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Polymeric Hollow Fiber Membrane Oxygenators as Artificial Lungs: A Review
Abstract
The oxygenator is one of the most important components of respiratory support devices, which began as a heart-lung machine for the treatment of heart diseases. Hollow fiber membranes have been widely used in oxygenators due to their outstanding performance in oxygen and carbon dioxide exchange with the blood. In this review, general information on the oxygenator historical evolutions is summarized. Then, the advantages and usage of hollow fiber membranes as oxygenators are explained. Modification strategies to prevent platelet adhesion, plasma leakage have been summarized. There has been some information given on design parameters for hollow fiber membrane oxygenators. In recent years, the rapid development of microchannel structures in oxygenators has been summarized. It is thought that this review will help the reader to find recent studies on the subject.
Supplementary resource (1)
... The hollow fibers used inside the disposable part of the sensor are produced directly at TPM using the TIPS method. 4 This requires the melting of a polymer, in our case an isotactic PP homopolymer for medical and pharmaceutical injection molding (ELTEX® MED 100-MG03, INEOS, United Kingdom), and a diluent (a mixture of soy and castor oil) to form a homogeneous solution which is then transported via a gear pump to a coaxial nozzle of a spinneret where the hollow fiber exits and undergoes phase separation during the cooling phase. After the extraction of the diluent via conventional solvents, a porous membrane is formed. ...
... After the extraction of the diluent via conventional solvents, a porous membrane is formed. 4 A scheme of the production process is shown in Figure (1). This allows hollow fibers to be produced from scratch with control over various parameters such as the inner and outer diameters. ...
... 4). These voltages are digitalized by a data acquisition module (USB-6001 OEM, National Instruments), which also controls the LEDs. ...
... Blood oxygenators, also known as artificial lungs, are biomedical devices developed to temporarily replace or support the lung function. They are routinely used in cardiopulmonary bypass during open-heart surgery and for extracorporeal membrane oxygenation (ECMO) for patients with respiratory failure [16,19]. Blood oxygenators exploiting hollow fiber membranes (HFM), arranged in bundle, have become a well-established solution over the years [16,19]. ...
... They are routinely used in cardiopulmonary bypass during open-heart surgery and for extracorporeal membrane oxygenation (ECMO) for patients with respiratory failure [16,19]. Blood oxygenators exploiting hollow fiber membranes (HFM), arranged in bundle, have become a well-established solution over the years [16,19]. To achieve blood oxygenation, such devices exploit hollow fibers, within which a gas flows, that are characterized by microporous walls permeable only to gas. ...
... A fiber arrangement such that gas and blood are cross-flowing was identified as optimal condition for gas exchange [19]. Two main solutions to ensure cross flow were studied and carried out in the current commercially available devices: the stacked and wrapped configuration of the fiber bundle [13,16]. In the stacked configuration, mats of parallel fibers are stacked on top of each other in the main direction of blood flow, with the fiber orientation rotated alternately 90° in each layer. ...
Mechanical loads on the polymeric fibers of oxygenating bundles are commonly present due to bundle press-fitting during device assembly and blood pressure load. However, computational fluid dynamics (CFD) simulations for fiber bundle optimization neglect possible changes in microstructure due to such deformations. The aim of this study is to investigate the impact of fiber deformability on bundle microstructure and fluid dynamics mainly in terms of permeability. Fibers from commercial mats typically used for blood oxygenators were mechanically tested and based on these experimental data, a material model was developed to simulate the structural deformations the fibers undergo under press-fitting and blood pressure loads. Then, CFD simulations were performed on deformed bundle repetitive units to investigate permeability under varying loading conditions. The effects of different bundle geometric parameters on the variation of bundle permeability due to press-fitting were evaluated. Bundle press-fitting results in significant changes in microstructure that are reflected in a bundle permeability more than halved for a 15% press-fitting. This impact on permeability is present in all the simulated fiber bundles and becomes more pronounced as the pitch between fibers and thus bundle porosity decreases. Instead, the analyses on pressurized bundle show only small deformations caused by pressure load, with permeability changes below 1%. While blood pressure effects could be neglected, bundle press-fitting turns out to have a significant impact on bundle microstructure and permeability. Neglecting such microstructure variations during CFD simulations could also lead to incorrect assessment of the local fluid dynamics within the bundle.
... Many types of materials, including polypropylene (PP), polysulfone (PSF), polydimethylsiloxane (PDMS), and polymethylpentene (PMP), have been employed to fabricate membranes for oxygenation [3]. Among these, PP membranes are efficient for exchange, yet the existence of pores of tens of nanometers brings about a wetting issue despite their hydrophobicity, and then leads to plasma leakage and efficiency attenuation, especially in operations lasting over several hours [4]. ...
... For hemocompatibility, when blood comes into contact with membranes, proteins may be adsorbed, thus promoting platelet adhesion and activation, resulting in coagulation, immune response, and thrombus formation [8,9]. To improve hemocompatibility, biomedical and biomimetic substances, e.g., heparin and polyphenol, have been immobilized to form antithrombotic surfaces [3,10]. Grafting surfaces by hydrophobic or hydrophilic reagents, which is still uncertain, is proposed to eliminate or suppress protein and platelet attachments as well [10][11][12][13][14]. ...
... Protein adsorption on foreign materials initiates coagulation cascade and thrombosis. Bovine serum albumin, a representative protein, adsorbed on AsNp with an amount of 10.5 μg cm −2 , which was lower than that of the widely biologically used PSF and PDMS and other biomedical materials ( Fig. 3A and Fig. S12) [3,11,13]. Platelet adhesion, activation, and clotting time were tested by using sheep blood. In contrast to PSF and PDMS showing few fluorescent speckles from platelet aggregation, almost no speckle could be observed on the AsNp membrane surface ( Fig. S12D to F). ...
Membrane technology has attracted considerable attention for chemical and medical applications, among others. Artificial organs play important roles in medical science. A membrane oxygenator, also known as artificial lung, can replenish O 2 and remove CO 2 of blood to maintain the metabolism of patients with cardiopulmonary failure. However, the membrane, a key component, is subjected to inferior gas transport property, leakage propensity, and insufficient hemocompatibility. In this study, we report efficient blood oxygenation by using an asymmetric nanoporous membrane that is fabricated using the classic nonsolvent-induced phase separation method for polymer of intrinsic microporosity-1. The intrinsic superhydrophobic nanopores and asymmetric configuration endow the membrane with water impermeability and gas ultrapermeability, up to 3,500 and 1,100 gas permeation units for CO 2 and O 2 , respectively. Moreover, the rational hydrophobic–hydrophilic nature, electronegativity, and smoothness of the surface enable the substantially restricted protein adsorption, platelet adhesion and activation, hemolysis, and thrombosis for the membrane. Importantly, during blood oxygenation, the asymmetric nanoporous membrane shows no thrombus formation and plasma leakage and exhibits fast O 2 and CO 2 transport processes with exchange rates of 20 to 60 and 100 to 350 ml m ⁻² min ⁻¹ , respectively, which are 2 to 6 times higher than those of conventional membranes. The concepts reported here offer an alternative route to fabricate high-performance membranes and expand the possibilities of nanoporous materials for membrane-based artificial organs.
... γ is the shear rate calculated by √ 2S : S, S = 1 2 ∇u + (∇u) T . The blood flowed in at three different flow rates: 0.25, 1, and 3 L/min, respectively, which were within the range of flow rates used in commercial ECMO devices (up to 7 L/min) [12]. The outlet boundary condition was set to the atmospheric pressure. ...
... However, with a constraint in the thickness of the device by the penetration of red light in the blood (~0.5 cm), the length, width, and height of the device was increased to 20 cm × 20 cm × 1 cm. Commercial oxygenators have a blood volume ranging from 150 cm 3 to 320 cm 3 for both pediatric and adult care [12]. The volume of the current model was 400 cm 3 for Geometry 1. ...
