Virus-removing hollow cellulose membrane and method for producing the same

Abstract

The application relates to the field of membrane separation technology, in particular to a virus-removing hollow cellulose membrane and a preparation method thereof. By adjusting the surface tension ratio among a casting solution, a core solution and a coagulation bath, the pore size of the finally obtained virus-removing hollow cellulose membrane is controlled. The prepared membrane has excellent virus retention capacity and maintains high water flux, high protein recovery rate and superior mechanical performance. The method in the application greatly reduces the difficulty of preparing the virus-removing hollow cellulose membrane by using natural cellulose as raw material, and greatly improves social benefits.

Description

Technical Field

[0001] This application relates to the field of membrane separation technology, and in particular to a virus-removing hollow cellulose membrane and a method for preparing the same. Background Technology

[0002] In the biopharmaceutical field, viral contamination poses a significant challenge, potentially contaminating products on the production line and negatively impacting their safety and efficacy. Therefore, taking appropriate measures to protect biopharmaceutical products from viral contamination is crucial.

[0003] Currently, numerous virus filtration methods and technologies have emerged in the biopharmaceutical field, such as microfiltration, gel chromatography, and protein A affinity chromatography. However, traditional virus filtration methods have some limitations and challenges.

[0004] First, microfiltration filters typically have large pore sizes, making them ineffective at filtering smaller viral particles. Second, methods such as gel chromatography and protein A affinity chromatography may have varying applicability to different virus types, and are complex and time-consuming, failing to meet the demands of high-efficiency production.

[0005] Membrane separation is a technology that uses the pressure difference across a membrane to separate, purify, and concentrate solutions. Due to its green, energy-saving, and highly efficient characteristics, membrane separation technology has been widely used in the food, chemical, and pharmaceutical industries.

[0006] Compared to flat sheet membranes, hollow fiber membranes offer significant advantages. Hollow fiber membrane modules have a larger specific surface area, lower pressure loss, lower pretreatment requirements, and a wider range of applications. The membrane modules have a simple structure, are easy to install, and exhibit high operability in practical applications. The separation devices are simple to use, easy to control, clean, and maintain. Furthermore, hollow fiber membrane modules possess excellent antifouling properties; contaminants do not easily adhere to the membrane surface, thus extending the service life of the membrane modules to a certain extent.

[0007] Chinese invention patent application CN113842792A discloses an asymmetric PES filter membrane for virus removal. This PES filter membrane comprises a main body, including a pre-filtration layer and a separation layer for virus retention. The PES membrane has a typical bilayer structure (a large-pore pre-filtration layer and a small-pore layer) and exhibits good virus retention (LRV > 4). However, the inherent hydrophobicity of the PES material results in a relatively low protein yield.

[0008] Application publication number CN115025641B describes a highly hydrophilic regenerated cellulose (RC) virus-removing hollow filtration membrane. This hollow cellulose membrane has a porous inlet surface and a porous outlet surface. That is, the pore size of the membrane gradually decreases, then gradually increases, and then gradually decreases again in the thickness direction. At the same time, the virus retention effect (LRV>4) is good. However, the preparation of the hollow membrane in this patent has high requirements for process and equipment, and the preparation process is complicated. Summary of the Invention

[0009] The present invention aims to overcome the problems of low water flux in existing antiviral cellulose membranes due to their wide pore size distribution and thick retention layer, as well as the low protein yield of PES membranes. The present invention provides an antiviral hollow cellulose membrane and its preparation method to overcome the above-mentioned shortcomings.

[0010] To achieve the above-mentioned objectives, the present invention is implemented through the following technical solution:

[0011] In a first aspect, the present invention provides a method for preparing a virus-free hollow cellulose membrane, which includes at least the following steps: (S.1) dissolving cellulose in a copper ammonia solution and preparing a casting solution;

[0012] (S.2) The step of adjusting the surface tension ratio of the casting solution to the core solution to 0.8-1.15;

[0013] (S.3) The step of adjusting the surface tension ratio of the casting solution to the coagulation bath to 0.5-0.8;

[0014] (S.4) The step of removing air bubbles from the casting solution to form the spinning solution;

[0015] (S.5) The step of extruding the core solution and the spinning solution together into the coagulation bath to obtain hollow fiber membrane filaments by wet spinning.

[0016] (S.6) The obtained hollow fiber membrane filaments are regenerated in a regeneration bath and washed with water to obtain the virus-free hollow cellulose membrane.

