4.7 Article

A microfluidic 3D hepatocyte chip for drug toxicity testing

Journal

LAB ON A CHIP
Volume 9, Issue 14, Pages 2026-2035

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/b900912d

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Funding

  1. Biomedical Research Council, Agency for Science, Technology and Research (A*STAR) of Singapore [R185-001-045-305]
  2. Ministry of Education [R-185-000-135-112]
  3. National Medical Research Council [R-185-000-099-213]
  4. Singapore-MIT Alliance Computational and Systems Biology Flagship

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We have developed a microfluidic 3D hepatocyte chip (3D HepaTox Chip) for in vitro drug toxicity testing to predict in vivo drug hepatotoxicity. The 3D HepaTox Chip is based on multiplexed microfluidic channels where a 3D microenvironment is engineered in each channel to maintain the hepatocytes' synthetic and metabolic functions. The multiplexed channels allow for simultaneous administration of multiple drug doses to functional primary hepatocytes while an incorporated concentration gradient generator enables the in vitro dose-dependent drug responses to predict in vivo hepatotoxicity. The IC50 values of 5 model drugs derived from the dose-dependent on-chip testing correlate well with the reported in vivo LD50 values. The 3D HepaTox Chip can be integrated with on-chip sensors and actuators as the next generation cell-based on-chip drug testing platform.

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