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Flow batteries are a promising energy storage solution. However, the footprint and capital cost need further reduction for flow batteries to be commercially viable. The flow cell, where electron exchange takes place, is a central component of flow batteries. Improving the volumetric power density of the flow cell (W/Lcell) can reduce the size and cost of flow batteries. While significant progress has been made on flow battery redox, electrode, and membrane materials to improve energy density and durability, conventional flow batteries based on the planar cell configuration exhibit a large cell size with multiple bulky accessories such as flow distributors, resulting in low volumetric power density. Here, we introduce a submillimeter bundled microtubular (SBMT) flow battery cell configuration that significantly improves volumetric power density by reducing the membrane-to-membrane distance by almost 100 times and eliminating the bulky flow distributors completely. Using zinc-iodide chemistry as a demonstration, our SBMT cell shows peak charge and discharge power densities of 1,322 W/Lcell and 306.1 W/Lcell, respectively, compared with average charge and discharge power densities of <60 W/Lcell and 45 W/Lcell, respectively, of conventional planar flow battery cells. The battery cycled for more than 220 h corresponding to >2,500 cycles at off-peak conditions. Furthermore, the SBMT cell has been demonstrated to be compatible with zinc-bromide, quinone-bromide, and all-vanadium chemistries. The SBMT flow cell represents a device-level innovation to enhance the volumetric power of flow batteries and potentially reduce the size and cost of the cells and the entire flow battery.
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Líquidos Corporais , Brometos , Tamanho Celular , Fibras na Dieta , ZincoRESUMO
Translating carbon molecular sieve (CMS) membranes into highly scalable hollow fiber geometry with ultra-thin selective layer (<1 µm) for gas separation remains as great challenge. The porous support layer of precursor hollow fiber membranes is prone to collapse during pyrolysis, which induces thick skin layer (15-50 µm) of CMS hollow fiber membranes. Here, a novel strategy is present to obtain an ultra-thin selective skin layer by carbonization of hollow fiber membranes with porous skin. P84-based defect-free CMS hollow fiber membranes with ultra-thin selective skin layer (0.9 µm) for gas separation are prepared without any coating or complex chemical pretreatment. Compared with the carbon membranes derived from defect-free fibers, the H2 permeance (93.9 GPU) of CMS membranes derived from the porous fibers increases ≈1353% with comparable selectivity of H2/CH4 (143) and higher H2/N2 (120). Furthermore, the porous fibers are pre-aged near the Tg in N2 conditions before carbonization, and the H2 permeance of the derived CMS hollow fiber membranes reached 147 GPU (increased 2180%). It is a new facile way to prepare CMS hollow fiber membranes with ultra-thin selective layer by porous fibers, demonstrating its versatile potential in gas separation or organic liquids separation.
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Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas transfer rate, biocompatibility, and durability. In Japan, the membrane oxygenator to assist circulation and ventilation is approved for ECMO support. However, in all cases, the maximum use period has been only 6 h, and so-called 'off-label use' is common for ECMO support of severely ill COVID-19 patients. Under these circumstances, the HLS SET Advanced (Getinge Group Japan K.K.) was approved in 2020 for the first time in Japan as a membrane oxygenator with a two-week period of use. Following this membrane oxygenator, it is necessary to establish a domestic ECMO system that is approved for long-term use and suitable for supporting patients. Looking back on the evolution of ECMO so far, Japanese researchers and manufacturers have also contributed to the developments of ECMO globally. Currently, excellent membrane oxygenators and systems have been marketed by Japanese manufacturers and some of them are globally acclaimed, but in fact, most of the ECMO membranes are not made in Japan. Fortunately, Japan has led the world in the fields of membrane separation technology and hollow fiber membrane production. In the wake of this pandemic, from the perspective of medical and economic security, the practical use of purely domestic hollow fiber membranes and membrane oxygenators for long-term ECMO is imperative in anticipation of the next pandemic.
