Ultrafiltration membrane for separating viruses and proteins and preparation method thereof

Abstract

An ultrafiltration membrane for separating viruses and proteins and a preparation method thereof, belonging to the technical field of virus removal flat membranes and virus removal filters. A casting liquid L for forming a sponge-like macroporous layer and a casting liquid S for forming a sponge-like microporous layer are prepared respectively, the casting liquid L is applied to a mobile carrier to form a sponge-like macroporous layer, a non-woven fabric layer is tightly attached to the liquid film of the sponge-like macroporous layer before the sponge-like macroporous layer is solidified, and then the casting liquid S is applied to the non-woven fabric layer to form a sponge-like microporous layer, and the carrier and the double-layer liquid film formed by the casting liquid L and the casting liquid S and the tightly attached non-woven fabric layer are immersed in a coagulation bath after passing through an air section for phase separation and forming, and then washed and dried to obtain an ultrafiltration membrane. The ultrafiltration membrane provided by the present invention has both high flux and high separation accuracy, and meets the actual needs of removing viruses from protein solutions.

Description

Technical Field

[0001] The invention belongs to the technical field of virus-removing flat membranes and virus-removing filters, and relates to an ultrafiltration membrane for separating viruses and proteins and a preparation method thereof. Background Art

[0002] Ultrafiltration membrane is a porous separation material composed of a very thin epidermal layer for separation and a thicker sponge-like or finger-like pore layer for support. The cut-off molecular weight ranges from hundreds to millions of Daltons, corresponding to a pore size of 1 to 100 nm. Early ultrafiltration membranes were made of cellulose acetate. With the development of technology, polymer materials and inorganic membrane materials such as polysulfones, polyolefins, fluorine-containing materials, and polyamides have also been developed for the preparation of ultrafiltration membranes. Ultrafiltration membranes are mainly used for the purification, separation, and concentration of solutions, especially in drinking water treatment, deep wastewater treatment, chemical material separation, wine and beverage concentration, and biopharmaceuticals.

[0003] In the biopharmaceutical process, protein therapeutic drugs based on cell expression are at risk of contamination by endogenous and exogenous viruses. Once viral contamination occurs, it will affect the safety of therapeutic products and cause harm to patients. The use of ultrafiltration membranes that only screen and filter viruses by physical means can achieve efficient removal of non-enveloped viruses without any effect on proteins. At present, there are two types of ultrafiltration membranes with virus removal functions on the market. One is an ultrafiltration membrane that intercepts viruses through fine pores in the cortex. Although this ultrafiltration membrane has a certain virus retention capacity, since the size of common parvoviruses is about 25nm, and the size of target proteins and their aggregates is about 15nm, the use of ultrafiltration membranes that only separate through the epidermis has poor separation accuracy, low permeation flux and protein yield, and there is a huge risk of virus penetration, making it difficult to use. The other is an ultrafiltration membrane that intercepts viruses through fine pores connecting layers. The ultrafiltration membrane with this structure has extremely fine capillary pores and relatively large interstitial pores. It can intercept viruses while allowing proteins to pass through smoothly. It has a high protein yield and realizes efficient separation of viruses and proteins.

[0004] Millipore's patent document CN1759924B discloses a multilayer composite membrane having at least one ultrafiltration layer, which includes an asymmetric ultrafiltration membrane layer with a skin connected to a second asymmetric ultrafiltration membrane layer, connected by a pore size having a gradient distribution, and the gradient distribution is a transition from the pore size of the second ultrafiltration layer near the connection to the pore size of the first ultrafiltration layer near the connection. The ultrafiltration membrane with this structure can be used to remove virus particles from a solution containing artificial proteins.

[0005] Patent document CN117942776A of Hangzhou Kebet Filter Equipment Co., Ltd. discloses a virus removal composite membrane, which has a porous substrate layer formed by a first polymer and a separation layer formed by a second polymer, and the porous substrate layer is close to the separation layer and the separation layer is close to the porous substrate layer. The side of the separation layer forms a bonding area, and the holes in the bonding area are interconnected. The composite membrane has improved membrane flux and separation layer bonding strength, and maintains other properties without significant attenuation, meeting the actual virus removal application needs.

