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

Abstract

A microscopy technique, spatial-domain low-coherence quantitative phase microscopy (SL-QPM) is proposed for speckle-free, quantitative phase imaging of subcellular structures with subnanometer sensitivity. We quantified, for the first time to our knowledge, the refractive index of the cell nuclei on original unmodified histology specimens. We demonstrate that the refractive index of cell nucleus is highly sensitive in detecting cancer, especially in histologically normal-appearing cells from cancer patients. Because this technique is sensitive and does not require special sample processing, it can be disseminated to all clinical settings.

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

“…SL-QPM takes advantage of the ultrahigh sensitivity of the light interference effect to achieve nanoscale sensitivity not attainable with a conventional microscope. 4,5 Compared with other biomarkers, the nano-morphology marker has a few major advantages. First, it can be extracted from the clinical tissue histology specimens (glass-slide-based) prepared according to standard routine clinical protocols without any additional processing, thus easily can be integrated with the existing workflow of current pathology laboratories.…”

“…1 The recent development in optical techniques has allowed the detection of these nanoscale structural properties. [1][2][3][4][5][6][7][8][9] These changes occur at a scale of about 20 to 1000 times smaller than what conventional optical microscope can detect. For example, partial-wave spectroscopy has shown that changes in the nano-structural properties could be highly sensitive for the detection of molecular alterations associated with carcinogenesis prior to the occurrence of phenotype.…”

“…The technical development of SL-QPM system has been described in detail in our previous publications. 4,5,20 We obtain an OPL map of the individual cell nucleus under observation, which is sensitive to subtle structural changes in the cell nucleus with nanoscale sensitivity.…”

“…12,13 Our group has recently developed a novel optical microscope, Spatial-domain low-coherence quantitative phase microscopy (SL-QPM), that can detect subtle structural changes at sub-nanometer sensitivity, which is about 1000 times more sensitive than what conventional microscopy can detect. [4][5][6]14 We derived nano-morphology markers quantified by nanoscale optical path length (OPL) properties from cell nuclei that showed a superior sensitivity in detecting carcinogenesis from histologically "normal" cells from cancer patients, suggesting that SL-QPM is a powerful tool to detect subtle nano-structural changes, not appreciated by conventional pathology. 4,5 SL-QPM also has the advantage of being directly applicable on the standard histology and cytology specimens, and has the potential for clinical translation.…”

“…[4][5][6]14 We derived nano-morphology markers quantified by nanoscale optical path length (OPL) properties from cell nuclei that showed a superior sensitivity in detecting carcinogenesis from histologically "normal" cells from cancer patients, suggesting that SL-QPM is a powerful tool to detect subtle nano-structural changes, not appreciated by conventional pathology. 4,5 SL-QPM also has the advantage of being directly applicable on the standard histology and cytology specimens, and has the potential for clinical translation.…”