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Microfluidic biochip for the perifusion of precision-cut rat liver slices for metabolism and toxicology studies

Authors

  • Paul M. van Midwoud,

    1. Pharmaceutical Analysis, Department of Pharmacy, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands; telephone: +31-50-363-3337; fax: +31-50-363-7582
    2. Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Groningen, the Netherlands
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  • Geny M.M. Groothuis,

    1. Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Groningen, the Netherlands
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  • Marjolijn T. Merema,

    1. Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Groningen, the Netherlands
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  • Elisabeth Verpoorte

    Corresponding author
    1. Pharmaceutical Analysis, Department of Pharmacy, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands; telephone: +31-50-363-3337; fax: +31-50-363-7582
    • Pharmaceutical Analysis, Department of Pharmacy, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands; telephone: +31-50-363-3337; fax: +31-50-363-7582.
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Abstract

Early detection of kinetic, metabolic, and toxicity (ADME-Tox) profiles for new drug candidates is of crucial importance during drug development. This article describes a novel in vitro system for the incubation of precision-cut liver slices (PCLS) under flow conditions, based on a poly(dimethylsiloxane) (PDMS) device containing 25-µL microchambers for integration of the slices. The microdevice is coupled to a perifusion system, which enables a constant delivery of nutrients and oxygen and a continuous removal of waste products. Both a highly controlled incubation environment and high metabolite detection sensitivity could be achieved using microfluidics. Liver slices were viable for at least 24 h in the microdevice. The compound, 7-ethoxycoumarin (7-EC), was chosen to test metabolism, since its metabolism includes both phase I and phase II metabolism and when tested in the conventional well plate system, correlates well with the in vivo situation (De Kanter et al. 2004. Xenobiotica 34(3): 229–241.). The metabolic rate of 7-EC was found to be 214 ± 5 pmol/min/mg protein in the microdevice, comparable to well plates, and was constant over time for at least 3 h. This perifusion system better mimics the in vivo situation, and has the potential to significantly contribute to drug metabolism and toxicology studies of novel chemical entities. Biotechnol. Bioeng. 2010;105: 184–194. © 2009 Wiley Periodicals, Inc.

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