By attaching molecular recognition agents such as DNA probes, aptamers, or antibodies on suspended or surface-bound nanoporous gold disks (NPGD), conjugation of target molecules can be detected with ultra-high sensitivity, in some cases at the single molecule level. The reporting signals can be from surface-enhanced Raman scattering (SERS), surface-enhanced fluorescence, and spectral shifts in localized surface plasmonic resonance extinction spectrum Using highly specific molecular probes, a platform technology can be implemented for various DNA fragment and protein biomarkers can be detected. NPGD provides extremely high plasmonic field enhancement and volumetric hot spot distribution with electric field enhancement as high as 100X and SERS enhancement exceeding 10^8. In addition, NPGD provides order-of-magnitude larger surface area which greatly promote molecular binding for enhanced detection sensitivity.