Hemorheological Considerations in the Development of Microfluidic Blood Oxygenation Devices

Abstract

Novel supersaturation oxygenation technology promises a leap forward in the enhancement of ECMO capabilities and deployment of a more efficient, versatile, and portable form of extracorporeal oxygenation technology. The showcased membrane bubble generation supersaturation technique offers superior oxygenation performance to conventional ECMO allowing for reductions in blood flow rate, thus promising to reduce the shear-based thrombosis that limits current oxygenation technology in medium to long-term treatment of severely aff licted patients. The membrane supersaturation concept promises to address that gap in reliable, extended treatment by greatly reducing shear to delay and prevent thrombus formation in the device and associated extracorporeal life support (ECLS) circuit. The bubbles produced by the membrane generator are small in size, sufficient to completely diffuse and fully oxygenate a larger volume of blood when combined with an additional deoxygenated blood flow. Further, the technique’s high oxygen flux will offer new options for reducing size footprint and ruggedization for austere conditions given further investment and development. This will necessitate the creation of custom membrane solutions and further optimization of device channel geometries via simulation using advanced blood models such as the tensorial enhanced structural stress thixotropic-viscoelastic (t-ESSTV) constitutive model developed and discussed in this work. A characteristic feature of human blood rheology is a distinctive stress hysteresis during a ramp up in the shear rate from zero, followed by a ramp back to zero. This is a result of the fact that human blood has a longer characteristic time of shear-induced rouleaux breakdown compared to the shear aggregation of the rouleaux. We demonstrate this telltale phenomenon of human blood rheology using a triangle ramp protocol to control time-dependent changes in the shear rate. The unique hysteresis data are then used along with steady state data to fit parameters of a recently published thixo-elasto-viscoplastic rheological model, the tESSTV model. These best-fit parameter values from the hysteresis ramps are then used to predict step-up/down in shear rate, small amplitude oscillatory shear, uni-directional large amplitude oscillatory shear, and large amplitude oscillatory shear flow. Additionally, correlations between the calculated fitting parameters and physiological data are analyzed to inform the interpretation of model behavior in physical terms. The goodness of fit of the triangle ramp protocol and rheological hysteresis data are then evaluated alongside recently developed techniques to assess thixotropy via computation of hysteresis loop area. The results indicate the efficacy of the t-ESSTV model in potentially predicting the complex characteristics of blood rheology in useful ways for future use in modeling circulating flows under a variety of mechanical and biological loading conditions and predicting understanding rheological effects on resulting pathologies.