Systems and methods are described for operating an electroporation system with single cell resolution. A micromanipulator assembly includes three orthogonally-positioned linear movement stages and a rotational stage to adjust the position of a tip of a micropipette. The system is configured to detect when the tip of the micropipette is placed in contact with an exterior surface of a cell based at least in part on a measured resistance from a first electrode positioned within the micropipette. In some implementations, the resistance is measured between the first electrode and a second electrode positioned at a defined distance from the tip of the micropipette and moved by the micromanipulator assembly with the micropipette. In some implementations, the control unit applies filtering and conditioning mechanisms to the measured resistance signal in order to detect contact between the tip of the pipette and the exterior surface of the cell. It also applies electroporation pulses of different shapes, durations, and frequencies.