Low-coherence Common-path Phase Microscopy for Nanoscale Detection of Malignancy in Stained Tissue Slides

This approach is distinguished by its reflectance-mode geometry and common-path design, which suppress stain absorption effects and external vibrations without requiring special sample preparation. Integration into existing pathology workflows is seamless, as it uses unmodified specimens and archived slides. Its nanoscale sensitivity and quantitative phase metrics exceed the capabilities of conventional microscopy, enabling early cancer detection, objective malignancy grading across multiple tissue types, and the ability to work with minimal cell numbers, making it well suited for fine-needle aspiration cytology and longitudinal monitoring of therapeutic response.

Description

Spatial-domain Low-Coherence Quantitative Phase Microscopy employs a broadband thermal light source and low spatial- and temporal-coherence common-path interferometric microscopy in reflectance mode to analyze standard stained histology or cytology slides. Illumination is collimated through a 4f relay and focused by a low-NA objective onto the sample, while backscattered light carrying phase information is spectrally analyzed by a scanning imaging spectrograph and recorded by a CCD camera. The glass slide and tissue share the same optical path, eliminating external disturbances and speckle noise. Custom software processes the recorded spectra to generate two-dimensional optical path length (OPL) maps with nanoscale sensitivity, extracting quantitative phase metrics—mean OPL, OPL standard deviation, and entropy—to reveal subtle alterations in nuclear refractive index and spatial heterogeneity associated with malignancy.

IP Status

https://patents.google.com/patent/US11105686B2