title: Modular microfluidic system for emulation of human phase I/phase II metabolism.
abstract: We present a microfluidic device for coupled phase I/phase II metabolic reactions in vitro. The chip consists of microchannels, which are used as packed bed reactor compartments, filled with superparamagnetic microparticles bearing recombinant microsomal phase I cytochrome P450 or phase II conjugating enzymes (UDP-glucuronosyltransferase). Online coupling of the microfluidic device with LC/MS enabled the quantitative assessment of coupled phase I/phase II transformations, as demonstrated for two different substrates, 7-benzyloxy-4-trifluoromethylcoumarin (BFC) and dextromethorphan (DEX). In contrast, conventional sequential one-pot incubations did not generate measurable amounts of phase II metabolites. Because the microfluidic device is readily assembled from standard parts and can be equipped with a variety of recombinant enzymes, it provides a modular platform to emulate and investigate hepatic metabolism processes, with particular potential for targeted small-scale synthesis and identification of metabolites formed by sequential action of specific enzymes.
authors.affiliation: Technische Universität Dortmund , Fakultät Chemie, Biologisch-Chemische Mikrostrukturtechnik, Otto Hahn Str. 6, 44227 Dortmund, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampe
authors.forename: Anna
authors.initials: A
authors.lastname: König
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schroeder
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Christof M
authors.initials: CM
authors.lastname: Niemeyer
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D044085:Microfluidics
chemical_list: D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase