Composite membrane for virus removal and preparation method therefor

Abstract

The present application provides a composite membrane for virus removal and a preparation method therefor. The composite membrane for virus removal has a porous structure formed by interweaving fibers, the composite membrane comprises a pre-filtering layer and a separation layer compounded on the pre-filtering layer, and the average fiber diameter of the separation layer is smaller than the average fiber diameter of the pre-filtering layer; the composite membrane further comprises a fusion layer formed by fusing the pre-filtering layer and the separation layer at the junction of the pre-filtering layer and the separation layer, and the fusion layer is used for increasing the bonding strength of the composite membrane; the fusion layer is formed by extending filter fibers of the separation layer and embedding the filter fibers into the pre-filtering layer, and in the fusion layer, the content ratio of fibers having a diameter greater than 300 nm to fibers having a diameter less than 300 nm is 1.5-4. The composite membrane provided by the present application has good bonding strength, and thus has good anti-peeling performance; meanwhile, the composite membrane has high flux and loading capacity.

Description

A composite membrane for removing viruses and preparation method thereof

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to the Chinese patent application filed with the China Patent Office on November 24, 2023, with application number 202311575461.7 and invention name “A composite membrane for virus removal and its preparation method”, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present application relates to the technical field of virus removal filter membranes, and in particular to a virus removal composite membrane and a preparation method thereof. Background Art

[0004] Virus removal membranes intercept viruses through physical filtration. Viruses of a specific size are retained by membranes with a specific pore size. Their retention efficiency is largely unaffected by differences in the physical and chemical properties of different viruses, as well as by operating conditions. Furthermore, because virus removal membranes intercept viruses through physical filtration, they do not alter the physical and chemical properties of viruses and useful proteins in the filtered solution. Therefore, virus removal membranes have important applications in the field of biological preparations.

[0005] Different filtration membranes have different filtration properties and are suitable for different application scenarios. For example, ultrafiltration membranes have an effective pore size range of 5-100 nanometers and are used to concentrate or filter soluble macromolecules such as proteins, DNA, and natural or synthetic polymers. Microfiltration membranes have an effective pore size range of 0.1-10 microns and are used to remove particles such as solid particles, bacteria, and microorganisms from liquid or gas streams. In real-world applications, multiple filtration membranes are often used in combination.

[0006] A common combination method in the prior art is to stack single-layer structural membranes of the same or different materials to obtain a laminated membrane. This method has the following shortcomings: First, each layer of the membrane needs to be prepared and stacked separately, which will increase costs and reduce production efficiency. In addition, breakage may occur during the preparation of the folded filter, causing foreign matter to enter the interlayer and affect the filter performance; second, it is very difficult to prepare a thinner single-layer membrane, which is prone to breakage or wrinkles, and if the membrane is too thick as a whole, it will undoubtedly reduce the flux of the membrane and lose its competitive advantage; third, the membrane fit obtained by stacking is bound to be affected, and it is easy to peel off when it is impacted by the liquid during the process of bearing higher pressure. For this reason, the industry has developed a co-casting technology, which forms a composite membrane by coating two layers of membrane in sequence in a relatively short period of time, greatly simplifying the preparation process of the composite membrane.

[0007] Actual research has found that existing composite membranes are prone to delamination during the phase inversion process due to differences in the properties of the two membrane materials and the solvent system, or the two casting solutions may become miscible, resulting in an uneven internal structure of the finished membrane and affecting the stability of the membrane performance. For example, U.S. Patent Publication No. US7208200B2 mentions that sequential casting may produce a clear dividing line or region with a dense, skin-like structure between the retention zone and the pre-filtration zone; however, because the areas above and below the dividing line are not interwoven and interconnected, particle accumulation is prone to occur, and the double-layer membrane may peel under external factors such as equipment vibration or high pressure. For another example, U.S. patent document with publication number US4824568A discloses a method of forming a composite membrane by coating a layer of PVDF or PES on a 0.22μm PVDF substrate to achieve a pre-filtration effect, and greatly improve the peel strength of the composite membrane by the permeability of the solvent in the casting liquid to the substrate during the coating process; however, this method will destroy the permeability between the membranes during the dissolution of the substrate, causing dense phenomena and blockages, resulting in a decrease in membrane flux.

[0008] In view of this, it is necessary to propose a new technical solution to overcome the shortcomings of the existing technology.

[0009] Summary of the Invention

[0010] The technical problem to be solved by the present application is to overcome the deficiencies of the above-mentioned prior art and provide a composite membrane for virus removal and a preparation method thereof, wherein the composite membrane has better bonding strength and at the same time has higher flux and loading capacity.

[0011] In order to achieve the above objectives, this application is implemented through the following technical solutions:

[0012] A composite membrane for virus removal, having a porous structure formed by interwoven fibers, the composite membrane comprising a pre-filtration layer and a separation layer composited with the pre-filtration layer, wherein the average fiber diameter of the separation layer is smaller than the average fiber diameter of the pre-filtration layer; the composite membrane further comprises:

[0013] A fusion layer formed by fusing the pre-filtration layer and the separation layer at their interface, which is used to increase the bonding strength of the composite membrane;

[0014] The fusion layer is formed by extending the filter fibers of the separation layer and embedding them into the pre-filtration layer, and in the fusion layer, the ratio of fibers with a diameter greater than 300 nm to fibers with a diameter less than 300 nm is 1.5-4.

[0015] Optionally, the ratio of the average pore size of the fusion layer to the average fiber diameter thereof is 0.5-1.8.

[0016] Optionally, the average fiber diameter of the fusion layer is 280-400 nm.

[0017] Optionally, the average pore size of the fusion layer is 200-600 nm.

[0018] Optionally, the thickness of the fusion layer is 5-30 μm.

[0019] Optionally, the thickness of the fusion layer is 3-25% of the total thickness of the composite film.

[0020] Optionally, the total thickness of the composite membrane is 100-150 μm, the thickness of the pre-filtration layer is 60-100 μm, the thickness of the separation layer is 20-45 μm, and the thickness ratio of the pre-filtration layer to the separation layer is 1-4.

[0021] Optionally, the fusion layer is formed by fusing a semi-solid pre-filtration layer and a liquid separation layer at their interface, which can increase the filtration gradient of the composite membrane.

[0022] Optionally, the pre-filtration layer forms the liquid inlet surface during filtration, and the initial water contact angle of the liquid inlet surface is 10°-30°; the separation layer forms the liquid outlet surface during filtration, and the initial water contact angle of the liquid outlet surface is 30°-60°.

[0023] Optionally, the average surface pore size of the liquid inlet surface is 500-1200 nm, and the membrane pore ratio is 30-55%; the average surface pore size of the liquid outlet surface is 15-30 nm, and the membrane pore ratio is 25-45%.

[0024] Optionally, the average pore size of the pre-filtration layer is 450-1000 nm, the average pore size of the separation layer is 55-100 nm, and the porosity of the composite membrane is 70-85%.

[0025] Optionally, the average fiber diameter of the pre-filtration layer is 200-350 nm, and the average fiber diameter of the separation layer is 50-80 nm.

[0026] Optionally, the ratio of the average pore size of the pre-filtration layer to its average fiber diameter is 1.28-5, and the ratio of the average pore size of the separation layer to its average fiber diameter is 0.65-2.

