WO2023140135A1

WO2023140135A1 - Hydrophilized base material

Info

Publication number: WO2023140135A1
Application number: PCT/JP2023/000247
Authority: WO
Inventors: 努高野
Original assignee: 株式会社朝日Ｆｒ研究所
Priority date: 2022-01-21
Filing date: 2023-01-10
Publication date: 2023-07-27

Abstract

Provided is a hydrophilized base material which is intended to be used in a microchip device, a cell culture container/organ chip and the like, and in which the surface thereof is a hydrophilization-treated surface for the purpose of improving hydrophilicity so as to prevent air bubbles from staying on the base material surface to be contacted with a liquid of interest or improving the hydrophilicity of a light-permeable product so as to prevent the deterioration in permeability due to water droplets or moisture. The hydrophilized base material is one in which a liquid of interest comes into contact with a portion of a contacting part that corresponds to at least a portion of the surface and/or the interior of the base material. In the hydrophilized base material, at least a portion of the contacting part is any one dry-treated part selected from an UV-treated part, an excimer UV-treated part, a corona discharge-treated part, a plasma-treated part, an electron beam-treated part and a γ-ray-treated part, and has, attached thereto, a hydrophilization treatment agent comprising a hydrophilicity-imparting component selected from a water-soluble polymer and a water-insoluble polymer. As a result, the at least a portion of the contacting part becomes a hydrophilization-treated surface.

Description

hydrophilic substrate

The present invention relates to a hydrophilized base material in which the exposed surface and/or inner cavity surface of the base material with which the target liquid comes into contact is a hydrophilized surface.

In recent years, with the development of analytical instruments and their improved sensitivity, microchip devices for microanalysis have come to be used. Microchip devices include, for example, microfluidic measurement devices, microbiochips, microreactor chips, and microbiochemical chips.

A microfluidic measurement device measures the physical properties of fluids and particles in fluids in microchannels.

In addition, as a method using a microbiochip, there is an analysis method that uses only a minute amount of the test object, which is a biological specimen such as blood or urine, in the order of μL, and uses the specific substrate selectivity of the enzyme to quantify the amount of enzyme reaction that acts with the substrate in the specimen and the amount of the substrate by the degree of coloring by the enzyme or the reagent that develops color with the substrate.

Furthermore, as methods using micro-biochemical chips, there are known quantitative analysis methods that use an enzyme-containing membrane to convert the amount of enzyme reaction into electrical signals with electrodes to quantify the amount of substrate, and test methods that proliferate useful cells or viruses and attach cancer cells for testing. In addition, as a method using a microreactor chip, a method of performing DNA extraction and its polymerase chain reaction (PCR) amplification, ion concentration measurement, microsynthesis of nucleic acids, sugars, proteins or peptides, etc. in μM order is also known.

In these microchip devices, if bubbles mixed in a fine channel or generated from the target liquid adhere to the channel surface, the bubbles will stay and cause a pulsating flow based on it, and the liquid feeding performance will deteriorate.

Furthermore, it is required to control the hydrophilicity of these products in order to improve the affinity with the culture solution in the cell culture vessel and the affinity between the organ chip and cells and body fluids to control the adsorption of cells.

Japanese Patent Publication No. 2011-501806

The present invention was made to solve the above-mentioned problems, and is used for microfluid measurement devices, pore chips, micro biochips, micro reactors, micro chip devices having micro biochemical chips, cell culture vessels, organ chips, etc. The hydrophilicity is improved so that air bubbles do not stay on the base material surface that comes into contact with the target liquid, especially the target liquid containing viruses, bacteria, and fine particles such as magnetic particles contained in magnetic paint, the target liquid containing biological specimens, and the target liquid containing trace synthetic raw materials. To provide a hydrophilized base material having a hydrophilized surface in order to improve the hydrophilicity of a light-transmitting product so that the permeability is not deteriorated by water droplets or moisture.

The hydrophilized base material used to achieve the above-mentioned object is a base material with which the target liquid contacts at least a part of the contact area on the surface and/or inside of the base material, wherein at least a part of the contact area is at least one dry-treated area selected from a UV-treated area, an excimer UV-treated area, a corona discharge-treated area, a plasma-treated area, an electron beam-treated area, and a gamma-ray-treated area, and a hydrophilic treatment agent containing a hydrophilicity-imparting component selected from a water-soluble polymer and a water-soluble non-polymer is applied to the base material to provide a hydrophilic treatment surface. It is said that there is

In this hydrophilizing base material, the hydrophilizing treatment agent has the solubility to at least partially dissolve in the target liquid.

