JPH04173841A - Method for partially forming polymer membrane having functional group - Google Patents

Abstract

PURPOSE:To produce an ion sensor, enzyme sensor, etc., by forming a hydrophobic part on the surface of a substrate for forming a polymer membrane, applying a solution of a polymeric compound having high affinity to the substrate and forming the polymer compound membrane on the substrate., CONSTITUTION:A part of the surface of a substrate on which a polymer membrane is to be formed is treated in such a manner as to make the part to be hydrophobic compared with the other part of the substrate. The substrate is coated with a solution of a polymer compound having functional group and high affinity to the hydrophobic part. A polymer membrane having functional group can be formed on a part of the substrate by forming a membrane of the polymer compound on the hydrophobic part by this process.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for partially forming a polymer membrane having functional groups with functionality.

(Prior Art) In recent years, many polymer compounds having functional groups with industrially useful functions have been synthesized. In addition to functional groups with positive or negative charges, ionophores that have a high affinity for specific ions, and metal complexes that catalyze specific chemical reactions are introduced into polymer chains as functional groups.

For example, ruthenium, iron, and copper complexes of polyvinylpyridine exhibit electrochemical activity (Polymer Functional Electrodes, p. 41
, Gakkai Publishing Center, 1983). Furthermore, polymer compounds having reactive groups such as amino groups, carboxyl groups, and aldehyde groups are used as excellent immobilization carriers for enzymes, microorganisms, antigens, and antibodies. The functional polymer compounds listed above are applied to ion sensors and biosensors by coating them on electrode surfaces and optical fibers. Furthermore, the surfaces of microplates and cell culture plates used in enzyme immunoassay are treated with hydrophobic or positively charged polymer compounds in order to promote immobilization of antibodies and cells.

On the other hand, attempts to miniaturize ion sensors and biosensors are actively underway. In the production of microsensors, a technique for accurately and uniformly forming a functional film on the sensitive part of a microsensor is essential. Attempts have been made to fabricate reference electrodes by depositing acrylic resins, epoxy resins, fluorine resins, and silicone resins on the sensitive part of ion-sensitive field effect transistors (ISFETs). Collection, p.

385), it has not yet been possible to fabricate a film only on the sensitive part of a minute sensor. Regarding the formation of immobilized enzyme membranes, this technology has been realized in biosensor fabrication using 15FET. For example, see Japanese Patent Publication No. 61-88135 (Japanese Patent Application No. 59-209165). This method uses photolithography, a semiconductor manufacturing technology, to spread a protein solution containing an enzyme and a crosslinking agent onto a substrate that exposes only a portion of the surface on which an immobilized enzyme film is to be formed, rotate it, and finally photophotograph it. This process consists of dissolving the resist and removing the immobilized enzyme film on areas other than the predetermined surface.

(Problem to be solved by the invention) In the case of a membrane made of a polymer compound having a functional group with a useful function in its side chain, an immobilized enzyme membrane is characterized by properties such as solvent solubility, stability, and physical strength. Therefore, it is impossible to form microscopic membranes of arbitrary dimensions using a method similar to the method used to form immobilized enzyme membranes.Therefore, ion sensors and devices using such polymeric compounds are required. miniaturization was difficult. For the same reason, polymer compounds with functional groups that have excellent affinity for enzymes, antibodies, and cells and have excellent functions are used for enzyme sensors, enzyme immunoassay plates, etc.
It was difficult to apply it to cell culture plates, etc.

An object of the present invention is to provide a method for providing a film of a polymer compound having a functional group with a useful function at an arbitrary position and size on a substrate surface.

(Means for Solving the Problems) The method for partially forming a polymer film having a functional group of the present invention is a method for forming a polymer film having a functional group on a part of a substrate surface. A process of treating a part of the surface of the substrate where it is desired to be formed to make it more hydrophobic than other parts, and a step of treating the surface of the substrate so that it becomes more hydrophobic than other parts, and a process of treating the surface of the substrate to make it more hydrophobic than other parts, and to make the part of the substrate that has a functional group and has an affinity with the hydrophobically treated part. The method is characterized by comprising a step of applying a solution of a high molecular compound to form a film of the high molecular compound on the hydrophobically treated portion.