[0027] Optionally, the peel strength between the pre-filtration layer and the separation layer is 0.1-0.3 N / mm.

[0028] Optionally, the pre-filtration layer is a nylon layer, and the separation layer is a polyethersulfone layer.

[0029] Optionally, the sulfur content in the fusion layer accounts for 1-7% of the total amount of carbon, nitrogen, oxygen and sulfur elements in the fusion layer, and the nitrogen content accounts for 3-9% of the total amount of carbon, nitrogen, oxygen and sulfur elements in the fusion layer.

[0030] Optionally, the separation layer comprises a virus retention region with a thickness of 5-15 μm and an average pore size of 25-35 nm.

[0031] Optionally, the fusion layer has a first interface with the pre-filtration layer and a second interface with the separation layer. The area of ​​the composite membrane that captures 50nm colloidal gold is 0-60% of the area below the second interface. The area of ​​the composite membrane that captures 30nm colloidal gold is 30-85% of the area below the second interface. The area of ​​the composite membrane that captures 20nm colloidal gold is 70-99.5% of the area below the second interface.

[0032] Optionally, the absorption peak of the composite membrane for 50nm colloidal gold is located at 20-30μm from the liquid surface, the absorption peak for 30nm colloidal gold is located at 2-15μm from the liquid surface, and the absorption peak for 20nm colloidal gold is located at 0.5-9μm from the liquid surface.

[0033] Optionally, the average pore size within the 5 μm region above and below the first interface is 300-800 nm, and the average pore size within the 5 μm region above and below the second interface is 150-450 nm, and the ratio between the two is 0.6-5.5.

[0034] This application is also implemented through the following technical solutions:

[0035] A method for preparing any of the above composite membranes for virus removal, characterized in that the method comprises:

[0036] Prepare casting liquid a and casting liquid b;

[0037] Placing the casting liquid a on a carrier to form a first film layer, and coating the first film layer with the casting liquid b before the first film layer is solidified to obtain a nascent composite film;

[0038] The nascent composite membrane is placed in a coagulation bath for phase separation to obtain the composite membrane.

[0039] Optionally, the solid content of the casting solution a is 12-20 wt%.

[0040] Optionally, the casting solution a comprises nylon with a density of 1.07-1.15.

[0041] Optionally, the solid content of the casting solution b is 15-22 wt%.

[0042] Optionally, the casting solution b comprises polyethersulfone with a molecular weight between 40,000 and 90,000.

[0043] Optionally, the casting solution b is applied on the first film layer before the first film layer reaches a whitening critical point.

[0044] Optionally, the casting solution a is allowed to stand on the carrier plate in air to form the first film layer, wherein the temperature of the carrier plate is set between 20-100° C. and the standing time is between 10-90 s.

[0045] Optionally, the solvent in the casting solution a does not dissolve the polymer in the casting solution b, and the solvent in the casting solution b does not dissolve the polymer in the casting solution a.

[0046] Optionally, the solvent in the casting solution a and the casting solution b is selected from one or more of dimethylformamide, dimethylacetamide, N-methylpyrrolidone, triethyl phosphate, tetrahydrofuran, formic acid, phosphoric acid, m-cresol, cresol, dimethyl sulfoxide and γ-butyrolactone.

[0047] Optionally, the non-solvent in the casting liquid a and the casting liquid b includes a porogen and an additive, wherein the porogen is selected from one or more of methanol, isopropyl alcohol, tert-amyl alcohol, triethylene glycol, diethylene glycol, n-butanol, polyethylene glycol, polyethylene oxide, citric acid, and polyvinyl pyrrolidone; and the additive is selected from one or more of acrylic acid monomers and their derivatives, acrylamide monomers and their derivatives, and caprolactam.

[0048] Optionally, the casting liquid a and the casting liquid b are coated on the carrier plate using a double-layer scraper, wherein the scraper thickness for coating the casting liquid a is 100-200 μm, and the scraper thickness for coating the casting liquid b is 200-400 μm.

[0049] Optionally, the coagulation bath comprises an organic solvent and water, and a mass ratio of the organic solvent to water is not greater than 0.15.

[0050] Optionally, the organic solvent is at least one of alcohol, ether or ketone compounds.

[0051] The composite membrane for virus removal provided in the present application has a separation layer in which the fibers are embedded in the pre-filtration layer fibers to form a fusion layer with a certain thickness. In the fusion layer, the relatively fine fibers of the separation layer and the relatively coarse fibers of the pre-filtration layer are embedded and interwoven with each other to form a non-mutational transition zone, which can enhance the bonding strength between the separation layer and the pre-filtration layer while increasing the filtration gradient, thereby helping to ensure the flux and load capacity of the membrane; and the ratio of the content of fibers with a diameter greater than 300 nm to the content of fibers with a diameter less than 300 nm in the fusion layer is 1.5-4, which can make the fusion layer have good pressure resistance, and the membrane pores will not shrink due to pressure, thereby ensuring stable flux. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings of the embodiments will be briefly introduced below. Obviously, the drawings described below only relate to some embodiments of the present application, and are not limitations to the present application.

[0053] FIG1 is a scanning electron microscope image of the liquid outlet surface of Example 1 of the virus removal composite membrane of the present application, with a magnification of 40K.

[0054] FIG2 is a scanning electron microscope image of the liquid inlet surface of Example 1 of the virus removal composite membrane of the present application, with a magnification of 5K.

[0055] FIG3 is a scanning electron microscope image of the interface between the pre-filtration layer and the fusion layer of Example 1 of the virus removal composite membrane of the present application, with a magnification of 10K.

[0056] FIG4 is a scanning electron microscope image of the interface between the fusion layer and the separation layer in Example 1 of the virus removal composite membrane of the present application, with a magnification of 5K.

[0057] FIG5 is a scanning electron microscope image of the entire cross section of the composite membrane for virus removal in Example 1 of the present application, with a magnification of 400.

[0058] FIG6 is a distribution diagram of the S element in the fusion layer and the surrounding area of ​​Example 1 of the virus removal composite membrane of the present application, with a magnification of 2K.

[0059] FIG7 is a distribution diagram of N elements in the fusion layer and the surrounding area of ​​Example 1 of the virus removal composite membrane of the present application, with a magnification of 2K.

[0060] FIG8 is a scanning electron microscope image of a cross section near the liquid outlet surface after the retention test of 20 nm colloidal gold by the composite membrane Example 1 for virus removal of the present application, with a magnification of 20K.

[0061] FIG9 is a scanning electron microscope image of the fusion layer in the cross-sectional area of ​​the composite membrane for virus removal in Example 6 of the present application, with a magnification of 5K. DETAILED DESCRIPTION

[0062] To make the purpose, technical solutions, and advantages of the embodiments of the present application more clear, the present application will be further described in detail below with reference to the accompanying drawings. Generally, the components of the embodiments of the present application described and shown in the drawings herein can be arranged and designed in various different configurations. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0063] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not require further definition or explanation in subsequent drawings.

