A virus-removing membrane, its wetting and preservation method, and a capsule-type filtration device

Abstract

This application relates to the field of virus-removing filters, specifically to a virus-removing membrane, its wetting and preservation method, and a capsule-type filtration device, comprising overlapping inlet screens and a filtration unit; the filtration unit includes sequentially overlapping filtrate screens and filter layers stacked on one or both sides of the filtrate screens; the inlet port, the first flow space, and the outlet port are connected to form a first flow space; the second flow space is connected to the permeate port to form a second flow space; at least the first flow space is filled with a cationic activator, and the inlet screen, filter layer, and filtrate screen are all wetted by the cationic activator, which is a cationic solution. This application has the effect of improving the virus removal capability of the virus-removing membrane.

Description

Technical Field

[0001] This invention relates to the field of virus-removing membrane packs, and more specifically, to a virus-removing membrane pack, a method for wetting and preserving it, and a capsule-type filtration device. Background Technology

[0002] In the biopharmaceutical field, virus removal filtration is a relatively robust method. Biological products are susceptible to viral contamination during production; therefore, virus removal filtration is an essential process for eliminating viruses.

[0003] Virus removal filtration typically employs virus-removing membranes, which generally remove viruses from the fluid flowing through them through a particle size exclusion mechanism. Particle size exclusion refers to the membrane's pore size being smaller than the virus size; when fluid passes through the membrane, the virus is trapped, thus achieving virus removal. Therefore, for removing smaller viruses, the smaller the pore size of the membrane required.

[0004] However, for filter membranes with higher precision, the preparation difficulty and cost increase significantly. Moreover, in the fluid to be devired, the size of the virus may vary. If only the precision is controlled to be high, the filter membrane can easily be blocked by large-sized viruses, resulting in a decrease in the virus removal efficiency and capacity of the filter membrane. Summary of the Invention

[0005] To address the problem that existing antiviral membrane packs do not have sufficient antiviral removal capabilities, the first objective of this invention is to provide an antiviral membrane pack that enhances the electrostatic adsorption and removal capability of small-sized viruses through the wetting and adsorption effect of a cationic activator, thereby improving the overall antiviral effect and capability of the antiviral membrane pack and reducing its usage cost.

[0006] The second objective of this invention is to provide a method for wetting and preserving a virus-removing membrane pack, which involves soaking the membrane pack in a cationic activator so that the cationic activator adheres to the filter membrane of the virus-removing membrane pack, thereby improving the virus removal capability of the virus-removing membrane pack.

[0007] The third objective of this invention is to provide a capsule-type filtration device comprising a virus-removing membrane. By filling the space between the sealed capsule and the virus-removing membrane with a cationic activator, the entire capsule-type filtration device is wetted with the cationic activator, thereby preventing a decrease in the concentration of the cationic activator in the virus-removing membrane and improving the virus removal capability of the capsule-type filtration device.

[0008] To achieve the first objective mentioned above, the present invention provides the following technical solution:

[0009] A virus-removing membrane package includes an interleaved liquid inlet screen and a filtration unit;

[0010] The filtration unit includes a filtrate screen that is stacked in sequence and a filter layer that is stacked on one or both sides of the filtrate screen.

[0011] The liquid inlet screen, the filter layer, and the filtrate screen are all provided with liquid inlet holes, liquid outlet holes, and permeate holes; the liquid inlet holes are interconnected, the liquid outlet holes are interconnected, and the permeate holes are interconnected.

[0012] A first flow guiding space is formed between the liquid inlet screen and the adjacent filter layer; a second flow guiding space is formed between the filtrate screen and the adjacent filter layer.

[0013] The inlet hole, the first guide space, and the outlet hole are connected to form a first flow space; the second guide space is connected to the permeate hole to form a second flow space;

[0014] At least the first flow space is filled with a cationic activator, and the inlet screen, filter layer and filtrate screen are all wetted by the cationic activator, which is a cationic solution.

[0015] The first and second flow channels of the virus-absorbing membrane specifically refer to the space between the two filter layers adjacent to the screen. This space generally takes two forms. The first is where the screen is suspended between the two filter layers; this space includes the gap between the screen and the two filter layers, as well as the mesh gaps on the screen. The second is where the screen is attached to the two filter layers; in this case, the space only includes the mesh gaps on the inlet screen.

[0016] Before use, the virus removal membrane should be rinsed to remove any cationic activator that has not adhered to the filter layer, so as to prevent it from mixing into the filtered fluid and causing adverse effects on the filtered fluid.

[0017] When the virus-removing membrane pack is in use, the fluid to be filtered flows into the first guiding space from the inlet and flows out from the first guiding space to the outlet. When the fluid flows through the first guiding space, the fluid will pass through the filter layer due to the pressure difference before and after the filter layer. The filter layer removes the virus from the fluid. The virus-removed fluid flows into the second guiding space, and then the virus-removed fluid flows out from the permeate hole for collection.

