Asymmetric PES filtration membrane for virus removal and its manufacturing method

Abstract

The present invention provides an asymmetric PES filtration membrane for virus removal and a manufacturing method thereof, the PES filtration membrane comprising a main body, the main body having a non-directed tortuous passage, one surface of the main body being a first outer surface, the first outer surface having an average pore size of 150-450 nm, which is a large pore surface, the other surface of the main body being a second outer surface, the second outer surface having an average pore size of 10-42 nm, which is a small pore surface, the average pore size of the main body being a continuous gradient change from one side region close to the first outer surface to one side region close to the second outer surface, the main body comprising a pre-filtration layer and a virus-blocking separation layer, the other side of the pre-filtration layer and the other side of the separation layer being continuously fiber transitioned, the PES filtration membrane is manufactured using only one kind of casting solution and is integrally molded without the need for compounding, and the manufacturing process is relatively simple, and the manufactured PES filtration membrane has a strong blocking effect on fine viruses with a particle size of 20 nm or more, and can obtain a relatively high protein yield, thereby meeting the needs of practical application.

Description

[Technical Field]

[0001] The present invention relates to the technical field of membrane materials, and more particularly to an asymmetric PES filtration membrane for virus removal and a method for producing the same. [Background technology]

[0002] Membrane technology is a new, modern, highly efficient separation technology, which has the advantages of higher separation efficiency, lower energy consumption, and smaller site area compared to traditional technologies such as distillation and rectification. The core of membrane separation technology is the separation membrane. Among them, polymer filtration membranes are separation membranes made from organic high molecular weight polymers as raw materials and manufactured according to a certain process. With the development of the petroleum industry and science and technology, the application fields of polymer filtration membranes are constantly expanding, and currently they are being used in various fields such as gas separation, seawater desalination, ultrapure water production, pollution waste treatment, artificial organ manufacturing, medicine, food, agriculture, and chemical industry.

[0003] Depending on the type of polymer, polymer filtration membranes can be further divided into cellulose-based polymer filtration membranes, polyamide-based polymer filtration membranes, sulfone-based polymer filtration membranes, polytetrafluoroethylene-based polymer filtration membranes, etc., and can also be divided into microfiltration membranes, ultrafiltration membranes, nanofiltration membranes, and reverse osmosis membranes depending on the pore size of the membrane.

[0004] In recent years, measures to enhance viral safety have become necessary not only for plasma fractions derived from human blood but also for biopharmaceuticals. Therefore, drug manufacturers have been researching the introduction of virus removal and inactivation processes into the manufacturing process. Among these, the virus removal method, which uses a membrane to filter out viruses, is an effective method for reducing viruses without denaturing useful proteins.

[0005] For example, Chinese Patent No. CN1759924B (filed by EMD Mitsuribo) discloses a multi-layer composite ultrafiltration membrane (Fig. 17) comprising at least one first porous membrane layer having a second surface equivalent to a first surface, and at least one second porous membrane layer having equivalent first and second surfaces. The first layer is connected to and overlapped with the second layer, and has a porosity-connected transition region from the equivalent first surface of the second layer to the equivalent second surface of the first layer. At least one of the layers is an asymmetric ultrafiltration membrane. This composite membrane structure has a strong blocking effect against microviruses and can simultaneously achieve a relatively high protein yield, meeting the needs of practical applications.

[0006] However, the composite ultrafiltration membrane can be fabricated using at least two different casting solutions. The composite process involves co-casting the two solutions using a single slot die coater (see Figure 18 for an apparatus diagram). The casting thickness of the first polymer solution is adjusted to an appropriate thickness, and the casting thickness of the second polymer solution is adjusted to a final layer thickness of 15 micrometers or approximately 10% of the total membrane thickness. The first solution is rapidly heated above its cloudiness point on the casting drum before being immersed in a water bath at 55°C, while the casting conditions are selected so that the second solution has not yet reached its cloudiness point. This results in the first polymer solution forming the microporous layer and the second polymer solution forming the ultrafiltration layer. The relatively cumbersome arrangement of the various casting solutions, the complex composite process, and the relatively high economic costs have limited the development of virus removal membranes to some extent. Summary of the Invention [Problem to be solved by the invention]

[0007] In response to the shortcomings of the current technology, the present invention provides an asymmetric PES filter membrane for virus removal and a manufacturing method thereof, which is manufactured using only a casting solution, is integrally molded, does not require compounding, and is a relatively simple manufacturing process. At the same time, the manufactured PES filter membrane has a strong blocking effect against viruses and can achieve a relatively high protein yield, thereby meeting the needs of practical applications. [Means for solving the problem]

[0008] To achieve the above object, the present invention provides an asymmetric PES filtration membrane for virus removal, comprising a main body having a non-directional tortuous path therein, one surface of the main body being a first outer surface and the other surface of the main body being a second outer surface, the first outer surface having an average pore size of 150-450 nm and the second outer surface having an average pore size of 10-42 nm.

[0009] The average pore size of the body is continuously graded from one side region near the first outer surface to one side region near the second outer surface.

[0010] The main body includes a pre-filtration layer and a separation layer that blocks viruses, one side of the pre-filtration layer is a first outer surface, one side of the separation layer is a second outer surface, and the other side of the pre-filtration layer and the other side of the separation layer have continuous fiber transitions.

[0011] It has been found that in the membrane body structure of the PES filtration membrane provided by the present invention, the pore sizes on the two outer surfaces of the filtration membrane are different and have a certain difference, and the pore size on one of the outer surfaces is larger. In the present invention, this outer surface with a larger pore size is the first outer surface, i.e., the first outer surface is the large-pore surface of the filtration membrane, and the average pore size of the first outer surface is 150 to 450 nm. Preferably, the average pore size of the first outer surface is 200 to 400 nm, and the presence of the large-pore surface improves the filtration speed of the entire membrane, which is advantageous for shortening the fluid filtration time and reducing the time cost.

[0012] However, the pore size of the other outer surface of the filtration membrane is small. In the present invention, this small-pore outer surface is the second outer surface, i.e., the second outer surface is the small-pore surface of the filtration membrane, and the average pore size of the second outer surface is 10-42 nm. Preferably, the average pore size of the second outer surface is 14-35 nm. The presence of a small-pore surface is advantageous for improving the filtration accuracy of the membrane and ensuring that the PES filtration membrane has a high blocking effect against microviruses. In the present invention, the average pore sizes of the first and second outer surfaces are different, with a certain difference. This indicates that the PES filtration membrane is an asymmetric membrane, ensuring a relatively fast filtration rate, a high contamination rate, and a long service life. It also ensures a strong capture ability for microviruses (especially those with particle diameters of approximately 20 nm), meeting practical needs.

