Near‐Infrared SERS Nanoprobes with Plasmonic Au/Ag Hollow‐Shell Assemblies for In Vivo Multiplex Detection

For the effective application of surface‐enhanced Raman scattering (SERS) nanoprobes for in vivo targeting, the tissue transparency of the probe signals should be as high as it can be in order to increase detection sensitivity and signal reproducibility. Here, near‐infrared (NIR)‐sensitive SERS nanoprobes (NIR SERS dots) are demonstrated for in vivo multiplex detection. The NIR SERS dots consist of plasmonic Au/Ag hollow‐shell (HS) assemblies on the surface of silica nanospheres and simple aromatic Raman labels. The diameter of the HS interior is adjusted from 3 to 11 nm by varying the amount of Au³⁺ added, which results in a red‐shift of the plasmonic extinction of the Au/Ag nanoparticles toward the NIR (700–900 nm). The red‐shifted plasmonic extinction of NIR SERS dots causes enhanced SERS signals in the NIR optical window where endogenous tissue absorption coefficients are more than two orders of magnitude lower than those for ultraviolet and visible light. The signals from NIR SERS dots are detectable from 8‐mm deep in animal tissues. Three kinds of NIR SERS dots, which are injected into live animal tissues, produce strong SERS signals from deep tissues without spectral overlap, demonstrating their potential for in vivo multiplex detection of specific target molecules.