Surface modification of silica nanoparticles to reduce aggregation and non-specific binding

In this paper, a systematic study of the design and development of surface modification schemes for silica nanoparticles is presented. The nanoparticle surface design involves an optimum balance of the use of inert and active surface functional groups to achieve minimal nanoparticle aggregation and reduce nanoparticle non-specific binding. Silica nanoparticles were prepared in a water-in-oil microemulsion and subsequently surface modified via co-hydrolysis with tetraethylorthosilicate (TEOS) and various organosilane reagents. Nanoparticles with different functional groups, including carboxylate, amine, amine/phosphonate, polyethylene glycol, octadecyl, and carboxylate/octadecyl groups were produced. Aggregation studies, using SEM, dynamic light scattering, and zeta potential analysis, indicate that severe aggregation among amine-modified silica nanoparticles can be reduced by adding inert functional groups, such as methyl phosphonate, to the surface. To determine the effect of various surface modification schemes on nanoparticle non-specific binding, the interaction between functionalized silica nanoparticles and a DNA chip was also studied using confocal imaging/fluorescence microscopy. Dye-doped silica nanoparticles functionalized with octadecyl and carboxylate groups showed minimal non-specific binding. Using these surface modification schemes, fluorescent dye-doped silica nanoparticles can be more readily conjugated with biomolecules and used as highly fluorescent, sensitive, and reproducible labels in bioanalytical applications.