient and oxygen for organs such as kidney and liver regeneration. The biodegradable polymers, PGS and APS, with controllable stiffness and degradation rate are able to mimic microvascular systems in vivo, while degrading slowly during new tissue regeneration.

Laser ablation is a rather simple fabrication method that can be easily controlled and is a safe process compared to conventional microfluidic system fabrication methods such as lithography and soft lithography. The channels depth can be controlled precisely and are high flexibility in the design of fabrication patterns by utilizing laser ablation. There are several fabrication parameters that require to be analyzed, including fluence (energy per unit area), beam size of laser pulse, beam velocity, beam firing frequency, and numbers of repeated ablation. In this study, the fluence was chosen as 6 J/cm^2 and the beam size of laser pulse was set as 150 μm. A few other parameters that can affect the fabrication of microfluidic devices are beam velocity, beam firing frequency, and numbers of repeated ablation. These parameters were thoroughly investigated, and are successfully applied in the fabrication of multiple devices. This study presents a revolutionary micropatterning methodology that enables the fabrication of a 3D microvascular system through a bottom-up process, and is expected to present new options for the field of tissue engineering.

並列關鍵字

Biomaterial ； Laser Ablation ； Microfluidics

參考文獻

1. Cascalho, M., J. Cascalho, and Platt, New Technologies for Organ Replacement and Augmentation.Mayo Clinic proceedings, Vol. 80, pp. 370-378, (2005).

3. U.S. Government Information on Organ and Tissue Donation and Transplantation. Available from: http://www.organdonor.gov/about/data.html.

5. Griffith, L.G. and G. Naughton, Opportunities Tissue Engineering--Current Challenges and Expanding.Science. Vol. 295, pp. 1009, (2002).

6. Agarwal S, Holton KL, and Lanza R, Efficient Differentiation of Functional Hepatocytes from Human Embryonic Stem Cells. Stem Cells. Vol. 26, pp. 1117-1127,(2008).

7. Kehat I, Kenyagin-Karsenti D, Snir M, et al., Human Embryonic Stem Cells Can Differentiate into Myocytes with Structural and Functional Properties of Cardiomyocytes.The Journal of Clinical Investigation, Vol.108, pp. 407-414, (2001).