Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis

A novel microscopy technique, spatial-domain low-coherence quantitative phase microscopy (SL-QPM), is proposed to obtain quantitative phase imaging of sub-cellular structures with sub-nanometer sensitivity. This technique utilizes a low spatial-coherence from a thermal light source and produces a speckle-free, nanoscale-sensitive quantitative phase map of scattering objects. With this technique, for the first time to our knowledge, we quantified the refractive index of the cell nuclei on the original unmodified histology specimens. The results show that the average refractive index of the cell nucleus is significantly increased in cells from cancer patients compared to that of the histologically normal cells from healthy patients. More importantly, we demonstrate the superior sensitivity of refractive index of cell nucleus in detecting cancer from histologically normal cells from cancer patients. Because this technique is simple, sensitive, does not require special tissue processing, and can be applied to archived specimens, it can be disseminated to all clinical settings.