CN116808850A

CN116808850A - Hollow cellulose membrane for removing viruses and preparation method thereof

Info

Publication number: CN116808850A
Application number: CN202310802852.1A
Authority: CN
Inventors: 马团锋; 童聪聪
Original assignee: Sepp Hangzhou Filtration Technology Co ltd
Current assignee: Sepp Hangzhou Filtration Technology Co ltd
Priority date: 2023-07-03
Filing date: 2023-07-03
Publication date: 2023-09-29

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. The pore size of the finally obtained virus-removing hollow cellulose membrane is controlled by adjusting the surface tension ratio among the membrane casting solution, the core solution and the coagulating bath. The prepared membrane has excellent virus interception capability, and maintains high water flux, high protein recovery rate and excellent mechanical properties. The method of the application greatly reduces the difficulty of preparing the virus-removing hollow cellulose membrane by taking the natural cellulose as the raw material, and greatly improves the social benefit.

Description

Hollow cellulose membrane for removing viruses and preparation method thereof

Technical Field

The application relates to the field of membrane separation technology, in particular to a virus-removing hollow cellulose membrane and a preparation method thereof.

Background

In the biopharmaceutical field, viral contamination is a serious challenge, which may lead to contamination of the products on the production line, thereby negatively affecting the safety and effectiveness of the biopharmaceutical product. It is therefore important to take appropriate measures to protect biopharmaceutical products from viral contamination.

Currently, the biopharmaceutical field has emerged numerous viral filtration methods and techniques, such as microporous filters, gel chromatography, protein a affinity chromatography, and the like. However, conventional virus filtration methods have some limitations and challenges.

First, microporous filters generally have larger pore sizes and cannot effectively filter smaller virus particles. Secondly, the methods such as gel chromatography and protein A affinity chromatography may have different applicability on different virus types, and have complex operation and long time consumption, and cannot meet the requirement of efficient production.

The separation membrane is a technology for separating, purifying and concentrating a solution by utilizing the pressure difference at two sides of the membrane. Due to their green, energy-saving and efficient properties, separation membrane technology has found wide application in the food, chemical and pharmaceutical industries.

Hollow fiber membranes offer significant advantages over flat sheet membranes. The specific surface area of the membrane component of the hollow fiber membrane is larger, the pressure loss is smaller, the pretreatment requirement is lower, and the application range is wider. The membrane module has a simple structure, is easy to install, and exhibits high operability in practical applications. The separating device is simple and easy to use, and is convenient to control, clean and maintain. In addition, the hollow fiber membrane component also has excellent anti-pollution performance, and pollutants are not easy to adhere to the surface of the membrane, so that the service life of the membrane component is prolonged to a certain extent.

In the chinese patent application publication No. CN113842792a, an asymmetric PES filter for virus removal is disclosed, which comprises a main body including a pre-filter layer and a separation layer for virus interception. The PES film has a typical double-layer structure (a large-pore pre-filter layer and a small-pore layering), and has a good virus retention effect (LRV > 4), but the PES material has certain hydrophobicity, so that the protein yield is low.

In the application publication No. CN115025641B, a Regenerated Cellulose (RC) virus-removing hollow filtration membrane with high hydrophilic performance is described, which has a porous liquid inlet surface and a porous liquid outlet surface, that is, the pore diameter of the filtration membrane in the membrane thickness direction is gradually reduced, then gradually increased, then gradually reduced, and at the same time, the virus trapping effect (LRV > 4) is good, however, the preparation of the hollow membrane in this patent has high requirements on the process and equipment, and the preparation process is complex.

Disclosure of Invention

The application provides a virus-removing hollow cellulose membrane and a preparation method thereof, which are used for overcoming the defects that the water flux of a regenerated cellulose virus-removing filter membrane is low due to wider pore size distribution and thicker interception layer of the virus-removing cellulose membrane in the prior art, and meanwhile, the PES filter membrane is low in protein yield.

In order to achieve the aim of the application, the application is realized by the following technical scheme:

in a first aspect, the present application provides a method for preparing a hollow cellulose membrane for virus removal, which at least comprises the following steps: (s.1) a step of dissolving cellulose in a cuprammonium solution and preparing a casting solution;

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

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

(S.4) a step of removing air bubbles in the casting solution to form a spinning dope;

(s.5) a step of co-extruding the core liquid and the spinning dope together into a coagulation bath to thereby obtain a hollow fiber membrane yarn by wet spinning;

(S.6) regenerating the obtained hollow fiber membrane filaments by a regeneration bath and washing with water to obtain the virus-removing hollow cellulose membrane.

