Biotechnology and Bioprocess Engineering 2022; 27(2): 221-233  
Development of a Pumpless Microfluidic System to Study the Interaction between Gut Microbes and Intestinal Epithelial Cells
Seung Yeon Lee, Hyun Jae Byun, Heelak Choi, Jong-In Won, Jeonghun Han, Sungsu Park, Donghyun Kim, and Jong Hwan Sung
Seung Yeon Lee, Hyun Jae Byun, Heelak Choi, Jong-In Won, Jong Hwan Sung*
Department of Chemical Engineering, Hongik University, Seoul 04066, Korea
Tel: +82-2-320-3067; Fax: +82-2-3143-1129
E-mail: jhsung22@hongik.ac.kr
Jeonghun Han
DOF Inc., Hwaseong 18468, Korea
Sungsu Park
Department of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Korea
Donghyun Kim
School of Electrical and Electronic Engineering, Yonsei University, Seoul 03722, Korea
Received: September 9, 2021; Revised: October 20, 2021; Accepted: October 22, 2021; Published online: April 30, 2022.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Gut microbiota dysbiosis and intestinal epithelial cell barrier dysfunction are associated with diseases such as inflammatory bowel disease and type 2 diabetes. To study the interaction of gut microbes and intestinal epithelial cells, in vitro model systems for co-culturing intestinal cells and gut microbes are essential. Since most gut microorganisms are anaerobic bacteria, it is difficult to co-culture microbes with intestinal epithelial cells that require oxygen during culture. We have developed a novel gut microbialepithelial cell (GMEC) co-culture system, a microfluidic chip in an anaerobic chamber with oxygen gradient within the chip. Appropriate co-culture flow rates were determined based on the experimental observation as well as fluid dynamics and molecular transport simulations. Using GMEC system, Escherichia coli and Lactobacillus plantarum were co-cultured with gut epithelial cell line, Caco-2. We expect that our GMEC co-culture system can potentially be a useful platform for studying the interaction between intestinal epithelial cells and gut microbes.
Keywords: gut microbiota, gut-on-a-chip, oxygen gradient

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