Microchannel device and manufacturing method thereof

Abstract

To provide a microchannel device according to the present invention in which the presence of a large amount of colorant on a front side of a porous substrate on a channel wall increases visibility, and a small amount of colorant inside the channel wall prevents elution of ions included in the colorant to an analyte, thereby increasing the measurement accuracy.SOLUTION: A microchannel device has a channel sandwiched by channel walls formed inside a porous substrate. The channel wall has thermoplastic resin and colorant, the abundance ratio of the colorant included in the channel wall is higher in a surface area of the porous substrate in the channel wall than the inside of the channel wall.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a microchannel device in which a microchannel is formed inside a porous substrate, and a method for manufacturing the same. [Background technology]

[0002] In recent years, the development of microfluidic devices that utilize micro-sized fine channels to efficiently perform biochemical analyses (microvolumes, rapid, and simple) on a single chip has attracted attention in a wide range of fields. Specifically, they have attracted attention not only in biochemical research but also in fields such as medicine, drug discovery, healthcare, the environment, and food. Among these, paper-based paper microanalysis chips offer advantages over conventional devices: they are lightweight and low-cost, do not require a power source, and are easily disposable. For these reasons, they are expected to be used in medical activities in developing countries and remote areas lacking medical facilities, as well as at disaster sites, and as testing devices in airports and other locations where the spread of infectious diseases must be prevented at the border. Furthermore, because they are inexpensive and easy to use, they are attracting attention as healthcare devices that can manage and monitor one's own health status.

[0003] In the early 1990s, photolithography and molds were used to form micron-sized fine channels on glass or silicon, resulting in the development of microanalysis chips that could perform sample pretreatment, stirring, mixing, reaction, and detection on a single chip. This resulted in the miniaturization of testing systems, rapid analysis, and reduced volumes of specimens, reagents, and waste liquids. However, while microchannels fabricated using photolithography possess extremely high precision, their manufacturing costs are high and they are difficult to incinerate, making them difficult to dispose of. Furthermore, because additional equipment such as syringe pumps is required to deliver test solutions through the channels, they have been limited to use in well-equipped environments and have primarily been used in biochemistry research institutions.

[0004] To address these challenges, paper microanalysis chips use inexpensive materials such as paper and cloth as a substrate, and by utilizing the capillary action of the material itself, they can drive specimens and test solutions, making them low-cost and usable in wireless environments. They are also easy to transport (distribute) and highly disposable (simply burn them for disposal). Furthermore, because they require no device maintenance, anyone (even the elderly or children with no technical knowledge) can easily perform point-of-care (POC) diagnosis at low cost, anywhere (even in places without power). Therefore, research institutes around the world are currently conducting research and development of paper microfluidic devices for various infectious diseases, specific diseases, and healthcare (chronic disease management and health management).

[0005] Microfluidic devices use liquids as specimens or test solutions and dispense the liquids to specified locations, so improving the visibility of the fluidic device is important for more accurate POC diagnosis. Therefore, in order to color the channel walls of a microchannel device, the channel wall forming material may contain a coloring agent.

[0006] Patent Document 1 proposes a microchannel device in which channel walls are formed in a porous layer (such as paper) using a thermal transfer printer. The channel wall-forming material layer that forms the channel walls contains a thermoplastic material that penetrates into the porous member, and a colorant is added as an additional component appropriately selected as needed to provide the channel walls with the ability to be identified within the porous layer. The channel wall-forming material layer is thermocompression bonded to the porous layer, and the voids in the porous layer are filled with the molten channel wall-forming material, thereby forming the channel walls.

[0007] However, in Patent Document 1, the voids in the porous layer are filled by melting the channel wall-forming material using a thermal transfer method and then thermocompression bonding, which means that there is a possibility that a large amount of colorant may be present inside the channel walls within the porous layer. As a result, when the colorant component comes into contact with the dispensed sample at the channel wall portion in contact with the channel within the porous layer, the properties of the sample itself may change, such as ions remaining in the colorant dissolving or ions adsorbing to the colorant. As a result, there is a possibility that the test accuracy may decrease. Based on these findings, we propose a microfluidic device that can ensure visibility of the flow channel even with a small amount of colorant, reduce changes in the properties of the sample flowing through the flow channel, and prevent a decrease in testing accuracy. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Laid-Open No. 2015-131257 Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention aims to provide a microchannel device that can accurately dispense samples to specified locations by ensuring visibility of the channel, and that can prevent a decrease in testing accuracy by reducing the effect on the sample of substances contained in the channel walls in the porous layer. [Means for solving the problem]

