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Automated phenotyping of Caenorhabditis elegans embryos with a high-throughput-screening microfluidic platform
Microsystems & Nanoengineering ( IF 7.9 ) Pub Date : 2020-04-06 , DOI: 10.1038/s41378-020-0132-8
Huseyin Baris Atakan 1 , Tunc Alkanat 2 , Matteo Cornaglia 1 , Raphaël Trouillon 1 , Martin A M Gijs 1
Affiliation  

The nematode Caenorhabditis elegans has been extensively used as a model multicellular organism to study the influence of osmotic stress conditions and the toxicity of chemical compounds on developmental and motility-associated phenotypes. However, the several-day culture of nematodes needed for such studies has caused researchers to explore alternatives. In particular, C. elegans embryos, due to their shorter developmental time and immobile nature, could be exploited for this purpose, although usually their harvesting and handling is tedious. Here, we present a multiplexed, high-throughput and automated embryo phenotyping microfluidic approach to observe C. elegans embryogenesis after the application of different chemical compounds. After performing experiments with up to 800 embryos per chip and up to 12 h of time-lapsed imaging per embryo, the individual phenotypic developmental data were collected and analyzed through machine learning and image processing approaches. Our proof-of-concept platform indicates developmental lag and the induction of mitochondrial stress in embryos exposed to high doses (200 mM) of glucose and NaCl, while small doses of sucrose and glucose were shown to accelerate development. Overall, our new technique has potential for use in large-scale developmental biology studies and opens new avenues for very rapid high-throughput and high-content screening using C. elegans embryos.



中文翻译:

使用高通量筛选微流体平台对秀丽隐杆线虫胚胎进行自动表型分析

线虫秀丽隐杆线虫已被广泛用作模型多细胞生物来研究渗透胁迫条件的影响和化合物对发育和运动相关表型的毒性。然而,此类研究所需的线虫培养数天已促使研究人员探索替代品。特别是,线虫胚胎,由于其较短的发育时间和不动的性质,可以用于此目的,尽管通常它们的收获和处理是乏味的。在这里,我们提出了一种多路复用、高通量和自动化的胚胎表型微流体方法来观察秀丽隐杆线虫应用不同化合物后的胚胎发生。在对每个芯片最多 800 个胚胎和每个胚胎最多 12 小时的延时成像进行实验后,通过机器学习和图像处理方法收集和分析个体表型发育数据。我们的概念验证平台表明,暴露于高剂量 (200 mM) 葡萄糖和 NaCl 的胚胎中发育滞后和诱导线粒体应激,而小剂量的蔗糖和葡萄糖则显示出加速发育。总体而言,我们的新技术具有用于大规模发育生物学研究的潜力,并为使用秀丽隐杆线虫胚胎进行非常快速的高通量和高内涵筛选开辟了新途径。

更新日期:2020-04-24
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