This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).<br/><br/>This Small Business Technology Transfer (STTR) Phase I project will result in the demonstration of non-toxic multi-modality nanoparticle-based molecular probes for in vivo imaging. The objective of the Phase I project is to demonstrate the synthesis and coating of luminescent bismuth sulfide nanoparticles emitting in the near infrared (NIR) for use as multi-modality probes. These probes may be detected by NIR fluorescence emission or as self-illuminated probes through Bioluminescence Resonance Energy Transfer to Luminescent Nanocrystals (BRET-LN). Moreover, bismuth sulfide can be used as a contrast agent for X-ray-based imaging. The presence of toxic metals such as Cd, As, In and Hg in most of the NIR emissive nanoparticles and the relative lack of detailed safety data establish a significant safety barrier for use in humans. Bismuth sulfide is a potentially non-toxic material for bioimaging. Bismuth compounds have been used in pharmaceutical formulations for more than a century to treat maladies such as diarrhea, syphilis, and peptic ulcers. In the U.S., approximately 500 tons of bismuth are used in chemical, cosmetic, and medical products with direct human experience each year. <br/><br/>The broader impacts of this research are the development of a sensitive multi-functional molecular imaging probe for use in medical imaging and inter-operative staining procedures. The new probe will ultimately provide a more efficient means to image disease in humans optically, circumventing inherent imaging depth and signal-to-noise limitations of other optical imaging technologies. This capability will translate to the development of important applications such as early cancer detection.