[0010] According to one aspect of the present invention, there is provided a microchannel device in which a channel sandwiched between channel walls is formed inside a porous substrate, the flow path wall contains a thermoplastic resin and a colorant; The microchannel device is characterized in that the colorant is present at a higher concentration in the surface region of the porous substrate in the channel wall than in the interior of the channel wall. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a microchannel device that has good visibility of the channel walls, undergoes little change in the properties of a sample flowing through the channel, and has high testing accuracy. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 2 is a diagram showing a channel pattern of a microchannel device formed by permeating a channel wall-forming material T1 into a porous substrate S1 in Example 1. [Figure 2] FIG. 2 is a configuration diagram of a flow path pattern image forming unit 100 in the first embodiment. [Figure 3] (a) is a schematic cross-sectional view of a microchannel device formed by infiltrating a porous substrate S1 with a channel wall-forming material T1 in Example 1. (b) is a schematic cross-sectional view of a microchannel device formed by infiltrating a porous substrate S1 with a channel wall-forming material T1. (c) is an enlarged schematic view showing a cross-section of a particle T before heating. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that the following embodiments are merely examples, and the present invention is not limited to the contents of the embodiments. Furthermore, in the following drawings, components that are not necessary for explaining the embodiments are omitted from the drawings.

[0014] In the microchannel device according to the present invention, a channel sandwiched between channel walls is formed inside a porous substrate. The flow path wall contains a thermoplastic resin and a colorant, and the colorant is present in a higher proportion in the region of the flow path wall on the surface of the porous substrate than in the interior of the flow path wall. The presence of a large amount of colorant on the surface side of the porous substrate in the flow path wall improves the visibility of the flow path, and the small amount of colorant inside the flow path wall suppresses the elution of ions contained in the colorant into the sample, thereby improving measurement accuracy.

[0015] The "abundance ratio of colorant" means the area ratio of the colorant to the channel wall material portion when observing a cross section of the microchannel device. "The surface of the porous substrate at the flow path wall" means the surface of the porous substrate in the region where the flow path wall is formed. Furthermore, "the surface region of the porous substrate at the flow path wall" preferably means "the region from the surface to a depth D (μm)." The "inside of the flow path wall" means the inside of the flow path wall that is not the surface of the porous substrate and does not face the flow path. Preferably, the "inside of the flow path wall" is a portion of the flow path wall that is at least D μm away from the surface of the porous substrate or the surface facing the flow path.

[0016] In addition, in the microchannel device, when the abundance ratio of the colorant in the portion of the channel wall excluding the porous substrate in a region from the surface to a depth D (μm) is X (%), and the abundance ratio of the colorant in the portion of the channel wall excluding the porous substrate in a region farther from the surface than the depth D is Y (%), it is preferable that X and Y satisfy the relationship X>Y. Here, the depth D is a depth expressed as (A / 2) / (1-B / 100) when the fiber diameter of the fibers forming the porous substrate is A (μm) and the porosity of the porous substrate is B (%).

[0017] Differences in the distribution of colorant in the cross-sectional direction within the microfluidic device occur when the colorant becomes entangled with the fibers of the porous substrate and remains there. The ease with which the colorant becomes entangled with the fibers is related to the fiber diameter and porosity; the thicker the fiber diameter, the more entangled the area becomes, and the smaller the porosity, the easier it becomes to become entangled, resulting in a greater amount of colorant in shallower areas. Furthermore, when the fiber is approximated as a cylinder, the colorant becomes entangled on the upper surface, so half the fiber diameter was considered as a parameter for the depth region. Based on these considerations, the relationship between X and Y above was defined. The fiber diameter A of the porous substrate was determined by measuring the fiber thickness at five points on the surface of the porous substrate using a microscope or the like and averaging the results.

[0018] The amount of colorant contained in the flow path wall is 1.0 × 10 based on the mass of the entire flow path wall (excluding the porous substrate). -6 The mass of the entire flow path wall (excluding the porous substrate) means the total mass of the components that make up the flow path wall excluding the porous substrate. When the mass of the colorant contained in the flow path wall is 0.4 mass% or less relative to the mass of the entire flow path wall, the dissolution of ions from the colorant into the sample can be reduced, thereby suppressing changes in the properties of the sample flowing through the flow path and improving measurement accuracy. In order to set the amount of colorant contained in the flow path wall within the above range, the content of the colorant in the flow path wall forming material is set to 1.0×10 based on the flow path wall forming material. -6 This can be achieved by making the content between 0.4% and 0.5% by mass.

