Fouling and particularly biofouling, presents a major impediment of membrane filtration processes, essential for water recycling and desalination. This lecture will cover part of our lab nano-scale strategies for studying and mitigating membrane biofouling scenarios. We combine Localized Surface Plasmon Resonance (LSPR) sensing and quartz crystal microbalance with dissipation monitoring (QCM-D). While LSPR analysis is sensitive to the interface – molecular and – colloidal interactions with a decay length of ~20–30 nm, QCM-D provides the mass and viscoelastic properties of the hydrated adsorbed fouling layer in a length scale of ~200-300 nm. This way, we characterize in real time, on one surface, both (i) adsorption interactions of biomacromolecules, conformational changes, and structural transformations of the adsorbate in spatial proximity of up to 30 nm from the surface; and (ii) the entire mechanical load on the surface, in a length scale of 300–500 nm, which includes the contribution of the fouling layer hydration. Related applications to be discussed, will include: (1) improved ultrafiltration membranes for purification of municipal secondary wastewater effluents and (2) rapid prediction of fouling rate, reduced membrane performance and membrane cleaning efficiency during desalination of municipal secondary wastewater effluents; (3) studying the function of hydrogels and polymer brushes for separation processes as well as antifouling behavior and mechanisms.