Design, fabrication, and characterization of a user-friendly microfluidic device for studying liver zonation-on-chip (ZoC)

IF 3 4区医学 Q3 ENGINEERING, BIOMEDICAL

Biomedical Microdevices Pub Date : 2025-02-14 DOI:10.1007/s10544-025-00738-1

Reza Mahdavi, Sameereh Hashemi-Najafabadi, Mohammad Adel Ghiass, Silmu Valaskivi, Hannu Välimäki, Joose Kreutzer, Charlotte Hamngren Blomqvist, Stefano Romeo, Pasi Kallio, Caroline Beck Adiels

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引用次数: 0

Abstract

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 (cell incubator air, 19% oxygen) and low oxygenated (nitrogen) 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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用于肝片上分区（ZoC）研究的用户友好型微流控装置的设计、制造和表征

肝分区是肝细胞空间异质性的基本特征，这在传统细胞培养中是具有挑战性的。本研究提出了一种新的微流体装置，旨在通过使用标准实验室气体建立氧梯度来诱导肝细胞培养的分区。该装置由两层组成；底层包含气体通道网络，输送高氧（细胞培养箱空气，含氧19%）和低氧（氮）气体，在上面一层的细胞培养室内创建三个不同的区域。采用计算模拟和比例氧传感来验证氧梯度，表明在两小时内达到稳定的氧水平。免疫荧光染色证实了肝分区，显示HepG2细胞的分区白蛋白产生与氧水平直接相关，并模仿体内的分区行为。这种用户友好的设备支持肝脏分区和相关代谢疾病机制的体外研究。它还可以用于需要精确气体浓度梯度的实验，例如专注于血管生成和癌症发展的缺氧相关研究领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Microdevices 工程技术-工程：生物医学

CiteScore

6.90

自引率

3.60%

发文量

审稿时长

6 months

期刊介绍： Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.