Preparation method of virus removal ultrafiltration membrane with low specific adsorption and virus removal ultrafiltration equipment

Abstract

This invention pertains to the field of polymer membrane materials technology, specifically a method for preparing a virus-removing ultrafiltration membrane with low specificity adsorption and a virus-removing ultrafiltration device. The preparation method includes steps such as energy radiation curing of a composition followed by energy radiation, phase separation in a coagulation bath, and drying. The energy radiation curing composition comprises polyethersulfone, an organic solvent, an active low-protein adsorbent, and a hydrophilic additive; the active low-protein adsorbent comprises compounds that can be quantitatively cured. The virus-removing ultrafiltration membrane prepared using this invention exhibits an asymmetric structure, resulting in a faster flow rate. It possesses excellent retention and flux, and high IgG permeability.

Description

Technical Field

[0001] This invention belongs to the field of polymer membrane material technology, and specifically relates to a method for preparing a virus-removing ultrafiltration membrane with low specific adsorption and a virus-removing ultrafiltration device. Background Technology

[0002] Membrane technology is a modern, highly efficient separation technology. Compared with traditional distillation and rectification techniques, it has advantages such as high separation efficiency, low energy consumption, and small footprint. The core of membrane separation technology is the separation membrane. Among them, polymer filter membranes are a type of separation membrane made from organic polymers according to a specific process. With the development of the petroleum industry and science and technology, the application fields of polymer filter membranes are constantly expanding. Currently, they are used in gas separation, seawater desalination, ultrapure water preparation, wastewater treatment, artificial organ manufacturing, medicine, food, agriculture, chemical industry, and many other fields.

[0003] Ultrafiltration, as a membrane separation technology, is widely used in wastewater treatment, pharmaceuticals, and the food industry due to its high flux, mild operating conditions, and ease of scale-up. Polyethersulfone (PES), as a special functional plastic, exhibits excellent antioxidant properties, thermal stability, hydrolysis resistance, and good mechanical properties, playing a crucial role in biomedicine and water treatment. Despite the significant success of ultrafiltration membranes, research on PES virus-removing ultrafiltration membranes remains scarce. This is because virus-removing membranes require precise pore size design to ensure effective virus retention and high flow rates to guarantee efficient recovery; simultaneously achieving both characteristics is extremely challenging. Therefore, research on PES virus-removing ultrafiltration membranes is essential. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing a virus-removing ultrafiltration membrane with low specific adsorption and a virus-removing ultrafiltration device. The specific technical solution is as follows:

[0005] The first aspect of the present invention provides a method for preparing a virus-removing ultrafiltration membrane with low specificity adsorption, comprising the steps of energy radiation curing composition subjected to energy radiation, phase separation in a coagulation bath, and drying, wherein the energy radiation curing composition comprises polyethersulfone, an organic solvent, an active low-protein adsorbent, and a hydrophilic additive; wherein the active low-protein adsorbent comprises a compound that may be cured in a certain amount.

[0006] Further, the compound that may be cured includes one or more of hydroxymethyl acrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, N-hydroxyethyl cellulose, or N-hydroxymethyl cellulose; preferably hydroxyethyl methacrylate.

[0007] Furthermore, the active low-protein adsorbent is preferably hydroxyethyl methacrylate.

[0008] Furthermore, the hydrophilic additive includes one or more of polyethylene glycol, triethylene glycol, polyvinylpyrrolidone, and isopropanol; preferably polyethylene glycol.

[0009] Further, the organic solvent includes one or more of dimethylformamide, dimethylacetamide, dimethyl sulfoxide, formamide, or N-vinylpyrrolidone; preferably dimethylacetamide.

[0010] Further, the mass ratio of the polyethersulfone, organic solvent, active low-protein adsorbent and hydrophilic additive is (14-25):(35-60):(1-10):(6-40).

[0011] Furthermore, the energy radiation includes ultraviolet radiation, thermal radiation, plasma radiation, or electron beam energy radiation, and the energy radiation time is 0.5-3 min; the coagulation bath time is 0.1-1 min.

[0012] The preparation method provided in the first aspect of the present invention specifically includes the following steps:

[0013] (1) The energy radiation curing composition is heated and stirred until it is uniformly mixed to obtain a casting liquid; wherein the heating temperature in step (1) is 40 to 80°C.

[0014] (2) The casting liquid obtained in step (1) is cast onto the substrate, and after being irradiated with energy, it is immersed in a water coagulation bath to separate phases and form a film. After drying, the virus-removing ultrafiltration membrane with low specific adsorption is obtained.

[0015] A second aspect of the present invention provides a low-specificity adsorption virus-removing ultrafiltration membrane, wherein the IgG permeability of the low-specificity adsorption virus-removing ultrafiltration membrane reaches more than 90%.

[0016] A third aspect of the present invention provides a virus removal ultrafiltration device, wherein the virus removal ultrafiltration device comprises a virus removal ultrafiltration membrane with low specific adsorption prepared by the preparation method provided in the first aspect of the present invention or a virus removal ultrafiltration membrane with low specific adsorption provided in the second aspect of the present invention.

[0017] The beneficial effects of this invention are as follows:

[0018] (1) The present invention can play a certain modification role before the complete phase separation by using an active low protein adsorbent and external energy irradiation. Before phase separation, the adsorbent can be more closely bound to PES, thus binding more firmly under radiation, which promotes a higher polymer density on the surface. As a result, the diffusion rate of the coagulation bath into the inner layer of the membrane is slower during phase separation, which can prevent the surface pores from being unevenly distributed due to the excessively rapid diffusion of non-solvents.

[0019] (2) The virus-removing ultrafiltration membrane prepared by the preparation process of the present invention has an asymmetrical structure, which results in a faster flow rate, excellent retention and flux, and high IgG permeability. Attached Figure Description

[0020] Figure 1a , 1b This is an electron microscope image of the virus-removing ultrafiltration membrane obtained in Example 2;

[0021] Figure 2a , 2b This is an electron microscope image of the virus-removing ultrafiltration membrane obtained in Example 4. Detailed Implementation

[0022] This invention provides a method for preparing a virus-removing ultrafiltration membrane with low specific adsorption and a virus-removing ultrafiltration device. The invention will be further described below with reference to the embodiments.

[0023] In some specific embodiments of the present invention, the first aspect of the present invention provides a method for preparing a virus-removing ultrafiltration membrane with low specific adsorption.

[0024] The first aspect of the present invention provides a method for preparing a virus-removing ultrafiltration membrane with low specificity adsorption, comprising the steps of energy radiation curing composition subjected to energy radiation, phase separation in a coagulation bath, and drying, wherein the energy radiation curing composition comprises polyethersulfone, an organic solvent, an active low-protein adsorbent, and a hydrophilic additive; wherein the active low-protein adsorbent comprises a compound that may be cured in a certain amount.

[0025] Furthermore, the compound that may be cured in quantity is a compound that can be cured by light or radiation, such as ultraviolet light radiation, thermal radiation, plasma radiation or electron beam energy radiation, including one or more of hydroxymethyl acrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, N-hydroxyethyl cellulose or N-hydroxymethyl cellulose; preferably hydroxyethyl methacrylate.

[0026] Furthermore, the active low-protein adsorbent is preferably hydroxyethyl methacrylate.

[0027] Furthermore, the hydrophilic additive includes one or more of polyethylene glycol, triethylene glycol, polyvinylpyrrolidone, and isopropanol; preferably polyethylene glycol.

[0028] Further, the organic solvent includes one or more of dimethylformamide, dimethylacetamide, dimethyl sulfoxide, formamide, or N-vinylpyrrolidone; preferably dimethylacetamide.

[0029] Further, the mass ratio of the polyethersulfone, organic solvent, active low-protein adsorbent and hydrophilic additive is (14-25):(35-60):(1-10):(6-40); preferably, the mass ratio of the polyethersulfone, organic solvent, active low-protein adsorbent and hydrophilic additive is 16:60:10:14.

[0030] Further, the energy radiation includes ultraviolet radiation, thermal radiation, plasma radiation, or electron beam energy radiation, and the energy radiation time is 0.5-3 min; the coagulation bath time is 0.1-1 min. The ultraviolet wavelength range is 200-400 nm; the electron beam energy range is 1 keV-500 keV, preferably 150-400 keV.

[0031] The preparation method provided in the first aspect of the present invention specifically includes the following steps:

[0032] (1) The energy radiation curing composition is heated and stirred until it is uniformly mixed to obtain a casting liquid; wherein the heating temperature in step (1) is 40 to 80°C.

[0033] (2) The casting liquid obtained in step (1) is cast onto the substrate, and after being irradiated with energy, it is immersed in a water coagulation bath to separate phases and form a film. After drying, the virus-removing ultrafiltration membrane with low specific adsorption is obtained.

[0034] The following example illustrates the specific steps involved:

[0035] (1) Preparation of casting solution

[0036] Polyethersulfone, organic solvent, active low-protein adsorbent and hydrophilic additive are mixed evenly and heated and stirred at 80°C for 3 hours until the mixture is uniform. The mixture is clear and transparent at room temperature, which is the casting solution.

[0037] (2) Preparation of virus-removing ultrafiltration membrane

[0038] The casting solution obtained in step (1) is cast onto a metal substrate, and after being irradiated by external energy to initiate a reaction for a period of time, it is immediately immersed in a water coagulation bath for 0.1-1 min to separate the phases and form a film. After drying, the virus-removing ultrafiltration membrane with low specific adsorption is obtained.

[0039] A second aspect of this invention provides a low-specificity adsorption virus-removing ultrafiltration membrane, prepared by the method provided in the first aspect of this invention. The membrane has an asymmetric structure comprising two parts: a first part is a dense layer that acts as a trapping layer, and a second part is a support layer that provides structural strength and contaminant holding capacity. The pore size of the support layer is larger than that of the dense layer. The IgG permeability of the low-specificity adsorption virus-removing ultrafiltration membrane reaches over 90%.

[0040] A third aspect of the present invention provides a virus removal ultrafiltration device, wherein the virus removal ultrafiltration device comprises a virus removal ultrafiltration membrane with low specific adsorption prepared by the preparation method provided in the first aspect of the present invention or a virus removal ultrafiltration membrane with low specific adsorption provided in the second aspect of the present invention.

[0041] Example 1

[0042] 14g of polyethersulfone resin, 60g of N-vinylpyrrolidone, 1g of N-hydroxymethyl cellulose, 5g of hydroxyethyl methacrylate and 14g of isopropanol were mixed evenly and heated and stirred at 60℃ for 3h until the mixture was uniform and clear and transparent at room temperature. The prepared casting solution was then cast onto a metal plate, irradiated with UV light for 2min, and then immediately immersed in a water coagulation bath for 0.5min to separate the phases and form a membrane. Finally, the membrane was dried to obtain the desired virus-removing ultrafiltration membrane.

[0043] Example 2

[0044] 16g of polyethersulfone resin, 55g of dimethyl sulfoxide, 5g of hydroxyethyl methacrylate, and 24g of polyethylene glycol 400 were mixed evenly and heated and stirred at 80℃ for 3 hours until homogeneous. The mixture was clear and transparent at room temperature. The prepared casting solution was then cast onto a metal plate, irradiated with UV light for 3 minutes, and then immediately immersed in a water coagulation bath for 1 minute to form a phase-separation membrane. Finally, the membrane was dried to obtain the desired virus-removing ultrafiltration membrane. Its electron micrograph is shown below. Figure 1a , 1b As shown, Figure 1a This is a cross-sectional view at 2000x magnification in the direction of the cut-off layer. Figure 1b A cross-sectional view at 5000x magnification in the direction of the cut-off layer shows a clear trend of gradually increasing pore size along the direction from the cut-off layer to the support layer.

[0045] Example 3

[0046] 18g of polyethersulfone resin, 44g of dimethylformamide, 8g of hydroxyethyl acrylate, and 30g of polyvinylpyrrolidone were mixed evenly and heated and stirred at 40°C for 3 hours until the mixture was homogeneous and clear at room temperature. The prepared casting solution was then cast onto a metal plate, irradiated with an electron beam for 1 minute, and then immediately immersed in a water coagulation bath for 0.15 minutes to separate the phases and form a membrane. Finally, the membrane was dried to obtain the desired virus-removing ultrafiltration membrane.

[0047] Example 4

[0048] 23g of polyethersulfone resin, 40g of dimethylacetamide, 10g of N-hydroxymethyl cellulose, and 14g of triethylene glycol were mixed evenly and heated and stirred at 80℃ for 3 hours until homogeneous. The mixture was clear and transparent at room temperature. The prepared casting solution was then cast onto a metal plate, irradiated with an electron beam for 0.5 min, and immediately immersed in a water coagulation bath for 1 min to separate the phases and form a membrane. Finally, the membrane was dried to obtain the desired virus-removing ultrafiltration membrane. Its electron micrograph is shown below. Figure 2a , 2b As shown, Figure 2a This is a cross-sectional view at 2000x magnification in the direction of the cut-off layer. Figure 2b A cross-sectional view at 5000x magnification in the direction of the cut-off layer shows a clear trend of gradually increasing pore size along the direction from the cut-off layer to the support layer.

[0049] Comparative Example 1

[0050] 16g of polyethersulfone resin, 55g of dimethyl sulfoxide, 3g of N-hydroxymethyl cellulose, 7g of hydroxyethyl methacrylate and 19g of polyethylene glycol 400 were mixed evenly and heated and stirred at 80℃ for 3h until the mixture was uniform and clear and transparent at room temperature. The prepared casting solution was cast onto a metal plate and then immediately immersed in a water coagulation bath for 0.83min to separate the phases and form a membrane. Finally, it was dried to obtain the desired virus-removing ultrafiltration membrane.

[0051] Comparative Example 2

[0052] 16g of polyethersulfone resin, 55g of dimethyl sulfoxide, and 29g of polyethylene glycol 400 were mixed evenly and heated and stirred at 80°C for 3 hours until the mixture was uniform and clear and transparent at room temperature. In the second step, the prepared casting solution was cast onto a metal plate, irradiated with UV light for 3 minutes, and then immediately immersed in a water coagulation bath for 1 minute to separate the phases and form a membrane. Finally, it was dried to obtain the desired virus-removing ultrafiltration membrane.

[0053] The membrane water flux, retention rate, and IgG permeability of the virus-removing ultrafiltration membranes obtained in Examples 1-4 and Comparative Examples 1 and 2 were tested. The retention rate (LRV) is the ability of the PES filter membrane to retain viral impurities with a particle size of 20 nm. The data are shown in Table 1.

[0054] Table 1

[0055]

[0056] As can be seen from the comparison of Examples 1-4 with Comparative Examples 1 and 2, when both active low-protein adsorbent and external energy irradiation are present, it has excellent retention and throughput, and can endow the PES virus membrane with good low-protein adsorption capacity, thereby increasing the IgG permeability. However, when either of the two conditions is lacking, the PES membrane will be blocked quickly, and the IgG volume protein permeability will be low.

[0057] The testing methods for each indicator in Table 1 are as follows:

[0058] Membrane water flux was tested using an ultrafiltration cup. During the test, the air pressure was adjusted to 0.4 MPa, and 50 ml of 25°C ultrapure water was poured into the ultrafiltration cup. The water output within 1 minute was measured. The calculation is shown in Equation 1 below:

[0059]

[0060] In Equation 1, J w --Membrane water flux unit: L / h*m 2 V -- Sampling volume (L); Δt -- Sampling time (h); A -- Effective membrane area (m²) 2 ).

[0061] Retention Experiment: Tests were conducted at a constant pressure of 30 Psi using a 25 mm stainless steel disc filter, with data automatically collected by a computer data acquisition system. The membrane was wetted with ultrapure water. At the start of all tests, the membrane was flushed with a buffer solution for 2 to 5 minutes to equilibrate. The feed solution was filtered from the open pore side of the membrane. The universal feed solution was 1 mg / ml human plasma 1gG (Sigma, batch number: SLL2006) containing 107 pfu / mL PP7 (ATCC, batch number: 70039088) in a 50 mM acetate buffer system at pH 5. The PP7 phage retention challenge test was performed using the plaque assay. The permeate was serially diluted to determine its titer. The viral rejection rate (LRV) was calculated as the logarithm of the ratio of feed titer to permeate titer.

[0062] IgG permeation rate: The ratio of protein content in the permeate after the feed solution passes through the virus-removing ultrafiltration membrane to the protein content in the initial feed solution.

Claims

1. A method for preparing a virus removal ultrafiltration membrane with low specific adsorption, characterized in that, The method includes the steps of energy radiation curing composition followed by energy radiation, phase separation in a coagulation bath, and drying. The energy radiation curing composition includes polyethersulfone, organic solvent, active low-protein adsorbent, and hydrophilic additive; the active low-protein adsorbent includes compounds that can be cured in large quantities. Including steps: (1) The energy radiation curing composition is heated and stirred until uniformly mixed to obtain a casting solution: (2) The casting solution obtained in step (1) is cast onto the substrate, and after being irradiated with energy, it is immersed in a water coagulation bath to separate the phases and form a film. After drying, the virus-removing ultrafiltration membrane with low specific adsorption is obtained; the energy irradiation time is 0.5-3 min. The mass ratio of the polyethersulfone, organic solvent, active low-protein adsorbent and hydrophilic additive is (14-25):(35-60):(1-10):(6-40); The compounds that may be cured include one or more of hydroxymethyl acrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, N-hydroxyethyl cellulose, or N-hydroxymethyl cellulose; The virus-removing ultrafiltration membrane has an asymmetric structure consisting of two parts: a dense layer that serves to trap viruses and a support layer that provides structural strength and contaminant capacity. The pore size of the support layer is larger than that of the dense layer.

2. The preparation method according to claim 1, characterized in that, The compound that may be cured is hydroxyethyl methacrylate.

3. The preparation method according to claim 1, characterized in that, The hydrophilic additive includes one or more of polyethylene glycol, triethylene glycol, polyvinylpyrrolidone, and isopropanol.

4. The preparation method according to any one of claims 1 to 3, characterized in that, The organic solvent includes one or more of dimethylformamide, dimethylacetamide, dimethyl sulfoxide, formamide, or N-vinylpyrrolidone.

5. The preparation method according to any one of claims 1 to 3, characterized in that, The energy radiation includes ultraviolet radiation, thermal radiation, plasma radiation, or electron beam energy radiation; the coagulation bath time is 0.1-1 min.

6. The preparation method according to claim 4, characterized in that, The energy radiation includes ultraviolet radiation, thermal radiation, plasma radiation, or electron beam energy radiation; the coagulation bath time is 0.1-1 min.

7. The preparation method according to claim 1, characterized in that, The heating temperature in step (1) is 40-80℃.

8. A virus-removing ultrafiltration membrane with low specific adsorption prepared by the preparation method according to any one of claims 1 to 7, characterized in that, The IgG permeability of the low-specificity adsorption antiviral ultrafiltration membrane reaches over 90%.

9. A virus-removing ultrafiltration device, characterized in that, The virus removal ultrafiltration device includes a virus removal ultrafiltration membrane with low specific adsorption prepared by any one of the preparation methods of claims 1 to 7 or a virus removal ultrafiltration membrane with low specific adsorption as described in claim 8.

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