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Fabrication and characterization of microfluidic liver-on-a-chip using microsomal enzymes

Paper ID Volume ID Publish Year Pages File Format Full-Text
17300 42658 2013 6 PDF Available
Title
Fabrication and characterization of microfluidic liver-on-a-chip using microsomal enzymes
Abstract

•Design and fabrication of microfluidic chip for reproducing liver metabolism.•Calculation of enzyme kinetic parameters for the P450 reaction of liver microsomes.•Construction and validation of a mathematical model of microsomal reaction inside the chip.

Biotransformation in the liver plays an important role in determining the pharmacokinetic profile of drugs and food components. Current in vitro platforms for testing the liver metabolism suffers from the lack of resemblance to the human liver metabolism, mainly due to the lost metabolic activity of cultured hepatocytes and the absence of transport phenomena that occurs in the liver tissue. Here we report a microfluidic device with liver microsome encapsulated in 3-D hydrogel matrix, which can mimic the metabolism reaction and the transport phenomena in the liver. Photopolymerization of poly(ethylene glycol) diacrylate (PEG-DA) allows controlling the mass transfer with matrix sizes, and a gravity-induced passive flow can reproduce the blood flow through the liver. We measured the reaction kinetics of P450 enzymes in the device, and simulated the convection-diffusion-reaction characteristics inside the device with a mathematical model. Combination of mathematical analytical tool and the experimental tool allowed us to analyze and optimize the reaction kinetics inside the microfluidic chip. This novel in vitro platform can serve as a tool for screening the liver metabolism of various compounds.

Keywords
Microfluidic; Liver metabolism; Microsome; Hydrogel
First Page Preview
Fabrication and characterization of microfluidic liver-on-a-chip using microsomal enzymes
Publisher
Database: Elsevier - ScienceDirect
Journal: Enzyme and Microbial Technology - Volume 53, Issue 3, 15 August 2013, Pages 159–164
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering