Polymer-coated glass base material

Abstract

To provide a polymer-coated glass base material on which the adsorption of normal cells such as blood cells is prevented and onto which a specific type of cells such as cancer cells, stem cells, and T cells can be selectively adsorbed.SOLUTION: The present invention pertains to a polymer-coated glass base material in which one or more polymer layers are formed on the surface of a glass base material, wherein the glass is a soda lime glass having a contact angle of an air bubble in water of 100 degrees to 120 degrees inclusive, and the surface of an outermost layer among the polymer layers has an elastic modulus of 1.20 MPa or less in water or in an aqueous solution.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a polymer-coated glass substrate.

Background Art

[0002] In order to produce an instrument for adsorbing specific cells (blood cells, cancer cells, stem cells, T cells, etc.) in blood and body fluids, a technique of coating the surface of a substrate with a special polymer has been proposed.

[0003] However, there is a concern that while specific cells such as cancer cells, stem cells, and T cells are adsorbed on the surface of the substrate, blood cells are also adsorbed. Therefore, there is a demand for providing a polymer-coated substrate that can more selectively adsorb specific cells such as cancer cells, stem cells, and T cells while suppressing the adsorption of normal cells such as blood cells.

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object of the present invention is to provide a polymer-coated glass substrate that solves the above problems, suppresses the adsorption of normal cells such as blood cells, and can selectively adsorb specific cells such as cancer cells, stem cells, and T cells.

Means for Solving the Problems

[0005] The present invention is a polymer-coated glass substrate in which one or two or more polymer layers are formed on the surface of a glass substrate, wherein the glass is soda-lime glass having a contact angle of bubbles in water of 100 degrees or more and 120 degrees or less, and the surface of the outermost layer of the polymer layer has an elastic modulus of 1.20 MPa or less in water or an aqueous solution.

Effects of the Invention

[0006] According to the present invention, there is provided a polymer-coated glass substrate having one or more polymer layers formed on the surface of a glass substrate, wherein the glass is soda-lime glass having a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less, and the surface of the outermost layer of the polymer layer is a polymer-coated glass substrate having an elastic modulus of 1.20 MPa or less in water or an aqueous solution. Therefore, adsorption of normal cells such as blood cells is suppressed, and selective adsorption of specific cells such as cancer cells, stem cells, and T cells is possible. Accordingly, improvement in the adsorption performance of specific cells such as cancer cells, stem cells, and T cells can be expected with the polymer-coated glass substrate.

Mode for Carrying Out the Invention

[0007] The above polymer-coated glass substrate is a polymer-coated glass substrate having one or more polymer layers formed on the surface of a glass substrate, wherein the glass is soda-lime glass having a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less, and the surface of the outermost layer of the polymer layer has an elastic modulus of 1.20 MPa or less in water or an aqueous solution.

[0008] Tumor cells (such as cancer cells) that appear in body fluids such as circulating tumor cells in blood (several to several hundred cells / 1 mL of blood) are extremely few in number. To use them for testing, it is considered important to adsorb as many tumor cells present in the collected body fluid as possible. The polymer-coated glass substrate uses soda-lime glass as the glass substrate coated with the polymer, and the contact angle of air bubbles in water is 100 degrees or more and 120 degrees or less. In addition, the elastic modulus of the outermost surface layer of the polymer layer formed on the substrate surface in water or an aqueous solution is 1.20 MPa or less. It is generally known that specific cells such as cancer cells are softer than normal cells such as blood cells. This is related to the fact that when specific cells such as cancer cells metastasize, they greatly deform the shape of the cells and move through the gaps. For this reason, normal cells such as blood cells that are difficult to deform and hard are less likely to be adsorbed to a polymer substrate with a soft surface. On the other hand, specific cells such as cancer cells that have acquired deformability are likely to be adsorbed even on a polymer substrate with a soft surface. Also, if the elastic modulus of the surface is too low, the adsorptivity will conversely decrease. That is, there is an optimal value for the elastic modulus of the surface. In the above polymer-coated glass substrate, soda-lime glass with a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less is used as the glass substrate, and one or more polymer layers with an elastic modulus of the surface in water or an aqueous solution of 1.20 MPa or less are formed on such a substrate. It is possible to significantly exert the effect of selectively adsorbing specific cells such as cancer cells, stem cells, and T cells while suppressing the adsorption of normal cells such as blood cells. By measuring the number of tumor cells adsorbed on the polymer layer of the polymer-coated glass substrate, the number of tumor cells in the body fluid can be known, and it is possible to expect confirmation of the cancer treatment effect and the like. In addition, by culturing the adsorbed tumor cells and confirming the efficacy of anticancer drugs and the like with the cultured cells, it is possible to confirm the efficacy of anticancer drugs and the like outside the body before administration of the anticancer drugs and the like, and at the same time, it is also useful for the selection of anticancer drugs and the like. Furthermore, by performing genetic analysis of the adsorbed tumor cells, it is useful for the selection of anticancer drugs and the like. Also, genetic analysis is performed on the adsorbed or cultured tumor cells to examine the mutation state and expression state of the tumor cells, which can be used for the selection of anticancer drugs and the like or for elucidating the mechanism of cancer.

[0009] The glass constituting the glass substrate is soda-lime glass. The soda-lime glass may have a group represented by -N(R 1 )2 and / or -N(R 2 )3 + (R 1 and R 2 are each independently a hydrogen atom or a substituted or unsubstituted hydrocarbon group which may contain a hetero atom). In this case, it tends to effectively exhibit the effect of suppressing the adsorption of normal cells such as blood cells and selectively adsorbing specific cells such as cancer cells, stem cells, and T cells.

[0010] Regarding the "group represented by -N(R 1 )2 and / or -N(R 2 )3 + ", R 1 in the group represented by -N(R 1 )2 and R 2 in the group represented by -N(R + )3 2 are each independently (1) a hydrogen atom or (2) a substituted or unsubstituted hydrocarbon group which may contain a hetero atom.

[0011] The substituted or unsubstituted hydrocarbon group which may contain a hetero atom for R 1 to R 2 may be any of linear, branched or cyclic groups. The hetero atom is not particularly limited and examples include oxygen, nitrogen, etc. The substituent is not particularly limited and examples include known groups such as a hydroxyl group, a halogen group (-Cl, -Br, etc.). These hetero atoms and substituents may be present singly or in plural.

[0012] The number of carbon atoms of the substituted or unsubstituted hydrocarbon group which may contain a hetero atom is preferably 1 to 20, more preferably 1 to 10, still more preferably 1 to 8.

[0013] Examples of the substituted or unsubstituted hydrocarbon group which may contain a heteroatom include a monovalent hydrocarbon group, a divalent hydrocarbon group, and the like.

[0014] Examples of the substituted or unsubstituted monovalent hydrocarbon group which may contain a heteroatom include a substituted or unsubstituted linear alkyl group, a branched alkyl group, a cyclic alkyl group, a cyclic ether group, an aryl group, an aralkyl group, an alkoxy group, and the like which may contain a heteroatom.

