Coating film-equipped member and method for manufacturing the same

Abstract

To provide a method for manufacturing a coating film-equipped member that can form a surface pattern having a partially different thickness at a surface of a coating film that is formed by drying a paint film applied at a surface of a member.SOLUTION: A method for manufacturing a coating film-equipped member includes: a heating step for partially heating a surface of a member 2 in a prescribed heating pattern to thereby provide a temperature difference between a portion heated by using the heating pattern and a portion other than the heated portion; an application step for applying the surface of the member 2 with a coating liquid to thereby form a coating; and a drying step for drying the coating to thereby form a coating film 3 having a surface pattern 4 in which a thickness difference from the portion other than the heated portion is generated according to the temperature difference.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a coated member and a method for producing the same. [Background technology]

[0002] In recent years, with the advancement of regenerative medicine, various types of culture dishes for culturing cell sheets have been developed. Furthermore, to properly detach the cultured cell sheet from the culture dish, a temperature-responsive polymer coating is formed on the inner surface of the culture dish. It is desirable for the coating to have a uniform thickness. Alternatively, a predetermined uneven pattern may be formed on the coating (see, for example, Patent Document 1 below).

[0003] Specifically, Patent Document 1 below describes the production of a substrate (stamp) on which a predetermined pattern is engraved in a convex shape using polydimethylsiloxane (PDMS), metal, silicone, glass, etc., by photolithography technology, and the formation of a biocompatible polymer layer on the surface of the resulting stamp (the stamp surface on which the pattern is engraved).

[0004] Furthermore, Patent Document 1 below describes a method of applying a solution of a biocompatible polymer or the like to the surface of a stamp by spin coating, and adjusting the rotation speed and rotation time of the spin coater to adjust the thickness of a nano-thin film made of a biocompatible polymer or the like applied to the surface of the stamp. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2017 / 183712 Summary of the Invention [Problem to be solved by the invention]

[0006] However, in the conventional methods described above, since the coating film is wetted and spread by the spin coating method, it is difficult to intentionally form a pattern with partially different thicknesses on the surface of the coating film formed by drying the coating film, because the spin coating method is a method for coating a coating film uniformly by wetting and spreading the coating film.

[0007] The present invention has been proposed in consideration of the above-mentioned conventional circumstances, and aims to provide a coated member and a method for manufacturing the same that make it possible to form a surface pattern having different thicknesses on the surface of a coating film formed by drying a coating film applied to the surface of the member. [Means for solving the problem]

[0008] In order to achieve the above object, the present invention provides the following means. [1] A member; a coating formed on the surface of the member, the coating is formed by drying a coating film applied to the surface of the member, Furthermore, the coated member is characterized by having a surface pattern in which thickness differences occur in accordance with temperature differences on the surface of the member when the coating film is dried. [2] The coated member according to [1], wherein the thickness of the portion of the coating where the surface pattern is formed is greater than the thickness of the coating around the surface pattern. [3] The member is a container having an open top, The coated member according to [1], wherein the coating is formed on at least the inner bottom surface of the container. [4] a temperature difference applying step of partially applying a temperature difference to the surface of the member in a predetermined pattern; a coating step of applying a coating liquid to a surface of the member to form a coating film; and a drying step of drying the coating film to form a coating film having a surface pattern in which thickness differences occur in response to the temperature difference. [5] a heating step of partially heating the surface of the member in a predetermined heating pattern to create a temperature difference between the heated portion and the heated portion; a coating step of applying a coating liquid to a surface of the member to form a coating film; and a drying step of drying the coating film to form a coating film having a surface pattern in which thickness differences occur in response to the temperature difference. [6] The method for producing a coated member according to [5], wherein the coating is formed so that the thickness of the portion where the surface pattern is formed is greater than the thickness of the periphery of the surface pattern. [7] The method for producing a coated member according to [5], wherein a resin film is formed as the coating. [8] The method for producing a coated member according to [5], wherein in the heating step, a heating medium heated in accordance with the heating pattern is brought into contact with or opposed to the surface of the member. [9] The method for producing a coated member according to [5], wherein in the coating step, the coating liquid is applied by a spin coating method.