[0019] The components contained in the flow path wall forming material will be described below. <Resin> It is the main component that forms the flow path wall. Usually, a resin is placed on the surface of a porous substrate to form a flow path pattern, and the resin is melted by heat and penetrates into the porous substrate. For this reason, a thermoplastic resin is used as the resin. The thermoplastic resin is not particularly limited, and for example, the following known resins can be used: polyester resin, vinyl resin, acrylic resin, styrene-acrylic resin, polyethylene, polypropylene, polyolefin, ethylene-vinyl acetate copolymer resin, ethylene-acrylic acid copolymer resin, etc. Among the above resins, polyester resin or styrene-acrylic resin is preferred, and styrene-acrylic resin is more preferred.

[0020] <Coloring agent> The colorant contained in the channel wall forming material is not particularly limited, and the following known pigments and dyes can be used. Considering the influence on the sample, pigments are preferable. Yellow dyes include the following: Solvent Yellow 33, 56, 79, 82, 93, 112, 162, 163; Disperse Yellow 42, 54, 64, 164, 201, 211, and the like.

[0021] Magenta dyes include the following: CI Solvent Red 1, 3, 8, 23, 24, 25, 27, 30, 49, 52, 81, 82, 83, 84, 100, 109, 111, 121, 135, 168, 179, 207; CI Disperse Red 9, 22, 60; CI Solvent Violet 8, 13, 14, 21, 27; CI Disperse Violet 1; CI Basic Red 1, 2, 9, 12, 13, 14, 15, 17, 18, 22, 23, 24, 27, 29, 32, 34, 35, 36, 37, 38, 39, 40; CI Basic Violet 1, 3, 7, 10, 14, 15, 21, 25, 26, 27, 28; CI Direct Red 1, 4; CI Acid Red 1; CI Mordant Red 30, etc.

[0022] Cyan dyes include CI Solvent Blue 14, 35, 36, 59, 63, 94, 197; CI Direct Blue 1, 2; CI Acid Blue 9, 15; CI Basic Blue 3, 5; CI Mordant Blue 7; CI Direct Green 6; CI Basic Green 4, 6, etc.

[0023] Yellow pigments include condensed azo compounds such as yellow iron oxide, Nabels Yellow, Naphthol Yellow S, Hansa Yellow G, Hansa Yellow 10G, Benzidine Yellow G, Benzidine Yellow GR, Quinoline Yellow Lake, Permanent Yellow NCG, and Tartrazine Lake, isoindolinone compounds, anthraquinone compounds, azo metal complexes, methine compounds, and allylamide compounds. Specific examples include CI Pigment Yellow 12, 13, 14, 15, 17, 62, 74, 83, 93, 94, 95, 109, 110, 111, 128, 129, 147, 155, 168, and 180.

[0024] Examples of magenta pigments include condensed azo compounds such as red iron oxide, permanent red 4R, lithol red, pyrazolone red, Watching Red calcium salt, lake red C, lake red D, brilliant carmine 6B, brilliant carmine 3B, eosin lake, rhodamine lake B, and alizarin lake, diketopyrrolopyrrole compounds, anthraquinone compounds, quinacridone compounds, basic dye lake compounds, naphthol compounds, benzimidazolone compounds, thioindigo compounds, and perylene compounds. Specific examples include CI Pigment Red 2, 3, 5, 6, 7, 23, 48:2, 48:3, 48:4, 57:1, 81:1, 122, 144, 146, 166, 169, 177, 184, 185, 202, 206, 220, 221, and 254.

[0025] Examples of cyan pigments include: Alkali Blue Lake, Victoria Blue Lake, Phthalocyanine Blue, Metal-Free Phthalocyanine Blue, Phthalocyanine Blue Partial Chloride, Fast Sky Blue, Copper phthalocyanine compounds such as Indanthrene Blue BG and their derivatives, anthraquinone compounds, and basic dye lake compounds. Specific examples include: CI Pigment Blue 1, 7, 15, 15:1, 15:2, 15:3, 15:4, 60, 62, 66, etc.

[0026] Examples of black pigments include carbon black and aniline black. It is also possible to include a magnetic material as a colorant. As magnetic materials, iron oxides such as magnetite, hematite, and ferrite, Metals such as iron, cobalt, nickel or Alloys and mixtures of metals such as iron, cobalt, and nickel with metals such as aluminum, copper, magnesium, tin, zinc, beryllium, calcium, manganese, selenium, titanium, tungsten, and vanadium Examples include: These colorants can be used alone or in combination, or in the form of a solid solution. The content of the colorant is 1.0×10 with respect to 100.0 parts by mass of the binder resin or polymerizable monomer. -6 It is more preferable that the amount is not less than 0.4 parts by mass. A colorant with a low content of ionic components, which can easily affect measurement accuracy, is preferred. In particular, since chloride ions are often contained in colorants and diagnosis is sometimes performed using chloride ion concentration, it is preferable to use a colorant with a low chloride ion content. Specifically, it is preferable to use a colorant with a chloride ion concentration of 10.0 mmol / L or less in a dispersion obtained by dispersing 3.00 g of the colorant in 100 mL of water. A colorant with a chloride ion concentration of 5.0 mmol / L or less is more preferred, and a colorant with a chloride ion concentration of 1.1 mmol / L or less is even more preferred.

[0027] <Other materials> In order to properly form a flow channel pattern image of a microchannel device or to adjust the surface properties, chargeability, adhesion, etc. of the flow channel wall of a microchannel device, known charge control agents, waxes, etc. may be appropriately contained in the flow channel wall forming material without any particular limitations.

[0028] <Porous base material> The porous substrate is preferably one that exhibits moderate porosity and hydrophilicity. The porous structure is preferably an open-cell or mesh (nanofiber, etc.) structure, and examples thereof include filter paper, plain paper, high-quality paper, watercolor paper, Kent paper, synthetic paper, synthetic resin porous film, fabric, and textile products. Among these, filter paper is preferred because of its high porosity and good hydrophilicity. To enhance visibility with a colorant, a light color is preferred, and white filter paper is particularly preferred. The porosity can be appropriately selected depending on the purpose, but is preferably 20% to 90%. If the porosity exceeds 90%, the strength required as a substrate may not be maintained, and if it is less than 20%, the permeability of the sample liquid may be reduced.

[0029] The porosity (%) is Porosity (%) = (true density - apparent density) / true density x 100 This is the value calculated as follows. Also, the apparent density (g / cm 3 )teeth, Apparent density (g / cm 3 ) = basis weight (g / m 2 ) / thickness (mm) x 1000 was calculated from

[0030] Hydrophilicity is a necessary property for allowing a biological fluid containing water, such as blood, urine, or saliva, to diffuse into the substrate as a sample liquid. The average thickness of the porous substrate can be selected appropriately depending on the purpose, but is often 0.02 mm to 0.3 mm. If the average thickness is less than 0.02 mm, the substrate may not be able to maintain its strength. In addition, the proportion of the interior of the channel wall relative to the overall thickness increases, making it difficult to achieve the desired effect. However, by selecting a substrate with a low porosity or a thin fiber diameter, it is possible to achieve the same effect even with a thin substrate. Depending on the application, a porous substrate with a thickness of about 0.6 mm may be used. Table 1 shows the weights of the porous substrates S1 and S2 used in the examples.

[0031] [Table 1]

[0032] <Flow path> A channel is a region of the porous substrate bounded by channel walls (described in more detail below). A liquid such as a sample is confined within the channel by the channel walls and flows through the channel due to capillary action occurring within the porous substrate.

[0033] <Channel wall> The flow path wall is composed of a porous substrate and a flow path wall-forming material (containing at least a thermoplastic resin and a colorant) filled into the pores of the porous substrate. A flow path pattern is formed on the porous substrate using the flow path wall-forming material, and the thermoplastic resin forming the flow path pattern is melted by a heating unit (not shown) described below and allowed to penetrate into the porous substrate, thereby forming the flow path wall.

[0034] <Flow path wall formation> In this embodiment, a flow channel pattern 80 shown in FIG. 1 was formed on porous substrates S1 and S2 using a flow channel pattern forming unit 100 shown in FIG. 2. To use the device as a microchannel device, a pattern 81 was formed surrounding a reagent section 83, a test solution section 84, and a flow channel 82. The reagent section 83 is an area for attaching a reagent, the test solution section 84 is an area for attaching a test solution (sample liquid), and the flow channel 82 is an area connecting the reagent section 83 and the test solution section 84. The width L1 of the pattern 81 surrounding the flow channel 82 was 4 mm, and the width L2 of the flow channel 82 was 1.5 mm. The diameter L3 of the test solution section 84 was 8 mm, and the longest portion L4 of the flow channel was 30 mm. As an example of use as a microchannel device, for example, a chemical that exhibits a color reaction may be attached to the reagent section 83, and then the test solution may be attached to the test solution section 84. This allows for testing whether the test solution diffuses through the flow channel 82 to the reagent section 83 and causes a color reaction. Furthermore, the amount of ions in the test liquid can be measured by attaching a commercially available ion selective electrode to the reagent section 83. However, the shape and size of the flow path pattern are not limited to this, and a combination of straight lines and curves, or a branched shape may also be used, and the width and cross-sectional area of ​​the flow path and flow path wall may be changed as appropriate midway through the flow path.

