Carraro Amedeo, Hsu Wen-Ming, Kulig Katherine M, Cheung Wing S, Miller Mark L, Weinberg Eli J, Swart Eric F, Kaazempur-Mofrad Mohammad, Borenstein Jeffrey T, Vacanti Joseph P, Neville Craig
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Department of Surgical and Gastroenterological Sciences, University of Padua, School of Medicine, Padova, Italy.
Biomed Microdevices. 2008 Dec;10(6):795-805. doi: 10.1007/s10544-008-9194-3.
A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.
本文描述了一种新型的基于微流控技术的双层装置，该装置具有一个基于肝器官结构建模的离散实质腔室。微流控网络是使用计算模型设计的，以便根据来自人体微脉管系统的生理数据提供适当的流动行为。通过软光刻技术，使用图案化的硅晶片模具来生成具有基于血管的微流控网络设计和实质腔室的薄膜。组装好的装置在纳米多孔膜后面容纳肝细胞，该膜允许代谢物和小蛋白质的运输，同时保护它们免受剪切应力的影响。通过持续的体外培养基灌注，该装置能够维持人肝癌细胞和原代大鼠肝细胞的生长，促进细胞增殖并维持肝功能，如血清蛋白合成和代谢。该设计和制造过程具有可扩展性，使该装置概念既能作为药物发现和毒性研究的平台技术，又能用于持续改进肝辅助装置的开发。