[10] The method for producing a coated member according to [5], wherein in the drying step, the coating film is dried at room temperature.

[11] The member is a container having an open top, The method for producing a coated member according to [5] above, wherein the coating is formed on at least the inner bottom surface of the container. [Effects of the Invention]

[0009] As described above, the present invention provides a coated member and a method for manufacturing the same that make it possible to form a surface pattern having different thicknesses on the surface of a coating film formed by drying a coating film applied to the surface of the member. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a plan view showing a coated member according to an embodiment of the present invention. [Figure 2] FIG. 2 is a cross-sectional view showing a coated member. [Figure 3] FIG. [Figure 4] 1A to 1C are cross-sectional views illustrating a manufacturing process of a coated member. [Figure 5] 1A to 1C are cross-sectional views illustrating a manufacturing process of a coated member. [Figure 6] 1A to 1C are cross-sectional views illustrating a manufacturing process of a coated member. [Figure 7] FIG. 10 is a diagram showing the results of image analysis in an example. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the drawings used in the following description, the dimensions of the components may be shown at different scales to make them easier to see, and the dimensional ratios of the components may not be the same as in reality. Furthermore, the materials, dimensions, etc. exemplified in the following description are merely examples, and the present invention is not necessarily limited to them, and can be implemented with appropriate changes within the scope of the present invention.

[0012] (Coated parts) First, as one embodiment of the present invention, a coated member 1 shown in, for example, FIGS. 1 and 2 will be described. 1 is a plan view showing the coated member 1. FIG. 2 is a cross-sectional view showing the coated member 1.

[0013] 1 and 2, the coated member 1 of this embodiment is an application of the present invention to, for example, a culture dish for culturing a cell sheet. In addition, a temperature-responsive polymer coating is formed on the inner bottom surface of the culture dish to allow the cultured cell sheet to be properly detached from the culture dish.

[0014] The member used for the coated member 1 is any member that can be coated, such as a circular or polygonal plastic plate (e.g., square or pentagonal), or a plastic dish with a rim. In addition to culture dishes, other materials such as petri dishes, insert dishes, and flasks can also be used.

[0015] The temperature-responsive polymer may be, for example, a polymer having a lower critical solution temperature (LCST), a homopolymer or copolymer thereof, or a mixture thereof. Such a polymer can be obtained, for example, by homopolymerization or copolymerization of the following monomers. Examples of usable monomers include N-isopropyl(meth)acrylamide, Nn-propyl(meth)acrylamide, N-ethoxyethylacrylamide, N,N-diethylacrylamide, N-methyl-N-isopropylacrylamide, and N-methyl-Nn-propylacrylamide.

[0016] Examples of comonomers for copolymerization include alkyl (meth)acrylates such as methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, n-butyl (meth)acrylate, etc. Furthermore, copolymerization with monomers other than the above-mentioned monomers, graft or copolymerization between polymers, or a mixture of polymers or copolymers may be used.

[0017] Furthermore, crosslinking is also possible to the extent that the inherent properties of the polymer are not impaired. The temperature-responsive polymer used in the present invention preferably has a molecular weight of 500 or more, preferably 3000 or more, more preferably 8000 or more, and most preferably 12000 or more. If the molecular weight is less than 500, cultured cells on the polymer are difficult to detach even when the temperature is changed, which is undesirable as it significantly reduces work efficiency.

[0018] The coated member 1 of this embodiment has a cylindrical container 2 with a bottom and an open top, and has a coating 3 formed on at least the inner bottom surface of the container 2 (in this embodiment, the inner bottom surface and inner peripheral surface of the container 2).

[0019] The coating 3 is made of a resin film of a temperature-responsive polymer, and is formed by drying a coating applied to the inner surface of the container 2. The coating 3 also has a surface pattern 4 in which thickness variations occur depending on the temperature difference on the inner bottom surface of the container 2 when the coating is dried. For example, in this embodiment, a grid-like convex pattern is formed on the surface of the coating 3 as the surface pattern 4. Here, the term "pattern" refers to an artificial shape or design formed by convex portions and concave portions. In this specification, the term "surface pattern" refers to a shape or design formed artificially by convex portions.

[0020] As a result, the thickness t1 of the coating 3 in the portion where the surface pattern 4 is formed is greater than the thickness t2 of the coating 3 around the surface pattern 4 (t1>t2).

[0021] As described above, the coated member 1 of this embodiment has a configuration in which the coating 3 having the surface pattern 4 with a thickness that varies partially is formed on the inner surface of the container 2.

[0022] (Method of manufacturing coated member) Next, a method for manufacturing the coated member 1 will be described with reference to FIGS. 3 is a plan view showing the heating medium 20. FIGS. 4 to 6 are cross-sectional views illustrating the manufacturing process of the coated member 1.

[0023] The method for manufacturing the coated member 1 includes a heating step in which the surface of the member, for example, in this embodiment, the inner bottom surface of the container 2, is partially heated in a predetermined heating pattern to create a temperature difference between the heated portion and the portion heated by the heating pattern; a coating step in which a coating liquid is applied to the surface of the member to form a coating film; and a drying step in which the coating film is dried to form a coating 3 having a surface pattern 4 with thickness differences occurring in accordance with the temperature difference.

[0024] Specifically, the heating step uses a heating medium 20 having a heating pattern 20a as shown in Fig. 3. The heating medium 20 is made of, for example, a cylindrical silicone rubber, and has the heating pattern 20a on its upper surface.

[0025] The heating pattern 20a has a shape corresponding to the surface pattern 4 of the coating 3. That is, the heating pattern 20a forms a grid-like convex pattern corresponding to the surface pattern 4.

[0026] 4, in the heating step, the heating medium 20 is heated to a predetermined temperature in a dry oven, and then the bottom surface of the container 2 is partially heated by the heating pattern 20a while the heating pattern 20a is in contact with or facing the bottom surface of the container 2, for example, the outer bottom surface in this embodiment. Note that in this embodiment, heating is performed by bringing the heating pattern 20a into contact with the bottom surface of the container 2, but heating may also be performed by bringing the heating pattern 20a facing the bottom surface of the container 2 in a non-contact state.

[0027] This allows a temperature difference to be created between the portion of the bottom surface of the container 2 that is heated by the heating pattern 20a and the other portion. That is, heating can be performed to increase the temperature of the portion of the bottom surface of the container 2 that is heated by the heating pattern 20a.

[0028] 5, in the coating step, a coating liquid L is prepared by dissolving a coating agent, which is the raw material of the coating film 3, in a solvent. The coating agent is a substance that is to be coated on the inner surface of the container 2, and any substance can be used as long as it can impart properties other than those of the material of the container 2.

[0029] In this embodiment, the coating material may be, for example, a temperature-responsive polymer, or a functional resin such as polytetrafluoroethylene, silicone, or polyethylene, or a general-purpose resin.

[0030] In the coating step, the coating liquid L is applied by spin coating to the inside of the container 2. That is, in this spin coating method, the container 2 is placed on a turntable of a spin coater (not shown) together with the heating medium 20, and the coating liquid L is dropped onto the inside bottom surface of the container 2 while the turntable is rotated around its axis.

[0031] As a result, the coating liquid L spreads from the inner bottom surface of the container 2 to the inner peripheral surface due to centrifugal force, forming a coating film (hereinafter referred to as "coating film L") over the entire inside surface of the container 2, i.e., the bottom surface and the inner peripheral surface.

[0032] In the drying step, the coating liquid (coating film) L applied by the spin coating method described above is dried as it spreads due to centrifugal force.

[0033] In the drying step, as shown in FIG. 6, the coating film L is dried at room temperature (so-called natural drying) to form a coating film 3 on the inner surface (inner bottom surface and inner circumferential surface) of the container 2.

[0034] In addition, in the drying step, since the drying of the coating film L proceeds simultaneously with the wetting and spreading, it is not necessary to rotate the container 2 during drying, and rotation may be stopped. On the other hand, drying can be accelerated by drying while rotating.

[0035] In the drying step, a temperature difference is created between the portion of the bottom surface of the container 2 heated by the heating pattern 20a and the other portion, thereby causing a thickness difference in the dried coating 3. That is, in the portion heated by the heating pattern 20a, the drying of the coating liquid L is accelerated, and the thickness of the coating 3 increases locally.

[0036] As a result, a surface pattern 4 having a shape corresponding to the heating pattern 20a described above is formed on the surface of the dried coating 3. In other words, it is possible to form a coating 3 in which the thickness t1 of the portion where the surface pattern 4 is formed is greater than the thickness t2 of the periphery of the surface pattern 4. As described above, the coated member 1 can be manufactured through three simultaneous steps, namely, the coating step is performed during the heating step, and the drying step is also performed.

[0037] As described above, in the manufacturing method of the coated member 1, it is possible to form a surface pattern 4 having a thickness that varies in parts on the surface of the above-mentioned member, for example, the surface of the coating 3 formed by drying the coating film L applied to the inner bottom surface of the container 2.

[0038] The present invention is not necessarily limited to the above-described embodiment, and various modifications can be made without departing from the spirit of the present invention.

[0039] For example, the method for producing the coated member 1 is not limited to the simultaneous progression of the three steps described above, and may involve the heating step and the coating step in that order, or the coating step followed by the heating step. The drying step may be initiated after the heating step and approximately simultaneously with the coating step, or after the coating step and approximately simultaneously with the heating step. When heating using a medium, it is preferable to perform the heating step first, as this simplifies the process.

[0040] The surface pattern 4 is not limited to the grid pattern described above, but may be any pattern that divides the inside bottom surface of the container 2, such as a radial pattern or a concentric pattern.

[0041] The coated member 1 is not limited to the above-mentioned culture dish, but may be any member on whose surface a coating is formed. The surface pattern 4 is also not particularly limited, and may be, for example, a figure, a design, a letter, a symbol, or the like.

[0042] Furthermore, the surface pattern 4 is not limited to the above-described convex pattern, but may be an inverted pattern of a concave-convex pattern, in other words, a shape in which the convex-convex relationship between the surface pattern 4 and its surroundings in Fig. 2 is reversed. In the case of this inverted pattern, the surface pattern 4 is a plurality of convex portions partitioned by concave portions formed in a grid pattern.

[0043] The heating medium 20 may be any medium that partially heats the surface of the member (the inner bottom surface of the container 2) in a predetermined heating pattern 20a, and may be configured as described above or may be electrically heated using a heating medium in which wiring such as nichrome wire is arranged as the predetermined heating pattern 20a. Electrical heating is preferable because it allows the application step and the heating step to be carried out almost simultaneously.

[0044] Furthermore, the heating process is not limited to the method using the heating medium 20 described above, but may also use a method in which the surface of the component (the inner bottom surface of the container 2) is partially heated in a predetermined heating pattern, for example, by irradiating it with an electron beam or infrared rays.

[0045] Furthermore, in the heating process, a method of creating a temperature difference between the heated part and the part heated by the above-mentioned heating pattern is used, but as the temperature difference creating process, in addition to the above-mentioned heating process, a method of creating a temperature difference between the part to be cooled as a cooling process may also be used.

[0046] Specifically, the cooling step may involve partially cooling the surface of the member, for example, the inner bottom surface of the container 2, in a predetermined cooling pattern using, for example, a Peltier element, to create a temperature difference between this cooled portion and the other portion. In this case, the thickness t1 of the portion of the coating 3 where the surface pattern 4 is formed is smaller than the thickness t2 of the periphery of the surface pattern 4 of the coating 3 (t1 <t2)。

[0047] In the coating process, in addition to the spin coating method described above, a method can be used in which the coating liquid L is applied and the coating film L is adhered to the surface of the member with a certain level of uniformity or more.For example, it is possible to apply the coating liquid L by spraying, applying the coating liquid L with a brush, or applying the coating liquid L by gravure coating.