[0035] In the examples described later, an electrophotographic image forming apparatus was used as the flow path pattern forming unit 100 in FIG. 2 in this embodiment to form a flow path pattern on a porous substrate. When an electrophotographic image forming apparatus is used, it is possible to freely form a high-resolution channel pattern on a porous substrate, making it possible to fabricate a highly accurate microchannel device with a desired channel pattern. An electrophotographic image forming apparatus as described below can be used as the flow path pattern forming unit 100. However, the method of forming the flow path pattern is not particularly limited to the method described below.

[0036] <Image formation unit (flow path pattern formation unit)> The image forming unit 100 houses a process cartridge P. The process cartridge P has a photosensitive drum 11 as an image carrier. Around the photosensitive drum 11, there are provided a charging roller 12 for charging the surface of the photosensitive drum 11, a developing device 20 for developing an electrostatic latent image formed on the surface of the photosensitive drum 11 with a developer (particles of a material forming the flow path walls), and a cleaning member 14 for cleaning the surface of the photosensitive drum 11. Voltages required for image formation can be applied by a charging high-voltage power supply 71, a developing high-voltage power supply 72, and a transfer high-voltage power supply 74, and are controlled by a control unit (not shown).

[0037] When image formation starts, a voltage for image formation is applied to the charging roller 12, and the surface of the photosensitive drum 11 is uniformly charged. After the surface of the photosensitive drum 11 is charged by the charging roller 12, the surface of the photosensitive drum 11 is irradiated with a laser beam 9 from an exposure unit 73, and an electrostatic latent image is formed.

[0038] <Image (flow path pattern) formation process> The developing roller 23 rotates in the direction of arrow C, and the supply roller 24, which serves as a supply member for developer (particles T: particles of a flow path wall-forming material), rotates in the direction of arrow D, driven by a connected motor M2 (not shown). When a development voltage is applied to the developing roller 23, the developing roller 23 supplies developer to the electrostatic latent image formed on the photosensitive drum 11, thereby developing the image. The ratio of the moving speed of the surface of the photosensitive drum 11 to the moving speed of the surface of the developing roller 23 (moving speed of the surface of the developing roller 23 / moving speed of the surface of the photosensitive drum 11) is called the developing peripheral speed ratio. By controlling this developing peripheral speed ratio, the amount of developer developed on the photosensitive drum 11 can be controlled. For example, if the developing peripheral speed ratio is 2.5, and all of the developer on the developing roller 23 is used to develop the electrostatic latent image on the photosensitive drum 11, the amount of developer per unit area on the surface of the photosensitive drum 11 will be 2.5 times the amount of developer per unit area on the surface of the developing roller 23. In the examples described later, the developing peripheral speed ratio was controlled so that an amount of developer suitable for forming microchannel walls inside the porous substrates S1 and S2 could be developed.

[0039] The porous substrates are placed on a paper feed tray 1 and are picked up one by one by a pickup roller 2. The developed developer image is transferred to the porous substrate by the potential difference with a transfer roller 4 applied by a transfer high voltage power supply 74. The porous substrate with the transferred developer image is discharged to the outside of the image forming unit with the developer image facing upward in the direction of gravity. After passing the transfer roller 4, the photosensitive drum 11 is scraped off any untransferred developer by the cleaning member 14 that is in contact with it. A series of processes starting with charging by the charging roller 12 is repeated to form images continuously.

[0040] <Heating process> The porous substrate onto which the flow path pattern has been transferred undergoes a heating process using a heating unit (not shown). The heating process causes the thermoplastic resin contained in the flow path wall-forming material to melt and penetrate into the porous substrate, forming hydrophobic flow path walls. While some of the colorant may penetrate along with the penetration of the thermoplastic resin, it is important that the colorant concentration on the surface side of the porous substrate be higher than that inside the flow path walls. The heating temperature must be such that the thermoplastic resin melts and penetrates into the porous substrate. In the examples described below, the heating conditions were 200°C and 2 minutes. An oven (Yamato Scientific Co., Ltd., constant temperature incubator with air blower, DN610H) was used as the heating unit. However, the heating method is not limited to this, and a far-infrared heater, a hot plate, or the like may also be used, and the heating conditions should be selected according to the physical properties of the particles T1 and the porous substrate.