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Oxigenação por Membrana Extracorpórea , Oxigenadores de Membrana , Humanos , Desenho de Equipamento , JapãoRESUMO
Since the COVID-19 pandemic of 2020-2023, extracorporeal membrane oxygenator (ECMO) has attracted considerable attention worldwide. It is expected that ECMO with long-term durability is put into practical use in order to prepare for next emerging infectious diseases and to facilitate manufacturing for novel medical devices. Polypropylene (PP) and polymethylpentene (PMP) capillary membranes are currently the mainstream for gas exchange membrane for ECMO. ECMO support days for COVID-19-related acute hypoxemic respiratory failure have been reported to be on average for 14 or 24 days. It is necessary to improve opposing functions such that promoting the permeation of oxygen and carbon dioxide and inhibiting the permeation of water vapor or plasma to develop sufficient durability for long-term use. For this purpose, accurately controlling the anisotropy of the pore structure of the entire cross section and functions of capillary membrane is significant. In this study, we focused on the cross-sectional ion-milling (CSIM) method, to precisely clarify the pore structure of the entire cross section of capillary membrane for ECMO, because there is less physical stress on the porous structure applied during the preparation of cross-sectional samples of porous capillary membranes. We attempted to observe the cross sections of commercially available PMP membranes using the CSIM method. As a result, we succeeded in fabricating fine-scale flat cross-sectional samples of PMP capillary membranes. The pore structures and the degree of anisotropy of the cross sections are quantitatively clarified. The achievements and the approaches of this study are being applied to the development of next-generation gas exchange membranes.
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A novel strategy based on gradient porous hollow fiber membrane (GPF) is proposed for the modular assembly of enzyme-nanozyme cascade systems. The porous structure of GPF provided sufficient specific surface area, while the gradient structure effectively minimized the leaching of enzymes and nanozymes. To enhance stability, we prepared and immobilized metal-organic framework (MOF) nanozymes, resulting in the fabrication of GPF-MOF with excellent stability and reusability for colorimetric H2O2 detection. To improve specificity and expand the detection range, micro-crosslinked natural enzymes were modularly assembled, using glucose oxidase as the model enzyme. The assembled system, GPF-mGOx@MOF, achieved a low detection limit of 0.009 mM and a linear range of 0.2 to 11 mM. The sensor retained 87.2% and 80.7% of initial activity after being stored for 49 days and 9 recycles, respectively. Additionally, the reliability of the biosensor was validated through glucose determination of human blood and urine samples, yielding comparable results to a commercial glucose meter.
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Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/química , Glucose/química , Peróxido de Hidrogênio/química , Reprodutibilidade dos Testes , Glucose Oxidase/químicaRESUMO
Polymers stand out as promising materials extensively employed in biomedicine and biotechnology. Their versatile applications owe much to the field of tissue engineering, which seamlessly integrates materials engineering with medical science. In medicine, biomaterials serve as prototypes for organ development and as implants or scaffolds to facilitate body regeneration. With the growing demand for innovative solutions, synthetic and hybrid polymer materials, such as polyethersulfone, are gaining traction. This article offers a concise characterization of polyethersulfone followed by an exploration of its diverse applications in medical and biotechnological realms. It concludes by summarizing the significant roles of polyethersulfone in advancing both medicine and biotechnology, as outlined in the accompanying table.
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Biotecnologia , Polímeros , Sulfonas , Animais , Humanos , Materiais Biocompatíveis/química , Biotecnologia/métodos , Polímeros/química , Sulfonas/química , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
As an important part of the membrane field, hollow fiber membranes (HFM) have been widely concerned by scholars. HFM fouling in the industrial application results in a reduction in its lifespan and an increase in cost. In recent years, various explorations on the HFM fouling control strategies have been carried out. In the current work, we critically review the influence of flow field characteristics in HFM-based bioreactor on membrane fouling control. The flow field characteristics mainly refer to the spatial and temporal variation of the related physical parameters. In the HFM field, the physical parameter mainly refers to the variation characteristics of the shear force, flow velocity and turbulence caused by hydraulics. The factors affecting the flow field characteristics will be discussed from three levels: the micro-flow field near the interface of membrane (micro-interface), the flow field around the membrane module and the reactor design related to flow field, which involves surface morphology, crossflow, aeration, fiber packing density, membrane vibration, structural design and other related parameters. The study of flow field characteristics and influencing factors in the HFM separation process will help to improve the performance of HFM in full-scale water treatment plants.
