An integrated patch-clamp amplifier for automated, high-throughput, whole-cell recording systems

The Patch-clamp amplifier is the "gold standard" to measure currents flowing through ion channels, the structures responsible for cell membrane conductivity. Ion channels are widely targeted by drugs used in therapy and hence the automated, high-throughput screening of drugs that affects the function of specific ion channels is of great interest. In this thesis, we present the design, fabrication, and test results from a fully integrated, dual-channel, patch-clamp amplifier system that occupies an area of only 3 x 3mm 2.;The system was fabricated in Silicon-on-Sapphire (SOS) technology and has series resistance and parasitic capacitive compensation capability. The system was designed to compensate for the distributed series resistance present in a population patch-clamp system and to achieve 100% series resistance compensation. Furthermore, the system was designed with the ability to compensate for leak currents that result from inadequate sealing between the cell membrane and the electrode. An anti-aliasing filter and an input-reconstruction filter was integrated to the system to minimize the number of external components necessary for integration into larger systems. The circuit employs selectable feedback resistors to enable the recording of currents of varying magnitude. All operational amplifiers in the design were implemented using a constant-transconductance, rail-to-rail operational amplifier. A supply-independent biasing circuit was designed to bias the operational amplifiers. A serial digital interface was integrated to the design to facilitate the control of the patch-clamp system with a personal computer.;We have demonstrated the circuit's usefulness by recording ion channel currents from live cells. The system can be used as is to substitute a rack-mounted commercial patch-clamp system that is a million times larger in volume. More importantly, it is ready to be integrated into a larger high-throughput system. The hope is that the integrated patch-clamp system would facilitate the fabrication of massively parallel high-throughput systems that would make the functional analysis of ion channels and genes and also the screening of drugs a much more efficient and failsafe process.