According to the findings of the inventor in daily researches, natural polymers (such as cellulose) have the problem that the pore diameter is difficult to accurately regulate and control when preparing a hollow cellulose membrane due to uncontrollable raw materials and molecular weight distribution.

In general, a wet spinning method is used for preparing the hollow fiber membrane, and the method comprises the following steps: and extruding the casting solution and the core solution into a coagulating bath simultaneously to obtain the hollow fiber membrane with uniform pipe diameter. However, in the method currently used, the core liquid and the coagulation bath are usually the same material, and thus the hollow fiber membrane is produced to have a symmetrical structure, and the pore diameter is usually uniform from inside to outside. This also results in difficulty in achieving both high water flux and high rejection requirements.

The inventor can effectively control the phase separation speed between the casting solution and the coagulating bath by adjusting the ratio of the surface tension between the casting solution and the coagulating bath, thereby adjusting the pore size of the membrane. Thus, the desired pore size control of the hollow fiber membranes can likewise be achieved by this adjustment method, in particular in the production of hollow fiber membranes of asymmetric structure.

Taking a flat plate membrane as an example, under the theoretical condition, the surface tension of the coagulating bath is closer to that of the casting solution, so that the phase separation speed of the casting solution is reduced, and the aperture of the flat plate membrane is enlarged; the larger the difference between the surface tension of the coagulation bath and the casting solution, the faster the phase separation speed of the casting solution, and the smaller the pore diameter of the flat membrane.

However, the inventors have attempted to use this theory in the preparation of hollow fiber membranes by setting the surface tension of the coagulation bath closer to the surface tension of the casting solution and the surface tension of the core solution farther away, and as a result have found that hollow cellulose membranes prepared by this method do not produce the desired pore size but rather result in a decrease in virus retention capacity. The inventors have conducted an extensive analysis of this phenomenon, and as a result, have found that the root cause of this phenomenon arises because the structures of hollow fiber membranes and flat sheet membranes are substantially different in nature. The preparation method of the application obtains the hollow cellulose membrane, and the preparation process needs to consider not only the ratio of the surface tension between the casting solution and the coagulating bath, but also the ratio of the surface tension between the casting solution and the core solution.

The surface tension of a liquid is caused by intermolecular interaction forces on the surface of the liquid, i.e. pulling forces on the surface of the liquid. The inventor finds that when the surface tension of the core liquid is smaller than the surface tension of the coagulating bath in the process of extruding the core liquid and the spinning solution together into the coagulating bath, the coagulating bath is easy to pull the core liquid outwards due to strong hydrogen bonding action, so that the core liquid is driven to permeate outwards, the phase separation speed of the hollow cellulose membrane is sequentially increased from outside to inside, and the obtained hollow cellulose membrane has the expected purpose of sequentially increasing the pore diameter from inside to outside.

In the application, the surface tension ratio of the casting solution to the core solution is regulated to be 0.8-1.15, and the surface tension ratio of the casting solution to the coagulating bath is regulated to be 0.5-0.8. Through practical tests, by adjusting these two parameters to the above ranges, the prepared hollow cellulose membrane can have an asymmetric porous tortuous structure. According to the electron microscope result, the aperture of the porous liquid inlet surface can reach 500nm-10000nm, which is far larger than the aperture of the liquid inlet surface of the existing hollow cellulose membrane. The aperture of the porous liquid surface is 16-20nm, so that substances such as viruses can be effectively trapped. Compared with the prior art, the cellulose membrane prepared by the method has larger proportion of the thickness of the loose layer containing the porous liquid inlet surface and the interception layer containing the porous liquid outlet surface. The bulk layer is one quarter to one third as thick as the whole membrane, as is the trapping layer. The design can greatly improve the water flux of the cellulose membrane, thereby remarkably improving the filtration efficiency and having important significance for industrial production. In addition, a nano-soil layer composed of continuous fibers is arranged between the loosening layer and the interception layer. The pore diameter of the nano-dirt layer is between 20 and 500 nm. When large protein aggregates exist in the filtrate, the nano-fouling layer can intercept the large protein aggregates and prevent the large protein aggregates from blocking the filter holes of the porous liquid surface, thereby reducing the protein recovery rate. This design may improve the stability and the service life of the cellulose membrane.