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Reatores Biológicos , Membranas Artificiais , Purificação da Água/métodos , Purificação da Água/instrumentaçãoRESUMO
Discharging improperly treated oily-produced water (OPW) into the environment can have significant negative impacts on environmental sustainability. It can lead to pollution of water sources, damage to aquatic ecosystems and potential health hazards for individuals living in the affected areas. Ceramic hollow fiber membrane (CHFM) technology is one of the most effective OPW treatment methods for achieving high oil removal efficiency while maintaining membrane water permeability. In this study, low-cost calcium bentonite hollow fiber membranes (CaB-HFMs) were prepared from high-alumina calcium bentonite clay with various preparation parameters, including calcium bentonite content, sintering temperature, air gap distance and bore fluid rate. The prepared CaB-HFMs were then subjected to characterization using scanning electron microscopy (SEM), a three-point bending test, porosity, average pore size, hydraulic resistance and flux recovery ratio (FRR) analysis. Statistical analysis employing central composite design (CCD) assessed the interaction between the parameters and their effect on CaB-HFM water permeability and oil removal efficiency. Higher ceramic content and sintering temperature led to reduced porosity, smaller pore size and higher mechanical strength. In contrast, increasing the air gap distance and bore fluid rate exhibit different trends, resulting in higher porosity and pore size, along with weaker mechanical strength. Other than that, all of the CaB-HFMs displayed low hydraulic resistance (<0.01 m2 h.bar/L) and high FRR value (up to 95.2%). Based on CCD, optimal conditions for CaB-HFM were determined as follows: a calcium bentonite content of 50 wt.%, a sintering temperature of 1096 °C, an air gap distance of 5 cm and a bore fluid rate of 10 mL/min, with the desirability value of 0.937. Notably, the optimized CaB-HFMs demonstrated high oil removal efficiency of up to 99.7% with exceptional water permeability up to 535.2 L/m2.h.bar. The long-term permeation study also revealed it was capable of achieving a high average water permeation and a stable oil rejection performance of 522.15 L/m2.h.bar and 99.8%, respectively, due to their inherent hydrophilic and antifouling characteristics, making it practical for OPW treatment application.
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Bentonita , Bentonita/química , Salinidade , Permeabilidade , Cálcio/química , Membranas ArtificiaisRESUMO
Understanding the mass transfer behaviors in hollow fiber membrane module of artificial liver is important for improving toxin removal efficiency. A three-dimensional numerical model was established to study the mass transfer of small molecule bilirubin and macromolecule bovine serum albumin (BSA) in the hollow fiber membrane module. Effects of tube-side flow rate, shell-side flow rate, and hollow fiber length on the mass transfer of bilirubin and BSA were discussed. The simulation results showed that the clearance of bilirubin was significantly affected by both convective and diffusive solute transport, while the clearance of macromolecule BSA was dominated by convective solute transport. The clearance rates of bilirubin and BSA increasd with the increase of tube-side flow rate and hollow fiber length. With the increase of shell-side flow rate, the clearance rate of bilirubin first rose rapidly, then slowly rose to an asymptotic value, while the clearance rate of BSA gradually decreased. The results can provide help for designing structures of hollow fiber membrane module and operation parameters of clinical treatment.
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Bilirrubina , Fígado Artificial , Membranas Artificiais , Soroalbumina Bovina , Soroalbumina Bovina/química , Bilirrubina/metabolismo , Animais , Bovinos , HumanosRESUMO
A novel boronic acid and carboxyl-modified glucose molecularly imprinted polymer were prepared through suspension polymerization, which is based on 1.0 mmol glucose as a template, 1.2 mmol methacrylamidophenylboronic acid, and 6.8 mmol methacrylic acids as monomers, 19 mmol ethyleneglycol dimethacrylate, and 1 mmol methylene-bis-acrylamide as crosslinkers. The prepared glucose-molecularly imprinted polymer had a particle size of 25-70 µm, and was thermally stable below 215°C, with a specific surface area of 174.82 m2/ g and average pore size of 9.48 nm. The best selectivity between glucose and fructose was 2.71 and the maximum adsorption capacity of glucose- molecularly imprinted polymer was up to 236.32 mg/ g which was consistent with the Langmuir adsorption model. The similar adsorption abilities in six successive runs and the good desorption rate (99.4%) verified glucose-molecularly imprinted polymer could be reused. It was successfully used for extracting glucose from cellulose hydrolysis. The adsorption amount of glucose was 2.61 mg/mL and selectivity between glucose and xylose reached 4.12. A newly established chromatography (glucose-molecularly imprinted polymer) mediated hollow fiber membrane method in time separated pure glucose from cellulose hydrolysates on a large scale, and purified glucose solution with a concentration of 3.84 mg/mL was obtained, which offered a feasible way for the industrial production of glucose from cellulose hydrolysates.