[0018] When viral removal membranes are used to filter protein solutions to remove viruses, the proteins in the solution are generally positively charged, while the viruses being removed are generally negatively charged. Therefore, the cationic activator attached to the filter layer, due to its positive charge, can both promote the passage of positively charged proteins through the filter layer and enhance the electrostatic adsorption of negatively charged viruses, thereby improving the virus removal capacity.

[0019] Furthermore, the cation-containing solution contains at least one of the following: primary ammonium ions, secondary ammonium ions, tertiary ammonium ions, quaternary ammonium ions, and sodium ions.

[0020] Ammonium-containing cations and sodium ions are both positively charged, which can electrostatically adsorb negatively charged viruses, thereby improving the virus removal capacity of the virus-removing membrane.

[0021] Furthermore, the cationic solution is a cationic solution with a mass concentration of 0.005% to 1%.

[0022] When the cation concentration in the cationic activator is below 0.005%, the cation concentration in the cationic solution is too low, making it difficult for cations to adhere to the filter layer. Even if cations do adhere, the amount is very low, failing to significantly improve the virus removal capacity of the virus-removing membrane. When the cation concentration in the cationic activator is above 1%, the concentration is too high, potentially leading to excessive cation retention on the filter layer. Even multiple rinses with ultrapure water are unlikely to remove enough cations to avoid affecting the filtered fluid.

[0023] Furthermore, the cationic solution is a benzalkonium chloride solution with a mass concentration of 0.05-0.15%.

[0024] Benzalkonium chloride is a cationic quaternary ammonium salt that can adhere to the filter layer. Within the mass concentration range of 0.05% to 0.15%, the amount of benzalkonium chloride adsorbed on the filter layer is at the optimal level to promote the filter layer's ability to remove viruses. The electrostatic adsorption effect of the cation is significant, and the virus removal ability of the filter layer is significantly improved.

[0025] Furthermore, the zeta potential of the filter layer in a 0.01 mol / L potassium chloride electrolyte solution at a pH of 4–6 is <0 mV.

[0026] The zeta potential of the filter layer before immersion in the cationic activator is less than 0mV, indicating that the membrane surface carries a negative charge when immersed in the cationic activator solution. This allows the cations in the cationic activator to adhere more firmly to the filter layer when it is wetted in the cationic activator solution.

[0027] Furthermore, the material of the filter layer of the virus removal membrane is selected from one or more of PES and RC, which have a zeta potential between -70mV and -20mV at a pH of 4 to 6 in a 0.01mol / L potassium chloride electrolyte solution.

[0028] Cationic activators are more effective at activating PES and RC membranes with a zeta potential between -70mV and -20mV.

[0029] Furthermore, the surface roughness Ra of the filter layer is 0.1 μm to 0.5 μm.

[0030] The roughness of the filter layer directly affects the amount of benzalkonium chloride adhering to it. When the roughness Ra of the filter layer is less than 0.1 μm, the surface of the filter layer is too smooth, which weakens its ability to bind cations. The cations on the surface of the filter layer are easily washed away during the rinsing process of the virus removal membrane, making the cation content on the filter layer almost negligible. When the roughness of the filter layer is greater than 0.5 μm, the surface of the filter layer is too rough, which binds more cations. Moreover, when rinsing the virus removal membrane, the rinsing water does not easily remove the cations on the surface of the filter layer, resulting in an excessive number of cations on the filter layer. These cations are more likely to enter the filtered fluid during filtration using the virus removal membrane, causing contamination to the filtered fluid.

[0031] Furthermore, the average pore size of the surface of the filter layer near the liquid inlet screen is 150–450 nm, and the average pore size of the surface of the filter layer near the filtrate screen is 10–42 nm.

[0032] The average pore size of the filter layer surface near the inlet screen is larger than that of the surface near the filtrate screen, indicating that the pore size distribution of the filter layer is asymmetrical. Furthermore, the larger average pore size on the side near the inlet screen allows the cationic activator to more easily penetrate into the filter pores; the smaller average pore size on the side near the filtrate screen makes it more difficult for the cationic activator to escape from the filter layer. This allows the cations in the cationic activator to better adhere to the filter pore surface, improving the electrostatic adsorption effect of the filter layer on viruses and enhancing the virus removal capacity of the virus-removing membrane.

[0033] Furthermore, the length and width of the inlet screen and the filtrate screen are between 100 and 3500 μm.

[0034] Furthermore, the length and width of the inlet screen and the filtrate screen are between 300 and 500 μm.

[0035] The mesh gaps between the inlet screen and the filtrate screen, serving as part of the first and second flow guiding spaces, greatly facilitate the wetting of the cationic activator and the filtration of the fluid. Controlling the mesh length and width to between 300 and 500 μm effectively ensures the uniform dispersion of the cationic activator, further enabling it to uniformly enter the filter layer, resulting in a uniform cation distribution and thus achieving a consistent and stable virus removal effect.

[0036] If the length and width of the mesh are less than 300 μm, the mesh is too dense, and the turbulence intensity generated during rinsing of the virus removal membrane is too weak, making it difficult to remove cations that have not adhered to the filter layer. If the length and width of the mesh are greater than 500 μm, the turbulence intensity generated during rinsing of the virus removal membrane is strong, and cations already attached to the filter layer will also be washed away, resulting in a decrease in the cation content on the filter layer and a decline in the virus removal capacity of the filter layer.

[0037] Furthermore, the contact angle between the liquid inlet screen and the filtrate screen at 25°C is 90°–150°.

[0038] When the contact angle of the screen is between 90° and 150°, the hydrophobic strength of the screen is within a suitable range. The screen can effectively reduce the amount of cationic activator adhering to the screen, and the cationic activator remaining on the screen is easier to remove from the screen. Some of the removed cationic activator can enter the filter layer, increasing the amount of cationic activator adhering to the filter layer.

[0039] Furthermore, both the liquid inlet screen and the filtrate screen are made of PP material.

[0040] Furthermore, the edges of the permeate holes of the inlet screen are sealed with silicone to prevent communication between the first flow guiding space and the permeate holes, and the edges of the inlet holes of the filter unit are sealed with silicone to prevent communication between the second flow guiding space and the inlet holes.

[0041] Silica gel is used to separate the first and second flow channels, ensuring that the first flow channel contains the feed flow and the second flow channel contains the permeation flow. The silica gel typically uses hydroxyl-containing silica gel, such as vinyl-modified MQ silicone resin. The hydroxyl groups on the silica gel have an affinity for the cations in the cationic activator, especially for amino cations. Hydrogen bonds can form between the hydroxyl groups and amino cations, allowing the amino cations to adhere to the silica gel surface. Dead zones can easily form at the edges of the silica gel, where positively charged proteins may become trapped without flowing with the fluid. The adhesion of cations strengthens the repulsive force of the silica gel against positively charged proteins in the fluid, thereby promoting fluid flow within the dead zones and preventing the trapping of positively charged proteins.

[0042] Furthermore, the virus-removing membrane pack filled with cation exchange solution has a weight of m1, and the virus-removing membrane pack is rinsed with ultrapure water at a rate of 100 L / m. 2 Afterwards, the moisture inside the virus membrane is evaporated and then weighed, with the weight being m2; m1 is 1.02 to 1.3 times m2.

[0043] The cationic activator content in the virus-removing membrane pack is maintained between 0.02 and 0.3 times its net weight to effectively wet all components. If the cationic activator content is less than 0.02 times its net weight, the activator is too weak and difficult to adhere evenly to the filter layer, resulting in a minimal improvement in virus removal capability. Conversely, if the activator content is greater than 0.3 times its net weight, the activator is too strong, leading to excessive cation retention within the pack. Even with multiple rinses before use, it's difficult to remove all cations not adhered to the filter layer, causing contamination when filtering certain fluids.

[0044] Furthermore, the virus-free membrane was subjected to a phage retention test, and its phage retention efficiency LRV > 4.0;

[0045] The phage retention test includes the following steps:

[0046] A1: Rinse the virus-removing membrane at 25℃ and 0.21MPa with 100L / m³ of water. 2 Deionized water and 20-50 L / m 2 Phosphate buffer solution;

[0047] A2: Filtration >10 at 0.21MPa pressure. 7 Pseudomonas aeruginosa PP7 phage challenge solution at pfu / ml, when the filtration rate reaches 50 L / ml 2 At that time, downstream filtrate was collected, and the phage concentrations in the challenge solution and downstream filtrate were measured.

[0048] Phage retention efficiency – LRV = lg(Phage concentration in challenge liquid / Phage concentration in downstream filtrate).

[0049] Furthermore, the virus-removing membrane was rinsed with ultrapure water at 100 L / m³ under a pressure of 25°C and 0.21 MPa. 2 Subsequently, the concentration of benzalkonium chloride in the downstream filtered water sample was less than 500 ppb.

[0050] Rinse with 100L / m of ultrapure water 2 Subsequently, the concentration of benzalkonium chloride in the downstream filtered water sample after the virus removal membrane was less than 500 ppb, indicating that the concentration of unattached cationic activator in the virus removal membrane of this application was within 100 L / m³. 2 After rinsing with water, it can be basically rinsed clean, and the concentration of benzalkonium chloride in the downstream filtrate can be reduced to a low level.

