DYNAMIC RAY-TRACING FOR MODELING CELL MANIPULATION USING HIGH-THROUGHPUT OPTICAL STRETCHERS

Optical stretchers have been recently used to identity cell types and to detect disease states. In this method, a cell is trapped within a laser beam then is stretched by optical forces from the interaction of light with the cell surface. Cell stretch is used to calculate cellular elastic properties using an appropriate numerical model. The current dual-beam optical stretcher was successfully used as an efficient and accurate cell biomarker compared to other contact methods such as Atomic Force Microscopy or micropipette aspiration. This is due to the no-direct contact with the cell thus less induced damage. However, in the dual-beam optical stretcher cells are sequentially trapped and stretched within static systems resulting in very low-throughput. In addition, there is a lack of numerical methods that take into account cell deformability, cell-fluid interaction, different cell membrane models, and high-throughput. In the first part of this dissertation, we present simulations of cell deformation by optical forces from a recently developed high-throughput optical stretcher using diode laser bars. The simulations were done using an implemented Dynamic Ray-Tracing method linked with the Immersed Boundary Method to account for both cell-fluid interaction and cell-light interaction. We modeled cell stretching by single and dual laser bar configurations. We showed that single diode laser bar induces cell stretching in addition to translation as opposed to the dual diode laser bar where the cell is fixed at a focus. We also presented a method to calculate cell stiffness from experimental measurements. We used this method to calculate red blood cells' shear modulus. Our calculated cell stiffness was in the range of reported values. In the second part of this dissertation, we investigate the effect of cell deformation on the calculation of optical forces. The implemented Dynamic Ray-Tracing allows calculating these forces on arbitrary cell shapes as opposed to the current Ray-Optics technique that was designed for spherical rigid cells only. We showed that the change in cell shape affects the optical forces calculation. A difference of up to 42% in the net optical force was observed at high laser powers that suggests considering cell deformability in the cell stiffness calculation. Non-spherical cells deformation simulations were also presented. Finally, high-throughput optical stretching simulations were presented by applying an external flow. It was shown that at the experimental average flow rate of 50 μm/sec, cell deformation caused by the external applied flow is insignificant and can be neglected. However, at a flow rate of 500 μm/sec net cell deformation was 10% less compared to the quiescent case. These findings suggest that the external flow rate can be increased to achieve faster cell throughput, however, its effect has to be considered in the calculation of elastic properties. The results of this study coupled with experimental measurements can be used to calculate individual cell's properties at high-throughput. We believe that the developed algorithm can be used to better design high-throughput optical stretchers for different cell models