A porous polyethersulfone membrane for virus removal and a method for preparing the same

Abstract

The application provides a virus-removing polyether sulfone porous membrane and a preparation method thereof. The virus-removing polyether sulfone porous membrane comprises, in sequence along a thickness direction, an outer layer region and an inner layer region, wherein the average pore size of the outer layer region is 10-20 nm, the thickness of the outer layer region is 20-50 microns, the average pore size of the inner layer region is 5-10 microns, and the thickness of the inner layer region is 60-150 microns; and the virus-removing polyether sulfone porous membrane is prepared by a method comprising at least the following process: taking polyether sulfone as a raw material, and obtaining the virus-removing polyether sulfone porous membrane under the action of a water-soluble diluent and a hydrophilic additive; wherein the water-soluble diluent comprises ethylene carbonate and polyethylene glycol. The virus-removing polyether sulfone porous membrane has a high virus removal rate and a high protein permeation rate.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of membrane materials, and particularly relates to a polyether sulfone porous membrane for removing viruses and a preparation method thereof. BACKGROUND

[0002] In recent years, biological medical products are widely used due to high treatment effect and few side effects. In the manufacturing process, a fluid containing biological macromolecules such as antibodies needs to be separated and purified to remove various viruses contained in the fluid. At present, membrane separation method is the most commonly used way to remove viruses in the fluid, because the membrane separation technology has high separation efficiency, low energy consumption, and can be carried out at room temperature, can efficiently intercept various viruses, and will not inactivate proteins, so as to efficiently recover various biological macromolecules. Polyether sulfone is the first choice for virus removal membrane material due to its excellent biocompatibility, good mechanical properties and good hydrophilicity. More than 60% of the virus removal membrane products on the market choose polyether sulfone as the membrane material. In order to obtain greater economic benefits, it is necessary to remove viruses in the separation and purification process of biological medical products (membrane) and to pass through as much protein as possible. The smallest virus particle is a small virus, only 18-24 nm in size, and the size of antibodies and other proteins is about 10 nm. Therefore, the pore size of the membrane used for separating proteins and viruses needs to be uniformly distributed between 10-20 nm, so as to maximize the removal of viruses and pass through as much protein as possible.

[0003] US20200238221A1 prepared a membrane mainly used for filtering viruses, proteins or macromolecules. The membrane has high protein flux and long service life, but the average pore size is large, and can only intercept large particle substances with a particle size of several hundred nanometers, and cannot intercept small viruses with a particle size of 20 nm.

[0004] Chinese patent CN202310435896.5 uses volatile poor solvents to prepare high-flux high-rejection asymmetric polyether sulfone ultrafiltration membranes with dense skin by using multiphase induced phase separation. The virus can be removed, but the bovine serum albumin (BSA) rejection rate is more than 96%, which is difficult to ensure the protein yield.

[0005] In order to simultaneously meet the requirements of high virus rejection and high protein permeation, Chinese patent CN1759924B discloses a multi-layer composite ultrafiltration membrane formed by co-casting different polymer solutions. The membrane structure formed by the composite can simultaneously meet the high rejection of viruses and the high permeability of proteins. However, since the membrane is a composite membrane, the different polymers have the problem of poor compatibility, which leads to easy peeling and damage between the two layers, which easily reduces the service life of the filter membrane.

[0006] Chinese patent CN202211637916.9 describes a process where a pre-phase separation is performed in a low-temperature, high-humidity environment to form a porous surface, followed by curing in a curing solution containing a permeation additive (preferably hexafluoroisopropanol or trifluoroethanol) to form an asymmetric porous membrane structure with a small, continuously varying gradient. This structure does not require composite casting and is formed entirely from a single casting solution. However, the resulting membrane structure exhibits a relatively small gradient, making it prone to contamination and blockage by aggregated protein clusters during actual filtration. This reduces the permeation flux of proteins and the lifespan of the filter membrane. Furthermore, the fluorinated permeation additives in the curing solution used in the preparation process are harmful to human health and the environment.

[0007] Therefore, how to prepare a polyethersulfone membrane in a simple and practical way that can simultaneously improve virus removal rate and protein permeability is an urgent problem to be solved. Summary of the Invention

[0008] This invention provides a polyethersulfone porous membrane for virus removal and its preparation method. The polyethersulfone porous membrane for virus removal has a high virus removal rate and protein permeability.

