The buildup of corrosion deposits, known as fouling or CRUD in PWRs, seriously hinders large-scale energy production. From nuclear power plants to geothermal reservoirs, fouling increases system pressure drops, impedes heat transfer, and accelerates corrosion, leading to derating and early failure. Here we propose and demonstrate a design principle for foulant-agnostic thin film (sub-micrometer) coatings, based on minimizing van der Waals (vdW) forces between a material surface and any foulant immersed in a fluid. First-principles calculations of Hamaker constants are used to determine candidate coating materials. These materials are then tested in the first documented high temperature (315 C), high pressure (14 MPa), liquid cell atomic force microscope (HPAFM) capable of performing colloidal probe measurements at in-situ PWR pressure and temperature. The results are compared to flow loop tests, and the coating stability is tested in an irradiated flow loop with PWR spectrum. A set of promising coating materials is found, with the best candidates proven to reduce CRUD fouling by approximately an order of magnitude in a PWR-representative internally heated test flow loop.Ph.D.