| Biomécanique et Bioingéniérie |  |
| Biomécanique et Bioingéniérie | |
| HAL : hal-00699575, version 1 |
| DOI : 10.1021/ac2011075 |
| Fiche détaillée |  Récupérer au format |
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| Analytical Chemistry 84, 4 (2012) 1840-1848 |
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| Metabolomics-on-a-Chip and Predictive Systems Toxicology in Microfluidic Bioartificial Organs |
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| Laetitia Shintu 1, 2Régis Baudoin 3 |
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| (21/02/2012) |
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| 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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| 1 : | Institut des Sciences Analytiques (ISA) |
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Université de Lyon – CNRS : UMR5280 – Université Claude Bernard - Lyon I – École Normale Supérieure - Lyon |
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| 2 : | Institut des Sciences Moléculaires de Marseille (ISM2) |
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CNRS : UMR7313 – Aix-Marseille Université - AMU – Ecole Centrale de Marseille |
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| 3 : | Biomécanique et Bioingéniérie |
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CNRS : UMR6600 – Université de Technologie de Compiègne |
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| 4 : | Institute of Food Research |
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Institute of Food Research |
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| 5 : | Institut National de l'Environnement Industriel et des Risques (INERIS) |
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Institut National de l'Environnement Industriel et des Risques (INERIS) |
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| 6 : | Department of Surgery and Cancer |
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Imperial College London |
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| Centre de RMN à très hauts champs |
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| Domaine | : | Chimie/Chimie analytique |
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| NUCLEAR-MAGNETIC-RESONANCE – HEPATIC-ENCEPHALOPATHY – CORRELATION SPECTROSCOPY – CAENORHABDITIS-ELEGANS – PATTERN-RECOGNITION – NMR-SPECTROSCOPY – OXIDATIVE STRESS – DRUG TOXICITY – DATA SETS – LIVER |
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| hal-00699575, version 1 | |
| http://hal.archives-ouvertes.fr/hal-00699575 | |
| oai:hal.archives-ouvertes.fr:hal-00699575 | |
| Contributeur : Agnès Bussy | |
| Soumis le : Lundi 21 Mai 2012, 11:41:16 | |
| Dernière modification le : Mardi 9 Avril 2013, 17:03:26 | |
