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.

衰老是身体和精神的逐渐退化，是一个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。了解细胞的进展随着几个著名模型的发现，衰老的分子基础正在迅速加速生物体的衰老方式有许多与人类相同。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能够不仅可以延长寿命，还可以提高老年人的生活质量（健康寿命）。最有之一衰老和健康跨度研究中强大的模型系统是微小线虫 Caenorhabditis 线虫因其寿命短（2-3周）、遗传易驯化和低成本而受到青睐。线虫研究是目前正在快速创新，因为它的小尺寸与微流体特别兼容 - 操纵尺寸为数十微米的通道中的流体。拟议的总体目标研究旨在通过开发一种可延长健康寿命的化合物来加速发现新型微流体装置可能会提高健康跨度筛查的通量和分辨率这个关键的有机体。传统的线虫健康跨度筛查方法目前面临三个问题：关键壁垒：缺乏严格标准化的生长条件，重复制作难度大对已识别个体的测量，以及高通量定量喂养的挑战行为，是衡量蠕虫健康状况最可靠的指标之一。拟议的研究采取了正面的通过将两个先前建立的微流体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分离的蠕虫，另一种用于制造喂养行为的非侵入性电子记录。拟议研究的第一阶段寻求基础组合设备的概念验证。该项目的第二阶段通过自动化健康扩展了这项工作跨越屏幕并提高其吞吐量。