Steel reinforced composite silicone membranes and its integration to microfluidic oxygenators for high performance gas exchange

Abstract

Respiratory distress syndrome (RDS) is one of the main causes of fatality in newborn infants, particularly in neonates with low birth-weight. Commercial extracorporeal oxygenators have been used for low-birth-weight neonates in neonatal intensive care units. However, these oxygenators require high blood volumes to prime. In the last decade, microfluidics oxygenators using enriched oxygen have been developed for this purpose. Some of these oxygenators use thin polydimethylsiloxane (PDMS) membranes to facilitate gas exchange between the blood flowing in the microchannels and the ambient air outside. However, PDMS is elastic and the thin membranes exhibit significant deformation and delamination under pressure which alters the architecture of the devices causing poor oxygenation or device failure. Therefore, an alternate membrane with high stability, low deformation under pressure, and high gas exchange was desired. In this paper, we present a novel composite membrane consisting of an ultra-thin stainless-steel mesh embedded in PDMS, designed specifically for a microfluidic single oxygenator unit (SOU). In comparison to homogeneous PDMS membranes, this composite membrane demonstrated high stability, low deformation under pressure, and high gas exchange. In addition, a new design for oxygenator with sloping profile and tapered inlet configuration has been introduced to achieve the same gas exchange at lower pressure drops. SOUs were tested by bovine blood to evaluate gas exchange properties. Among all tested SOUs, the flat design SOU with composite membrane has the highest oxygen exchange of 40.32 ml/min m. The superior performance of the new device with composite membrane was demonstrated by constructing a lung assist device (LAD) with a low priming volume of 10 ml. The LAD was achieved by the oxygen uptake of 0.48-0.90 ml/min and the CO release of 1.05-2.27 ml/min at blood flow rates ranging between 8 and 48 ml/min. This LAD was shown to increase the oxygen saturation level by 25% at the low pressure drop of 29 mm Hg. Finally, a piglet was used to test the gas exchange capacity of the LAD . The animal experiment results were in accordance with results, which shows that the LAD is capable of providing sufficient gas exchange at a blood flow rate of ∼24 ml/min.

A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress

“…The custom and modular design was also critical for pumpless operation as hydraulic resistance of the oxygenator could be tailored to produce adequate blood perfusion and oxygen uptake based on the baby's weight and an external pump could be eliminated. Since the arteriovenous pressure difference in a neonate is typically between 20 -60 mm Hg [12,16,[29][30][31] , such a pressure head applied to this LAD would generate a flow rate between 65 -86 mL min -1 in this optimized LAD which meets the requirement of a blood flow rate of 20 -30 mL min -1 kg -1 of a neonate typically needed to provide lung assist function (Figure 4. a and e). In this range of flow rates and under in-vitro conditions, this LAD was able to increase the oxygen saturation level from ~ 75 % to ~ 100 % which would be sufficient to fulfill oxygenation need for these preterm babies [12,16,[29][30][31] .…”

“…Microfabrication technologies have been employed to fabricate blood oxygenators that can address some of the limitations of current ECMO devices by using biomimetic architecture similar to the vascular network in the lung in order to enhance gas transfer efficiency, increase effective surface area for transfer as well as reduce shear stress in blood flow and avoid the formation of blood stagnation zones [14,15] . Several microfluidic blood oxygenators [12,16,[25][26][27][28][29][30][31][32][17][18][19][20][21][22][23][24] have been introduced aimed at improving gas exchange efficiency but all of them use external pumps to perfuse the blood through them. An alternate approach is to use the arterio-venous pressure difference in the body as a natural pumping mechanism to circulate the blood through an oxygenatora concept known as the artificial placenta.…”

“…Traditionally used hollow fiber ECMO devices have high priming volume and are not suitable for neonatal application. Only some of microfluidic oxygenators [12,16,[29][30][31] have been explicitly designed for use as an artificial placenta device. Most artificial placenta-type microfluidic blood oxygenators have been only been examined in vitro [12,29,30] and even those [16,31] tested in vivo have not been shown to provide adequate oxygenation in room air to support a suitable animal model in respiratory distress.…”

Understanding blood oxygenation in a microfluidic meander double side membrane contactor

“…Selvaganapathy et al fabricated interesting stainless steel reinforced composite silicone membranes to improve gas exchange performance. The composite membrane consisted of ultra-thin stainless-steel mesh embedded in PDMS that demonstrated high stability, low deformation under pressure and high gas exchange [13].…”

“…Essential points that need to be further studied are the optimization of liquid chamber geometries easy to fabricate and suitable for scaling up that keep cardiovascular parameters and blood specifications in desired range; and, the creation of the right balance between chip mechanical stability and good oxygenation performance. Crucial restrictions for the liquid side that need to be obeyed in order to keep the blood at physiological level include three main aspects: i) shear stress should not exceed the normal range in the human vascular system of 0.1 to 7 N/m 2 [12], ii) pressure drop, the arteriovenous pressure difference for neonates is in the range of 26.7 to 79.9 mbar [13] iii) the distribution of blood flow should be homogenous [14][15].…”