Hollow Fiber Filter Research Articles

Exosomes as a tumor immune escape mechanism: possible therapeutic implications

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

Extracorporeal immunoadsorption therapy on rats. In vivo depletion of specific antibodies

A technique for extracorporeal immunoadsorption of circulating specific antibodies from the plasma of rats is described. Catheterization of rats was performed using the carotid and the jugular blood vessels. The rats were treated non-anaesthetized. Blood was pumped continuously through a hollow-fibre plasma filter at a rate of 1.5 ml/min and plasma was separated and passed through an adsorbent column at a flow of 0.2 ml/min. The treated plasma was mixed with the blood cells before being returned to the rat. The column contained the antigen covalently linked to agarose beads. About three plasma volumes were treated during a period of 3 h and 30 min, which resulted in an antibody depletion of about 90-95%. The antibody levels returned to pre-adsorption levels after 4-5 days, or in some cases even exceeded the titres before treatment.

Hollow fiber ultrafiltration: The concept of partial backwashing

In dead-end hollow fiber filtration with humic acid solutions, we observed that the humic material accumulates in the final part of the fiber. We proved the hypothesis that backwashing of the last part of the fiber is sufficient to operate the filtration process in a sustainable manner. This strategy works very well for feed solutions that result in either local accumulation of the material at the end of the fiber, or that form a well-defined concentration polarization layer that does not lead to deposition. When deposition throughout the whole module occurs, the proposed cleaning strategy is unsuccessful. This overall deposition occurs when a force balance over the particle, results in net transport to the membrane surface over the entire length of the module. We simulated such conditions by the addition of calcium to the feed solutions. The latter results in large aggregates carried towards the whole membrane area by convective water flow, and an increased interaction between the aggregates and the membrane.

BPA transfer rate increase using molecular imprinted polyethersulfone hollow fiber membrane

Bisphenol A (BPA) imprinted polyethersulfone (PES) hollow fiber membrane was spun using a dry–wet spinning method, the membrane was then prepared as a filter with an effective area of 200 cm 2. The hollow fiber filter was employed to study the BPA transport behavior. The transport ability of the prepared hollow fiber membrane was measured using 100 μmol/l BPA aqueous solutions at a flow flux of 50 and 75 ml/min, respectively. The BPA transfer rate increased for the imprinted hollow fiber membranes due to the larger amount of binding sites, comparing with the non-imprinted one. In the present study, hollow fiber membrane and the molecular imprinting technique were combined for advanced separation and the data suggested that small molecules could transfer in the direction opposite to the concentration gradient due to different pH.

Quality and stability of red cells derived from gravity‐separated placental blood with a hollow‐fiber system

Several studies show that donor red blood cells (RBCs) can be processed by gravity separation with a hollow-fiber filtration system. This study investigated whether fetal blood could be filtered in the same way. Twelve newborns born after healthy pregnancies were included in the study. Placental blood was sampled with standard procedures. The sampled blood was separated with a specially designed hollow-fiber filtration system (Sangofer neonatal, Heim Group). The RBC bag contained 10 mL of saline, adenine, glucose-mannitol (SAG-M) for stabilization. After processing, the resulting RBC volume was estimated. Quality variables (blood counts, hemolysis rate) were measured before and after 35 days of storage at +4 degrees C. The 12 processed RBC units had a mean volume of 62.3 +/- 13.5 mL and a mean hematocrit level of 0.56 +/- 0.06. No white blood cell contamination could be detected in any of the RBC units tested. After 35 days of storage, the hemolysis was 0.1 +/- 0.07 and the amount of free hemoglobin was 0.28 +/- 0.017 mmol per L. This study shows that it is possible to process placental blood to RBCs by gravity separation with a hollow-fiber system. The quality of the RBCs thus processed was suitable for 35 days storage. The use of placental blood in the treatment of children with anemia (e.g., malaria) in the underresourced world is widely discussed. Because the separation device used here needs no additional equipment or electrical devices, it is considered to be an ideal method for use in these countries.

Highly effective rhizobacterial soil inoculants: Large-scale production of cyst form cultures in hollow fibre filters

Highly effective rhizobacterial soil inoculants: Large-scale production of cyst form cultures in hollow fibre filters

Selection of membranes for deadend micro- and ultrafiltration outside-in hollow fiber filters

A mathematical model taking into account the adsorption of particles around a membrane pore mouth at the stage of standard blocking is developed. The model is used to study the effect of the average membrane pore size, the cutoff coefficient, and the ratio of the length of the pore inlet region to be blocked to the whole pore length on the product flow rate of a deadend outside-in hollow fiber filter. It is shown that the use of membranes with an average pore size higher than the cutoff diameter for the particles to be removed from the suspension will be profitable only for the first 15–20 min of operation. In this case, the membrane should have an average pore size as large as possible, but not exceeding a limit value at which the membrane selectivity can drop; the cutoff coefficient as low as possible; and a pore inlet region to be blocked as long as possible.