[0006] Patent document CN112892229A of the Guangzhou Institute of Advanced Technology of the Chinese Academy of Sciences discloses a virus composite filtration membrane. The composite structure includes a three-level membrane pore structure of a pre-filtration membrane, an intermediate support layer and a small-pore ultrafiltration membrane. It has high separation efficiency and can achieve rapid filtration of viruses.

[0007] The ultrafiltration membranes reported above are all suitable for separating viruses from proteins in biopharmaceutical processes, but they all have problems such as complex control methods for the preparation process, low binding strength of the composite structure, cumbersome preparation processes, and difficulty in achieving continuous production. Summary of the invention

[0008] The present invention aims at solving the problems in the prior art and provides an ultrafiltration membrane for separating viruses and proteins and a preparation method thereof.

[0009] An ultrafiltration membrane for separating viruses and proteins comprises a sponge-like macroporous layer, a non-woven fabric layer closely connected to the sponge-like macroporous layer, and a sponge-like microporous layer connected to the non-woven fabric, wherein the sponge-like macroporous layer completely penetrates into the non-woven fabric layer, and the sponge-like microporous layer partially penetrates into the non-woven fabric layer.

[0010] The outer surface of the sponge-like macroporous layer is the upstream surface, and the surface pore size is 50-1500nm. The outer surface of the sponge-like microporous layer is the downstream surface, and the surface pore size is 15-50nm. The overall pore size of the ultrafiltration membrane is 20-25nm.

[0011] The pore structure of the sponge-like macroporous layer is composed of interconnected grid-like pores stacked together, and the pore structure of the sponge-like microporous layer is composed of tortuous interconnected channels with grooves, which represent the pore structures formed by different film-forming mechanisms.

[0012] The thickness of the sponge-like macroporous layer is 150 μm, the thickness of the sponge-like microporous layer is 40 μm, and the overall thickness of the ultrafiltration membrane is 190 μm. The materials of the sponge-like macroporous layer and the sponge-like microporous layer are both polyethersulfone, and the material of the non-woven fabric layer is polypropylene or polyphenylene sulfide.

[0013] In the ultrafiltration membrane provided by the present invention, the pore size difference between the sponge-like macroporous layer and the sponge-like microporous layer is very large. The sponge-like macroporous layer is on the upstream surface of the ultrafiltration membrane, and can provide a pre-filtration effect for the sponge-like microporous layer to prevent the sponge-like microporous layer from being blocked. As the main retention layer, the sponge-like microporous layer mainly provides the function of pore size retention. Due to the large difference in pore size between the two layers, the inventor must overcome the problem of connection between the two layers. The published patent CN1759924B uses a co-cast coating device to achieve this, but a large number of related variables need to be controlled to prevent new problems. The published patent application CN117942776A describes a method for forming a bonding zone in a porous substrate, but this method requires prefabricating the porous substrate in advance, and the bonding zone structure is susceptible to the stress release of the phase separation process. If you want to achieve one-piece molding without changing the structure between the two layers and eliminate the mutual interference caused by the two casting solutions during the coating process, you need to consider adding an intermediate layer between the two layers. The intermediate layer avoids direct contact between the two layers of casting liquid, thereby reducing the solute migration between the upper and lower layers of casting liquid during the phase change process and the stress stretching or extrusion caused by the uneven phase separation at the interface of the two layers, so that there is no interface bonding problem between the two layers, and the viscosity selection range of the upper and lower layers of casting liquid is increased.

[0014] At the same time, the middle layer is made of porous material with good chemical resistance and solvent resistance, which can make the upper and lower layers of casting liquid closely bonded to it through penetration. The thickness of the middle layer is moderate, which ensures that the upper and lower layers will not have large-area contact and will not produce large-area gaps. The middle layer has ultra-high strength and can also play a supporting role, enhancing the overall strength of the ultrafiltration membrane.

[0015] A method for preparing an ultrafiltration membrane for separating viruses and proteins comprises the following steps:

[0016] Step P1, respectively prepare a casting liquid L for forming a sponge-like macroporous layer and a casting liquid S for forming a sponge-like microporous layer, apply the casting liquid L to a mobile carrier to form a sponge-like macroporous layer, and before the sponge-like macroporous layer is solidified, tightly adhere the non-woven fabric layer to the liquid film of the sponge-like macroporous layer, and then apply the casting liquid S to the non-woven fabric layer to form a sponge-like microporous layer.

