Biosensors that could monitor interactions between biologically-active compounds and a target receptor would facilitate the process of drug discovery. The study will test the feasibility of using a capacitive sensor based on an interdigitated electrode army to monitor the interaction of volatile anesthetics and calcium channel antagonists with cardiac membrane proteins that play a role in calcium homeostasis and are thought to be the sites at which volatile anesthetics act to depress cardiac contractility. If it can be shown that such sensors are sufficiently sensitive and that the outputs can be related to specific biomolecular processes, then this technology has enormous potential for screening pharmacologic activity and elucidating the functions of integral membrane proteins. Membrane proteins from cardiac muscle will be reconstituted into membrane-like structures at the surface of a planar capacitive sensor. The system's capacitance response to the application of agonists, antagonists, and halothane will be measured. Fourier transform infrared spectroscopy-(FIP,) will be used to characterize surface-bound structures. An improved design for the interdigitated array sensor will be evaluated for its stability and suitability in the commercialization of capacitive biosensors for use in pharmaceutical research.Awardee's statement of the potential commercial applications of the research:As pharmaceuticals are increasingly designed for individual receptor targets, systems that provide a convenient means to evaluate the interaction of candidate drugs with specific receptors are important parts of the drug discovery process. The system will have application as a research tool to assay the molecular responses of receptors to natural and synthetic ligands and inhibitors.National Institute of General Medical Sciences (NIGMS)
