A new architectural nanohybrid multilayer has been explored and built on various substrates. The building blocks of positive and negative charged polyelectrolyte-coated nanoparticles (NPs) could be obtained by tuning the electrical properties of the amphoteric oxide NPs in acid and basic environments. The nanohybrid films were, thereafter, formed by layer-by-layer (LbL) assembly of polycation- and polyanion-coated NPs. It was demonstrated that this approach could incorporate single component NPs into both polycation and polyanion layers, and in turn improve the NP loading, maintain good dispersion of NPs within the film. For separation applications, a dynamic LbL assembly was attempted as a means of fabricating such nanohybrid multilayers on both 2-D and 3-D polymeric porous substrates. The nanohybrid multilayer membrane renders both much higher selectivity and flux in the separation of solvent-water mixtures. Moreover, such assembly of nanohybrid multilayers allows us to efficiently simplify the procedures by reducing 3040-fold process cycles. (c) 2011 American Institute of Chemical Engineers AIChE J, 2012