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

Fuente: arXiv
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Hauptverfasser: Mahdavi, Reza, Najafabadi, Sameereh Hashemi, Ghiass, Mohammad Adel, Valaskivi, Silmu, Välimäki, Hannu, Kreutzer, Joose, Blomqvist, Charlotte Hamngren, Romeo, Stefano, Kallio, Pasi, Adiels, Caroline Beck
Format: Preprint
Veröffentlicht: 2024
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author Mahdavi, Reza
Najafabadi, Sameereh Hashemi
Ghiass, Mohammad Adel
Valaskivi, Silmu
Välimäki, Hannu
Kreutzer, Joose
Blomqvist, Charlotte Hamngren
Romeo, Stefano
Kallio, Pasi
Adiels, Caroline Beck
author_facet Mahdavi, Reza
Najafabadi, Sameereh Hashemi
Ghiass, Mohammad Adel
Valaskivi, Silmu
Välimäki, Hannu
Kreutzer, Joose
Blomqvist, Charlotte Hamngren
Romeo, Stefano
Kallio, Pasi
Adiels, Caroline Beck
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2407_12976
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC)
Mahdavi, Reza
Najafabadi, Sameereh Hashemi
Ghiass, Mohammad Adel
Valaskivi, Silmu
Välimäki, Hannu
Kreutzer, Joose
Blomqvist, Charlotte Hamngren
Romeo, Stefano
Kallio, Pasi
Adiels, Caroline Beck
Tissues and Organs
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.
title Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC)
topic Tissues and Organs
url https://arxiv.org/abs/2407.12976