We designed a photo-ECMO device to speed up the rate of carbon monoxide (CO) removal by using visible light to dissociate CO from hemoglobin (Hb). Using computational fluid dynamics, fillets of different radii (5 cm and 10 cm) were applied to the square shape of a photo-ECMO device to reduce stagnant blood flow regions and increase the treated blood volume while being constrained by full light penetration. The blood flow at different flow rates and the thermal load imposed by forty external light sources at 623 nm were modeled using the Navier-Stokes and convection–diffusion equations. The particle residence times were also analyzed to determine the time the blood remained in the device. There was a reduction in the blood flow stagnation as the fillet radii increased. The maximum temperature change for all the geometries was below 4 °C. The optimized device with a fillet radius of 5 cm and a blood priming volume of up to 208 cm³ should decrease the time needed to treat CO poisoning without exceeding the critical threshold for protein denaturation. This technology has the potential to decrease the time for CO removal when treating patients with CO poisoning and pulmonary gas exchange inhibition.
... Hollow fiber membranes have been used as an oxygenator and are usually obtained via a phase inversion process [191,192]. The commonly used polymers for hollow fiber membranes are hydrophobic polymers, such as polymethylpentene (PMP), polypropylene (PP), PDMS, polysulfone (PSf), polyethersulfone (PES), polyethylene (PE) and polyvinylidene fluoride (PVDF) [26,[192][193][194][195][196][197][198]. ...
... Hollow fiber membranes have been used as an oxygenator and are usually obtained via a phase inversion process [191,192]. The commonly used polymers for hollow fiber membranes are hydrophobic polymers, such as polymethylpentene (PMP), polypropylene (PP), PDMS, polysulfone (PSf), polyethersulfone (PES), polyethylene (PE) and polyvinylidene fluoride (PVDF) [26,[192][193][194][195][196][197][198]. Wang et al. [194] reported the production of poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite (TFC) with a PVA/PSS coating was anchored on the membrane surface via crosslinking and PDA binding for membrane oxygenator application. ...
Polymeric membranes are selective materials used in a wide range of applications that require separation processes, from water filtration and purification to industrial separations. Because of these materials’ remarkable properties, namely, selectivity, membranes are also used in a wide range of biomedical applications that require separations. Considering the fact that most organs (apart from the heart and brain) have separation processes associated with the physiological function (kidneys, lungs, intestines, stomach, etc.), technological solutions have been developed to replace the function of these organs with the help of polymer membranes. This review presents the main biomedical applications of polymer membranes, such as hemodialysis (for chronic kidney disease), membrane-based artificial oxygenators (for artificial lung), artificial liver, artificial pancreas, and membranes for osseointegration and drug delivery systems based on membranes.
... In recent decades, blood oxygenators have been mainly developed based on hollow fiber membranes (HFM) technology that allows gas exchange without direct contact to the blood. [4][5][6][7] These modern oxygenators usually consist of a single chamber with a fiber bundle with blood flow path passing through it. In general, there are four types of blood flow paths: 1) longitudinal (axial) flow through an annular bundle; 2) circumferential flow around an annular bundle; 3) transverse flow through a bundle with a substantially rectangular/circular cross-section; and 4) radial flow through an annular bundle. ...
Although extracorporeal membrane oxygenation (ECMO) systems have been used to provide temporary support for patients with severe respiratory or cardiac failure, they are often bedridden, in part because of their bulky size which relies solely on an unlimited source of wall oxygen. However, there is an unmet clinical need for ambulatory ECMO which necessitates downsizing the ECMO system. We sought to develop a new oxygenator to reduce the dependence on the oxygen supply source. The proposed oxygenator features a dual-chamber gas exchangers, with one chamber primarily responsible for carbon dioxide removal using ambient air and a subsequent chamber primarily responsible for oxygen transfer using pure oxygen. Computational fluid dynamics was used to analyze the blood flow field to avoid adverse stagnation and optimize gas exchange performance. Bovine blood was used for in vitro gas transfer test. This new oxygenator demonstrated the capability to provide adequate respiratory support (both carbon dioxide removal and oxygen transfer) to adult patients at blood rate of 4–6 L/min with an oxygen supply of only 2 L/min. The reduced use of oxygen with this new oxygenator may pave the way for the development of potable ECMO systems.
... For these devices even small blood clots can impede blood flow and result in device failure due to increased hydraulic resistance and reduced gas exchange capacity [14]. In addition, artificial lungs have relatively large surface areas and complicated structures and are used for extended periods ranging from days to months, further emphasizing the need for antithrombotic materials [16][17][18][19]. ...
... For the majority of oxygenators, fibers are warp knitted into mats, which then are either stacked or cylindrically wound, resulting in 90 • or 24 • angles between fiber mats, respectively. The latter angle is predefined by the manufacturing process [2]. ...
Oxygenators take over lung function in the event of severe lung injuries by exchanging gas into the blood stream using hollow fiber membrane mats. A central limitation of oxygenators is their large foreign surface area and priming volume, which cause blood damage.
Thus, gas exchange efficiency needs to be improved through an understanding of the interaction between fiber arrangement and blood flow directions. This has only been investigated in two
dimensional or simplified nonrealistic fiber bundles. The aim of this study was to quantify gas exchange in realistic 3D fiber bundles.
We performed three dimensional micro scale CFD simulations of different realistic fiber arrangements and flow directions that we validated in corresponding test oxygenators using porcine blood.
Fiber-configurations influence gas transfer by factor 2, with highest transfer rates for blood flowing in circumferential direction, and lowest for longitudinal direction in wound oxygenators. The CFD model correlates with the experiments with an R2 = 0.88.
For the first time, the configuration of realistic 3D fiber bundles was proven to strongly influence gas transfer in oxygenators, in simulations and experiments. The CFD model serves for investigation of further configurations and to derive transfer coefficients for full scale oxygenators.
... Although PP has extensive clinical applications, its use in membrane oxygenators is limited by its short lifespan. Currently, most promising oxygenation membranes are composed of PMP, which is a crystalline polymer that exhibits exceptional gas permeability [7], high resistance to plasma leakage, and excellent hemocompatibility [6,[8][9][10]. PMP membranes possess an asymmetric structure comprising a uniform and bi-continuous microporous interior and a thin and dense skin layer to ensure high gas permeability and resistance to plasma leakage [5,11,12]. ...
... The core component of a membrane oxygenator is the hollow fiber membrane (HFM) material, the performance of which directly determines the performance of the oxygenator. Commonly used hollow fiber membrane materials are polypropylene (PP-HFM), cellulose acetate (CA-HFM), polyvinylidene fluoride (PVDF-HFM), and polymethylpentene (PMP-HFM) [2,3]. PP-HFM is the most widely used membrane material in clinical practice; however, directly prepared PP-HFM suffers problems such as a short life span and a tendency to fracture. ...
A phosphorylcholine polymer (poly(MPC–co–BMA–co–TSMA), PMBT) was prepared by free radical polymerization and coated on the surface of the polymethylpentene hollow fiber membrane (PMP–HFM). ATR–FTIR and SEM analyses showed that the PMBT polymer containing phosphorylcholine groups was uniformly coated on the surface of the PMP–HFM. Thermogravimetric analysis showed that the PMBT had the best stability when the molar percentage of MPC monomer in the polymer was 35%. The swelling test and static contact angle test indicated that the coating had excellent hydrophilic properties. The fluorescence test results showed that the coating could resist dissolution with 90% (v/v%) ethanol solution and 1% (w/v%) SDS solution. The PMBT coating was shown to be able to decrease platelet adherence to the surface of the hollow fiber membrane, and lower the risk of blood clotting; it had good blood compatibility in tests of whole blood contact and platelet adhesion. These results show that the PMBT polymer may be coated on the surface of the PMP–HFM, and is helpful for improving the blood compatibility of membrane oxygenation.
... Thus, CO 2 diffuses from the blood into the sweep fluid and gets removed to the ambient, while O 2 diffuses through the membrane into the blood. For a detailed review of membrane oxygenators, the interested reader is referred to [5]. ...
