William E. Doering

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

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. (R2 = 0.998) or i.v. (R2 = 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.

Detection of biomolecules using nanoparticle surface enhanced Raman scattering tags

Detection tags based upon surface enhanced Raman scattering provide an alternative to the widely used fluorescence methods. Several aspects of these tags are presented in this report. The tags can be made to display many different spectra, thus they can be used for multiplexed detection schemes. They generate a large enough number of photons to be readily detected, and spectra acquired from mixtures of tags can be analyzed giving accurate amounts of the components. The surface of the tags can be easily modified to present common biological molecules (streptavidin and analogues). Finally, we demonstrate their use to quantitatively detect interleukin-4 (IL4) and interleukin-7 (IL7) in a microarray format.