[0064] Unless otherwise defined, technical or scientific terms used in this patent document shall have the ordinary meanings understood by persons of ordinary skill in the art to which this application belongs. The terms "first," "second," and similar terms used in this patent specification and claims do not denote any order, quantity, or importance, but are simply used to distinguish different components. Similarly, terms such as "a," "an," or "the" do not denote a limitation of quantity, but rather denote the presence of at least one. Terms such as "include" or "comprising" mean that the elements or objects preceding the term "include" or "comprising" include the elements or objects listed after the term and their equivalents, and do not exclude other elements or objects. Terms such as "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," "outer," "far," and "near" are used solely to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly. These terms are used solely to facilitate the description of this application and to simplify the description. They are not intended to indicate or imply that the device or component referred to must have a specific orientation, be constructed, or operate in a specific orientation, and are not to be construed as limitations on this application.

[0065] Some implementation methods of the present application are described in detail below with reference to the accompanying drawings.

[0066] Referring to Figures 1 to 8 , the present application discloses a composite membrane for virus removal having a porous structure formed by interwoven fibers. The composite membrane includes a pre-filtration layer and a separation layer composited to the pre-filtration layer, wherein the average fiber diameter of the pre-filtration layer is greater than the average fiber diameter of the separation layer. The composite membrane also includes a fusion layer formed by fusing the pre-filtration layer and the separation layer at their junction, which is used to increase the bonding strength of the composite membrane. The fusion layer is formed by extending the filter fibers of the separation layer and embedding them into the pre-filtration layer; wherein the ratio of the fiber content with a fiber diameter greater than 300 nm to the fiber content with a fiber diameter less than 300 nm in the fusion layer is 1.5-4.

[0067] In the fusion layer, coarse fibers with larger diameters can play a supporting role, and fine fibers with smaller diameters can improve the bonding strength. By setting the ratio of coarse fibers to fine fibers within the above range, the composite membrane can have better anti-peeling properties. At the same time, the fusion layer has good pressure resistance, and the membrane pores will not shrink due to pressure, thereby ensuring stable flux. Since the fusion layer is formed by embedding and fusing the fibers of the pre-filtration layer and the separation layer, the relatively fine fibers of the separation layer and the relatively coarse fibers of the pre-filtration layer are embedded and interwoven with each other to form a non-mutated transition zone, which can enhance the bonding strength between the separation layer and the pre-filtration layer, while avoiding mutations in the microstructure at the junction between the pre-filtration layer and the separation layer, thereby increasing the filtration gradient and helping to ensure the flux and load of the membrane.

[0068] In this application, fibers with a diameter greater than 300nm are referred to as coarse fibers, and fibers with a diameter less than 300nm are referred to as fine fibers. The proportion of coarse fibers in the fusion layer is 60-80%. When the coarse fiber content is greater than 80%, the interweaving effect between the fibers is poor, the bonding is poor, and the feed liquid is easily blocked in the membrane pores at the junction surface between the layers of the composite membrane, resulting in poor flux; when the coarse fiber content is less than 60%, the formed fusion layer is insufficiently supported, and during the pressure-driven filtration process, the membrane will be compressed and collapsed. Correspondingly, the proportion of fine fibers in the fusion layer is 20-40%, which can make the interpenetration between layers better, while ensuring that the holes in the fusion layer are not filled too much with fine fibers, so as to ensure the stability of the membrane flux and the membrane has better anti-peeling properties. When the fine fiber content is less than 20%, the bonding between the pre-filtration layer and the separation layer of the composite membrane is not very good, and the membrane is prone to peeling during the filtration process; when the fine fiber content is greater than 40%, the excessive proportion of fine fibers can easily cause the holes in the fusion layer to be blocked, resulting in a decrease in the membrane flux.

[0069] In some embodiments, the average pore size of the fusion layer is in the range of 200-600 nm, the thickness is in the range of 5-30 μm, and the thickness of the fusion layer is 3-25% of the total thickness of the composite membrane. The present application controls the thickness of the fusion layer between 3-25% of the overall membrane thickness, which can make the structure of the composite membrane more robust and also make the flux of the composite membrane better. Controlling the proportion of the fusion layer to the overall membrane thickness can effectively adjust the performance of the membrane. When the thickness of the fusion layer accounts for less than 3% of the overall membrane thickness, the membrane's anti-peeling performance will be poor; when the thickness of the fusion layer accounts for more than 25% of the overall membrane thickness, it is easy to cause congestion in the pore structure and reduce the flux. In some embodiments, the total thickness of the composite membrane is 100-150 μm, the thickness of the pre-filtration layer is 60-100 μm, the thickness of the separation layer is 20-45 μm, and the thickness ratio of the pre-filtration layer to the separation layer is 1-4.

[0070] The fusion layer is formed by the fusion of a semi-solid pre-filtration layer and a liquid separation layer at their interface, and can increase the filtration gradient of the composite membrane. Since the fusion layer is formed by the mutual penetration of the pre-filtration layer membrane and the separation layer membrane before phase separation and solidification in a coagulation bath, and has a microstructure different from that of both the pre-filtration layer and the separation layer, the structure of this layer can serve as a transition, which is beneficial for ensuring the flux and load of the membrane. Since the fusion layer is formed by the fibers of the pre-filtration layer and the separation layer extending and embedding into each other, although it does not have an absolute interface with the pre-filtration layer and the separation layer, the interface can still be reasonably divided based on their different microstructural appearances. The interface between the fusion layer and the pre-filtration layer is called the first interface, and the interface between the fusion layer and the separation layer is called the second interface. The exposed surface of the pre-filtration layer is the liquid inlet surface during filtration, and the exposed surface of the separation layer is the liquid outlet surface during filtration. The area from the liquid inlet surface to the first interface is the pre-filtration layer, the area from the first interface to the second interface is the fusion layer, and the area from the second interface to the liquid outlet surface is the separation layer.

[0071] In some embodiments, the ratio of the average pore size of the fusion layer to its average fiber diameter is 0.5-1.8, the average fiber diameter of the fusion layer is 280-400 nm, and the average pore size of the fusion layer is 200-600 nm. In some embodiments, the average pore size of the pre-filtration layer is 450-1000 nm, the average pore size of the separation layer is 55-100 nm, and the porosity of the composite membrane is 70-85%. The average fiber diameter of the pre-filtration layer is 200-350 nm, and the average fiber diameter of the separation layer is 50-80 nm. The ratio of the average pore size of the pre-filtration layer to its average fiber diameter is 1.28-5, and the ratio of the average pore size of the separation layer to its average fiber diameter is 0.65-2. Optionally, the peel strength of the pre-filtration layer and the separation layer is 0.1-0.3 N / mm.

[0072] In some embodiments, the pre-filtration layer forms the liquid inlet surface during filtration, and the initial water contact angle of the liquid inlet surface is 10°-30°; the separation layer forms the liquid outlet surface during filtration, and the initial water contact angle of the liquid outlet surface is 30°-60°. The average surface pore size of the liquid inlet surface is 500-1200 nm, and the membrane pore ratio is 30-55%; the average surface pore size of the liquid outlet surface is 15-30 nm, and the membrane pore ratio is 25-45%.

