JPWO2020100976A1 - Object surface processing method, laminate, and method for manufacturing laminate - Google Patents

Abstract

From (a) a resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate and (b) a surface of the substrate opposite to the side on which the resin layer is formed, light is emitted from the resin layer. (C) An object placement step of arranging an object having a non-flat surface on the resin layer irradiated with the light, and (d) the resin layer of the substrate are formed. A secondary irradiation step of further irradiating the resin layer with light from the surface opposite to the side facing the resin layer is provided, and the primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object. The arranging step is a method for processing the surface of an object, in which the non-flat surface of the object faces the resin layer.

Description

The present disclosure relates to a method for processing the surface of an object, a laminated body, and a method for manufacturing the laminated body.

In the in vitro cell culture technology, studies on a method of culturing cells in a three-dimensional environment instead of the conventional two-dimensional environment have been studied in recent years. By culturing cells in a three-dimensional environment, it is possible to carry out experiments that imitate an environment closer to the living body. It is also expected to be used in the field of regenerative medicine in which self-cells are cultured to form biological tissues and then transplanted into the body.

As a material (scaffolding material) for culturing cells in a three-dimensional environment, a porous body having excellent biocompatibility has been proposed (see, for example, Patent Document 1). On the other hand, a method of producing a fine structure having a complicated three-dimensional shape by using a photolithography technique has been proposed (see, for example, Patent Document 2).

JP-A-2009-160302 International Publication No. 2011/046169

It is an effective means to modify the surface structure by applying the photolithography method cultivated in the fields of semiconductor processing, MEMS (Micro Electro Mechanical Systems) fabrication, etc. for the purpose of imparting some function to the porous body. it is conceivable that. However, since the surface of the porous body is not flat like the semiconductor substrate, there are some points to be improved in order to apply these methods to the surface processing of the porous body.

In view of the above circumstances, the problem to be solved by one embodiment of the present invention is a method of surface processing an object capable of forming a high-definition surface structure on a non-flat surface, a high-definition surface on a non-flat surface of an object. It is an object of the present invention to provide a laminated body having a structure and a method for producing a laminated body having a high-definition surface structure formed on a non-flat surface of an object.

Means for solving the above problems include the following embodiments.
<1> (a) A resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate, and
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
The primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. ..
<2> The method for surface processing an object according to <1>, wherein the object is a porous body.
<3> The surface processing method according to <1> or <2>, wherein the photosensitive resin is a photocurable resin.
<4> An object having a non-flat surface and a resin layer arranged on the non-flat surface of the object are provided, the resin layer is a cured product of a photosensitive resin, and at least a part of the resin layer is A laminate that penetrates the non-flat surface of the object.
<5> The laminate according to <4>, wherein the object is a porous body.
<6> The laminate according to <4> or <5>, wherein the photosensitive resin is a photocurable resin.
<7> The laminate according to any one of <4> to <6>, wherein the portion where the resin layer penetrates into the non-flat surface of the object is an edge portion of the resin layer.
<8> The laminate according to any one of <4> to <7>, wherein the portion where the resin layer penetrates into the non-flat surface of the object is 50% or less of the total area of the resin layer.
<9> A portion in which the resin layer has a portion that has entered the non-flat surface of the object and a portion that has not entered the non-flat surface of the object, and has entered the non-flat surface of the object. The laminated body according to any one of <4> to <8>, wherein is in a state of being fixed to the object, and a portion not entering the non-flat surface of the object is in a state of not being fixed to the object. ..
<10> (a) A resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate, and
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
The primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. <4> to < The method for producing a laminate according to any one of 9>.

According to one embodiment of the present invention, a method for surface processing an object capable of forming a high-definition surface structure on a non-flat surface, a laminate having a high-definition surface structure on the non-flat surface of the object, and an object. A method for producing a laminate having a high-definition surface structure formed on a non-flat surface is provided.

It is a process drawing which shows an example of the surface processing method of this disclosure. It is an electron microscope image of the surface of the cell culture base material which formed the resin layer in an Example. It is an enlarged image of the mesh part of the cell culture equipment shown in FIG.

Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
In the present specification, the term "process" is included in this term not only as an independent process but also as long as the intended purpose of the process is achieved even if it cannot be clearly distinguished from other processes. Is done.
Further, in the present specification, the amount of each component in the composition is the total amount of the plurality of substances present in the composition unless otherwise specified, when a plurality of substances corresponding to each component are present in the composition. means.