[0017] According to the inventors' research, the uncontrollable nature of the raw materials and molecular weight distribution of natural polymers (such as cellulose) makes it difficult to precisely control the pore size when preparing hollow cellulose membranes.

[0018] Hollow fiber membranes are typically prepared using a wet spinning method, which involves simultaneously extruding the casting solution and core solution into a coagulation bath to obtain a hollow fiber membrane with a uniform pore size. However, in current methods, the core solution and coagulation bath are usually made of the same material, resulting in hollow fiber membranes with a symmetrical structure and generally uniform pore size from the inside out. This makes it difficult to simultaneously achieve the requirements of high water flux and high rejection rate.

[0019] The inventors effectively controlled the phase separation rate between the casting solution and the coagulation bath by adjusting the ratio of surface tension between the casting solution and the coagulation bath, thereby adjusting the pore size of the membrane. Therefore, this adjustment method can also help achieve the desired pore size control of hollow fiber membranes, especially in the preparation of hollow fiber membranes with asymmetric structures.

[0020] Taking flat sheet membranes as an example, under theoretical conditions, if the surface tension of the coagulation bath is closer to that of the casting solution, the phase separation rate of the casting solution will be slowed down, resulting in a larger pore size of the flat sheet membrane; while if the surface tension of the coagulation bath is greater than that of the casting solution, the phase separation rate of the casting solution will be faster, resulting in a smaller pore size of the flat sheet membrane.

[0021] However, the inventors attempted to apply this theory to the preparation of hollow fiber membranes, specifically by setting the surface tension of the coagulation bath to be closer to that of the casting solution and more distant from that of the core solution. The results showed that this method failed to produce hollow cellulose membranes with the desired pore size, and instead led to a decrease in virus retention capacity. The inventors conducted a detailed analysis and discovered that the root cause lies in the fundamentally different structures of hollow fiber membranes and flat sheet membranes. The preparation method described in this application yields hollow cellulose membranes, and its preparation process requires consideration not only of the surface tension ratio between the casting solution and the coagulation bath, but also of the surface tension ratio between the casting solution and the core solution.

[0022] The surface tension of a liquid is caused by the intermolecular forces on the liquid surface, i.e., the pulling force exerted on the liquid surface. The inventors discovered that when the core liquid and spinning solution are extruded together into the coagulation bath, if the surface tension of the core liquid is less than that of the coagulation bath, the coagulation bath, due to stronger hydrogen bonding, easily pulls the core liquid outward, thereby driving the core liquid to permeate outward. This causes the phase separation rate of the hollow cellulose membrane to increase sequentially from the outside to the inside, resulting in a hollow cellulose membrane exhibiting the desired effect of progressively increasing pore size from the inside to the outside.

[0023] In this application, the surface tension ratio between the casting solution and the core solution is adjusted to 0.8-1.15, while the surface tension ratio between the casting solution and the coagulation bath is adjusted to 0.5-0.8. Actual testing shows that by adjusting these two parameters to the above ranges, the prepared hollow cellulose membrane can possess an asymmetric porous tortuous structure. Electron microscopy results show that the pore size of the porous inlet surface can reach 500nm-10000nm, significantly larger than the inlet pore size of existing hollow cellulose membranes. The pore size of the porous outlet surface is 16-20nm, effectively trapping substances such as viruses. Compared to existing technologies, the cellulose membrane prepared by this method has a larger proportion of both the porous inlet layer (with a porous inlet surface) and the trapping layer (with a porous outlet surface). The porous layer accounts for one-quarter to one-third of the total membrane thickness, as does the trapping layer. This design can significantly increase the water flux of the cellulose membrane, thereby significantly improving filtration efficiency, which is of great significance for industrial production. Furthermore, a contaminant-holding layer composed of continuous fibers exists between the porous layer and the trapping layer. The pore size of the fouling layer is between 20-500 nm. When large protein aggregates are present in the filtrate, the fouling layer can trap these aggregates, preventing them from clogging the porous pores at the filtrate outlet and thus reducing protein recovery. This design improves the stability and lifespan of the cellulose membrane.