[0073] In one embodiment, the material of the pre-filtration layer is nylon, and the material of the separation layer is polyethersulfone (PES). Nylon has good hydrophilicity, and the membrane pore size formed is large, which can intercept large-pore protein aggregates, etc., and play a pre-filtration effect. The PES membrane is hydrophobic, but the PES membrane has a good effect in intercepting viruses and has excellent flux. When the membrane material of the pre-filtration layer is the same as the membrane material of the separation layer, due to the mutual solubility phenomenon in the solvent system, a dense cortex is easily generated at the junction between the two layers of the prepared membrane, resulting in a sharp decrease in membrane flux. One embodiment of the present application uses nylon as the pre-filtration layer and polyethersulfone as the main material of the separation layer. The overall trend of the pore size change of each layer is relatively uniform, and the fusion zone connection of the prepared composite membrane is smoother. At the same time, by controlling the solid content and molecular weight of the two in the casting liquid preparation process, the thickness of the fusion layer can be effectively adjusted to obtain a composite membrane with a fusion layer fiber distribution in an ideal range. Nylon is a hydrophilic organic polymer material. The membrane prepared from it has good hydrophilicity and low protein adsorption properties, which can play an excellent pre-filtration effect in this application. The overall trend of the pore size change of each layer is relatively uniform, and the fusion layer between the pre-filtration layer and the separation layer has good permeability, ensuring the stability of the flux and playing a secondary pre-filtration effect, alleviating the blockage problem, thereby reducing protein adsorption and increasing the loading capacity.

[0074] During the formation of the fused layer, the interpenetration of fibers between the pre-filtration layer and the separation layer is subject to the interaction of various solvents. This process causes slight phase separation and changes in fiber morphology in the fused layer. The average fiber diameter of the fused layer ranges from 280 to 400 nm. This range of average fiber diameters allows for a good connection between the pre-filtration layer and the separation layer, enhancing the internal stability of the composite membrane. The ratio of average pore size to average fiber diameter within the fused layer is maintained at (0.5-1.8):1, indicating the absence of a dense layer within the fused layer, thus ensuring the overall flux of the composite membrane. Furthermore, due to interfiber penetration and diffusion, the sulfur content in the fused layer accounts for 1-7% of the total carbon, nitrogen, oxygen, and sulfur in the fused layer, while the nitrogen content accounts for 3-9% of the total carbon, nitrogen, oxygen, and sulfur in the fused layer. When the sulfur and nitrogen content of the fused layer falls within this range, it indicates a relatively uniform distribution of PES and nylon within the resulting fused layer, overcoming polarity differences during penetration and ensuring good interlayer bonding. It can be seen from the electron microscope images of Figures 6 and 7 that the distribution of S and N elements in the fusion layer is relatively uniform, indicating that the composite membrane layers are tightly bonded and the membrane as a whole is not prone to separation.

[0075] In the composite membrane provided by the present application, the pre-filtration layer plays a pre-filtration role, while the virus retention is mainly achieved by the separation layer. In some embodiments, the separation layer includes a virus retention area with a thickness of 5-15 μm and an average pore size of 25-35 nm. The virus retention effect can be measured by passing colloidal gold solutions with diameters of 20 nm, 30 nm, and 50 nm through the clean and wet composite membrane of the present application from the liquid inlet surface. Specifically, in some embodiments, the position where the 50 nm colloidal gold is captured by the composite membrane is the area 0-60% below the second interface, the area where the 30 nm colloidal gold is captured is the area 30-85% below the second interface, and the area where the 20 nm colloidal gold is captured is the area 70-99.5% below the second interface. The composite membrane has an absorption peak for 50nm colloidal gold at a distance of 20-30μm from the liquid surface, an absorption peak for 30nm colloidal gold at a distance of 2-15μm from the liquid surface, and an absorption peak for 20nm colloidal gold at a distance of 0.5-9μm from the liquid surface. The above illustrates that the composite membrane of the present application has an effective range of retention thickness and can effectively retain viruses of different sizes.

[0076] In some embodiments, the average pore size in the region of 5 μm above and below the first interface is 300-800 nm, and the average pore size in the region of 5 μm above and below the second interface is 150-450 nm, and the ratio of the two is 0.6-5.5. The average pore size in the region of 5 μm above and below the interface has a significant effect on the performance of the composite membrane. It is effective and feasible to control the pore size range within 5 μm above and below the composite membrane interface during the preparation process, while the pore size control in the region exceeding 5 μm is more difficult. The present application controls the average pore size of the region of 5 μm above and below the interface to the above range, so that the transition between layers is relatively smooth, avoiding a cliff-like mutation in the pore size near the interface, avoiding a sudden change in flow rate, causing rapid accumulation of proteins to cause blockage and a rapid decrease in flux. For the convenience of description, in the embodiment, the region of 5 μm above and below the first interface is referred to as the first interface area, and the region of 5 μm above and below the second interface is referred to as the second interface area.

[0077] In some embodiments, the water flux of the composite membrane is 600-1200 L / (m 2 h) @ 30 psi, the composite membrane has an LRV value greater than 4, a liquid loading capacity Vmax of 700-1000, and a peel strength of 0.10-0.30 N / mm.

[0078] The present application also provides a method for preparing a composite membrane for virus removal, which includes: preparing casting liquid a and casting liquid b; placing casting liquid a on a carrier to form a first membrane layer, and covering the first membrane layer with casting liquid b before the first membrane layer is solidified to obtain a nascent composite membrane; and placing the nascent composite membrane into a coagulation bath for phase separation to obtain the composite membrane.

[0079] Specifically, the preparation method comprises the following steps:

[0080] 1) preparing a casting solution a: mixing nylon, a solvent and a non-solvent to obtain a casting solution a;

[0081] 2) preparing a casting solution b; mixing polyethersulfone, a solvent, and a non-solvent to obtain a casting solution b;

[0082] 3) heating the carrier to a predetermined temperature, applying the casting solution a to the carrier surface to form a first film layer, leaving the film layer in the air, and then applying the casting solution b to the first film layer to form a second film layer, thereby obtaining a nascent composite film;

[0083] 4) Immersing the nascent composite membrane in a coagulation bath for phase separation to obtain a virus removal composite membrane.

[0084] In some embodiments, the density of the nylon selected in step 1) is maintained between 1.07 and 1.15, and the solid content of the prepared casting solution a is 12-20 wt%.

[0085] In some embodiments, the molecular weight of the polyethersulfone selected in step 2) is maintained between 40,000 and 90,000, and the solid content of the prepared casting solution b is 15-22 wt%.

[0086] By controlling the molecular weight and solid content of the two polymers, the thickness of the fusion zone and the fiber diameter can be varied, resulting in a composite membrane with optimal performance. Excessively high polymer molecular weight and solid content can easily reduce the fluidity of the casting solution, resulting in a thin fusion zone between layers and poor anti-peeling performance. Excessively low polymer molecular weight and solid content can easily lead to a thick fusion zone, affecting flux.

[0087] In some embodiments, the solvents in step 1) and step 2) are both selected from one or more of dimethylformamide, dimethylacetamide, N-methylpyrrolidone, triethyl phosphate, tetrahydrofuran, formic acid, phosphoric acid, m-cresol, cresol, dimethyl sulfoxide and γ-butyrolactone.

[0088] Furthermore, the solvent in the casting liquid a does not dissolve the polymer in the casting liquid b, and the solvent in the casting liquid b does not dissolve the polymer in the casting liquid a. In this way, in the process of forming the fusion layer, the part of the casting liquid b that penetrates into the casting liquid a will undergo weak phase separation, resulting in a unique microstructure.