In this hydrophilic substrate, the hydrophilicity imparting component is, for example, the water-soluble polymer selected from polyether-modified silicone oil, polyvinyl alcohol, starch, polyacrylic acid, polyacrylamide, polyethylene oxide, poly(vinylpyrrolidone), polyvinylamide, polyamine, polyethylene glycol, cellulose derivative, polyethyleneimine, poly(acrylic acid), poly(4-sodium styrenesulfonate), and poly(2-oxazoline); and/or the water-soluble non-polymer selected from glycerol and a nonionic surfactant. There is.

The hydrophilized base material may have the hydrophilized surface by being provided with at least one coated portion selected from a coating, a coating layer, a coating spot, a coating dot, a coating patch, and a coating mosaic formed with a hydrophilization treatment agent.

In this hydrophilized base material, for example, the coating portion has an average film thickness of the coating, an average layer thickness of the coating layer, an average height of the coating spots, an average height of the coating dots, an average height of the coating patches, and/or an average height of the coating mosaic of 0.005 to 5 μm.

It is preferable that the hydrophilized substrate has a coating amount of the hydrophilicity imparting component per unit area of 1.0×10 ⁻⁶ to 1.0×10 ⁻³ g/cm ² at the coated portion.

According to the hydrophilized base material of the present invention, the hydrophilicity of the surface and/or the inside of the base material is improved by the dry treatment and the addition of the hydrophilizing agent, so the contact angle with respect to target liquids such as water, aqueous solutions, and suspensions, such as test liquids and chemicals containing trace amounts of synthetic ingredients, is small.

According to this hydrophilized base material, when used in microchip devices having microfluid measurement devices, pore chips, micro biochips, microreactors, micro biochemical chips, cell culture vessels, organ chips, etc., it is possible to prevent air bubbles from accumulating on the surface and/or inside of the base material that comes into contact with the target liquid, especially the target liquid containing viruses, bacteria, and fine particles such as magnetic particles contained in magnetic paint, the target liquid containing biological specimens, and the target liquid containing trace amounts of synthetic raw materials.

Therefore, by using a microchip device having a microfluid measurement device made of this hydrophilized base material, the target liquid, such as an electrolyte suspension containing fine particles to be measured, can be pushed out and discharged without leaving even the air originally present in the channel. Therefore, a process that is performed only for removing air bubbles is unnecessary, so that after unpacking these unused chips or microchip devices equipped with them, the diameters and particle size distributions of biological components of microparticles and biological specimens can be measured and analyzed, or microsynthesis can be performed.

Moreover, at any liquid transfer speed from low speed to high speed, not only is it possible to suppress the generation of air bubbles from air bubbles in the pores and flow paths of these chips, but also the remaining air bubbles and generated air bubbles can be quickly discharged, preventing pulsating flow and uneven flow rates.

In addition, if the cell culture vessel/organ chip formed of this hydrophilic base material is used, the target liquid, such as the culture solution containing the cells being cultured, becomes more familiar with the surface of the cell culture vessel/organ chip, thereby preventing the adsorption of floating cells.

By dry treatment and treatment with a hydrophilic treatment agent, this hydrophilic substrate can maintain excellent hydrophilicity with a small contact angle even when stored for a long period of time not only under normal temperature, normal pressure, and normal humidity conditions, but also under high temperature and high humidity conditions.

1 is a photograph of an untreated base material to which the present invention is not applied and a hydrophilized base material to which the present invention is applied, in a state of contact with water.

Embodiments for carrying out the present invention will be described in detail below, but the scope of the present invention is not limited to these embodiments.

The hydrophilic base material of the present invention is a base material with which the target liquid comes into contact with at least a part of the contact area on the surface and/or inside of the base material, and at least a part of the contact area is a hydrophilic surface.

At least a portion of the substrate surface and/or interior of the hydrophilized substrate is first subjected to at least one dry treatment selected from UV treatment, excimer UV treatment, corona discharge treatment, plasma treatment, electron beam treatment, and gamma ray treatment, thereby forming at least one dry treated portion selected from a UV treated portion, an excimer UV treated portion, a corona discharge treated portion, a plasma treated portion, an electron beam treated portion, and a γ ray treated portion. Further, the dry-treated portion is coated with a hydrophilizing agent containing a hydrophilicity-imparting component selected from water-soluble polymers and water-soluble non-polymers to form a hydrophilized surface.

The hydrophilized surface of the hydrophilized base material is formed on a contact portion that is at least a part of the surface of the base material and/or the interior with which the target liquid contacts. Such a contact portion is not limited in position, range, size, etc., as long as it is in contact with the target liquid, and may be the entire surface or a patterned partial region. Specifically, it may be a channel formed on at least one of the hydrophilic substrate bonding surfaces to which a plurality of hydrophilic substrates are bonded, may be at least a part of one surface of a single hydrophilic substrate, or may be the entire surface.

