A simultaneous two-colour diagnostic scheme for nucleic acids operating on the basis of fluorescence resonance energy transfer (FRET) will be described. Upon ultraviolet excitation, two-colours of CdSe/ZnS quantum dots with conjugated oligonucleotide probes act as energy donors yielding FRET-sensitized acceptor emission upon hybridization with fluorophore (Cy3 and Alexa 647) labeled target oligonucleotides. Energy transfer efficiencies, Förster distances, changes in quantum yield and lifetime, and signal-to-noise with respect to non-specific adsorption have been investigated. The dynamic range and limit-of-detection are tunable with the concentration of QD-DNA conjugate. The Cy3 and Alexa647 acceptor schemes can detect target from 4-100% or 10-100% of the QD-DNA conjugate concentration, respectively. The results indicate that picomolar detection limits for short oligonucleotides can be achieved with standard fluorescence instrumentation. The use of an intercalating dye (ethidium bromide) as an acceptor to alleviate non-specific adsorption is also described and increases signal-to-noise from S/N < 2 to S/N = 9-10. The ethidium bromide system had a dynamic range from 8%-100% of the QD-DNA conjugate concentration and could detect target in a matrix containing a significant excess of non-complementary nucleic acid.