Gold-based SERS tags for biomedical imaging

The use of SERS tags in biomedical imaging is described. SERS tags are a novel entity that has recently emerged in the SERS community, mainly spurred by the necessity of carrying out experiments in the biomedical and clinical fields, where the heterogeneity and constant evolution of the environment hamper the application of direct SERS sensing concepts. Direct sensing would in fact require the use of nanoparticles with bare metallic surfaces to allow for intense signal responses; however, the high salt contents typical of physiological conditions and issues such as fouling lead the nanoparticles to aggregate and precipitate out of solution, thus limiting reproducibility and quantitative target identification. As a consequence, the concept of indirect detection has gained importance, in which the SERS signal provided by the SERS tag indirectly provides identification and localization of the target. In this brief review, aimed both at the expert scientist and the novice, the anatomy of a SERS tag is first described, which includes the gold nanoparticle, Raman reporter molecules, a coating layer, and targeting moieties, and the concept of hot spot is explained. A brief overview of the most recent imaging applications in vitro, ex vivo, and in vivo is also provided, along with specific recommendations toward the synthesis of effective SERS tags that could find application in the biomedical field, and meet specific needs of the clinical community. Major emphasis is placed on the concept of multiplexing, which is perhaps the most important feature of SERS tags that could render their clinical application a reality.