CBET-0722422 Teraoka The present proposal is to develop a biosensor instrument to detect and quantify binding of unlabeled receptor biomolecules to surface-immobilized ligands. The instrument will have a sensitivity more than a few orders of magnitude higher compared with state-of-the-art surface plasmon resonance instruments. The instrument will also provide information on the status of bound protein (surface orientation, conformation). The high sensitivity relies on extremely sharp resonance photonic modes, called whispering gallery modes (WGM), in a transparent microsphere less than 0.5 mm across. Light travels the interior side of the sphere surface via total internal reflection to come back in phase after one cycle around the sphere. The light path becomes slightly longer when biomolecules such as protein bind to the sphere surface, which can be detected as a small red shift of the resonance by an optical fiber touching the sphere. The project will utilize recent discovery and demonstration of enhancing the already high sensitivity of WGM sensor by coating the sphere surface with a sub-wavelength layer of a high refractive index, thus forming a ring ribbon resonator around the sphere for an increased resonance shift.