Empirical and Computational Evaluation of Hemolysis in a Microfluidic Extracorporeal Membrane Oxygenator (ECMO) Prototype

Abstract

3Microfluidic devices may overcome the limitations of conventional hemodialysis and 4 oxygenation technology to improve patient outcomes. Namely, the small form of this technology 5 and parallel development of highly permeable membranes may facilitate the development of 6 portable, low-volume, and efficient alternatives to conventional membrane-based equipment. 7However, the characteristically small dimensions of these devices may also inhibit transport and 8 may also induce flow-mediated nonphysiologic shear stresses that may damage red blood cells 9 (RBCs). In vitro testing is commonly used to quantify these phenomenon, but is costly and only 10 characterizes bulk device performance. Here we developed a computational model that predicts 11 the blood damage and solute transport for an abitrary microfluidic geometry. We challenged the 12 predictiveness of the model with three geometric variants of a prototype design and validated 13 hemolysis predictions with in vitro blood damge of prototype devices in a recirculating loop. We 14 found that six of the nine tested damage models statistically agree with the experimental data for 15 at least one geometric variant. Additionally, we found that one geometrical variant, the 16 herringbone design, improved toxin (urea) transport to the dialysate by 38% in silico at the 17 expense of a 50% increase in hemolysis. Our work demonstrates that computational modeling 18 may supplement in vitro testing of prototype microdialyzer/micro-oxygenators to expedite the 19 design optimization of these devices. Furthermore, the low device-induced blood damage 20 measured in our study at physiologically relevant flow rates is promising for the future 21 development of microfluidic dialyzers and oxygenators. 22 reduce the required device size and thus blood volume, a critical parameter for smaller patients. 31Small volume oxygenation of blood for neonatal application can be addressed by microfluidic 32 oxygenators, where it is vital to keep the oxygenator volume appropriately small due to the low 33 blood volume of the neonatal patient. Furthermore, the associated decrease in membrane surface 34 area and blood-contacting artificial materials reduces complications and blood damage[5], [6]. 35