We have developed an efficient numerical method to investigate light scattering from plasmonic nanospheres on a substrate covered by a shell, based on the half-space Green's function approach. We use this method to study optical scattering from DNA molecules attached to metallic nanoparticles on a substrate and compare with experiment. We obtain fairly good agreement between theoretical predictions and the measured ellipsometric spectra. The metallic nanoparticles were used to detect the binding with DNA molecules in a microfluidic setup via spectroscopic ellipsometry (SE), and a detectable change in ellipsometric spectra was found when DNA molecules are captured on Au nanoparticles surface. Our theoretical simulation indicates that the coverage of Au nanosphere by a submonolayer of DNA molecules, which is modeled by a thin layer of dielectric material, can indeed lead to a small but detectable change in ellipsometric spectra. Our studies demonstrated the ultrasensitive capability of SE for sensing submonolayer coverage of DNA molecules on Au nanospheres.