Membrane oxygenators are devices that benefit from automatic control. This is especially true for implantable membrane oxygenators—a class of wearable rehabilitation devices that show high potential for fast recovery after lung injury. We present a performance comparison for reference tracking of carbon dioxide partial pressure between three control algorithms—a classical proportional-integral (PI) controller, a modern non-linear model predictive controller, and a novel deep reinforcement learning controller. The results are based on simulation studies of an improved compartmental model of a membrane oxygenator. The compartmental model of the oxygenator was improved by decoupling the oxygen kinetics from the system and only using the oxygen saturation as an input to the model. Both the gas flow rate and blood flow rate were used as the manipulated variable of the controllers. All three controllers were able to track references satisfactorily, based on several performance metrics. The PI controller had the fastest response, with an average rise time and settling time of 1.18 s and 2.24 s and the lowest root mean squared error of 1.06 mmHg. The NMPC controller showed the lowest steady state error of 0.17 mmHg and reached the reference signal with less than 2% error in 90% of the cases within 15 s. The PI and RL reached the reference with less than 2% error in 84% and 50% of the cases, respectively, and showed a steady state error of 0.29 mmHg and 0.5 mmHg.
With the emergence of global challenges, sustainability has become a pivotal element in the world’s development agendas. To achieve global development, 17 sustainability development goals (SDGs) were developed by the United Nations in 2012. Recently, membrane technologies have been rising to the spotlight as a promising green alternative for the accomplishment of these SDGs. This is due to their numerous advantages, including high selectivity, lower cost, relatively easy upscaling, mild processing conditions, compact system with minimized steel usage, and reduced energy consumption. Despite its growing importance in sustainable development, membrane technologies have not been reviewed and rigorously analyzed for all SDGs. This review critically analyzes membrane technologies' significant position in SDGs to fill this gap in the literature. More precisely, this review uniquely delves into the versatile role of membrane technologies in contributing to the SDGs with state-of-the-art examples, hence, aiding in solving pressing global challenges such as clean water, affordable and clean energy, climate action, poverty, life below water, etc. Furthermore, by evaluating the economic and social dimensions of membrane technologies in sustainable development, this review comprehensively highlights the holistic advantages offered by various membrane processes in the accomplishment of SDGs. This paper concludes by discussing future directions that could be implemented to harness the full potential of membrane technologies in SDGs accomplishment.
The trade‐off between gas permeability and resistance to plasma leakage imposes a great challenge for the practical use of membranes in extracorporeal membrane oxygenation (ECMO). Herein, a polypropylene (PP) hollow‐fiber composite membrane is fabricated by simply grafting mesoporous silica nanoparticles onto the commercial PP membrane, which shows a significantly enhanced gas permeability and superior resistance to plasma leakage. The performance metrics such as gas permeability, bubble point, surface hydrophobicity, and plasma leakage resistance are largely influenced by the type of functional groups on the silica nanoparticles (hydroxyl, vinyl, or trifluoropropyl). It is shown that the trifluoropropyl‐group functionalized mesoporous silica nanoparticle grafted composite membrane demonstrates a superior performance than the commercial ECMO membrane of poly(4‐methyl‐1‐pentene) (PMP). The bubble point is greatly elevated from 0.36 to 1.20 MPa while the decrease in gas flux is negligible within 4%. And the leakage resistance time is significantly prolonged from 600 to 4140 min. The gained benefits are originated from the enhanced mass transfer area and diminished surface pores of the composite membrane are grafted with the mesoporous nanoparticles. The high‐performance PP‐based composite membranes are cost‐effective and promising in practical applications of ECMO.
Blood oxygenators are used to saturate oxygen levels and remove carbon dioxide from the body during cardiopulmonary bypass. Although the natural lung is hydrophilic, commercially used oxygenator materials are hydrophobic. Surface hydrophobicity weakens blood compatibility, as long‐term contact with the blood environment may lead to different degrees of blood activity. Polysulfone may be considered an alternative hydrophilic material in the design of oxygenators. Therefore, it may be directed toward developing hydrophilic membranes. This study aims to investigate the feasibility of achieving blood gas transfer with a polysulfone‐based microporous hollow fiber membrane and compare it with the commercially available polypropylene membranes. Structural differences in the membrane morphology, surface hydrophilicity, tortuosity, mass transfer rate, and material properties under different operation conditions of temperature and flow rates are reported. The polysulfone membrane has a water contact angle of 81.3°, whereas a commercial polypropylene membrane is 94.5°. The mass transfer resistances (s/m) for the polysulfone and polypropylene membranes are calculated to be 4.8 × 10⁴ and 1.5 × 10⁴ at 25°C, respectively. The module made of polysulfone was placed in the cardiopulmonary bypass circuit in parallel with the commercial oxygenator, and pH, pO2, pCO2 levels, and metabolic activity were measured in blood samples.
Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750–800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group). The objective was to assess feasibility, safety, and biocompatibility. Circuits remained patent and operated with stable pressures throughout 24 hours. No group differences in vital signs or evidence of end-organ damage occurred. No change in plasma free hemoglobin and von Willebrand factor multimer size distribution were observed. Platelet count decreased in BLOx at 6 hours (37% dec, P = 0.03), but not in HFMO; however, thrombin generation potential was elevated in HFMO (596 ± 81 nM·min) versus BLOx (323 ± 39 nM·min) at 24 hours ( P = 0.04). Other coagulation and inflammatory mediator results were unremarkable. BLOx required higher mechanical ventilator settings and showed lower gas transfer efficiency versus HFMO, but the stable device performance indicates that this technology is ready for further performance scaling and testing in lung injury models and during longer use conditions.
The oxygenation membrane, a core material of extracorporeal membrane oxygenation (ECMO), is facing challenges in balancing anti‐plasma leakage, gas exchange efficiency, and hemocompatibility. Here, inspired by the asymmetric structural features of alveolus pulmonalis, a novel triple‐functional membrane for blood oxygenation with a Janus architecture is proposed, which is composed of a hydrophobic polydimethylsiloxane (PDMS) layer to prevent plasma leakage, an ultrathin polyamide layer to enhance gas exchange efficiency with a CO2:O2 permeance ratio of ≈10.7, and a hydrophilic polyzwitterionic layer to improve the hemocompatibility. During the simulated ECMO process, the Janus oxygenation membrane exhibits excellent performance in terms of thrombus formation and plasma leakage prevention, as well as adequate O2 transfer rate (17.8 mL min⁻¹ m⁻²) and CO2 transfer rate (70.1 mL min⁻¹ m⁻²), in comparison to the reported oxygenation membranes. This work presents novel concepts for the advancement of oxygenation membranes and demonstrates the application potential of the asymmetric triple‐functional Janus oxygenation membrane in ECMO.
Extracorporeal membrane oxygenator (ECMO) has been in development for nearly 70 years, and the oxygenator has gone through several generations of optimizations, with advances from bubble oxygenators to membrane oxygenators leading to more and more widespread use of ECMO. Membrane is the core of a ECMO system and the working mechanism of membrane oxygenator depends on the membrane material, from PDMS flat membrane to PMP hollow fiber membrane, which have experienced three generations. Blood compatibility on the surface of the membrane material is very vital, which directly determines the use duration of the oxygenator and can reduce the occurrence of complications. The mechanism of mass transfer is the basis of oxygenator operation and optimization. This review summarizes the membrane development history and preparation technology, modification approaches and mass transfer theory in the process of oxygen and blood exchange. We hoped that this review will provide more ideas for the study of gas blood exchange membrane.
A novel module of hollow fiber membranes with knitted braid-like structures has been successfully developed for process intensification via generation of Dean vortices. In the curved channels of hollow fiber membranes with three-fiber knitted braid-like structures, Dean vortices are effectively generated if the feed flowrates are higher than the critical flowrate. With proper structural parameters and feed flowrates, Dean vortices generated in hollow fiber membranes with three-fiber knitted braid-like structures effectively suppress the membrane fouling caused by fine particles in feed solutions no matter how the shape, size and concentration of particles vary; as a result, the transmembrane water fluxes of hollow fiber membranes with three-fiber knitted braid-like structures are evidently higher than those of straight hollow fiber membranes under the same operation conditions. The increase ratio of transmembrane water flux of hollow fiber membranes with three-fiber knitted braid-like structures increases with increasing the feed flowrate or increasing the particle concentration. The hollow fiber membranes with three-fiber knitted braid-like structures exhibit good long-term anti-fouling performances. The proposed strategy and findings in this study provide valuable guidance for developing efficient modules for hollow fiber membranes to achieve process intensification with low energy consumption, which are highly promising for industrial applications.
Inter-facility transport of a critically ill patient with Acute Respiratory Distress Syndrome (ARDS) may be necessary for a higher level of care and/or initiation of extracorporeal membrane oxygenation (ECMO). During the COVID19 pandemic, ECMO has been used for patients with severe ARDS with successful results. Transporting a patient after ECMO cannulation by the receiving facility brings forth logistic challenges including availability of adequate Personal Protective Equipment (PPE) for the transport team and hospital capacity management issues. We report our designated ECMO transport team’s experience with five patients with COVID19 associated severe ARDS after cannulation at the referring facility. Focusing on transport associated logistics, creation of checklists, and collaboration with EMS partners is necessary for safe and good outcomes for patients while maintaining team safety.
This chapter presents a literature review on the use of various materials in devices providing gas exchange in artificial (extracorporeal) blood circulation. The issues related to the history of artificial blood circulation systems development are considered. Most of authors have noted the need to avoid direct contact between the gas phase and the blood when the latter is saturated with oxygen. Thus, solid polymer membrane devices have become most common to date. The most promising materials for oxygenator membranes are amorphous fluoropolymers as they have high gas permeability and hemocompatibility. Amorphous poly-perfluoro(2-methyl-2-ethyl-1,3-dioxol) and Teflon AF2400 are the most promising materials for oxygenator membranes as they have a 1.5-2-fold greater hemocompatibility and gas permeability than polydimethylsiloxane. Liquid oxygenators using fluorocarbon liquids as the gas transport medium were also considered. These devices may have a great future, as liquid-liquid systems are “ideal”-they have no direct contact of gas with blood, no diffusion resistance of the membrane, the surface of gas exchange is also the surface of heat exchange.
Artificial lungs support patients undergoing open‐heart surgery, organ transplantation, and in serious lung injury by providing oxygenation support through an extracorporeal circuit. Some patients require partial support for durations of a few weeks or months even after the surgery. Therefore, a portable or wearable lung assist device which can be operated for several weeks with minimum maintenance would be ideal. Miniaturization of blood oxygenators, using microfluidic technology, is a promising avenue for the realization of such portable artificial lungs. The microfluidic blood oxygenators (MBOs) are also suitable for neonates with respiratory failure due to their low priming volume and pressure drop. Herein, the history of microfluidic oxygenator development and recent progress in miniaturized artificial lungs are discussed. The MBOs have made significant advances in 1) reducing device size, 2) providing biomimetic blood flow paths, 3) enabling operation in room air, and 4) operating without the need of an external pump. Recent work has demonstrated throughput of up to 150 mL min‐1 of blood and oxygen transfer rate of 60 mL O2 per L of blood. The challenges faced by this technology in practical applications as well as future improvements to meet the requirements for older neonates and even adults are also presented.
With ongoing progress of components of extracorporeal membrane oxygenation including improvements of oxygenators, pumps, and coating materials, extracorporeal membrane oxygenation became increasingly accepted in the clinical practice. A suitable testing in an adequate setup is essential for the development of new technical aspects. Relevant tests can be conducted in ex vivo models specifically designed to test certain aspects. Different setups have been used in the past for specific research questions. We conducted a systematic literature review of ex vivo models of extracorporeal membrane oxygenation components. MEDLINE and Embase were searched between January 1996 and October 2017. The inclusion criteria were ex vivo models including features of extracorporeal membrane oxygenation technology. The exclusion criteria were clinical studies, abstracts, studies in which the model of extracorporeal membrane oxygenation has been reported previously, and studies not reporting on extracorporeal membrane oxygenation components. A total of 50 studies reporting on different ex vivo extracorporeal membrane oxygenation models have been identified from the literature search. Models have been grouped according to the specific research question they were designed to test for. The groups are focused on oxygenator performance, pump performance, hemostasis, and pharmacokinetics. Pre-clinical testing including use of ex vivo models is an important step in the development and improvement of extracorporeal membrane oxygenation components and materials. Furthermore, ex vivo models offer valuable insights for clinicians to better understand the consequences of choice of components, setup, and management of an extracorporeal membrane oxygenation circuit in any given condition. There is a need to standardize the reporting of pre-clinical studies in this area and to develop best practice in their design.
Extracorporeal membrane oxygenation (ECMO) in blood-outside devices equipped with hydrophobic membranes has become routine treatment of respiratory or cardiac failure. In spite of membrane hydrophobicity, significant amounts of plasma water may form in the gas compartment during treatment, an event termed plasma water breakthrough. When this occurs, plasma water occludes some gas pathways and ultimately cripples the oxygenator gas exchange capacity requiring its substitution. This causes patient hemodilution and increases the activation of the patient's immune system. On these grounds, the resistance to plasma water breakthrough is regarded as an important feature of ECMO devices. Many possible events may explain the occurrence of plasma breakthrough. In spite of this, the resistance to plasma breakthrough of ECMO devices is commercially characterized only with respect to the membrane maximal pore size, evaluated by the bubble pressure method or by SEM analysis of membrane surfaces. The discrepancy between the complexity of the events causing plasma breakthrough in ECMO devices (hence determining their resistance to plasma breakthrough), and that claimed commercially has caused legal suits on the occasion of the purchase of large stocks of ECMO devices by large hospitals or regional institutions. The main aim of this study was to identify some factors that contribute to determining the resistance to plasma breakthrough of ECMO devices, as a means to minimize litigations triggered by an improper definition of the requirements of a clinically efficient ECMO device. The results obtained show that: membrane resistance to breakthrough should be related to the size of the pores inside the membrane wall rather than at its surface; membranes with similar nominal maximal pore size may exhibit pores with significantly different size distribution; membrane pore size distribution rather than the maximal pore size determines membrane resistance to breakthrough; the presence of surfactants in the patient's blood (e.g., lipids, alcohol, etc.) may significantly modify the intrinsic membrane resistance to breakthrough, more so the higher the surfactant concentration. We conclude that the requirements of ECMO devices in terms of resistance to plasma breakthrough ought to account for all these factors and not rely only on membrane maximal pore size.
In this study, a commercial polyimide is examined in the capacity of membrane oxygenator. The effects of polymer concentration, cosolvent, and nonsolvent additives in dope solution on the performance and morphology of membranes are investigated. In order to improve the performance, surface modification is carried out by using plasma‐enhanced chemical vapor deposition. The obtained results reveal that CO2 permeance decreased from 495 to 78 GPU upon increasing Matrimid concentration at constant tetrahydrofuran (THF) and ethanol (EtOH) concentrations. It was also found that increasing nonsolvent concentration as well as decreasing cosolvent concentration in dope led to increase in membrane gas permeance. According to morphological characterizations, increase in polymer concentration resulted in transformation of membranes from porous into spongy like microstructure with formation of a denser skin layer. In addition, membrane porosity and mean pore size reduced by increasing THF and decreasing EtOH concentrations. On the other hand, plasma treatment successfully introduced fluorine groups onto the membrane surface which promoted biocompatibility of the membranes. Energy‐dispersive X‐ray spectroscopy results revealed that fluorination of membrane surface was attained up to 23% and contact angle of membrane enhanced up to 120°. Membrane permeance was also increased slightly upon modification. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48824.
The endothelium is the largest organ in the body and recent studies have shown that the endothelial glycocalyx (eGCX) plays a major role in health and disease states. The integrity of eGCX is vital for homoeostasis and disruption of its structure and function plays a major role in several pathologic conditions. An increased understanding of the numerous pathophysiological roles of eGCX may lead to the development of potential surrogate markers for endothelial injury or novel therapeutic targets. This review provides a state-of-the-art update on the structure and function of the eGCX, emphasizing the current understanding of interorgan crosstalk between the eGCX and other organs that might also contribute to the pathogenesis of kidney diseases.
