JP2014239675A - Structure, micro passage device, and method for using structure - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a structure which can suppress adsorption of a liquid component or can maintain liquid repellency of a substrate when contacting the liquid with the substrate.SOLUTION: A structure 10 can suppress adsorption to a liquid component or can maintain liquid repellency to a liquid. This structure 10 is equipped with a substrate 11 having a surface 11a in contact with a liquid containing a biopolymer; and multiple micropores 20 opening toward the surface 11a side of the substrate 11, and capable of maintaining gases inside when contacting the surface 11a of the substrate 11 with the liquid. Each micropore 20 has an independent space 24 surrounded by a side face 22 linked to the surface 11a of the substrate 11, and a bottom 23 linked to the side face 22.

Description

  The present invention relates to a structure capable of suppressing adsorption to a component contained in a liquid or maintaining liquid repellency with respect to a liquid, a microchannel device including such a structure, and a method of using the structure.

  Conventionally, various biochemical instruments (containers, flow paths, infusion bags, pipettes, syringes, etc.) having surfaces that come into contact with liquids (proteins, cells, etc.) containing biopolymers have been used. In general, it is desirable that non-specific adsorption of biopolymers is not desirable on the surface of such biochemical instruments. However, most materials that are actually used in biochemical instruments currently undergo nonspecific adsorption.

  In biochemical instruments, in order to suppress the adsorption of biopolymers on the material surface, a method of applying a material having an adsorption inhibiting action on the material surface is known (see Patent Document 1 and Non-Patent Document 1). ). Examples of the material having an adsorption suppressing action include polyethylene glycol and MPC polymer.

  However, when the above method is used, there is a problem that the manufacturing process becomes complicated because it is necessary to coat the material surface. In addition, since a material having an adsorption inhibiting action is coated on the material surface, there is a problem that such a material is eluted into the solution.

  Conventionally, test kits such as immunoassay kits and enzyme reaction kits, and microchannels are generally used. When such a test kit or microchannel is subjected to a cleaning process, a solution replacement process, a reaction block process, or the like, a solution containing a surfactant may be used.

  As a microchannel in which a solution containing a surfactant is used, for example, the one described in Patent Document 2 is known. In the microchannel described in Patent Document 2, the movement of the solution is controlled by a capillary force and a centrifugal force. However, the flow path once contacted with a solution containing a surfactant becomes lyophilic, and the surface properties of the flow path change before and after contact with the solution, which hinders the use of the micro flow path. Sometimes. For this reason, when a solution containing a surfactant is allowed to flow through the microchannel a plurality of times, it is difficult to maintain the microchannel in a liquid repellent state.

Japanese Patent No. 5001015 JP 2012-242150 A

Ishihara, J. Biomed. Mater. Res. 39, 323-330 (1998)

  The present invention has been made to solve the above-described problems, and the object thereof is to provide a structure that can suppress the adsorption of liquid components or maintain the liquid repellency of the liquid, such as It is an object of the present invention to provide a microchannel device including a structure and a method of using the structure.

  A structure according to an embodiment of the present invention is a structure capable of suppressing adsorption to a liquid component or maintaining liquid repellency with respect to a liquid, and a substrate having a surface in contact with the liquid, A plurality of micropores that open to the surface side of the base material and can hold a gas inside when the liquid contacts the surface of the base material, and each micropore is formed on the surface of the base material It has an independent space surrounded by a side surface to be connected and a bottom surface to be connected to the side surface.

  In the structure according to an embodiment of the present invention, the contact angle of the base material with respect to the liquid is 40 ° to 60 °, the opening width of each micropore is 100 nm to 20 μm, and the aspect of each micropore is The ratio may be 0.8-17.

  In the structure according to an embodiment of the present invention, the contact angle of the substrate with respect to the liquid is 80 ° to 100 °, the width of each micropore is 500 nm to 100 μm, and the aspect ratio of each micropore is The ratio may be 0.1-3.

  In the structure according to an embodiment of the present invention, the liquid includes a biopolymer, the opening width of each micropore is 500 nm to 100 μm, and the aspect ratio of each micropore is 0.1 to 3. There may be.

  In the structure according to an embodiment of the present invention, the porosity of the plurality of micropores in the base material may be 25% or more.

  In the structure according to one embodiment of the present invention, the base material may be made of a resin material having a contact angle with water of 30 ° or more.

  In the structure according to an embodiment of the present invention, the base material is a microchannel, a liquid storage bag, a cell culture bag, a cell culture base material, a centrifuge tube, a centrifuge tube, a medical tube, a vascular catheter, and an artificial blood vessel. Or a contact lens may be sufficient.

  In the structure according to an embodiment of the present invention, the structure can maintain liquid repellency with respect to the liquid after contact with a solution containing a surfactant, and the opening width of each micropore is 100 nm. 0.8-20, and the aspect ratio of each micropore may be 0.8-17.

  In the structure according to the embodiment of the present invention, the aspect ratio of each micropore may be 1.5 to 7.

  In the structure according to the embodiment of the present invention, the opening width of each micropore may be 600 nm to 12 μm.

  In the structure according to one embodiment of the present invention, the surface of the base material may include a resin.

  In the structure according to an embodiment of the present invention, the structure can maintain liquid repellency with respect to the liquid after contact with a solution containing a surfactant, and the liquid contains a biopolymer, The opening width of the fine holes may be 500 nm to 10 μm, and the aspect ratio of each fine hole may be 0.8 to 3.

  In the structure according to an embodiment of the present invention, an angle formed by the surface of the base material and the side surface of each micropore may be a right angle or an acute angle in a vertical cross section.

  In the structure according to an embodiment of the present invention, the planar shape of the opening may be a circular shape, an elliptical shape, or a polygonal shape.

  A microchannel device according to an embodiment of the present invention includes the structure.

  The method for using a structure according to an embodiment of the present invention is a method for using the structure, comprising: preparing a solution containing the surfactant; and bringing the solution into contact with the surface of the substrate. And a step of bringing the liquid into contact with the surface of the substrate.

