The ultimate goal of this research is to develop the microcantilever platform technology for broad commercial application in high throughput (HTP) screening for ligands to various types of cell signaling receptors. Here we propose to develop a device for screening of ligands to nuclear hormone receptors. This device consists of arrays of microcantilevers having nuclear hormone receptors attached. Ligand binding to receptors causes a conformational change that produces surface stress that actuates microcantilever deflection, which is detected using an optical readout system. Microcantilevers are established to be a sensitive platform technology for detecting gases or proteins or DNA in solution. Because the receptors are tethered to cantilevers, multiple types of receptors can be located in a single incubation chamber, enabling multiplexed detection and HTP capacity. In the proposed Phase I work, three nuclear hormone receptors will be the targets used to optimize the screening device for development of a commercial screening platform for detecting endocrine disrupting chemicals (EDCS) in phases II and III. Biosensor devices based on nanomechanical motion could conceivably revolutionize HTP screening to the point where chemical libraries with millions of compounds could be screened against numerous cell signaling receptors in an array format.
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