[0015] Examples of the substituted or unsubstituted linear alkyl group or branched alkyl group which may contain a hetero atom include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an iso-butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, a 2-ethylhexyl group, an octyl group, a nonyl group, a decyl group, and groups containing these hetero atoms. Examples of the substituted or unsubstituted cyclic alkyl group which may contain a hetero atom include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, an adamantyl group, a 1-ethylcyclopentyl group, a 1-ethylcyclohexyl group, and groups containing these hetero atoms. Examples of the substituted or unsubstituted cyclic ether group which may contain a hetero atom include an oxirane group, an oxetane group, an oxolane group, an oxane group, an oxepane group, an oxocane group, an oxonan group, an oxecane group, an oxet group, an oxol group, a dioxolane group, a dioxane group, a dioxepane group, a dioxecane group, etc., and groups containing these hetero atoms. Examples of the substituted or unsubstituted aryl group which may contain a hetero atom include a phenyl group, a tolyl group, a xylyl group, a biphenyl group, a naphthyl group, an anthryl group, a phenanthryl group, and groups containing these hetero atoms. Examples of the substituted or unsubstituted aralkyl group which may contain a hetero atom include a benzyl group, a phenethyl group, and groups containing these hetero atoms. Examples of the substituted or unsubstituted alkoxy group which may contain a hetero atom include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a sec-butoxy group, an iso-butoxy group, a t-butoxy group, an n-pentyloxy group, an n-hexyloxy group, and groups containing these hetero atoms.

[0016] Examples of the substituted or unsubstituted divalent hydrocarbon group which may contain a hetero atom include, for example, a substituted or unsubstituted alkylene group, alkenylene group, cycloalkylene group, cycloalkylalkylene group, arylene group, aralkylene group, oxyalkylene group, etc., which may contain a hetero atom.

[0017] Specific examples of the substituted or unsubstituted alkylene group which may contain a hetero atom include a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, an octylene group, a nonylene group, a decylene group, a 1,2-propylene group, and groups containing these hetero atoms. Specific examples of the substituted or unsubstituted alkenylene group which may contain a hetero atom include a vinylene group, a 1-propenylene group, a 2-propenylene group, and groups containing these hetero atoms. Specific examples of the substituted or unsubstituted cycloalkylene group which may contain a hetero atom include a cyclohexylene group, and groups containing this hetero atom. Specific examples of the substituted or unsubstituted cycloalkylalkylene group which may contain a hetero atom include a cyclohexylmethylene group, and groups containing this hetero atom. Specific examples of the substituted or unsubstituted arylene group which may contain a hetero atom include a phenylene group, a tolylene group, a xylylene group, and groups containing these hetero atoms. Specific examples of the substituted or unsubstituted aralkylalkylene group which may contain a hetero atom include a benzylidene group, and groups containing this hetero atom. Specific examples of the substituted or unsubstituted oxyalkylene group which may contain a hetero atom include an oxyethylene group, an oxypropylene group, an oxybutylene group, an oxytetramethylene group, and groups containing these hetero atoms.

[0018] "-N(R 1 )2 and / or -N(R 2 )3 + The substrate surface of the soda-lime glass having a group represented by" can be produced by using any method capable of introducing a group represented by -N(R 1 )2 and / or -N(R 2 )3 + onto the surface of the substrate. Examples of the introduction method include, for example, treatment of the substrate surface with a silane coupling agent having a group represented by -N(R 1 )2 and / or -N(R 2 )3 + (treatment with a silane coupling agent), treatment of the substrate surface with NH3 gas (NH3 gas treatment), and the like. Among them, treatment with a silane coupling agent is preferred.

[0019] -N(R 1 )2 and / or -N(R 2 )3 + The silane coupling agent having a group represented by is not particularly limited. For example, a compound having a group represented by -N(R 1 )2 and / or -N(R 2 )3 + and a group represented by -Si(R 3 )3 (R 1 and R 2 are each the same or different and are a hydrogen atom or a substituted or unsubstituted hydrocarbon group which may contain a hetero atom. R 3 is a substituted or unsubstituted hydrocarbon group which may contain a hetero atom, the same or different.) etc. can be used.

[0020] In the “group represented by -Si(R 3 )3”, R 3 is a substituted or unsubstituted hydrocarbon group which may contain a hetero atom, the same or different. Examples of the substituted or unsubstituted hydrocarbon group which may contain a hetero atom include, for example, the same groups as the substituted or unsubstituted monovalent hydrocarbon groups which may contain a hetero atom of the aforementioned R 1 and R 2 . Among them, a linear alkyl group, a branched alkyl group, a cyclic alkyl group, and an alkoxy group are preferable. Specific examples of the linear alkyl group, the branched alkyl group, the cyclic alkyl group, and the alkoxy group include the same groups as the aforementioned R 1 and R 2 (methyl group, ethyl group, methoxy group, ethoxy group, etc.). Further, it is preferable that at least one of R 3 is an alkoxy group, more preferably 2, and even more preferably 3.

[0021] -N(R 1 )2 and / or -N(R 2 )3 + and a group represented by -Si(R 3)Examples of the compound having a group represented by 3 include compounds represented by the following formulas (A-1) and (A-2), which can be preferably used.

[0022]

Chemical formula

[0023]

Chemical formula

[0024] Examples of the "substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom" of R 11 , R 12 , R 13 in formulas (A-1) and (A-2) include, for example, the same groups as the substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom of the aforementioned R 1 ~R 2 . Among them, R 11 , R 12 , R 13 are preferably a hydrogen atom, a linear alkyl group or a branched alkyl group which may contain a hetero atom, a hydrogen atom, a linear alkyl group, a branched alkyl group, -Cp H 2p -O-C q H 2q+1 (p, q are integers) is more preferred.

[0025] R in formulas (A-1) and (A-2) 16 , R 17 , R 18 Examples of the "optionally substituted or unsubstituted monovalent hydrocarbon group which may contain a heteroatom" of are, for example, the same groups as the optionally substituted or unsubstituted monovalent hydrocarbon group which may contain a heteroatom of the aforementioned R 1 ~R 2 . Among them, R 16 , R 17 , R 18 is preferably an optionally substituted or unsubstituted alkoxy group which may contain a heteroatom, more preferably an alkoxy group, and even more preferably a methoxy group or an ethoxy group.

[0026] R in formulas (A-1) and (A-2) 19 Examples of the "optionally substituted or unsubstituted divalent hydrocarbon group which may contain a heteroatom" of are, for example, the same groups as the optionally substituted or unsubstituted divalent hydrocarbon group which may contain a heteroatom of the aforementioned R 1 ~R 2 . In addition to those exemplified as specific examples of the optionally substituted or unsubstituted divalent hydrocarbon group which may contain a heteroatom of the aforementioned R 1 , groups represented by -CO-N(R 111 )-(R 112 )- (R 111 represents a hydrogen atom or an alkyl group. R 112 is -C p H 2p -(p is an integer from 1 to 8) and the like can also be mentioned. Among them, R 19 is preferably an optionally substituted or unsubstituted alkylene group which may contain a heteroatom, or a group represented by -CO-N(R 111 )-(R 112 )-, and more preferably a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, or a group represented by -CO-N(R 111 )-(R 112 )-.

