A hybrid patch clamp amplifier

The current-to-voltage convertor used in patch clamping is analyzed for noise generation and the major noise sources determined. A hybrid patch clamp amplifier design is theoretically analyzed. Here it is shown that by differentiation and recombining of signals the original input signal can be reconstructed. Several circuits of this design are described and their performance compared. The optimal signal detection obtained for a 1 ms current pulse width with a signal-to-noise ratio of 1 is 0.025 pA. In these circuits, high frequency attenuation is readily accomplished with a single control. In addition, compensation for the transients which occur with step control voltages is effectively accomplished. With this circuitry, it is shown that for most patch clamp situations, the minimum pulse width and current which can be detected is determined by the patch clamp seal resistance.