A cationic water-soluble tetrahedral molecule bearing four phenylene-bis(fluorene) optical units, namely tetrakis[4-(2(9,9,9',9'-tetrakis(N,N,N-trimethylammoniumhexyl)-7,2'-bifl uorenyl))-phenyl]methane hexadecanebromide, was designed and synthesized. Fluorescence resonance energy transfer (FRET) experiments between the tetrahedral molecule and fluorescein-labeled double stranded DNA (dsDNA-Fl) or single stranded DNA (ssDNA-Fl) were undertaken. Due to its specific shape and spatial registry, the tetrahedral molecule shows improved FRET efficiencies to dsDNA-Fl as well as improved selectivity between dsDNA and ssDNA, when compared to a cationic conjugated polymer with similar repeat units. 30-Fold signal amplification for dsDNA/ethidium bromide (EB) and selective response between complementary and non-complementary DNA indicates that tetrahedral molecules could be useful to amplify the optical response from EB-based DNA protocols.