Flow Induced Dispersion Analysis (FIDA) can screen de novo designed protein binders directly in unpurified bacterial lysate. The researchers used FIDA on a Fida 1 instrument to measure the hydrodynamic radius of fluorescently labeled targets — the ALFA-tag peptide and the PSD-95 GK domain — and detect the size increase that occurs when an RFdiffusion-designed binder binds. Using heat-treated lysates, successful, thermostable binders were identified in a single measurement, so primary hits could be found within one day of expression without purification. Follow-up titrations gave micromolar affinities for ALFA-tag binders and nanomolar affinities for GK-domain binders. Because FIDA needs no immobilization, uses minimal sample and tolerates complex biological samples, it offers a fast, cost-effective way to screen and characterize computationally generated protein binders.