Abstract: Systems and methods to facilitate automated image-guided experiments including in vivo electrophysiology and electroporation are disclosed. Exemplary systems and methods utilize three-dimensional image data to estimate coordinates of target cells and calculate a path for a probe to carry out an initial approaching toward a target location. Visualization and real-time image analysis is then employed to modify the path based on updated three-dimensional data of the probe location and target location, compensating displacement of target location due to the insertion of the probe into the tissue. Precise control of the probe then performs final approaching of the probe to the target location. This adaptive pipette positioning technique provides a platform for future advances in automated in vivo experiments.