This award supports a project that will improve instrumentation used for patch-clamp measurements for recording the electrical potential of individual cells. The patch-clamp method is the most widely used method for this purpose; 26,000 research publications have cited the method since 1975, half of these appearing in the last five years. Despite this widespread use, the method has a number of well known limitations that arise from the equipment used. In particular, it is difficult to obtain and to sustain more than one recording at a time, making studies of the electrical activity of individual members of cellular networks difficult. Moreover, the quality of recordings deteriorates with time, and the recording bandwidth is limited. Through the development of new instrumentation undertaken with the support of this award, long-duration, multiple-site recordings will be easier to obtain, and high bandwidth signals will be more accessible. Traditional patch clamp systems employ a glass pipette to contact the cell with an Ag/AgCl electrode located at a fixed position far from the pipette tip. Introduction of any cellular or other debris near the tip interferes with reliable measurement. In the device to be developed, a movable nanoelectrode can be advanced forward and through the tip to clear such debris. This modification alone is expected to alleviate most of the current patch clamp limitations. While the proposed device will be more complex than a standard patch clamp electrode, the project's goal is development of a device that will integrate easily into existing patch clamp systems. This approach of adapting the design to systems currently in use should encourage rapid acceptance of the new tool among electrophysiologists, significantly increasing the likely impact it will have on the progress of biological research over the next decade. The PI has been active in development of new curricula and other activities that serve both neuroscience and bioengineering. Because of the extensive use of the patch-clamp in a variety of areas of neuroscience and cell biology, successful development of the proposed device can be expected to have a broad impact on biological research.
