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.

The evolution of hemodialysis membranes (dialyzer, artificial kidney) was remarkable, since Dow Chemical began manufacturing hollow fiber hemodialyzers in 1968, especially because it involved industrial chemistry, including polymer synthesis and membrane manufacturing process. The development of hemodialysis membranes has brought about the field of medical devices as a major industry. In addition to conventional electron microscopy, scanning probe microscopy (SPM), represented by atomic force microscopy (AFM), has been used in membrane science research on porous membranes for hemodialysis, and membrane science contributes greatly to the hemodialyzer industry. Practical studies of membrane porous structure-function relationship have evolved, and methods for analyzing membrane cross-sectional morphology were developed, such as the ion milling method, which was capable of cutting membrane cross sections on the order of molecular size to obtain smooth surface structures. Recently, following the global pandemic of SARS-CoV-2 infection, many studies on new membranes for extracorporeal membrane oxygenator have been promptly reported, which also utilize membrane science researches. Membrane science is playing a prominent role in membrane-based technologies such as separation and fabrication, for hemodialysis, membrane oxygenator, lithium ion battery separators, lithium recycling, and seawater desalination. These practical studies contribute to the global medical devices industry.

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.

When using the extracorporeal capillary membrane oxygenator (sample A) for ECMO treatments of COVID-19 severely ill patients, which is dominantly used in Japan and worldwide, there is a concern about the risk of SARS-CoV-2 scattering from the gas outlet port of the membrane oxygenator. Terumo has launched two types of membranes (sample A and sample B), both of which are produced by the microphase separation processes using polymethylpentene (PMP) and polypropylene (PP), respectively. However, the pore structures of these membranes and the SARS-CoV-2 permeability through the membrane wall have not been clarified. In this study, we analyzed the pore structures of these gas exchange membranes using our previous approach and verified the SARS-CoV-2 permeation through the membrane wall. Both have the unique gradient and anisotropic pore structure which gradually become denser from the inside to the outside of the membrane wall, and the inner and outer surfaces of the membrane have completely different pore structures. The pore structure of sample A is also completely different from the other membrane made by the melt-extruded stretch process. From this, the pore structure of the ECMO membrane is controlled by designing various membrane-forming processes using the appropriate materials. In sample A, water vapor permeates through the coating layer on the outer surface, but no pores that allow SARS-CoV-2 to penetrate are observed. Therefore, it is unlikely that SARS-CoV-2 permeates through the membrane wall and scatter from sample A, raising the possibility of secondary ECMO infection. These results provide new insights into the evolution of a next-generation ECMO membrane.

The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient's blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

This article developes a pediatric membrane oxygenator that is compact, high performance, and highly safe. This novel experimental approach, which imaging the inside of a membrane oxygenator during fluid perfusion using high-power X-ray CT, identifies air and blood retention in the local part of a membrane oxygenator. The cause of excessive pressure drop in a membrane oxygenator, which has been the most serious dysfunction in cardiovascular surgery and extracorporeal membrane oxygenation (ECMO), is the local retention of blood and air inside the oxygenator. Our designed blood flow channel for a membrane oxygenator has a circular channel and minimizes the boundary between laminated parts. The pressure drop in the blood flow channel is reduced, and the maximum gas transfer rates are increased by using this pediatric membrane oxygenator, as compared with the conventional oxygenator. Furthermore, it would be possible to reduce the incidents, which have occurred clinically, due to excessive pressure drop in the blood flow channel of the membrane oxygenator. The membrane oxygenator is said to be the "last stronghold" for patients with COVID-19 receiving ECMO treatment. Accordingly, the specification of our prototype is promising for low weight and pediatric patients.

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.

Thomas Grahamが拡散の原理を1854年に発見し、Dow Chemical社が1968年に中空糸型血液浄化器の量産を始めてから、血液浄化技術は大きな進化を遂げた。その中でも血液浄化膜の進歩には特筆すべきものがあり、特に高分子の合成と中空糸膜の製膜技術などの工業化学を巻き込んだ進歩は一大医療機器産業へと発展した。さらに、走査型プローブ顕微鏡技術などによる細孔構造評価・解析法が確立され、並行して理論的・定量的アプローチによる膜透過理論が進化した。そうした膜科学と実用化技術は、米国、ドイツおよび日本が先行するが、最近は中国、インド、東南アジアおよび中東諸国の追い上げが凄まじい。血液浄化膜のイノベーションは中空糸膜とポリスルホン膜の登場であった。そこでこの総説では、膜工学(血液浄化膜)における最近の進歩についてレビューする。血液浄化膜の最新技術について生体適合性と細孔構造解析という二つの観点から検討する。企業への適正利潤は次世代医療機器開発のモチベーションであり、イノベーションの製品化に奏功する。逆の場合、当該医療機器産業の衰退に繋がり、ひいては当該医療水準の劣化にも繋がりかねない。血液浄化膜(器)は日本が誇る治療用医療機器の一つである。日本人らしい繊細な匠の技の長年の積み上げが奏功している。次の破壊的イノベーションを見据えつつ、日本発の血液浄化膜が持続的イノベーションを積み上げながら、今後も世界の血液浄化医療に貢献することを願う。(著者抄録)

Thomas Grahamが拡散の原理を1854年に発見し、Dow Chemical社が1968年に中空糸型血液浄化器の量産を始めてから、血液浄化技術は大きな進化を遂げた。その中でも血液浄化膜の進歩には特筆すべきものがあり、特に高分子の合成と中空糸膜の製膜技術などの工業化学を巻き込んだ進歩は一大医療機器産業へと発展した。さらに、顕微鏡観察技術などの評価法が確立され、並行して理論的・定量的アプローチによる膜透過理論が進化した。そうした膜科学と実用化技術は、米国、ドイツおよび日本が先行するが、最近は中国、インドおよび中東諸国の追い上げがすさまじい。血液浄化膜のイノベーションは中空糸膜とポリスルホン膜の登場であった。そこでこの特別寄稿では、血液浄化膜の誕生とその後の進化についてレビューする。血液浄化膜の最新技術について生体適合性と膜透過理論という二つの観点から検討し、今後の持続的および破壊的イノベーションにも触れたい。(著者抄録)