Phenomenological theory of depth membrane filtration

A phenomenological theory of depth membrane filtration (DMF), in which outside-in hollow fiber membranes are used as collectors of colloidal particles, is developed to study the performance of a hollow fiber membrane filter with two product streams, permeate (clarified liquid that passed through semipermeable membrane) and filtrate (clarified liquid due to the collection of suspended particles on the external surface of hollow fibers). The theory is based on the general phenomenological expression for the rate of particle deposition on the membrane surface, in which the deposition rate is proportional to the product of the particle deposition coefficient and the concentration of suspended particles, with the deposition coefficient being an arbitrary function of the mass of deposited particles and permeate velocity. The system of governing equations is solved by the generalized Crank–Nicholson finite-difference method and the approximate method using the averaging of the permeate velocity in the mass conservation equation. The effect of membrane permeability on the filter productivity is studied. It is shown that the approximate solution can be used as a relatively simple and accurate tool to study and design hollow fiber filters for DMF.

New Methods for Hemoglobin Detection in a Microparticle-Plasma Suspension

In the extracorporeal adsorption system, MDS (Microspheres based Detoxification System), micro-adsorbent particles measuring 1-25 micrometers circulate in a filtrate circuit for highly specific blood purification/adsorption. The MDS circuit containing the adsorbent microparticles is linked to the patient's blood line by a hollow fiber plasma filter. When the transmembrane pressure or the shear forces due to the red blood cells in the hollow fiber filter are too high, they can be damaged and hemoglobin will be released. In order to detect free hemoglobin (fHb) by optical means, we have designed a new flow-dynamic filter system, placed in the microadsorbent circuit for continuous separation of microparticles from the filtrate. In the flow dynamic filter, we use a high velocity liquid vortex to remove sedimentation and particle plugs on the filter membrane. In our investigations, 3 and 8 micron cellulose nitrate filter membranes for particle separation are used. The obtained particle free bypass filtrate flow rates are typically 0.5 and 0.8 ml/min respectively. The typical sensitivity for fHb detection by the applied noninvasive optical method is 0.15 g/dL. Medical safety regulations require a fail-safe mechanism for fHb detection which monitors the bypass filtrate flow in the flowdynamic filter and shuts down the system in case of membrane occlusion. The bypass filtrate flow is monitored by periodically occluding and releasing the bypass line by means of a clamp. The resulting back pressure profile gives information about the actual filtration rate. This safety principle was proven by statistical analysis and shows its clear functionality.

Kiss1 Neurons in the Forebrain as Central Processors for Generating the Preovulatory Luteinizing Hormone Surge

Kisspeptins are neuropeptides encoded by the Kiss1 gene, which have been implicated in the neuroendocrine regulation of gonadotropin-releasing hormone (GnRH) secretion. The goal of this study was to test the hypothesis that activation of Kiss1 neurons in the anteroventral periventricular nucleus (AVPV) is linked to the induction of the preovulatory luteinizing hormone (LH) surge in the rat. First, we determined that levels of Kiss1 mRNA in the AVPV peaked during the evening of proestrus, whereas Kiss1 mRNA in the arcuate nucleus (Arc) was at its nadir. Second, we corroborated this observation by demonstrating that Kiss1 mRNA is increased in the AVPV at the time of an estrogen (E)- and progesterone-induced LH surge in ovariectomized animals, whereas in the Arc, the expression of Kiss1 mRNA was decreased. Third, we found that most Kiss1 neurons in the AVPV coexpress the immediate early gene Fos coincidently with the LH surge, but virtually none coexpressed Fos on diestrus. In contrast, Kiss1 neurons in the Arc were Fos negative at the time of the LH surge as well as on diestrus. Finally, we found that most Kiss1 neurons in the AVPV and Arc express estrogen receptor alpha mRNA, suggesting that E acts directly on these neurons. These results suggest that Kiss1 neurons in the AVPV play an active role in mediating the effects of E on the generation of the preovulatory GnRH/LH surge on proestrus.

Deadend outside-in hollow fiber membrane filter: Mathematical model

A mathematical model describing the performance of deadend outside-in hollow fiber filters developed on the basis of Darcy's law and the theory of depth filtration accounting for the decrease in the liquid flow rate with filter depth coordinate due to permeate withdrawal is studied. The system of governing equations is solved with the generalized Crank–Nicholson method of central finite differences and approximate methods based on averaging certain process parameters, which use simple Laplace transform solutions for particular cases. It is shown that some of the approximate methods provide an accuracy acceptable for engineering calculations, implying that they can be used in designing more efficient filters.

