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Microfluidic biochip for the perifusion of precision‐cut rat liver slices for metabolism and toxicology studies
Author(s) -
van Midwoud Paul M.,
Groothuis Geny M.M.,
Merema Marjolijn T.,
Verpoorte Elisabeth
Publication year - 2009
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.22516
Subject(s) - metabolite , in vivo , metabolism , drug metabolism , chemistry , adme , incubation , toxicokinetics , toxicity , microfluidics , in vitro , biochemistry , pharmacology , biology , nanotechnology , materials science , microbiology and biotechnology , organic chemistry
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.