[0017] Step P2, the carrier and the double-layer liquid membrane formed by the casting liquid L and the casting liquid S and the tightly fitted non-woven fabric layer are passed through an air section and then immersed in a coagulation bath for phase separation and forming, and then washed and dried to obtain an ultrafiltration membrane.

[0018] Preferably, the casting solutions L and S both contain a hydrophobic polymer, a hydrophilic polymer, a solvent and a non-solvent in a ratio of 15-25 parts: 3-10 parts: 15-50 parts: 40-70 parts.

[0019] Preferably, the hydrophobic polymer is polyethersulfone with a molecular weight between 48000 and 90000 Da; the hydrophilic polymer is one or more of sulfonated polysulfone, sulfonated polyethersulfone, and polyvinylpyrrolidone; the solvent is one or more of dimethylformamide, dimethylacetamide, N-methylpyrrolidone, triethyl phosphate, dimethyl sulfoxide, caprolactam, and propylene carbonate; and the non-solvent is one or more of ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, and glycerol.

[0020] Preferably, the casting liquid L is transferred to a mobile carrier by scraper or groove coating, wherein the mobile carrier should not have the ability to combine with the casting liquid L and should be easy to separate from the mobile carrier after the casting liquid L is formed, preferably a smooth polyethylene terephthalate film.

[0021] Preferably, the casting liquid S is applied onto the non-woven fabric layer by extrusion through a pressure die, wherein the non-woven fabric layer is tightly adhered to the liquid film formed by the casting liquid L before the casting liquid S is applied after the casting liquid L is applied.

[0022] Preferably, the air section is controlled by a constant temperature and humidity control system, with the temperature range being 20 to 50° C. and the humidity range being 20 to 80 RH%.

[0023] Preferably, the coagulation bath is pure water or a mixture of pure water and a solvent, wherein the proportion of the solvent does not exceed 10%.

[0024] The entire coating process is transmitted by a mechanical device. The casting liquid L used to form a sponge-like macroporous layer is first coated onto a mobile carrier. The carrier is immiscible with the casting liquid, and the casting liquid only stays on the surface of the carrier and does not penetrate into the interior of the carrier. After the casting liquid is phase-separated and formed, it can be peeled off from the carrier. The carrier is preferably a polyester film.

[0025] In a preferred embodiment, the sponge-like macroporous layer is a pore structure formed by heating a casting solution with a low critical solution temperature to above the critical temperature and maintaining it for a period of time to induce phase separation, and the pore size range is controlled by controlling the heating temperature and the holding time. The critical temperature of the sponge-like macroporous layer is preferably 30 to 60°C. The temperature required for partial phase separation is provided to the sponge-like macroporous layer on the carrier by a heatable supporting bottom roller, so the carrier thickness is required to be controlled within a certain range to control the heat transfer rate, and the preferred thickness is 0.036 to 0.25 mm.

[0026] There are many options for coating the casting liquid onto the carrier. One preferred method is roller-lined blade coating. The thickness of the sponge-like macroporous layer can be controlled by adjusting the gap between the blade and the backing roller. The preferred gap is 130-300 μm. In addition, coating can also be achieved by using pressure die grooves and other methods. It is worth noting that the choice of coating method is related to the viscosity of the casting liquid. When the viscosity of the casting liquid is greater than 15000 cp, it is no longer suitable for blade coating.

[0027] After the casting liquid is applied to the mobile carrier and before the casting liquid is phase-separated and formed, the non-woven fabric is attached to the sponge-like macroporous layer through the wrap angle formed by the additional guide roller and the bottom roller, and then the casting liquid that can form the sponge-like microporous layer is applied to the other side of the non-woven fabric. The function of the non-woven fabric layer is to connect the sponge-like macroporous layer and the sponge-like microporous layer, and to isolate the mutual mass transfer between the two layers, so that the phase separation process of the two layers can be carried out simultaneously and separately without interfering with each other. The material of the non-woven fabric layer is preferably polyethylene terephthalate or polypropylene. The thickness of the non-woven fabric layer is preferably 90 to 140 μm.