[0027] Examples of the halogen of X in formula (A-2) include chlorine (chloride ion), bromine (bromide ion), and the like.

[0028] -NR 1 2 and / or -NR 1 3 + As the compound having a group represented by and a group represented by -Si(R 2 )3, a compound represented by the following formula (A-3) can also be preferably used.

[0029]

Chemical formula

[0030] Examples of the "substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom" of R 21 , R 22 , R 23 in formula (A-3) include, for example, the same groups as the substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom of R 1 ~R 2 described above. Among them, R 21 , R 22 , R 23 are preferably a hydrogen atom, a linear alkyl group or a branched alkyl group which may contain a hetero atom, and more preferably a hydrogen atom.

[0031] Examples of the "substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom" of R 24 , R 25 , R 26 in formula (A-3) include, for example, the same as those of R1 ~R 2 Examples of the group similar to a substituted or unsubstituted monovalent hydrocarbon group which may contain a hetero atom are as follows. Among them, R 24 、R 25 、R 26 is preferably a substituted or unsubstituted alkoxy group which may contain a hetero atom, more preferably an alkoxy group, and still more preferably a methoxy group or an ethoxy group.

[0032] Examples of the "substituted or unsubstituted divalent hydrocarbon group which may contain a hetero atom" of R 27 、R 28 、R 29 、R 30 in formula (A-3) include, for example, groups similar to the substituted or unsubstituted divalent hydrocarbon groups which may contain a hetero atom of R 1 ~R 2 described above. Among them, R 27 、R 28 、R 29 、R 30 is preferably a substituted or unsubstituted alkylene group which may contain a hetero atom, and more preferably a methylene group, an ethylene group, a trimethylene group or a tetramethylene group.

[0033] Examples of the halogen of X in formula (A-3) include chlorine (chloride ion), bromine (bromide ion) and the like.

[0034] The degree of polymerization of the structural unit represented by formula (A-3) is not particularly limited, and may be appropriately selected in consideration of the processability (coating property) of the compound, the adhesiveness to the hydrophilic polymer layer, and the like.

[0035] The number average molecular weight (Mn) of the compound (polymer) represented by the above formula (A-3) is preferably 500 to 6000, more preferably 1000 to 4000, and still more preferably 1000 to 3000.

[0036] -N(R 1)Specific examples of the silane coupling agent having a group represented by 2 include 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltriisopropoxysilane, 3-aminopropylmethyldimethoxysilane, 3-aminopropylmethyldiethoxysilane, 3-(2-aminoethyl)aminopropyltrimethoxysilane, 3-(2-aminoethyl)aminopropylmethyldimethoxysilane, 3-(2-aminoethyl)aminopropyltriethoxysilane, 3-(2-aminoethyl)aminopropylmethyldiethoxysilane, 3-(2-aminoethyl)aminopropyltriisopropoxysilane, 3-(2-(2-aminoethyl)aminoethyl)aminopropyltrimethoxysilane, 3-(6-aminohexyl)aminopropyltrimethoxysilane, 3-(N-ethylamino)-2-methylpropyltrimethoxysilane, N-phenyl-3-aminopropyltrimethoxysilane, N-benzyl-3-aminopropyltrimethoxysilane, N-vinylbenzyl-3-aminopropyltriethoxysilane, N-cyclohexylaminomethyltriethoxysilane, N-cyclohexylaminomethyldiethoxymethylsilane, N-phenylaminomethyltrimethoxysilane, (2-aminoethyl)aminomethyltrimethoxysilane and other amino group-containing silane coupling agents;3-Ureidopropyltrimethoxysilane (1-[3-(trimethoxysilyl)propyl]urea), 3-ureidopropyltriethoxysilane, 3-ureidopropyltriisopropoxysilane, 3-ureidopropylmethyldimethoxysilane, 3-ureidopropylmethyldiethoxysilane, ureidomethyltrimethoxysilane, ureidomethyltriethoxysilane, ureidomethyltriisopropoxysilane, ureidomethylmethyldimethoxysilane, ureidomethylmethyldiethoxysilane, 3-[(2-ureidoethyl)amino]propyltrimethoxysilane, 1,3-bis[3-(trimethoxysilyl)propyl]urea, 1,3-bis[3-(triethoxysilyl)propyl]urea, 1-[3-(triethoxysilyl)propyl]-3-phenylurea, 1,3-bis[3-(tripropylsilyl)propyl]urea, 1-[3-(triethoxysilyl)propyl]-3,3-dioctylurea, 1-[3-(triethoxysilyl)propyl]-3,3-dihexadecylurea, 1-[3-(triethoxysilyl)propyl]-3-propylurea, 3-(3-dodecylureido)propyltriethoxysilane, N-(1-phenylethyl)-N’-[3-(triethoxysilyl)propyl]urea and other silane coupling agents having a urea group; etc. are mentioned.;

[0037] -N(R 1 )3 +Specific examples of the silane coupling agent having a group represented by include N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (N-TRIMETHOXYSILYLPROPYL-N,N,N-TRI-METHYLAMMONIUM CHLORIDE), N-trimethoxysilylpropyl-N,N,N-tri-n-butylammonium chloride (N-TRIMETHOXYSILYLPROPYL-N,N,N-TRI-n-BUTYLAMMONIUM CHLORIDE), octadecyldimethyl(3-trimethoxysilyl-propyl)ammonium chloride (OCTADECYLDIMETHYL(3-TRIMETHOXYSILYL-PROPYL)AMMONIUM CHLORIDE), N-(trimethoxysilylethyl)benzyl-N,N,N-trimethylammonium chloride (N-(TRIMETHOXYSILYLETHYL)BENZYL-N,N,N-TRIMETHYLAMMONIUM CHLORID), N,N-didecyl-N-methyl-N-(3-trimethoxysilyl-propyl)ammonium chloride (N,N-DIDECYL-N-METHYL-N-(3-TRIMETHOXYSILYL-PROPYL)AMMONIUM CHLORIDE), bis(methoxyethyl)-3-trimethoxysilylpropylammonium chloride (BIS(METHOXYETHYL)-3-TRIMETHOXYSILYLPROPYLAMMONIUM CHLORIDE), trimethoxysilylpropyl modified (polyethyleneimine) (TRIMETHOXYSILYLPROPYL MODIFIED(POLYETHYLENIMINE)), dimethoxymethylsilylpropyl modified (polyethyleneimine) (DIMETHOXYMETHYLSILYLPROPYL MODIFIED(POLYETHYLENIMINE)), and the like.

[0038] Among them, 3-aminopropyltriethoxysilane, bis(methoxyethyl)-3-trimethoxysilylpropylammonium chloride, trimethoxysilylpropyl modified (polyethyleneimine), N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride are preferred. These -N(R 1 )2 and / or -N(R 1 )3 + groups represented by -N(R 1 )2 and / or -N(R 1 )3 + The silane coupling agent having the group represented by may be used alone or in combination of two or more.