[0024] Finally, as mentioned above, due to the traction effect of the casting solution on the core liquid, cellulose molecules can achieve directional alignment along the permeation direction of the core liquid during the phase separation process of the casting solution, thus maintaining a close packing of cellulose molecules. This alignment results in higher tensile strength and elongation at break for the overall hollow fiber membrane. Actual testing shows that the hollow fiber membrane prepared using the technical solution of this application exhibits a tensile strength of 5-20 MPa and an elongation at break of 60-150%. Therefore, the performance of the hollow fiber membrane prepared in this application far exceeds the levels achievable by existing hollow fiber membranes. This demonstrates that by controlling the surface tension ratio between the casting solution and the core liquid, and the surface tension ratio between the casting solution and the coagulation bath, not only can the pore size of the cellulose filter membrane be controlled, but its mechanical properties can also be improved, thereby obtaining a cellulose filter membrane with higher tensile strength and elongation at break.

[0025] Preferably, the casting solution in step (S.1) contains, by weight percentage: 1.5-5% copper, 6%-15% ammonia, 6-15% cellulose, and 0.1-3% antioxidant.

[0026] Generally speaking, the lower the solid content of cellulose in the casting solution, the lower the density of the prepared membrane, and therefore the larger the pore size of the prepared membrane. However, the mechanical properties of the membrane, such as strength and toughness, will be correspondingly lower. On the other hand, the higher the solid content of cellulose, the higher the density of the membrane, and the more compact the cellulose molecules are arranged, so the mechanical properties of the membrane will be correspondingly improved. However, this will reduce the pore size of the membrane and the membrane flux.

[0027] In the preparation of cellulose filter membranes, a cellulose solids content of 1% to 4% is generally common. However, the casting solution in this application has a higher cellulose solids content, ranging from 6% to 15%, which is significantly higher than that of traditional casting solutions. Theoretically, filter membranes prepared using casting solutions with high solids content will have smaller pore sizes, thus reducing water flux.

[0028] However, this application achieves control over the phase separation rate of the casting solution in the coagulation bath and the core solution by adjusting two key parameters: the surface tension ratio of the casting solution to the coagulation bath and the surface tension ratio of the casting solution to the core solution. This adjustment method results in a cellulose filter membrane with a larger pore size on the porous inlet surface and a larger pore area while maintaining a smaller pore size on the porous outlet surface. Therefore, this method effectively ensures the membrane flux and mechanical properties.

[0029] Preferably, the casting solution in step (S.1) contains, by weight percentage: 3-5% copper, 8-12% ammonia, 6-10% cellulose, and 1-2% antioxidant.

[0030] Preferably, the raw material for the copper is one or a combination of copper hydroxide, basic copper sulfate, and basic copper carbonate.

[0031] Preferably, the raw material for the cellulose is one or more of bamboo cellulose, broadleaf / softwood pulp, and cotton pulp.

[0032] Preferably, the molecular weight of the cellulose is 8 × 10⁻⁶. 4 -1.6×10 5 between.

[0033] Preferably, the antioxidant is one or a combination of phenolic antioxidants, ketone antioxidants, amine antioxidants, organic acid antioxidants, inorganic acid antioxidants and their salts.

[0034] Preferred antioxidants include: 1. Phenolics: 2,6-di-tert-butyl-p-cresol, propyl gallate, nordihydroguaiacol, tocopherol (vitamin E) and its derivatives; 2. Ketones: tert-butylhydroquinone, etc.; 3. Amines: ethanolamine, isohydroxy acids, glutamic acid, casein and hemp protein, lecithin, cephalin, etc.; 4. Organic acids, alcohols and esters: oxalic acid, citric acid, tartaric acid, propionic acid, malonic acid, thiopropionic acid, vitamin C and its derivatives, glucuronic acid, galacturonic acid, mannitol, sorbitol, dilauryl thiodipropionate, distearate thiodipropionate, etc.; 5. Inorganic acids and their salts: phosphoric acid and its salts, phosphorous acid and its salts, with inorganic salts and phenolic antioxidants being preferred.

[0035] Preferably, the present invention adjusts the surface tension ratio between the casting solution and the core solution by changing the surface tension of at least one of the casting solution or the core solution.

[0036] Preferably, the present invention adjusts the surface tension ratio between the casting liquid and the coagulation bath by changing the surface tension of at least one of the casting liquid or the coagulation bath.

[0037] Preferably, a surface tension modifier is added to the casting solution to adjust its surface tension.

[0038] There are various ways to adjust the surface tension of the casting solution and the core solution, as well as the ratio of the surface tension of the casting solution to the coagulation bath, in this application. For example, the steps of adjusting the surface tension of the casting solution itself and adjusting the surface tension of the core solution and the coagulation bath can be used.