The main function of the lungs is oxygen transport from the atmosphere into the blood circulation, while it is necessary to keep the pulmonary tissue relatively free of pathogens. This is a difficult task because the respiratory system is constantly exposed to harmful substances entering the lungs by inhalation or via the blood stream. Individual types of lung cells are equipped with the mechanisms that maintain pulmonary homeostasis. Because of the clinical significance of acute respiratory distress syndrome (ARDS) the article refers to the physiological role of alveolar epithelial cells type I and II, endothelial cells, alveolar macrophages, and fibroblasts. However, all these cells can be damaged by lipopolysaccharide (LPS) which can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local and systemic inflammation and toxicity. We also highlight a negative effect of LPS on lung cells related to alveolar-capillary barrier and their response to LPS exposure. Additionally, we describe the molecular mechanism of LPS signal transduction pathway in lung cells.
HF spinning is a potential configuration in membrane technology due to its self-supporting properties and high productivity per unit volume. The fabrication of HF membrane is affected by many parameters and it is important to explore the effect of these parameters on membrane properties. The amount of researches on traveling distance are minimal and inadequate to conclude their influence on fiber properties. The draw ratio has always been neglected (often taken as 1), cannot in most cases equal to 1 as it is influenced by take-up speed, dope flowrate and solution. Future insights on the above mentioned parameters are important.
Gas-liquid membrane contactors that were based on hollow fiber membranes are the example of highly effective hybrid separation processes in the field of membrane technology. Membranes provide a fixed and well-determined interface for gas/liquid mass transfer without dispensing one phase into another while their structure (hollow fiber) offers very large surface area per apparatus volume resulted in the compactness and modularity of separation equipment. In many cases, stated benefits are complemented with high separation selectivity typical for absorption technology. Since hollow fiber membrane contactors are agreed to be one of the most perspective methods for CO2 capture technologies, the major reviews are devoted to research activities within this field. This review is focused on the research works carried out so far on the applications of membrane contactors for other gas-liquid separation tasks, such as water deoxygenation/ozonation, air humidity control, ethylene/ethane separation, etc. A wide range of materials, membranes, and liquid solvents for membrane contactor processes are considered. Special attention is given to current studies on the capture of acid gases (H2S, SO2) from different mixtures. The examples of pilot-scale and semi-industrial implementation of membrane contactors are given.
Extracorporeal membrane oxygenation (ECMO) is an emerging tool for supporting cardiopulmonary function in patients with cardiorespiratory failure or arrest. The oxygenator of the ECMO circuit requires effective oxygenation and removal of carbon dioxide from the blood. Major problems that can occur with the oxygenator include plasma leakage, one of the late-onset serious complications necessitating device replacement. However, the rapid onset of plasma leakage is rare. We present a 1-year-old boy with acute respiratory failure due to Pneumocystis and Aspergillus pneumonia. He presented with tachypnea, tachycardia, and hypoxemia despite the ventilatory support, and was therefore placed on venoarterial ECMO with a drainage catheter from the right internal jugular vein (12 Fr) and a return catheter to the right internal carotid artery (10 Fr). Extracorporeal circulation was initiated at a blood flow of 1 L/min (145 mL/kg/min) and a sweep gas flow of 1 L/min with FiO2 of 0.7. Although he was successfully weaned from the venoarterial ECMO on day 15 with an improvement of cardiopulmonary function, he was later placed on venoarterial ECMO again because of the progression of pulmonary hypertension. Laboratory tests showed increased concentrations of hepatic enzymes and hyperbilirubinemia (total bilirubin 31.6 mg/dL). Six hours after starting ECMO circulation, plasma leakage from the oxygenator occurred. Although we replaced the oxygenator with a new one, the replacement showed plasma leakage after 6 h. Disassembly of the oxygenator revealed congestion from bilirubin in the membrane fibers. We described a case of repeated, rapid-onset plasma leakage after implementation of ECMO. Hyperbilirubinemia was likely associated with the plasma leakage of this patient.
Multiple biological, synthetic and hybrid polymers are used for multiple medical applications. A wide range of different polymers is available, and they have further the advantage to be tunable in physical, chemical and biological properties in a wide range to match the requirements of specific applications. This review gives a brief overview about the introduction and developments of polymers in medicine in general, addressing first stable polymers, then polymers with degradability as a first biological function, followed by various other functional and responsive polymers. It is shown up that biomedical polymers comprise not only bulk materials, but also coatings and pharmaceutical nano-carriers for drugs. There is subsequently an overview of the most frequently used polymer classes. The main body of the review then is structured according to the medical applications, where key requirements of the applications and the currently used polymer solutions are indicated.
Blood oxygenators play key role in Extra Corporeal Membrane Oxygenator (ECMO) system using for patients with acute respiratory problems, immature fetal and also in open heart surgery. Interaction between blood and blood oxygenator polymeric membrane surface lead to fouling phenomena which have negative effect on performance of this important medical device. A modification comprising surface activation, PEG immersing and PEG graft polymerization carried out to provide acceptable blood oxygenator performance, blood compatibility and reduction in heparin consumption at the same time. Modified membranes characterized by FTIR, contact angle measurements and Atomic Force Microscopy (AFM) analyses. Blood compatibility of modified surface was also detected by SEM images. Results clearly indicate that modifying membranes by PEG is an effective way for anti-fouling properties. Water contact angel reduction from 110ْ to 72ْ shows hydrophilicity enhancement, roughness increasing from 15 to 20 and blood compatibility improvement was investigated by SEM and AFM analysis results respectively.
Microfluidic or microchannel artificial lungs promise to enable a new class of truly portable, therapeutic artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. These new artificial lungs could potentially: 1) have surface areas and priming volumes that are a fraction of current technologies thereby decreasing device size and reducing the foreign body response; 2) contain blood flow networks in which cells and platelets experience pressures, shear stresses, and branching angles that copy those in the human lung thereby improving biocompatibility; 3) operate efficiently with room air, eliminating the need for gas cylinders and complications associated with hyperoxemia; 4) exhibit biomimetic hydraulic resistances, enabling operation with natural pressures and eliminating the need for blood pumps; and, 5) provide increased gas exchange capacity enabling respiratory support for active patients. This manuscript reviews recent research efforts in microfluidic artificial lungs targeted at achieving the advantages above, investigates the ultimate performance and scaling limits of these devices using a proven mathematical model, and discusses the future challenges that must be overcome in order for microfluidic artificial lungs to be applied in the clinic. If all of these promising advantages are realized and the remaining challenges are met, microfluidic artificial lungs could revolutionize the field of pulmonary rehabilitation.
This paper presents the design, fabrication and first results for a microfabricated artificial lung with feature sizes that are comparable to that of the natural lung. The device is targeted at an increased gas transfer efficiency and portability compared to its current commercial alternatives and boasts the thinnest silicone gas transfer membrane and the lowest membrane diffusional resistance for a silicone-based device to date. Devices with 15 um-thick membranes and 30 um-tall channels achieved membrane and blood-side diffusional resistances of 27x103 and 118x103 ml-1*s*cm2*cmHg, respectively, for oxygen.
THIS PAPER is a general review of the development of the artificial heart-lung to facilitate open-heart surgery. At the close of World War II many centers began investigating the possibility of total cardiac bypass. Oven the past decade, pump oxygenerators of various types have become popular and recent clinical successes throughout the world have given further impetus to the study of problems posed by the artificial heart-lung apparatus.
The subject divides itself into three separate parts, the first two being concerned with the maintenance of life in an experimental animal during a total cardiac bypass. One must take all the blood from the animal and return it to the animal by means of a pump. Secondly, one must oxygenate the blood before returning it. The third part of the problem confronting the surgeon is the selection of cases and correction of defects in human subjects.
