An experimental nanoparticle preparation process by solvent displacement in passive mixers is considered. The problem under investigation is to estimate the operating conditions in a target device (Mixer B) in order to obtain a product of assigned properties that has already been manufactured in a source device of different geometry (Mixer A). A large historical database is available for Mixer A, whereas a limited historical database is available for Mixer B. The difference in device geometries causes a different mixing performance within the devices, which is very difficult to capture using mechanistic models. The problem is further complicated by the fact that Mixer B can only be run under an experimental setup that is different from the one under which the available historical dataset was obtained. A joint-Y projection to latent structures (JY-PLS) model inversion approach is used to transfer the nanoparticle product from Mixer A to Mixer B. The Mixer B operating conditions estimated by the model are tested experimentally and confirm the model predictions within the experimental uncertainty. Since the inversion of the JY-PLS model generates an infinite number of solutions that all lie in the so-called null space, experiments are carried out to provide (to the authors' knowledge) the first experimental validation of the theoretical concept of null space. Finally, by interpreting the JY-PLS model parameters from first principles, the understanding of the system physics is improved. © 2013 American Institute of Chemical Engineers AIChE J, 60: 123–135, 2014