  In the method for using the structure according to the embodiment of the present invention, the solution may be either a cleaning solution or a blocking solution.

  In the method of using the structure according to an embodiment of the present invention, the surfactant contained in the solution may be a nonionic surfactant.

According to the present invention, by providing a plurality of micropores that can hold air inside, when the liquid and the substrate are in contact, it is possible to suppress the adsorption of the liquid components, Alternatively, a structure capable of maintaining liquid repellency can be obtained.

FIG. 1 is a plan view showing a structure according to an embodiment of the present invention. FIG. 2 is a cross-section (a cross-sectional view taken along the line II-II in FIG. 1) showing a structure according to an embodiment of the present invention. FIGS. 3A to 3C are vertical sectional views showing fine holes, respectively. 4A and 4B are schematic cross-sectional views showing the operation of the structure. FIG. 5 is a schematic plan view showing a microchannel device according to an embodiment of the present invention. FIG. 6 is a schematic plan view showing a microchannel device according to another embodiment of the present invention. FIGS. 7A and 7B are schematic perspective views showing an original plate and a structure in the examples, respectively. FIG. 8 is a graph showing the relationship between the aspect ratio of micropores and the amount of protein adsorbed in Examples. 9, in the embodiment, is a graph showing the relationship between the width W _c of the aspect ratio and the opening of the fine pores.

  Embodiments of the present invention will be described below with reference to the drawings. Drawing is an illustration and may exaggerate a characteristic part for explanation, and may differ from an actual thing. In addition, the present invention can be implemented with appropriate modifications without departing from the technical idea. Note that, in the following drawings, the same portions are denoted by the same reference numerals, and some detailed description may be omitted.

(Structure)
First, the structure of the structure according to an embodiment of the present invention will be described. 1 and 2 are views showing a structure according to an embodiment of the present invention.

  The structure 10 according to the present embodiment has a function capable of suppressing adsorption to a liquid component (for example, a biopolymer) or a function capable of maintaining liquid repellency with respect to a liquid. For example, the structure 10 has a function of suppressing the adsorption of biopolymers (for example, proteins, cells, etc.) and a function of maintaining liquid repellency with respect to the solution even after contact with the solution containing the surfactant. It has something. The structure 10 includes a substrate 11 having a surface 11a that comes into contact with a liquid.

  As shown in FIGS. 1 and 2, a large number (plurality) of fine holes 20 are formed in the surface 11 a of the substrate 11. Each fine hole 20 is opened on the surface 11a side of the base material 11, and has a planar circular opening 21 respectively. The planar shape of each opening 21 may be an elliptical shape, a polygonal shape such as a square shape, or the like, but is preferably a circular shape from the viewpoint of facilitating air retention in the micropores 20.

  Each micropore 20 has a structure capable of holding gas (air) inside when a liquid comes into contact with the surface 11 a of the base material 11. That is, each fine hole 20 has a bottomed cylindrical shape as a whole, and has an independent space 24 surrounded by a side surface 22 connected to the surface 11 a of the base material 11 and a bottom surface 23 connected to the side surface 22. Have. In addition, the shape of each fine hole 20 is not restricted to a bottomed cylindrical shape. Various types of bottomed cylindrical shapes can be employed according to the planar shape of the opening 21. Moreover, each fine hole 20 may be comprised from a part of spherical body (refer FIG.3 (c)). In this case, air can be more easily retained in each micropore 20.

  The liquid flowing on the surface 11 a of the substrate 11 moves so as to block the surface of the opening 21 before filling the micropores 20, so that air can be held in each micropore 20. Therefore, by controlling the width of the opening 21 and the aspect ratio of the fine hole 20, it is possible to control the moving speed of the liquid and move the liquid so as to block the surface of the opening 21 before filling the fine hole 20. It becomes possible. Specifically, when the liquid is easily wetted with respect to the base material 11, the liquid having the fine holes 20 is narrower when the width of the opening 21 is narrow and the aspect ratio of the fine holes 20 is larger than blocking the surface of the opening 21. It takes time to fill, and air can be easily held in each micropore 20. Further, when the liquid is difficult to wet with respect to the base material 11, even if the opening 21 is wide and the aspect ratio of the micropore 20 is small, it takes time for the liquid to fill the micropore 20. It is easy to keep air inside.

  In FIG. 1, a large number of micro holes 20 have the same shape as each other and are arranged in a square triangle shape (finely packed shape) at equal intervals in the vertical and horizontal directions when viewed from the plane. Thus, by arranging a large number of micropores 20 in a square triangular shape (finely packed shape), the ratio of the openings 21 of the micropores 20 to the surface 11a of the substrate 11 is increased, and a liquid component (for example, a living body) The area of the surface 11a to which the polymer) may adhere can be reduced. In addition, the liquid repellency of the surface 11a can be easily maintained. Specifically, the pitch p of the fine holes 20 is preferably 1 μm to 200 μm (refers to 1 μm or more and 200 μm or less; the same applies hereinafter). Here, the pitch p of the fine holes 20 is a distance from the center to the center of the fine holes 20 adjacent to each other. In addition, when the planar shape of the fine holes 20 is a square, a large number of fine holes 20 may be arranged in a square lattice shape.

  When the contact angle of the substrate 11 with respect to the liquid is 40 ° to 60 °, the width (diameter) w of the opening 21 of each microhole 20 is set to 100 nm to 20 μm, and the aspect ratio of each microhole 20 is 0.8. It is preferable to set it to -17 (refer FIG. 2). For example, the contact angle of a solution containing a surfactant (PBS containing 0.05% Tween 20 (manufactured by Wako Pure Chemical Industries, Ltd.)) with respect to a polymethyl methacrylate (PMMA) substrate is about 47 °, and the cycloolefin polymer group The contact angle to the material is about 53 °. Thus, when the contact angle is small, it is preferable to reduce the width (diameter) w of the opening 21 and increase the aspect ratio. The reason is that since the liquid is easily wetted with respect to the base material 11, the time for the liquid to enter the opening 21 to fill the micropores 20 is slower than the time for the liquid in contact with the base material 11 to block the surface of the opening 21. This is because air can be held in the fine holes 20. The aspect ratio of the fine hole 20 is calculated by {(depth d of the fine hole 20) / (width w of the opening 21 of the fine hole 20)}. The depth d of the fine hole 20 is set so that the width w of the opening 21 and the aspect ratio of the fine hole 20 satisfy the above-described relationship, specifically, 80 nm to 340 μm.

