In vivo imaging technologies such as confocal endomicroscopy used for clinical histology applications, as well as in vivo patch clamping electrodes used in neuroscience research require very precise and stable positioning of probes within a living test subject [1-2]. For these procedures to be as minimally invasive as possible the probes need to navigate through the body’s canals and cavities to reach the region of interest and are often guided using flexible and reconfigurable guide tubes in complicated non-rectilinear trajectories. Current technology used for controlling the translation of such probes within the guide tubes do not have the requisite axial resolution (1-2 μm) that will allow imaging or recording of electrophysiological activity from single cells . Understanding the mechanical parameters that affect the performance of such systems will allow the development of micrometer resolution actuation systems. We have developed an experimental methodology in combination with flexible multibody simulations to study the translation of flexible polyimide coated fused silica micropipettes (typically used for in vivo electrophysiology studies) telescoping within Teflon tubing that are configured in rigid predetermined curved configurations. We are investigating the performance of this translation system over a wide spectrum of geometrical (bend radii, arc length, tubing to capillary diameter clearance) and physical (preload, frictional force) parameters and the results of this study will help in developing a basis for design of more complex non-rectilinear probes.