[0028] The method of applying the casting liquid that can form a sponge-like small pore layer to the non-woven fabric layer is preferably a die groove pressure coating method. A slot mold includes a closed reservoir with a small cross-section outlet groove. The casting liquid is fed into the reservoir at a constant rate under a certain pressure by a feed pump, and all the liquid entering the mold is squeezed out from the outlet groove onto the non-woven fabric by pressure. The groove is installed perpendicular to the non-woven fabric. Ultrafiltration membranes including a large-pore sponge layer and a small-pore sponge layer are mostly gradient pore structures or gradual pore structures. Structures with sudden changes in pore size in the middle position often need to be realized by double-layer stacking. However, in the process of double-layer membrane superposition casting, whether from the coating perspective or the phase separation perspective, there is a problem that the casting process is difficult to control. Especially near the interface, the two layers of casting liquid will inevitably merge due to the similar solvent polarity, which increases the difficulty of controlling the pore size. By separating the two layers of casting liquid by porous materials and separately controlling the phase change process of the two layers of casting liquid, the pore size and pore structure of the double layer can be accurately controlled, thereby increasing the feasibility and operability of the ultrafiltration membrane preparation process.

[0029] After coating, the carrier and the double-layer casting liquid are passed through an air section with uniform and controllable temperature and humidity. The temperature in the air section is preferably set at 20-50°C, and the relative humidity is preferably set at 20-80RH%. The surface pore structure of the spongy microporous layer is opened by steam-induced phase separation, that is, the humid air in the air section is used as a non-solvent to complete the partial phase separation process. This phase separation process is carried out independently and is not interfered by the phase separation process of the spongy macroporous layer. After entering the air section, the spongy macroporous layer continues to undergo a reverse thermally induced phase separation process, which is independent and is not affected by the phase separation process of the spongy microporous layer. In addition, since the spongy macroporous layer is located on the inner side of the non-woven fabric layer at this time and is isolated from the air by the spongy microporous layer, the phase separation process of the spongy macroporous layer is only related to temperature.

[0030] After passing through the air section, the carrier and the double-layer membrane layer that has completed partial phase separation are immersed in a gel bath to complete the entire phase separation process. The gel bath is preferably pure water or a mixture of pure water and a solvent, wherein the proportion of the solvent does not exceed 10%. The gel bath temperature is preferably 30 to 60°C. The process is controlled by a non-solvent. Since the intermediate layer of non-woven fabric is a porous material, the gel bath is allowed to enter the interior. At this time, the casting liquid that has completed the partial phase separation process is fully exchanged with the non-solvent to complete the entire phase separation process, forming a sponge-like macroporous layer and a sponge-like microporous layer, respectively. Finally, the ultrafiltration membrane that has been completely phase-separated is peeled off from the carrier, and undergoes an additional cleaning step to remove the residual solvent in the membrane, and then is dried to obtain the final ultrafiltration membrane.

[0031] The present invention is realized by a roll-to-roll membrane process, which can realize continuous batch production. At the same time, the method combines the reverse thermally induced phase separation method and the steam-induced phase separation method to perform high-precision pore size control, so that the membrane has both high throughput and high separation accuracy, meeting the practical application of removing viruses from protein solutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the prior art descriptions. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work. As shown in the figure:

[0033] Figure 1 This is a cross-sectional scanning electron microscope image of Example 1 of the present invention.

[0034] Figure 2 This is an electron microscope image of the upstream surface of Example 1 of the present invention.

[0035] Figure 3 This is an electron microscope image of the downstream surface of Example 1 of the present invention.

[0036] Figure 4 This is an electron microscope image of the downstream surface of Example 2 of the present invention.

[0037] Figure 5 This is an electron microscope image of the downstream surface of Example 3 of the present invention.

[0038] Figure 6 This is an electron microscope image of the upstream surface of Example 4 of the present invention. DETAILED DESCRIPTION

[0039] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0040] The structure and performance of the ultrafiltration membrane are characterized by the following method to obtain the structure and performance of the ultrafiltration membrane in the embodiment.

