Cuprammonium Regenerated Cellulose Hollow Fiber Research Articles

Removal of small viruses (parvovirus) from IgG solution by virus removal filter Planova ®20N

To clarify virus removability from IgG solutions by Planova ®20N, which is composed of cuprammonium regenerated cellulose hollow fiber membranes, we investigated the effects of virus spiking conditions as well as IgG concentration on the filtration performance (i.e. protein filterability and virus removability). The relationship between the performance and the membrane structure was also discussed. We used human IgG as the model protein and porcine parvovirus (PPV) as the model virus. The results revealed Planova ®20N's IgG permeability at 5 mg/ml IgG concentration was independent of PPV spiking as well as PPV purity, and its flux decay was small. The filter also maintained a high virus logarithmic rejection value (LRV) (>4) regardless of virus spiking conditions and filtration volume. For a wide range of IgG concentrations of 1–30 mg/ml, the flux decay was negligibly small keeping the high LRV. We consider these outcomes are due to the Planova ®20N's unique membrane structure (i.e. the multi-layered, capillary-void structure, having the thick effective layer with high porosity), which enables a high virus trapping capacity (volume) with a low plugging rate of protein. These results indicate that Planova ®20N has a well-balanced performance, eminently efficient viral removal capability and robust feature.

Permeation mechanism of DNA molecules in solution through cuprammonium regenerated cellulose hollow fiber (BMM tm)

We tried to clarify the membrane permeation mechanism of biopolymer DNA molecule in solution through cuprammonium regenerated cellulose hollow fiber (BMM tm) from the dependence of the permeability of the DNA molecule on the molecular weight (MW), the transmembrane pressure ( ΔP), the total challenge dose, the original concentration of DNA and on the conformation of DNA and from the observation of the shape of the DNA molecule remaining in the membrane wall. The shape of the DNA molecule was observed using transmission electron microscopy (TEM). The permeability of DNA molecules decreased with an increase in the MW of the DNA molecule. The MW of the molecule which showed a permeability of more than 0.9 was 1 × 10 6 for the protein with global configuration and 1 × 10 8 for DNA. The linear protein of the blood coagulation factor VIII combined with von Willebrand factor (F-VIII with vWF) with MW of 2 × 10 7 showed a permeability similar to that of DNA rather than that of the global protein. When ΔP decreased, the permeability of DNA decreased. Electron microscope observation showed that the DNA molecules were elongated by the shear stress originated in the flow of the solution in pores. We can conclude that: (1) Protein and DNA permeate through BMM mainly based on sieving effects. (2) The molecules of DNA and F-VIII with vWF are considered to deform into a string shape along the stream line. The chemical structure of a molecule and the shear stress of filtration govern its deformability. The deformation of the molecule contributes to the permeability through BMM. (3) The sieving effect in working on the permeation of molecules should take into account their deformability in addition to their geometrical size.

Mechanism of virus removal by regenerated cellulose hollow fiber (BMM).

We intended to elucidate the mechanism of virus removal by cuprammonium regenerated cellulose hollow fiber (BMMTM). The removability of viruses with various sizes was examined as a function of the mean pore size of BMM and the population distribution of virus captured in BMM was evaluated through electron microscopy. The removability of viruses was dependent on their sizes and the viruses caught in the membrane distributed in void pore stepwise along the filtration direction. The virus removability decreases with an increase in the concentration of coexisting protein and with an increase in the filtration volume. The changes in the virus removability due to the changes in the filtration condition could be interpreted through the pore structure change caused by the filtration and the contribution of plugging in the capillary pore and trapping in the void pore. It was found that the BMM filtered viruses through multi-step filtration. We conclude that mechanism of the virus removal is the sieving effect and thus, the removability of viruses can be predicted from their sizes using the proposed empirical relationship.

Mechanism of Removing Japanese Encephalitis virus (JEV) and Gold Particles Using Cuprammonium Regenerated Cellulose Hollow Fiber (i-BMM or BMM) from Aqueous Solution Containing Protein

We intended to clarify the mechanism of virus removal in aqueous protein solution and human plasma solution through conventional and high performance regenerated cellulose hollow fiber (i.e., BMM and i-BMM). We employed Japanese encephalitis virus (JEV) as a typical virus. Two kinds of disperse gold particles (GP) with different size were represented as model particles of a virus and protein particles. We investigated the filtration characteristics concerning removability of GP and JEV (Φg and Φv, respectively) and the frequency distribution of GP and JEV within the walls of hollow fibers using a transmission electron microscope. The results were that (1) Φg depended on the particle size, (2) the maximum population of captured GP moved to the outer wall with increase in challenge number, (3) i-BMM showed higher Φg and Φv than those of BMM. (4) Both Φg and Φv depend on the concentration of protein and total volume filtered. (5) The effects of coexistence of proteins on Φg and Φv are classified as initial change in the pore structure and local concentration of proteins in the pores (expressed as Φg0) and subsequent change in the pore structure with filtration volume (φg0). These indicate that JEV and GP under the coexistence of protein are caught by BMM and i-BMM mainly through a sieving mechanism.

