Microfluidic screening devices for health-span extending drugs -
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.
