Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R 2 ‫؍‬ 0.998) or i.v. (R 2 ‫؍‬ 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.imaging in vivo ͉ multiplex ͉ SERS ͉ nanoparticles I n recent years, the biomedical research community has come to realize that no single targeting agent is likely to provide sufficient information needed to characterize or detect a specific disease process. As a result, several efforts have been made toward the discovery of multiple biomarkers and targeting ligands in the hope of improving earlier detection and management of specific diseases. The ability to simultaneously detect multiple targets, sensitively and in vivo, is an attractive feat; but it is a task often difficult to accomplish. Thus far, nanoparticles have played an important role in this endeavor; however most nanostructure-based platforms for multiplex detection methods have been tailored for in vitro applications (1-6), leading to little progress in the field of in vivo multiplex imaging.Recently, there has been an overwhelming interest in sensitive imaging of nanoparticles for both diagnostic and therapeutic applications (7-11). As a result, new preclinical imaging modalities optimized for nanoparticle imaging have been developed, further expanding the field of molecular imaging. Thus far, fluorescence and Raman spectroscopy, in conjunction with quantum dots and surface enhanced Raman scattering (SERS) nanoparticles, respectively, have been the predominant imaging modalities to evaluate in vivo multiplex imaging (12)(13)(14). Raman imaging, in particular, has generated quite a bit of interest recently; we have demonstrated its ability to detect picomolar concentrations in vivo along with its unique ability to multiplex using SERS nanoparticles and others have developed novel Raman nanoparticles with the potential to be used in vivo as well (14-17).Both quantum dots and SERS nanoparticles have shown great potential as multiplexed imaging probes ex vivo, whether for cellular imaging or for biosensor applications; however, seve...

Surface-enhanced Raman scattering is capable of providing rich vibrational information at the level of single molecules and single nanoparticles, but the practical applications of this enormous enhancement effect are still a challenge. Here we report a new class of dye-embedded core-shell nanoparticles that are highly efficient for surface Raman enhancement and could be used as spectroscopic tags for multiplexed detection and spectroscopy. The core-shell particles contain a metallic core for optical enhancement, a reporter molecule for spectroscopic signature, and an encapsulating silica shell for protection and conjugation. A surprising finding is that organic molecules with an isothiocyanate (-N=C=S) group or multiple sulfur atoms are compatible with silica encapsulation. In comparison with fluorescent dyes and quantum dots, enhanced Raman probes contain a built-in mechanism for signal amplification and provide rich spectroscopic information under ambient experimental conditions.

Au and Ag nanoparticles have optical properties that have made them useful as tags in a wide variety of measurement schemes. This Progress Report discusses several different schemes in which Au and Ag nanoparticles have been used as surface‐enhanced Raman scattering (SERS) tags for the measurement of biomolecules. As an example application, results using glass‐coated nanotags (Nanoplex Biotags) in a lateral flow immunoassay kit are presented.

This Nano Focus article reviews recent developments in surface-enhanced Raman spectroscopy (SERS) and its application to homeland security. It is based on invited talks given at the "Nanorods and Microparticles for Homeland Security" symposium, which was organized by one of the authors and presented at the 238th ACS National Meeting and Exhibition in Washington, DC. The three-day symposium included approximately 25 experts from academia, industry, and national laboratories and included both SERS and non-SERS approaches to detection of chemical and biological substances relevant to homeland security, as well as fundamental advances. Here, we focus on SERS and how it is uniquely positioned to have an impact in a field whose importance is increasing rapidly. We describe some technical challenges that remain and offer a glimpse of what form solutions might take.