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Article Dans Une Revue Analytical Chemistry Année : 2012

Metabolomics-on-a-Chip and Predictive Systems Toxicology in Microfluidic Bioartificial Organs

Cécile Legallais

Résumé

The world faces complex challenges for chemical hazard assessment. Microfluidic bioartificial organs enable the spatial and temporal control of cell growth and biochemistry, critical for organ-specific metabolic functions and particularly relevant to testing the metabolic dose-response signatures associated with both pharmaceutical and environmental toxicity. Here we present an approach combining a microfluidic system with H-1 NMR-based metabolomic footprinting as a high-throughput small-molecule screening approach. We characterized the toxicity of several molecules: ammonia (NH3), an environmental pollutant leading to metabolic acidosis and liver and kidney toxicity; dimethylsulfoxide (DMSO), a free radical-scavenging solvent; and N-acetyl-para-aminophenol (APAP, or paracetamol), a hepatotoxic analgesic drug. We report organ-specific NH3 dose-dependent metabolic responses in several microfluidic bioartificial organs (liver, kidney, and cocultures), as well as predictive (99% accuracy for NH3 and 94% for APAP) compound-specific signatures. Our integration of microtechnology, cell culture in microfluidic biochips, and metabolic profiling opens the development of so-called "metabolomics-on-a-chip" assays in pharmaceutical and environmental toxicology.
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Dates et versions

hal-00699575 , version 1 (21-05-2012)

Identifiants

Citer

Laetitia Shintu, Régis Baudoin, Vincent Navratil, Jean-Matthieu Prot, Clément Pontoizeau, et al.. Metabolomics-on-a-Chip and Predictive Systems Toxicology in Microfluidic Bioartificial Organs. Analytical Chemistry, 2012, 84 (4), pp.1840-1848. ⟨10.1021/ac2011075⟩. ⟨hal-00699575⟩
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