Finally, as described above, the cellulose molecules can be aligned in the permeation direction of the core liquid during the phase separation of the casting liquid due to the traction of the casting liquid to the core liquid, thereby maintaining the close alignment of the cellulose molecules. This arrangement provides the overall hollow fiber membrane with higher tensile strength and elongation at break. Through practical tests, the tensile strength of the hollow fiber membrane prepared by the technical scheme of the application can reach 5-20MPa, and the elongation at break can reach 60-150%. Therefore, the performance of the hollow fiber membrane prepared by the method is far higher than that of the hollow fiber membrane in the prior art. This means that the pore diameter of the cellulose filter membrane can be controlled and the mechanical properties of the cellulose filter membrane can be improved by controlling the surface tension ratio of the casting solution to the core solution and the surface tension ratio of the casting solution to the coagulation bath, so that the cellulose filter membrane with higher tensile strength and elongation at break can be obtained.

Preferably, the casting solution in the step (s.1) comprises the following components in percentage by weight: 1.5-5% of copper, 6-15% of ammonia, 6-15% of cellulose and 0.1-3% of antioxidant.

Generally, the lower the solid content of cellulose in the casting solution, the lower the density of the prepared film, and thus the larger the pore size of the prepared film, but the lower the mechanical properties of the film, such as strength, toughness, etc., are correspondingly. The higher the solid content of the cellulose is, the higher the density of the membrane is, and the arrangement of cellulose molecules is compact, so that the mechanical property of the membrane is correspondingly improved, but the pore diameter of the membrane is reduced, and the flux of the membrane is correspondingly reduced.

In the preparation of cellulose filter membranes, the solid content of cellulose is generally between 1% and 4%. However, the solid content of cellulose in the casting solution is higher, and is 6-15%, which is obviously higher than that of the traditional casting solution. According to theoretical conditions, the pore diameter of a filter membrane prepared by adopting the high-solid-content membrane casting solution is smaller, so that the water flux is reduced.

However, the application realizes the control of the phase separation speed of the casting solution in the coagulating bath and the core solution by adjusting two key parameters, namely the surface tension ratio of the casting solution to the coagulating bath and the surface tension ratio of the casting solution to the core solution. The adjusting method ensures that the porous liquid inlet surface of the prepared cellulose filter membrane has larger pore diameter, and the porous liquid outlet surface has smaller pore diameter and larger pore area. Therefore, the flux and mechanical properties of the membrane are effectively ensured by the method.

Preferably, the casting solution in the step (s.1) comprises the following components in percentage by weight: 3-5% of copper, 8-12% of ammonia, 6-10% of cellulose and 1-2% of antioxidant.

Preferably, the copper raw material is one or a combination of more of copper hydroxide, basic copper sulfate and basic copper carbonate.

Preferably, the raw material of the cellulose is one or a combination of a plurality of bamboo cellulose, broad/needle pulp and cotton pulp.

Preferably, the cellulose has a molecular weight of 8X 10 ⁴ -1.6×10 ⁵ Between them.

Preferably, the antioxidant is one or more of phenolic antioxidants, ketone antioxidants, amine antioxidants, organic acid antioxidants, inorganic acid and salt antioxidants thereof.

Preferably, the antioxidant is selected from 1, phenols: 2, 6-di-t-butyl-p-cresol, propyl gallate, nordihydroguaiaretic acid and the like, tocopherol (vitamin E) and derivatives thereof; 2. ketones: tertiary butylhydroquinone, and the like; 3. amines: ethanolamine, iso-hydroxy acid, glutamic acid, casein, and edestin. Lecithin, cephalin, and the like; 4. organic acids, alcohols and esters: oxalic acid, citric acid, tartaric acid, propionic acid, malonic acid, thiopropionic acid, vitamin C and derivatives thereof, glucuronic acid, galacturonic acid, mannitol, sorbitol, dilauryl thiodipropionate, distearate thiodipropionate and the like; 5. inorganic acid and salts thereof: phosphoric acid and its salts, phosphorous acid and its salts, and inorganic salts and phenolic antioxidants are preferably used.

Preferably, the application adjusts the ratio of the surface tension 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.