[0051] Furthermore, the virus-removing membrane was rinsed with ultrapure water at 100 L / m³ under a pressure of 25°C and 0.21 MPa. 2 Subsequently, its water flux NWP1 was measured; the Pseudomonas aeruginosa PP7 phage challenge solution with a viral removal membrane filter >107 pfu / ml was filtered and then rinsed with ultrapure water at 25℃ and 0.21 MPa pressure for 100 L / m³. 2 After 10 cycles, the water flux NWP2 is measured; the NWP2 result is not less than 95% of the NWP1 result.

[0052] Even after multiple filtrations to remove viruses, the water flux of the virus-removing membrane pack does not decrease significantly, indicating that the cationic activator in this application not only improves the virus removal capability of the virus-removing membrane pack but also enhances the durability of the filter layer.

[0053] A method for wetting and preserving a virus-removing membrane package includes the following steps: immersing the virus-removing membrane package in a cationic solution for 6–24 hours, then removing the virus-removing membrane package from the solution and sealing it for preservation.

[0054] The cationic activator is infiltrated into the virus removal membrane by immersion. The cationic activator enters both the first and second flow channels simultaneously, which ensures that the filter layer of the virus removal membrane is fully wetted both before and after, thereby improving the activation effect of the cationic activator, increasing the amount of cationic ions adhering to the filter layer, and enhancing the virus removal capability of the virus removal membrane.

[0055] A capsule-type filtration device including the virus-removing membrane pack includes a virus-removing membrane pack and a sealed capsule. The virus-removing membrane pack is installed inside the sealed capsule. The sealed capsule is provided with a first channel communicating with the liquid inlet of the virus-removing membrane pack, a second channel communicating with the liquid outlet of the virus-removing membrane pack, and a third channel communicating with the permeate hole of the virus-removing membrane pack. The first channel, the second channel, and the third channel are all filled with a cationic activator.

[0056] A cationic activator is filled into a capsule filter containing a virus-removing membrane. The connecting channel between the sealed capsule of the capsule filter and the virus-removing membrane is also filled with cationic activator, so that the entire capsule filter is wetted by the cationic activator. The cationic activator on the virus-removing membrane diffuses into the space on the sealed capsule, resulting in a reduction in the amount of cationic activator attached to the filter layer on the virus-removing membrane.

[0057] Furthermore, the sealed capsule is also provided with multiple buffer spaces, which are located between the first channel and the liquid inlet, the second channel and the liquid outlet, and the third channel and the permeate hole. Each buffer space is filled with a cationic activator.

[0058] The cationic activator is also filled in the buffer space, which wets the entire capsule filter with the cationic activator, thus preventing the cationic activator on the filter layer from being diluted and causing a decrease in cationic content.

[0059] Secondly, the capsule filter can also be assembled by first assembling the dry virus removal membrane and the sealed capsule, and then pouring the cationic activator into the entire capsule filter through the first channel to fill or partially fill the capsule filter. The cationic activator poured in must be able to fully wet each filter layer.

[0060] In summary, the present invention has the following beneficial effects:

[0061] First, the virus-removing membrane is activated by a cationic activator, which causes cationic ions to adhere to the filter layer, thereby improving the virus-removing ability and effectiveness of the membrane.

[0062] Secondly, by controlling the pore size and surface roughness of the filter layer, the virus removal membrane allows the cationic activator to adhere better to the filter layer, and the unattached cationic activator can be more easily washed away.

[0063] Third, by controlling the hydrophobicity of the screen and the size of the mesh, the virus removal membrane allows more cationic activators to enter the filter layer from the screen, increasing the content of attached cationic activators in the filter layer and reducing the amount of cationic activators attached to the screen. This makes it easier to wash away any cationic activators that are not attached to the filter layer. Attached Figure Description

[0064] Figure 1 This is a three-dimensional schematic diagram of the virus-removing membrane in Embodiment 1 of this application;

[0065] Figure 2 This is an exploded view of the virus-free sample packet in Embodiment 1 of this application;

[0066] Figure 3 This is a perspective view of the capsule filter device in Embodiment 1 of this application;

[0067] Figure 4 This is a cross-sectional view of the capsule filter device in Embodiment 1 of this application.

[0068] Figure descriptions: 1. Virus-removing membrane; 11. Liquid inlet screen; 12. Filtration unit; 121. Filtrate screen; 122. Filtration layer; 13. Liquid inlet hole; 14. Permeate hole; 15. Liquid outlet hole; 2. Encapsulated filter device; 21. Sealed capsule; 22. First channel; 23. Second channel; 24. Third channel; 25. Buffer space. Detailed Implementation

[0069] The following is in conjunction with the appendix Figures 1-4The present invention will be further described in detail with reference to the embodiments.

[0070] Example

[0071] Example 1

[0072] Example 1 discloses a virus removal membrane package 1, which includes an interlaced liquid inlet screen 11 and a filter unit 12.

