Abstract
We describe a novel fabrication method that creates microporous, polymeric membranes that are either flat or contain controllable 3-dimensional shapes that, when populated with Caco-2 cells, mimic key aspects of the intestinal epithelium such as intestinal villi and tight junctions. The developed membranes can be integrated with microfluidic, multi-organ cell culture systems, providing access to both sides, apical and basolateral, of the 3D epithelial cell culture. Partial exposure of photoresist (SU-8) spun on silicon substrates creates flat membranes with micrometer-sized pores (0.5–4.0 μm) that—supported by posts—span across 50 μm deep microfluidic chambers that are 8 mm wide and 10 long. To create three-dimensional shapes the membranes were air dried over silicon pillars with aspect ratios of up to 4:1. Space that provides access to the underside of the shaped membranes can be created by isotropically etching the sacrificial silicon pillars with xenon difluoride. Depending on the size of the supporting posts and the pore sizes the overall porosity of the membranes ranged from 4.4 % to 25.3 %. The microfabricated membranes can be used for integrating barrier tissues such as the gastrointestinal tract epithelium, the lung epithelium, or other barrier tissues with multi-organ “body-on-a-chip” devices.
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Acknowledgments
Financial support for this work was provided by the Nanobiotechnology Center (NBTC), an STC Program of the National Science Foundation, under Agreement No. ECS-9876771, by the Army Corps of Engineers under Agreement ID W9132T-07-2-0010 and by the NSF under grant No. CBET-1106153. This work was performed in part at the Cornell NanoScale Science & Technology Facility, a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation (Grant ECS-0335765). This work was in part supported by the National Research Foundation of Korea (NRF, Grant no. 2012-0003408), KFRI (Korea Food Research Institute, grant no: E0121705), Hongik University new faculty research support fund, and 2012 Hongik University Research Fund. Caco-2 samples for SEM imaging were prepared at the Cornell Center for Materials Reserach (CCMR, NSF DMR-1120296).
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Mandy Brigitte Esch and Jong Hwan Sung have contributed equally to the work.
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Esch, M.B., Sung, J.H., Yang, J. et al. On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices. Biomed Microdevices 14, 895–906 (2012). https://doi.org/10.1007/s10544-012-9669-0
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DOI: https://doi.org/10.1007/s10544-012-9669-0