Preferably, the present application adjusts the ratio of the surface tension between the casting solution and the coagulation bath by changing the surface tension of at least one of the casting solution or the coagulation bath.

Preferably, a surface tension regulator is added to the casting solution to regulate its surface tension.

In the present application, there are various ways of controlling the surface tension of the casting solution and the core solution and controlling the ratio of the surface tension of the casting solution and the surface tension of the coagulation bath, and for example, a step of adjusting the surface tension of the casting solution itself and a step of adjusting the surface tension of the core solution and the surface tension of the coagulation bath may be employed.

When the surface tension of the casting solution is regulated, the step of adding the surface tension regulator into the casting solution can be adopted, so that the surface tension of the casting solution can be accurately regulated, and the difficulty of regulating the surface tension of the casting solution and the core solution and regulating the surface tension ratio of the casting solution and the coagulating bath is reduced.

Preferably, the surface tension regulator is at least one of acetone, dimethylacetamide, N-dimethylformamide, ethanol, methanol and ethylene glycol.

Preferably, the surface tension of the core liquid solution is adjusted by changing the concentration thereof;

the surface tension of the coagulation bath solution is adjusted by changing its concentration.

Preferably, the core liquid is an ethanol solution with the concentration of 60-90%, and the coagulating bath is an ethanol solution with the concentration of 10-40%.

Preferably, the core liquid is an ethanol solution with the concentration of 70-80%, and the coagulating bath is an ethanol solution with the concentration of 20-40%.

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

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

In the process of preparing a hollow cellulose filter membrane by wet spinning, the wet spinning speed, the coagulating bath and the core liquid temperature are key operation parameters affecting the performance of the hollow fiber. The wet spinning speed refers to the speed at which the cellulose solution flows out of the spinning holes. The variation of the wet spinning speed affects the degree of stretching and extension of the cellulose solution and thus the diameter, pore structure and distribution of the cellulose fibers. Excessive wet spinning speeds can lead to increased fiber diameter and uneven pore distribution, while excessive low wet spinning speeds can lead to smaller fiber diameter and less porosity, thereby affecting the separation performance and throughput of the hollow cellulose filter membrane.

According to the application, the hollow cellulose filter membrane with high separation performance and flux is obtained by controlling the wet spinning speed in the wet spinning process within the range of 0.5-5ml/min and the temperature of the coagulating bath and the core liquid within the range of 10-40 ℃.

Variations in coagulation bath and core liquid temperature affect the rate of coagulation and degree of crystallization of cellulose fibers. At high temperature, the solidification speed of the cellulose solution can be accelerated, so that the solidification process of the cellulose fiber is too fast, the crystallization degree of the fiber is not complete, the pore structure of the cellulose fiber is poor, and the mechanical property and the compression resistance of the filter membrane are affected. In addition, an excessively high coagulation bath temperature contributes to rapid coagulation of cellulose molecules and rapid aggregation of colloidal particles, so that cellulose fibers are more compact. This will limit the porosity and flux of the filter membrane, reducing the separation effect of the filter membrane. At low temperatures, however, the rate of solidification of the cellulose solution is slowed, resulting in an extended time for the stretching and solidification of the cellulose fibers. This can lead to difficulties in stretching the fibers radially, smaller fiber diameters, and reduced flux of the filter membrane. Meanwhile, too low a coagulation bath temperature can lead to insufficient crystallization degree when cellulose molecules are coagulated, the diffusion rate of colloid particles is reduced, the interval between cellulose fibers is increased, and the porosity is large. This may lead to poor mechanical properties of the filter membrane, which is prone to holes and defects.

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

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

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

In a second aspect, the application also provides a virus-removing hollow cellulose membrane prepared by the method, which comprises a tubular main body with a hollow structure, wherein the tubular main body comprises a loose layer and a interception layer, one side of the loose layer is a porous liquid inlet surface, one side of the interception layer is a porous liquid outlet surface, the loose layer and the interception layer are in transition by a nano-dirty layer formed by continuous fibers,

the aperture of the porous liquid inlet surface is 500nm-10000nm;

the aperture of the porous liquid outlet surface is 16-20nm;

the aperture of the nano-dirt layer is 20-500nm;

the thickness of the loose layer accounts for one fourth to one third of the whole film;

the thickness of the interception layer is one quarter to one third of the whole membrane.

