Microfluidic screening devices for health-span extending drugs

衰老，即身体和精神的逐渐退化，是一个以组织衰退为标志的普遍问题 组织和功能，以及死亡可能性的增加。细胞免疫学研究进展 衰老的分子基础正在迅速加速，继发现几个著名的模型， 生物体衰老的方式与人类有许多相同之处。除了他们对我们的基本贡献之外， 随着对衰老生物学的了解，这些生物体现在被用来筛选化合物， 不仅延长寿命，而且延长老年人的生活质量（健康寿命）。一个最 在衰老和健康寿命的研究中，一个强大的模型系统是一种微小的线虫--小杆线虫 elegans，因其寿命短（2-3周），遗传易处理性和低成本而受到青睐。C. elegans研究是 目前正在进行快速创新，因为它的小尺寸特别适合微流体- 在几十微米的通道中操纵流体。拟议的总体目标 研究的目的是通过开发一种新的药物来加速发现延长健康寿命的化合物。 一种新的微流体装置，可能会提高健康跨度筛选的通量和分辨率， 这个关键的有机体。采用传统的健康寿命筛选方法，对C。目前，Elegans面临三个 关键障碍：缺乏严格标准化的生长条件，难以重复 对已识别个体的测量，以及高通量定量摄食的挑战 这是衡量蠕虫健康状况最可靠的指标之一。这项拟议中的研究采取了正面的 通过将两个先前建立的微流体装置组合到单个装置中来解决这些挑战， 技术，一种用于长期培养大量单独分离的蠕虫，另一种用于制造 进食行为的非侵入性电子记录。第一阶段的拟议研究寻求基本的 组合器械的概念验证。该项目的第二阶段通过自动化健康- 跨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.