Or, in a method of forming a polymer film having a functional group on a part of the surface of a substrate, a step of forming a film of a monomer having a functional group on the entire surface of the substrate, and forming a polymer film is desired. A step of irradiating a portion of the surface of the substrate with ultraviolet rays to polymerize monomers to form a polymer film, and a step of cleaning the substrate with a solvent that dissolves only the monomers to remove them. It is characterized by

Or, in a method of forming a polymer film having a functional group on a part of the surface of a substrate, the step of forming a film of a polymer compound having a functional group on the entire surface of the substrate, and coating the substrate with a photoresist. A step of removing the photoresist on the surface on which a polymer film is desired to be formed by a post-photolithography method, a step of removing the exposed polymer film on the surface of the substrate by a plasma etching method, and a step of removing the photoresist. It is characterized by

Alternatively, a method for forming a polymer film having a functional group on a part of the substrate surface includes a step of applying a photoresist to the substrate and then removing the photoresist on the surface on which the polymer film is desired to be formed using a photolithography method. , is characterized by a step of applying a solution containing a polymer compound having a functional group, albumin, and a crosslinking agent to the substrate, and dissolving the photoresist to remove the polymer film on areas other than a predetermined surface.

(Function) If you first perform hydrophobic treatment on the part of the substrate where you want to provide a polymer film, and then apply a solution of a polymer compound that has high affinity for the hydrophobic surface, the high molecular weight will be applied only to the part on the hydrophobic surface. Films of molecular compounds can be formed. In this case, since the polymer compound is not exposed to heat, light, acid, alkali, or other chemical substances, a film of any size can be produced without decomposing or deactivating the functional group portion of the polymer compound. can do.

In addition, after forming a film of monomers having functional groups on the substrate, when UV rays are irradiated to the part where the polymer film is to be provided, the monomers in the parts irradiated with UV rays polymerize and form a polymer film. .

In this case, it is necessary that the monomer undergoes a polymerization reaction under ultraviolet light and that the functional group portion is not decomposed by ultraviolet light, but it is possible to produce a film with a more precise shape than the above method.

After forming a polymer film with functional groups on a substrate, photolithography is performed so that the photoresist covers only the areas where the polymer film is desired to remain, and plasma etching is performed to remove the areas not covered by the photoresist. Since the substrate surface is exposed by etching, a polymer film of any size and shape can be obtained by removing the photoresist.

After exposing the parts of the substrate where the polymer compound is to be provided by photolithography and covering the other parts with photoresist, a solution containing a polymer compound having a functional group, albumin, and a crosslinking agent is applied, and finally photo-coating is applied. When the resist is removed, an albumin crosslinked film containing a polymer compound having a functional group is formed only in desired areas. This method is particularly effective in the case of water-soluble polymer compounds, and it is possible to produce membranes with excellent biocompatibility, so it is suitable for application to biosensors, cell culture plates, etc.

(Example) Embodiments of the present invention will be explained using drawings.

Example 1 FIGS. 1(a) to (C) are shown in claim 1 of the present invention,
FIG. 3 is a cross-sectional view for explaining the manufacturing process of an example of a method for partially forming a polymer film having functional groups.

The manufacturing process will be explained in order. As shown in FIG. 1(a), a hydrophobic photoresist film 2 (0MR83 manufactured by Tokyo Ohka Chemical Co., Ltd.) was spin-coated on the surface of a clean sapphire substrate 1.

Next, as shown in FIG. 1(b), exposure using a photomask,
Image processing was then performed to remove the photoresist film from areas other than those to which the polymer film was to be applied. 1 at 150°C
After heat treatment for an hour, a chlorobenzene solution of 1% polyvinylferrocene (manufactured by Polyscience) was spin-coated and dried at room temperature. The polymer film 3 made of a chlorobenzene solution of polyvinylferrocene remained only on the hydrophobic surface of the photoresist, and the polymer film 3 was patterned as shown in FIG. 1(C).

