斑马鱼
发育毒性
达尼奥
畸形学
毒性
微流控
胚胎干细胞
胚胎
生物
脊索
细胞生物学
药理学
胚胎发生
化学
纳米技术
胎儿
遗传学
材料科学
怀孕
基因
有机化学
作者
Fan Yang,Zuanguang Chen,Jianbin Pan,Xinchun Li,Jufu Feng,Hui Yang
出处
期刊:Biomicrofluidics
[American Institute of Physics]
日期:2011-06-01
卷期号:5 (2)
被引量:70
摘要
Seeking potential toxic and side effects for clinically available drugs is considerably beneficial in pharmaceutical safety evaluation. In this article, the authors developed an integrated microfluidic array system for phenotype-based evaluation of toxic and teratogenic potentials of clinical drugs by using zebrafish (Danio rerio) embryos as organism models. The microfluidic chip consists of a concentration gradient generator from upstream and an array of open embryonic culture structures by offering continuous stimulation in gradients and providing guiding, cultivation and exposure to the embryos, respectively. The open culture reservoirs are amenable to long-term embryonic culturing. Gradient test substances were delivered in a continuous or a developmental stage-specific manner, to induce embryos to generate dynamic developmental toxicity and teratogenicity. Developmental toxicity of doxorubicin on zebrafish eggs were quantitatively assessed via heart rate, and teratological effects were characterized by pericardial impairment, tail fin, notochord, and SV-BA distance /body length. By scoring the teratogenic severity, we precisely evaluated the time- and dose-dependent damage on the chemical-exposed embryos. The simple and easily operated method presented herein demonstrates that zebrafish embryo-based pharmaceutic assessment could be performed using microfluidic systems and holds a great potential in high-throughput screening for new compounds at single animal resolution.
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