  On the other hand, when the contact angle of the substrate 11 with respect to the liquid is 80 ° to 100 °, the width (diameter) w of the opening 21 of each micropore 20 is set to 500 nm to 100 μm, and the aspect ratio of each micropore 20 is 0.1. It is preferable to set to -3 (refer FIG. 2). For example, the contact angle of Alexa488-labeled anti-rabbit IgG antibody (dilution ratio 1/100 with PBS) to a polymethyl methacrylate (PMMA) substrate is about 83 °, and the contact angle to a cycloolefin polymer substrate is about 94 °. It is. When the contact angle is large as described above, the width (diameter) w of the opening 21 may be increased to some extent and the aspect ratio may be decreased to some extent. The reason for this is that since the liquid is difficult to wet with respect to the base material 11, the time for the liquid to enter the opening 21 to fill the micropores 20 is slower than the time for the liquid in contact with the base material 11 to block the surface of the opening 21. This is because air can be held in the fine holes 20. The depth d of the fine hole 20 is set so that the width w of the opening 21 and the aspect ratio of the fine hole 20 satisfy the above-described relationship, and specifically, 50 nm to 300 μm.

(When the structure has an adsorption suppression function)
Next, a case where the liquid includes a biopolymer and the structure (biopolymer adsorption suppression structure) 10 has a function (adsorption suppression function) of suppressing adsorption to the biopolymer (liquid component) will be described.

  In this case, the width (diameter) w of the opening 21 of each fine hole 20 is preferably 500 nm to 100 μm, and more preferably 5 μm to 50 μm. By setting the width (diameter) w of the opening 21 to 500 nm or more, it is negligible that the air in the micropores 20 is eluted into the liquid, and the air can be reliably held inside the micropores 20. In addition, since the width (diameter) w of the opening 21 is set to 100 μm or less, it is prevented that it becomes difficult to hold air in the micropore 20 due to the liquid entering the micropore 20. In this case, the aspect ratio of the fine holes 20 is preferably 0.1 to 3, and more preferably 0.5 to 3. By setting the aspect ratio of the fine holes 20 to 0.1 or more, air can be easily retained. Moreover, the fine hole 20 can be reliably shape | molded because the aspect-ratio of the fine hole 20 was 3 or less. The depth d of the fine hole 20 is set so that the width w of the opening 21 and the aspect ratio of the fine hole 20 satisfy the above-described relationship, and specifically, 50 nm to 300 μm.

  Furthermore, the porosity of the fine holes 20 is preferably 25% or more, and more preferably 50% to 90%. By setting the porosity of the micropores 20 to 25% or more, the area of the surface 11a of the base material 11 to which the biopolymer adheres can be reduced, and the biopolymer to the surface 11a of the base material 11 can be reduced. Adsorption can be suppressed. Here, the porosity (%) of the fine holes 20 is the total area of the plurality of openings 21 existing in the region, which occupies the entire area of the region in which the fine holes 20 are provided, and {100 × (fine The total area of the plurality of openings 21 existing in the region where the holes 20 are provided) / (the total area of the region where the micro holes 20 are provided)}.

  Further, as shown in FIGS. 3A to 3C, in the vertical cross section perpendicular to the surface 11a of the base material 11, the angle θ formed by the surface 11a of the base material 11 and the side surface 22 of each fine hole 20 is a right angle. (See FIG. 3A) or an acute angle (see FIGS. 3B and 3C). This makes it difficult for the air contained in the micropores 20 to escape to the outside and makes it easier to hold the air inside the micropores 20, thereby further suppressing the adsorption of the biopolymer to the surface 11 a of the substrate 11. be able to.

  The fine holes 20 may be formed in the entire area of the surface 11a of the substrate 11, and may be formed only in a partial region (hole forming region) of the surface 11a, such as the central portion of the surface 11a. good. In addition, a first region and a second region are provided on the surface 11a of the substrate 11, a plurality of first micro holes 20 are provided in the first region, and a width, an aspect ratio, and the like are provided in the second region. However, a plurality of second micro holes 20 different from the first micro holes 20 may be provided.

  Such a base material 11 is preferably made from a resin material having a contact angle with water, which is the main component of a liquid containing a biopolymer, of 30 ° or more. By making the base material 11 from a resin material having a contact angle with water of 30 ° or more, the effect of easily holding air in the micropores 20 is enhanced, and the amount of biopolymer adsorbed on the base material 11 is increased. It can be further reduced. Furthermore, the base material 11 is more preferably made of a resin material having a contact angle with water of 60 ° or more. Thereby, the ratio of the micropores 20 that retain air among the many micropores 20 is increased, and the effect of reducing the amount of adsorption of the biopolymer is further enhanced. When there is a region where the fine holes 20 of the surface 11a of the base material 11 are not formed, the contact angle with water is the contact angle with water in the region. In addition, the contact angle is determined based on the angle of the straight line connecting the left and right end points and the apex of the dropped liquid 10 seconds after the drop of pure water 1.0 μL is dropped on the surface of the base material, and the contact angle. Is the contact angle measured according to the θ / 2 method. As the measuring device, for example, a contact angle meter DM 500 manufactured by Kyowa Interface Science Co., Ltd. can be used.

  Specifically, the base material 11 is made of a synthetic resin material such as polymethyl methacrylate, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyester, polytetrafluoroethylene, polyhydroxyhydromethacrylate, polyvinylpyrrolidone and the like. May be.

  The method for producing the structure 10 is not limited, but various molding methods used for plastic molding, such as a thermal nanoimprint method, a hot embossing method, an extrusion molding method, an injection molding method, and a blow molding method, can be used.

