JP6637764B2 - Method for manufacturing structure having microchannel - Google Patents

Description

  Some aspects of the present invention relate to a structure or the like suitable for analysis of a biological sample such as a biochip and a microchip.

  2. Description of the Related Art In recent years, expectations for microchips and biochips capable of analyzing or separating even a small amount of sample have been increasing as elements used for sample analysis and separation and purification of substances. However, there has been almost no method for imparting a surface structure, affinity, or the like for stable analysis or separation to a biochip.

  For example, it is described that a surface suitable for immobilizing a physiologically active substance is formed by performing gamma ray or plasma treatment regardless of the atmosphere (see Patent Document 1). However, such a method has a problem that a stable surface cannot be maintained as a product.

JP 2006-132943 A

  In view of such circumstances, it is an object of some aspects of the present invention to provide a method for manufacturing a structure suitable for analysis of a biological sample such as a biochip and a microchip.

  The method for manufacturing a structure according to the present invention includes a first step of preparing a first base having a first surface and a second surface, and a step of applying a composition to at least a part of the first surface. A second step of disposing, and a third step of curing a first portion of the composition by applying energy to at least a part of the composition to form a cured product, After the completion of the step 3, at least a second portion of the composition other than the first portion is in a removable state.

  The method for manufacturing a product according to the present invention includes a first step of preparing a first substrate having a first surface and a second surface, and disposing a composition on at least a part of the first surface. And a third step of curing the first portion of the composition by applying energy to the composition to form a cured product, wherein the third step comprises: Performed in a state where the first substrate and the composition are packaged with packaging materials for packaging, and after the third step, at least a part of the composition other than the first part. A certain second portion is characterized in that it can be removed.

  A structure according to the present invention includes: a first base having a first surface and a second surface; and a first organic substance disposed in a first region of the first surface. The surface of the first region and the surface of the second region which is one of the regions other than the first region on the first surface are both made of a second organic material, The lyophilicity of the surface of the first region with respect to the first liquid is different from the lyophilicity of the first organic substance with respect to the first liquid, and the lyophilicity of the surface of the first region with respect to the first liquid. The lyophilicity of the second region is substantially the same as the lyophilicity of the surface of the second region with respect to the first liquid.

  The folder according to the present invention can fix the above structure. The folder can fix or hold a plurality of the above structures.

  The molded article according to the present invention is the first base used for manufacturing the above-mentioned structure.

  The method for purifying a biological sample according to the present invention includes a first step of preparing the biological sample, and a second step of bringing the biological sample into contact with at least a part of the structure. I do.

  An inspection apparatus according to the present invention uses the above structure.

  The compound according to the present invention includes a first unit represented by the following general formula (1), a second unit represented by the following general formula (2), and a second unit represented by the following general formula (3). And the first unit, the second unit, and the third unit have different structures from each other.

（一般式（１）中、置換基A及びBの各々は炭素を含む２価の置換基であり、置換基Cは炭素を含む１価の基であり、R₁は水素原子又は有機基であり、w、a、及びbは自然数である。）

(In the general formula (1), each of the substituents A and B is a divalent substituent containing carbon, the substituent C is a monovalent group containing carbon, and R ₁ is a hydrogen atom or an organic group. And w, a, and b are natural numbers.)

（一般式（２）中、置換基D及びEの各々は炭素を含む２価の置換基であり、置換基Fは重合性基を有する１価の置換基であり、R₂は水素原子又は有機基であり、x、d及びeは自然数である。）

(In the general formula (2), each of the substituents D and E is a divalent substituent containing carbon, the substituent F is a monovalent substituent having a polymerizable group, and R ₂ is a hydrogen atom or It is an organic group, and x, d and e are natural numbers.)

（一般式（３）中、置換基G及びHの各々は炭素を含む２価の置換基であり、置換基Iは官能基を有する１価の置換基であり、R₃は水素原子又は有機基であり、y、g及びhは自然数である。）

(In the general formula (3), each of the substituents G and H is a divalent substituent containing carbon, the substituent I is a monovalent substituent having a functional group, and R ₃ is a hydrogen atom or an organic And y, g and h are natural numbers.)

It is a figure explaining the manufacturing process of the structure which has a microchannel. It is a figure which shows the structure of a sorting chip. FIG. 3 is a diagram illustrating a manufacturing process of the sorting chip shown in FIG. This is a sorting apparatus configured using a structure having a microchannel. This is a sorting apparatus configured using a structure having a microchannel, and has a configuration different from that of the sorting apparatus in FIG. FIG. 3 is a diagram when a structure having a plurality of microchannels is stacked and arranged in a folder. This is an inspection apparatus using a structure having a plurality of stacked microchannels. It is a figure explaining the case where a part of manufacturing process of a structure which has a microchannel in a packaging material is performed.

  The method for manufacturing a structure according to the present invention includes a first step of preparing a first base having a first surface and a second surface, and a step of applying a composition to at least a part of the first surface. A second step of disposing, and a third step of curing a first portion of the composition by applying energy to at least a part of the composition to form a cured product, After the completion of the step 3, at least a second portion of the composition other than the first portion is in a removable state.

  According to the method for manufacturing a structure described above, it is possible to manufacture a structure having a partially different surface state. In the structure manufacturing method, the “removable state” can be achieved, for example, by changing the cured state of the composition between the first portion and the second portion. Specifically, for example, by adjusting the curing conditions such as the oxygen concentration between the first region and the second region, even if the energy is applied to the entire composition, This can be achieved by setting a part (second region) in an unreacted or uncured state. Alternatively, the “removable state” can also be achieved by applying the energy only to a desired portion (first region) of the composition via a mask or the like. Further, the “composition” may be composed of a single compound, or may be composed of a plurality of compounds.

  Examples of a method for “removing” the second portion include wet etching, dry etching, ashing, and a YAG laser.

  In the above manufacturing method, the first portion is formed in a first region of the first surface, and the second portion is formed in a second region of the first surface. It is preferable that the lyophilic property of the object with respect to the first liquid is different from the lyophilic property of the second region with respect to the first liquid. In this manner, a structure having a plurality of regions having different affinities for a desired liquid can be manufactured.

  The above aspect can be achieved, for example, by changing at least one of the material constituting the surface, the physical properties, the surface shape, and the like between the first region and the second region.

  In the above structure manufacturing method, the surface of the second region is preferably made of an organic material. By doing so, for example, an organic substance can easily adjust the polarity and affinity for a specific liquid or molecule as compared with an inorganic substance, so that desired surface properties can be easily obtained.

  In the above method of manufacturing a structure, the first step preferably includes a first sub-step of forming or forming the second region by arranging or forming an organic substance on at least a part of a substrate. By doing so, for example, an organic substance can easily adjust the polarity and affinity for a specific liquid or molecule as compared with an inorganic substance, so that desired surface properties can be easily obtained.

  The term “arrange or form an organic substance” specifically includes, for example, arranging or forming a coating film or an adsorption film of a composition as an organic substance.

  The method for manufacturing a structure described above further includes a fifth step of preparing a second base before the third step, and a period during which the energy is applied to the composition in the third step. It is preferable that at least a part of the first part be in contact with at least a part of the second base. By doing so, for example, the degree of the effect of oxygen can be changed between the portion of the composition that is in contact with the second substrate and the portion that is not in contact with the second substrate, so that there is a difference in the progress of the reaction and the degree of curing. Can be caused.

  In the method of manufacturing a structure described above, a fourth step of removing the second portion may be further included. By doing so, for example, the lyophilicity, affinity, and the like can be changed between the first portion and the second portion, specifically, depending on the region or location.

  In the method for manufacturing a structure described above, a first distance that is a distance between the first surface and the second surface in the first region is equal to a distance between the first surface and the second surface in the second region. It is preferable that the distance is different from the second distance which is the distance to the second surface. As an example of such a configuration, for example, a configuration in which a concavo-convex pattern, a groove, or the like is formed on any one of the first surface and the second surface is given.

  In the method for manufacturing a structure described above, it is preferable that the first distance is larger than the second distance. As an example of such a configuration, for example, there is a configuration in which the second region is formed as a concave portion or a groove of a concave-convex pattern. In such a configuration, the recesses or grooves can be used for locating or capturing the components of the sample. Further, the groove can be used as a liquid or gas flow path.

  The method for manufacturing a product according to the present invention includes a first step of preparing a first substrate having a first surface and a second surface, and disposing a composition on at least a part of the first surface. And a third step of curing the first portion of the composition by applying energy to the composition to form a cured product, wherein the third step comprises: Performed in a state where the first substrate and the composition are packaged with packaging materials for packaging, and after the third step, at least a part of the composition other than the first part. A certain second portion is characterized in that it can be removed. In this way, by applying energy to the composition in a packaged state, for example, the atmosphere can be controlled, and the conditions for the curing reaction of the composition can be easily adjusted. Further, for example, it is possible to sterilize the above product together with applying energy to the composition, which is particularly advantageous when the above product is used for inspection or separation of a biological sample.