<Method of surface processing of objects>
The surface processing method of the object of the present disclosure is described.
(A) A resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate, and
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
The primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. Is.

According to the method of the present disclosure, high-definition surface processing can be applied to an object whose surface is not flat.
Further, in the method of the present disclosure, a surface structure made of resin is formed on the surface of an object by utilizing the adhesive force of the resin. Therefore, it can be carried out by a simpler and cheaper method than the adhesive bonding technique using high temperature, high vacuum, plasma, or the like. In addition, the material to be used can be selected from a wider range.

(A) Resin layer forming step In the resin layer forming step, a resin layer containing a photosensitive resin is formed on the substrate.
The substrate used in the method of the present disclosure is not particularly limited as long as it can transmit the light irradiated in the light irradiation step. For example, it may be a substrate made of an inorganic material such as glass or a substrate made of an organic material such as resin.

The photosensitive resin contained in the resin layer is not particularly limited as long as it can react with the light irradiated in the light irradiation step. For example, it may be selected from photosensitive resins used as photoresists in photolithography technology. The photosensitive resin is a type of photosensitive resin whose solubility in a developing solution is reduced by light irradiation (negative type, photocurable), but its solubility in a developing solution is increased by light irradiation (positive). It may be a type, photodegradable) photosensitive resin.

Specific examples of the photosensitive resin include epoxy resin, acrylic resin, polyester acrylate resin, urethane acrylate resin, and oxetane resin.

The method of forming the resin layer on the substrate is not particularly limited. For example, it can be formed by a known method such as a spin coater, a roll coater, screen printing, and transfer. The resin layer may be formed in a pattern or uniformly (without a pattern).

The thickness of the resin layer formed on the substrate is not particularly limited. For example, it may be selected from the range of 0.1 μm to 100 μm. From the viewpoint of forming the resin layer having a uniform thickness, the resin forming the resin layer preferably has fluidity at the time of forming the resin layer, and more preferably liquid or paste.

(B) Primary Irradiation Step In the primary irradiation step, the resin layer is irradiated with light from the surface (hereinafter, also referred to as the back surface) opposite to the side on which the resin layer of the substrate is formed.
The light applied to the resin layer may be applied to the entire surface of the resin layer or may be applied in a pattern. By irradiating the resin layer with light in a pattern, the cured portion (exposed portion in the case of a photocurable resin) and the uncured portion (unexposed portion in the case of a photocurable resin) are patterned in the resin layer. Can be formed into. By removing the uncured portion of the resin layer, a patterned structure made of a cured product of the photosensitive resin can be formed on the surface of the object.

The method of irradiating the resin layer with light in a pattern is not particularly limited. For example, a method of forming a pattern on the surface of a substrate with a light-shielding material or using a photomask to prevent light from partially reaching the resin layer, a method of irradiating light in a pattern, and the like can be mentioned. Be done. From the viewpoint of forming a high-definition pattern, a method of forming a pattern on the surface of the substrate with a light-shielding material or using a photomask is preferable, and a method of forming a pattern on the surface on the side where the resin layer of the substrate is formed. Is more preferable.

The type of light irradiated to the resin layer is not particularly limited as long as it can cause a reaction in the photosensitive resin. Above all, ultraviolet rays are preferable from the viewpoint of processing accuracy, ease of processing, and the like. The light source used for light irradiation is not particularly limited, and may be selected from, for example, light sources generally used in photolithography technology. Specific examples thereof include light emitting diodes (LEDs), semiconductor lasers, excimer lasers, metal halide lamps, and high-pressure mercury lamps.

In the method of the present disclosure, the resin layer is irradiated with light under the condition that a part of the resin layer is not cured. As a result, when the object is placed on the resin layer after light irradiation, the uncured portion of the resin layer enters the unevenness of the non-flat surface of the object. When the resin in a state of being embedded in the unevenness of the non-flat surface of the object is cured in the secondary irradiation step described later, in addition to the adhesive force originally possessed by the resin, an anchor effect is exhibited and the resin firmly adheres to the object.

In the method of the present disclosure, light irradiation is performed from the back surface of the substrate. As a result, it is possible to effectively create a uncured portion in the portion where the resin layer is in contact with the non-flat surface of the object (that is, the side opposite to the side irradiated with light).