[0013] Furthermore, by observing the membrane body structure, it was found that the average pore size of the membrane body gradually changes from one side region near the first outer surface to one side region near the second outer surface, indicating that no mutations have occurred. This also proves that the PES filtration membrane is integrally molded and has not undergone any "composite" or other processes. The entire membrane body of the present invention is divided into two main regions in the thickness direction. One region is a pre-filtration layer including the first outer surface, which has relatively large internal pores and is primarily used to block large particle impurities in fluids. The pre-filtration layer has a relatively large contamination load and a relatively fast flow rate. The other region is a separation layer including the second outer surface, which has relatively small internal pores and is primarily used to block fine particle impurities such as microviruses in proteins. This ensures that the filtration membrane has a high virus capture capacity, making the PES filtration membrane particularly suitable for use as a virus removal membrane.

[0014] Furthermore, there is a continuous fiber transition between the other side of the pre-filtration layer (the side where the pre-filtration layer is separated from the first outer surface) and the other side of the separation layer (the side where the separation layer is separated from the second outer surface). "Continuous" is understood to mean that substantially all of the fibers are integrally connected to each other without the need for a separate adhesive or the like so that the reticulated fibers cannot be separated unless torn by an external force. At the same time, the continuous reticulated fibers are also connected to each other with the first outer surface and the second porous surface, and the material of each part of the PES filtration membrane of the present invention is uniform; that is, the entire membrane is made of PES material, and there is no change in material.

[0015] In the present invention, asymmetric membranes should be understood as membranes in which the pre-filtration layer and the separation layer are both made of the same material, and the two layers are combined into an integral structure, which is directly formed during membrane production.The transition from the pre-filtration layer to the separation layer only changes in membrane structure, while, for example, composite membranes have multi-layer structures, which are dense layers as separation layers that are porously coated in the separation process, and are always microporous support layers or support membranes, and the materials constituting the support layer and separation layer in composite membranes are often different.

[0016] The average pore size on the membrane surface can be measured by morphologically characterizing the membrane structure using a scanning electron microscope, then using computer software (Matlab, NIS-Elements, etc.), manually measuring, and performing corresponding calculations. During the membrane manufacturing process, each feature, such as pore size distribution, is nearly uniform and essentially consistent in the direction perpendicular to the membrane thickness (if the membrane is in the form of a flat membrane, this direction is the planar direction; if the membrane is in the form of a hollow fiber membrane, this direction is perpendicular to the radial direction). Therefore, the average pore size of a partial area on the corresponding plane can reflect the overall average pore size on the plane. In actual measurements, the membrane surface is first characterized using an electron microscope, and the corresponding SEM image can be obtained. However, since the pores on the membrane surface are nearly uniform, it is difficult to measure the pore size within a certain area, e.g., 1 μm 2 (1 μm multiplied by 1 μm) or 25 μm 2(5 μm multiplied by 5 μm) can be selected, the specific area size is determined according to the actual situation, and the pore diameters of all pores on the area are measured by corresponding computer software or manually, and then the average pore diameter of the surface is obtained by calculation. Of course, those skilled in the art can also obtain the above parameters by other measurement means, and the above measurement means are for reference only.

[0017] As a further improvement of the present invention, the first outer surface has a number of first holes in the shape of circular holes, and the pore area ratio of the first holes on the first outer surface is 0.1%-15%.

[0018] There are several circular second holes on the second outer surface, and the hole area ratio of the second holes on the second outer surface is 2%-10%.

[0019] In the membrane structure of the PES filtration membrane provided by the present invention, a certain number of first pores with a certain pore size are present on the first outer surface of the membrane. It is well known that factors such as the size, number, and shape of the membrane pores have a significant impact on the membrane's filtration accuracy (interception efficiency), membrane flow rate, and other properties. The first pores on the first outer surface of the present invention have a circular pore structure, some of the first pores are circular and some of the first pores are elliptical, and the pore area ratio of the first pores on the first outer surface (the ratio of the first pore area to the membrane area) is 0.1% to 15%. At the same time, a certain number of second pores with a certain pore size are also present on the second outer surface of the membrane. The second pores on the second outer surface of the present invention also have a circular pore structure, some of the second pores are circular and some of the second pores are elliptical, and the pore area ratio of the second pores on the second outer surface (the ratio of the second pore area to the membrane area) is 2% to 10%. The interaction between the pore area ratio of the first pores on the first outer surface and the pore area ratio of the second pores on the second outer surface ensures that the PES filtration membrane has a high flow rate, facilitates the fluid to pass through the porous membrane quickly, shortens the filtration time, and has a high tensile strength, which meets the needs of practical applications.

[0020] As a further improvement of the present invention, the gradient of the average pore size of the filtration membrane is 1.5-6 nm / 1 μm, and the ratio of the average pore size of the first outer surface to the average pore size of the second outer surface is 7-23.

[0021] In the present invention, the pore size of the membrane pores changes gradually with thickness, gradually decreasing from the large-pore surface to the small-pore surface. The ratio of the average pore sizes of the two outer surfaces is called the asymmetry factor; a smaller value (closer to 1) indicates a stronger symmetry between the two outer surfaces of the membrane. A larger value indicates a stronger asymmetry between the two outer surfaces of the membrane. Measurements have shown that the ratio of the average pore size of the first outer surface to the average pore size of the second outer surface is between 7 and 23. Preferably, the ratio of the average pore sizes is between 10 and 20, which explains why the two outer surfaces of the PES membrane of the present invention are asymmetric, but not significantly so. This asymmetry not only ensures a high flux and a long service life of the membrane, but also ensures a high virus blocking efficiency during filtration, meeting practical needs.

[0022] The pore size of a PES filtration membrane changes at a gradient with membrane thickness. In this invention, the magnitude of the gradient of the average pore size change reflects the rate of change in membrane pore size with thickness; the larger this value, the faster the pore size change, and the smaller this value, the smaller the pore size change. This value can be obtained by (average pore size of the first outer surface - average pore size of the second outer surface) / thickness, and is expressed in units of nm (representing pore size) / 1 μm (representing thickness). The gradient of the average pore size change in this filtration membrane is 1.5 to 6 nm / 1 μm, and this gradient is small. In this invention, the membrane pore size changes at a small gradient with thickness, and the change in membrane pore size is not too rapid, and there are no pores that are too large (if the pores in the pre-filtration layer are too large, the overall mechanical strength of the membrane will be too low, it will not be pressure-resistant, and it will be easily damaged under pressure). Here, the pre-filtration layer can provide a certain level of support for the separation layer, and the entire membrane will have good mechanical strength, pressure resistance, and will not be easily damaged under high pressure. Furthermore, the filtration membrane can ensure an efficient blocking of viruses, and the filtration membrane also has a relatively fast flux and can have a relatively large amount of contamination.

