I-Corps: A microfluidic technology for drug testing on small nematodes

I-Corps项目的广泛影响/商业潜力是一种创新的高通量技术，用于在小动物中筛选药物，包括流行的模式生物线虫线虫，一种毫米大小的线虫。年龄是多种疾病的重要风险因素，包括癌症、心血管疾病和神经退行性疾病。据预测，到2030年，美国将有20%的人口年龄在65岁或以上，这表明随着人口老龄化的加剧，这些疾病的发病率预计将上升。同样，土壤传播的蠕虫感染在世界各地普遍存在，越来越多的证据表明，寄生线虫正在对现有药物产生抗药性。线虫是一种低成本和高通量的动物模型，用于识别与年龄相关的疾病和寄生虫感染的候选药物。I-Corps项目有可能解决目前在线虫模型中进行高通量药物分析的瓶颈，从而为药物发现管道铺平道路。这个项目的影响是减轻与年龄相关的疾病和寄生虫感染相关的社会经济负担。这个i-Corps项目寻求开发一种基于微流体的技术，用于对小线虫进行自动药物测试。目前对线虫进行药物测试的方法包括繁琐的人工采摘和转移培养在琼脂平板上的动物的步骤，而且不允许对培养环境进行灵活控制。这项拟议的技术建立在微尺度流动、活跃的游泳者和爬行者的运动以及低成本的广域成像的基本原理上。药物检测技术的新特点包括优化的微流控柱竞技场，形成了生长动物的栖息地，对试剂输送和培养环境进行了前所未有的控制。低成本的广域成像可以方便地视频记录动物对不同药物的反应。这项拟议的创新将显著提高体内药物和毒性分析的吞吐量，建立一个已建立的、高通量和低成本的动物模型。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broad impact/commercial potential of this I-Corps project is an innovative high throughput technology for screening drugs in small animals including the popular model organism C. elegans, a millimeter-sized nematode. Age is a significant risk factor for a variety of diseases including cancer, cardiovascular ailments and neurodegenerative disorders. It is projected that by 2030, 20% of the US population will be 65 years or older indicating that with the growing aging population the incidence of these diseases is expected to rise. Likewise, soil-transmitted helminthic infections are prevalent worldwide and there is increasing evidence that parasitic nematodes are becoming resistant to available drugs. C. elegans is a low-cost and high throughput animal model for identifying drug candidates for age-related diseases and parasitic infections. The I-Corps project has the potential to address current bottlenecks in conducting high throughput drug assays in the C. elegans model, thereby paving the path for a drug discovery pipeline. The impact of this project is on alleviating the socio-economic burden associated with age-associated diseases and parasitic infections.This I-Corps project seeks to develop a microfluidics-based technology for automated drug testing on small nematodes. Current approaches to drug testing on C. elegans involve tedious steps of manual picking and transferring animals cultured on agar plates and moreover do not allow flexible control of culture environment. The proposed technology builds on basic principles of microscale flows, locomotion of active swimmers and crawlers, and low-cost wide-field imaging. Novel features of the technology for drug testing include an optimized microfluidic pillar arena that forms a habitat for growing animals, with unprecedented control over reagent delivery and culture environment. The low-cost wide-field imaging allows facile video recording of animal response to different drugs. The proposed innovation will markedly advance the throughput of in vivo drug and toxicity assays in an established, high throughput and low-cost animal model.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.