The method of irradiating the resin layer with light under the condition that a part of the resin layer is not cured is not particularly limited. For example, the irradiation conditions (irradiation intensity, irradiation time, etc.) may be adjusted, or other conditions may be adjusted.

(C) Object placement step In the object placement step, an object having a non-flat surface is placed on the resin layer irradiated with light.
The morphology of an object having a non-flat surface is not particularly limited. For example, it may be an object having a non-flat surface and a dense interior, an object having voids inside (porous body) such as a sponge, or an object of other forms. .. Further, the surface of the object may be completely non-flat or partially non-flat.

The specific aspect of the non-flat surface of the object is not particularly limited as long as the uncured portion of the resin layer can enter. For example, there may be a state in which pores are present on the surface, a state in which the surface is undulating, a state in which the surface is raised, and the like.

The material of the object having a non-flat surface is not particularly limited. For example, it may be an object made of an organic material such as resin, an object made of an inorganic material such as glass, carbon, or ceramics, or a composite thereof.

The placement of the object is such that the non-flat surface of the object faces the resin layer. As a result, a part of the uncured resin layer penetrates into the unevenness of the non-flat surface of the object. The object may be arranged without pressurization or with pressurization.

(D) Secondary Irradiation Step In the secondary irradiation step, after the object placement step, the resin layer is further irradiated with light from the back surface of the substrate.
By performing the secondary irradiation step on the resin layer, the uncured resin that has entered the unevenness of the non-flat surface of the object is cured, and the resin is firmly adhered to the object.

The method of carrying out the secondary irradiation step is not particularly limited. For example, it can be performed according to the method of irradiating the resin layer with light in the primary irradiation step.

The region for irradiating the resin layer with light in the secondary irradiation step may be the entire surface or a part of the resin layer.
When the region for irradiating the resin layer with light in the secondary irradiation step is a part of the resin layer, the position of the region for irradiating the light is not particularly limited. For example, it may be an edge portion of the resin layer or another portion. The ratio of the area of the area to be irradiated with light is not particularly limited. For example, it may be 50% or less, 30% or less, or 10% or less of the total area of the resin layer. Further, it may be 1% or more, 5% or more, or 10% or more of the total area of the resin layer.

When the resin layer has a region irradiated with light in the secondary irradiation step and a region not irradiated with light, the region irradiated with light is in a state of being fixed to the object, and the region not irradiated with light is fixed to the object. It may not be in the state.

When the light irradiation in the primary irradiation step is performed in a pattern and the uncured portion (in the case of a negative type photocurable resin, the unexposed portion) is removed in the removal step described later to form a pattern on the resin layer, Light may be applied only to the portion that does not form the pattern of the resin layer (for example, the edge portion of the resin layer).

(E) Removal Step In the method of the present disclosure, the uncured portion of the resin layer may be removed after the secondary irradiation step.
When the resin layer is irradiated with light in a pattern, the uncured portion (unexposed portion when a photocurable resin is used) is removed to form a patterned resin on the surface of the object. A surface structure can be formed.
In the method of the present disclosure, even if the resin layer (photosensitive resin) having fluidity at the time of adhesion flows to an unintended portion, it can be removed in the subsequent removal (development) step. Therefore, it can be applied to a fine structure on a microscale.

The method for removing the uncured portion of the resin layer is not particularly limited. For example, it may be removed using a developer commonly used in photolithography techniques.

(F) Peeling Step In the method of the present disclosure, the substrate may be peeled from the resin layer.
When the resin layer is peeled from the substrate, a layer (sacrificial layer or the like) for facilitating the peeling may be formed in advance on the surface of the substrate on which the resin layer is formed. Further, the substrate after the resin layer is peeled off may be reused.

Hereinafter, the method of the present disclosure will be specifically described with reference to the drawings. FIG. 1 is a process diagram schematically showing an example of the surface processing method of the present disclosure. In this step, a resin layer is formed using a photocurable photosensitive resin.

First, as shown in FIG. 1A, the resin layer 2 is formed on the substrate 1 (resin layer forming step). A pattern is formed on the surface of the substrate 1 on the side where the resin layer is formed with a material that does not transmit light used in the temporary light irradiation step. Further, a sacrificial layer 3 is formed to facilitate peeling of the resin layer from the substrate.

