? The long-term goal of the proposed research is to achieve a clear understanding of the optical response of biological cells and build the foundation for noninvasive determination of structure and function of the cells. The objective of the proposed research is to conduct comprehensive study of light scattering from biological cells through numerical simulations to establish correlations between the biochemical and morphological structure of cells and the distribution of the elastically scattered light. The finite-difference time-domain method (FDTD), enhanced with parallel computation techniques, will be used to accurately and efficiently model light scattering from cells with arbitrary structural complexity. The proposed research is based on the following hypotheses: (1) Distribution of elastically scattered light by a biological cell depends on cell morphology, or the size, shape and structure of the cell, and it can be accurately modeled by the FDTD method; (2) The morphology of the cell can be inversely determined from the measurements and modeling of elastic light scattering. The following research specific aims are proposed to test these hypotheses: (1) upgrade an existing parallel computing PC cluster that will be used in the parallel FDTD numerical simulations; (2) develop and validate a high-performance parallel FDTD code that is capable of accurately simulating light scattering by single biological cells with size up to 30 times of the wavelength of the incident light; (3) establish numerical models of """"""""optical cell"""""""" for two cell types - B-cell and HL-60 (promyelocytic) cell - and their precursors and/or differentiated cells based on light and electron microscopy data; (4) Investigate the dependence of the scattered light distribution on cell morphology and the corresponding sensitivity to establish an initial spectral database of light scattering from 400 to 1200nm using the newly developed parallel FDTD code and the numerical models of the two cell types; (5) Model the experimental data of polarized angular dependent light scattered from multiple epithelial cells and epithelial cell nuclei from a previous study using the techniques developed in Aim #3 and Aim #-4. 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. ? ?
