A nitrocellulose chromatography membrane and a method for preparing the same

Abstract

The application provides a nitrocellulose chromatographic membrane and a preparation method thereof, and mainly relates to the technical field of nitrocellulose chromatographic membrane, and is characterized by the following steps: forming a film by evaporation-induced phase separation reaction of a casting solution containing nitrocellulose, wherein the nitrocellulose membrane comprises a first coating layer and a second coating layer, which are respectively formed by an upper casting solution and a lower casting solution; the concentration of nitrocellulose in the upper casting solution is lower than that in the lower casting solution, and the concentration of a non-solvent in the upper casting solution is higher than that in the lower casting solution. The casting solution of the nitrocellulose membrane has different internal compositions, and can obtain an NC membrane without a backing or with a backing; the double-layer structure is used in the internal part of the casting solution; the concentration of nitrocellulose on the upper surface coating layer is relatively low, and the concentration of the non-solvent is relatively high, so that the solidification speed can be delayed to make the micropores fully grow, and the micropores with symmetrical upper and lower surfaces are obtained.

Description

TECHNICAL FIELD

[0001] The present application mainly relates to the technical field of nitrocellulose chromatography membrane, and particularly relates to a nitrocellulose chromatography membrane and a preparation method thereof. BACKGROUND

[0002] The immunochromatography technology is a rapid diagnosis technology based on specific binding of antigen and antibody, and has the advantages of convenient operation and rapid detection. Taking the colloidal gold immunochromatography technology as an example, the principle is that the antigen or antibody with specific binding capacity is fixed on the microporous membrane carrier, when the sample to be detected moves to the region fixed with the antigen or antibody on the microporous membrane, specific binding occurs and is intercepted, and an intuitive color development result is obtained through the colloidal gold marker. The colloidal gold antigen detection kit generally includes four main parts: a sample pad, a conjugate release pad, a fixed antibody membrane and an adsorption pad. Among them, the nitrocellulose membrane (NC membrane) is the most core component, and usually must have excellent protein adsorption capacity, high wettability, high porosity and uniform pore size distribution. The production process of the NC membrane usually includes: dissolving nitrocellulose in a ketone or ester organic solvent, adding a non-solvent to uniformly stir to form a homogeneous nitrocellulose membrane solution, then standing for several hours to remove the bubbles in the casting solution; then, the nitrocellulose membrane solution is coated on a continuously rotating conveying belt, and a phase separation reaction is induced by evaporation to obtain a nitrocellulose chromatography membrane. Then, the nitrocellulose chromatography membrane product is obtained through the steps of water washing, drying, winding and slitting.

[0003] In the production process of the nitrocellulose chromatography membrane, the control of the phase separation of the nitrocellulose membrane solution into pores is the most critical and most difficult step. The pore formation principle is based on the evaporation-induced phase separation reaction. When the homogeneous nitrocellulose membrane solution is coated into a film, due to the fact that the volatilization speed of the organic solvent is significantly faster than that of the non-solvent, the solubility of the nitrocellulose in the nitrocellulose membrane solution inside is greatly reduced, thereby inducing phase separation, and further forming a polymer concentrated phase and a polymer dilute phase. With the complete drying of the solvent and the non-solvent, the polymer concentrated phase forms the skeleton of the microporous membrane, and the dilute phase forms the micropores in the membrane.

[0004] At present, there are still several bottlenecks in the manufacturing of nitrocellulose chromatography membrane. First, in the process of evaporation-induced phase separation reaction, the evaporation rate of the nitrocellulose membrane solution on the upper surface is significantly faster than that on the bottom, so that a dense skin layer is formed on the upper surface. Therefore, the nitrocellulose chromatography membrane usually forms an asymmetric microporous structure, i.e. the pore size gradually increases from top to bottom. The asymmetric microporous structure will cause the liquid absorption speed to be inconsistent when the nitrocellulose chromatography membrane is applied to lateral chromatography technology, thereby affecting the accuracy of detection. On the other hand, when producing NC membrane with backing, the nitrocellulose microporous membrane cannot be tightly attached to the backing, which causes the NC membrane to easily fall off from the backing during use, thereby affecting the use of the membrane. SUMMARY

[0005] The purpose of the present application is to provide a nitrocellulose chromatography membrane and a preparation method thereof, which solves the technical problem that the nitrocellulose chromatography membrane in the prior art usually forms an asymmetric microporous structure, i.e. the pore size gradually increases from top to bottom.

[0006] The present application discloses a nitrocellulose chromatography membrane, which is formed by evaporation-induced phase separation reaction of a casting solution containing nitrocellulose. The nitrocellulose membrane comprises a first coating layer and a second coating layer, which are respectively formed by an upper casting solution and a lower casting solution. The concentration of nitrocellulose in the upper casting solution is lower than that in the lower casting solution, and the concentration of non-solvent in the upper casting solution is higher than that in the lower casting solution.

[0007] Further, the upper casting solution comprises the following raw materials by weight: 3-8 parts of nitrocellulose, 20-60 parts of ester or ketone compound solvent, 30-70 parts of alcohol mixed solvent, 2-10 parts of non-solvent, and 0.005-2 parts of humectant.

[0008] Further, the lower casting solution comprises the following raw materials by weight: 5-15 parts of nitrocellulose, 30-60 parts of ester or ketone compound solvent, 40-75 parts of alcohol mixed solvent, 5-18 parts of non-solvent, and 0.005-2 parts of humectant.

[0009] Further, the ester or ketone compound solvent is selected from at least one of ethyl acetate, methyl acetate, acetone, and butanone.

[0010] Further, the mixed solvent is selected from at least one of alcohol solvents such as methanol, ethanol, propanol, isopropanol, and n-butanol.

[0011] Further, the non-solvent is deionized water.

[0012] Further, the humectant is any one of glycerol, propylene glycol, polyethylene glycol, and glycerol polyoxyethylene ether.

[0013] Further, it further comprises a third coating layer and a backing layer.

[0014] Further, the third coating layer is an adhesive.

[0015] Further, the adhesive is a polyacrylic resin pressure-sensitive adhesive or a hot-melt adhesive.

[0016] Further, the backing is a woven fabric, polyester, polyvinyl chloride, polypropylene, polyethylene or polystyrene.

[0017] A second object of the present application is to protect a method for preparing a nitrocellulose chromatography membrane, comprising the following steps:

[0018] S1. Dissolve nitrocellulose in an ester compound solvent and stir until uniform, then add an alcohol compound, a non-solvent and a humectant and stir until uniform, the temperature of the stirred liquid is 20-40°C, filter and stand to remove bubbles, respectively obtaining an upper casting solution and a lower casting solution, the concentration of nitrocellulose in the upper casting solution is lower than in the lower casting solution, and the concentration of the non-solvent in the upper casting solution is higher than in the lower casting solution;

[0019] S2. Merge the upper casting solution and the lower casting solution into a multi-layer composite die through different delivery channels provided with pumps, and respectively control the flow rates of the upper casting solution and the lower casting solution through the pumps on the respective delivery channels;

[0020] S3. Coat the upper casting solution and the lower casting solution on a continuously moving transport belt below the composite die through uniform speed delivery of the composite die, to obtain a nitrocellulose chromatography membrane initial product with uniform thickness, the lower casting solution directly contacts the transport belt to form a second coating layer, and the upper casting solution is coated on the second coating layer to form a first coating layer;

[0021] S4. Transport the nitrocellulose chromatography membrane initial product into an oven channel through the transport belt, and prepare a nitrocellulose chromatography membrane intermediate product through an evaporation-induced phase separation reaction;

[0022] S5. After removing internal impurities by immersing the nitrocellulose chromatography membrane intermediate product in clean water, immerse it in a surfactant to improve the surface hydrophilicity, then dry, roll, and cut to obtain a nitrocellulose chromatography membrane finished product.

[0023] Further, the surfactant in step S5 is selected from any one of AES, sodium dodecyl sulfate, sodium dodecyl sulfonate, and sodium dodecyl benzene sulfonate, and the drying temperature is 20-50°C.

[0024] Further, the thickness of the upper surface coating layer of the nitrocellulose chromatography membrane initial product is less than the thickness of the lower surface coating layer.

[0025] Further, the thickness of the upper surface coating layer is 100-500μm, and the thickness of the lower surface coating layer is 500-1000μm.

[0026] Further, the conditions of the evaporation-induced phase separation in step S4 include: temperature of 15-50℃, humidity of 20-60%, and air flow rate of 1-3m / s.

[0027] Further, the conditions of the evaporation-induced phase separation include: temperature of 20-40℃, humidity of 20-60%, air flow rate of 2-3m / s, and drying temperature of 20-50℃.

[0028] A third object of the present application is to protect the use of a method for preparing a nitrocellulose chromatography membrane.

[0029] Compared with the prior art, the present application has the beneficial effects that:

[0030] 1. The casting solution of the nitrocellulose membrane of the present application has different internal compositions, and can obtain NC membranes with / without backing. The internal double-layer structure of the casting solution has a lower concentration of nitrocellulose and a higher concentration of non-solvent on the upper surface coating, which can delay the solidification speed and make the micropores grow fully, so that larger micropores are obtained.

[0031] 2. When preparing the NC membrane with backing, a three-layer structure is used for the coating film head, in addition to the upper and lower surface coatings, a third layer of adhesive is used to more closely adhere the nitrocellulose membrane to the backing. The gradient coating obtained by the nitrocellulose microporous membrane has large pore size, high porosity, and uniform pore size distribution on the upper and lower surfaces. It can effectively improve the problem of asymmetric microporous structure commonly existing in the production of nitrocellulose membranes. In addition, the use of gradient coating technology can appropriately reduce the time in the forming oven, thereby improving the production line speed and production efficiency. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 It is a schematic diagram of the nitrocellulose microporous membrane of the present application;

[0033] Figure 2 It is an electron microscope photo of the upper and lower surface morphology of the nitrocellulose microporous membrane prepared by using single-layer coating in Comparative Example 1;

[0034] Figure 3 It is an electron microscope photo of the upper and lower surface morphology of the nitrocellulose microporous membrane prepared by using double-layer coating in Example 1 without backing;

[0035] Figure 4 It is an electron microscope photo of the cross-section of the nitrocellulose microporous membrane prepared by using double-layer coating in Example 1 without backing;

[0036] Figure 5Electron microscope photos of the top and bottom surface morphology of the nitrocellulose microporous membrane with polyester film backing prepared in Example 2 using three-layer coating;

[0037] Figure 6 Electron microscope photo of the cross-section of the nitrocellulose microporous membrane with polyester film backing prepared in Example 2 using three-layer coating. DETAILED DESCRIPTION

[0038] In order to make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments of the present application.

[0039] Example 1

[0040] A preparation method of a nitrocellulose chromatography membrane, comprising the following steps:

[0041] (1) Two kinds of casting solutions of nitrocellulose with different compositions are configured. The composition of the casting solution of the first layer of the top surface coating is specifically 4 parts by weight of nitrocellulose, 32 parts by weight of methyl acetate, 16 parts by weight of ethanol, 39.3 parts by weight of isopropanol, 7.7 parts by weight of deionized water and 1 part by weight of glycerol. The composition of the casting solution of the second layer of the bottom surface coating is specifically 7.2 parts by weight of nitrocellulose, 40 parts by weight of methyl acetate, 13.8 parts by weight of ethanol, 30 parts by weight of isopropanol, 8 parts by weight of deionized water and 1 part by weight of glycerol. The nitrocellulose is dissolved in methyl acetate, and then uniformly stirred at 30°C; subsequently, isopropanol, deionized water and glycerol are added and uniformly stirred at 20°C, and the casting solution of nitrocellulose is obtained after filtration and deaeration by standing;

[0042] (2) The first and second casting solutions of nitrocellulose are respectively introduced into a multi-layer coating die through a delivery channel (1, 2) to form a double-layer composite casting solution;

[0043] (3) The composite casting solution is directly coated on a conveying belt using a multi-layer coating die, and the coating thickness of the first layer of the top surface coating is 100 μm, and the coating thickness of the second layer of the bottom surface coating is 700 μm.

[0044] (4) The composite casting solution is transmitted to an oven channel through the conveying belt, and the film is formed through evaporation-induced phase separation reaction. The temperature in the oven channel is set to 30°C, the humidity is set to 45%, and the air flow rate is 1.5 m / s.

[0045] (5) The formed nitrocellulose microporous membrane is immersed in water to clean the residual solvent, immersed in a surfactant, and then dried by drying at a temperature of 40°C. Finally, the NC membrane product without backing is obtained by winding and slitting.

[0046] The electron microscope photos of the upper and lower surface topography and cross section of the obtained nitrocellulose microporous membrane are shown in Figure 3 .

[0047] Example 2

[0048] A preparation method of a nitrocellulose chromatography membrane, comprising the following steps: (1) configuring two kinds of casting solution of nitrocellulose with different compositions. The composition of the first layer of the upper surface coating is specifically 6 parts by weight of nitrocellulose, 48 parts by weight of methyl acetate, 21 parts by weight of ethanol, 17.495 parts by weight of isopropanol, 7.5 parts by weight of deionized water, and 0.005 parts by weight of glycerol. The composition of the second layer of the lower surface coating is specifically 8.5 parts by weight of nitrocellulose, 46.1 parts by weight of methyl acetate, 34.5 parts by weight of isopropanol, 10.4 parts by weight of deionized water, and 0.5 parts by weight of glycerol. The nitrocellulose is dissolved in methyl acetate, and then uniformly stirred at 35°C; then, isopropanol, deionized water and glycerol are added and uniformly stirred at 25°C, and the obtained casting solution of nitrocellulose is filtered and left to stand for defoaming;

[0049] (2) The first and second casting solutions of nitrocellulose are respectively fed into a multi-layer coating die through the delivery channels (1, 2), and the adhesive is fed through the delivery channel (3) to form a three-layer composite coating;

[0050] (3) The multi-layer coating die is used to coat the composite casting solution on the polyester film backing, the coating thickness of the first layer of the upper surface coating is 100 μm, the coating thickness of the second layer of the lower surface coating is 950 μm, and the coating thickness of the third layer of the adhesive is 25 μm.

[0051] (4) The composite casting solution is transported to the oven channel through the conveying belt, and the film is formed through evaporation induced phase separation reaction. The temperature in the oven channel is set to 25°C, the humidity is set to 60%, and the air flow rate is 2.5 m / s.

[0052] (5) The formed nitrocellulose microporous membrane is immersed in water to clean the residual solvent, immersed in a surfactant, and then dried at a drying temperature of 35°C. Then the product with polyester film backing is wound and cut.

[0053] The electron microscope photos of the upper and lower surface topography and cross section of the obtained nitrocellulose microporous membrane are shown in Figure 4 .

[0054] Comparative Example 1

[0055] A gradient coating method, the specific process is as follows:

[0056] (1) The casting solution of nitrocellulose is configured, and the specific composition is 3.5 parts by weight of nitrocellulose, 27.4 parts by weight of acetone, 13.5 parts of ethanol, 49.6 parts by weight of n-butanol, 4.5 parts by weight of deionized water, and 1.5 parts by weight of glycerol. The nitrocellulose is dissolved in methyl acetate, and then uniformly stirred at 25°C; then, isopropyl alcohol, deionized water and glycerol are added, and the mixture is uniformly stirred at 20°C; the casting solution of nitrocellulose is filtered and deaerated.

[0057] (2) The casting solution of nitrocellulose is directly coated on the conveying belt through the delivery channel and the coating head, and the coating thickness is 800 μm.

[0058] (3) The composite casting solution is transported to the oven channel through the conveying belt, and the film is formed through evaporation-induced phase separation reaction. The temperature in the oven channel is set to 40°C, the humidity is set to 35%, and the air flow rate is 1 m / s.

[0059] (4) The formed nitrocellulose microporous membrane is immersed in water to clean the residual solvent, soaked in a surfactant, and then dried by drying at a temperature of 45°C. Finally, the NC membrane product without backing is obtained by winding and cutting.

[0060] The electron microscope photos of the upper and lower surface topography of the obtained nitrocellulose microporous membrane are shown in Figure 2 .

[0061] Table 1. Nitrocellulose membrane result table

[0062]

[0063] The results of the above examples show that, in the comparative Figure 2 example, the nitrocellulose microporous membrane is obtained by using a single-layer coating technology. In the present application, the internal composition of the nitrocellulose casting solution coating can be flexibly adjusted by gradient coating, and a nitrocellulose microporous membrane with uniform pore size, large pore size and high porosity on the upper and lower surfaces is prepared by fully utilizing thermodynamic factors. Moreover, the production line speed of the nitrocellulose chromatographic membrane is higher.

[0064] The above is the implementation mode listed in the present embodiment, but the present embodiment is not limited to the above optional implementation mode, and those skilled in the art can obtain other various implementation modes by arbitrarily combining the above modes with each other. Any person can obtain other various forms of implementation modes under the inspiration of the present embodiment. The above specific implementation mode should not be understood as a limitation on the protection scope of the present embodiment, and the protection scope of the present embodiment should be defined by the claims, and the specification can be used to explain the claims.

Claims

1. A nitrocellulose chromatography membrane, characterized in that: It includes a first coating formed by an upper casting solution and a second coating formed by a lower casting solution, wherein the concentration of nitrocellulose in the upper casting solution is lower than that in the lower casting solution and the concentration of non-solvents is higher than that in the lower casting solution; The method for preparing the nitrocellulose chromatography membrane includes the following steps: S1. Prepare an upper casting solution and a lower casting solution respectively, wherein the concentration of nitrocellulose in the upper casting solution is lower than that in the lower casting solution, and the concentration of non-solvent is higher than that in the lower casting solution; S2. Input the upper casting solution and the lower casting solution into different delivery channels, and adjust the flow rates of the upper casting solution and the lower casting solution respectively; S3. The upper and lower casting solutions are uniformly conveyed onto a continuously moving conveyor belt to obtain a nitrocellulose chromatography membrane initial product with uniform thickness. The lower casting solution directly contacts the conveyor belt to form a second coating layer, and the upper casting solution is coated on the second coating layer to form a first coating layer. S4. The initial nitrocellulose chromatographic membrane is transported into the oven channel, and the intermediate nitrocellulose chromatographic membrane is obtained by evaporation-induced phase separation reaction. S5. After immersing the intermediate nitrocellulose chromatography membrane in clean water to remove internal impurities, it is soaked in a surfactant, and then dried, rolled up, and cut to obtain the finished nitrocellulose chromatography membrane.

2. The nitrocellulose chromatography membrane according to claim 1, characterized in that: The upper casting solution comprises the following raw materials in parts by weight: 3-8 parts nitrocellulose, 20-60 parts ester or ketone compound solvents, 30-70 parts mixed alcohol solvents, 2-10 parts non-solvents, and 0.005-2 parts humectant.

3. The nitrocellulose chromatography membrane according to claim 1, characterized in that: The lower casting solution comprises the following raw materials in parts by weight: 5-15 parts nitrocellulose, 30-60 parts ester or ketone compound solvents, 40-75 parts mixed alcohol solvents, 5-18 parts non-solvents, and 0.005-2 parts humectant.

4. The nitrocellulose chromatography membrane according to claim 1, characterized in that: It also includes a third coating and a backing layer.

5. The nitrocellulose chromatography membrane according to claim 4, characterized in that: The third coating is an adhesive.

6. The nitrocellulose chromatography membrane according to claim 4, characterized in that: The backing is made of woven fabric, polyester, polyvinyl chloride, polypropylene, polyethylene, or polystyrene.

7. A method for preparing a nitrocellulose chromatography membrane according to any one of claims 1-6, characterized in that: Includes the following steps: S1. Prepare an upper casting solution and a lower casting solution respectively, wherein the concentration of nitrocellulose in the upper casting solution is lower than that in the lower casting solution, and the concentration of non-solvent is higher than that in the lower casting solution; S2. Input the upper casting solution and the lower casting solution into different delivery channels, and adjust the flow rates of the upper casting solution and the lower casting solution respectively; S3. The upper and lower casting solutions are uniformly conveyed onto a continuously moving conveyor belt to obtain a nitrocellulose chromatography membrane initial product with uniform thickness. The lower casting solution directly contacts the conveyor belt to form a second coating layer, and the upper casting solution is coated on the second coating layer to form a first coating layer. S4. The initial nitrocellulose chromatographic membrane is transported into the oven channel, and the intermediate nitrocellulose chromatographic membrane is obtained by evaporation-induced phase separation reaction. S5. After immersing the intermediate nitrocellulose chromatography membrane in clean water to remove internal impurities, it is then soaked in a surfactant, dried, rolled up, and slit to obtain the finished nitrocellulose chromatography membrane.

8. The method for preparing a nitrocellulose chromatography membrane according to claim 7, characterized in that: The surfactant mentioned in step S5 is selected from any one of AES, sodium dodecyl sulfate, sodium dodecylamine sulfonate, and sodium dodecylbenzene sulfonate.

9. The method for preparing a nitrocellulose chromatography membrane according to claim 7, characterized in that: The thickness of the coating on the upper surface of the initial nitrocellulose chromatography membrane is less than the thickness of the coating on the lower surface.

10. The application of the method for preparing a nitrocellulose chromatography membrane according to any one of claims 7-9, characterized in that: Used to prepare nitrocellulose chromatography membranes.

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