[0039] In the process of adjusting the surface tension of the casting solution itself, a surface tension regulator can be added to the casting solution to achieve precise control of the surface tension of the casting solution. This reduces the difficulty of adjusting the surface tension of the casting solution and the core solution, as well as the ratio of the surface tension of the casting solution to that of the coagulation bath.

[0040] Preferably, the surface tension modifier is at least one selected from acetone, dimethylacetamide, N,N-dimethylformamide, ethanol, methanol, and ethylene glycol.

[0041] Preferably, the surface tension is adjusted by changing the concentration of the core fluid solution;

[0042] The surface tension is adjusted by changing the concentration of the coagulation bath solution.

[0043] Preferably, the core fluid is an ethanol solution with a concentration of 60-90%, and the coagulation bath is an ethanol solution with a concentration of 10-40%.

[0044] Preferably, the core liquid is an ethanol solution with a concentration of 70-80%, and the coagulation bath is an ethanol solution with a concentration of 20-40%.

[0045] Preferably, in step (S.3), the wet spinning speed is 0.5-5 mL / min, and the temperature of the coagulation bath and the core liquid is 10-40℃.

[0046] Preferably, in step (S.3), the wet spinning speed is 1-2 mL / min, and the temperature of the coagulation bath and the core liquid is 20-30℃.

[0047] In the wet spinning process for preparing hollow cellulose membranes, the wet spinning speed, coagulation bath, and core liquid temperature are key operating parameters affecting the performance of the hollow fibers. The wet spinning speed refers to the rate at which the cellulose solution flows out of the spinning holes. Variations in the wet spinning speed affect the stretching and elongation of the cellulose solution, thus influencing the diameter, pore structure, and distribution of the cellulose fibers. Excessively high wet spinning speeds lead to increased fiber diameter and uneven pore distribution, while excessively low wet spinning speeds result in smaller fiber diameter and lower porosity, ultimately affecting the separation performance and flux of the hollow cellulose membrane.

[0048] In this application, by controlling the wet spinning speed in the wet spinning process to be in the range of 0.5-5 ml / min and the temperature of the coagulation bath and the core liquid to be in the range of 10-40℃, a hollow cellulose filter membrane with high separation performance and flux is obtained.

[0049] Variations in the coagulation bath and core solution temperature affect the coagulation rate and crystallinity of cellulose fibers. At high temperatures, the coagulation rate of the cellulose solution accelerates, leading to an excessively rapid coagulation process and incomplete crystallization. This results in a poor pore structure and negatively impacts the mechanical and compressive properties of the filter membrane. Furthermore, excessively high coagulation bath temperatures promote rapid coagulation of cellulose molecules and the rapid aggregation of colloidal particles, making the cellulose fibers more compact. This limits the porosity and flux of the filter membrane, reducing its separation efficiency. Conversely, at low temperatures, the coagulation rate of the cellulose solution slows down, prolonging the stretching and coagulation process of the cellulose fibers. This makes radial stretching of the fibers more difficult, reducing fiber diameter and decreasing the filter membrane flux. Simultaneously, excessively low coagulation bath temperatures result in insufficient crystallinity during cellulose molecule coagulation, slower colloidal particle diffusion, increased spacing between cellulose fibers, and higher porosity. This can lead to poor mechanical properties of the filter membrane, making it prone to pores and defects.

[0050] Preferably, in step (S.4), the regeneration bath is an acid solution with a concentration of 1-10%, the regeneration temperature is 10-40℃, and the regeneration time is 3-15 min.

[0051] Preferably, in step (S.6), the regeneration bath is an acid solution with a concentration of 1-10%, the regeneration temperature is 10-40℃, and the regeneration time is 3-15 min.

[0052] Preferably, the acid solution is one or a combination of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, citric acid, and malic acid. Sulfuric acid is particularly preferred.

[0053] Secondly, this application also provides a virus-removing hollow cellulose membrane prepared by the above method, comprising a tubular main body with a hollow structure, the tubular main body including a loose layer and a retaining layer, one side of the loose layer being a porous liquid inlet surface, and one side of the retaining layer being a porous liquid outlet surface, wherein the loose layer and the retaining layer are transitioned by a continuous fiber-based contaminant-holding layer, characterized in that...

[0054] The pore size of the porous liquid inlet surface is between 500 nm and 10000 nm;

[0055] The pore size of the porous liquid outlet surface is 16-20 nm;

[0056] The pore size of the dirt-absorbing layer is 20-500 nm;

[0057] The thickness of the porous layer accounts for one-quarter to one-third of the total thickness of the membrane;

[0058] The thickness of the retention layer accounts for one-quarter to one-third of the total thickness of the membrane.