[0041] FIG. 3(a) is a schematic cross-sectional view taken along the dashed line 80a in FIG. 1, showing a state in which particles T containing a flow path wall-forming material are placed on the surface of the porous substrate S1. FIG. 3(b) shows a state in which the particles T shown in FIG. 3(a) are heated, the resin in the particles T is melted, and the resin has permeated into the porous substrate S1. FIG. 3(c) is an enlarged schematic diagram showing the cross section of particle T before heating.

[0042] As shown in Figure 3(b), when the resin Tb in the channel wall-forming material is heated to a predetermined temperature, it melts, but the colorant Tp does not melt due to the heat. Therefore, when the resin Tb penetrates into the porous substrate, the colorant Tp becomes entangled with the paper fibers that form the open cell and network structure of the porous substrate, and is therefore more likely to remain near the device surface in the cross-sectional direction of the microchannel device. As a result, the colorant content in the channel walls in the cross-sectional direction of the microchannel device is higher on the surface side of the channel wall than inside the channel wall, resulting in the formation of a microchannel device having channels surrounded by such resin walls. [Example]

[0043] The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. In the text, "parts" and "%" are by mass unless otherwise specified.

[0044] Example 1 In this example, S1 was used as the porous substrate. Furthermore, the flow path wall forming material in this example was particles T1 with a number average particle size of 6.5 μm, which were produced by the following manufacturing method.

[0045] <Production of Particle T1> [Preparation of Polymerizable Monomer Composition] The following composition was mixed and dispersed in a ball mill for 3 hours. Styrene 70.0 parts n-Butyl acrylate 30.0 parts Divinylbenzene 0.1 parts ·PV Fast Blue BG 0.4 parts Polyester resin 5.0 parts (Polycondensation polymer of propylene oxide-modified bisphenol A and isophthalic acid (glass transition temperature 65°C, weight average molecular weight (Mw) 10,000, number average molecular weight (Mn) 6,000)) The obtained dispersion was transferred to a reactor equipped with a propeller stirring blade and heated to 60°C while stirring at a rotation speed of 300 rpm. Then, 3.0 parts of 2,2'-azobis(2,4-dimethylvaleronitrile) was added and dissolved to obtain a polymerizable monomer composition.

[0046] [Preparation of aqueous dispersion medium] 710 parts of ion-exchanged water and 450 parts of 0.1 mol / L sodium phosphate aqueous solution were added to a 2 L four-neck flask equipped with a high-speed stirring device TK Homomixer (manufactured by Primix Corporation), and the mixture was heated to 60°C while stirring at 12,000 rpm. 68.0 parts of 1.0 mol / L calcium chloride aqueous solution were added to the flask to prepare an aqueous dispersion medium containing calcium phosphate (a poorly water-soluble dispersion stabilizer).

[0047] [Granulation / Polymerization] The polymerizable monomer composition was added to the aqueous dispersion medium, and the rotation speed was maintained at 12,000 rpm. 10 parts of the polymerization initiator t-butyl peroxypivalate was added and granulated for 15 minutes. The high-speed agitator was then replaced with a propeller agitator, and the internal temperature was maintained at 60°C to continue the polymerization reaction for 5 hours. The internal temperature was then increased to 80°C and maintained at this temperature, and the polymerization reaction was continued for another 3 hours. After the polymerization reaction was completed, the remaining monomer was distilled off at 80°C under reduced pressure, and the mixture was cooled to 30°C to obtain a polymer microparticle dispersion.

[0048] [Cleaning] The polymer microparticle dispersion was transferred to a washing container, and while stirring, dilute hydrochloric acid was added to adjust the pH to 1.5. The dispersion was stirred for 2 hours, and then subjected to solid-liquid separation using a filter to obtain polymer microparticles. This was then added to 1,200 parts of ion-exchanged water and stirred, and the resulting dispersion was again prepared, and then subjected to solid-liquid separation using a filter. This operation was repeated three times to obtain base particles of particle T1.

[0049] [External attachment] Furthermore, 100.0 parts of the obtained base particles were dry-mixed with 1.0 part of a flowability improver (silica having a number-average particle diameter of 7 nm) surface-treated with hexamethyldisilazane for 5 minutes in a Henschel mixer to obtain particles T1 for forming flow path pattern images having a number-average particle diameter D1 of 6.5 μm. <Fabrication of microfluidic devices> Using the obtained particles T1, a microchannel device was produced under the above-mentioned conditions using an electrophotographic image forming apparatus.

[0050] <Example 2> In this example, a microchannel device was produced in the same manner as in Example 1, except that the amount of the colorant PV Fast Blue BG was changed to 3.0 parts.

