Cellulose composite virus-removing membrane and its preparation process

Abstract

The application relates to a cellulose composite virus-removing membrane and a preparation process thereof. The composite virus-removing membrane comprises a microporous membrane support layer and a cellulose layer. A region for capturing 40nm colloidal gold in the virus-removing membrane is D 40 The membrane layer junction is taken as a position with a membrane thickness of 0%, the liquid inlet surface is taken as a position with a membrane thickness of -100%, and the liquid outlet surface is taken as a position with a membrane thickness of 100%. A region with a membrane thickness of -10% to 0% is a pre-retention region. The absorption peak height of D 40 gradually increases in the pre-retention region. The absorption peak of D 40 is the highest in a region with a membrane thickness of 1% to 40%. The application further discloses a preparation process of the composite virus-removing membrane. The composite virus-removing membrane has a pre-retention region for the 40nm colloidal gold retention capacity, and the retention peak value is controlled to be in the cellulose layer, so that the pre-retention region has the impurity retention capacity but does not cause concentrated impurity retention. The composite virus-removing membrane not only has high pressure resistance, but also has high loading capacity.

Description

Technical Field

[0001] This application relates to the field of membrane separation technology, and in particular to a cellulose composite virus removal membrane and its preparation process. Background Technology

[0002] Ensuring the viral safety of various biological agents is of paramount importance in their production. Both the new edition of the Chinese Pharmacopoeia and the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidance document "ICH Q5A Biotechnology Products – Viral Safety Evaluation" (of which the China Food and Drug Administration is a member) explicitly require high standards for the viral safety of biological agents. Therefore, viral clearance and / or viral inactivation steps in the preparation of biological agents are indispensable.

[0003] Membrane separation technology is widely used in the virus removal steps of various biological agents due to its advantages such as high separation efficiency, ease of process scale-up, and minimal risk of denaturation of active substances during separation. When applied to virus filtration processes, membrane separation technology often employs dead-end filtration. Since the primary driving force for dead-end filtration is the pressure difference across the membrane after pressurizing the feed solution, further increasing the pressure of the feed solution is expected to improve filtration efficiency. However, higher pressure feed solutions place greater demands on the pressure resistance of the membrane to prevent a decrease or even damage to its virus retention performance under higher pressure.

[0004] For example, Chinese invention patent application CN105980038A (application by Asahi Kasei Corporation) discloses a virus-removing membrane comprising cellulose, having a first surface for supplying a protein-containing solution and a second surface for discharging permeate through the membrane. This membrane achieves a logarithmic removal rate of over 4 (LRV > 4) for porcine parvovirus (approximately 18–26 nm). This membrane is a cellulose membrane, and the good hydrophilicity of cellulose gives it low protein adsorption. However, the inherently soft texture of cellulose raw materials results in poor mechanical strength of the cellulose fiber skeleton, often leading to insufficient self-supporting properties. The cellulose membrane in this application can only withstand 15 psi of pressure and is unable to withstand higher pressures. During use, the filter membrane is likely to be impacted by the feed liquid. Whether it is the pressure of the feed liquid itself, which requires pressure as a driving force during virus filtration, on the filter membrane, or the impact caused by equipment vibration, etc., filter membranes that cannot withstand high pressure may not only have a shorter service life, but may also lead to the risk of virus leakage due to insufficient stability in certain special application scenarios.

[0005] Currently, there are already filter membranes on the market with high pressure resistance, such as... The membrane, available from Millipore Corporation of Billerica, Massachusetts, is a bilayer PVDF ultrafiltration membrane. It achieves the desired bilayer structure by casting an ultrafiltration layer onto a pre-fabricated PVDF microporous membrane. The pre-fabricated PVDF microporous membrane enhances the membrane's pressure resistance to some extent. However, because both layers of this composite ultrafiltration membrane are made of PVDF, the solvent in the casting solution dissolves the PVDF microporous membrane after casting, resulting in an abnormally high solids content at the interface. This high-solids content often solidifies after phase separation, resulting in a relatively dense pore structure. This often leads to localized trapping, causing a rapid decrease in membrane flux and a shorter service life. The company's related patent, US patent application US4824568A (MILLIPORE CORP application), discloses a high bubble point filter membrane. This membrane is formed by coating PVDF or PES onto a 0.22μm PVDF microporous substrate. During coating, the solvent in the casting solution softens a portion of the PVDF substrate, significantly improving the peel strength of the composite membrane. However, it also suffers from the problem of the microporous substrate dissolving and re-separating to form a dense structure. This dense structure leads to a rapid decrease in service life due to localized trapping. Therefore, the high peel strength of this composite membrane comes at the cost of a reduced service life.

[0006] For example, Chinese invention patent application CN114173911A (Sartorius application) discloses a mechanically stable ultrafiltration membrane and its preparation method. This method involves coating a first polymer solution and a second polymer solution onto a support layer, and then briefly treating the first polymer solution with a non-solvent-containing gas to form a damping region after the first polymer solution solidifies. This damping region enables the composite membrane to have strong impact resistance (i.e., pressure resistance). The support layer can be a nonwoven mesh, woven fabric, or polyester nonwoven fabric, or it can be a polypropylene, polyethylene, polyfiber, polyethersulfone, or regenerated cellulose microfiltration membrane. This ultrafiltration membrane achieves stronger impact resistance by forming a damping structure that is dense in the middle and loose on both sides; however, this membrane pore structure is not suitable for use as a virus-removing filter membrane. This is because, unlike ultrafiltration membranes which often use tangential flow filtration (the direction of the feed liquid flow is parallel to the membrane surface), virus removal membranes often use dead-end filtration (the direction of the feed liquid flow is perpendicular to the membrane surface). The dense damping structure inside the membrane is likely to cause concentrated retention of particulate impurities in the feed liquid, resulting in a rapid decrease in membrane flux and an excessively short service life.

[0007] Therefore, while commonly used composite filter membranes can improve their mechanical strength by introducing a support layer structure, this often comes at the cost of a reduced service life. Obtaining a filter membrane that combines high mechanical strength and long service life is a pressing yet difficult technical challenge to solve. Summary of the Invention

[0008] This application provides a cellulose composite virus removal membrane and its preparation process. The composite virus removal membrane of this application introduces a pre-retention region with the ability to retain 40nm colloidal gold in the region near the composite interface of the microporous membrane support layer, and controls the retention peak region of 40nm colloidal gold to be located within the cellulose layer. This ensures that the pre-retention region has the ability to retain impurities but does not result in concentrated and large-scale impurity retention, so that large-particle impurities are dispersed and retained in the pre-retention region and the cellulose layer. This ensures that the composite virus removal membrane not only has high pressure resistance but also a long service life.

[0009] In a first aspect, this application provides a cellulose composite virus-removing membrane, employing the following technical solution:

[0010] A cellulose composite virus removal membrane includes a microporous membrane support layer and a cellulose layer. The side of the microporous membrane support layer away from the cellulose layer is the liquid inlet surface, and the side of the cellulose layer away from the microporous membrane support layer is the liquid outlet surface. Both the microporous membrane support layer and the cellulose layer have non-directional tortuous pathways, and the microporous membrane support layer and the cellulose layer are connected by non-directional tortuous pathways.

[0011] In a wetted state, the virus-removing membrane traps 40nm colloidal gold. The region in the virus-removing membrane that traps 40nm colloidal gold is D. 40 The junction of the microporous membrane support layer and the cellulose layer is taken as the position of 0% membrane thickness, the liquid inlet surface of the virus-removing membrane is taken as the position of -100% membrane thickness, and the liquid outlet surface of the virus-removing membrane is taken as the position of 100% membrane thickness.

[0012] The region of membrane thickness from -10% to 0% is the pre-retention zone, and D is located within the pre-retention zone. 40 The height of the absorption peak gradually increases;

[0013] The D 40 The highest absorption peak is located in the region of 1% to 40% of the film thickness.

[0014] Optionally, the film-forming material of the microporous membrane support layer is at least one selected from PVDF, PES, PTFE, Nylon, cellulose, and polyolefin.

[0015] Optionally, the polyolefin is UPE or PP.

[0016] By adopting the above technical solution, this application obtains a composite virus-removing membrane by combining a microporous membrane support layer with a cellulose layer. The cellulose layer uses a hydrophilic cellulose-based film-forming material, resulting in a low protein adsorption rate in the composite virus-removing membrane, thus ensuring the concentration and purity of active proteins in the filtrate. However, the inherently soft texture of cellulose-based film-forming materials means that ordinary cellulose-based filter membranes often lack sufficient mechanical strength. For virus removal filtration processes driven by pressure, this means that further increasing the pressure cannot improve filtration efficiency. Introducing a microporous membrane support layer, which provides support and reinforcement, can improve the pressure resistance of the composite virus-removing membrane, enabling it to possess both a low protein adsorption rate and high pressure resistance.

[0017] Composite membranes offer higher pressure resistance, enabling their use under higher pressure conditions (e.g., not less than 20 psi, not less than 30 psi, or even higher). However, compared to monolithic membrane structures, composite membrane structures often have a shorter lifespan. For example, as mentioned earlier, the US patent application (MILLIPORE CORP application) with publication number US4824568A softens the support layer using a solvent system in the casting solution, allowing the casting solution and support layer to fuse to some extent and reduce the possibility of composite membrane delamination. However, the softened support layer area generally has a denser pore structure after re-curing, and impurities in the feed solution are likely to be concentrated and trapped in large quantities in this area, leading to a rapid decrease in lifespan.

[0018] For example, the Chinese invention patent application with publication number CN114173911A (application by Sartorius) does not include any special treatment for anti-delamination performance. However, the additionally introduced damping zone with higher density will also lead to the concentration and large-scale retention of impurity particles, resulting in a lower service life.

[0019] It is understandable that concentrated and substantial retention occurs in high-density regions. Retention refers to the fact that due to the high density of the pore structure in these regions, there is a significant retention capacity for impurities of different particle sizes, which is considered to indicate concentrated and substantial retention. If we characterize this using colloidal gold retention curves, we will find that there are rapidly rising and peaking colloidal gold retention curves in the high-density regions of the film structure, indicating that colloidal gold is concentratedly retained within a relatively small area.

[0020] In this application, the region of the microporous membrane support layer near the composite interface and whose thickness is 10% of the thickness of the microporous membrane support layer is designated as the pre-retention region. Within the pre-retention region, D... 40 The absorption peak height gradually increased, and the colloidal gold cutoff curve did not reach the peak value.

[0021] Among them, D in the pre-retention area 40The gradually increasing absorption peak height indicates that the region of the microporous membrane support layer near the composite interface has the ability to retain impurity particles (i.e., 40nm colloidal gold), and the closer to the composite interface, the higher the retention capacity of the microporous membrane support layer for impurity particles. This differs from the rapidly rising and peak-reaching retention curve of concentrated retention colloidal gold, indicating that although the pre-retention region in this application has a gradually increasing retention capacity for impurity particles, the impurity particles are dispersed within the pre-retention region, rather than being concentratedly retained to a rapid peak. The dispersed retention of impurity particles within the pre-retention region allows for good pre-filtration and reduces the likelihood of localized pore blockage. Therefore, the introduction of the microporous membrane support layer not only improves the pressure resistance of the composite virus removal membrane but also further enhances the load capacity (or service life) of the composite virus removal membrane through the pre-filtration effect of the pre-retention region.

[0022] In addition, D in this application 40 The highest absorption peak (i.e., the peak value) is not located within the pre-retention zone, but rather in the region of 1%–40% of the cellulose layer membrane thickness. This indicates that not only does the pre-retention zone in the microporous membrane support layer have a pre-retention effect on impurities, but the region near the composite interface in the cellulose layer also has a gradually increasing retention effect on impurity particles. Therefore, impurity particles in the feed solution are dispersed and retained in the pre-retention zone and the region of the fiber layer near the composite interface. This makes it difficult for either the pre-retention zone or the region of the fiber layer near the composite interface to become rapidly clogged due to the concentrated retention of impurity particles. Therefore, the composite virus removal membrane, due to its "primary pre-filtration in the pre-retention zone" and "secondary pre-filtration in the fiber layer," has a significantly higher loading capacity compared to ordinary composite membrane structures. This is quite unexpected, unlike current general composite virus removal membranes, which, while improving pressure resistance, often come at the cost of reduced service life.

[0023] It should be noted that, based on the fact that the pre-retention region in this application has impurity retention capability and the absorption peak of 40nm colloidal gold gradually increases within the pre-retention region, D in this application... 40 The highest absorption peak should not be too close to the composite interface (i.e., D). 40 The absorption peak is located in the region where the film thickness is less than 1% or too far away from the composite interface (i.e., D). 40 The highest absorption peak is located in the region where the film thickness is greater than 40%.

[0024] This is because when D 40When the absorption peak is located in the region where the film thickness is less than 1%, it indicates that the absorption curve of 40nm colloidal gold rises rapidly in the pre-cutoff region, and the absorption curve in the pre-cutoff region is relatively "steep," so that the absorption peak value can be found near the composite interface. This means that the amount of colloidal gold trapped in the pre-cutoff region increases rapidly, and a large amount of colloidal gold is trapped near the composite interface. This increases the possibility that the pore structure at the composite interface is blocked by a large amount of trapped colloidal gold. Correspondingly, the possibility of blockage by impurity particles at this point is also greater, and the load capacity of the composite virus-removing membrane inevitably decreases. When D 40 When the highest absorption peak is located in the region where the membrane thickness is greater than 40%, it indicates that the pre-retention zone and the area near the composite interface of the cellulose layer have weaker retention capacity for impurity particles. Whether in the pre-retention zone or the area near the composite interface of the cellulose layer, the absorption curve of colloidal gold at 40 nm rises slowly, resulting in a relatively "flat" absorption curve. While this can further improve the dispersion of impurity particles in the membrane structure and reduce the possibility of localized blockage, the weak retention capacity of these two regions also means an increased possibility of impurity particles leaking into the virus-retention area of ​​the cellulose layer. Once the virus-retention area of ​​the cellulose layer is blocked by impurity particles, the viral load of the membrane will also decrease (even if the pre-filtration area is not blocked, blockage in the virus-retention area will still lead to a decrease in the overall membrane flux, resulting in a lower viral load).

[0025] In summary, unlike the common composite membrane structures that have concentrated and large retention areas for impurity particles, the composite virus removal membrane in this application greatly reduces the possibility of local blockage of the membrane pore structure by dispersing and retaining large impurities in the pre-retention area and the cellulose layer. This ensures that the composite virus removal membrane not only has high support strength but also a long service life (high load capacity).

[0026] The colloidal gold retention curve in this application is obtained by the following method: A colloidal gold retention experiment is performed using the composite antiviral membrane described in this application, and the distribution of colloidal gold in the composite antiviral membrane is determined according to the test method in Chinese Patent CN105980038B - Antiviral Membrane. Specifically, the composite antiviral membrane after retaining the colloidal gold solution is sliced, and the brightness distribution of multiple sites in the colloidal gold-stained portion of the slice is measured using an optical microscope. Since colloidal gold absorbs light, the brightness shift depends on the amount of colloidal gold captured. It should be noted that background noise can be removed from the brightness distribution as needed. Then, a graph is constructed with the film thickness on the horizontal axis and the brightness shift on the vertical axis; thus, the region where colloidal particles of a certain size are retained in the film thickness direction is obtained. It should be noted that in measurements by optical microscopes, when the absolute value of the position of the region of the spectrum obtained by subtracting the measured brightness distribution from the constant (255) is less than 10% of the maximum absolute value of the spectrum, the capture of colloidal gold in this region can also be considered within the error range from the point of view of the virus removal capacity of the virus-removing membrane.

[0027] Alternatively, it can be understood that although there is a certain amount of colloidal gold in some regions along the film thickness direction, it is very low. Therefore, these regions are not considered as areas where colloidal gold is trapped; they are merely areas where some colloidal gold remains. Thus, in virus-removing membranes, it is preferable to form regions that continuously trap colloidal gold with a diameter of 20 nm along the film thickness direction, which are the regions that truly trap colloidal gold of the corresponding particle size.

[0028] It is understandable that, in addition to optical microscopy, those skilled in the art can also characterize the retention area and amount of colloidal gold using known methods. For example, by using energy dispersive spectroscopy (EDS) to analyze the cross-section of a filter membrane containing colloidal gold, a distribution curve of gold in the thickness direction of the filter membrane can be obtained, yielding a similar spectrum.

[0029] Furthermore, the absolute thickness values ​​of the microporous membrane support layer and the cellulose layer in this application are often not the same. Therefore, the absolute thickness value corresponding to -10% of the membrane thickness is not the same as the absolute thickness value corresponding to 10% of the membrane thickness; both only represent their relative positions within their respective layer structures. Non-directional tortuous pathways refer to randomly oriented groove structures and / or discretely distributed pore structures, with each non-directional tortuous pathway interconnected. During filtration, the feed liquid flows within the tortuous pore structure, trapping impurities in the feed liquid through sieving, adsorption, and other methods. It is easy to understand that the position of 0% membrane thickness is the interface between the microporous membrane support layer and the cellulose layer, referring to the surface of the microporous membrane support layer away from the inlet liquid surface, or the composite interface.

[0030] Optionally, the region of the cellulose layer near the microporous membrane support layer and with the same thickness as the pre-retention region is a high-efficiency retention region, and the absorption peak area of ​​the high-efficiency retention region is larger than the absorption peak area of ​​the pre-retention region.

[0031] By adopting the above technical solution, the peak area of ​​the absorption peak within a certain region of the colloidal gold retention curve can effectively reflect the amount of colloidal gold retained in that region. In this application, the region within the cellulose layer near the composite interface with the same absolute thickness as the pre-retention region is defined as the high-efficiency retention region (it should be noted that this is not necessarily the location of 10% of the film thickness). Furthermore, the absorption peak area of ​​40nm colloidal gold in the high-efficiency retention region is greater than that in the pre-retention region. This indicates that, under the premise of the same thickness, although both the pre-retention region and the high-efficiency retention region have the ability to retain 40nm colloidal gold, the main retention area of ​​40nm colloidal gold is still the high-efficiency retention region, not the pre-retention region.

[0032] The high-efficiency retention zone has a greater 40nm colloidal gold retention capacity than the pre-retention zone, which means that the high-efficiency retention zone has a better 40nm colloidal gold retention capacity than the pre-retention zone, enabling the composite virus removal membrane to have a longer service life.

[0033] This may be because the pre-retention zone primarily functions as a primary pre-filtration zone, increasing the load on the composite virus-removing membrane by improving the dispersion of impurity particles. However, the 40nm colloidal gold retention capacity within the pre-retention zone should not be too high to avoid concentrated retention at the composite interface of the virus-removing membrane. Even if the pre-retention zone experiences leakage of colloidal gold particles due to its poor retention capacity, the leaked particles will be retained by the impurity-filtering area of ​​the cellulose layer, preventing direct impact on the virus-removing area within the cellulose layer. Conversely, the high-efficiency retention zone must ensure efficient retention of colloidal gold particles to prevent leakage and blockage of the virus-removing area within the cellulose layer.

[0034] If the 40nm colloidal gold retention capacity in the pre-retention region is greater than that in the high-efficiency retention region, whether due to membrane structure blockage caused by the large-scale retention of colloidal gold particles near the composite interface or blockage of the virus-retention area in the cellulose layer caused by leakage of colloidal gold particles in the high-efficiency retention region, the viral load of the composite antiviral membrane will decrease. Therefore, this approach is not a further preferred option. It should be noted that even this non-preferred approach still has a significantly higher viral load compared to conventional composite antiviral membranes.

[0035] Optionally, the D 40The endpoint is located in the region where the film thickness is 15% to 60%.

[0036] By adopting the above technical solution, D 40 The endpoint position, to some extent, characterizes the region in the cellulose layer that performs impurity filtration. Given that a pre-retention region with impurity retention capability already exists in the microporous membrane support, the thickness of the impurity filtration region in the cellulose layer can be optimally controlled, allowing D to... 40 The endpoint is located at a position no more than 60% of the film thickness.

[0037] If the thickness of the region in the cellulose layer that serves to filter impurities is too small (D) 40 The endpoint is located in the region where the membrane thickness is less than 15%, indicating that 40nm colloidal gold is largely retained in the cellulose layer within a small thickness range. Although the risk of leakage of colloidal gold particles is low, the concentrated retention of colloidal gold particles is likely to cause local blockage of the pore structure of the cellulose layer membrane, resulting in a decrease in loading capacity. In addition, a low proportion of the region in the cellulose layer that plays a role in impurity filtration often means that a high proportion of the region in the cellulose layer that plays a role in virus retention is present. Regions with high virus retention capacity often also have high feed resistance, and the flux of the composite virus removal membrane is often low. Therefore, D 40 The endpoint being located in the region where the film thickness is less than 15% is not a preferred option.

[0038] If the thickness of the region in the cellulose layer that serves as an impurity filter is too large (D) 40 The endpoint is located in the region where the membrane thickness is greater than 60%. A large amount of 40nm colloidal gold is trapped over a wider thickness range. Although the dispersion of colloidal gold particles is higher and the possibility of membrane pore blockage is lower, the risk of colloidal gold particle leakage is also increased, which will also lead to a decrease in the viral load of the composite antiviral membrane. Therefore, D... 40 The endpoint being located in the region where the film thickness is greater than 60% is not the preferred option.

[0039] Optionally, the D 40 The ratio of the distance between the highest and lowest absorption peaks to the thickness of the cellulose layer is 0.05 to 0.5.

[0040] By adopting the above technical solution, D 40 The distance between the highest and lowest absorption peaks largely reflects the changing trend of the cellulose layer's membrane pore structure in terms of its ability to retain colloidal gold. If D 40 The ratio of the distance between the highest and lowest absorption peaks to the thickness of the cellulose layer is less than 0.05, indicating that D... 40 The region before the highest absorption peak has a strong retention capacity for colloidal gold; a large amount of colloidal gold is retained in this region, with only a small amount leaking out. Therefore, D...40 Reaching the endpoint quickly, a large amount of trapped colloidal gold is likely to clog the membrane pore structure, resulting in a lower viral load on the composite virus-removing membrane. If D 40 The ratio of the distance between the highest and lowest absorption peaks to the thickness of the cellulose layer is greater than 0.5, indicating that D... 40 Even after reaching the highest absorption peak, the thick membrane pore structure still retains colloidal gold, indicating that the region before reaching the highest absorption peak has a relatively weak retention capacity for colloidal gold. As mentioned earlier, once the area in the cellulose layer that plays a role in virus retention is blocked by impurities, the viral load of the composite antiviral membrane will also be low.

[0041] Optionally, the D 40 The absorption peak height at 0% of film thickness is related to D 40 The ratio of the absorption peak heights located at -10% of the film thickness is not less than 1.3.

[0042] By adopting the above technical solution, D 40 The absorption peak height at 0% of film thickness is related to D 40 The ratio of the absorption peak heights at -10% of the film thickness characterizes, to some extent, the trend of colloidal gold retention capacity in the pre-retention zone, and also to some extent, the "steepness" of the colloidal gold retention curve within the pre-retention zone. When the ratio is small, the colloidal gold retention curve in the pre-retention zone rises in a relatively gentle manner. This indicates that the retention capacity of the pre-retention zone for colloidal gold particles varies little in the thickness direction (from 10% to 0% of the film thickness), and the overall retention capacity of the pre-retention zone for colloidal gold particles is relatively weak. This results in more colloidal gold particles leaking into the cellulose layer and being retained by it. A large number of colloidal gold particles retained in the cellulose layer are likely to cause blockage of the cellulose layer membrane pore structure.

[0043] Since the peak position of the colloidal gold retention curve in this application is not located within the pre-retention zone, the improved retention capacity of the pre-retention zone for near-traffic particles can, to a certain extent, increase the dispersion of colloidal gold particles in the entire composite virus removal membrane and reduce the possibility of the cellulose layer being blocked by colloidal gold particles. Therefore, the relatively "steep" (ratio of the two is not less than 1.3) colloidal gold retention curve allows the composite virus removal membrane to preferably obtain a higher loading capacity.

[0044] Optionally, the D 40 The absorption peak height at 0% of the film thickness is related to the D 40 The ratio of the height of the highest absorption peak to that of the peak is 0.3 to 0.9.

[0045] By adopting the above technical solution, D 40 The absorption peak height at 0% of film thickness is related to D 40The ratio of the peak height at the highest absorption peak to the peak height indicates, to some extent, the changing trend of colloidal gold retention capacity in the region near the composite interface of the cellulose layer, and also indicates, to some extent, the "steepness" of the colloidal gold retention curve in this region.

[0046] When the ratio of the two is less than 0.3, it indicates that D 40 The absorption peak height at 0% of the film thickness is too small, and / or, D 40 If the height of the absorption peak is too high, whether it is due to insufficient colloidal gold retention in the pre-retention zone leading to excessive retention of colloidal gold particles in the fiber layer, or excessive retention of colloidal gold particles in the cellulose within a small area due to excessive retention capacity of colloidal gold in the fiber layer, it is easy to cause local blockage of the cellulose layer, which in turn leads to the composite antiviral membrane having a non-preferred and low service life.

[0047] Similarly, the ratio of the two should not be too high. When the ratio of the two is higher than 0.9, it indicates that D... 40 The absorption peak height at 0% of the film thickness is too large, and / or, D 40 If the height of the highest absorption peak is too small, whether it is due to the excessive retention of colloidal gold particles in the pre-retention zone caused by the excessive retention capacity of colloidal gold in the pre-retention zone, or the excessive dispersion of colloidal gold particles in the cellulose layer caused by the poor retention capacity of the cellulose layer, the colloidal gold particles are prone to leakage and blockage of the virus retention area in the cellulose layer. Both of these factors can easily lead to the composite virus removal membrane having a non-preferred and low service life.

[0048] Optionally, the D 40 The starting point is located in the region of -100% to -10% of the film thickness, and the D 40 The average height of the absorption peak from the starting point to 0% of the film thickness is less than that of D. 40 The height of the absorption peak located at 0% of the film thickness.

[0049] Optionally, the film-forming material of the microporous membrane support layer is nylon, and the D 40 The starting point is located in the region of -100% to -70% of the film thickness.

[0050] By adopting the above technical solution, the entire microporous membrane support layer has a large pore structure, and therefore has no obvious particle size exclusion effect (or pore size sieving effect) for colloidal gold particles with significantly smaller size. Therefore, when the microporous membrane support layer is selected with a film-forming material with weak adsorption effect, the microporous plate membrane support layer itself has a weak retention effect based on particle size exclusion or adsorption (adsorption can be of various types, such as hydrophilic adsorption, electrostatic adsorption, etc.). Therefore, the retention starting point of the composite virus removal membrane for colloidal gold is mainly located near the composite interface.

[0051] When the microporous membrane support layer is made of nylon, which has good adsorption properties (the same applies to other adsorption-based film-forming materials), even if the microporous membrane support layer does not have a significant particle size exclusion effect on colloidal gold, it can still retain colloidal gold through the adsorption mechanism. In this case, not only does the pre-retention zone have a pre-filtration effect on colloidal gold, but the entire microporous membrane support layer will also have the ability to retain colloidal gold. Therefore, when the microporous membrane support layer is made of materials such as nylon, the microporous membrane support layer has already played a more basic pre-filtration role before the pre-filtration effect of the pre-retention zone. This makes the composite virus removal membrane have a three-layer pre-filtration effect: "microporous membrane support layer pre-filtration", "primary pre-filtration of the pre-retention zone" and "secondary pre-filtration of the fiber layer", resulting in a significantly better loading capacity compared to ordinary composite membrane structures.

[0052] And D 40 The average height of the absorption peak from the starting point to 0% of the film thickness is less than D. 40 The absorption peak height located at 0% of the membrane thickness indicates that the pre-retention zone has a higher colloidal gold retention capacity than the microporous membrane support layer. This means that regardless of whether the microporous membrane support layer itself has colloidal gold retention capacity, the pre-retention zone can play a good primary pre-filtration role, thereby ensuring that the composite virus removal membrane has a high loading capacity.

[0053] Optionally, the D 40 The absorption peak height at 0% of the film thickness is related to the D 40 The ratio of the average absorption peak height from the starting point to the region with 0% film thickness is 1.1 to 3.

[0054] By adopting the above technical solution, based on the continuously improving colloidal gold retention effect in the pre-retention zone, the microporous membrane support layer's retention capacity for colloidal gold can further improve the loading capacity of the composite virus-removing membrane. However, the pre-filtration effect of the microporous membrane support layer should not be too strong, which is reflected in the colloidal gold absorption curve as D. 40 The absorption peak height at 0% of film thickness is related to D 40 The ratio of the average absorption peak height from the starting point to the region with 0% film thickness should not be less than 1.1; based on this, the ratio should be controlled to not exceed 3.

[0055] This is likely because the adsorption and retention mechanism of the microporous membrane support layer dictates that it not only has a certain adsorption capacity for impurity particles but also often exhibits a certain adsorption effect on active substances (such as proteins) to be recovered from the feed solution. Although the larger pore size of the microporous membrane support layer and the smaller particle size of the active substances (smaller than 40nm colloidal gold) mean that the adsorption capacity of the microporous membrane support layer for active substances is often lower, this may still reduce the yield of active substances, which is undesirable. Therefore, the ratio of the two should preferably be no less than 1.1 to avoid a decrease in the yield of active substances due to excessively high adsorption capacity of the microporous membrane support layer.

[0056] When the ratio of the two is greater than 3, it indicates that, based on the colloidal gold retention capacity of the microporous membrane support layer, the pre-retention zone has a stronger colloidal gold retention capacity than the entire microporous membrane support layer. However, the retention capacity of the pre-retention zone is much greater than that of the microporous membrane layer, which easily leads to concentrated retention in the pre-retention zone.

[0057] Therefore, a ratio of 1.1 to 3 indicates that the composite virus-removing membrane has a three-layer pre-filtration membrane pore structure with progressively increasing retention capacity, ensuring a high loading capacity. Furthermore, along the feed flow direction, the retention capacity of the microporous membrane support layer itself, the pre-retention zone within the microporous membrane support layer, and the cellulose layer for colloidal gold progressively increases, ensuring uniform dispersion of colloidal gold particles and significantly reducing the possibility of low loading capacity due to localized concentrated retention. This progressively increasing retention capacity also means that even with high colloidal gold particle dispersion, leakage to the cellulose layer's virus-retention area is unlikely. It is important to note that it is generally believed that higher colloidal gold particle dispersion increases the likelihood of leakage. However, to reduce the risk of leakage, increasing the concentration of colloidal gold particles often means a decrease in loading capacity. Therefore, there is a certain contradiction between high colloidal gold particle dispersion and low leakage risk. By controlling the ratio of the two to 1.1 to 3, the interception capacity can be gradually improved, enabling the composite virus-removing membrane to have both the effect of high dispersion of colloidal gold particles and the effect of preventing leakage of colloidal gold particles.

[0058] Optionally, the D 40 The average absorption peak height from the starting point to 0% of the film thickness and the D 40 The ratio of the absorption peak heights at the highest point of absorption is 0.2 to 0.5.

[0059] By adopting the above technical solution, when the ratio of the two is preferably controlled to be 0.2 to 0.5, it can further ensure that the area of ​​the fiber layer near the composite interface has good colloidal gold retention capacity, and ensure that although the microporous membrane support layer itself has a certain colloidal gold adsorption and retention capacity, the yield of active substances will not decrease due to excessive adsorption effect.

[0060] This is because if the ratio of the two is less than 0.2, it indicates that the highest value of the absorption peak of the colloidal gold rejection curve is too low and / or the absorption peak value of the colloidal gold rejection curve in the microporous membrane support layer is too high. If the highest value of the absorption peak of the colloidal gold rejection curve is too low, it means that the colloidal gold rejection capacity in the area of ​​the cellulose layer near the composite interface is insufficient. Larger colloidal gold particles may block the area of ​​the cellulose layer where viruses are rejected, thus leading to a rapid decrease in flux. If the absorption peak value of the colloidal gold rejection curve in the microporous membrane support layer is too high, it means that the microporous membrane support layer itself has a strong adsorption and rejection effect on colloidal gold particles, which may lead to a decrease in the yield of active substances.

[0061] If the ratio of the two is greater than 0.5, it indicates that the highest value of the absorption peak of the colloidal gold rejection curve is too high and / or the absorption peak value of the colloidal gold rejection curve in the microporous membrane support layer is too low. This will cause the cellulose layer to be quickly blocked due to its excessive colloidal gold rejection capacity, or the composite virus removal membrane will have a non-preferred loading capacity due to the low adsorption and retention effect of the microporous membrane support layer.

[0062] Optionally, the D 40 The height of the absorption peak located at 0% of the film thickness is not lower than that of D. 40 The absorption peak height from the starting point to any point in the region where the film thickness is 0%.

[0063] By adopting the above technical solution, in the entire microporous membrane support layer, except for some points that obviously violate the trend of the retention curve and are abnormally high (these points should be considered as noise and ignored), the area with the highest amount of colloidal gold retention is at the composite interface (that is, at 0% of the membrane thickness). In conjunction with the continuous rise of the colloidal gold retention curve in the pre-retention zone, it can be further explained that the colloidal gold retention capacity in the pre-retention zone does not only come from the adsorption and retention effect of the microporous membrane support layer, and this further improved colloidal gold retention capacity can further reduce the risk of colloidal gold leakage.

[0064] Optionally, the microporous membrane support layer is divided into ten regions of equal thickness, starting from the junction of the microporous membrane support layer and the cellulose layer, namely W1 to W10, where W1 is the pre-retention region, and D... 40 The absorption peak area located in the pre-retention region is larger than that of D. 40 The absorption peak area located in any region from W2 to W10.

[0065] By adopting the above technical solution, under the same membrane thickness, the pre-retention zone in the microporous membrane support layer has a higher colloidal gold retention capacity. Even if the microporous membrane support layer does not have an adsorption retention effect, the pre-retention zone can still play a good colloidal gold retention role, thereby increasing the load capacity of the composite virus removal membrane.

[0066] Optionally, the film-forming material of the microporous membrane support layer is nylon, and the standard deviation of the absorption peak areas of W2 to W8 is not greater than 0.3.

[0067] By adopting the above technical solution, when the film-forming material of the microporous membrane support layer is nylon, the microporous membrane support layer itself has a certain adsorption and retention effect, which is reflected in the colloidal gold rejection curves of W2 to W9 having a certain peak height, thus achieving a further pre-retention effect. Furthermore, the standard deviation of the absorption peak area of ​​W2 to W8 is no greater than 0.3, indicating that the colloidal gold rejection curves within W2 to W8 not only have a certain peak height, but the peak height differences are also not large, and the curves are relatively flat. This indicates that there is no concentrated rejection region for colloidal gold within W2 to W8, and also indicates that the adsorption and retention effect of the microporous membrane support layer is relatively stable.

[0068] Optionally, the D 40 In the middle, the region where the height of the absorption peak is not less than 0.85 times the peak height of the highest absorption peak is the concentrated retention region D. 集 D 集 The thickness and the D 40 The thickness ratio at the endpoint is 0.45 to 0.85.

[0069] By adopting the above technical solution, the centralized interception area D 集 It may be located solely within the cellulose layer, or it may include a portion of the cellulose layer and a portion of the pre-retention zone, regardless of the concentrated retention area D. 集 Regardless of its location, this area will inevitably trap a large number of colloidal gold particles. If the trapping area D is concentrated... 集 thickness and D 40 The thickness ratio at the endpoint is greater than 0.85, indicating that D 集 Excessive thickness and / or D 40 The thickness at the endpoint is too small, which means that the curve near the peak of the colloidal gold retention curve forms a relatively gentle plateau, and / or the colloidal gold retention curve reaches its endpoint rapidly within the cellulose layer. This indicates that the membrane pore structure near the peak of the colloidal gold retention curve not only has strong retention capacity but also a large thickness. A thick membrane pore structure with high retention capacity often also means greater resistance to the feed solution, resulting in lower flux of the composite virus removal membrane. If the concentrated retention area D... 集 thickness and D 40 The thickness ratio at the endpoint is less than 0.45, indicating that D 集 The thickness is too small and / or D 40 The excessive thickness at the endpoint of the colloidal gold retention curve, the relatively low thickness of the membrane pore structure near the peak of the colloidal gold retention curve, and the weak colloidal gold retention capacity of the downstream cellulose layer will greatly increase the risk of colloidal gold leakage.

[0070] Understandably, D 40 The thickness at the endpoint refers to the thickness within the cellulose layer from 0% thickness to D. 40 The absolute value of the thickness at the endpoint, and the intercepted region D. 集 The thickness refers to its absolute value, not the relative value of the thickness within each layer.

[0071] Optionally, in a wetted state, the virus-removing membrane retains 20 nm colloidal gold, and the region in the virus-removing membrane that captures 20 nm colloidal gold is D. 20 The D 20 Located in the region of 10-98% of the thickness of the cellulose layer membrane, the D 20 The ratio of the thickness of the cellulose layer to the thickness of the cellulose layer is 0.2 to 0.6.

[0072] By adopting the above technical solution, D 20 The region is located within the cellulose layer, and its thickness is 0.2–0.6 times the thickness of the cellulose layer, indicating that D… 20 The presence of a certain thickness in the region indicates that the 20nm colloidal gold has a relatively wide distribution range in the film thickness direction (thickness ratio greater than 0.2%), and is not concentrated in a small area. Therefore, it is less likely to cause filter membrane clogging and flux reduction due to concentrated retention in a small area. 20 The thickness ratio of the region should not be too large (e.g., greater than 0.6), because D 20 The excessive thickness of the region indicates a poor retention effect of the composite antiviral membrane on 20nm colloidal gold. This allows the 20nm colloidal gold to continuously permeate towards the liquid outlet of the filter membrane, resulting in a large-scale distribution of 20nm colloidal gold along the thickness direction of the filter membrane. 20 The thickness of the region is relatively high. However, because the pore size distribution of the filter membrane forms a near-normal distribution, smaller pores generally clog more quickly. In this case, the feed liquid can more easily permeate through the unclogged, larger pores, significantly increasing the risk of virus leakage and decreasing LRV (Liquidity Ratio). That is, D 20 If the thickness of the region is too small, the flux can easily decrease rapidly due to concentrated retention in a small area of ​​the filter membrane; while D 20 If the thickness of the region is too large, the large pore size of the filter membrane can increase the risk of virus leakage and reduce LRV.

[0073] In addition, D 20 The distribution of the region along the thickness direction of the composite virus-removing membrane cellulose layer should not be too close to the composite interface and the effluent surface (i.e., the retention area should not be less than 10% and not more than 98%). If D 20A region too close to the composite interface, while often indicating a high LRV (Liquidity Ratio) for the composite virus-removing membrane, also suggests that the small-pore structure of the membrane is too close to the interface. Small-pore structures offer greater resistance to the feed solution, often resulting in lower flux of the composite virus-removing membrane. If D 20 The area is too close to the liquid outlet, and D 20 The greater the thickness of the area, the higher the flux of the filter membrane, which often means a significantly increased risk of virus leakage.

[0074] Optionally, the D 40 The side closer to the liquid outlet surface and the D 20 The area between the liquid inlet and the liquid outlet is a transition zone, and the thickness of the transition zone is 0.05 to 0.3 times the thickness of the cellulose layer.

[0075] By adopting the above technical solution, the transition zone can be D. 40 and D 20 The partially overlapping area between them can also be located in D. 40 and D 20 In areas where they do not overlap, the ratio of the thickness of the transition zone to the thickness of the cellulose layer can preferably be controlled to be 0.05 to 0.3.

[0076] If the transition region is D 20 Region and D 40 The overlapping regions of the region, and D 20 Region and D 40 The overlapping area is large, which means that there are regions in the composite virus removal membrane that not only retain 40nm colloidal gold but also 20nm colloidal gold. Within this region, the 40nm and 20nm colloidal gold respectively block the pore structures of different sizes, which could potentially lead to localized blockage of the composite virus removal membrane and a rapid decrease in flux. If the transition region is located in D... 20 Region and D 40 Between regions, and D 20 Region and D 40 The large distance between the regions indicates that some areas in the composite virus-removing membrane fail to retain either 40nm or 20nm colloidal gold. While these areas can significantly reduce the impact of 40nm colloidal gold on the small-pore structure, excessively thick transition zones often create significant resistance to the feed solution, resulting in low flux of the composite virus-removing membrane. Therefore, the ratio of the transition zone thickness to the cellulose layer thickness can be preferably controlled between 0.05 and 0.3 to ensure both good pre-filtration performance and high flux with a low risk of virus leakage.

[0077] Optionally, the D 20The endpoint is located in the region where the film thickness is 50% to 95%.

[0078] By adopting the above technical solution, in order to reduce the leakage risk of 20nm colloidal gold, the retention area of ​​20nm colloidal gold cannot reach the liquid outlet surface of the filter membrane. Therefore, D 20 The endpoint should not be too close to the liquid outlet (more than 95%); while if D 20 The endpoint is located at a position where the membrane thickness is less than 50%. Although this can reduce the risk of virus leakage, it also means that there is a large thickness of membrane pore structure with virus interception capability in the cellulose layer. This part of the membrane pore structure with virus interception capability has a large resistance to the feed liquid, which often leads to the composite virus removal membrane having a low flux.

[0079] Optional, D 20 The highest absorption peak and the D 40 The ratio of the distance between endpoints to the thickness of the cellulose layer is 0.05 to 0.2.

[0080] By adopting the above technical solution, D 20 The highest absorption peak and D 40 The ratio of the distance between endpoints to the thickness of the cellulose layer can, to some extent, characterize the distance between the concentrated retention areas of 20nm colloidal gold and 40nm colloidal gold in the thickness direction of the microfiber layer, and also to some extent characterize the effect of 40nm colloidal gold on D. 20 The region may be affected, potentially leading to localized blockage of the composite virus-removing membrane.

[0081] If D 20 The highest absorption peak and D 40 If the distance between the endpoints is too small (e.g., the ratio is less than 0.05), it means that D... 20 The curve rises rapidly and is quite steep, indicating that a large amount of 20nm colloidal gold is trapped within a small thickness range. Furthermore, the areas within the cellulose layer that trap viruses often have small pore sizes and low porosity, resulting in low contaminant holding capacity. The large amount of trapped colloidal gold will quickly clog the already limited membrane pore structure, leading to a decrease in loading capacity. In addition, once 40nm colloidal gold leaks, it can rapidly leak to D... 20 The highest absorption peak is located at this point, thus easily having a significant impact on flux. However, if D... 20 The highest absorption peak and D 40 If the distance between endpoints is too large (e.g., the ratio is greater than 0.2), although 40nm colloidal gold requires a relatively thick film structure to pass through after leakage, it will not be able to reach D. 20 It has an impact, but D 20 The curve rises in a relatively gentle manner, meaning that D... 40The membrane structure after the endpoint exhibits weaker retention capacity for 20nm colloidal gold, which also often implies weaker retention capacity for 40nm colloidal gold in this region. This means that 40nm colloidal gold still has a relatively high probability of penetrating into the D region. 20 The highest absorption peak is located at the membrane pore structure, leading to blockage of the membrane pore structure at that point.

[0082] Optionally, the D 20 In the middle, the region where the height of the absorption peak is not less than 0.85 times the peak height of the highest absorption peak is the region with a large amount of retention (D). 大 D 大 The thickness and the D 40 The thickness ratio at the endpoint is 0.2 to 0.7.

[0083] By adopting the above technical solution, in D 20 Regions with a peak capture rate greater than 0.85 times are considered to be areas of significant retention. Within these regions, a large amount of 20nm colloidal gold is retained. If the thickness of the significant retention region is greater than D... 40 If the thickness ratio at the endpoint is too small (e.g., less than 0.2), it indicates that a large amount of 20nm colloidal gold is trapped in a small, concentrated area. 20 The pore size of the region is already small; therefore, concentrated retention in a small area can easily lead to localized blockage of the composite virus removal membrane, resulting in a rapid decrease in flux. If the thickness of a large retention area is similar to D... 40 A high thickness-to-weight ratio at the endpoint (e.g., greater than 0.7) indicates that a large amount of the intercepted region forms a plateau-like absorption curve, suggesting that 20nm colloidal gold can pass through the D-phase relatively smoothly. 20 The small-aperture pore structure in the region greatly increases the risk of leakage of 20nm colloidal gold.

[0084] Understandably, D 40 The thickness at the endpoint refers to the thickness within the cellulose layer from 0% thickness to D. 40 The absolute value of the thickness at the endpoint.

[0085] Secondly, this application provides a preparation process for a cellulose composite virus-removing membrane, employing the following technical solution:

[0086] A process for preparing a cellulose composite virus-removing membrane includes the following steps:

[0087] S1. Preparation of casting solutions: Small-pore casting solution and macropore casting solution are prepared separately. The small-pore casting solution includes a small-pore film-forming polymer and a small-pore diluent. The macropore casting solution includes a macropore film-forming polymer and a macropore diluent. Both the small-pore film-forming polymer and the macropore film-forming polymer are made from cellulose-based raw materials. The solid content of the macropore casting solution is 10-18%, and the solid content of the small-pore casting solution is 20-30%.

[0088] S2. Casting film: Small-pore casting liquid and macropore casting liquid are sequentially cast onto a carrier to form a double-layer liquid film. Then, a microporous membrane support layer is conveyed by a conveyor roller to cover and composite the double-layer liquid film, obtaining a composite semi-finished film. The covering process of the microporous membrane support layer satisfies the composite coefficient F of 1 to 1.25. The composite coefficient F is calculated by the following formula: F = (h1 + h2) / h3; where h1 is the thickness of the double-layer liquid film, h2 is the thickness of the microporous membrane support layer, and h3 is the minimum distance between the conveyor roller and the carrier.

[0089] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is transported to a pretreatment atmosphere for pretreatment to obtain a pretreated membrane. The pretreatment atmosphere is a good solvent vapor of macroporous film-forming polymer.

[0090] S4. Curing: Immerse the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and cured to obtain a green film. The coagulation bath is at least one of water or ethanol.

[0091] S5. Post-treatment: Place the raw membrane in a regeneration bath to hydrolyze and regenerate the raw membrane, obtaining a cellulose virus-removing membrane.

[0092] By adopting the above-mentioned technical solutions, the current membrane fabrication process for composite membranes with support layers generally involves directly coating a casting solution onto the microporous membrane support layer, followed by a series of post-processing steps to obtain the desired composite membrane. For example, Chinese invention patent CN1108853C explicitly describes a process of preparing a polymer solution (i.e., casting solution) with a mass concentration of approximately 8–25% of cellulose ester or cellulose polymer, applying the prepared casting solution to a microporous substrate, and controlling the coating thickness to form a dry membrane 1–20 μm thick on the microporous substrate. While this membrane fabrication process can produce composite membranes with good pressure resistance, as the thickness of the casting solution increases, the pressure resistance of the composite membrane improves, but the loading capacity and flux of the composite membrane often decrease significantly.

[0093] This application employs a specific support layer back cover + roll forming process. First, a double-layer casting solution is poured onto the carrier. A macroporous casting solution with a relatively low solids content forms the region within the cellulose layer that traps impurities (such as impurities with a particle size similar to 40nm colloidal gold), while a microporous casting solution with a relatively high solids content forms the region within the cellulose layer that traps viruses (such as viruses with a particle size similar to 20nm colloidal gold). Because the thickness of the double-layer casting solution can be easily adjusted, such as by controlling the width of the slits during casting, the thickness ratio of each region within the cellulose layer can be controlled. Specifically, the membrane pore structure formed by the microporous casting solution with a solids content of 20-30% ensures good trapping effect of the composite antiviral membrane for small viruses, while the membrane pore structure formed by the macroporous casting solution with a solids content of 10-18% ensures that the cellulose layer has regions with good trapping effect for impurities.

[0094] Based on the double-layer casting method, this application employs a roller pressing process to control the composite coefficient F during the composite process. This allows the conveying rollers to apply force to the microporous membrane support layer, promoting interpenetration between the microporous membrane support layer and the macroporous casting solution. This interpenetrating structure, after phase separation and solidification, possesses a certain 40nm colloidal gold retention capacity, thus enabling the microporous membrane support layer to have a pre-filtration effect before the cellulose layer. Specifically, the composite coefficient F in this application should not be too large or too small. If the composite coefficient F is less than 1, it indicates that the conveying rollers are not applying force to the microporous membrane support layer, and the microporous membrane support layer is embedded into the macroporous casting solution solely by its own gravity. This can easily lead to insufficient interpenetration between the macroporous casting solution and the microporous membrane support layer (especially when the solid content of the macroporous casting solution is high), resulting in insufficient pressure resistance of the composite virus-removing membrane. If the composite coefficient F is greater than 1.25, it indicates that the conveying roller applies a large force to the microporous membrane support layer, promoting the mutual penetration between the microporous membrane support layer and the macroporous casting liquid. Since the double liquid film is still in a liquid state at this time, the large pushing force of the microporous membrane support layer under the action of excessive external force may cause the double liquid film to be over-compressed and produce defects.

[0095] Furthermore, since the film-forming polymers of the two casting solutions forming the cellulose layer in the composite virus-removing membrane of this application are both cellulose-based materials, and cellulose-based materials inherently have the defect of being difficult to open pores, they easily form a dense skin structure with low porosity and small pore size. By treating the macroporous casting solution with good solvent vapor, the good solvent vapor is absorbed by the macroporous casting solution, forming a further concentration gradient in the macroporous casting solution. That is, the closer to the external atmosphere, the lower the solid content of the macroporous casting solution, and the easier it is to form a membrane pore structure with a larger pore size during phase separation and solidification. Moreover, the size of this membrane pore structure often changes with the change of the concentration gradient of the macroporous casting solution. This part of the membrane pore structure with a larger pore size has a large dirt holding capacity and can hold a large number of impurity particles. Furthermore, the gradient membrane pore structure can improve the dispersion of impurity particles and reduce the possibility of blockage caused by concentrated retention.

[0096] Therefore, a specific rolling process combined with a specific good solvent vapor pretreatment process can ensure that there is a permeation zone of macroporous casting solution in the microporous membrane support layer and form a concentration gradient change, so that the pre-retention zone of the microporous membrane support layer has a good pre-filtration effect and ensures that the composite virus removal membrane has a good loading capacity.

[0097] It should be noted that if the conventional preparation process of sequentially casting macroporous and microporous membrane casting liquids onto the microporous membrane support layer (i.e., the support layer cover process not described in this application) is adopted, the resulting composite virus-removing membrane is likely to have a low viral load.

