Design and Analysis of Electrical Resistance Feedback for Automated Patch Clamp on Adherent Cells

Conventional patch clamp techniques require complex manual work. Automated patch clamp systems have been recently developed to eliminate the need of manual handling, but these systems can only perform recordings on suspended cells and require cell dissociation for recordings on adherent cells. Here, we develop a systematic approach to apply electrical resistance feedback for automated patch clamp recording on adherent cells. By developing resistance thresholds in the electrical resistance feedback algorithm, the engaging condition of the adherent cell was automatically determined. We analyze the critical parameters that affect the performance of the automated patch clamp recording. By using the new algorithm for automated engaging and formation, the cell-attached and whole-cell recordings on adherent cells were performed in less than 5 min with the yield of over 70%. The system is designed to directly measure the adherent cells and so, cell dissociation (e.g., trypsin treatment and cell scrapers) can be avoided and the cell properties can be maintained. By using the system, the efficiency of performing the automated patch clamp on adherent cells can be improved, which is of great importance in electrophysiological studies of single cells.