© 2019, Japanese Society for Medical and Biological Engineering. All rights reserved. A hemoconcentrator is installed as a part of cardiopulmonary bypass to concentrate the blood by removing excess water and unnecessary electrolytes from the blood diluted with myocardial protection fluid. The hemoconcentrator must remove water from diluted blood efficiently and quickly and remove proinflamma-tory cytokines and other unwanted molecules, without losing useful proteins such as albumin. Especially, the pore diameter and diameter distribution of the innermost surface greatly affect the pure water permeability and sieving coefficient of the solutes. In this study, the pore structure of the inner surface of the membrane was observed, and pore measurement of hollow fiber hemoconcentrator membranes was attempted using a scanning probe microscope (SPM). The samples studied were commercially available hemoconcentrator membranes PUREMA A and B (JMS Co. Ltd., Japan) having asymmetric structures. A SPM was used using the dynamic force microscopy (DFM), cyclic contact mode. The deep and tortuous pore structure on the inner surface of the hemoconcentrator membrane was observed for the first time using DFM. The pores had an elliptical shape, elongated in the longitudinal direction. When the elliptical area on the inner surface of the hemoconcentrator membrane was larger, pure water permeability was higher, showing a correlation between the elliptical area and membrane functions. The mean major pore diameters and minor pore diameters as well as the equivalent pore diameter calculated from the tortuous capillary pore model were consistent. Using DFM, the three-dimensional tortuous capillary pores at the inner surface of a hollow fiber hemoconcentrator membrane could be studied, and pore diameter and distribution could be measured by image analysis. The results were supported by the tortuous capillary pore model. In the future, we need to clearly show the further superior innovations or creative/ ingenious techniques related to this study. Further the state of new findings which contribute to development of a new hemoconcentrator and other semipermeable membranes will help to increase the value of this paper. This study is one of the key studies to achieve the targeted function for the transport phenomena through semipermeable membranes including hemoconcentrator.

The objective of the present study is to evaluate the effect of filtration coefficient and internal filtration on dialysis fluid flow and mass transfer coefficient in dialyzers using dimensionless mass transfer correlation equations. Aqueous solution of vitamin B-12 clearances were obtained for REXEED-15L as a low flux dialyzer, and APS-15EA and APS-15UA as high flux dialyzers. All the other design specifications were identical for these dialyzers except for filtration coefficient. The overall mass transfer coefficient was calculated, moreover, the exponents of Reynolds number (Re) and film mass transfer coefficient of the dialysis-side fluid (k(D)) for each flow rate were derived from the Wilson plot and dimensionless correlation equation. The exponents of Re were 0.4 for the low flux dialyzer whereas 0.5 for the high flux dialyzers. Dialysis fluid of the low flux dialyzer was close to laminar flow because of its low filtration coefficient. On the other hand, dialysis fluid of the high flux dialyzers was assumed to be orthogonal flow. Higher filtration coefficient was associated with higher k(D) influenced by mass transfer rate through diffusion and internal filtration. Higher filtration coefficient of dialyzers and internal filtration affect orthogonal flow of dialysis fluid.

Some dialysis patients are treated with post-hemodiafiltration (HDF); the blood viscosity of the patients who undergo post-HDF is higher than that of the patients who undergo conventional hemodialysis. This study aims to evaluate poly(N-vinyl-2-pyrrolidone) (PVP) elution from PSf dialysis membranes by varying solvents and high wall shear stress caused by blood viscosity. We tested three commercial membranes: APS-15SA (Asahi Kasei Kuraray), CX-1.6U (Toray) and FX140 (Fresenius). Dialysate and blood sides of the dialyzers were primed with reverse osmosis (RO) water and saline. RO water, saline and dextran solution (2.9 and 5.8 mPa s) were circulated in the blood side. The amount of eluted PVP was determined by 0.02 N iodometry. The hardness and adsorption force of human serum albumin (HSA) on the membrane surfaces were measured by the atomic force microscope. When wall shear stress was increased using dextran, the amount of PVP eluted by the 2.9 mPa s solution equaled that eluted by the 5.8 mPa s solution with APS-15SA and CX-1.6U sterilized by gamma rays. The amount of PVP eluted by the 5.8 mPa s solution was higher than that eluted by the 2.9 mPa s solution with FX140 sterilized by autoclaving. The wall shear stress increased the PVP elution from the surface, hardness and adsorption force of HSA. Sufficient gamma-ray irradiation is effective in decreasing PVP elution.

Removal rate of renal toxic substances in a dialyzer depends on the mass transfer rate through a dialysis membrane and in the dialysate-side boundary films. To increasing dialysis fluid-side mass transfer rate, the most important factors are jacket structure and hollow fiber shape, so newly developed dialyzers with improved jacket structure and hollow fiber shape that optimize dialysis fluid flow have been made available on the market in recent years.
The overall mass transfer resistance is the sum of the resistances due to the membrane itself and the thin boundary film that is formed in the fluids on both sides of the membrane (Series Boundary Film Resistance Model). The boundary film mass transfer coefficient for a fluid flowing within a straight tube has been obtained theoretically. Colburn's equation converted to mass transfer by analogy with the theoretical approximation equation that yields the boundary film coefficient of heat transmission when laminar flow occurs in a straight tube, can be used to calculate the boundary film transfer in laminar mass transfer.
In the present study, mass transfer correlation equations between Sherwood number (Sh) containing dialysis fluidside mass transfer film coefficient and Reynolds number (Re) were formed for newly developed dialyzers. The exponents of Re were 0.62 for APS-15S whereas approximately 0.5 for the newly developed dialyzers. The dialysis fluid-side mass transfer film coefficients of the newly developed dialyzers were higher than those of the conventional dialyzer. Based on the mass transfer correlation equations, introduction of short taper, full baffle of dialyzer jacket and further wave-shaped hollow fiber improves the dialysis fluid flow.

Reactive oxygen species (ROS) generated during hemodialysis treatment cause dialysis complications because of the high reactivity of ROS. To prevent dialysis complications caused by oxidative stress, it is important to evaluate the generation and dismutation of ROS during hemodialysis treatment. In this study, our aim was to develop a device to determine superoxide (O(2) (-)) generated inside a dialysis hollow fiber, and also to examine whether this device could detect O(2) (-) separated from plasma using hollow fibers. Experimental apparatus was set up so that hypoxanthine (HX) solution flowed inside the hollow fibers and 2-methyl-6-p-methoxyphenylethynyl-imidazopyrazinone (MPEC) solution flowed outside the hollow fibers. Then, xanthine oxidase (XOD) solution was added to the HX solution to generate O(2) (-), and chemiluminescence resulting from the reaction of O(2) (-) with MPEC was measured with an optical fiber. Chemiluminescence intensity was measured at different HX concentrations, and the peak area of relative luminescence intensity yielded a first-order correlation with the HX concentration. Based on the relationship between HX and O(2) (-) concentrations determined by the cytochrome c reduction method, the relative luminescence intensity measured by this device was linearly dependent on the O(2) (-) concentration inside the hollow fibers. After modifications were made to the device, XOD solution injection into plasma including HX resulted in an increase in the relative luminescence intensity. We concluded that this novel device based on chemiluminescence is capable of determining aqueous O(2) (-) generated inside a hollow fiber and also of detecting O(2) (-) in plasma.

