High-throughput hierarchical single-cell biophysical phenotyping for predicting sensitivity to targeted drug response

Abstract

Using a high-throughput imaging flow cytometer (10,000 cells/sec) multi-ATOM, we established a hierarchical biophysical phenotyping approach for label-free single-cell analysis. We demonstrate that the label-free multi-ATOM contrasts can be derived into a set of spatially hierarchical biophysical features that reflect optical density and dry mass density distributions in local and global scales. This phenotypic profile enables us to delineate subtle cellular response of molecularly targeted drug even at an early time point after the drug administration (6 hours). Based on fluorescence image analysis, we further interpreted how these biophysical phenotypes correlate with specific intracellular organelles alteration upon drug treatment.