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Extremely preterm infants have poor clinical outcomes due to lung immaturity. An artificial placenta could provide extracorporeal gas exchange, allowing normal lung growth outside of the uterus, thus improving outcomes. However, current devices in development use hollow-fiber membrane oxygenators, which have a high rate of bleeding and clotting complications. Here, we present a novel style of oxygenator composed of a stacked array of rigid and flat silicon semi-permeable membranes. Using computational fluid dynamic (CFD) modeling, we demonstrated favorable hemocompatibility properties, including laminar blood flow, low pressure drop, and minimal cumulative shear stress. We then constructed and tested prototype devices on the benchtop and in an extracorporeal pig model. At 20 mL/min of blood flow, the oxygenators exhibited an average oxygen flux of 0.081 ± 0.020 mL (mean ± standard error) and a pressure drop of 2.25 ± 0.25 mmHg. This study demonstrates the feasibility of a building a...
Artificial Organs, 2012
The concept of an artificial placenta has been pursued in experimental research since the early 1960s. The principle has yet to be successfully implemented in neonatal care despite the constant evolution in extracorporeal life support technology and advancements in neonatal intensive care in general. For more than three decades, the physical dimensions of the required equipment necessitated pump-driven circuits; however, recent advances in oxygenator technology have allowed exploration of the simpler and physiologically preferable concept of pumpless arteriovenous oxygenation. We expect that further miniaturization of the extracorporeal circuit will allow the implementation of the concept into clinical application as an assist device. To this end, NeonatOx , a custommade miniaturized oxygenator with a filling volume of 20 mL, designed by our own group, has been successfully implemented with a preterm lamb model of less than 2000 g body weight as an assist device. We provide an overview of milestones in the history of extracorporeal membrane oxygenation of the preterm newborn juxtaposed against current and future technological advancements. Key limitations, which need to be addressed in order to make mechanical gas exchange a clinical treatment option of prematurity-related lung failure, are also identified.
IFMBE Proceedings
Membrane oxygenators or artificial lungs have become an important, reliable and lifesaving clinical technique. To limit side effects on blood platelet parameters and to reduce hemolysis the gas exchange in such devices has to be improved while the size of the membrane packing has to be reduced to meet geometric constraints. Computational fluid dynamics (CFD) provides a spatial and temporal resolution of the membrane oxygenation process and enables systematic optimization of artificial lungs. An innovative CFD approach was developed to examine the gas exchange performance of oxygenators. Blood and sweep gas flow in the fiber packing as well as blood gas exchange through the membrane between blood and sweep fluid were fully resolved and simulated. The results were compared to in vitro experiments comprising determination of blood side pressure loss and CO 2 exchange performance of a prototype membrane module. This simulation approach provides a sound basis for the design of future artificial lungs.
Artificial Organs, 2014
A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 μL/min/cm 2 (0.3-0.5 mL/kg/min) and 6.4-10.1 μL/min/cm 2 (0.8-1.3 mL/ kg/min) for O 2 and CO 2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary
Artificial Organs, 1994
Abstract: In vitro testing of a new prototype intravenous membrane oxygenator (IMO) is reported. The new IMO design consists of matted hollow fiber membranes arranged around a centrally positioned tripartite balloon. Short gas flow paths and consistent, reproducible fiber geometry after insertion of the device result in an augmented oxygen flux of up to 800% with balloon activation compared with the static mode (balloon off). Operation of the new IMO device with the balloon on versus the balloon off results in a 400% increase in carbon dioxide flux. Gas flow rates of up to 9. 5 L/min through the 14–cm–long hollow fibers have been achieved with vacuum pressures of 250 mm Hg. Gas exchange efficiency for intravenous membrane oxygenators can be increased by emphasizing the following design features: short gas flow paths, consistent and reproducible fiber geometry, and most importantly, an active means of enhancing convective mixing of blood around the hollow fiber membranes
Perfusion, 2005
To review the performance of polymethyl pentene versus silicone oxygenators in terms of efficiency in priming and oxygenation, oxygenator resistance, requirements for coagulation proteins and consumption of blood products, for neonatal extracorporeal membrane oxygenation (ECMO) patients. Forty consecutive neonates were selected retrospectively pre- and post-introduction of the new polymethyl pentene (PMP) oxygenators. They formed two equal groups. After calculation of the sample size, data were collected from ELSO registry forms and patient records. Results were analysed using parametric and non-parametric tests. Neonatal PMP (N-PMP) oxygenators were smaller, faster and easier to prime. They were less efficient than silicone oxygenators, especially in carbon dioxide elimination, and, therefore, required higher sweeps. The preservation of coagulation proteins was significantly better, but there was no reduction in the consumption of blood products, despite having less than half the s...