  By providing a large number of micropores 20 on the surface 11a of the substrate 11 in this way, when the liquid L containing a biopolymer contacts the surface 11a, air (gas) A is held in the multiplicity of micropores 20. (See FIGS. 4A and 4B). By interposing the air A between the base material 11 and the liquid L, the substantial contact area between the liquid L and the surface 11a of the base material 11 can be reduced. Thereby, it is suppressed that the biopolymer contained in the liquid L adsorbs to the surface 11a of the base material 11 (non-specific adsorption). In particular, the adsorption of the biopolymer can be suppressed without coating the surface 11a of the substrate 11 or the like. Therefore, it is not necessary to provide a process for coating the surface 11a of the substrate 11, and the process for manufacturing the structure 10 can be simplified. Further, it is possible to prevent the material coated on the surface 11a of the base material 11 from being eluted into the liquid L. Further, the adsorption of the biopolymer to the surface 11a of the substrate 11 can be suppressed regardless of the material of the substrate 11 and regardless of the size of the biopolymer.

  Although it is desirable that the air A is held in all the numerous micro holes 20, it is considered difficult to hold the air A in all the micro holes 20 in practice. However, when the aspect ratio of the micropores 20 is increased (see FIG. 4B), the number of microscopic holes 20 is larger than that when the aspect ratio of the micropores 20 is decreased (see FIG. 4B). The ratio of the fine holes 20 in which the air A occupying the holes 20 is increased. For this reason, it is thought that it is easier to suppress the adsorption of biopolymers when the aspect ratio of the micropores 20 is increased.

  1 and 2, the base material 11 has a rectangular parallelepiped shape as a whole, but is not limited thereto. The substrate 11 may be a sheet shape, a tube shape, or a dome shape. That is, the surface 11a of the substrate 11 may be a flat surface or a curved surface.

  Such a structure 10 includes, for example, a micro flow channel, a liquid storage bag, a cell culture bag, a cell culture substrate, a centrifuge tube, a centrifuge tube, a medical tube, a vascular catheter, an artificial blood vessel, or the like as described below. It is suitably used for contact lenses and the like.

  For example, when the base material 11 consists of microchannels, such as a biochip, protein adheres to the surface 11a of a microchannel (base material 11) is prevented. Thereby, it can prevent that the flow of the substance used as a measuring object is prevented in a microchannel due to protein adhering. In addition, as a material which comprises such a base material 11, transparent polymethylmethacrylate etc. can be mentioned.

  For example, when the base material 11 consists of liquid storage bags, such as a chemical | medical solution bag and an infusion bag, it is prevented that biopolymers, such as protein, adhere to the surface 11a of a liquid storage bag (base material 11), and the amount of useful ingredients Can be prevented from decreasing. In addition, as a material which comprises such a base material 11, polyethylene, a polypropylene, etc. can be mentioned.

  In addition, for example, when the base material 11 is a cell culture bag or a cell culture base material (flask, dish, plate, etc.), the cells adhere to the surface 11a of the cell culture base material (base material 11) and the properties of the cells change. To prevent the cell yield from decreasing. In addition, as a material which comprises the base material 11 which consists of cell culture bags, polyethylene and a polypropylene can be mentioned, As a material which comprises the base material 11 which consists of a cell culture base material, polyethylene, a polypropylene, a polystyrene etc. are mentioned. be able to.

  For example, when the base material 11 consists of a centrifuge tube and a centrifuge tube, it can prevent that a trace amount useful substance adheres to the surface 11a of a centrifuge tube or a centrifuge tube (base material 11), and a yield falls. . In addition, as a material which comprises such a base material 11, polyethylene, a polypropylene, a polystyrene etc. can be mentioned.

  For example, when the base material 11 consists of a medical tube, it can prevent that biopolymers, such as protein, adhere to the surface 11a of a medical tube (base material 11), and the amount of useful components falls. In addition, as a material which comprises such a base material 11, a polypropylene, a polyurethane, a polyvinyl chloride etc. can be mentioned.

  For example, when the base material 11 consists of a vascular catheter, it can prevent that a vascular catheter (base material 11) clogs, or an active ingredient adheres to the surface 11a and a dosage falls. Further, when the vascular catheter is introduced into the body, the vascular catheter can be prevented from adhering to the organ. In addition, as a material which comprises such a base material 11, a polyurethane, polyvinyl chloride, etc. can be mentioned.

  For example, when the base material 11 consists of an artificial blood vessel, it can prevent that blood adheres to the surface 11a of the artificial blood vessel (base material 11), a thrombus is formed, and clogging occurs in the artificial blood vessel. In addition, as a material which comprises such a base material 11, polyester, polytetrafluoroethylene, etc. can be mentioned.

  Further, for example, when the base material 11 is made of a contact lens, the safety or quality of the contact lens is deteriorated due to adhesion of protein or the like on the surface 11a of the contact lens (base material 11), or the contact lens can be used. It is possible to prevent the period from becoming shorter. In addition, as a material which comprises such a base material 11, polyhydroxy hydromethacrylate, polyvinylpyrrolidone, etc. can be mentioned.

(When the structure has a liquid repellency maintenance function)
Next, the case where the structure (liquid repellent structure) 10 has a function of maintaining liquid repellency with respect to the solution even after contact with the solution containing the surfactant (liquid repellency maintaining function) will be described. .

  In this case, the width (diameter) w of the opening 21 of each fine hole 20 is preferably 100 nm to 20 μm, and more preferably 600 nm to 12 μm. By setting the width (diameter) w of the opening 21 to 100 nm or more, it is negligible that the air in the micropores 20 is eluted into the solution, and the air can be reliably held inside the micropores 20. In addition, by setting the width (diameter) w of the opening 21 to 20 μm or less, it is prevented that it becomes difficult to hold air in the micropore 20 due to the solution entering the micropore 20. In this case, the aspect ratio of the fine holes 20 is preferably 0.8 to 17, and more preferably 1.5 to 7. By setting the aspect ratio of the fine holes 20 to 0.8 or more, air can be easily retained. Moreover, the fine hole 20 can be reliably shape | molded because the aspect-ratio of the fine hole 20 was 17 or less. The depth d of the fine hole 20 is set so that the width w of the opening 21 and the aspect ratio of the fine hole 20 satisfy the above-described relationship, specifically, 80 nm to 340 μm.

