This Small Business Innovation Research (SBIR) Phase I project will demonstrate the detection of an established target in cancer diagnosis and treatment using new targeted Bioluminescence Resonance Energy Transfer to Quantum Dots (BRET-QD) technology. BRET-QD offers substantial advantages over fluorescence or luminescence imaging by: (1), circumventing the need for external illumination while delivering comparable or better sensitivity; (2), providing compatibility with existing image capturing technology; (3), providing superior probe stability compared to radiolabel technology, enabling longitudinal studies; and (4), delivering greater in vivo penetration-depth than fluorescence-based probes. The project will demonstrate the direct detection of the HER2 cancer marker in breast cancer cell lines. Successful detection of HER2 in live cells from a breast cancer cell line will provide the proof-of-concept necessary for advancing to direct tumor and tissue imaging with BRET-QD probes in small animals.<br/><br/>The broader impacts of this research are the development of a sensitive and convenient targeted imaging probe platform and its application to breast cancer detection. In order to understand the molecular mechanisms underlying diseases such as cancer, there is increasing interest in advancing from cell-based assays to in vivo imaging of disease states in small animal models. The targeted BRET-QD platform will provide a cost-effective, convenient and effective alternative to fluorescence and bioluminescence imaging probe technology. In addition to cancer applications, this platform will be applicable to virtually any investigation requiring sensitive detection of a known molecule that can be targeted via a biotinylated antibody or other biotinylated molecule.