Multiplexed Cell-Based Sensors for Assessing the Impact of Engineered Systems and Methods on Cell Health

Bioinstrumentation engineers have long been creating platforms to study cell health and disease. It becomes necessary to ensure that such cell-probing tools do not themselves harm cells through complex stressors resulting from their design or operational conditions. Here, we present multiplexed cell-based sensors to simultaneously quantify stress induced by diverse mechanisms such as shear stress, DNA damage, and heat shock. Our sensors do not require additional reagents and can be conveniently quantified by flow cytometry and real-time imaging. Successful adaptation of our sensors by external users enabled systematic assessment of multiple flow sorters, alongside their operational parameters using the same cells and preparation. Our results provide insight into "gentle" and stressful sorting parameters that had not been quantified previously. Overall, this work presents a facile and quantitative approach to investigate multifactorial cell-stress emergent from diverse bioinstrumentation, which can be utilized to discover design and operation conditions ideal for cell health.