We propose a multimodal quantitative, label-free and nondestructive diagnostic metrology technique by integrating off-axis interferometric phase microscopy (IPM) and Raman spectroscopy (RS), for analyzing normal and malignant bladder tissue samples. We built a Mach–Zehnder interferometer connected to a commercial confocal microscope for imaging a large area of tissue slices, up to a few millimeters, by semi-automatic scanning of the tissue. Bright-field image of hematoxylin and eosin stained tissue slice of the same area was also acquired. Measurements of Raman spectra were acquired using our RS system with excitation wavelength of 561 nm. Using the quantitative phase information, we obtained various spatial and morphological parameters of the tissues such as the anisotropy factor, which demonstrated their direct correlation with tumor presence. This method is expected to be useful for stain-free cancer diagnosis, while obtaining both quantitative information about tissue morphological modifications and changes in tissue Raman scattering properties induced by cancer.
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