The long-term goal of the proposed research is to develop noninvasive, fast and accurate methods to determine the structure and function of biological cells by elastic light scattering. The objective of this proposed research is to develop accurate and fast simulation tools for modeling of light scattering by biological cells of a large range of sizes and structure complexity, and apply the tools to study the scattered light distributions of myeloid leukemia blast cells at multiple wavelengths. In addition to a parallel finite-difference time-domain (FDTD) method developed under the support of a current R15 grant, we will further employ a discrete dipole approximation (DDA) method to significantly improve the simulation speed for modeling of light scattering by the blast cells. The proposed research will test the following hypothesis: """"""""The detailed morphological features of the biological cells can be correlated with the angle-resolved light scattering signals at multiple wavelengths."""""""" The specific aims of the proposed research are: (1) To optimize the performance and improve the accuracy of our recently developed parallel FDTD code for better modeling of light scattering from biological cells; (2) To evaluate the applications and identify valid regions of the DDA method in simulation of light scattering by biological cells of large size parameters (up to 200) by comparing the accuracy and performance of a parallel DDA code with those of our parallel FDTD code; (3) To improve our current cell optical structure modeling by introducing heterogeneity into the nucleus and cytoplasm in the 3D structure constructed from confocal images; (4) To acquire confocal images of 200 myeloid leukemic blast cells and to investigate the correlation between morphological features of the blast cells and their angle-resolved light scattering patterns for the establishment of a cell-optics based classification system and a cell morphology and optics database. Successful completion of the proposed research will lay a solid foundation for future development of light scattering based automated differential cell count method to improve significantly the diagnosis accuracy of leukemia and other diseases. Successful completion of this project will fill in critical gaps in our understanding of elastic light scattering at the cellular level, and provide the foundation for exploration of opportunities such as noninvasive, automated and fast determination of structure and function of biological cells through inverse reconstruction from light scattering data. The significance of these applications can be of high impact to the study of cell biology and diagnosis and treatment of cancers at the cell level. ? ? ?
