THE ACOUSTIC WAVE SENSOR AND SOFT LITHOGRAPHY TECHNOLOGIES FOR CELL BIOLOGICAL STUDIES

Recently, cell-based biosensors have attracted many attentions because of their potential applications in fundamental biological research, drug development, and other fields. Acoustic wave biosensors offer powerful tools to probe cell behaviors and properties in a non-invasive, simple, and quantitative manner. Current studies on cell-based acoustic wave sensors are focused on experimental investigation of thickness shear mode (TSM) sensors for monitoring cell attachment and spreading. There are no theoretical models for cell-based TSM biosensors. No studies on other cell biological applications of TSM sensors or on surface acoustic wave cell-based biosensors have been performed. The reliability and sensitivity of current cell-based biosensors are low. Improving them requires studies on engineering cells and understanding the effects of cell morphology on cell function.The overall objective of this dissertation is to develop acoustic wave sensor systems for cell biological studies and to determine the effects of cell shape on cell function. Our study includes three parts: (1) Development of cell-based TSM sensor system; (2) Studies of Love mode devices as cell-based biosensors; (3) Studies of the effects of cell shape on cell function. In the first part, a theoretical model was developed, changes in cell adhesion were monitored and cell viscoelasticity was characterized by TSM sensor systems. The TSM sensor systems were demonstrated to provide a non-invasive, simple, and reliable method to monitor cell adhesion and characterize cell viscoelasticity. In the second part, a theoretical model was developed to determine signal changes in Love mode sensors due to cells attaching on their surface. Experimental results validated the model. In the third part, cell shape was patterned to different aspect ratios. Elongated tendon cells were found to express higher collagen type I than shorter cells. Changes in cell shape induced alterations in cytoskeleton, focal adhesions, and traction forces in cells, which may collectively prompt the observed differential collagen type I expression in cells with different shapes. Overall, our research expanded the applications of acoustic wave cell-based biosensors. Studies on cell shape control and the effects of cell shape on cell function will be useful for increasing the sensitivity of cell-based biosensors in future research