title: Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity.
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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; School of Pharmaceutical Sciences, Gannan Medical University, Ganzhou, JiangXi, China.
authors.forename: Yinbao
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Laboratory Medcine, Hubei University of Chinese Medicine, Wuhan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zuanguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Pan
authors.affiliation: School of Pharmaceutical Sciences, Guangxi Medical University, Nanning, China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Duanping
authors.initials: D
authors.lastname: Sun
authors.affiliation: The third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Yang
mesh_terms: D000628:Aminophylline / Q000633:toxicity*; D000818:Animals; D003199:Computer Systems; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects*; D005306:Fertilization / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D044085:Microfluidics / Q000379:methods*; D012212:Rheology / Q000187:drug effects; D012640:Seizures / Q000473:pathology; D016019:Survival Analysis; D013723:Teratogens / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D013723:Teratogens; D000628:Aminophylline
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