  In the above method for manufacturing a product, it is preferable that the second portion can be removed by using a second liquid. By doing so, for example, after opening the package, it is possible to remove the second portion by using a pretreatment step using a liquid, so that the number of steps can be reduced. .

  In the above-described method for producing a product, it is preferable that the energy be applied to the composition using an electromagnetic wave. Since a typical electromagnetic wave has a property of transmitting through a packaging material, for example, energy can be applied to the composition after packaging.

  In the above manufacturing method, the electromagnetic wave is preferably a gamma ray or an X-ray. By doing so, for example, it becomes possible to sterilize while applying energy.

  A structure according to the present invention includes: a first base having a first surface and a second surface; and a first organic substance disposed in a first region of the first surface. The surface of the first region and the surface of the second region which is one of the regions other than the first region on the first surface are both made of a second organic material, The lyophilicity of the surface of the first region with respect to the first liquid is different from the lyophilicity of the first organic substance with respect to the first liquid, and the lyophilicity of the surface of the first region with respect to the first liquid. The lyophilicity of the second region is substantially the same as the lyophilicity of the surface of the second region with respect to the first liquid.

  Specifically, as the structure in the above aspect, for example, the surface of the first region and the second region in the first substrate in which the first substrate itself is made of the second organic substance or made of an arbitrary material A layer made of a second organic substance is formed on the surface of the first surface, and the first organic substance is disposed in a first region of the first surface. In any configuration, the first organic substance is preferably made of a material having a lyophilic property different from that of the second organic substance with respect to the first liquid.

  In the above structure, the structure is used for separating or purifying a first component contained in a biological sample, and when performing the separation or purification, the first component is used for the first component. It is preferable that the existence density on the second region is higher than that on the organic material.

  In the above aspect, since the biological sample is often an aqueous solvent, the affinity of the surface of the second region for the first component in the structure is determined by the first component of the first organic substance. It may be different from the affinity for. More specifically, the affinity of the surface of the second region for the first component is higher than the affinity of the first organic substance for the first component, that is, the affinity for water is improved. What should I do?

  The folder according to the present invention can fix the above structure. The folder can fix or hold a plurality of the above structures.

  The molded article according to the present invention is the first base used for manufacturing the above-mentioned structure. The molded product may be formed by, for example, etching, injection molding, a cutting process, or the like.

  The method for purifying a biological sample according to the present invention includes a first step of preparing the biological sample, and a second step of bringing the biological sample into contact with at least a part of the structure. I do. Examples of a method of bringing a biological sample into contact with at least a part of the structure include, for example, a method of passing a liquid containing the biological sample through a groove structure or the like using a pressing force, a suction force, a centrifugal force, or a capillary force. Can be

  An inspection apparatus according to the present invention uses the above structure.

  In the method for manufacturing a second structure according to the present invention, a first base having a first surface and a second surface and a second base having a third surface and a fourth surface are prepared. A first step of disposing a composition on at least a part of at least one of the first surface and the third surface; and a first step of disposing the composition on the first surface of the first surface. And applying a energy to the composition in a state of being in contact with the region of the third surface and the third region of the third surface, thereby curing the composition. By doing so, for example, the conditions for curing the composition can be locally changed.

  In the third step of the method for manufacturing a structure, a first portion of the composition that is in contact with both the first region and the third region; The degree of hardening can be made different from the second portion which is in contact with only one of the third regions. Here, if the third step is performed in an atmosphere in which oxygen is present, such as under air, using the composition whose curing speed is reduced by oxygen or the like, the first process of the composition is performed. The curing of the second portion can be delayed as compared to the portion. Therefore, if the time for applying the energy is appropriately adjusted, the second portion can be removed by washing with a solvent, distillation under reduced pressure, or the like. On the other hand, if a composition that exhibits an adhesive function by its curing is used as the composition, the third step allows the first substrate and the second substrate to intervene via the cured first portion. It is more preferable because it is adhered.

  In order to have a second portion that is in contact only with either one of the second region and the third region, the second portion must be in contact with one of the second region and the third region. A method in which a concave portion is formed in one of the regions so as to make contact with only the first region, or a method in which a coating film of the composition in the first region is thickly applied by screen printing or the like is given.

  In the above-mentioned method for manufacturing a second structure according to the present invention, the first surface may have a pattern having an uneven portion or a groove. For example, by appropriately setting the distance between the first surface and the second surface when performing the third step, the concave portion or the concave portion of the uneven portion when performing the second step Since the composition disposed in the groove can be prevented from contacting the second base, the composition disposed in the recess or the groove can be in an uncured state. . It is possible to remove the uncured composition and form a flow path using the recess or the groove. Here, if the composition is selected to have a predetermined level of affinity for a predetermined liquid due to its curing, for example, the cured product of the composition may be located on the side of the flow path. Can be In other words, if the liquid flowing through the flow path is hydrophilic, select a composition that becomes hydrophobic by its curing, and if the liquid flowing through the flow path is hydrophobic, select a composition that becomes hydrophilic by its curing. Select Thereby, the penetration of the sample or the liquid flowing through the flow path from the flow path is suppressed, or the force acting between the liquid in the flow path and the inner surface of the flow path, such as surface tension, is adjusted. Therefore, the generation of bubbles in the flow channel can be suppressed. In addition, if the composition is selected so that a predetermined substance permeates by curing, a desired sample can be preferentially flown through the flow channel.

  In the case of using a structure manufactured by the above-described method for manufacturing a structure for analyzing biological components such as blood components or blood cells, the composition has a contact angle to water of 60 ° due to its curing. The above may be used. At this time, if a hydrophilic material that can be removed with a solvent containing water is used as the composition, the hydrophilicity of a cured product formed by curing the composition is low. This has the advantage that damage can be suppressed and the uncured composition is easily removed.

  The compound according to the present invention has at least a first unit represented by the following general formula (1), a second unit represented by the following general formula (2), and a compound represented by the following general formula (3) And a third unit, and these units have different structures from each other.

  Note that each of the first to third units does not necessarily have to be connected and blocked in a continuous manner, but may be blocked in accordance with the application or affinity with the substrate to be contacted.

  W, x, and y of the above-mentioned first to third units are natural numbers. For example, in order to manufacture a phase separation structure, the numbers of w, x, and y in the first to third units may be appropriately set according to a desired phase separation structure. In the above compounds, the substituents A, B, C, D, E, F, G, and H are carbon-containing substituents. The substituents A, B, D, E, G, and H are preferably divalent substituents containing carbon, the substituents C and F are monovalent substituents containing carbon, and I is a functional group. It is preferably a monovalent substituent having a group. It is preferable that among the substituents A, B, C, D, E, F, G, H, and I, C, F, and I have different hydrophilicities from each other. Thereby, for example, a site having a different affinity for another molecule in one molecule can be provided.

  The above compound preferably has a fourth unit represented by the following in addition to the above three types of units.

  In the above compounds, the substituents J, K, and L are carbon-containing substituents. Preferably, the substituents J and K are divalent substituents containing carbon, and the substituent L is a monovalent substituent containing carbon. It is preferable that the fourth unit has a structure different from any of the above-described first to third units.

In the above compound, z is a natural number.
In the above compounds, a, b, d, e, g and h are natural numbers.

  In the above compounds, the substituent F preferably has a polymerizable group. When the substituent F has a polymerizable group, the above compound can be further polymerized. Thereby, for example, a more stable film can be manufactured.

In the above compound, the functional group in the substituent I has a reactivity with another molecule such as a hydroxy group, an amino group, a silicon group, a carboxy group, or can be converted to another substituent. It is preferable that it is possible. Thus, for example, the above compound can be further reacted after being applied to the substrate.
The silicon group will be described later.

  In the above compound, the substituent A, the substituent D, and the substituent G are preferably a divalent substituent represented by the following general formula (5). When the substituent A, the substituent D and the substituent G are represented by the following general formula (5), a, d and g in the above general formulas (1), (2) and (3) Is preferably 1. The substituent A, the substituent D, and the substituent G may be -CONH- or the like in addition to the divalent substituent represented by the following general formula (5).

  In the above compound, the substituent B, the substituent E, and the substituent H are preferably divalent substituents represented by the following general formula (6). When the substituent B, the substituent E, and the substituent H are represented by the following general formula (6), b, e, and h in the above general formulas (1), (2), and (3) Is preferably an integer of 1 to 100, respectively. The substituent B, the substituent E, and the substituent H may be an alkylene group, a polypropylene oxide group, a polybutylene oxide group, or the like in addition to the divalent substituent represented by the following general formula (6). preferable.

