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Biotechnol Bioeng. 2010 Jan 1;105(1):184-94. doi: 10.1002/bit.22516.

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

Author information

1
Pharmaceutical Analysis, Department of Pharmacy, Toxicology and Targeting, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands.

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-microL 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.

PMID:
19718695
DOI:
10.1002/bit.22516
[Indexed for MEDLINE]

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