Cellulose virus-removing membrane having high mechanical strength, and preparation process therefor

Abstract

A cellulose virus-removing membrane and a preparation process therefor. The virus-removing membrane comprises a microporous membrane support layer and a cellulose layer, which at least partially permeates into the microporous membrane support layer, wherein the region into which the cellulose layer permeates of the microporous membrane support layer is a permeation region; the cellulose layer further comprises a pre-filtering region and a separating region; the thickness of the permeation region is not less than 10 μm; the permeation region comprises microporous fibers and cellulose fibers, the average diameter of the microporous fibers is larger than that of the cellulose fibers, and the average diameter of the cellulose fibers is not greater than 180 nm; and the microporous fibers mutually encircle each other to form basic holes, the cellulose fibers are located in the basic holes, and the cellulose fibers mutually encircle each other to divide the basic holes into a plurality of secondary holes. Further disclosed is a preparation process for the virus-removing membrane.

Description

A cellulose virus removal membrane with high mechanical strength and its preparation process Technical Field

[0001] The present application relates to the field of membrane separation technology, and in particular to a cellulose virus removal membrane with high mechanical strength and a preparation process thereof. Background Art

[0002] Ensuring viral safety is paramount in the production of various biologics. Both the newly released Chinese Pharmacopoeia and the guidance document "ICH Q5A: Biotechnology Products - Viral Safety Evaluation," issued by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), of which the China Food and Drug Administration is a member, clearly set high standards for the viral safety of biologics. Consequently, viral clearance and / or inactivation steps have become essential during the preparation of biologics.

[0003] Membrane separation technology is widely used in the virus removal process of various biological agents due to its advantages such as high separation efficiency, easy process scale-up, and low risk of denaturation of active substances during the separation process. When membrane separation technology is applied to virus filtration processes, dead-end filtration is often used. Since the primary filtration driving force of dead-end filtration is the pressure difference between the two ends of the filter membrane after the pressurized liquid to be filtered, further increasing the pressure of the liquid to be filtered can be expected to improve filtration efficiency. However, higher pressure of the liquid to be filtered places higher pressure resistance requirements on the filter membrane to avoid degradation of virus retention performance or even damage to the filter membrane under higher pressure.

[0004] For example, the Chinese invention patent application document with application publication number CN105980038A (applied by Asahi Kasei Corporation) discloses a virus removal membrane comprising cellulose, having a first surface for supplying a protein-containing solution, and a second surface for discharging the permeate passing through the virus removal membrane. The membrane has a logarithmic removal rate of 4 or greater (LRV>4) for porcine parvovirus (approximately 18-26 nm). The membrane is a cellulose membrane, and its good hydrophilicity gives it low protein adsorption. However, the inherent softness of cellulose raw materials determines that the mechanical strength of the cellulose fiber skeleton is poor, and the self-supporting performance of the cellulose membrane is often insufficient. The cellulose membrane in this application can only withstand a pressure of 15 psi and is difficult to withstand higher pressures. During use, the filter membrane is likely to be impacted by the feed liquid, whether it is the pressure on the filter membrane caused by the feed liquid itself, which requires pressurization as a driving force during the virus filtration process, or the impact caused by equipment vibration and other reasons. Filter membranes that are unable to withstand higher pressures may not only have a shorter service life, but in some special application scenarios, they may also lead to the risk of virus leakage due to insufficient stability.

[0005] For example, the Chinese invention patent application document with application publication number CN115569521A (applied by Cobetter Co., Ltd.) discloses a cellulose composite ultrafiltration membrane and its preparation method. The membrane comprises an ultrafiltration layer, a transition layer, a bonding layer, and a substrate layer in the direction of fluid flow. The ultrafiltration layer and the transition layer are both formed from a cellulose polymer, while the substrate layer is formed from a non-natural polymer microporous membrane. The bonding layer comprises a cellulose polymer and a non-natural polymer. Within the bonding layer, first fibers formed from the cellulose polymer and second fibers formed from the non-natural polymer are intertwined but not adhered to each other. Instead, they are separated from each other to form gaps for fluid to pass through, forming a structure similar to "interlocking rings." The advantage of this structure is that the intertwined yet interlocking fiber structure not only gives the composite membrane a high peel strength and is less susceptible to peeling, but also the gaps formed between the interlocking fibers provide less resistance to the fluid as it flows through the bonding layer, resulting in a relatively high flux (faster flow rate). However, in reality, the cellulose polymer casting liquid penetrates into the membrane pore structure of the non-natural polymer microporous membrane. After solidification, the cellulose polymer casting liquid forms a first fiber structure. The first fiber fills the membrane pore structure of the microporous membrane, thereby forming a large degree of blockage of the membrane pore structure in the bonding area of ​​the microporous membrane. The gap formed can only reduce the effect to a small extent, and thus it is inevitable that there is still a large impact on the flux.

[0006] For example, in a Chinese invention patent with authorization publication number CN1108853C (applied by Milipol), a back-pressure-resistant cellulose ultrafiltration membrane is disclosed, which includes a polymer microporous alkali-resistant substrate and an ultrafiltration membrane layer formed of a polymer. The thickness of the ultrafiltration layer is about 1-20 microns, and the distance that the polymer extends into the microporous alkali-resistant substrate is between 5-30 microns. This patent also raises the issue of flux reduction caused by permeation, that is, as the degree of penetration of cellulose ester or cellulose into the alkali-resistant microporous polymer layer (the thickness of the permeation layer) increases, the degree of blockage of the substrate pores also increases, thus leading to a rapid decrease in flux; however, as the degree of penetration of cellulose ester or cellulose into the alkali-resistant microporous polymer layer (i.e., thickness) decreases, although the flux will increase accordingly, the bonding strength between the two layers is insufficient, which often leads to insufficient anti-delamination properties of the cellulose membrane (insufficient peel strength). Therefore, this patent achieves a balance between flux and anti-delamination properties by controlling the degree of penetration of cellulose ester into the alkali-resistant microporous polymer layer, but cannot achieve both high flux and high anti-delamination properties.

[0007] Therefore, obtaining a composite virus removal membrane with high peel strength and less impact on flux is a technical problem that needs to be solved urgently but is difficult to solve.

[0008] Summary of the Invention

[0009] The present application provides a cellulose virus removal membrane with high mechanical strength and a preparation process thereof. The virus removal membrane in the present application can ensure a tight bond between the microporous membrane support layer and the cellulose layer by controlling the thickness of the permeation zone to be not less than 10 μm, and has a high peel strength; and by setting the cellulose layer in the permeation zone to have a secondary pore structure located in the basic pore, and the average diameter of the cellulose fibers constituting the secondary pores is not greater than 180 nm, the finer cellulose fibers combined with the further introduced secondary pore structure means that there are a large number of interconnected flow channels in the basic pores in the permeation zone, and these flow channels have less resistance to the feed liquid, which greatly reduces the influence of the permeation zone on the flux, thereby obtaining a virus removal membrane with both high flux and high peel strength.

[0010] In a first aspect, the present application provides a cellulose virus removal membrane with high mechanical strength, which adopts the following technical solution:

[0011] A cellulose virus removal membrane with high mechanical strength comprises a microporous membrane support layer and a cellulose layer at least partially permeated into the microporous membrane support layer, wherein the side of the microporous membrane support layer away from the fiber layer is a liquid inlet surface, and the side of the cellulose layer away from the microporous membrane support layer is a liquid outlet surface, the microporous membrane support layer and the cellulose layer both have non-directional tortuous pathways, and the microporous membrane support layer and the cellulose layer are connected through the non-directional tortuous pathways, the area in the microporous membrane support layer infiltrated by the cellulose layer is a permeation zone, the cellulose layer further comprises a pre-filtration zone and a separation zone, the permeation zone, the pre-filtration zone and the separation zone are transitioned through continuous fibers, and the separation zone includes the liquid outlet surface;

[0012] The thickness of the permeable zone is not less than 10 μm;

[0013] The permeation zone includes microporous fibers constituting the microporous membrane support layer and cellulose fibers constituting the cellulose layer, wherein the average diameter of the microporous fibers is greater than the average diameter of the cellulose fibers, and the average diameter of the cellulose fibers is no greater than 180 nm;

[0014] The microporous fibers surround each other to form basic pores, and the cellulose fibers are located in the basic pores. The cellulose fibers surround each other and divide the basic pores into a plurality of secondary pores.

[0015] Optionally, the thickness of the permeation zone is not less than 15 μm.

[0016] Optionally, the membrane-forming material of the microporous membrane support layer is at least one of PVDF, PES, PTFE, Nylon, cellulose, and polyolefin.

[0017] Optionally, the polyolefin is UPE or PP.

[0018] By adopting the above technical solution, cellulose-based membrane materials have the highest hydrophilicity among conventional virus removal membrane materials, resulting in lower protein adsorption rates, enabling the production of high-purity, high-concentration biological agents. However, the inherent softness of cellulose-based membrane materials means that conventional cellulose-based filter membranes lack sufficient mechanical strength. This means that for virus removal filtration processes that rely on pressure as the driving force for filtration, further increasing pressure cannot improve filtration efficiency.

[0019] In order to improve the pressure resistance of cellulose virus removal membranes, the current common practice is to compound the cellulose filter membrane with a microporous membrane support layer with higher mechanical properties to obtain a cellulose virus removal membrane with higher pressure resistance, thereby achieving both higher protein yield and higher pressure resistance.

[0020] The higher pressure resistance of the composite virus removal membrane enables it to be used under conditions with higher pressure (such as not less than 20psi, or even not less than 30psi). However, higher pressure application conditions also bring new problems. For example, the composite virus removal membrane is more prone to stratification under higher pressure conditions. This is because, during the filtration process, due to equipment vibration, slurry stability and other reasons, the composite virus removal membrane, which is already under higher pressure, often further withstands a greater impact force from the slurry, which can easily lead to stratification. In order to improve the peel strength (or anti-stratification performance) of the composite virus removal membrane, the bonding strength between the layers can be improved by increasing the penetration thickness of the casting liquid in the microporous membrane support layer; however, after the casting liquid penetrates into the microporous membrane support layer, it will partially or even completely block the pore structure of the microporous membrane support layer, resulting in a significant decrease in the actual porosity of the permeation zone and a significant increase in the resistance to the slurry, which significantly reduces the flux of the composite virus removal membrane. In addition, the junctions between membrane layers in composite virus removal membranes are prone to sudden changes in pore size. This sudden change in pore size is very likely to lead to the retention of large-size particles in the feed liquid (i.e., not only large-size particles are retained, but also small-size particles), thus forming a situation similar to filter cake blockage. The reduction in porosity in the permeation zone will also lead to a reduction in load capacity. Therefore, the service life of composite virus removal membranes is often short. Obviously, for the current conventional composite virus removal membranes, good anti-stratification performance and high flux and high load are a pair of relatively contradictory and difficult to achieve properties.

[0021] In response to the above-mentioned problems, the inventors of the present application have found that for a composite virus removal membrane having a microporous membrane support layer, high peel strength and high flux (and high load) are not incompatible. The virus removal membrane in the present application controls the mutual penetration between the membrane layers to ensure a permeation zone with a thickness of not less than 10 μm (the starting point of the permeation zone is the surface of the microporous membrane support layer away from the liquid inlet surface, i.e., the composite interface), and ensures that the microporous membrane support layer and the cellulose layer have sufficiently high anti-delamination performance through the mutual entanglement and mutual anchoring between the microporous fibers and the cellulose fibers, and can be used for a long time at a working pressure of at least 20 psi without delamination. It is understandable that as the thickness of the permeation zone increases, the anti-delamination performance between the membrane layers gradually improves. When the thickness of the permeation zone is not less than 15 μm, the virus removal membrane can be used for a long time at a working pressure of at least 30 psi without delamination.

[0022] On the basis of having high anti-stratification performance, the composite virus removal membrane in this application forms cellulose fibers with an average diameter of no more than 180nm by controlling the cellulose layer in the permeation zone, and through these cellulose fibers with smaller diameters that surround and entangle with each other, the basic pores of the microporous membrane support layer are separated into a large number of secondary pores, forming a special "pore in pore" or "large pore within small pore" structure in the permeation zone. This is different from the "interlocking" structure in the aforementioned Chinese patent application with application publication number CN115569521A, and is also different from the Chinese patent with authorization announcement number CN1108853C, in which only the casting liquid penetrates without forming secondary pores. It is a very special structure. This specific large pore within small pore structure greatly reduces the resistance of the permeation zone to the feed liquid and increases the pollution-receiving space in the permeation zone, thereby making the composite virus removal membrane not only have high anti-stratification performance, but also have high flux and load.

[0023] Among them, in a composite membrane structure that only permeates without forming secondary pores, although the composite membrane structure has good anti-stratification performance due to its relatively thick permeation zone, the flow path of the feed liquid in the permeation zone is only the pore portion that is not completely filled. Since the pore structure of the microporous membrane support layer in the permeation zone is largely blocked, there are fewer incompletely filled pores in the permeation zone that can provide space for the feed liquid to flow and serve as a contaminant storage space. The feed liquid will encounter greater resistance in the permeation zone, affecting the flux and loading capacity of the composite membrane. Since the interlocking composite membrane structure inevitably has slits between the fibers, it ensures that although the pore structure of the microporous membrane support layer in the permeation zone is partially blocked, there are slit channels for the feed liquid to flow, which can solve the problem of reduced flux to a certain extent. However, the fiber portion with a larger diameter and being essentially solid will still cause a large degree of blockage to the pore structure of the microporous membrane in the permeation zone, thereby affecting the flux and loading capacity of the composite membrane.

[0024] In the present application, a large number of secondary pore structures formed in the pore structure of the microporous membrane supporting layer in the permeation zone become channels for the feed liquid to flow through the permeation zone, and the diameter of the solid part of the cellulose fiber that forms the main resistance to the feed liquid does not exceed 180nm. This makes the resistance encountered by the feed liquid in the permeation zone smaller and has sufficient flow channels. This part of the flow channel can provide the feed liquid with flow and serve as a contamination space for impurity particles, greatly reducing the influence of the thicker permeation zone on the flux and load capacity of the virus removal membrane.

[0025] Therefore, the combination of the permeation zone with a thickness of not less than 10 μm and the secondary pore structure formed by cellulose fibers with an average diameter of not more than 180 nm makes the composite virus removal membrane of the present application not only have good anti-stratification performance under high pressure conditions, but also have significantly higher flux and load, which is a very unexpected result.

[0026] On this basis, the pre-filtration area in the fiber layer of the present application can further ensure that the virus removal membrane has a higher load capacity, and the separation area can intercept viruses in the feed liquid to ensure the virus safety of the feed liquid.

[0027] It is understandable that the measurement method of various surface morphological parameters (such as thickness, fiber diameter, pore size, pore area ratio, etc.) of the virus removal membrane can be achieved by using a scanning electron microscope to characterize the morphology of the membrane structure, and then using computer software (such as Matlab, NIS-Elements, etc.) or manually measuring and performing corresponding calculations; in the preparation process of the membrane, in the direction perpendicular to the thickness of the membrane (if the membrane is in the form of a flat membrane, this direction is the planar direction; if the membrane is in the form of a hollow fiber membrane, this direction is perpendicular to the radial direction), its various characteristics such as pore size distribution are roughly uniform and basically consistent; therefore, the average pore size of the entire surface can be reflected by measuring the average pore size of a portion of the area on the corresponding plane. When actually measuring, the membrane surface (or cross-section) can be characterized by an electron microscope first, the corresponding SEM image can be obtained, and a certain area can be selected, such as 1μm 2 (1 μm times 1 μm) or 25 μm 2 (5 μm multiplied by 5 μm), the specific area size depends on the actual situation, and then the pore size, fiber diameter and other morphological parameters of all holes in the area are measured using corresponding computer software or manually, and then calculated to obtain the average pore size, average fiber diameter and other morphological parameters of the area; of course, those skilled in the art can also obtain the above parameters by other measurement methods, and the above measurement methods are for reference only.

[0028] The so-called non-directional tortuous path in this application refers to a randomly oriented groove structure and / or a discretely distributed pore structure, and each non-directional tortuous path is interconnected. During filtration, the feed liquid flows in the tortuous pore structure, and impurities in the feed liquid are retained by screening, adsorption, etc.

[0029] Optionally, the thickness of the permeable zone is 15 to 45 μm, and the ratio of the thickness of the permeable zone to the thickness of the cellulose layer is 25 to 65%.

[0030] By adopting the above technical solution, it is generally believed that the greater the thickness of the permeation zone, the higher the proportion of the area where the pore structure in the microporous membrane support layer is blocked, and the higher the proportion of the area with greater resistance to the feed liquid, therefore, the greater the thickness of the permeation zone, the greater the impact on the flux and load of the virus removal membrane. However, the inventors of the present application found that for the virus removal membrane with a secondary pore structure permeation zone in the present application, even if the thickness of the permeation zone is further increased (such as from 10 to 15 μm to 15 to 45 μm), the flux of the virus removal membrane has decreased as expected, but the decline is not large. This result is unexpected and different from conventional cognition. This may be because there is a secondary pore structure in the permeation zone of the virus removal membrane in the present application that is less blocked by the pore structure of the microporous membrane support layer. The presence of these secondary pores makes the permeation zone still have resistance to the feed liquid, but the resistance of the permeation zone to the feed liquid is not large. Therefore, in the various layers of the virus removal membrane, the permeation zone where the feed liquid is less obstructed is naturally not the main area affecting the flux of the virus removal membrane. At this time, even if the thickness of the permeation zone is increased, it will still cause a decrease in the flux of the virus removal membrane. However, the decrease in flux will be much lower than expected.

[0031] In addition, as the thickness of the permeation zone continues to increase, the anti-stratification performance of the virus removal membrane does not increase linearly, but generally presents a trend of first rising rapidly and then slowing down the rate of improvement, that is, the thickness of the permeation zone has a marginal diminishing effect on the anti-stratification performance. This may be because, when the composite layer structure is peeled off, the area where the peeling phenomenon is most likely to occur is often located near the composite interface of the layer structure, that is, the anti-stratification performance of the virus removal membrane mainly depends on the structure near the composite interface of the layer structure. Therefore, the farther the distance from the composite interface, the smaller the impact on the anti-stratification performance between the layer structures. For this reason, when the thickness of the permeation zone is too large (such as greater than 45μm), it is too far from the composite interface, and the impact on the anti-stratification performance of the virus removal membrane is already small. As mentioned above, further improvement of the thickness of the permeation zone will inevitably lead to a slight decrease in the flux of the virus removal membrane. Therefore, when the thickness of the permeation zone is preferably 15 to 45μm, the virus removal can further preferably obtain higher anti-stratification performance and only a slight decrease in flux and load.

[0032] Furthermore, while the permeable zone thickness is preferably 15-45 μm, the ratio of the permeable zone to the cellulose layer thickness also needs to be controlled to achieve both high flux and high virus retention. This is because, compared to the microporous membrane support layer with a larger pore structure, the cellulose layer must ensure high virus retention (e.g., at least reaching the LRV>4 specified in PDATR41). High virus retention often also means higher feed resistance. If the ratio of the permeable zone thickness to the cellulose layer thickness is too small (e.g., less than 25%), it often means that the total thickness of the cellulose layer is too large. While this can ensure better virus retention for the virus removal membrane, it also often means higher feed resistance. On the other hand, if the ratio of the permeable zone thickness to the cellulose layer thickness is too large (e.g., greater than 65%), it means that the total thickness of the fiber layer is too small (or the thickness of the pre-filtration zone and separation zone is too small). Although the feed resistance is reduced and higher flux can be achieved, the risk of virus leakage also increases. Ensuring the viral safety of biological agents is a must. Therefore, not only the thickness of the permeable zone needs to be strictly controlled, but also the ratio of the thickness of the permeable zone to the thickness of the cellulose layer needs to be controlled to obtain more preferred virus retention capacity, flux and other properties.

[0033] Optionally, the area with a thickness of 10 μm on the side of the permeation zone close to the pre-filtration zone is the junction area, the area with a thickness of 5 μm on the side of the junction area close to the liquid inlet surface is the upper junction area, and the area with a thickness of 5 μm on the side of the junction area close to the liquid outlet surface is the lower junction area, the SEM-measured average pore size of the secondary pores in the permeation zone is larger than the SEM-measured average pore size of the secondary pores in the junction area; the average diameter of the cellulose fibers in the junction area is not less than 50 nm.

[0034] By adopting the above technical solution, as mentioned above, different parts of the permeation zone have different effects on the anti-delamination performance of the virus removal membrane. Among them, the area with the greatest impact on the anti-delamination performance of the virus removal membrane is located near the composite interface of the various membrane structures. The inventors of this application have discovered that for the virus removal membrane of the specific structure of this application, the region of the permeation zone with a thickness of approximately 10 μm near the composite interface (i.e., the interface region) has a greater impact on the anti-delamination performance of the virus removal membrane.

[0035] In order to ensure that the resistance of cellulose fiber to the feed liquid in the permeation zone is smaller, to reduce the impact on the flux of the virus removal membrane, the cellulose fiber average diameter in the permeation zone in the present application is smaller (not more than 180nm), and this often means that the breaking strength of cellulose fiber in the permeation zone is smaller, therefore, if the position near the composite interface in the permeation zone is subjected to excessive external force, the cellulose fiber is easily torn, thereby causing the problem of delamination. The present application is further preferred, and the SEM measurement average pore size of the secondary pores in the permeation zone is set to be greater than the SEM measurement average pore size of the secondary pores in the junction zone, which means that the secondary pore size in the junction zone is smaller and the density is higher. Although the cellulose fiber diameter in the junction zone is smaller, the cellulose fiber with a denser and higher degree of mutual entanglement in the junction zone can still ensure that the virus removal membrane has sufficiently high anti-stratification performance. Of course, although the cellulose fiber with a smaller diameter in the junction zone has a smaller flow resistance for the feed liquid, the cellulose fiber with a diameter too small (such as less than 50nm) may still cause the cellulose fiber at the junction where the anti-stratification performance of the composite membrane is most affected to break easily, therefore, the diameter of the cellulose fiber in the junction zone should not be too low.

[0036] Therefore, the present application controls the interface area to have a smaller pore size than the entire permeation area to obtain a denser three-dimensional cellulose fiber skeleton structure, and cooperates with the diameter of the cellulose fibers in the interface area to be not less than 50nm but not more than 180nm, which not only makes the virus removal membrane have higher anti-stratification performance, but also has higher flux.

[0037] It should be noted that although the "interlocking" structure in the Chinese patent application with application publication number CN115569521A can also make the composite membrane have a higher anti-stratification performance, the coarser fibers near the composite interface form a greater resistance to the flow of the feed liquid, resulting in a decrease in flux; the small-diameter and denser cellulose fibers in the permeation zone of the present application can not only ensure that the composite membrane has a higher anti-stratification performance, but also significantly reduce the resistance to the flow of the feed liquid to obtain a higher flux. This is not only a new technical route, but also achieves better technical effects.

[0038] Optionally, the average pore size of the secondary pores in the lower boundary area measured by SEM is not larger than the average pore size of the secondary pores in the upper boundary area measured by SEM, and the average pore size of the secondary pores in the upper boundary area measured by SEM is smaller than the average pore size of the secondary pores in the permeation area measured by SEM.

[0039] By adopting the above technical solution, the average pore size of the secondary pores in the lower junction region measured by SEM is no larger than the average pore size of the secondary pores in the upper junction region measured by SEM, indicating that the secondary pores in the junction region exhibit an asymmetric structure, and that the closer to the composite interface, the smaller the average pore size of the secondary pores in the junction region measured by SEM. In contrast, the average pore size of the secondary pores in the upper junction region measured by SEM is smaller than the average pore size of the secondary pores in the permeation region, indicating that the pore size of the secondary pores in the upper junction region is still smaller than that of the secondary pores in the entire permeation region. Because the phase-separation driving force that causes pore size changes is not prone to sudden changes, the secondary pores in the entire permeation region also generally exhibit an asymmetric structure.

[0040] Compared with the upper junction area, the lower junction area has a greater impact on the anti-stratification performance of the composite virus removal membrane. This is because the stratification behavior of the composite virus removal membrane tends to occur more near the composite interface. Therefore, in order to further ensure that the composite virus removal membrane has more preferred anti-stratification performance, the secondary pore structure of the junction area is further set to an asymmetric structure in this application. Such an asymmetric secondary pore structure can ensure that the cellulose fibers are denser the closer they are to the composite interface, and thus have stronger anti-stratification performance.

[0041] In addition, the roughly asymmetric secondary pore structure of the interface area and even the permeation area also means that in the entire permeation area, the area with greater resistance to the feed liquid (that is, the area with smaller pore size in the secondary pores) only exists in the area near the composite interface of the permeation area, that is, in the entire permeation area, the thickness of the small-pore secondary pore area with greater resistance to the flow of the feed liquid is not high, and the large-pore secondary pore area in the permeation area accounts for a large proportion, and the large-pore secondary pore area does not have much resistance to the feed liquid. This means that even if the composite virus removal membrane in this application has a thicker permeation area, the flux will inevitably decrease, but the decline will be significantly lower than expected.

[0042] Optionally, the average pore size of the secondary pores in the lower boundary region measured by SEM is 100-200 nm, and the average pore size of the basic pores in the lower boundary region measured by SEM is 600-1500 nm.

[0043] By adopting the above technical solution, as mentioned above, the area with the greatest impact on the anti-stratification performance of the composite virus removal membrane is located in the area near the composite interface, that is, the area with the greatest impact on the anti-stratification performance of the virus removal membrane in the permeation zone is the interface area, and the area with the greatest impact on the anti-stratification performance of the virus removal membrane in the interface area is the lower interface area. In addition, since the secondary pores in the permeation zone of the virus removal membrane in this application are roughly asymmetric structures, the secondary pores in the interface area are also roughly asymmetric structures. Therefore, in the entire permeation zone, the secondary pores with the smallest pore size are located in the interface area, and further, near the lower interface area. Therefore, the area with the greatest impact on the flux of the virus removal membrane in the permeation zone is also the lower interface area. It is very necessary to adjust and control the pore structure, fiber structure, etc. of the secondary pores in the lower interface area.

[0044] Since the lower interface area has a secondary pore structure with relatively small pore size, in order to ensure that the entire permeation area has low impact on the flux of the virus removal membrane, it is necessary to ensure that the lower interface area has a low feed-liquid resistance pore structure of "large pores within small pores"; however, in order to ensure that the virus removal membrane still has high anti-stratification performance, the secondary pore structure in the "large pores within small pores" structure should not have an excessively large pore size, so as to avoid insufficient density of the cellulose fiber skeleton structure, which may easily cause stratification.

[0045] Therefore, based on the average pore size of the basic pores in the lower interface area measured by SEM of 600 to 1500 nm, if the pore size of the secondary pores in the lower interface area is too large (such as greater than 200 nm), since the fiber diameter in the lower interface area is not thick, the larger pore size combined with the finer fiber structure will often lead to the less than optimal anti-stratification performance of the virus removal membrane. Although such a virus removal membrane can preferably obtain a larger flux, it is more likely to cause layer separation problems under higher pressure application conditions. If the pore size of the secondary pores in the lower interface area is too small (such as less than 100 nm), although the lower interface area still has a special pore structure of "large pores within small pores", the secondary pore structure with too small pore size means a greater impact on the fluid flux. Although such a virus removal membrane can preferably obtain a greater anti-stratification performance, the decrease in the flux of the virus removal membrane often means an increase in production costs.

[0046] Optionally, the average pore size of the secondary pores in the upper boundary region measured by SEM is 120 to 220 nm, and the average pore size of the basic pores in the upper boundary region measured by SEM is 600 to 1500 nm.

[0047] By adopting the above technical solution, based on the fact that the lower boundary area has secondary pores with relatively small pore size (100-200nm) and the secondary pores in the boundary area are roughly asymmetric, the morphology structure of the upper boundary area also has a relatively large influence on the material and liquid resistance in the permeation area and the anti-stratification performance of the composite virus removal membrane. Based on the average pore size of the basic pores in the upper junction area measured by SEM of 600-1500nm, if the pore size of the secondary pores in the upper junction area is too large (such as greater than 220nm), it means that the density of the cellulose fiber skeleton in the upper junction area is low. Although the resistance of the upper junction area to the slurry is reduced, the mutual entanglement of the cellulose fibers between the upper and lower junction areas is reduced. The cellulose fibers in the upper junction area are difficult to inhibit the breakage of the cellulose fibers in the lower junction area, resulting in insufficient anti-stratification performance of the composite virus removal membrane; in addition, based on the secondary pore structure with a smaller pore size in the lower junction area, if the pore size of the secondary pore structure in the upper junction area is too large, it means that there is a large pore size change gradient in the secondary pores in the junction area along the thickness direction, which can easily lead to concentrated retention of impurity particles (concentrated retention refers to large particles and small particles being retained in a small area), and the concentrated retention of impurity particles often means rapid blockage of the local pore structure of the virus removal membrane, resulting in a too low service life of the virus removal membrane. If the pore size of the secondary pores in the upper boundary area is too small (such as less than 120nm), although the denser cellulose fiber skeleton in the upper boundary area can further improve the anti-stratification performance of the composite virus removal membrane by forming entanglements with the cellulose fiber skeleton in the lower boundary area; however, on the basis of the lower boundary area having a denser secondary pore structure, further introducing an upper boundary area having a denser secondary pore structure will make the entire boundary area have a denser secondary pore structure, forming a larger material liquid resistance, resulting in a lower flux of the virus removal membrane. Therefore, on the basis of the lower boundary area having a denser secondary pore structure, by further preferably controlling the pore size of the secondary pore structure of the upper boundary area, the virus removal membrane can have further preferred flux and anti-stratification performance.

[0048] Optionally, the ratio of the average pore size of the basic holes measured by SEM to the average pore size of the secondary holes in the lower boundary area is 4 to 10; the ratio of the average pore size of the basic holes measured by SEM to the average pore size of the secondary holes in the upper boundary area is 3 to 9.

[0049] By adopting the above technical solution, both the upper and lower interface regions have a unique structure of large pores within small pores. The larger base pores determine the porosity of the microporous membrane support layer, and thus largely determine the flux and support capacity of the microporous membrane support layer. If the base pore diameter is too large, although the flux of the microporous membrane support layer is greater, it often has a lower support capacity. If the base pore diameter is too small, although the microporous membrane support layer provides better support, it cannot guide the slurry through and enter the cellulose layer at a higher flux.

[0050] In addition, although the size of the basic pores largely determines the flux of the microporous membrane, for the entire virus removal membrane, the size of the flux is still determined by the superposition of the resistance of the feed liquid at various locations, and in the interface area, in addition to the basic fibers with larger fiber sizes, there are also secondary pores with relatively small pore sizes that have greater resistance to the feed liquid. By limiting the pore size ratio of the basic pores and the secondary pores, it can largely reflect the density of the basic fibers with greater resistance to the feed liquid in the basic pores, and it can also reflect the density of the cellulose fibers with greater resistance to the feed liquid in the secondary pores. Among them, whether it is the upper interface area or the lower interface area, the pore size ratio of the basic pores and the secondary pores is too large, which often means that the basic pores are too large to obtain sufficient support effect and the basic pores have a secondary pore structure with too small pore size. Secondary pores with too small pore size will produce greater resistance to the feed liquid. The ratio of the pore size of the basic pores to the secondary pores is too small, which often means that the basic pores are too small and have relatively dense basic fibers, while the pore size of the secondary pores in the basic pores is larger. Although the secondary pores with larger pore size have less resistance to the feed liquid, the overly loose cellulose fiber structure will lead to insufficient anti-stratification performance of the virus removal membrane, and the relatively dense basic fiber structure will also form greater resistance to the feed liquid, resulting in a decrease in the flux of the virus removal membrane.

[0051] Optionally, the average diameter of the cellulose fibers in the permeation zone is greater than the average diameter of the cellulose fibers in the interface zone; the average diameter of the cellulose fibers in the upper interface zone is greater than the average diameter of the cellulose fibers in the lower interface zone.

[0052] By adopting the above technical solution, the resistance to the flow of the feed liquid in the permeation zone is mainly formed by the basic fibers and cellulose fibers of the solid part. On the basis that the pore size of the microporous membrane support layer is significantly larger than the pore size of the cellulose layer, the resistance of the cellulose fibers to the feed liquid in the permeation zone is a more important factor affecting the feed liquid flux.

[0053] In the present application, the average diameter of the cellulose fibers in the permeation zone is greater than the average diameter of the cellulose fibers in the junction zone, and the diameter of the cellulose fibers in the upper junction zone is greater than the average diameter of the cellulose fibers in the lower junction zone; this means that the diameter of the cellulose fibers in the entire permeation zone presents a trend of decreasing gradient. The cellulose fibers with a specific diameter gradient change in the permeation zone mean that the closer the permeation zone is to the composite interface, the smaller the diameter of the cellulose fibers. Since the permeation zone has a secondary pore structure with smaller pore size as it is closer to the composite interface, the permeation zone has a morphological structure with smaller pore size and finer fibers as it is closer to the composite interface. This structure has a relatively low thickness ratio, and therefore has little effect on the overall flux of the virus removal membrane. However, the denser three-dimensional network skeleton structure of this structure can significantly improve the anti-stratification performance of the composite virus removal membrane.

[0054] Optionally, the average diameter of the cellulose fibers in the lower boundary region is not less than 40 nm, and the ratio of the average pore diameter of the basic pores in the lower boundary region measured by SEM to the average diameter of the cellulose fibers is 10-25.