[0048] In the manufacture of culture dishes, after the formation of coating 3, the following steps are carried out: a step of measuring the thickness of coating 3 using an absolute reflectance type (spectral reflectance type / optical interference type) film thickness measuring device (measurement step); a step of removing non-conforming products (removal step); a step of placing the culture dish in a sterilization bag (packaging step); and a step of sterilizing with ethylene oxide gas (sterilization step). [Example]

[0049] The effects of the present invention will be made clearer by the following examples. Note that the present invention is not limited to the following examples and can be practiced with appropriate modifications within the scope of the present invention.

[0050] In this example, a cylindrical culture dish with a bottom was first prepared. The culture dish was a surface-treated dish (Corning: 430165, culture area: approximately 8 cm). 2 ) was used. This culture dish was made of polystyrene.

[0051] Next, a heating medium was prepared with a grid-like heating pattern formed on the top surface of a cylindrical silicone rubber. The heating pattern was a grid-like convex pattern with a width of 2 mm and a spacing of 6 mm between the convex patterns. The heating medium was produced using a Keyence 3D printer (AGILISTA-3000).

[0052] Next, this heating medium was heated in a dry oven at 60°C for 30 minutes. The heating medium only needs to be sufficiently heated, and may be heated, for example, for 1.5 hours in a dry oven at 35°C. Furthermore, the heating conditions for the heating medium are not limited to these, as long as a temperature difference of 10°C or more is established between the heated portion and the heating pattern.

[0053] Next, the bottom surface of the culture dish was partially heated with the heating pattern while the heating pattern was in contact with the bottom surface of the culture dish.

[0054] At this time, the temperature of the inner bottom surface of the culture dish was measured using a non-contact thermometer (BOSCH: radiation thermometer GIS500). As a result, the temperature of the part in contact with the heating pattern was 54.8°C, and the temperature of the part not in contact with the heating pattern was 28.2°C.

[0055] Next, a coating agent consisting of polybutyl methacrylate-polyisopropylacrylamide block copolymer (hereinafter referred to as "PBMA-b-PIPAAm") was dissolved in a mixed solvent of dimethylformamide and isopropanol (mass ratio 1:4) to prepare a coating solution with a concentration of 0.225 vol%.

[0056] Next, this solution was applied to the inside of a culture dish by spin coating. Specifically, the heating medium and the culture dish were placed on top of each other on the rotating table of a spin coater, and negative pressure (suction) was applied from below the rotating table to fix the culture dish and the heating medium to the rotating table.

[0057] Then, 40 μL of the coating solution was dropped onto approximately the center of the inner bottom surface of the culture dish, and the rotation speed of the rotating table was increased to 5000 rpm at 500 rpm / sec, and the rotation was maintained for 15 seconds.

[0058] As a result, the coating solution was spread from the inner bottom surface to the inner peripheral surface of the culture dish by centrifugal force, and the coating film was dried at room temperature.

[0059] Through the above steps, a coated member was produced in which a PBMA-b-PIPAAm coating was formed on the inner surface of the culture dish.

[0060] In this example, the thickness of the coating formed on this coated member was measured using a film thickness measuring device (OPTM manufactured by Otsuka Electronics Co., Ltd.). In this measurement, 441 points were measured in a 20 mm x 20 mm area near the center of the inner bottom surface of the culture dish, and three-dimensional data was collected. This was then subjected to image analysis. The image analysis results are shown in Figure 7. Interpolation was performed between the measurement points to create a three-dimensional surface.

[0061] As a result, it was confirmed that a convex pattern was formed on the surface of the coating as a grid-like surface pattern. The height of the surface pattern of the coating measured 13 nm at the lowest point and 23 nm at the highest point from the inner bottom surface of the container 2. In other words, the difference in thickness of the coating was about 10 nm.