[0041] The surface and cross-sectional structural images of the ultrafiltration membranes obtained in the embodiments of the present invention and the comparative embodiments are obtained by scanning electron microscopy and field emission scanning electron microscopy, and the pore size of the ultrafiltration membrane surface can be obtained with the aid of image tools.

[0042] The pure water flux of the ultrafiltration membrane was tested using an ultrafiltration cup (MSC300) at 0.2MPa and 25°C. The pure water flux of the membrane was calculated using the following formula:

[0043]

[0044] Where V is the volume of permeable water (L), A is the effective filtration area of ​​the membrane (m 2 ), t is the filtering time (h).

[0045] The ultrafiltration cup (MSC050) was used to test the virus retention level and protein permeation level of the ultrafiltration membrane. The test was carried out under the conditions of 0.2MPa and 25℃. The data was collected by a balance connected to the acquisition software. First, the membrane was moistened with ultrapure water and the membrane was rinsed with a buffer solution until it was balanced. The feed liquid was filtered through the membrane from the inlet side of the membrane. The permeate was composed of a concentration of 10 7 The buffer system is composed of 100 / ml MS2 bacteriophage and 1mg / ml bovine serum albumin (BSA) solution, and the buffer system is PBS solution with pH=7.4. The MS2 phage concentration is detected by plaque method, and the BSA concentration is detected by UV spectrophotometer. After gradient dilution of the permeate, the virus titer is determined by double-layer plate method, and the LRV is calculated by the logarithm of the titer ratio of the feed liquid to the filtrate. The protein permeability of the membrane is obtained by calculating the ratio of the BSA concentration of the permeate to the raw liquid.

[0046] Embodiment 1:

[0047] Step P1: Add 16.5 parts of polyethersulfone (E6020P) and 3.5 parts of sulfonated polysulfone to 32 parts of N-methylpyrrolidone and 40 parts of polyethylene glycol 200 at 60°C, and stir for 6 hours until completely dissolved. Then cool the formed solution to 30°C, add 8 parts of diethylene glycol, and continue stirring for 2 hours to obtain a uniform casting liquid S. Add 15 parts of polyethersulfone (E6020P) and 3 parts of polyvinylpyrrolidone K90 to 42 parts of N-methylpyrrolidone and 20 parts of diethylene glycol at 60°C and stir for 6 hours until completely dissolved. Then cool the formed solution to 25°C, add 20 parts of diethylene glycol and continue stirring for 2 hours to obtain a uniform casting liquid L.

[0048] Step P2: The prepared casting liquid L is then applied to the PET film with a scraper, the PET film is heated to 35°C, a layer of PP non-woven fabric is tightly attached to the casting liquid, and then a layer of casting liquid S is cast on the non-woven fabric using a pressure mold. The PET film passes through an air section with a temperature of 30°C and a humidity of 36RH%, and then is immersed in a pure water gel bath at 45°C to complete phase separation, and the desired ultrafiltration membrane is obtained after cleaning and drying.

[0049] The ultrafiltration membrane prepared in Example 1 has a three-layer structure of a sponge-like macroporous layer, a non-woven fabric layer completely combined with the sponge-like macroporous layer, and a sponge-like microporous layer ( Figure 1 to Figure 3 The average pore size of the sponge-like macroporous layer is about 1000nm, and the pore size gradually decreases from the upstream surface to the downstream surface. The average pore size of the sponge-like microporous layer is 20nm. The pure water flux of this membrane is about 800L / (m 2 h), LRV = 5.2, BSA transmittance is about 95%.

[0050] Embodiment 2:

[0051] The procedure is the same as in Example 1, except that the humidity of the air section in step P2 is 48 RH%. The average pore size of the sponge-like microporous layer produced by the prepared ultrafiltration membrane is 25 nm ( Figure 4 The pure water flux of the membrane is about 1000L / (m 2 h), LRV = 4.1, BSA transmittance is about 97%.

[0052] Embodiment 3:

[0053] The procedure is the same as in Example 1, except that the humidity of the air section in step P2 is 29 RH%. The average pore size of the sponge-like microporous layer of the ultrafiltration membrane thus obtained is 15 nm ( Figure 5 The pure water flux of the membrane is about 600L / (m 2 h), LRV>7, BSA transmittance is about 90%.

