Caenorhabditis elegans is an excellent model organism for studying chemosensation as a significant part of its nervous system and genome are devoted to the detection of chemical cues. Studies of decision-making, learning, mating behaviour, and intraspecies communication require measuring the acute behavioural response to chemical stimulation. Such assays require precise and repeatable chemical delivery and are often arduous when performed manually. Microfluidic platforms have been developed for chemosensation studies in C. elegans. However, these platforms lack temporal resolution in chemical delivery necessary for screening acute behaviour and cannot selectively recover animals, a necessary feature for genetic screens. Here we present a droplet array for screening acute behavioural responses of C. elegans to chemical stimulation. Using droplets enables isolating the worms and controlling the chemical environment. The chamber design of the static array allows continuous monitoring of animal behaviour. By combining a gradient of confinement and flow restriction features, we demonstrate selective and sequential trapping of multiple droplets as well as their release on demand. These functions enable repeated capture of animals, monitoring of their behaviour upon chemical stimulation and subsequent release. To demonstrate the ability to screen multiple conditions, we measured worm thrashing activity in response to different concentrations of tetramisole. To illustrate the ability to capture acute behavioural responses, we monitored the behavioural response of male to pheromone stimulation. Due to the versatility of the chamber operation and its ultra-low volume uses of reagents, we envision this platform to be highly suited to combinatorial screening and drug discovery.

中文翻译：

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液滴阵列筛选秀丽隐杆线虫对化学药品的急性行为反应

秀丽隐杆线虫是研究化学感受器的优秀模型生物，因为其神经系统的重要部分和基因组致力于化学线索的检测。对决策，学习，交配行为和种内交流的研究需要测量对化学刺激的急性行为反应。这样的测定需要精确且可重复的化学递送，并且在手动进行时通常很费力。微流体平台已经被开发用于秀丽隐杆线虫的化学传感研究。然而，这些平台缺乏筛选急性行为所必需的化学传递的时间分辨率，并且不能选择性地恢复动物，这是遗传筛选的必要特征。在这里，我们提出了一种液滴阵列，用于筛查小鼠的急性行为反应秀丽隐杆线虫进行化学刺激。使用液滴可以隔离蠕虫并控制化学环境。静态阵列的腔室设计允许对动物行为进行连续监控。通过结合限制和流量限制功能的梯度，我们证明了多个液滴的选择性和顺序捕集以及按需释放。这些功能使得能够重复捕获动物，并在化学刺激和随后释放时监测其行为。为了证明筛选多种条件的能力，我们测量了响应于不同浓度的丁草醚的蠕虫rash动活性。为了说明捕获急性行为反应的能力，我们监测了男性对信息素刺激的行为反应。