Suitable polymer compounds that can be used in this method include polyethylene, polystyrene, and derivatives thereof, which are soluble in organic solvents. In addition, the method mentioned here to make the substrate surface hydrophobic was to apply a hydrophobic negative photoresist film, but if the film is hydrophobic, it can be applied using a positive deep photoresist or a monomolecular film containing an alkyl group. , a metal film, a metal oxide film, or the like.

Embodiment 2 FIGS. 2(a) to 2(c) are sectional views for explaining the manufacturing process of an embodiment of claim 1 of the present invention. The manufacturing process will be explained in order. As shown in FIG. 2(a), a pullulan film 4 was formed by spin coating an aqueous solution containing pullulan (manufactured by Wako Pure Chemical Industries, Ltd., average molecular weight 50,000 to 100,000) and potassium dichromate on the surface of a clean sapphire substrate 1. . Next, Figure 2(b)
Exposure and development were performed using a photomask as described above, and the part of the pullulan film 4 on which the polymer film was to be applied was washed with water and removed. A 1% polyvinylferrocene solution in chlorobenzene was then spin applied and allowed to dry at room temperature. The polymer film 3 made of a chlorobenzene solution of polyvinylferrocene remained on the part of the pullulan film 4 other than the coated hydrophilic surface, and the polymer film 3 was patterned as shown in FIG. 2(C).

As the hydrophilic film, a gel film made of a polysaccharide such as pullulan is suitable, and by treating a portion of the substrate surface to be hydrophilic using these, it is possible to prevent the formation of a polymer film. It is clear that by combining the hydrophilic film and the hydrophobic film mentioned in Example 1, good patterning of the polymer film is possible.

Embodiment 3 FIGS. 3(a) to 3(C) are sectional views of manufacturing steps for explaining an embodiment of claim 2. The manufacturing process will be explained in order. As shown in FIG. 3(a), a sodium p-styrene sulfonate aqueous solution was spin coated on the surface of a clean sapphire substrate 1 and dried to form a monomer film 5. Next, as shown in FIG. 3(b), a portion where a polymer film was to be formed was irradiated with a mercury lamp for 20 minutes using a photomask. Next, as shown in FIG. 3(c), the entire substrate was washed with water to remove the monomer, thereby obtaining a patterned polymer film 3.

The polymer film that can be produced by this method only needs to have monomers that have active groups, such as vinyl groups, that cause a polymerization reaction when irradiated with ultraviolet rays. This creates a polymer membrane.

Furthermore, if necessary, a sensitizer or a drug that promotes the polymerization reaction may be mixed into the monomer.

Embodiment 4 FIGS. 4(a) to 4(e) are sectional views for explaining an embodiment of claim 3 of the present invention. The manufacturing process will be explained in order. As shown in FIG. 4(a), a polymer film 3 consisting of a benzene solution of polystyrene sulfonic acid (manufactured by Polyscience Co., Ltd., molecular weight: 500,000) was spin-coated on the surface of a clean sapphire substrate 1 and dried. Next, as shown in FIG.
7) was spin-coated, exposed to light using a photomask, and developed to remove the photoresist film 7 at the portion where the polymer film 3 was to be removed, as shown in FIG. 4(C). Next, as shown in FIG. 4(d), the wafer was heat-treated at 150°C for 1 hour, and then heated to 13.56MH in oxygen at 0.1 Torr.
Etching was performed by applying a high frequency wave of 200 W for 2 hours. Finally, the remaining photoresist was dissolved and removed with acetone to form a polymer film 3 as shown in FIG. 4(e).

Since the photoresist used here is partially etched during the plasma etching process, the thickness of the photoresist should preferably be at least 10 times thicker than the thickness of the polymer film.

