Asymmetric copper-ammonium cellulose filter membrane for virus removal and preparation process thereof

Abstract

The application relates to an asymmetric copper-ammonia cellulose filter membrane for removing viruses and a preparation process thereof. The filter membrane comprises a porous main body with non-oriented tortuous channels, and the two sides of the porous main body are respectively a first surface and a second surface. The porous main body comprises a pre-filter layer, a separation layer for intercepting viruses and a protection layer. The bubble point of the filter membrane is 1-1.7 MPa. The SEM measured average pore diameter of the protection layer is larger than that of the separation layer and smaller than that of the pre-filter layer. The protection coefficient B of the protection layer is 5-100 nm / mum. The protection coefficient B is calculated by the following formula: B=d / h. The SEM measured average pore diameter d of the pore structure of the second outer surface is 100-500 nm. The thickness of the filter membrane is 20-80 mum. The application further discloses a preparation process of the filter membrane. On the basis of the filter membrane thickness of 20-80 mum, by controlling the protection coefficient B of the protection layer and the SEM measured average pore diameter d of the second outer surface of the filter membrane being 100-500 nm, the protection layer can have high protection effect and low flux influence.

Description

Technical Field

[0001] This application relates to the field of membrane separation technology, and in particular to an asymmetric cuprammonium cellulose filter membrane for virus removal and its preparation process. Background Technology

[0002] Membrane separation technology refers to the techniques used to separate, classify, enrich, and purify mixed systems by means of concentration difference, pressure difference, potential difference, or chemical potential difference. Due to its advantages such as low pollution, high separation efficiency, low energy consumption, no need for external chemical reagents, ability to separate systems that conventional methods cannot (such as azeotropic systems), and mild separation conditions that do not easily cause changes in the properties of active substances, membrane separation technology is widely used in the biomedical field.

[0003] Various biopharmaceutical products may contain viruses due to contamination from raw materials or introduction during the manufacturing process. If these viruses are not eliminated and are directly injected into patients, they pose serious safety risks. Therefore, documents such as the 2020 edition of the Chinese Pharmacopoeia and "ICH Q5A Biotechnology Products – Virus Safety Evaluation" set clear and high requirements for the viral safety of biopharmaceuticals. Virus elimination and / or virus inactivation steps must be performed during the production of all types of biopharmaceuticals to ensure their safety. Furthermore, a report on the viral safety assessment test results must be attached to the drug application for review, and the content of the report directly affects the review outcome.

[0004] US Patent 4,629,563 discloses a method for preparing asymmetric microporous membranes using a solvent-free phase separation method. Subsequent patent US 5,171,445 improved this method by lowering the casting and gelation temperatures and simplifying the process. Furthermore, patents US 5,866,059, US 7,125,493, US 6,045,899, and US 4,976,859 all disclose polyethersulfone membranes with significantly asymmetric structures. However, these membranes all suffer from the same problem: the membrane-forming material is polyethersulfone, and even after hydrophilic modification, its hydrophilicity remains poor, resulting in a high protein adsorption rate. This not only leads to a decrease in the quality of biological agents and an increase in cost but also causes rapid clogging of the membrane, rapid flux decay, and a short service life. Moreover, these membranes all share the same problem: the separation layer is located on the membrane surface, making it susceptible to mechanical damage.

[0005] Chinese invention patent application CN113842792A discloses an asymmetric PES filter membrane for virus removal. This PES filter membrane comprises a main body, including a pre-filtration layer and a separation layer for virus retention. The other side of the pre-filtration layer and the other side of the separation layer are transitioned by continuous fibers. This PES filter membrane is prepared using only a casting solution, integrally molded, and does not require composite materials. This PES membrane has a typical bilayer structure (a large-pore pre-filtration layer and a small-pore separation layer) and exhibits good virus retention (LRV > 4). However, due to the use of PES material, this PES filter membrane also suffers from a low virus loading capacity. Furthermore, the average pore size of the filter membrane decreases from one side to the other along the thickness direction, causing the smallest pore size separation layer to be located on the membrane surface, making it susceptible to mechanical damage and often resulting in poor mechanical stability.

[0006] Japanese invention patent JP1984204911A discloses that regenerated cellulose membranes (RC membranes) have good clearance ability for HIV (approximately 100 nm), and due to the good hydrophilic properties of cellulose, their adsorption of active substances (proteins) is low, often resulting in good protein yields. However, their clearance ability for viruses with a size of 20–100 nm, such as hepatitis B virus (approximately 42 nm), nAnB virus (30–60 nm), and mouse parvovirus (approximately 20 nm), is poor (LRV < 4), therefore, they can no longer meet the current stringent requirements for virus clearance.

[0007] For example, Chinese patent application CN114887500A discloses an asymmetric cellulose-based filter membrane for virus removal and its preparation method. This cellulose-based filter membrane comprises a main body with a first outer surface and a second outer surface on its two sides. The pore size of the first outer surface is at least four times that of the second outer surface, and the average pore size of the second outer surface is 15-40 nm. The main body includes a contaminant-holding layer and a retention layer. The average pore size of the contaminant-holding layer is larger than that of the retention layer, and the gradient of the average pore size variation of the contaminant-holding layer is greater than that of the retention layer. This cellulose-based filter membrane exhibits good retention of small-sized viruses, and because the membrane-forming material is cellulose, it has good hydrophilicity (cellulose is generally considered the most hydrophilic organic membrane-forming material), thus ensuring low protein adsorption. Although this filter membrane has both high LRV (Limited-Retention Virus) and high protein yield, its retention layer is also located on the membrane surface, making it susceptible to mechanical damage.

[0008] Chinese invention patent application CN105980038A discloses a virus-removing membrane comprising cellulose. It has a first surface for supplying a protein-containing solution and a second surface for discharging permeate through the membrane. The membrane achieves a logarithmic removal rate (LRV) of over 4 for porcine parvovirus (approximately 18-26 nm). By adding inorganic salts to the casting solution, the diffusion rate of particles formed by the cellulose condensate phase changes, thus affecting the microphase separation rate and controlling the size of pores from the membrane surface to the interior, as well as the degree of pore size variation along the membrane thickness direction. The application mentions that in the cross-section of the membrane, the pore size decreases from the first side to the second side and then increases. Therefore, the membrane structure responsible for virus retention is located inside the membrane, making it less susceptible to mechanical damage. Furthermore, because the membrane-forming material is cellulose-based, the membrane exhibits low specificity for protein adsorption. However, the pre-filtration layer of this cellulose membrane is relatively thin and is prone to clogging, which affects its service life. More importantly, although the separation layer of this cellulose membrane is located inside, the large-pore layer structure near the liquid outlet can protect the separation layer. However, it is foreseeable that the additional layer structure will cause a certain decrease in the flux of the filter membrane.

[0009] In the patent with authorization announcement number CN101227965B, the separation layer of the membrane is also located inside the membrane, and its average pore size increases from the separation layer to both sides along the thickness direction. Although the separation layer located inside is not easily damaged by mechanical force, the flux of such a membrane structure is not high.

[0010] Therefore, obtaining a filter membrane that not only has a good virus retention effect, but also has a layer structure that is not easily damaged and has a high flux is a problem that urgently needs to be solved but is difficult to solve. Summary of the Invention

[0011] To address the shortcomings of existing technologies, this application aims to provide an asymmetric cuprammonium cellulose filter membrane for virus removal and its preparation process. The separation layer responsible for virus retention is located inside the filter membrane, making it less susceptible to mechanical damage. Furthermore, the bubble point of the filter membrane is 1–1.7 MPa, enabling it to effectively retain small-sized viruses. Further, by controlling the protection coefficient B of the protective layer to 5–100 nm / μm, combined with an average pore size d of 100–500 nm measured by SEM on the second outer surface of the filter membrane, not only is it ensured that the separation layer structure is not easily damaged by machinery, but the introduction of the protective layer structure also has a minimal impact on the filter membrane's flux, maintaining a high flux. Therefore, the filter membrane in this application not only has excellent virus retention but also possesses high flux and resistance to mechanical damage.

[0012] The technical solution provided in this application for an asymmetric cuprammonium cellulose filter membrane for virus removal and its preparation process is as follows:

[0013] In a first aspect, this application provides an asymmetric cuprammonium cellulose filter membrane for virus removal, employing the following technical solution:

[0014] An asymmetric cuprammonium cellulose filter membrane for virus removal comprises a porous body with non-directional tortuous pathways within the porous body. One side surface of the porous body is a first outer surface, and the other side surface of the porous body is a second outer surface.

[0015] The porous body includes a pre-filter layer, a separation layer for intercepting viruses, and a protective layer. One side of the pre-filter layer is a first outer surface, and one side of the protective layer is a second outer surface. The pre-filter layer, the separation layer, and the protective layer are connected by continuous fibers.

[0016] The bubble point of the filter membrane is 1 to 1.7 MPa;

[0017] The average pore size measured by SEM of the protective layer is greater than that of the separation layer but smaller than that of the pre-filter layer.

[0018] The protection coefficient B of the protective layer is 5–100 nm / μm; the protection coefficient B is calculated using the following formula:

[0019] B = d / h;

[0020] In the above formula, d is the average pore diameter of the hole structure on the second outer surface measured by SEM, in nm; h is the thickness of the protective layer, in μm.

[0021] The value of d is 100–500 nm.

[0022] The thickness of the filter membrane is 20–80 μm.

[0023] By adopting the above technical solution, the filter membrane in this application uses cellulose raw materials with good hydrophilicity as the film-forming material, thus having a low protein adsorption rate and a high protein yield. In addition, the bubble point of the filter membrane in this application is 1 to 1.7 MPa, which can ensure that the filter membrane has a good retention effect on small-sized viruses (such as PP7 bacteriophage, a model virus of small viruses specified in PDA TR41, or common mouse parvovirus), thereby ensuring the viral safety of various biological agents.

[0024] Furthermore, in the filter membrane structure of this application, the separation layer is located between the pre-filtration layer and the protective layer, rather than being exposed on the surface of the filter membrane. Since the separation layer is located inside the protective layer, external mechanical forces must first damage the protective layer before further damaging the separation layer structure. Because the separation layer is the area in the filter membrane responsible for virus interception, even if part of the protective layer structure is damaged, the risk of virus leakage from the filter membrane remains low if the separation layer structure is not damaged. Therefore, placing the separation layer inside the protective layer significantly reduces the possibility of virus leakage due to external mechanical damage, thus improving safety. It should be noted that different protective layer structures have varying protective effects on the separation layer and on the filter membrane flux.

[0025] With a filter membrane thickness of 20–80 μm, when the average pore diameter d of the pore structure on the second outer surface of the filter membrane measured by SEM is 100–500 nm and the protection coefficient of the protective layer is 5–100 nm / μm, the protective layer can not only provide good protection for the separation layer and reduce the possibility of damage to the separation layer, but also maintain a high flux of the filter membrane. Thus, the filter membrane of this application has the characteristics of high virus retention, high flux and high resistance to mechanical damage.

[0026] This may be because filter membranes of different thicknesses have different mechanical properties. When the pore structure of the filter membrane changes, the degree to which properties such as flux are affected also varies. Therefore, the protection coefficient B of the protective layer needs to be based on the filter membrane of a specific thickness to ensure that after the filter membrane of that thickness is introduced with a protective layer having a specific protection coefficient B, it not only has good resistance to mechanical damage but also has a high flux. For filter membranes with a thickness of 20–80 μm, if the protection coefficient B of the protective layer is too small (e.g., less than 5 nm / μm), it indicates that the protective layer thickness is too large and / or the average pore size of the pore structure on the second outer surface of the filter membrane, measured by SEM, is too small. A protective layer structure with a large thickness and small pore size creates significant resistance to the feed liquid, potentially leading to a substantial decrease in filter membrane flux. Conversely, if the protection coefficient B of the protective layer is too large (e.g., greater than 100 nm / μm), it indicates that the protective layer thickness is too small and / or the average pore size of the pore structure on the second outer surface of the filter membrane, measured by SEM, is too large. A protective layer structure with a small thickness and large pore size not only increases the likelihood of defects in the separation layer during membrane fabrication but also often indicates insufficient resistance to mechanical damage, making the filter membrane separation layer susceptible to damage during assembly and use. Therefore, the protection coefficient B of the protective layer needs to be controlled within a certain range to ensure that the filter membrane possesses both high flux and high resistance to mechanical damage.

[0027] It is important to note that discussing the thickness h of the protective layer or the average pore size d measured by SEM of the pore structure on the second outer surface in isolation is not very meaningful. This is because even if the protective layer is thick, its impact on flux may be small if the pore size is large; conversely, even if the protective layer is thin, its impact on flux may be significant if the pore size is small. Therefore, it is necessary to comprehensively consider the relationship between the thickness of the protective layer and the average pore size measured by SEM of the pore structure on the second outer surface. A protection coefficient B of 5–100 nm / μm is recommended to ensure that the protective layer not only provides good protection for the separation layer but also has minimal impact on the flux of the filter membrane, thus enabling the filter membrane to simultaneously possess high flux and good resistance to mechanical damage.

[0028] It is understood that in this application, the separation layer refers to the region in the relevant field of view of the SEM image where the average pore size measured by SEM is less than 50 nm. Since the pore size of the filter membrane in this application decreases from the first outer surface to the second outer surface and then increases, the two sides of the separation layer in this application have regions with larger pore sizes than the separation layer. The large pore region near the first outer surface (liquid inlet side) is the pre-filtration layer, and the large pore region near the second outer surface (liquid outlet side) is the protective layer. Furthermore, the average pore size measured by SEM of the protective layer is smaller than that of the pre-filtration layer.

[0029] The measurement of various surface morphology parameters of filter membranes (such as thickness, fiber diameter, pore size, area porosity, etc.) can be achieved by characterizing the membrane structure using a scanning electron microscope (SEM), followed by measurement using computer software (such as Matlab, NIS-Elements, etc.) or manual measurement, and then performing corresponding calculations. During the membrane fabrication process, in the direction perpendicular to the membrane thickness (if the membrane is a flat sheet, this direction is planar; if the membrane is a hollow fiber membrane, this direction is perpendicular to the radius), its various characteristics, such as pore size distribution, are roughly uniform and consistent. Therefore, the average pore size of the entire plane can be reflected by measuring the average pore size of a portion of the corresponding plane. In actual measurement, the membrane surface (or cross-section) can be characterized first using an electron microscope to obtain the corresponding SEM image, and a certain area, such as 1 μm, can be selected. 2 (1μm x 1μm) or 25μm 2 (5μm x 5μm), the specific area size depends on the actual situation. Then, use appropriate computer software or manual measurement to measure the morphological parameters such as the pore diameter and fiber diameter of all holes in this area. Then, calculate to obtain the average pore diameter (i.e., the average pore diameter measured by SEM) and average fiber diameter (i.e., the average fiber diameter measured by SEM) of this area. Of course, those skilled in the art can also obtain the above parameters through other measurement methods. The above measurement methods are for reference only.

[0030] In this application, the bubble point of the filter membrane refers to the pressure at which nitrogen gas is slowly applied to the wetted filter membrane after it has been wetted with a liquid with a surface tension of 0.012 N / m (the liquid is 3M FX3250 perfluorocarbon). When bubbles are continuously generated on the surface of the wetted filter membrane, the pressure of the nitrogen gas at this time is recorded, which is the bubble point of the filter membrane. The unit of bubble point is MPa.

[0031] Optionally, the protection coefficient B of the protective layer is 10–90 nm / μm, the d is 150–450 nm, and the porosity of the second outer surface is 5–20%.

[0032] By adopting the above technical solution, with a protection coefficient B of 10–90 nm / μm and a d of 150–450 nm for the protective layer, and when the pore area ratio of the second outer surface of the filter membrane is 5–20%, the filter membrane further exhibits higher flux and resistance to mechanical damage. This is likely because the density of the second outer surface, as the area directly exposed to external mechanical forces, has a significant impact on the protective layer's resistance to mechanical damage. Besides the average pore size measured by SEM, the pore area ratio of the second outer surface also has a substantial influence. If the pore area ratio of the second outer surface is too low (e.g., below 5%), it indicates that the second outer surface is relatively dense. Although a denser second outer surface has better resistance to mechanical damage, a low pore area ratio often means that the feed liquid encounters greater resistance near the second outer surface during filtration, resulting in a lower flux of the filter membrane. If the pore area ratio of the second outer surface is too high (e.g., above 20%), it indicates that the second outer surface is less dense. Although the resistance encountered by the feed liquid is lower, and thus it often has a relatively higher flux, a high pore area ratio of the second outer surface means that its resistance to mechanical damage is poor, and it cannot form good protection for the separation layer, greatly increasing the possibility of mechanical damage to the separation layer.

[0033] Optionally, the SEM measurement average pore size of the protective layer is 100–300 nm, and the porosity of the protective layer is 35–65%.

[0034] By adopting the above technical solution, since external mechanical forces often need to first damage the protective layer structure before further damaging the separation layer structure located inside the protective layer, the protective layer's resistance to mechanical damage has a significant impact on the protective effect of the separation layer. To ensure that the protective layer provides good protection for the separation layer while also taking other benefits into account, the average pore size and porosity of the protective layer measured by SEM need to be controlled within a certain range. This is because if the average pore size and / or porosity of the protective layer measured by SEM is too small (e.g., the average pore size measured by SEM is less than 100 nm and / or the porosity is less than 35%), it indicates that the protective layer has a relatively dense three-dimensional network structure, thus having stronger resistance to mechanical damage and therefore a better protective effect on the separation layer; however, an overly dense three-dimensional network structure also means excessive resistance to the feed liquid, leading to a decrease in the flux of the filter membrane. If the average pore size and / or porosity of the protective layer measured by SEM is too large (e.g., the average pore size measured by SEM is greater than 300 nm and / or the porosity is greater than 65%), it indicates that the three-dimensional network structure of the protective layer has low density. Although a three-dimensional network structure with low density has lower resistance to the feed liquid and less impact on the flux of the filter membrane, a three-dimensional network structure with excessively low density also means weak resistance to mechanical damage. Once the protective layer structure is damaged, the possibility of damage to the exposed separation layer increases significantly, and the risk of virus leakage increases significantly.

[0035] Optionally, the average aperture of the protective layer measured by SEM gradually increases from the side closer to the first outer surface to the side closer to the second outer surface, and the rate of increase of the average aperture of the protective layer measured by SEM on the side closer to the first outer surface is less than the rate of increase of the average aperture of the protective layer measured by SEM on the side closer to the second outer surface.

[0036] By adopting the above technical solution, the average pore size of the protective layer measured by SEM increases at a slower rate than that measured by SEM on the side closer to the first outer surface. In other words, the pore size of the protective layer first increases slowly and then rapidly along the direction of liquid flow. This means that the protective layer's resistance to mechanical damage increases rapidly in the opposite direction of liquid flow (i.e., along the direction of external mechanical force) and maintains a high level of resistance within a certain range, thus ensuring good protection for the separation layer. It is important to note that the average pore size measured by SEM of the protective layer should not change at a consistently rapid rate. This is because, although a rapid decrease in the average pore size measured by SEM along the direction of external mechanical force can ensure further improvement in the protective layer's resistance to mechanical damage, a rapid decrease in pore size often means a rapid decrease in membrane flux. Similarly, the average pore size measured by SEM of the protective layer should not change at a consistently slow rate to avoid insufficient resistance to mechanical damage and thus inadequate protection for the separation layer.

[0037] Optionally, the average fiber diameter measured by SEM of the protective layer is greater than the average fiber diameter measured by SEM of the separation layer, but less than the average fiber diameter measured by SEM of the pre-filter layer; the average fiber diameter measured by SEM of the separation layer is 30–100 nm.

[0038] By adopting the above technical solution, the average pore size of the protective layer measured by SEM is larger than that of the separation layer. It is more likely to collapse under the action of external mechanical destructive force. Therefore, the pore structure of the protective layer needs to be supported by a larger fiber structure.

[0039] It is important to note that current virus filtration generally employs dead-end filtration, meaning the entire filter membrane is subjected to significant pressure from the filtered liquid. Cellulose-based raw materials are inherently soft and prone to structural collapse under pressure. The separation layer, as the primary structure in the filter membrane responsible for virus retention, has a relatively small pore size and a dense three-dimensional network structure. It significantly impacts the membrane's virus retention capacity and flux. Collapse of the pore structure in the separation layer will lead to a substantial decrease in membrane flux. This is because, if the edges of the pore structure in the separation layer are considered as virtual three-dimensional spheres, when the pore size is halved, the volume of this virtual sphere decreases to one-eighth, and the cross-sectional area of ​​the channel through which the feed liquid passes decreases to one-quarter. Therefore, even a slight reduction in the pore size of the separation layer can lead to a significant decrease in membrane flux. Strict control of the fiber structure size in the separation layer is necessary. If the average fiber diameter measured by SEM is too small (e.g., less than 30 nm), although the separation layer has a relatively dense three-dimensional network structure, the small fiber diameter is insufficient to effectively support the pore structure. When the membrane is subjected to significant feed pressure (e.g., 30 psi), the fiber structure cannot effectively support the pore structure, and once the pore structure collapses under pressure, it will likely lead to a significant decrease in membrane flux. If the average fiber diameter measured by SEM is too small (e.g., greater than 100 nm), although the larger fiber diameter combined with the relatively dense three-dimensional network structure can effectively support the pore structure, the fiber structure itself, as the solid part of the separation layer, has a large resistance to the feed, resulting in low membrane flux even when not under pressure. Therefore, the size of the fiber structure in the separation layer needs strict control.

[0040] Optionally, the ratio of the average fiber diameter measured by SEM of the protective layer to the average fiber diameter measured by SEM of the separation layer is 1.1 to 1.7; the ratio of the average fiber diameter measured by SEM of the pre-filter layer to the average fiber diameter measured by SEM of the protective layer is 1.2 to 2; and the average fiber diameter measured by SEM of the protective layer is 40 to 130 nm.

[0041] By adopting the above technical solution, although the protective layer is located near the second outer surface of the filter membrane (i.e., the liquid outlet surface) and is not directly subjected to the pressure of the feed liquid, the pressure on the pore structure of the protective layer is relatively small. However, in order to obtain good resistance to mechanical damage, the size of the fiber structure in the protective layer still needs to be relatively large. If the average fiber diameter measured by SEM in the protective layer is too small (e.g., less than 40 nm), the pore structure of the protective layer is less supported by the fiber structure, and the pore structure is easily damaged even under low pressure. In addition, the fiber structure with too small a size has relatively weak resistance to mechanical damage, resulting in a weaker protective effect on the separation layer. If the average fiber diameter measured by SEM in the protective layer is too large (e.g., greater than 130 nm), although the protective layer has strong resistance to mechanical damage and is not easily deformed under pressure, the fiber structure, as the solid part of the protective layer, hinders the flow of the feed liquid. An excessively large average fiber diameter measured by SEM means excessive resistance to the feed liquid, thereby leading to a decrease in the filter membrane flux.

[0042] Compared to the protective layer, the pre-filtration layer is the part of the filter membrane structure directly subjected to feed pressure. Since the pore size of the pre-filtration layer is larger than that of the separation and protective layers, a larger diameter fiber structure is needed to support the pore structure in order to ensure that the pre-filtration layer does not deform excessively under pressure. Therefore, the diameter of the fiber structure in the pre-filtration layer is larger than that of the protective layer (e.g., the ratio of the fiber diameter to that of the protective layer is not less than 1.2 times) to ensure that the filter membrane is less prone to pore collapse under high feed pressure. However, the fiber diameter of the pre-filtration layer should not be too large (e.g., the ratio of the fiber diameter to that of the protective layer is greater than 2 times). Although the pre-filtration layer does achieve stronger self-support, the greater resistance of the coarser fiber structure to the feed can easily lead to a decrease in flux. Furthermore, the larger fiber size can also reduce the dirt-holding capacity of the pre-filtration layer.