[0073] The filtration unit 12 includes sequentially stacked filtrate screens 121 and filter layers 122 stacked on one or both sides of the filtrate screens 121. Specifically, the filter layers 122 of the filtration units 12 located at both ends of the thickness direction of the virus removal membrane 1 are only disposed on the side of the filtrate screens 121 near the center of the virus removal membrane 1; the filter layers 122 of the filtration units 12 located in the middle part of the thickness direction of the virus removal membrane 1 are disposed on both sides of the filtrate screens 121. The filter layers 122 are made of PES material, while the inlet screen 11 and the filtrate screen 121 are made of PP material.

[0074] The inlet screen 11, the filter layer 122, and the filtrate screen 121 are provided with inlet holes 13 and permeate holes 14 at one end along their length, and outlet holes 15 and permeate holes 14 at the other end. The inlet holes 13 are interconnected, the outlet holes 15 are interconnected, and the permeate holes 14 are interconnected.

[0075] A first flow-guiding space is formed between the inlet screen 11 and the adjacent filter layer 122; a second flow-guiding space is formed between the filtrate screen 121 and the adjacent filter layer 122. The first and second flow-guiding spaces of the virus membrane 1 generally take two forms. The first is when the screen is suspended between the two filter layers 122; this space includes the gap between the screen and the two adjacent filter layers 122, as well as the mesh gaps on the inlet screen 11. The second is when the screen is attached to the two filter layers 122; in this case, the space only includes the mesh gaps on the screen.

[0076] The edges of the permeate holes 14 of the inlet screen 11 are sealed with silicone to prevent communication between the first flow guiding space and the permeate holes. The edges of the inlet holes 13 of the filter unit 12 are sealed with silicone to prevent communication between the second flow guiding space and the inlet holes 13. The inlet holes 13, the first flow guiding space, and the outlet holes 15 are connected to form a first flow space; the second flow guiding space is connected to the permeate holes 14 to form a second flow space. The silicone is hydroxyl-containing silicone, specifically vinyl-modified MQ silicone resin.

[0077] Both the first and second flow spaces are filled with cationic activators. The inlet screen 11, the filter layer 122, and the filtrate screen 121 are all wetted by the cationic activator. The cationic activator is a cationic solution, and the cationic ions can be selected from primary ammonium ions, secondary ammonium ions, tertiary ammonium ions, quaternary ammonium ions, and sodium ions. In this embodiment, a benzalkonium chloride solution containing quaternary ammonium ions is used with a mass concentration of 0.1%.

[0078] Example 1 also discloses a method for wetting and preserving the virus-removing membrane package 1, comprising the following steps:

[0079] The virus-removing membrane pack 1 was immersed in cationic surfactant for 24 hours. After that, the virus-removing membrane pack 1 was removed from the solution and vacuum-sealed for preservation.

[0080] Example 1 also discloses a capsule-type filtration device 2 including the virus removal membrane pack 1, comprising a virus removal membrane pack 1 and a sealed capsule 21. The virus removal membrane pack 1 is installed inside the sealed capsule 21. The sealed capsule 21 is provided with a first channel 22 communicating with the liquid inlet 13 of the virus removal membrane pack 1, a second channel 23 communicating with the liquid outlet 15 of the virus removal membrane pack 1, and a third channel 24 communicating with the permeate hole 14 of the virus removal membrane pack 1. The sealed capsule 21 is also provided with a plurality of buffer spaces 25, which are located between the first channel 22 and the liquid inlet 13, between the second channel 23 and the liquid outlet 15, and between the third channel 24 and the permeate hole 14.

[0081] The first channel 22, the second channel 23, the third channel 24, and the buffer space 25 are all filled with cationic activators.

[0082] Samples were taken from the filter layer 122 in the virus removal membrane package 1 in Example 1 and tested in a zeta potential meter. The zeta potential of the filter layer 122 was measured to be -63mV to -23mV at pH = 4 to 6 and -23mV at pH = 4.

[0083] The difference between Examples 2 to 6 and Example 1 is that different cationic activators were used; the virus removal membrane in Comparative Example 1 was a dry membrane and was not treated with a cationic activator; the virus removal membrane in Comparative Example 2 used pure water instead of a cationic activator.

[0084] Table 1 below shows the test results of LRV, rinse residue, and water flux changes of virus membrane 1 after using different cationic activators.

[0085] Table 1

[0086]

[0087] Table 1 shows that cationic activators containing ammonium salts and sodium ions can promote the virus removal capacity of the virus-removing membrane and improve its virus removal effect. Furthermore, benzalkonium chloride shows the best effect on improving the virus removal capacity of the virus-removing membrane compared to other cationic activators. Moreover, from a rinsing rate of 100 L / m³... 2 After being purified into ultrapure water, benzalkonium chloride has the lowest residual amount in the downstream filtrate of the virus removal membrane, resulting in the highest safety for filtration. Furthermore, the water flux did not decrease significantly after multiple uses, indicating that benzalkonium chloride, as a cationic activator, can also improve the durability of the virus removal membrane.