  Furthermore, the porosity of the fine holes 20 is preferably 25% or more, and more preferably 50% to 90%. By setting the porosity of the micropores 20 to 25% or more, the liquid repellency of the surface 11a of the substrate 11 can be maintained even after contact with the solution containing the surfactant.

  Further, as shown in FIGS. 3A to 3C, in the vertical cross section perpendicular to the surface 11a of the base material 11, the angle θ formed by the surface 11a of the base material 11 and the side surface 22 of each fine hole 20 is A right angle (see FIG. 3A) or an acute angle (see FIGS. 3B and 3C) is preferable. Thereby, the air accommodated in the inside of the fine hole 20 is difficult to escape to the outside, and the air is easily held inside the fine hole 20, so that the liquid repellency of the surface 11a of the substrate 11 is more reliably maintained. be able to.

  The material of the base material 11 is not limited. For example, polymethyl methacrylate, cycloolefin polymer, polycarbonate, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl chloride, polyester, polytetrafluoroethylene, polyhydroxyhydromethacrylate It is preferable to contain a synthetic resin material such as polyvinylpyrrolidone. In particular, the material of the substrate 11 preferably includes a material in which the difference between the contact angle with pure water and the contact angle with a solution containing a surfactant is 20 ° or less. The base material 11 is made of a material in which the difference between the contact angle with respect to pure water and the contact angle with the solution containing the surfactant is 20 ° or less, so that the surfactant is stabilized on the surface 11 a of the base material 11. The liquid repellency of the surface 11a of the substrate 11 is unlikely to decrease. The contact angle measurement method is the same as described above.

  Moreover, the base material 11 may be comprised from the single material, and may be comprised by combining several material. In the latter case, it is preferable that at least the surface 11a of the substrate 11 is made of the above material.

  When the structure 10 is used as a test kit or a microchannel device, the solution that contacts the surface 11a of the substrate 11 may be either a cleaning solution or a blocking solution. Examples of the cleaning liquid include a solution containing phosphate buffered saline (PBS) and sodium chloride. Examples of the blocking solution include a solution containing milk-derived protein in phosphate buffered saline (PBS). The surfactant contained in the solution is preferably a nonionic surfactant that is easily soluble in water, has a relatively low ionic strength, and does not contain a polyvalent cation. Examples of preferable nonionic surfactants from this point include Tween 20 (polyoxyethylene sorbitan monolaurate), Span-80 (sorbitan monooleate), Triton X-100 (polyethylene glycol paraisooctyl phenyl ether) and the like. be able to.

  As described above, by providing a large number of micropores 20 on the surface 11 a of the base material 11, when the solution L containing a surfactant contacts the surface 11 a, air (gas) A is contained in the large number of micropores 20. Is held (see FIGS. 4A and 4B). As a result, the surface 11a of the substrate 11 can be made liquid repellent. In addition, it is known as Cassie-Baxter theory that liquid repellency can be improved by trapping air through the large number of fine holes 20 as described above. Further, since the air A is interposed between the base material 11 and the solution L, the substantial contact area between the solution L and the surface 11a of the base material 11 can be reduced. Thereby, it is suppressed that the surfactant contained in the solution L adheres to the surface 11a of the base material 11. As a result, even after the surfactant contained in the solution L comes into contact with the surface 11a of the base material 11, the liquid repellency of the surface 11a of the base material 11 can be maintained.

  In this specification, “maintaining liquid repellency even after contact with a solution containing a surfactant” means that the surface 11a of the substrate 11 after contact with a solution containing a surfactant is used. The liquid repellency is maintained higher than the liquid repellency of the surface of the substrate 11 that is flat (that is, the micropores 20 are not present) after contact with the solution containing the surfactant.

  Although it is desirable that the air A is held in all the numerous micro holes 20, it is considered difficult to hold the air A in all the micro holes 20 in practice. However, when the aspect ratio of the micropores 20 is increased (see FIG. 4B), the number of microscopic holes 20 is larger than that when the aspect ratio of the micropores 20 is decreased (see FIG. 4B). The ratio of the fine holes 20 in which the air A occupying the holes 20 is increased. For this reason, it is thought that it is easier to maintain the liquid repellency of the surface 11a of the base material 11 when the aspect ratio of the fine holes 20 is increased.

(Operation when the structure has a liquid repellency maintaining function)
Next, the operation when the structure has a liquid repellency maintaining function will be described.

  In the structure 10 shown in FIGS. 1 and 2, first, a solution containing a surfactant is prepared (preparation step). Examples of such a solution include a cleaning solution or a blocking solution as described above. In addition, as the surfactant contained in the solution, a nonionic surfactant such as Tween 20 can be used as described above.

  Next, this solution is supplied to the structure 10 from the outside. The solution supplied to the structure 10 contacts the surface 11a of the base material 11 (first contact process). At this time, the solution may flow along the surface 11a of the substrate 11 or may stay on the surface 11a of the substrate 11 for a certain period of time. Thereafter, the solution flows out of the structure 10. At this time, the surfactant is applied (coated) to the surface 11a of the base material 11 by the solution, and the liquid repellency of the surface 11a of the base material 11 is lowered (made lyophilic).

  In contrast, in the present embodiment, since a large number of micropores 20 are provided on the surface 11a of the substrate 11, air (gas) is generated in the multiplicity of micropores 20 when the solution contacts the surface 11a. Is held (see FIGS. 4A and 4B). Thereby, it is suppressed that the surfactant contained in the solution adheres to the surface 11 a of the substrate 11. As a result, even after the surfactant contained in the solution comes into contact with the surface 11a of the base material 11, the liquid repellency of the surface 11a is not greatly reduced, and the liquid repellency of the surface 11a is reduced. Can be maintained.

  When the solution moves in the structure 10 as described above, external force is applied to the solution from the outside. As such an external force, a suction force from the outside of the structure 10, a gravity force or a centrifugal force applied to the entire structure 10, and the like can be given.

  Next, the solution is removed from the surface 11a of the substrate 11 and the solution on the surface 11a is dried (drying step). As a method for drying the solution, the solution may be blown off by air blowing on the surface 11a of the substrate 11, or the solution may be shaken off by applying a centrifugal force to the structure 10.

  After the solution on the surface 11a of the substrate 11 is dried in this way, the solution is brought into contact with the surface 11a of the substrate 11 again (second contact step). The method for bringing the solution into contact with the surface 11a of the substrate 11 may be the same as in the first contact step described above.

  Then, you may further repeat the drying process and 2nd contact process which were mentioned above once or more.

  As described above, according to the present embodiment, even after the surfactant contained in the solution contacts the surface 11a of the substrate 11 (that is, after the first contact step), the surface 11a of the substrate 11 Since the liquid repellency is maintained, it is possible to prevent problems that make it difficult to control the flow of the solution in the structure 10.

  In the above, the solution that is brought into contact with the surface 11a of the substrate 11 in the first contact step and the solution that is brought into contact with the surface 11a of the substrate 11 in the second contact step are the same as each other. Yes. However, the present invention is not limited to this, and the solution brought into contact with the surface 11a of the substrate 11 in the first contact step and the solution (liquid) brought into contact with the surface 11a of the substrate 11 in the second contact step are mutually It may be different. For example, the liquid that is brought into contact with the surface 11a of the substrate 11 in the second contact step may be a liquid that does not contain a surfactant. Even in this case, the liquid repellency of the surface 11a of the substrate 11 with respect to the liquid (different from the solution) can be maintained after contacting the solution containing the surfactant.

(Configuration of microchannel device)
Such a structure 10 is suitably used for a test kit such as an immunoassay kit and an enzyme reaction kit, a microchannel device, and the like. Hereinafter, a case where the structure 10 is used in a microchannel device will be described as an example.

  FIG. 5 is a schematic plan view showing one embodiment of the microchannel device. In FIG. 5, the microchannel device 30 </ b> A includes a first lyophilic part 31 </ b> A located on the upstream side, a structure 10 located on the downstream side of the first lyophilic part 31 </ b> A, and a downstream side of the structure 10. It has the 2nd lyophilic part 31B located. Further, the first lyophilic part 31A and the structure 10 are in communication with each other via the first connection channel 32A, and the structure 10 and the second lyophilic part 31B are in the second connection. They communicate with each other via the flow path 32B.

  The first lyophilic part 31A and the second lyophilic part 31B are not particularly limited as long as they have lyophilic properties. As the configuration of the first lyophilic part 31A and the second lyophilic part 31B, for example, a shape in which a large number (plurality) of pillars protrude in the recess or on a plane, such as a shape in which the unevenness of the structure 10 is inverted. You may have.

  In FIG. 5, the first lyophilic part 31A can be used as a liquid reservoir for storing a solution containing a surfactant, and the second lyophilic part 31B can be used as a waste liquid tank for discarding the solution. The structure 10 serves as a valve. In such a configuration, when an external force exceeding a predetermined threshold is applied to the solution, the solution passes from the liquid reservoir (first lyophilic part 31A) through the valve (structure 10) to the waste liquid tank (first 2 lyophilic part 31B). That is, the microchannel device 30A can function as a valve channel. In FIG. 5, the arrows indicate the flow direction of the solution.

  FIG. 6 is a schematic plan view showing another embodiment of the microchannel device. In FIG. 6, the microchannel device 30 </ b> B includes a structure 10 located on the upstream side, a connection channel 32 located on the downstream side of the structure 10, and a lyophilic part 31 located on the downstream side of the connection channel 32. And have. The structure 10 and the connection channel 32 are in communication with each other, and the connection channel 32 and the lyophilic part 31 are in communication with each other.

  The lyophilic part 31 is not particularly limited as long as it has lyophilicity. As a configuration of the lyophilic part 31, for example, a shape in which a large number (plural) of pillars protrude in a recess or on a plane, such as an inverted shape of the structure 10, may be used. Moreover, the connection flow path 32 may include a flat surface that does not have unevenness.

  In FIG. 6, the structure 10 can be used as a liquid reservoir for storing a solution containing a surfactant, and the lyophilic part 31 can be used as a waste liquid tank for discarding the solution. From the reservoir (structure 10), it flows into the waste liquid tank (lyophilic part 31) via the connecting channel 32. In this case, the solution can be allowed to flow from the liquid reservoir (structure 10) to the waste liquid tank (lyophilic part 31) with almost no external force applied to the solution. In FIG. 6, the arrows indicate the flow direction of the solution.

  When the structure 10 has the above two functions, that is, when the structure 10 has both an adsorption suppressing function and a liquid repellency maintaining function, the width of the opening 21 of each microhole 20 is 500 nm to 10 μm. The aspect ratio of each fine hole 20 is preferably 0.8-3.

  EXAMPLES The present invention will be described more specifically with reference to examples. However, the present invention is not limited to the description of the following examples unless it exceeds the gist.

(Evaluation of adsorption suppression function)
First, the function (adsorption suppression function) which suppresses adsorption | suction with respect to components, such as biopolymer contained in a liquid, was evaluated.

(Example)
(1) Production of original plate 80 First, an original plate 80 for producing the structure 10 was produced (see FIG. 7A). Specifically, a square lattice groove pattern (recess) 81 was formed on the surface of a 6.35 mm thick, 50 mm square metal plate (BeCu) using a mechanical cutting device (FANUC, ROBONANO). . Between each concave part 81, the planar square-shaped convex part 82 was formed. In addition, each convex part 82 respond | corresponds to the micropore 20 of the structure 10, respectively. Three levels of the width w _{b of the} concave portion 81 were produced: 5 μm, 10 μm, and 20 μm. The depth _{d a} of the recess 81 was set to 5 [mu] m (1 level). The ratio of the width _{w b} of width _{w a} and the recess 81 of the projections 82, 1: 1, 1: 2, 1: 3 levels of 5.