The concentrations of hepatitis C virus (HCV) are reported to be lower in dialysis patients than in HCV-positive non-dialysis patients. We investigated the elimination dynamics of HCV antigens (core proteins) levels pre- and post-dialysis using a regenerated cellulose membrane (CU ; AM-FP1.3), cellulose triacetate membrane (CTA ; FB-150E), polymethylmethacrylate membrane (PMMA ; BK-1.6P), or polysulfone membrane (PS ; F-70S). The rates of HCV antigen decrease by a single dialysis session were as follows 32.7&plusmn;10.5% with the F-70S, 19.0&plusmn;2.2% with the BK-1.6P, 10.4&plusmn;1.7% with the FB-150E, and 8.8&plusmn;2.2% with the AM-FP1.3. Furthermore, we compared the HCV antigen elimination ability of each dialysis membrane material in an <I>in vitro</I> experiment. We perfused albumin (Alb) containing HCV in the blood circuit connected to AM-FP1.3, FB-130U, BK-1.3P, and F-60S, and measured quantities of HCV antigen and Alb over time. The quantity of HCV antigen decreased 25.8% with the F-60S, 20.5% with the BK-1.3P, 16.0% with the FB-130U, and 10.5% with the AM-FP1.3. Furthermore, to confirm HCV adsorption to the dialysis membrane, we perfused washing solution containing non-ionic surfactant in the blood circuit used in the above investigation, and measured quantities of HCV antigen in the washing solution. The quantities of HCV antigen eluted in the washing solution were nearly equivalent to the decreases in HCV observed in the <I>in vitro</I> experiment. In conclusion, HCV in blood is adsorbed and eliminated by dialysis membranes.

Dialyzer performance strongly depends on the flow of blood and dialysis fluid as well as membrane performance. It is necessary, particularly to optimize dialysis fluid flow, to develop a highly efficient dialyzer. The objective of the present study is to evaluate by computational analysis the effects of dialyzer jacket baffle structure, taper angle, and taper length on dialysis fluid flow. We modeled 10 dialyzers of varying baffle angles (0, 30, 120, 240, and 360 degrees) with and without tapers. We also modeled 30 dialyzers of varying taper lengths (0, 12.5, 25.0, and 50.0 mm) and angles (0, 2, 4, and 6 degrees) based on technical data of APS-SA dialyzers having varying surface areas of 0.8, 1.5, and 2.5 m(2) (Rexeed). Dialysis fluid flow velocity was calculated by the finite element method. The taper part was divided into 10 sections of varying fluid resistances. A pressure of 0 Pa was set at the dialysis fluid outlet, and a dialysis fluid flow rate of 500 mL/min at the dialysis fluid inlet. Water was used as the dialysis fluid in the computational analysis. Results for dialysis fluid flow velocity of the modeled dialyzers indicate that taper design and a fully surrounded baffle are important in making the dialysis fluid flow into a hollow-fiber bundle easily and uniformly. However, dialysis fluid flow channeling occurred particularly at the outflowing part with dialyzers having larger taper lengths and angles. Optimum design of dialysis jacket structure is essential to optimizing dialysis fluid flow and to increasing dialyzer performance.

Dialysis fluid flow and mass transfer rate of newly developed dialyzers were evaluated using mass transfer correlation equations of dialysis fluid-side film coefficient. Aqueous creatinine clearance and overall mass transfer coefficient for APS-15S (Asahi Kasei Kuraray) as a conventional dialyzer, and APS-15SA (Asahi Kasei Kuraray), PES-150S alpha (Nipro), FPX140 (Fresenius), and CS-1.61U (Toray) as newly developed dialyzers were obtained at a blood-side flow rate (Q,) of 200 ml/min, dialysis fluid-side flow rates (Q(D)) of 200-800 ml/min and a net filtration rate (Q,) of 0 ml/min. Mass transfer correlation equations between Sherwood number (Sh) containing dialysis fluid-side mass transfer film coefficient and Reynolds number (Re) were formed for each dialyzer. The exponents of Re were 0.62 for APS-15S whereas approximately 0.5 for the newly developed dialyzers. The dialysis fluid-side mass transfer film coefficients of the newly developed dialyzers were higher than those of the conventional dialyzer. Based on the mass transfer correlation equations, introduction of short taper, full baffle of dialyzer jacket and further wave-shaped hollow fiber improves the dialysis fluid flow of the newly developed dialyzers. ASAIO journal 2009; 55:231-235.

The objective of the present study was to evaluate the characteristics of protein adsorption on the inner surface of various dialysis membranes, to develop protein adsorption-resistant biocompatible dialysis membranes. The adsorption force of human serum albumin (HSA) on the inner surface of a dialysis membrane and the smoothness of the membrane were evaluated from a nanoscale perspective by atomic force microscopy. The content ratio of the hydrophilic polymer, polyvinylpyrrolidone (PVP), was determined by attenuated total reflection Fourier transform infrared spectroscopy. Nine synthetic-polymer dialysis membranes on the market made of polysulfone (PSF), polyethersulfone (PES), polyester polymer-alloy (PEPA), and ethylene vinylalcohol (EVAL) were used in the present study. The HSA adsorption force on the surface of the hydrophobic polymer PEPA membrane was higher than that on the hydrophilic polymer EVAL membrane surface. It has been considered beneficial, for decreasing the HSA adsorption force, to cover a hydrophobic polymer membrane surface with PVP. However, there were some areas on PVP-containing membrane surfaces at which much higher HSA adsorption forces were observed. The HSA adsorption force gave a nearly linear correlation with the surface roughness on the PSF membrane surface. However, the HSA adsorption force was uncorrelated with the PVP content ratio for any of the PSF membrane surfaces tested. in conclusion, protein adsorption can be minimized by the use of dialysis membranes made of hydrophobic polymers containing PVP with a smooth surface. ASAIO journal 2009; 55:236-242.

When uremic blood flows through dialyzers during hemodialysis, dialysis membrane surfaces are exposed to shear stress and internal filtration, which may affect the surface characteristics of the dialysis membranes. In the present study, we evaluated changes in the characteristics of membrane surfaces caused by shear stress and internal filtration using blood substitutes: water purified by reverse osmosis and 6.7 wt% dextran70 solution. We focused on the levels of a hydrophilic modifier, polyvinylpyrrolidone (PVP), on the membrane surface measured by attenuated total reflectance Fourier transform infrared spectroscopy. Experiments involving 4 h dialysis, 0-144 h shear-stress loading, and 4 h dead-end filtration were performed using polyester-polymer alloy (PEPA) and polysulfone (PS) membranes. After the dialysis experiments with accompanying internal filtration, average PVP retention on the PEPA membrane surface was 93.7% in all areas, whereas that on the PS membrane surface was 98.9% in all areas. After the shear-stress loading experiments, PVP retention on the PEPA membrane surface decreased as shear-stress loading time and the magnitude of shear stress increased. However, with the PS membrane, PVP retention scarcely changed. After the dead-end filtration experiments, PVP retention decreased in all areas for both PEPA and PS membranes, but PVP retention on the PEPA membrane surface was lower than that on the PS membrane surface. PVP on the PEPA membrane surface was eluted by both shear stress and internal filtration, while that on the PS membrane surface was eluted only by internal filtration.

