Molecular Sensing and Imaging of Human Disease Cells and Their Responses to Biochemical Stimuli

Advancement in microscopic and spectroscopic techniques could significantly improve our ability in the study and diagnosis of diseases. Especially, being able to image and detect human diseases at the cellular and molecular level allows people to diagnose diseases at early stages and to study the molecular mechanisms behind various diseases. Currently, histopathological techniques are most widely used for prognosis and diagnosis of human diseases. However, conventional histopathology requires a complex process of sample preparation, which limits the diagnostic efficiency of this technique. More importantly, it requires fixation of tissue or cell sample, making it unsuitable for the study of dynamic cellular activities in the progress of diseases. This dissertation mainly discusses the progress in development of noninvasive imaging techniques that can be applied to study human diseases at the cellular level. One approach is to use atomic force microscopy (AFM) and Raman spectroscopy to quantitatively measure the biomechanical and biochemical properties of cells, and then use these properties to differentiate between different cell types, or cells at different states. Here we have utilized our tandem AFM-Raman spectroscopy system to differentiate between cancerous and healthy human lung epithelial cells, and monitor their different responses to anticancer drug treatments. Generally, this technique (AFM-Raman) can serve as a complementary approach to study various diseased cells, providing additional information to help doctors identify diseases at an early stage and investigate the progress of diseases. Another approach is specifically target and image disease marker molecules using advanced microscopic and spectroscopic techniques. Epidermal growth factor receptor (EGFR), as a cancer marker molecule, has been used as a model to develop noninvasive imaging methods. A nanoparticle-based imagine probe has been synthesized for specific imaging of EGFR at a single cell surface using surface-enhance Raman spectroscopy ...