Microfabricated Patch-Clamp Array for Neural Mems Applications
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MICROFABRICATED PATCH-CLAMP ARRAY FOR NEURAL MEMS APPLICATIONS Timothy M. Kubow, Karen C. Cheung, Loren F. Bentley, and Luke P. Lee Joint Graduate Group in Bioengineering University of California San Francisco / Berkeley Department of Bioengineering, University of California, Berkeley Berkeley Sensor and Actuator Center, University of California, Berkeley Berkeley, CA 94720, U.S.A.
Abstract Microfabricated patch clamping devices comprising planar arrays of individually addressable nozzles, fluidic channels and electrodes have been developed. Patch clamp based electrophysiological techniques are among the most widespread methods in neurophysiology and are used to address a broad range of cellular physiology and quantitative biological questions. Among the limitations of the technique are the difficulty of obtaining multiple patches on connected cells or on the same cell, limited stability of patches, and constraints on chemical and optical access to the patched membrane. The parallel array device will enable the formation of multiple seals simultaneously. The structure facilitates visualization of the interior of the patched membrane during electrical recording, as well as delivery of chemicals. The microfabrication technique gives precise control over the capacitive and resistive characteristics of the electrode channels, as well as the flow resistance, which are important factors in patch clamp recording. The device is fabricated using an SOI wafer and Deep Reactive Ion Etching to create an array of cylindrical nozzles, each of which has a core of silicon dioxide and interior walls of silicon nitride. Vertical channel segments and plumbing holes are fabricated by deep reactive ion etching through the wafer. Important electrical properties of the device were characterized, and patch clamping was attempted.
Introduction Patch clamp electrophysiology is one of the most important techniques in modern biology. The awarding of the Nobel Prize to its inventors Neher and Sakmann in 1991 highlighted its significance to the field. Its continued relevance to biology is illustrated by the over 1500 citations with it as a subject in 2001. The original technique [1] allowed the first direct recording of electrical currents through a single membrane channel. Since then the technique has branched out to include many variations, including whole-cell patch, inside-out patch, and outside-out patch. For a thorough discussion of the technique see [2]. Its use in the study of membrane channels has led to many important findings about the fundamentals of biology as well as to the discovery and understanding of innumerable pharmaceutical products [3]. Despite the fact that it is an extremely important technique and is now commonplace, patch clamping still requires a skilled researcher to perform the procedure, thus leading to a recent surge in interest in automating the technique. Many researchers have now begun to make patch clamp devices in novel ways [4, 5, 6]. Many companies are now selling or are developing automated patch clamp de
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