[0039] The method of treating with a silane coupling agent (treatment of the substrate surface with a silane coupling agent having a group represented by -N(R 1 )2 and / or -N(R 1 )3 + ) is not particularly limited, and any method capable of coating (treating) the silane coupling agent on the substrate surface can be used. Specifically, a substrate coated (treated) with a silane coupling agent can be produced by a known method such as applying (coating), spraying (spraying), or dipping a silane coupling agent solution or dispersion in which the silane coupling agent is dissolved or dispersed in various solvents onto the substrate surface. Known methods can be used for the coating method, spraying method, and dipping method.

[0040] The solvent is not particularly limited as long as it can dissolve and disperse the silane coupling agent, and can be appropriately selected according to the silane coupling agent to be used. For example, water, organic solvents, and mixed solvents thereof can be mentioned. Examples of organic solvents include alcohols such as methanol, ethanol, n-propanol, i-propanol, and methoxypropanol; ketones such as acetone and methyl ethyl ketone; tetrahydrofuran, acetonitrile, ethyl acetate, toluene, and the like.

[0041] The concentration of the silane coupling agent solution / dispersion can be appropriately set according to the type of silane coupling agent, solvent, treatment method (coating method, spraying method, dipping method), etc.

[0042] The treatment conditions such as the treatment temperature and treatment time for the silane coupling agent treatment can be appropriately set according to the type of silane coupling agent, solvent, treatment method, etc. However, when treating (coating, spraying, dipping, etc.) the silane coupling agent solution / dispersion on the substrate surface, it is preferable to carry out the treatment (holding) under the condition of a humidity of 50% or more. Thereby, the chemical bond between the substrate surface and the silane coupling agent tends to become stronger. The above humidity is more preferably 60% or more, and even more preferably 80% or more. The upper limit is not particularly limited, but for example, 100% or less is preferable.

[0043] When carrying out the treatment (holding) under the condition of a humidity of 50% or more, the treatment time and treatment temperature can be appropriately set from viewpoints such as the strengthening of the chemical bond between the substrate surface and the silane coupling agent and economic viewpoints. For example, the treatment time (holding time) is preferably 1 to 60 hours, and more preferably 1 to 20 hours. The treatment temperature (holding temperature) is preferably 20 to 65°C, and more preferably 25 to 50°C.

[0044] As the substrate whose surface is coated (treated) with the silane coupling agent, in addition to those produced by the aforementioned method, commercially available products can also be used. As commercially available products treated with the silane coupling agent, for example, MAS-coated slide glass, MAS-GP type coated slide glass, Frontier-coated slide glass, APS-coated slide glass (manufactured by Matsunami Glass Industry Co., Ltd.), etc. can be used.

[0045] At least a part (part or all) of the substrate surface having a group represented by -N(R 1 )2 and / or -N(R 2 )3 + From the viewpoint of the adhesion of the polymer layer to the substrate surface, the contact angle of water is preferably 50 to 120 degrees, more preferably 70 to 100 degrees.

[0046] The soda-lime glass has a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less. The soda-lime glass having a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less can be appropriately selected from commercially available products and the like.

[0047] The contact angle of air bubbles in water of the soda-lime glass is more preferably 103 degrees or more, and more preferably 117 degrees or less. In this specification, the "contact angle of air bubbles in water" is a value obtained by attaching air bubbles to the substrate surface in water and measuring the contact angle between the air bubbles and the substrate surface. It can be measured under the measurement conditions of a water temperature of room temperature (20 °C) and air bubbles of 2 μL.

[0048] The thickness of the glass substrate made of the soda-lime glass is not particularly limited, but the average thickness is preferably 100 μm or more and 5000 μm or less, more preferably 500 μm or more and 3000 μm or less. The average thickness is a value obtained by measuring the thickness at any 10 locations using a micrometer and averaging the measured values.

[0049] The above polymer-coated glass substrate has one or more polymer layers formed on the surface of the above glass substrate. The polymer layer may be formed of one layer or two or more layers. In particular, when the surface of the above soda-lime glass substrate has a group represented by -N(R 1 )2 and / or -N(R 2 )3 + (R 1 and R 2 are each independently a hydrogen atom or a substituted or unsubstituted hydrocarbon group which may contain a hetero atom.), it is desirable that two or more polymer layers are formed.

[0050] As the polymer constituting the above one or more polymer layers, known ones can be appropriately used. Examples of the above polymer include a homopolymer of one kind of monomer and a copolymer of two or more kinds of monomers. For example, a polymer having hydrophilicity (hydrophilic polymer) can be preferably used as the polymer. The above polymers may be used alone or in combination of two or more.

[0051] The above polymer can be produced by a known method. For example, it can be synthesized by polymerizing a monomer by a known method using a solution of the monomer constituting the polymer. The solvent of the monomer solution is not particularly limited, and for example, the solvents described below can be used. Among them, toluene and methanol are preferable.

[0052] From the viewpoint of obtaining more effects, it is desirable that the outermost surface layer (the polymer layer formed on the outermost (surface side)) of the above one or more polymer layers of the above polymer-coated glass substrate is formed of a hydrophilic polymer.

[0053] Examples of the above hydrophilic polymer include homopolymers and copolymers of one or more hydrophilic monomers, copolymers of one or more hydrophilic monomers and one or more other monomers, and the like. These may be used alone or in combination of two or more.

[0054] The above hydrophilic monomer is not particularly limited, and for example, various monomers having a hydrophilic group can be used. Examples of the hydrophilic group include known hydrophilic groups such as an amide group, a sulfate group, a sulfonic acid group, a carboxylic acid group, a hydroxyl group, an amino group, and an oxyethylene group.

[0055] Specific examples of the above hydrophilic monomer include (meth)acrylic acid, (meth)acrylate esters (such as alkoxyalkyl (meth)acrylates like methoxyethyl (meth)acrylate and hydroxyalkyl (meth)acrylates like hydroxyethyl (meth)acrylate), (meth)acrylamide, (meth)acrylamide derivatives having a cyclic group ((meth)acryloylmorpholine, etc.). Among them, (meth)acrylic acid, (meth)acrylate esters, and alkoxyalkyl (meth)acrylates are preferred, alkoxyalkyl (meth)acrylates are more preferred, and 2-methoxyethyl acrylate is particularly preferred. These may be used alone or in combination of two or more.

[0056] The above other monomers may be appropriately selected within the range that does not inhibit the action and effect of the hydrophilic polymer. Specific examples of the above other monomers include, for example, aromatic monomers such as styrene, vinyl acetate, and N-isopropylacrylamide that can impart temperature responsiveness. These may be used alone or in combination of two or more.

