Hemocompatibility challenge of membrane oxygenator for artificial lung technology.

The artificial lung (AL) technology is one of the membrane-based artificial organs that partly augments lung functions, i.e. blood oxygenation and CO2 removal. It is generally employed as an extracorporeal membrane oxygenation (ECMO) device to treat acute and chronic lung-failure patients, and the recent outbreak of the COVID-19 pandemic has re-emphasized the importance of this technology. The principal component in AL is the polymeric membrane oxygenator that facilitates the O2/CO2 exchange with the blood. Despite the considerable improvement in anti-thrombogenic biomaterials in other applications (e.g., stents), AL research has not advanced at the same rate. This is partly because AL research requires interdisciplinary knowledge in biomaterials and membrane technology. Some of the promising biomaterials with reasonable hemocompatibility - such as emerging fluoropolymers of extremely low surface energy - must first be fabricated into membranes to exhibit effective gas exchange performance. As AL membranes must also demonstrate high hemocompatibility in tandem, it is essential to test the membranes using in-vitro hemocompatibility experiments before in-vivo test. Hence, it is vital to have a reliable in-vitro experimental protocol that can be reasonably correlated with the in-vivo results. However, current in-vitro AL studies are unsystematic to allow a consistent comparison with in-vivo results. More specifically, current literature on AL biomaterial in-vitro hemocompatibility data are not quantitatively comparable due to the use of unstandardized and unreliable protocols. Such a wide gap has been the main bottleneck in the improvement of AL research, preventing promising biomaterials from reaching clinical trials. This review summarizes the current state-of-the-art and status of AL technology from membrane researcher perspectives. Particularly, most of the reported in-vitro experiments to assess AL membrane hemocompatibility are compiled and critically compared to suggest the most reliable method suitable for AL biomaterial research. Also, a brief review of current approaches to improve AL hemocompatibility is summarized. STATEMENT OF SIGNIFICANCE: The importance of Artificial Lung (AL) technology has been re-emphasized in the time of the COVID-19 pandemic. The utmost bottleneck in the current AL technology is the poor hemocompatibility of the polymer membrane used for O2/CO2 gas exchange, limiting its use in the long-term. Unfortunately, most of the in-vitro AL experiments are unsystematic, irreproducible, and unreliable. There are no standardized in-vitro hemocompatibility characterization protocols for quantitative comparison between AL biomaterials. In this review, we tackled this bottleneck by compiling the scattered in-vitro data and suggesting the most suitable experimental protocol to obtain reliable and comparable hemocompatibility results. To the best of our knowledge, this is the first review paper focusing on the hemocompatibility challenge of AL technology.

Effect of Additives during Interfacial Polymerization Reaction for Fabrication of Organic Solvent Nanofiltration (OSN) Membranes.

Thin film composite (TFC) membranes is the dominant type of desalination in the field of membrane technology. Most of the TFC membranes are fabricated via interfacial polymerization (IP) technique. The ingenious chemistry of reacting acyl chlorides with diamines at the interface between two immiscible phases was first suggested by Cadotte back in the 1980s, and is still the main chemistry employed now. Researchers have made incremental improvements by incorporating various organic and inorganic additives. However, most of the TFC membrane literature are focused on improving the water desalination performance. Recently, the application spectrum of membrane technology has been expanding from the aqueous environment to harsh solvent environments, now commonly known as Organic Solvent Nanofiltration (OSN) technology. In this work, some of the main additives widely used in the desalination TFC membranes were applied to OSN TFC membranes. It was found that tributyl phosphate (TBP) can improve the solubility of diamine monomer in the organic phase, and sodium dodecyl sulfate (SDS) surfactant can effectively stabilize the IP reaction interface. Employing both TBP and SDS exhibited synergistic effect that improved the membrane permeance and rejection in solvent environments.

The Roles of Membrane Technology in Artificial Organs: Current Challenges and Perspectives.