[0009] This invention provides a polyethersulfone porous membrane for virus removal. The polyethersulfone porous membrane for virus removal comprises, along its thickness direction, an outer layer region and an inner layer region. The average pore size of the outer layer region is 10–20 nm, and the thickness of the outer layer region is 20–50 μm. The average pore size of the inner layer region is 5–10 μm, and the thickness of the inner layer region is 60–150 μm. The polyethersulfone porous membrane for virus removal is prepared by a method comprising at least the following steps: using polyethersulfone as a raw material, and under the action of a water-soluble diluent and a hydrophilic additive, the polyethersulfone porous membrane for virus removal is obtained. The water-soluble diluent includes ethylene carbonate and polyethylene glycol 400.

[0010] Optionally, the tensile strength of the polyethersulfone porous membrane for virus removal is 3 to 8 MPa.

[0011] Optionally, the bovine serum albumin permeability of the polyethersulfone porous membrane for virus removal is not less than 95%.

[0012] Optionally, the polyethersulfone porous membrane for virus removal has a removal rate of not less than 4% for colloidal gold particles, wherein the particle size of the colloidal gold ions is 18-22 nm.

[0013] This invention provides a method for preparing a polyethersulfone porous membrane for virus removal as described above, comprising: Step 1: melting a mixture containing polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive at 180-200°C to obtain a casting solution; the water-soluble diluent includes ethylene carbonate and polyethylene glycol 400; Step 2: coating the casting solution onto the surface of a steel plate to obtain a nascent membrane on the surface of the steel plate; the temperature of the steel plate is 160-200°C; Step 3: immersing the nascent membrane and the steel plate in ice water at 0-10°C for curing treatment, so that the nascent membrane is peeled off from the steel plate to obtain an initial membrane; Step 4: washing the initial membrane with water, then placing it in an aqueous solution containing Na2S2O8, and soaking it at 80-100°C for 4-8 hours to obtain an intermediate membrane; Step 5: washing the intermediate membrane with water to obtain the polyethersulfone porous membrane for virus removal.

[0014] Optionally, based on 100 parts by weight of the mixture, the polyethersulfone powder has a mass fraction of 12-18, preferably 13-16; the water-soluble diluent has a mass fraction of 70-82, preferably 74-79; and the hydrophilic additive has a mass fraction of 6-12, preferably 8-10.

[0015] Optionally, based on 100 parts by weight of the water-soluble diluent, the mass fraction of the acetate carbonate is 70-90, preferably 75-85.

[0016] Optionally, the hydrophilic additive includes one or more of polyvinylpyrrolidone K17, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K90; preferably, polyvinylpyrrolidone K17.

[0017] Optionally, before step 2, the process further includes: degassing the casting solution.

[0018] Optionally, in step 2, the casting solution is scraped onto the surface of the steel plate to obtain a nascent film on the surface of the steel plate; the temperature of the steel plate is 160-200°C, including: scraping the casting solution onto the surface of the steel plate at 160-200°C to form a casting solution layer with a thickness of 80-200μm, preferably 100-150μm, to obtain a nascent film on the surface of the steel plate.

[0019] The implementation of this invention has at least the following beneficial effects:

[0020] This invention provides a polyethersulfone porous membrane for virus removal and its preparation method. The polyethersulfone porous membrane for virus removal comprises, along its thickness direction, an outer region (a tightly packed dendritic nanopore structure or a dendritic pore structure) and an inner region (a loose anthill-like pore structure or an anthill-like pore structure). The average pore size of the outer region is 10–20 nm, and the average pore size of the inner region is 5–10 μm. Since the pore size of the outer region is nanometer-scale and the pore size of the inner region is micrometer-scale, the difference in pore size between the two regions is relatively small. At the transition between the inner and outer layers, the pore size rapidly decreases, forming a significant abrupt change in structure. The outer region (dendritic pore structure) exhibits high permeability, while the inner region (anthill-like pore structure) combines high porosity and high permeability. This abrupt change in structure ensures that the porous membrane has a higher flux, improves its virus retention rate, guarantees efficient virus removal, and also has a high protein permeability. Attached Figure Description

[0021] Figure 1 This is a cross-sectional SEM image of the polyethersulfone porous membrane used for virus removal in Example 1;

[0022] Figure 2 This is a cross-sectional SEM magnified image of the outer layer (dense layer) of the polyethersulfone porous membrane used for virus removal in Example 1;

[0023] Figure 3 This is a cross-sectional SEM magnified image of the inner layer region (support layer) of the polyethersulfone porous membrane used for virus removal in Example 1;

[0024] Figure 4 This is a SEM image of the outer surface layer of the polyethersulfone porous membrane used for virus removal in Example 1.

[0025] Figure 5 This is a cross-sectional SEM image of the polyethersulfone porous membrane used for virus removal in Comparative Example 1.