[0059] The hollow cellulose membrane in this application uses cellulose as the raw material. Compared to polyethersulfone (PES) filter membranes, it has good hydrophilicity and lower protein adsorption. Therefore, it can effectively reduce protein loss during filtration. Furthermore, its structure shows a significant difference in pore size between the porous inlet and outlet surfaces. The average pore size of the pores on the outlet surface, measured by SEM, is 16-20 nm, exhibiting a strong filtration effect for small viruses. The pore size on the inlet surface is even 25-500 times larger than that on the outlet surface. It can effectively filter large particulate impurities in the liquid being filtered and maintain the inlet rate at the porous inlet surface. In addition, the loose layer and the retaining layer are transitioned by a dirt-holding layer composed of continuous fibers. Therefore, the cellulose filter membrane provided in this application has a uniform thickness variation. Since the average pore size of the dirt-holding layer is 20-500nm as measured by SEM, it can effectively trap large protein aggregates of various sizes, preventing them from clogging the porous filter pores at the liquid outlet and reducing the protein recovery rate.

[0060] Furthermore, in the filter membrane provided in this application, the thickness of the porous layer and the retention layer accounts for a relatively large proportion. The thickness of the porous layer is approximately one-quarter to one-third of the overall membrane thickness, as is the thickness of the retention layer. Therefore, compared with current hollow cellulose filter membranes, the filter membrane in this application far exceeds the general level. Consequently, the hollow cellulose membrane in this application has the characteristic of high pore area ratio, allowing the liquid to be filtered to pass through the cellulose membrane quickly. It can maintain a high water flux, shorten the filtration time, and meet the needs of practical applications.

[0061] Preferably, the water flux of the virus-removing hollow cellulose membrane is 60-300 L / m³. 2 / h@30psi; the PP7 retention test result of the virus-removing hollow cellulose membrane is LRV>6; the PMI pore size distribution result of the virus-removing hollow cellulose membrane is 15-100nm; the thickness of the virus-removing hollow cellulose membrane is 60-150μm.

[0062] Preferably, the tensile strength of the virus-removing hollow cellulose membrane is 5-20 MPa;

[0063] The breaking elongation of the virus-free hollow cellulose membrane is 60-150%.

[0064] Tensile strength and elongation at break of hollow cellulose membranes are key indicators for evaluating the mechanical strength of filter membranes. Under certain conditions, the greater the tensile strength of the filter membrane, the better its mechanical strength. Tensile strength refers to the membrane material's ability to withstand parallel tensile forces. During the test, the membrane sample is subjected to tensile loads until it fails. By recording the maximum tensile load at failure and the change in membrane sample length, the tensile strength and elongation at break of the membrane can be calculated.

[0065] The filter membrane of this invention exhibits excellent mechanical properties, with a tensile strength of 5-20 MPa and an elongation at break of 60-150%. This means that the filter membrane of this invention possesses high tensile strength and elongation at break, demonstrating outstanding mechanical properties and high industrial applicability. It fully meets market demands.

[0066] Therefore, the present invention has the following beneficial effects:

[0067] This application controls the pore size of the final virus-removing hollow cellulose membrane by adjusting the surface tension ratio between the casting solution, core solution, and coagulation bath. The prepared membrane exhibits excellent virus retention capacity while maintaining high water flux, high protein recovery rate, and superior mechanical properties. This method significantly reduces the difficulty of preparing virus-removing hollow cellulose membranes from natural cellulose and greatly improves social benefits. Detailed Implementation

[0068] The present invention will be further described below with reference to specific embodiments. Those skilled in the art will be able to implement the present invention based on these descriptions. Furthermore, the embodiments of the present invention described below are generally only some, not all, of the embodiments of the present invention. Therefore, all other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort should fall within the scope of protection of the present invention.

[0069] Example 1

[0070] With a molecular weight of 1.1 × 10 5 Cotton pulp and the antioxidant sodium sulfite were dissolved in a prepared copper ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 8 wt%, a copper concentration of 3.2 wt%, an ammonia concentration of 6 wt%, an acetone concentration of 10%, and a sodium sulfite concentration of 1 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (30% ethanol aqueous solution at 25°C), while the core solution (70% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in the continuous curing and output of the hollow fiber membrane. The cured hollow fiber was placed in a sulfuric acid solution at 25°C for 5 minutes to ensure that the membrane fiber completely changed from light blue to translucent. Finally, it was placed in pure water at 50°C to further clean the organic solvent and metal ions on the membrane.

