Patch-Clamp Advances in biology come from advances in instrumentation and techniques. We are working in two areas of technology development. We are developing fully integrated patch-clamp amplifier systems that would facilitate the fabrication of automatic, high-throughput recording systems that can patch 384 or more cells in parallel. To simplify the structure determination of membrane proteins (such as ion channels) we are pursuing technical advances in electron microscopy of frozen single-molecule specimens (single-particle cryo-EM) and the mathematical reconstruction of 3D structures from electron microscope images.
- Patch Clamp
- Cryo-EM Technologies
Fully-Integrated Patch-Clamp Systems for High-Throughput, Automated, Whole-Cell Recording Systems
The patch clamp technique (Neher, 1992) is the central method in modern electrophysiology. It allows the recording of single ion-channel currents, or alternatively currents from entire small cells (whole-cell recording). In traditional patch-clamping, a glass pipette is gently applied to the cell membrane as an "electrode" through control by a skilled operator; a slow and labor intensive process. Recent developments in planar patch-clamp technology has now made it possible to envision high-throughput patch-clamp systems where recordings can be made from 384 or more cells in parallel. A limiting factor in these systems is the size and cost of the amplifiers. By miniaturizing the entire patch-clamp system in silicon as an integrated circuit, both these problem can be resolved. We have designed, fabricated and tested the first fully integrated patch-clamp amplifier system using silicon-on-sapphire (SOS) technology. This project was a collaboration with Prof. Eugenio Culurciello.