Electrophysiology as a Real-time Biomarker for Human Red Blood Cell Monitoring in Extracorporeal Membrane Oxygenation

Blood monitoring in extracorporeal membrane oxygenation (ECMO) is critical to managing the precarious balance between bleeding and thrombosis in ECMO support. Conventional monitoring including plasma free hemoglobin and activated clotting time are limited to once-daily measurements. Considering this limitation, we investigated surface zeta (ζ) potential, as a real-time biomarker for monitoring RBCs in ECMO. RBC ζ-potential is a negative electrical charge on the cell surface, providing repulsive force to prevent RBC aggregation in circulation. Human RBCs from 7, 14, 21, and 49 days stored blood were circulated through an ECMO circuit for 12 hours. Every 2 hours, ζ-potential, RBC concentration, intracellular Ca ²⁺ , and sialic acid were measured. The ζ-potential of RBCs decreased with blood circulation after only 8 hours of circulation. The decrease in ζ-potential was further amplified by blood storage from just 21 days. Ca ²⁺ and sialic acid were also shown to increase with flow and storage duration. This suggests prolonged blood storage compounds the risk of RBC aggregation. Our results demonstrate ζ-potential can detect changes in RBCs in ECMO circuits ex vivo . The high temporal sensitivity of ζ-potential offers real-time detection of changes in RBC physiology to better predict cell aggregation and clotting risk, improving treatment outcomes for patients.