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. 2018 Jun 12;8:8951. doi: 10.1038/s41598-018-27179-6

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Zonation of primary (a) rat and (b) human hepatocytes in nitrogen metabolism in the MPOC platform. Hepatocytes induced with a hormonal gradient (one inlet: 100 nM glucagon, 0 U/L insulin and the other inlet: 0 nM glucagon, 100 U/L insulin) at a flow rate of 120 µL/hr displayed a descending CPS1 expression level along with the width of the device. Image quantification of CPS1 staining in hepatocytes induced by a gradient of the insulin-to-glucagon ratio indicated a descending profile of CPS1 expression level which demonstrates nitrogen metabolism. (a) All data met p < 0.05 except that non-induced vs ch4, non-induced vs ch5, ch1 vs ch2, and ch4 vs ch5 are not significant (ANOVA n = 4, Tukey’s test). (b) All data met p < 0.05 except that non-induced vs ch5, ch1 vs ch2, and ch3 vs ch4 are not significant (ANOVA n = 6, Tukey’s test). Each experiment was replicated using at least three different cell pools. Scale bar: 400 µm.