Next, as shown in FIG. 1 (b), the light 4 is irradiated from the surface (back surface) opposite to the surface on which the resin layer 2 of the substrate 1 is formed (primary irradiation step). As a result, the resin in the light-irradiated region (exposed portion) of the resin layer 2 is cured. The irradiation of the light 4 is performed under the condition that the side of the resin layer 2 in contact with the object 5 is not cured.

Next, as shown in FIG. 1C, the object 5 is placed on the resin layer 2 (object placement step). The object 5 has a non-flat surface, and the surface is arranged so as to face the resin layer 2. As a result, the uncured portion of the resin layer 2 enters the unevenness of the non-flat surface of the object 5.

Next, as shown in FIG. 1 (d), light 6 is further irradiated from the back surface of the substrate 1 (secondary irradiation step). In this step, the mask 7 is used so that the light 6 is irradiated only to the edge portion of the resin layer 2. As a result, at the edge of the resin layer 2, the portion of the object 5 that has entered the unevenness of the non-flat surface is hardened and firmly adhered to the object 5.

Next, as shown in FIG. 1 (e), the uncured portion of the resin layer is removed (removal step). As a result, a patterned structure composed of the unremoved portion of the resin layer 2 is formed on the surface of the object 5.

Next, as shown in FIG. 1 (f), the substrate 1 is peeled from the resin layer 2 (peeling step). As a result, the object 5 in which the patterned structure formed by the resin layer 2 is formed on the surface is obtained.

Objects whose surface has been surface-processed by the method of the present disclosure can be used for various purposes. For example, by providing a resin layer having a pattern having an opening of a predetermined size on the surface of the porous body, it can be used for the purpose of selectively passing or blocking a specific object.

In certain embodiments, the object surfaced by the methods of the present disclosure is used as a substrate (scaffolding material) for culturing cells.
Specifically, for example, by forming a resin layer having a pattern having an opening smaller than the size of a cell existing outside the blood vessel on the surface of a porous body made of a biocompatible material, the resin layer in the living body is formed. The environment near the blood vessel can be created in a simulated manner. By using the surface-processed object as a scaffold material, three-dimensional culture of cells outside the blood vessel is performed in the porous part (corresponding to the outside of the blood vessel), and vascular endothelium is used in the resin layer part (corresponding to the blood vessel wall). Two-dimensional culture of cells can be performed in parallel (co-culture).

<Laminated body>
The laminate of the present disclosure includes an object having a non-flat surface and a resin layer arranged on the non-flat surface of the object, and the resin layer is a cured product of a photosensitive resin, and the resin layer of the resin layer. It is a laminate in which at least a part of the object has penetrated into the non-flat surface of the object.

The laminate of the present disclosure comprises a resin layer arranged on a non-flat surface of an object, the resin layer being formed using a photosensitive resin. Therefore, even if the surface of the object is not flat, a high-definition surface structure is formed on the surface structure using photolithography technology.

Further, in the laminate of the present disclosure, at least a part of the resin layer penetrates into the non-flat surface of the object. As a result, in addition to the adhesive force originally possessed by the resin layer, an anchor effect is exhibited, and the resin layer is firmly adhered to the object.

The position of the portion where the resin layer penetrates into the non-flat surface of the object is not particularly limited. For example, it may be an edge portion of the resin layer or another portion. The ratio of the area where the resin layer penetrates the non-flat surface of the object is not particularly limited. For example, it may be 50% or less, 30% or less, or 20% or less of the total area of the resin layer. Further, it may be 1% or more, 5% or more, or 10% or more of the total area of the resin layer.

If the resin layer has a portion that penetrates the non-flat surface of the object and a portion that does not penetrate the non-flat surface of the object, the portion of the resin layer that penetrates the non-flat surface of the object sticks to the object. The portion of the resin layer that has not entered the non-flat surface of the object may be in a state of not being fixed to the object.

The details and preferred embodiments of the object and the resin layer constituting the laminate of the present disclosure are the same as the details and preferred embodiments of the object and the resin layer used in the above-described method for processing the surface of the object.

The laminate of the present disclosure can be used for various purposes. For example, in the above-mentioned method for surface processing an object, use as a base material for culturing cells as described as an application of a surface-processed object can be mentioned.

<Manufacturing method of laminated body>
The method for producing a laminate of the present disclosure is the above-mentioned method for producing a laminate, which includes (a) a resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate.
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
The primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. Is.