  In the above compounds, the substituent C is preferably a monovalent substituent containing 3 or more carbon atoms. It is more preferably a long-chain alkyl group having 3 or more carbon atoms, further preferably a long-chain alkyl group having 5 to 20 carbon atoms, and particularly preferably a long-chain alkyl group having 5 to 18 carbon atoms. The substituent C may be a linear alkyl group or a branched alkyl group.

  The substituent F in the second unit represented by the general formula (2) is preferably a monovalent substituent having a polymerizable group. Preferred examples of the polymerizable group in the substituent F include a (meth) acryloyl group, a vinyl group, an allyl group, and an epoxy group, and a (meth) acryloyl group is more preferred. The substituent F may be the polymerizable group itself.

  Examples of the functional group in the substituent I in the third unit represented by the general formula (3) include a hydroxy group, an amino group, a silicon group, and a carboxy group. Examples of the silicon group include a trialkylsilyl group, a triarylsilyl group, and a trialkoxysilyl group.

  Examples of the substituent I include a hydroxyethyl group, an aminomethyl group, an aminoethyl group, a trialkylsilylethyl group, a triarylsilylethyl group, a trialkoxysilylethyl group, and a carboxyethyl group.

  Examples of the substituent J in the fourth unit represented by the general formula (4) include the same substituents as the substituents A, D, and G in the first to third units. As the substituent K in the fourth unit, the same substituents as the substituents B, E and H in the first to third units can be mentioned. The substituent L in the fourth unit is preferably a substituent containing 2 or less carbon atoms. The substituent L is more preferably an alkyl group having 2 or less carbon atoms, further preferably a methyl group or an ethyl group, and particularly preferably a methyl group.

Each of R ₁ , R ₂ , R ₃ and R ₄ is a hydrogen atom or an organic group. Examples of the organic group include an alkyl group such as a methyl group and an ethyl group.

  The compound is obtained by polymerizing using a corresponding monomer for constituting the first unit, the second unit, and the third unit.

  It is more preferable that the monomer for constituting the first unit, the second unit, and the third unit is a unit derived from a polyalkylene glycol (meth) acrylate monomer. Specifically, preferred combinations of the first to third units include the following. The first unit is preferably a unit derived from a polyalkylene glycol (meth) acrylate having a long-chain alkyl group having 3 or more carbon atoms as the substituent C, and the second unit is preferably a substituted unit. The group F is preferably a unit derived from a polyalkylene glycol (meth) acrylate having a monovalent substituent containing the above polymerizable group. The third unit is preferably a unit derived from polyalkylene glycol (meth) acrylate having a monovalent substituent containing a functional group as the substituent I. The fourth unit, which is an arbitrary unit, is preferably a unit derived from polyalkylene glycol (meth) acrylate having a monovalent hydrocarbon group containing 2 or less carbon atoms as the substituent L.

  The content ratio of each unit may be appropriately adjusted depending on the desired physical properties. For example, when changing the contact angle or improving the applicability to the substrate, the first unit, the second unit, the third unit, and the fourth unit may be changed depending on the type of the substrate used. The content with respect to the whole compound can be adjusted optimally. For example, by increasing the content of the first unit and the second unit, a composition having a high contact angle can be obtained, and the affinity with a hydrophobic plastic substrate can be improved. More specifically, in order to improve the affinity with the hydrophobic plastic substrate, the content of the first unit is preferably 0.01 to 50 mol%, more preferably 1 to 50 mol%, and 1 to 50 mol%. 20 mol% is more preferred.

  Further, for example, by increasing the number of the third units, the composition becomes a hydrophilic composition and the affinity with a hydrophilic substrate such as glass can be improved.

  The preferred range of the content ratio of each unit other than the first unit is as follows. The content of the second unit is preferably 0.1 to 50 mol%. The content of the third unit is preferably from 3 to 80 mol%, more preferably from 5 to 50 mol%. The content of the fourth unit is preferably 0 to 90 mol%, more preferably 30 to 90 mol%, and even more preferably 50 to 90 mol%.

  The compound of the present invention can improve the adjustment of the contact angle, the applicability to a substrate, the adsorbability to proteins, and the like by appropriately adjusting the content of each unit described above.

  The weight average molecular weight of the compound in the above combination is preferably MW 20,000 to 80,000. In order to make the weight average molecular weight fall within the above range, polymerization conditions may be appropriately adjusted.

  In the present invention, the weight average molecular weight is obtained in terms of polyethylene glycol.

  In the present invention, “(meth) acryl” means acrylyl and / or methacryl, and “(meth) acrylate” means acrylate and / or methacrylate.

  Materials and processes according to some aspects of the present invention will be specifically described below.

(1) Synthesis of composition

As the composition used in the method for producing a structure of the present invention, the above compound is suitably used.
A typical composition according to the present invention is synthesized using the following PA, PM and PH as starting materials. First, a thermal polymer is synthesized by applying heat to PA, PM, and PH, and then the polymer is obtained by applying AM to the polymer to convert at least a part of the hydroxy group to a methacryloyl group. The composition is a polymer having units of the following general formulas (7) to (10). The unit represented by the following general formula (10) has a methacryloyl group having a polymerizable group at a terminal. Note that a plurality of raw materials having different numbers of m, o, and p for each of PA, PM, and PH can be used.

  In the above structural formulas of PA, PM, and PH, m, o, and p are natural numbers, and n represents a natural number of 3 or more. Each of m, o, and p is a natural number, and is preferably an integer of 1 to 100.

  The polymer can be produced under known polymerization conditions. The mixing ratio of each raw material may be appropriately adjusted depending on the desired physical properties.

  As the corresponding monomer constituting the first unit, for example, PH can be used. In addition to a monomer having a hydroxy group as a functional group, a monomer having an epoxy group, an amino group, or the like can be used. Specific examples include glycidyl (meth) acrylate, 4-hydroxybutyl acrylate glycidyl ether, allylamine, N-formamide capable of inducing an amino group, and the like.

  The third unit can be obtained, for example, by bonding a monomer having a polymerizable group to the functional group of the second unit as described above. 2-isocyanatoethyl methacrylate, 2-isocyanatoethyl acrylate, 2-[(3,5-dimethylpyrazolyl) carbonylamino] ethyl (meth) acrylate and (meth) acryloyl chloride, which are derivable to isocyanate groups. No.

(2) Production of Structure Having Micro Channel A typical manufacturing procedure of a structure having a micro channel according to the present invention will be described with reference to FIG. First, a first base 1 on which a pattern such as unevenness is formed is prepared, a composition is applied on a first region of a first surface of the first base 1, and a coating film 3 of the composition is applied. (A). Next, the first base 1 and the second base 2 are brought into close contact with each other in a state where the composition is applied to the first region of the first base 1 (b). The coating film 3 of the composition is irradiated with light such as ultraviolet rays or radiation (electromagnetic waves) through the coating to cure the composition in the convex portion, thereby forming a resin film 4 as a cured product (c). Preferred examples of the electromagnetic wave include gamma rays and X rays.

  After the step (c), by washing with a solvent, the uncured composition in the gap (recess) between the first substrate 1 and the second substrate 2 is removed, and The void serves as a microchannel, and a structure including the first base 1 and the second base 2 in which the microchannel is formed is manufactured. In the above aspect, the convex portion becomes the first region, and the concave portion becomes the second region.

  The members used for the first base and the second base are appropriately selected depending on the use and desired properties. For example, a resin can be used. Specific examples of the resin include polycarbonate, polymethyl methacrylate, polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, nylon 6, nylon 66, polyvinyl acetate, polyvinylidene chloride, polypropylene, polyisoprene, polyethylene, and polydimethyl. Examples include siloxane and cyclic polyolefin. Also, copper, aluminum, iron, silicon, nickel, other various metals and their alloys, metal oxides such as silica, alumina, zirconia and titania, and mixtures thereof, glass materials, silicon carbide and boron nitride And the like can also be used as a member used for the first base and the second base.

  As shown in FIG. 1, when a first substrate having a pattern of concavities and convexities is used as the first base, polymethyl methacrylate mainly composed of an organic polymer excellent in injection moldability and mass productivity is used as a member. , Polystyrene, polycarbonate, cyclic polyolefin, polyacrylonitrile, polyvinyl chloride and the like are preferred.

  As the groove shape, a triangle, a semicircle, or the like other than the rectangle shown in FIG. 1 can be adopted, and can be appropriately selected according to an application, desired performance, and the like. The dimensions of the micro flow channel, such as the width W of the groove, are appropriately set according to the inspection object flowing through the micro flow channel. Typically, the width W is about several μm to several mm, the groove depth is several μm to several mm, and the groove length (the depth direction of the paper) is about several mm to 10 cm.

  The grooves may be formed by etching, transfer molding using a mold, cutting, or the like.

