A New 3D Cultured Liver Chip and Real-Time Monitoring System Based on Microfluidic Technology.

Yao Zhang,Ning Yang,Fangyu Shu,Naila Shaheen,Liangliang Xie,Qian Shi

doi:10.3390/mi11121118

Abstract

In vitro models of the liver have a good simulation of the micro-liquid environment inside the human liver and the communication between cell tissues, which provides an important research tool for drug research and liver disease treatment. In this paper, we designed a 3D liver chip and real-time monitoring system based on microfluidic technology. The in vitro model of the liver on the chip was established by the three-dimensional microfluidic chip pipeline and the corresponding microwell array. Meanwhile, the culture medium is continuously injected on the chip, and the electrochemical impedance spectroscopy and near-infrared spectroscopy of the liver chip are recorded and analyzed from day one to day five. When the 3D cultured liver chip in vitro model reached a certain period and stabilized, paracetamol with varying gradients of concentration was applied to the cultured cells for drug resistance testing. The experimental results show that the liver chip and its monitoring system designed in this paper can maintain 100% cell viability of hepatocytes in vitro for a long time. Furthermore, it can meet the requirements of measurement technologies such as electrical impedance measurement and near-infrared spectroscopy in real-time, providing a stable culture platform for the further study of organ chips.

Highlights

The liver is the largest parenchymal organ in the human body, which is responsible for various proteins, urea secretion and metabolism detoxification [1,2]
Most researchers focus on the construction of liver models [18,19], more and more people realize that the real-time monitoring system of liver chips can quickly reflect the influence of drugs on the liver state, and is more conducive to accurate drug screening
The impedance value of the cells under the three conditions became larger and the culture medium had the lowest impedance value, while the impedance value of the liver cells cultured on the liver chip exceeded that of two-dimensionally cultured liver cells on the fourth day, and stabilized on the fifth day

Summary

Introduction

The liver is the largest parenchymal organ in the human body, which is responsible for various proteins, urea secretion and metabolism detoxification [1,2]. The liver chip system has a good simulation of the communication between the internal microenvironment and cell tissues of the human liver [7,8], can predict the effectiveness of drugs in the human body and provides an important research direction for the treatment of liver diseases [9]. The two-dimensional cultured tissue model and the human liver model have large physiological differences and physical environment differences, so it is impossible to accurately predict liver metabolism and drug screening. Most researchers focus on the construction of liver models [18,19], more and more people realize that the real-time monitoring system of liver chips can quickly reflect the influence of drugs on the liver state, and is more conducive to accurate drug screening. The light transmittance of the chip is not fully utilized, and real-time and effective electrochemical and optical monitoring cannot be achieved

Methods

Results

Conclusion