[0089] Furthermore, the non-solvent in both step 1) and step 2) comprises a porogen and an additive. The porogen is selected from one or more of methanol, isopropyl alcohol, tert-amyl alcohol, triethylene glycol, diethylene glycol, n-butanol, polyethylene glycol, polyethylene oxide, citric acid, and polyvinyl pyrrolidone; and the additive is selected from one or more of acrylic acid monomers and their derivatives, acrylamide monomers and their derivatives, and caprolactam.

[0090] Furthermore, in step 3), the first film layer is allowed to stand in air for a time shorter than the whitening critical point of the polymer a solution. That is, the casting solution b is applied to the first film layer before the first film layer reaches the whitening critical point. Before reaching the whitening critical point, the first film layer is in a semi-solid state. In some embodiments, the carrier plate temperature is set between 20°C and 100°C, and the predetermined time is between 10 and 90 seconds.

[0091] Furthermore, in step 3), a dual-layer scraper is used to extend the time interval between the first and second film layers. The first scraper is used to scrape a film layer onto the surface of the moving carrier. After a brief air gap, the second scraper is used to scrape another film layer onto the surface. The thickness of the first film layer scraped by the scraper is controlled to be 100-200 μm, and the thickness of the second film layer scraped by the scraper is controlled to be 200-400 μm.

[0092] Directly coating a casting solution onto an existing microporous membrane support layer to prepare a multilayer composite membrane presents challenges. The microporous membrane support layer itself may dissolve in the solvent system of the casting solution applied to it, potentially causing the solvent to erode the microporous support layer, leading to erosion and clogging of the membrane pores at the interface. Furthermore, stress may be exerted between the microporous membrane support layer and the casting solution applied thereto during phase transition, causing the multilayer composite membrane to curl or deform. The present invention avoids these drawbacks by coating the two membrane layers before phase transition and then undergoing phase transition together in a coagulation bath.

[0093] Furthermore, in step 4), the coagulation bath is a mixed solution of an organic solvent and water, wherein the organic solvent is at least one of an alcohol, an ether, or a ketone. Optionally, the alcohol compound has a molecular formula of CxHyFzO, where x = 1-10, y = 2-20, and z = 0-40; further, the organic solvent can be at least one of ethanol, isopropanol, and hexafluoroisopropanol. Optionally, the mass ratio of the organic solvent to water in the mixed solution is (0-0.15):1.

[0094] The following examples and comparative examples demonstrate the performance of composite membranes prepared using the present application and preparation method. Unless otherwise specified, the raw materials and equipment used in the following examples and comparative examples were all commercially available. The testing methods involved are briefly described below.

[0095] Virus Retention Test: The virus challenge test method is performed in accordance with the relevant provisions of PDA TR41, using PP7 phage or hepatitis B virus as the model virus, IVIG as the model protein, and PBS as the buffer. During the test, the changes in flux and load over time are recorded to obtain the LRV, flux, and load of the filter membrane.

[0096] Anti-peeling test: The multi-layer composite films obtained in the embodiments and comparative examples were tested for 180° peeling strength using a universal testing machine and a YGJ-02A adhesive tape roller.

[0097] Whitening critical point test: A sealed glass container containing a polymer solution is placed in a temperature-controlled heating tank. The temperature in the tank is slowly increased. The point in time when the polymer solution begins to whiten is called the whitening critical point. This method is described in U.S. Patent No. 5,444,097 and is classified as a thermally induced phase separation method. It was first proposed by AJ Castro of the United States as a method for preparing polymer microporous membranes.

[0098] Vmax test: Vmax is a measure of the amount of solution that a membrane can filter before becoming clogged and reducing the flow rate to approximately zero. Vmax is measured by filtering the solution at a predetermined pressure and recording the volume of filtered solution (V) as a function of time (t). The relationship between t / V and V is plotted, and the reciprocal of the slope of the plot is Vmax.

[0099] Water flux test: Under an operating pressure of 30 Psi, an ultrafiltration cup (Merck) was used to measure the effective area of ​​13.4 cm 2 The membrane was tested for water flux.

[0100] Pore ​​size test: Analyze and count the membrane pores on the SEM image using Image J or Nano measurer software.

[0101] Example 1

[0102] 1) Prepare casting solution a:

[0103] Polymer nylon 6 particles (density 1.13), porogen polyethylene glycol, and additive caprolactam are added to a formic acid solvent and mixed in a mass ratio of nylon, polyethylene glycol, caprolactam, and formic acid of 15:18:10:57. The mixture is then heated to 40° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0104] 2) preparing casting solution b;

[0105] Polyethersulfone (molecular weight of about 50,000), polyethylene glycol (porogen), and hydroxyethyl methacrylate (additive) were added to a dimethylformamide solvent and mixed in a mass ratio of 15:18:4:63. The mixture was then heated to 60° C. and stirred until the solution became clear, thereby obtaining a casting solution b.

[0106] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 200 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 50° C., leaving the carrier in an air zone for 30 seconds, and then casting solution b to obtain a nascent composite membrane;

[0107] 4) Immersing the nascent composite membrane in a 5% isopropyl alcohol aqueous solution at 45° C. for phase separation to obtain a multilayer composite membrane.

[0108] Example 2

[0109] 1) Prepare casting solution a:

[0110] Polymer nylon 66 particles (density 1.15), porogen polyethylene glycol, and additive caprolactam are added to a formic acid solvent and mixed in a mass ratio of nylon, polyethylene glycol, caprolactam, and formic acid of 15:18:10:55. The mixture is then heated to 40° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0111] 2) preparing casting solution b;

[0112] Polymer polyethersulfone (molecular weight of about 55,000), porogens triethylene glycol and polyvinyl pyrrolidone, and additive N-hydroxyethyl acrylamide are added to N-methyl pyrrolidone solvent and mixed, with the mass ratio of polyethersulfone, triethylene glycol, N-hydroxyethyl acrylamide, and N-methyl pyrrolidone being 16:19:5:2:58, and then heated to 70° C. and stirred until the solution becomes clear, thereby obtaining a casting solution b;

[0113] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 180 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 60° C., leaving the air section for 60 seconds, and then casting solution b to obtain a nascent composite membrane;

[0114] 4) Immersing the nascent composite membrane in a 5 wt % hexafluoroisopropanol aqueous solution at 25° C. for phase separation to obtain a multilayer composite membrane.

[0115] Example 3

[0116] 1) Prepare casting solution a:

[0117] Polymer nylon 66 particles (density 1.15), porogen polyethylene oxide, and additive caprolactam are dissolved in a mixed solvent of m-cresol and formic acid, with the mass ratio of nylon, polyethylene oxide, caprolactam, m-cresol, and formic acid being 18:15:2:10:55, and then heated to 60°C until the solution becomes clear, thereby obtaining a casting solution a;

[0118] 2) preparing casting solution b;

[0119] Polymer polyethersulfone (molecular weight of about 45,000), porogen diethylene glycol, and additive hydroxyethyl methacrylate are added to dimethyl sulfoxide solvent and mixed in a mass ratio of polyethersulfone, diethylene glycol, hydroxyethyl methacrylate, and dimethyl sulfoxide of 15:18:2:65. The mixture is then heated to 60° C. and stirred until the solution becomes clear, thereby obtaining a casting solution b.