[0043] Optionally, the ratio of the average pore size measured by SEM to the average fiber diameter measured by SEM of the protective layer is 0.8 to 3.

[0044] By adopting the above technical solution, although the protective layer is not directly subjected to the pressure of the feed liquid, it needs to have sufficient resistance to mechanical damage to ensure a good protective effect on the separation layer. Based on a protection coefficient of 5–100 nm / μm, further limiting the ratio of the average pore size measured by SEM to the average fiber diameter measured by SEM further ensures the good protective effect of the protective layer on the separation layer and its impact on the filter membrane flux.

[0045] If the ratio of the average pore size of the protective layer measured by SEM to the average fiber diameter measured by SEM is too large (e.g., greater than 3), it indicates that the pore size of the protective layer is too large or the diameter of the fiber structure is too small. Although such a structure has little impact on the flux of the filter membrane, it has weak resistance to mechanical damage and is easily damaged by external forces. If the ratio of the average pore size of the protective layer measured by SEM to the average fiber diameter measured by SEM is too small (e.g., less than 0.8), it indicates that the pore size of the protective layer is too small or the diameter of the fiber structure is too large. Although such a structure has relatively good resistance to mechanical damage, the resistance of the feed liquid is too large, resulting in a low flux of the filter membrane.

[0046] Optionally, the first outer surface includes a plurality of long strip-shaped and interlaced first fibers, the interlacing parts of the first fibers form nodes, and adjacent and interlaced first fibers surround each other to form holes. The average diameter of the first fibers measured by SEM is 50-180 nm, and the hole area ratio of the first outer surface is 10-50%.

[0047] By adopting the above technical solution, when observing the surface morphology of the filter membrane through SEM images, it can be found that the first outer surface has a relatively obvious fibrous structure (i.e., the first fiber). These fibers are slender strip-shaped structures that interweave to form node structures. Because these node structures have a larger radial dimension than the fiber structures, they can provide better support for the three-dimensional network structure near the first outer surface. The reasonable size of the node structure and the first fiber can ensure that the first outer surface with a large pore size has good pressure resistance. If the diameter of the first fiber is too large (e.g., greater than 180 nm), although the thicker first fiber can make the first outer surface have stronger pressure resistance, its ability to guide the liquid is weaker; if the diameter of the first fiber is too small (e.g., less than 50 nm), the support effect on the pore structure of the first outer surface is weak, and the pressure resistance of the first outer surface, which directly bears the pressure of the liquid, is insufficient.

[0048] The pores formed by the first fiber, which is a solid part, are used to guide the feed liquid into the interior of the filter membrane. Therefore, the first outer surface needs a large pore area ratio (e.g., not less than 10%) to prevent the feed liquid from being obstructed by too much solid part of the second outer surface and thus not easily entering the interior of the filter membrane. The pore area ratio of the first outer surface should not be too large (e.g., greater than 50%). This is because the main area affecting the filter membrane flux is the separation layer. Further increasing the pore area ratio of the first outer surface will not further increase the filter membrane flux, but will instead lead to an excessive decrease in the pressure resistance of the first outer surface.

[0049] Optionally, the average aperture of the first outer surface measured by SEM is 300-4500 nm, and the ratio of the average aperture of the first outer surface measured by SEM to the average aperture of the second outer surface measured by SEM is 2-40.

[0050] By employing the above technical solution, if the average pore size measured by SEM on the first outer surface is too small (e.g., less than 300 nm), it may result in insufficient guidance of the feed liquid, making it difficult for the feed liquid to enter the filter membrane. Although theoretically, the feed liquid pressure can be further increased to encourage its entry into the filter membrane, the soft texture of the cellulose membrane makes it prone to structural collapse and damage under high pressure. Therefore, it is not advisable to set the feed liquid pressure too high. If the average pore size measured by SEM on the first outer surface is too large (e.g., greater than 4500 nm), although the feed liquid can more easily enter the filter membrane through the pore structure on the first outer surface, the pore structure with an excessively large pore size requires greater support; otherwise, structural collapse may easily occur.

[0051] Optionally, the SEM measurement average pore size of the pre-filter layer is 200–700 nm, and the porosity of the pre-filter layer is 40–75%.

[0052] By employing the above technical solution, the pre-filter layer primarily functions to filter large particles in the feed liquid. If the average pore size of the pre-filter layer measured by SEM is too large (e.g., greater than 700 nm), although the pre-filter layer with a larger pore structure generally has a greater dirt-holding capacity, its retention capacity for large particles is insufficient. Once large particles leak from the pre-filter layer, it is likely to cause rapid clogging of the separation layer and a rapid decline in membrane flux. Furthermore, an excessively large average pore size measured by SEM also means a reduction in the pressure resistance of the pre-filter layer. Once the pre-filter layer collapses under the pressure of the feed liquid, both membrane flux and loading capacity will decrease. Therefore, although increasing the average pore size measured by SEM of the pre-filter layer within a certain range is beneficial for increasing the membrane loading capacity and reducing the rate of flux decline, the average pore size should not be too large, as this could lead to a decrease in membrane loading capacity and an accelerated rate of flux decline. The average pore size of the pre-filter layer measured by SEM should not be too small (e.g., less than 200 nm). As a pre-filter layer that plays the role of pre-filtering large particles in the feed liquid, it needs to have a large dirt-holding space for large particles to avoid being quickly blocked by large particles and causing a rapid decline in flux.

[0053] Optionally, the average pore size of the pre-filter layer measured by SEM gradually decreases from the side near the first outer surface to the side near the second outer surface. The rate of increase of the average pore size of the pre-filter layer measured by SEM on the side near the first outer surface is greater than the rate of increase of the average pore size of the pre-filter layer measured by SEM on the side near the second outer surface. The gradient of the average pore size of the pre-filter layer measured by SEM is (60~200) nm / μm.

[0054] By adopting the above technical solution, in order to reduce the possibility of large particles in the feed liquid clogging the separation layer, the pre-filtration layer needs to have a good retention effect on large particles in the feed liquid and sufficient space to accommodate the retained large particles. In this application, the pore size of the pre-filtration layer initially decreases at a relatively rapid rate, thus rapidly improving the pre-filtration layer's retention capacity for large particles and reducing the possibility of large particles leaking and clogging the separation layer; the pore size of the pre-filtration layer then decreases at a relatively slow rate to avoid rapid and excessive reduction of the pore size, thereby reducing the possibility of insufficient dirt-holding space and localized concentrated retention of impurities leading to rapid decay of the pores. To ensure that the pre-filter not only has a high dirt-holding capacity and is not easily clogged, but also has a good retention effect on large particles, the average pore size variation gradient measured by SEM of the pre-filter layer should not be too large or too small. When the average pore size variation gradient measured by SEM is too small (e.g., less than 60 nm / μm), the pre-filter layer can only retain large particles through a combination of large pore size and stacked pore structure. Although the dirt-holding capacity is large, the risk of leakage of large particles is high. When the average pore size variation gradient measured by SEM is too large (e.g., greater than 200 nm / μm), the pore size of the pre-filter layer decreases rapidly. Although it can form a good retention of large particles, the rapidly decreasing pore size also means a rapid decrease in dirt-holding space, resulting in insufficient dirt-holding capacity of the pre-filter layer and easy clogging.

[0055] Optionally, the average pore size of the separation layer measured by SEM is 20–45 nm, the thickness of the separation layer is 5–45 μm, and the thickness ratio of the separation layer to the porous body is 20–60%.

[0056] By adopting the above technical solution, the virus-removing filter membrane must ensure a low risk of virus leakage, and the separation layer in the filter membrane is the area responsible for virus retention. To ensure good virus retention, the average pore size of the separation layer measured by SEM should not be too large (e.g., greater than 45 nm) and its thickness should not be too small (e.g., less than 5 μm), to prevent virus leakage from the separation layer with a thinner thickness and / or larger pore size. The protective layer structure, due to its relatively larger pore size, cannot form a good virus retention effect. Therefore, once the virus leaks from the separation layer, there is a high probability that it will penetrate the protective layer, causing a leakage risk.

[0057] Optionally, the porosity of the filter membrane is 10-60%; the tensile strength of the filter membrane is 6-15 MPa, the elongation at break is 5-40%, and the elastic modulus is 20-80 MPa; the flux of the filter membrane is greater than 60 L·h. -1 m -2 @30psi; the protein yield of the filter membrane is not less than 98%.

[0058] By adopting the above technical solution, the filter membrane with the specific structure in this application not only has good virus interception ability, but also has high throughput and good protection effect on the separation layer structure.

[0059] Secondly, this application provides a process for preparing an asymmetric cellulose filter membrane for virus removal, employing the following technical solution:

[0060] A process for preparing an asymmetric cellulose filter membrane for virus removal includes the following steps:

[0061] S1. Preparation of casting solution: Cotton fibers are dissolved in a copper ammonia solution to form a casting solution. The casting solution has a solid content of 7-10% and a copper content of 3-5%.

[0062] S2, casting: casting liquid is cast onto a carrier to obtain a liquid flat plate-shaped molded film, wherein the first outer surface of the molded film is in contact with the carrier, and the second outer surface of the molded film is exposed to the environment;

[0063] S3. Pretreatment: The second outer surface of the molded film is pretreated by blowing acetone vapor with a relative humidity of 40-80%, an acetone concentration of 15-55 v / v%, and a wind speed of 0.05-0.5 m / s onto the second outer surface of the molded film. The molded film is exposed to the acetone vapor for 30-120 seconds to form a raw film.

[0064] S4. Solidification and Phase Separation: The raw membrane is immersed in a coagulation bath for further phase separation and solidification to obtain a hydrated cellulose membrane. The coagulation bath is an aqueous solution of an acid, with a hydrogen ion concentration of 0.5–3 mol / L and a penetrant concentration of 0.1–5 wt%. The acid is at least one of acetic acid and sulfuric acid; the penetrant is at least one of ethanol, 1-propanol, isopropanol, n-butanol, 1-pentanol, and 2-pentanol.

[0065] S5. Post-treatment: The hydrated cellulose membrane is sequentially acid-washed and regenerated, and then washed with water to obtain a cellulose filter membrane.

[0066] By adopting the above technical solution, the membrane-forming material of the filter membrane in this application is cuprammonium fiber. As a type of regenerated fiber, cuprammonium fiber has obvious advantages. Unlike compounds such as cellulose acetate esters and cellulose nitrate esters, which are regenerated into cellulose by hydrolysis to remove acetate and nitrate groups, cuprammonium fiber does not have a degree of hydrolysis problem (insufficient hydrolysis will leave residual cellulose ester compounds with poor hydrophilicity, while excessive hydrolysis may lead to hydrolytic damage to the regenerated cellulose). Cellulose cuprammonium compound is a five-membered chelate, and its regeneration process is actually the release of cellulose from its cyclic chelate state. This process is not only easy to carry out, but also causes almost no damage to cellulose molecules. Even if there are unreleased cellulose cuprammonium compounds, they cannot form fibers and will not become components of the filter membrane. Therefore, the filter membrane prepared by the cuprammonium method has a very high proportion of cellulose, and the cellulose fiber structure is almost undamaged. Thus, it can have both good hydrophilicity and high mechanical properties.

[0067] In step S3, this application further pre-treats the liquid molded film obtained by casting. This is because it is relatively difficult to open pores on the surface of cellulose raw materials. If the liquid film is directly immersed in the coagulation bath, the second outer surface in direct contact with the coagulation bath is likely to rapidly separate phases and form a relatively dense film structure, making it impossible to form the required protective layer structure with a large pore size. Therefore, this application specifically places the liquid molded film in acetone vapor for treatment. Acetone can promote the phase separation of the casting liquid on the surface of the molded film. However, compared with the liquid coagulation bath, the acetone content in the acetone vapor is limited, and the effect of promoting phase separation is relatively weak. Therefore, the casting liquid on the surface separates phases at a relatively slow rate. The relatively slow separation rate, combined with a longer pre-treatment time, ensures that the casting liquid has sufficient time to form a large polymer-rich phase and a large solvent-rich phase. After the solvent-rich phase is removed, the required protective layer structure can be formed.

[0068] To ensure that the protective layer has a good protective effect on the separation layer while having a small impact on the filter membrane flux, the protective layer has a specific range of protection coefficients. In this application, acetone vapor is limited. By controlling the relative humidity, concentration, airflow velocity, and pretreatment time of the acetone vapor, the dilution of the casting solution near the second outer surface, the phase separation rate, and the pretreatment phase separation time are controlled to ensure that a protective layer with both good protective effect and low flux impact is obtained.

[0069] Placing the molded film in a humid airflow with a relative humidity of 40–80%, an acetone concentration of 15–55 v / v%, and an air velocity of 0.05–0.5 m / s can promote the condensation of moisture in the humid air onto the surface of the casting solution. During a relatively long pretreatment time (30–120 s), mass transfer within the casting solution promotes a gradient change in solid content along the thickness direction, thereby forming the desired protective layer structure when immersed in the coagulation bath. Meanwhile, acetone can promote the initial phase separation of the casting solution, forming the corresponding pore structure.

[0070] The acetone gas flow has a crucial impact on the pretreatment effect. If the relative humidity, acetone concentration, and air velocity in the acetone gas flow are too low (e.g., less than 40%), the acetone concentration is too low (e.g., less than 15 v / v%), or the air velocity is too low (e.g., less than 0.05 m / s), the low concentration of acetone vapor will have a poor effect on promoting phase separation of the casting solution. During a longer pretreatment time, the uniformity of the casting solution will decrease, which can easily lead to a decrease in the pore size uniformity of the final filter membrane. In addition, the moisture in the acetone vapor is difficult to condense and dilute the casting solution, making it difficult to form a gradient change in solid content in the casting solution. As a result, when the casting solution near the second outer surface comes into contact with the coagulation bath, it solidifies and separates into a denser structure, which has a significant impact on the flux of the filter membrane. However, if the relative humidity of the acetone gas stream is too high (e.g., greater than 80%), the acetone concentration is too high (e.g., greater than 55v / v%), or the wind speed is too high (e.g., greater than 0.5 m / s), excessive moisture condenses and dilutes the casting solution during a prolonged pretreatment period. This can easily lead to the formation of excessively large pores on the second outer surface, resulting in insufficient protection of the protective layer and making it difficult to achieve a good protective effect on the separation layer. Furthermore, excessively high concentrations of acetone vapor have an overly strong effect on promoting the separation of the casting solution, easily causing phase separation and solidification before the casting solution is sufficiently diluted, leading to the formation of a dense structure. Therefore, the relative humidity, acetone concentration, and wind speed of the acetone vapor need to be strictly controlled to ensure a protective layer structure with a suitable protection coefficient.

[0071] It should be noted that, in order to better dilute the casting solution with the moisture in the humid airflow, the temperature of the humid airflow can be controlled to be higher than that of the casting solution, so that the moisture in the humid airflow is more likely to condense on the surface of the casting solution.

[0072] In step S4, the pretreated green membrane is placed in a dilute acid solution, which promotes phase separation of the casting solution into a solvent-rich phase and a polymer-rich phase. The polymer-rich phase solidifies to form the solid structure of the filter membrane, while the solvent-rich phase, after removal, becomes the porous structure of the filter membrane. During this process, the coagulation bath needs to penetrate into the casting solution to initiate phase separation. However, the high viscosity of the casting solution results in significant resistance to the coagulation bath, leading to poor uniformity of its distribution. The added penetrant improves the permeability of the coagulation bath, promoting its penetration into the casting solution and thus enhancing its uniformity, resulting in a pore structure with high pore size uniformity.

[0073] The penetrant added to the coagulation bath can promote the rapid penetration of the coagulation bath into the casting solution and cause the casting solution to separate phases quickly, thereby obtaining a separation layer structure with relatively small pore size. The separation layer region with a smaller pore size structure will greatly hinder the further penetration of the coagulation bath, reduce the phase separation rate of the casting solution near the carrier side, and thus form a pre-filtration layer structure with a larger pore size than the separation layer.

[0074] Optionally, ammonia gas is introduced during the dissolution of the cotton fibers, and 0.1-1.5% of inorganic salt by total mass of the casting solution is added to the casting solution. The cation of the inorganic salt is one or more of sodium, potassium, calcium, and magnesium, and the anion of the inorganic salt is one or more of sulfate, sulfite, silicate, or carbonate.

[0075] While employing the aforementioned technical solution, cuprammonium cellulose also has certain drawbacks compared to regenerated fibers such as acetate and nitrocellulose. For example, the mechanism by which cuprammonium solution dissolves cellulose is primarily through the interaction of cuprammonium ions in the solution with hydrogen ions in the cellulose, reducing hydrogen bonds and thus breaking intramolecular and interchain hydrogen bonds, thereby dissolving the cellulose. Throughout the dissolution process, a sufficient number of cuprammonium ions in the solution are necessary to ensure stable and rapid dissolution of the cotton fibers. The inventors of this application have discovered that introducing ammonia gas significantly increases the dissolution rate and amount of cotton fibers when dissolving them with cuprammonium solution, and this effect is significantly better than conventional methods such as adding concentrated ammonia. This is likely because as the cuprammonium solution continuously dissolves cellulose, the concentration of cuprammonium complex ions in the system decreases, inevitably reducing the dissolution performance of the cellulose. Introducing ammonia gas promotes the further conversion of copper hydroxide and other compounds into cuprammonium ions, thereby replenishing the concentration of cuprammonium ions in the system and ensuring the dissolution rate and amount of cotton fibers. While adding concentrated ammonia can replenish ammonium ions, it also dilutes the entire system and can significantly reduce the solid content, thus affecting subsequent extrusion film formation. Adding ammonia, however, increases the concentration of ammonium ions in the system with minimal impact. Furthermore, the introduced ammonia gas has a self-stirring effect; therefore, introducing ammonia into the system can significantly improve the dissolution rate and amount of cotton fibers.

[0076] The addition of inorganic salts can regulate the phase separation rate of the casting solution in the coagulation bath, ensuring a high degree of phase separation uniformity of the casting solution, thereby obtaining a more uniform pore structure.

[0077] Optionally, step S1 specifically includes the following process steps:

[0078] S11. To prepare a copper ammonia solution, mix copper hydroxide powder with ammonia water and stir. During the stirring process, ammonia gas is introduced. Stir until copper hydroxide no longer dissolves to obtain a copper ammonia solution.

[0079] S12. Dissolve cellulose, keep stirring and put cotton fibers into copper ammonia solution. After the addition is complete, continue stirring until the cotton fibers are completely wetted. Then, introduce ammonia gas and stir until the cotton fibers are completely dissolved. Then add inorganic salts to obtain casting solution.

[0080] While adding inorganic salts to the casting solution can improve its phase separation properties, the timing of this addition is crucial. The inventors of this application unexpectedly discovered that adding inorganic salts and cotton fibers simultaneously to a cuprammonium solution significantly reduces the dissolution rate of the cotton fibers. Furthermore, changing the addition time of the inorganic salts to after the cotton fibers have dissolved results in a significantly faster dissolution rate without the addition of inorganic salts. This phenomenon is quite surprising, as it is generally believed that the dissolution rate of cellulose in a cuprammonium solution is not directly related to the amount of inorganic salts.

[0081] This may be because cuprammonium ions in cuprammonium solution generally exist in two forms: complex base and complex salt. The complex base is the main component that can dissolve cellulose. Adding inorganic salts too early may promote the formation of complex salts and reduce the content of complex bases, thereby reducing the proportion of complex bases that promote cellulose dissolution. In this case, even if the concentration of cuprammonium ions is the same, its dissolving ability will decrease.

[0082] It is understood that the filter membrane in this application can be a flat sheet membrane or a hollow fiber membrane. When the filter membrane is a hollow fiber membrane, its preparation process can be as follows:

[0083] S1. Preparation of casting solution: Cotton fibers are dissolved in a copper ammonia solution to form a casting solution. The casting solution has a solid content of 7-10%, a copper content of 3-5%, and an inorganic salt content of 0.1-1.5%. The cations of the inorganic salts are one or more of sodium, potassium, calcium, and magnesium, and the anions of the inorganic salts are one or more of sulfate, sulfite, or carbonate.

[0084] S2. Extrusion: The casting liquid is extruded into a film at a die temperature of 15-35°C to obtain the molded film.

[0085] S3, pre-phase separation

[0086] S31, internal phase separation: When spinning with casting solution, casting solution and inner core solution are extruded together to obtain hollow membrane fibers. The hollow membrane fibers are exposed to air, causing phase separation on the inner surface of the membrane fibers. The inner core solution is a 60-80 wt% aqueous solution of acetone.

[0087] S32. External phase separation: The membrane fibers are immersed in the core solution from the air, causing phase separation on the outer surface of the membrane fibers. The core solution is a 30-50 wt% aqueous solution of acetone, and an ammonium salt is added to the core solution at a concentration of 0.1-1 mol / L.

[0088] S4. Solidification and phase separation: The nascent membrane is immersed in a coagulation bath for further phase separation and solidification to obtain a hydrated cellulose membrane. The coagulation bath is an aqueous solution of an acid, with a hydrogen ion concentration of 0.5–3 mol / L and a permeabilizer addition of 0.1–5 wt%. The acid is at least one of acetic acid and sulfuric acid.

[0089] S5. Post-treatment: The hydrated cellulose membrane is sequentially acid-washed and water-washed to obtain a cellulose filter membrane.

[0090] In summary, this application includes at least one of the following beneficial technical effects:

[0091] 1. In the filter membrane of this application, the separation layer that plays a role in virus interception is located inside the filter membrane, and is therefore not easily damaged by mechanical means; and the bubble point of the filter membrane is 1 to 1.7 MPa, which can play a good role in intercepting small-sized viruses; furthermore, based on the filter membrane thickness of 20 to 80 μm, by controlling the protection coefficient B of the protective layer to be 5 to 100 nm / μm and combining the average pore size d of the second outer surface of the filter membrane measured by SEM to be 100 to 500 nm, it is possible not only to ensure that the separation layer structure of the filter membrane is not easily damaged by mechanical means, but also to ensure that the introduction of the protective layer structure has little impact on the flux of the filter membrane, and the filter membrane still has a high flux.

[0092] 2. The filter membrane in this application is prepared by the copper ammonia method, and by introducing ammonia gas during the dissolution of cotton fibers and pretreating the liquid membrane obtained by casting, it is possible to ensure that a filter membrane with good performance is obtained. Attached Figure Description

[0093] Figure 1 This is a typical cross-sectional structural diagram of the filter membrane of this application, and the filter membrane in the figure is a flat sheet membrane. The magnification of this scanning electron microscope image is 4k×.

[0094] Figure 2 This is a typical cross-sectional structural diagram of the filter membrane of this application, and the filter membrane in the figure is a hollow fiber membrane. The magnification of this scanning electron microscope image is 2.5k×.

[0095] Figure 3 This is a scanning electron microscope (SEM) image of the cross-sectional structure of the filter membrane of Embodiment 6 of this application, with a magnification of 4k×.

[0096] Figure 4 This is a scanning electron microscope image of the first outer surface of the filter membrane of Embodiment 6 of this application, with a magnification of 5k×.

[0097] Figure 5 This is a scanning electron microscope image of the second outer surface of the filter membrane of Embodiment 6 of this application, with a magnification of 5k×.

[0098] Figure 6This is a scanning electron microscope (SEM) image of the cross-sectional structure of the filter membrane of Embodiment 7 of this application, with a magnification of 6k×.

[0099] Figure 7 This is a scanning electron microscope image of the first outer surface of the filter membrane of Embodiment 7 of this application, with a magnification of 5k×.

