PUBLICATION

Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity

Authors
Li, Y., Yang, F., Chen, Z., Shi, L., Zhang, B., Pan, J., Li, X., Sun, D., Yang, H.
ID
ZDB-PUB-140513-143
Date
2014
Source
PLoS One   9: e94792 (Journal)
Registered Authors
Yang, Fan
Keywords
Embryos, Zebrafish, Microfluidics, Larvae Toxicity, Flow rate, Convulsions, Heart rate
MeSH Terms
  • Aminophylline/toxicity*
  • Animals
  • Computer Systems*
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/pathology
  • Embryonic Development/drug effects*
  • Fertilization/drug effects
  • Heart Defects, Congenital/embryology
  • Heart Defects, Congenital/pathology
  • Heart Defects, Congenital/physiopathology
  • Heart Rate/drug effects
  • Larva/drug effects
  • Microfluidics/methods*
  • Rheology/drug effects
  • Seizures/pathology
  • Survival Analysis
  • Teratogens/toxicity
  • Toxicity Tests/methods*
  • Zebrafish/embryology*
PubMed
24733308 Full text @ PLoS One
Abstract
Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping