Preterm infants are at risk for respiratory distress syndrome (RDS) due to immature lungs, leading to notable neonatal mortality. About 10% of US births are premature. While mechanical ventilation is a common RDS treatment, it can cause complications. If it fails, extracorporeal membrane oxygenation (ECMO) is employed, but standard ECMO devices are not suited for preterm babies. The limitations of hollow fiber membrane oxygenators used in ECMO have spurred interest in an artificial placenta that connects to the umbilical cord and supports lung growth. Microfluidic blood oxygenators, with their biomimetic designs, have being explored for this purpose. This thesis advances microfabrication techniques for Lung Assist Devices (LADs), focusing on two main objectives: I. Improving Throughput for Elevated Blood Flow Rates: This section delves into refining Microfluidic Blood Oxygenators (MBOs) to accommodate greater blood flow rates. By combining parallel units, we increased throughput and optimized LAD designs. Newly designed MBOs, with an expanded gas exchange surface area, can manage blood flow rates up to 60 mL/min. Using these enhanced MBOs, we constructed a novel LAD achieving superior oxygenation compared to predecessors. Our in vitro tests confirmed that this LAD can sustain blood flow rates of up to 150 ml/min, elevating oxygen saturation by approximately 20%—equivalent to an oxygen transfer of 7.48 mL/min, a leading figure for AP-type devices. II. Hierarchically Designed Microchannels: The second objective revolves around developing microchannels with a hierarchical layout to mitigate stagnation and high shear stress regions. Traditional photolithography poses challenges at channel intersections, inducing clotting risks. We pioneered alternative microfabrication methods, yielding diverse microchannels and intricate hierarchical designs that emulate natural vascular networks devoid of dead zones. These advancements have propelled the microfabrication domain for artificial placenta-like LADs. Utilizing our method, we produced channels varying from hundreds to a few microns in height with a single exposure and an opal diffuser. Thin membranes (~60 µm top and ~45 µm bottom) were amalgamated, culminating in a total depth of about 200 µm. Such oxygenators excel in oxygenating blood even at intense flow rates of up to 15 mL/min per unit. Leveraging these hierarchically designed MBOs, we crafted a LAD supporting a flow rate of 100 mL/min, offering an oxygen transfer of 5.21 mL/min. Both LADs developed in this research proficiently support premature neonates weighing up to 2 kg. Notably, the priming volume of the LAD using the enhanced MBOs has been substantially minimized, underscoring its advancements over earlier models. Realizing these objectives can transform neonatal care, addressing respiratory challenges in premature neonates and bolstering their chances for a healthier life. / Thesis / Master of Science (MSc)

<p>Respiratory distress syndrome is a major cause of mortality among pre-term and term neonatal population. To overcome the limitations of current therapies, a new form of respiratory support termed the, “Artificial Placenta” has been proposed. The Artificial Placenta is a type of oxygenator that is attached postnatally via the umbilical vessels to provide pumpless respiratory support to pre-term and term neonates. To develop this concept, our group previously reported on a novel polycarbonate membrane lung assist device (LAD). To build upon its development, the objectives of this thesis are to determine the optimal interface for gas exchange, and characterize the gas exchange properties of the LAD under ambient and oxygen rich atmosphere. Subsequently, its feasibility was determined by studying the effects of extracorporeal flow rates on cardiovascular parameters and gas exchange performance was assessed in a newborn piglet model.</p> <p>In vitro testing demonstrated that PDMS based membrane is the optimal interface for gas exchange in the LAD. In vitro testing of the LAD demonstrated 2.4 µL/min/cm² -3.8 µL/min/cm² and 6.4 µL/min/cm²- 10.1 µL/min/cm² of O₂ and CO₂ transfer respectively under ambient air and oxygen rich atmospheric conditions. Based on these results, the LAD theoretically could provide 6-11% of metabolic O₂ while eliminating 18-26% of CO₂in a newborn healthy pre term infant. Experiments in newborn piglet models achieved pumpless configuration with flow rates up to 60.9ml/kg/min without presenting decompensation. Preliminary, in vivo gas exchange experiments demonstrated O₂ transfer of 3ul/min/cm², which matches closely to in vitro data.</p> <p>A novel pumpless LAD is reported, which provides sufficient respiratory support. High extracorporeal flow rates with stable cardiovascular parameters demonstrate feasibility of the artificial placenta concept. This novel LAD could potentially serve as a rescue device when all other therapies such as nasal continuous positive airway and mechanical ventilation fail.</p> / Master of Applied Science (MASc)