Perfusion, 2011
The cardiopulmonary bypass (CPB) procedure has been shown to be a possible cause of postoperative neurological morbidity for various reasons, including: large amounts of gaseous microemboli (GME) reaching the patient and hypoperfusion of the patient due to "stolen" blood flow. This study used a simulated CPB circuit identical to that in a clinical setting to examine three different hollow-fiber membrane oxygenators without intergrated arterial filters -the Capiox RX05, the Quadrox-i neonatal, and the KIDS D100 -to determine their ability to reduce the number of GME delivered to the neonatal patient and their hemodynamic properties in response to varying flow rates, normothermic vs hypothermic conditions, and open vs closed purge line. The circuit was primed with Ringer's Lactate and then human blood with a hematocrit of 30%. Injections of 5cc bolusses of air were injected into the venous line proximal to the venous reservoir over a thirty-second interval. Six injections were done for each oxygenator at each of the eight different experimental conditions for a total of 64 experiments per oxygenator (192 total injections). A flow probe, pressure transducer, and Emboli Detection and Classification (EDAC) quantifier transducer were positioned both upstream and downstream of the oxygenator to measure differences in each parameter. Results demonstrated that the Capiox RX05 is the most effective oxygenator at reducing the number of microemboli that potentially can be delivered to the neonatal patient. In regards to the hemodynamic properties, the Quadrox-i has the most favorable results, with the lowest mean pressure drop and the best energy retention across the oxygenator.
Biomechanics and Modeling in Mechanobiology, 2012
The onset of thromboembolic phenomena in blood oxygenators, even in the presence of adequate anticoagulant strategies, is a relevant concern during extracorporeal circulation (ECC). For this reason, the evaluation of the thrombogenic potential associated with extracorporeal membrane oxygenators should play a critical role into the preclinical design process of these devices. This study extends the use of computational fluid dynamics simulations to guide the hemodynamic design optimization of oxygenators and evaluate their thrombogenic potential during ECC. The computational analysis accounted for both macro-(i.e., vortex formation) and micro-scale (i.e., flow-induced platelet activation) phenomena affecting the performances of a hollowfiber membrane oxygenator with integrated heat exchanger. A multiscale Lagrangian approach was adopted to infer the trajectory and loading history experienced by platelet-like particles in the entire device and in a repetitive subunit of the fiber bundles. The loading history was incorporated into a damage accumulation model in order to estimate the platelet activation state (PAS) associated with repeated passes of the blood within the device. Our results highlighted the presence of blood stagnation areas in the inlet section that significantly increased the platelet activation levels in particles remaining trapped in this region. The order of magnitude of PAS in the device was the same as the one calculated for the components of the ECC tubing system, chosen as a term of comparison for their extensive diffusion. Interpolating the mean PAS
2016
Abstract: Respiratory function is mandatory for extrauterine life, but is sometimes impaired in newborns due to prematurity, congenital malformations, or acquired pathologies. Mechanical ventilation is standard care, but long-term complications, such as bronchopulmonary dysplasia, are still largely reported. Therefore, continuous medical education is mandatory to correctly manage devices for assistance. Commercially available breathing function simulators are rarely suitable for the anatomical and physiological realities. The aim of this study is to develop a high-fidelity mechatronic simulator of neonatal airways and lungs for staff training and mechanical ventilator testing. The project is divided into three different phases: (1) a review study on respiratory physiology and pathophysiology and on already available single and multi-compartment models; (2) the prototyping phase; and (3) the on-field system validation.
Journal of Membrane Science, 2001
In this paper, we report on the characterisation of transport in membrane modules for blood oxygenation where blood is circulated outside hollow fibre membranes arranged in double layer cross-laid mats at an angle with respect to the main direction of blood flow. The effect of design and operating variables on module performance was investigated with respect to oxygen transfer into water, as gaseous oxygen and water are circulated counter-currently, respectively inside the membrane lumen and through the membrane assembly. Increasing water flow rates and membrane angles enhanced oxygen transfer across the membrane and resulted in robust operation but also in high pressure drops. Module pressure drop and oxygen transfer rate were correlated to module geometry, fibre packing density, water flow rate and membrane angle with respect to the main direction of the liquid flow in non-dimensional equations that can be used by membrane module manufacturers for the design of optimal ELF blood oxygenators. The results suggest that an optimum membrane angle exists, beyond which module operation is not convenient in terms of energy.
