Measuring toxicant effects on cellular function in a microarray format

DESCRIPTION provided by applicant The EPA maintains a Toxics Release Inventory of over toxic chemicals that are disposed or released from more than industrial sites in the United States The Department of Health and Human Services and USDA maintain a list of over select agents and toxins that pose a severe risk to both human animal and plant health These compounds represent only a fraction of the toxins and toxicants at environmental concentrations that pose substantial risk to human health At present assays that assess the impact of exposure to stem cell differentiation and programming are not capable of the throughput necessary to stay apace the speed of new toxicants entering the environment Such measurements are critical to our understanding of the risks these agents represent and to our ability to moderate or eliminate those risks The goal of this project is the development of instrumentation capable of detecting toxicant effects on stem cell differentiation processes in a sensitive high content assay based on the detection of changes in the differentiation profile of stem cells exposed to these toxicants Since stem cells are critical elements of embryonic development and for the ongoing maintenance of adult tissues an effective assessment of their function will be important of our understanding of environmental risks for autoimmune disease immunodeficiencies and neoplasia to name only a few of the health risks when stem cell behavior is altered The assay is based on instrumentation that can measure grating coupled surface plasmon resonance GCSPR and grating coupled surface plasmon coupled emissions SPCE This assay system will incorporate a reliable fluidic system and a simple to use sensor chip array that can be used for assessment of toxicant effects on stem cell differentiation and may ultimately also have value as a point of care diagnostic

PUBLIC HEALTH RELEVANCE There is a critical need for highly sensitive and specific techniques capable of defining the risk levels to human health that result from exposure to a broad range of toxicants found in the environment To address this need we propose to build upon our extensive experience with microarray Surface Plasmon Resonance SPR systems to develop a high content instrument platform that can assess the impact of toxicant exposure on stem cell differentiation and is not constrained by the important limitations of existing technologies This multi mode multi fluor SPR analysis will identify and quantitate the effects o toxicant exposure on stem cell functioning without foreknowledge of the contaminantandapos s identity or toxic concentration profile The technology will require small sample volumes and will be suitable for use in both research and clinical laboratories and with further development will be extensible to a point of care environment