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A Kinetic Pump Integrated Microfluidic Plate (KIM-Plate) with High Usability for Cell Culture-Based Multiorgan Microphysiological Systems

Shinha, Kenta, Nihei, Wataru, Nakamura, Hiroko, Goto, Tomomi, Kawanishi, Takumi, Ishida, Naoki, Yamazaki, Nao, Imakura, Yuki +7 more·2021·Micromachines
DOI 10.3390/mi12091007PMC PMC8471412
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Abstract

Microphysiological systems (MPSs), including organ-on-a-chip (OoC), have attracted attention as a novel method for estimating the effects and side effects of drugs in drug discovery. To reproduce the dynamic in vivo environment, previous MPSs were connected to pump systems to perfuse culture medium. Therefore, most MPSs are not user-friendly and have poor throughput. We aimed to develop a kinetic pump integrated microfluidic plate (KIM-Plate) by applying the stirrer-based micropump to an open access culture plate to improve the usability of MPSs. The KIM-Plate integrates six multiorgan MPS (MO-MPS) units and meets the ANSI/SBS microplate standards. We evaluated the perfusion function of the kinetic pump and found that the KIM-Plate had sufficient agitation effect. Coculture experiments with PXB cells and hiPS intestinal cells showed that the TEER of hiPS intestinal cells and gene expression levels related to the metabolism of PXB cells were increased. Hence, the KIM-Plate is an innovative tool for the easy coculture of highly conditioned cells that is expected to facilitate cell-based assays in the fields of drug discovery and biology because of its usability and high throughput nature.

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  • In cell-culture insert systems, cellular uptake and transport across the cell barrier can be studied with the porous membrane.

    “For the cell-culture insert system, cellular uptake and transport across the cell barrier (e.g., endothelial cells and intestinal epithelial cells) can be studied with the porous membrane;”

    From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [11]

    Methods §2.6 describes using culture inserts to measure apical-to-basolateral transport in intestinal cells, and Results §3.2 calculates permeability using the membrane surface area. The paper does not show a cellular uptake assay or an endothelial-cell barrier experiment, so those examples extend beyond what it demonstrates. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Reported GLA-MPSs showed better predictive capabilities of organ-to-organ interaction compared to normal static cell-culture models.

    “They showed better predictive capabilities of organ to organ interaction, compared to normal static cell-culture models.”

    From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [11]

    The Introduction says multiorgan MPSs can evaluate interorgan interactions in real time and may improve pharmacokinetic predictions. But the paper studies a KIM-Plate, not a system it calls a GLA-MPS, and does not show better predictive capability than static cell-culture models; its static-culture comparison in Results and Discussion §3.1 concerns cell number and morphology. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Current GLA-MPSs are based on two approaches: the cell-culture insert in microtiter plates and microfluidic devices.

    “The current GLA-MPSs are based on two approaches: the cell-culture insert in the microtiter plates 7,11 and microfluidic devices.12,13”

    From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [11]

  • A number of MPSs as an in vitro GLA model (GLA-MPS) have been reported, such as GLA for metabolism and inflammation axes.

    “Thus far, a number of MPSs as an in vitro GLA model (GLA-MPS) have been reported, such as GLA for metabolism and inflammation axess.3,7- 11”

    From Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction (2022) · cites this paper as [11]

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Authors
Shinha, K., Nihei, W., Nakamura, H., Goto, T., Kawanishi, T., Ishida, N., Yamazaki, N., Imakura, Y., Mima, S., Inamura, K., Arakawa, H., Nishikawa, M., Kato, Y., Sakai, Y., & Kimura, H.
Affiliations
  • Department of Mechanical Engineering, School of Engineering, Tokai University, 4-1-1 Kitakaname, Hiratsuka 259-1292, Japan
  • Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
  • Bio Science & Engineering Laboratory, FUJIFILM Corporation, 577 Ushijima, Kaisei-machi 258-8577, Japan
  • Department of Chemical System Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8654, Japan
ORCID
Venue
Micromachines
Publisher
MDPI AG
Published
2021-08-24
Volume
12
Issue
9
Pages
1007
ISSN
2072-666X
DOI
10.3390/mi12091007
PMC
PMC8471412
Cited by
35
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Japan Agency for Medical Research and Development (17be0304201h0001)
  • Japan Society for the Promotion of Science (18H01849)

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