PES sterilizing membrane with low non-specific adsorption and preparation method thereof

Abstract

The present application relates to a kind of low non-specific adsorption PES sterilization membrane and its preparation method, including porous body, porous body has non-directional tortuous path in it, one side of porous body is first outer surface, the other side of porous body is second outer surface, porous body includes pre-filter layer and separation layer, the SEM average pore size of pre-filter layer is greater than the SEM average pore size of separation layer;The PMI average pore size of sterilization membrane is 0.15-0.4 μm;Separation layer includes retention fiber, retention fiber is connected to form the three-dimensional network structure of separation layer, the SEM average diameter of retention fiber is 150-300 nm, and the acid density S of sterilization membrane is 0.5-2.Suitable thickness of retention fiber means that membrane has suitable dense separation layer, meanwhile, suitable acid density means that separation layer has suitable hydrophilicity, under the joint action of both, sterilization membrane has significantly reduced protein adsorption rate, high retention efficiency and higher flux.

Description

Technical Field

[0001] This invention relates to the field of membrane materials technology, and more specifically to a PES antibacterial membrane with low non-specific adsorption and its preparation method. Background Technology

[0002] In the 1960s, membranes with a pore size of 0.45 μm were considered "sterilization-grade" filtration membranes and were used in the pharmaceutical industry for sterilization filtration. With advancements in technology, a researcher in the United States discovered that a certain microorganism could survive in 10... 4 -10 6 cfu / cm 2 Under certain conditions, it can penetrate a 0.45μm filter membrane, causing contamination of the culture medium after "sterilization" filtration. In the early 1980s, a filter membrane based on polyvinylidene fluoride (PVDF) was developed based on the ASTM F838 bacterial retention standard method. Because the bubble point value of this membrane is about twice that of the traditional 0.45μm "sterilization-grade" membrane, it was named a 0.22μm membrane (sterilization membrane). It is generally believed in the industry that the pore size of a filter membrane that can pass the ASTM F838 test is labeled as 0.22μm or 0.2μm. Here, 0.22μm does not actually measure the pore size of the filter membrane. A new chapter in sterilization-grade filters was thus opened.

[0003] Currently, the main materials used for sterilization membranes include nylon, polyethersulfone (PES), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE). PVDF is not resistant to alkalis, and PTFE is not resistant to gamma rays, while PES sterilization membranes have excellent resistance to strong acids and alkalis, as well as gamma rays, playing a very important role in fields such as biopharmaceuticals. However, PES sterilization membranes also have some drawbacks. For example, polyethersulfone (PES) is a hydrophobic membrane material. When these microporous membranes are applied to feed systems containing proteins, a certain amount of protein may be adsorbed onto the membrane, causing unnecessary losses.

[0004] Ye Yingqi, ed., *Industrial Water Treatment Technology*, page 214, clearly states that hydrophilic polymer membranes adsorb proteins significantly less than hydrophobic membranes. Therefore, in protein ultrafiltration applications, hydrophilic ultrafiltration membranes should be selected whenever possible. In existing technologies, hydrophilic modification methods are generally used to improve the hydrophilicity of PES membranes, thereby addressing the protein adsorption problem. For example, Chinese invention patent application CN109603592A (applied by Wuxi Lingjie Purification Equipment Co., Ltd.) discloses a method for hydrophilic modification of polyethersulfone microporous membranes. During the casting process, a modifier containing free hydroxyl groups is added to the coagulation bath, introducing hydrophilic groups (hydroxyl groups) into the polyethersulfone microporous membrane, thereby improving its hydrophilicity. Introducing hydrophilic groups (such as hydroxyl and sulfonic acid groups) is one method for hydrophilic modification of PES. Sulfonic acid groups are more polar than hydroxyl groups; therefore, PES membranes with sulfonic acid groups and those with hydroxyl groups are more hydrophilic. Generally, it is believed that the higher the content of sulfonic acid groups introduced, the stronger the hydrophilicity of the membrane material, the weaker the non-specific adsorption of the membrane, and the less likely it is to adsorb effective substances such as proteins.

[0005] Chinese invention patent application CN108246115A discloses a method for preparing a flat-plate microfiltration membrane for biological detection. In preparing the polyethersulfone microporous membrane, sulfonated polyethersulfone is added to the casting solution to achieve hydrophilicity. The microporous membrane has a thickness between 100-115 μm, a maximum bubble point between 0.26-0.33 MPa, and uniform pore size. Its performance completely exceeds the industry standard for 0.45 μm pore size microfiltration membranes.

[0006] However, the guidance document PDA TR26 issued by the American Society for Injectable Drugs (PDA) clearly states that B. diminuta (deficient Pseudomonas) can penetrate at high challenge levels (typically ≥10). 7 A small number of membranes at the 0.45µm level are used, hence the term "sterilizing membrane" for 0.45µm membranes. Although the aforementioned microporous membranes have better bacterial retention performance than 0.45µm membranes, they may not necessarily meet the requirements of 0.22µm (sterilizing grade) filter membranes specified in PDA TR26, and there is still a risk of bacterial leakage under high-challenge conditions.

[0007] To address these issues, researchers typically employ the following approach: appropriately reducing the pore size of the filter membrane. While smaller pore sizes and thicker microporous membranes mean that polyethersulfone (PES) microporous membranes have a higher bacterial retention capacity, the relatively large internal surface area of ​​these membranes increases the probability of contact and collision between the feed solution and the solid portion within the membrane. This means a higher probability of protein adsorption and retention. Even with hydrophilic modification, the protein yield of PES microporous membranes may still be unsatisfactory; in other words, low protein adsorption and high retention performance cannot be simultaneously achieved.

[0008] In summary, the preparation of a PES sterilization membrane with high sterilization performance, high protein yield, and relatively high flux is a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0009] To address the shortcomings of existing technologies, the present invention aims to provide a PES sterilization membrane with low non-specific adsorption and its preparation method. This sterilization membrane has high sterilization performance, high protein yield, and relatively high flux.

[0010] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, this application provides a PES antibacterial membrane with low non-specific adsorption, employing the following technical solution: A PES sterilization membrane with low nonspecific adsorption comprises a porous body having non-directional tortuous pathways within it. One side of the porous body is a first outer surface, and the other side is a second outer surface. The porous body includes a pre-filtration layer and a separation layer for retaining bacteria. The SEM average pore size of the pre-filtration layer is larger than that of the separation layer. The PMI average pore size of the sterilization membrane is 0.15-0.4 μm. The separation layer includes retention fibers interconnected to form a three-dimensional network structure. The SEM average diameter of the retention fibers is 150-300 nm, preferably 150-250 nm. The acid density S of the sterilizing membrane is 0.5-2; the acid density S is calculated by the following formula: S=-lg[C] / M, where C is the concentration of hydrogen ions in the sodium chloride solution after the sterilizing membrane is soaked in 1mol / L HCl solution for 24h and then soaked in 100mL of 2mol / L sodium chloride solution at 60℃ for 24h, and the unit of C is: mol / L; M is the mass of the sterilizing membrane before soaking in sodium chloride solution, and M is 2g.

[0011] By adopting the above technical solution, the main body of the PES sterilization membrane of the present invention has non-directional tortuous pathways. These non-directional tortuous pathways refer to randomly oriented groove structures and / or discretely distributed pore structures, and each non-directional tortuous pathway is interconnected. Furthermore, the fibers forming the porous structure of the membrane are continuous. It can be understood that "continuous" means that essentially all the fibers are integrally connected to each other, as if formed as a single piece, without the need for additional adhesives or the like to connect them. Unless torn by external force, the network of fibers cannot be separated from each other. The sterilization membrane in this application has an asymmetrical membrane structure, and along its thickness direction, a pre-filtration layer with a larger average pore size and a separation layer with a smaller average pore size can be seen.

[0012] In practical use, the feed liquid passes sequentially through the pre-filtration layer and the separation layer. The pre-filtration layer is used to trap large particulate impurities in the feed liquid, preventing them from clogging the separation layer and thus increasing the service life of the sterilization membrane. The separation layer is used to trap bacteria. The sterilization membrane of this application has an average pore size of 0.15-0.4 μm, which ensures that the sterilization membrane has a good retention effect on bacteria.

[0013] The inventors of this application unexpectedly discovered that when the acid density of the PES sterilization membrane is between 0.5 and 2, and the average SEM diameter of the retained fibers in the separation layer is between 150 and 300 nm, the protein adsorption rate of the PES sterilization membrane is significantly reduced. At the same time, the PES sterilization membrane also has both high throughput and high bacterial retention efficiency.

[0014] This is likely because the separation layer is primarily used to retain bacteria. Therefore, within the main body of the membrane, the average pore size of the separation layer is relatively the smallest. The separation layer is a key region affecting the protein adsorption rate of the PES sterilization membrane. If the protein adsorption rate of the separation layer is low, the overall protein adsorption rate of the PES sterilization membrane will generally not be high. The separation layer includes retention fibers, which are interconnected to form a three-dimensional network structure. Specifically, the retention fibers in the solid part of the separation layer intersect and connect with each other, forming a three-dimensional network structure with a porous structure. The separation fibers act as the pore walls of this porous structure. Therefore, the retention fibers in the separation layer can, to some extent, characterize the morphology of the solid part of the separation layer.

[0015] The retaining fibers should have a suitable diameter (neither too thick nor too thin). If the diameter of the retaining fibers in the separation layer is too small (too fine), while it's true that along the thickness direction of the membrane bulk, the lower retaining fibers will achieve a more ideal staggered layering with the upper retaining fibers, forming a denser three-dimensional network structure and more tortuous flow channels, which is more conducive to improving the retention efficiency of bacteria, excessively fine retaining fibers also mean that the separation layer as a whole has a high specific surface area, leading to a greater probability of contact and collision between the feed liquid and the solid part of the separation layer, resulting in a higher adsorption rate of proteins in the membrane bulk. Simultaneously, the three-dimensional network structure of the separation layer is too "dense." To some extent, this will lead to a decrease in the overall flux of the sterilization membrane. If the diameter of the retention fibers is too large (too thick), although it will reduce the overall specific surface area of ​​the separation layer to some extent, thereby reducing the protein adsorption rate of the membrane body, it also means that the cross-lamination between the lower and upper retention fibers along the thickness direction of the membrane body is relatively loose, that is, the three-dimensional network structure formed by the separation layer is relatively loose, and the overall bacterial retention capacity of the sterilization membrane is low. However, as a sterilization membrane, its high-efficiency bacterial retention capacity must be guaranteed. Therefore, the fibers of the separation layer cannot be too thick (greater than 300 nm).

[0016] Furthermore, to ensure the economic benefits of the sterilization membrane, especially when filtering protein-containing liquids, its flux and protein yield must be guaranteed. Therefore, the fibers in the separation layer cannot be too fine (less than 150 nm). Of course, the diameter of the retained fibers should not exceed 300 nm, which will to some extent increase the overall protein adsorption rate of the PES sterilization membrane and decrease the flux. Therefore, in this application, the acid density of the PES sterilization membrane is further controlled. The acid density reflects the hydrophilicity of the solid part in the separation layer to some extent. In this application, by controlling the diameter of the retained fibers to 150-300 nm and controlling the acid density to not exceed 2, the three-dimensional network structure of the separation layer is not too dense, the specific surface area of ​​the separation layer is relatively suitable, and at the same time, the separation layer has suitable hydrophilicity, so that the overall protein adsorption capacity of the sterilization membrane is still relatively low. That is, the diameter of the retention fiber in the separation layer is 150-300nm and the acid density is within 2. At the same time, the sterilization membrane as a whole has a suitable average pore size of PMI. Under the synergistic effect of the three, the sterilization membrane has a high bacterial retention capacity and a relatively high flux, and significantly reduces the adsorption rate of protein in the separation layer.

[0017] Understandably, the acid density S in this application is calculated using the following formula: S = -lg[C] / M, where C is the concentration of hydrogen ions in the sodium chloride solution after the sterile membrane has been soaked in the sodium chloride solution for 24 hours, and the unit of C is mol / L; M is the mass of the sterile membrane before soaking in the sodium chloride solution, and the unit of M is g. -lg[C] is the negative value of the common logarithm of the hydrogen ion concentration in the sodium chloride solution. The higher the concentration of hydrogen ions in the sodium chloride aqueous solution, the smaller the value of -lg[C], that is, the smaller the value of the acid density S. Concentration C and mass M were obtained by the following method: Weigh 2g of the shredded PES sterilization membrane sample (sample mass is mass M), immerse the PES sterilization membrane sample in HCl solution (1mol / L 50℃) for 24 h to ensure that the sulfonic acid matrix of the PES sterilization membrane is ionized, then wash away the excess HCl solution on the surface of the PES sterilization membrane with deionized water, and then immerse the PES sterilization membrane sample in 100mL of 2mol / L NaCl solution at 60℃ for 24 h. The concentration of hydrogen ions in the sodium chloride solution after immersion is the concentration C.

[0018] As mentioned above, it is generally believed that the better the hydrophilicity of the membrane, the lower the protein adsorption of the membrane. However, the inventors of this application unexpectedly discovered that as the acid density of the PES sterilization membrane decreases, the hydrophilicity of the PES sterilization membrane continuously increases, and the protein adsorption rate of the PES sterilization membrane gradually decreases. However, when the acid density of the PES sterilization membrane is less than 0.5, as the acid density value continues to decrease, the protein adsorption rate of the PES sterilization membrane gradually increases. That is, for the PES sterilization membrane in this application (the diameter of the retained fiber in the separation layer is 150-300 nm; the average pore size of the PMI is 0.15-0.4 μm), the protein adsorption rate of the PES sterilization membrane does not continuously decrease with the increase of the membrane's hydrophilicity. Instead, as the membrane's hydrophilicity increases, the protein adsorption rate shows a trend of first decreasing and then increasing. This is different from the current general understanding and is quite unexpected.

[0019] This may be because, for PES sterilization membranes, hydrophilicity is not the only factor affecting their protein adsorption rate. The protein adsorption rate of PES sterilization membranes is determined by multiple factors (such as particle size exclusion (sieving retention), hydrophilic and hydrophobic adsorption retention, etc.). In other words, the factors affecting the protein adsorption rate of PES sterilization membranes vary depending on their degree of hydrophilicity.

[0020] When the hydrophilicity of the PES sterilization membrane is poor, hydrophilic-hydrophobic adsorption and retention are the main factors affecting the protein adsorption rate. Therefore, improving the hydrophilicity of the membrane significantly reduces protein adsorption, i.e., the acid density of the PES sterilization membrane should be below 2. Simultaneously, during the filtration process, the feed liquid will, to some extent, remove the H+ from the sulfonic acid groups introduced into the PES sterilization membrane. +Elution occurs because proteins carry an electrical charge (most proteins are negatively charged, a small portion are positively charged; proteins form electrostatic repulsion to maintain their dispersed state and reduce the possibility of aggregation). Among these, negatively charged proteins react with the eluted H+. + Binding, protein binding H + After being neutralized, the electrostatic forces between the proteins are lost. Because the protein particles are small and their surface energy is relatively high, the proteins may aggregate. The aggregated protein particles are larger and easier to trap (sieving trapping).

[0021] Of course, due to the relatively poor hydrophilicity of PES antibacterial membranes (H... + (Small quantity), H washed off + The quantity of proteins is relatively small, the proportion of electrically neutral proteins is relatively low, and the number of protein particles retained due to aggregation is also relatively small. In other words, when the hydrophilicity of the PES sterilization membrane is relatively low, the influence of sieving retention on the protein adsorption rate is relatively low, while the influence of adsorption retention is relatively high. Therefore, as the hydrophilicity of the PES sterilization membrane increases, the protein adsorption rate gradually decreases. Furthermore, aggregated proteins are prone to degradation; even if the protein particles are not retained, protein aggregation degradation is undesirable.

[0022] As the acid density decreases (below 0.5), although the hydrophilicity of the membrane continues to increase, the eluted H+... + As the quantity of protein increases, the concentration of proteins in the feed solution, which lose electrostatic repulsion due to the binding of hydrogen ions, continuously increases (even exponentially), leading to a higher probability of protein aggregation. The PES sterilization membrane of this application possesses a relatively dense three-dimensional network structure (with a fiber diameter of 150-300 nm and an average PMI pore size of 0.15-0.4 μm), exhibiting strong retention capacity. The PES sterilization membrane retains a large number of aggregated protein particles, resulting in a decrease in protein yield. In other words, when the hydrophilicity of the PES sterilization membrane is relatively high, the sieving retention factor accounts for a relatively high proportion of the protein adsorption rate, while the adsorption retention factor accounts for a relatively low proportion. Conversely, as the hydrophilicity of the PES sterilization membrane increases, the protein adsorption rate of the PES sterilization membrane actually shows an upward trend.

[0023] Furthermore, when H + After being washed, the PES sterilization membrane will exhibit a certain electronegativity. When filtering a liquid containing positively charged proteins, the positively charged proteins are easily adsorbed by the PES sterilization membrane under the action of electrostatic force, further increasing the protein adsorption rate of the filter membrane.

[0024] In summary, for PES sterilization membranes, hydrophilicity is not the sole factor affecting protein adsorption rate; it is determined by multiple factors (such as particle size exclusion (sieving retention), hydrophilic / hydrophobic adsorption retention, etc.), and these factors have different effects at different degrees of hydrophilicity. While acid density less than 0.5 certainly endows PES sterilization membranes with higher hydrophilicity, H... + The probability of being washed away is also relatively high. At this time, the probability of protein aggregation continues to increase, and the effect of particle size exclusion is greater than the effect of hydrophilic and hydrophobic adsorption. Although the PES sterilization membrane has high hydrophilicity, its protein yield shows a decreasing trend.

[0025] It is understood that the morphological parameters of the cross-section of the bactericidal membrane in this application can be measured by characterizing the membrane structure using a scanning electron microscope, followed by measurement and calculation using computer software (such as Matlab, NIS-Elements, etc.) or manually. During membrane fabrication, the direction perpendicular to the membrane thickness (if the membrane is a flat sheet, this direction is planar; if the membrane is a hollow fiber membrane, this direction is perpendicular to the radius) is considered. When measuring the diameter of the retained fibers, the membrane cross-section can first be characterized using an electron microscope to obtain the corresponding SEM image, and a certain area, such as 1 μm, can be selected. 2 (1μm x 1μm) or 25μm 2 (5μm x 5μm), the specific area size depends on the actual situation. Then, use appropriate computer software or manual measurement to determine the diameter of all the retained fibers on this area, and then calculate the average value to obtain the average diameter of the retained fibers in this cross section. Of course, those skilled in the art can also obtain the above parameters through other measurement methods. The above measurement methods are for reference only. In the following text, the average diameter of the pre-filtered fibers in the pre-filter layer can also be measured by the above method.

[0026] The average pore size of the sterilization membrane (PMI) can be directly measured using a PMI pore size tester.

[0027] Optionally, the ratio of the SEM average diameter of the retained fiber to the acid density is 0.10-0.35.

[0028] By adopting the above technical solution, a suitable ratio is achieved between the average SEM diameter of the retained fibers and the acid density (the ratio should not be too high, for example, above 0.35; nor should it be too low, for example, below 0.10), thereby further ensuring that the sterilization membrane as a whole has a low protein adsorption rate and relatively high flux and retention performance. That is, there is a positive correlation between the average SEM diameter of the retained fibers and the acid density; when the average SEM diameter of the retained fibers is small, the acid density is also small; when the average SEM diameter of the retained fibers is large, the acid density is also large.

[0029] When the average SEM diameter of the retained fibers is small (the fibers are fine, close to 0.15 μm), the overall acid density of the membrane is also relatively small (close to 0.5, meaning the overall H₂ of the membrane is low). + The PES sterilization membrane has relatively high retention capacity and relatively strong hydrophilicity. It also features finer fibers and a denser overall three-dimensional network structure, ensuring its retention capacity. However, this denser separation layer also means a relatively higher overall protein adsorption rate. Therefore, the PES sterilization membrane requires a higher overall hydrophilicity to reduce its protein adsorption rate. Conversely, excessive hydrophilicity can actually increase the protein adsorption rate.

[0030] If the average SEM diameter of the retained fibers is large (the fibers are thicker, close to 0.3 μm), the overall acid density of the membrane is also large (close to 2, meaning the overall H+ of the membrane is high). + When the amount of hydrophilicity is relatively small and the fiber density is relatively weak, the overall specific surface area of ​​the separation layer is relatively low and the separation layer is relatively loose. In this case, even if the PES sterilization membrane has a high acid density (weak hydrophilicity), it can still ensure a low overall protein adsorption rate. At the same time, the introduction of fewer hydrophilic groups can also reduce the production cost of the sterilization membrane to some extent and improve its film-forming performance. Of course, the hydrophilicity of the PES sterilization membrane cannot be too low. The separation layer remains a key area affecting protein adsorption in the PES sterilization membrane. Therefore, it is still necessary to ensure that the separation layer has appropriate hydrophilicity to guarantee low overall protein adsorption in the PES sterilization membrane.

[0031] Optionally, the thickness of the separation layer is 10-30 μm, and the ratio of the thickness of the separation layer to the average SEM diameter of the retained fiber is 0.06-0.15 μm / nm.

[0032] By adopting the above technical solution, the separation layer has a suitable three-dimensional network structure and an appropriate thickness, thereby further ensuring the protein yield, retention performance, and flux of the sterilization membrane. If the separation layer is too thick (thickness greater than 30 μm), the high-thickness separation layer has a denser three-dimensional network structure, which will obviously improve the retention performance of the sterilization membrane. However, at the same time, it will inevitably cause a decrease in flux (reduction in feed flow rate). Furthermore, if the separation layer is too thick and the feed flow rate is reduced, it means that the contact area between the feed and the solid part of the separation layer is larger and the contact time is longer, thus increasing the overall protein adsorption rate of the separation layer. If the separation layer is too thin (thickness less than 10 μm), even if the separation layer has a denser three-dimensional network structure, its retention capacity may still be unsatisfactory.

[0033] Meanwhile, a suitable ratio exists between the thickness of the separation layer and the average SEM diameter (thickness) of the retained fibers. If this ratio is too large, it means the separation layer is relatively thick and the retained fibers are relatively thin, resulting in a low overall flux of the sterilizing membrane. Furthermore, a highly dense and thick separation layer does not significantly improve the retention performance of the sterilizing membrane. This is because a dense separation layer inherently possesses superior retention performance; during liquid filtration, the separation layer near the first outer surface (inlet surface) has already largely retained the bacteria and other fine particles mixed in the liquid, leading to a relatively low effective retention rate on the separation layer near the second outer surface (outlet surface). Conversely, if the ratio is too small, it means the separation layer is relatively thin and the retained fibers are relatively coarse, thus the performance of the PES sterilizing membrane cannot be fully guaranteed.

[0034] In summary, the PES sterilization membrane possesses a separation layer of suitable thickness (10-30 μm), a suitable acid density (0.5-2), and a separation layer with retention fibers of suitable thickness (150-300 nm). Furthermore, the ratio between the SEM average diameter of the retention fibers and the acid density is suitable (0.1-0.3 μm), and the ratio between the acid density and the thickness of the separation layer is suitable (0.05-0.1 / (g·μm)). Under the synergistic effect of the above characteristics, the PES sterilization membrane further exhibits high retention efficiency, high throughput, and excellent protein yield.

[0035] Understandably, the thickness of the separation layer can be determined by characterizing the membrane structure using a scanning electron microscope, followed by calculation using computer software (such as Matlab, NIS-Elements, etc.) or by manual measurement. The thicknesses of the pre-filter layer, protective layer, and support layer, as described later, can also be measured using the same method.

[0036] Optionally, the average SEM pore size of the pores in the cross-section of the separation layer is 150-450 nm, preferably 150-350 nm, and the pore area ratio of the cross-section of the separation layer is 15-25%.

[0037] By adopting the above technical solution, this application ensures that the PES sterilization membrane has a suitable acid density (suitable hydrophilicity), the separation layer has a suitable thickness (10-30μm), and the separation layer has a suitable thickness of retention fibers (150-300nm). Furthermore, the separation layer also has a suitable cross-sectional pore size (150-450nm) and a suitable cross-sectional pore area ratio (15-25%), further ensuring the retention efficiency, flux, and protein yield of the sterilization membrane.

[0038] If the pore size of the separation layer is too small or the pore area ratio of the separation layer is too small (pore size less than 150 nm, pore area ratio less than 15%), although the retention efficiency of the sterilization membrane can be further guaranteed, the overall flux of the sterilization membrane will be low and the protein adsorption rate of the sterilization membrane will increase. If the pore size of the separation layer is too large or the pore area ratio of the separation layer is too large (pore size greater than 450 nm, pore area ratio greater than 25%), the retention performance of the sterilization membrane will be low.

[0039] Understandably, the average pore size and porosity of the separation layer can be measured using the following method: first, the cross-section of the PES sterilization membrane can be characterized using an electron microscope to obtain the corresponding SEM image, and then a certain area, such as 1 μm, can be selected. 2 (1μm x 1μm) or 25μm 2 (5μm x 5μm), the specific area size depends on the actual situation. Then, use appropriate computer software or manually measure the pore diameter of all pores in this area, and calculate their average value to obtain the average pore diameter of the separation layer at this cross-section. At the same time, measure the area of ​​all pores in this area, and calculate the pore area ratio of the separation layer at this cross-section. In the following text, the average pore diameter of the pre-filter layer, the average pore diameter of the protective layer, the pore area ratio of the protective layer cross-section, the average pore diameter of the support layer, and the pore area ratio of the support layer cross-section can also be measured by the above method.

[0040] Optionally, the ratio of the thickness of the separation layer to the average SEM pore size of the separation layer is 0.04-0.12 μm / nm.

[0041] By adopting the above technical solution, a suitable ratio is achieved between the thickness of the separation layer and the average SEM pore size of the separation layer. If the ratio is too large, it means that the separation layer is too thick and / or the pore size is too small (high thickness and small pores in the separation layer), resulting in a low overall flux of the PES sterilization membrane and a high overall protein adsorption rate, leading to low economic benefits. If the ratio is too small, it means that the separation layer is too thin and / or the pore size is too large (low thickness and large pores in the separation layer), thus the overall sterilization performance of the sterilization membrane cannot be guaranteed. A suitable thickness, pore size, and acid density in the separation layer ensure, to a certain extent, that the PES sterilization membrane possesses high retention capacity, high flux, and low protein adsorption rate.

[0042] Optionally, one side of the pre-filter layer is the first outer surface, the thickness of the pre-filter layer is 60-90μm, the SEM average pore size of the pre-filter layer is 400-900nm, and the pore area ratio of the cross section of the pre-filter layer is 25%-45%.

[0043] By adopting the above technical solution and setting a pre-filtration layer, compared with the separation layer, the pre-filtration layer has a relatively large thickness (60-90μm), relatively large pores (average pore diameter greater than 400nm), and a relatively large number of pores (pore area ratio greater than 25%). This can effectively filter out large particles in the feed liquid, reduce the probability of large particles directly clogging the separation layer, and thus extend the service life of the PES sterilization membrane.

[0044] Of course, the average pore size and pore area ratio of the pre-filter layer are not necessarily better the larger they are. This is because if the average pore size of the pre-filter layer is too large (average pore size greater than 900nm) and the number of pores is too large (pore area ratio greater than 45%), it means that the pre-filter layer is relatively "loose". During filtration, the pressure of the liquid directly acts on the pre-filter layer. An overly "loose" pre-filter layer is prone to deformation and compression due to the pressure of the liquid, resulting in a decrease in the overall flux and dirt holding capacity of the sterilization membrane.

[0045] Furthermore, although the pre-filter layer is relatively thick, its average pore size is large, and the sterilization membrane as a whole has a suitable acid density (good hydrophilicity). As a result, the protein yield of the pre-filter layer remains at a low level. In other words, the presence of the pre-filter layer does not affect the overall protein yield of the PES sterilization membrane (or rather, it has very little impact on the overall protein yield of the PES sterilization membrane).

[0046] Optionally, the pre-filter layer includes pre-filter fibers, which are interconnected to form a three-dimensional network structure of the pre-filter layer. The SEM average diameter of the pre-filter fibers is 300-450 nm, and the ratio of the SEM average pore size of the pre-filter layer to the SEM average diameter of the pre-filter fibers is 1.5-2.

[0047] By adopting the above technical solution, the pre-filtration layer also has pre-filtration fibers of suitable diameter (suitable thickness), which enables the sterilization membrane to have high throughput and high pressure resistance. If the pre-filtration fibers are too fine (average diameter less than 300nm), the overall pressure resistance of the pre-filtration layer is insufficient. When the liquid pressure is relatively high, the probability of pore collapse in the pre-filtration layer is relatively high. Once the pores collapse, the overall throughput of the sterilization membrane will decrease. If the pre-filtration fibers are too coarse (average diameter greater than 450nm), the excessive diameter will create greater resistance to the liquid, thereby causing the overall throughput of the sterilization membrane to decrease.

[0048] Furthermore, there is a suitable relationship between the diameter of the pre-filter fiber and the pore size of the pre-filter layer. The larger the pore size of the pre-filter layer, the larger the pre-filter fiber needs to be to support it.

[0049] Optionally, the porous body includes a protective layer, the separation layer is located between the pre-filter layer and the protective layer, the SEM average pore size of the protective layer is larger than the SEM average pore size of the separation layer, one side of the protective layer is the second outer surface, and the thickness of the protective layer is not less than 10 μm.

[0050] As mentioned earlier, the separation layer is the key area for bacterial retention; damage to it poses a risk of bacterial leakage. The separation layer is located between the pre-filtration layer and the protective layer, rather than being exposed on the surface of the PES sterilization membrane. Furthermore, the protective layer is at least 10 μm thick. This appropriately thick protective layer protects the separation layer (external mechanical damage often requires first destroying the protective layer before further damaging the separation layer structure). Even if the protective layer structure is damaged, as long as the separation layer structure remains intact, the risk of bacterial leakage from the PES sterilization membrane remains low. Therefore, the protective layer significantly reduces the possibility of bacterial leakage due to external mechanical damage.

[0051] Optionally, the thickness of the protective layer is 12-20 μm, and the ratio of the thickness of the protective layer to the thickness of the porous body is 0.1-0.15.

[0052] By adopting the above technical solution, the thickness of the protective layer should be controlled within a certain range. If the thickness of the protective layer is too large (greater than 20 μm or more than 15% of the thickness of the porous body), although the protective layer has a better protective effect on the separation layer, an excessively thick protective layer also means that the probability of the liquid material contacting / colliding with the solid part inside the protective layer is higher, which leads to a decrease in the overall protein yield of the sterilization membrane. If the thickness of the protective layer is too small (less than 12 μm, or even less than 10 μm or less than 10% of the thickness of the porous body), it often means that the protective layer is not effective enough in protecting the separation layer.

[0053] In summary, a protective layer with appropriate thickness and pore size (the average pore size of the protective layer is greater than that of the separation layer), combined with the overall suitable acid density (hydrophilicity) of the sterilization membrane, allows the protective layer to provide better protection for the separation layer without increasing the overall protein adsorption rate of the PES sterilization membrane.

[0054] Optionally, the SEM average pore size of the protective layer is 450-750 nm, and the pore area ratio of the cross-section of the protective layer is 18-38%. The protective layer should not only ensure good protection of the separation layer (reducing the probability of bacterial leakage), but also take into account its impact on the overall flux of the PES sterilization membrane. Therefore, the SEM average pore size and pore area ratio of the protective layer should be controlled within a certain range. This is because if the SEM average pore size and / or porosity of the protective layer is too small (e.g., the average pore size measured by SEM is less than 450 nm and / or the porosity is less than 18%), it indicates that the protective layer has a relatively dense three-dimensional network structure, thus having stronger resistance to mechanical damage (better protective effect). However, a relatively dense three-dimensional structure also means that the protective layer has greater resistance to the feed liquid, which may lead to a decrease in the overall flux of the PES sterilization membrane. If the SEM average pore size and / or porosity of the protective layer is too large (e.g., the average pore size measured by SEM is greater than 750 nm and / or the porosity is greater than 38%), the density of the three-dimensional network structure of the protective layer is low. Although it ensures the flux of the PES sterilization membrane to a certain extent, the low density of the three-dimensional network structure also means weak resistance to mechanical damage. Once the protective layer structure is damaged, the possibility of damage to the exposed separation layer increases significantly, and the risk of bacterial leakage increases significantly.

[0055] Optionally, the porous body further includes a support layer, the pre-filter layer is located between the support layer and the separation layer, one side of the support layer is the first outer surface, the SEM average pore size of the support layer is smaller than the SEM average pore size of the pre-filter layer, and the SEM average pore size of the support layer is larger than the SEM average pore size of the separation layer, and the thickness of the support layer is 4-10 μm.

[0056] By adopting the above technical solution, the sterilization membrane comprises four layers along its thickness direction: a support layer, a pre-filtration layer, a separation layer, and a protective layer. With the introduction of the support layer, it replaces the pre-filtration layer and becomes the layer directly facing the pressure of the feed liquid. Since the average pore size of the support layer is smaller than that of the pre-filtration layer, this means that the three-dimensional network structure of the support layer is denser than that of the pre-filtration layer, significantly improving the pressure resistance of the sterilization membrane. Even with high feed liquid pressure, the porous structure on the first outer surface (inlet surface) of the sterilization membrane is less prone to collapse. Furthermore, high feed liquid pressure also implies a relatively faster feed flow rate, resulting in a significant increase in the overall throughput of the sterilization membrane.

[0057] Furthermore, the support layer has a suitable thickness (4-10 μm). Since the sterilization membrane has a tortuous flow path, if the support layer is too thick (greater than 10 μm), the overall flow path of the support layer becomes relatively tortuous, making it prone to trapping large particles. Similarly, large particles are also relatively easy to clog the support layer, thus reducing the membrane's capacity. Of course, the support layer thickness cannot be too low (less than 4 μm). If the support layer is too thin, it also means that the pressure resistance of the porous structure near the liquid inlet is insufficient, and the flux of the sterilization membrane cannot be significantly improved. A support layer of relatively suitable thickness (not too thick) allows for a significant increase in the flux of the PES sterilization membrane.

[0058] Optionally, the SEM average pore size of the support layer is 350-650nm, and the pore area ratio of the cross-section of the support layer is 15%-30%.

[0059] By adopting the above technical solution, the support layer has a suitable thickness, and also has a suitable size (average pore size of 350-650nm) and a suitable number (pore area ratio of 15%-30%) of pores. This means that the support layer as a whole has a relatively ideal three-dimensional network structure, which can improve the flux of PES sterilization membrane under high pressure environment, while maintaining the PES sterilization membrane with a relatively high amount of nanomaterials.

[0060] If the pores in the support layer are too small and the number of pores is too small (average pore diameter less than 350nm / pore area ratio less than 15%), the dense support layer will significantly improve the overall pressure resistance of the sterilization membrane. However, an overly dense support layer also means that large particles are relatively easy to clog the support layer, resulting in a reduction in the packing capacity of the PES sterilization membrane. If the pores in the support layer are too large and the number of pores is too large (average pore diameter greater than 650nm / pore area ratio greater than 30%), the relatively loose support layer cannot give the PES sterilization membrane sufficiently high pressure resistance, and the flux of the PES sterilization membrane cannot be significantly improved.

[0061] Secondly, this application provides a method for preparing a PES antibacterial membrane, which adopts the following technical solution: S1. The casting solution is prepared and cast onto a carrier to form a liquid film. The casting solution includes at least the following raw materials in parts by weight: 20-40 parts of polyethersulfone resin, 5-10 parts of sulfonated polyethersulfone resin, 60-80 parts of solvent and 10-25 parts of pore-forming agent. The degree of sulfonation of the sulfonated polyethersulfone resin is 5-25%, the mass ratio of polyethersulfone resin to sulfonated polyethersulfone resin is 3-7, the casting solution temperature is 40-60℃, the molecular weight of polyethersulfone is 20,000-100,000, and the molecular weight of sulfonated polyethersulfone is 20,000-100,000. S2. Pretreatment: The carrier loaded with the liquid film is placed in a pretreatment bath for pretreatment for 3-10 seconds to obtain a pretreated film. The pretreatment bath includes a good pretreatment solvent and a non-pretreatment solvent. The concentration of the good pretreatment solvent in the pretreatment bath is 85-95%. The temperature of the pretreatment bath is 15-30°C lower than the temperature of the casting solution. S3. Curing: The carrier loaded with the pretreated membrane is immersed in a coagulation bath for phase separation and curing. During the phase separation and curing process, the membrane is stretched by 1.05-1.55 times. After phase separation, a green membrane is obtained. The coagulation bath includes a good phase separation solvent and a non-phase separation solvent. The concentration of the non-phase separation solvent in the coagulation bath is 80-95 wt%. The phase separation and curing time is 30-150 s. The temperature of the coagulation bath is 15-30°C higher than that of the casting solution. S4. Film formation: The raw film is washed with pure water and then dried to obtain the PES antibacterial film.

[0062] When preparing a PES sterilization membrane using the above technical solution, the first step is to prepare the casting solution and then cast it onto a carrier to form a liquid film. The casting solution includes at least the following raw materials by weight: 20-40 parts of polyethersulfone (PES) resin, 5-10 parts of sulfonated polyethersulfone (SPES) resin, 60-80 parts of solvent, and 5-15 parts of pore-forming agent. The solvent is used to fully dissolve the polyethersulfone resin and the sulfonated polyethersulfone resin, thereby forming a homogeneous and stable casting solution (homogeneous system).

[0063] In this application, by controlling the casting solution to have a suitable solid content, which refers to the mass ratio of film-forming substances (including polyethersulfone and sulfonated polyethersulfone) in the casting solution, and further controlling the polyethersulfone resin to have a suitable mass ratio (3-7), and the sulfonated polyethersulfone resin to have a suitable degree of sulfonation (5-25%), the PES sterilization membrane is ensured to introduce suitable hydrophilic groups under the combined effect of the three factors, thereby ensuring that the PES sterilization membrane has a suitable acid density, and thus ensuring that the PES sterilization membrane has suitable hydrophilicity (low protein adsorption rate).

[0064] If the solid content in the casting solution is too low and / or the sulfonated polyethersulfone content is too low and / or the sulfonation degree of sulfonated polyethersulfone is too low (e.g., sulfonation degree below 5%), the overall acid density of the PES sterilizing membrane will be low (acid density value will be high), resulting in insufficient hydrophilicity and high protein adsorption rate. Conversely, if the solid content in the casting solution is too high and / or the sulfonated polyethersulfone content is too high and / or the sulfonation degree of sulfonated polyethersulfone is too high (e.g., sulfonation degree above 25%), the overall acid density of the PES sterilizing membrane will be high (acid density value will be low). Although the PES sterilizing membrane has relatively superior hydrophilicity, a large amount of H... +The protein adsorption rate of PES antibacterial membranes is also high due to the elution and binding of negatively charged proteins, which leads to the aggregation of a large number of electrically neutral (lacking electrostatic repulsion) protein particles and their sieving and retention. In addition, excessive sulfonated polyethersulfone content will reduce the mechanical strength and make the PES antibacterial membrane brittle during the film formation process, thereby affecting the mechanical properties of the PES antibacterial membrane.

[0065] Therefore, this application controls the presence of appropriate mass fractions of polyethersulfone and appropriate mass fractions of sulfonated polyethersulfone with appropriate sulfonation degree in the casting solution, so that the PES sterilization membrane as a whole has an appropriate acid density, thereby giving the PES sterilization membrane relatively ideal hydrophilicity and relatively ideal mechanical properties. At the same time, the relatively ideal hydrophilicity can also give the PES sterilization membrane a relatively ideal flux to a certain extent.

[0066] A pore-forming agent is introduced into the casting solution. During the subsequent phase separation and solidification process, the pore-forming agent, through its interaction with the coagulation bath, makes the solvent easier to dissolve in the coagulation bath, thereby making it easier for the film-forming material to precipitate out. This makes it easier to form a PES sterilization membrane with a suitable pore size and a gradient (the average pore size of PMI is 0.15-0.4μm, which is easy to retain bacteria).

[0067] Meanwhile, by selecting polyethersulfone (PES) resin and sulfonated polyethersulfone (SEPS) resin with a certain number-average molecular weight, the PVDF sterilization membrane produced has sufficient mechanical strength and relatively high flux. Furthermore, the temperature of the casting solution is maintained at 40-60℃. Under the combined effect of these two factors, the casting solution becomes more uniform, thereby making the fiber diameter and pore size of the PES sterilization membrane more uniform (ensuring that there are no excessively coarse or fine fibers, nor excessively large or small pores in the membrane). This further ensures the overall bacterial retention performance, flux, and low protein adsorption of the sterilization membrane.

[0068] The second step is pretreatment, specifically, placing the carrier loaded with the liquid film in a pretreatment bath. Since the pretreatment bath cannot penetrate the carrier side (second outer surface), it treats the non-carrier side (first outer surface) of the liquid film, causing the first outer surface of the liquid film to form the pre-filtration layer required for the PES sterilization membrane of this application. The pretreatment bath includes a good pretreatment solvent and a non-pretreatment solvent, wherein the content of the good pretreatment solvent is relatively high (the concentration of the good pretreatment solvent in the pretreatment bath is 85~95%). The pretreatment bath acts as a dilution, and the solid content on the side of the liquid film near the first outer surface is relatively low, thereby forming a pre-filtration layer with a larger pore structure on the side of the liquid film near the first outer surface.

[0069] The pretreatment bath contains a small amount of pretreatment non-solvent, and the liquid film has a certain probability of gelation (phase separation) in the pretreatment bath. Due to the small amount of pretreatment non-solvent, its phase separation rate is relatively slow, and the pore size structure of the pre-filter layer formed is relatively large (the phase separation rate is slow, and the casting solution has relatively sufficient time to form a large polymer-rich phase and a large solvent-rich phase. After the solvent-rich phase is removed, the required pore size structure can be formed).

[0070] Furthermore, to avoid excessively large pore sizes in the pre-filter layer (which would reduce the overall pressure resistance and tensile strength of the PES sterilization membrane), this application further controls the temperature of the pretreatment bath (15-30°C lower than the casting solution) and the pretreatment time (3-10 seconds). Lowering the pretreatment bath temperature by 15-30°C, under the influence of thermodynamic driving force, appropriately "accelerates" the phase separation rate of the liquid membrane, preventing the pre-phase separation rate from becoming too fast; simultaneously, controlling the phase separation time prevents it from becoming too long. The combined effect of these two factors ensures that the pore size of the pre-filter layer is not excessively large. In addition, controlling the pretreatment time further controls the thickness of the pre-filter layer. A longer pretreatment time allows for deeper penetration of the pretreatment bath towards the carrier side (near the second outer surface), resulting in a thicker pre-filter layer.

[0071] The third step is the curing step, in which the carrier loaded with the pretreated membrane is immersed in a coagulation bath for phase separation and curing for 30-150 seconds. The coagulation bath includes a good phase separation solvent and a phase separation non-solvent, and the content of the phase separation non-solvent (water) in the coagulation bath is relatively high (its concentration is 80-95wt%). The phase separation rate of the pretreated liquid membrane is relatively fast, which is conducive to the formation of a separation layer with a smaller pore size structure.

[0072] To avoid the pore size of the separation layer being too small, this application further controls the temperature of the coagulation bath (the temperature of the coagulation bath is 15-30℃ higher than that of the casting solution). Through the influence of thermodynamic driving force, the phase separation rate of the separation layer is prevented from being too fast to a certain extent, thereby relatively extending the phase separation time (30-150s). Under the combined effect of a suitable coagulation bath (suitable solvent and non-solvent ratio), a suitable temperature, and a suitable phase separation time, the separation layer forms a suitable pore structure (the pore size is neither too large nor too small, and the pores are more uniform, i.e., there are no particularly large pores or particularly small pores) and a fiber structure (suitable thickness of retained fibers).

[0073] It is understandable that when the concentration of the non-solvent for phase separation is relatively high (close to 95 wt%) and the thickness of the pretreatment membrane is relatively thin, the coagulation bath (non-solvent) can easily enter and quickly separate phase to the support side due to the larger pore size of the pre-filtration layer, forming a two-layer flat membrane, namely a two-layer membrane structure of pre-filtration layer + separation layer; when the concentration of the non-solvent for phase separation is relatively low (close to 80 wt%) and the thickness of the pretreatment membrane is relatively thick, the coagulation bath can easily enter at first and quickly separate phase to obtain the separation layer. Subsequently, due to the relatively large resistance of the separation layer, the permeation of the coagulation bath is hindered, the phase separation rate slows down, and a protective layer is formed on the support side, namely a three-layer membrane structure of pre-filtration layer + separation layer + protective layer.

[0074] Furthermore, during the phase separation curing process, the pretreated membrane undergoes a 1.05-1.55 times stretching treatment. That is, the phase separation curing includes a primary phase separation curing (15-70s) and a secondary phase separation curing (15-80s). After the carrier loaded with the pretreated membrane is immersed in the coagulation bath, primary phase separation curing is performed first. After the primary phase separation curing is completed, the pretreated membrane undergoes a stretching treatment with a stretching ratio of 1.05-1.55 times, while the secondary phase separation curing is performed simultaneously. The stretching treatment can be achieved by unidirectional stretching through the speed difference between the front and rear rollers, or by bidirectional stretching of the pretreated membrane. Stretching the pretreated membrane (neither a pure liquid membrane nor a pure solid membrane) during the phase separation process further ensures the formation of the appropriate fiber thickness required by this application. The appropriate phase separation time (30-150s), appropriate phase separation temperature, and appropriate phase separation rate, combined with the appropriate stretching ratio (1.05-1.55 times) during the phase separation process, enable the separation layer of the sterilization membrane to have fibers of appropriate thickness and pores of appropriate size, that is, the separation layer has a three-dimensional network structure with appropriate density and appropriate acid density, thereby significantly reducing the protein adsorption rate of the PES sterilization membrane of this application.

[0075] The fourth step is the film-forming step, in which the raw film is washed with pure water and then dried to obtain the PES antibacterial film.

[0076] Preferably, the viscosity of the casting solution is 5000~25000cps@25℃.

[0077] This application further controls the viscosity of the casting solution to 5000~25000cps@25℃. The appropriate temperature and viscosity of the casting solution (the viscosity of the casting solution is an important factor affecting the formation of polymer films. If the viscosity is too high, the membrane porosity will be low; if the viscosity is too low, the mechanical strength of the membrane will be low) make the casting solution more uniform, thereby making the fiber diameter and pore size of the PES sterilization membrane more uniform (ensuring that there are no excessively coarse or fine fibers, nor excessively large or small pores in the membrane).

[0078] Preferably, in step S3, the temperature of the carrier is 5-10°C lower than the temperature of the coagulation bath.

[0079] By adopting the above technical solution, the temperature on the carrier side is slightly lower than the coagulation bath temperature, and the viscosity of the casting solution on the carrier side is relatively high. Due to the small pore size of the separation layer and the high viscosity of the casting solution near the carrier side, the rate of coagulation bath permeation (the coagulation bath passing through the separation layer and moving towards the carrier side) is relatively slow. At this time, the phase separation rate of the casting solution near the carrier side is relatively slow, and the side of the PES sterilization membrane near the carrier side (second outer surface) is more likely to form a protective layer. In summary, the thickness of the pretreatment membrane is relatively thin, and it is also easy to form a three-layer PES sterilization membrane (pre-filtration layer + separation layer + protective layer).

[0080] As previously mentioned, a 15-30°C decrease in the coagulation bath temperature increases the phase separation rate of the liquid film. However, unlike the previous method, in this scheme, the temperature on the carrier side is slightly lower than the coagulation bath temperature by 5-10°C, which actually decreases the phase separation rate of the liquid film. This may be because, on the one hand, the phase separation rate of the liquid film is affected by multiple factors, such as temperature (including liquid film temperature and ambient temperature) and viscosity. When the temperature decreases slightly, the viscosity of the casting solution increases. At this time, the effect of the casting solution viscosity on the phase separation rate is greater than the effect of thermodynamic factors on the phase separation rate. Although the temperature decreases, the phase separation rate of the liquid film also decreases slightly. On the other hand, when the temperature decreases significantly, thermodynamic factors become dominant. At this time, the effect of temperature on the phase separation rate is greater than the effect of the casting solution on the phase separation rate, and the phase separation rate of the liquid film increases.

[0081] Preferably, the pretreated membrane is subjected to temperature conditioning treatment before being immersed in the coagulation bath. Specifically, the pretreated membrane is placed in an atmosphere with a relative humidity of 30-50% and a temperature of 60-80°C for 30-40 seconds. During the temperature conditioning treatment, the relative velocity between the atmosphere and the pretreated membrane is 0.5-1 m / s.

[0082] By adopting the above technical solution, before immersing the pretreated membrane in the coagulation bath, the pretreated membrane is treated in an atmosphere with a relative humidity of 30-50% and a temperature of 60-80℃ for 30-40 seconds. This allows the solvent near the first outer surface of the pretreated membrane to evaporate appropriately, increasing the solid content at the first outer surface of the pretreated membrane. This results in the formation of a support layer with suitable pore size during phase separation and solidification (generally, the higher the solid content, the smaller the pore size after phase separation and solidification). Furthermore, by controlling the relative velocity between the atmosphere and the pretreated membrane to 0.5-1 m / s, a suitable relative velocity means a suitable amount of solvent evaporation near the first outer surface of the pretreated membrane, thereby ensuring that the pore size of the support layer of the pretreated membrane is appropriate and reducing the overall dirt-holding capacity loss of the PES sterilization membrane to a certain extent.

[0083] Preferably, the solvent, the pretreatment solvent, and the phase separation solvent are all one or a mixture of at least two of the following: butyl lactate, dimethyl sulfoxide, dimethylformamide, caprolactam, methyl acetate, ethyl acetate, N-ethylpyrrolidone, dimethylacetamide, and N-methylpyrrolidone; the pretreatment non-solvent and the phase separation non-solvent are both water.

[0084] Preferably, the pore-forming agent is one or a mixture of at least two of polyvinyl alcohol, polyethylene glycol, polyethyleneimine, and polyvinylpyrrolidone.

[0085] This application provides the following beneficial effects: the PES sterilization membrane and the method for preparing the sterilization membrane provided in this application exhibit significantly reduced protein adsorption rate, high retention efficiency, and relatively high flux, greatly improving the performance of the PES sterilization membrane. The preparation method provided by this invention allows for the convenient, rapid, and effective preparation of the aforementioned sterilization membrane. Attached Figure Description

[0086] Figure 1 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the three-layer antibacterial membrane prepared in Example 1, with a magnification of 300×. Figure 2 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the three-layer antibacterial membrane prepared in Example 1, with a magnification of 1000×. Figure 3 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the three-layer antibacterial membrane prepared in Example 1, with a magnification of 5000×. Figure 4 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the two-layer sterilization membrane prepared in Example 5, with a magnification of 500×. Figure 5 This is a scanning electron microscope (SEM) schematic diagram of the cross-section of the four-layer sterilization membrane prepared in Example 7, with a magnification of 500×. Detailed Implementation Example 1

[0087] This application discloses a method for preparing a PES antibacterial membrane with low non-specific adsorption, comprising the following steps: S1. The casting solution is prepared and cast onto a carrier to form a liquid film. The casting solution includes the following raw materials in parts by weight: 30 parts polyethersulfone resin, 7 parts sulfonated polyethersulfone resin, 70 parts solvent, and 20 parts pore-forming agent. The degree of sulfonation of the sulfonated polyethersulfone resin is 15%, the molecular weight of the polyethersulfone is 70,000, the molecular weight of the sulfonated polyethersulfone is 75,000, the mass ratio of polyethersulfone resin to sulfonated polyethersulfone resin is 4.29, the casting solution temperature is 50℃, the viscosity of the casting solution is 15,000 cps@25℃, the solvent is butyl lactate, and the pore-forming agent is polyvinyl alcohol. S2. Pretreatment: The carrier loaded with the liquid film is placed in a pretreatment bath for pretreatment for 7 seconds to obtain a pretreated film. The pretreatment bath includes a good pretreatment solvent and a non-pretreatment solvent. The concentration of the good pretreatment solvent in the pretreatment bath is 90 wt%, the temperature of the pretreatment bath is 30°C, the good pretreatment solvent is butyl lactate, and the non-pretreatment solvent is water. S3. Curing: The carrier loaded with the pretreated membrane is immersed in a coagulation bath for phase separation and curing. The phase separation and curing time is 90s. Phase separation and curing includes primary phase separation and secondary phase separation and curing. The primary phase separation and curing time is 40s, and the secondary phase separation and curing time is 50s. After the primary phase separation and curing, the pretreated membrane is stretched by a stretching ratio of 1.30 times. During the stretching of the pretreated membrane, secondary phase separation and curing are carried out simultaneously. After phase separation, a green membrane is obtained. The coagulation bath includes a good phase separation solvent and a non-phase separation solvent. The concentration of the non-phase separation solvent in the coagulation bath is 88wt%, the coagulation bath temperature is 70℃, the good phase separation solvent is butyl lactate, and the non-phase separation solvent is water. S4. Film formation: The raw film is washed with pure water and then dried to obtain the PES antibacterial film.

[0088] Examples 2-6

[0089] The differences between Examples 2-6 and Example 1 lie in the casting solution formulation and various process parameters, as detailed in Tables 1 and 2. It is particularly noteworthy that in step S3 of Example 3, the temperature on the carrier side is 8°C lower than the temperature of the coagulation bath; and in step S3 of Example 4, the temperature on the carrier side is 2°C lower than the temperature of the coagulation bath. Example 7

[0090] The difference between Example 7 and Example 1 is that the casting solution formula and various process parameters are different, as detailed in Tables 1 and 2. Between steps S2 and S3 in Example 7, the pretreated membrane is subjected to temperature conditioning treatment before being immersed in the coagulation bath. Specifically, the pretreated membrane is placed in an atmosphere with a relative humidity of 40% and a temperature of 70°C for 35 seconds. Comparative Example 1

[0091] The difference between Comparative Example 1 and Example 3 lies in the different casting solution formulations and process parameters, as detailed in Tables 1 and 2. It should be noted that the content and degree of sulfonated polyether sulfone in Comparative Example 1 are relatively high. Comparative Example 2

[0092] The difference between Comparative Example 1 and Example 1 is that the casting solution formulation and various process parameters are different, as detailed in Tables 1 and 2. In particular, it should be noted that the stretching ratio in step S3 of Comparative Example 2 is relatively high, and the pore-forming agent content in Comparative Example 2 is relatively high. Comparative Example 3

[0093] The difference between Comparative Example 3 and Example 1 is that the casting solution formulation does not contain sulfonated polyethersulfone.

[0094] Table 1. Casting solution formulations and process parameters for step S1 in each embodiment and comparative example.

[0095] Table 2. Process parameters for steps S2 and S3 in each embodiment and comparative example.

[0096] Performance testing and data The detection methods are as follows: Acid density: Using the PES sterilization membranes prepared in each example and comparative example as samples, taking the PES sterilization membrane of Example 1 as an example, about 2g of the pre-cut PES sterilization membrane sample was weighed and immersed in HCl solution (1mol / L, 50℃) for 24 h to ensure the sulfonic acid matrix of the PES sterilization membrane was ionized. Then, the excess HCl solution on the surface of the PES sterilization membrane was washed away with deionized water, and the sample was then immersed in 100mL of 2mol / L NaCl solution at 60℃ for 24 h. The acid density S was calculated by the following formula: S=-lg[C] / M, where C is the concentration of hydrogen ions in the sodium chloride solution after the sterilization membrane was immersed in the sodium chloride solution for 24 h, and the unit of C is: mol / L; M is the mass of the sterilization membrane before immersion in the sodium chloride solution, and the unit of M is: g.

[0097] PMI average pore size: The PES sterilization membranes prepared in each example and comparative example were used as samples, and the PMI average pore size of each sample was tested using a CFP-1J00AEX PMI pore size tester.

[0098] LRV: The PES sterilization membranes prepared in each example and comparative example were used as samples for bacterial retention challenge tests. The detection method referred to the guidance document TR26 issued by PDA. During the test, Pseudomonas degenerativeae (ATCC 19146) with a bacterial diameter of 0.3-0.4 μm was used as the retained bacteria. The bacterial retention test was carried out on the samples according to the standard ASTM F838-2015ae1 to test the LRV value of the filter membrane.

[0099] Protein Adsorption Test: The PES sterilization membranes prepared in each example and comparative example were used as samples. The membranes were cut into 25mm diameter discs, moistened with anhydrous ethanol, and 5mL of test buffer (20mM Tris-HCl) was applied. The vacuum pressure was adjusted to between -0.01 and 0.02MPa, and the membranes were rinsed using slow suction filtration. 2mL of the test protein solution (1mg / mL BSA (20mM Tris-HCl)) was taken and slowly filtered to ensure sufficient contact between the protein solution and the membrane surface and pores. After filtration, the discs were repeatedly washed with the buffer solution, and the adsorption capacity of BSA protein on the discs (μg / cm³) was measured. 2 ).

[0100] Preparation of buffer solutions: Accurately weigh 12.1000 g of Tris using an analytical balance, dissolve it in 4.8 L of ultrapure water, stir to dissolve, adjust the pH of the solution to about 7.5 with 1 mol / L hydrochloric acid (dilute hydrochloric acid), and make up to 5 L with a volumetric flask to obtain a 20 mmol / L Tris-HCl buffer solution with pH=7.5.

[0101] Preparation of protein solution: 1 mg / mL BSA (20 mM Tris-HCl): Accurately weigh 0.1000 g BSA, dissolve it in 20 mM Tris-HCl, and then make up to volume.

[0102] It is understandable that when the protein adsorption of the PES antibacterial membrane prepared in Comparative Example 3 was tested, it was found that its protein adsorption capacity was relatively high (due to the lack of sulfonated polyether sulfone, the membrane had poor hydrophilicity), which obviously did not meet the application requirements of the present invention. Therefore, the morphological parameters and other performance parameters of the PES antibacterial membrane prepared in Comparative Example 3 were not characterized in the present invention.

[0103] The morphological parameters of the PES antibacterial membranes prepared in each embodiment and comparative example are detailed in Tables 3 and 4, and the performance parameters are detailed in Table 5.

[0104] Table 3. Morphological parameters of the separation layer of the PES sterilization membranes prepared in each embodiment and comparative example.

[0105] Note: The unit for the average diameter of the retained fibers is nm; the unit for the thickness of the separation layer is μm; the unit for the ratio of the separation layer thickness to the diameter of the retained fibers is μm / nm; the unit for the average pore size of the cross-section of the separation layer is nm. The porosity ratio of the separation layer refers to the porosity ratio of the pores in the cross-section of the separation layer, and its unit is % (%). The unit for the ratio of the separation layer thickness to the average pore size of the separation layer is μm / nm.

[0106] Table 4. Morphological parameters of the pre-filter layer, protective layer, and support layer of the PES antibacterial membranes prepared in each embodiment and comparative example.

[0107] Note: The thickness of the pre-filter layer, protective layer, and support layer are all in μm. The units for the average pore size of the pre-filter layer, the average pore size of the protective layer, and the average pore size of the support layer are all in nm. The units for the pore area ratio of the pre-filter layer, the protective layer, and the support layer are all: % . The unit for the average diameter of the pre-filtered fiber is nm; the pre-filter pore size ratio specifically refers to the ratio between the average pore size of the pre-filter layer and the average diameter of the pre-filtered fiber.

[0108] Table 5 Performance parameters of PES antibacterial films prepared in each embodiment and comparative example

[0109] Note: The unit for PMI average pore size is μm; the unit for membrane thickness is μm; the unit for BSA dynamic adsorption is μg / cm³. 2 .

[0110] in conclusion By comparing Example 3 and Comparative Example 1, it is easy to see that the acid density value of Comparative Example 1 is much lower than that of Example 3, that is, the hydrophilicity of the PES sterilization membrane of Comparative Example 1 is much higher than that of the PES sterilization membrane of Example 3. Furthermore, by comparing the pore size and thickness of the separation layer and the overall PMI average pore size of the sterilization membranes, it is easy to see that the PMI average pore size and separation layer pore size of the PES sterilization membrane of Comparative Example 1 are slightly larger, and the separation layer thickness is slightly thinner.

[0111] The comparative PES sterilization membrane possesses better hydrophilicity, a relatively larger average pore size, a relatively thin separation layer, and a relatively large PMI average pore size. The expected effect is that the protein adsorption rate of the comparative example's PES sterilization membrane should be significantly lower than that of the PES sterilization membrane in Example 3. However, the protein adsorption rate of the comparative example's PES sterilization membrane is very high. This may be because the comparative example's PES sterilization membrane contains a large number of sulfonic acid groups. When filtering the feed liquid, a large amount of H+... + The protein particles are eluted and bind to negatively charged proteins, leading to the aggregation of a large number of electrically neutral (lacking electrostatic repulsion) protein particles, which are then sieved and retained, resulting in a higher protein adsorption rate in the PES sterilization membrane. In summary, the higher the sulfonic acid group content introduced into the PES sterilization membrane, the stronger the hydrophilicity of the membrane material, the weaker the non-specific adsorption of the filter membrane, and the less likely it is to adsorb effective substances such as proteins. This is, to some extent, a technological bias.

[0112] By comparing Example 1 and Comparative Example 2, it is easy to see that the acid density value of Comparative Example 2 is lower than that of Example 1, that is, the hydrophilicity of the PES sterilizing membrane of Comparative Example 2 is much higher than that of the PES sterilizing membrane of Example 1. Furthermore, the average PMI pore size of the PES sterilizing membrane of Comparative Example 2 is slightly larger than that of the PES sterilizing membrane of Example 1. It is expected that the protein adsorption rate of the PES sterilizing membrane of Comparative Example 2 should be relatively lower than that of the PES sterilizing membrane of Example 1. However, the protein adsorption rate of the PES sterilizing membrane of Comparative Example 2 is much higher than that of the PES sterilizing membrane of Example 1. This may be because the cutoff diameter of Comparative Example 2 is too fine, resulting in an overly dense three-dimensional network structure of the separation layer. Although the PES sterilizing membrane has good hydrophilicity, the overly dense three-dimensional network structure still leads to a higher protein adsorption rate.

[0113] By comparing Examples 2 and 4, it is not difficult to find that although the hydrophilicity of the PES sterilization membrane in Example 4 is slightly higher than that in Example 2, the protein adsorption rate of the PES sterilization membrane in Example 4 is significantly higher than that in Example 2. The reason for this may be that the ratio of the average diameter of the retained fibers in the SEM to the acid density is less than 0.1, that is, the retained fibers are relatively too fine while the acid density of the sterilization membrane is relatively too large. In other words, the separation layer has a relatively dense three-dimensional network structure, but the hydrophilicity of the separation layer is relatively insufficient.

[0114] By comparing Examples 1 and 5, it is easy to find that although the hydrophilicity of the PES sterilization membrane in Example 5 is slightly higher than that in Example 1, the protein adsorption rate of the PES sterilization membrane in Example 5 is significantly higher than that in Example 1. The reason for this may be that the ratio of the separation layer thickness to the fiber diameter of the retention layer is greater than 0.15 μm / nm, the separation layer is relatively thick, and the retention fibers are relatively thin. The separation layer has a relatively dense three-dimensional network structure. Although its hydrophilicity is good, the overly dense three-dimensional network structure still leads to a higher protein adsorption rate of the PES sterilization membrane.

[0115] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A PES sterilization membrane with low non-specific adsorption, comprising a porous body having non-directional tortuous pathways within the porous body, one side of the porous body being a first outer surface, and the other side of the porous body being a second outer surface, characterized in that: The porous body includes a pre-filtration layer and a separation layer for retaining bacteria, wherein the SEM average pore size of the pre-filtration layer is larger than the SEM average pore size of the separation layer. The average pore size of the sterilization membrane (PMI) is 0.15-0.4 μm; The separation layer includes retained fibers, which are interconnected to form a three-dimensional network structure of the separation layer. The average SEM diameter of the retained fibers is 150-300 nm. The acid density S of the sterilization membrane is 0.5-2; The acid density S is calculated using the following formula: S = -lg[C] / M, where C is the concentration of hydrogen ions in the sodium chloride solution after the sterile membrane has been soaked in 1 mol / L HCl solution for 24 h and then in 100 mL of 2 mol / L sodium chloride solution at 60 °C for 24 h, and the unit of C is mol / L; M is the mass of the sterile membrane before soaking in the sodium chloride solution, and M is 2 g.

2. The PES sterilizing membrane with low non-specific adsorption according to claim 1, characterized in that: The ratio of the average SEM diameter of the retained fiber to the acid density is 0.1-0.

35.

3. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The thickness of the separation layer is 10-30 μm, and the ratio of the thickness of the separation layer to the average SEM diameter of the retained fiber is 0.06-0.15 μm / nm.

4. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The average SEM pore size of the pores in the cross-section of the separation layer is 150-450 nm, and the pore area ratio of the cross-section of the separation layer is 15-25%.

5. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The ratio of the thickness of the separation layer to the average SEM pore size of the separation layer is 0.04-0.12 μm / nm.

6. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The surface of one side of the pre-filter layer is the first outer surface. The thickness of the pre-filter layer is 60-90 μm, the SEM average pore size of the pre-filter layer is 400-900 nm, and the pore area ratio of the cross section of the pre-filter layer is 25%-45%.

7. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The pre-filter layer includes pre-filter fibers, which are interconnected to form a three-dimensional network structure. The SEM average diameter of the pre-filter fibers is 300-450 nm, and the ratio of the SEM average pore size of the pre-filter layer to the SEM average diameter of the pre-filter fibers is 1.5-2.

8. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The porous body includes a protective layer, the separation layer is located between the pre-filter layer and the protective layer, the SEM average pore size of the protective layer is larger than the SEM average pore size of the separation layer, one side of the protective layer is the second outer surface, and the thickness of the protective layer is not less than 10 μm.

9. The PES sterilization membrane with low non-specific adsorption according to claim 8, characterized in that: The thickness of the protective layer is 12-20 μm, and the ratio of the thickness of the protective layer to the thickness of the porous body is 0.1-0.

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10. The PES sterilization membrane with low non-specific adsorption according to claim 8, characterized in that: The SEM average pore size of the protective layer is 450-750 nm, and the pore area ratio of the cross-section of the protective layer is 18-38%.

11. The PES sterilization membrane with low non-specific adsorption according to claim 1, characterized in that: The porous body further includes a support layer, the pre-filter layer is located between the support layer and the separation layer, one side of the support layer is the first outer surface, the SEM average pore size of the support layer is smaller than the SEM average pore size of the pre-filter layer, and the SEM average pore size of the support layer is larger than the SEM average pore size of the separation layer, and the thickness of the support layer is 4-10 μm.

12. The PES sterilization membrane with low non-specific adsorption according to claim 11, characterized in that: The average SEM pore size of the support layer is 350-650 nm, and the pore area ratio of the cross-section of the support layer is 15%-30%.

13. The preparation process of a low-nonspecific adsorption PES sterilization membrane according to any one of claims 1-12, characterized in that: The process includes the following steps: S1. The casting solution is prepared and cast onto a carrier to form a liquid film. The casting solution includes at least the following raw materials in parts by weight: 20-40 parts of polyethersulfone resin, 5-10 parts of sulfonated polyethersulfone resin, 60-80 parts of solvent and 10-25 parts of pore-forming agent. The degree of sulfonation of the sulfonated polyethersulfone resin is 5-25 wt%, the mass ratio of polyethersulfone resin to sulfonated polyethersulfone resin is 3-7, the casting solution temperature is 40-60℃, the molecular weight of polyethersulfone is 20,000-100,000, and the molecular weight of sulfonated polyethersulfone is 20,000-100,000. S2. Pretreatment: The carrier loaded with the liquid film is placed in a pretreatment bath for pretreatment for 3-10 seconds to obtain a pretreated film. The pretreatment bath includes a good pretreatment solvent and a non-pretreatment solvent. The concentration of the good pretreatment solvent in the pretreatment bath is 85-95%. The temperature of the pretreatment bath is 15-30°C lower than the temperature of the casting solution. S3. Curing: The carrier loaded with the pretreated membrane is immersed in a coagulation bath for phase separation and curing. During the phase separation and curing process, the membrane is stretched by 1.05-1.55 times. After phase separation, a green membrane is obtained. The coagulation bath includes a good phase separation solvent and a non-phase separation solvent. The concentration of the non-phase separation solvent in the coagulation bath is 80-95 wt%. The phase separation and curing time is 30-150 s. The temperature of the coagulation bath is 15-30°C higher than that of the casting solution. S4, film formation; The raw film is washed with pure water and then dried to obtain the PES antibacterial film.

14. The preparation process of a PES sterilization membrane with low non-specific adsorption according to claim 13, characterized in that: The viscosity of the casting solution is 5000~25000cps@25℃; in step S3, the temperature of the carrier is 5~10℃ lower than the temperature of the coagulation bath.

15. The preparation process of a PES sterilization membrane with low non-specific adsorption according to claim 14, characterized in that: The pretreated membrane is subjected to temperature conditioning before being immersed in the coagulation bath. Specifically, the pretreated membrane is placed in an atmosphere with a relative humidity of 30-50% and a temperature of 60-80℃ for 30-40 seconds.

16. The preparation process of a PES sterilization membrane with low non-specific adsorption according to claim 15, characterized in that: During the temperature control process, the relative velocity between the atmosphere and the pretreated membrane is 0.5~3m / s.

17. The preparation process of a PES sterilization membrane with low non-specific adsorption according to claim 13, characterized in that: The solvent, pretreatment solvent, and phase separation solvent are all one or a mixture of at least two of the following: butyl lactate, dimethyl sulfoxide, dimethylformamide, caprolactam, methyl acetate, ethyl acetate, N-ethylpyrrolidone, dimethylacetamide, and N-methylpyrrolidone. Both the pretreatment non-solvent and the phase separation non-solvent are water.

18. The preparation process of a PES sterilization membrane with low non-specific adsorption according to claim 13, characterized in that: The pore-forming agent is one or a mixture of at least two of polyvinyl alcohol, polyethylene glycol, polyethyleneimine, and polyvinylpyrrolidone.

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