[0026] Figure 6 This is a cross-sectional SEM image of the polyethersulfone porous membrane used for virus removal in Comparative Example 2. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0028] This invention provides a polyethersulfone porous membrane for virus removal. The membrane comprises an outer layer and an inner layer along its thickness direction. The outer layer has an average pore size of 10–20 nm and a thickness of 20–50 μm, while the inner layer has an average pore size of 5–10 μm and a thickness of 60–150 μm. The membrane is prepared by a method comprising at least the following steps: using polyethersulfone as a raw material, a water-soluble diluent and a hydrophilic additive are used to obtain the membrane. The water-soluble diluent includes ethylene carbonate and polyethylene glycol 400.

[0029] According to the inventor's research and analysis, the polyethersulfone porous membrane for virus removal has a porous structure, exhibiting an asymmetric structure with one side being dense and the other side being loose. Specifically, along the thickness direction, the polyethersulfone porous membrane for virus removal includes an outer region (dense layer) and an inner region (support layer). The average pore size of the outer region is 10-20 nm, and the thickness is 20-50 μm. The outer region has a tightly packed dendritic nanopore structure. The average pore size of the inner region is 5-10 μm, and the thickness is 60-150 μm. The inner region has a loose ant-like pore structure. Due to the smaller average pore size and porosity of the outer region, it is conducive to virus separation. Due to the larger average pore size and porosity of the inner region, it is conducive to fluid permeation. Thus, the polyethersulfone porous membrane for virus removal has both good virus separation performance and water permeability. When this polyethersulfone porous membrane for virus removal is applied to remove viruses from fluids, the fluid flows in from the inner region (loose, ant-like pore structure) and flows out from the outer region (dense, dendritic pore structure). Viruses enter the membrane with the fluid, pass through the inner region (loose, ant-like pore structure), and are then trapped in the outer region (dense, dendritic pore structure), thus completing virus separation without affecting protein permeation. Therefore, the polyethersulfone porous membrane for virus removal provided in this invention has a high virus retention rate and a high protein permeability, enabling the separation of biological components, especially antibodies and other proteins, from viruses at low pressure and in a short time.

[0030] In some embodiments, the bovine serum albumin permeability of the polyethersulfone porous membrane for virus removal is not less than 95%.

[0031] In some embodiments, the polyethersulfone porous membrane for virus removal has a removal rate of colloidal gold particles of not less than 4%, wherein the particle size of the colloidal gold ions is 18-22 nm.

[0032] The virus-removing polyethersulfone porous membrane also has high tensile strength; specifically, the tensile strength of the polyethersulfone porous membrane can be 3 to 8 MPa.

[0033] This invention also provides a method for preparing the above-mentioned polyethersulfone porous membrane for virus removal, comprising: Step 1: Melting a mixture containing polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive at 180-200°C to obtain a casting solution; the water-soluble diluent includes ethylene carbonate and polyethylene glycol 400; Step 2: Coating the casting solution onto the surface of a steel plate to obtain a nascent membrane on the surface of the steel plate; the temperature of the steel plate is 160-200°C; Step 3: Immersing the nascent membrane and the steel plate in ice water at 0-10°C for curing treatment, so that the nascent membrane is peeled off from the steel plate to obtain an initial membrane; Step 4: Washing the initial membrane with water, then placing it in an aqueous solution containing Na2S2O8, and then soaking it at 80-100°C for 4-8 hours to obtain an intermediate membrane; Step 5: Washing the intermediate membrane with water to obtain a polyethersulfone porous membrane for virus removal.

[0034] According to the inventors' research and analysis: In the preparation system provided in the embodiments of this invention, polyethylene glycol (water-soluble non-solvent) and hydrophilic additives, as pore-forming agents, can improve the pore interconnectivity of the polyethersulfone porous membrane for virus removal, increase the porosity of the polyethersulfone porous membrane for virus removal, and make the pores on the surface of the polyethersulfone porous membrane for virus removal more uniform; ethylene carbonate (water-soluble high-temperature solvent) dissolves polyethersulfone powder at high temperature to form a casting solution, and ethylene carbonate (water-soluble high-temperature solvent), polyethylene glycol (water-soluble non-solvent), and polyvinylpyrrolidone (hydrophilic additive) can undergo mass transfer with ice water during subsequent curing and film formation, promoting the curing and film formation of polyethersulfone, and promoting... The nascent membrane exhibits a denser dendritic pore structure on the surface near the ice water, forming a compact outer layer. Simultaneously, a heat transfer reaction occurs on the surface near the steel plate, resulting in a looser, ant-like pore structure, forming a porous inner layer. Polyethylene glycol, acting as a non-solvent, can regulate the compatibility of the reaction system to form a macroporous structure. The additive, polyvinylpyrrolidone (PVP), undergoes a self-crosslinking reaction catalyzed by Na₂S₂O₈, forming an interpenetrating network structure within the membrane pores. This slightly reduces the pore size, increasing the rejection rate without affecting the flux. Furthermore, the interpenetrating network structure permanently retains PPVP within the pores, achieving permanent hydrophilicity. Therefore, the preparation method of this invention can produce a polyethersulfone porous membrane for virus removal with high virus removal and protein permeability.

