© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Arrays of electrodeposited silica nanowires (SiO2 NWs) have been fabricated over large areas (cm(2)) on fluoropolymer thin films attached to glass substrates by a combination of photolithography and electrochemically triggered sol-gel nanoscale deposition. Optical and scanning electron microscopy (SEM) measurements revealed that the SiO2 NW arrays had an average spacing of ten micrometers and an average width of 700 nm with a significant grain structure that was a result of the sol-gel deposition process. The optical diffraction properties at 633 nm of the SiO2 NW arrays were characterized when placed in contact with solutions by using a prism-coupled total internal reflection geometry; quantification of changes in these diffraction properties was applied in various sensing applications. Bulk refractive index sensing by using the SiO2 NW grating was demonstrated with a sensitivity of 1.30×10(-5) RIU. Toposelectively chemically modified SiO2 NW arrays were used for diffraction biosensing measurements of surface binding events, such as the electrostatic adsorption of gold nanoparticles and the bioaffinity adsorption of streptavidin onto a biotin monolayer. Finally, the application of the SiO2 NW arrays for practical medical-diagnostic applications was demonstrated by monitoring the diffraction of SiO2 NW arrays functionalized with a single-stranded (ss)DNA aptamer to detect human α-thrombin from solutions at sub-pathologic nanomolar concentrations.