  The size and thickness of the substrate are not particularly limited, but the size is preferably about 1 cm to 10 cm, and the thickness is preferably about several tens μm to several mm.

  As the first base or the second base, a base material subjected to a surface treatment can be used. When performing the hydrophilic treatment as the surface treatment, the base material may be subjected to, for example, vacuum ultraviolet irradiation, plasma irradiation, UV ozone irradiation, ion beam irradiation, acid washing, alkali washing, or the like. It may be made hydrophilic by forming a monomolecular film having a polar group such as a group and an amino group. Further, the surface of the substrate may be modified using a silane coupling agent. As silane coupling agents, vinylmethoxysilane, γ-glycidoxypropyltrimethoxysilane, γ-isocyanatopropyltriethoxysilane, γ-methacryloxypropyltrimethoxysilane, γ-methacryloxypropyltriethoxysilane and γ-aminopropyl One or more selected from methoxysilane and the like can be used.

  In order to obtain a more stable hydrophilic surface, a hydrophilic resin film obtained by polymerizing a polymerizable monomer such as ethylene glycol di (meth) acrylate and polyethylene glycol di (meth) acrylate is disposed on at least the surface. May be. An azide compound such as 4,4'-diazidostilbene-2,2'-disulfonic acid or 4,4'-diazidodibenzalacetone-2,2'-disulfonic acid, and N-vinylpyrrolidone, acrylamide, or A resin film synthesized from a mixture with a compound having a polymerizable double bond such as dimethylacrylamide can also be used as the hydrophilic resin film.

  As shown in FIG. 1 (c), when the coating 3 of the composition is applied to the first substrate 1 or the second substrate 2 and then cured by light or radiation, the first substrate is used. At least one of the second substrate and the second substrate desirably transmits light or radiation used for curing. As a material of the substrate, for example, polymethyl methacrylate, polystyrene, or the like is preferable as an organic material, and a glass mainly containing silicon oxide is preferable as an inorganic material.

  The same material or different materials may be used for the first base and the second base. For example, the uncovered portion of the resin film 4 from the joint 6 shown in FIG. In order to reduce the degree of protrusion of the resin film to the surface of the substrate 5, a method of lowering the affinity of the surface of the second substrate to the composition compared to the affinity of the composition of the first substrate can be used.

  As shown in FIG. 1B, as a method for bringing the first base 1 and the second base 2 into close contact with each other, for example, the own weight of the second base (when the top and bottom are reversed, the first base 1 is used). And the method of applying pressure from at least one direction of the first base or the second base. In the latter method, a force of typically about 500 to 3000 N is applied to the first substrate or the second substrate.

  In FIG. 1, the composition disposed in the concave portions of the concave-convex pattern comes into contact with oxygen because there is a gap between the composition and the second substrate. When a chemical species deactivated by oxygen, such as heat or a radical or an ion generated by the application of energy such as light or radiation, plays a central role in the polymerization reaction, the applied composition is first. The portion (joining portion 6) that is in contact with both the substrate and the second substrate is cured, and the polymerization reaction of the composition in the portion that comes into contact with oxygen, such as a concave portion, is suppressed. For this reason, by performing cleaning or development in the process from (c) to (d) shown in FIG. 1, according to the surface shape of the first substrate such as a concavo-convex pattern without applying energy through a mask. The composition can be cured.

  The composition in which the chemical species deactivated by oxygen plays a central role in the polymerization reaction is not particularly limited. For example, a composition cured by radical polymerization having a (meth) acryloyl group or the like, Among them, the compounds described in the preceding section are suitable as compositions for producing the microchannel shown in FIG. In addition to the above, a composition in which a reactive intermediate which is deactivated by oxygen such as nitrene due to application of energy such as a compound having an azide group to generate and polymerize is also used in the production of the microchannel shown in FIG. It is suitable as a composition.

  However, in order to more reliably suppress the hardening of the portion that comes into contact with oxygen as in the manufacture of the microchannel shown in FIG. 1, it is preferable to secure a certain or more oxygen permeability of the composition. For example, it is preferable to make the composition easy for oxygen to permeate by making the compound constituting the composition have a weight average molecular weight of 100,000 or less, more preferably 80,000 or less, more preferably 50,000 or less. Incidentally, the weight average molecular weight of the compound constituting the composition described in the preceding paragraph is preferably 50,000 or less, and the oxygen permeability can be adjusted by the thickness of the coating film, and the thickness is 10 μm or less. Further, it is preferable that the oxygen permeability is secured to 5 μm or less, more preferably 1 μm or less. Thereby, the curing reaction of the composition arranged in the concave portion is further suppressed.

  Examples of the method of removing the composition that has undergone the curing inhibition as described above include, for example, pressure-filling the solvent as the second liquid into the microchannel, pressure-reducing filling, centrifugal filling, and capillary force. After dissolving the uncured composition in the solvent by filling in the tunnel structure of the body, the uncured composition is removed by removing the solvent by a method such as pressurized drainage, reduced pressure drainage, or centrifugal drainage. Can be substantially removed. In the above-mentioned solvent filling step, heating or heating may be performed in order to shorten the time for dissolving the uncured composition in the solvent.

  As the polymerization initiator, when light is irradiated as energy, α-hydroxyalkylphenones that absorb light having a wavelength of 300 nm or more, α-aminoalkylphenones, benzyldimethyl ketals, and azo-based polymerization initiators are used. By using one or more selected from the group, the range of materials used for the first base or the second base can be expanded.

  The composition disposed in the concave portion can be dissolved and removed by a solvent after applying energy, but when a plastic substrate mainly composed of an organic resin is used as the first substrate, the first substrate is not damaged. As described above, the solvent (second liquid) used for the dissolution and removal is appropriately selected so that the composition can be dissolved. For example, when a resin that is hydrophilic in an uncured state is used as the composition, a highly polar solvent such as water, methanol, ethanol, dimethyl sulfoxide, acetonitrile, and dimethylformamide is used as the second liquid. Is preferred.

  A resin film 4 (cured product) after curing the coating film of the composition is formed at the joint 6 (first portion) shown in FIG. 1D. When flowing the test object using water as a solvent as the first liquid, it is preferable to suppress the penetration of water into the joint 6. For this purpose, for example, the resin film 4 formed by curing the composition may have a certain degree of hydrophobicity. Specifically, the contact angle of water of the resin film 4 may be set to 60 ° or more, and more preferably 80 ° or more.

  As a composition for forming a resin film having a water contact angle of 60 ° or more, a composition in which the content of the first unit or the second unit in the above compound is increased may be used.

  Conversely, when flowing a sample dissolved or dispersed in a low-polarity solvent through the microchannel, it is preferable to make the resin film 4 more hydrophilic.

  Also, by making the resin film 4 denser, the penetration of the solvent or the like into the resin film 4 can be suppressed.

  A dense resin film can be achieved by using a composition having a polyfunctional group as the composition.

  By adding a surfactant or the like to the composition, the degree of hydrophilicity or hydrophobicity of the surface of the resin film 4 and the adhesion to the first substrate or the second substrate can be controlled. As the surfactant, for example, one or two or more of ammonium lauryl sulfate, polyoxyethylene alkyl ether sulfate, lauryl dimethylamine oxide, polyoxyethylene lauryl ether, polyoxyethylene stearyl ether, sorbitan monostearate and the like are used. Can be used. Further, a silane coupling agent or the like may be added. As the silane coupling agent, one or two or more of γ-glycidoxypropyltrimethoxysilane, γ-isocyanatopropyltriethoxysilane, γ-methacryloxypropyltrimethoxysilane, γ-methacryloxypropyltriethoxysilane, etc. Can be used.

  After FIG. 1D, the adhesive strength between the first base and the second base via the resin film 4 may be further improved by light irradiation, heating, or the like.

  The structure obtained by the method described above can be used as a microchip for analysis or fractionation. Examples of the microchip include a blood cell separation chip, a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip.

(3) Preparation of sorting chip FIG. 2 shows a plan view of the sorting chip. The sorting tip has a plurality of holes formed therein, and by making the surface characteristics different between the inside and the periphery of the hole, it is possible to more efficiently sort an object.

  Hereinafter, the manufacturing process of the sorting chip will be described with reference to FIG. First, after applying the first composition 8 on the third substrate 7 on which the concavo-convex pattern is formed as shown in FIG. 3 (a), the third substrate 7 is applied as shown in FIG. 3 (b). Rotates about an axis perpendicular to the main surface of the rotation axis. As a result, as shown in FIG. 3C, the excess first composition is removed, and the first coating film 9 is formed. Next, as shown in FIG. 3D, the entire surface of the first coating film 9 is exposed, so that the first coating film 9 is changed to a first resin film (cured product) 10.