[0035] The embodiments of the present invention do not limit the specific process of melting treatment. For example, a mixture containing polyethersulfone powder, water-soluble diluent, and hydrophilic additives can be placed in a three-necked flask and stirred and melted at 180-200°C for 2-6 hours to obtain a clear and transparent casting solution.

[0036] The embodiments of the present invention do not limit the mass percentage of each substance in the mixture.

[0037] In some embodiments, based on 100 parts by weight of the mixture, the polyethersulfone powder has 12 to 18 parts by weight, preferably 13 to 16 parts by weight; the water-soluble diluent has 76 to 86 parts by weight, preferably 78 to 84 parts by weight; and the hydrophilic additive has 1 to 6 parts by weight, preferably 2 to 4 parts by weight.

[0038] Based on 100 parts by weight of water-soluble diluent, the mass fraction of acetate carbonate can be 70-90, preferably 75-85.

[0039] In the mixture, the mass ratio of polyethersulfone powder, hydrophilic additive, and water-soluble diluent can be (12-18):(1-6):(76-86); preferably (13-16):(2-4):(78-84).

[0040] The weight-average molecular weight of the aforementioned polyethylene glycol can be 360 ​​to 440, for example, 360, 400, 440, or any combination thereof. In specific implementations, the polyethylene glycol may include polyethylene glycol 400, that is, the weight-average molecular weight of the polyethylene glycol is 400. This helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane used for virus removal, and avoids the problem of poor compatibility of the reaction system and difficulty in melting caused by excessively high molecular weight of polyethylene glycol, which would degrade the virus removal rate and protein permeability of the polyethersulfone porous membrane used for virus removal.

[0041] The aforementioned hydrophilic additive may include polyvinylpyrrolidone (PVP), the weight-average molecular weight of which may be 1,700 to 1,100,000, for example, 1,700, 49,000, 1,100,000 or any combination thereof. In specific implementations, the aforementioned PPVP includes one or more of PPVP K17, PPVP K30, and PPVP K90; preferably PPVP K17, which helps to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal, and avoids the fact that an excessively high molecular weight of PPVP will result in poor hydrophilicity after membrane cross-linking, thereby deteriorating the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal.

[0042] In the preparation system provided in this invention embodiment, polyethylene glycol (water-soluble non-solvent) and polyvinylpyrrolidone (hydrophilic additive) serve as pore-forming agents, which can improve the pore interconnectivity of the polyethersulfone porous membrane for virus removal, increase the porosity of the polyethersulfone porous membrane for virus removal, and make the pores on the surface of the polyethersulfone porous membrane for virus removal more uniform. Ethylene carbonate (water-soluble high-temperature solvent) dissolves polyethersulfone powder at high temperature to form a casting solution, and ethylene carbonate (water-soluble high-temperature solvent), polyethylene glycol (water-soluble non-solvent), and polyvinylpyrrolidone (hydrophilic additive) can undergo mass transfer with ice water during subsequent curing and film formation, promoting the curing and film formation of polyethersulfone and promoting initial... The surface of the ecological membrane near the ice water forms a relatively dense dendritic pore structure, i.e., a compact outer layer. At the same time, the surface of the nascent ecological membrane near the steel plate undergoes a heat transfer reaction, forming a relatively loose ant-like pore structure, i.e., a loose inner layer. Meanwhile, polyethylene glycol, as a non-solvent, can regulate the compatibility of the reaction system to form a macroporous structure. The additive polyvinylpyrrolidone can undergo a self-crosslinking reaction under the catalysis of Na2S2O8, forming an interpenetrating network structure within the membrane pores. This can slightly reduce the membrane pore size and increase the rejection rate without affecting the flux. At the same time, the interpenetrating network structure allows polyvinylpyrrolidone to remain permanently within the membrane pores, achieving permanent hydrophilicity.

[0043] In step 2, the casting solution can be scraped onto the surface of a steel plate at a temperature of 160–200°C to obtain a nascent film on the surface of the steel plate. One side of the nascent film faces outward (away from the steel plate), while the other side (closer to the steel plate) is in contact with the steel plate at a temperature of 160–200°C.