[0100] Figure 8 This is a scanning electron microscope image of the second outer surface of the filter membrane of Embodiment 7 of this application, with a magnification of 5k×. Detailed Implementation

[0101] The following is in conjunction with the appendix Figures 1-8 This application will be described in further detail.

[0102] Example 1

[0103] This application discloses a process for preparing an asymmetric cellulose filter membrane for virus removal, comprising the following steps:

[0104] S1. Preparation of casting solution, specifically:

[0105] S11. To prepare a copper ammonia solution, mix copper hydroxide powder with ammonia water and stir. During the stirring process, ammonia gas is introduced. Stir until copper hydroxide no longer dissolves to obtain a copper ammonia solution.

[0106] S12. Dissolve the cellulose while stirring, and then add the cotton fibers to the copper ammonia solution. After the addition is complete, continue stirring until the cotton fibers are completely wetted. Then, introduce ammonia gas and stir until the cotton fibers are completely dissolved. Finally, add inorganic salts to obtain the casting solution. The prepared casting solution has a solid content of 9.1% and a copper content of 4.2%.

[0107] S2, casting: casting liquid is cast onto a carrier to obtain a liquid flat plate-shaped molded film, wherein the first outer surface of the molded film is in contact with the carrier, and the second outer surface of the molded film is exposed to the environment.

[0108] S3. Pretreatment: The second outer surface of the film obtained by casting is pretreated by blowing acetone vapor with a relative humidity of 65%, an acetone concentration of 35v / v, and a wind speed of 0.25m / s onto the second outer surface of the film exposed to the air. The film is exposed to acetone vapor for 70s. After the pretreatment, the raw film is obtained.

[0109] S4. Solidification and phase separation: The obtained green film is immersed in a coagulation bath to promote further phase separation and solidification of the casting solution to obtain a hydrated cellulose membrane; wherein, the coagulation bath is an aqueous solution of acetic acid with a hydrogen ion concentration of 1.7 mol / L, and a permeate with a concentration of 2.5 wt% is present in the coagulation bath. In this embodiment, ethanol is selected as the permeate.

[0110] S5. Post-treatment: The hydrated cellulose membrane is subjected to acid washing and regeneration followed by water washing. The acid washing solution used during acid washing and regeneration is a 10wt% sulfuric acid aqueous solution. The hydrated cellulose membrane is acid washed until its color changes from blue to white, and then it is washed with water until the pH is neutral. After washing, the cellulose filter membrane is obtained.

[0111] Example 2

[0112] The main difference between Example 2 and Example 1 is that inorganic salt is added to the system when preparing the casting solution. The inorganic salt is added after all the cotton fibers have dissolved, and the amount of inorganic salt added is 0.8% of the total mass of the casting solution. Sodium sulfate is used as the inorganic salt. Other process parameters are detailed in Table 1.

[0113] Example 3

[0114] The main difference between Example 3 and Example 2 is that, in preparing the casting solution, the inorganic salt was added together with the cotton fibers into the copper ammonia solution; other process parameters are detailed in Table 1. During the preparation of the casting solution, it was observed that the dissolution rate of the cotton fibers was slower than that in Example 2. However, in both Example 3 and Example 2, the cotton fibers were eventually completely dissolved, indicating that the timing of the inorganic salt addition does affect the dissolution rate of the cotton fibers, but has little impact on the solubility of the cotton fibers.

[0115] Examples 4-6

[0116] The main difference between Examples 4-6 and Example 2 is that the formulation of the casting solution and the various process parameters are different, as detailed in Table 1.

[0117] The main difference between Example 7 and Example 2 is that ammonia gas was not introduced in steps S11 and S21, and the formulation of the casting solution and various process parameters were appropriately adjusted, as detailed in Table 1.

[0118] It should be noted that in Example 7, when preparing the casting solution with a higher solids content, ammonia gas was not introduced during the preparation of the copper ammonia solution and the dissolution of the cotton fibers. Therefore, even after a long period of stirring and dissolution, flocculent cotton fibers could still be observed in the casting solution. This indicates that the cotton fibers were not completely dissolved, and the solids content in the casting solution should be lower than the theoretical value (the solids content of the casting solution is calculated based on the added mass of cotton fibers; in Examples 1-6, the cotton fibers were almost completely dissolved, so the solids content of the casting solution is considered to be the same as the theoretically calculated value). Furthermore, because no ammonia gas was introduced, the dissolution rate of the cotton fibers was significantly slower than in Examples 1-6. To avoid undissolved flocculent cotton fibers clogging the equipment, the casting solution was filtered before subsequent film-forming processes.

[0119] Comparative Example 1

[0120] The main difference between Comparative Example 1 and Example 2 is that step S3 pretreatment was not performed. Instead, the liquid molding film obtained by casting was directly immersed in the coagulation bath for phase separation and solidification. The formulation of the casting solution and various process parameters were adjusted, as detailed in Table 1.

[0121] Comparative Example 2

[0122] The main difference between Comparative Example 2 and Example 2 is that, in step S3, the relative humidity of acetone vapor is less than 40%, the acetone concentration is less than 15 v / v%, and the formulation of the casting solution and various process parameters are adjusted, as detailed in Table 1.

[0123] Comparative Example 3

[0124] The main difference between Comparative Example 3 and Example 2 is that, in step S3, the relative humidity of acetone vapor is higher than 80%, the acetone concentration is higher than 55 v / v%, and the formulation of the casting solution and various process parameters are adjusted, as detailed in Table 1.

[0125] Table 1. Casting solution formulations and process parameters for each embodiment and comparative example.

[0126]

[0127]

[0128] Performance testing and data

[0129] The morphological parameters of the filter membranes prepared in each embodiment and comparative example are detailed in Table 2:

[0130] Table 2 shows the morphological parameters of the filter membranes prepared in each embodiment and comparative example.

[0131]

[0132]

[0133] The performance parameters of the filter membranes prepared in each embodiment and comparative example are detailed in Table 3:

[0134] Table 3. Filter membrane performance parameters obtained in each embodiment and comparative example.

[0135]

[0136] in conclusion

[0137] By comparing the schemes and data of Example 1 and Examples 2-3, it is easy to see that whether or not inorganic salt is added has little effect on the solubility of cotton fibers, but has a certain impact on the dissolution rate of cotton fibers, especially the timing of inorganic salt addition. If inorganic salt is added together with cotton fibers, the dissolution rate of cotton fibers will be reduced. This may be because the addition of inorganic salt leads to the formation of complex salts and a decrease in the concentration of complex alkali.

[0138] By comparing the schemes and data of Example 2 and Example 7, it is easy to see that when preparing the copper ammonia solution and dissolving cotton fibers, introducing ammonia gas can not only increase the solubility of cotton fibers, but also increase the dissolution rate of cotton fibers.

[0139] By comparing the schemes and data of Example 2 and Comparative Example 1, it is clear that, due to the lack of pretreatment, the filter membrane did not form a protective layer structure, but instead formed a dense skin structure. Although a higher LRV was achieved, its flux and filtration efficiency were low. Furthermore, due to the absence of a protective layer structure, the LRV retention rate significantly decreased after 10 disassembly and reassembly cycles. This indicates that repeated disassembly and reassembly damaged the separation layer responsible for virus interception, resulting in a significant reduction in its virus interception capacity and failing to meet virus safety requirements.

[0140] By comparing the schemes and data of Example 2 and Comparative Example 2, it is easy to see that inappropriate pretreatment processes (ultra-long processing time, low humidity, low acetone concentration, etc.) will increase the thickness of the protective layer but reduce the pore size, resulting in a low protection coefficient B. Although a thick and dense protective layer can significantly improve the protection effect on the separation layer, the flux of the filter membrane is obviously low.

[0141] By comparing the schemes and data of Example 2 and Comparative Example 3, it is easy to see that inappropriate pretreatment processes (shorter processing time, higher humidity, higher acetone concentration, etc.) will result in a protective layer structure with too small a thickness and a larger pore size, thus leading to an excessively high protection coefficient B. Although the thin and loose protective layer has little impact on the flux and LRV of the filter membrane, the LRV retention rate is significantly reduced after 10 disassembly and assembly cycles. This indicates that when the protection coefficient B is too high, the protective effect of the protective layer on the separation layer is significantly reduced.