[0088] The difference between Examples 7-18 and Example 1 is that different concentrations of benzalkonium chloride were used.

[0089] Table 2 below shows the test results of changes in LRV, flushing residue, and water flux after using different mass concentrations of benzalkonium chloride cationic activator.

[0090] Table 2

[0091]

[0092] Table 2 shows that when the benzalkonium chloride concentration is in the range of 0.05% to 0.15%, it significantly improves the virus removal capacity of the virus-removing membrane, with a concentration of 0.1% showing the best improvement. Furthermore, when the benzalkonium chloride concentration is too low, although the residual amount of benzalkonium chloride in the downstream filtrate after rinsing the virus-removing membrane is very low, it has almost no effect on improving the virus removal capacity of the membrane.

[0093] The difference between Example 19 and Example 1 is that the filter layer material is RC material, and Comparative Example 3 uses pure water instead of cationic activator. Table 3 below shows the test results of LRV of virus membrane, rinsing residue and water flux change after using different filter layer materials.

[0094] Table 3

[0095]

[0096] The difference between Examples 20-27 and Example 1 is that they use filter layers with different surface roughness.

[0097] Table 4 below shows the test results of LRV, rinsing residue and water flux changes after using filter layers with different surface roughness.

[0098] Table 4

[0099]

[0100] Table 4 shows that the surface roughness of the filter layer has a certain impact on the virus removal capacity of the virus-removing membrane pack. When the roughness is small, the retention capacity of the cationic activator on the filter layer surface is poor, resulting in a low content of cations adhering to the filter layer and a low virus removal capacity of the virus-removing membrane pack. Conversely, when the roughness increases, the virus removal capacity of the membrane pack is significantly improved. However, excessive roughness leads to excessive retention of the cationic activator and a large number of cations not adhering to the filter layer, resulting in a high residual amount of benzalkonium chloride in the downstream filtrate after rinsing, which can easily affect the use of the virus-removing membrane pack. Table 4 also shows that when the surface roughness of the filter layer is controlled between 0.2 and 0.4 μm as specified in this application, the virus-removing membrane pack can achieve both good virus removal capacity and low rinsing residue.

[0101] The difference between Examples 28-31 and Example 1 is that they use filter layers with different pore sizes.

[0102] Table 4 below shows the test results of LRV, rinsing residue and water flux changes after using filter layers with different pore sizes.

[0103] Table 5

[0104]

[0105] In Table 5, filter layer pore size 1 represents the average pore size of the surface of the filter layer near the liquid inlet screen; filter layer pore size 2 represents the average pore size of the surface of the filter layer near the filtrate screen.

[0106] As shown in Table 5, the pore size on both sides of the filter layer has a certain impact on the virus removal capacity of the virus removal membrane. Since pore size 1 of the filter layer is mainly used for fluid inlet and pore size 2 is mainly used for fluid outlet, it can be seen from Table 5 that the larger the pore size 1 of the filter layer, the more cationic activator flows into the filter pores. On the other hand, the smaller the pore size 2 of the filter layer, the slower the cations flow out of the filter pores, which increases the residence time of the cationic activator in the pores. This increases the amount of cations attached to the filter layer and improves the virus removal capacity of the virus removal membrane.

[0107] The difference between Examples 32-35 and Example 1 is that the mesh length and width of the screens used for the inlet screen and the filtrate screen are different. Table 6 below shows the test results of LRV of the virus membrane, washing residue and water flux change when different mesh screens are used.

[0108] Table 6

[0109]

[0110] The test results in Table 6 show that smaller mesh sizes significantly improve the uniformity of cationic activator dispersion, thus enhancing the virus removal efficiency of the membrane to some extent. However, smaller mesh sizes also reduce the rinsing power of the rinsing solution on the filter layer during washing, resulting in a greater amount of cationic activator residue remaining in the downstream filtrate after multiple washes. Conversely, larger mesh sizes tend to lead to less uniform cationic activator dispersion, and the excessive turbulence during rinsing can easily wash away cations attached to the filter pores, reducing the cation content and thus limiting the virus removal efficiency of the membrane.

[0111] The difference between Examples 36-41 and Example 1 is that the contact angles of the inlet screen and the filtrate screen are different. Table 7 below shows the test results of LRV of the virus membrane, rinsing residue and water flux change when screens with different contact angles are used.