The hollow cellulose membrane in the present application uses cellulose as a raw material. It has good hydrophilicity and low adsorption amount to protein compared to Polyethersulfone (PES) filter membrane. Therefore, protein loss can be effectively reduced in the filtration process. Meanwhile, the structure of the cellulose filter membrane provided by the application shows that the pore diameter difference of the pores on the porous liquid inlet surface and the porous liquid outlet surface is very large. The SEM measurement average pore diameter of the holes on the porous liquid surface is 16-20nm, and the filter effect on parvovirus is extremely strong. The aperture of the porous liquid inlet surface is even 25-500 times that of the porous liquid outlet surface. The device can play a good filtering effect on large-particle impurities in the liquid to be filtered, and can maintain the liquid inlet rate of the porous liquid inlet level. In addition, the loose layer and the interception layer are transited by a nano-pollution layer formed by continuous fibers. Thus, the cellulose filter membrane provided by the application is uniformly changed in the thickness direction. Since the average pore diameter of the nano-dirt layer is 20-500nm by SEM measurement, the nano-dirt layer can well intercept large protein aggregates with various sizes, prevent the large protein aggregates from blocking the filter holes of the porous liquid surface, and reduce the protein recovery rate.

In addition, in the filter membrane provided by the application, the thicknesses of the loose layer and the interception layer are relatively large. The bulk layer is about one-fourth to one-third the overall film thickness, as is the thickness of the trapping layer. Thus, the filter membrane in the present application is far beyond the general level compared to the current hollow cellulose filter membrane. Therefore, the hollow cellulose membrane has the characteristic of high hole area ratio, so that the liquid to be filtered can pass through the cellulose membrane quickly. The filter can keep higher water flux, shorten the filtering time and meet the actual application requirements.

Preferably, the water flux of the virus-removing hollow cellulose membrane is 60-300L/m ² H@30psi; the PP7 interception 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 60-150 mu m.

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

the elongation at break of the virus-removing hollow cellulose membrane is 60-150%.

The tensile strength and the elongation at break of the hollow cellulose membrane are one of the key indexes for evaluating the mechanical strength of the filter membrane. Under certain conditions, the greater the tensile strength of the filter membrane, the more excellent the mechanical strength. Tensile strength refers to the ability of a film material to withstand parallel tensile forces. During the test, the film sample was subjected to a tensile load until failure, and the tensile strength and elongation at break of the film could be calculated by recording the maximum tensile load at which the sample failed and the change in the length of the film sample.

The filter membrane has excellent mechanical properties, the tensile strength can reach 5-20MPa, and the elongation at break is 60-150%. This means that the filter membrane of the present application has high tensile strength and elongation at break, is excellent in mechanical properties, and has high industrial practical value. It can fully meet the market demand.

Therefore, the application has the following beneficial effects:

the pore size of the finally obtained virus-removing hollow cellulose membrane is controlled by adjusting the surface tension ratio among the membrane casting solution, the core solution and the coagulating bath. The prepared membrane has excellent virus interception capability, and maintains high water flux, high protein recovery rate and excellent mechanical properties. The method of the application greatly reduces the difficulty of preparing the virus-removing hollow cellulose membrane by taking the natural cellulose as the raw material, and greatly improves the social benefit.

Detailed Description

The application is further described below in connection with specific embodiments. Those of ordinary skill in the art will be able to implement the application based on these descriptions. In addition, the embodiments of the present application referred to in the following description are typically only some, but not all, embodiments of the present application. Therefore, all other embodiments, which can be made by one of ordinary skill in the art without undue burden, are intended to be within the scope of the present application, based on the embodiments of the present application.

Example 1

Molecular weight was 1.1X10 ⁵ The cotton pulp and the antioxidant sodium sulfite are dissolved in the prepared cuprammonium solution, and the filtering and the defoaming treatment are carried out, so as to obtain the casting solution with the cellulose solid content of 8wt%, the copper concentration of 3.2wt%, the ammonia concentration of 6wt%, the acetone concentration of 10% and the sodium sulfite of 1 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (30% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (70% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 2

Molecular weight is 8×10 ⁴ Dissolving cotton pulp and antioxidant tocopherol in the prepared cuprammonium solution, and carrying out filtration and defoaming treatment to obtain a casting solution with cellulose solid content of 6wt%, copper concentration of 1.5wt%, ammonia concentration of 8wt%, DMAc concentration of 5wt% and tocopherol concentration of 0.1 wt%. Then the spinning solution was discharged from the outer nozzle of the spinneret into a coagulation bath (10% aqueous ethanol solution at 25 ℃ C.) at a speed of 0.8ml/min by a spinning pump, and the core solution (60% aqueous ethanol solution at 25 ℃ C.) was also discharged from the inner nozzle of the spinneret at a speed of 1.6ml/min, wherein the outer nozzle size of the spinneret was 0.6mm in outside diameter and innerThe diameter size is 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 3

Molecular weight is 1.0X10 ⁵ The cotton pulp and antioxidant tertiary butyl hydroquinone are dissolved in the prepared cuprammonium solution, and the filtration and the deaeration treatment are carried out, so as to obtain the casting solution with the cellulose solid content of 10wt%, the copper concentration of 2.5wt%, the ammonia concentration of 10wt%, the DMF concentration of 8% and the tertiary butyl hydroquinone of 1.5 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (20% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (75% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 4

Molecular weight was 1.3X10 ⁵ Dissolving cotton pulp and antioxidant glutamic acid in the prepared cuprammonium solution, and carrying out filtration and defoaming treatment to obtain the casting solution with the cellulose solid content of 12wt%, the copper concentration of 4.5wt%, the ammonia concentration of 12wt%, the methanol concentration of 12% and the glutamic acid concentration of 2 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (35% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (80% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. Placing the solidified hollow fiber in sulfuric acid at 25 DEG CAnd (3) in the solution for 5min, ensuring that the membrane filaments are completely converted into semitransparent light blue, and finally, putting the membrane filaments into pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 5

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared cuprammonium solution, and carrying out filtration and defoaming treatment to obtain the casting solution with the cellulose solid content of 15wt%, the copper concentration of 5wt%, the ammonia concentration of 15wt%, the glycol concentration of 15% and the vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (40% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (90% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 6

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared copper ammonia solution, and filtering and defoaming to obtain the casting solution with cellulose solid content of 15wt%, copper concentration of 5wt%, ammonia concentration of 15wt% and vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (10% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (70% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 7

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared copper ammonia solution, and filtering and defoaming to obtain the casting solution with cellulose solid content of 15wt%, copper concentration of 5wt%, ammonia concentration of 15wt% and vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (20% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and core solution (70% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 8

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared copper ammonia solution, and filtering and defoaming to obtain the casting solution with cellulose solid content of 15wt%, copper concentration of 5wt%, ammonia concentration of 15wt% and vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (10% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (75% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Example 9

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared copper ammonia solution, filtering and defoaming to obtain copper with cellulose solid content of 15wt%A casting solution having a concentration of 5wt%, an ammonia concentration of 15wt% and a vitamin C concentration of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (20% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (75% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Comparative example 1

Molecular weight was 1.1X10 ⁵ The cotton pulp and the antioxidant sodium sulfite are dissolved in the prepared cuprammonium solution, and are subjected to filtration and deaeration treatment to obtain the spinning stock solution with the cellulose solid content of 8wt%, the copper concentration of 3.2wt%, the ammonia concentration of 6wt% and the sodium sulfite of 1 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (30% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (70% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Comparative example 2

Molecular weight is 8×10 ⁴ Dissolving cotton pulp and tocopherol serving as an antioxidant in a prepared cuprammonium solution, and carrying out filtering and defoaming treatment to obtain a casting solution with the cellulose solid content of 6wt%, the copper concentration of 1.5wt%, the ammonia concentration of 8wt% and the tocopherol content of 1 wt%. Then the spinning solution was discharged from the outer nozzle of the spinneret into a coagulation bath (30% ethanol aqueous solution at 25 ℃) at a rate of 0.8ml/min by a spinning pump, and the core solution was discharged(70% aqueous ethanol at 25 ℃ C.) is also simultaneously ejected from the spinneret inside nozzle at a rate of 1.6ml/min, wherein the spinneret outside nozzle size is 0.6mm in outside diameter and 0.4mm in inside diameter; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Comparative example 3

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared cuprammonium solution, and carrying out filtration and defoaming treatment to obtain the casting solution with the cellulose solid content of 15wt%, the copper concentration of 5wt%, the ammonia concentration of 15wt%, the glycol concentration of 15% and the vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (10% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (90% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; the spinning speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

