A microfluidic 3D hepatocyte chip for drug toxicity testing.
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 IC(50) values of 5 model drugs derived from the dose-dependent on-chip testing correlate well with the reported in vivo LD(50) 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.
Toh
Yi-Chin
YC
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, Singapore, 138669, Singapore.
Lim
Teck Chuan
TC
Tai
Dean
D
Xiao
Guangfa
G
van Noort
Danny
D
Yu
Hanry
H
D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000295:instrumentation*