Automated cell patch clamping method and apparatus

Abstract

In an automated method for in vivo multiple cell patch clamping, cell patch clamping devices are automatically moved into position and targeted to multiple corresponding cells. Cell contact is determined by analyzing the temporal series of measured resistance levels at the clamping devices as they are moved. The difference between successive resistance levels is computed and compared to a threshold, which must be exceeded for a minimum number of computations before neuron contact is assumed. Pneumatic control methods are used to achieve cell-attached or gigaseal formation and subsequent cell break-in, leading to whole-cell patch clamp formation. An automated robotic system automatically performs patch clamping in vivo, automatically detecting cells according to the methodology by analyzing the temporal sequence of electrode impedance changes. By continuously monitoring the patching process and rapidly executing actions triggered by specific measurements, the robot can rapidly find neurons in the living brain and establish recordings.