[0055] By adopting the above technical solution, the morphological structure of small pores and fine fibers in the lower junction area can greatly improve the anti-delamination performance of the composite virus removal membrane through a relatively dense three-dimensional network skeleton structure. However, if the diameter of the cellulose fibers in the lower junction area is too small, even if a relatively dense three-dimensional network skeleton structure can still be formed by these cellulose fibers, since the diameter of the cellulose fibers is halved, the cross-sectional area will become one-quarter, and the mechanical properties of the fibers will not decrease linearly, but will decrease exponentially. Therefore, the skeleton structure formed by cellulose fibers with a diameter that is too small (such as less than 40nm) cannot obtain the required mechanical properties even if it is relatively dense. Under the action of external forces, the fibers are still prone to breakage and delamination.

[0056] Furthermore, the specific secondary pore structure within the base pores of this application creates a unique structure of large pores within small pores and fine fibers within the large pores within the lower interface region. For the lower interface region, which already has a larger pore size, the presence of the secondary pores combined with the fine fibers reduces the resistance the feed experiences within the secondary pores. Therefore, this unique structure of large pores within small pores and fine fibers within the large pores in the lower interface region not only imparts excellent anti-stratification properties to the virus removal membrane, but also provides minimal resistance to the feed, resulting in a higher flux.

[0057] Optionally, the average diameter of the cellulose fibers in the upper boundary region is not less than 60 nm, and the ratio of the average pore diameter of the basic pores in the upper boundary region measured by SEM to the average diameter of the cellulose fibers is 8-20.

[0058] By adopting the above technical solution, since the upper boundary area has a secondary pore structure with a larger pore size than that of the lower boundary area, even if there are cellulose fibers with relatively larger diameters (such as not less than 60nm), the secondary pore structure with a larger pore size and the basic pore structure with a larger pore size (the ratio of 8 to 20 to the diameter of the cellulose fiber) can ensure that there are sufficient channels for the feed liquid to flow in the upper boundary area. The upper boundary area has a special structure of large holes inside small holes (the small holes are larger than the small holes in the lower boundary area) and fine fibers in the large holes (the fiber diameter is larger than the fiber diameter in the lower boundary area), which can ensure that the upper boundary area has less resistance to the feed liquid.

[0059] In addition, the larger secondary pore structure in the upper junction area relative to the lower junction area means that the three-dimensional network skeleton structure formed by the cellulose fibers in the upper junction area is looser, and the looser three-dimensional network skeleton combined with the cellulose fibers with relatively larger diameters can ensure that the cellulose fibers in the upper junction area still have good breaking strength even if they are looser; thereby, the upper junction area closer to the composite interface not only has low material-liquid resistance, but also can further improve the anti-stratification performance of the composite virus removal membrane.

[0060] Optionally, the boundary area is divided into ten equal parts along the thickness direction, with the side of the boundary area close to the pre-filtration area as the starting point, and the ten parts are H1 to H2. 10 , wherein the area of ​​H1 to H5 is the lower boundary area, and the area of ​​H6 to H 10 The area is the upper boundary area; the average pore size of the secondary pores measured by SEM in the H1 area is not greater than H 10 Average pore size of secondary pores within the region measured by SEM.

[0061] By adopting the above technical solution, the interface area is divided into ten equal parts according to the thickness, and the aperture of the secondary hole in the H1 area is not larger than H 10 The pore size of the secondary pores in the region is such that not only is the pore size of the secondary pores in the entire upper interface region larger than that in the entire lower interface region, but the pore size of the secondary pores also varies in a gradient across the entire interface region. The combination of a secondary pore structure that decreases in gradient toward the composite interface and a cellulose fiber structure that decreases in gradient toward the composite interface but gradually increases in density means that even in the region closest to the composite interface in the interface region, a secondary pore structure exists, thus enabling the composite virus removal membrane to possess both high anti-stratification performance and high flux and loading capacity.

[0062] Optionally, the average pore size of the secondary pores in the H1 region measured by SEM is 100-200 nm, and the ratio of the average pore size of the secondary pores in the H1 region measured by SEM to the average pore size of the secondary pores in the H5 region measured by SEM is 0.8-0.98.

[0063] Optional, H 10 The average pore size of the secondary pores in the region measured by SEM is 150-250 nm. The average pore size of the secondary pores in the region H6 measured by SEM is similar to that in H 10 The average pore diameter ratio of the secondary pores in the region measured by SEM is 0.5-0.9.

[0064] By adopting the above technical solution, the H1 area, which is closest to the composite interface in the junction area, has a relatively small-sized secondary pore structure in the junction area, and therefore has a correspondingly larger resistance to the feed liquid. In order to ensure that the entire junction area has a smaller resistance to the feed liquid, the SEM-measured average pore size of the secondary pores in the H1 area should not be too small (such as less than 100 nm); however, the H1 area is also a more important area affecting the anti-stratification performance of the composite virus removal membrane. Therefore, the SEM-measured average pore size of the secondary pores in the H1 area should not be too large (such as greater than 200 nm). Therefore, on the basis of ensuring the presence of secondary pores of appropriate pore size to reduce the resistance to the feed liquid, combined with a larger permeation zone thickness, the influence of the existence of secondary pores on the anti-stratification performance of the composite virus removal membrane is further ensured.

[0065] In addition, the ratio of the pore size of the secondary pores in the H1 region and the H5 region to a certain extent characterizes the pore size change gradient of the secondary pores in the lower junction area (the larger the pore size change gradient, the smaller the pore size ratio of the two regions); if the pore size change gradient of the secondary pores in the lower junction area is too large (the pore size ratio of the two regions is less than 0.8), although the proportion of the secondary pores with smaller pore sizes in the lower junction area is reduced and the resistance to the feed liquid is reduced, the lower junction area has a greater influence on the anti-stratification performance of the composite virus removal membrane. The excessive pore size change gradient in the lower junction area often means that cellulose fibers are formed. The looseness of the three-dimensional network skeleton structure increases rapidly, and the anti-stratification performance of the composite virus removal membrane is often poor; and if the pore size change gradient of the secondary pores in the lower junction area is too small (the pore size ratio of the two areas is greater than 0.98), although the three-dimensional network skeleton structure formed by cellulose fibers with a relatively large thickness ratio and high density in the lower junction area can make the composite virus removal membrane have better anti-stratification performance, the small pore size and high density secondary pore structure with a large thickness ratio often means that the feed liquid is subject to greater resistance and smaller dirt holding space, which leads to a decrease in flux and load.

[0066] Compared to the lower interface region, the pore size gradient in the upper interface region is greater. Given that the lower interface region already has a high-density three-dimensional network structure, if the upper interface region further develops a similar, high-density three-dimensional network structure, the composite virus removal membrane's anti-stratification performance can be further improved, but the interface region's resistance to the liquid will also be significantly increased. Because the fiber structure in the upper interface region has a lower impact on the composite virus removal membrane's anti-stratification performance than the fiber structure in the lower interface region, introducing a secondary pore structure with a larger pore size gradient in the upper interface region can significantly increase the composite virus removal membrane's flux while having less impact on its anti-stratification performance.

[0067] By adopting the above technical solution, the thickness of the pre-filtration zone is 20 to 60 μm, the thickness of the separation zone is 20 to 40 μm; and the separation zone has a symmetrical pore structure.

[0068] By adopting the above-mentioned technical scheme, the secondary pore structure specifically introduced in the permeation zone in the present application can not only ensure that the composite membrane has both high anti-stratification performance and high flux and high loading capacity; its pore size gradient change and appropriate pore size (such as the SEM-measured average pore size of the secondary pores in the upper junction area is 120-220nm, and the SEM-measured average pore size of the secondary pores in the lower junction area is 100-200nm), so that the permeation zone (at least part of the permeation zone) has the ability to retain large-particle impurities. Therefore, the permeation zone not only ensures that the composite virus removal membrane has high anti-stratification performance, but also has a pre-filtration effect.

[0069] Therefore, by cooperating with the pre-filtration effect of the permeation zone and the pre-filtration zone with a thickness of 20 to 60 μm to form a multi-stage pre-filtration effect, a good retention capacity for large-particle impurities in the feed liquid can be formed, which greatly reduces the possibility of large-particle impurities leaking into the separation zone and causing blockage in the separation zone, thereby further improving the load capacity of the composite virus removal membrane. This is different from the general composite membrane which often has a lower load capacity due to pore size mutation, and is a very unexpected result.

[0070] In addition, the separation zone of the filter membrane in this application is specifically set to a basic symmetrical structure (basic symmetry means that the average pore size change gradient measured by SEM is not greater than 5nm / μm, not that the pore size remains completely unchanged), which can ensure that the separation zone has a good virus retention capacity and a higher dirt holding capacity and flux. This is because the separation zone with a large asymmetry forms a virus retention through the continuous reduction of the pore size. When the pore size is reduced to a certain extent, it will have a strong retention effect on viruses of corresponding sizes; therefore, for the separation zone with a large asymmetry, the virus tends to form a large amount of retention within a smaller thickness range. Combined with the smaller pore size there, a large amount of virus retention can easily lead to local blockage of the filter membrane, thereby causing rapid attenuation of the flux.

[0071] It should be noted that a specific basic symmetrical separation zone needs to be combined with a specific secondary pore structure in order to preferably obtain a composite virus removal membrane with high flux and high virus retention capacity. This is because, as is well known, a basically symmetrical membrane structure has an inherent characteristic of low load capacity. The reason is that a symmetrical membrane structure has difficulty retaining particles of different particle sizes in different areas, and the concentrated retention of particles in a local large particle size range will lead to rapid clogging of the membrane pore structure, resulting in a low load capacity. The specific secondary pore structure in this application is combined with the pre-filtration zone structure to form a multi-stage pre-filtration effect, thereby greatly reducing the possibility of large particle impurities leaking into the separation zone.

[0072] On the basis of basically no large particle impurities leaking into the separation zone, the thickness range of the basically symmetrical separation zone for virus retention is often larger. This is because the pore structure with relatively small pore size in the separation zone is combined with the certain thickness of the separation zone, and the pores are continuously stacked in the thickness direction. The retention effect will be smaller than the actual size of the pore structure. For example, the projection surface of the upper pore structure may be the fiber structure of the lower pores, and the fiber structure separates the upper pore structure, thereby improving the retention effect of the pore structure for smaller particulate matter; by stacking this pore structure in the thickness direction of the membrane, it can be ensured that the pore structure has a good retention effect for smaller particles, and the more uniform distribution of viruses makes the separation zone less prone to blockage and the flux decays more slowly.

[0073] Therefore, even if the separation zone adopts a basically symmetrical structure, it is not prone to clogging. In fact, since the virus retention area in the separation zone is wider and the contamination space is larger, it has a larger load capacity. This result is also very unexpected.

[0074] Regardless of whether the permeation zone of the composite membrane structure is the "interlocking" structure as described in the aforementioned Chinese patent application with application publication number CN115569521A, or the structure in which only the casting liquid permeates without forming a secondary pore structure as described in the Chinese patent application with authorization announcement number CN1108853C, since the permeation zone does not form a clear pre-filtration effect, large particles of impurities in the feed liquid must be intercepted by the pre-filtration zone, and the risk of leakage of large particles of impurities is relatively higher. If a basically symmetrical separation zone is used, due to the weak ability to intercept large particles of impurities and viruses in different regions, the basically symmetrical separation zone is likely to be quickly blocked by leaking large particles of impurities, resulting in a rapid decrease in flux and a small load.

[0075] Therefore, the introduction of a basic symmetrical structure separation zone requires the introduction of a secondary pore structure in the permeation zone that has less resistance to the feed and liquid and has a pre-filtration effect in order to achieve unexpected high flux and high load effects.

[0076] Optionally, the average pore size of the pre-filtration zone measured by SEM is 80 to 120 nm; the average pore size of the separation zone measured by SEM is 35 to 70 nm.

[0077] By adopting the above technical solution, on the basis that the secondary pores in the permeation zone have already preliminarily pre-filtered the large particle impurities in the feed liquid, the pre-filtration zone in the cellulose layer is mainly used to intercept relatively small impurities (of course, still larger than viruses) that are not retained by the secondary pores, and to intercept large particle impurities leaked from the permeation zone. Therefore, the pore size of the pore structure in the pre-filtration zone should not be too large (such as greater than 120nm) to ensure good impurity retention ability. Of course, the pore size of the pore structure in the pre-filtration zone should not be too small (such as less than 80nm) to ensure low feed liquid resistance and high pollution holding space.

[0078] In addition, the basically symmetrical separation zone structure is limited to a thickness of 20 to 40 μm, and the average pore size measured by SEM is 35 to 70 nm. Combined with the multi-stage pre-filtration effect of the permeation zone and pre-filtration zone, it can not only ensure efficient virus retention and reduce the risk of virus leakage, but also reduce the impact on flux and load.

[0079] Optionally, the SEM-measured average pore size change gradient of the pre-filtration zone is at least 2 nm / μm greater than the SEM-measured average pore size change gradient of the separation zone, and the SEM-measured average pore size change gradient of the separation zone is not greater than 3 nm / μm.

[0080] By adopting the above technical solution, the change in the pore size of the pore structure will bring about greater changes in the cross-sectional area and volume of the pore structure, which means that the pore structure with smaller pore size in the separation zone has a greater impact on the flux of the composite virus removal membrane. The SEM-measured average pore size change gradient of the separation zone of the composite virus removal membrane in this application is no more than 3nm / μm. Combined with the SEM-measured average pore size of the separation zone of 35-70nm, it shows that there is no extremely small pore structure in the separation zone, ensuring that the composite virus removal membrane has a larger flux. The SEM-measured average pore size change gradient of the pre-filtration zone should not be too small. This is because if the pre-filtration zone forms a basic symmetrical structure similar to the separation zone, the pre-filtration zone needs a larger thickness to ensure the retention effect for large-sized particles and is more likely to cause blockage due to local concentrated retention.

[0081] Optionally, the fiber diameter measured by SEM in the pre-filtration zone is 60 to 150 nm, and the fiber diameter measured by SEM in the separation zone is 20 to 40 nm.

[0082] By adopting the above technical solution, although the pressure resistance of the composite virus removal membrane can be significantly improved by introducing a microporous membrane support layer, the pre-filtration area and the separation area are still formed of a softer cellulose material. In order to improve the pressure resistance of the pre-filtration area and the separation area, the fiber diameters of the pre-filtration area and the separation area should not be too low; and since the introduction of the microporous membrane support layer will inevitably lead to a decrease in flux, the fiber diameters of the pre-filtration area and the separation area should not be too high, thereby causing excessive resistance to the flow of the feed liquid.

[0083] Optionally, there are liquid outlet holes in the form of round holes on the liquid surface, and the average pore diameter of the liquid outlet holes measured by SEM is 25-65 nm.

[0084] By adopting the above technical solution, different from the virus retention behavior of the asymmetric separation zone structure occurring in a relatively small thickness range, since the separation zone in this application has a substantially symmetric pore structure, the virus retention behavior occurs in a relatively large thickness range area in the separation zone. Although appropriately increasing the thickness of the separation zone (20-40 μm) can reduce the virus leakage risk through the continuous stacking of the pore structure in the thickness direction, further controlling the liquid outlet holes to have a smaller pore diameter (such as not greater than 45 nm) can further preferably reduce the virus leakage risk. Of course, since the pore structure with a smaller size in the separation zone has a greater resistance to the feed liquid and does not increase linearly (when the pore diameter is reduced by half, the pore area becomes one-fourth), therefore, the pore diameter of the liquid outlet holes should not be too small (such as less than 25 nm) to ensure that the virus removal membrane still has a relatively high flux while ensuring a low virus leakage risk.

[0085] Optionally, the pore size mutation coefficient B of the permeation zone and the pre-filtering zone is ≤ 30%, and the mutation coefficient B is calculated by the following formula: B = 100% × 丨D 渗 -D 预 丨 / D 均 ;

[0086] In the above formula, D 渗 is the SEM average pore diameter within 5 μm on the side of the permeation zone close to the pre-filtering zone, D<00,00013>is the SEM average pore diameter within 5 μm on the side of the pre-filtering zone close to the permeation zone, D<00,00014>is the average value of D n<00,00015>and D<00,00016> .

[0087] By adopting the above technical solution, for the composite membrane structure, in addition to being prone to delamination, the composite interface between the two-layer structure is prone to sudden changes in the pore structure, thereby causing a wide range of retention of particles with different particle sizes in the feed liquid, resulting in the formation of a filter cake and rapid blockage of the composite interface, which is also an easy problem to occur. In this application, the pore size mutation coefficient B of the permeation zone and the pre-filtering zone near the composite interface is not greater than 30%, which means that the pore diameter of the secondary pore structure in the permeation zone and the pore diameter of the pore structure of the pre-filtering layer transition in a relatively gentle manner.

[0088] In addition, due to the pre-filtration effect of the secondary pores in the permeation zone, some impurities have been trapped in the permeation zone. When the feed liquid flows through the composite interface, the impurity particle content in the feed liquid has been reduced. Therefore, even if the pore structure near the composite interface changes to a certain extent, it is not easy to quickly clog the pore structure due to concentrated retention. That is, the pore size mutation coefficient in this application is associated with the secondary pore structure introduced in the permeation zone. Accordingly, based on the fact that a permeation zone with a thickness of at least 10 μm has been introduced into the composite virus removal membrane of this application and secondary pores are present in the permeation zone, the pore size mutation coefficient B of the permeation zone and pre-filtration zone near the composite interface in this application only needs to be preferably no greater than 30%.

[0089] In a second aspect, the present application provides a process for preparing a cellulose virus removal membrane with high mechanical strength, using the following technical solution:

[0090] A process for preparing a cellulose virus removal membrane with high mechanical strength comprises the following steps:

[0091] S1. Preparing a casting solution: preparing a first-level casting solution, wherein the first-level casting solution has a viscosity of 3000 to 8000 mPa·s, a surface tension of 35 to 55 dyne / cm, and a content of the first-level film-forming polymer in the first-level casting solution of 5 to 15 wt %;

[0092] S2, casting film, casting the first-level casting liquid to form a liquid film, and then covering the liquid film with a microporous membrane support layer to obtain a composite semi-finished film;

[0093] S3, pretreatment, immersing the composite semi-finished film into a pretreatment bath to obtain a pretreated film, wherein the pretreatment bath is at least one of the good solvents for the primary film-forming polymer when preparing the primary casting solution, and the temperature of the pretreatment bath is 40-60° C., and the pretreatment time is 15-25 s;

[0094] S4, solidification, immersing the pretreated film in a coagulation bath until the pretreated film is completely phase-separated and solidified to obtain a green film, wherein the coagulation bath comprises a coagulation good solvent and a coagulation non-solvent;

[0095] S5. Post-treatment: placing the raw membrane in a regeneration bath to hydrolyze and regenerate the raw membrane to obtain a cellulose virus-removing membrane.

[0096] By adopting the above technical solution, the current film-making process of the composite membrane with a support layer is generally to directly apply the casting solution on the microporous membrane support layer, and after a series of post-treatments, the desired composite membrane is obtained. As mentioned above, in the Chinese invention patent with the authorization announcement number CN1108853C, it is clearly recorded that it is prepared by preparing a polymer solution (i.e., casting solution) of cellulose ester or cellulose polymer with a mass concentration of about 8 to 25%, and applying the prepared casting solution to the microporous substrate, and controlling the coating thickness to form a 1 to 20 μm thick dry film on the microporous substrate. Although this film-making process can also obtain a composite membrane with good anti-delamination performance, it is often at the expense of a significant reduction in flux and load.

[0097] Moreover, this preparation process of coating the casting liquid onto the microporous membrane support layer has other disadvantages. For example, when the casting liquid penetrates into the microporous membrane support layer, it will inevitably squeeze the air in the pore structure of the microporous membrane support layer to discharge the air. Since the air tends to be discharged upward, and the microporous membrane support layer is above the casting liquid with higher viscosity, it is not easy for all the air to pass through the casting liquid. The bubbles remaining in the casting liquid will become macroporous defects in the membrane layer after the casting liquid solidifies (this is why the casting liquid is often degassed before pouring, but the degassed treatment can only remove the bubbles in the casting liquid, and cannot control the bubbles in the microporous membrane support layer); therefore, the preparation process of coating the casting liquid on the surface is prone to introduce defects in the membrane layer, affecting the virus retention effect of the composite membrane.

[0098] In addition, it is more difficult to open pores on the surface of cellulose raw materials (this is related to its own characteristics. The phase separation speed in the solidified liquid is faster, and the rapid phase separation easily forms a small pore structure with a higher density). The preparation process of coating the casting liquid on the surface means that even if a certain pretreatment method is used to pretreat the casting liquid, on the one hand, since the microporous membrane support layer is located on the carrier side, it is difficult for the pretreatment system to penetrate the microporous membrane support layer whose pores are blocked; on the other hand, the pretreatment system needs to penetrate the entire layer of casting liquid to pretreat the junction of the casting liquid and the microporous membrane support layer, which is not realistic. Therefore, even if pretreatment is performed, a larger pore structure can only be obtained on the side of the casting liquid away from the microporous membrane support layer, and a relatively dense pore structure is still easily formed at the junction of the casting liquid and the microporous membrane support layer. This is also one of the reasons why the Chinese invention patent with the authorization announcement number CN1108853C clearly states that the thicker the permeation layer, the lower the flux.

[0099] The present application adopts a specific support layer back cover process, that is, first pouring a primary casting liquid to obtain a liquid film, and then covering the liquid film obtained by pouring a microporous membrane support layer. The process of supporting layer back cover solves the problem that the air in the pore structure of the microporous membrane support layer enters the casting liquid to form bubbles, thereby causing defects. This is because after the casting liquid compresses the air in the microporous membrane support layer, the air in the pore structure of the microporous membrane support layer tends to be discharged upward, and the microporous membrane support layer is located on the air side. The pore structure of the microporous membrane support layer is not shielded in any way. Therefore, the air inside the microporous membrane support layer can easily escape upward; even if the casting liquid is not completely degassed, it is easy to escape through the pore structure of the microporous membrane support layer above. In addition, during pretreatment, the pretreatment system can pretreat the casting liquid that has penetrated into the microporous membrane support layer after passing through the microporous membrane support layer, thereby introducing a macroporous structure in the permeation zone.

[0100] It can be understood that the casting liquid in this application can be cast onto a carrier such as a steel belt or a roller, or onto a release film, a release layer, or even onto a microporous membrane, as long as the casting liquid does not leak. For the sake of ease of description, the carrier is used in this application for a unified description.

[0101] It should be noted that due to the use of the support layer back cover process, in order to ensure that a permeation zone of sufficient thickness is obtained so that the composite virus removal membrane has good anti-stratification performance, it is necessary to strictly control the viscosity, surface tension and solid content of the first-level casting liquid. On the basis of the support layer back cover process, if the viscosity of the first-level casting liquid is too high (such as greater than 8000mPa·s), the surface tension is too large (such as greater than 55dyne / cm), and the solid content is too high (such as greater than 15wt%), the first-level casting liquid will be difficult to penetrate into the microporous membrane support layer, and it will be difficult to ensure the anti-stratification performance of the composite virus removal membrane; secondly, even after pretreatment, the first-level casting liquid with too high viscosity and too high solid content will be difficult to form a cellulose fiber three-dimensional network structure with a high degree of looseness, which will easily lead to excessive liquid resistance and too low pollution holding space in the permeation zone, resulting in too low flux and load of the composite virus removal membrane. On the basis of adopting the support layer back cover process, the viscosity, surface tension and solid content of the first-level casting liquid should not be too low (such as viscosity lower than 3000mPa·s, surface tension lower than 35dyne / cm, solid content lower than 5wt%), so as to avoid excessive penetration of the first-level casting liquid into the microporous membrane support layer, thereby causing excessive reduction in the flux loading capacity of the composite virus removal membrane.

[0102] In addition, the support layer back cover process and the specific first-level casting liquid in this application also need to be combined with a pretreatment process to ensure that the required secondary pore structure is present in the permeation zone of greater thickness. It is essential to ensure that the pretreatment bath has a good pretreatment effect on the first-level casting liquid in the permeation zone during pretreatment. Therefore, based on the support layer back cover process and the viscosity of the first-level casting liquid of 3000-8000 mPa·s, the surface tension of 35-55 dyne / cm, and the solid content of 5-15 wt%, it is necessary to strictly control the pretreatment time to 15-25 s during pretreatment, and also strictly control the temperature of the pretreatment bath to 40-60 ° C, and use a good solvent pretreatment bath with good dilution effect. This is because, if the temperature of the pretreatment bath is too low (such as below 40°C), the viscosity of the primary casting liquid increases at a lower temperature and it is difficult to be penetrated by the pretreatment bath; if the pretreatment time is too short (such as below 15s), the pretreatment bath is difficult to penetrate the permeation zone which already has a large thickness, and thus it is difficult to ensure that the entire permeation zone has a secondary pore structure; if the temperature of the pretreatment bath is too high (such as above 60°C) and the pretreatment time is too long (such as above 25s), it is likely to cause the primary casting liquid in the permeation zone to be over-diluted and the primary casting liquid in the pre-filtration zone to be over-diluted, resulting in the three-dimensional network structure formed by the cellulose fibers in the permeation zone being too loose. Even if the thickness of the permeation zone is large, it is difficult to obtain a high anti-stratification performance, and an overly loose secondary pore structure may also mean that the permeation zone and the pre-filtration layer have insufficient retention capacity for large particle impurities. Once large particle impurities leak and affect the area of ​​virus retention in the composite membrane, the composite membrane load will be reduced.

[0103] Therefore, on the basis of the specific use of the support layer back cover process, it is necessary to comprehensively and indivisibly adjust the various parameters of the primary casting liquid and the pretreatment process parameters, so that the thicker permeation area can ensure that the composite virus removal membrane has a higher anti-stratification performance, and by further introducing a secondary pore structure, the impact on the flux of the composite virus removal membrane can be reduced.

[0104] It is understood that the surface tension in this application refers to the surface tension of the material at a temperature of 25°C.

[0105] Optionally, in step S1, in addition to preparing the primary casting liquid, a secondary casting liquid is also prepared, and the solid content of the secondary casting liquid is greater than the solid content of the primary casting liquid; in step S2, the secondary casting liquid and the primary casting liquid are sequentially cast to form a liquid film, and the liquid film is a double-layer liquid film, and the microporous membrane support layer covers the secondary casting liquid side of the liquid film.

[0106] By adopting the above technical solution, compared with the preparation of the cellulose layer by the single-layer casting process, the cellulose layer prepared by the double-layer casting process can control the load and flux of the composite membrane by controlling the thickness of the primary casting liquid and the secondary casting liquid. This is because the single-layer casting process requires that the casting liquid of a single composition not only forms a region in the composite membrane that serves as a virus interception, but also forms a region in the composite membrane that serves as a pre-filtration function. In order to ensure that the composite membrane has a low risk of virus leakage, the solid content of the casting liquid should not be too low, and a pre-filtration area with a larger pore structure is introduced into the composite membrane through a pretreatment process; in order to introduce a pre-filtration area with a good pre-filtration effect into the cellulose layer, the casting liquid needs to be properly pretreated, which often means excessive pretreatment of the permeation zone, resulting in the formation of a cellulose fiber skeleton structure with a lower density in the permeation zone, thereby causing a decrease in the anti-delamination performance of the composite membrane. The use of a double-layer casting process allows the first-level casting liquid with a relatively low solid content to form a pre-filtration zone with a relatively large pore structure, and after the permeation zone is pretreated, the casting liquid in the permeation zone has a relatively low solid content and a higher good solvent content. The higher concentration of good solvent means that the coagulation bath actually forms a mixed system of good solvent and non-solvent after passing through the permeation zone. The driving force when the mixed system induces the first-level casting liquid to separate phases is relatively small, and the phase separation speed of the first-level casting liquid is relatively slow. The relatively lower solid content and slower phase separation speed make the first-level casting liquid easy to form a pre-filtration zone with a large pore structure. In addition, the solid content of the second-level casting liquid in this application is greater than that of the first-level casting liquid. The second-level casting liquid with a higher solid content can form a separation zone structure with a higher virus retention capacity, thereby ensuring that the composite virus removal membrane has a lower risk of virus leakage.

[0107] In summary, the thicker pre-filtration zone combined with the permeation zone with a secondary pore structure enables the composite membrane to have a higher load capacity, while the separation zone formed mainly by the secondary casting liquid with a higher solid content can ensure that the composite membrane has a lower risk of virus leakage (the primary casting liquid and the secondary casting liquid are inevitably miscible due to mutual mass transfer, but the separation zone is mainly formed by the secondary casting liquid, and the pre-filtration zone is mainly formed by the secondary casting liquid). Therefore, it is preferred to use a double-layer casting process in conjunction with a microporous membrane back cover process, so that the prepared composite membrane can not only have high anti-stratification performance, but also have high flux, high load and high virus retention capacity.

[0108] Optionally, the coagulation bath includes a coagulation good solvent and a coagulation non-solvent, and the mass proportion of the coagulation non-solvent in the coagulation bath is 80 to 95%; the coagulation good solvent is at least one of the primary film-forming polymer good solvents for preparing the primary casting solution; the coagulation non-solvent is at least one of water or ethanol.

[0109] By adopting the above technical solution, on the basis of adopting the support layer back cover and pre-treating with a good solvent, the microporous membrane support layer has a relatively thick permeation zone and the primary casting liquid in the permeation zone is diluted to a certain extent. At this time, it is preferred to control the ratio of the coagulation bath (the mass ratio of the good solvent and the non-solvent) to adjust the phase separation speed of the primary casting liquid in the permeation zone. If the proportion of non-solvent in the coagulation bath is too low (such as less than 80%), the effect of the non-solvent in promoting phase separation is poor due to its low concentration, resulting in a too low phase separation speed of the primary casting liquid in the permeation zone. During phase separation, the polymer-rich phase has sufficient time to move and merge, forming an oversized cellulose fiber structure, which not only easily leads to excessive resistance to the liquid in the permeation zone, but also may cause the anti-stratification performance of the composite virus removal membrane to decrease. If the proportion of non-solvent in the coagulation bath is too high (such as higher than 95%), for the primary casting liquid in the permeation zone that has been diluted due to pretreatment, the excessively high concentration of non-solvent in the coagulation bath means an overly fast phase separation rate. During phase separation, the polymer-rich phase solidifies into cellulose fibers without fully merging, so the size of the cellulose fibers is smaller. In fact, due to the excessively fast phase separation rate, the polymer-rich phase fails to connect with each other and solidifies in a short period of time. The obtained cellulose fibers may not be able to form a three-dimensional network structure that is interconnected, resulting in a decrease in the anti-stratification performance of the composite virus removal membrane.

[0110] It should be noted that due to the high proportion of good solvent in the primary casting solution in the permeation zone, the good solvent obtained through continuous phase separation during the solidification phase separation process will dissolve into the coagulation bath, thereby diluting the non-solvent in the coagulation bath. After dilution, the non-solvent concentration in the coagulation bath decreases, reducing the effect of promoting phase separation. Therefore, in order to ensure that the coagulation bath has a good and desired effect of promoting phase separation, it is preferred to determine the coagulation bath system based on the primary casting solution after specific pretreatment to ensure that the coagulation bath system has the desired effect of promoting phase separation not only for the primary casting solution in the permeation zone, but also for the casting solution in the prefiltration zone and separation zone.

[0111] Optionally, the primary casting solution includes the following raw materials in parts by mass:

[0112] 5-15 parts of a primary film-forming polymer;

[0113] 85-95 parts of the first good solvent;

[0114] The secondary casting solution comprises the following raw materials in parts by mass:

[0115] 20-40 parts of secondary film-forming polymer;

[0116] 60-80 parts of the second good solvent;

[0117] The secondary film-forming polymer and the primary film-forming polymer are at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, and cellulose acetate propionate;

[0118] The first good solvent and the second good solvent are both at least one of acetone, dioxane, dimethylacetamide, N-methylpyrrolidone, acetic acid, propionic acid, butyric acid, and valeric acid.

[0119] Optionally, 2 to 10 parts by mass of a penetrant is further added to the secondary casting solution, and the surface tension of the penetrant is not higher than 25 dyne / cm.

[0120] Optionally, the penetrant is at least one of ethanol, 1-propanol, hexafluoroisopropanol or trifluoroethanol.

[0121] Optionally, the viscosity of the secondary casting solution is 15,000 to 40,000 mPa·s, and the surface tension is not higher than 45 dyne / cm.

[0122] By adopting the above technical solution, as mentioned above, in order to form a separation zone structure with good virus retention ability, the secondary casting liquid has a higher solid content than the primary casting liquid, and a higher solid content often means a higher viscosity and greater penetration difficulty, making it difficult for the coagulation bath to penetrate and causing the secondary casting liquid to separate into phases. Further adding 2 to 10 parts by mass of a penetrant with a surface tension not higher than 25 dyne / cm to the secondary casting liquid can further reduce the surface tension of the secondary casting liquid, so that the surface tension of the secondary casting liquid is not greater than 45 dyne / cm, and by further controlling the viscosity of the secondary casting liquid, the possibility of the coagulation bath being difficult to penetrate due to excessive viscosity can be reduced. Therefore, by adding a penetrant to control the surface tension of the secondary casting liquid and controlling the viscosity of the secondary casting liquid, the mutual penetration difficulty between the coagulation bath and the casting liquid can be greatly reduced, so that the coagulation bath can quickly and evenly penetrate into the carrier side of the secondary casting liquid. Accordingly, the secondary casting liquid has a faster and more uniform phase separation speed, thereby obtaining a separation zone structure with a smaller pore size, higher uniformity and a roughly symmetrical pore size.

[0123] Optionally, before preparing the casting solution, the primary film-forming polymer and the secondary film-forming polymer are dried to a moisture content of no more than 5%; after the casting solution is prepared and before film casting, vacuum degassing treatment is performed.

[0124] By adopting the above technical solution, in addition to the non-solvent in the coagulation bath promoting phase separation of the casting solution, a small amount of non-solvent is inevitably introduced into the casting solution. For the casting solution system, if the non-solvent content in the system is too high, it may cause the casting solution to reach the cloud point more easily (the interaction between the polymer and the good solvent is retrieved, making phase separation easier). As mentioned above, the specific preparation process in this application makes excessively fast phase separation speed unacceptable. Therefore, by drying both the primary film-forming polymer and the secondary film-forming polymer to a moisture content of no more than 5%, it is possible to ensure that the unnecessary introduction of non-solvent during the preparation of the casting solution can be avoided, thereby affecting the subsequent pretreatment and curing steps.

[0125] In summary, this application includes at least one of the following beneficial technical effects:

[0126] 1. The composite virus removal membrane of the present application has a permeation zone with a thickness of not less than 10 μm, ensuring that the microporous membrane support layer and the cellulose layer have sufficiently high anti-delamination performance through the mutual entanglement and mutual anchoring between the microporous fibers and the cellulose fibers. In addition, the composite virus removal membrane of the present application controls the cellulose layer in the permeation zone to form cellulose fibers with an average diameter of not more than 180 nm. These smaller-diameter cellulose fibers are intertwined and entangled with each other, dividing the basic pores of the microporous membrane support layer into a large number of secondary pores, forming a unique large-pore-within-small-pore structure in the permeation zone. This special structure greatly reduces the resistance of the permeation zone to the feed liquid and increases the contaminant-holding space in the permeation zone. As a result, the composite virus removal membrane not only has high anti-delamination performance, but also has high flux and loading capacity.

[0127] 2. The influence of different parts in the permeation zone on the anti-stratification performance of the virus removal membrane is not the same. By limiting the morphological parameters in the interface area closest to the composite interface, especially in the lower interface area, the composite virus removal membrane can further obtain more preferred anti-stratification performance and high flux and high load.

[0128] 3. The present application specifically adopts a composite membrane preparation process with a microporous membrane back cover, and preferably adopts a double-layer casting process, so that the prepared composite membrane not only has good anti-stratification performance, but also has a higher load capacity and flux, overcoming the technical difficulty that the general composite membrane anti-stratification performance needs to be improved at the expense of flux reduction. BRIEF DESCRIPTION OF THE DRAWINGS

[0129] FIG1 is a scanning electron microscope image of the overall cross section of the composite virus removal membrane of Example 1 of the present application. The upper layer in the image is the microporous membrane support layer, and the magnification in the image is 500×.

[0130] Figure 2 is a scanning electron microscope image of the permeation area of ​​the composite virus removal membrane in Example 1 of the present application. The upper layer in the figure is the microporous membrane support layer, and the magnification in the figure is 2000×.

[0131] FIG3 is a further enlarged view of the permeation area in FIG2 , used to show the structure of the interface area. The upper layer in the figure is the microporous membrane support layer, and the magnification in the figure is 5000×.

[0132] FIG4 is a scanning electron microscope image of the composite interface of the composite virus removal membrane of Example 1 of the present application. The upper layer in the image is the microporous membrane support layer, and the magnification in the image is 20,000×.

[0133] FIG5 is a scanning electron microscope image of the liquid outlet surface of the composite virus removal membrane in Example 1 of the present application, and the magnification in the image is 10000×.

[0134] FIG6 is a scanning electron microscope image of the side of the microporous membrane support layer of the composite virus removal membrane in Example 1 of the present application close to the liquid inlet surface, and the magnification in the image is 5000×. DETAILED DESCRIPTION

[0135] The present application is further described in detail below with reference to Figures 1 to 6 .

[0136] The embodiments of the present application disclose a cellulose virus removal membrane with high mechanical strength and a preparation process thereof.

[0137] Example 1

[0138] This embodiment discloses a process for preparing a cellulose virus removal membrane with high mechanical strength, comprising the following process steps:

[0139] S1. Preparation of casting solution: prepare secondary casting solution and primary casting solution respectively. The formula and various parameters of primary casting solution and secondary casting solution are shown in Table 1.

[0140] S2, casting film, casting the secondary casting liquid and the primary casting liquid onto the carrier in turn to form a double-layer liquid film, and then covering the double-layer liquid film with a microporous membrane support layer to obtain a composite semi-finished film. In this embodiment, the carrier is a steel belt.

[0141] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is immersed in a pretreatment bath to obtain a pretreated membrane. The formula of the pretreatment bath and various process parameters used in the pretreatment are detailed in Table 1.

[0142] S4, curing, immersing the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and solidified to obtain a green membrane. The formula of the coagulation bath used in the curing stage and various process parameters are detailed in Table 1.

[0143] S5, post-treatment: placing the raw membrane in a regeneration bath for hydrolysis and regeneration. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral, thereby obtaining a cellulose virus-removing membrane. In this embodiment, the regeneration bath is a sodium hydroxide aqueous solution with a concentration of 0.05 mol / L and a temperature of 60°C. The raw membrane is hydrolyzed and regenerated in the regeneration bath for 100 minutes.

[0144] Examples 2 to 9

[0145] The main difference between Examples 2 to 9 and Example 1 is that the formula of the casting solution and the process parameters of each process are different, see Table 1 for details.

[0146] Among them, Examples 1 to 8 all adopt a double-layer casting process, while Example 9 adopts a single-layer casting process.

[0147] Comparative Example 1

[0148] Comparative Example 1 of the present application discloses a composite virus removal membrane. The main difference between its preparation process and that of Example 1 is that a preparation process of pouring a single layer of casting liquid on a microporous membrane support layer is adopted. The specific process steps are as follows:

[0149] S1. Preparation of casting solution. The casting solution formula and various parameters are detailed in Table 1.

[0150] S2, casting film, placing the microporous membrane support layer on the carrier, and casting the prepared casting liquid onto the microporous membrane support layer to form a liquid film, thereby obtaining a composite semi-finished film.

[0151] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is immersed in a pretreatment bath to obtain a pretreated membrane. The formula of the pretreatment bath and various process parameters used in the pretreatment are detailed in Table 1.

[0152] S4, curing, immersing the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and solidified to obtain a green membrane. The formula of the coagulation bath used in the curing stage and various process parameters are detailed in Table 1.

[0153] S5, post-treatment: The green membrane is placed in a regeneration bath for hydrolysis and regeneration. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral, thereby obtaining a cellulose virus-removing membrane. In this embodiment, the regeneration bath is a sodium hydroxide aqueous solution with a concentration of 0.05 mol / L and a temperature of 60°C. The green membrane is hydrolyzed and regenerated in the regeneration bath for 120 minutes.

[0154] Comparative Example 2

[0155] Comparative Example 2 of the present application discloses a composite virus removal membrane. The main difference between its preparation process and that of Example 1 is that a single layer of casting solution is first cast and then covered with a microporous membrane support layer without pretreatment. The specific process steps are as follows:

[0156] S1. Preparation of casting solution. The casting solution formula and various parameters are detailed in Table 1.

[0157] S2, casting film, casting the casting liquid onto the carrier to form a liquid film, and then covering the liquid film with a microporous membrane support layer to obtain a composite semi-finished film.

[0158] S3, curing, immersing the carrier loaded with the composite semi-finished film into a coagulation bath until the pretreated film is completely phase-separated and solidified to obtain a green film. The formula of the coagulation bath used in the curing stage and various process parameters are detailed in Table 1.

[0159] S4, post-treatment: The raw membrane is placed in a regeneration bath for hydrolysis and regeneration. After hydrolysis and regeneration, the membrane is removed and washed with water until neutral, thereby obtaining a cellulose virus-removing membrane. In this embodiment, the regeneration bath is a sodium hydroxide aqueous solution with a concentration of 0.05 mol / L and a temperature of 60°C. The raw membrane is hydrolyzed and regenerated in the regeneration bath for 100 min.

[0160] Comparative Example 3

[0161] The main difference between Comparative Example 3 and Comparative Example 2 is that a casting solution with a higher viscosity and a higher solid content is used, and further pretreatment is performed. The specific process steps are as follows:

[0162] S1. Preparation of casting solution. The casting solution formula and various parameters are detailed in Table 1.

[0163] S2, casting film, casting the casting liquid onto the carrier to form a liquid film, and then covering the liquid film with a microporous membrane support layer to obtain a composite semi-finished film.

[0164] S3. Pretreatment: The carrier loaded with the composite semi-finished membrane is immersed in a pretreatment bath to obtain a pretreated membrane. The formula of the pretreatment bath and various process parameters used in the pretreatment are detailed in Table 1.

[0165] S4, curing, immersing the carrier loaded with the pretreated membrane into a coagulation bath until the pretreated membrane is completely phase-separated and solidified to obtain a green membrane. The formula of the coagulation bath used in the curing stage and various process parameters are detailed in Table 1.

[0166] S5, post-treatment, placing the raw membrane in a regeneration bath to hydrolyze and regenerate the raw membrane, taking out the membrane after hydrolysis and regeneration and washing it with water until it is neutral to obtain a cellulose virus removal membrane.

[0167] Table 1 Casting solution formula and process parameters of each embodiment and comparative example

[0168] It should be noted that in each example, cellulose diacetate was used as the primary and secondary film-forming polymers; a mixture of equal volumes of dimethylacetamide and N-methylpyrrolidone was used as the first and second good solvents; the pretreatment bath had the same composition as the first and second good solvents; the coagulation bath contained dimethylacetamide as the good solvent; both the primary and secondary film-forming polymers were dried to a water content of no more than 5 wt% before preparing the casting solution; and the casting solution was vacuum degassing after preparation. Furthermore, Comparative Examples 1-3 all used single-layer casting solutions, and their formulations are recorded as secondary casting solutions in Table 1.

[0169] Performance testing and performance data

[0170] 1. Virus Challenge Test

[0171] The virus challenge test method is carried out in accordance with the relevant provisions of PDATR41, and the model virus is PP7 phage or hepatitis B virus, the model protein is IVIG, and the buffer is PBS. During the test, the changes in flux and load over time are recorded to obtain the LRV, flux, and load of the filter membrane.

[0172] 2. Anti-delamination performance

[0173] The 180° peel strength test of the composite virus removal membranes obtained in the embodiments and comparative examples was performed using a universal tensile tester.

[0174] The surface morphology parameters of the various examples and comparative examples are listed in Table 2.

[0175] Table 2 Surface morphology parameters of each embodiment and comparative example

[0176] It should be noted that since the microporous membrane support layer in Comparative Example 1 is located on the downstream side of the composite virus removal membrane, the liquid outlet surface is the microporous membrane support layer, so the liquid outlet surface diameter data is not recorded; no obvious secondary pore structure is formed in the permeation area of ​​Comparative Example 1 and Comparative Example 2, so the relevant morphological parameters are not recorded.