[0120] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 150 μm and the scraper thickness of casting solution b adjusted to 250 μm. Casting solution a on a mobile carrier rapidly heated to 80° C., leaving the air section for 30 seconds, and then casting solution b to obtain a nascent composite membrane;

[0121] 4) The nascent composite membrane was immersed in a 5 wt % ethanol aqueous solution at 35° C. to perform phase separation, thereby obtaining a multilayer composite membrane.

[0122] Example 4

[0123] 1) Prepare casting solution a:

[0124] Polymer nylon 6 particles (density 1.13), porogen methanol, and additive caprolactam are added to a phosphoric acid solvent and mixed in a mass ratio of nylon, methanol, caprolactam, and phosphoric acid of 18:10:5:67. The mixture is then heated to 40° C. until the solution becomes clear, thereby obtaining a casting solution a.

[0125] 2) preparing casting solution b;

[0126] Polyethersulfone (molecular weight of about 60,000), porogens polyethylene glycol and polyvinyl pyrrolidone, and additive hydroxyethyl acrylate were added to a dimethylformamide solvent and mixed in a mass ratio of polyethersulfone, polyethylene glycol, polyvinyl pyrrolidone, hydroxyethyl acrylate, and dimethylformamide of 15:10:4:2:69. The mixture was then heated to 70° C. until the solution became clear, thereby obtaining a casting solution b.

[0127] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 180 μm and the scraper thickness of casting solution b adjusted to 280 μm. Casting solution a on a mobile carrier rapidly heated to 80° C., leaving the air section for 45 seconds, and then casting solution b to obtain a nascent composite membrane;

[0128] 4) The nascent composite membrane was immersed in a 10 wt % ethanol aqueous solution at 25° C. for phase separation to obtain a multilayer composite membrane.

[0129] Example 5

[0130] 1) Prepare casting solution a:

[0131] Polymer nylon 6 particles (density 1.13), porogens ethanol and citric acid, and additive caprolactam are added to a formic acid solvent and mixed in a mass ratio of nylon, ethanol, citric acid, caprolactam, and formic acid of 18:10:5:4:63. The mixture is then heated to 40° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0132] 2) preparing casting solution b;

[0133] Polymer polyethersulfone (molecular weight of about 58,000), porogens triethylene glycol and polyvinyl pyrrolidone, and additive hydroxyethyl methacrylate are added to dimethylformamide solvent and mixed, with the mass ratio of polyethersulfone, triethylene glycol, polyvinyl pyrrolidone, hydroxyethyl methacrylate, and dimethylformamide being 16:20:1:4:59, and then heated to 60°C and stirred until the solution becomes clear, thereby obtaining a casting solution b;

[0134] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 200 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 60° C., leaving the air section for 20 seconds, and then casting solution b to obtain a nascent composite membrane;

[0135] 4) Immersing the nascent composite membrane in a 6 wt % isopropyl alcohol aqueous solution at 35° C. for phase separation to obtain a multilayer composite membrane.

[0136] Example 6

[0137] 1) Prepare casting solution a:

[0138] Polymer nylon 610 particles (density 1.07), porogen polyethylene glycol, and additive caprolactam are added to a formic acid solvent and mixed in a mass ratio of nylon, polyethylene glycol, caprolactam, and formic acid of 14:10:10:66. The mixture is then heated to 50° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0139] 2) preparing casting solution b;

[0140] Polyethersulfone (molecular weight of about 55,000), porogens polyethylene glycol and polyvinyl pyrrolidone, and additive N-hydroxymethyl acrylamide are added to a dimethylformamide solvent and mixed. The mass ratio of polyethersulfone, polyethylene glycol, polyvinyl pyrrolidone, N-hydroxymethyl acrylamide, and dimethylformamide is 15:18:2:4:61. The mixture is then heated to 60° C. and stirred until the solution becomes clear, thereby obtaining a casting solution b.

[0141] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 150 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 70° C., leaving the carrier in an air zone for 60 seconds, and then casting solution b to obtain a nascent composite membrane;

[0142] 4) Immersing the nascent composite membrane in a 2 wt % hexafluoroisopropanol aqueous solution at 35° C. for phase separation to obtain a virus removal composite membrane.

[0143] Example 7

[0144] 1) Prepare casting solution a:

[0145] Polymer nylon 610 particles (density 1.07), porogen polyethylene glycol, and additive caprolactam were added to phosphoric acid solvent and dissolved in a mass ratio of nylon, polyethylene glycol, caprolactam, and phosphoric acid of 17:18:10:55, and then heated to 40° C. and stirred until the solution became clear to obtain a casting solution a;

[0146] 2) preparing casting solution b;

[0147] Polyethersulfone (molecular weight of about 65,000), polyvinylpyrrolidone (porogen), and caprolactam (additive) were added to a γ-butyrolactone solvent and mixed in a mass ratio of 18:2:8:72. The mixture was then heated to 60° C. and stirred until the solution became clear, thereby obtaining a casting solution b.

[0148] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 200 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 80° C., leaving the air section for 40 seconds, and then casting solution b to obtain a nascent composite membrane;

[0149] 4) Immersing the nascent composite membrane in a 2% isopropyl alcohol aqueous solution at 25° C. for phase separation to obtain a multilayer composite membrane.

[0150] Example 8

[0151] 1) Prepare casting solution a:

[0152] Polymer nylon 6 particles (density 1.13), porogen citric acid, and additive acrylamide are added to a phosphoric acid solvent and mixed in a mass ratio of nylon, citric acid, acrylamide, and phosphoric acid of 16:10:3:71. The mixture is then heated to 30° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0153] 2) preparing casting solution b;

[0154] Polyethersulfone (molecular weight of about 70,000), tert-amyl alcohol (porogen), and hydroxyethyl acrylate (additive) were dissolved in a mixed solvent of dimethylacetamide and triethyl phosphate in a mass ratio of 16:10:4:35:35. The mixture was then heated to 60° C. and stirred until the solution became clear, thereby obtaining a casting solution b.

[0155] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 200 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 50° C., leaving the carrier in an air zone for 25 seconds, and then casting solution b to obtain a nascent composite membrane;

[0156] 4) Immersing the nascent composite membrane in a 5% ethanol aqueous solution at 35° C. for phase separation to obtain a multilayer composite membrane.

[0157] Comparative Example 1

[0158] 1) Prepare casting solution a:

[0159] Polymer nylon 6 particles (density 1.13), porogen polyethylene glycol, and additive caprolactam are added to a formic acid solvent and mixed in a mass ratio of nylon, polyethylene glycol, caprolactam, and formic acid of 15:18:10:57. The mixture is then heated to 40° C. and stirred until the solution becomes clear, thereby obtaining a casting solution a.

[0160] 2) preparing casting solution b;

[0161] Polymer polyethersulfone (molecular weight above 90,000), porogen polyethylene glycol, and additive hydroxyethyl methacrylate are added to dimethylformamide solvent and mixed, with the mass ratio of polyethersulfone, polyethylene glycol, hydroxyethyl methacrylate, and dimethylformamide being 15:18:4:63, and then heated to 60° C. and stirred until the solution becomes clear, thereby obtaining a casting solution b;

[0162] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 200 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 50° C., leaving the carrier in an air zone for 30 seconds, and then casting solution b to obtain a nascent composite membrane;

[0163] 4) Immersing the nascent composite membrane in a 5% isopropyl alcohol aqueous solution at 45° C. for phase separation to obtain a multilayer composite membrane.