[0054] Embodiment 4:

[0055] Step P1: Add 16.5 parts of polyethersulfone (E6020P) and 3.5 parts of sulfonated polysulfone to 32 parts of N-methylpyrrolidone and 40 parts of polyethylene glycol 200 at 60°C, and stir for 6 hours until completely dissolved. Then cool the formed solution to 30°C, add 8 parts of diethylene glycol, and continue stirring for 2 hours to obtain a uniform casting liquid S. Add 15 parts of polyethersulfone (E6020P) to 44.5 parts of N-methylpyrrolidone and 20.5 parts of diethylene glycol at 60°C and stir for 6 hours until completely dissolved. Then cool the formed solution to 25°C, add 20 parts of diethylene glycol and continue stirring for 2 hours to obtain a uniform casting liquid L.

[0056] Step P2: The prepared casting liquid L is then applied to the PET film with a scraper, the PET film is heated to 35°C, a layer of PP non-woven fabric is tightly attached to the casting liquid, and then a layer of casting liquid S is cast on the non-woven fabric using a pressure mold. The PET film passes through an air section with a temperature of 30°C and a humidity of 36RH%, and then is immersed in a pure water gel bath at 45°C to complete phase separation, and the desired ultrafiltration membrane is obtained after cleaning and drying.

[0057] Due to the change in the composition of the casting solution L, the pore size of the sponge-like macroporous layer of the ultrafiltration membrane prepared in Example 5 changed. The surface electron microscope image of the upstream surface of the membrane obtained thereby ( Figure 6 ) It can be seen that the average pore size of the sponge-like macroporous layer produced by the membrane is 500nm. The pure water flux of the membrane is about 800L /

[0058] (m 2 h), LRV = 4.3, BSA transmittance about 97%.

[0059] Comparative Example 1:

[0060] The procedure was the same as in Example 1, except that the water temperature of the gel bath was set to 50°C.

[0061] Therefore, the average pore size of the sponge-like pore layer produced by the membrane is 30nm, and the pure water flux of the membrane is 1600L / (m 2 h), LRV <1, BSA transmittance is about 99%.

[0062] Comparative Example 2:

[0063] Step P1: Add 16.5 parts of polyethersulfone (E6020P) and 3.5 parts of sulfonated polysulfone to 25 parts of N-methylpyrrolidone and 36 parts of polyethylene glycol 200 at 60°C, and stir for 6 hours until completely dissolved. Then cool the formed solution to 30°C, add 24 parts of diethylene glycol, and continue stirring for 2 hours to obtain a uniform casting solution S. Add 15 parts of polyethersulfone (E6020P) and 3 parts of polyvinylpyrrolidone K90 to 42 parts of N-methylpyrrolidone and 20 parts of diethylene glycol at 60°C and stir for 6 hours until completely dissolved. Then cool the formed solution to 25°C, add 20 parts of diethylene glycol and continue stirring for 2 hours to obtain a uniform casting solution L.

[0064] Step P2: The prepared casting liquid L is then applied to the PET film with a scraper, the PET film is heated to 35°C, a layer of PP non-woven fabric is tightly attached to the casting liquid, and then a layer of casting liquid S is cast on the non-woven fabric using a pressure mold. The PET film passes through an air section with a temperature of 35°C and a humidity of 25RH%, and then is immersed in a pure water gel bath at 40°C to complete phase separation, and the desired ultrafiltration membrane is obtained after cleaning and drying.

[0065] Due to the change of the component L in the casting solution, the pore size of the sponge-like pore layer of the ultrafiltration membrane prepared in Example 2 changed. The average pore size of the sponge-like pore layer produced by the membrane was 25 nm. The pure water flux of the membrane was about 1000 L / (m 2 h), LRV <1, BSA transmittance is about 98%.

[0066] Comparative Example 3:

[0067] Step P1 is the same as Example 2. Step P2 is different from Example 2 in that the humidity of the air section is 30 RH%, and the temperature of the pure water gel bath is 35°C.

[0068] The average pore size of the sponge-like pore layer produced by the membrane is 20nm. The pure water flux of the membrane is about 800L / (m 2 h), LRV <1, BSA transmittance is about 90%.