[0051] Example 3 In this example, a microchannel device was fabricated in the same manner as in Example 1, except for the following changes. The colorant was changed from PV Fast Blue BG to Toner Yellow 3GP (manufactured by Clariant), and the amount used was changed to 0.3 parts.

[0052] Example 4 In this example, a microchannel device was fabricated in the same manner as in Example 1, except for the following changes. The colorant was changed from PV Fast Blue BG to Irgalite Toner Yellow L 1257 (manufactured by BASF), and the amount used was changed to 0.2 parts.

[0053] <Example 5> In this example, a microchannel device was fabricated in the same manner as in Example 1, except for the following changes. The colorant was changed from PV Fast Blue BG to Toner Magenta E (manufactured by Clariant), and the amount used was changed to 0.1 parts.

[0054] Example 6 In this example, a microchannel device was fabricated in the same manner as in Example 1, except that the porous substrate was changed from S1 to S2.

[0055] <Comparative Example 1> In this comparative example, a microchannel device was fabricated in the same manner as in Example 1, except that the channel wall forming material did not contain a colorant.

[0056] <Evaluation of microfluidic devices> [Visibility check evaluation: measuring the difference in reflectance] In order to compare the visibility of the microchannel devices fabricated in this example, the concentration on the channel walls was measured by the following method. The reflectance D1 (%) of the portion of the microfluidic device surface where the channel walls were formed and the reflectance D2 (%) of the portion of the device surface where the channel walls were not formed (the portion that was left as a porous substrate) were measured at three points each using a white light meter TC-6DS / A manufactured by Tokyo Denshoku Co., Ltd. Furthermore, the arithmetic mean values ​​D1avg and D2avg were calculated using the measurements at each of the three points. Then, the visibility was judged using the value of (D2avg-D1avg) according to the following criteria. A: Very good (reflectance difference of 2.0% or more) B: Good (reflectance difference is 1.0% or more and less than 2.0%) C: Poor (reflectance difference less than 1.0%) If the difference in reflectance is 1.0% or more, the boundary between the presence and absence of flow path walls can be visually confirmed, and therefore it was determined that visibility was excellent.

[0057] <Measurement accuracy evaluation: Chloride ion concentration measurement> To confirm the influence of the microfluidic device fabricated in this example on the measurement accuracy, a commercially available chloride ion electrode sensor was used to confirm the change in chloride ion concentration. 20 mL of a sodium chloride solution adjusted to 1.00 mmol / L was dropped into the test solution section 84 of the flow channel shown in Figure 1, and the flow channel 82 of the microfluidic device was filled with the solution. Then, the measurement terminal of a calibrated chloride ion electrode (Shimadzu Rika Co., Ltd.: CI-6732) connected to a multi-chemical sensor (Shimadzu Rika Co., Ltd.: PS-2170) was pressed against the reagent section 83. The reference potential E0 (V) and proportionality coefficient S (V / (mol / L)) obtained by calibration, and the voltage value (stable voltage) E obtained by measurement were substituted into the following equation 1 to calculate the chloride ion concentration C (mmol / L).

[0058] C=10((E-E0) / S) (Formula 1) The difference between the measurement result of chloride ion concentration and the concentration of the sample solution was calculated, and the measurement accuracy was judged based on the calculated difference according to the following criteria. A: Very high (difference less than 0.02 mmol / L) B: High (difference is 0.02mmol / L or more but less than 0.10mmol / L) C: Low (difference is 0.10mmol / L or more) If the difference was less than 0.10 mmol / L, the measurement accuracy was judged to be good. Table 2 shows the measurement results of the colorant abundance ratio, the difference in reflectance, and the chloride ion concentration for each example and comparative example.

[0059] <Comparative Experiment Example 1> For comparison, 100 mL of the sodium chloride aqueous solution adjusted to 1.00 mmol / L was placed in a beaker, and the chloride ion electrode described above was immersed in the sample solution to measure the chloride ion concentration. The results are shown as Comparative Experimental Example 1.

[0060] <Comparative Experiment Example 2> 3.0 g of the colorant PV Fast Blue BG used in Example 1 was mixed with 100 mL of the above-mentioned 1.00 mmol / L aqueous sodium chloride solution and stirred for 1 hour. After that, the mixture was left to stand for 12 hours, and the supernatant was extracted and the chloride ion concentration of the sample solution was measured. The results are shown in Comparative Experimental Example 2. When 3.0 g of the colorant PV Fast Blue BG was dispersed in 100 mL of water, the chloride ion concentration was measured and found to be 1.02 mmol / L.

