Characterization of Different Sequences of DNA on Si Substrate by Atomic Force Microscopy and Gold Nanoparticle Labeling

In this paper, different sequences of single-strand DNA modified on Si substrate were studied taking advantages of the high resolution of atomic force microscopy (AFM) and signal enhancement of gold nanoparticles. Two sequences of single-strand DNA, as a model, were immobilized on Si substrate and hybridized with their sequence-complementary DNA molecules modified respectively with two sizes of gold nanoparticles. The surface of Si substrate was characterized through detecting the size and coverage of gold nanoparticles by AFM. Results demonstrated that different sizes of gold nanoparticles represented different sequences of DNA immobilized on the substrate. Density and distribution of DNA on Si substrate can be investigated by AFM imaging using gold nanoparticles as topographic markers. Compared to other sensitive methods such as fluorescence energy transfer, X-ray photoelectron, and radiolabeling experiments, this approach is advantageous in terms of high spatial resolution in sub-micrometer scale. This new method will be beneficial in the characterization of DNA immobilized on chip surfaces.