The hydrophilized surface of such a hydrophilized substrate is subjected to dry treatments such as UV treatment, excimer UV treatment, corona discharge treatment, plasma treatment, electron beam treatment, and gamma ray treatment to generate hydrophilic intrinsic groups such as hydroxyl groups inherent in the raw material substrate before hydrophilization, as well as newly generate hydrophilic active groups such as hydroxyl groups, carboxy groups, carbonyl groups, or hydroxysilyl groups, and these hydrophilic groups act to develop hydrophilicity. At this time, the hydrophilic groups produced by the dry treatment gradually lose their hydrophilicity due to exposure to heat such as 80° C., or exposure for a long period of time under normal temperature, normal pressure, and normal humidity. However, it is presumed that the application of the hydrophilicity-imparting component of the hydrophilization treatment agent exerts a so-called masking effect, stabilizes the hydrophilic groups, allows the hydrophilic groups to remain exposed on the substrate, prevents them from entering into the substrate surface molecules, and maintains the activity of the substrate surface and/or the interior to maintain a high contact angle.

The hydrophilized surface of such a hydrophilized substrate is formed using a hydrophilizing agent having a hydrophilicity-imparting component. The hydrophilized surface is obtained by applying, dipping, spraying, or dropping a hydrophilizing agent to the base material of the hydrophilic base material, and if necessary, by drying means such as heating, air drying, or standing.

It is preferable that such a hydrophilizing agent has a solubility of at least partially dissolving in the target liquid. If the hydrophilizing treatment agent has solubility, it will start to dissolve rapidly when it comes into contact with the target liquid, improving the hydrophilicity and eliminating adhesion of air bubbles and foreign matter.

The hydrophilizing agent contains a hydrophilicity-imparting component selected from water-soluble polymers and water-soluble non-polymers, and, if necessary, water, an organic solvent such as a water-soluble organic solvent, specifically a solvent such as alcohol.

Among the hydrophilizing agents, hydrophilic polymers include polyether-modified silicone oils and hydrophilic group-containing acrylic compounds.

As a hydrophilic polymer, such a polyether-modified silicone oil is a copolymer having a polysiloxane skeleton in its main chain and hydroxyl-terminated polyether groups as hydrophilic groups in its side chains. The side chain is a hydrophilic group-containing silicone compound that is repeated according to the repetition of the monomers that constitute the main chain. Specifically, the following chemical formula (1)

(In the chemical formula (1), x and y are the number of repeating units of the siloxy structure of the compound, and the repeating unit represented by x or y may be a block copolymer unit or a random copolymer unit. n is the number of ether structure repeating units in the polyether group, more specifically, the number is about 12 on average. Each R is a methyl group or a phenyl group.).

A hydrophilizing agent made of a polyether-modified silicone oil containing such a hydrophilic group-containing silicone compound has an HLB value (Hydrophilic-Lipophilic Balance) of 3.5 to 14.5, and can exhibit sufficient hydrophilicity. If the HLB value is smaller than this range, imparting hydrophilicity will be insufficient, and if it is larger than this range, the dispersibility in the hydrophilizing treatment agent will be significantly reduced. Regarding the HLB value, for ester-based surfactants, the saponification value is S, the acid value of the fatty acid that constitutes the surfactant is A, and the HLB value is defined as 20 (1−S/A). The B value is defined as 7 + the total number of hydrophilic groups - the total number of lipophilic groups, and the HLB value is defined as 7 + 11.7 × log (sum of formula weights of hydrophilic moieties/sum of formula weights of lipophilic moieties).

In addition, the polyether-modified silicone oil may be an amphipathic surfactant. Such amphipathic surfactant polyether-modified silicone oils are specifically TI-2011 (manufactured by Dow Corning Toray; trade name; see chemical formula (1)), TI-6021 (manufactured by Dow Corning Toray; trade name), TSF-4445 (manufactured by Momentive Performance Materials Japan; trade name), and TSF-4446 (manufactured by Momentive Performance Materials Japan; trade name). , KF-6011 (manufactured by Shin-Etsu Chemical Co.; trade name), KF-6011P (manufactured by Shin-Etsu Chemical Co.; trade name), KF-6012 (manufactured by Shin-Etsu Chemical Co.; trade name), KF-6015 (manufactured by Shin-Etsu Chemical Co.; trade name), KF-6004 (manufactured by Shin-Etsu Chemical Co.;

Furthermore, among the hydrophilizing agents, hydrophilicity-imparting components include, as water-soluble polymers, polyvinyl alcohol, starch, polyacrylic acid, polyacrylamide, polyethylene oxide, poly(vinylpyrrolidone), polyvinylamide, polyamine, polyethylene glycol, cellulose derivatives, polyethyleneimine, poly(acrylic acid), poly(sodium 4-styrenesulfonate), and poly(2-oxazoline).

In addition, as hydrophilicity-imparting components, cellulose derivatives such as water-soluble cellulose include nonionic water-soluble cellulose ethers obtained by treating cellulose with caustic soda and then reacting it with an etherifying agent such as methyl chloride, propylene oxide, or ethylene oxide.