  Next, as shown in FIG. 3E, the second composition 11 is applied on the third substrate 7 on which the first resin film 10 is formed. Similarly to the rotation step shown in FIG. 3B, the third base 7 is rotated about an axis perpendicular to the main surface of the third base 7 as a rotation axis (f), and the second coating film 12 is placed on the first resin film 10. (G). By exposing through the mask 13 as shown in FIG. 3H, the curing of the second coating film arranged in the recess does not progress, and the uncured second coating film is removed with a solvent or the like. Then, as shown in FIG. 3 (i), a fractionating chip in which the first resin film is exposed in the concave portion and the second resin film is exposed in the convex portion can be manufactured.

  As a member used for the third base 7, a material similar to the first base 1 and the second base 3 described with reference to FIG. 1 can be used. However, as shown in FIGS. 3D and 3H, when light is irradiated from the side of the surface on which the first coating film 9 or the second coating film 12 is formed, the third substrate is used. Those that do not transmit light can be used. In the example shown in FIG. 3, the third base 7 has a concavo-convex pattern in which a groove dug vertically to the main surface thereof is formed, but has a convex pattern having a tapered groove. Is also good.

  Examples of the first composition 8 include monomers such as ethylene glycol di (meth) acrylate and polyethylene glycol di (meth) acrylate, and 4′-diazidostilbene-2,2′-disulfonic acid or 4,4′-disulfonic acid. A mixture (hydrophilic resin film) containing an azide compound such as azidodibenzalacetone-2,2'-disulfonic acid and a compound having a polymerizable double bond such as N-vinylpyrrolidone, acrylamide or dimethylacrylamide May be used.

  In the rotation shown in FIGS. 3B and 3F, the first coating film 9 and the second coating film 2 are rotated by so-called rotation around a rotation axis perpendicular to the main surface of the third base 7, respectively. In addition, the first coating film 9 is formed by so-called revolving around the position of the third substrate 7 about a rotation axis passing through other than the third substrate. And the second coating film 12 may be formed. Furthermore, the first composition 8 or the second composition 11 can be wet-spread by combining the above-described rotation and revolution.

  The first resin film 10 formed by curing the first composition 8 and the second resin film 14 formed by curing the second composition 11 have hydrophilicity or hydrophobicity. It is preferable to determine the combination of the composition of the first composition and the composition of the second composition differently. For example, when the first composition 8 is a composition of a hydrophilic resin film as described above, the second composition 11 is, for example, a unit represented by the following general formulas (7) to (11). Can be used. The compound has an affinity for the first resin film 10 because it has a hydrophilic group called a hydroxy group at the terminal as represented by the general formula (9), and also has the general formula (7) As shown, at least one of the surfaces of the second resin film 14 formed by curing the second composition 11 because it has a hydrocarbon group having 3 or more carbon atoms as a hydrophobic group at the terminal. The part can be hydrophobic. In other words, the second resin film maintains the adhesion at the interface with the first resin film, and is more hydrophobic than the first resin film in a portion not in contact with the first resin film. It can be.

  The composition to be used as the first composition 8 and the composition to be used as the second composition 11 can be appropriately interchanged and used according to the intended use, desired performance, and the like.

  As the combination of the composition used as the first composition 8 and the composition used as the second composition 11, in addition to the above, the following combinations are also preferably exemplified.

  As the first composition 8 and the second composition 11, for example, a photosensitive resin in which a radical compound or a cation compound is bonded to a polyvinyl alcohol-based polymer or the like can be appropriately used. Examples of the radical compound include compounds having a photoreactive group such as an azo group, a carbonyl group, and a group having a double bond between a phosphorus atom and oxygen. Examples of the cation compound include onium salts such as iodonium salts and sulfonium salts.

  More specifically, a compound having a photoreactive group such as an azide group or the like can be used in combination with a polyvinyl alcohol polymer or the like and a photosensitive resin pendant with an acetal bond. Examples of the photosensitive resin include a photosensitive resin disclosed in WO2013 / 153873. More specifically, the photosensitive composition prepared in Example 11 of WO2013 / 153873 is used as the first composition 8, and the photosensitive composition prepared in Examples 9 and 10 is used as the second composition 11. At least one of the photosensitive compositions can be used.

  The above combinations can be used by appropriately replacing the first composition and the second composition depending on the target substance to be analyzed.

(4) Sorting device 1 using a structure having a microchannel
FIG. 4 shows a configuration of a sorting apparatus using the above-described structure having a microchannel. In order to explain the configuration of the sorting apparatus, FIG. 4 shows a state in which the reservoir 15, the structures 16 to 18 having microchannels, and the stopper 19 are not connected. The reservoir 15 and the structure 16 having the first micro flow channel are fitted using the female connection portion 21, and the plug 19 and the structure 16 having the first micro flow channel are connected using the female connection portion 21. The structures 16 to 18 having the microchannels are fitted to each other using the male connecting portion 20 and the female connecting portion 21 before use.

  In the sorting apparatus shown in FIG. 4, a plug having a structure in which a hole is formed so as to penetrate the structure having the first micro flow path from the reservoir 15 to the structure 17 having the second micro flow path is used. 19 may not be used.

(5) Sorting device 2 using a structure having a microchannel
FIG. 5 shows a sorting apparatus using a structure having another microchannel according to the present invention. Instead of using the male connecting portion 20 and the female connecting portion 21 as in the sorting apparatus shown in FIG. 4, an O-ring 29 is used to connect the reservoir 23 and the plug 27 to the structure 24 having the fourth micro flow path. The structures 24 to 26 having micro flow paths are connected by an O-ring 29. By doing so, there is no need to provide a part for fitting to the structure having the microchannel, and it is possible to reduce the manufacturing cost and the manufacturing time.

(6) Structure for Fixing Structure Having Micro Flow Channel FIG. 6 shows a structure for fixing the structure 30 having a micro flow channel. By fixing the structures 30 having the microchannels by the folders 31 in an overlapping state, the alignment of the holes between the structures 30 having the microchannels becomes easy. When the configuration as shown in FIG. 6 is adopted, it may not be necessary to provide a portion for fitting to the structure itself as shown in FIGS. 4 and 5, or to use an O-ring.

(7) Inspection Apparatus FIG. 7 shows a configuration of an inspection apparatus intended for a structure in which the structure having the microchannel shown in FIG. 6 is gripped by a folder (hereinafter, referred to as a “grip” 32). In the inspection device, it is possible to perform detection by irradiating a detection light source such as a laser from below the holding body 32.

(8) Structure Manufactured in Packaging Material FIG. 8 shows a manufacturing process in the case where the composition is cured in the packaging material in the manufacture of the structure having the microchannel shown in FIG. Was. After the fourth substrate 33 and the fifth substrate 34 are placed in the packaging material 38 in a state where the fourth substrate 33 and the fifth substrate 34 are in close contact with each other via the coating film 35 of the composition, the coating of the composition is performed in the packaging material. The film 35 is cured by irradiating radiation such as X-rays or gamma rays. Thereby, the coating film of the composition in contact with the fourth substrate 33 and the fifth substrate 34 becomes the resin film 36, and the other portions become the uncured portions 37. Even if the product is shipped with the uncured portion 37 in this manner, the uncured portion 37 can be removed by washing with pure water or the like before use in an inspection application such as a blood test. May not interfere. Since sterilization can be performed by irradiation with X-rays or gamma rays, the structure obtained by the present manufacturing method, which does not require opening the packaging material until immediately before use, is particularly useful as a test chip for biological substances.

  As the packaging material, it is preferable to use a material that is permeable to radiation and the like.

  Hereinafter, the present invention will be described based on examples, but the present invention is not limited to these examples.

<Synthesis of Compound>
Typical examples of the materials used as the coating film 3 of the composition shown in FIG. 1 and the second composition 11 shown in FIG. 3 are shown below.

(Synthesis example 1 of compound)
28.1 g of propylene glycol monomethyl ether acetate (PGMEA) was placed in a reaction vessel equipped with a stirrer, a cooler, a thermometer, a nitrogen introduction pipe and a monomer introduction pipe, and the inside of the reaction vessel was replaced with nitrogen while keeping at 90 ° C. 16.7 g (15.4 mmol) of glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-1000), 18.7 g (9.0 mmol) of methoxypolyethylene glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-2000) ), 2.41 g (1.4 mmol) of stearyloxy polyethylene glycol monomethacrylate (manufactured by NOF Corp., Blemmer PSE-1300), 1.86 g of polyethylene glycol monomethacrylate (manufactured by NOF Corp., Blemmer PE-350) (4.3 mol), azo-based polymerization initiator (manufactured by Wako Pure Chemical Industries, Ltd., V-40) over 0.23g and PGMEA26.5g mixture 4 hours was fed and reacted for 4 hours at 90 ° C.. The resulting reaction solution was fed over 1 hour to a mixture of 200 ml of isopropyl ether and 600 ml of hexane cooled with ice, filtered, and dried under vacuum to obtain Compound A. GPC measurement of the obtained Compound A showed that the molecular weight was MW32160.

