Snapshot sickle cell morphological imaging and analysis using interferometric phase and absorption microscopy (iPAM)

Sickle cell disease (SCD) is a widespread genetic disorder where afflicted patients experience painful vaso-occlusive crisis events and significantly increased morbidity due to the presence of malformed hemoglobin in the patient. Sickle red blood cells (sRBCs) containing this hemoglobin exhibit unique morphological, biophysical, and mechanical properties that could relate to the disease’s clinical outcomes, but specific connections between these micro-scale cellular changes and macro-scale events are still elusive. To bridge this gap, we have developed interferometric phase and amplitude microscopy (iPAM), a high-throughput diffraction phase microscope coupled with efficient linear computational models, that extracts single-cell morphological and biophysical information from snapshot sRBC images. Across 67 patients, we show iPAM’s unique recovery of morphological and morphometric sRBC metrics at single-cell resolution matches clinically recovered global cellular volume and hemoglobin information and correlates well in predicting the patient’s hemoglobin chemical composition just from the sRBC morphological information.