An intelligent dual-network magnetic separation microgels with real-time microenvironment monitoring for 4 °C refrigerated erythrocyte preservation

Erythrocyte preservation requires maintaining cellular activity and functional integrity to ensure transfusion safety and efficacy. However, conventional cryopreservation methods suffer from operational complexity, while standard 4 °C refrigeration cannot prevent cellular damage caused by oxidative stress and metabolic dysregulation. Herein, we designed an intelligent control system based on a dual-network magnetic separation microgels, which can monitor changes to the microenvironment of erythrocyte preservation in real time during refrigerated storage at 4 °C. Red blood cells (RBCs) can be encapsulated in magnetic microgels self-assembled with reactive oxygen species (ROS)-sensitive phenylboronic acid ester bonds and pH-sensitive Schiff base bonds. Stored at 4 °C in a bacteriostatic environment, the microgels prevent the overproduction of ROS and mitigate pH decline caused by lactate accumulation. Its magnetic component enables efficient and convenient separation of RBCs. The intelligent control system enables real-time monitoring of ROS and pH variations within the preserved microenvironment, as indicated by the increase in resistance signal of the microgels. When the microgels' resistance exceeds the set threshold (ΔR/R₀ = 0.08), the computer then intelligently controls the addition of the antioxidant. Using Balb/c mice RBCs as a model, the microgel system extends the preservation of RBCs for up to 20 days, outperforming a commercial protectant in all preservation parameters. Thus, this work provides an innovative solution for long-term hypothermic preservation and real-time monitoring of RBCs, which will effectively alleviate the supply pressure of clinical blood banks by reducing the RBCs scrapping rate.