Continuous Renal Replacement Therapy for Congestive Heart Failure: The Wearable Continuous Ultrafiltration System

Ultrafiltration is effective in the treatment of fluid and sodium overload in congestive heart failure. There is no available device to provide this therapy to ambulatory patients. We built and tested in vivo a wearable belt that can provide continuous ultrafiltration, 168 hours a week. Nine pigs underwent ureteral ligation and subsequently were allowed fluids ad lib, producing fluid overload. Next day, ultrafiltration was performed for 8 hours. The device consists of a hollow-fiber filter, a 9 V battery-operated pulsatile blood pump, a micro pump for heparin infusion, and another micro pump to control ultrafiltration rate. Blood flow was 65 ml/min and the weight of the device is less than 2.5 lb. Fluid removal rate ranged from 0 to 700 ml/h and averaged 106 ml/h. Salt removed was 7.6 g. No complications were observed. The potential impact on the quality of life of these patients by reducing the shortness of breath, leg swelling, and returning their ability to enjoy salt in their food might be significant, and a reduction in morbidity could be expected. The economic impact in reducing hospital admissions and length of stay, intensive care unit utilization, and drug consumption could be significant. Further studies are needed to compare this innovative approach with traditional drug-based therapy.

Particle deposition in outside-in hollow fiber filters and its effect on their performance

Effect of transmembrane pressure (TMP), particle deposition and reentrainment coefficients, and specific cake resistance on the performance of a dead-end outside-in hollow fiber (DOIHF) filter and hollow fiber membrane (HFM) adsorber is studied using the adsorption–peptization model. It is shown that the increase in TMP causes a higher decline in the permeate velocity for both a DOIHF filter and HFM adsorber. The rise in the adsorption (particle deposition) coefficient can considerably increase the productivity (produced volume of clarified liquid) of these membrane devices. The increase in the peptization (particle reentrainment) coefficient can noticeably decrease their productivity. The volume of clarified liquid produced by the HFM adsorber is 1.6–2 times higher than that produced by the DOIHF filter for the same operation time and process parameters. The values of the particle deposition coefficient, particle reentrainment coefficient, and specific cake resistance are suggested to be adjusted by changing process parameters such as the ionic strength, TMP, and pH, as well as by choosing the material of hollow fibers that provides favorable (attractive) surface interactions between the membrane and particles.

Membrane Separation in Deadend Hollow Fiber Filters at Constant Transmembrane Pressure

A mathematical model of cake formation in deadend outside-in hollow fiber filters accounting for nonuniform cake deposition throughout the filter is developed. The model is used to study two possible mechanisms of cake growth: conventional (convective) and adsorption-peptization. The system of equations describing the cake formation is numerically solved with the generalized Crank-Nicholson finite-difference scheme. Comparison of the numerical solutions with experimental data shows that the cake formation in deadend out-side-in hollow fiber filters is governed by the adsorption-peptization mechanism.

Membrane Filtration with Reversible Adsorption: The Effect of Transmembrane Pressure, Feed Flow Rate, and the Geometry of Hollow Fiber Filters on Their Performance

The effect of transmembrane pressure, feed flow rate, and the geometry of hollow-fiber filters on their performance is studied for depth membrane filtration with reversible adsorption. Mathematical models for rectangular and radial filters are used to find the maximal operation times with a filter retention of not less than 0.9 at constant product (permeate plus filtrate) flow rates for the treatment of a latex suspension in continuous-flow and batch operations. It is shown that the maximal operation time and, hence, product volume is achieved when the feed flow rate approaches the initial permeate flow rate. It is also found that several filters with a lower initial permeate flow rate allow one to achieve a much longer operation time than one filter with the same total initial permeate flow rate.

Membrane filtration with reversible adsorption: Hollow fiber membranes as collectors of colloidal particles

A novel membrane separation process in which outside-in hollow fiber (HF) membranes with axes normal to the flow of the suspension under treatment are used as collectors of the colloidal particles is proposed. This process, called depth membrane filtration, yields two product streams: permeate, the liquid that passed through the semipermeable HF membranes, and filtrate, the liquid that was clarified by collection of the colloidal particles on the HF shells. A mathematical model in which convective transport and reversible adsorption account for the deposition of colloids onto the membrane surface is developed. Analytical expressions for the coefficients of adsorption and peptization are derived. The concentrations of suspended particles in the product water of an HF filter treating a dilute latex suspension in continuous-flow and batch operations were calculated. The calculations based on the values of the latex-solution properties and the HF operating and design parameters available in the literature demonstrated the feasibility of the process.

