Microfluidic screening devices for health-span extending drugs

用于延长健康寿命药物的微流体筛选装置

基本信息

批准号：
8647832
负责人：
SHAWN R LOCKERY
金额：
$ 15.84万
依托单位：
NEMAMETRIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8647832
关键词：
Age Aging American Animal Model Behavior Biological Biological Assay Biological Models Biology of Aging Biomedical Engineering Businesses Caenorhabditis elegans Cessation of life Detection Development Devices Dimensions Environment Face Feeding behaviors Frequencies Genetic Goals Grant Growth Head Health Human Individual Laboratory Research Licensing Life Liquid substance Longevity Longitudinal Studies Marketing Measurement Measures Methods Microfluidic Microchips Microfluidics Microscopic Modeling Molecular Movement Nematoda Optical Methods Optics Organism Pharmaceutical Preparations Phase Population Genetics Pump Quality of life Research Research Contracts Resolution Services Signal Transduction System Technology Time Tissues United States National Institutes of Health Work age effect aged base body-mind cost innovation member movie new technology novel public health relevance research study screening seal success

项目摘要

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.

衰老是身心的进行性变性，是组织下降的普遍问题组织和功能，以及死亡的可能性增加。了解细胞的进展经过发现，衰老的分子基础正在迅速加速生物体以与人类相同的方式年龄。除了他们对我们的基本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了寿命，还延长了老年人的生活质量（健康范围）。最大的衰老和健康跨度研究中强大的模型系统是微观线虫Caenorhabditis 秀丽隐杆线，寿命短（2-3周），遗传性障碍性和低成本。秀丽隐杆线虫研究是目前正在进行快速创新，因为其尺寸较小，与微流体特别兼容 - 在具有数十微米的尺寸的通道中操纵流体。拟议的总体目标研究是为了加速通过开发健康扩展健康范围的化合物的发现新型微流体设备可能会增强健康跨度筛查的吞吐量和分辨率这个关键的有机体。秀丽隐杆线虫中的常规健康跨度筛查方法目前面临三个关键障碍：缺乏严格标准化的生长条件，重复重复的困难对已识别的个体的测量以及对喂养的高通量定量的挑战行为是蠕虫中最可靠的健康措施之一。拟议的研究进行了直接的通过将两个先前建立的微流体组合到单个设备中，应对这些挑战的方法技术，一种用于大量单独隔离蠕虫的长期文化，一种用于制造进食行为的非侵入性电记录。拟议研究的第一阶段寻求基本合并设备的概念验证。该项目的第二阶段通过自动化健康来扩展这项工作 - 跨越屏幕并增加其吞吐量。