Can you screen protein binders without purifying them first? In this Fidabio webinar, a computational protein-design lab at Aarhus University shows how Flow Induced Dispersion Analysis (FIDA) screens de novo designed protein binders directly in unpurified bacterial lysate. By tracking the change in hydrodynamic radius of a fluorescent target as it binds, FIDA gives a binary binder/non-binder call from a single measurement and an affinity from a titration — using a capillary-mixing (cap-mix) format and heat-lysate purification in 96-well plates, with sample dilution to handle lysate autofluorescence. The approach identified nanomolar binders against ALFA-tag and GK-domain targets without any protein purification. It is an example of using FIDA to screen and rank designed protein binders in solution.