Hydrophilizing synthetic polymer dialysis membranes with polyvinylpyrrolidone (PVP) play an important role for inhibition of protein adsorption on membrane surface. In the present study, the effect of PVP on protein adsorption was evaluated from a nano-scale perspective. Swelling behavior of PVP present on wet polysulfone (PS)/PVP film surfaces was observed by atomic force microscopy (AFM). Fibrinogen and human serum albumin (HSA) were immobilized on the tip of AFM probes, with which a force-curve between protein and wet PS/PVP film surface was measured by AFM while scanning in order to visualize two-dimensional protein adsorbability on film surfaces. Furthermore, HSA adsorbability on non-PVP containing PEPA dialysis membrane (FLX-15GW) and PVP containing PEPA dialysis membrane (FDX-150GW) was evaluated by the AFM force-curve method. As a result, PS/PVP film surface was completely covered with hydrated and swollen PVP at 5 wt% or more PVP content. Protein adsorbability on PS/PVP film surfaces decreased greatly with increasing content of PVP. The adsorption of HSA was inhibited by the presence of PVP on film surfaces more significantly than that of more hydrophobic fibrinogen. HSA adsorbability on wet FLX-15GW dialysis membrane surface was 428+/-174 pN whereas that on wet FDX-150GW dialysis membrane surface was 42+/-29 pN. (C) 2007 Elsevier B.V. All rights reserved.

透析で用いられている合成高分子膜のうち、ポリスルホン(PS)とポリエステル系ポリマアロイ(PEPA)は、親水化剤であるポリビニルピロリドン(PVP)を添加することによって膜表面を親水化し、生体適合性の向上を図っている。しかし、透析により生じる中空糸膜表面のPVP分布の変化を定量的に検討した例はない。そこで、本研究では、透析器内の中空糸膜を軸方向および断面方向のいくつかのエリアに分け、各エリアにおける膜表面PVP残存率を測定し、PVPの溶出性を評価した。APS-15EX(試作品:PS膜、旭化成メディカル)およびFDX-15GW(PEPA膜、日機装)の透析器を用いて、血液側流量200mL/min、透析液側流量500mL/minで4時間透析を行った。このとき、血液側には血液と同粘度を有する6.7wt%デキストラン70水溶液、透析液側には逆浸透水を用いた。透析終了後に透析器ジャケットを取り外し、各エリア(透析器軸方向に3分割、断面方向に12分割、合計36エリア)から中空糸を取り出した。全反射減衰フーリエ変換赤外分光法(FTIR/ATR)で透析前後の中空糸膜内表面におけるPVP残存率を測定した。APS-15EXおよびFDX-15GWのいずれの透析器も、透析によって膜表面PVP残存率はすべてのエリアで減少しており、すべてのエリアでPVPが溶出したことがわかった。なお、APS-15EXとFDX-15GWの平均PVP残存率は、それぞれ94.1%、90.8%となり、APS-15EXの方が若干高いPVP残存率を示した。さらに、断面方向と軸方向で比較したところ、いずれの透析器も次のように同様の傾向を示した。断面方向では各断面にPVP残存率の偏りがみられた。軸方向では、中空糸束中央部に比較して、内部濾過量の多い中空糸束両端部においてPVP残存率が著しく低下した。特に、濾過が生じている血液出口部において、この傾向は顕著であった。(著者抄録)

The antioxidation property of vitamin E-coated dialysis membrane is effective for reduction of oxidative stress. Effect of amount of vitamin E coating on antioxidation property has been poorly understood yet. In the present study, we evaluated a relationship between amount of vitamin E coating and antioxidation property using a superoxide probe of 2-methyl-6-p-methoxyphenylethynylimidazopyrazinone (MPEC) by the optical fiber method to determine optimum amount of vitamin E coating and to improve antioxidation property of the vitamin E-coated dialysis membrane. Furthermore, from the viewpoint of reuse, we examined recovery of oxidized vitamin E by vitamin C treatment. In conclusion, it is necessary to coat polysulfone dialysis membranes with vitamin E at over 74 mg/m(2). The antioxidation property is recoverable by treating dialysis membrane containing oxidized vitamin E with vitamin C. By administrating vitamin C, higher antioxidation property may be realized with a small amount of vitamin E coating. (c) 2007 Elsevier B.V. All rights reserved.

Rexeed was developed by Asahi Kasei Medical using wave-shaped hollow fibers, a full baffle, and a short taper housing to improve dialysate flow. The present study is clarifies improvement in dialysate flow with Rexeed-15 compared with that of a conventional dialyzer. Dialysate flow was evaluated by the pulse-response method. Dialysate pressure and tracer concentration were measured at a blood-side flow rate (Q(B)) of 200 ml/min, a dialysate-side flow rate (Q(D)) of 500 ml/min, and a net filtration rate (Q(F)) of 0 ml/min using needles placed in the test dialyzer. Dialyzer performance was evaluated by measuring urea and vitamin B-12 clearance at Q(B) = 200 and 400 ml/min, Q(D) = 300-800 ml/min, and Q(F) = 0 ml/min. In the conventional dialyzer, dialysate channeling was observed. In contrast, Rexeed-15 had a uniform dialysate flow. Urea and vitamin B-12 clearance with Rexeed-15 was slightly sensitive to Q(D). The overall mass transfer coefficient for urea with Rexeed-15 was more than 50% higher than that of the conventional dialyzer, indicating the possibility of reduced dialysate usage with Rexeed. Rexeed has a highly optimal dialysate flow, due to the wave-shaped hollow fibers and the new housing, and gives increased clearance for lower-molecular-weight substances.

The tortuous capillary pore diffusion model (TCPDM) has been used for estimating diffusive and pure water permeability from simple structure parameters such as pore diameter, surface porosity, wall thickness and tortuosity. The validity of this model for evaluation of homogeneous membrane has been already confirmed. Recently, there is a trend toward the use of asymmetrical dialysis membranes made of synthetic polymer such as poly(acrylonitrile) (PAN), polysulfone (PS) and a polyethersulfone polyarylate (PEPA) blend polymer. The purpose of the present study is to apply the TCPDM to evaluation of commercially available hollow-fiber dialysis membranes with asymmetrical structures by simplifying them to a double-layer membrane. The TCPDM is capable of estimating pore tortuosity of asymmetrical dialysis membranes having skin and supporting layers from data on membrane thickness, pore diameter, pure water permeability and water content. Values for diffusive permeability obtained by the TCPDM are in a good agreement with experimental data. This TCPDM model is useful for evaluation of not only homogeneous membrane but also asymmetrical membrane. (c) 2006 Elsevier B.V. All rights reserved.