Embodiment 5 FIGS. 5(a) to 5(d) are sectional views for explaining an embodiment of claim 4 of the present invention. The manufacturing process will be explained in order. As shown in FIG. 5(a), a photoresist film 7 (MP-130 manufactured by Silapray Co., Ltd.) is coated on the surface of a clean sapphire substrate 1.
0-37) was spin-coated, exposed and developed using a photomask as shown in FIG. 5(b), and the photoresist film in the portion where the polymer film was to be formed was removed. 1%
After primer treatment with aminopropyltriethoxysilane, an aqueous solution of 1% polyvinyl alcohol, 15% bovine serum albumin, and 1% glutaraldehyde was spin-coated as shown in FIG. 5(C). Finally, the remaining photoresist was removed by dissolving it with acetone, and an albumin film (polymer film) 8 containing a polymer compound was formed as shown in FIG. 5(d).

This method is particularly effective for water-soluble polymer compounds such as polyacrylamide, carboxymethylcellulose, and polyamino acids, but it can also be used for non-water-soluble polymers.
It is possible to disperse it and introduce it into the albumin membrane.

Furthermore, since the polymer membrane produced by this method is based on an albumin membrane, it has excellent biocompatibility.

(Effects of the Invention) As described above, it is possible to pattern a polymer film using the hydrophobicity of a polymer compound, to polymerize a monomer with ultraviolet rays, to pattern a polymer film using plasma etching, or to pattern a polymer film using an albumin film. By taking methods such as forming a film, films of various polymer compounds having functional groups with useful functions, which are currently widely used, can be provided at arbitrary positions and dimensions on the substrate surface. It became possible. In particular, this method of patterning highly functional polymer compounds, which are not necessarily stable, into minute parts can be applied to the production of minute ion cells, enzyme sensors, immunoassay plates, cell culture plates, etc. be able to.

[Brief explanation of the drawing]

FIG. 1 is a sectional view of the manufacturing process for explaining the first embodiment of the present invention. FIG. 2 is a sectional view of the manufacturing process for explaining the second embodiment of the present invention. FIG. 3 is a sectional view of the manufacturing process for explaining the third embodiment of the present invention. FIG. 4 is a sectional view of the manufacturing process for explaining the fourth embodiment of the present invention. FIG. 5 is a sectional view of the manufacturing process for explaining the fifth embodiment of the present invention. In the figure, 1 is a sapphire substrate, 2 is a hydrophobic photoresist, 3 is a polymer film, 4 is a pullulan film, 5 is a monomer film, 6 is a photomask, 7 is a photoresist, and 8 is a polymer compound. It is an albumin membrane containing.

Claims (4)

[Claims] (1) In a method of forming a polymer film having a functional group on a part of the substrate surface, the surface of the substrate is made so that a part of the substrate surface on which the polymer film is desired to be formed is more hydrophobic than other parts. and coating the substrate with a solution of a polymer compound that has a functional group and has a high affinity with the hydrophobically treated area to form a film of the polymeric compound on the hydrophobically treated area. 1. A method for partially forming a polymer film having a functional group, comprising the steps of: (2) A method for forming a polymer film having functional groups on a part of the substrate surface, which includes the step of forming a monomer film having functional groups on the entire surface of the substrate, and the formation of the polymer film. A step of irradiating a desired part of the surface of the substrate with ultraviolet rays to polymerize the monomers to form a polymer film, and a step of cleaning the substrate with a solvent that dissolves only the monomers to remove them. 1. A method for partially forming a polymer membrane having a functional group, characterized by comprising: (3) A method for forming a polymer film having a functional group on a part of the surface of a substrate, which includes a step of forming a film of a polymer compound having a functional group on the entire surface of the substrate, and applying a photoresist to the substrate. After coating, a step of removing the photoresist on the surface on which a polymer film is desired to be formed using a photolithography method, a step of removing the exposed polymer film on the surface of the substrate using a plasma etching method, and a step of removing the photoresist. A method for partially forming a polymer membrane having a functional group, comprising: (4) In the method of forming a polymer film having a functional group on a part of the substrate surface, a photoresist is applied to the substrate and then the photoresist on the surface on which the polymer film is desired to be formed is removed by photolithography. a step of applying a solution containing a polymer compound having a functional group, albumin, and a crosslinking agent to the substrate; and dissolving the photoresist and removing the polymer film on areas other than the predetermined surface. , a method for partially forming a polymer membrane having functional groups.