Use of hollow fiber membrane filtration for the removal of DMSO from platelet concentrates

It has been hypothesized that, in addition to freezing injury, some damage to platelets may result from the cell packing that occurs during removal of the cryoprotectant. This study examined DMSO removal by fluid exchange across hollow-fiber (HF) filters as an alternative to centrifugation. The DMSO solution with or without cell suspension was passed once through the filter. The optimum exchange during unloading of DMSO was determined by varying the flow rates in the external and internal compartments of the HF filter. Initially, buffered solutions of a 5% DMSO solution in the absence of platelets were pumped into the fibers and exchanged against PBS. The residual DMSO was determined by osmometry. The exchange of DMSO across the membrane was flow dependent and also influenced by the chemical nature of the HF fibers. No protocol using a reasonable rate flow through the fibers removed more than 95% of the DMSO in a single pass. The optimum protocol was achieved with polysynthane fibers with an internal flow rate of approximately 20 ml/min and an external flow rate of 100 ml/min. Subsequently, frozen/thawed platelet concentrates in DMSO were washed using centrifugation and compared to the HF filtration method. Platelet quality was assayed by flowcytometry, cell count, morphology and osmotic stress test. Both filtration and centrifugal washing techniques resulted in comparable morphological scores and numbers of discoid cells. When agents reducing platelet activation were added, platelet quality was improved after washing by either technique. The lower platelet osmotic response with HF filtration than with centrifugation while using activation inhibitors was attributed to the remaining amount of the inhibitors. All other parameters tested were similar. The expression of CD62P was equivalent with both techniques, and centrifugation did not activate platelets more than filtration contrary to what was originally anticipated. In conclusion, platelet quality was comparable after washing by either technique but hollow fiber filtration does remove cryoprotectant more rapidly than does centrifugation.

Development of Vibrating Hollow-Fiber Filtration Device

A miniature vibrating hollow-fiber filtration device, in which a hollow-fiber cartridge mounted on a bridge held by two plate springs is vibrated to axial direction by a vibration motor, has been developed. The device can restrain the deposition of particles on the membrane surface by the vibration. A device, which has two hollow-fiber (length of 190 mm, an inside diameter of 1 mm and pore diameter of 0.1 μm), was tested at a membrane vibration frequency of 40 Hz and an amplitude of 2.5 mm p-p. During the test the liquid (Kaolin suspension ; turbridity : 1000) was filtered through the membrane for two weeks. It was found that the rate of permeation is almost constant after the test. However, when it was not vibrated, the end permeation rate was one quarter of the rate when vibrated.

Tritium Handling Experience in 165MWE Power Generating Station, Fugen

ABSTRACTTwo heavy water upgraders have been developed and operated in the Fugen Nuclear Power Station to keep the isotopic purity of the moderator around 99.7 wt% and to recover tritium from the degraded heavy water. One of the upgraders is a combined electrolysis catalyst exchange (CECE) process that consists of 90 stages of catalytic water-hydrogen isotopic separation units. This upgrader treats 10 m3/y of degraded heavy water, produces reactor grade heavy water, and lowers the tritium and heavy water in the waste to <3700 Bq/cm3 and <0.1wt%, respectively. The other one is simple electrolysis system and terminated its operation in 1999. Heavy water recycle is completed with these two upgraders in the Fugen.A filter-separation-type tritium monitor was developed. Daughter species of Rn-Tn are separated from sampled gas with hollow fiber filters made of perfluorosulfuric-acid resin before introducing to an ionization chamber. The detection limit of the monitor is 7.4E-03 Bq/cm3-air.The upgraders and monitor contributed to control airborne and liquid tritium releases from the Fugen lower than 18 TBq/y and 11 TBq/y, respectively.

A NOVEL DETOXIFICATION DEVICE FOR THE TREATMENT OF HEPATIC FAILURE (HF)

Blood purification in patients with HF remains still difficult as many toxins are strongly hound to albumin. Hence, current systems exhibit low removal efficacy or poor biocompatibility. In this paper we present a novel device, Prometheus, for the removal of toxins derived from HF. Prometheus represents a fractionated plasma separation and adsorption (FPSA) technology. Blood flows through a hollow-fiber filter, Albu-Flow, which enables albumin to enter a closed-loop circuit containing two adsorbent cartridges, prometh 01 and prometh 02. Exposure to adsorbents depletes albumin from toxic substances by direct adsorption. Purified albumin finally re-enters the blood stream, which passes through a downstream high-flux dialyzer for HD. Laboratory investigations revealed effective elimination of HF markers such als unconjugated bilirubin (clearance at 200 ml blood flow: 23 ml/min), cholic acid (48 ml/min), tryptophan (93 ml/min), and phenol (177 ml/min). Removal was selective as albumin, ATIII, fibrinogen, immunoglobulins and other plasma components were not affected. Cellular and humoral indices (e.g., PLT, complement, cytokine induction) proved biocompatibility of the treatment. Fractionated plasma separation with direct adsorption translates into effective, selective and biocompatible blood purification for patients with HF. Preliminary multicenter experience with Prometheus confirms excellent performance and showed easy handling in the clinical setting.