[0069] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An ultrafiltration membrane for separating viruses and proteins, characterized in that: It includes a sponge-like macroporous layer, a non-woven fabric layer closely connected to the sponge-like macroporous layer, and a sponge-like microporous layer connected to the non-woven fabric. The sponge-like macroporous layer completely penetrates into the non-woven fabric layer, and the sponge-like microporous layer partially penetrates into the non-woven fabric layer.

2. The ultrafiltration membrane for separating viruses and proteins according to claim 1, characterized in that: The outer surface of the sponge-like macroporous layer is the upstream surface, and the surface pore size is 50-1500nm. The outer surface of the sponge-like microporous layer is the downstream surface, and the surface pore size is 15-50nm. The overall pore size of the ultrafiltration membrane is 20-25nm.

3. The ultrafiltration membrane for separating viruses and proteins according to claim 1, characterized in that: The pore structure of the sponge-like macroporous layer is composed of interconnected grid-like pores stacked together, and the pore structure of the sponge-like microporous layer is composed of tortuous interconnected channels with grooves, which represent the pore structures formed by different film-forming mechanisms.

4. The ultrafiltration membrane for separating viruses and proteins according to claim 1, characterized in that: The thickness of the sponge-like macroporous layer is 150 μm, the thickness of the sponge-like microporous layer is 40 μm, and the overall thickness of the ultrafiltration membrane is 190 μm. The materials of the sponge-like macroporous layer and the sponge-like microporous layer are both polyethersulfone, and the material of the non-woven fabric layer is polypropylene or polyphenylene sulfide.

5. A method for preparing an ultrafiltration membrane for separating viruses and proteins, characterized in that: Contains the following steps: Step P1, respectively preparing a casting liquid L for forming a sponge-like macroporous layer and a casting liquid S for forming a sponge-like microporous layer, applying the casting liquid L to a mobile carrier to form a sponge-like macroporous layer, and closely attaching a non-woven fabric layer to the liquid film of the sponge-like macroporous layer before the sponge-like macroporous layer is solidified, and then applying the casting liquid S to the non-woven fabric layer to form a sponge-like microporous layer. Step P2, the carrier and the double-layer liquid membrane formed by the casting liquid L and the casting liquid S and the tightly fitted non-woven fabric layer are passed through an air section and then immersed in a coagulation bath for phase separation and forming, and then washed and dried to obtain an ultrafiltration membrane.

6. The method for preparing an ultrafiltration membrane for separating viruses and proteins according to claim 5, characterized in that: The casting solutions L and S both contain a hydrophobic polymer, a hydrophilic polymer, a solvent and a non-solvent in a ratio of 15-25 parts: 3-10 parts: 15-50 parts: 40-70 parts.

7. The method for preparing an ultrafiltration membrane for separating viruses and proteins according to claim 6, characterized in that: The hydrophobic polymer is polyethersulfone with a molecular weight between 48000 and 90000Da; the hydrophilic polymer is one or more of sulfonated polysulfone, sulfonated polyethersulfone, and polyvinylpyrrolidone; the solvent is one or more of dimethylformamide, dimethylacetamide, N-methylpyrrolidone, triethyl phosphate, dimethyl sulfoxide, caprolactam, and propylene carbonate; and the non-solvent is one or more of ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, and glycerol.

8. The method for preparing an ultrafiltration membrane for separating viruses and proteins according to claim 5, characterized in that: The casting liquid L is coated onto a mobile carrier by a scraper, wherein the mobile carrier should not be able to combine with the casting liquid L and should be easy to separate from the mobile carrier after the casting liquid L is formed, and is preferably a smooth polyethylene terephthalate film.

9. The method for preparing an ultrafiltration membrane for separating viruses and proteins according to claim 5, characterized in that: The casting liquid S is applied onto the non-woven fabric layer by extrusion through a pressure die groove, wherein the non-woven fabric layer is tightly attached to the liquid film formed by the casting liquid L before the casting liquid S is applied after the casting liquid L is applied.

10. The method for preparing an ultrafiltration membrane for separating viruses and proteins according to claim 5, characterized in that: The air section is controlled by a constant temperature and humidity control system, the temperature range is 20-50°C, the humidity range is 20-80RH%, and the coagulation bath is pure water or a mixture of pure water and solvent, wherein the proportion of the solvent does not exceed 10%.

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