[0098] In addition, the preparation process of coating the casting solution onto the microporous membrane support layer has certain drawbacks. For example, when the casting solution penetrates into the microporous membrane support layer, it inevitably squeezes the air in the pore structure of the microporous membrane support layer, causing this air to be expelled. The air tends to be expelled upwards, and the casting solution above the microporous membrane support layer has a higher viscosity. This air cannot easily pass through the casting solution, and the air bubbles in the casting solution become large pore defects in the membrane layer after the casting solution solidifies (which is why the casting solution is often degassed before casting). Therefore, the preparation process of coating the casting solution on top can easily introduce defects into the membrane layer, affecting the virus interception effect.

[0099] As mentioned earlier, it is difficult to create pores on the surface of cellulose-based raw materials. Furthermore, the casting process, where the casting solution is coated on top, means that even with pretreatment, the microporous membrane support layer is located on the carrier side. The pretreatment system cannot penetrate this layer because its pores are obscured. The pretreatment system would need to penetrate the entire casting solution layer to pretreat the interface between the casting solution and the microporous membrane support layer, which is impractical. Therefore, even with pretreatment, a larger pore size can only be obtained on the side of the casting solution furthest from the microporous membrane support layer. This is one of the reasons why Chinese invention patent CN1108853C explicitly states that the greater the thickness of the permeation layer, the lower the flux.

[0100] Optionally, in step S2, the covering process of the microporous membrane support layer satisfies a composite coefficient F of 1.05 to 1.15; in step S3, the temperature of the pretreatment atmosphere is 30 to 60°C higher than the temperature of the composite semi-finished membrane, and the residence time of the composite semi-finished membrane in the pretreatment atmosphere is 40 to 60 seconds.

[0101] By adopting the above technical solution, and further optimizing and controlling the composite coefficient F to 1.05–1.15, the mutual permeation thickness between the microporous membrane support layer and the macroporous casting solution can be further controlled. To ensure that the macroporous casting solution permeating the microporous membrane support layer forms the required concentration gradient, it needs to be treated in a pretreatment atmosphere for a sufficient time (not less than 40 seconds) to ensure that although the pre-retention layer in the composite virus-removing membrane has good impurity retention capacity, it does not lead to concentrated retention of impurity particles due to abrupt changes in pore size, as reflected in D. 40 The highest absorption peak is located within the cellulose layer, not within the pre-retention zone. Furthermore, the residence time of the composite semi-finished membrane in the pretreatment atmosphere should not be too long (e.g., exceeding 60 seconds), to prevent excessive dilution of the macroporous casting solution penetrating the microporous membrane support layer, and even excessive dilution of the macroporous casting solution located within the cellulose layer. This would cause the pre-retention zone to almost lose its ability to retain impurity particles (without considering the adsorption and retention effect of the microporous membrane support layer itself).

[0102] Optionally, in step S2, both the small-pore casting solution and the large-pore casting solution are at 30-40°C, and the temperature of the carrier is 40-60°C.

[0103] By adopting the above technical solution, both the small-pore casting solution and the large-pore casting solution have temperatures higher than room temperature, and the temperature of the carrier is not lower than that of the cast double-layer liquid film. As the temperature of the double-layer liquid film increases, its viscosity decreases. Furthermore, due to the high temperature of the double-layer liquid film itself, the carrier acts as a heat-insulating and appropriately heating agent, which can reduce the viscosity gradient along the thickness direction of the double-layer liquid film to a certain extent. Specifically, based on a solid content of 10–18% and a composite coefficient F of 1–1.25 for the large-pore casting solution, further controlling the temperature of the double-layer liquid film to adjust its viscosity, especially that of the large-pore casting solution, can appropriately reduce the resistance to the large-pore casting solution penetrating into the microporous membrane support layer. Of course, the carrier temperature should not be too high (e.g., above 60℃) to avoid excessively low viscosity of the double-layer liquid film, which would lead to a decrease in the dimensional stability of the double-layer liquid film. Especially after the microporous membrane support layer is compressed and the force is transferred to the double-layer liquid film, if the viscosity of the double-layer liquid film is too low, resulting in poor self-support, membrane defects may occur under the force of the microporous membrane support layer.

[0104] Optionally, step S3 further includes a cooling step, specifically, conveying the carrier loaded with the pretreated membrane to a cooling atmosphere at a temperature of 10-20°C for a cooling time of 5-10 seconds, wherein the cooling atmosphere is air or an inert gas.

[0105] Optionally, the cellulose raw material is at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, and cellulose acetate propionate.

[0106] Both the microporous diluent and the macroporous diluent are selected from good solvents of cellulose raw materials. The good solvent is at least one of acetone, dioxane, dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), acetic acid, propionic acid, butyric acid, and valeric acid.

[0107] By employing the above technical solution, during the composite process of the bilayer liquid membrane and the microporous membrane support layer, the thickness of the macroporous casting solution penetrating into the microporous membrane support layer can be effectively controlled by adjusting the temperature of the bilayer liquid membrane and the composite coefficient F. During pretreatment, the temperature of the composite membrane also needs to be appropriately controlled to prevent the viscosity of the macroporous casting solution from being too low at low temperatures, which would hinder the penetration and dilution of the coagulated good solvent, thus making it difficult to form a concentration gradient along the thickness direction of the macroporous casting solution within the microporous membrane support layer. However, after composite formation and pretreatment, the microporous membrane support layer inevitably continues to embed into the macroporous casting solution under its own gravity. Because this process is relatively uncontrollable, it not only easily leads to uncontrollable thickness of the macroporous casting solution penetrating into the microporous membrane support layer, resulting in unpredictable impurity particle retention capacity in the pre-retention zone (such as excessive retention leading to local blockage), but also easily causes over-permeation, affecting the virus retention capacity of the composite virus-removing membrane. In particular, since the macroporous casting solution that continues to penetrate into the microporous membrane support layer after pretreatment is not further diluted, during subsequent phase separation and solidification, it is easier to form a relatively dense structure under the constraint of the cavity formed by the microporous membrane support layer, resulting in a more concentrated and large-scale retention of impurity particles.

[0108] Based on the aforementioned problems, the inventors of this application further optimized the cooling treatment of the pretreated membrane obtained after pretreatment. During a short cooling time (at least 5 seconds) and at a low temperature (not exceeding 20°C), the microporous membrane support layer and the area of ​​the bilayer liquid film near the microporous membrane support layer rapidly cool down. Consequently, the viscosity of the casting solution in this area rapidly increases, thereby reducing the possibility that the microporous membrane support layer will continuously embed itself into the macroporous casting solution due to its own gravity after pretreatment. Of course, the cooling time should not be too long (more than 10 seconds) and the treatment temperature should not be too low (below 10°C) to avoid excessive temperature drop in the overall temperature of the pretreated membrane, resulting in excessively high viscosity of the casting solution, which would affect the subsequent phase separation and solidification step in the coagulation bath. In addition, the cooling treatment after pretreatment also promotes the condensation of good solvent vapor and better dilutes the macroporous casting solution within the microporous membrane support layer, thus better forming a concentration gradient. Therefore, the cooling treatment after pretreatment has the combined effects of reducing excessive embedding of the microporous membrane support layer and improving the pre-phase separation effect.

[0109] In summary, this application includes at least one of the following beneficial technical effects:

[0110] 1. The composite virus removal membrane of this application introduces a pre-retention region with the ability to retain 40nm colloidal gold in the region near the composite interface of the microporous membrane support layer, and controls the retention peak region of 40nm colloidal gold to be located in the cellulose layer. This ensures that the pre-retention region has the ability to retain impurities but does not cause concentrated and large-scale impurity retention, so that large-particle impurities are dispersed and retained in the pre-retention region and the cellulose layer. This ensures that the composite virus removal membrane not only has high pressure resistance but also a long service life.

[0111] 2. By further controlling the amount of 40nm colloidal gold retained in the high-efficiency retention zone of the cellulose layer to be higher than that in the pre-retention zone, this application can ensure that the pre-retention zone plays a primary pre-filtration role and also ensure that impurity particles are stably retained in the cellulose layer near the high-efficiency retention zone, which greatly reduces the possibility of impurity particles leaking into the area of ​​the cellulose layer that plays a role in virus retention. Attached Figure Description

[0112] Figure 1 This is a graph showing the retention curve of 40nm colloidal gold in the thickness direction of the composite virus-removing membrane in Example 1 of this application after it retains 40nm of colloidal gold.

[0113] Figure 2 This is a curve showing the retention of 20nm colloidal gold in the thickness direction of the composite virus-removing membrane in Embodiment 1 of this application after it retains 20nm colloidal gold. It should be noted that since the microporous membrane support layer does not retain 20nm colloidal gold, only the 20nm colloidal gold retention curve of the cellulose layer is shown in the figure.

[0114] Figure 3 This is a graph showing the retention curve of 40nm colloidal gold in the thickness direction after the composite virus-removing membrane in Embodiment 2 of this application retains 40nm colloidal gold.

[0115] Figure 4 This is a graph showing the retention curve of 20nm colloidal gold in the thickness direction of the composite virus-removing membrane in Embodiment 2 of this application after it retains 20nm colloidal gold. It should be noted that since the microporous membrane support layer does not retain 20nm colloidal gold, the graph only shows the 20nm colloidal gold retention curve of the cellulose layer.

[0116] Figure 5 This is a scanning electron microscope (SEM) image of the liquid inlet surface after the composite virus-removing membrane in Example 1 of this application retains 40nm colloidal gold. The white particles in the image are 40nm colloidal gold, and the magnification in the image is 20000×.

[0117] Figure 6 This is a cross-sectional scanning electron microscope image of the composite virus-removing membrane after it retains 40nm colloidal gold in Example 1 of this application. It is used to demonstrate the 40nm colloidal gold retention behavior in the pre-retention area. The white particles in the image are 40nm colloidal gold, and the magnification in the image is 10000×.

[0118] Figure 7 This is a cross-sectional scanning electron microscope (SEM) image of the composite virus-removing membrane near the liquid inlet surface after it retains 40nm colloidal gold in Example 2 of this application. The white particles in the image are 40nm colloidal gold, and the magnification in the image is 20000×.

[0119] Figure 8 This is a cross-sectional scanning electron microscope image of the composite virus-removing membrane after it retains 40nm colloidal gold in Example 2 of this application. It is used to demonstrate the 40nm colloidal gold retention behavior in the pre-retention area. The white particles in the image are 40nm colloidal gold, and the magnification in the image is 20000×. Detailed Implementation

[0120] The following is in conjunction with the appendix Figures 1-8 This application will be described in further detail.

[0121] This application discloses a cellulose composite virus-removing membrane and its preparation process.

[0122] Example 1

[0123] This embodiment discloses a preparation process for a cellulose composite virus-removing membrane, including the following process steps:

[0124] S1. Preparation of casting solutions: Prepare small-pore casting solutions and macro-pore casting solutions separately. The small-pore casting solution includes a small-pore film-forming polymer and a small-pore diluent. The macro-pore casting solution includes a macro-pore film-forming polymer and a macro-pore diluent. Both the small-pore and macro-pore film-forming polymers are made of cellulose diacetate. For other formulations and parameters, please refer to Table 1.

[0125] S2. Casting and Film Formation: Small-pore and large-pore casting solutions are sequentially cast onto a carrier to form a double-layer liquid film. During casting, the temperatures of both the large-pore and small-pore solutions are controlled at 35°C. In this embodiment, the carrier is a steel strip, and its temperature is controlled at 50°C. The film-forming material of the microporous membrane support layer is nylon. After obtaining the double-layer liquid film, a microporous membrane support layer is conveyed onto the double-layer liquid film via a conveyor roller to obtain a composite semi-finished film. The covering process of the microporous membrane support layer satisfies a composite coefficient F of 1.13, which is calculated using the following formula: F = (h1 + h2) / h3; where h1 is the thickness of the double-layer liquid film, h2 is the thickness of the microporous membrane support layer, and h3 is the minimum distance between the conveyor roller and the carrier. The microporous membrane support layer's own gravity and the downward pressure provided by the conveyor roller promote mutual penetration between the microporous membrane support layer and the large-pore casting solution.

[0126] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is transported to a pretreatment atmosphere for pretreatment to obtain a pretreated membrane. In this embodiment, the pretreatment atmosphere is a DMAC vapor atmosphere, and the temperature of the pretreatment atmosphere is 40°C higher than the temperature of the composite semi-finished membrane. The residence time of the composite semi-finished membrane in the pretreatment atmosphere is 50 seconds. After the pretreatment atmosphere treatment is completed, the carrier loaded with the pretreated membrane is transported to a cooling atmosphere at a temperature of 15°C for cooling treatment for 7 seconds. In this embodiment, the cooling atmosphere is air.

[0127] S4. Curing: Immerse the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and cured to obtain a green membrane. In this embodiment, the coagulation bath is water.

[0128] S5. Post-treatment: The raw membrane is placed in a regeneration bath to hydrolyze and regenerate. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral to obtain a cellulose virus-removing membrane. In this embodiment, the regeneration bath uses a 0.05 mol / L sodium hydroxide aqueous solution at a temperature of 50°C, and the raw membrane is hydrolyzed and regenerated in the regeneration bath for 120 min.

[0129] Examples 2-6

[0130] The main difference between Examples 2-6 and Example 1 is that the formulation of the casting solution and the process parameters of each process are different, as detailed in Table 1.

[0131] Comparative Example 1

[0132] The main difference between Comparative Example 1 and the embodiments lies in the film-forming process of casting a single layer of casting solution onto a microporous membrane support layer, and the pretreatment of the casting solution cast onto the microporous membrane support layer to create a concentration gradient in the thickness direction of the casting solution. It should be noted that in this comparative example, the inlet surface of the composite virus-removing membrane is the side of the cellulose layer away from the microporous membrane support layer, while the outlet surface is the side of the microporous membrane support layer adjacent to the cellulose layer. The specific preparation process is as follows:

[0133] S1. Preparation of casting solution: The casting solution is prepared. The formula and parameters of the casting solution are detailed in Table 1.

[0134] S2. Casting film: First, the microporous membrane support layer is placed on the carrier, and the prepared casting liquid is cast onto the microporous membrane support layer to form a liquid film, thus obtaining a composite semi-finished film. In this comparative example, the carrier is a steel strip and the temperature is 50°C. The film-forming material of the microporous membrane support layer is nylon.

[0135] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is transported to a pretreatment atmosphere for pretreatment to obtain a pretreated membrane. In this comparative example, the pretreatment atmosphere is a DMAC vapor atmosphere, and the temperature of the pretreatment atmosphere is 40°C higher than the temperature of the composite semi-finished membrane. The residence time of the composite semi-finished membrane in the pretreatment atmosphere is 50 seconds. No cooling treatment is performed after pretreatment to allow the casting solution to better penetrate into the microporous membrane support layer.

[0136] S4. Curing: Immerse the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and cured to obtain a green membrane. In this embodiment, the coagulation bath is water.

[0137] S5. Post-treatment: The raw membrane is placed in a regeneration bath to hydrolyze and regenerate. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral to obtain a cellulose virus-removing membrane. In this embodiment, the regeneration bath uses a 0.05 mol / L sodium hydroxide aqueous solution at a temperature of 50°C, and the raw membrane is hydrolyzed and regenerated in the regeneration bath for 120 min.

[0138] Comparative Example 2

[0139] The main difference between Comparative Example 2 and Example 1 is that Comparative Example 2 uses a larger composite coefficient when combining the double-layer liquid film and the microporous membrane support layer, and uses a shorter treatment time and a lower treatment temperature during the good solvent vapor pretreatment. The specific preparation process is as follows:

[0140] S1. Preparation of casting solutions: Prepare small-pore casting solutions and macro-pore casting solutions separately. The small-pore casting solution includes a small-pore film-forming polymer and a small-pore diluent. The macro-pore casting solution includes a macro-pore film-forming polymer and a macro-pore diluent. Both the small-pore and macro-pore film-forming polymers are made of cellulose diacetate. For other formulations and parameters, please refer to Table 1.

[0141] S2. Casting and Film Formation: Small-pore and large-pore casting solutions are sequentially cast onto a carrier to form a double-layer liquid film. During casting, the temperatures of both the large-pore and small-pore solutions are controlled at 35°C. In this embodiment, the carrier is a steel strip, and its temperature is controlled at 40°C. The film-forming material of the microporous membrane support layer is nylon. After obtaining the double-layer liquid film, a microporous membrane support layer is conveyed onto the double-layer liquid film via a conveyor roller to obtain a composite semi-finished film. The covering process of the microporous membrane support layer satisfies a composite coefficient F of 1.5.

[0142] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is transported to a pretreatment atmosphere for pretreatment to obtain a pretreated membrane. In this embodiment, the pretreatment atmosphere is a DMAC vapor atmosphere, and the temperature of the pretreatment atmosphere is 10°C higher than the temperature of the composite semi-finished membrane. The residence time of the composite semi-finished membrane in the pretreatment atmosphere is 20 seconds. No cooling treatment is performed after the pretreatment.

[0143] S4. Curing: Immerse the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and cured to obtain a green membrane. In this embodiment, the coagulation bath is water.

[0144] S5. Post-treatment: The raw membrane is placed in a regeneration bath to hydrolyze and regenerate. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral to obtain a cellulose virus-removing membrane. In this embodiment, the regeneration bath uses a 0.05 mol / L sodium hydroxide aqueous solution at a temperature of 50°C, and the raw membrane is hydrolyzed and regenerated in the regeneration bath for 120 min.

[0145] Table 1. Casting solution formulations and process parameters for each embodiment and comparative example.

[0146]

[0147]

[0148] It should be noted that, since a single-layer casting solution was used in Comparative Example 1, its formula is recorded as a small-hole casting solution in Table 1 for ease of understanding.

[0149] I. Virus Challenge Test

[0150] The viral challenge test was performed in accordance with the relevant provisions in PDA TR41, with the model virus being PP7 bacteriophage or hepatitis B virus, the model protein being IVIG, and the buffer being PBS. During the test, the changes in flux and load over time were recorded to obtain the LRV, flux, and load of the filter membrane.

[0151] II. Colloidal Gold Retention Test

[0152] The specific scheme for the colloidal gold retention test is recorded in the invention content section and will not be repeated here.

[0153] The colloidal gold retention data for each embodiment and comparative example are recorded in Table 2:

[0154] Table 2 Colloidal gold retention data for each example and comparative example.

[0155]

[0156]

[0157] Table 2 does not record the colloidal gold retention data for Comparative Example 1. This is because the inlet and outlet surfaces of the composite antiviral membrane in Comparative Example 1 are reversed compared to those in the other examples, making it impossible to characterize using the aforementioned parameters. During the 40nm and 20nm colloidal gold retention tests, the side of the cellulose layer furthest from the microporous membrane support layer was designated as the inlet surface, and this surface was taken as the 0% membrane thickness position. The interface between the cellulose layer and the microporous membrane support layer, i.e., the composite interface, was taken as the 100% membrane thickness position. Wherein, D... 40 Located at 5%–17% of the film thickness, while D 20 Located at 15%–43%, the area in the composite membrane that pre-retains impurity particles has a relatively low proportion.

[0158] The virus retention data of the filter membranes in each embodiment and comparative example are recorded in Table 3:

[0159] Table 3. Virus retention data for each embodiment and comparative example.

[0160] Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 LRV 7.5 7.8 6.4 >8 7.2 7.9 >8 >8 <![CDATA[Flux / L / (h·m 2 )]]> 102 94 127 77 114 84 23 45 <![CDATA[Loading amount / L / m 2 > 466 438 442 347 279 454 124 234

[0161] in conclusion

[0162] By comparing the technical solutions and performance data of various embodiments and Comparative Example 1, it is easy to find that, compared with the double-layer casting + microporous membrane support layer back cover composite process, the composite virus-removing membrane prepared by directly casting a single layer of casting liquid on the microporous membrane support layer has good LRV and pressure resistance (the introduction of the microporous membrane support layer inevitably leads to an improvement in pressure resistance), but its flux and loading capacity are both low. This may be because, in Comparative Example 1, after the casting liquid penetrates into the microporous membrane support layer, the pretreatment atmosphere during pretreatment cannot penetrate the entire casting liquid layer to pretreat the casting liquid at the composite interface. Under the constraint of the pore structure of the microporous membrane support layer, the structure formed by the casting liquid in the microporous membrane support layer will block the pore structure of the microporous membrane support layer. Furthermore, the pretreatment effect of the pretreatment atmosphere on the single layer of casting liquid is insufficient to form a pre-retention structure of sufficient thickness, ultimately resulting in the composite virus-removing membrane having low flux and loading capacity.

