SBIR Phase I: Mobility Based Label Free Detection

This Small Business Innovation Research Phase I project will develop a novel mobility based label free detection of receptor / ligand binding in lipid bilayer membranes. This label - free detection will be incorporated into the MembraneChip technology for array sensors to replace costly fluorescent labeling methods. The cell membrane is the richest source of targets with high therapeutic values. Recent advances in automated membrane deposition techniques, combined with the discovery of membrane-compatible surfaces and membrane diffusion barrier materials, allow for the creation of discrete, spatially-addressable membrane array elements which retain their biological functionality and natural fluid character. These characteristics make this technology an attractive format for displaying native or reconstituted membrane targets in an industrialized drug discovery assay platform. In order to fully exploit this platform's potential, a lipid mobility based detection scheme which is effectively label free in that it does not require any label on the ligand or the target, has been discovered. Small quantities of fluorescent lipid doped into the membrane bilayer exhibit changes in lateral diffusion coefficient upon binding without being directly involved in the interaction. This project will explore the feasibility of extending this label free detection discovery to study universal membrane receptor-ligand binding interactions by characterizing the technique with respect to detection sensitivity, quantitation and binding interactions. The commercial application of this project is in drug discovery research. Fluid membrane microarray technology is applicable to both native and reconstituted membrane proteins, and should therefore provide a well-controlled and systematic drug discovery platform for membrane-mediated cell signaling events.