SERS diagnostic process summary. (a) Synthesis of cubic nanorattles, beginning with single-crystal, spherical gold nanoparticle (AuNP) cores. The AuNP cores are coated with cubic Ag shells to obtain AuNP@AgCube. Galvanic replacement transforms cubic Ag shells into cubic Au–Ag cages containing AuNP in the interior. Raman reporters are loaded, and the porous cubic cages are turned into complete shells by a final Au coating to obtain cube nanorattles. (b) Structure of individual hybridization complex. Gold nanorattles (Au-NR) are functionalized with DNA reporter probes, and streptavidin beads are functionalized with DNA capture probes. Both probes are complimentary to the specific cytokeratin sequence. (c) Extracted nucleic acids are incubated with functionalized nanorattles and beads, then washed away. Remaining complexes undergoing successful hybridization are isolated using a strong magnet and concentrate to a spot for laser excitation in order to yield a SERS signal. Reproduced from [205].