Microfluidic system for on-chip high-throughput whole-animal sorting and screening at subcellular resolution
Microfluidic system for on-chip high-throughput whole-animal sorting and screening at subcellular resolution
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DOI：
10.1073/pnas.0706513104
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发表时间：
2007-08-28
影响因子：
11.1
通讯作者：
Yanik, Mehmet Fatih
中科院分区：
文献类型：
--
作者：
Rohde, Christopher B.;Zeng, Fei;Yanik, Mehmet Fatih
我们报告了一套用于复杂的高通量全动物遗传和药物筛选的关键微流体装置。我们展示了一个高速的微流控分选机，可以隔离，并在一个良好定义的几何形状秀丽隐杆线虫筛选表型功能在生理活性动物的亚细胞分辨率。我们展示了一种集成芯片，其中包含可单独寻址的筛选室设备，用于孵育和暴露个体动物的生化化合物，以及在单个芯片上对许多动物进行高分辨率延时成像，而无需麻醉。我们描述了一种设计，用于将标准多孔板中的化合物文库递送到微流体装置，并且还用于将筛选的动物快速分配到多孔板中。当以各种组合使用时，这些设备将促进使用整个动物的各种高通量测定，包括诱变和RNAi以及亚细胞分辨率的药物筛选，以及高通量高精度操作，例如用于大规模体内神经变性和再生研究的飞秒激光显微手术。
We report a suite of key microfluiclic devices for complex high-throughput whole-animal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize Caenorhabditis elegans in a well defined geometry for screening phenotypic features at subcellular resolution in physiologically active animals. We show an integrated chip containing individually addressable screening-chamber devices for incubation and exposure of individual animals to biochemical compounds and high-resolution time-lapse imaging of many animals on a single chip without the need for anesthesia. We describe a design for delivery of compound libraries in standard multiwell plates to microfluidic devices and also for rapid dispensing of screened animals into multiwell plates. When used in various combinations, these devices will facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond laser microsurgery for large-scale in vivo neural degeneration and regeneration studies.