Composite antibacterial coating on surface of chip as well as preparation method and application of composite antibacterial coating

Abstract

The invention provides a composite antibacterial coating on the surface of a chip as well as a preparation method and application of the composite antibacterial coating. The raw materials of the composite antibacterial coating at least comprise a dopamine-containing substance, a zinc salt and a curcumin compound. The composite antibacterial coating is prepared by utilizing the antibacterial properties of natural polyphenol curcumin and nano zinc oxide and utilizing polydopamine which has super-strong adhesion performance and good biocompatibility and can almost form coatings on the surfaces of all types of materials, so that the chip is endowed with good antibacterial performance and antifouling performance.

Description

TECHNICAL FIELD

[0001] The present application relates to a composite antibacterial coating of a chip surface and a preparation method and application thereof. BACKGROUND

[0002] Since the alloy or polymer material itself does not have active antibacterial ability, bacteria are easy to adhere to its surface and even proliferate to form a biofilm to cause pollution, which brings many inconveniences and adverse effects to the use of the chip. It is very important to modify the surface of the chip with antibacterial properties to inhibit the formation of biofilm. Coating a physical coating on the surface is a relatively direct method, which can change the surface interface properties of the material without destroying the characteristics of the chip material body, and endow it with resistance to bacterial infection or other abilities.

[0003] At present, the construction of antibacterial coating can be divided into graphene-based antibacterial coating, hydrogel antibacterial coating and polymer composite coating. By using the good film-forming properties, good biocompatibility and strong loading capacity of graphene, hydrogel or polymer, substances with antibacterial ability are loaded to form an antibacterial film layer on the material surface. The substances with antibacterial ability include natural antibacterial materials, organic antibacterial materials and inorganic antibacterial materials. Natural antibacterial materials and organic antibacterial materials are easy to cause bacteria to develop drug resistance, thereby reducing the antibacterial effectiveness of the coating. Relatively speaking, inorganic antibacterial materials, such as metal nano-ions Ag + , Cu 2+ , Zn 2+ , have the advantages of wide antibacterial spectrum, long-lasting antibacterial effect and excellent high-temperature resistance, and are widely used antibacterial materials. Moreover, inorganic antibacterial materials will not cause bacteria to develop drug resistance during use. However, inorganic antibacterial materials also have some disadvantages, such as the easy agglomeration of metal nanoparticles to form secondary particles, resulting in a decrease in antibacterial effect. Moreover, a large amount of a single metal nanoparticle needs to be added to achieve an ideal antibacterial effect, which is high in cost. How to further improve the firm chemical combination between the inorganic antibacterial material and the substrate is also an important point in the design of the coating.

[0004] At present, some composite antibacterial materials or antibacterial coatings have been applied to alloys or polymer materials, such as adding silver nitrate to a zinc salt solution to prepare Ag / ZnO composite materials of silver nanoparticles mixed with zinc oxide nanoparticles as antibacterial materials; and like by compounding nucleotide-modified nano-titanium dioxide with amino acid-modified nano-zinc oxide at a certain proportion, the secondary agglomeration phenomenon between the nano-zinc oxide and the nano-titanium dioxide particles is effectively prevented, the dispersion performance of the nano-materials is improved, thereby ensuring the antibacterial performance of the nano-zinc oxide and the nano-titanium dioxide. However, these methods are complex in preparation, the adhesion and bonding force between the obtained antibacterial materials and the substrate are weak, the biocompatibility is insufficient, and the dispersion performance is poor, which may cause the coating to be uneven, thereby affecting the use effect of the chip. SUMMARY

[0005] To solve the above problems, the present application provides the following technical solutions:

[0006] A composite antibacterial coating on a chip surface, the raw material of the composite antibacterial coating at least includes dopamine-containing substances, zinc salts and curcumin compounds.

[0007] According to the embodiments of the present application, the dopamine-containing substances, zinc salts and curcumin-containing substances are assembled into the composite antibacterial coating by chemical combination, for example, by non-covalent interaction co-assembly.

[0008] According to the embodiments of the present application, the non-covalent interaction can be at least one of electrostatic interaction, hydrophobic effect, hydrogen bonding, van der Waals force and π-π conjugation effect.

[0009] According to the embodiments of the present application, the zinc salt is selected from soluble zinc salts, for example, zinc chloride, zinc nitrate, zinc acetate.

[0010] According to the embodiments of the present application, the curcumin compound is selected from at least one of curcumin, demethoxycurcumin and bisdemethoxycurcumin, for example.

[0011] According to the embodiments of the present application, the composite antibacterial coating has strong adhesion.