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Impressão Molecular , Adsorção , Ácidos Borônicos , Celulose , Cromatografia , Glucose , Hidrólise , Polímeros Molecularmente Impressos , Extratos Vegetais/química , Polímeros/químicaRESUMO
Polymethylmethacrylate (PMMA) hollow fiber membranes are one of the synthetic polymer hollow fiber membranes used to the hollow fiber artificial kidney. A PMMA hollow fiber membrane (PMMA membrane) has unique properties including the uniform structure and the adsorption property. Hemodialyzers using PMMA membranes, Filtryzer®, were approved in Japan in 1977 and have been used worldwide for over 40 years and so is a historical hemodialyzer.Various types in Filtryzer® having different pore sizes are developed and used in the clinical field. Filtryzer® B3 is a low-flux dialyzer. Filtryzer® BK has three types having different pore sizes, and above all, BK-F has the largest pores in the Filtryzer® series. Filtryzer® BG has a more uniform membrane structure by using weak anionic polymers compared with the earlier Filtryzer® series to remove ß2-MG more. Filtryzer® NF is the latest Filtryzer® series and was developed as a dialyzer having improved antithrombogenicity compared with previous models and having protein adsorption property as the same with them. There have been many reports concerning Filtryzer® including improvement of patients' symptoms such as pruritus and nutrition on the advantages for dialysis patients. Although PMMA membranes are historic dialysis tools used for over 40 years, they are also modern dialysis membranes that have been updated to respond to dialysis therapy at those time.
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The impact of water hyacinth (Eichhornia crassipes) root biomass (WHRB) on pharmaceutical wastewater treatment with an aerobic hollow-fiber membrane bioreactor (HF-MBR) was investigated. The performance of the bioreactor was assessed in terms of COD (Chemical Oxygen Demand) and antibiotic removal and membrane biofouling rate. For deeper insight, microbial communities in sludge and biofilm layers were analyzed through Illumina sequencing. The addition of WHRB into the HF-MBR increased the COD (by 6%), as well as antibiotics and transformation products removal efficiency. Removal efficiencies of 97%, 98% and 84% were obtained for removal of erythromycin, sulfamethoxazole, and tetracycline. Furthermore, WHRB modified the biodegradation network, increased the relative abundances of Chloroflexi, Proteobacteria and Nitrospirae and decreased Firmicutes, compared with the control with antibiotics. The addition of WHRB also enriched Actinobacteria and Bacteroidetes while decreasing the phylla Chloroflexi and Saccharibacteria in the biofilm.
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Eichhornia , Poluentes Químicos da Água , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental , Biofilmes , Biomassa , Reatores Biológicos/microbiologia , Eichhornia/metabolismo , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Most researchers focused on developing highly selective membranes for CO2/CH4 separation, but their developed membranes often suffered from low permeance. In this present work, we aimed to develop an ultrahigh permeance membrane using a simple coating technique to overcome the trade-off between membrane permeance and selectivity. A commercial silicone membrane with superior permeance but low CO2/CH4 selectivity (in the range of 2-3) was selected as the host for surface modification. Our results revealed that out of the three silane agents tested, only tetraethyl orthosilicate (TEOS) improved the control membrane's permeance and selectivity. This can be due to its short structural chain and better compatibility with the silicone substrate. Further investigation revealed that higher CO2 permeance and selectivity could be attained by coating the membrane with two layers of TEOS. The surface integrity of the TEOS-coated membrane was further improved when an additional polyether block amide (Pebax) layer was established atop the TEOS layer. This additional layer sealed the pin holes of the TEOS layer and enhanced the resultant membrane's performance, achieving CO2/CH4 selectivity of ~19 at CO2 permeance of ~2.3 × 105 barrer. This performance placed our developed membrane to surpass the 2008 Robeson Upper Boundary.
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Amidas , Dióxido de Carbono , Humanos , Pesquisadores , Silanos , SiliconesRESUMO
Cell-assisted lipotransfer (CAL) is an advanced lipoinjection method that uses autologous lipotransfer with addition of a stromal vascular fraction (SVF) containing adipose-derived stromal stem cells (ASCs). The CAL procedure of manual isolation of cells from fat requires cell processing to be performed in clean environment. To isolate cells from fat without the need for a cell processing center, such as in a procedure in an operation theater, we developed a novel method for processing SVF using a closed cell washing concentration device (CCD) with a hollow fiber membrane module. The CCD consists of a sterilized closed circuit, bags and hollow fiber, semi-automatic device and the device allows removal of >99.97% of collagenase from SVF while maintaining sterility. The number of nucleated cells, ASCs and viability in SVF processed by this method were equivalent to those in SVF processed using conventional manual isolation. Our results suggest that the CCD system is as reliable as manual isolation and may also be useful for CAL. This approach will help in the development of regenerative medicine at clinics without a cell processing center.
