This is an exploratory grant for technology development which proposes to identify and engineer novel classes of nanoparticle contrast agents that could enable multi-label molecular imaging of living cells and tissues. Our long-term goal is to develop a novel optical molecular imaging technique for non-destructive imaging and analysis of the structure and molecular composition of living ceUs and tissues. The strategy builds upon the development of light scattering spectroscopic imaging, as tools for non-invasive characterization of tissue structure. There is a growing need to develop methods of molecular to image the spatial localization of specific molecular markers or events within living tissue. By adding molecular imaging capabilities to the structural imaging capabilities of light scattering spectroscopic imaging, we hope to develop a technique that would allow imaging and monitoring the interrelation between molecular and morphological events in living cells and tissues. Towards this goal, we will utilize resonance light scattering nanoparticles, such as metallic nanoshells and nano-multishells, conjugated with specific molecular markers to achieve molecular specificity in spectroscopic imaging. The spectra of light elastically scattered by certain types of metal nanoparticles exhibit sharp resonances (peaks at specific wavelengths), which can be identified on the background of indigenous tissue scattering, whose spectra are comparatively broad. Importantly, the spectral position and width of the resonance peak depends on the size, shape, structure, and composition of a nanoparticle. Therefore, if several types of nanoparticles are used as contrast agents, with each type uniquely corresponding to a specific molecular recognition, numerous molecular species can be identified within a living tissue simultaneously. To enable such multi-label spectroscopic molecular imaging it is crucial to design nanoparticle contrast agents with optimal properties. An ideal nanoparticle contrast agent should exhibit a sharp and strong resonance peak, which can be controlled throughout a broad wavelength range, and a weak non-resonant scattering. These properties allow distinguishing the contrast agent on the background of tissue scattering and, importantly, using multiple contrast agents for multi-marker imaging. We propose to conduct exploratory studies to identify, design, and synthesize novel classes of nanoparticle contrast agents, particularly nanoshells and nano-multishells, which hold a promise to provide ultra-sharp and highly controllable peaks.