[0012] According to the embodiments of the present application, the composite antibacterial coating has high antibacterial capacity, for example, high antibacterial capacity against Escherichia coli.

[0013] The present application also provides a preparation method of the above-mentioned composite antibacterial coating, the preparation method comprising:

[0014] (1) soaking the substrate in a dopamine solution to form a polydopamine coating;

[0015] (2) preparing a mixed solution of zinc salt and curcumin, and reacting the substrate containing the polydopamine coating on the surface in the mixed solution to obtain the composite antibacterial coating.

[0016] According to the embodiments of the present application, the substrate can also be pretreated to remove surface grease, which can be optionally performed by methods known in the art. For example, the pretreatment refers to soaking the substrate in a sodium hydroxide solution or a hydrochloric acid solution after cleaning, or soaking the substrate in a sodium hydroxide solution or a hydrochloric acid solution after polishing and polishing.

[0017] According to the embodiments of the present application, the material of the substrate includes but is not limited to at least one of glass, silicon wafer, stainless steel, magnesium alloy, titanium alloy, PDMS, polyethylene, polypropylene and the like.

[0018] According to an embodiment of the present invention, the size of the substrate can be selected from sizes known in the art, for example, different sizes can be designed according to chip requirements, including but not limited to 20*20mm, 20*50mm, 50*50mm, 100*100mm, etc.

[0019] According to an embodiment of the present invention, the dopamine solution is weakly alkaline (pH greater than 7, for example 7.5, 8, 8.5, or 9), and includes at least a dopamine-containing substance and a buffer solution. Preferably, the buffer solution is selected from buffer solutions known in the art, such as Tris-HCl buffer solution (5-20 mM).

[0020] According to an embodiment of the present invention, the concentration of dopamine in the dopamine solution is 1-10 mg / mL, for example, 5 mg / mL.

[0021] According to an exemplary embodiment of the present invention, the dopamine solution is prepared by the following method: mixing a Tris-HCl buffer solution and a dopamine-containing substance, and then adding an inorganic alkali solution to adjust the pH to 8-9.

[0022] The inventors discovered that, under weakly alkaline conditions, the dopamine-containing substance can spontaneously polymerize to obtain polydopamine-like substances. The resulting polydopamine-like substances have super strong adhesion properties and good biocompatibility. They can be modified on the surface of various substrates through covalent or non-covalent bonds, thereby forming a uniform polydopamine coating on the substrate.

[0023] According to an embodiment of the present invention, in step (2), the molar ratio of zinc ions to curcumin in the mixed solution is 0.01-0.5:0.01-0.1, for example, 0.05:0.02.

[0024] According to an embodiment of the present invention, in step (2), the concentration of zinc ions in the mixed solution is 0.01-0.5 mol / L, for example, 0.1 mol / L, 0.2 mol / L, 0.3 mol / L, or 0.4 mol / L.

[0025] According to an embodiment of the present invention, the concentration of curcumin in the mixed solution is 0.01-0.1 mol / L, for example, 0.02 mol / L, 0.03 mol / L, 0.04 mol / L, 0.05 mol / L, 0.06 mol / L, 0.07 mol / L, or 0.08 mol / L.

[0026] According to an embodiment of the present invention, in step (2), the mixed solution further includes an organic amine salt, such as hexamethylenetetramine. Preferably, the molar ratio of the organic amine salt to zinc ions is 1:1.

[0027] According to an embodiment of the present invention, in step (2), the reaction refers to a reaction at 100°C or above (e.g., 120°C, 150°C) for 0.1-5 hours, for example, 2 hours.

[0028] The inventors discovered that chips with a composite antibacterial coating prepared by polydopamine, zinc salt and curcumin can achieve good antibacterial effects; at the same time, the coating improves the hydrophilicity of the chip surface, reduces the surface roughness, gives the chip surface certain anti-fouling properties, and can resist the non-specific adsorption of interfering substances.

[0029] The present invention also provides the application of the above-mentioned composite antibacterial coating in inhibiting or inactivating bacteria or fungi.

[0030] According to an embodiment of the present invention, the bacteria are Gram-negative or Gram-positive bacteria.

[0031] Preferably, the Gram-negative bacterium is Escherichia coli.

[0032] Preferably, the Gram-positive bacteria are Staphylococcus aureus, lactic acid bacteria, or streptococci.

[0033] According to an embodiment of the present invention, the fungus is Candida albicans, mold, or yeast.