  Next, 10.5 g (7.9 mmol) of compound A, 0.0642 g (0.39 mmol) of dimethacrylic anhydride (manufactured by Aldrich), 263 ml of dichloromethane, 0.023 g of N, N-dimethyl-4-aminopyridine and triethylamine After putting 0.042 g in a reaction vessel and stirring overnight at room temperature, the reaction solution was transferred to a separating funnel, washed with 8% by mass sodium hydrogen carbonate and 1 M HCl, and the separated reaction solution was evaporated, and ethyl acetate was removed. 60 ml was added, and the mixture was fed into a mixture of ice-cooled 80 ml of isopropyl ether and 240 ml of hexane in 30 minutes, followed by filtration and vacuum drying to obtain Compound B. When the GPC measurement of the obtained compound B was performed, the molecular weight was MW44440.

(Synthesis example 2 of compound)
29.1 g (8.7 mmol) of polyethylene glycol-polypropylene glycol-polyethylene glycol block polymer (Profon 204, EO: PO = 40: 60, average molecular weight 3330, manufactured by NOF Corporation), dimethacrylic anhydride (manufactured by Aldrich) ) 3.0 g (19.4 mmol), dichloromethane (300 ml), N, N-dimethyl-aminopyridine (0.03 g), and triethylamine (1.97 g) were placed in a reaction vessel, stirred at room temperature overnight, and then the reaction solution was transferred to a separating funnel. After washing with water by mass% sodium bicarbonate and 1 M HCl, the separated reaction solution was evaporated to obtain compound C. GPC measurement of the obtained compound C showed that the molecular weight was MW3870.

(Synthesis example 3 of compound)
Similarly to Example 2 described in WO2013 / 153873, (3- (4-azidophenyl) -N- (4,4′-dimethoxybutyl) -2- (4-morpholinomethylphenyl) represented by the following formula: Thus, carbonylamino-prop-2-enamide (hereinafter referred to as “photosensitive compound 1”) was obtained.

  40 g of polyvinyl alcohol (Gozenol EG-30, average degree of polymerization: 1700, manufactured by Nippon Synthetic Chemical Co., Ltd.) was dissolved in 400 g of water, and 4 g of the photosensitive compound 1 obtained above and 2 g of phosphoric acid were added thereto. The reaction was performed at 60 ° C. for 24 hours. The acetalization reaction rate was measured by GPC (gel permeation chromatography) and was 98%. From the measurement results, the acetalization amount was calculated to be an amount corresponding to 0.8% with respect to polyvinyl alcohol. Thereafter, the phosphoric acid was removed by treating with an ion exchange resin to obtain a photosensitive solution containing the compound D in which the photosensitive compound 1 was pendant to polyvinyl alcohol by an acetal bond. This photosensitive solution was diluted with a mixed solution of water: IPA = 80: 20% by mass to prepare a photosensitive composition D having a photosensitive resin concentration of 3% by mass.

(Synthesis example 4 of compound)
40 g of diacetone acrylamide copolymer polyvinyl alcohol (DF-20, manufactured by Nippon Vine Povar Co., Ltd.) is dissolved in 400 g of water, and 4 g of the photosensitive compound 1 obtained above and 2 g of phosphoric acid are added thereto. At 50 ° C. for 48 hours. The acetalization reaction rate was measured by GPC (gel permeation chromatography) and was 98%. From the measurement results, the acetalization amount was calculated to be an amount corresponding to 0.8% with respect to polyvinyl alcohol. Thereafter, the phosphoric acid was removed by treating with an ion-exchange resin to obtain a photosensitive solution containing the compound E in which the photosensitive compound 1 was pendant with diacetone acrylamide copolymerized polyvinyl alcohol through an acetal bond. This photosensitive solution was diluted with a mixed solution of water: IPA = 80: 20% by mass to prepare a photosensitive composition E having a photosensitive resin concentration of 6% by mass.

(Synthesis example 5 of compound)
40 g of polyvinyl alcohol-polyethylene glycol graft copolymer (Killicoat IR, manufactured by BASF) is dissolved in 300 g of water, 4 g of the photosensitive compound A obtained above and 2 g of phosphoric acid are added thereto, and the mixture is added at 50 ° C. for 48 hours. Reacted. The acetalization reaction rate was measured by GPC (gel permeation chromatography) and was 98%. From the measurement results, the acetalization amount was calculated as an amount corresponding to 0.8% with respect to the polymer. Thereafter, the phosphoric acid was removed by treating with an ion exchange resin to obtain a photosensitive solution containing the compound F in which the photosensitive compound 1 was pendant with an acetal bond to a polyvinyl alcohol-polyethylene glycol graft copolymer. This photosensitive solution was diluted with a mixed solution of water: IPA = 80: 20% by mass to prepare a photosensitive composition F having a photosensitive resin concentration of 6% by mass.

(Synthesis example 6 of compound)
28.1 g of propylene glycol monomethyl ether acetate (PGMEA) was placed in a reaction vessel equipped with a stirrer, a cooler, a thermometer, a nitrogen introduction pipe and a monomer introduction pipe, and the inside of the reaction vessel was replaced with nitrogen while keeping at 90 ° C. 22.3 g (20.6 mmol) of glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-1000), 2.9 g (1.4 mmol) of methoxypolyethylene glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-2000) ), 3.9 g (2.3 mmol) of stearyloxy polyethylene glycol monomethacrylate (manufactured by NOF Corporation, Blemmer PSE-1300), 3.0 g of polyethylene glycol monomethacrylate (Blemmer PE-350, manufactured by NOF Corporation) ( 6.8 mmol , Azo-based polymerization initiator (manufactured by Wako Pure Chemical Industries, Ltd., V-40) over 0.24g and PGMEA26.5g mixture 4 hours was fed and reacted for 4 hours at 90 ° C.. The obtained reaction solution was fed over 1 hour to a mixture of 200 ml of isopropyl ether and 600 ml of hexane cooled with ice, filtered, and dried under vacuum to obtain a compound G. When the GPC measurement of the obtained compound G was performed, the molecular weight was MW26330.

  Next, 10.51 g (10.2 mmol) of compound G, 0.127 g (0.77 mmol) of dimethacrylic anhydride (manufactured by Aldrich), 263 ml of dichloromethane, 0.046 g of N, N-dimethyl-4-aminopyridine and triethylamine After placing 0.083 g in a reaction vessel and stirring overnight at room temperature, the reaction solution was transferred to a separating funnel, washed with 8% by mass of sodium hydrogen carbonate and 1 M HCl, and the separated reaction solution was evaporated, and ethyl acetate was removed. 60 ml was added, and the mixture was fed to a mixture of ice-cooled 80 ml of isopropyl ether and 240 ml of hexane in 30 minutes, followed by filtration and vacuum drying to obtain a compound H. When the GPC measurement of the obtained compound H was performed, the molecular weight was MW34300.

(Synthesis example 7 of compound)
28.1 g of propylene glycol monomethyl ether acetate (PGMEA) was placed in a reaction vessel equipped with a stirrer, a cooler, a thermometer, a nitrogen introduction pipe and a monomer introduction pipe, and the inside of the reaction vessel was replaced with nitrogen while keeping at 90 ° C. 16.7 g (15.4 mmol) of glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-1000), 18.7 g (9.0 mmol) of methoxypolyethylene glycol monomethacrylate (manufactured by NOF Corporation, Blenmer PME-2000) ), 1.86 g (4.3 mmol) of polyethylene glycol monomethacrylate (Blenmer PE-350, manufactured by NOF Corporation), 0.22 g of azo-based polymerization initiator (V-40, manufactured by Wako Pure Chemical Industries, Ltd.) And a mixture of 26.5 g of PGMEA are fed over 4 hours It was reacted for 4 hours at 90 ° C.. The obtained reaction solution was fed over 1 hour to a mixture of 200 ml of isopropyl ether and 600 ml of hexane cooled with ice, filtered, and dried in vacuo to obtain Compound I. GPC measurement of the obtained compound I showed that the molecular weight was MW28610.

  Next, 10.5 g (8.1 mmol) of compound I, 0.0684 g (0.42 mmol) of dimethacrylic anhydride (manufactured by Aldrich), 263 ml of dichloromethane, 0.023 g of N, N-dimethyl-4-aminopyridine and triethylamine After putting 0.042 g in a reaction vessel and stirring overnight at room temperature, the reaction solution was transferred to a separating funnel, washed with 8% by mass sodium hydrogen carbonate and 1 M HCl, and the separated reaction solution was evaporated, and ethyl acetate was removed. 60 ml was added, and the mixture was fed into a mixture of ice-cooled 80 ml of isopropyl ether and 240 ml of hexane in 30 minutes, followed by filtration and vacuum drying to obtain a compound J. GPC measurement of the obtained compound J showed that the molecular weight was MW32300.