[0044] In a specific implementation, the casting solution is scraped onto the surface of the steel plate at 160–200°C to obtain a nascent film on the surface of the steel plate. This includes: scraping the casting solution onto the surface of the steel plate at 160–200°C to form a scraped casting solution layer with a thickness of 80–200 μm, preferably 100–150 μm, to obtain a nascent film on the surface of the steel plate.

[0045] In step 3, the steel plate with the nascent membrane attached (the nascent membrane and the steel plate) is immersed in ice water at 0-10°C for curing. The outer surface of the nascent membrane comes into contact with the ice water first, undergoing a mass transfer reaction. The rapid mass transfer of ethylene carbonate (a water-soluble high-temperature solvent), polyethylene glycol (a water-soluble non-solvent), and polyvinylpyrrolidone (a hydrophilic additive) with water promotes the formation of a dense skin layer. This is because: firstly, reducing the mass transfer rate increases surface porosity, reducing the formation of a dense skin layer; secondly, the viscosity of the casting solution has a significant impact on the final filter membrane structure and performance. Firstly, the higher the viscosity of the casting solution, the greater the mass transfer resistance and the slower the mass transfer rate. Secondly, the solid content of the casting solution plays a decisive role in its viscosity. A lower solid content results in a lower viscosity and an increase in the pore size of the surface pores. Ethylene carbonate is a water-soluble high-temperature solvent, and its mass transfer rate is lower than that of N,N-dimethylacetamide (DMAc) used in conventional non-solvent-induced phase separation methods, thus leading to delayed phase separation. A lower solid content also results in a lower viscosity and an increase in the pore size of the surface pores. Therefore, under the combined effect of the above factors, an outer layer region (first outer surface) with a large number of uniform small pores is formed.

[0046] Meanwhile, the other side of the nascent membrane, which is in contact with the steel plate, is closer to the hotter steel plate. During the heat transfer reaction with the ice water, the ethylene carbonate-polyethersulfone system exhibits a high-temperature compatibility and low-temperature phase separation phenomenon, a typical thermally induced phase separation process. This promotes the formation of a ant-like pore structure on the cross-section, resulting in a relatively loose porous structure, i.e., the formation of the inner layer region. Simultaneously, the addition of polyethylene glycol as a non-solvent additive to the system worsens the system's compatibility, making it easier to cool down and separate, thus forming the inner layer region with a large pore structure. Under the combined effect of these two factors, a loose ant-like pore structure is formed, i.e., the formation of the inner layer region (second outer surface). Thus, as heat and mass transfer continues on both surfaces, an initial membrane gradually forms, with porosity and average pore size increasing (e.g., a gradient increase) from the outer layer region (first outer surface) to the inner layer region (second outer surface).

[0047] As the curing process proceeds, the initial film gradually peels off from the steel plate, yielding the initial film.

[0048] Furthermore, the embodiments of the present invention do not limit the specific operations of steps 2 (film formation treatment) and 3 (curing treatment). For example, in some embodiments, the casting solution is allowed to stand at 160-200°C for 0.5-4.5 hours to remove bubbles, and then poured onto a steel plate at 160-200°C. A stainless steel scraper is used to coat the steel plate to form a film, thereby obtaining a nascent film. This helps to improve the film formation effect because if the temperature of the film formation treatment is too low, the casting solution system will solidify and it will be difficult to coat the film; if the temperature of the film formation treatment is too high, the water-soluble diluent will evaporate, which is not conducive to the subsequent mass transfer process.

[0049] Furthermore, if the temperature of the ice water used in the curing process is too high or too low, it is difficult to form abrupt asymmetric structures and bicontinuous structures. The embodiments of the present invention, by limiting the temperature of the film-forming process and the curing process, facilitate the formation of polyethersulfone porous membranes with the above-mentioned structures.

[0050] In step 4, the initial membrane is washed with water and then placed in an aqueous solution containing Na2S2O8, and then soaked at 80-100°C for 4-8 hours to allow the hydrophilic additive to undergo a self-crosslinking reaction, resulting in an intermediate membrane. Exemplarily, the soaking temperature can be 80°C, 90°C, 100°C, or any combination thereof, preferably 90°C, and the soaking time can be 4 hours, 6 hours, 8 hours, or any combination thereof, preferably 6 hours. This helps improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal. The reason for this is that if the soaking temperature is too low and the crosslinking reaction time is too short, the crosslinking reaction will be incomplete, making it difficult to achieve the effects of increasing hydrophilicity and narrowing the pores; if the soaking temperature is too high and the crosslinking reaction time is too long, it will lead to over-crosslinking, clogging the pores and reducing the flux. Therefore, by limiting the temperature and time of the above-mentioned soaking, the embodiments of the present invention help to ensure sufficient cross-linking and improve the pore structure and surface hydrophilicity of the polyethersulfone porous membrane, thereby helping to improve the virus removal rate and protein permeability of the polyethersulfone porous membrane for virus removal.

