Taylor dispersion analysis (TDA) is a technique dedicated to the determination of the molecular diffusion coefficient (D)
of species, using band broadening of an analyte in a laminar flow. Two modes are com- monly used to perform TDA: pulse and frontal modes. In each case, a fitting of the signal is required. We propose here a third mode denoted as cross-frontal mode, combining two crossed sample fronts without modification of a classical CE device for the rapid and accurate determination of D of caffeine, reduced glutathione (GSH), insulin from bovine pancreas, bovine serum albumin (BSA) and citrate-capped gold nanoparticles (AuNP). Theoretical aspects and methodology are described, showing a good correlation between the so-called cross-frontal mode and usual frontal mode. Limitations of the techniques are also assessed, and are similar to regular modes while no fitting is required. This new methodology allows improving the sensitivity toward low concentrated sample compared to pulse mode, and an alternative mathematical treatment compared to regular TDA modes.