The recent outbreak of the COVID-19 pandemic in 2020 reasserted the necessity of artificial lung membrane technology to treat patients with acute lung failure. In addition, the aging world population inevitably leads to higher demand for better artificial organ (AO) devices. Membrane technology is the central component in many of the AO devices including lung, kidney, liver and pancreas. Although AO technology has improved significantly in the past few decades, the quality of life of organ failure patients is still poor and the technology must be improved further. Most of the current AO literature focuses on the treatment and the clinical use of AO, while the research on the membrane development aspect of AO is relatively scarce. One of the speculated reasons is the wide interdisciplinary spectrum of AO technology, ranging from biotechnology to polymer chemistry and process engineering. In this review, in order to facilitate the membrane aspects of the AO research, the roles of membrane technology in the AO devices, along with the current challenges, are summarized. This review shows that there is a clear need for better membranes in terms of biocompatibility, permselectivity, module design, and process configuration.

Sustainable Fabrication of Organic Solvent Nanofiltration Membranes.

Organic solvent nanofiltration (OSN) has been considered as one of the key technologies to improve the sustainability of separation processes. Recently, apart from enhancing the membrane performance, greener fabricate on of OSN membranes has been set as a strategic objective. Considerable efforts have been made aiming to improve the sustainability in membrane fabrication, such as replacing membrane materials with biodegradable alternatives, substituting toxic solvents with greener solvents, and minimizing waste generation with material recycling. In addition, new promising fabrication and post-modification methods of solvent-stable membranes have been developed exploiting the concept of interpenetrating polymer networks, spray coating, and facile interfacial polymerization. This review compiles the recent progress and advances for sustainable fabrication in the field of polymeric OSN membranes.

Transport Membrane Condenser Heat Exchangers to Break the Water-Energy Nexus-A Critical Review.

Under the notion of water-energy nexus, the unsustainable use of water in power plants has been largely accepted in silence. Moreover, the evaporated water from power plants acts as a primary nucleation source of particulate matter (PM), rendering significant air pollution and adverse health issues. With the emergence of membrane-based dehydration processes such as vapor permeation membrane, membrane condenser, and transport membrane condenser, it is now possible to capture and recycle the evaporated water. Particularly, the concept of transport membrane condensers (TMCs), also known as membrane heat exchangers, has attracted a lot of attention among the membrane community. A TMC combines the advantages of heat exchangers and membranes, and it offers a unique tool to control the transfer of both mass and energy. In this review, recent progress on TMC technology was critically assessed. The effects of TMC process parameters and membrane properties on the dehydration efficiencies were analyzed. The peculiar concept of capillary condensation and its impact on TMC performance were also discussed. The main conclusion of this review was that TMC technology, although promising, will only be competitive when the recovered water quality is high and/or the recovered energy has some energetic value (water temperature above 50 ∘C).

Blood Oxygenation Using Fluoropolymer-Based Artificial Lung Membranes.

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.

Bio-Inspired Robust Membranes Nanoengineered from Interpenetrating Polymer Networks of Polybenzimidazole/Polydopamine.

Marine mussel inspired polydopamine (PDA) has received increased attention due to its good thermal and chemical stability as well as strong adhesion on most materials. In this work, high-performance nanofiltration membranes based on interpenetrating polymer networks (IPN) incorporating PDA and polybenzimidazole (PBI) were developed for organic solvent nanofiltration (OSN). Generally, in order to obtain solvent stability, polymers need to be covalently cross-linked under harsh conditions, which inevitably leads to losses in permeability and mechanical flexibility. Surprisingly, by in situ polymerization of dopamine within a PBI support, excellent solvent resistance and permeance of polar aprotic solvents were obtained without covalent cross-linking of the PBI backbone due to the formation of an IPN. The molecular weight cutoff and permeance of the membranes can be fine-tuned by changing the polymerization time. Robust membrane performance was achieved in conventional and emerging green polar aprotic solvents (PAS) in a wide temperature range covering -10 °C to +100 °C. It was successfully demonstrated that the in situ polymerization of PDA-creating an IPN-can provide a simple and green alternative to covalent cross-linking of membranes. To elucidate the nature of the solvent stability, a detailed analysis was performed that revealed that physical entanglement along with strong secondary interaction synergistically enable solvent resistance with as low as 1-3% PDA content.

