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Optical probing of spatial structural abnormalities in cells/tissues due to cancer, drug-effect, and brain abnormalities using mesoscopic physics-based spectroscopic techniquesAdhikari, Prakash 06 August 2021 (has links) (PDF)
The quantitative measurement of structural alterations at the nanoscale level is important for understanding the physical states of weakly disordered optical mediums such as cells/tissues. Progress in certain diseases, such as cancer or abnormalities in the brain, is associated with the nanoscale structural alterations at basic building blocks of the cells/tissues. Elastic light scattering, especially at visible wavelengths range provides non-invasive ways to probe the cells/tissues up to nanoscale level. Therefore, a mesoscopic physics-based open light scattering technique with added finer focusing, partial wave spectroscopy (PWS), is developed to probe nanoscale changes. Then, molecular-specific light localization technique, a close scattering approach called inverse participation ratio (IPR) is proposed that is sensitive to nano to microstructural cell/tissue alterations. In this dissertation, we have introduced the further engineered PWS system with the finer focus for precise volume scattering and molecular-specific light localization IPR techniques. As an application of PWS, we first probe precise scattering volume in commercially available tissue microarrays (TMA) tissue samples to standardize the existing cancer diagnostic methods by distinguishing the cancer stages. We also apply the PWS technique to probe chemotherapy drug-treated metastasizing cancer patients by xenografting prostate cancer cells using a mouse model and identify drug-sensitive and drug-resistance treatment cases. On the other hand, as an illustration of another mesoscopic physics-based molecular specific light localization technique, Confocal-IPR, we study the effects of a probiotic on chronic alcoholic mice brains by targeting the molecular specific alteration in glial cells, astrocytes and microglia, and chromatin of the brain cells through staining with appropriate dyes/proteins. Using structural disorder of IPR as a biomarker, the results show that probiotics in the presence of alcohol are beneficial and help overall brain health. Finally, a TEM-IPR study was performed using nanoscale resolution TEM imaging to support the optical IPR method by studying the anti-cancerous drug effect in ovarian cancer cells. The result shows that we can quantitatively measure the effect of anti-cancerous drugs in cancer treatment and the level of tumorigenicity far below the diffraction limit, and it has a similar effect and supports the optical IPR method.
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