Comparative example 4

Molecular weight was 1.6X10 ⁵ Dissolving cotton pulp and antioxidant vitamin C in the prepared cuprammonium solution, and carrying out filtration and defoaming treatment to obtain the casting solution with the cellulose solid content of 15wt%, the copper concentration of 5wt%, the ammonia concentration of 15wt%, the glycol concentration of 20% and the vitamin C of 3 wt%. Then, the spinning solution is sprayed from an outer spray head of the spinneret into a coagulating bath (40% ethanol water solution at 25 ℃) at a speed of 0.8ml/min by a spinning pump, and the core solution (80% ethanol water solution at 25 ℃) is also sprayed from an inner spray head of the spinneret at a speed of 1.6ml/min, wherein the outer spray head of the spinneret has an outer diameter of 0.6mm and an inner diameter of 0.4mm; spinning machineThe filament speed is 9m/min, the average residence time of the spinning solution is ensured to be 60s, and the hollow membrane is continuously solidified and discharged. And (3) placing the cured hollow fiber in a sulfuric acid solution at 25 ℃ for 5min to ensure that the membrane filaments are completely converted into semitransparent light blue, and finally placing the hollow fiber in pure water at 50 ℃ to further clean the organic solvent and metal ions on the membrane.

The surface tension of the casting solutions, core solutions, and casting solutions in examples 1 to 9 and comparative examples 1 to 4 are shown in table 1 below.

Table 1 surface tension summary table for each example and comparative example

[ Performance test ]

The detection method comprises the following steps:

average pore size test: the membrane was cut to size with a pore size distribution tester PMI, the original wet membrane was then wetted with a low surface tension (15.6 mN/m) solvent (supplied by PMI equipment manufacturer, USA) with different concentrations of ethanol, then placed in a test tank, and finally the average pore size and the onset of bubble formation were obtained by a dry-wet line.

Bubble pressure test: after the obtained film was wetted with a low surface tension liquid of 13.6mN/m (MTMNOVEC 7100)), a pressure was slowly applied to the film with compressed nitrogen until continuous bubbles were generated on the film surface, and the gas pressure at this time was referred to as bubble pressure (MPa).

Flow rate: the test is carried out by using a Millipore virus sm ax test device and a stainless steel exchangeable membrane filter with the thickness of 25mm (the device is used for protein transmittance experiments and virus filtration experiments), and the effective filtration area is 4.1cm ² The filtration test was carried out using ultrapure water at a temperature of 25℃under pressure control at 2 bar.

Surface tension test: in the environment of 25 ℃, using DataPhysics OCA20 (Germany) equipment and taking a hanging piece method as a core to dynamically test the surface tension of the copper ammonia solution, and keeping the surface tension value stable without obvious change.

Interception layer thickness test: the thickness of the dense layer was tested by SEM cross-section.

Tensile strength test: the test sample is cut into small films with the width of 1cm and the length of 8-10cm by a film cutter, and the tensile strength is tested by controlling the range of 0-50N of the range of an electronic universal tester LD22.501 by a microcomputer.

Protein transmittance test: a igg protein solution (such as 1g/L, 5g/L, etc.) was prepared at a concentration and pre-filtered to remove particles and pre-polymers of the protein solution by 0.22 μm pre-filtration. The test was then carried out using a Millipore virus max test apparatus with a 25mm stainless steel membrane-changing filter, and the absorbance was measured at a wavelength of 280nm using an ultraviolet spectrophotometer UV-5 (manufactured by Metrele). The transmittance calculation formula is as follows: transmittance=c1/c0×100%, C1 is the permeate concentration, and C0 is the stock concentration.

Virus retention experimental test: using polyclonal antibody IgG as an antibody solution, 5% of MVM murine parvovirus and BVDV bovine viral diarrhea virus were added to the obtained antibody solution, and the mixture was thoroughly stirred to obtain an antibody solution containing the virus. The test was performed using a Millipore virus max test unit plus a 25mm stainless steel membrane change filter: lrv=log10 (C0/CF);

wherein: c0 represents the infectious titer of the stock solution containing the virus antibody, and CF represents the infectious titer in the filtrate after removal of the virus filtration membrane using regenerated cellulose.

The properties of the virus-removal filtration membranes in examples 1 to 9 and comparative examples 1 to 4 are shown in Table 2 below.