Artificial Organs, 2006
A finite volume-based computational model was developed to investigate the uniformity of the fluid flow across the hollow fiber membranes in blood oxygenation devices. A two-dimensional annular cross section of a blood oxygenation device including about 3300 hollow fiber membranes was used in the computation model. The equations governing the steady incompressible laminar flow in the blood oxygenation device were solved numerically and the results were compared with those obtained from the equivalent porous medium approximation. For
Artificial Organs, 2010
Perfusion quality is an important issue in extracorporeal life support (ECLS); without adequate perfusion of the brain and other vital organs, multiorgan dysfunction and other deficits can result. The authors tested three different pediatric oxygenators (Medos Hilite 800 LT, Medtronic Minimax Plus, and Capiox Baby RX) to determine which gives the highest quality of perfusion at flow rates of 400, 600, and 800 mL/min using human blood (36°C, 40% hematocrit) under both nonpulsatile and pulsatile flow conditions. Clinically identical equipment and a pseudo-patient were used to mimic operating conditions during neonatal ECLS. Traditionally, the postoxygenator surplus hemodynamic energy value (SHEpost, extra energy obtained through pulsatile flow) is the one relied upon to give a qualitative determination of the amount of perfusion in the patient; the authors also examined SHE retention through the membrane, as well as the contribution of SHEpost to the postoxygenator total hemodynamic energy (THEpost). At each experimental condition, pulsatile flow outperformed nonpulsatile flow for all factors contributing to perfusion quality: the SHEpost values for pulsatile flow were 4.6-7.6 times greater than for nonpulsatile flow, while the THEpost remained nearly constant for pulsatile versus nonpulsatile flow. For both pulsatile and nonpulsatile flow, the Capiox Baby RX oxygenator was found to deliver the highest quality of perfusion, while the Minimax Plus oxygenator delivered the least perfusion. It is the authors' recommendation that the Baby RX oxygenator running under pulsatile flow conditions be used for pediatric ECLS, but further studies need to be done in order to establish its effectiveness beyond the FDA-approved time span.
Journal of Biomechanical Engineering, 2021
Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 40 years as a bridge to transplantation, with hollow-fiber membrane (HFM) oxygenators gaining in popularity due to their high gas transfer and low flow resistance. In spite of the technological advances in ECMO devices, the inevitable contact of the perfused blood with the polymer hollow-fiber gas-exchange membrane, and the subsequent thrombus formation, limits their clinical usage to only 2–4 weeks. In addition, the inhomogeneous flow in the device can further enhance thrombus formation and limit gas-transport efficiency. Endothelialization of the blood contacting surfaces of ECMO devices offers a potential solution to their inherent thrombogenicity. However, abnormal shear stresses and inhomogeneous blood flow might affect the function and activation status of the seeded endothelial cells (ECs). In this study, the blood flow through two HFM oxygenators, including the commercially available iLA® MiniL...
Artificial Organs, 2001
It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future.
Journal of Pediatric Intensive Care, 2017
In extracorporeal life support (ECLS), there are two main types of oxygenators in clinical use for neonates: polymethylpentene (PMP) hollow fiber and polypropylene (PP) hollow fiber. A retrospective study was performed on neonates (n = 44) who had undergone ECLS for noncardiac indications from 2009 to 2015. Between the two groups (PMP n = 21, PP n = 23), the PP oxygenators failed 91% of the time, whereas the PMP oxygenators failed 43% of the time (p < 0.05). Analysis suggests PMP oxygenators are less prone to failure than PP oxygenators, and they require fewer number of oxygenator changes during a neonatal ECLS.
The International Journal of Artificial Organs, 2013
Respiratory insufficiency is a major cause of neonatal mortality and long-term morbidity, especially in very low birth weight infants. Today, non-invasive and mechanical ventilation are commonly accepted procedures to provide respiratory support to newborns, but they can reach their limit of efficacy. To overcome this technological plateau and further reduce mortality rates, the technology of an "artificial placenta", which is a pumpless lung assist device connected to the umbilical vessels, would serve to expand the therapeutic spectrum when mechanical ventilation becomes inadequate to treat neonates with severe respiratory insufficiency. The first attempts to create such an artificial placenta took place more than 60 years ago. However, there has been a recent renaissance of this concept, including developments of its major components like the oxygenator, vascular access via umbilical vessels, flow control, as well as methods to achieve hemocompatibility in extracorporeal circuits. This paper gives a review of past and current development, animal experiments and human case studies of artificial placenta technology.
