Automated Sickle Cell Disease diagnosis based on spatio-temporal cell dynamics analysis using 3D printed shearing digital holographic microscopy

We present a spatio-temporal analysis of cell membrane fluctuations to distinguish healthy red blood cells (h-RBCs) from sickle cell disease red blood cells (SCD-RBCs). A video hologram containing either h-RBCs or SCD-RBCs was recorded using a low-cost, compact, 3D printed shearing interferometer. Reconstructions were created for each hologram frame (time steps), forming a spatio-temporal data cube. Features were extracted by computing the standard deviations and the mean of the height fluctuations over time and for every location on the cell membrane, resulting in two-dimensional standard deviation and mean maps, followed by taking the standard deviations of these maps. The optical flow algorithm was used to estimate the apparent motion fields between subsequent frames (reconstructions). The standard deviation of the magnitude of the optical flow vectors across all frames was then computed. In addition, seven morphological cell (spatial) features based on optical path length were extracted from the cells to further improve the classification accuracy. A random forest classifier was trained to perform automatic cell identification to distinguish between SCD-RBCs and h-RBCs. To the best of our knowledge, this is the first report of automatic cell identification based on cell membrane fluctuations and morphology using both spatio-temporal and spatial analysis.