[0061] <Measurement of colorant abundance ratio> To confirm the location of the colorant in the channel wall, a portion of the channel wall of the fabricated microchannel device was cut out, immersed in a photocurable epoxy resin, and cured. Then, a thin sample measuring 300 μm square and 70 μm thick was cut out of the cured product using an ultramicrotome equipped with a diamond knife. The sample was magnified at 10,000 times using the scanning image mode of a scanning transmission electron microscope, and a cross-sectional image of the channel wall of the microchannel device was obtained.

[0062] The coloring agent in the cross-sectional image was identified using an energy dispersive X-ray spectrometer (EDX) and other instruments. As a result of the observation, it was confirmed that in each microchannel device manufactured in the examples, the proportion of colorant present in the surface region of the porous substrate in the channel wall was higher than the proportion of colorant present inside the channel wall.

[0063] In the porous substrate S1, the average fiber diameter was 18.3 μm and the porosity was 54%, so the depth D, expressed as (A / 2) / (1−B / 100), was 19.9 μm. In the region from the surface to a depth of 19.9 μm of the microchannel device produced in Example 1, the abundance ratio X (%) of the colorant in the portion of the channel wall excluding the porous substrate was 0.330%. Furthermore, in a region farther from the surface than 19.9 μm and also 19.9 μm from the back surface (i.e., a region 19.9 μm to 62.1 μm from the surface), the abundance ratio Y (%) of the colorant in the portion of the channel wall excluding the porous substrate was 0.057%. That is, the microchannel device produced in Example 1 satisfied X>Y. For the microchannel devices fabricated in Examples 2 to 6, X and Y were measured in the same manner as for the microchannel device fabricated in Example 1, and the results are shown in Table 2.

[0064] [Table 2]

[0065] As described above, according to the present invention, a microchannel device can be realized that has high reflection density and excellent visibility, allowing samples to be accurately dispensed to designated locations and preventing a decrease in testing accuracy. [Explanation of symbols]

[0066] 80...Flow path pattern 81. Image of channel wall forming material 82. Flow path 83. Reagent Department 84. Testing liquid section 100: Flow path pattern image forming unit

Claims

1. A method for manufacturing a microchannel device in which a channel sandwiched between channel walls is formed inside a porous substrate, comprising: a step of electrophotographically depositing a flow path wall forming material containing a thermoplastic resin and a colorant on the surface of the porous substrate to form a flow path pattern on the surface of the porous substrate; and a step of heating in an oven to melt the thermoplastic resin contained in the flow path pattern by heat, and causing the thermoplastic resin to permeate into the porous substrate, thereby forming flow path walls inside the porous substrate; and The content of the colorant in the flow path wall forming material is 1.0×10 －６ % by mass or more and 0.4% by mass or less, In the obtained microfluidic device, the flow path wall contains the thermoplastic resin and the colorant; the amount of the colorant contained in the flow path wall is 1.0 × 10 -6 mass % or more and 0.4 mass % or less based on the total mass of the components constituting the flow path wall excluding the porous substrate; A method for producing a microchannel device, wherein the colorant is present in a higher proportion in a surface region of the porous substrate in the channel wall than in an interior of the channel wall.

2. A method for manufacturing a microchannel device in which a channel sandwiched between channel walls is formed inside a porous substrate, comprising: a step of electrophotographically depositing a flow path wall forming material containing a thermoplastic resin and a colorant on the surface of the porous substrate to form a flow path pattern on the surface of the porous substrate; and a step of heating in an oven to melt the thermoplastic resin contained in the flow path pattern by heat, and causing the thermoplastic resin to permeate into the porous substrate, thereby forming flow path walls inside the porous substrate; and The content of the colorant in the flow path wall forming material is 1.0×10 －６ % by mass or more and 0.4% by mass or less, In the obtained microfluidic device, the flow path wall contains the thermoplastic resin and the colorant; the amount of the colorant contained in the flow path wall is 1.0 × 10 −6 mass % or more and 0.4 mass % or less based on the total mass of components constituting the flow path wall excluding the porous substrate; In the microchannel device, when the abundance ratio of the colorant in the portion of the channel wall excluding the porous substrate in a region from the surface to a depth D (μm) is X (%), and the abundance ratio of the colorant in the portion of the channel wall excluding the porous substrate in a region farther from the surface than the depth D is Y (%), X and Y satisfy the relationship X>Y (wherein the depth D is a depth (μm) expressed by (A / 2) / (1-B / 100) where A is the fiber diameter of the fibers forming the porous substrate and B is the porosity of the porous substrate).

3. The method for manufacturing a microchannel device according to claim 1 , wherein the colorant is a magenta pigment or a cyan pigment.

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