Artificial Organs, 2011
Gas exchange in premature neonates is regularly impaired by structural and functional immaturity of the lung. Mechanical ventilation, which is vitally important to sustain oxygenation and CO2 elimination, causes, at the same time, mechanical and inflammatory destruction of lung tissue. To date, extracorporeal oxygenation is not a treatment option, one reason among others being the size of available oxygenators and cannulas. We hypothesized that a substantial improvement in gas exchange can be achieved by maintenance of the fetal cardiopulmonary bypass and interposition of a suitable passively driven (arteriovenous) membrane oxygenator. In close cooperation between engineers and neonatologists, we developed a miniaturized oxygenator and adapted cannulas to be used as a pumpless extracorporeal lung support that is connected to the circulation via cannulation of the umbilical cord vessels. First in vitro and in vivo studies show promising results. We regard this as one step on the way to clinical application of the artificial placenta.
Artificial Organs, 2008
We compared various methods to control blood flow for extrauterine incubation of goat fetuses without lung respiration using arterio-venous extracorporeal membrane oxygenation via umbilical vessels to develop a suitable system for a long-term life support system for premature neonates. In twenty-seven consecutive preparations of goat fetuses, 4 designs (System 1, manual flow control without a reservoir; System 2, manual flow control with an arterial open-top reservoir; System 3, semiautomatic flow control with an arterial open top reservoir; and System 4, semiautomatic flow control with a tube occluder and an arterial open top reservoir) were tested in terms of the duration of incubation periods during which fetuses were kept under stable conditions. The incubation periods be
Artificial organs, 2017
Neurologic complications during neonatal extracorporeal life support (ECLS) are associated with significant morbidity and mortality. Gaseous microemboli (GME) in the ECLS circuit may be a possible cause. Advances in neonatal circuitry may improve hemodynamic performance and GME handling leading to reduction in patient complications. This study compared hemodynamic performance and GME handling using two centrifugal pumps (Maquet RotaFlow and Medos Deltastream DP3) and polymethylpentene oxygenators (Maquet Quadrox-iD and Medos Hilite 800LT) in a neonatal ECLS circuit model. The experimental circuit was primed with Lactated Ringer's solution and packed human red blood cells (hematocrit 40%) and arranged in parallel with the RotaFlow and DP3 pump, Quadrox-iD and Hilite oxygenator, and Better-Bladder. Hemodynamic trials evaluating pressure drops and total hemodynamic energy (THE) were conducted at 300 and 500 mL/min at 36°C. GME handling was measured after 0.5 mL of air was injected ...
Premature neonates suffer from respiratory morbidity as their lungs are immature and current supportive treatment such as mechanical ventilation or extracorporeal membrane oxygenation (ECMO) cause iatrogenic injuries. A non-invasive and biomimetic concept known as the “artificial placenta” would be beneficial to overcome complications associated with the current respiratory support of preterm infants. Here, a pumpless oxygenator connected to the systemic circulation supports the lung function to relieve respiratory distress. In this paper, we demonstrate the first successful operation of a microfluidic, artificial placenta type neonatal lung assist device (LAD) on a newborn piglet model which is the closest representation of preterm human infants. This LAD has high oxygenation capability in both pure oxygen and room air as the sweep gas. It was able to relieve the respiratory distress that the newborn piglet was put under during experimentation, repeatedly and over significant durat...
Membranes
Extracorporeal membrane oxygenators are essential medical devices for the treatment of patients with respiratory failure. A promising approach to improve oxygenator performance is the use of microstructured hollow fiber membranes that increase the available gas exchange surface area. However, by altering the traditional circular fiber shape, the risk of low flow, stagnating zones that obstruct mass transfer and encourage thrombus formation, may increase. Finding an optimal fiber shape is therefore a significant task. In this study, experimentally validated computational fluid dynamics simulations were used to investigate transverse flow within fiber packings of circular and microstructured fiber geometries. A numerical model was applied to calculate the local Sherwood number on the membrane surface, allowing for qualitative comparison of gas exchange capacities in low-velocity areas caused by the microstructured geometries. These adverse flow structures lead to a tradeoff between in...