Specifically, such water-soluble cellulose has the following chemical formula

Those represented by are mentioned.

More specifically, this water-soluble cellulose includes Metolose (manufactured by Shin-Etsu Chemical Co., Ltd.; registered trademark), which is made water-soluble by eliminating hydrogen bonds by replacing some of the hydrogen atoms of the hydroxyl groups of cellulose with methyl groups, hydroxypropyl groups, or hydroxyethyl groups. More specifically, Metolose SM, which is methyl cellulose and has a methoxy group substitution degree of 1.8; Metolose 60SH, which is hydroxypropyl methylcellulose and has a methoxy group substitution degree of 1.9 and a hydroxypropoxy group substitution mole number of 0.25; Metolose 65SH, which has a methoxy group substitution degree of 1.8 and a hydroxypropoxy group substitution mole number of 0.15; Metolose SEB, which is ethyl methyl cellulose and has a methoxy group substitution degree of 1.5 and a hydroxyethoxy group substitution mole number of 0.20, and Metolose SNB, which has a methoxy group substitution degree of 1.5 and a hydroxyethoxy group substitution mole number of 0.30 (both manufactured by Shin-Etsu Chemical Co., Ltd.; trade names). average number of moles of oxy groups).

In addition, water-soluble non-polymers such as glycerol and nonionic surfactants can be mentioned as hydrophilicity-imparting components in the hydrophilization treatment agent.

Such hydrophilizing agents include those in which a hydrophilicity-imparting component is dissolved or dispersed in an appropriate medium such as an organic solvent or water, specifically methanol, ethanol, n-propanol, isopropyl alcohol, n-butyl alcohol, ethyl acetate, toluene, acetone, methyl ethyl ketone, ethylene glycol, propylene glycol, octaacetylated sucrose, denatured ethanol, water, or a mixed solvent thereof. More specific examples of denatured ethanol include Neoethanol PM, MIP, IPM, IE, PHI, MHI, PIP, HIMTE, PHM, IPME, and P-7 (all manufactured by Daishin Chemical Co., Ltd.; trade names).

Such a hydrophilic treatment agent contains 0.001 to 5% by weight, preferably 0.005 to 1% by weight, more preferably 0.01 to 0.4% by weight of a hydrophilicity imparting component.

In such a hydrophilized surface, the site to which the hydrophilizing agent is applied may be at least one of the coated sites selected from a coating, a coating layer, a coating spot, a coating dot, a coating patch, and a coating mosaic. In this coated portion, the average film thickness of the coating, the average layer thickness of the coating layer, the average height of the coated spots, the average height of the coated dots, the average height of the coated patches, and the average height of the coated mosaic is 0.005 to 5 μm, preferably 0.01 to 1 μm.

In such a coated portion, the coating amount of the hydrophilicity imparting component per unit area is 1.0×10 ⁻⁶ to 1.0×10 ⁻³ g/cm ² , preferably 5.0×10 ⁻⁶ to 4.0×10 ⁻⁴ g/cm ² .

The contact angle with water on the surface of the substrate material, which is not dry-treated and is not treated with a hydrophilic treatment agent, varies depending on the raw material of the substrate material.

On the other hand, if a hydrophilic treatment agent is applied to the surface of these untreated base materials to form a hydrophilic treatment surface, the wettability of the base material surface is low, so the hydrophilic treatment agent becomes uneven and uniform treatment cannot be performed.

However, when dry treatments such as UV treatment, excimer UV treatment, corona discharge treatment, plasma treatment, electron beam treatment, and γ-ray treatment are applied to the surface of these untreated substrate materials, the contact angle with water becomes less than about 10° and hydrophilicity is expressed. However, when subjected to a severe test at 80° C. in an oven for 1.5 hours, the contact angle with water becomes about 20 to about 103°, and the hydrophilicity is lost or deteriorated.

On the other hand, when a hydrophilizing agent was applied after such dry treatment to form a hydrophilized surface, the contact angle with water was about 10° even after the same severe test, and it was maintained almost the same as immediately after dry treatment.

Thus, regardless of the type of substrate material, for example, resin/rubber such as SUS, glass, COP, SiN, Si, silicone rubber, etc., the dry treatment alone significantly reduces the contact angle with heating and aging. However, if a hydrophilic treatment agent is applied to form a hydrophilic treatment surface, hydrophilicity can be maintained for a long period of time under normal temperature, pressure, and humidity conditions, but even if the substrate material is a composite material, hydrophilicity can be imparted by similar treatment.

