This study developed RBD-PB6, a serum-stable RNA aptamer that binds the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and neutralizes viral entry, and showed that multimerizing it into dimers and trimers strongly enhances binding avidity and neutralizing potency. Flow Induced Dispersion Analysis (FIDA), on a Fida 1 instrument, was used to characterize the aptamer–spike interaction under native conditions by monitoring the change in hydrodynamic radius of the fluorescently labeled aptamer as it binds RBD, fitting a 1:1 model and quantifying the multimers' avidity gain (apparent KD ~0.8 nM trimer, ~1.4 nM dimer). It is an example of using FIDA to measure aptamer–target binding affinity in solution.