[0023] In a further improvement of the present invention, the filtration membrane has a PMI average pore size of 15-25 nm, a thickness of 40-150 μm, and a porosity of 70%-85%.

[0024] The average pore size of the filtration membrane was tested using a PMI pore size tester, and it was found that the average PMI pore size of the filtration membrane of the present invention is 15 to 25 nm. Furthermore, the tortuous path of the main body structure and the uniform thickness of the membrane ensure that this PES filtration membrane has a strong blocking effect against nanometer-level microviruses (even microviruses of mice with a particle diameter of 20 nm), which can meet the needs of actual applications and is suitable for use as a virus membrane.

[0025] Membrane thickness can be measured by morphologically characterizing the membrane structure using a scanning electron microscope, then calculating using computer software (e.g., Matlab, NIS-Elements, etc.) or by manual measurement. Of course, those skilled in the art can obtain these parameters through other measurement methods; the above measurement methods are for reference only. If the membrane thickness is too small, the membrane's mechanical strength will be low. At the same time, the filtration time will be too short, making effective filtration impossible. If the membrane thickness is too large, the filtration time will be long, resulting in excessive time costs. The thickness of the PES filtration membrane of the present invention is 40 to 150 μm, ensuring not only high mechanical strength but also effective filtration, with high filtration efficiency, short filtration time, and low time costs.

[0026] If the membrane porosity is too high, the membrane's tensile strength is too low, its mechanical performance is poor, its industrial practical value is low, and it cannot meet market needs.However, if the membrane porosity is too low, on the one hand, it will affect the membrane's flow rate, the membrane's filtration rate will be slow, the filtration time will be long, and the time cost will be high.On the other hand, the membrane's fouling amount will be too low, the service life will be too short, and the membrane will need to be replaced in a short time, which will significantly increase the economic cost.The porosity of the porous membrane in the present invention is 70% to 85%, so that the membrane not only has good tensile strength, but also has a relatively fast filtration rate, a large flow rate, a relatively high fouling amount, can block a relatively large amount of impurity particles, has a long service life, and is relatively low economic cost.

[0027] In a further improvement of the present invention, the pre-filtration layer has a PMI average pore size of 50-200 nm, a porosity of 75%-93%, and a thickness of the pre-filtration layer accounts for 70%-90% of the membrane thickness.

[0028] Compared to the separation layer, the pre-filtration layer has a larger pore size and a higher porosity. Tests have shown that the average PMI pore size of this pre-filtration layer is 50-200 nm (preferably 60-180 nm), ensuring a high filtration membrane flow rate and sufficient blocking effect on large-particle impurities (large-particle viruses) without affecting the blocking of subsequent microscopic viruses. The thickness of the pre-filtration layer accounts for 70%-90% of the total membrane thickness, accounting for the majority of the membrane area. The combined effect of the large pore size and porosity (the porosity of the pre-filtration layer is 75%-93%) ensures that the entire membrane has a high flux, fast filtration speed, low time cost, high contamination load, and long service life.

[0029] In the present invention, the parameters of the pre-filtration layer, such as the PMI average pore size, porosity, and thickness, can be measured by first tearing the PES membrane and separating it into the separation layer and membrane, and then testing the parameters corresponding to the membrane. Alternatively, the cross-sectional structure of the membrane can be characterized morphologically using a scanning electron microscope, and then the parameters can be calculated using computer software (e.g., Matlab, NIS-Elements, etc.) or manually. Of course, those skilled in the art can obtain the above parameters using other measurement methods, and the above measurement methods are provided for reference only.

[0030] As a further improvement of the present invention, the preliminary filtration layer includes a skin region and a pre-filtration region, one side of the skin region includes a first outer surface, the pore area ratio of the first holes on the first outer surface is smaller than the pore area ratio of the second holes on the second outer surface, the thickness of the skin region is 0.3-3.2 μm, and the pore area ratio of the first holes on the first outer surface is 0.15%-1.5%.

[0031] It has been discovered that some filtration membranes have a low porosity and a small number of pores in a certain region of the prefiltration layer. This region is called the cortical region, and is located on the side of the prefiltration layer away from the separation layer. The most notable feature of this region is the small number of pores and very low porosity. When the prefiltration layer of a filtration membrane includes a cortical region, the surface of this cortical region away from the separation layer is the first outer surface. In this case, the number of first pores on the first outer surface is small. Although the average pore size of the first pores is still large, the pore area ratio of the first pores on the first outer surface is still smaller than the pore area ratio of the second pores on the second outer surface. After testing, the pore area ratio of the first pores on the first outer surface is 0.15% to 1.5%. The presence of the cortical region is beneficial for increasing the tensile strength of the membrane, providing support and protection for the separation layer, making the entire membrane more pressure-resistant, less prone to rupture, and longer-lasting. In addition, measurements showed that the thickness of the cortical region was 0.3 to 3.2 μm, which is small enough to increase the support strength of the membrane without affecting the filtration rate and contamination amount of the entire membrane.

[0032] In a further improvement of the present invention, the separating layer has an average pore size of 15-25 nm, a porosity of 60%-80%, and a thickness of 2-20 μm.

[0033] Compared with the pre-filtration layer, the pore size of the separation layer is smaller, with an average pore size (PMI average pore size) of 15 to 25 nm. Therefore, the PES filtration membrane has a high blocking efficiency for fine impurities (especially microscopic viruses with a particle size of 20 nm), which meets the needs of practical applications and is particularly suitable for use in the field of virus removal.

[0034] The thickness of the separation layer is 2-20μm, which ensures the efficiency of impurity blocking and also ensures high flux throughout the membrane, fast filtration speed, and low time cost. At the same time, the porosity of this separation layer is 60%-80%, which explains that this separation layer has sufficient retention effect on microscopic viruses and further extends the service life of the membrane.

[0035] The parameters of the separation layer in the present invention, such as the average pore size, porosity, and thickness, can be determined by first tearing the PES filtration membrane and separating it into a separation layer and a pre-filtration layer, and then performing a parameter test on the separation layer. Alternatively, the cross-sectional structure of the membrane can be morphologically characterized using a scanning electron microscope, and then the parameters can be calculated using computer software (e.g., Matlab, NIS-Elements, etc.) or manually measured. The thickness of the separation layer can also be measured by a blocking test using 20 nm colloidal gold as impurity particles, and the length of the blocking region of the 20 nm colloidal gold in the filtration membrane is the thickness of the separation layer. Specific testing methods can be found in Chinese Patent CN105980037B - Virus Removal Membrane. Of course, those skilled in the art can obtain the above parameters by other measurement methods, and the above measurement methods are for reference only.

