Identification of cell death mechanisms, particularly distinguishing between apoptotic versus non-apoptotic pathways, is of paramount importance for a wide range of applications related to cell signaling, interaction with pathogens, therapeutic processes, drug discovery, drug resistance and even pathogenesis of diseases like cancers and neurogenerative disease among others. Here we present a novel high-throughput method of identifying apoptotic vs necrotic vs other non-apoptotic cell death processes, based on lensless digital holography. This method relies on identification of the temporal changes in the morphological features of mammalian cells, which are unique to each cell death processes. Different cell death processes were induced by known cytotoxic agents. A deep learning-based approach was used to automatically classify the cell death mechanism (apoptotic vs necrotic vs non-apoptotic) with more than 93% accuracy. This label free approach can provide a low cost (<$250) alternative to some of the currently available high content imaging-based screening tools.

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