[0062] In the field of cell culture, the thicker the temperature-responsive polymer coating formed on the inside bottom surface of a culture dish, the poorer the adhesion of the cultured cells to the coating in the early stages of culture. Therefore, the culture dish of this example is expected to improve the detachability of the cell sheet formed on the coating.

[0063] Furthermore, in the culture dish of this embodiment, by forming a surface pattern with varying thicknesses on the coating, the cells are cultured in sufficient adhesion to the coating in the thinner parts at the beginning of the culture, while after the culture is completed, the cells can be preferentially detached from the thicker parts.

[0064] Furthermore, as the cells contract in the detached area, tensile force is generated between the thin and thick parts of the coating, facilitating the detachment of the cultured cell sheet.

[0065] A culture dish with a circular bottom is used for culturing cell sheets, and the cultured cell sheet depends on the shape of the dish, so it takes on a circular shape roughly equal to the diameter of the dish.

[0066] Furthermore, cultured cell sheets are applied to various sites in regenerative medicine, and the shapes of the affected areas to which they are applied may vary.

[0067] In such a situation, the technician must cut the cell sheet, which has been cultured to the same shape as the bottom of the culture dish, to fit the shape of the affected area and apply it by matching the shape.

[0068] However, cell sheets are flexible and fragile. Therefore, cutting them into any desired shape requires advanced techniques. Furthermore, cutting a cell sheet means discarding some of the cultured cells.

[0069] In contrast, the culture dish of this embodiment can culture, for example, four thin square cell sheets with a diameter of 1 cm, eight cell sheets with an approximately square shape, and four cell sheets with an approximately triangular shape.

[0070] Furthermore, the shape of the thin part of the temperature-responsive polymer coating can be freely changed, so multiple cell sheets with a predetermined outer shape can be cultured from a single culture dish. [Explanation of symbols]

[0071] 1... Coated member 2... Container 3... Coating 4... Surface pattern 20... Heating medium 20a... Heating pattern L... Coating liquid (coating film)

Claims

1. The components and a coating formed on the surface of the member, the coating is formed by drying a coating film applied to the surface of the member, Furthermore, the coated member is characterized in that it has a surface pattern in which thickness differences occur in accordance with temperature differences on the surface of the member when the coating film is dried.

2. 2. The coated member according to claim 1, wherein the thickness of the portion of the coating where the surface pattern is formed is greater than the thickness of the coating around the surface pattern.

3. the member is an open-topped container, 2. The coated member according to claim 1, wherein the coating is formed on at least the inner bottom surface of the container.

4. a temperature difference applying step of partially applying a temperature difference to a surface of the member in a predetermined pattern; a coating step of applying a coating liquid to a surface of the member to form a coating film; and a drying step of drying the coating film to form a coating film having a surface pattern in which thickness differences occur in response to the temperature difference.

5. a heating step of partially heating the surface of the member in a predetermined heating pattern to create a temperature difference between the heated portion and the heated portion; a coating step of applying a coating liquid to a surface of the member to form a coating film; and a drying step of drying the coating film to form a coating film having a surface pattern in which thickness differences occur in response to the temperature difference.

6. 6. The method for producing a coated member according to claim 5, wherein the thickness of the coating where the surface pattern is formed is greater than the thickness of the periphery of the surface pattern.

7. 6. The method for producing a coated member according to claim 5, wherein a resin film is formed as the coating.

8. 6. The method for producing a coated member according to claim 5, wherein in the heating step, a heating medium heated in accordance with the heating pattern is brought into contact with or opposed to the surface of the member.

9. 6. The method for producing a coated member according to claim 5, wherein the coating liquid is applied by spin coating in the coating step.

10. 6. The method for producing a coated member according to claim 5, wherein the coating film is dried at room temperature in the drying step.

11. the member is an open-topped container, 6. The method for producing a coated member according to claim 5, wherein the coating is formed on at least the inner bottom surface of the container.

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