Abstract: The invention generally relates to fluorescent nanoparticles and more specifically to silica-based fluorescent nanoparticles of less than 30 nm with covalently attached organic dyes. The invention provides a fluorescent monodisperse silica nanoparticle comprising fluorophore center core and a silica shell wherein the radiative properties of the nanoparticle are dependent upon the chemistry (composition) of the core and presence of the silica shell. In one aspect of the invention, the core-shell architecture provides an enhancement in fluorescence quantum efficiency. The invention generally provides control of photophysical properties of dye molecules encapsulated within silica particles with sizes down to 30 nm and below. This control is accomplished through changes in silica chemistry and particle architecture on the nanometer size scale and results in significant brightness enhancement compared to free dye.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.