A multifaceted microfluidic in vitro assay is helping to identify the role of hypoxia on red blood cell aging via the biomechanical pathways. It holds promise for investigating hypoxic effects on the metastatic potential and relevant drug resistance of cancer cells. It also can be a useful tool to predict the mechanical performance of natural and artificial red blood cells for transfusion purposes and to further extend to red blood cells in other blood diseases and other cell types.