<Manufacture of structure>
(Production Example 1 of Structure)
A molded product having a hydrophobic surface made of an acrylic resin having a through hole (diameter 0.7 mm) and a groove structure (rectangular shape, width 100 μm, depth 20 μm, length 10 mm) as a first base (vertical) 20 mm, width 30 mm, thickness 1 mm) and a substrate (a flat plate made of acrylic resin, length 20 mm, width 30 mm, thickness 0.2 mm) serving as a lid as a second base were prepared. Plasma contact was performed in advance to reduce the contact angle of the substrate from 75 ° to 50 °. Next, the compound C (EO-PO-EO dimethacrylate, EO: PO = 40: 60, average molecular weight 3870), IRUGACURE-2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy Photosensitive composition C (water of a cured film) obtained by mixing 2-methyl-1-propan-1-one (manufactured by BASF), methanol and pure water at a mixing ratio of 10: 0.3: 45: 45 parts by mass. Is prepared, a photosensitive composition C is applied by spin coating on the entire surface of the substrate serving as the lid and the groove structure side of the molded product, and dried at 50 ° C. for 10 minutes by an oven drier. went.

Subsequently, the coating surface of the molded product and the coating surface of the lid substrate are brought into close contact with each other at a pressure of 1000 N in an air atmosphere, and the substrate is exposed to 3000 mJ with an LED lamp (illuminance: 20 mW / cm ³ , wavelength: 365 nm). A composite (structure) was obtained. Pure water is passed through the flow path of the obtained substrate composite at a rate of 20 μl / min by a micro syringe pump, and the pure water filled in the groove structure is removed by suction under reduced pressure. Then, vacuum drying is performed at 50 ° C. for 10 minutes. Was done. When a 1% by mass aqueous solution of rhodamine B (used as a fluorescent dye and a fluorescent dye for a cured film) was passed through the obtained substrate composite at 20 μl / min and observed under fluorescence, the rhodamine B fluorescent dye solution wrapped around the bonding surface. No bleeding was observed on the bonding surface, and the bonding surface was good. Further, after the dyeing solution was suctioned and removed, the inner surface of the flow channel was washed by passing pure water through, and the substrate composite was observed under a microscope. The inner surface of the flow channel was dyed by curing of the photosensitive composition. There was no evidence and the photosensitive composition was removed by development.

  The contact angle was determined by a dynamic contact angle meter using a droplet method using pure water.

(Structure Production Example 2)
First, a molded product (first substrate) and a substrate (second substrate) similar to those used in Production Example 1 of the above structure are prepared, and a plasma treatment is performed in advance to increase the contact angle of the substrate from 75 °. Reduced to 50 °.

Next, 29.2 g (8.7 mmol) of polyethylene glycol (manufactured by Aldrich, average molecular weight 3350), 3.0 g (19.5 mmol) of dimethacrylic anhydride (manufactured by Aldrich), 300 ml of dichloromethane, N, N-dimethyl-4 -Aminopyridine (0.03 g) and triethylamine (1.97 g) were placed in a reaction vessel and stirred overnight at room temperature. The reaction solution was transferred to a separating funnel, washed with 8% by mass sodium hydrogen carbonate and 1 M HCl, and separated. Was evaporated, 60 ml of ethyl acetate was added, and the mixture was fed over 1 hour to a mixture of 200 ml of ice-cooled isopropyl ether and 600 ml of hexane, followed by filtration and vacuum drying to obtain compound K (polyethylene glycol dimethacrylate). GPC measurement of the obtained Compound K showed that the molecular weight was MW3650. Thereafter, compound K (polyethylene glycol dimethacrylate, average molecular weight 3650), IRUGACURE-2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy-2-methyl-1-propan-1-one, BASF), and a photosensitive composition K prepared by mixing methanol and pure water at a mixing ratio of 10: 0.3: 45: 45 parts by mass, and spinning on the groove structure side of the molded product and the entire surface of the lid substrate. The photosensitive composition K was applied by a coat, and dried at 50 ° C. × 10 minutes using a vacuum dryer. Subsequently, each substrate was subjected to 3000 mJ exposure with an LED lamp (illuminance: 20 mW / cm ³ , wavelength: 365 nm) in a nitrogen atmosphere, washed with pure water, and subjected to hydrophilic treatment by vacuum drying at 50 ° C. × 10 minutes for a molded product. And a hydrophilized lid substrate was obtained. When the contact angles of the cured films on both substrates obtained were measured, both were 35 °.

  Using the hydrophilized molded product and the hydrophilized lid substrate, in the same manner as in Production Example 1, application and drying of the photosensitive composition C, contact exposure in an air atmosphere, development, and drying were performed. The complex was obtained. When pure water was passed through the obtained substrate composite by a natural flow, water could be passed very smoothly without clogging. Further, 1% by mass rhodamine B fluorescent dye was injected at 20 μl / min. And observed under fluorescent light. As a result, it was found that the bonded surface had no bleeding and was a good adhesive surface.

(Structure Production Example 3)
A structure was obtained as follows by a method similar to the manufacturing method shown in FIG.

First, a molded product (third base) similar to that used in Production Example 1 of the above-mentioned structure was prepared, and plasma treatment was performed in advance to reduce the contact angle of the substrate from 75 ° to 50 °. Next, as shown in FIG. 3B, the photosensitive composition F was applied onto the molded product by rotating the molded product with an axis perpendicular to the main surface as a rotation axis. Thereafter, as shown in FIG. 3D, the entire surface of the coating film of the photosensitive composition F is exposed to light (ultra high pressure mercury lamp, wavelength of 350 nm, 5 mw / cm ² , 1000 mJ) in an air atmosphere, thereby obtaining The photosensitive composition F was cured, developed with pure water, and vacuum dried at 50 ° C. × 10 minutes to obtain a first resin film. When the contact angle of the first resin film was measured, it was 30 °.

Next, as shown in FIG. 3E, the photosensitive composition D (contact angle 65 °) was applied on the first resin film. The molded product was rotated around an axis perpendicular to the main surface of the molded product to form a coating film of the photosensitive composition D on the first resin film. Thereafter, as shown in FIG. 3 (h), exposure was performed through a mask 13 in an air atmosphere (ultra high pressure mercury lamp, wavelength 350 nm, 5 mw / cm ² , 1000 mJ), and development and drying were performed with pure water. When pure water was dropped on the obtained molded product, it was confirmed that pure water preferentially flowed into a groove having a lower contact angle than the periphery.

(Production Example 4 of Structure)
A structure was obtained as follows by a method similar to the manufacturing method shown in FIG.

First, a molded product (third substrate) similar to that used in Production Example 1 of the above-mentioned substrate composite was prepared, and plasma treatment was performed in advance to reduce the contact angle of the substrate from 75 ° to 50 °. Next, as shown in FIG. 3B, the photosensitive composition F was applied onto the molded product by rotating the molded product with an axis perpendicular to the main surface as a rotation axis. Thereafter, as shown in FIG. 3D, the entire surface of the coating film of the photosensitive composition F is exposed to light (ultra high pressure mercury lamp, wavelength of 350 nm, 5 mw / cm ² , 1000 mJ) in an air atmosphere, thereby obtaining The photosensitive composition F was cured, developed with pure water, and vacuum dried at 50 ° C. × 10 minutes to obtain a first resin film. When the contact angle of the first resin film was measured, it was 30 °.

Next, as shown in FIG. 3E, the photosensitive composition E (contact angle: 60 °) was applied on the first resin film. By rotating around an axis perpendicular to the main surface of the molded product as a rotation axis, a coating film of the photosensitive composition E was formed on the first resin film. Thereafter, as shown in FIG. 3 (h), exposure was performed through a mask 13 in an air atmosphere (ultra high pressure mercury lamp, wavelength 350 nm, 5 mw / cm ² , 1000 mJ), and development and drying were performed with pure water. When pure water was dropped on the obtained molded product, it was confirmed that pure water preferentially flowed into a groove having a lower contact angle than the periphery.

  Since the photosensitive compositions D to F are mainly composed of polyvinyl alcohol having low oxygen permeability in photocrosslinking, they are hardly deactivated by oxygen, and have an effect of being easily manufactured.

(Structure Manufacturing Example 5)
First, a molded product (first base) and a substrate (second base) similar to those used in Production Example 1 of the above structure were prepared.