[0057] Specific examples of the above homopolymer and copolymer include homopolymers composed of one kind of hydrophilic monomer such as polyacrylic acid, polyacrylate ester, polymethacrylic acid, polymethacrylate ester, polyacryloylmorpholine, polymethacryloylmorpholine, polyacrylamide, polymethacrylamide, polyalkoxyalkyl acrylate, and polyalkoxyalkyl methacrylate; copolymers composed of two or more of the above-exemplified hydrophilic monomers; copolymers composed of one or more of the above-exemplified hydrophilic monomers and one or more of the above-exemplified other monomers; and the like. The above hydrophilic polymer may be used alone or in combination of two or more.

[0058] Among them, as the hydrophilic polymer, a polymer represented by the following formula (I) is preferable. These may be used alone or in combination of two or more kinds.

Chemical formula

[0059] As the polymer represented by the above formula (I), for example, a polymer represented by the following formula (I-1) can be preferably used. These may be used alone or in combination of two or more kinds.

Chemical formula

[0060] R 52 The alkyl group preferably has 1 to 10 carbon atoms, more preferably 1 to 5 carbon atoms. Among them, R 52 is particularly preferably a methyl group or an ethyl group. p is preferably 1 to 5, more preferably 1 to 3. m is preferably 1 to 3. n (the number of repeating units) is preferably 15 to 1500, more preferably 40 to 1200.

[0061] As the hydrophilic polymer, a copolymer of a compound represented by the following formula (II) and another monomer can also be preferably used. These may be used alone or in combination of two or more kinds.

[0062]

Chemical formula

[0063] As the compound represented by the above formula (II), for example, a compound represented by the following formula (II-1) can be preferably used. These may be used alone or in combination of two or more.

Chemical Formula

[0064] Among the above hydrophilic polymers, from the viewpoint of obtaining better effects, the hydrophilic polymer represented by the above formula (I) is preferable, and the hydrophilic polymer represented by the above formula (I-1) is particularly preferable.

[0065] The number average molecular weight (Mn) of the polymer constituting the outermost surface layer of the above one or more polymer layers is preferably 8,000 to 150,000, more preferably 10,000 to 60,000, and still more preferably 10,000 to 39,000 from the viewpoint of obtaining better effects. When the polymer is a hydrophilic polymer, it is desirable that the number average molecular weight (Mn) is the same.

[0066] In this specification, the number average molecular weight (Mn) and the weight average molecular weight (Mw) can be determined by standard polystyrene conversion based on the measured values by gel permeation chromatography (GPC) (GPC-8000 series manufactured by Tosoh Corporation, detector: differential refractometer, column: TSKGEL SUPERMULTIPORE HZ-M manufactured by Tosoh Corporation).

[0067] The total thickness of the above one or more polymer layers (the total thickness of the polymer layer composed of one or more layers) is preferably 10 to 4,000 nm, more preferably 30 to 2,000 nm, and still more preferably 50 to 500 nm. By adjusting within the above range, good low adsorption to proteins and cells and selective adsorption to cancer cells can be expected. In addition, when the outermost surface layer is a hydrophilic polymer layer (a layer formed by a hydrophilic polymer), it is desirable that the total thickness (total film thickness) is the same. In this specification, the total thickness of the polymer layer can be measured by a transmission electron microscope (TEM).

[0068] At least a part (part or all) of the surface of the polymer layer (the outermost surface layer of one or more polymer layers in the polymer-coated glass substrate) preferably has a water contact angle of 65 degrees or less, more preferably 60 degrees or less, and still more preferably 55 degrees or less. Also, the water contact angle is preferably 25 degrees or more, and more preferably 35 degrees or more.

[0069] The polymer-coated glass substrate in which a polymer layer (hereinafter, also referred to as a "blended polymer layer") composed of a blend of polymers having different molecular weights is formed on the surface of the soda-lime glass substrate can also be preferably used. The hydrophilic polymers having different molecular weights may include two polymers of the same polymer having different molecular weights (for example, a blend of polymers containing poly(2-methoxyethyl acrylate) having a number average molecular weight of 16,000 and poly(2-methoxyethyl acrylate) having a number average molecular weight of 80,000), or may include polymers having different molecular weights of different polymers (polymers having different structures) (for example, a blend of polymers containing poly(2-methoxyethyl acrylate) having a number average molecular weight of 16,000 and polyacryloylmorpholine having a number average molecular weight of 80,000). Among them, it is desirable that the blended polymer layer is formed of polymers of the same polymer having different molecular weights.

[0070] The polymer constituting the blend polymer layer preferably contains polymers represented by the above formula (I) having different molecular weights. Here, the polymers represented by the above formula (I) having different molecular weights may include two or more polymers composed of the same structural units and having different molecular weights (for example, those containing poly(2-methoxyethyl acrylate) with a number average molecular weight of 16,000 and poly(2-methoxyethyl acrylate) with a number average molecular weight of 80,000), or may include two or more polymers composed of different structural units and having different molecular weights (for example, those containing poly(2-methoxyethyl acrylate) with a number average molecular weight of 16,000 and poly(2-ethoxyethyl methacrylate) with a number average molecular weight of 80,000). The polymer represented by the above formula (I) may be either one kind or two or more kinds.

[0071] In the polymers having different molecular weights as described above, the molecular weight is not particularly limited, and examples include number average molecular weight (Mn), weight average molecular weight (Mw), and the like. Among them, blends of polymers having different Mn can be preferably used.

[0072] When using a blend of polymers having different Mn as described above, it preferably contains a polymer having a difference in Mn of 30,000 or more, and more preferably contains a hydrophilic polymer having a difference in Mn of 50,000 or more.

[0073] The blend of polymers having different molecular weights as described above preferably contains a low molecular weight polymer having a number average molecular weight (Mn) of 5,000 or more and 25,000 or less. The Mn of the above low molecular weight polymer is preferably 10,000 or more, more preferably 14,000 or more, and preferably 23,000 or less. Further, the blend of polymers having different molecular weights as described above preferably contains a high molecular weight polymer having a number average molecular weight (Mn) of 35,000 or more and 200,000 or less. The Mn of the above high molecular weight polymer is preferably 40,000 or more, more preferably 50,000 or more, and preferably 150,000 or less, more preferably 130,000 or less.

[0074] The above polymer layer can be formed on all or part of the surface of a glass substrate to produce a polymer-coated glass substrate by known methods such as (1) injecting a polymer solution or dispersion in which the polymer is dissolved or dispersed in various solvents onto the surface of the glass substrate (such as in a substrate recess), holding for a predetermined time, and drying; or (2) coating (spraying) the polymer solution or dispersion onto the surface of the glass substrate and drying if necessary. Then, by adding other components to the polymer-coated glass substrate as needed, an apparatus capable of adsorbing, culturing, and inspecting specific cells can be manufactured.

[0075] Conventionally known materials and methods can be applied to the solvent, injection method, coating (spraying) method, etc. The holding and drying times in (1) and (2) can be appropriately set according to the size of the substrate, the type of liquid to be introduced, etc. The holding time is preferably 10 seconds to 10 hours, more preferably 1 minute to 5 hours, and even more preferably 5 minutes to 2 hours. Drying is preferably carried out at room temperature (about 23°C) to 80°C, and more preferably at room temperature to 60°C. Also, drying under reduced pressure may be carried out. Further, after holding for a certain time, the excess polymer solution or dispersion may be appropriately discharged and then dried.