[0164] Comparative Example 2

[0165] 1) Prepare casting solution a:

[0166] Polymer polyethersulfone (molecular weight of about 45,000), porogens diethylene glycol and polyvinyl pyrrolidone, and additive N-hydroxyethyl acrylamide are added to dimethyl sulfoxide solvent and mixed, wherein the mass ratio of polyethersulfone, diethylene glycol, polyvinyl pyrrolidone, N-hydroxyethyl acrylamide, and dimethyl sulfoxide is 16:18:4:2:60, and then heated to 60° C. and stirred until the solution becomes clear to obtain a casting solution a;

[0167] 2) preparing casting solution b;

[0168] Polymer polyethersulfone (molecular weight of about 55,000), porogen polyethylene glycol, and additive hydroxyethyl methacrylate are added to dimethylformamide solvent and mixed in a mass ratio of polyethersulfone, polyethylene glycol, hydroxyethyl methacrylate, and dimethylformamide of 15:18:4:63. The mixture is then heated to 60° C. and stirred until the solution becomes clear, thereby obtaining a casting solution b.

[0169] 3) Casting two casting solutions using a double scraper method, with the scraper thickness of casting solution a adjusted to 150 μm and the scraper thickness of casting solution b adjusted to 300 μm. Casting solution a on a mobile carrier rapidly heated to 50° C., leaving the carrier in an air zone for 30 seconds, and then casting solution b to obtain a nascent composite membrane;

[0170] 4) Immersing the nascent composite membrane in a 5% ethanol aqueous solution at 45° C. for phase separation to obtain a multilayer composite membrane.

[0171] Comparative Example 3

[0172] The polymer polyethersulfone (molecular weight of about 50,000), the porogen polyethylene glycol, and the additive hydroxyethyl methacrylate are added to the dimethylformamide solvent and mixed. The mass ratio of polyethersulfone, polyethylene glycol, hydroxyethyl methacrylate, and dimethylformamide is 15:18:4:63. Then, the mixture is heated to 60°C and stirred until the solution becomes clear to obtain a casting solution. Then, a nylon membrane with a pore size of 0.45 μm (Thermo Fisher) is used as a supporting carrier, and a layer of PES membrane is scraped on it. After staying in the air section for 5 seconds, the membrane is immersed in a 35°C 5% isopropanol aqueous solution for phase separation to obtain a multilayer composite membrane.

[0173] Comparative Example 4

[0174] A method for preparing a multilayer composite film comprises the following steps:

[0175] The polymer polyethersulfone (molecular weight of about 50,000), the porogen polyethylene glycol, and the additive hydroxyethyl methacrylate are added to the dimethylformamide solvent and mixed. The mass ratio of polyethersulfone, polyethylene glycol, hydroxyethyl methacrylate, and dimethylformamide is 15:18:4:63. Then, the mixture is heated to 60°C and stirred until the solution becomes clear to obtain a casting solution. Then, a polyethersulfone membrane (3M) with a pore size of 0.45 μm is used as a supporting carrier, and a layer of PES membrane is scraped on it. After staying in the air section for 5 seconds, the membrane is immersed in a 35°C 5% isopropyl alcohol aqueous solution for phase separation to obtain a multilayer composite membrane.

[0176] The composite films prepared in Examples 1 to 8 and Comparative Examples 1 to 4 were tested, and the obtained test data are shown in Tables 1 to 4 below.

[0177] Table 1

[0178] Table 2

[0179] Table 3

[0180] Table 4

[0181] Combining the data in the above tables, it can be seen that the composite membranes obtained in the Examples of the present application maintain a reasonable ratio of the average pore size to the average fiber diameter in the fusion layer and in the interface region formed by the fusion layer, pre-filtration layer, and separation layer, enabling the preparation of composite membranes with high flux, high load, and good virus retention. Specifically, the average fiber diameter of the fusion layer is within the range of 280-400 nm. A fusion layer with an average fiber diameter within this range provides a good connection between the pre-filtration layer and the separation layer, enhancing the internal stability of the composite membrane.

[0182] The composite membrane prepared in this application can effectively solve the problem of membrane clogging caused by protein aggregates. The pre-filtration layer plays an early pre-filtration effect, the fusion layer can achieve pre-filtration and support effects, and the separation layer achieves the effect of separating viruses. The composite membrane combines the common advantages of ultrafiltration membrane and microfiltration membrane, as well as better anti-stripping performance, and adapts to more complex filtration environments. During the filtration process of this composite membrane, viruses with diameters of basically 20 to 100 nanometers can be retained on the membrane.

[0183] The data in the table show that the composite membrane obtained by compounding two casting liquids of different materials by the preparation method in this application has significantly improved permeation flux, Vmax and peel strength compared with the composite membrane obtained by casting a layer on the finished membrane (Comparative Example 3) and the composite membrane obtained by bathing two layers of the same material together (Comparative Example 2); for the composite membrane obtained by casting the casting liquid of the same material and the finished membrane (Comparative Example 4), due to the strong corrosiveness of the solvent to the material, the peel strength of this membrane is often higher, but it is easy to cause a sharp drop in the flux of the membrane; and when the molecular weight of the selected polyethersulfone is too high (Comparative Example 1), it will also lead to a downward trend in membrane flux and peel strength.

[0184] From the above description, it can be seen that the multi-layer composite filter membrane prepared in the present application compounds membranes of different materials, expands the characteristics of the composite membrane itself, and by adjusting the viscosity difference between the casting liquids, forms a through-and-through fusion layer in the composite membrane, deepens the connection between the double-layer membranes, and connects the upper and lower layers of the membrane like a "snap", preventing the membrane from peeling off due to the impact of the liquid when it is under high pressure.

[0185] The composite membrane prepared in the present application has a relatively smooth transition in the pore size between the fusion layer and the pre-filtration layer, which can play a secondary pre-filtration effect, greatly alleviating the clogging problem, thereby reducing protein adsorption and increasing the loading capacity.

[0186] The composite membrane prepared in this application is a multilayer composite membrane comprising a pre-filtration layer, a fusion layer, and a separation layer, obtained by scraping a double-layer membrane with a double blade and then phase-inverting the membrane in a coagulation bath. This multilayer composite filtration membrane combines the advantages of both ultrafiltration and microfiltration membranes, possessing properties not found in single-layer membranes. This reduces the additional cost of pretreatment and the likelihood of rapid flux decay due to localized, concentrated retention in the filtration membrane, thereby achieving a greater load capacity and virus retention.

[0187] The above are only specific embodiments of the present application, but the scope of protection of this application is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in this application should be included in the scope of protection of this application. Therefore, the scope of protection of this application should be based on the scope of protection of the claims.

Claims

1. A composite membrane for virus removal, having a porous structure formed by interweaving fibers, the composite membrane comprising a pre-filtration layer and a separation layer composited with the pre-filtration layer, wherein the average fiber diameter of the separation layer is smaller than the average fiber diameter of the pre-filtration layer; characterized in that: Also includes: A fusion layer formed by fusing the pre-filtration layer and the separation layer at their interface, which is used to increase the bonding strength of the composite membrane; The fusion layer is formed by extending the filter fibers of the separation layer and embedding them into the pre-filtration layer, and in the fusion layer, the content ratio of fibers with a diameter greater than 300 nm to fibers with a diameter less than 300 nm is 1.5-4.

