Microfluidic biochip for the perifusion of precision-cut rat liver slices for metabolism and toxicology studies

Biotechnol Bioeng. 2010 Jan 1;105(1):184-94. doi: 10.1002/bit.22516.


Early detection of kinetic, metabolic, and toxicity (ADME-Tox) profiles for new drug candidates is of crucial importance during drug development. This article describes a novel in vitro system for the incubation of precision-cut liver slices (PCLS) under flow conditions, based on a poly(dimethylsiloxane) (PDMS) device containing 25-microL microchambers for integration of the slices. The microdevice is coupled to a perifusion system, which enables a constant delivery of nutrients and oxygen and a continuous removal of waste products. Both a highly controlled incubation environment and high metabolite detection sensitivity could be achieved using microfluidics. Liver slices were viable for at least 24 h in the microdevice. The compound, 7-ethoxycoumarin (7-EC), was chosen to test metabolism, since its metabolism includes both phase I and phase II metabolism and when tested in the conventional well plate system, correlates well with the in vivo situation (De Kanter et al. 2004. Xenobiotica 34(3): 229-241.). The metabolic rate of 7-EC was found to be 214 +/- 5 pmol/min/mg protein in the microdevice, comparable to well plates, and was constant over time for at least 3 h. This perifusion system better mimics the in vivo situation, and has the potential to significantly contribute to drug metabolism and toxicology studies of novel chemical entities.

MeSH terms

  • Animals
  • Cell Survival
  • Coumarins / chemistry
  • Coumarins / toxicity*
  • Hydrogen-Ion Concentration
  • Inactivation, Metabolic*
  • Liver / metabolism*
  • Male
  • Microfluidics* / economics
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Tissue Culture Techniques
  • Toxicology / instrumentation*
  • Toxicology / methods


  • Coumarins
  • 7-ethoxycoumarin