Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC)

Liver zonation is a fundamental characteristic of hepatocyte spatial heterogeneity, which is challenging to recapitulate in traditional cell cultures. This study presents a novel microfluidic device designed to induce zonation in liver cell cultures by establishing an oxygen gradient using standard...

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Veröffentlicht in:arXiv.org 2024-07
Hauptverfasser: Mahdavi, Reza, Sameereh Hashemi Najafabadi, Mohammad Adel Ghiass, Valaskivi, Silmu, Välimäki, Hannu, Kreutzer, Joose, Blomqvist, Charlotte Hamngren, Romeo, Stefano, Kallio, Pasi, Caroline Beck Adiels
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container_title arXiv.org
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creator Mahdavi, Reza
Sameereh Hashemi Najafabadi
Mohammad Adel Ghiass
Valaskivi, Silmu
Välimäki, Hannu
Kreutzer, Joose
Blomqvist, Charlotte Hamngren
Romeo, Stefano
Kallio, Pasi
Caroline Beck Adiels
description Liver zonation is a fundamental characteristic of hepatocyte spatial heterogeneity, which is challenging to recapitulate in traditional cell cultures. This study presents a novel microfluidic device designed to induce zonation in liver cell cultures by establishing an oxygen gradient using standard laboratory gases. The device consists of two layers; a bottom layer containing a gas channel network that delivers high and low oxygenated gases to create three distinct zones within the cell culture chamber in the layer above. Computational simulations and ratiometric oxygen sensing were employed to validate the oxygen gradient, demonstrating that stable oxygen levels were achieved within two hours. Liver zonation was confirmed using immunofluorescence staining, which showed zonated albumin production in HepG2 cells directly correlating with oxygen levels and mimicking in-vivo zonation behavior. This user-friendly device supports studies on liver zonation and related metabolic disease mechanisms in vitro. It can also be utilized for experiments that necessitate precise gas concentration gradients, such as hypoxia-related research areas focused on angiogenesis and cancer development.
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subjects Cell culture
Concentration gradient
Heterogeneity
Immunofluorescence
Liver
Metabolic disorders
Microfluidic devices
Oxygen
title Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC)
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