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Tecido Adiposo , Células Estromais , Contagem de Células , Medicina Regenerativa , Células-TroncoRESUMO
Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 40 years as a bridge to transplantation, with hollow-fiber membrane (HFM) oxygenators gaining in popularity due to their high gas transfer and low flow resistance. In spite of the technological advances in ECMO devices, the inevitable contact of the perfused blood with the polymer hollow-fiber gas-exchange membrane, and the subsequent thrombus formation, limits their clinical usage to only 2-4 weeks. In addition, the inhomogeneous flow in the device can further enhance thrombus formation and limit gas-transport efficiency. Endothelialization of the blood contacting surfaces of ECMO devices offers a potential solution to their inherent thrombogenicity. However, abnormal shear stresses and inhomogeneous blood flow might affect the function and activation status of the seeded endothelial cells (ECs). In this study, the blood flow through two HFM oxygenators, including the commercially available iLA® MiniLung Petite Novalung (Xenios AG, Germany) and an experimental one for the rat animal model, was modeled using computational fluid dynamics (CFD), with a view to assessing the magnitude and distribution of the wall shear stress (WSS) on the hollow fibers and flow fields in the oxygenators. This work demonstrated significant inhomogeneity in the flow dynamics of both oxygenators, with regions of high hollow-fiber WSS and regions of stagnant flow, implying a variable flow-induced stimulation on seeded ECs and possible EC activation and damage in a biohybrid oxygenator setting.
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Oxigenadores de Membrana , HidrodinâmicaRESUMO
The effects of bioaugmentation with immobilized Penicillium restrictum on the removal efficiency of sulfamethoxazole (SMX), erythromycin (ERY) and tetracycline (TC) antibiotics as well as membrane biofouling was studied using hollow-fiber membrane bioreactor (HF-MBR). Bioaugmentation with P. restrictum led to a significant change in the antibiotic removal efficiency and relative abundance of aerobic microbial community, most probably as a result of its quorum quenching activity. Furthermore, in addition to its role in the increase of SMX and ERY removal efficiencies and the decrease of their sorption on solid phase, bioaugmentation significantly reduced the transmembrane pressure which in turn reduced membrane clogging. The most abundant phyla in sludge and biofilm samples in the presence of P. restrictum were observed to be Proteobacteria, Bacteroidetes and Firmicutes. Differences in bacterial compositions and their specificity in biodegradation of antibiotics in different reactors showed that bacteria were specifically selected under the pressure of antibiotics and growing fungus.
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Antibacterianos/metabolismo , Reatores Biológicos/microbiologia , Penicillium/fisiologia , Bactérias/metabolismo , Biodegradação Ambiental , Biofilmes , Incrustação Biológica , Eritromicina/metabolismo , Membranas Artificiais , Microbiota , Percepção de Quorum , Sulfametoxazol/metabolismo , Tetraciclina/metabolismo , Águas Residuárias/microbiologiaRESUMO
The use of bioreactors coupled to membrane-based perfusion systems enables very high cell and product concentrations in vaccine and viral vector manufacturing. Many virus particles, however, are not stable and either lose their infectivity or physically degrade resulting in significant product losses if not harvested continuously. Even hollow fiber membranes with a nominal pore size of 0.2 µm can retain much smaller virions within a bioreactor. Here, we report on a systematic study to characterize structural and physicochemical membrane properties with respect to filter fouling and harvesting of yellow fever virus (YFV; ~50 nm). In tangential flow filtration perfusion experiments, we observed that YFV retention was only marginally determined by nominal but by effective pore sizes depending on filter fouling. Evaluation of scanning electron microscope images indicated that filter fouling can be reduced significantly by choosing membranes with (i) a flat inner surface (low boundary layer thickness), (ii) a smooth material structure (reduced deposition), (iii) a high porosity (high transmembrane flux), (iv) a distinct pore size distribution (well-defined pore selectivity), and (v) an increased fiber wall thickness (larger effective surface area). Lowest filter fouling was observed with polysulfone (PS) membranes. While the use of a small-pore PS membrane (0.08 µm) allowed to fully retain YFV within the bioreactor, continuous product harvesting was achieved with the large-pore PS membrane (0.34 µm). Due to the low protein rejection of the latter, this membrane type could also be of interest for other applications, that is, recombinant protein production in perfusion cultures.