[0112] Table 7

[0113]

[0114] As shown in Table 7, the contact angle of the screen affects the virus removal capability of the virus-removing membrane to some extent. The contact angle represents the hydrophobicity of the screen; better hydrophobicity allows more cationic activators to penetrate the filter layer and avoid retention on the screen, thus increasing the cationic content on the filter layer of the virus-removing membrane. However, excessive hydrophobicity can hinder fluid flow, affecting normal filtration. Therefore, a contact angle of 90–150° is optimal.

[0115] The difference between Examples 42-49 and Example 1 is that the amount of cationic activator is different. Table 8 below shows the test results of LRV, rinsing residue and water flux change of the virus removal membrane with different cationic activator filling contents.

[0116] Table 8

[0117]

[0118]

[0119] As shown in Table 8, the amount of cationic activator in the virus removal membrane pack has a significant impact on the cationic activation of the filter layer. The more space the cationic activator occupies in the virus removal membrane pack, the higher the content of cations that can adhere to the filter layer, and the higher the virus removal capacity of the virus removal membrane pack. Conversely, excessive cationic activator has little impact on the virus removal capacity, but requires more rinsing cycles to remove any cations that have not adhered to the filter layer.

[0120] The difference between Examples 42-49 and Example 1 is that the zeta potential of the filter layer without cationic activator is different at pH 4 in a 0.01 mol / L potassium chloride electrolyte solution. Table 8 below shows the test results of LRV, rinsing residue and water flux change of the virus removal membrane with filter layers using different zeta potentials.

[0121] Table 9

[0122]

[0123] As can be seen from the table above, a zeta potential of less than 0 in the absence of cationic activator activation can effectively promote the activation of the filter layer by the cationic activator. Secondly, within the preferred range of this application, the larger the absolute value of the zeta potential, the stronger the interaction between the filter layer and the cationic activator, resulting in a greater amount of cations from the cationic activator adhering to the filter layer and better virus removal capability.

[0124] Performance testing methods

[0125] 1. Phage Retention Test

[0126] The phage retention test includes the following steps:

[0127] A1: Rinse the virus-removing membrane at 25℃ and 0.21MPa with 100L / m³ of water. 2 Deionized water and 50L / m 2 Phosphate buffer solution;

[0128] A2: Filtration >10 at 0.21MPa pressure. 7 Pseudomonas aeruginosa PP7 phage challenge solution at pfu / ml, when the filtration rate reaches 50 L / ml 2 At that time, downstream filtrate was collected, and the phage concentrations in the challenge solution and downstream filtrate were measured.

[0129] Phage retention efficiency – LRV = lg(Phage concentration in challenge liquid / Phage concentration in downstream filtrate).

[0130] 2. Benzalkonium chloride rinse residue test

[0131] The virus-removing membrane was rinsed with ultrapure water at 25℃ and 0.21MPa pressure for 100L / m³. 2 Then, the concentration of benzalkonium chloride in the downstream filtered water sample was tested.

[0132] 3. Water Flow Rate (NWP) Test

[0133] The virus-removing membrane was rinsed with ultrapure water at 25℃ and 0.21MPa pressure for 100L / m³. 2 Then, its water flux NWP1 was measured; the virus-removing membrane filter was filtered for >10 7 Pseudomonas aeruginosa PP7 phage challenge solution (pfu / ml) was filtered and then rinsed with ultrapure water at 25°C and 0.21 MPa for 100 L / ml. 2 After 10 cycles, the water flux NWP2 was measured.

[0134] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A virus-removing membrane, characterized in that, Includes overlapping inlet screens and filtration units; The filtration unit includes a filtrate screen that is stacked in sequence and a filter layer that is stacked on one or both sides of the filtrate screen. The liquid inlet screen, the filter layer, and the filtrate screen are all provided with liquid inlet holes, liquid outlet holes, and permeate holes; the liquid inlet holes are interconnected, the liquid outlet holes are interconnected, and the permeate holes are interconnected. A first flow guiding space is formed between the liquid inlet screen and the adjacent filter layer; a second flow guiding space is formed between the filtrate screen and the adjacent filter layer. The inlet hole, the first guide space, and the outlet hole are connected to form a first flow space; the second guide space is connected to the permeate hole to form a second flow space; At least the first flow space is filled with a cationic activator, and the inlet screen, filter layer and filtrate screen are all wetted by the cationic activator, which is a cationic solution. The contact angle between the liquid inlet screen and the filtrate screen at 25°C is 90°–150°.

2. The virus-removing membrane according to claim 1, characterized in that, The cation-containing solution contains at least one of the following: primary ammonium ion, secondary ammonium ion, tertiary ammonium ion, quaternary ammonium ion, and sodium ion.

3. The virus-removing membrane according to claim 2, characterized in that, The cationic solution is a cationic solution with a mass concentration of 0.005% to 1%.

4. The virus-removing membrane according to claim 3, characterized in that, The cationic solution is a benzalkonium chloride solution with a mass concentration of 0.05-0.15%.