[0076] The solvent is not particularly limited as long as it can dissolve the polymer, and can be appropriately selected according to the polymer to be used. For example, water, organic solvents, and mixed solvents thereof can be mentioned. Examples of organic solvents include alcohols such as methanol, ethanol, n-propanol, i-propanol, and methoxypropanol; ketones such as acetone and methyl ethyl ketone; tetrahydrofuran, acetonitrile, ethyl acetate, toluene, etc.

[0077] The concentration of the above polymer solution or dispersion is not particularly limited and can be appropriately selected considering injectability, coatability, sprayability, productivity, etc. However, the concentration of the polymer in the polymer solution or dispersion (100% by mass) is preferably 0.1 to 10.0% by mass, and more preferably 0.2 to 5.0% by mass.

[0078] The outermost surface layer of the one or more polymer layers formed on the surface of the glass substrate has an elastic modulus in water or an aqueous solution of 1.20 MPa or less. From the viewpoint of suppressing the adsorption of normal cells such as blood cells and selectively adsorbing specific cells such as cancer cells, the elastic modulus is preferably 1.00 MPa or less, more preferably 0.85 MPa or less, and still more preferably 0.75 MPa or less. The lower limit is preferably 0.02 MPa or more, more preferably 0.04 MPa or more, still more preferably 0.45 MPa or more, and particularly preferably 0.50 MPa or more.

[0079] The elastic modulus in water or an aqueous solution of the surface of the outermost surface layer can be adjusted by changing the molecular weight and film thickness of the polymer forming the outermost surface layer. Specifically, as the molecular weight of the polymer increases, the elastic modulus tends to increase, and as the film thickness of the polymer layer increases, the elastic modulus tends to decrease. The elastic modulus in water or an aqueous solution of the surface of the outermost surface layer can also be adjusted by previously subjecting the glass substrate to surface treatments such as primer treatment and silane coupling agent treatment.

[0080] In this specification, unless otherwise specified, the elastic modulus in water or an aqueous solution of the surface of the outermost surface layer means the elastic modulus in water or an aqueous solution measured using an atomic force microscope (AFM).

[0081] An atomic force microscope (AFM) is a type of scanning probe microscope that detects the force acting between the atoms of a sample and a probe. The probe is attached to the tip of a cantilever (a single-sided spring), and while changing the distance between the sample and the probe, the force (deflection amount) acting on the cantilever is measured to obtain a curve (force curve) plotting the relationship between the two. By analyzing this force curve, the elastic modulus (hardness) of the sample surface can be determined, and the elastic modulus can be measured at the nanolevel. The method of obtaining the elastic modulus of the sample surface by force curve measurement is a method known to those skilled in the art, and it is possible to obtain the elastic modulus by such a known method.

[0082] As a method for calculating the elastic modulus from the force curve, for example, there is a method of fitting the force curve by the JKR (Johnson - Kendall - Roberts) theory to calculate the elastic modulus. In the JKR theory, the force F applied to the cantilever and the sample deformation amount δ are expressed by the following formulas (1) and (2) with the adhesion energy as w. [Number] In the formula, a represents the radius of the contact line between the probe and the sample, R represents the radius of curvature of the probe tip, and K represents the elastic coefficient.

[0083] The elastic modulus can be obtained by fitting the F - δ curve obtained by force curve measurement and the formulas (1) and (2).

[0084] Here, the elastic modulus of the surface of the outermost surface layer in water or an aqueous solution specifically means the measured value measured by the following method. The measured value of the surface of the outermost surface layer in water or an aqueous solution can be measured by AFM by dropping water or an aqueous solution onto the surface of the outermost surface layer of the sample so that a liquid droplet (convex meniscus) is formed. As the aqueous solution, for example, phosphate - buffered saline (PBS) can be preferably used.

[0085] And the elastic modulus of the sample (the surface of the outermost surface layer) can be obtained, for example, by scanning within a predetermined range on the surface of the outermost surface layer of the sample, obtaining force curves at a large number of points within the predetermined range, calculating the elastic modulus from each force curve, and calculating the average value.

[0086] The polymer-coated glass substrate produced by the foregoing method has one or more polymer layers formed on the surface of a glass substrate composed of soda-lime glass having a contact angle of bubbles in water of 100 degrees or more and 120 degrees or less, and the elastic modulus of the outermost surface layer of the polymer layer in water or an aqueous solution is 1.20 MPa or less, and the surface is soft. Therefore, the above polymer-coated glass substrate has low adsorbability to normal cells such as blood cells, while having high adsorbability to specific cells such as cancer cells, stem cells, and T cells, and is excellent in selective adsorbability of specific cells.

Example

[0087] Hereinafter, the present invention will be specifically described based on examples, but the present invention is not limited thereto.

[0088] <Example 1> (Production of polymer) Using an AIBN (azobisisobutyronitrile) 12.5 mg / ml toluene solution, 2-methoxyethyl acrylate (2.5 wt% toluene) was thermally polymerized at 60 °C for 7 hours to produce poly 2-methoxyethyl acrylate (PMEA).

[0089] 80 μL of a 0.25 wt% methanol solution of PMEA was injected into a 2-chamber type chamber slide (non-coated, made of soda-lime glass, average thickness 1300 μm, contact angle of bubbles in water 109.9 degrees, manufactured by Matsunami Glass Industry Co., Ltd.). Then, it was immediately vacuum dried in an oven at 50 °C for 20 minutes (coating) to produce a polymer-coated glass substrate.

[0090] <Example 2> (Production of polymer) Using an AIBN (azobisisobutyronitrile) 12.5 mg / ml toluene solution, 2-methoxyethyl acrylate (2.5 wt% toluene) was thermally polymerized at 60 °C for 7 hours to produce poly 2-methoxyethyl acrylate (PMEA).

[0091] A 0.155 wt% methanol solution of PMEA (145 μL) was injected into a two-chamber type chamber slide (non-coated, made of soda-lime glass by Matsunami Glass Industry Co., Ltd., average thickness 1300 μm, contact angle of bubbles in water 109.9 degrees). Immediately afterwards, it was dried at normal pressure for 15 minutes in an oven at 60 °C (coating) to produce a polymer-coated glass substrate.

[0092] <Example 3> (Preparation of Polymer) Using an AIBN (azobisisobutyronitrile) 12.5 mg / ml toluene solution, 2-methoxyethyl acrylate (2.5 wt% toluene) was thermally polymerized at 60 °C for 7 hours to produce poly(2-methoxyethyl acrylate) (PMEA).

[0093] A 0.50 wt% methanol solution of PMEA (90 μL) was injected into a two-chamber type chamber slide (non-coated, made of soda-lime glass by Matsunami Glass Industry Co., Ltd., average thickness 1300 μm, contact angle of bubbles in water 109.9 degrees). Immediately afterwards, it was dried under vacuum for 20 minutes in an oven at 50 °C (coating) to produce a polymer-coated glass substrate.

