Surveilling cellular vital signs: toward label-free biosensors and real-time viability assays for bioprocessing

Cell viability is an essential facet of mammalian and microbial bioprocessing. While robust methods of monitoring cellular health remain critically important to biomanufacturing and biofabrication, the complexity of advanced cell culture platforms often poses challenges for conventional viability assays. This review surveys novel approaches to discern the metabolic, morphological, and mechanistic hallmarks of living systems - spanning subcellular and multicellular scales. While fluorescent probes coupled with 3D image analysis generate rapid results with spatiotemporal detail, molecular techniques like viability PCR can distinguish live cells with genetic specificity. Notably, label-free biosensors can detect nuanced attributes of cellular vital signs with single-cell resolution via optical, acoustic, and electrical signals. Ultimately, efforts to integrate these modalities with automation, machine learning, and high-throughput workflows will lead to exciting new vistas across the cell viability landscape.