2. The virus removal composite membrane according to claim 1, wherein: The peel strength between the pre-filter layer and the separation layer is 0.1-0.3 N / mm.

3. The virus removal composite membrane according to claim 1, characterized in that: The pre-filtering layer is a nylon layer, and the separation layer is a polyethersulfone layer.

4. The virus removal composite membrane according to claim 3, characterized in that: The sulfur content in the fusion layer accounts for 1-7% of the total amount of carbon, nitrogen, oxygen and sulfur in the fusion layer, and the nitrogen content accounts for 3-9% of the total amount of carbon, nitrogen, oxygen and sulfur in the fusion layer.

5. The virus removal composite membrane according to claim 1, wherein: The ratio of the average pore size of the fusion layer to the average fiber diameter thereof is 0.5-1.

8.

6. The virus removal composite membrane according to claim 1, wherein: The average fiber diameter of the fused layer is 280-400 nm.

7. The virus removal composite membrane according to claim 1, wherein: The average pore size of the fusion layer is 200-600 nm.

8. The virus removal composite membrane according to claim 1, wherein: The thickness of the fusion layer is 5-30 μm.

9. The virus removal composite membrane according to claim 1, wherein: The thickness of the fusion layer is 3-25% of the total thickness of the composite film.

10. The virus removal composite membrane according to claim 9, characterized in that: The total thickness of the composite membrane is 100-150 μm, the thickness of the pre-filter layer is 60-100 μm, the thickness of the separation layer is 20-45 μm, and the thickness ratio of the pre-filter layer to the separation layer is 1-4.

11. The virus removal composite membrane according to claim 1, wherein: The fusion layer is formed by fusing the semi-solid pre-filtration layer and the liquid separation layer at the interface between the two, which can increase the filtration gradient of the composite membrane.

12. The virus removal composite membrane according to claim 1, wherein: The side of the pre-filtration layer away from the separation layer is the liquid inlet surface, and the initial water contact angle of the liquid inlet surface is 10°-30°; the side of the separation layer away from the pre-filtration layer is the liquid outlet surface, and the initial water contact angle of the liquid outlet surface is 30°-60°.

13. The virus removal composite membrane according to claim 12, wherein: The average surface pore size of the liquid inlet surface is 500-1200nm, and the membrane pore ratio is 30-55%; the average surface pore size of the liquid outlet surface is 15-30nm, and the membrane pore ratio is 25-45%.

14. The virus removal composite membrane according to claim 1, wherein: The average pore size of the pre-filtration layer is 450-1000 nm, the average pore size of the separation layer is 55-100 nm, and the porosity of the composite membrane is 70-85%.

15. The virus removal composite membrane according to claim 1, wherein: The average fiber diameter of the pre-filtration layer is 200-350 nm, and the average fiber diameter of the separation layer is 50-80 nm.

16. The virus removal composite membrane according to claim 14 or 15, characterized in that: The ratio of the average pore size of the pre-filtration layer to its average fiber diameter is 1.28-5, and the ratio of the average pore size of the separation layer to its average fiber diameter is 0.65-2.

17. The virus removal composite membrane according to claim 1, wherein: The separation layer comprises a virus retention region with a thickness of 5-15 μm and an average pore size of 25-35 nm.

18. The virus removal composite membrane according to claim 1, wherein: There is a first interface between the fusion layer and the pre-filtration layer, and a second interface between the fusion layer and the separation layer. The area of ​​the composite membrane that captures 50nm colloidal gold is 0-60% of the area below the second interface, the area of ​​the composite membrane that captures 30nm colloidal gold is 30-85% of the area below the second interface, and the area of ​​the composite membrane that captures 20nm colloidal gold is 70-99.5% of the area below the second interface.

19. The virus removal composite membrane according to claim 1, wherein: The absorption peak of the composite film for 50nm colloidal gold is located at 20-30μm in the thickness direction from the liquid surface, the absorption peak of the composite film for 30nm colloidal gold is located at 2-15μm in the thickness direction from the liquid surface, and the absorption peak of the composite film for 20nm colloidal gold is located at 0.5-9μm in the thickness direction from the liquid surface.

20. The virus removal composite membrane according to claim 18, wherein: The average pore size in the 5 μm region above and below the first interface in the thickness direction is 300-800 nm, and the average pore size in the 5 μm region above and below the second interface in the thickness direction is 150-450 nm, and the ratio between the two is 0.6-5.

5.

21. A method for preparing a composite membrane for virus removal as claimed in any one of claims 1 to 20, characterized in that: The method comprises: Prepare casting liquid a and casting liquid b; Placing the casting liquid a on a carrier to form a first film layer, and coating the first film layer with the casting liquid b before the first film layer is solidified to obtain a primary composite film; The nascent composite membrane is placed in a coagulation bath for phase separation to obtain the composite membrane.

22. The preparation method according to claim 21, characterized in that: The solid content of the casting solution a is 12-20wt%, and the casting solution a comprises nylon with a density of 1.07-1.

15.

23. The preparation method according to claim 21, characterized in that: The solid content of the casting solution b is 15-22 wt %, and the casting solution b comprises polyethersulfone with a molecular weight between 40,000 and 90,000.

24. The preparation method according to claim 21, characterized in that: The casting liquid b is coated on the first film layer before the first film layer reaches the whitening critical point, and the casting liquid a is left to stand in the air on the carrier to form the first film layer, wherein the temperature of the carrier is set between 20-100°C, and the standing time is between 10-90s.

25. The preparation method according to claim 21, characterized in that: The solvent in the casting solution a does not dissolve the polymer in the casting solution b, and the solvent in the casting solution b does not dissolve the polymer in the casting solution a.

26. The preparation method according to claim 21, characterized in that: The solvent in the casting solution a and the casting solution b is selected from one or more of dimethylformamide, dimethylacetamide, N-methylpyrrolidone, triethyl phosphate, tetrahydrofuran, formic acid, phosphoric acid, m-cresol, cresol, dimethyl sulfoxide and γ-butyrolactone.

27. The preparation method according to claim 21, characterized in that: The non-solvent in the casting liquid a and the casting liquid b includes a porogen and an additive, wherein the porogen is selected from one or more of methanol, isopropanol, tert-amyl alcohol, triethylene glycol, diethylene glycol, n-butanol, polyethylene glycol, polyethylene oxide, citric acid, and polyvinyl pyrrolidone; the additive is selected from one or more of acrylic acid monomers and their derivatives, acrylamide monomers and their derivatives, and caprolactam.

28. The preparation method according to claim 21, characterized in that: The casting liquid a and the casting liquid b are scraped onto the carrier plate by a double-layer scraper, wherein the thickness of the scraper used for scraping the casting liquid a is 100-200 μm, and the thickness of the scraper used for scraping the casting liquid b is 200-400 μm.

29. The preparation method according to claim 21, characterized in that: The coagulation bath comprises an organic solvent and water, the mass ratio of the organic solvent to water is not greater than 0.15, and the organic solvent is at least one of alcohol, ether or ketone compounds.

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