The proposed project is to develop a vibrational spectroscopic system that can obtain good signal to noise ratio (S/N) Raman spectra in the presence of strong fluorescence. For many tissue samples the presence of strong native fluorescence prohibits molecular level analysis using Raman or resonance Raman spectroscopic techniques. Based on a novel combination of tunable diode laser technology and an array detection scheme, Physical Sciences Inc. (PSI) has devised a technology that is capable of efficiently extracting Raman signals in the presence of strong overlying fluorescence. The magnitude of fluorescence rejection can be as high as 100 dB or more. In the Phase I period, the system will be optimized from the current proof-of-concept setup. The system will be subsequently used to perform Raman spectroscopy analysis of tissue samples. PSI will demonstrate that our system has the capability to obtain excellent S/N ratio Raman spectra from a variety of tissue samples in the presence of strong overlying fluorescence. This will ultimately facilitate in vitro and in vivo molecular disease diagnosis using Raman spectroscopy. Using this technique, it will also be demonstrated that Resonance Raman spectroscopy can be performed in strongly fluorescent tissue samples to analyze trace molecules. The Phase II objective will be building and testing a prototype system for research and clinical applications. ? ?