[0036] In a further improvement of the present invention, the ratio of the average pore size of the pre-filtration layer to the average pore size of the separation layer is 4-13:1.

[0037] The main structure of the PES filtration membrane of the present invention is mainly divided into two regions, of which the region with relatively large pore size is the pre-filtration layer and the region with relatively small pore size is the separation layer. Measurements have shown that the ratio of the average pore size of the pre-filtration layer to the average pore size of the separation layer is 4 to 13:1 (preferably 6-11:1). The PES filtration membrane of the present invention is an asymmetric membrane, and its pore size varies with thickness. Meanwhile, the pore size of the membrane of the present invention varies with thickness at a small gradient, meaning that the change in membrane pore size is not too rapid and there are no pores that are too large. This further ensures the PES filtration membrane's efficient virus blocking, relatively fast flux, and relatively large contamination load.

[0038] As a further improvement of the present invention, the pre-filtration layer comprises first fibers forming a porous structure, the first fibers having a sheet-like structure, the separating layer comprises second fibers forming a porous structure, the second fibers having a stripe-like structure, the average diameter of the first fibers being larger than the average diameter of the second fibers, and the average diameter of the second fibers being 30-75 nm.

[0039] It has been found that the fiber structure of the PES filtration membrane provided by the present invention varies with membrane thickness. The first fibers in the pre-filtration layer have a sheet-like structure, while the second fibers in the separation layer have a stripe-like structure. The average diameter of the first fibers is larger than that of the second fibers. This is because the pores in the pre-filtration layer are relatively large, and the pores formed by the relatively thick first fibers are highly stable and less prone to collapse or shrinkage, thereby ensuring stable fluid flow rates. At the same time, the pre-filtration layer formed with the sheet-like first fibers is more stable and pressure-resistant, providing support and protection to the separation layer. The sheet-like fiber structure distribution promotes fluid diffusion and enhances the blocking effect of small pores. The separation layer formed with the stripe-like second fibers has an appropriate porosity and pore distribution to ensure a higher overall membrane flow rate and high virus blocking efficiency. The average diameter of the second fibers is 30 to 75 nm, ensuring the stability of the pores within the separation layer and providing good retention of fine viral impurities. The first and second fibers with such a structure and thickness are advantageous in ensuring that the entire membrane has relatively high mechanical strength and filtration stability, allowing for efficient filtration over a long period of time, making PES filtration membranes particularly suitable for applications in the field of virus removal.

[0040] The thickness of the fiber cross section can be considered as the diameter of the fiber. The average diameter of the second fiber in the present invention can be calculated by morphologically characterizing the cross-sectional structure of the filtration membrane using a scanning electron microscope, using computer software (e.g., Matlab, NIS-Elements, etc.), or by manually measuring the average value. Of course, those skilled in the art can also obtain the above parameters by other measurement means, and the above measurement means are for reference only.

[0041] As a further improvement of the present invention, the pre-filtration layer further comprises a transition region, the transition region being located on one side of the pre-filtration layer closer to the separating layer, the continuous fibers forming a porous structure of the transition region, the continuous fibers gradually changing from a sheet-like structure to a stripe-like structure, and the one side of the continuous fibers closer to the separating layer being continuous with the one side of the second fibers closer to the pre-filtration layer.

[0042] In a further refinement of the present invention, the average pore size of said transition region is 60-170 nm, the porosity is 75%-82%, and the thickness of said transition region is 4-20 μm.

[0043] The pore size, fiber structure, and other characteristics of the PES filtration membrane of the present invention all gradually change with thickness, rather than undergo mutations. This ensures that the entire membrane has relatively high mechanical strength, high tensile strength, and can meet the needs of practical applications. The pre-filtration layer also has a transition region on the side closer to the separation layer. The continuous fibers in the transition region form a porous structure in the transition region, ensuring appropriate pore sizes and excellent porosity within the transition region. As the pre-filtration layer approaches the separation layer, the continuous fibers gradually change from a sheet-like structure to a stripe-like structure. At the same time, the side of the continuous fibers closer to the separation layer and the side of the second fibers closer to the pre-filtration layer are continuous. "Continuous" means that substantially all of the fibers (the continuous fibers and the second fibers) are integrally connected, e.g., integrally formed, without the need for additional adhesives or other means to connect the mesh-like fibers together, so that they cannot be separated unless torn by external force. Therefore, the material of each portion of this PES filtration membrane is uniform, i.e., the entire membrane is made of PES material and molded as a single unit, with no material variation. The average pore size of the transition region is 60-170 nm, the porosity is 75%-82%, and the thickness is 4-20 μm. The combined effect of these three factors further ensures that the filtration membrane has a relatively high capture capacity for various viruses, a large flux, a fast filtration speed, and high economic efficiency.

[0044] As a further improvement of the present invention, the tensile strength of the PES filtration membrane is 5-10 MPa, the elongation at break is 8%-30%, and the flux of the PES filtration membrane is 600 L*h -1 *m -2 @30 psi or greater, the PES membrane has an LRV of 4 or greater against viral impurities, and the protein yield of the PES membrane is 98% or greater.

[0045] Important indicators for evaluating the mechanical strength of a filtration membrane are its tensile strength and elongation at break. Under certain conditions, the higher the tensile strength of a filtration membrane, the better its mechanical strength. Stretching strength refers to the membrane's ability to withstand parallel stretching. When tested under certain conditions, a membrane sample is subjected to a tensile load until it breaks. The tensile strength and elongation at break of the membrane can be calculated based on the corresponding maximum tensile load and the change in membrane sample size (length) at the time of membrane breakage. Both tensile strength and elongation at break can be measured using a universal tensile tester. Tensile strength testing methods are well known in the art, such as ASTM D790 or ISO 178, which provide detailed descriptions of tensile strength testing procedures. The filtration membrane of the present invention has a tensile strength of 5-10 MPa and an elongation at break of 8%-30%. The present invention also demonstrates that the filtration membrane of the present invention has a relatively high tensile strength and elongation at break, good mechanical performance, high industrial value, and the ability to fully meet market demand.

[0046] Permeation flux, also known as permeation rate or simply "flux," refers to the amount of material passing through a unit membrane area per unit time under a certain operating pressure during the separation process. The magnitude of the flux reflects the filtration rate, and the higher the flux, the faster the membrane filtration rate. The flux of the PES filtration membrane in this invention is 600 L*h -1 *m -2 At pressures above 30 psi, the flux is large, the filtration rate of the filtration membrane is fast, and the blocking efficiency is guaranteed. At the same time, the fluid can pass through the filtration membrane quickly, which reduces the time cost and improves the economic efficiency.

