Machine-learning-guided quantitative delineation of cell morphological features and responses to nanomaterials

Delineation of cell morphological features is essential to decipher cell responses to external stimuli like theranostic nanomaterials. Conventional methods rely on labeled approaches, such as fluorescence imaging and flow cytometry, to assess cell responses. Besides potentially perturbing cell structure and morphology, these approaches are relatively complex, time-consuming, expensive, and may not be compatible with downstream analysis involving live cells. Herein, leveraging label-free phase-contrast or brightfield microscopy imaging and machine learning, the delineation of different cell types, phenotypes, and states for monitoring live cell responses is reported. Notably, pixel classification based on a supervised random forest classifier is used to distinguish between cells and backgrounds from the microscopy images, followed by cell segmentation and morphological feature extraction. Quantitative analysis shows that most of the compared cell groups have distinguishable size and shape features. Principal component analysis and unsupervised k-means clustering of morphological features reveal the possible existence of heterogenous cell subpopulations and treatment responses among the seemingly homogenous cell groups. This shows the merit of the reported approach in complementing conventional techniques for cell analysis. It is anticipated that the demonstrated method will further aid the implementation of machine learning to streamline the analysis of cell morphology and responses for early disease diagnosis and treatment response monitoring.