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

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• 作者：Laetitia Shintu ; R茅gis Baudoin ; Vincent Navratil ; Jean-Matthieu Prot ; Cl茅ment Pontoizeau ; Marianne Defernez ; Benjamin J. Blaise ; C茅line Domange ; Alexandre R. P茅ry ; Pierre Toulhoat ; C茅cile Legallais ; C茅line Brochot ; Eric Leclerc ; Marc-Emmanuel Dumas
• 刊名：Analytical Chemistry
• 出版年：2012
• 出版时间：February 21, 2012
• 年：2012
• 卷：84
• 期：4
• 页码：1840-1848
• 全文大小：486K
• 年卷期：v.84,no.4(February 21, 2012)
• ISSN：1520-6882

文摘

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鈥搑esponse signatures associated with both pharmaceutical and environmental toxicity. Here we present an approach combining a microfluidic system with ¹H 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 鈥渕etabolomics-on-a-chip鈥?assays in pharmaceutical and environmental toxicology.