[0047] The viruses blocked by this invention are primarily those with particle diameters of 20 nm or greater (e.g., the mouse microvirus, which has a particle diameter of approximately 20 nm). Through blocking tests, the PES membrane of the present invention was found to have an LRV of 4 or greater against various viruses, demonstrating that this PES membrane has a very high virus blocking rate and sufficient retention of viral impurities, meeting practical needs. The protein yield of the PES membrane is greater than 98%, demonstrating that the proteins of active substances in fluids are less likely to adsorb to the membrane, preventing membrane pore blockage and ensuring the membrane's long service life. The protein content of the active substance in the fluid changes little, with essentially no protein loss, ensuring economic benefits. For viral impurity testing methods, see patents CN105980037B - Virus Removal Membrane; CN101816898B - Ultrafiltration Membrane and Manufacturing Method; and CN1759924B - Ultrafiltration Membrane and Manufacturing Method.

[0048] As a further improvement of the present invention, the PES filtration membrane has an LRV of 2.5 or more and less than 4 for viral impurities.

[0049] It has been found that some of the PES membranes produced by the present invention have relatively large pores, resulting in a very high flux. However, the large pores also reduce the membrane's ability to block microviruses. For microviruses with particle sizes of approximately 20 nm, the LVR value cannot reach 4 (although the LRV value can reach 2.5 or higher). These membranes are typically stacked in two layers for practical use (the two layers have the same LRV; for example, if the LRV of a single layer is 3, the LRV of a double layer is 6). Even in this case, the membranes can still efficiently block various microviruses with sizes of 20 nm or larger, while still providing a high flux. The large pores also result in a high protein yield.

[0050] Furthermore, the present invention provides a method for producing an asymmetric PES filtration membrane for virus removal, comprising the following steps:

[0051] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane, wherein the casting solution comprises 15-25 parts by weight of polyethersulfone, 55-90 parts by weight of organic solvent, and 6-25 parts by weight of polar additive, and the viscosity of the casting solution is 5000-10000 cps;

[0052] S2: The liquid membrane and the carrier are immersed in the solidifying liquid for at least 10 seconds, and the solidifying liquid penetrates into the liquid membrane, gradually diffuses into the interior, and solidifies to form a separation layer and a pre-filtration layer, the surface energy of the solidifying liquid is 22-35 dyn / cm, the solidifying liquid contains water and a penetrating additive whose surface energy does not exceed 35 dyn / cm, the content of the penetrating additive is 25%-70%, and the temperature of the carrier is lower than that of the solidifying liquid.

[0053] In a further improvement of the present invention, the organic solvent is at least one of butyl lactate, dimethyl sulfoxide, dimethylformamide, caprolactam, methyl acetate, ethyl acetate, N-ethylpyrrolidone, dimethylacetamide, and N-methylpyrrolidone.

[0054] The polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol in a mass ratio of 2:1:1.

[0055] As a further refinement of the present invention, the penetration additive is at least one of isopropanol, ethanol, and ethylene glycol.

[0056] In a further improvement of the present invention, the temperature of the carrier is at least 5° C. lower than the solidification liquid temperature.

[0057] In a further refinement of the present invention, the solidification liquid temperature is 25-50°C and the carrier temperature is 0-40°C.

[0058] To fabricate the PES membrane of the present invention, a casting solution containing the membrane-forming material polyethersulfone (PES), an organic solvent (for the PES material), and a polar additive is first prepared. The polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol. The addition of polyvinyl alcohol controls the viscosity of the system, inhibits the formation of large pores in the membrane during phase separation, and effectively enhances membrane flux stability. The synergistic effect of these three substances significantly improves the hydrophilicity of the organic solvent. During phase separation, the polar solvent dissolves in the coagulation bath, facilitating the precipitation of polyethersulfone, facilitating the formation of PES membranes with a small pore size gradient. The viscosity of the resulting casting solution is 5,000-10,000 cps. The viscosity of the casting solution significantly affects the structure and performance of the final membrane, including the membrane's pore size, thickness, and flow rate. This viscosity setting ensures that the final filtration membrane has the appropriate thickness and ideal pore size. The liquid viscosity of the casting membrane can be directly measured using a viscometer, and the casting solution is then cast onto a support to form a liquid membrane. The casting solution of the present invention can be cast manually (e.g., by hand pouring, casting, or spreading on a casting surface) or automatically (e.g., by pouring onto a moving bed or casting independently). Various casting devices known in the art can be used for casting. Examples of casting devices include mechanical coaters, including coating blades, doctor blades, or spray / intensifier systems. As known in the art, various casting speeds are appropriate, such as a casting speed of about 2 to 6 feet per minute (fpm), with the specific casting speed depending on the circumstances.

[0059] The liquid membrane and the carrier are then immersed in the solidification liquid for at least 10 seconds, with a preferred phase separation / solidification time of 20-60 seconds. A suitable phase separation / solidification time, in conjunction with the membrane casting liquid system, can be beneficial for obtaining a filtration membrane with an ideal membrane pore size. The solidification liquid penetrates the liquid membrane, gradually diffuses into the interior, and solidifies to form a separation layer and a pre-filtration layer. In current technology, the solidification liquid is typically water, and the mutual solubility of water and organic solvents is low, resulting in a slow phase separation rate. This can be explained by the large pore size formed in the later phase separation stage, the large average pore size of the pre-filtration layer, and the strong asymmetry of the filtration membrane. In the present invention, to accelerate the phase separation rate, the solidification liquid is adjusted to have a surface energy of 22-35 dyn / cm. This surface energy is close to that of the organic solvent, allowing for rapid mutual dissolution with the organic solvent, thereby rapidly separating the polyethersulfone from the organic solvent and subsequently forming a filtration membrane with a small pore size gradient. In addition to ordinary water, the solidification liquid contains a low-surface-energy penetration additive, which can reduce the surface energy of the entire solidification liquid, further increase the speed at which the solidification liquid penetrates into the liquid membrane, and speed up the penetration speed of the solidification liquid. This makes the phase separation speed of the entire membrane faster, makes it less likely for large pores to appear, reduces the asymmetry of the entire membrane, and makes it easier to form a PES filtration membrane with a continuously changing small pore gradient.