Next, the above compound H, IRUGACURE-2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy-2-methyl-1-propan-1-one, manufactured by BASF), methanol and pure A photosensitive composition H (contact angle 62 °) was prepared by mixing water at a mixing ratio of 5: 0.2: 47.5: 47.5 parts by mass. When the photosensitive composition H was applied by spin coating to the groove structure side of the molded product and the entire surface of the lid substrate, a good coating film was formed on a hydrophobic substrate (contact angle 75 °) not subjected to plasma treatment. was gotten. Next, drying was performed at 50 ° C. × 10 minutes using an oven dryer. Then, the coating surface of the molded product and the coating surface of the lid substrate were brought into close contact with each other under a pressure of 1000 N under an air atmosphere, and the substrate was exposed to 3000 mJ with an LED lamp (illuminance: 20 mW / cm ³ , wavelength: 365 nm). Thus, a substrate composite (structure) was obtained. Pure water is passed through the flow path of the obtained substrate composite at a rate of 20 μl / min by a micro syringe pump, and the pure water filled in the groove structure is removed by suction under reduced pressure. Then, vacuum drying is performed at 50 ° C. for 10 minutes. Was done. When a 1% by mass aqueous solution of rhodamine B (used as a fluorescent dye and a fluorescent dye for a cured film) was passed through the obtained substrate composite at 20 μl / min and observed under fluorescence, the rhodamine B fluorescent dye solution wrapped around the bonding surface. No bleeding was observed on the bonding surface, and the bonding surface was good. After the dyeing solution was removed by suction, the inner surface of the flow channel was washed by passing pure water through it, and then the substrate composite was observed under a microscope. The inner surface of the flow channel was stained with the hardened photosensitive composition. There was no evidence and the photosensitive composition was removed by development.

(Example 6 of manufacturing structure)
A structure was obtained as follows by a method similar to the manufacturing method shown in FIG.

First, a molded product (third substrate) similar to that used in Production Example 1 of the structure was prepared, and the compound B and IRUGACURE were placed on the molded product as shown in FIG. -2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy-2-methyl-1-propan-1-one, manufactured by BASF), methanol and pure water 5: 0.2: As shown in FIG. 3 (b), the photosensitive composition B mixed at a mixing ratio of 47.5: 47.5 parts by mass was applied while being rotated about an axis perpendicular to the main surface of the molded product as a rotation axis. A good coating film was obtained on a hydrophobic substrate not subjected to plasma treatment (contact angle: 75 °). Next, drying was performed at 50 ° C. × 10 minutes using an oven dryer. Thereafter, as shown in FIG. 3D, the entire surface of the coating film is exposed to light (ultra high pressure mercury lamp, 350 nm, 5 mw / cm ² , 1000 mJ) in a nitrogen atmosphere to cure the photosensitive composition G. Then, pure water development and vacuum drying at 50 ° C. for 10 minutes were performed to obtain a first resin film. The measured contact angle of the first resin film was 35 °.

Next, as shown in FIG. 3E, the compound H, IRUGACURE-2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy-2) was formed on the first resin film. -Methyl-1-propan-1-one, manufactured by BASF, methanol and pure water at a mixing ratio of 5: 0.2: 47.5: 47.5 parts by mass (contact angle H) 62 °). By rotating around an axis perpendicular to the main surface of the molded product as a rotation axis, a coating film of the composition H was formed on the first resin film. Thereafter, as shown in FIG. 3H, exposure (ultra high pressure mercury lamp, wavelength 350 nm, 5 mw / cm ² , 1000 mJ) was performed through a mask 13 in a nitrogen atmosphere, and development and drying were performed with pure water. When pure water was dropped onto the obtained molded product, it was confirmed that pure water preferentially flows into the flow path of the groove having a lower contact angle than the periphery.

(Structure Manufacturing Example 7)
A structure was obtained as follows by a method similar to the manufacturing method shown in FIG.

  First, a molded product (third substrate) similar to that used in Production Example 1 of the above structure was prepared, and as shown in FIG. 3A, compound J and IRUGACURE were placed on the molded product. -2959 (1- [4- (2-hydroxyethoxy) -phenyl] -2-hydroxy-2-methyl-1-propan-1-one, manufactured by BASF), methanol and pure water 5: 0.2: A photosensitive composition J mixed at a mixing ratio of 47.5: 47.5 parts by mass was prepared, and the photosensitive composition J was applied. Upon application, repelling occurred on the surface of the hydrophobic acrylic resin molded product that had not been subjected to the plasma treatment, and a good coating film could not be obtained.

1: first substrate 2: second substrate 3: coating film of composition 4: resin film 7: third substrate 8: first composition 11: second composition 15: reservoir 19: stopper 31 : Folder 38: Packaging material

Claims (10)

A first step of preparing a first base having a first surface having a concavo-convex pattern and a second surface;
A second step of disposing a composition on at least a part of the first surface;
And providing a second substrate is brought into close contact with a front Symbol first substrate and the second substrate, and a convex portion of the first substrate and the second substrate is brought into close contact through the composition,
A third step of applying the energy to at least a part of the composition without using a mask to cure the composition of the protrusions of the first base to form a cured product;
A fourth step of removing the uncured composition of the concave portions of the first base with a solvent to obtain a structure having the concave portions and the convex portions and the cured product formed on the convex portions . And a process,
The composition, the polymerization reaction is suppressed by oxygen, hydrophilic in an uncured state and after curing has a contact angle to water of 60 ° or more,
A method for producing a structure having a microchannel, wherein the solvent is a highly polar solvent. The method for producing a structure having a microchannel according to claim 1, wherein the composition contains any of the following compounds (a), (b), and (c).
(A) Compound: a first unit represented by the following general formula (1), a second unit represented by the following general formula (2), and a fourth unit represented by the following general formula (4) And a unit,
A compound in which the first unit and the second unit have structures different from each other.

(In the general formula (1), the substituent A is a divalent substituent containing carbon represented by the following general formula (5), and the substituent B is a carbon atom represented by the following general formula (6). And any one selected from the group consisting of a divalent substituent, an alkylene group, a polypropylene oxide group and a polybutylene oxide group, wherein the substituent C is an alkyl group having 3 to 20 carbon atoms, and R ₁ is A hydrogen atom or an alkyl group, w is a natural number, a is 1, and b is 1 to 100.)

(In the general formula (2), the substituent D is a divalent substituent containing carbon represented by the general formula (5), and the substituent E contains carbon represented by the general formula (6). Any one selected from the group consisting of a divalent substituent, an alkylene group, a polypropylene oxide group and a polybutylene oxide group, wherein the substituent F is composed of a (meth) acryloyl group, a vinyl group, an allyl group and an epoxy group R ₂ is a hydrogen atom or an alkyl group, x is a natural number, d is 1 and e is 1 to 100.)

(In the general formula (4), the substituent J is a bivalent substituent containing carbon represented by the general formula (5), and the substituent K contains carbon represented by the general formula (6). Any one selected from the group consisting of a divalent substituent, an alkylene group, a polypropylene oxide group and a polybutylene oxide group, wherein the substituent L is an alkyl group having 2 or less carbon atoms, and R ₄ is a hydrogen atom or an alkyl Group, z is a natural number, j is 1 and k is 1 to 100.)
(B) Compound: a photosensitive resin in which an azide group is bonded to a polyvinyl alcohol-based polymer.
(C) Compound: a compound obtained by reacting polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer with a dimethacrylic anhydride compound.   3. The method according to claim 1, wherein the highly polar solvent includes any one selected from the group consisting of water, methanol, ethanol, dimethyl sulfoxide, acetonitrile, and dimethylformamide. 4.   3. The method according to claim 1, wherein the highly polar solvent includes any one selected from the group consisting of water, methanol, and ethanol. 4. The method for producing a structure having a microchannel according to any one of claims 1 to 4, wherein the compound (a) further includes a third unit represented by the following general formula (3).

(In the general formula (3), the substituent G is a carbon-containing substituent represented by the general formula (5), and the substituent H is a divalent carbon-containing substituent represented by the general formula (6). A substituent, an alkylene group, any one selected from the group consisting of a polypropylene oxide group and a polybutylene oxide group, and the substituent I is any one selected from the group consisting of a hydroxy group, an amino group, a silyl group and a carboxy group R ₃ is a hydrogen atom or an alkyl group, y is a natural number, g is 1, and h is 1 to 100.)   The method for manufacturing a structure having a microchannel according to any one of claims 1 to 5, wherein the substituent C of the first unit is a substituent containing 5 or more carbon atoms.   The structure having a microchannel according to any one of claims 1 to 6, wherein the first step includes a first sub-step of arranging or forming a hydrophilic resin film in at least the concave portion of the substrate. Manufacturing method.   The structure having a microchannel according to any one of claims 1 to 7, wherein the third step is performed in a state where the first substrate and the composition are packaged with a packaging material for packaging. How to make the body.   The method for manufacturing a structure having a microchannel according to any one of claims 1 to 8, wherein the energy is applied to the composition using an electromagnetic wave.   The method according to claim 9, wherein the electromagnetic wave is a gamma ray or an X-ray.

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