Moreover, even if a hydrophilic treatment agent is used, the properties of the base material itself can be maintained without losing the properties of the base material itself, such as flexibility, gas permeability, and transparency in the case of silicone rubber such as PDMS, or the properties of transparency and low autofluorescence in the case of COP, glass, etc. Furthermore, even if the base material surface and/or the interior have structural characteristics, such as fine processing such as hole processing and uneven processing, the hydrophilic processing agent on the hydrophilic processing surface dissolves in the solvent of the target liquid, so the original fineness can be maintained. In addition to being able to maintain the characteristics of the processed shape, due to its high hydrophilicity and small contact angle with water, the surface and/or inside of the base material that comes into contact with the solvent of the liquid to be contacted, especially water, gets wet.

As the contact portion on the base material surface and/or inside where the target liquid contacts, the entire surface of the base material may be a hydrophilic treatment surface, or the exposed surface of the base material or the inner channel surface may be a hydrophilic treatment surface.

This hydrophilic substrate can be used to measure target liquids using microfluidic measurement devices, microbiochips, microreactor chips, and microbiochemical chips.

According to this hydrophilized substrate, the air on the surface and/or inside of the substrate can be discharged, and the air bubbles do not stay. Therefore, unlike the conventional microfluidic measurement device, the process performed only for discharging the air bubbles is not required, and the target liquid can be quickly brought into contact with the contact portion on the surface and/or inside of the substrate sufficiently and uniformly. Among other things, it is possible to ensure a sufficient and homogeneous flow of the liquid of interest inside, for example, in the channel.

The material of the base material to be hydrophilized is not particularly limited, such as resin, rubber, metal, ceramics, and glass.

The materials of the base material include, for example, silicone resins such as addition-type silicone resins, condensation-type silicone resins, peroxide-crosslinking silicone resins, ultraviolet-curable silicone resins, and radiation-crosslinking silicone resins; polycarbonates; cycloolefin resins; acrylic resins; epoxy resins; polyethylene terephthalate resins; Polystyrene resins such as styrene and s-polystyrene; coumarone-indene resins; terpene resins; styrene-divinylbenzene copolymers; ABS resins; Halogenated resins such as ridene, vinylidene fluoride-ethylene copolymer, vinylidene fluoride-propylene copolymer; 1,4-trans polybutadiene; polyoxymethylene, polyethylene glycol, polypropylene glycol; phenol-formalin resin; cresol-formalin resin; Polyimide; Polybenzimidazole; Polyamideimide; Silicone resin; Silicone rubber; Silicone resin; Furan resin; Polyurethane resin; PSF), sulfur-based resins such as polyethersulfone (PES); polyetheretherketone (PEEK); polyimides (PPI, Kapton); polytetrafluoroethylene (PTFE); Also, these resins may be reinforced with polyamide fibers, carbon fibers, or glass fibers.

The material of the base material is rubber, for example, addition cross-linking silicone rubber; silicone rubbers such as VMQ, PVMQ, FVMQ, and MQ, peroxide cross-linking silicone rubber, condensation cross-linking silicone rubber, ultraviolet cross-linking silicone rubber, radiation cross-linking silicone rubber, ethylene-propylene-diene rubber (EPDM), vinylidene fluoride (FKM), tetrafluoroethylene-propylene (FEPM), and fluororubber such as tetrafluoroethylene-purple vinyl ether (FFKM). , butadiene rubber (BR), isoprene rubber (IR), isobutylene-isoprene rubber (IIR), natural rubber (NR), urethane rubber (U), acrylic rubber (ACM), and co-blends of these crosslinked rubbers with olefins.

The material of the base material is any metal such as beryllium, magnesium, calcium, strontium, barium, radium, scandium, yttrium, titanium, zirconium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, iron, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver, gold, zinc, cadmium, mercury, aluminum, germanium, tin, lead, antimony, bismuth, or neodymium, and alloys. In terms of composition, iron alloys (steel, carbon steel, cast iron), copper alloys (phosphor bronze, brass, Nipronickel, beryllium copper, titanium copper), aluminum alloys (copper, manganese, silicon, magnesium, zinc, nickel alloys, etc.), magnesium alloys (Mg/Zn alloys, Mg/Ca alloys, etc.), zinc alloys, tin and tin alloys, nickel alloys, gold alloys, silver alloys, platinum alloys, palladium alloys, lead alloys, titanium alloys (α-type, β-type and α+β-type alloys), cadmium aluminum, zirconium alloys, cobalt alloys, chromium alloys, molybdenum alloys, tungsten alloys, manganese alloys, ferritic stainless steels, martensitic stainless steels, austinitic stainless steels, precipitation-strengthened stainless steels, nickel-titanium alloys, iron-manganese-titanium alloys, superelastic alloys (nickel-titanium alloys), Si crystals (silicon wafers), and the like.

　The material of the base material is ceramics such as ceramics, cement, gypsum, and enamel that have been hardened at high temperatures.₂O.₃), zirconia-based, hydroxide-based (hydroxyapatite), carbide-based (silicon carbide, SiC), carbonate-based, nitride-based (silicon nitride), (7-halide-based (fluorite), phosphate-based (apatite), specifically barium titanate, Bi₂Sr₂Ca₂Cu₃O.₁₀, high-temperature superconducting ceramics, boron nitride, ferrite, lead zirconate titanate, silicon carbide, silicon nitride, steatite (MgOSiO₂), YBa₂Cu₃O._7-δ, high-temperature superconducting ceramics, zinc oxide, aluminum nitride (AlN), silicon carbide (SiC), silicon nitride (Si₃N.₄), forsterite (2MgO SiO₂), steatite (MgO SiO₂), cordierite (2MgO 2Al₂O.₃・5SiO₂), sialon (Si₃N.₄・Al₂O.₃), machinable ceramics, zircon (ZrO₂・SiO₂)_,Barium titanate (BaTiO₃), lead zirconate titanate (Pb (Zr, Ti) O_3,), ferrite (M₂+ O Fe₂O.₃), mullite (3Al₂O.₃・2SiO₂) and the like.

Materials for the base material include various optical glasses such as silicate glass, quartz glass, soda-lime glass, borosilicate glass, and lead glass.

The hydrophilic substrate can be produced as follows.

First, prepare a base material that the target liquid comes into contact with at least a part of the contact part of the base material surface and/or inside, and if necessary, clean it by washing with water and drying. Next, at least a portion of the contact portion is subjected to at least one dry treatment selected from UV treatment, excimer UV treatment, corona discharge treatment, plasma treatment, electron beam treatment, and gamma ray treatment. As a result, new reactive active groups are generated in addition to those originally present on the base material surface.

By dissolving or suspending the hydrophilicity-imparting component in various media such as water, water-soluble organic media such as alcohol and acetone, and water-insoluble organic media such as methylene chloride, chloroform and ether, it is used as a diluted solution as a hydrophilization treatment agent. High hydrophilicity can be obtained when the concentration of the hydrophilicity imparting component is 0.001 to 10% by mass, and it is more preferably 0.005 to 1.0% by mass. Next, a hydrophilizing agent containing a hydrophilicity imparting component selected from water-soluble polymers and water-soluble non-polymers is sprayed, applied, or immersed on the dry-treated site to give it to the surface, and if necessary, the medium is removed by a method such as volatilization, and/or washed with water and dried to prepare a hydrophilized substrate.

When the hydrophilized substrate is used as a microfluidic measurement device, the liquid passing point is not only water, but also lower alcohols such as methanol, ethanol, 1-propanol, and 2-propanol; (tris(hydroxymethyl)aminomethane), HEPES buffer (2-[4-(2-Hydroxyethyl)-1-piperazinyl]ethanesulfonic acid), and phosphate buffered saline; solutions containing anionic surfactants such as fatty acid sodium, fatty acid potassium, sodium lauryl sulfate, and dioctyl sodium sulfosuccinate; A solution containing a cationic surfactant such as a quaternary ammonium salt, a quaternary ammonium methacrylic acid polymer, and a polyethyleneimine quaternary ammonium salt; a solution containing a nonionic surfactant such as polyoxyethylene fatty acid ester, glycerin ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene alkyl ether; may be
In that case, methods for removing the liquid from the liquid passage include a method of evaporating or volatilizing the liquid by drying using heat, a method of sucking and removing the liquid from the liquid passage, and a method of pressurizing and discharging the liquid.

Examples of hydrophilic substrates to which the present invention is applied and comparative examples of substrates to which the present invention is not applied are shown below.

(Preparation of base material)
SUS304 (manufactured by The Nilaco Corporation) is used as the SUS plate, Tempax glass plate (manufactured by Sekiya Rika Co., Ltd.) is used as the glass plate, Zeonor Film ZF16-188 (manufactured by Nippon Zeon Co., Ltd.) is used as the COP plate, a commercial product is used as the SiN plate, a commercial product is used as the Si plate, and 100 parts by mass of methyl vinyl silicone rubber (manufactured by Toray Dow Corning Co., Ltd., product name: SH851) as the silicone rubber plate, and peroxide. As a system vulcanizing agent, 0.5 parts by mass of 2,5-dimethyl-2,5-di(t-butylperoxy)hexane (manufactured by Dow Corning Toray Co., Ltd., product name: PC-4, 50% silica solution) was kneaded, molded at 170°C for 10 minutes, and then secondary vulcanized at 200°C for 2 hours. These were cut into 6×3 cm and used as test pieces.

(Preparation of hydrophilic treatment agent)
Metolose 60SH-03 (manufactured by Shin-Etsu Chemical Co., Ltd.) as a hydrophilic component was swollen with ultrapure water and then dissolved in ethanol to prepare a hydrophilizing agent having a Metolose concentration of 0.05 wt %.

(Water contact angle measurement 1-1: Comparative example 1)
A water contact angle measurement was performed on each specimen while it was left untreated. The water contact angle measurement was performed using an automatic contact angle diameter DM-501 (manufactured by Kyowa Interface Science Co., Ltd.). The results are summarized in Table 1.

(Water contact angle measurement 1-2: Comparative example 2)
Each untreated specimen as in Comparative Example 1 was subjected to plasma treatment prior to water contact angle measurements. The plasma processing conditions are 250 W for 3 minutes. The results are summarized in Table 1.

(Water contact angle measurement 1-3: Comparative example 3)
Each plasma-treated test piece as in Comparative Example 2 was allowed to stand under accelerated test conditions and then subjected to water contact angle measurement. Note that the accelerated test conditions were to stand still at 80° C. for 1.5 hours. The results are summarized in Table 1.

(Water contact angle measurement 1-4: Example 1)
Each plasma-treated test piece as in Comparative Example 2 was hydrophilized with 2.2 μL of 0.05 wt % hydrophilizing agent per 1 cm ² , and then the water contact angle was measured. The results are summarized in Table 1.

(Water contact angle measurement 1-5: Example 2)
Each test piece that had been plasma-treated as in Comparative Example 2 was hydrophilized with a hydrophilizing agent as in Comparative Example 4, then allowed to stand under an acceleration condition of 80° C. for 1.5 hours, and then the water contact angle was measured. The results are summarized in Table 1.

(Water contact angle measurement 1-6: Reference example 1)
After each test piece subjected to plasma treatment, hydrophilization treatment and accelerated test as in Example 2 was washed with water and dried, the water contact angle was measured. The results are summarized in Table 1.

As is clear from Table 1, each untreated test piece as in Comparative Example 1 showed a high water contact angle of about 39.2 to 107°, but plasma treatment as in Comparative Example 2 improved to less than 10°.
However, as in Comparative Example 3, the plasma-treated test pieces had a higher water contact angle after the accelerated test, although not as high as the untreated test pieces, indicating that the improvement in hydrophilicity due to plasma treatment cannot be maintained for a long period of time.
On the other hand, each test piece subjected to plasma treatment and hydrophilic treatment as in Example 1 had a contact angle of less than 10°, and even after an accelerated test at 80 ° C. for 1.5 hours as in Example 2, the water contact angle hardly changed, indicating that the improvement in hydrophilicity could be maintained for a long time.

(Comparative Example 4)
After the SiN test piece was plasma-treated in the same manner as in Comparative Example 2, 100 parts by mass of methyl vinyl silicone rubber (manufactured by Dow Corning Toray Co., Ltd., product name: SH851) and 0.5 parts by mass of 2,5-dimethyl-2,5-di(t-butylperoxy)hexane (manufactured by Toray Dow Corning Co., Ltd., product name: PC-4, 50% silica solution) as a peroxide vulcanizing agent were kneaded and kneaded at 170°C. After molding for 1 minute, it was placed in an airtight container together with a non-secondary vulcanized sheet, left to stand under accelerated conditions of 80° C. for 1.5 hours, and then subjected to water contact angle measurement. The results are summarized in Table 2.

(Example 3)
A SiN test piece was subjected to plasma treatment as in Comparative Example 2, and then subjected to hydrophilization treatment as in Comparative Example 4 and Example 1. After that, it was placed in a sealed container together with a vulcanized silicone rubber sheet that had not been secondary vulcanized as in Comparative Example 4, left to stand under accelerated conditions of 80° C. for 1.5 hours, and then subjected to water contact angle measurement. The results are summarized in Table 2.

As is clear from Table 2, masking with a hydrophilizing agent prevented deterioration of the contact angle due to adhesion of volatile components. The mechanism is not necessarily clear, but if the vulcanized rubber plate is placed in a sealed container together so as not to come into contact with the test piece and is not subjected to secondary vulcanization, low-molecular-weight siloxane and volatile components remain in the vulcanized rubber.

Next, the silicone rubber substrate was subjected to plasma treatment and metolose treatment, the contact angle was measured, and the stability was examined.

(Water contact angle measurement 2-1: Comparative Example 5)
The contact angle of a silicone rubber test piece made of methyl vinyl silicone rubber (manufactured by Dow Corning Toray Co., Ltd., product name: SH851) was measured in the same manner as described above. Table 3 shows the results.

(Water contact angle measurement 2-2: Comparative Example 6)
Untreated silicone rubber specimens prepared as in Comparative Example 5 were subjected to water contact angle measurements after plasma treatment. The plasma processing conditions are 200 W for 120 seconds. The results are summarized in Table 3.

(Water contact angle measurement 2-3: Example 4)
The plasma-treated silicone rubber test piece prepared as in Comparative Example 6 was hydrophilized with a hydrophilizing agent as in Comparative Example 4, dried, and then subjected to water contact angle measurement. Table 3 shows the results.