TABLE 2 Performance of different virus removal filtration membranes

From the test results of examples 1 to 9 and comparative examples 1 to 4, it was found that the regenerated cellulose virus-removing hollow filtration membrane capable of trapping 20nm could be finally produced by adjusting the surface tension ratio of the casting solution to the core solution to 0.8 to 1.15, and adjusting the surface tension ratio of the casting solution to the coagulation bath to 0.5 to 0.8 to control the surface tension of the whole casting solution by using solvents having different low surface tensions, and reducing the surface tension ratio with the coagulation bath. The ratio of the surface tension between the casting solution and the core solution and between the casting solution and the coagulating bath can be realized by adding solvents with different low surface tension into the casting solution, so that the whole surface tension of the casting solution is regulated and controlled.

Claims

1. A preparation method of a virus-removing hollow cellulose membrane comprises the following steps:

(S.1) dissolving cellulose in copper ammonia solution and preparing a casting solution;

(S.2) removing bubbles in the casting solution to form spinning solution;

(S.3) extruding the spinning solution and the core solution into a coagulating bath together, and obtaining hollow fiber membrane filaments through wet spinning;

(S.4) regenerating the hollow fiber membrane filaments by a regeneration bath and washing with water to obtain the virus-free hollow cellulose membrane,

before the step (S.3), the ratio of the surface tension between the casting solution and the core solution is regulated to be 0.8-1.15, and the ratio of the surface tension between the casting solution and the coagulating bath is regulated to be 0.5-0.8.

2. The method for preparing a virus-free hollow cellulose membrane according to claim 1, wherein,

the casting solution in the step (S.1) comprises the following components in percentage by weight: 1.5-5% of copper, 6-15% of ammonia, 6-15% of cellulose and 0.1-3% of antioxidant.

3. The method for preparing a virus-free hollow cellulose membrane according to claim 2, wherein,

the raw material of the copper is at least one of copper hydroxide, basic copper sulfate and basic copper carbonate;

the raw material of the cellulose is at least one of bamboo cellulose, broad/needle pulp and cotton pulp;

the antioxidant is at least one of phenolic antioxidant, ketone antioxidant, amine antioxidant, organic acid antioxidant, inorganic acid and its salt antioxidant.

4. The method for preparing a virus-free hollow cellulose membrane according to claim 1, wherein,

adjusting the ratio of the surface tension 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;

the ratio of the surface tension between the casting solution and the coagulation bath is adjusted by changing the surface tension of at least one of the casting solution or the coagulation bath.

5. The method for preparing a virus-free hollow cellulose membrane according to claim 4,

adding a surface tension regulator to the casting solution to regulate the surface tension of the casting solution;

the surface tension of the core solution is adjusted by changing the concentration of the core solution;

6. The method for preparing a virus-free hollow cellulose membrane according to claim 5, characterized in that,

the surface tension regulator is at least one of acetone, dimethylacetamide, N-dimethylformamide, ethanol, methanol and ethylene glycol.

7. The method for producing a virus-free hollow cellulose membrane according to any one of claims 4 to 6,

the core liquid is an ethanol solution with the concentration of 60-90%, and the coagulating bath is an ethanol solution with the concentration of 10-40%.

8. The method for preparing a virus-free hollow cellulose membrane according to claim 1, wherein the wet spinning speed in the step (s.3) is 0.5-5mL/min, and the coagulation bath and core liquid temperatures are 10-40 ℃.

9. The method for preparing a virus-free hollow cellulose membrane according to claim 1, wherein,

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

10. A virus-free hollow cellulose membrane prepared by the method according to any one of claims 1 to 9, comprising a tubular body with a hollow structure, wherein the tubular body comprises a loose layer and a interception layer, one side of the loose layer is a porous liquid inlet surface, one side of the interception layer is a porous liquid outlet surface, and a nano-pollution layer formed by continuous fibers is transited between the loose layer and the interception layer, and the virus-free hollow cellulose membrane is characterized in that the pore diameter of the porous liquid inlet surface is 500nm-10000nm;

the aperture of the porous liquid outlet surface is 16-20nm;

the aperture of the nano-dirt layer is 20-500nm;

11. The virus-free hollow cellulose membrane according to claim 10, characterized in that,

the water flux of the virus-removing hollow cellulose membrane is 60-300L/m ² H@30psi; the PP7 interception 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 60-150 mu m,

the tensile strength of the virus-removing hollow cellulose membrane is 5-20MPa;