Optical-mechanical properties of diseased cells measured by interferometry

Interferometric phase microscopy (IPM) enables to obtain quantitative optical thickness profiles of transparent samples, including live cells in-vitro, and track them in time with sub-nanometer accuracy without any external labeling, contact or force application on the sample. The optical thickness measured by IPM is a multiplication between the cell integral refractive index differences and its physical thickness. Based on the time-dependent optical thickness profile, one can generate the optical thickness fluctuation map. For biological cells that are adhered to the surface, the variance of the physical thickness fluctuations in time is inversely proportional to the spring factor indicating on cell stiffness, where softer cells are expected fluctuating more than more rigid cells. For homogenous refractive index cells, such as red blood cells, we can calculate a map indicating on the cell stiffness per each spatial point on the cell. Therefore, it is possible to obtain novel diagnosis and monitoring tools for diseases changing the morphology and the mechanical properties of these cells such as malaria, certain types of anaemia and thalassemia. For cells with a complex refractive-index structure, such as cancer cells, decoupling refractive index and physical thickness is not possible in single-exposure mode. In these cases, we measure a closely related parameter, under the assumption that the refractive index does not change much within less than a second of measurement. Using these techniques, we lately found that cancer cells fluctuate significantly more than healthy cells, and that metastatic cancer cells fluctuate significantly more than primary cancer cells.

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