A two-stage yeast-display and mammalian seeding-assay screen identified novel VHH nanobodies, VHH(510) and VHH(50), that selectively recognize pathological tau seeds over monomeric tau, with the lead candidate detecting tau pathology in mouse and human brain tissue in patterns distinct from conventional phospho-tau markers. Flow Induced Dispersion Analysis (FIDA), on a Fida 1 instrument, was used to measure the binding affinity of the stabilized VHH(510M) and VHH(50M) variants to monomeric tau, confirming weak monomer binding consistent with their seed-selective avidity. It is an example of using FIDA to quantify weak antibody–antigen binding affinities in solution.