[0071] Example 2

[0072] With a molecular weight of 8×10 4 Cotton pulp and the antioxidant tocopherol were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 6 wt%, a copper concentration of 1.5 wt%, an ammonia concentration of 8 wt%, a DMAc concentration of 5%, and a tocopherol concentration of 0.1 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (10% ethanol aqueous solution at 25°C), while the core solution (60% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 min to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0073] Example 3

[0074] With a molecular weight of 1.0 × 10 5 Cotton pulp and the antioxidant tert-butylhydroquinone were dissolved in a prepared copper ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 10 wt%, a copper concentration of 2.5 wt%, an ammonia concentration of 10 wt%, a DMF concentration of 8%, and a tert-butylhydroquinone concentration of 1.5 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (20% ethanol aqueous solution at 25°C), while the core solution (75% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in the continuous curing and output of the hollow fiber membrane. The cured hollow fiber was placed in a sulfuric acid solution at 25°C for 5 minutes to ensure that the membrane fiber completely changed from light blue to translucent. Finally, it was placed in pure water at 50°C to further clean the organic solvent and metal ions on the membrane.

[0075] Example 4

[0076] With a molecular weight of 1.3 × 10 5 Cotton pulp and antioxidant glutamic acid were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 12 wt%, a copper concentration of 4.5 wt%, an ammonia concentration of 12 wt%, a methanol concentration of 12%, and glutamic acid concentration of 2 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (35% ethanol aqueous solution at 25°C), while the core solution (80% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0077] Example 5

[0078] The molecular weight is 1.6 × 10 5Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, an ethylene glycol concentration of 15%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (40% ethanol aqueous solution at 25°C), while the core solution (90% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0079] Example 6

[0080] The molecular weight is 1.6 × 10 5 Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (10% ethanol aqueous solution at 25°C), while the core solution (70% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0081] Example 7

[0082] The molecular weight is 1.6 × 10 5Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (20% ethanol aqueous solution at 25°C), while the core solution (70% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0083] Example 8

[0084] The molecular weight is 1.6 × 10 5 Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (10% ethanol aqueous solution at 25°C), while the core solution (75% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0085] Example 9

[0086] The molecular weight is 1.6 × 10 5Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (20% ethanol aqueous solution at 25°C), while the core solution (75% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0087] Comparative Example 1

[0088] With a molecular weight of 1.1 × 10 5 Cotton pulp and the antioxidant sodium sulfite were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a spinning solution with a cellulose solids content of 8 wt%, a copper concentration of 3.2 wt%, an ammonia concentration of 6 wt%, and a sodium sulfite concentration of 1 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (30% ethanol aqueous solution at 25°C), while the core solution (70% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0089] Comparative Example 2

[0090] With a molecular weight of 8×10 4Cotton pulp and the antioxidant tocopherol were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 6 wt%, a copper concentration of 1.5 wt%, an ammonia concentration of 8 wt%, and a tocopherol concentration of 1 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (30% ethanol aqueous solution at 25°C), while the core solution (70% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0091] Comparative Example 3

[0092] The molecular weight is 1.6 × 10 5 Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, an ethylene glycol concentration of 15%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (10% ethanol aqueous solution at 25°C), while the core solution (90% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0093] Comparative Example 4

[0094] The molecular weight is 1.6 × 10 5Cotton pulp and antioxidant vitamin C were dissolved in a prepared copper-ammonia solution, filtered, and degassed to obtain a casting solution with a cellulose solids content of 15 wt%, a copper concentration of 5 wt%, an ammonia concentration of 15 wt%, an ethylene glycol concentration of 20%, and a vitamin C concentration of 3 wt%. The spinning solution was then pumped from the outer nozzle of the spinneret at a rate of 0.8 ml / min into a coagulation bath (40% ethanol aqueous solution at 25°C), while the core solution (80% ethanol aqueous solution at 25°C) was simultaneously pumped from the inner nozzle of the spinneret at a rate of 1.6 ml / min. The outer nozzle of the spinneret had an outer diameter of 0.6 mm and an inner diameter of 0.4 mm. The spinning speed was 9 m / min, ensuring an average residence time of 60 s for the spinning solution, resulting in continuously cured hollow fiber membranes. The cured hollow fibers were then placed in a 25°C sulfuric acid solution for 5 minutes to ensure the membrane fibers completely transformed from pale blue to translucent. Finally, they were placed in 50°C pure water for further cleaning to remove organic solvents and metal ions from the membrane.

