ABSTRACT
Preterm neonates with immature lungs require a lung assist device (LAD) to maintain oxygen saturation at normal levels. Over the last decade, microfluidic blood oxygenators have attracted considerable interest due to their ability to incorporate unique biomimetic design and to oxygenate in a physiologically relevant manner. Polydimethylsiloxane (PDMS) has become the main material choice for these kinds of devices due to its high gas permeability. However, fabrication of large area ultrathin microfluidic devices that can oxygenate sufficient blood volumes at clinically relevant flow rates, entirely made of PDMS, have been difficult to achieve primarily due to failure associated with stiction of thin PDMS membranes to each other at undesired locations during assembly. Here, we demonstrate the use of a modified fabrication process to produce large area ultrathin oxygenators entirely made of PDMS and robust enough to withstand the hydraulic conditions that are encountered physiologically. We also demonstrate that a LAD assembled from these ultrathin double-sided microfluidic blood oxygenators can increase the oxygen saturation level by 30% at a flow rate of 30 ml/min and a pressure drop of 21 mm Hg in room air which is adequate for 1 kg preterm neonates. In addition, we demonstrated that our LAD could withstand high blood flow rate of 150 ml/min and increase oxygen saturation by 26.7% in enriched oxygen environment which is the highest gas exchange reported so far by any microfluidic-based blood oxygenators. Such performance makes this LAD suitable to provide support to 1 kg neonate suffering from respiratory distress syndrome.
ABSTRACT
Preterm neonates suffering from respiratory distress syndrome require assistive support in the form of mechanical ventilation or extracorporeal membrane oxygenation, which may lead to long-term complications or even death. Here, we describe a high performance artificial placenta type microfluidic oxygenator, termed as a double-sided single oxygenator unit (dsSOU), which combines microwire stainless-steel mesh reinforced gas permeable membranes on both sides of a microchannel network, thereby significantly reducing the diffusional resistance to oxygen uptake as compared to the previous single-sided oxygenator designs. The new oxygenator is designed to be operated in a pumpless manner, perfused solely due to the arterio-venous pressure difference in a neonate and oxygenate blood through exposure directly to ambient atmosphere without any air or oxygen pumping. The best performing dsSOUs showed up to â¼343% improvement in oxygen transfer compared to a single-sided SOU (ssSOU) with the same height. Later, the dsSOUs were optimized and integrated to build a lung assist device (LAD) that could support the oxygenation needs for a 1-2 kg neonate under clinically relevant conditions for the artificial placenta, namely, flow rates ranging from 10 to 60 ml/min and a pressure drop of 10-60 mmHg. The LAD provided an oxygen uptake of 0.78-2.86 ml/min, which corresponded to the increase in oxygen saturation from 57 ± 1% to 93%-100%, under pure oxygen environment. This microfluidic lung assist device combines elegant design with new microfabrication methods to develop a pumpless, microfluidic blood oxygenator that is capable of supporting 30% of the oxygen needs of a pre-term neonate.
