Abstract
The cell refractive index has been proposed as a putative cancer biomarker of great potential, being correlated with cell content and morphology, cell division rate and membrane permeability. We used digital holographic microscopy to compare the refractive index and dry mass density of two B16 murine melanoma sublines of different metastatic potential. Using statistical methods, the distribution of phase shifts within the reconstructed quantitative phase images was analyzed by the method of bimodality coefficients. The observed correlation of refractive index, dry mass density and bimodality profile with the metastatic potential of the cells was validated by real time impedance‐based assay and clonogenic tests. We suggest that the refractive index and bimodality analysis of quantitative phase image histograms could be developed as optical biomarkers useful in label‐free detection and quantitative evaluation of cell metastatic potential.
Highlights
IntroductionThe cell refractive index has been proposed as a putative cancer biomarker of great potential, being correlated with cell content and morphology, cell division rate and membrane permeability
The cellular refractive index (RI) and height were calculated in a square area of 3 9 3 pixels characterized by maximum phase shift in quantitative phase image (QPI)
We found that the refractive index of the F10 subline was significantly higher than that of F1 (P = 0.01) in the specified area (Fig. 3A)
Summary
The cell refractive index has been proposed as a putative cancer biomarker of great potential, being correlated with cell content and morphology, cell division rate and membrane permeability. We used digital holographic microscopy to compare the refractive index and dry mass density of two B16 murine melanoma sublines of different metastatic potential. The observed correlation of refractive index, dry mass density and bimodality profile with the metastatic potential of the cells was validated by real time impedance-based assay and clonogenic tests. We suggest that the refractive index and bimodality analysis of quantitative phase image histograms could be developed as optical biomarkers useful in label-free detection and quantitative evaluation of cell metastatic potential. Abbreviations CI, cell index; DHM, digital holographic microscopy; QPI, quantitative phase image; RI, refractive index; RTCA, real time cell analysis
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