Dialyzer performance seems to greatly depend on the hollow-fiber membrane performance, the morphology of the hollow-fiber membrane bundles (e.g., wave-shaped hollow-fiber membrane bundles), and the design of the dialyzer housing. Consequently, we developed the APS dialyzer APS-SA series, equipped with wave-shaped hollow-fiber membrane bundles as an optimal three-dimensional morphology along with new housings, to realize enhanced dialysis performance. Incorporation of a new type of housing, including a full baffle structure and a short taper section, and a new type of morphology for the hollow-fiber membrane bundles have been verified to allow the dialysate to diffuse uniformly along the full baffle panel around the circumference and to fully permeate into the core of the hollow-fiber bundle. As a result, the APS-SA series has been proved to have achieved enhanced diffusion performance and increased clearance of small molecule solutes such as urea and creatinine, compared with conventional dialyzers. This series is expected to provide increased Kt/V values and dialysate-saving performance in future clinical use. © 2006 The Japanese Society for Artificial Organs.

For efficient removal of large molecular weight solutes by dialysis, several types of internal filtration-enhancing dialyzers (IFEDs) are commercially available. However, in a pressure-driven membrane separation process (i.e., filtration), membrane fouling caused by adhesion of plasma proteins is a severe problem. The objective of the present study is to investigate the effects of internal filtration on membrane fouling based on the membrane's pure-water permeability, diffusive permeability, and sieving coefficient. Hemodialysis experiments were performed with two different dialyzers, IFEDs and non-IFEDs. Local membrane fouling in each dialyzer was evaluated by measuring the pure-water permeability, the diffusive permeability, and the sieving coefficient of native membranes and membranes treated with bovine blood. The effects of packing ratio on dialysate flow pattern were also evaluated by measuring the time required for an ion tracer to reach electrodes placed in the dialyzers. In the IFED, membrane fouling caused by protein adhesion is increased because of enhanced internal filtration only at the early stage of dialysis, and this fouling tends to occur only near the dialysate outlet port. However, enhanced internal filtration has little effect on measured membrane transfer parameters. © The Japanese Society for Artificial Organs 2005.

Accumulated low molecular weight proteins in hemodialysis patients require a high-flux dialyzer. There have been several methods proposed for enhancing internal filtration, including narrowing the inside diameter of the hollow fibers, lengthening the fibers, and increasing the fiber density ratio. We tried to enhance the internal filtration by increasing the pressure drop in the dialysate compartment through increasing the fiber density ratio. If the fiber density ratio is too high, however, an irregular dialysate path may result, thus decreasing dialysis performance. Therefore, we took note of the shape of the inner housing and added a short taper structure, which improved the dialysate path dramatically. Consequently, we developed an internal filtration-enhanced dialyzer (APS-Prototype) to improve dialysis performance. The internal filtration rate in water (measured by Doppler ultrasound) was 13.2l/session for the APS-Prototype and 5.3l/session for the APS-15E. The amount of α1-microglobulin (α1-MG) in bovine plasma was 0.34 g for the APS-Prototype and 0.11 g for the APS-15E. In addition, the amount of α1-MG in vivo was 29.0% ± 5.8% for the APS-Prototype, significantly higher than that for the APS-15E (13.6% ± 1.9%). The desirable loss of albumin is 2-4 g in hemodiafiltration, and it was 3.92 ± 1.03 g for the APS-Prototype. The prototype showed excellent solute removal performance with no clinical or engineering problems.

In a hollow-fiber dialyzer, uremic toxins are removed by diffusion and convection, which are influenced by the dialysate flow patterns in the dialyzer. Recently available high-performance dialyzers have complicated dialysate flow patterns, because both positive filtration and negative filtration occur. The objective of the present study was to evaluate dialysate flow in high-performance dialyzers experimentally. Glass-coated 0.1 mmφ platinum electrodes were used for the electrode counter and the working electrode. A counter electrode was placed at the inlet of the dialyzer, and working electrodes were placed at 20 different positions. A voltage of 0.5V was applied between the counter and the working electrodes with a potentiostat, and after the dialyzer was filled with water purified by reverse osmosis, 0.9% NaCl solution was caused to flow. The time at which the 0.9% NaCl solution reached each working electrode from the counter electrode was then measured at a dialysate-side flow rate of 300ml/min and blood-side flow rates of 0 and 200 ml/min. It was found that in dialyzers with high permeability to pure water, dialysate flow was affected by both positive and negative filtration. A comparison was then made between the experimental results and the results of simulation by the finite element method at positions at which positive and negative filtration occurred, good agreement was obtained. This method makes possible the experimental evaluation of dialysate flow in a high-performance dialyzer in which positive and negative filtration occur.

〈BIOREX AM-BC-X〉 is a new cellulosic membrane whose pore size is distributed asymmetrically in the membrane wall. The objectives of the present study are to clarify the phenomenon of solute transfer occurring inside dialyzers made from asymmetric membranes, to examine the structure of the asymmetric membrane capable of suppressing the inflow of endotoxins from dialysate, and thereby to contribute to the design of a more effective dialysis membrane. Using membranes that have tight layers on both sides (drum-shaped membrane, 〈BIOREX AM-BC-X〉 with the outer one tighter, solutes are more easily transferred from the inside out than from the outside in, leading to effective removal of pathogenic substances from blood and a significant lowering of endotoxin inflow from the dialysate. In asymmetric dialysis membranes, the anisotropy of solute permeability is caused by the difference in the amount of solute transfer due to filtration from the inside out and from the outside in.

«BIOREX AM-BC-X» is a new cellulosic membrane whose pore size is distributed asymmetrically in the membrane wall. The objectives of the present study are to clarify the phenomenon of solute transfer occurring inside dialyzers made from asymmetric membranes, to examine the structure of the asymmetric membrane capable of suppressing the inflow of endotoxins from dialysate, and thereby to contribute to the design of a more effective dialysis mem-brane. Using membranes that have tight layers on both sides (drum-shaped membrane), «(BIOREX AM-BC-X») with the outer one tighter, solutes are more easily transferred from the inside out than from the outside in, leading to effective removal of pathogenic substances from blood and a significant lowering of endotoxin inflow from the dialysate. In asymmetric dialysis membranes, the anisotropy of solute permeability is caused by the difference in the amount of solute transfer due to filtration from the inside out and from the outside in.

A great deal of research has been conducted focusing on membrane materials with reference to their blood compatibility, but blood compatibility is influenced both by the material used in membranes and their structure, and by the flow conditions at the membrane surface. Accordingly, the relationship between membrane surface roughness and hemocompatibility has been evaluated using five types of membranes of differing surface roughness by evaluating the inner surfaces of the hollow fibers by atomic force microscopy (AFM) and by measuring platelet adhesion ratios using bovine blood. The yield stress, which equates to flow characteristics, was also evaluated using a glycerol suspension of polymethylmethacrylate (PMMA), a Bingham fluid. It was found that membranes having rough surfaces had high platelet adhesion ratios and poor hemocompatibility, whereas those with smoother surfaces had lower platelet adhesion ratios and better hemocompatibility. Measurement of the yield stresses for these membranes revealed higher values far those with rough surfaces, and lower values for those with smoother polyethylene glycol (PEG) grafted surfaces. This suggests that flow conditions at the membrane surface differ according to its surface roughness, and that this difference in flow conditions also influences hemocompatibility.