[0051] The present invention will be further described below through specific embodiments and comparative examples. Unless otherwise specified, the reagents, materials and instruments used below are all conventional reagents, materials and instruments, all of which are commercially available, and the reagents and materials involved can also be synthesized by conventional synthetic methods.

[0052] Example 1

[0053] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0054] 12g of polyethersulfone powder (Solvay) 3000 MPa), 10.75 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 75.25 g ethylene carbonate were stirred and melted in a three-necked flask at 180 °C for 4 h to prepare a clear and transparent casting solution.

[0055] The casting solution was allowed to stand at 180°C for 2.5 hours to remove bubbles, and then poured onto a steel plate at 180°C. A uniform initial film was formed on the surface of the steel plate using a stainless steel scraper, wherein the distance between the stainless steel scraper and the steel plate was 150 μm.

[0056] The initial membrane is obtained by immersing the nascent membrane and steel plate in a 0°C ice-water solidification bath to solidify them into a membrane.

[0057] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0058] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0059] Example 2

[0060] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0061] 14g of polyethersulfone powder (Solvay) 3000 MPa), 10.5 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 73.5 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0062] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0063] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0064] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0065] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0066] Example 3

[0067] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0068] 18g of polyethersulfone powder (Solvay) 3000MP), 10g polyethylene glycol 400, 2g polyvinylpyrrolidone (K17, molecular weight 8000), and 70g ethylene carbonate were stirred and melted in a three-necked flask at 180℃ for 4 hours to prepare a clear and transparent casting solution.

[0069] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0070] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0071] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0072] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0073] Example 4

[0074] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0075] 14g of polyethersulfone powder (Solvay) 3000 MPa), 8.4 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 75.6 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0076] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0077] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0078] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0079] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0080] Example 5

[0081] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0082] 14g of polyethersulfone powder (Solvay) 3000 MPa), 5.6 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 78.4 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0083] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0084] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0085] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0086] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0087] Example 6

[0088] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0089] 14g of polyethersulfone powder (Solvay) 3000 MPa), 16.8 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 67.2 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0090] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0091] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0092] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0093] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0094] Example 7

[0095] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0096] 14g of polyethersulfone powder (Solvay) 3000MP), 10g polyethylene glycol 400, 6g polyvinylpyrrolidone (K17, molecular weight 8000), and 70g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0097] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0098] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0099] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0100] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0101] Example 8

[0102] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0103] 14g of polyethersulfone powder (Solvay) 3000 MPa), 10.625 g polyethylene glycol 400, 1 g polyvinylpyrrolidone (K17, molecular weight 8000), and 74.375 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0104] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0105] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0106] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0107] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0108] Example 9

[0109] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0110] 14g of polyethersulfone powder (Solvay) 3000 MPa), 10.5 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 73.5 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0111] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 80μm between the stainless steel scraper and the steel plate.

[0112] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0113] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0114] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0115] Example 10

[0116] The preparation process of the virus-removing polyethersulfone porous membrane in this embodiment includes the following steps:

[0117] 14g of polyethersulfone powder (Solvay) 3000 MPa), 10.5 g polyethylene glycol 400, 2 g polyvinylpyrrolidone (K17, molecular weight 8000), and 73.5 g ethylene carbonate were stirred and melted in a three-necked flask at 180°C for 4 hours to prepare a clear and transparent casting solution.

[0118] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 200μm between the stainless steel scraper and the steel plate.

[0119] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0120] The initial membrane was placed in a 0.4% (w / w) Na2S2O8 aqueous solution and soaked at 90°C for 6 hours to allow polyvinylpyrrolidone to undergo self-crosslinking, thus obtaining the intermediate membrane.

[0121] The intermediate membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a polyethersulfone porous membrane for virus removal.

[0122] Comparative Example 1

[0123] The preparation process of the virus-removing polyethersulfone porous membrane in this comparative example includes the following steps:

[0124] 14g of polyethersulfone powder (Solvay) 3000MP), 10g polyethylene glycol 400, 2g polyvinylpyrrolidone (K17, molecular weight 8000), and 74g N,N-dimethylacetamide were stirred and dissolved in a three-necked flask at 50°C for 6 hours to prepare a clear and transparent casting solution.

[0125] The casting solution was allowed to stand at 25°C for 12 hours to remove bubbles, and then poured onto a 25°C steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150 μm between the stainless steel scraper and the steel plate.

[0126] The nascent membrane was immersed in a 0°C ice-water solidification bath to solidify it into a membrane, thus obtaining the initial membrane.

