Gold nanorattle probes are provided that are highly tunable, physiologically stable, and ultra-bright Raman probes for in vitro and in vivo surface-enhanced Raman scattering (SERS) applications. The nanorattles contain an essentially uniform gap between core and shell that is tunable and can range from 2nm to 10nm in width. This provides numerous advantages including allowing for increased loading with a variety of dye molecules that exhibit SERS in various spectral regions, including the “tissue optical window” for in vivo studies. In addition, the nanorattle probes provide an internal label when used in diagnostic methods to detect nucleic acids, proteins and other biotargets. The nanorattles have an essentially spherical gold metal nanoparticle core, a porous material of silver metal of an essentially uniform width surrounding the nanoparticle core that is loaded with one or more SERS reporter molecules, and an outer gold metal shell encapsulating the porous material.