[0060] To further ensure that the membrane pore size changes continuously with membrane thickness at a small gradient, the present invention dictates that the temperature of the support be lower than the solidifying liquid temperature. Preferably, the support temperature is at least 5°C lower than the solidifying liquid temperature. The solidifying liquid temperature is preferably controlled to 25-50°C, and the support temperature is preferably controlled to 0-40°C. This configuration is necessary because the phase separation rate of the liquid membrane is related not only to the exchange rate between the solvent and non-solvent but also to temperature. The greater the change in temperature difference, the faster the phase separation rate of the liquid membrane. This is because the solidifying liquid first penetrates the air side of the liquid membrane (the side away from the support). Small pores then form first on the air side of the liquid membrane, and larger pores form on the support side of the liquid membrane. Due to the temperature difference between the two sides of the liquid membrane, the temperature on the liquid membrane support side becomes lower, forming larger pores on the membrane support side. However, the membrane pores are adjusted by changing the temperature difference to prevent the pore size from becoming too large, ensuring the formation of a PES filtration membrane with a pore size that changes continuously with a small gradient.

[0061] The beneficial effect of the present invention is that the asymmetric PES filtration membrane for virus removal provided by the present invention includes a main body, one surface of which is a first outer surface, and the first outer surface is a large-pore surface, the average pore diameter of which is 150 to 450 nm.

[0062] The other surface is the second outer surface, which is a small-pore surface with an average pore size of 10-42 nm. The average pore size of the main body changes continuously from the region closest to the first outer surface to the region closest to the second outer surface, and the pore size of this filtration membrane changes continuously with a small gradient along the thickness. The main body includes a pre-filtration layer and a separation layer for blocking viruses. One side of the pre-filtration layer is the first outer surface, and one side of the separation layer is the second outer surface. The other side of the pre-filtration layer and the other side of the separation layer are continuously fiber-transferred. The PES filtration membrane is manufactured using only a membrane casting solution and is integrally molded, requiring no compounding, making the manufacturing process relatively simple. The manufactured PES filtration membrane has a strong blocking effect against microviruses, a relatively high protein yield, a relatively high flux, and a fast filtration rate, meeting the needs of practical applications. It is particularly suitable for the field of virus removal, and the present invention provides a method for producing this filtration membrane, which is convenient, rapid, effective, easy to operate, environmentally friendly, and suitable for large-scale popularization. [Brief explanation of the drawings]

[0063] [Figure 1] 1 is a scanning electron microscope (SEM) image of the first outer surface of the PES filtration membrane prepared in Example 1, the magnification of which is 500×. [Figure 2] 1 is a scanning electron microscope (SEM) image of the first outer surface of the PES filtration membrane prepared in Example 1, the magnification of which is 2000×. [Figure 3] 1 is a scanning electron microscope (SEM) image of the second outer surface of the PES filtration membrane prepared in Example 1, the magnification of which is 50K×. [Figure 4] 1 is a scanning electron microscope (SEM) image of the second outer surface of the PES filtration membrane prepared in Example 1, the magnification of which is 100K×. [Figure 5] 1 is a scanning electron microscope (SEM) image of the longitudinal section of the PES filtration membrane prepared in Example 1, the magnification of which is 700×. [Figure 6]1 is a scanning electron microscope (SEM) image of a longitudinal section of the PES filtration membrane prepared in Example 1, close to the second outer surface, at a magnification of 50K×. [Figure 7] 1 is a scanning electron microscope (SEM) image of a longitudinal section of a PES filtration membrane prepared in Example 1, close to the first outer surface, at a magnification of 20K×. [Figure 8] 1 is a scanning electron microscope (SEM) image of a vertical cross section of the PES filtration membrane prepared in Example 1, showing a further enlargement of a portion near the first outer surface, the magnification of which is 50K×. [Figure 9] 1 is a scanning electron microscope (SEM) image of the first outer surface of the PES filtration membrane prepared in Example 5, the magnification of which is 5K×. [Figure 10] 1 is a scanning electron microscope (SEM) image of the first outer surface of the PES filtration membrane prepared in Example 5, the magnification of which is 10K×. [Figure 11] 1 is a scanning electron microscope (SEM) image of the second outer surface of the PES filtration membrane prepared in Example 5, the magnification of which is 5K×. [Figure 12] 1 is a scanning electron microscope (SEM) image of the second outer surface of the PES filtration membrane prepared in Example 5, the magnification of which is 10K×. [Figure 13] 1 is a scanning electron microscope (SEM) image of a longitudinal section of the PES filtration membrane prepared in Example 5, close to the second outer surface, at a magnification of 20×. [Figure 14] 1 is a scanning electron microscope (SEM) image of a vertical cross section of the PES filtration membrane prepared in Example 5, showing a further enlargement of a portion near the second outer surface, the magnification of which is 50K×. [Figure 15] 1 is a schematic diagram of a test device for the PES filtration membrane flux of the present invention. [Figure 16] 1 is a schematic diagram of a test device used to test the blocking efficiency of colloidal gold for PES filtration membranes of the present invention. [Figure 17]is a scanning electron microscope (SEM) image of the cross section of a multi-layer composite ultrafiltration membrane manufactured according to patent CN1759924B. [Figure 18] 1 is a schematic diagram of a composite device for a multi-layer composite ultrafiltration membrane manufactured according to patent CN1759924B. DETAILED DESCRIPTION OF THE INVENTION

[0064] To more clearly explain the overall concept of the present application, the following examples are provided in detail. Unless otherwise specified, all raw materials and equipment used in the following examples for the manufacture of filtration membranes can be purchased commercially. Among these, a Hitachi S-5500 scanning electron microscope was used to characterize the structure and morphology of the filtration membranes. Example 1

[0065] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0066] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 20 parts polyethersulfone, 75 parts organic solvent, and 20 parts polar additive by weight. The viscosity of the casting solution is 7500 cps. The organic solvent is dimethylformamide, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0067] S2: The liquid membrane and the carrier are immersed in the solidification liquid for at least 40 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive isopropanol, and the penetrating additive content is 50%, of which the solidification liquid temperature is 35°C and the carrier temperature is 20°C. Example 2

[0068] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0069] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane, the casting solution containing 21 parts polyethersulfone, 70 parts organic solvent, and 18 parts polar additive by weight, the viscosity of the casting solution is 8000 cps, the organic solvent is dimethylformamide, the polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol in a mass ratio of 2:1:1, the organic solvent is N-ethylpyrrolidone, and the polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol in a mass ratio of 2:1:1.