[0127] The initial membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a porous membrane.

[0128] Comparative Example 2

[0129] The preparation process of the virus-removing polyethersulfone porous membrane in this comparative example includes the following steps:

[0130] 14g of polyethersulfone powder (Solvay) 3000 MPa) and 86 g of ethylene carbonate were stirred and melted in a three-necked flask at 180 °C for 4 h to prepare a clear and transparent casting solution.

[0131] The casting solution was allowed to stand at 180℃ for 2.5 hours to remove bubbles, and then poured onto a 180℃ steel plate. A uniform initial film was formed on the steel plate using a stainless steel scraper with a distance of 150μm between the stainless steel scraper and the steel plate.

[0132] The nascent membrane is immersed in a liquid nitrogen solidification bath to solidify it into a film, thus obtaining the initial membrane;

[0133] The initial membrane was soaked in pure water for 48 hours to remove polyethylene glycol 400 and polyvinylpyrrolidone (to extract diluent and unreacted additives), thus obtaining a porous membrane.

[0134] Test case

[0135] 1. Scanning electron microscope image

[0136] The above-mentioned polyethersulfone porous membrane (membrane product) for virus removal was sampled multiple times and observed directly using a scanning electron microscope;

[0137] 2. Determination of porosity and average pore size

[0138] Porosity: ImageJ image analysis software was used to characterize and analyze the SEM images to obtain the porosity of different regions of the membrane cross section.

[0139] Average pore size: Multiple samples of the membrane product were taken and observed and measured using a scanning electron microscope;

[0140] The thickness of the support layer (inner region) and the separation layer (outer region) were measured by taking multiple samples of the membrane product and observing them with a scanning electron microscope.

[0141] 3. Mechanical strength test

[0142] The membrane product with a length of 30mm was clamped at both ends on a tensile testing machine and tested using an AGS-J type electronic universal testing machine. The tensile speed used was 250mm / min, and the tensile strength was measured.

[0143] 4. Determination of pure water flux

[0144] The membrane product and membrane housing are encapsulated into a membrane module, which is then used as the filter membrane. Pure water at a pressure P (bar) and a temperature of 25°C is introduced into the filter membrane. After stabilizing for 30 minutes, samples are taken at regular intervals (T) and the permeate flow rate (V) is measured over a total of three times. The average value is calculated, and the effective area of ​​the filter membrane through which pure water permeates is defined as A (m²). 2 The pure water flux J corresponding to the membrane product is calculated using J = V / (A×T×P), with units of L / (m³). 2 ·h·bar).

[0145] 5. Determination of removal rate and permeability

[0146] The procedure for determining the removal rate of 20nm colloidal gold particles (logarithmic removal rate (LRV) of 20nm colloidal gold) is as follows:

[0147] (1) Preparation of colloidal gold solution: Purchase a colloidal gold solution with a particle size of 20 nm (Nanopartz) and a concentration of 0.05 mg / ml. Add 0.2 wt% sodium dodecyl sulfate (SDS) to the solution to prepare the raw material solution.

[0148] (2) Filtration of colloidal gold solution: Pure water at a pressure of 0.1 MPa and a temperature of 25°C was passed through the filter membrane and stabilized for 30 min. Then, 0.2 wt% SDS solution was passed through the membrane module for 5 min to wet the membrane and reduce the adsorption of gold nanoparticles. The prepared colloidal gold raw material solution was then passed through the membrane module. The filtration area of ​​the virus-removing membrane was 0.001 m². 2 .

[0149] (3) Removal rate of colloidal gold particles: The raw material solution and the permeate of the prepared 20nm colloidal gold solution were collected, and the absorbance of the raw material solution (A) and the permeate (B) at the maximum absorption wavelength were measured using a UV spectrophotometer. According to LRV = log 10 (A / B) Calculate the logarithmic removal rate (LRV) of colloidal gold at 20 nm.

[0150] (4) BSA protein particle permeability:

[0151] A 600 ppm bovine serum albumin (BSA) solution was prepared in PBS buffer as the feed solution. Pure water at 0.1 MPa and 25°C was passed through the filter membrane and allowed to stabilize for 30 min. Then, PBS buffer was passed through the membrane module for 5 min to wet the membrane, followed by permeation of the BSA feed solution through the membrane module. The BSA feed solution and permeate were collected and measured using a UV spectrophotometer. The concentrations of the BSA feed solution (C0) and permeate (C1) were calculated. The permeability S (%) of the membrane product to BSA protein particles was calculated using the formula S = C1 / C0 × 100%.

[0152] The test results are shown in Table 1.

