We develop single molecule approaches to characterize the dynamics of macromolecular assemblies of nucleic acids with basic science and application- driven objectives. The first objective comprises the physical and biochemical principles of the organization of the bacterial nucleoid, in relation with genome repair functions in particular, and the role of repeated sequences in molecular mechanisms altered by cancer. The second objective evaluates the combination of our high-throughput Tethered Particle Motion technique with recognition elements as a sensor for water micropollutants or biomarkers.