[0095] The surface tensions of the casting solution, core solution, and casting solution in Examples 1-9 and Comparative Examples 1-4 are shown in Table 1 below.

[0096] Table 1. Summary of surface tension in each embodiment and comparative example.

[0097]

[0098] [Performance Testing]

[0099] The detection methods are as follows:

[0100] Average pore size test: The test is performed using a PMI pore size distribution tester. First, a membrane of a certain size is cut. The membrane is then wetted with ethanol of different concentrations, followed by a low surface tension (15.6 mN / m) solvent (provided by the US PMI equipment manufacturer). The membrane is then placed in the test tank. Finally, the average pore size and the initial pore size of the bubble are obtained by passing through a dry-wet line.

[0101] Bubble pressure test: After wetting the obtained membrane with a low surface tension liquid (13.6 mN / m (MTMNovecTM7100)), pressure is slowly applied to the membrane with compressed nitrogen until continuous bubbles are generated on the membrane surface. The gas pressure at this time is called bubble pressure (MPa).

[0102] Flow rate: Tested using a Millipore Virusmax testing device with a 25mm stainless steel replaceable membrane filter (this device is used for both protein permeability and virus filtration experiments), with an effective filtration area of ​​4.1cm². 2 The filtration test was conducted using ultrapure water at a temperature of 25°C and a pressure of 2 bar.

[0103] Surface tension test: In an environment of 25℃, the surface tension of the copper ammonia solution was dynamically tested using a Dataphysics OCA20 (Germany) instrument with the hanging plate method as the core, and the surface tension value was stabilized without significant change.

[0104] Thickness test of the cut-off layer: The thickness of the dense layer was measured by SEM cross-sectional images.

[0105] Tensile strength test: Cut the test sample into small films 1cm wide and 8-10cm long using a film cutter, and test the tensile strength using a microcomputer-controlled electronic universal testing machine LD22.501 with a range of 0-50N.

[0106] Protein transmittance test: Prepare a protein solution of a certain concentration (e.g., 1 g / L, 5 g / L, etc.), and pre-filter it through a 0.22 μm filter to remove particles and prepolymers of the protein solution. Then, use a Millipore Virusmax test device with a 25 mm stainless steel membrane filter for testing. Use a UV-5 ultraviolet spectrophotometer (Mettler) at a wavelength of 280 nm to measure the absorbance. The transmittance calculation formula is as follows: Transmittance = C1 / C0 × 100%, where C1 is the concentration of the permeate and C0 is the concentration of the original solution.

[0107] Virus retention assay: Polyclonal antibody IgG was used as the antibody solution. 5% MVM (mouse parvovirus) and BVDV (bovine viral diarrhea virus) were added to the resulting antibody solution, and the mixture was thoroughly stirred to obtain an antibody solution containing the virus. The assay was performed using a Millipore Virusmax assay device with a 25mm stainless steel membrane filter: LRV = log10(CO / CF);

[0108] Where: C0 represents the infection titer of the stock solution containing antibodies against the virus, and CF represents the infection titer of the filtrate after using a regenerated cellulose virus-removing filter membrane.

[0109] The performance of the virus-removing filter membranes in Examples 1-9 and Comparative Examples 1-4 is shown in Table 2 below.

[0110] Table 2 Performance of different virus-removing filter membranes

[0111]

[0112] The test results from Examples 1-9 and Comparative Examples 1-4 show that a regenerated cellulose virus-removing hollow fiber filtration membrane capable of retaining 20 nm can be finally obtained by adjusting the surface tension ratio of the casting solution to the core solution to 0.8-1.15 and the surface tension ratio of the casting solution to the coagulation bath to 0.5-0.8 using solvents with different low surface tensions to regulate the overall surface tension of the casting solution and reduce its ratio with the surface tension of the coagulation bath. The surface tension ratio between the casting solution and the core solution, and between the casting solution and the coagulation bath, can be adjusted by adding solvents with different low surface tensions to the casting solution, thereby regulating the overall surface tension of the casting solution. This method is highly operable and simple, and most importantly, the reagents used to adjust the surface tension are readily available.