[0153] Table 1

[0154]

[0155]

[0156] Combination Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6As shown in Table 1, the porosity and average pore size of the virus-removing polyethersulfone porous membrane in the embodiments of the present invention increase from the loose, ant-like pore structure side to the dense, stacked, dendritic pore structure side. Comparing Examples 1-10 and Comparative Examples 1-2, the polyethersulfone porous membrane provided by the present invention has a unique structure with one side dense and the other loose, and possesses excellent water flux, high colloidal gold rejection rate, high BSA permeability, and good fouling resistance. Specifically, comparing Examples 1-10 and Comparative Examples 1-2 shows that the present invention, by selecting specific hydrophilic additives and combining them with a specific preparation process, can obtain a high-performance polyethersulfone porous membrane. The membrane structures prepared in Comparative Examples 1 and 2 do not meet the limitation on average pore size. Comparative Example 1, prepared from pure NIPS, has poor mechanical strength, low BSA permeability, and poor fouling resistance; Comparative Example 2, prepared from pure TIPS, has poor colloidal gold rejection rate.

[0157] The preferred embodiments and experimental verifications of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the protection scope of the present invention.

Claims

1. A method for preparing a polyethersulfone porous membrane for virus removal, characterized in that, include: Step 1: Melt a mixture containing polyethersulfone powder, a water-soluble diluent, and a hydrophilic additive at 180-200°C to obtain a casting solution; the water-soluble diluent includes ethylene carbonate and polyethylene glycol; the hydrophilic additive includes one or more of polyvinylpyrrolidone K17, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K90. Step 2: Apply the casting solution to the surface of the steel plate to obtain a nascent film on the surface of the steel plate; The temperature of the steel plate is 160~200 ℃; Step 3: Immerse the primary ecological membrane and the steel plate in ice water at 0~10 ℃ for solidification treatment, so that the primary ecological membrane can be peeled off from the steel plate to obtain the initial membrane; Step 4: Wash the initial membrane with water, then place it in an aqueous solution containing Na2S2O8, and soak it at 80~100 ℃ for 4~8 h to obtain the intermediate membrane; Step 5: After washing the intermediate membrane with water, the virus-removing polyethersulfone porous membrane is obtained.

2. The preparation method according to claim 1, characterized in that, Based on 100 parts by weight of the mixture, the polyethersulfone powder has a mass of 12-18 parts by weight; the water-soluble diluent has a mass of 76-86 parts by weight; and the hydrophilic additive has a mass of 1-6 parts by weight.

3. The preparation method according to claim 2, characterized in that, Based on 100 parts by weight of the mixture, the polyethersulfone powder has a mass of 13-16 parts by weight; the water-soluble diluent has a mass of 78-84 parts by weight; and the hydrophilic additive has a mass of 2-4 parts by weight.

4. The preparation method according to any one of claims 1-3, characterized in that, Based on 100 parts by weight of the water-soluble diluent, the mass fraction of the acetate carbonate is 70-90.

5. The preparation method according to claim 4, characterized in that, The mass fraction of the carbonate acetate is 75-85%.

6. The preparation method according to claim 1, characterized in that, The hydrophilic additive is polyvinylpyrrolidone K17.

7. The preparation method according to any one of claims 1-3 or 5-6, characterized in that, The polyethylene glycol includes polyethylene glycol 400.

8. The preparation method according to any one of claims 1-3 or 5-6, characterized in that, In step 2, the casting solution is scraped onto the surface of the steel plate to obtain a nascent film on the surface of the steel plate. The temperature of the steel plate is 160~200℃, including: The casting solution is scraped onto the surface of the steel plate to form a scraped casting solution layer with a thickness of 80~200μm, thus obtaining a nascent film on the surface of the steel plate.

9. The preparation method according to claim 8, characterized in that, The thickness of the coating liquid layer is 100~150μm.

10. A polyethersulfone porous membrane for virus removal, said polyethersulfone porous membrane for virus removal is prepared based on the method according to any one of claims 1-9, characterized in that, The virus-removing polyethersulfone porous membrane comprises, along its thickness direction, an outer layer region and an inner layer region. The outer layer region is a tightly packed dendritic nanopore structure with an average pore size of 10-20 nm and a thickness of 20-50 μm. The inner layer region is a loose, ant-like pore structure with an average pore size of 5-10 μm and a thickness of 60-150 μm. The bovine serum albumin permeability of the virus-removing polyethersulfone porous membrane is not less than 95%, and the removal rate of colloidal gold ions with a particle size of 18-22 nm is not less than 4%.

11. The polyethersulfone porous membrane for virus removal according to claim 10, characterized in that, The tensile strength of the polyethersulfone porous membrane used for virus removal is 3~8 MPa.

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