Quantitative phase microscopy for label-free high-contrast cell imaging

Abstract

Systems and methods described herein employ multiple phase-contrast images with various relative phase shifts between light diffracted by a sample and light not diffracted by the sample to produce a quantitative phase image. The produced quantitative phase image may have sufficient contrast for label-free auto-segmentation of cell bodies and nuclei.

Description

technical field [0001] In general, embodiments relate to phase contrast microscopy. More specifically, some embodiments relate to quantitative phase microscopy for high-contrast cellular imaging. Background technique [0002] The identification of the boundaries of cell bodies and / or nuclei in a microscope image of a sample is referred to as segmentation of cell bodies and / or nuclei in the image. To image cellular structures in a sample (eg for segmentation), staining or labeling techniques are often used to enhance the contrast between different types of cellular structures. For example, a specimen can be stained with a dye that reacts with DNA or RNA (eg, ethidium bromide) or that interacts differently with the nucleus and cytoplasm (eg, hematoxylin-eosin). As another example, labels, which may be one or more colorants (chromophores) and / or one or more fluorescers (fluorophores), are useful in identifying expected species in cellular structures based on the presence of s...

AI Technical Summary

Problems solved by technology

While providing images with enhanced edge features, the contrast is often insufficient to ensure reliable automatic segmentation of cells and / or nuclei

[0005] Furthermore, neither conventional optical imaging with labeling and staining nor conventional phase-contrast imaging provided quantitative thickness information with respect to cell monolayers

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