Xie Xin, Maharjan Sushila, Kelly Chastity, Liu Tian, Lang Robert J, Alperin Roger, Sebastian Shikha, Bonilla Diana, Gandolfo Sakura, Boukataya Yasmine, Siadat Seyed Mohammad, Zhang Yu Shrike, Livermore Carol
Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115, USA.
Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Adv Mater Technol. 2022 May;7(5). doi: 10.1002/admt.202100677. Epub 2021 Nov 30.
The design and manufacture of an origami-based liver-on-a-chip device are presented, together with demonstrations of the chip's effectiveness at recapitulating some of the liver's key in vivo architecture, physical microenvironment, and functions. Laser-cut layers of polyimide tape are folded together with polycarbonate nanoporous membranes to create a stack of three adjacent flow chambers separated by the membranes. Endothelial cells are seeded in the upper and lower flow chambers to simulate sinusoids, and hepatocytes are seeded in the middle flow chamber. Nutrients and metabolites flow through the simulated sinusoids and diffuse between the vascular pathways and the hepatocyte layers, mimicking physiological microcirculation. Studies of cell viability, metabolic functions, and hepatotoxicity of pharmaceutical compounds show that the endothelialized liver-on-a-chip model is conducive to maintaining hepatocyte functions and evaluation of the hepatotoxicity of drugs. Our unique origami approach speeds chip development and optimization, effectively simplifying the laboratory-scale fabrication of on-chip models of human tissues without necessarily reducing their structural and functional sophistication.
本文介绍了一种基于折纸技术的芯片上肝脏装置的设计与制造,并展示了该芯片在重现肝脏一些关键的体内结构、物理微环境和功能方面的有效性。激光切割的聚酰亚胺带层与聚碳酸酯纳米多孔膜折叠在一起,形成由膜分隔的三个相邻流动腔室的堆叠。将内皮细胞接种在上部和下部流动腔室中以模拟肝血窦,将肝细胞接种在中间流动腔室中。营养物质和代谢产物流经模拟的肝血窦,并在血管途径和肝细胞层之间扩散,模拟生理微循环。对药物化合物的细胞活力、代谢功能和肝毒性的研究表明,内皮化的芯片上肝脏模型有助于维持肝细胞功能和评估药物的肝毒性。我们独特的折纸方法加快了芯片的开发和优化,有效地简化了人体组织芯片模型的实验室规模制造,而不一定降低其结构和功能的复杂性。