The pumping mechanism must duplicate as nearly as possible the action of the chambers of the heart. Pumping action must be smooth so as to prevent hemolysis and to avoid turbulence with thrombosis. It is not difficult to construct a pump with which hemolysis can be kept to relatively negligible amounts. Most of the pumps in use throughout the world give an hemolysis of less than 50 mg of hemoglobin per 100 ml of blood, which is perfectly safe. Turbulence with thrombosis can be overcome by removing valves inside the stream and placing valves outside of, rather than within the stream of blood. Furthermore, heparinization of the blood lessens the tendency to thrombosis.
Artificial lung (AL) membranes are used for blood oxygenation for patients undergoing open-heart surgery or acute lung failures. Current AL technology employs polypropylene and polymethylpentene membranes. Although effective, these membranes suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis over a long term. In this work, we propose a new generation of AL membranes based on amphiphobic fluoropolymers. We employed poly(vinylidene-co-hexafluoropropylene), or PVDF-co-HFP, to fabricate macrovoid-free membranes with an optimal pore size range of 30-50 nm. The phase inversion behavior of PVDF-co-HFP was investigated in detail for structural optimization. To improve the wetting stability of the membranes, the fabricated membranes were coated using Hyflon AD60X, a type of fluoropolymer with an extremely low surface energy. Hyflon-coated materials displayed very low protein adsorption and a high contact angle for both water and blood. In the hydrophobic spectrum, the data showed an inverse relationship between the surface free energy and protein adsorption, suggesting an appropriate direction with respect to biocompatibility for AL research. The blood oxygenation performance was assessed using animal sheep blood, and the fabricated fluoropolymer membranes showed competitive performance to that of commercial polyolefin membranes without any detectable hemolysis. The data also confirmed that the bottleneck in the blood oxygenation performance was not the membrane permeance but rather the rate of mass transfer in the blood phase, highlighting the importance of efficient module design.
The effects of cardiopulmonary bypass with bubble and membrane oxygenator systems on platelet function were studied in 26 patients who had elective coronary arterial bypass grafts. Fourteen patients were perfused with spiral coil membrane oxygenator systems, 12 with bubble oxygenator systems. During and after bypass, platelet counts decreased in both groups; however, when corrected for dilution, platelet counts did not change significantly in patients perfused with membrane oxygenators and increased slightly but significantly in those perfused with membrane oxygenators and increased slightly but significantly in those perfused with bubble oxygenator systems. During and 1 hour after bypass, the concentration of adenosine diphosphate (ADP) required to cause complete aggregation increased in both groups. Plasma low affinity platelet factor 4 (LA-PF4) increased significantly during and after bypass in both groups. However, the concentration of platelet adenine nucleotides and LA-PF4, measured only in patients perfused with membrane oxygenator systems, did not change. Bleeding times increased postoperatively in both groups and 18 hour blood losses were similar. Cardiopulmonary bypass with membrane and bubble oxygenator systems causes qualitatively similar losses in sensitivity to ADP and similar increases in bleeding times. The mechanism by which platelets are altered during cardiopulmonary bypass is obscure but is not due to partial depletion of granule contents in patients perfused with membrane oxygenators.
Extreme prematurity, defined as a gestational age of fewer than 28 weeks, is a significant health problem worldwide. It carries a high burden of mortality and morbidity, in large part due to the immaturity of the lungs at this stage of development. The standard of care for these patients includes support with mechanical ventilation, which exacerbates lung pathology. Extracorporeal life support (ECLS), also called artificial placenta technology when applied to extremely preterm (EPT) infants, offers an intriguing solution. ECLS involves providing gas exchange via an extracorporeal device, thereby doing the work of the lungs and allowing them to develop without being subjected to injurious mechanical ventilation. While ECLS has been successfully used in respiratory failure in full term neonates, children, and adults, it has not been applied effectively to the EPT patient population. In this review, we discuss the unique aspects of EPT infants and the challenges of applying ECLS to these patients. In addition, we review recent progress in artificial placenta technology development. We then offer analysis on design considerations for successful engineering of a membrane oxygenator for an artificial placenta circuit. Finally, we examine next generation oxygenators that might advance the development of artificial placenta devices.
Traditionally, cylindrical hollow fibers have been used as gas exchange interfaces in commercial oxygenators due to their simplicity of fabrication and the ability to oxygenate a large volume of blood by flowing blood around a bundle of cylindrical hollow fibers, which are served for the introduction of the gases. Over the past decade, newer microfluidic designs have been developed to overcome some of the limitations of the hollow fiber technology such as the lack of the ability to provide biomimetic flow paths to reduce shear stress and hence potentially initiation of the blood coagulation cascade as well as the difficulty to reduce the distance between fibers to decrease the resistance to diffusion of gases on the blood compartment while achieving higher efficiency of gas exchange. Nevertheless, the microfluidic designs that have been reported in the literature only provide gas exchange interfaces on one or two sides of their rectangular cross-section blood perfusion channels, thereby limiting gas exchange efficiency. Here, we report on a new design where closed gas chambers are placed adjacent to the blood perfusion channels so that the gas exchange into the blood can occur on all four sides. We demonstrate that such a design will increase the gas exchange surface area without affecting the channel's geometry or its flow characteristics. The gas exchange performance of the new design is enhanced up to 223% Compared with its equivalent double-sided gas exchange design. These new designs are expected, in the future, to help microfluidic oxygenators combine the best characteristics of both the microfluidic and hollow fiber designs to achieve superior performance.
The development and implementation of the extracorporeal membrane oxygenation (ECMO) technique for the treatment of patients in critical conditions make it possible to effectively and safely support gas exchange processes in the blood for a long time. One of the main components of the ECMO unit is a gas permeable membrane which is a barrier separating the blood from the gas phase. Since the 1950s, the development of this technology has been aimed at improving the safety and duration of use of membranes, which led to the creation of oxygenators that provide life support for several weeks. This review is devoted to the development of the extracorporeal membrane oxygenation technology including the choice of materials, methods to improve their hemocompatibility, and approaches to the design of the membrane contactor.
In this work, poly (tetrafluoroethylene-co-hexafluoropropylene) (FEP) hollow fiber membranes were fabricated by melt-spinning method with solvent-free condition, while no coagulation bath was involved. The robust and solvent-free method for preparation of FEP hollow fiber greatly reduced environmental pollution for no solvent recovery problem. Calcium carbonate (CaCO 3 ) as pore-forming agent, and dioctyl phthalate (DOP) as plasticizer as well as dispersant were used in this study. Meanwhile, the formation mechanism of multi-microporous structure with stretching pores, interface microvoids and dissolved micropores was studied, that the addition of CaCO 3 brought about interfacial microvoids during the hot stretching-setting treatment and a dissolved pore structure after soaking and washing with hydrochloric acid bath. Furthermore, the effects of hot stretching-setting and hydrochloric acid solution treatment on the membranes’ structure and performance were characterized. The morphology exhibited that the prepared FEP hollow fiber membrane presented a kind of homogeneous membrane and the pore size distribution range remained relatively stable and narrow. Moreover, FEP membrane revealed excellent stability and solvent resistance with the mechanical strength retention rate up to 90%. These findings suggest that the FEP hollow fiber membrane prepared by this method will be great potential in the field of separation and purification in harsh conditions.
Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for respiratory and cardiac failure, was first used in neonates in the 1970s. The indications and criteria for ECMO have changed over the years, but it continues to be an important option for those who have failed other medical therapies. Since the Extracorporeal Life Support Organization (ELSO) Registry was established in 1989, more than 29,900 neonates have been placed on ECMO for respiratory failure, with 84% surviving their ECMO course, and 73% surviving to discharge or transfer. In this chapter, we will review the basics of ECMO, patient characteristics and criteria, patient management, ECMO complications, special uses of neonatal ECMO, and patient outcomes.
Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for patients with respiratory and cardiac failure refractory to maximal medical management. The extracorporeal life support organization registry is the largest available resource for describing the population and outcomes of patients treated with this therapy. The use of ECMO for neonatal patients is decreasing in proportion to the total annual ECMO runs most likely due to advancements in medical management. Although the overall survival for neonatal ECMO has decreased, this is likely a reflection of the increasingly complex neonatal patients treated with this therapy. Although many patient and mechanical complications are decreasing over time, there remains a high percentage of morbidities and risks associated with ECMO. Continued refinements in management strategies are important to improving overall patient outcomes.
The purpose of this study was to compare the Capiox FX15 oxygenator with integrated arterial filter to the Capiox RX15 oxygenator with separate Capiox AF125 arterial filter in terms of hemodynamic properties and gaseous microemboli (GME) capturing. Trials were conducted at varying flow rates (2.0 L/min, 3.0 L/min, 4.0 L/min), temperatures (30°C, 35°C), and flow modalities (pulsatile, nonpulsatile). Pressure and flow waveforms were recorded using a custom-made data acquisition system. GME data were recorded using an Emboli Detection and Classification Quantifier after injecting a 5 mL air bolus into the venous line. Maximum instantaneous pre-oxygenator flows reached 7.4 L/min under pulsatile conditions when the roller pump was set to a flow rate of 4 L/min. Mean pressure drops were slightly greater in the FX15 group (P < 0.0001), and the diverted flow from the arterial purge line was slighter greater in the FX15 group at 3 L/min and 4 L/min (P < 0.0001). There was a slight generation of surplus hemodynamic energy (SHE) at the pre-oxygenator site for both oxygenators under “nonpulsatile mode.” However, higher pre-oxygenator SHE levels were recorded for both groups with “pulsatile mode.” The RX15 and FX15 groups were both able to remove all microemboli from the circuit at 2 L/min and 3 L/min in “nonpulsatile mode.” Microemboli were delivered to the patient at 4 L/min with pulsatile flows in both groups. The RX15 oxygenator with separate AF125 arterial filter and FX15 oxygenator with integrated arterial filter performed similarly in terms of hemodynamic performance and microemboli capturing. Pulsatile flows at 4 L/min produced instantaneous flow rates that surpassed the documented maximum flow rates of the oxygenators and might have contributed to the delivery of GME to the pseudo-patient.
Membrane technologies are widely used in separation processes because of their compact size, mild operating conditions and ability to conduct separations that may not be technically or economically viable by other technologies. Relative to flat-sheet membranes, hollow fibers possess unique advantages including high membrane area, self-supporting structure and ease of handling. However, they must be assembled as large modules for industrial application. Fluid hydrodynamics within these modules is as important as intrinsic membrane separation properties. Companies have explored myriad design strategies to improve fluid hydrodynamics and mass transfer inside modules as documented in the patent literature. This review summarizes the techniques taught to fabricate high performance hollow fiber bundles. More importantly, designs to (1) promote uniform shell flow, (2) enhance mixing and (3) incorporate internal sweep within modules are discussed to inspire novel designs for next-generation hollow fiber modules.
Gas permeable membranes are a vital component of extracorporeal membrane oxygenation systems. Over more than half a century, membrane fabrication and packaging technology have progressed to enable safer and longer duration use of respiratory life support. Current research efforts seek to improve membrane efficiency and hemocompatibility, with the aim of producing smaller and more robust systems for ambulatory use. This review explores past and present innovations in oxygenator technology, suggesting possible applications of state-of-the-art membrane fabrication methods to address shortcomings of earlier concepts.
Platelet adhesion on the cardiopulmonary bypass oxygenator membrane is associated with impaired hemostasis. We investigated the effects of heparin coating of the oxygenator membrane on protein adsorption and platelet adhesion on the surface. Noncoated and heparin-coated polypropylene membranes were incubated in whole blood with small- (1 U/mL) or large-dose (5 U/mL) heparin as an anticoagulant for 3 h at 37°C. The amount of platelets adhering on each fiber was assessed by using enzyme immunoassays using monoclonal antibodies directed against CD42b (GP Ib) and CD61 (GP IIb/IIIa). Platelet activation was assessed by measuring plasma guanosine monophosphate 140 levels. The amount and composition of the adsorbed proteins on the surface were analyzed by using a bicinchoninic acid protein assay and by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting technique. The heparin coating of the fibers significantly reduced platelet adhesion on the surface. However, platelet activation was reduced by heparin coating only with small-dose heparinization. The adsorption of platelet adhesive proteins such as fibrinogen and von Willebrand factor was not altered, whereas that of fibronectin was increased by heparin coating. We conclude that heparin coating of the oxygenator fibers can decrease platelet adhesion without affecting adsorption of major adhesive proteins. Surface heparin coating is associated with an increased fibronectin adsorption on the fibers.
Implications: Heparin coating can reduce platelet adhesion and activation in the presence of small-dose heparinization, potentially reducing the inflammatory response and activation of thrombosis and fibrinolysis.
In this study, polysulfone (PSF) was grafted chemically with polyethylene glycol (PEG) of different molecule weight (400, 2000, 10000, and 20000) and heparin to prepare respective PSF-PEG-Hep membranes (PSF-PEG400-Hep, PSF-PEG2000-Hep, PSF-PEG10000-Hep, and PSF-PEG20000-Hep) for membrane oxygenator via the following steps: (a) PSF chloromethylation; (b) PEGylation; and (c) heparin-immobilization process. Water contact angle, critical water permeation pressure, ATR-FTIR, 1H NMR, UV-visible spectrophotometry and X-ray photoelectron spectroscopy were conducted to prove the grafting success and fix the optimal reaction parameters during chemical modification processes. For further evaluating the application potential of PSF-PEG-Hep membrane in membrane oxygenator, pure CO2 and O2 gas permeation tests as well as gas exchange rates of CO2 and O2 through membrane oxygenator using porcine blood were measured, meanwhile hemocompatibility of membrane was analyzed and compared by protein adsorption, platelet adhesion and blood coagulation tests. Results of pure gas permeation experiments indicated that excellent gas transmission properties through PSF membrane were preserved after modification. Blood oxygenation experiments through PSF-PEG10000-Hep membrane have showed that when the flowrate of porcine blood was 1.5 L·min-1, CO2 and O2 exchange rates reached 102 ml·min-1 and 110 ml·min-1, which could satisfy basically the gas exchange potential of commercial membrane oxygenator. Besides, PSF-PEG-Hep membrane has demonstrated more prominent blood compatibility than PSF.
Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to line the channels and mitigate coagulation represents a promising avenue for therapy for patients suffering from a range of acute and chronic lung diseases.
The thermally induced phase separation (TIPS) method is regaining momentum as a competitive platform to fabricate highly porous microporous membranes. In membrane technology, there has been an active search for more sustainable ways to fabricate polymeric membranes using green solvents. Rhodiasolv PolarClean® is a recently identified environmentally friendly TIPS solvent that shows high potential for the preparation of microporous PVDF membranes. Interestingly, its high miscibility with water induces a nonsolvent-induced phase separation (NIPS) effect on the membrane surface and this simultaneous NIPS-TIPS effect is referred to as the combined NIPS-TIPS (N-TIPS) method. In this work, a thorough investigation was carried out to understand the underlying phenomena in the membrane formation kinetics during the N-TIPS process. It was found that the NIPS and TIPS morphology can be tailored to control the mechanical properties, pore size distribution, and flux of the prepared membranes. For instance, increasing the coagulation bath solvent concentration facilitated the formation of a spherulitic morphology, whereas increasing the bath temperature induced the formation of a bicontinuous morphology free of macrovoids. It was determined that by controlling the phase separation kinetics, the mechanical properties of the prepared PVDF membranes could be remarkably improved from 0.9 MPa to 6.1 MPa. Several pore-forming additives including polyvinylpyrrolidone, Pluronics F-127, LiCl, and glycerol were employed to induce surface pores and their effects were thoroughly characterized. The membranes prepared with Pluronic additives exhibited high water permeabilities up to 2,800 L.m−2.hr−1.bar−1 with narrow pore size distributions.
