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Issue 2, 2009
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Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device

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Abstract

An integrated microfluidic device was developed for the characterization of drug metabolites and a cytotoxicity assay simultaneously. The multi-layer device was composed of a quartz substrate with embedded separation microchannels and a perforated three-microwell array containing sol-gel bioreactors of human liver microsome (HLM), and two PDMS layers. By aligning the microwell array on the quartz substrate with cell culture chambers on the bottom PDMS layer, drug metabolism studies related to functional units, including metabolite generation, detection and incubation with cultured cells to assess metabolism induced cytotoxicity, were all integrated into the microfluidic device. To validate the feasibility of drug metabolism study on the microfluidic chip, UDP-glucuronosyltransferase (UGT) metabolism of acetaminophen (AP) and its effect on hepG2 cytotoxicity were studied first. Then metabolism based drug-drug interaction between AP and phenytoin (PH), which resulted in increased hepG2 cytotoxicity, was proved on this device. All this demonstrated that the developed microfluidic device could be a potential useful tool for drug metabolism and metabolism based drug-drug interaction research.

Graphical abstract: Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device

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Publication details

The article was received on 29 May 2008, accepted on 02 Oct 2008 and first published on 19 Nov 2008


Article type: Paper
DOI: 10.1039/B809117J
Citation: Lab Chip, 2009,9, 232-238
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    Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device

    B. Ma, G. Zhang, J. Qin and B. Lin, Lab Chip, 2009, 9, 232
    DOI: 10.1039/B809117J

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