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. 2021 Sep 9;9:721338. doi: 10.3389/fcell.2021.721338

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Copyright © 2021 Malik, Yang, Fathi, Mahler and Esch.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Examples of modes of flow circulation in a microphysiological system (MPS). (A) (i) Single-loop flow: unidirectional flow of medium across the organ chambers without recirculation. (B) Pump-based recirculating flow of medium using (i) an external peristaltic pump and medium reservoir to represent organs not cultured in any of the cell culture chambers in the system, (ii) an integrated on-chip pump, (iii) multiple integrated or external pumps to circulate medium through the apical side of a barrier tissue as well as the basolateral side of the tissue plus any other organ chambers (for example a liver-gastrointestinal tract MPS). (C) Gravity-based recirculating flow of medium following (i) unidirectional or (ii) bidirectional flow patterns with on-chip medium reservoirs. (iii) Medium reservoirs with flow rectifiers (or a valve) can be used in a liver-gastrointestinal tract model to regulate unidirectional flow in both apical and basolateral/liver chambers. (iv) The flow in pumpless systems is created by placing the device on a rocker platform at an angle, alternating the rocking motion every 30–60 s. Illustration is created using BioRender.com ^‡.