Design and In Vitro Evaluation of an Artificial Placenta Made From Hollow Fiber Membranes

Abstract

For infants born at the border of viability, care practices and morbimortality rates vary widely between centers. Trends show significant improvement, however, with increasing gestational age and weight. For periviable infants, the goal of critical care is to bridge patients to improved outcomes. Current practice involves ventilator therapy, resulting in chronic lung injuries. Research has turned to artificial uterine environments, where infants are submerged in an artificial amniotic fluid bath and provided respiratory assistance via an artificial placenta. We have developed the Preemie-Ox, a hollow fiber membrane bundle that provides pumpless respiratory support via umbilical cord cannulation. Computational fluid dynamics was used to design an oxygenator that could achieve a carbon dioxide removal rate of 12.2 ml/min, an outlet hemoglobin saturation of 100%, and a resistance of less than 71 mmHg/L/min at a blood flow rate of 165 ml/min. A prototype was utilized to evaluate in-vitro gas exchange, resistance, and plasma-free hemoglobin generation. In-vitro gas exchange was 4% higher than predicted results and no quantifiable plasma-free hemoglobin was produced.

Figure 1:

Preemie-Ox prototype. The HFMO is assembled into a custom machined test housing shown in the image of the prototype.

Figure 2:

Resistance apparatus configuration. Fluid from the apparatus drains into a collection reservoir (not pictured). Scissor lab jacks were used to keep the reservoir and device level.

Figure 3:

Schematic of gas exchange circuit. Clamps direct the recirculation of blood through the venous reservoir during conditioning. Once conditioning is complete blood flow is directed through the circuit to the empty reservoir. During this single pass flow gas flow via the de-oxygenator is stopped and pure oxygen sweep gas is flowed through the artificial placenta. Once the conditioned blood is depleted, the circuit is converted back to a recirculation circuit so blood can be conditioned to venous values.

Figure 4:

CFD analysis results for 165 mL/min flow showing (a) fluid velocity through the fiber bundle (m/s) and (b) streamlines of velocity magnitude through the device (m/s).

Figure 5:

Graph of elapsed time vs. ln(h_i/h_f). The slope of the linear relationship was used to determine the device resistance according to Eq. 3.

Figure 6:

Plasma free hemoglobin (pfHb) concentration over time for experimental and control circuits. Levels of pfHb did not statistically increase over time for either circuit (repeated measures ANOVA, p=0.24).