Microfluidic screening devices for health-span extending drugs

衰老，即身体和精神的进行性退化，是一种以组织衰退为特征的普遍问题 组织和功能，以及死亡可能性的增加。细胞因子的研究进展 随着几个著名模型的发现，老化的分子基础正在迅速加速 生物体的衰老方式与人类许多相同。除了他们对我们的基础设施的贡献 了解衰老的生物学，这些生物现在被用来筛选 不仅延长寿命，而且延长老年人的生活质量(健康跨度)。其中最 在衰老和健康范围研究中强大的模式系统是微小线虫线虫 雅致，因其寿命短(2-3周)、遗传易驯化和低成本而受到青睐。线虫的研究是 目前正在进行快速创新，因为它的小尺寸与微流体特别兼容- 操纵尺寸为几十微米的通道中的流体。建议的总体目标是 研究是通过开发一种能够延长健康寿命的化合物来加速发现 一种新型微流控设备，可能提高健康范围筛查的吞吐量和分辨率 这种关键的有机体。线虫健康寿命筛查的传统方法目前面临三个 关键障碍：缺乏严格标准化的增长条件，难以重复 对已识别的个体进行测量，以及高通量量化喂食的挑战 行为，这是衡量蠕虫健康的最可靠指标之一。拟议中的研究是正面的。 通过将先前建立的两个微流控芯片组合到一个设备中来应对这些挑战 技术，一种用于长期培养大量单独隔离的蠕虫，另一种用于制造 摄食行为的非侵入性电子记录。拟议研究的第一阶段寻求基本的 组合设备的概念验证。该项目的第二阶段通过将健康- 跨越屏幕并增加其吞吐量。

Aging, the progressive degeneration of body and mind, is a universal problem marked by a decline in tissue organization and function, and an increase in the likelihood of death. Progress in understanding the cellular and molecular basis of aging is rapidly accelerating, following the discovery that several well-known model organisms age in many of the same ways as humans. In addition to their contributions to our basic understanding of the biology of aging, these organisms are now being used to screen for compounds that extend not only lifespan, but also the quality of life in older individuals (health span). One of the most powerful model systems in aging and health span research is the microscopic nematode Caenorhabditis elegans, favored for its short lifespan (2-3 weeks), genetic tractability, and low cost. C. elegans research is currently undergoing rapid innovation as its small size is particularly compatible with microfluidics - the manipulation of fluids in channels with dimensions of tens of micrometers. The overall goal of the proposed research is to accelerate the discovery of compounds that extend health span through the development of a novel microfluidic device that is likely to enhance the throughput and resolution of health span screening in this key organism. The conventional method of health span screening in C. elegans currently faces three critical barriers: the absence of rigorously standardized growth conditions, the difficulty of making repeated measurements on identified individuals, and the challenge of high-throughput quantification of feeding behavior, one of the most reliable measures of health in the worm. The proposed research takes a head-on approach to these challenges by combining, into a single device, two previously established microfluidic technologies, one for long-term culture of large numbers of individually isolated worms, and one for making non-invasive electrical recordings of feeding behavior. Phase I of the proposed research seeks fundamental proof of concept for the combined device. Phase II of the project extends this work by automating health- span screens and increasing their throughput.