A preparation method and application of an anti-non-specific protein adsorption coating based on normal pressure low-temperature plasma enhanced chemical vapor deposition technology

Abstract

The application provides a preparation method and application of an anti-non-specific protein adsorption coating based on normal pressure low-temperature plasma enhanced chemical vapor deposition technology. The preparation method can rapidly modify a stable anti-protein non-specific adsorption ultrathin coating on a substrate surface under normal pressure environment, and form a covalent bond with the substrate surface. The anti-non-specific protein adsorption coating preparation method provided by the application is simple to operate, has a wide range of applicable materials, can improve the biocompatibility and blood compatibility of a medical device surface, reduce problems such as blood coagulation and thrombosis caused by non-specific protein adsorption, and biofilm infection caused by bacterial adhesion and growth, and the like; and the stable covalent bond and the ultrathin coating reduce the risk caused by the peeling of the coating during use.

Description

Technical Field

[0001] This invention relates to the field of surface modification of medical devices, and in particular to a method for preparing and applying a coating for resisting nonspecific protein adsorption based on atmospheric pressure low-temperature plasma-enhanced chemical vapor deposition technology. Background Technology

[0002] Bioattachment mainly refers to the non-specific adsorption and adhesion of proteins, cells, microorganisms, etc., to the surface of therapeutic and diagnostic devices or other medical materials. Bioattachment can cause a number of problems, including hemolysis, thrombosis, immune responses, chronic inflammation, formation of isolation capsules on implanted devices, bacterial infection, and biofilm growth.

[0003] Zwitterionic polymers have attracted widespread attention due to their excellent resistance to nonspecific protein adsorption and bioattachment. Zwitterionic polymers are a class of materials with a homogeneous mixture of anionic and cationic groups, resulting in near-electrical neutrality. Mixed ionic polymers share common characteristics with traditional zwitterionic polymers, including resistance to nonspecific protein adsorption and bioattachment. Both achieve high efficiency and excellent resistance to nonspecific protein adsorption and bioattachment through the strong hydration of ions, thus improving blood compatibility and biocompatibility. However, due to their strong hydration characteristics, these polymers exhibit strong hydrophilicity, making it difficult to form stable and low-defect coatings on the surfaces of medical devices. In particular, preparing ultrathin coatings of these strongly hydrophilic polymers with high efficiency in resisting nonspecific protein adsorption and bioattachment and low risk of detachment becomes especially challenging.

[0004] Commonly used methods for preparing such strongly hydrophilic polymer coatings are mainly divided into two categories: "grafting-from" and "grafting-to". "Grafting-from" methods involve growing polymers from a surface, offering advantages such as a dense polymer layer with few defects. However, existing methods rely on polymerization reactions in solution, leading to problems such as high consumption of monomers and solvents, complex reaction steps, harsh conditions, and the introduction of difficult-to-remove catalysts, making low-cost, large-scale production based on "grafting-from" methods very difficult. Therefore, "grafting-to" surface modification and coating based on strongly hydrophilic polymers containing anchoring functional groups is an existing method for preparing coatings against non-specific protein adsorption and bio-attachment on medical device surfaces. This type of method mainly includes: 1) methods combining polymer crosslinking and surface grafting, such as zwitterionic polymers containing benzophenone groups; 2) surface grafting methods, such as zwitterionic polymers containing dopamine end groups; and 3) surface adsorption methods. Crosslinking-dependent surface grafting is a common method for amphoteric ionization of medical device surfaces. However, the resulting thick coating increases the likelihood of detachment and the associated risks. Furthermore, due to the surface tension of the solution, it tends to accumulate in depressions, making it unsuitable for medical devices with complex structures. The latter two methods, on the other hand, often result in low surface modification density or insufficient adsorption stability due to the physical structure and size of the polymer itself, leading to poor resistance to non-specific protein adsorption and bio-attachment, thus limiting their application in medical device surface modification.

