Characterization and identification of cell death dynamics by quantitative phase imaging

SIGNIFICANCE: Investigating cell death dynamics at the single-cell level plays an essential role in biological research. Quantitative phase imaging (QPI), a label-free method without adverse effects of exogenous labels, has been widely used to image many types of cells under various conditions. However, the dynamics of QPI features during cell death have not been thoroughly characterized. AIM: We aim to develop a label-free technique to quantitatively characterize single-cell dynamics of cellular morphology and intracellular mass distribution of cells undergoing apoptosis and necrosis. APPROACH: QPI was used to capture time-lapse phase images of apoptotic, necrotic, and normal cells. The dynamics of morphological and QPI features during cell death were fitted by a sigmoid function to quantify both the extent and rate of changes. RESULTS: The two types of cell death mainly differed from normal cells in the lower phase of the central region and differed from each other in the sharp nuclear boundary shown in apoptotic cells. CONCLUSIONS: The proposed method characterizes the dynamics of cellular morphology and intracellular mass distributions, which could be applied to studying cells undergoing state transition such as drug response.