The new biocompatible cellulosic membrane (AM-BC-F [AM-BIO-HX], Asahi-Medical Co. Ltd., Tokyo, Japan) has been developed, which has a higher flux than conventional membranes and more excellent antithrombogenicity because of its smoother membrane surface. The roughness of the inner surface of the AM-BC-F membrane was smaller than that of conventional membranes, as observed by Atomic Force Microscopy, because it was produced by the newly developed spinning method of cuprammonium cellulose solution, which has a different composition from that of a conventional cuprammonium cellulose solution. The degree of platelet adhesion (number of platelets adhered) on the membrane surface was evaluated in vitro by the measurement of the amount of the LDH released from the adhered platelets on the membrane surface after contact with fresh blood of Japanese male white rabbits weighing 2.5-3.0 kg. The number of platelets adhered of AM-BC-F was far smaller than that of conventional membranes. It was deduced from the smoother surface of the membrane. It can be expected that AM-BC-F will have an excellent antithrombogenicity on a dynamic state during actual dialysis treatments, because it is considered that the shearing stress of blood on the inner surface and the interaction between platelets and the membrane surface are less than that of conventional membrane2s. (C) 1999 John Wiley & Sons, Inc.

A new biocompati ble cellulosic membrane «BIOREX AM-BC-F» has been developed, which has a higher flux than conventional membranes and more excellent anti-thrombogenicity. These improvements are due to the membrane's smoother surface. The inner surface of the «AM-BC-F» membrane was less rough than that of conventional membranes, an observation conducted by Atomic Force Microscopy. The membrane was produced by the newly developed cuprammonium cellulose solution spinning, which has a different composition from that of a conventional cuprammonium cellulose solution. The degree of platelet adhesion (number of platelet adhered) on the membrane surface was evaluated in vitro. The number of platelet that adhered to the «AM-BC-F» was far smaller than that of conventional membranes. It was thought that these results were due to the membrane's smoother surface.

«BIOREX AM-BC-X» is a new cellulosic membrane with a symmetrical gradient morphology in pore size distribution in the membrane wall. The pore radius surrounding the middle part of the membrane wall is larger than that of the «BIOREX AM-BC-F». The inner surface is as smooth as that of the «AM-BC-F». «BIOREX AM-BC-X» has some advantages required for hemodialysis membranes, (1) reduced mass transfer resistance, (2) reduced backfiltration of pyrogens from dialysate side into blood side, (3) reduced albumin penetration and adhesion onto membrane wall, (4) adequate mechanical strength, compared with symmetrical, gradient, reversed gradient pore structure membranes, respectively. These characteristic advantages are brought about by the symmetrical gradient pore structure.

<BIOREX AM-BC-X> is a new cellulosic membrane with a symmetrical gradient morphology in pore size distribution in the membrane wall. The pore radius surrounding the middle part of the membrane wall is larger than that of the <BIOREX AM-BC-F>. The inner surface is as smooth as that of the <AM- BC-F>. <BIOREX AM-BC-X> has some advantages required for hemodialysis membranes, (1) reduced mass transfer resistance, (2) reduced backfiltration of pyrogens from dialysate side into blood side, (3) reduced albumin penetration and adhesion onto membrane wall, (4) adequate mechanical strength, compared with symmetrical, gradient, reversed gradient pore structure membranes, respectively. These characteristic advantages are brought about by the symmetrical gradient pore structure.

A new biocompatible cellulosic membrane (BIOREX AM-BC-F) has been developed, which has a higher flux than conventional membranes and more excellent anti-thrombogenicity. These improvements are due to the membrane's smoother surface. The inner surface of the (AM-BC-F) membrane was less rough than that of conventional membranes, an observation conducted by Atomic Force Microscopy. The membrane was produced by the newly developed cuprammonium cellulose solution spinning, which has a different composition from that of a conventional cuprammonium cellulose solution. The degree of platelet adhesion (number of platelet adhered) on the membrane surface was evaluated in vitro. The number of platelet that adhered to the <AM-BC-F> was far smaller than that of conventional membranes. It was thought that these results were due to the membrane's smoother surface.

The objectives of the present study are to clarify the phenomenon of solute transfer occurring inside dialyzers made from asymmetric membranes, to examine the structure of asymmetric membranes capable of suppressing the inflow of endotoxins from the dialysate, and thereby to contribute to the design of a more effective dialysis membrane. Using membranes that have tight layers on both sides (drum-shaped membrane) with the outer one tighter, solutes are more easily transferred from the inside out than from the outside in, leading to effective removal of pathogenic substances from the blood and a significant lowering of endotoxin inflow from the dialysate. The anisotropy of solute permeability of asymmetric dialysis membranes is caused by the difference in the amount of solute transfer due to filtration from the inside out and from the outside in. (C) 1998 Elsevier Science S.A. All rights reserved.

Biocompatibility of dialysis membrane has been studied directing our attention to difference in membrane material. To clarify a membrane of thrombus formation, it should be evaluated with respect to not only membrane material but also flow characteristics on membrane surface depending on surface roughness. Platelet adhesion on the membrane surface was measured using 5 dialysis membranes of different surface roughneses. Bovine blood (500ml) added with trisodium citrate dihydrate (approximately 2g) as an anticoagulant was circulated in a test dialyzer at a flow rate of 200ml/min. Pressure drop and flow rate of PMMA (particle diameter: 1μm) suspension in glycerol(Bingham fluid)(glycerol: PMMA=2: 1 by weight ratio) were measured to determine yield stress. The yield stress of the membranes and increased with surface roughness. The amount of platelet adhesion increased with yield stress, indicating that the platelet adhesion depends on surface roughness.

((BIOREX AM-BC-F)) is the new cellulosic membrane of which the inner surface is smoother than that of conventional cellulosic membrane, and alkyl ether carboxylic acid(polyethylene glycol) chain is grafted onto the inner surface of the membrane. ((AM-BC-F)) is produced by the new spinning method ((FIS(Fine Inner Surface) Technology)). It can be expected that it reduces hydrodynamic resistance between blood and the membrane. And it reduces complement activation in vivo, because rapid movement of the flexible PEG chain, ((Diffusive Layer)), leads to less interaction between blood and membrane.

<<BIOREX AM-BC-F>> is the new cellulosic membrane of which the inner surface is smoother than that of conventional cellulosic membrane, and alkyl ether carboxylic acid(polyethylene glycol) chain is grafted onto the inner surface of the membrane. <<AM-BC-F>> is produced by the new spinning method <<FIS(Fine Inner Surface) Technology>>. It can be expected that it reduces hydrodynamic resistance between blood and the membrane. And it reduces complement activation in vivo, because rapid movement of the flexible PEG chain, <<Diffusive Layer>>, leads to less interaction between blood and membrane.

