||The purpose of this research is to characterize the molecular origin of the Raman peaks associated with the diseased tissues, and to explore the feasibility in obtaining Raman spectra via different optical settings. The goal is to develop a Raman-based optical sensor for clinical and biomedical applications. Diseased tissues studied by the author were calcified human coronary artery and human gallstones. The Raman peaks associated with the calcification of human artery was identified by comparing the Raman spectrum of healthy human coronary artery with that of the calcified human coronary artery. The chemical origin of the Raman peaks characteristic to calcification was identified by comparing with the Raman spectra of model chemical compounds. The major marker for calcification is the Raman peak at 960 cm-1 which is attributed to the symmetric stretching of PO43- group of precipitation in the calcified tissue. The major chemical components of different gallstones were identified by comparing the Raman spectra of gallstones with that of selected model compounds. The major chemical components of three gallstones were cholesterol bilirubin, and fatty acid salts, respectively. Raman spectra of the aforementioned diseased tissues were taken via the macro-sampling with a standard setting of a Raman spectrometer, referred as the macro setting in this thesis. Then the Raman spectra were taken via microsampling through a microscope coupled to a Raman spectrometer, referred as the microscope setting. Finally, the Raman spectra were collected via an optical fiber coupled to a Raman spectrometer, referred as the optical fiber setting. It was demonstrated in this thesis that Raman spectroscopy can provide molecule-specific identification of calcified human coronary artery and gallstones. The feasibility in obtaining Raman spectra of the diseased tissues via the macro setting, the microscope setting and the optical fiber setting is also demonstrated. The success in obtaining Raman spectra via different optical settings is a major step towards the development of a clinically-oriented Raman-based optical sensor for the purpose of the diagnosis of diseased tissues.