[0177] The virus retention data of the filter membranes of the embodiments and comparative examples are recorded in Table 3:

[0178] Table 3 Virus retention related data of each embodiment and comparative example

[0179] in conclusion

[0180] By comparing the technical solutions and various performance data of Example 1 and Comparative Examples 1 to 3, it is not difficult to find that as the thickness of the permeable zone increases, the anti-delamination performance of the composite membrane tends to improve, but the flux tends to decrease accordingly. For example, Comparative Examples 1 and 2 do not introduce a secondary pore structure in the permeable zone. Although the thicker permeable zone gives the composite membrane good anti-delamination performance, its flux is too low, almost losing its practical application value. For example, although the permeable zone in Comparative Example 3 introduces a secondary pore structure, the permeable zone is too thin and the diameter of the cellulose fibers is too large, resulting in not only unsatisfactory anti-delamination performance but also low flux.

[0181] By comparing the technical solutions and various performance data of Examples 1 to 8, it is not difficult to find that by controlling the thickness of the permeation zone and the diameter of the cellulose fibers in the permeation zone and introducing a secondary pore structure in the permeation zone, it is possible to ensure that the composite virus removal membrane has both high flux and anti-stratification performance; in addition, further preferably controlling the morphological parameters of the interface zone can enable the composite virus removal membrane to have more preferred comprehensive performance.

[0182] By comparing the technical solutions and various performance data of Example 1 and Example 9, it is not difficult to find that compared with the membrane-making process using a single-layer casting, the membrane-making process using a double-layer casting can achieve better overall performance in terms of LRV, flux, load and anti-stratification performance.

[0183] By further comparing the technical solutions and various performance data of Example 9 and Comparative Example 2, it is not difficult to find that even if the same single-layer casting process and microporous membrane back cover process are used, if the corresponding pretreatment process is not combined, the composite virus removal membrane finally obtained has higher anti-stratification performance and higher LRV, but its flux and load are low, and it has almost no practical application value.

[0184] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A cellulose virus removal membrane with high mechanical strength, characterized in that: The invention comprises a microporous membrane support layer and a cellulose layer at least partially penetrated into the microporous membrane support layer, wherein the side of the microporous membrane support layer away from the fiber layer is a liquid inlet surface, and the side of the cellulose layer away from the microporous membrane support layer is a liquid outlet surface, the microporous membrane support layer and the cellulose layer both have non-directional tortuous passages, and the microporous membrane support layer and the cellulose layer are connected through the non-directional tortuous passages, the area in the microporous membrane support layer penetrated by the cellulose layer is a permeation zone, the cellulose layer also comprises a pre-filtration zone and a separation zone, the permeation zone, the pre-filtration zone and the separation zone are transitioned through continuous fibers, and the separation zone comprises the liquid outlet surface; The thickness of the permeable zone is not less than 10 μm; The permeation zone includes microporous fibers constituting the microporous membrane support layer and cellulose fibers constituting the cellulose layer, wherein the average diameter of the microporous fibers is greater than the average diameter of the cellulose fibers, and the average diameter of the cellulose fibers is no greater than 180 nm; The microporous fibers surround each other to form basic pores, and the cellulose fibers are located in the basic pores. The cellulose fibers surround each other and separate the basic pores into a plurality of secondary pores.

2. A cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The thickness of the permeable zone is 15-45 μm, and the ratio of the thickness of the permeable zone to the thickness of the cellulose layer is 25-65%.

3. A cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The area with a thickness of 10 μm on the side of the permeation zone close to the pre-filtration zone is the junction area, the area with a thickness of 5 μm on the side of the junction area close to the liquid inlet surface is the upper junction area, and the area with a thickness of 5 μm on the side of the junction area close to the liquid outlet surface is the lower junction area. The average pore size of the secondary pores in the permeation zone measured by SEM is larger than the average pore size of the secondary pores in the junction area measured by SEM; the average diameter of the cellulose fibers in the junction area is not less than 50 nm.

4. A cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average pore size of the secondary pores in the lower boundary zone measured by SEM is not greater than the average pore size of the secondary pores in the upper boundary zone measured by SEM, and the average pore size of the secondary pores in the upper boundary zone measured by SEM is smaller than the average pore size of the secondary pores in the permeation zone measured by SEM.

5. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average pore size of the secondary pores in the lower junction area measured by SEM is 100-200 nm, and the average pore size of the basic pores in the lower junction area measured by SEM is 600-1500 nm.

6. A cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average pore size of the secondary pores in the upper interface region measured by SEM is 120-220 nm, and the average pore size of the basic pores in the upper interface region measured by SEM is 600-1500 nm.

7. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The ratio of the average pore size of the basic holes measured by SEM to the average pore size of the secondary holes in the lower boundary area is 4-10; the ratio of the average pore size of the basic holes measured by SEM to the average pore size of the secondary holes in the upper boundary area is 3-9.

8. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average diameter of the cellulose fibers in the permeation zone is greater than the average diameter of the cellulose fibers in the interface zone; the average diameter of the cellulose fibers in the upper interface zone is greater than the average diameter of the cellulose fibers in the lower interface zone.

9. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average diameter of the cellulose fibers in the lower junction area is not less than 40 nm, and the ratio of the average pore diameter of the basic pores in the lower junction area measured by SEM to the average diameter of the cellulose fibers is 10-25.

10. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: The average diameter of the cellulose fibers in the upper junction area is not less than 60nm, and the ratio of the average pore diameter of the basic pores in the upper junction area measured by SEM to the average diameter of the cellulose fibers is 8-20.

11. The cellulose virus removal membrane with high mechanical strength according to claim 3, characterized in that: Taking the side of the interface area close to the pre-filtration area as the starting point, the interface area is divided into ten equal parts along the thickness direction, which are H1 to H2. 10 , wherein the area H1 to H5 is the lower boundary area, and the area H6 to H 10 The area of ​​H1 is the upper boundary area; the average pore size of the secondary pores measured by SEM in the H2 area is not greater than H 10 The average pore size of the secondary pores in the area was measured by SEM.

12. A cellulose virus removal membrane with high mechanical strength according to claim 11, characterized in that: The average pore size of the secondary pores in the H1 region measured by SEM is 100-200 nm, and the ratio of the average pore size of the secondary pores in the H1 region measured by SEM to the average pore size of the secondary pores in the H5 region measured by SEM is 0.8-0.

98.

13. The cellulose virus removal membrane with high mechanical strength according to claim 11, characterized in that: H 10 The average pore size of the secondary pores in the H6 region measured by SEM is 150-250 nm. The average pore size of the secondary pores in the H6 region measured by SEM is similar to that in the H 10 The average pore diameter ratio of the secondary pores in the region measured by SEM is 0.5-0.

9.

14. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The thickness of the pre-filtration zone is 20-60 μm, the thickness of the separation zone is 20-40 μm; and the separation zone has a symmetrical pore structure.

15. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The average pore size of the pre-filtration zone measured by SEM is 80-120 nm; the average pore size of the separation zone measured by SEM is 35-70 nm.

16. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The average pore size variation gradient measured by SEM in the pre-filtration zone is at least 2 nm / μm greater than the average pore size variation gradient measured by SEM in the separation zone, and the average pore size variation gradient measured by SEM in the separation zone is not greater than 3 nm / μm.

17. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The fiber diameter measured by SEM in the pre-filtration zone is 60-150 nm, and the fiber diameter measured by SEM in the separation zone is 20-40 nm.

18. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: There are circular liquid outlet holes on the liquid outlet surface, and the average pore diameter of the liquid outlet holes measured by SEM is 25-65 nm.

19. The cellulose virus removal membrane with high mechanical strength according to claim 1, characterized in that: The pore size mutation coefficient B of the penetration zone and the pre-filtering zone is ≤ 30%, and the mutation coefficient B is calculated by the following formula: B = 100% × 丨D 渗 - D 预 丨 / D 均 ; In the above formula, D 渗 D is the average pore size of the permeation zone within 5 μm near the pre-filtration zone. 预 D is the average pore size of the pre-filtration area within 5 μm near the permeation area. 均 D 渗 and D 预 The average value of .

20. The process for preparing the cellulose virus-removing membrane with high mechanical strength according to any one of claims 1 to 19, characterized in that: The process steps include: S1, preparing a casting solution, preparing a primary casting solution, wherein the primary casting solution has a viscosity of 3000-8000 mPa·s, a surface tension of 35-55 dyne / cm, and a content of a primary film-forming polymer in the primary casting solution of 5-15 wt %; S2, casting film, casting the primary casting liquid to form a liquid film, and then covering the liquid film with a microporous membrane support layer to obtain a composite semi-finished film; S3, pretreatment, immersing the composite semi-finished film into a pretreatment bath to obtain a pretreated film, the pretreatment bath is at least one of the primary film-forming polymer good solvents when preparing the primary casting solution, and the temperature of the pretreatment bath is 40-60° C., and the pretreatment time is 15-25 s; S4, solidification, immersing the pretreated film in a solidification bath until the pretreated film is completely solidified by phase separation to obtain a green film, wherein the solidification bath comprises a solidification good solvent and a solidification non-solvent; S5, post-treatment, placing the raw membrane in a regeneration bath to hydrolyze and regenerate the raw membrane to obtain a cellulose virus-removing membrane.

21. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 20, characterized in that: In the step S1, in addition to preparing the primary casting liquid, a secondary casting liquid is also prepared, and the solid content of the secondary casting liquid is greater than the solid content of the primary casting liquid; in the step S2, the secondary casting liquid and the primary casting liquid are cast in sequence to form a liquid film, and the liquid film is a double-layer liquid film, and the microporous membrane support layer covers the secondary casting liquid side of the liquid film.

22. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 20 or 21, characterized in that: The coagulation bath comprises a coagulation good solvent and a coagulation non-solvent, and the mass proportion of the coagulation non-solvent in the coagulation bath is 80-95%; the coagulation good solvent is at least one of the primary film-forming polymer good solvents for preparing the primary casting solution; the coagulation non-solvent is at least one of water or ethanol.

23. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 21, characterized in that: The primary casting solution comprises the following raw materials in parts by weight: 5-15 parts of a primary film-forming polymer; 85-95 parts of the first good solvent; The secondary casting solution comprises the following raw materials in parts by weight: 20-40 parts of secondary film-forming polymer; 60-80 parts of the second good solvent; The secondary film-forming polymer and the primary film-forming polymer are at least one of cellulose diacetate, cellulose triacetate, cellulose propionate, cellulose acetate phthalate, cellulose acetate butyrate, and cellulose acetate propionate; The first good solvent and the second good solvent are at least one of acetone, dioxane, dimethylacetamide, N-methylpyrrolidone, acetic acid, propionic acid, butyric acid and valeric acid.

24. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 23, characterized in that: The secondary casting solution is further added with 2 to 10 parts by weight of a penetrant, and the surface tension of the penetrant is not higher than 25 dyne / cm.

25. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 24, characterized in that: The penetrant is at least one of ethanol, 1-propanol, hexafluoroisopropanol or trifluoroethanol.

26. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 21, characterized in that: The viscosity of the secondary casting liquid is 15000-40000 mPa·s, and the surface tension is not higher than 45 dyne / cm.

27. The process for preparing a cellulose virus-removing membrane with high mechanical strength according to claim 21, characterized in that: Before preparing the casting solution, the primary film-forming polymer and the secondary film-forming polymer are dried to a moisture content of no more than 5%; after the casting solution is prepared and before the film is cast, a vacuum degassing treatment is performed.

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