[0005] Therefore, it is of great significance to study efficient, stable, and widely adaptable methods for preparing coatings that resist non-specific protein adsorption and bio-adhesion. Summary of the Invention

[0006] Based on this, this invention proposes a method for preparing and applying a coating resistant to nonspecific protein adsorption using atmospheric pressure low-temperature plasma-enhanced chemical vapor deposition (PECVD). This method enables the rapid modification of a stable, ultrathin coating resistant to nonspecific protein adsorption onto a substrate surface under atmospheric pressure. The nonspecific protein adsorption capacity of the modified surface is defined as less than 20% of the adsorption amount per unit area relative to tissue culture polystyrene (TCPS) sheets, with a minimum relative adsorption amount of less than 1%. The rapid modification refers to a modification time ≤300 s, with a minimum modification time of only 10 s. The ultrathin coating thickness can be less than 200 nm, and it forms covalent bonds with the substrate surface.

[0007] The present invention is achieved through the following technical solution: a method for preparing a coating against nonspecific protein adsorption based on atmospheric pressure low temperature plasma enhanced chemical vapor deposition technology. The method uses organic monomers that provide positive and negative charges as raw materials, adopts an atmospheric pressure low temperature plasma process to initiate the free radicalization of organic monomers, then polymerizes them on the surface of a substrate material, and then obtains a coating against nonspecific protein adsorption after activation and cleaning.

[0008] Furthermore, the preparation method includes the following process steps:

[0009] 1) Clean the substrate material to be coated;

[0010] 2) Prepare an organic monomer solution containing allyl ester and allyl amine and store it in a storage bottle;

[0011] 3) Compressed carrier gas is used to bubble through the storage bottle containing the organic monomer solution, carrying the monomer to the reaction chamber containing the substrate material;

[0012] 4) Turn on the plasma power supply, adjust the voltage and airflow, and use the electric field to ionize the carrier gas and monomers, and diffuse them to the surface to form a polymer film;

[0013] 5) Activate the polymer film by alkaline or acid hydrolysis, hydrolyze the ester groups on the surface of the polymer film, then dry it with clean compressed air and wash it with pure water to obtain a coating that resists non-specific protein adsorption.

[0014] Furthermore, the substrate material is a non-water-soluble polyurethane or nylon polymer containing amide groups. The substrate material is ultrasonically cleaned and dried with ethanol and ultrapure water, respectively, and / or cleaned with oxygen or nitrogen plasma. Preferably, the ultrasonic cleaning time with ethanol and ultrapure water is 15 minutes each.

[0015] Furthermore, the monomers for preparing the coating against nonspecific protein adsorption and bioattachment are carried by a compressed carrier gas, wherein the carrier gas is nitrogen and / or argon.

[0016] Furthermore, the two monomers, allyl ester and allylamine, are mixed in a certain ratio. Allyl ester and allylamine are organic monomers that provide negative and positive charges, respectively, so that the surface has a uniform mixture of positive and negative charges, and the amount of positive and negative charges is basically the same. The allyl-containing ester is one or more of methyl acrylate, tert-butyl acrylate, or methyl methacrylate. The allyl-containing amine is one or more of N,N-dimethylpropenylamine, N-methylpropenylamine, or propenylamine.

[0017] Furthermore, the allyl-containing ester is methyl acrylate, and the allyl-containing amine is N,N-dimethylpropenylamine. When nitrogen is used as the carrier gas, the volume ratio of the former to the latter is 1:1 to 3:1, and the storage bottle containing the organic monomer solution is immersed in an ice-water bath. Preferably, when nitrogen is used as the carrier gas, the ratio of the former to the latter is 1.7:1 to 2.2:1.

[0018] Furthermore, the plasma processing power is 0.2 W / cm². 2 -0.8W / cm 2 The processing time is 30-120 seconds. Preferably, the processing time is 90 seconds.

[0019] Furthermore, the flow rate of the nitrogen carrier gas is 0.01 m / min to 1.8 m / min. Preferably, the flow rate of the nitrogen carrier gas is 0.3 m / min.

[0020] Furthermore, the plasma-treated substrate material is washed with ethanol to remove unfixed monomers and oligomers.

[0021] Furthermore, hydrolysis is performed using an inorganic strong acid or base, including hydrochloric acid or sulfuric acid, and an inorganic base including at least one of sodium bicarbonate solution, sodium carbonate solution, and sodium hydroxide solution. Preferably, a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide is used, and the hydrolysis time is 3 hours.

[0022] On the other hand, the present invention also provides an application of an anti-nonspecific protein adsorption coating based on atmospheric pressure low-temperature plasma-enhanced chemical vapor deposition technology on medical devices that come into contact with blood and tissue.

[0023] The beneficial effects of this invention are as follows: This invention is based on an atmospheric pressure PECVD-based coating preparation technology for resisting non-specific protein adsorption and bio-adhesion. It employs a low-temperature plasma process below 100 degrees Celsius at atmospheric pressure to initiate the free radicalization of organic monomers, followed by polymerization on the substrate surface. After activation and cleaning, a coating resisting non-specific protein adsorption is obtained. Utilizing the rapid gas-phase diffusion characteristic of free radicals, stable covalent bonds can be formed on different substrate surfaces, resulting in a uniform coating suitable for rapid ultrathin coating preparation and modification of complex surface structures. Furthermore, the coating preparation of this invention can be achieved under mild conditions, simplifying the preparation steps and making it easier to control and scale up industrial processing. This is of great significance for the development of medical devices with the ability to resist non-specific protein adsorption. Experimental verification shows that the hybrid ionomer coating of this invention can effectively reduce non-specific protein adsorption on the substrate surface. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the preparation process of the anti-nonspecific protein adsorption coating provided by the present invention;

[0025] Figure 2 This is a schematic diagram of the bacterial adsorption results of the samples in Example 3 and Comparative Example 1;

[0026] Figure 3 This is a schematic diagram of the platelet adhesion results of the samples in Example 3 and Comparative Example 1. Detailed Implementation

[0027] Referring to the above content, in order to make the technical method of the present invention clearer and more specific, specific solutions are given as examples. However, it should be noted that the content protected by the application includes, but is not limited to, the following embodiments.

[0028] Example 1

[0029] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60°C for 90 min, and then placed in a reaction chamber. A mixture of allyl esters and amines in different proportions, cooled in an ice-water bath, was bubbled through nitrogen gas to carry the monomers into the reaction chamber. The reaction was then carried out in plasma at 0.375 W / cm². 2 The membrane was treated at high power for 90 seconds to initiate the grafting and polymerization of monomers on the membrane surface. It was then washed with ethanol and deionized water for 15 minutes, hydrolyzed with a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide at 37°C for 3 hours, washed with deionized water after hydrolysis, and dried at room temperature for 27 hours to obtain the final product.

[0030] The method for testing relative protein adsorption capacity is described in Performance Test (1) Relative Protein Adsorption Capacity Test.

[0031] As shown in Table 1, compared with Comparative Example 1, the relative protein adsorption amount of the sample in Example 1 was significantly reduced, demonstrating that methyl acrylate and tert-butyl acrylate can serve as negative charge sources for the mixed ionomer coating through hydrolysis, while allylamine, N-methylallylamine, and N,N-dimethylallylamine can serve as positive charge sources for the mixed ionomer coating. The formed mixed ionomer coating exhibited good resistance to non-specific protein adsorption. Among them, the best resistance to non-specific protein adsorption was achieved when methyl acrylate and N,N-dimethylallylamine were used as monomers, with a ratio of 2:1.

[0032] Table 1. Sample test results for Example 1 and Comparative Example 1

[0033]

[0034]

[0035] Example 2

[0036] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60°C for 90 min, and then placed in the reaction chamber. A mixture of methyl acrylate and N,N-dimethylallylamine cooled in an ice-water bath was bubbled through the material with nitrogen gas to carry the monomer into the reaction chamber. The reaction was then carried out in a plasma at 0.2 W / cm². 2 0.375W / cm 2 0.8W / cm 2 The membrane was treated at high power for 90 seconds to initiate the grafting and polymerization of monomers on the membrane surface. It was then washed with ethanol and deionized water for 15 minutes, hydrolyzed with a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide at 37°C for 3 hours, washed with deionized water after hydrolysis, and dried at room temperature for 27 hours to obtain the final product.

[0037] The method for testing relative protein adsorption capacity is described in Performance Test (1) Relative Protein Adsorption Capacity Test.

[0038] As shown in Table 2, compared with Comparative Example 1, the relative protein adsorption of the sample in Example 2 was significantly reduced, demonstrating that the adsorption capacity was significantly lower with 0.2 W / cm². 2 -0.8W / cm 2 After plasma power treatment, a hybrid ionomer coating was successfully applied to the material surface, exhibiting good resistance to non-specific protein adsorption. Specifically, at a power of 0.375 W / cm², the coating was successfully applied. 2 Plasma power treatment exhibits the best resistance to non-specific protein adsorption.

[0039] Table 2. Sample test results for Example 2 and Comparative Example 1

[0040] sample <![CDATA[Plasma power (W / cm 2 )]]> Relative protein adsorption capacity (%) Sample 7 0.2 17.9 Sample 8 0.375 6.99 Sample 9 0.8 13.5 Comparative Example 1 / 100

[0041] Example 3

[0042] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60°C for 90 min, and then placed in the reaction chamber. A mixture of methyl acrylate and N,N-dimethylallylamine cooled in an ice-water bath was bubbled through nitrogen gas to carry the monomer into the reaction chamber, where it was subjected to a plasma of 0.375 W / cm². 2 The monomers were grafted and polymerized on the membrane surface by treatment at power for 30s, 60s, 90s, and 120s. The membrane was then washed with ethanol and deionized water for 15 min, hydrolyzed with a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide at 37°C for 3 h, washed with deionized water after hydrolysis, and dried at room temperature for 27 h to obtain the final product.

[0043] Among them, the relative protein adsorption test method is shown in Performance Test (1) Relative Protein Adsorption Test, the antibacterial adhesion test method is shown in Performance Test (2) Antibacterial Adhesion, and the antiplatelet adhesion test method is shown in Performance Test (3) Antiplatelet Adhesion.

[0044] As shown in Table 3, compared with Comparative Example 1, the relative protein adsorption amount of the sample in Example 3 was significantly reduced, proving that the mixed ionomer coating was successfully modified onto the material surface and exhibited good resistance to non-specific protein adsorption. Among them, the anti-non-specific protein adsorption effect was the best when plasma treatment was performed for 90 s.

[0045] Table 3. Test results of samples from Example 3 and Comparative Example 1

[0046] sample Plasma processing time (s) Relative protein adsorption capacity (%) Sample 10 30 11.6 Sample 11 60 7.79 Sample 12 90 6.99 Sample 13 120 7.45 Comparative Example 1 / 100

[0047] from Figure 2 As can be seen, compared with Comparative Example 1, the number of Escherichia coli adsorbed on the sample surface of Example 3 was significantly reduced, proving that the mixed ion polymer coating is stably bonded to the substrate surface and exhibits excellent antibacterial adhesion ability.

[0048] Figure 3 The Comparative Example 1 showed that platelets adhered and activated on the sample, leading to thrombus formation. The Sample 3 effectively inhibited platelet adhesion and thrombus formation. Therefore, the prepared hybrid ionomer coating can resist non-specific protein adsorption in plasma, thereby effectively reducing platelet adhesion and activation, indicating that the hybrid ionomer coating prepared based on PECVD has high blood compatibility.

[0049] Example 4

[0050] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60℃ for 90 min, and then placed in the reaction chamber. Nitrogen gas was bubbled through a mixture of methyl acrylate and N,N-dimethylallylamine cooled in an ice-water bath at flow rates of 0.01 m / min, 0.3 m / min, and 1.8 m / min, carrying the monomer into the reaction chamber. The reaction was carried out in a plasma at 0.375 W / cm². 2 The membrane was treated at high power for 90 seconds to initiate the grafting and polymerization of monomers on the membrane surface. It was then washed with ethanol and deionized water for 15 minutes, hydrolyzed with a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide at 37°C for 3 hours, washed with deionized water after hydrolysis, and dried at room temperature for 27 hours to obtain the final product.

[0051] The method for testing relative protein adsorption capacity is described in Performance Test (1) Relative Protein Adsorption Capacity Test.

[0052] As shown in Table 4, compared with Comparative Example 1, the relative protein adsorption amount of the sample in Example 4 was significantly reduced, proving that the mixed ion polymer coating was successfully modified onto the material surface and exhibited good resistance to non-specific protein adsorption.

[0053] Table 4. Test results of samples from Example 4 and Comparative Example 1

[0054]

[0055]

[0056] Example 5

[0057] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60°C for 90 min, and then placed in the reaction chamber. A mixture of methyl acrylate and N,N-dimethylallylamine cooled in an ice-water bath was bubbled through nitrogen gas to carry the monomer into the reaction chamber, where it was subjected to a plasma of 0.375 W / cm². 2 The membrane was treated at high power for 90 seconds to initiate the grafting and polymerization of monomers on the membrane surface. It was then washed with ethanol and deionized water for 15 minutes, followed by hydrolysis with 0.1 mol / L hydrochloric acid solution for 3 hours, 0.1 mol / L sodium bicarbonate solution overnight, saturated sodium carbonate solution overnight, and saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide for 3 hours at 37°C. After hydrolysis, it was washed with deionized water and dried at room temperature for 27 hours to obtain the final product.

[0058] The method for testing relative protein adsorption capacity is described in Performance Test (1) Relative Protein Adsorption Capacity Test.

[0059] As shown in Table 5, compared with Comparative Example 1, the relative protein adsorption amount of the sample in Example 5 was significantly reduced, proving that the mixed ionomer coating was successfully modified onto the material surface and exhibited good resistance to non-specific protein adsorption. Among them, the resistance to non-specific protein adsorption was strongest when hydrolyzed with a saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide.

[0060] Table 5. Test results of samples from Example 5 and Comparative Example 1

[0061] sample Hydrolysis solution Relative protein adsorption capacity (%) Sample 17 hydrochloric acid 12.8 Sample 18 Sodium bicarbonate 24.1 Sample 19 Sodium carbonate 7.18 Sample 20 Sodium hydroxide and saturated sodium chloride 6.99 Comparative Example 1 / 100

[0062] Example 6

[0063] Polyurethane and nylon membranes were ultrasonically cleaned with ethanol and deionized water for 15 min, dried at 60°C for 90 min, and then placed in a reaction chamber. A mixture of methyl acrylate and N,N-dimethylallylamine cooled in an ice-water bath was bubbled through nitrogen gas to carry the monomers into the reaction chamber. The reaction was carried out in a plasma at 0.375 W / cm². 2 The membrane was treated at high power for 90 seconds to initiate the grafting and polymerization of monomers on the membrane surface. It was then washed with ethanol and deionized water for 15 minutes, followed by hydrolysis with 0.1 mol / L hydrochloric acid solution for 3 hours, 0.1 mol / L sodium bicarbonate solution overnight, saturated sodium carbonate solution overnight, and saturated sodium chloride solution containing 0.1 mol / L sodium hydroxide for 3 hours at 37°C. After hydrolysis, it was washed with deionized water and dried at room temperature for 27 hours to obtain the final product.

[0064] The method for testing relative protein adsorption capacity is described in Performance Test (1) Relative Protein Adsorption Capacity Test.

[0065] As shown in Table 6, compared with Comparative Example 1 and Comparative Example 2, the relative protein adsorption amount of the sample in Example 6 was significantly reduced, proving that the mixed ion polymer coating was successfully modified onto the material surface and exhibited good resistance to non-specific protein adsorption.

[0066] Table 6. Test results of samples from Example 6 and Comparative Example 1

[0067] sample substrate material Relative protein adsorption capacity (%) Sample 21 polyurethane 6.99 Comparative Example 1 polyurethane 100 Sample 22 nylon 10.2 Comparative Example 2 nylon 73.5

[0068] Comparative Example 1

[0069] The polyurethane membrane was ultrasonically cleaned with ethanol and deionized water for 15 minutes and then dried at 60°C for 90 minutes.

[0070] Comparative Example 2

[0071] The nylon membrane is obtained by ultrasonically cleaning it with ethanol and deionized water for 15 minutes and then drying it at 60°C for 90 minutes.

[0072] Performance testing:

[0073] 1. Relative protein adsorption capacity test

[0074] Protein adsorption tests were performed on samples from Examples 1-6 and Comparative Examples 1-2 using fibrinogen. The method was as follows: 1 cm diameter discs were punched out from the samples of Examples 1-6 and Comparative Examples 1-2 and placed in 48-well plates. A certain amount of fibrinogen solid was weighed and dissolved in 1X PBS solution to prepare a 0.2 mg / mL solution. 500 μL of this solution was added to each well and incubated at 37°C for 75 min. The supernatant was discarded, and the plate was rinsed 5 times with 1X PBS solution. The PBS solution was removed, and 600 μL of blocking buffer was added to each well. The plate was blocked at 37°C for 1 h. HRP-labeled goat anti-human fibrinogen IgG was diluted 1:1000 in 1X PBS and thoroughly mixed. The supernatant in the plate was discarded, and 500 μL of the diluted antibody solution was added. The plate was incubated at 37°C for 30 min. Discard the supernatant, wash 5 times with 1X PBS solution, add 500 μL of TMB chromogenic solution to each well, and incubate at 37℃ for 15 min. A positive result will be blue. Add 500 μL of 1 mol / L hydrochloric acid to each well to stop the reaction; the solution will turn yellow. Measure the OD values ​​at 450 nm and 620 nm using a microplate reader. The final OD value is the difference between the OD value at 450 nm and the OD value at 620 nm.

[0075] Relative protein adsorption capacity = OD 实施例 / OD 对比例 ×100%

[0076] 2. Antibacterial adhesion

[0077] Weigh 2.50 g sodium chloride, 1.25 g yeast extract, and 2.50 g tryptone using an analytical balance. Dissolve them thoroughly in pure water and adjust the pH to 7.40. Make up to volume in a 250 mL volumetric flask. Aliquot the sample and sterilize it in a pressure steam sterilizer at 121°C for 30 minutes to obtain sterile LB medium. Inoculate 5 μL of preserved *E. coli* culture into 6 mL of sterile LB medium. Incubate overnight in a horizontal shaker at 37°C and 220 rpm. Note that inoculation should be performed in a clean bench, 1-2 cm away from an alcohol lamp, to ensure a strictly aseptic environment. Add 1 mL of the overnight culture + 1 mL of medium to a well plate and place the slide inside. Incubate for 6 hours in a horizontal shaker at 37°C and 220 rpm. Examples 3 and 1 control were washed 5 times with PBS and fixed with 4% paraformaldehyde solution. After fixation, the fixative was washed off with PBS, and the sample was stained with propidium iodide solution in the dark for 30 minutes. Finally, the staining solution was washed off with deionized water. The bacterial adsorption on the sample surface was observed using a fluorescence microscope.

[0078] 3. Antiplatelet adhesion

[0079] Platelet-rich plasma (PRP) was used to test the platelet adhesion of samples from Example 3 and Comparative Example 1. Blood donated by healthy volunteers was centrifuged at 1000 rpm for 10 minutes to obtain PRP. 0.5 cm diameter discs were obtained by punching holes in the samples from Example 3 and Comparative Example 1 and placed in 96-well plates. The discs were incubated with 0.1 ml of PRP at 37°C for 2 hours. The samples were washed three times with PBS, and the supernatant was discarded. The samples were fixed with 2.5% glutaraldehyde solution at 4°C for 45 minutes. The samples were washed three times with PBS, dried with a gradient of ethanol, and then lyophilized. Platelet adhesion on the sample surface was observed using a scanning electron microscope.

[0080] The above embodiments are used to explain and illustrate the present invention, but not to limit the present invention. Any modifications and changes made to the present invention within the spirit and scope of the claims shall fall within the protection scope of the present invention.

Claims

1. A method for preparing a coating with resistance to non-specific protein adsorption based on atmospheric pressure low-temperature plasma-enhanced chemical vapor deposition technology, characterized in that, This method uses zwitterionic organic monomers containing allyl ester and allylamine as raw materials to provide positive and negative charges. The zwitterions are designed to create a uniform mixture of positive and negative charges on the surface, with the amounts of positive and negative charges being approximately equal. A low-temperature plasma process at ambient pressure is employed, with a plasma processing power of 0.2 W / cm². 2 -0.8W / cm 2 The processing time is 30-120s, the carrier gas is nitrogen, the flow rate is 0.01m / min-1.8m / min, the allyl ester is methyl acrylate, and the allylamine is N,N-dimethylallylamine, with a volume ratio of 2:

1. The storage bottle containing the organic monomer solution is immersed in an ice-water bath. The carrier gas carries the monomers used to prepare the zwitterionic polymer layer. The carrier gas and monomers are ionized by an electric field, which initiates the free radicalization of the organic monomers. Stable covalent bonds are formed on the surface of the non-water-soluble polyurethane or nylon polymer material containing amide groups, and grafting and polymerization occur to form a polymer film. The surface ester groups of the polymer film are then activated by inorganic strong acid or alkali hydrolysis and cleaned to obtain a coating that resists non-specific protein adsorption.

2. The method for preparing an anti-nonspecific protein adsorption coating based on atmospheric pressure low-temperature plasma-enhanced chemical vapor deposition technology according to claim 1, wherein the process steps include the following: 1) Clean the substrate material to be coated; 2) Prepare an organic monomer solution containing allyl ester and allyl amine and store it in a storage bottle; 3) Compressed carrier gas is used to bubble through the storage bottle containing the organic monomer solution, carrying the monomer to the reaction chamber containing the substrate material; 4) Turn on the plasma power supply, adjust the voltage and airflow, and use the electric field to ionize the carrier gas and monomers, and diffuse them to the surface to form a polymer film; 5) Hydrolyze the ester groups on the surface of the polymer film, then dry it with clean compressed air and wash it with pure water to obtain an anti-protein non-specific adsorption coating.

3. The method for preparing an anti-nonspecific protein adsorption coating based on ambient pressure low-temperature plasma-enhanced chemical vapor deposition technology according to claim 1, characterized in that, The substrate material is ultrasonically cleaned and dried with ethanol and ultrapure water, respectively, and / or cleaned with oxygen or nitrogen plasma.

4. The method for preparing an anti-nonspecific protein adsorption coating based on ambient pressure low-temperature plasma-enhanced chemical vapor deposition technology according to claim 1, characterized in that, The plasma-treated substrate material was washed with ethanol to remove unfixed monomers and oligomers.

5. The method for preparing an anti-nonspecific protein adsorption coating based on ambient pressure low-temperature plasma-enhanced chemical vapor deposition technology according to claim 1, characterized in that, Inorganic strong acids include hydrochloric acid or sulfuric acid, and inorganic bases include at least one of sodium bicarbonate solution, sodium carbonate solution, and sodium hydroxide solution.

6. The application of an anti-nonspecific protein adsorption coating obtained by the preparation method of claim 1 on a medical device that comes into contact with blood and tissue.

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