This award supports efforts to develop a new class of nanobiosensors based on electron transfer quenching of CdSe fluorescence. The sensors will be based on CdSe nanoparticles of known fluorescence properties to which proteins with known, highly specific affinities for small molecules have been linked chemically. Presence of the protein on the nanoparticle will reduce (quench) the strong fluorescence normally exhibited by such particles. The binding of the small molecule of interest is expected to alter protein structure and result in the reduction or elimination of the quenching of the fluorescence. The planned studies are aimed at development of sensors for maltose, based on the maltose binding protein found in the periplasmic space of gram-negative bacteria, and for arsenite/antimonite and Pb2+/Cd2+, based on two members of a family of metal ion binding transcription factors (ArsR and CadC, respectively). These novel sensors will belong to a class of nanobiosensors usually termed reagentless nanobiosensors because they do not require reagents other than the sensor itself. In the past, such single component sensors have employed oligonucleotides to provide specificity needed for the detection of the molecule of interest. However, use of oligonucleotides limits the range of target molecules that can be detected. Existing protein-based sensors, which have a potentially larger range, require multiple components, which complicates their use. In addition to the potential utility of such reagentless nanobiosensors, the project will provide research training for graduate students, and will provide the basis for new activities in a summer program for students in the Detroit public schools.