Polyethylene Battery Separator as a Porous Support for Thin Film Composite Organic Solvent Nanofiltration Membranes.

Organic solvent nanofiltration (OSN) has made significant advances recently, and it is now possible to fabricate thin film composite (TFC) membranes with a selective layer thickness below 10 nm that gives ultrafast solvent permeance. However, such high permeance is inadvertently limited by the support membrane beneath the selective layer, and thus there is an urgent need to develop a suitable support to maximize TFC performance. In this work, we employed a commercially available polyethylene (PE) battery separator as a porous support to fabricate high performance TFC OSN membranes. To deposit a uniform polyamide selective layer onto the porous support via interfacial polymerization, the PE support was hydrophilized with O2 plasma and the reaction efficiency was optimized using a surfactant. Owing to the high surface porosity of the PE support and the high permselectivity of the PA layer, the PE-supported TFC membrane outperformed the previously reported OSN membranes and its performance exceeded the current performance upper bound. A solvent activation step dramatically improved the solvent permeance by 5-fold while maintaining nanoseparation properties. In addition to the superior OSN performance, the commercial availability of the PE support and simplified TFC fabrication protocol would make the PE-supported OSN membranes commercially attractive.

Exploring and Exploiting the Effect of Solvent Treatment in Membrane Separations.

It is well-known that solvent treatment and preconditioning play an important role in rejection and flux performance of membranes due to solvent-induced swelling and solvent adsorption. Investigations into the effect of solvent treatment are scarce and application specific, and were limited to a few solvents only. This study reveals the trend in solvent treatment based on solvent polarity in a systematic investigation with the aim to harness such effect for intensification of membrane processes. Nine solvents with polarity indices ranging from 0.1 to 5.8 (hexane to acetonitrile) were used as treatment and process solvents on commercial Borsig GMT-oNF-2, Evonik Duramem 300, and emerging tailor-made polybenzimidazole membranes. TGA-GCMS, HS-GC-FID, and NMR techniques were employed to better understand the effect of solvent treatment on the polymer matrix of membranes. In this work, apart from the solvent treatment's direct effect on the membrane performance, a subsequent indirect effect on the ultimate separation process was observed. Consequently, a pharmaceutical case study employing chlorhexidine disinfectant and antiseptic was used to demonstrate the effect of solvent treatment on the nanofiltration-based purification. It is shown that treatment of polybenzimidazole membranes with acetone resulted in a 25% increase in product recovery at 99% impurity removal. The cost of the process intensification is negligible in terms of solvent consumption, mass intensity, and processing time.

Liquid-Phase Synthesis of 2'-Methyl-RNA on a Homostar Support through Organic-Solvent Nanofiltration.

Due to the discovery of RNAi, oligonucleotides (oligos) have re-emerged as a major pharmaceutical target that may soon be required in ton quantities. However, it is questionable whether solid-phase oligo synthesis (SPOS) methods can provide a scalable synthesis. Liquid-phase oligo synthesis (LPOS) is intrinsically scalable and amenable to standard industrial batch synthesis techniques. However, most reported LPOS strategies rely upon at least one precipitation per chain extension cycle to separate the growing oligonucleotide from reaction debris. Precipitation can be difficult to develop and control on an industrial scale and, because many precipitations would be required to prepare a therapeutic oligonucleotide, we contend that this approach is not viable for large-scale industrial preparation. We are developing an LPOS synthetic strategy for 2'-methyl RNA phosphorothioate that is more amenable to standard batch production techniques, using organic solvent nanofiltration (OSN) as the critical scalable separation technology. We report the first LPOS-OSN preparation of a 2'-Me RNA phosphorothioate 9-mer, using commercial phosphoramidite monomers, and monitoring all reactions by HPLC, (31)P NMR spectroscopy and MS.