Letizia M C, Cornaglia M, Tranchida G, Trouillon R, Gijs M A M
Microsystems Laboratory, École Polytechnique Fédérale de Lausanne, EPFL-STI-IMT-LMIS2, Station 17, Ch-1015 Lausanne, Switzerland.
Integr Biol (Camb). 2018 Jan 22;10(1):48-56. doi: 10.1039/c7ib00184c.
When studying the drug effectiveness towards a target model, one should distinguish the effects of the drug itself and of all the other factors that could influence the screening outcome. This comprehensive knowledge is crucial, especially when model organisms are used to study the drug effect at a systemic level, as a higher number of factors can influence the drug-testing outcome. Covering the entire experimental domain and studying the effect of the simultaneous change in several factors would require numerous experiments, which are costly and time-consuming. Therefore, a design of experiment (DoE) approach in drug-testing is emerging as a robust and efficient method to reduce the use of resources, while maximizing the knowledge of the process. Here, we used a 3-factor-Doehlert DoE to characterize the concentration-dependent effect of the drug doxycycline on the development duration of the nematode Caenorhabditis elegans. To cover the experimental space, 13 experiments were designed and performed, where different doxycycline concentrations were tested, while also varying the temperature and the food amount, which are known to influence the duration of C. elegans development. A microfluidic platform was designed to isolate and culture C. elegans larvae, while testing the doxycycline effect with full control of temperature and feeding over the entire development. Our approach allowed predicting the doxycycline effect on C. elegans development in the complete drug concentration/temperature/feeding experimental space, maximizing the understanding of the effect of this antibiotic on the C. elegans development and paving the way towards a standardized and optimized drug-testing process.
在研究药物对目标模型的有效性时，应区分药物本身的作用以及所有其他可能影响筛选结果的因素的作用。这种全面的知识至关重要，尤其是在使用模式生物在系统水平上研究药物作用时，因为更多的因素会影响药物测试结果。涵盖整个实验领域并研究多个因素同时变化的影响需要进行大量实验，这些实验既昂贵又耗时。因此，药物测试中的实验设计（DoE）方法正在成为一种强大而有效的方法，既能减少资源使用，又能最大限度地增加对该过程的了解。在此，我们使用三因素多勒特实验设计（3-factor-Doehlert DoE）来表征强力霉素药物浓度对线虫秀丽隐杆线虫发育持续时间的影响。为了涵盖实验空间，设计并进行了13次实验，测试了不同的强力霉素浓度，同时还改变了温度和食物量，已知这些因素会影响秀丽隐杆线虫的发育持续时间。设计了一个微流控平台来分离和培养秀丽隐杆线虫幼虫，同时在整个发育过程中完全控制温度和喂食的情况下测试强力霉素的作用。我们的方法能够在完整的药物浓度/温度/喂食实验空间中预测强力霉素对秀丽隐杆线虫发育的影响，最大限度地加深对这种抗生素对秀丽隐杆线虫发育影响的理解，并为标准化和优化的药物测试过程铺平道路。