5. The virus-removing membrane according to claim 1, characterized in that, The zeta potential of the filter layer in a 0.01 mol / L potassium chloride electrolyte solution at a pH of 4–6 is <0 mV.

6. The virus-removing membrane according to claim 5, characterized in that, The filter layer of the virus removal membrane is made of one or more of PES and RC, which have a zeta potential between -70mV and -20mV at a pH of 4 to 6 in a 0.01 mol / L potassium chloride electrolyte solution.

7. The virus-removing membrane according to claim 1, characterized in that, The surface roughness Ra of the filter layer is 0.1 μm to 0.5 μm.

8. The virus-removing membrane according to claim 7, characterized in that, The average pore size of the filter layer on the side of the surface near the liquid inlet screen is 150–450 nm, and the average pore size of the filter layer on the side of the surface near the filtrate screen is 10–42 nm.

9. The virus-removing membrane according to claim 1, characterized in that, The length and width of the inlet screen and the filtrate screen are between 100 and 3500 μm.

10. A virus-removing membrane according to claim 9, characterized in that, The length and width of the inlet screen and the filtrate screen are between 300 and 500 μm.

11. The virus-removing membrane according to claim 1, characterized in that, Both the liquid inlet screen and the filtrate screen are made of PP material.

12. The virus-removing membrane according to claim 1, characterized in that, The edges of the permeate holes of the inlet screen are sealed with silicone to prevent communication between the first flow guiding space and the permeate holes, and the edges of the inlet holes of the filter unit are sealed with silicone to prevent communication between the second flow guiding space and the inlet holes.

13. The virus-removing membrane according to claim 1, characterized in that, The virus-removing membrane pack filled with cationic activator has a weight of m1, and the virus-removing membrane pack is rinsed with ultrapure water at a rate of 100 L / m. 2 Afterwards, the water inside the virus-free membrane is evaporated until the weight remains constant, and then it is weighed. The weight is m2; m1 is 1.02 to 1.3 times m2.

14. The virus-removing membrane according to claim 4, characterized in that, The virus-removing membrane was tested for phage retention, and its phage retention efficiency (LRV) was >4.

0. The phage retention test includes the following steps: A1: Rinse the virus-removing membrane at 25℃ and 0.21MPa with 100L / m³ of water. 2 Deionized water and 20-50 L / m 2 Phosphate buffer solution; A2: Filtration >10 at 0.21MPa pressure. 7 Pseudomonas aeruginosa PP7 phage challenge solution at pfu / ml, when the filtration rate reaches 50 L / ml 2 At that time, downstream filtrate was collected, and the phage concentrations in the challenge solution and downstream filtrate were measured. Phage retention efficiency – LRV = lg(Phage concentration in challenge liquid / Phage concentration in downstream filtrate).

15. The virus-removing membrane according to claim 4, characterized in that, The virus-removing membrane was rinsed with ultrapure water at 25℃ and 0.21MPa pressure for 100L / m³. 2 Subsequently, the concentration of benzalkonium chloride in the downstream filtered water sample was less than 500 ppb.

16. The virus-removing membrane according to claim 4, characterized in that, The virus-removing membrane was rinsed with ultrapure water at 25℃ and 0.21MPa pressure for 100L / m³. 2 Then, its water flux NWP1 was measured; the virus-removing membrane filter was filtered for >10 7 Pseudomonas aeruginosa PP7 phage challenge solution (pfu / ml) was filtered and then rinsed with ultrapure water at 25°C and 0.21 MPa for 100 L / ml. 2 After 10 cycles, the water flux NWP2 is measured; the NWP2 result is not less than 95% of the NWP1 result.

17. A method for wetting and preserving the virus-removing membrane package according to any one of claims 1 to 16, characterized in that, The process includes the following steps: immersing the virus-removing membrane pack in a cationic solution for 6–24 hours, then removing the virus-removing membrane pack from the solution and sealing it for storage.

18. A capsule-type filtration device comprising the virus-removing membrane capsule as described in any one of claims 1 to 16, characterized in that, The device includes a virus-removing membrane pack and a sealing capsule. The virus-removing membrane pack is installed inside the sealing capsule. The sealing capsule is provided with a first channel communicating with the inlet hole of the virus-removing membrane pack, a second channel communicating with the outlet hole of the virus-removing membrane pack, and a third channel communicating with the permeate hole of the virus-removing membrane pack. The first, second, and third channels are all filled with cationic activators.

19. A capsule-type filtration device comprising a virus-removing membrane according to claim 18, characterized in that, The sealed capsule is also provided with multiple buffer spaces, which are located between the first channel and the liquid inlet, the second channel and the liquid outlet, and the third channel and the permeate hole. Each buffer space is filled with a cationic activator.

Images