The escalating research in membrane fabrication for gas separation applications signifies that membrane technology is currently growing and becoming the major focus for industrial gas separation processes. Material selection and method of preparation are the most important parts in fabricating a membrane. Different preparation methods result in various isotropic and anisotropic membranes, which are related to different membrane processes. The commercial value of a membrane is determined by its transport properties—permeability and selectivity. The method of membrane fabrication can have considerable influence on its effectiveness and there are a range of techniques available to create membranes, such as melt-pressing, solution casting, phase inversion, sputtering, extruding, and interfacial polymerization. Membranes can be fabricated either in a hollow fiber or spiral wound format.
Membranes used for blood oxygenation and blood plasma separation represent well-proven applications as artificial organs. Although the absolute consumption is much less compared with dialysis membranes, their relevance for medical devices and healthcare around the world does not hide behind the big brother. This chapter illustrates the cornerstones for production and application of these products. Blood oxygenation membranes produced by different methods, both symmetrical and asymmetrical, are discussed first. The second part describes hydrophobic and hydrophilic synthetic blood plasma separation membranes. For both types of membranes, membrane make-up and medical device implications are considered.
This chapter outlines methods and concerns in evaluating the blood-compatibility of biomaterials, and the blood-compatibility of medical devices. It does not automatically follow that if the materials comprising a device are blood-compatible, a device fabricated from those materials will also be blood-compatible. This important point should be clear upon completion of this chapter.
Extracorporeal circulation is any procedure in which blood is taken from a patient, treated, and then returned. Most of these procedures are performed intermittently, or as a temporary partial or total replacement. This chapter considers artificial organs which undertake mass transfer to and from the blood. This includes devices used for dialysis in renal replacement therapy, plasma separation (plasmapheresis), and extracorporeal oxygenation.
This chapter reviews surface modifying coatings for extracorporeal circuits such as cardiopulmonary bypass, mechanical circulatory support, right- and left-ventricular assist devices, left heart bypass, and shunts. Surface modifying coatings reviewed for the experimental setting and clinical applications include heparin surface coating, end-point attached heparin, biomembrane mimicry, polymeric phospholipids, and phosphorylcholine. The main findings for the various applications and surface modifications are described, referenced, and illustrated.
Medical devices and medical device materials must be designed to achieve specific criteria for safety and performance. The criteria themselves may be bound by physical, chemical, and material limitations, and by biochemical, molecular, and cellular processes within the body recognized to take place upon contact. In the latter case, responses can be favorable or unfavorable, partially controlled by learned approaches, for example drugs, or be uncontrollable by current experience and know-how. As such, determining what testing is required and which test results are acceptable and meaningful in the development of a new medical device can be complex. This chapter highlights some of the main considerations in the specific area of evaluation of blood-contacting medical devices and materials. It discusses the main factors that may impact the blood-device/ material responses that can occur, and it provides examples of some of the most common observations and approaches to manage the response. As the international standard ISO 10993-4 has been and continues to be a major driving influence behind this aspect of the biological safety evaluation of materials and devices, the evolving direction of the standard is covered and controversies in testing are reviewed. Ultimately, appropriate care taken to evaluate and understand critical blood-device/material interactions in each unique application leads to predictive and safe use in humans.
Introduction Basic Understanding Recent Progresses on Single-Layer Asymmetric Hollow-Fiber Membranes Dual-Layer Hollow Fibers Concluding Remarks Acknowledgments References
A modified poly(dimethyl siloxane) (PDMS) material is under development for use in an extracorporeal microfluidic blood oxygenator designed as an artificial placenta to treat newborn infants suffering from severe respiratory insufficiency. To prevent thrombosis triggered by blood-material contact, an antithrombin-heparin (ATH) covalent complex was coated on PDMS surface using polydopamine (PDA) as a "bioglue". Experiments using radiolabelled ATH showed that the ATH coating on PDA-modified PDMS remained substantially intact after incubation in plasma, 2% SDS solution, or whole blood over a three day period. The anticoagulant activity of the ATH-modified surfaces was also demonstrated: in contact with plasma the ATH-coated PDMS was shown to bind antithrombin (AT) selectively from plasma and to inhibit clotting factor Xa. It is concluded that modification of PDMS with polydopamine and ATH shows promise as a means of improving the blood compatibility of PDMS and hence of the oxygenator device.
Polyethersulfone (PES) based membranes are used for dialysis, but exposure to blood can result in numerous interactions between the blood elements and the membrane. Adsorption and transformation of plasma proteins, activation of blood cells, adherence of platelets and thrombosis reactions against PES membrane can invoke severe blood reactions causing the increase rate of mortality and morbidity of hemodialysis (HD) patients. In order to minimize blood immune response, different biomimetic, zwitterionic, non-ionic, anticoagulant molecules and hydrophilic brushes were immobilized or blended with PES polymers. These additives modified the nature of the membrane, enhanced their biocompatibility and also increased the uremic waste dialysis properties. In this review, current perspectives of the different additives which are used with PES are highlighted in relation with PES membrane-associated blood reactions. The additive's purpose, compatibility, preparation techniques, methods of addition to polymer and influence on the chemistry and performance of hemodialysis membranes are described.
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This work presents an investigation of local gas side overall mass transfer coefficient (KG) of the membrane gas absorption process determined from CO2 concentration gradients. The experimental KG was compared with simulation results of non-wetted and partially wetted modes of operation from a plug flow and rated based model to study the effects of various operating parameters on the partial wetting of the membrane and its process performance. The experiments were performed using two types of membranes (polytetrafluoroethylene, PTFE and polyvinylidene fluoride PVDF), and two absorbents (monoethanolamine, MEA and 2-amino-2-methyl-1-propanol, AMP). A comparison showed that the membrane wetting fraction was lowest at the liquid outlet and varied along the length of the membrane module due to the effect of pressure drop. The effect of liquid velocity on membrane wetting was very obvious at a low membrane wetting fraction whereas it was less noticeable at a higher membrane wetting fraction. The average membrane wetting fractions were lower when PTFE was used with MEA solution than when PVDF and AMP solution were used in experiments. In addition, the results further showed that the use of CO2 loaded MEA solution could significantly reduce membrane wetting.
1.A unitized, disposable, inexpensive bubble diffusion oxygenator constructed of two sheets of polyvinyl plastic has been used successfully in 11 clinical cases.
2.This oxygenator is commercially available as a sterile packaged unit ready to hang up, prime, and use.
3.Seven of 11 patients had intracardiac defects completely corrected and are living and well at this time. The remaining four patients (three were seriously ill infants) succumbed from complications including pulmonary hypertension and complete atrio-ventricular heart block. In none of these four patients did it appear that the performance of the pump or oxygenator could be incriminated in the unsuccessful outcome.
4.Biochemical perfusion data on these 11 patients compares favorably with determinations made on 250 patients perfused with the three dimensional prototype of this unit.
In the present work, inspired by the chemical structure of heparin molecules, we designed a polyethersulfone (PES) membrane with a heparin-like surface for the first time by physically blending sulfonated polyethersulfone (SPES), carboxylic polyethersulfone (CPES), and PES at rational ratios. Evaporation and phase-inversion membranes of PES/CPES/SPES were prepared by evaporating the solvent in a vacuum oven, and by a liquid-liquid phase separation technique, respectively. Scanning electron microscopy (SEM) images revealed that the structures of the PES/CPES/SPES membranes were dependent on the proportions of the additives and no obvious phase separation was detected. The blood compatibility of the modified membrane surfaces was characterized in terms of bovine serum fibrinogen (BFG) adsorption, platelet adhesion, thrombin-antithrombin (TAT) generation, percentage of platelets positive for CD62p expression, clotting times (activated partial thromboplastin time (APTT) and prothrombin time (PT)), and comp
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/cm2 (0.3–0.5 mL/kg/min) and 6.4–10.1 μL/min/cm2 (0.8–1.3 mL/kg/min) for O2 and CO2, respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm2). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65–2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (FiO2 = 0.15) and was found to be 3.0 μL/min/cm2. These results are encouraging and support the feasibility of an artificial placental design for an LAD.