[0070] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 45 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethanol, and the penetrating additive content is 55%. The solidification liquid temperature is 30°C, and the carrier temperature is 15°C. Example 3

[0071] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0072] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 23 parts polyethersulfone, 65 parts organic solvent, and 16 parts polar additive by weight. The viscosity of the casting solution is 9000 cps. The organic solvent is N-methylpyrrolidone, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0073] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 50 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethylene glycol, and the penetrating additive content is 60%. The solidification liquid temperature is 30°C, and the carrier temperature is 10°C. Example 4

[0074] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0075] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 15 parts polyethersulfone, 85 parts organic solvent, and 10 parts polar additive by weight. The viscosity of the casting solution is 5500 cps. The organic solvent is N-ethylpyrrolidone, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0076] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 20 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive isopropanol, and the penetrating additive content is 35%, of which the solidification liquid temperature is 45°C and the carrier temperature is 35°C. Example 5

[0077] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0078] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 17 parts polyethersulfone, 83 parts organic solvent, and 12 parts polar additive by weight. The viscosity of the casting solution is 6000 cps. The organic solvent is dimethyl sulfoxide, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0079] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 25 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethanol, and the penetrating additive content is 40%, of which the solidification liquid temperature is 40°C and the carrier temperature is 40°C. Example 6

[0080] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0081] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 19 parts polyethersulfone, 81 parts organic solvent, and 14 parts polar additive by weight. The viscosity of the casting solution is 7000 cps. The organic solvent is butyl lactate, and the polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0082] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 30 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethylene glycol, and the penetrating additive content is 45%, of which the solidification liquid temperature is 35°C and the carrier temperature is 25°C. Example 7

[0083] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0084] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 16 parts polyethersulfone, 60 parts organic solvent, and 9 parts polar additive by weight. The viscosity of the casting solution is 6800 cps. The organic solvent is dimethylacetamide, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0085] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 55 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethanol, and the penetrating additive content is 40%. The solidification liquid temperature is 25°C, and the carrier temperature is 13°C. Example 8

[0086] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0087] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 18 parts polyethersulfone, 70 parts organic solvent, and 8 parts polar additive by weight. The viscosity of the casting solution is 6400 cps. The organic solvent is dimethyl sulfoxide, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0088] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 60 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive ethanol, and the penetrating additive content is 35%, of which the solidification liquid temperature is 25°C and the carrier temperature is 15°C. Example 9

[0089] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0090] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 22 parts polyethersulfone, 80 parts organic solvent, and 7 parts polar additive by weight. The viscosity of the casting solution is 7200 cps. The organic solvent is ethyl acetate, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0091] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 65 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive isopropanol, and the penetrating additive content is 45%. The solidification liquid temperature is 20°C, and the carrier temperature is 12°C. Example 10

[0092] The manufacturing method of the asymmetric PES filtration membrane for virus removal includes the following steps:

[0093] S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane. The casting solution contains 24 parts polyethersulfone, 90 parts organic solvent, and 6 parts polar additive by weight. The viscosity of the casting solution is 7400 cps. The organic solvent is N-ethylpyrrolidone, and the polar additive is a mixture of glycerin, azodimethyl-N-2-hydroxybutylpropionamide, and polyvinyl alcohol, in a mass ratio of 2:1:1.

[0094] S2: The liquid membrane and the carrier are immersed in the solidification liquid for 70 seconds, and the solidification liquid penetrates into the liquid membrane, gradually diffuses inside, and solidifies to form a separation layer and a pre-filtration layer. The solidification liquid contains water and the penetrating additive isopropanol, and the penetrating additive content is 40%. The solidification liquid temperature is 20°C, and the carrier temperature is 15°C.

[0095] 1: Structural characteristics

[0096] The nanometer-scale polymer filtration membrane obtained in each example was subjected to morphological characterization using a scanning electron microscope, and then the desired data was obtained. The specific results are shown in the following table:

[0097] JPEG0007741972000001.jpg122147

[0098] JPEG0007741972000002.jpg66147

[0099] JPEG0007741972000003.jpg77147

[0100] JPEG0007741972000004.jpg74147

[0101] As can be seen from Tables 1 to 4, the PES membranes produced in Examples 1 to 6 of the present invention all have ideal membrane structures, are integrally formed, do not require composite processes, and are easy to manufacture. Furthermore, these PES membranes are asymmetric, with pore sizes that vary with thickness at a small gradient and no particularly large pores. This not only ensures efficient virus blocking, but also has high flux, making them suitable for use in virus removal applications.

[0102] Performance characteristics

[0103] The membrane flux is calculated by the following formula:

[0104] Calculation formula for membrane flux (J): J = V / (T × A)

[0105] J--Membrane flux unit: L*h-1*m-2

[0106] V - sampling volume (L), T - sampling time (h), A - effective membrane area (m 2 )

[0107] The operating conditions used to measure the separation performance of the PES filtration membrane in this invention are: feed liquid is deionized water, operating pressure is 30 psi, operating temperature is 25°C, solution pH is 7, and the flux test apparatus is shown in Figure 15. JPEG0007741972000005.jpg91148

[0108] As can be seen from the above table, all of the samples prepared in Examples 1 to 10 have good mechanical properties (high tensile strength and elongation at break), are suitable for various processing, have high practicality, are easy to process, and at the same time have good flux and fast filtration rate.

[0109] In addition, the test method used in paragraph 114 of CN201010154974.7 - Ultrafiltration membrane and its manufacturing method can be used to conduct a virus blocking test.

[0110] The virus used is the minute virus of mice with a particle diameter of 20 nm.

[0111] After testing, the PES filtration membranes manufactured in Examples 1 to 6 had an LRV of 4 or more against viral impurities with a particle diameter of 20 nm, indicating that the PES filtration membrane of the present invention has sufficient blocking effect against viruses of 20 nm or more. The protein yield of the PES filtration membrane is 98% or more, making the PES filtration membrane particularly suitable for application in the field of virus removal.

[0112] However, the LRV value of Example 7 is 3.5, the LRV value of Example 8 is 3, the LRV value of Example 9 is 2.7, and the LRV value of Example 10 is 2.5, and it is detected that none of these LRV values ​​reach 4 or more. In actual use, two PES filtration membranes with the same LRV value can be stacked and used, in which case the LRV value of the entire assembly will be at least 5 or more, which meets practical needs and has good flux and protein yield, while still being economical.

[0113] Filtration accuracy test: The PES filtration membrane obtained in each example was tested for blocking efficiency, and blocking particles were colloidal gold with a particle diameter of 20 nm.

[0114] Experimental equipment: Tianjin Logan particle counter KB-3. Experimental preparation: Assemble the experimental equipment according to Figure 16, ensure the cleanliness of the equipment, wash the equipment with ultrapure water, take a 47mm diameter filter membrane and attach it to the butterfly filter, and ensure the airtightness of the assembled filter.

[0115] Testing Procedure:

[0116] Pour the test liquid into the tank, pay attention to the venting of the butterfly filter, pressurize to 10 kPa, and use a clean bottle to catch the filtrate downstream of the butterfly.

[0117] The particle count in the filtrate and the raw solution was tested using a particle counter.

[0118] JPEG0007741972000006.jpg1055

[0119] During the ceremony:

[0120] η───Interruption efficiency, %,

[0121] n0──Number of particles in the original solution, average of 5 counts, number,

[0122] n1───Number of particles in the filtrate, average of five counts, number.