[0094] <Comparative Example 1> (Preparation of Polymer) Using an AIBN (azobisisobutyronitrile) 12.5 mg / ml methanol solution, 2-methoxyethyl acrylate (5.0 wt% methanol) was thermally polymerized at 60 °C for 7 hours to produce poly(2-methoxyethyl acrylate) (PMEA).

[0095] A 0.155 wt% methanol solution of PMEA (145 μL) was injected into a two-chamber type chamber slide (non-coated, made of soda-lime glass by Matsunami Glass Industry Co., Ltd., average thickness 1300 μm, contact angle of bubbles in water 109.9 degrees). Immediately afterwards, it was dried under vacuum for 20 minutes in an oven at 50 °C (coating) to produce a polymer-coated glass substrate.

[0096] <Example 4> (Preparation of Polymer 1) Using an AIBN (azobisisobutyronitrile) 1.25 mg / ml methanol solution, 2-methoxyethyl acrylate (50 wt% methanol) was thermally polymerized at 60 °C for 7 hours to prepare poly(2-methoxyethyl acrylate) (PMEA) (Mn 80,000). (Preparation of Polymer 2) Using an AIBN (azobisisobutyronitrile) 1.25 mg / g toluene solution, 2-methoxyethyl acrylate (25 wt% toluene) was thermally polymerized at 60 °C for 7 hours to prepare poly(2-methoxyethyl acrylate) (PMEA) (Mn 16,000).

[0097] 80 μl of a 0.0375% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above Polymer 1 was injected into one well of a slide chamber (2-well type) (non-coated, manufactured by Matsunami Glass Industries Co., Ltd., bottom: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 μm). Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes. After cooling to room temperature, 90 μl of a 0.16% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above Polymer 2 was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes to prepare a polymer-coated glass substrate.

[0098] <Example 5> 80 μl of a 0.0375% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above Polymer 1 was injected into one well of a slide chamber (2-well type) (non-coated, manufactured by Matsunami Glass Industries Co., Ltd., bottom: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 μm). Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes. After cooling to room temperature, 90 μl of a 0.19% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above Polymer 2 was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes to prepare a polymer-coated glass substrate.

[0099] <Example 6> Into one well of a slide chamber (2-well type) (non-coated, manufactured by Matsunami Glass Industry Co., Ltd., bottom surface: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 μm), 80 μl of a 0.0375% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above polymer 1 was injected. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes. After cooling to room temperature, 90 μl of a 0.23% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above polymer 2 was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes to prepare a polymer-coated glass substrate.

[0100] <Example 7> NH3 on the surface + Into one well of a slide chamber (2-well type) (MAS-coated type, manufactured by Matsunami Glass Industry Co., Ltd., bottom surface: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 μm) with an NH3 group introduced on the surface, 80 μl of a 0.0375% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above polymer 1 was injected. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes. After cooling to room temperature, 90 μl of a 0.19% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above polymer 2 was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes to prepare a polymer-coated glass substrate.

[0101] <Example 8> NH3 on the surface + Into one well of a slide chamber (2-well type) (MAS-coated type, manufactured by Matsunami Glass Industry Co., Ltd., bottom surface: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 μm) with an NH3 group introduced on the surface, 80 μl of a 0.0750% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above polymer 1 was injected. Then, it was immediately vacuum dried in an oven at 40 °C for 5 minutes. After cooling to room temperature, 90 μl of a 0.19% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above polymer 2 was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 40°C for 5 minutes to prepare a polymer-coated glass substrate.

[0102] <Example 9> 640 μl of a 0.0375 wt% methanol solution of PMEA (Mn 80,000) prepared in the preparation of the above polymer 1 (the methanol solution was heated to 40°C) and 720 μl of a 0.19 wt% methanol solution of PMEA (Mn 16,000) prepared in the preparation of the above polymer 2 (the methanol solution was heated to 40°C) were mixed, and 85 μl of the resulting solution was injected into one well of a slide chamber (2-well type) (non-coated, manufactured by Matsunami Glass Industry Co., Ltd., bottom surface: soda-lime glass, contact angle of bubbles in water: 109.9 degrees, average thickness 1.35 mm) (the methanol solution was heated to 40°C). Then, it was immediately vacuum dried in an oven at 40°C for 5 minutes. After cooling to room temperature, 85 μl of the above mixed solution was injected onto the PMEA coating layer. Then, it was immediately vacuum dried in an oven at 50°C for 20 minutes to prepare a polymer-coated glass substrate.

[0103] Regarding the polymer-coated glass substrates prepared in the above examples and comparative examples, the thickness of the polymer layer and the elastic modulus by AFM in PBS (phosphate buffer aqueous solution) were measured by the following method. The results are shown in Table 1.

[0104] 〔Thickness of polymer layer〕 The thickness (film thickness) of the polymer layer formed on the polymer-coated glass substrate was measured by TEM, and the measurement conditions were an acceleration voltage of 200 kV (manufactured by JEOL Ltd., JEM-2800).

[0105] 〔Measurement of elastic modulus by AFM in PBS (phosphate buffer aqueous solution)〕 Phosphate-buffered saline was dropped onto the surface of the polymer layer of the polymer-coated glass substrate so that a droplet (convex meniscus) was formed, and the elastic modulus was measured by the following method using the following apparatus (AFM). The obtained elastic modulus was taken as the elastic modulus measured in water or an aqueous solution. In addition, when measuring the elastic modulus, analysis based on the JKR contact theory was performed on the obtained force curve to determine the elastic modulus. <Method for Measuring Elastic Modulus> Apparatus (AFM): Jupiter XR manufactured by Oxford Instruments Measurement mode: AFM force curve mapping Cantilever: Material: Si, tip radius of curvature R = 150 nm, spring constant 0.67 N / m Measurement range: 20 μm × 20 μm scan, elastic modulus calculated by JKR two-point method Scan speed: 1 Hz Measurement atmosphere: In PBS Measurement temperature: 23 °C

[0106]

Table 1

[0107]

Table 2

[0108] In Comparative Example 1, the elastic modulus is 2 MPa or more, and it is considered that the adsorptivity of specific cells such as cancer cells decreases. Also, it is considered that the adsorptivity of white blood cells is high.

[0109] In contrast, in Example 3, the elastic modulus is 1.20 MPa or less, and it is considered that the adsorptivity of specific cells such as cancer cells is improved compared to Comparative Example 1. Also, it is considered that the adsorptivity of white blood cells is lower than that in Comparative Example 1. In Example 1, the elastic modulus is around 0.057 MPa, and it is considered that the adsorptivity of specific cells such as cancer cells is improved compared to Example 3 where the elastic modulus is less than 0.04 MPa. Also, it is considered that the adsorptivity of white blood cells is lower than that in Example 3.

[0110] In Example 2, since the elastic modulus is around 0.07 MPa, it is considered that the adsorptivity for specific cells such as cancer cells is improved compared to Example 1. Also, it is considered that the adsorptivity for white blood cells is lower than that in Example 1.