(2) Production of structure 10 After preparing a sheet-like polymethyl methacrylate (PMMA) base material (manufactured by Mitsubishi Rayon Co., Ltd.) having a thickness of 2 mm and heating the base material at 150 ° C. to soften the base material, The original plate 80 was brought into contact with the substrate and pressurized at 10 MPa. The contact angle of the PMMA base material with respect to water was 66.0 °. The base material was cooled while being pressurized, and then the original plate 80 was peeled off to obtain a structure 10 having a shape in which the convex portions 82 and the concave portions 81 of the original plate 80 were inverted (see FIG. 7B). The depth _{d b} of the micropores 20 was 5 [mu] m. The ratio between the width _{w c} and micropores 20 interval _{w d} between the fine pores 20, 1: 1, 1: 2, 1: 3 levels of 5.

(Comparative example)
A sheet-like polymethyl methacrylate (PMMA) base material (manufactured by Mitsubishi Rayon Co., Ltd.) having a thickness of 2 mm was prepared and used as a comparative example. The contact angle of the PMMA base material with respect to water was 66.0 °.

(Evaluation)
The following evaluation was performed on the structure 10 obtained in the example and the structure according to the comparative example.

<Protein adsorption inhibition evaluation>
The structure 10 according to the example and the structure according to the comparative example were each immersed in Alexa488-labeled anti-rabbit IgG antibody (manufactured by Molecular Probes) (dilution ratio 1/100 with PBS) for 1 hour. The unadsorbed antibody (protein) was sufficiently removed by washing by repeating immersion for 1 minute in a phosphate buffer (PBS) containing 0.05% Tween 20 (manufactured by Wako Pure Chemical Industries, Ltd.) three times. Each of the obtained structures was excited with light having a wavelength of 488 nm by a single scan of a confocal microscope (manufactured by Carl Zeiss), and the fluorescence intensity in the wavelength region of 520 nm was measured. The values normalized with the absorbance of the structure according to the comparative example as 1 are shown in the graph (see FIG. 8). In the graph of FIG. 8, the horizontal axis indicates the aspect ratio of the micropores 20, and the vertical axis indicates the absorbance (protein adsorption amount) of the structure 10.

  From the graph results, it was revealed that the structure 10 of the example was excellent in the protein adsorption suppression effect.

(Evaluation of liquid repellency maintenance function)
Next, the function of maintaining the liquid repellency with respect to the solution (liquid repellency maintaining function) was evaluated even after contact with the solution containing the surfactant.

(Example)
(1) Production of original plate 80 First, an original plate 80 for producing the structure 10 was produced (see FIG. 7A). Specifically, a square lattice groove pattern (recess) 81 was formed on the surface of a 6.35 mm thick, 50 mm square metal plate (BeCu) using a mechanical cutting device (FANUC, ROBONANO). . Between each concave part 81, the planar square-shaped convex part 82 was formed. In addition, each convex part 82 respond | corresponds to the micropore 20 of the structure 10, respectively. In this case, the original 80, the width _{w a} of the convex portion 82, the depth _{d a} width _{w b} and the concave portion 81 of the recess 81 are different from each other, to form a plurality of regions.

(2) Production of structure 10 made of PMMA base material A sheet-like polymethyl methacrylate (PMMA) base material (manufactured by Mitsubishi Rayon Co., Ltd., trade name acrylite) having a thickness of 2 mm is prepared, and the base material is 150 ° C. After being softened by heating, the original plate 80 was brought into contact with the substrate and pressurized at 10 MPa. Thereafter, the substrate was cooled to 40 ° C. while being pressurized, and then the original plate 80 was peeled off to obtain the structure 10 having a shape in which the convex portions 82 and the concave portions 81 of the original plate 80 were inverted (FIG. 7B). )reference). The structure 10 was formed with a plurality of micropore regions in which the width w _{c of} the micro holes 20, the interval w _d between the micro holes 20, and the depth d _b of the micro holes 20 were different from each other.

(3) Production of Structure 10 Consisting of Cycloolefin Polymer Base Material A sheet-like cycloolefin polymer base material (manufactured by Nippon Zeon Co., Ltd., trade name ZEONOR) was used in the same manner as above, A structure 10 made of a cycloolefin polymer substrate was produced. The structure 10 was formed with a plurality of micropore regions in which the width w _{c of} the micro holes 20, the interval w _d between the micro holes 20, and the depth d _b of the micro holes 20 were different from each other.

(Evaluation)
The shape of the micropore 20 in each micropore area | region of the structure 10 which consists of a PMMA base material and the structure 10 which consists of a cycloolefin polymer base material was measured. Specifically, by using a laser microscope (manufactured by Olympus Corporation), a width w _c, the depth d _b of the micropores 20 between distance w _d and micropores 20 of the measured (Tables 1 and micropore 20 Example 1-1 to 1-6, Comparative Examples 1-1 to 1-5, Examples 2-1 to 2-6, and Comparative Examples 2-1 to 2-7 shown in FIG. It was also calculated each aspect ratio with width w _c and depth d _b of the measured micropore 20.

  Next, a solution containing a surfactant (PBS containing 0.05% Tween 20 (manufactured by Wako Pure Chemical Industries, Ltd.)) was prepared.

  Next, the contact angle after solution contact was measured in each fine pore region of the structure 10 made of a PMMA base material and the structure 10 made of a cycloolefin polymer base material.

  Specifically, each of these structures 10 was immersed in a solution for 10 minutes (first contact step), and then these structures 10 were pulled up from the solution and dried by air blowing. As a result, the surface of the base 11 of the structure 10 was coated with the surfactant. Next, a droplet of 1.0 μL of the above solution is dropped into each micropore region of each structure 10 (second contact step), and the left and right end points and vertices of the dropped droplet are set 10 seconds after the landing. The contact angle was calculated from the angle of the connecting straight line to the surface 11a (θ / 2 method). In this case, the contact angle was measured using a measuring device (contact angle meter DM500 (manufactured by Kyowa Interface Science)).

