Polyvinylidene fluoride separation membrane, and preparation method and application thereof

Abstract

The application provides a polyvinylidene fluoride separation membrane and a preparation method and application thereof. The preparation method of the polyvinylidene fluoride separation membrane comprises the following steps: mixing polyvinylidene fluoride, a solvent and an additive, stirring and dissolving uniformly, standing and defoaming, and preparing a membrane preparation liquid; then starting a flat plate film casting machine, controlling the temperature and air humidity of a film casting area, setting the moving speed of a scraper and the film casting thickness, pouring the casting liquid uniformly on the flat plate with a substrate on the surface for film casting; then immersing in a coagulation bath for exchange; after the exchange, moving into pure water for standing and solidification to obtain a wet original membrane; performing heat treatment and wet heat sterilization treatment on the wet original membrane; and finally drying the wet original membrane after the wet heat sterilization. The compact pore structure of the membrane is opened through heat treatment, the porosity is effectively improved, the effect of cleaning the membrane structure is achieved, the membrane is sterilized and heat set through wet heat sterilization treatment, and the structure change of a later assembly after leaving the factory for wet heat sterilization is avoided, so that the separation precision is changed.

Description

Technical Field

[0001] This invention relates to the field of membrane separation technology, specifically to a polyvinylidene fluoride separation membrane, its preparation method, and its application. Background Technology

[0002] Membrane separation technology is a special physical separation method with relatively mild separation conditions, making it suitable for the biopharmaceutical field. By using external pressure, concentration gradients, or other driving forces, specific substances can be separated from solution, achieving purification. Compared to conventional separation methods, this process offers advantages such as high separation efficiency, a wide range of separation systems, safe operation, environmental friendliness, and high product yield. Furthermore, it ensures that the separated active substances do not denature when applied in the biopharmaceutical field, reducing cost losses and demonstrating the unique suitability of this technology for biopharmaceutical applications. In the field of biopharmaceutical technology, virus isolation is a crucial step; therefore, virus separation membranes have attracted widespread attention from researchers due to their high separation efficiency, low production cost, and environmental friendliness.

[0003] PVDF, as a semi-crystalline polymer, possesses excellent mechanical properties, weather resistance, and chemical stability. Furthermore, hydrophilically modified PVDF exhibits improved resistance to protein adsorption, resulting in higher protein yields. Therefore, PVDF is currently the most commonly used membrane material for virus separation. PVDF membrane fabrication methods generally include non-solvent-induced phase separation (NIPS) and thermally induced phase separation (TIPS). Most TIPS membranes are hollow fiber membranes for virus filtration. The fabrication process for the accompanying virus-removing membrane components and filter elements is complex. Moreover, hollow fiber membranes typically use a single-layer filtration method, which cannot guarantee against virus leakage due to membrane defects during prolonged filtration, thus compromising membrane integrity. Additionally, TIPS membranes have very small pore sizes, leading to strong protein retention and reduced protein yield. For high-concentration protein solutions, the high protein retention rate often results in easier membrane pore blockage, shortening the membrane's lifespan. Therefore, non-solvent-induced phase separation (NIPS) with higher porosity is more valuable for application.

[0004] Chinese invention patent CN101069750A discloses a double-layer composite virus filtration membrane. Its main structure includes a pre-filtration microporous membrane and a virus-removing microporous membrane. The pre-filtration microporous membrane is made of porous fiber material and polyvinylidene fluoride, and the virus-removing microporous membrane is made of polyvinylidene fluoride and polytetrafluoroethylene. Due to its unique composite structure, the membrane can maintain a high flux and retain viruses with a particle size of 50 nm or larger, with a separation efficiency of 99.99%. However, it still cannot meet the requirements for retaining small viruses of about 20 nm.

[0005] Chinese invention patent CN114653222B discloses a virus-removing filter membrane with low non-specific adsorption and its preparation method. The filter membrane is made of PVDF, and the main structure of the membrane includes a pre-filtration zone, a separation zone for retaining viruses, and a hydrophilic cross-linking layer. The pre-filtration zone accounts for 70-90% of the overall thickness of the membrane. By cross-linking hydrophilic monomers with a cross-linking agent to form a hydrophilic cross-linking base layer, which covers the fibrous entity of the pre-filtration zone, the hydrophilicity of the membrane is improved, the non-specific adsorption of proteins by the membrane is reduced, and the loading capacity is increased. However, if the hydrophilic modification is not properly controlled, it may cause blockage of the membrane pores in the separation zone, resulting in a decrease in the overall porosity of the membrane, which cannot meet the needs of practical applications.

[0006] In summary, for biopharmaceutical separation membranes, how to ensure both high retention efficiency for smaller viruses and high protein yield is an urgent problem to be solved. Summary of the Invention

[0007] In view of this, it is necessary to provide a polyvinylidene fluoride (PVDF) separation membrane, its preparation method, and its application to solve the above problems. This invention improves the membrane's porosity and cleans residual impurities in the membrane structure through heat treatment, reducing pore blockage and promoting long-term stability. Furthermore, it employs moist heat sterilization for heat setting, effectively preventing structural changes during post-shipment moist heat sterilization that could alter separation accuracy. The separation membrane prepared by this invention exhibits uniform pore size, stable structure, excellent strength, and uniform pore size distribution on its surface. While maintaining a certain rejection rate, it achieves a large initial flux of the filtered liquid, and the final flux after attenuation remains within a reasonable range, demonstrating high separation efficiency and high flux.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] In a first aspect, the present invention provides a method for preparing a polyvinylidene fluoride separation membrane, comprising the following steps:

[0010] Step 1: Mix polyvinylidene fluoride, solvent and additives, stir to dissolve evenly, let stand to remove bubbles, and prepare a film-forming solution;

[0011] Step 2: Turn on the flatbed film coating machine, control the temperature and humidity of the coating area, set the scraper movement speed and coating thickness, pour the casting liquid evenly onto the flatbed with the substrate on the surface for coating; then immerse the flatbed coated with casting liquid in the coagulation bath for exchange; after the exchange is completed, transfer it to pure water for static solidification to obtain the wet original film.

[0012] Step 3: Heat-treat the wet original film;

[0013] Step 4: Perform moist heat sterilization on the heat-treated wet original membrane;

[0014] Step 5: Dry the wet original film after moist heat sterilization.

[0015] Furthermore, in step 1, the mass fraction of polyvinylidene fluoride in the casting solution is 10-30%, the mass fraction of the solvent is 30-70%, and the mass fraction of the additive is 5-20%.

[0016] Furthermore, the solvent includes one or a mixture of several of N-methylpyrrolidone, dimethylformamide, dimethylacetamide, and acetone; the additive includes one or a mixture of several of isobutanol, polyethylene glycol, polymethylpyrrolidone, polyether, glycerol, ethanol, isopropanol, n-butanol, and n-octanol.

[0017] Furthermore, the temperature for stirring and dissolving in step 1 is 30–100°C, and the time for standing and degassing is 4–24 hours.

[0018] Furthermore, in step 2, the temperature of the scraping area is 20–40°C, the air humidity is 40%–100%, the scraper moving speed is 1–8 m / min, and the scraping thickness is 0.050–0.200 mm.

[0019] Furthermore, in step 2, before the coagulation bath is exchanged, the casting solution is pre-evaporated by air residence, with the air residence time being 10–180 s.

[0020] Furthermore, the coagulation solution in step 2 is a mixture of the solvent and water in step 1; the exchange time is 1 to 5 minutes.

[0021] Furthermore, the temperature of the pure water in step 2 is 20–60°C, and the settling time is 3–10 hours.

[0022] Furthermore, the heat treatment method in step 3 is to immerse the wet original membrane in hot water at 30-90°C for 2-10 hours.

[0023] Furthermore, in step 4, the moist heat sterilization process involves sterilizing at a temperature of 100–200°C for 0–3 hours.

[0024] Furthermore, in step 5, the drying conditions are to maintain a constant temperature of 40–100°C for 5–30 minutes.

[0025] Secondly, the present invention provides a polyvinylidene fluoride separation membrane, which is prepared by the above-described preparation method.

[0026] Thirdly, this invention provides the application of the polyvinylidene fluoride (PVDF) separation membrane prepared by the above-mentioned preparation method in virus separation. The PVDF separation membrane is stacked in two layers with the macropore side as the feed surface before filtration and separation. This two-layer stacking method enhances the pressure resistance of the separation membrane during filtration and improves the membrane's integrity, preventing virus leakage.

[0027] The beneficial effects of this invention are as follows:

[0028] 1. This invention provides a method for preparing a polyvinylidene fluoride (PVDF) separation membrane. This method is simple to operate and low in cost. Heat treatment opens the dense porous structure of the membrane, effectively increasing porosity and cleaning the membrane structure. Then, moist heat sterilization sterilizes and heat-sets the membrane, preventing structural changes during post-factory moist heat sterilization that could alter separation accuracy.

[0029] 2. The separation membrane prepared by this invention has uniformly distributed pores on its surface and uniform pore size in its cross-section, possessing advantages such as high mechanical strength, large membrane flux, good separation effect, and wide applicability. The separation membrane structure has non-directional tortuous pathways, transitioning from a large-diameter inlet surface to a small-diameter outlet surface, achieving effective retention of substances of specific sizes while maintaining a large flux, thus improving separation efficiency. Attached Figure Description

[0030] Figure 1 This is a cross-sectional pore structure diagram of the wet original membrane obtained after step 2 of Example 1, after it has been naturally dried.

[0031] Figure 2 This is a cross-sectional pore structure diagram of the wet original membrane obtained after step 3 of Example 1, after it has been naturally dried.

[0032] Figure 3 The image shows the surface structure of the polyvinylidene fluoride separation membrane prepared in Example 1, where a is the surface structure of the large pore side and b is the surface structure of the small pore side. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be further described clearly and completely below in conjunction with the embodiments of this invention. It should be noted that the described embodiments are merely some embodiments of this invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0034] In the description of this invention, it should be noted that unless specific conditions are specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0035] Example 1

[0036] A method for preparing a polyvinylidene fluoride (PVDF) separation membrane includes the following steps:

[0037] Step 1: Mix and dissolve polyvinylidene fluoride, dimethylacetamide, polyethylene glycol, glycerol, and polyether in a mass ratio of 27:60:7:4:2, and stir at 70°C for 12 hours until the mixed solution becomes clear and transparent; let stand for 10 hours to remove bubbles to prepare the film-forming solution.

[0038] Step 2: Turn on the flatbed film casting machine, control the temperature of the casting area to 25-30℃, the air humidity to 60-70%, set the doctor blade moving speed to 5m / min, and the film thickness to 0.060mm. Pour the casting solution evenly onto the flatbed with the substrate on its surface, parallel to the doctor blade. After the doctor blade reaches its end, allow the casting solution evenly spread on the flatbed to remain in the air for 70-90 seconds for pre-evaporation. Then immerse the flatbed coated with the casting solution in a room-temperature coagulation bath for 3 minutes. The coagulation bath is an aqueous solution containing 40-50% solvent by mass. After the exchange is complete, transfer it to room-temperature pure water and let it stand for 5 hours to solidify, obtaining a wet film. The cross-sectional pore structure diagram of the prepared wet film after natural drying is shown in the figure below. Figure 1 As shown;

[0039] Step 3: Heat-treat the wet original membrane; the heat treatment involves immersing the wet original membrane in hot water at 70°C for 8 hours; the resulting wet original membrane, after natural drying, exhibits the following porous structure: Figure 2 As shown;

[0040] Step 4: Place the heat-treated wet membrane into a high-pressure steam furnace and sterilize it with pure water steam at 121°C under pressure for 20 minutes.

[0041] Step 5: Dry the wet membrane after moisture heat sterilization; the drying method is to dry it in an oven at 50°C for 10 minutes. The surface structure diagram of the prepared polyvinylidene fluoride separation membrane is shown below. Figure 3 As shown.

[0042] Depend on Figure 1 and Figure 2 The comparison shows that after heat treatment, the original membrane's dense structure with low porosity is transformed into a fibrous network structure with high porosity, resulting in a significant increase in the membrane's cross-sectional porosity. Figure 3 It can be seen that the polyvinylidene fluoride separation membrane prepared by this invention has a non-directional tortuous path, with the side having a large pore size serving as the liquid inlet surface (e.g. Figure 3 a) The side with the smaller orifice is used as the liquid outlet surface (e.g. Figure 3 b) enables the effective retention of substances of a specific size.

[0043] The separation membrane prepared by the above method was soaked in pure water, and two layers were stacked with the macropore side as the feed surface. Testing showed that the pure water flux of this separation membrane reached 241.8 L·m³. -2 ·h -1 At 0.30 MPa, the retention rate of 15 nm and 20 nm gold nanoparticles at a concentration of 10 mg / L reached 99.99%, and the initial flux of human immunoglobulin solution (IVIG) at a concentration of 50 g / L reached 35.82 L·m -2 ·h -1 At 0.30 MPa, the flux after 6 hours of continuous filtration attenuation is 17.91 L·m⁻¹. -2 ·h -1 At 0.30 MPa, its IVIG permeability can reach 98.05% to 99.17%.

[0044] Example 2

[0045] A method for preparing a polyvinylidene fluoride (PVDF) separation membrane includes the following steps:

[0046] Step 1: Mix and dissolve polyvinylidene fluoride, dimethylacetamide, polyethylene glycol, isopropanol, and polyether in a mass ratio of 24:62:8:5:2, and stir at 60°C until the mixed solution becomes clear and transparent; let stand for 6 hours to remove bubbles and prepare the film-forming solution.

[0047] Step 2: Turn on the flatbed film casting machine, control the temperature of the casting area to be 24-28℃, the air humidity to be 50-60%, set the squeegee moving speed to 7m / min, and the film thickness to 0.100mm. Pour the casting solution evenly onto the flatbed with the substrate on its surface, parallel to the squeegee, and then cast the film. After the squeegee moves to the end, let the casting solution evenly spread on the flatbed remain in the air for 1-2 minutes for pre-evaporation. Then immerse the flatbed coated with the casting solution in a 60℃ coagulation bath for 4 minutes. The coagulation bath is an aqueous solution containing 60-80% solvent by mass. After the exchange is completed, transfer it to pure water at room temperature and let it stand for 5 hours to solidify, thus obtaining a wet film.

[0048] Step 3: Heat-treat the wet original membrane; the heat treatment is to immerse the wet original membrane in hot water at 60°C for 8 hours.

[0049] Step 4: Place the heat-treated wet membrane into a high-pressure steam furnace and sterilize it with pure water steam at 121°C under pressure for 20 minutes.

[0050] Step 5: Dry the wet original film after moist heat sterilization; the drying method is to dry it in an oven at 50°C for 10 minutes.

[0051] The separation membrane prepared by the above method was soaked in pure water for 15 minutes, and two layers were stacked with the macropore side as the feed surface. The pure water flux reached 340.25 L·m -2 ·h -1 At 0.30 MPa, the initial flux of a 50 g / L human immunoglobulin solution (IVIG) can reach 41.19 L·m⁻¹. -2 ·h -1 At 0.30 MPa, the flux after 6 hours of continuous filtration attenuation is 19.70 L·m⁻¹. -2 ·h -1 At 0.30 MPa, its IVIG permeability can reach 99.99%.

[0052] Example 3

[0053] A method for preparing a polyvinylidene fluoride (PVDF) separation membrane includes the following steps:

[0054] Step 1: Mix and dissolve polyvinylidene fluoride, dimethylacetamide, isobutanol, glycerol, and polymethylpyrrolidone in a mass ratio of 29:58:8:6:1, and stir at 90°C until the mixed solution becomes clear and transparent; let stand for 12 hours to remove bubbles to prepare the film-forming solution.

[0055] Step 2: Turn on the flatbed film casting machine, control the temperature of the film casting area to be 26-30℃, the air humidity to be 60-90%, set the doctor blade moving speed to 3m / min, and the film thickness to be 0.050mm. Pour the casting solution evenly onto the flatbed with the substrate on the surface, parallel to the doctor blade, and then cast the film. After the doctor blade moves to the end, let the casting solution evenly spread on the flatbed remain in the air for 0-90s for pre-evaporation. Then immerse the flatbed coated with the casting solution in a 50℃ coagulation bath for 3 minutes. The coagulation bath is an aqueous solution containing 50-60% solvent by mass. After the exchange is completed, transfer it to pure water at room temperature and let it stand for 5 hours to solidify, thus obtaining a wet film.

[0056] Step 3: Heat-treat the wet original membrane; the heat treatment is to immerse the wet original membrane in hot water at 80°C for 6 hours.

[0057] Step 4: Place the heat-treated wet membrane into a high-pressure steam furnace and sterilize it with pure water steam at 121°C under pressure for 20 minutes.

[0058] Step 5: Dry the wet original film after moist heat sterilization; the drying method is to dry it in an oven at 50°C.

[0059] The separation membrane prepared by the above method was soaked in pure water, and two layers were stacked with the macropore side as the feed surface. The pure water flux reached 223.9 L·m -2 ·h -1 At 0.30 MPa, the initial throughput of human immunoglobulin solution (IVIG) with a test protein concentration of 50 g / L can reach 26.86 L·m -2 ·h -1 At 0.30 MPa, the flux after 6 hours of continuous filtration attenuation is 12.53 L·m⁻¹. -2 ·h -1 @0.30MPa, and its IVIG permeability can reach 97.23% to 98.86%.

[0060] Comparative Example 1

[0061] This comparative example uses the wet membrane prepared according to step 2 of Example 1. Performance testing was performed, and the pure water flux of the membrane was measured to be 116.4 L·m⁻¹. -2 ·h -1 At 0.30 MPa, the initial flux measured with a 50 g / L human immunoglobulin solution (IVIG) was 10.75 L·m⁻¹. -2 ·h -1 At 0.30 MPa, the IVIG flux decreased to 3.58 L·m after 1 hour of filtration. -2 ·h -1At 0.30 MPa, the IVIG permeability was 65.69%–79.28%. Compared with the examples, the membrane prepared in this comparative example had a lower initial IVIG flux, faster flux decay, and lower protein permeability. This was observed in the scanning electron microscope image of the membrane cross-section. Figure 1 Analysis suggests that the membrane's internal structure is relatively dense with low porosity, making it difficult for protein molecules to pass through during filtration and causing them to accumulate and clog, resulting in a low protein yield. This result indicates that the membrane in this form cannot meet the needs of actual production.

[0062] Comparative Example 2

[0063] This comparative example uses the wet membrane prepared according to step 3 of Example 1. Performance testing was performed, and the pure water flux of the heat-treated membrane was measured to be 196.9 L·m⁻¹. -2 ·h -1 At 0.30 MPa, the initial flux measured with a 50 g / L human immunoglobulin solution (IVIG) was 25.07 L·m⁻¹. -2 ·h -1 At 0.30 MPa, after 6 hours of filtration, the IVIG flux decreased to 14.33 L·m⁻¹. -2 ·h -1 At 0.30 MPa, its IVIG permeability is 96.53% to 98.27%. Compared with the membrane after moist heat sterilization in Example 1, the membrane in this comparative example without moist heat sterilization has a smaller flux. In practical applications, the dry membrane obtained after moist heat sterilization in Example 1 is easier to preserve, and the membrane performance after heat setting is more stable.

[0064] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for preparing a polyvinylidene fluoride (PVDF) separation membrane, characterized in that, Includes the following steps: Step 1: Mix polyvinylidene fluoride, solvent and additives, stir to dissolve evenly, let stand to remove bubbles, and prepare casting solution; Step 2: Turn on the flatbed casting machine, control the temperature and humidity of the casting area, set the blade movement speed and casting thickness, pour the casting liquid evenly onto the flatbed with the substrate on the surface and then cast the film; then immerse the flatbed coated with the casting liquid in the coagulation bath for exchange. After the exchange is completed, the membrane is transferred into pure water and allowed to stand and solidify to obtain a wet original membrane. Step 3: Heat-treat the wet original film; Step 4: Perform moist heat sterilization on the heat-treated wet original membrane; Step 5: Dry the wet original film after moist heat sterilization; The heat treatment method in step 3 is to immerse the wet original membrane in hot water at 30~90℃ for 2h~10h; In step 4, the moist heat sterilization process involves sterilizing at 100-200℃ for 0-3 hours.

2. The method for preparing the polyvinylidene fluoride separation membrane according to claim 1, characterized in that, In step 1, the casting solution contains 10-30% polyvinylidene fluoride, 30-70% solvent, and 5-20% additives by mass.

3. The method for preparing the polyvinylidene fluoride separation membrane according to claim 1, characterized in that, The solvent includes one or a mixture of several of N-methylpyrrolidone, dimethylformamide, dimethylacetamide and acetone; the additive includes one or a mixture of several of isobutanol, polyethylene glycol, polymethylpyrrolidone, polyether, glycerol, ethanol, isopropanol, n-butanol and n-octanol.

4. The method for preparing the polyvinylidene fluoride separation membrane according to claim 1, characterized in that, In step 2, the temperature of the scraping area is 20~40℃, the air humidity is 40%~100%, the scraper moving speed is 1~8m / min, and the scraping thickness is 0.050~0.200mm.

5. The method for preparing the polyvinylidene fluoride separation membrane according to claim 1, characterized in that, In step 2, before the coagulation bath is exchanged, the casting solution is pre-evaporated by air residence, with an air residence time of 10~180s.

6. The method for preparing the polyvinylidene fluoride separation membrane according to claim 1, characterized in that, In step 5, the drying conditions are to keep the temperature constant at 40~100℃ for 5~30 minutes.

7. A polyvinylidene fluoride separation membrane, characterized in that, The polyvinylidene fluoride separation membrane was prepared using the preparation method described in any one of claims 1 to 6.

8. The application of the polyvinylidene fluoride separation membrane according to claim 7 in virus isolation, characterized in that, The polyvinylidene fluoride separation membrane is stacked in two layers with the macropore side as the feed surface, and then filtered and separated.

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