[0111] In Examples 4 to 6 in which two polymer layers with different molecular weights were formed on the surface of non-coated soda-lime glass, in Examples 7 to 8 in which two polymer layers with different molecular weights were formed on the surface of soda-lime glass with an NH3 group introduced thereon, and in Example 9 in which two polymer layers composed of blend polymers with different molecular weights were formed on the surface of non-coated soda-lime glass, they also have a low elastic modulus, and it is considered that the adsorptivity for specific cells such as cancer cells is improved. Also, it is considered that the adsorptivity for white blood cells is lower. + In Examples 4 to 6 in which two polymer layers with different molecular weights were formed on the surface of non-coated soda-lime glass, in Examples 7 to 8 in which two polymer layers with different molecular weights were formed on the surface of soda-lime glass with an NH3 group introduced thereon, and in Example 9 in which two polymer layers composed of blend polymers with different molecular weights were formed on the surface of non-coated soda-lime glass, they also have a low elastic modulus, and it is considered that the adsorptivity for specific cells such as cancer cells is improved. Also, it is considered that the adsorptivity for white blood cells is lower.

[0112] The present invention (1) is a polymer-coated glass substrate in which one or two or more polymer layers are formed on the surface of a glass substrate, wherein the glass is soda-lime glass having a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less, and the surface of the outermost layer of the polymer layer is a polymer-coated glass substrate having an elastic modulus in water or an aqueous solution of 1.20 MPa or less.

[0113] The present invention (2) is the polymer-coated glass substrate according to the present invention (1), wherein the elastic modulus is 0.85 MPa or less.

[0114] The present invention (3) is the polymer-coated glass substrate according to the present invention (1), wherein the elastic modulus is 0.75 MPa or less.

[0115] The present invention (4) is the polymer-coated glass substrate according to the present invention (1), wherein the elastic modulus is 0.04 MPa or more.

[0116] The present invention (5) is a polymer-coated glass substrate in any combination of the present inventions (1) to (4), wherein the outermost layer is formed of a polymer represented by the following formula (I). [Chemical formula] (In the formula, R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. p represents an integer from 1 to 8, m represents an integer from 1 to 5, and n represents the number of repetitions.)

[0117] The present invention (6) is a polymer-coated glass substrate in any combination of the present inventions (1) to (4), wherein the outermost surface layer is formed of a polymer represented by the following formula (I-1). [Chemical formula] (In the formula, R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. m represents an integer from 1 to 5, and n represents the number of repetitions.)

[0118] The present invention (7) is a polymer-coated glass substrate in any combination of the present inventions (1) to (4), wherein the outermost surface layer is formed of a copolymer of a compound represented by the following formula (II) and another monomer. [Chemical formula] (In the formula, R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. p represents an integer from 1 to 8, and m represents an integer from 1 to 5.)

[0119] The present invention (8) is a polymer-coated glass substrate in any combination of the present inventions (1) to (4), wherein the outermost surface layer is formed of a copolymer of a compound represented by the following formula (II-1) and another monomer. [Chemical formula] (In the formula, R 51 represents a hydrogen atom or a methyl group, and R 52 represents an alkyl group. m represents an integer from 1 to 5.)

[0120] The present invention (9) is a polymer-coated glass substrate in any combination with any one of the present inventions (5) to (8) in which the outermost surface layer is formed of the polymer having a number average molecular weight of 10,000 to 60,000.

[0121] The present invention (10) is a polymer-coated glass substrate in any combination with any one of the present inventions (1) to (9) in which the total thickness of the polymer layer is 10 to 4000 nm.

[0122] The present invention (11) is a polymer-coated glass substrate in any combination with any one of the present inventions (1) to (10) in which the elastic modulus is a value measured using an atomic force microscope.

[0123] The present invention (12) is such that two or more polymer layers are formed, the surface of the glass substrate has a group represented by -N(R 1 )2 and / or -N(R 2 )3 + (R 1 and R 2 are each independently a hydrogen atom or a substituted or unsubstituted hydrocarbon group which may contain a hetero atom.)), and is a polymer-coated glass substrate in any combination with any one of the present inventions (1) to (11).

[0124] The present invention (13) is a polymer-coated glass substrate in any combination with any one of the present inventions (1) to (12) in which the outermost surface layer is formed of a blend of hydrophilic polymers having different molecular weights.

Claims

1. A polymer-coated glass substrate having one or more polymer layers formed on the surface of a glass substrate, wherein the glass is soda-lime glass having a contact angle of air bubbles in water of 100 degrees or more and 120 degrees or less, and the surface of the outermost layer of the polymer layer is a polymer-coated glass substrate having an elastic modulus of 1.20 MPa or less in water or an aqueous solution.

2. The polymer-coated glass substrate according to claim 1, wherein the elastic modulus is 0.85 MPa or less.

3. The polymer-coated glass substrate according to claim 1, wherein the elastic modulus is 0.75 MPa or less.

4. The polymer-coated glass substrate according to claim 1, wherein the elastic modulus is 0.04 MPa or more.

5. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the outermost layer is formed of a polymer represented by the following formula (I). 【Chemical 1】 (wherein, R ５１ represents a hydrogen atom or a methyl group, and R ５２ represents an alkyl group. p is from 1 to 8, m is from 1 to 5, and n represents the number of repetitions.)

6. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the outermost layer is formed of a polymer represented by the following formula (I-1). 【Chemical 2】 (wherein, R ５１ represents a hydrogen atom or a methyl group, and R ５２ represents an alkyl group. m is an integer from 1 to 5, and n represents the number of repetitions.)

7. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the outermost layer is formed of a copolymer of a compound represented by the following formula (II) and another monomer. [Chemical Formula 3] (wherein, R ５１ represents a hydrogen atom or a methyl group, and R ５２ represents an alkyl group. p represents an integer of 1 to 8, and m represents an integer of 1 to 5.)

8. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the outermost layer is formed of a copolymer of a compound represented by the following formula (II-1) and another monomer. 【Chemical Formula 4】 (wherein, R ５１ represents a hydrogen atom or a methyl group, and R ５２ represents an alkyl group. m represents an integer of 1 to 5.)

9. The polymer-coated glass substrate according to claim 5, wherein the outermost layer is formed of the polymer having a number average molecular weight of 10,000 to 60,000.

10. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the total thickness of the polymer layer is 10 to 4000 nm.

11. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the elastic modulus is a value measured using an atomic force microscope.

12. The above two or more polymer layers are formed, The surface of the glass substrate is —N(R １ ) ２ and / or —N(R ２ ) ３ ＋ (R １ and R ２ are each independently the same or different and are a hydrogen atom or a substituted or unsubstituted hydrocarbon group which may contain a hetero atom.) The polymer-coated glass substrate according to any one of claims 1 to 4 having a group represented by

13. The polymer-coated glass substrate according to any one of claims 1 to 4, wherein the outermost layer is formed of a blend of hydrophilic polymers having different molecular weights.

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