Biosensors that could monitor interactions between biologically-active compounds and a target receptor would facilitate the process of drug discovery. The proposed study will test the feasibility of using a capacitive sensor based on an interdigitated electrode array 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 capacitance response of the system to application of agonists, antagonists, and halothane will be measured. Fourier transform infrared spectroscopy (FTIR) will be used to characterize surface-bound structures. An improved design for the interdigitated array sensor will be evaluated in terms of its stability and suitability for commercialization of capacitive biosensors to be used in pharmaceutical research.