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Técnicas de Cultura Celular por Lotes/instrumentação , Reatores Biológicos/virologia , Filtração/instrumentação , Tamanho da Partícula , Perfusão/métodos , Vírus/crescimento & desenvolvimento , Linhagem Celular , Membranas Artificiais , Vírus/isolamento & purificaçãoRESUMO
We examined typical commercial poly(ethersulfone) (PESf) hemodialysis and hemoconcentration membranes successfully used in manufacturing, and employed scanning probe microscope (SPM) to achieve a structural observation of the pores in the inner membrane surfaces, as well as measure the pore diameters and their distribution, verifying the relationship between the typical mass transfer properties. We focused on the differences between the PESf membranes which were expected to further improve the advanced pore structure control and functional design for various medical uses. The three-dimensional tortuous capillary pores on the inner surface of hollow fiber hemodialysis and hemoconcentrator membranes were investigated using dynamic force microscopy (DFM), and the pore diameter and distribution were measured through a line analysis. Compared with PUREMA-A, PES-Sα hemodialysis membranes have smaller three-dimensional tortuous capillary pore diameters and pore areas, as well as a smaller pore diameter distribution and pore area distribution, which make the accurate measurements of the pore diameter using FE-SEM impossible. These PESf membranes are almost the same in pure water permeability, but greatly differ in pore diameter and pore diameter distribution. By comparing and verifying as above, we may gain insight into the flexibility, versatility, and superior structural and functional controllability of PESf membrane pore structures, which could advance the development of pore structure control. Pending issues include the fact that, using a line analysis software of SPM devices, it is very difficult to measure hundred pores which clearly reflects the poor quality of pore size distributions obtained in this study, measurement accuracy must be improved further.
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Membranas Artificiais , Polímeros/química , Sulfonas/química , Permeabilidade , Diálise Renal/métodos , ÁguaRESUMO
The hollow fiber membrane bioreactor (HFMB) has been investigated for the cultivation of mammalian Chinese hamster ovary cell expansion. The experiments were carried out in Petri's dishes and in the hollow fiber membrane bioreactor having 20 fibers (S2025 from FiberCell Systems). The approach to HFMB modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. The hydrodynamic model is made using ANSYS Fluent software. The mathematical model of HFMB was developed, allowing the study of the hydrodynamics into the lumen and the extracapillary spaces, the filtration through the membrane fiber with the cell expansion on outer membrane surface. The direct nutrient medium flow variant into the extracapillary space was suggested. Based on the numerical simulations, the optimal parameters were selected for daily changes in the medium flow-rate into the lumen space. The HFMB scaling up was performed for the larger size HFMB (60 fibers).
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Reatores Biológicos , Técnicas de Cultura de Células , Membranas Artificiais , Modelos Teóricos , Animais , Células CHO , Cricetinae , CricetulusRESUMO
The tendency of highly supersaturated solutions of poorly water-soluble drugs to undergo liquid-liquid phase separation (LLPS) into drug-rich and water-rich phases when the concentration exceeds the amorphous solubility, for example, during dissolution of some amorphous solid dispersions, is thought to be advantageous from a bioavailability enhancement perspective. Recently, we have developed a high surface area, flow-through absorptive dissolution testing apparatus that enables fast mass transfer providing more in vivo relevant conditions and time frames for formulation testing. Using this apparatus, the absorption behaviors of solutions with different extents of supersaturation below and above the amorphous solubility were evaluated. In addition, simultaneous dissolution-absorption testing of amorphous solid dispersions (ASDs) with varying drug loadings and polymer types was carried out to study and distinguish the absorption behavior of ASDs that do or do not undergo LLPS. When compared with closed-compartment dissolution testing, a significant influence of the absorptive compartment on the dissolution rate of ASDs, particularly at high drug loadings, was observed. The formation of drug-rich nanodroplets, generated by both solvent-addition and ASD dissolution, resulted in a higher amount of drug transferred across the membrane. Moreover, the mass transfer was further enhanced with increasing concentration above the amorphous solubility, thereby showing correlation with an increase in the number of drug-rich particles. The importance of including an absorptive compartment in dissolution testing is highlighted in this study, enabling coupling of dissolution to membrane transport, and providing a more meaningful comparison between different formulations.