[0123] After testing, it was found that the blocking efficiency of 20 nm colloidal gold according to Examples 1-6 was over 99.99%.

[0124] The above are only preferred embodiments of the present invention, and the scope of protection of the present invention is not limited to the above examples, and all technical solutions that fall within the concept of the present invention are within the scope of protection of the present invention. It should be noted that those skilled in the art may make some improvements and refinements without departing from the principles of the present invention, and these improvements and refinements should also be considered within the scope of protection of the present invention.

Claims

1. An asymmetric PES filtration membrane for virus removal, comprising a main body, a non-directed tortuous passageway formed within the main body, one surface of the main body being a first outer surface, and the other surface of the main body being a second outer surface, The first outer surface has an average pore size of 150-450 nm, and the second outer surface has an average pore size of 10-42 nm; The average pore size of the body varies continuously from a region adjacent to the first outer surface to a region adjacent to the second outer surface; The main body includes a pre-filtration layer and a separation layer that blocks viruses, one side of the pre-filtration layer is a first outer surface, one side of the separation layer is a second outer surface, and the other side of the pre-filtration layer and the other side of the separation layer have continuous fiber transition.

2. the first outer surface has a number of circular first holes, and the hole area ratio of the first holes in the first outer surface is 0.1% to 15%; The asymmetric PES virus removal filtration membrane according to claim 1, characterized in that the second outer surface has several circular second holes, and the opening area ratio of the second holes on the second outer surface is 2% to 10%.

3. The gradient of the average pore size of the filtration membrane is 1.5-6 nm / 1 μm; 2. The asymmetric PES virus removal filtration membrane according to claim 1, wherein the ratio of the average pore size of the first outer surface to the average pore size of the second outer surface is 7-23.

4. The asymmetric PES filtration membrane for virus removal according to claim 1, characterized in that the filtration membrane has a PMI average pore size of 15-25 nm, a thickness of 40-150 μm, and a porosity of 70%-85%.

5. 2. The asymmetric PES virus removal filtration membrane according to claim 1, wherein the pre-filtration layer has an average PMI pore size of 50-200 nm, a porosity of 75%-93%, and a thickness of the pre-filtration layer that accounts for 70%-90% of the membrane thickness.

6. 2. The asymmetric PES virus removal filtration membrane according to claim 1, wherein the pre-filtration layer comprises a skin region and a pre-filtration region, one side of the skin region comprises a first outer surface, the pore area ratio of the first holes in the first outer surface is smaller than the pore area ratio of the second holes in the second outer surface, the skin region has a thickness of 0.3-3.2 μm, and the pore area ratio of the first holes in the first outer surface is 0.15%-1.5%.

7. 2. The asymmetric PES virus removal filtration membrane according to claim 1, wherein the separation layer has an average pore size of 15-25 nm, a porosity of 60%-80%, and a thickness of 2-20 μm.

8. 2. The asymmetric virus removal PES filtration membrane according to claim 1, wherein the ratio of the average pore size of the pre-filtration layer to the average pore size of the separation layer is 4-13:

1.

9. 2. The asymmetric PES virus removal filtration membrane according to claim 1, wherein the pre-filtration layer comprises first fibers that form a porous structure, the first fibers having a sheet-like structure, the separation layer comprises second fibers that form a porous structure, the first fibers having an average diameter larger than the average diameter of the second fibers, and the second fibers having an average diameter of 30-75 nm.

10. 10. The asymmetric virus removal PES filtration membrane according to claim 9, wherein the pre-filtration layer further comprises a transition region, the transition region being located on one side of the pre-filtration layer closer to the separation layer.

11. The asymmetric virus removal PES filtration membrane according to claim 10, characterized in that the transition region has an average pore size of 60-170 nm, a porosity of 75%-82%, and a thickness of 4-20 μm.

12. The tensile strength of the PES filtration membrane is 5-10 MPa, and the elongation at break is 8%-30%; The PES filtration membrane has an LRV of 4 or more against viral impurities, 2. The asymmetric PES filtration membrane for virus removal according to claim 1, wherein the protein yield of the PES filtration membrane is 98% or more.

13. 2. The asymmetric PES filtration membrane for virus removal according to claim 1, wherein the PES filtration membrane has an LRV of 2.5 or more and less than 4 with respect to viral impurities.

14. A method for producing the asymmetric virus removal PES filtration membrane according to any one of claims 1 to 13, comprising: S1: A casting solution is prepared and cast onto a carrier to form a liquid membrane, wherein the casting solution comprises 15-25 parts by weight of polyethersulfone, 55-90 parts by weight of organic solvent, and 6-25 parts by weight of polar additive, and the viscosity of the casting solution is 5000-10000 cps; S2: A method for producing an asymmetric PES virus removal filtration membrane, characterized in that the liquid membrane and the carrier are immersed in the solidifying liquid for at least 10 seconds, the solidifying liquid penetrates into the liquid membrane, gradually diffuses into the interior, and solidifies to form a separation layer and a pre-filtration layer, the surface energy of the solidifying liquid is 22-35 dyn / cm, the solidifying liquid contains water and a penetrating additive whose surface energy does not exceed 35 dyn / cm, the content of the penetrating additive is 25%-70%, and the temperature of the carrier when the liquid membrane and the carrier are immersed in the solidifying liquid is lower than that of the solidifying liquid.

15. The organic solvent is at least one of butyl lactate, dimethyl sulfoxide, dimethylformamide, caprolactam, methyl acetate, ethyl acetate, N-ethylpyrrolidone, dimethylacetamide, and N-methylpyrrolidone; 15. The method for producing an asymmetric PES virus removal filtration membrane according to claim 14, wherein the polar additive is a mixture of glycerin, azodimethyl N-2-hydroxybutylpropionamide, and polyvinyl alcohol in a mass ratio of 2:1:

1.

16. The method for producing an asymmetric PES virus removal filtration membrane according to claim 14, wherein the penetration additive is at least one of isopropanol, ethanol, and ethylene glycol.

17. A method for manufacturing an asymmetric PES filtration membrane for virus removal as described in Claim 14, characterized in that the temperature of the carrier when the liquid membrane is immersed in the solidification liquid together with the carrier is at least 5°C lower than the temperature of the solidification liquid when the liquid membrane is immersed in the solidification liquid together with the carrier.

18. A method for producing an asymmetric PES filtration membrane for virus removal as described in Claim 17, characterized in that the temperature of the solidifying liquid when the liquid membrane and the carrier are immersed in the solidifying liquid is 25-50°C, and the temperature of the carrier when the liquid membrane and the carrier are immersed in the solidifying liquid is 0-40°C.

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