[0034] Beneficial effects:

[0035] This invention utilizes the antibacterial properties of a natural polyphenol curcumin and nano zinc oxide, and uses polydopamine, which has super adhesion and good biocompatibility and can form a coating on almost all types of material surfaces, to prepare a composite antibacterial coating, giving the chip good antibacterial and antifouling properties. Attached Figure Description

[0036] Figure 1 This is a comparison chart showing the antibacterial effects on the chip surface.

[0037] Figure 2 This is a graph showing the stability test results of the composite antibacterial coating on the chip surface. Detailed Implementation

[0038] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0039] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0040] Example 1

[0041] A 20*20mm glass slide (i.e., glass substrate) was ultrasonically cleaned with anhydrous ethanol and deionized water, then immersed in 1M (1mol / L) NaOH solution for 60 min. After removal, it was rinsed with deionized water and dried under nitrogen. A Tris-HCl buffer solution of 2 mg / mL dopamine (pH = 8.5, 10 mM) was prepared, and the glass slide was immersed in the dopamine solution overnight at room temperature. After rinsing with deionized water, it was dried at 60°C to form a polydopamine coating on the surface of the glass slide. Ethanol solutions of 0.05 mol / L hexamethylenetetramine and 0.05 mol / L zinc chloride were prepared separately and mixed thoroughly at room temperature. Curcumin (0.02 mol / L) was added and stirred thoroughly to obtain a mixed solution. The glass slide with the polydopamine coating was immersed in the above mixed solution, rapidly heated to 100°C, reacted for 2 h, ultrasonically cleaned with deionized water, and dried at 100°C for 60 min to obtain a chip with a composite antibacterial coating.

[0042] Example 2

[0043] A 20*20mm glass slide was ultrasonically cleaned with anhydrous ethanol and deionized water, then immersed in 1M NaOH solution for 60 min. After removal, it was rinsed with deionized water and dried under nitrogen. A Tris-HCl buffer solution of 2 mg / mL dopamine (pH = 8.5, 10 mM) was prepared, and the slide was immersed in the dopamine solution overnight at room temperature. After rinsing with deionized water, it was dried at 60°C to form a polydopamine coating on the slide surface. Ethanol solutions of 0.1 mol / L hexamethylenetetramine and 0.1 mol / L zinc chloride were prepared separately and mixed thoroughly at room temperature. Curcumin (0.03 mol / L) was added and stirred thoroughly to obtain a mixed solution. The glass slide with the polydopamine coating was immersed in the above mixed solution, rapidly heated to 120°C, reacted for 2 h, ultrasonically cleaned with deionized water, and dried at 120°C for 30 min to obtain a chip with a composite antibacterial coating.

[0044] Comparative Example 1

[0045] A 20*20mm glass slide was ultrasonically cleaned with anhydrous ethanol and deionized water, then immersed in 1M NaOH solution for 60 min. After removal, it was rinsed with deionized water and dried under nitrogen. A Tris-HCl buffer solution of 2 mg / mL dopamine (pH = 8.5, 10 mM) was prepared, and the slide was immersed in the dopamine solution overnight at room temperature. After rinsing with deionized water, it was dried at 60°C to form a polydopamine coating on the slide surface. Ethanol solutions of 0.01 mol / L hexamethylenetetramine and 0.01 mol / L zinc chloride were prepared separately and mixed thoroughly at room temperature to obtain a mixture. The glass slide with the polydopamine coating was immersed in the above mixture, rapidly heated to 120°C, reacted for 2 h, ultrasonically cleaned with deionized water, and dried at 120°C for 30 min to obtain a chip with a contrast antibacterial coating.

[0046] Comparative Example 2

[0047] A 20*20mm glass slide was ultrasonically cleaned with anhydrous ethanol and deionized water, then immersed in 1M NaOH solution for 60 min. After removal, it was rinsed with deionized water and dried under nitrogen. A Tris-HCl buffer solution of 2 mg / mL dopamine (pH = 8.5, 10 mM) was prepared, and the slide was immersed in the dopamine solution overnight at room temperature. After rinsing with deionized water, it was dried at 60°C to form a polydopamine coating on the slide surface. The glass slide with the polydopamine coating was immersed in a 0.01 mol / L curcumin solution at room temperature for 2 h, ultrasonically cleaned with deionized water, and dried at 60°C for 60 min to obtain a chip with a contrast antibacterial coating.

[0048] Comparative Example 3

[0049] This comparative example is basically the same as Example 1, except that the glass slide with polydopamine coating was immersed in the mixed solution, reacted at 30°C for 2 hours, ultrasonically cleaned with deionized water, and dried at 60°C for 60 minutes to obtain a chip with a composite antibacterial coating.