Biocompatibility of dialysis membrane has been studied directing our attention to difference in membrane material. To clarify a membrane of bus formation, it should be evaluated with respect to not only membrane material but also flow characteristics on membrane surface depending on surface roughness. Platelet adhesion on the membrane surface was measured using 5 dialysis membranes of different surface roughneses. Bovine blood (500 ml) added with trisodium citrate dihydrate (approximately 2 g) as an anticoagulant was circulated in a test dialyzer at a flow rate of 200 ml/min. Pressure drop and flow rate of PMMA (particle diameter : 1 μm) suspension in glycerol (Bingham fluid) (glycerol : PMMA = 2: 1 by weight ratio) were measured to determine yield stress. The yield stress of the membranes and increased with surface roughness. The amount of platelet adhesion increased with yield stress, indicating that the platelet adhesion depends on surface roughness.

Highly permeable dialysis membranes of asymmetrical structure were developed to mitigate amyloidosis which patients undergoing long-term dialysis treatment caught. Filtration and backfiltration through the membranes play an important part in solute transport. The rejections of the asymmetrical membranes are different between transport directions. To design high performance membranes, it is important to clarify the effects of the difference in rejection between directions of solute transport. Rejection and overall mass transfer coefficient of dextran were determined by filtration and counter-current dialysis experiments to compare transport characteristics of gradient structure membranes having a skin layer inside the wall of hollow fibers with those of the reverse gradient structure membranes having a skin layer outside. Overall mass transfer resistance and rejection of the gradient structure membranes are lower for transport from outside to inside than for that from inside to outside, indicating that solutes are easy to move from outside to inside. On the other hand, those of the reverse gradient structure membranes are lower for transport from inside to outside than for that from outside to inside, indicating that solutes are easy to move from inside to outside. The solute transport characteristics of the reverse gradient structure membranes are suitable for dialysis treatment. We conclude that thee overall mass transfer coefficient of the asymmetrical dialysis membrane increases by providing them with differences in rejection between transport directions.

It is well known that performances of hemodialysis membrane depend on its pore structure. Herein the new pore structure membrane‹PT-X› is proposed. ‹PT-X› has a symmetrical gradient morphology in pore size distribution in the membrane wall. The pore radius around middle part of the membrane wall is larger than that of surface parts. ‹PT-X› has some advantages required for hemodialysis membranes, (1) reduced mass transfer resistance, (2) reduced backfiltration of pyrogens from dialysate side into blood side, (3) reduced albumin penetration and adhesion onto membrane wall, (4) adequate mechanical strength, compared with symmetrical, gradient, reversed gradient and symmetrical pore structure membranes, respectively. These characteristic advantages are brought about for the symmetrical gradient pore structure.

Most of requirements for hemodialysis hollow fiber membranes depend on their micro pore structure and distribution. Therefore, not only the averaged pore radius but also the pore radius distribution should be noted in the optimal design of hollow fiber hemodialysis membranes. Herein some advantageous characteristics of newly developed cellulose hemodialysis membrane, pore radius distribution pattern of which may be so called "symmetricall gradient structure", are presented with those of the conventional and well known homogeneous, gradient, and reverse gradient structure membranes.

It is well known that performances of hemodialysis membrane depend on its pore structure. Herein the new pore structure membrane <PT-X> is proposed <PT-X> has a symmetrical gradient morphology in pore size distribution in the membrane wall. The pore radius around middle part of the membrane wall is larger than that of surface parts <PT-X> has some advantages requied for hemodialysis membranes, (1) reduced mass transfer resistance, (2) reduced backfiltration of pyrogens from dialysate side into blood side, (3) reduced albumin penetration and adhesion onto membrane wall, (4) adequate mechanical strength, compared with symmetrical, gradient, reversed gradient and symmetrical pore structure membranes, respectively. These characteristic advantages are brought about for the symmetrical gradient pore structure.

The distribution volume of water contained in 31 hemodialysis membranes made from seven polymers was measured by three different methods, Water contained in the membranes was classified into three groups according to thermal mobility of the molecules, Structural analysis of the membranes was feasible through determining proportion of nonfreezing water to total water contained in the membranes. (C) 1995 Academic Press, Inc.

Swelling layers formed by poly(ethylene glycol) (PEG) chains grafted onto surfaces of a cellulosic membrane are known to improve hemocompatibility of the membrane. Three types of hemodialysis membranes were derived from the same regenerated-cellulose hollow-fiber membrane by grafting PEG with different formulas onto the surfaces to clarify the influence of the grafted PEG chains on solute permeability of the membranes. Determination of volume fractions of nonfreezing water contained in the membranes by differential scanning calorimetry revealed that most of the PEG chains were grafted onto the external surfaces and less into the pores in the membranes. Permeability of vitamin B-12 for the PEG-grafted membranes except for the one with the shortest PEG chains was reduced as compared with the original membrane, while that of tritium-labeled water for all the PEG-grafted membranes was the same as that of the original membrane. Structural parameters only of the PEG-grafted membrane with the largest alkyl groups at the terminal of the PEG chains were different from those of the other PEG grafted and original membranes. The shorter PEG chains with the larger terminal alkyl groups are suitable for grafting onto a cellulosic membrane to increase hemocompatibility of the membrane without significant reduction in the solute permeability of the membrane. (C) 1995 John Wiley & Sons, Inc.

Absorbancy of a solution in the narrow lumen of a tubular membrane under dialysis is continuously measurable with a newly-developed apparatus using quartz optical fibers. The solute permeability of the membrane was determined by calculating time-dependent changes in the absorbancy measured with the apparatus by the mathematical solution derived for unsteady-state concentration profiles in an infinitely long composite cylinder. This method was independent of convective mass transport and osmotic flow through membranes, leading to superiority to ordinary techniques with respect to accuracy.

Intramembrane diffusivity and water permeability are essential for characterization of dialysis membranes. The physical state of water present in the membrane may affect the solute diffusivity because solutes diffuse into only a fraction of water in the membrane and water inside the membrane changes places with that outside the membrane. Water content was measured in 31 dialysis membranes made of 7 polymers. The physical state of water was determined from data on water content by the conventional method and the differential scanning calorimetry and on partition coefficient measured by the use of tritium-labeled water. Three kinds of water state of varying molecular mobilities were found in the membranes and their volume ratio was dependent on the membrane material. The mechanism of solute transport through hydrophilic dialysis membranes of regenerated cellulose that strongly put restrictions on the movement of water in the membrane was different from that through hydrophobic dialysis membranes. Analysis of the intramembrane diffusivity of the regenerated cellulose membrane based on the free volume theory revealed that the solute diffusivity was dependent on water content.

