Biological interfaces constitute one of the most dynamic and expanding fields in science and technology and affect such disciplines as tissue engineering, biomaterials, and biosensors. A typical biological interface consists of several distinct layers representing such processes as protein binding, cell adhesion and many others. It is important to know quantitative characteristics of those layers, specifically their mechanical and geometrical properties. One of very powerful technique for characterization of mechanical and geometrical properties of layered systems has been the technique based on multi-resonant thickness-shear monitor (MTSM) measurement technology. However, until this moment, the thickness shear mode (TSM) measurement technique has provided only incomplete set of quantitative data. In this project, a combination of multi-resonant thickness shear mode (MTSM) measurement technique and genetic algorithm (GA)-based data analysis method is proposed for quantitative characterization of multi-layer biological processes, and for determination of mechanical and geometrical properties of the layered structures. Specifically, MTSM measurement technique provides a unique tool capable of simultaneous interrogation of the interface at different depths ranging from tens of nanometers to several microns in real time with high accuracy. Next, a genetic algorithm (GA)-based data analysis technique capable of accurate extraction of material properties was developed and integrated with the MTSM technique. The strengths and limitations of the MTSM/GA technique were studied both theoretically and experimentally. For example, it was shown that MTSM/GA can provide the mechanical and structural properties of single and two-layer viscoelastic systems theoretically with less than %1 error. The proposed MTSM/GA was experimentally verified with several chemical systems (polymers) and biological systems (collagen, cells, and antibody). Finally, mechanical and structural properties of the antibody and bovine aortic endothelial cells (BAECs) monolayers attached on the MTSM sensor surface were determined. The obtained results demonstrated that this novel approach can be a very useful tool in quantification and interpretation of biological, chemical, and physical interfacial structures and processes.Ph.D., Biomedical Engineering -- Drexel University, 201