According to the above method, even if the surface of the object is not flat, it is possible to manufacture a laminate in which a high-definition surface structure is formed on the surface of the object by using photolithography technology.

The details and preferred embodiments of each step in the above method are the same as the details and preferred embodiments of each step in the above-described method for processing the surface of an object.

<Surface processing test>
A mesh pattern having a pore diameter of 5 μm and a lattice size of 4 μm was formed on one side of the glass substrate using chromium, and a sacrificial layer (Omnicoat, film thickness: 20 nm or less) was formed on the mesh pattern. Next, a resin layer was formed on the sacrificial layer using an epoxy-based negative resist (SU-8, Nippon Kayaku Co., Ltd.) as a photosensitive resin (thickness: 10 μm).

Ultraviolet rays (wavelength: 365 nm) were irradiated from the surface of the glass substrate opposite to the surface on which the resin layer was formed, and the light-irradiated portion of the resin layer was cured. At this time, the irradiation conditions were adjusted so that the portion of the resin layer opposite to the light irradiation surface was not cured.

A porous cell culture substrate (Alvetex Scaffold, diameter 8 mm, thickness: 200 μm) was placed on the resin layer after light irradiation. At this time, the uncured portion of the resin layer entered the pores of the surface of the cell culture substrate in contact with the resin layer due to surface tension.

Further, ultraviolet rays (wavelength: 365 nm) were irradiated from the surface of the glass substrate opposite to the surface on which the resin layer was formed. At this time, the resin was completely cured by irradiating only the resin layer corresponding to the edge of the cell culture equipment with light using a mask.

Next, the uncured resin was dissolved and removed using a developing solution (SU-8 Developer, Nippon Kayaku Co., Ltd.), and the glass substrate was peeled off. When the surface of the obtained cell culture substrate was observed with a scanning electron microscope, as shown in FIGS. 2 and 3, a portion (mesh portion) in which a mesh-like resin layer made of a cured product of a photosensitive resin was formed. ), And a portion (adhesive portion) in which the photosensitive resin entered the pores of the cell culture substrate and was cured was formed around the mesh portion.

<Cell culture test>
The cell culture substrate provided with the mesh-like resin layer prepared by the above method was regarded as a two-dimensional and three-dimensional structure in a living body, and HeLa cells and HepG2 cells were co-cultured. As a result, HeLa cells could be cultured on the cell culture substrate side, and HepG2 cells could be cultured on the resin layer side.

1 ... substrate, 2 ... resin layer, 3 ... sacrificial layer, 4 ... light, 5 ... object, 6 ... light, 7 ... mask

Claims (10)

(A) A resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate, and
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
The primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. .. The method for surface processing an object according to claim 1, wherein the object is a porous body. The surface processing method according to claim 1 or 2, wherein the photosensitive resin is a photocurable resin. An object having a non-flat surface and a resin layer arranged on the non-flat surface of the object are provided, the resin layer is a cured product of a photosensitive resin, and at least a part of the resin layer is the object. A laminate that penetrates into a non-flat surface. The laminate according to claim 4, wherein the object is a porous body. The laminate according to claim 4 or 5, wherein the photosensitive resin is a photocurable resin. The laminate according to any one of claims 4 to 6, wherein the portion where the resin layer penetrates into the non-flat surface of the object is an edge portion of the resin layer. The laminate according to any one of claims 4 to 7, wherein the portion where the resin layer penetrates into the non-flat surface of the object is 50% or less of the total area of the resin layer. The resin layer has a portion that penetrates into the non-flat surface of the object and a portion that does not penetrate into the non-flat surface of the object, and the portion that penetrates into the non-flat surface of the object is the object. The laminate according to any one of claims 4 to 8, wherein the portion that is stuck to the object and does not enter the non-flat surface of the object is not stuck to the object. (A) A resin layer forming step of forming a resin layer containing a photosensitive resin on a substrate, and
(B) A primary irradiation step of irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed.
(C) An object arranging step of arranging an object having a non-flat surface on the resin layer irradiated with light.
(D) A secondary irradiation step of further irradiating the resin layer with light from a surface of the substrate opposite to the side on which the resin layer is formed is provided.
Claims 4 to claim that the primary irradiation step is performed under a condition that a part of the resin layer is not cured, and the object placement step is performed so that the non-flat surface of the object faces the resin layer. Item 9. The method for producing a laminate according to any one of Items 9.

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