Complement activation is reduced by grafting polyethylene glycol (PEG) on the surface of conventional regenerated cellulose (RC) membranes. However, the solute permeability of PEG-grafted RC membranes may be lower than that of conventional RC membranes because of the presence of swollen-layers formed with PEG chains on the PEG-grafted RC membranes. The objective of the present study is to clarify the difference in membrane structure between conventional RC (AM-SD) and PEG-grafted RC (AM-PC) membranes, and to characterize three PEG-grafted cellulosic membranes (AM-PC(l), PC(m), PC(s)) with varying PEG chain lengths based on the tortuous capillary pore model using data on tritium-labeled water (HTO) permeability and filtration coefficient.<br>The pore radius and surface porosity of the AM-SD, PC (m) and PC (s) membranes were calculated to be 2.8nm and 35%, respectively. On the other hand, the pore radius and surface porosity of the PC(l) membrane grafted with the longest PEG chains were lower than those of the conventional RC membrane (SD). This indicates that the pores of the PC (l) membrane are partially covered with the PEG chains.

Solute permeability is available using Wilson-Plot Method, Klein's Method, RI Method with radioisotope-labeled solute and a new method with optical fibers. Each method gives different values for solute permeability of same membranes, and little is known real values for solute permeability. This paper describes characteristics of methods of measuring solute permeability, and effects of membrane structure on solute permeability of highly permeable (HP) dialysis membranes.
Real values for solute permeability of hollow-fiber dialysis membranes can be measured by a new method with optical fibers. Structural parameters of pore radius, surface porosity and tortuosity were determined for HP membranes from pure water permeability, solute permeability and water content data using the tortuous pore model. PAN-DX membrane has higher solute permeability than AM-EP membrane for substances of molecular weight ranging from 6, 000 to 20, 000, because PAN-DX membrane has huge pores.

A few highly permeable dialysis membranes have been developed so far to remove beta-2-microglobulin having a molecular weight of 11, 800 that was identified as a new form of amyloid protein from patients on long-term hemodialysis. The present study is to evaluate the solute permeability for low molecular weight proteins such as beta-2-microglobulin of the highly permeable dialysis membranes by varying technical methods.<BR>The membranes tested included conventional and highly permeable dialysis membranes made of regenerated cellulose, and also highly permeable dialysis membranes of polysulfone and polyacrylonitrile as a reference. Solute permeability was determined by 1) the Wilson-plot method, 2) the microanalysis method with radioisotope-labeled solutes and 3) the photometric measurement. Test solutes were vitamin B<SUB>12</SUB> beta-2-microglobulin, cytochrome-C and myoglobin.<BR>The highly permeable dialysis membranes of regenerated cellulose had higher surface porosities and pore sizes calculated from solute and pure water permeabilities and water content data that were practically the same as synthetic polymer membranes. This demonstrates that advanced membrane preparation techniques are capable of forming great surface porosity and large pore size on regenerated cellulose dialysis membranes.<BR>The Wilson-plot method is incapable of determination of diffusive permeability without ultrafiltration. Continuous measurements of optical density of a test solution in a hollow with optical fibers are well suited for precise determination of solute permeability by diffusion.<BR>The removed amount of beta-2-microglobulin calculated from solute permeability data of the most highly permeable dialysis membranes may not exceed the generated amount of beta-2-microglobulin.

Highly permeable (HP) membranes have higher solute permeabilities than conventional ones. Contribution of blood- and dialysate-side mass transfer resistances to solute removal performance is more increased in HP dialyzers than conventional ones. To reduce blood- and dialysate-side mass transfer resistances effectively increases solute removal performance especially of HP dialyzers. This paper describes the technical design of dialyzers with being reduced blood-side mass transfer resistance. Dialyzers consisting of hollow-fiber membranes of 19.4cm in length was superior in solute removal perormance to dialyzers consisting of hollow-fiber membranes of 23.5cm in length. Overall mass transfer coefficient and blood-side mass transfer coefficient were independent of blood-side flow rate. Overall mass transfer coefficient was independent of inner diameter of hollow fibers.

Solute permeability is available using Wilson-Plot Method, Klein's Method, RI Method with radioisotope-labeled solute and a new method with optical fibers. Each method gives different values for solute permeability of same membranes, and little is known real values for solute permeability. This paper describes characteristics of methods of measuring solute permeability, and effects of membrane structure on solute permeability of highly permeable (HP) dialysis membranes.<br>Real values for solute permeability of hollow-fiber dialysis membranes can be measured by a new method with optical fibers. Structural parameters of pore radius, surface porosity and tortuosity were determined for HP membranes from pure water permeability, solute permeability and water content data using the tortuous pore model. PAN-DX membrane has higher solute permeability than AM-EP membrane for substances of molecular weight ranging from 6, 000 to 20, 000, because PAN-DX membrane has huge pores.

Relationship between mass transfer and flow patttern in dialyzers is very important for optimal design of dialyzers. Mass transfer in dialysate-side is extremely complex to understand due to complexity of flow pattern. In this work, the basic analysis about mass transfer of dialysate was performed with single follow fiber membrane, which is considered as a simplest laminar flow condition. The experiment was carried out by the new method with optical fibers. The unsteady mass transfer model in a capillary membrane was applied to the new calculation method for the mass transfer coefficient of outside film of the hollow fiber membrane. AM-SD-10M which is conventional membrane and AM-FP-15 which is highly permeaole membrane were used in the experiment. No matter which membrane was concerned, mass transfer resistances of outside film were equal. Sherwood number measured experimentally fitted in with the Leveque's equation which was led by the theoretical analysis of heat transfer in laminar flow.

Complement activation is reduced by grafting polyethylene glycol (PEG) on the surface of conventional regenerated cellulose (RC) membranes. However, the solute permeability of PEG-grafted RC membranes may be lower than that of conventional RC membranes because of the presence of swollen-layers formed with PEG chains on the PEG-grafted RC membranes. The objective of the present study is to clarify the difference in membrane structure between conventional RC (AM-SD) and PEG-grafted RC (AM-PC) membranes, and to characterize three PEG-grafted cellulosic membranes (AM-PC(l), PC(m), PC(s)) with varying PEG chain lengths based on the tortuous capillary pore model using data on tritium-labeled water (HTO) permeability and filtration coefficient.
The pore radius and surface porosity of the AM-SD, PC (m) and PC (s) membranes were calculated to be 2.8nm and 35%, respectively. On the other hand, the pore radius and surface porosity of the PC(l) membrane grafted with the longest PEG chains were lower than those of the conventional RC membrane (SD). This indicates that the pores of the PC (l) membrane are partially covered with the PEG chains.

Highly permeable (HP) membranes have higher solute permeabilities than conventional ones. As a result, the contribution of dialysate film mass transfer resistance increased on HP dialyzers. It should be reduced to improve the mass transfer performance of HP dialyzers. Little is known concerning the technical design of dialyzers, considering dialysate film mass transfer resistance. This paper describes the technical design of dialyzers to reduce the dialysate film mass transfer resistance. The dialysate film mass transfer coefficient increased with the fiber density. The increase in fiber density increased the mass transfer rate of HP dialyzers more effectively than that of conventional dialyzers. Keller's equation, commonly used for the technical design of dialyzers, should be modified because the dialysate film mass transfer coefficient calculated from the equation did not agree with those determined by a dialysis experiment.