  Then, when the contact angle with respect to the said solution of the structure 10 which consists of a PMMA base material and the structure 10 which consists of a cycloolefin polymer base material with respect to the flat (namely, no micropore 20) was measured, 46. 7 ° and 52.2 °. In addition, the measuring method of a contact angle is the same as the measuring method in each micropore area | region of the structure 10 mentioned above.

As a result, in the structure 10, the width w _c of the opening 21 of the micropore 20 is 100 nm to 20 μm, and the micropore region where the aspect ratio of the micropore 20 is 0.8 to 17 is a surfactant. The liquid repellency with respect to the solution containing a surfactant was still maintained after contact with the solution containing (see Examples 1-1 to 1-6 and Examples 2-1 to 2-6). That is, a contact angle smaller than the contact angle of the flat substrate was maintained (see Tables 1, 2 and 9). As described above, the structure 10 was able to maintain liquid repellency even after being subjected to contact with a solution containing a surfactant that usually has an effect of improving lyophilicity.

  In addition, after making the solution containing surfactant in the 1st contact process contact the surface 11a of the base material 11, whether the liquid made to contact the surface 11a of the base material 11 in the 2nd contact process contains surfactant Regardless of whether or not, the liquid repellency of the surface 11a of the substrate 11 is considered to be maintained. That is, in general, when the solution containing the surfactant is brought into contact in the second contact step, the surface of the substrate 11 is compared with the case where the solution not containing the surfactant is brought into contact in the second contact step. It will be more difficult for 11a to maintain liquid repellency. For this reason, in this example, even if a solution containing a surfactant is used in the second contact step, the surface 11a of the base material 11 still maintains liquid repellency. Therefore, as a solution used in the second contact step, It is considered that the liquid repellency of the surface 11a of the substrate 11 can be maintained even when a material that does not contain a surfactant is used.

Moreover, the droplet of the said solution was dripped at the structure 10 after coating with surfactant, respectively, and the micropore 20 was observed. As a result, in particular, the micropore region (Examples 1-1 to 1-6 and Examples 1-1 and 1-6) in which the width w _c of the opening 21 of the micropore 20 is 100 nm to 20 μm and the aspect ratio of the micropore 20 is 0.8 to 17. In Examples 2-1 to 2-6), the fine pores 20 were formed at a higher rate than other fine pore regions (see Comparative Examples 1-1 to 1-5 and Comparative Examples 2-1 to 2-7). It was observed that air was trapped. In addition, as a method of observing the fine holes 20, a method of immersing the structure 10 in a petri dish filled with a solution and observing with an inverted phase contrast microscope (manufactured by Olympus) can be mentioned.

DESCRIPTION OF SYMBOLS 10 Structure 11 Base material 11a Surface 20 Fine hole 21 Opening 22 Side surface 23 Bottom surface 24 Space

Claims (18)

A structure capable of suppressing adsorption to liquid components or maintaining liquid repellency to liquid,
A substrate having a surface in contact with the liquid;
Each having an opening on the surface side of the base material, and a plurality of micropores capable of holding gas inside when the liquid contacts the surface of the base material,
Each fine hole has an independent space surrounded by a side surface connected to the surface of the substrate and a bottom surface connected to the side surface.   The contact angle of the substrate with respect to the liquid is 40 ° to 60 °, the opening width of each micropore is 100 nm to 20 μm, and the aspect ratio of each micropore is 0.8 to 17. The structure according to claim 1.   The contact angle of the substrate with respect to the liquid is 80 ° to 100 °, the opening width of each micropore is 500 nm to 100 μm, and the aspect ratio of each micropore is 0.1 to 3. The structure according to claim 1.   2. The structure according to claim 1, wherein the liquid contains a biopolymer, the opening width of each micropore is 500 nm to 100 [mu] m, and the aspect ratio of each micropore is 0.1 to 3. body.   The structure according to claim 4, wherein a porosity of the plurality of micropores in the base material is 25% or more.   The structure according to claim 4 or 5, wherein the base material is made of a resin material having a contact angle with water of 30 ° or more.   The base material is a microchannel, a liquid storage bag, a cell culture bag, a cell culture base material, a centrifuge tube, a centrifuge tube, a medical tube, a vascular catheter, an artificial blood vessel, or a contact lens. The structure according to any one of 4 to 6.   The structure can maintain liquid repellency with respect to the liquid after contact with a solution containing a surfactant, the width of each micropore is 100 nm to 20 μm, and the aspect ratio of each micropore is The structure according to claim 1, which is 0.8 to 17.   The structure according to claim 8, wherein the aspect ratio of each micropore is 1.5-7.   The structure according to claim 8 or 9, wherein the opening width of each micropore is 600 nm to 12 µm.   The structure according to any one of claims 8 to 10, wherein the surface of the base material contains a resin.   The structure can maintain liquid repellency with respect to the liquid after contact with a solution containing a surfactant, the liquid contains a biopolymer, and the opening width of each micropore is 500 nm to 10 μm. The structure according to claim 1, wherein the aspect ratio of each micropore is 0.8-3.   The structure according to any one of claims 1 to 12, wherein an angle formed by the surface of the substrate and the side surface of each micropore is a right angle or an acute angle in a vertical cross section.   The structure according to any one of claims 1 to 13, wherein a planar shape of the opening is a circular shape, an elliptical shape, or a polygonal shape.   A microchannel device comprising the structure according to any one of claims 8 to 12. A method of using the structure according to any one of claims 8 to 12,
Preparing a solution containing the surfactant;
Contacting the solution with the surface of the substrate;
And a step of bringing the liquid into contact with the surface of the substrate.   The method of using a structure according to claim 16, wherein the solution is any one of a cleaning liquid and a blocking liquid.   The method for using a structure according to claim 16 or 17, wherein the surfactant contained in the solution is a nonionic surfactant.

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