(Water contact angle measurement 2-4: Example 5)
Plasma-treated/Metrose-treated silicone rubber test pieces prepared as in Example 4 were subjected to accelerated tests at 80° C. for 1 hour, 2 hours, 16 hours, 42 hours, 88 hours, and 168 hours, and then the water contact angle was measured. Table 4 shows the results.

(Water contact angle measurement 2-5: Comparative Example 7)
The plasma-treated silicone rubber test piece prepared as in Comparative Example 6 was subjected to an accelerated test at 80° C. for 1 hour, 2 hours, 16 hours, 42 hours, 88 hours, and 168 hours, and then subjected to water contact angle measurement. Table 4 shows the results.

(Water contact angle measurement 2-6: Example 6)
A silicone rubber test piece subjected to plasma treatment, METOLOSE treatment, and accelerated test in the same manner as in Example 5 was washed with water, dried, and subjected to water contact angle measurement. Table 4 shows the results.

(Water contact angle measurement 2-6: Reference example 2)
The silicone rubber test piece that had been subjected to the plasma treatment, METOLOSE treatment, accelerated test, and water washing/drying as in Example 6 was again subjected to an accelerated test at 80° C. for 24 hours. Table 4 shows the results.

As is clear from Tables 3 and 4, as in Example 5, the contact angle was slightly changed by storage at 80°C (accelerated test), but sufficient hydrophilicity was exhibited even after 168 hours. However, as in Comparative Example 7, Example 6, and Reference Example 2, by masking with Metolose, the penetration of the functional groups generated by the plasma treatment was suppressed, and the activity of the substrate surface could be maintained for a long time.

(Comparative Example 8)
100 parts by mass of methyl vinyl silicone rubber (manufactured by Dow Corning Toray Co., Ltd., product name: SH851) and 0.5 parts by mass of 2,5-dimethyl-2,5-di(t-butylperoxy)hexane (manufactured by Dow Corning Toray Co., Ltd., product name: PC-4, 50% silica solution) as a peroxide vulcanizing agent are kneaded and crosslinked in a mold to form a rectangular parallelepiped depression of 1 mm on a side and 0.5 mm in depth. and used as an untreated test piece. When water is dripped onto this test piece, air is entrained in the depressions (see FIG. 1(a)).

(Example 7)
The untreated test piece of Comparative Example 3 was hydrophilized by coating 2.2 μL per 1 cm ² of the hydrophilizing agent containing 0.05 wt % of Metolose prepared as described above to obtain a hydrophilized test piece. When this test piece was dripped with water, the depressions were filled with water without entrainment of air bubbles (see FIG. 1(b)).

The hydrophilic base material of the present invention is used for microfluidic measurement devices such as microbiochips, microreactor chips, and microbiochemical chips that measure the shape, particle size, and particle size distribution of fine particles, as well as windshields, optical parts, eyeglasses, optical members, and the like.

Claims

A substrate that is in contact with a target liquid on at least a part of the contact portion of the surface and/or inside of the substrate, wherein at least a portion of the contact portion is a dry-treated portion selected from a UV-treated portion, an excimer UV-treated portion, a corona discharge-treated portion, a plasma-treated portion, an electron beam-treated portion, and a γ-ray-treated portion, and a hydrophilized surface is formed by applying a hydrophilic treatment agent containing a hydrophilicity-imparting component selected from a water-soluble polymer and a water-soluble non-polymer.
The hydrophilic base material according to claim 1, wherein the hydrophilic treatment agent has a solubility of at least partially dissolving in the target liquid.
Claim 2, wherein the hydrophilicity imparting component is the water-soluble polymer selected from polyether-modified silicone oil, polyvinyl alcohol, starch, polyacrylic acid, polyacrylamide, polyethylene oxide, poly(vinylpyrrolidone), polyvinylamide, polyamine, polyethylene glycol, cellulose derivatives, polyethyleneimine, poly(acrylic acid), poly(sodium styrenesulfonate), and poly(2-oxazoline); and/or the water-soluble non-polymer selected from glycerol and nonionic surfactants. A hydrophilized substrate as described.
The hydrophilized base material according to any one of claims 1 to 3, wherein the hydrophilized surface is formed by providing at least one coated portion selected from a coating, a coating layer, a coating spot, a coating dot, a coating patch, and a coating mosaic formed with the hydrophilization agent.
The hydrophilic substrate according to claim 4, wherein the coating portion has an average film thickness of the coating, an average layer thickness of the coating layer, an average height of the coating spots, an average height of the coating dots, an average height of the coating patches, and/or an average height of the coating mosaic of 0.005 to 5 μm.
6. The hydrophilic substrate according to any one of claims 4 and 5, wherein the coated portion has a coating amount of the hydrophilicity-imparting component per unit area of 1.0 × 10 -6 to 1.0 × 10 -3 g/cm 2 .