Abstract
Tumor heterogeneity is a primary factor that contributes to treatment failure. Predictive tools, capable of classifying cancer cells based on their functions, may substantially enhance therapy and extend patient life span. The connection between cell biomechanics and cancer cell functions is used here to classify cells through mechanical measurements, via particle uptake. Machine learning (ML) was used to classify cells based on single-cell patterns of uptake of particles with diverse sizes. Three pairs of human cancer cell subpopulations, varied in their level of drug resistance or malignancy, were studied. Cells were allowed to interact with fluorescently labeled polystyrene particles ranging in size from 0.04 to 3.36 μm and analyzed for their uptake patterns using flow cytometry. ML algorithms accurately classified cancer cell subtypes with accuracy rates exceeding 95%. The uptake data were especially advantageous for morphologically similar cell subpopulations. Moreover, the uptake data were found to serve as a form of "normalization" that could reduce variation in repeated experiments.