Dynamic Light Scattering (DLS) is a proven technique for determining the hydrodynamic size and polydispersity of biologics with applications spanning from sample quality to colloidal stability. In every DLSsystem, engineering choices drive sensitivity, minimize interference and maximize the range of molecules that can be analyzed. Here we explore the effect of detection angle, the advantages of a 660 nm laser over shorter wavelengths, and the impact a sample holder can have on sensitivity. Attendees will gain an understanding of industrystandard configurations for DLS and why those choices provide the best approach, while compromises may mean less robust analyses.