Removal of causative agent of Creutzfeldt-Jakob disease(CJD) through membrane filtration method.

We intended to show the possibility of the removal of the Creutzfeldt-Jakob disease (CJD) causative agent by the filtration using the virus removal membrane BMM®, that is, cuprammonium regenerated cellulose hollow fiber. The BMMs with various mean pore size 2rf ranging between 35 and 75 nm were employed. The supernatant of the centrifuged homogenate obtained from the mouse brains infected with CJD was filtered through BMMs and each filtrate was injected intracerebrally into mice. The concentration of the CJD infectious agent was evaluated through the mean death day caused by CJD after the injection. The dependence of this concentration of the filtrate on 2rf the change in this concentration of the double filtration, and the change in the concentration of the filtrate from the solution after the treatment of the surfactant “Sarkosyl” was investigated. The infection of CJD was judged from the pathology of spongiform encephalopathy and from the generation of the CJD isoform of Prion Protein (PrPCJD).The results were summerized as follows : (1) The infectivity of the filtrate decreased when 2rf decreases, and after the filtration using the BMM with 2rf value of 35 nm, this infectivity desappeared completely indicating the logarithmic rejection coefficient was more than 6. (2) The double step filtration using two BMMs with 2rf of 60nm gave about 10% increase in the rejection coefficient comparing with the case of the single step filtration. (3) The treatment of the Sarkosyl made the permeability of the CJD causative agent through the BMM with 2rf of 40nm increased to 100% and the infectivity increased to about five hundreds times of that of the original solution.

Structure and Filtration Performances of Improved Cuprammonium Regenerated Cellulose Hollow Fiber (Improved BMM Hollow Fiber) for Virus Removal

Structure and Filtration Performances of Improved Cuprammonium Regenerated Cellulose Hollow Fiber (Improved BMM Hollow Fiber) for Virus Removal

Structure of Cuprammonium Regenerated Cellulose Hollow Fiber (BMM Hollow Fiber) for Virus Removal

An attempt to analyze the pore structure of the cuprammonium regenerated cellulose hollow fiber (BMM hollow fiber) in order to clear up its filtration mechanism was made. The electron microscopy was employed to get the concrete images of the structure. The cellulose particles of rod-like shape with circular cross section having mean diameter of about 50 nm were its constructing units. The pores were classified into two types, i.e., the pore with the average diameter of about 50 nm and another with the diameter of several hundreds to several thousands nm. The former was estimated to be the capillary formed among neighboring cellulose particles and the latter to be the void formed as a vacant space which was originated by the phase separation as polymer lean phase. The frequency distribution curve of the void size showed several peaks indicating the occurrence of the boundary breakage between voids originated by the elongation of the fiber in the spinning process. The performances of BMM depends mainly on the existence of capillaries, then BMM with higher ability may be obtained by means of the spinning method which can decrease the occurrence of structure breakage due to the elongation during spinning.

Mechanism of Removing Monodisperse Gold Particles from a Suspension Using Cuprammonium Regenerated Cellulose Hollow Fiber (BMM Hollow Fiber)

In order to clarify the mechanism of removing viruses with cuprammonium regenerated cellulose hollow fiber (BMM hollow fiber), monodisperse gold particles were used. The dependences of the concentration of gold particles in the filtrate on the particle concentration and the particle size were investigated. The particles were considered to be caught by BMM through two mechanisms, that is, plugging of capillaries and trapping within voids. Here, the capillaries stand for the narrow pathway among neighboring cellulose particles which construct the membrane and the voids the bulky space surrounded by the aggregated cellulose particles. In the initial stage, the plugging of the capillaries causes decrease in the particle concentration. On the other hand, trapping leads to the occupation of spaces within the voids. When the voids near the inner surface are occupied by gold particles, the particles proceed inwards through channels formed by voids and finally fiow out from the outer surface of the membrane. This leads to increase in the particle concentration in the preceding stage. The removability of the particles depends both on the relative size bewtween the capillary (or the void) and the particle and on the trapping capacity.