[0050] Test Example 1

[0051] Antibacterial tests against Escherichia coli were conducted on Examples 1-2 and Comparative Examples 1-2. The specific test method was as follows: the prepared chip with antibacterial coating was placed in a petri dish, and 50 μL of a 10% concentration was added. 7 CFU / mL *E. coli* bacterial suspension was incubated at 37°C for 2 hours, then eluted with sterile water. The 0-hour suspension and the 2-hour eluent were placed in sterile petri dishes and incubated at 37°C for 24 hours. The inhibition rate was calculated based on changes in colony count. The test results are as follows: Figure 1 As shown. From Figure 1 It can be seen that, compared with the comparative example, the composite coating prepared by the present invention has a better antibacterial effect.

[0052] Test Example 2

[0053] The adhesion performance between the coating and the substrate was tested using the tape peeling method.

[0054] (1) Place the chip with the composite antibacterial coating from Example 1 horizontally on the experimental stage and fix it in place; (2) Completely cover the chip surface with tape and press it firmly onto the surface, then slowly peel off the entire tape; (3) Replace with a new tape and repeat step (2). During the test, test the static water contact angle of the sample surface at certain intervals. After the test is completed, allow the surface to air dry naturally with deionized water before continuing the tape peeling experiment. The test results are as follows: Figure 2 As shown.

[0055] from Figure 2As can be seen from the entire tape peeling test, the static water contact angle of the coating surface initially increased slightly, then gradually stabilized. This is because there is a small amount of physically adsorbed material on the chip surface. In the initial stage of the tape peeling test, this physically adsorbed material was peeled off by the tape, hence the slight increase in the contact angle. The remaining stable part is the composite antibacterial coating. Since the composite antibacterial coating is almost impossible to peel off, the contact angle did not change significantly. The experiment shows that the composite antibacterial coating has strong adhesion to the substrate chip, and the composite antibacterial coating on the substrate chip surface has good stability.

[0056] The exemplary embodiments of the present invention have been described above. However, the scope of protection of this application is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made by those skilled in the art within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A composite antibacterial coating on the surface of a chip, characterized in that, The raw materials for the composite antibacterial coating include at least dopamine-containing substances, zinc salts, and curcumin-like compounds.

2. The composite antibacterial coating on the chip surface according to claim 1, characterized in that, The composite antibacterial coating is obtained by chemically combining dopamine-containing substances, zinc salts, and curcumin-containing substances.

3. The composite antibacterial coating on the chip surface according to claim 1 or 2, characterized in that, The zinc salt is selected from soluble zinc salts.

4. The composite antibacterial coating on the chip surface according to any one of claims 1-3, characterized in that, The curcumin compounds are selected from at least one of curcumin, demethoxycurcumin, and bisdemethoxycurcumin.

5. The composite antibacterial coating on the chip surface according to any one of claims 1-4, characterized in that, The composite antibacterial coating has strong adhesion. Preferably, the composite antibacterial coating has high antibacterial ability.

6. The method for preparing the composite antibacterial coating on the chip surface according to any one of claims 1-5, characterized in that, The preparation method includes: (1) The substrate is immersed in a dopamine solution to form a polydopamine coating; (2) Prepare a mixed solution of zinc salt and curcumin, and react the substrate with polydopamine coating on the surface in the mixed solution to obtain a composite antibacterial coating.

7. The preparation method according to claim 6, characterized in that, The substrate is also pretreated. Preferably, the substrate material includes at least one of glass, silicon wafer, stainless steel, magnesium alloy, titanium alloy, PDMS, polyethylene, polypropylene, etc.

8. The preparation method according to claim 6 or 7, characterized in that, The dopamine solution is weakly alkaline and includes at least a dopamine-containing substance and a buffer solution. Preferably, the concentration of dopamine in the dopamine solution is 1-10 mg / mL.

9. The preparation method according to any one of claims 6-8, characterized in that, In step (2), the molar ratio of zinc ions to curcumin in the mixed solution is 0.01-0.5:0.01-0.

1. Preferably, in step (2), the concentration of zinc ions in the mixed solution is 0.01-0.5 mol / L. Preferably, the concentration of curcumin in the mixed solution is 0.01-0.1 mol / L. Preferably, in step (2), the mixed solution further includes an organic amine salt. Preferably, the molar ratio of the organic amine salt to zinc ions is 1:

1. Preferably, in step (2), the reaction refers to a reaction at 100°C or above for 0.1-5 hours.

10. The use of the composite antibacterial coating according to any one of claims 1-5 in inhibiting or inactivating bacteria or fungi.

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