[0163] By comparing the technical solutions and performance data of Example 1 and Comparative Example 2, it is easy to see that an excessively high composite coefficient (e.g., too large) and pretreatment process (too low temperature, too short pretreatment time) will result in a significantly lower flux and loading capacity of the prepared composite virus-removing membrane. This may be because, under a large composite coefficient, a large amount of macroporous casting solution is forced into the microporous membrane support layer. However, due to insufficient pretreatment time and low temperature, the pretreatment atmosphere is insufficient to effectively dilute the macroporous casting solution that has penetrated into the microporous membrane support layer. Under the constraint of the pore structure of the microporous membrane support layer, the macroporous casting solution forms a relatively dense pore structure. Therefore, D 40 The highest and lowest absorption peaks are both located within the microporous membrane support layer, which means that a relatively large number of particles are concentrated and trapped within the microporous membrane support layer, resulting in a decrease in flux and loading.

[0164] By comparing the technical solutions and performance data of Examples 1 and 4, as well as Comparative Examples 1-2, it is not difficult to find that although the peak area ratio of the absorption peaks of the high-efficiency retention zone and the pre-retention zone of the composite virus-removing membrane in Example 4 is less than 1 (of course, there are also influences such as the use of PP as a microporous membrane support layer), it has a lower flux and load capacity than Example 1, but it still has a significantly higher flux and load capacity than Comparative Examples 1-2.

[0165] Similarly, by comparing the technical solutions and performance data of Examples 1 and 5 and Comparative Examples 1-2, it is not difficult to find that although the pre-filtration effect of the pre-retention zone of the composite virus-removing membrane in Example 5 is worse than that in Example 1 and has a lower load, it still has a significantly higher flux and load than Comparative Examples 1-2.

[0166] 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. A cellulose composite virus-removing membrane, characterized in that: It includes a microporous membrane support layer and a cellulose layer. The side of the microporous membrane support layer away from the cellulose layer is the liquid inlet surface, and the side of the cellulose layer away from the microporous membrane support layer is the liquid outlet surface. Both the microporous membrane support layer and the cellulose layer have non-directional tortuous pathways, and the microporous membrane support layer and the cellulose layer are connected through non-directional tortuous pathways. In a wetted state, the virus-removing membrane traps 40nm colloidal gold. The region in the virus-removing membrane that traps 40nm colloidal gold is D. 40 The junction of the microporous membrane support layer and the cellulose layer is taken as the position of 0% membrane thickness, the liquid inlet surface of the virus-removing membrane is taken as the position of -100% membrane thickness, and the liquid outlet surface of the virus-removing membrane is taken as the position of 100% membrane thickness. The region of membrane thickness from -10% to 0% is the pre-retention zone, and D is located within the pre-retention zone. 40 The height of the absorption peak gradually increases; The D 40 The highest absorption peak is located in the region of 1% to 40% of the film thickness.

2. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The region of the cellulose layer that is close to the microporous membrane support layer and has the same thickness as the pre-retention zone is the high-efficiency retention zone, and the absorption peak area of ​​the high-efficiency retention zone is larger than the absorption peak area of ​​the pre-retention zone.

3. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The D 40 The endpoint is located in the region where the film thickness is 15% to 60%.

4. The cellulose composite virus-removing membrane according to claim 3, characterized in that: The D 40 The ratio of the distance between the highest and lowest absorption peaks to the thickness of the cellulose layer is 0.05 to 0.

5.

5. The cellulose composite antiviral membrane according to claim 1, characterized in that: The D 40 The absorption peak height at 0% of film thickness is related to D 40 The ratio of the absorption peak heights located at -10% of the film thickness is not less than 1.

3.

6. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The D 40 The absorption peak height at 0% of the film thickness is related to the D 40 The ratio of the height of the highest absorption peak to that of the peak is 0.3 to 0.

9.

7. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The D 40 The starting point is located in the region of -100% to -10% of the film thickness, and the D 40 The average height of the absorption peak from the starting point to 0% of the film thickness is less than that of D. 40 The height of the absorption peak located at 0% of the film thickness.

8. The cellulose composite virus-removing membrane according to claim 7, characterized in that: The D 40 The absorption peak height at 0% of the film thickness is related to the D 40 The ratio of the average absorption peak height from the starting point to the region with 0% film thickness is 1.1 to 3.

9. The cellulose composite virus-removing membrane according to claim 7, characterized in that: The D 40 The average absorption peak height from the starting point to 0% of the film thickness and the D 40 The ratio of the absorption peak heights at the highest point of absorption is 0.2 to 0.

5.

10. The cellulose composite virus-removing membrane according to claim 7, characterized in that: The D 40 The height of the absorption peak located at 0% of the film thickness is not lower than that of D. 40 The absorption peak height from the starting point to any point in the region where the film thickness is 0%.

11. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The microporous membrane support layer is divided into ten regions of equal thickness, starting from the junction of the microporous membrane support layer and the cellulose layer, and labeled W1 to W10, with W1 being the pre-retention region. 40 The absorption peak area located in the pre-retention region is larger than that of D. 40 The absorption peak area located in any region from W2 to W10.

12. The cellulose composite virus-removing membrane according to claim 11, characterized in that: The microporous membrane support layer is made of nylon, and the standard deviation of the absorption peak areas of W2 to W8 is no greater than 0.

3.

13. The cellulose composite virus-removing membrane according to claim 1, characterized in that: The D 40 In the middle, the region where the height of the absorption peak is not less than 0.85 times the peak height of the highest absorption peak is the concentrated retention region D. 集 D 集 The thickness and the D 40 The thickness ratio at the endpoint is 0.45 to 0.

85.

14. The cellulose composite virus-removing membrane according to claim 1, characterized in that: In a wetted state, the virus-removing membrane traps 20nm colloidal gold. The region in the virus-removing membrane that captures 20nm colloidal gold is D. 20 The D 20 Located in the region of 10-90% of the thickness of the cellulose layer membrane, the D 20 The ratio of the thickness of the cellulose layer to the thickness of the cellulose layer is 0.2 to 0.

6.

15. The cellulose composite virus-removing membrane according to claim 14, characterized in that: The D 40 The side closer to the liquid outlet surface and the D 20 The area between the liquid inlet and the liquid outlet is a transition zone, and the thickness of the transition zone is 0.05 to 0.3 times the thickness of the cellulose layer.

16. The cellulose composite virus-removing membrane according to claim 14, characterized in that: The D 20 The endpoint is located in the region where the film thickness is 50% to 95%.

17. The cellulose composite virus-removing membrane according to claim 14, characterized in that: D 20 The highest absorption peak and the D 40 The ratio of the distance between endpoints to the thickness of the cellulose layer is 0.05 to 0.

2.

18. The cellulose composite virus-removing membrane according to claim 14, characterized in that: The D 20 In the middle, the region where the height of the absorption peak is not less than 0.85 times the peak height of the highest absorption peak is the region with a large amount of retention (D). 大 D 大 The thickness and the D 40 The thickness ratio at the endpoint is 0.2 to 0.

7.

19. The preparation process of the cellulose composite virus-removing membrane according to any one of claims 1-18, characterized in that: The process includes the following steps: S1. Preparation of casting solutions: Small-pore casting solution and macropore casting solution are prepared separately. The small-pore casting solution includes a small-pore film-forming polymer and a small-pore diluent. The macropore casting solution includes a macropore film-forming polymer and a macropore diluent. Both the small-pore film-forming polymer and the macropore film-forming polymer are made from cellulose-based raw materials. The solid content of the macropore casting solution is 10-18%, and the solid content of the small-pore casting solution is 20-30%. S2. Casting film: Small-pore casting liquid and macropore casting liquid are sequentially cast onto a carrier to form a double-layer liquid film. Then, a microporous membrane support layer is conveyed by a conveyor roller to cover and composite the double-layer liquid film, obtaining a composite semi-finished film. The covering process of the microporous membrane support layer satisfies the composite coefficient F of 1 to 1.

25. The composite coefficient F is calculated by the following formula: F = (h1 + h2) / h3; where h1 is the thickness of the double-layer liquid film, h2 is the thickness of the microporous membrane support layer, and h3 is the minimum distance between the conveyor roller and the carrier. S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is transported to a pretreatment atmosphere for pretreatment to obtain a pretreated membrane. The pretreatment atmosphere is a good solvent vapor of macroporous film-forming polymer. S4. Curing: Immerse the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and cured to obtain a green film. The coagulation bath is at least one of water or ethanol. S5. Post-treatment: Place the raw membrane in a regeneration bath to hydrolyze and regenerate the raw membrane, obtaining a cellulose virus-removing membrane.

20. The preparation process of the cellulose composite virus-removing membrane according to claim 19, characterized in that: In step S2, the covering process of the microporous membrane support layer satisfies a composite coefficient F of 1.05 to 1.15; in step S3, the temperature of the pretreatment atmosphere is 30 to 60°C higher than the temperature of the composite semi-finished membrane, and the residence time of the composite semi-finished membrane in the pretreatment atmosphere is 40 to 60 seconds.

21. The preparation process of the cellulose composite virus-removing membrane according to claim 19, characterized in that: In step S2, both the small-pore casting solution and the large-pore casting solution are at 30-40°C, and the temperature of the carrier is 40-60°C.

22. The preparation process of the cellulose composite virus-removing membrane according to claim 19, characterized in that: Step S3 further includes a cooling step, specifically, transporting the carrier loaded with the pretreated membrane to a cooling atmosphere at a temperature of 10-20°C for a cooling time of 5-10 seconds, wherein the cooling atmosphere is air or an inert gas.

23. The preparation process of the cellulose composite virus-removing membrane according to claim 19, characterized in that: The cellulose raw material is at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, and cellulose acetate propionate. Both the microporous diluent and the macroporous diluent are selected from good solvents of cellulose raw materials. The good solvent is at least one of acetone, dioxane, dimethylacetamide, N-methylpyrrolidone, acetic acid, propionic acid, butyric acid and valeric acid.

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