Claims

1. A method for preparing a virus-removing hollow cellulose membrane, comprising the following steps: (S.1) Dissolve cellulose in a copper ammonia solution and prepare a casting solution; (S.2) Remove air bubbles from the casting solution to form the spinning solution; (S.3) The spinning solution and the core solution are extruded together into a coagulation bath, and hollow fiber membrane filaments are obtained by wet spinning; (S.4) The hollow fiber membrane filaments are regenerated in a regeneration bath and washed with water to obtain the virus-removing hollow cellulose membrane, characterized in that, Before step (S.3), the surface tension ratio between the casting liquid and the core liquid is adjusted to 0.8-1.15, the surface tension ratio between the casting liquid and the coagulation bath is adjusted to 0.5-0.8, and the surface tension of the core liquid is less than that of the coagulation bath.

2. The method for preparing the virus-free hollow cellulose membrane according to claim 1, characterized in that, The casting solution in step (S.1) contains, by weight percentage: 1.5-5% copper, 6%-15% ammonia, 6-15% cellulose, and 0.1-3% antioxidant.

3. The method for preparing the virus-removing hollow cellulose membrane according to claim 2, characterized in that, The raw material for the copper is at least one of copper hydroxide, basic copper sulfate, and basic copper carbonate. The raw material for the cellulose is at least one of bamboo cellulose, broad / softwood pulp, and cotton pulp; The antioxidant is at least one of phenolic antioxidants, ketone antioxidants, amine antioxidants, organic acid antioxidants, and inorganic acid and its salt antioxidants.

4. The method for preparing the virus-free hollow cellulose membrane according to claim 1, characterized in that, The ratio of surface tension between the casting solution and the core solution is adjusted by changing the surface tension of at least one of the casting solution or the core solution. The ratio of surface tension between the casting solution and the coagulation bath can be adjusted by changing the surface tension of at least one of the casting solution or the coagulation bath.

5. The method for preparing the virus-removing hollow cellulose membrane according to claim 4, characterized in that, A surface tension modifier is added to the casting solution to adjust its surface tension; The surface tension is adjusted by changing the concentration of the core fluid solution; The surface tension is adjusted by changing the concentration of the coagulation bath solution.

6. The method for preparing the virus-removing hollow cellulose membrane according to claim 5, characterized in that, The surface tension modifier is at least one of acetone, dimethylacetamide, N,N-dimethylformamide, ethanol, methanol, and ethylene glycol.

7. The method for preparing the virus-removing hollow cellulose membrane according to any one of claims 4-6, characterized in that, The core fluid is an ethanol solution with a concentration of 60-90%, and the coagulation bath is an ethanol solution with a concentration of 10-40%.

8. The method for preparing the virus-removing hollow cellulose membrane according to claim 1, characterized in that, In step (S.3), the wet spinning speed is 0.5-5 mL / min, and the temperature of the coagulation bath and core liquid is 10-40℃.

9. The method for preparing the virus-free hollow cellulose membrane according to claim 1, characterized in that, In step (S.4), the regeneration bath is an acid solution with a concentration of 1-10%, the regeneration temperature is 10-40℃, and the regeneration time is 3-15 min.

10. A virus-removing hollow cellulose membrane prepared according to any one of claims 1 to 9, comprising a tubular main body with a hollow structure, the tubular main body comprising a loose layer and a retaining layer, one side of the loose layer being a porous liquid inlet surface and one side of the retaining layer being a porous liquid outlet surface, the loose layer and the retaining layer being transitioned by a continuous fiber-based contaminant-holding layer, characterized in that... The pore size of the porous liquid inlet surface is between 500 nm and 10000 nm; The pore size of the porous liquid outlet surface is 16-20 nm; The pore size of the dirt-absorbing layer is 20-500 nm; The thickness of the porous layer accounts for one-quarter to one-third of the total thickness of the membrane; The thickness of the retention layer accounts for one-quarter to one-third of the total thickness of the membrane.

11. The virus-removing hollow cellulose membrane according to claim 10, characterized in that, The water flux of the virus-removing hollow cellulose membrane was 60-300 L / m³. 2 / h@30psi; the PP7 rejection test result of the virus-removing hollow cellulose membrane is LRV>6; the PMI pore size distribution result of the virus-removing hollow cellulose membrane is 15-100nm; the thickness of the virus-removing hollow cellulose membrane is 60-150μm. The tensile strength of the virus-removing hollow cellulose membrane is 5-20 MPa; The breaking elongation of the virus-free hollow cellulose membrane is 60-150%.

Images