[0142] This specific embodiment is merely an explanation of this application and is not intended to limit it. 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 fall within the scope of the claims of this application.

Claims

1. An asymmetric cellulose filter membrane for virus removal, comprising a porous body having non-directional tortuous pathways within the porous body, one side surface of the porous body being a first outer surface, and the other side surface of the porous body being a second outer surface, characterized in that: The porous body includes a pre-filter layer, a separation layer for intercepting viruses, and a protective layer. One side of the pre-filter layer is a first outer surface, and one side of the protective layer is a second outer surface. The pre-filter layer, the separation layer, and the protective layer are connected by continuous fibers. The bubble point of the filter membrane is 1~1.8 MPa; The average pore size measured by SEM of the protective layer is greater than that of the separation layer but smaller than that of the pre-filter layer. The protection coefficient B of the protective layer is 5~100nm / μm; The protection coefficient B is calculated using the following formula: B = d / h; In the above formula, d is the average pore diameter of the hole structure on the second outer surface measured by SEM, in nm; h is the thickness of the protective layer, in μm. The value of d is 100~500 nm; The thickness of the filter membrane is 20~80μm; The average aperture of the protective layer measured by SEM gradually increases from the side closer to the first outer surface to the side closer to the second outer surface. The rate of increase of the average aperture of the protective layer measured by SEM on the side closer to the first outer surface is less than the rate of increase of the average aperture of the protective layer measured by SEM on the side closer to the second outer surface.

2. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The protection coefficient B of the protective layer is 10~90nm / μm, the d is 150~450nm, and the porosity of the second outer surface is 5~20%.

3. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average pore size of the protective layer, as measured by SEM, is 100-300 nm, and the porosity of the protective layer is 35-65%.

4. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average fiber diameter measured by SEM of the protective layer is greater than that of the separation layer but less than that of the pre-filter layer; the average fiber diameter measured by SEM of the separation layer is 30~100nm.

5. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The ratio of the average fiber diameter measured by SEM of the protective layer to that of the separation layer is 1.1 to 1.7; the ratio of the average fiber diameter measured by SEM of the pre-filter layer to that of the protective layer is 1.2 to 2; and the average fiber diameter measured by SEM of the protective layer is 40 to 130 nm.

6. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The ratio of the average pore size of the protective layer measured by SEM to the average fiber diameter measured by SEM is 0.8 to 3.

7. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The first outer surface includes a plurality of long strip-shaped and interlaced first fibers, the interlacing parts of the first fibers form nodes, and adjacent and interlaced first fibers surround each other to form holes. The average diameter of the first fibers measured by SEM is 50~180nm, and the hole area ratio of the first outer surface is 10~50%.

8. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average aperture measured by SEM on the first outer surface is 300~4500nm, and the ratio of the average aperture measured by SEM on the first outer surface to the average aperture measured by SEM on the second outer surface is 2~40.

9. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average pore size of the pre-filter layer measured by SEM is 200~700nm, and the porosity of the pre-filter layer is 40~75%.

10. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average pore size of the pre-filter layer measured by SEM gradually decreases from the side near the first outer surface to the side near the second outer surface. The rate of increase of the average pore size of the pre-filter layer measured by SEM on the side near the first outer surface is greater than the rate of increase of the average pore size of the pre-filter layer measured by SEM on the side near the second outer surface. The gradient of the average pore size of the pre-filter layer measured by SEM is (60~200) nm / μm.

11. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The average pore size of the separation layer measured by SEM is 20~45nm, the thickness of the separation layer is 5~45μm, and the thickness ratio of the separation layer to the porous body is 20~60%.

12. The asymmetric cellulose filter membrane for virus removal according to claim 1, characterized in that: The filter membrane has a porosity of 10-60%; a tensile strength of 6-15 MPa, an elongation at break of 5-40%, and an elastic modulus of 20-80 MPa; and a flux of more than 60 L·h. -1 m -2 @30psi; the protein yield of the filter membrane is not less than 98%.

13. The preparation process of the asymmetric cellulose filter membrane for virus removal according to any one of claims 1 to 12, characterized in that: The process includes the following steps: S1. Preparation of casting solution: Cotton fibers are dissolved in a copper ammonia solution to form a casting solution. The casting solution has a solid content of 7-10% and a copper content of 3-5%. S2, film formation: The casting solution is extruded to form a film, thus obtaining the molded film; S3. Pretreatment: Pretreatment is performed on the second outer surface of the formed film to promote pre-phase separation on the second outer surface of the formed film and obtain the film. S4. Solidification and Phase Separation: The raw membrane is immersed in a coagulation bath for further phase separation and solidification to obtain a hydrated cellulose membrane. The coagulation bath is an aqueous solution of an acid, with a hydrogen ion concentration of 0.5~3 mol / L and a penetrant concentration of 0.1~5 wt%. The acid is at least one of acetic acid and sulfuric acid; the penetrant is at least one of ethanol, 1-propanol, isopropanol, n-butanol, 1-pentanol, and 2-pentanol. S5. Post-treatment: The hydrated cellulose membrane is sequentially acid-washed and regenerated, and then washed with water to obtain a cellulose filter membrane.

14. The preparation process of an asymmetric cellulose filter membrane for virus removal according to claim 13, characterized in that: Ammonia gas is introduced during the dissolution of the cotton fibers. The casting solution also contains 0.1-1.5% inorganic salt by mass of the total casting solution. The cation of the inorganic salt is one or more of sodium, potassium, calcium, and magnesium, and the anion of the inorganic salt is one or more of sulfate, sulfite, silicate, or carbonate.

15. The preparation process of an asymmetric cellulose filter membrane for virus removal according to claim 14, characterized in that: Step S1 specifically includes the following process steps: S11. To prepare a copper ammonia solution, mix copper hydroxide powder with ammonia water and stir. During the stirring process, ammonia gas is introduced. Stir until copper hydroxide no longer dissolves to obtain a copper ammonia solution. S12. Dissolve cellulose, keep stirring and put cotton fibers into copper ammonia solution. After the addition is complete, continue stirring until the cotton fibers are completely wetted. Then, introduce ammonia gas and stir until the cotton fibers are completely dissolved. Then add inorganic salts to obtain casting solution.

16. The preparation process of the asymmetric cellulose filter membrane for virus removal according to any one of claims 13 to 15, characterized in that: The process includes the following steps: the filter membrane is a flat sheet membrane, and steps S2 and S3 specifically include the following process steps: S2, casting: casting liquid is cast onto a carrier to obtain a liquid flat plate-shaped molded film, wherein the first outer surface of the molded film is in contact with the carrier, and the second outer surface of the molded film is exposed to the environment; S3. Pretreatment: The second outer surface of the formed film is pretreated by blowing acetone vapor with a relative humidity of 40-80%, an acetone concentration of 15-55 v / v, and a wind speed of 0.05-0.5 m / s onto the second outer surface of the formed film. The formed film is exposed to the acetone vapor for 30-120 seconds to form a raw film.

17. The preparation process of the asymmetric cellulose filter membrane for virus removal according to any one of claims 13 to 15, characterized in that: The process includes the following steps: the filter membrane is a hollow fiber membrane, and steps S2 and S3 specifically include the following process steps: S2. Extrusion: The casting liquid is extruded into a film at a die temperature of 15~35℃ to obtain the molded film. S3, pre-phase separation S31, internal phase separation: When spinning with casting solution, casting solution and inner core solution are extruded together to obtain hollow membrane fibers. The hollow membrane fibers are exposed to air, causing phase separation on the inner surface of the membrane fibers. The inner core solution is a 60~80wt% acetone aqueous solution. S32. External phase separation: The membrane fibers are immersed in the core liquid from the air, causing phase separation on the outer surface of the membrane fibers. The core liquid is a 30-50 wt% acetone aqueous solution, and an ammonium salt is added to the core liquid. The concentration of the ammonium salt is 0.1-1 mol / L.

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