JP2019015610A - Ultraviolet curable resin composition used in bonding of biosensor board and biosensor board using the same - Google Patents

Abstract

To realize a sample holding carrier with which, as a member for forming a sample holding carrier or an ultraviolet curable resin composition for pasting the members together, it is possible to prevent adverse effects such as infiltration, elution, etc., into cells and read out exact cell information even under various cell information detection environments.SOLUTION: Provided is (1) an ultraviolet curable resin composition 50 for a biosensor board 1 characterized by containing (meth)acrylate compound (A), a softener (B) and a photoinitiator (C); (2) an ultraviolet curable resin composition for biosensor boards stated in (1) which is characterized by containing (meth)acrylate oligomer (A1) and (meth)acrylate monomer (A2) as the (meth)acrylate compound (A).SELECTED DRAWING: Figure 1

Description

  The present invention relates to a member for forming a sample holding carrier used in a cell detection method or an ultraviolet curable resin composition for bonding the member, and a cured product layer obtained by curing the ultraviolet curable resin composition. The present invention relates to a sample holding carrier provided.

Until now, cell detection methods include, for example, methods of staining cells and detecting cells stained with a microscope, etc., and examining / diagnosing the presence / absence / density of specific cells using immunochromatography, PCR, etc. The method has been done. However, in these methods, it is necessary for a skilled person with a high technical skill to perform, and observation must also depend on human eyes. There is a problem that it is extremely difficult to confirm the state. In addition, an expensive instrument is required for the immunochromatography method and the PCR method, and methods for detecting target cells inexpensively and simply have been limited.
Therefore, in recent years, as a method for detecting labeled cells, a specific carrier is used by holding a large number of cells in a well provided in the holding carrier using a holding carrier such as a microarray chip and acting on a cell holding laser light or the like. Devices for detecting cells have been developed.

  For example, Patent Document 1 describes a technique for detecting cells. In such a technique, by using a microarray chip in which wells are formed, cells labeled with fluorescent labels are injected into the wells, irradiated with laser light, and the state of cells labeled with each fluorescent label is observed. A specific target cell of interest is detected.

On the other hand, Patent Document 2 describes a technique for detecting another cell. In such a technique, a well is formed on a disk-shaped substrate, and cells labeled with a fluorescent label are injected into the well. Then, the well is scanned with laser light, and the fluorescently labeled cells are excited by the laser light to emit fluorescence. Here, since the information pit is formed at the position corresponding to the well into which the cell is injected, the fluorescence emission area is compared with the optical information from the information pit corresponding to the area and read. This makes it possible to accurately grasp the area.
As described above, information related to the interaction between substances is obtained from the reaction region on the substrate by the optical pickup means similar to the reproducing device of the optical disc, and at the same time, the information of the information pit group formed on the substrate is more stably By providing a bioassay substrate that can be obtained, a large amount of fluorescently labeled cells can be detected quickly and accurately.

Here, various methods such as Patent Document 1 and Patent Document 2 have been sought as detection methods of fluorescently labeled cells, but it is preferable to use any component for the well forming member of the sample holding carrier such as a biosensor substrate. It was not decided. In order to prevent cells from flowing out of the well, the base substrate on which the well is formed is bonded to the cover member to form a reaction chamber. The base substrate on which the well is formed and the cover It has not been determined what kind of adhesive is suitable for bonding with the member.
Since the well is filled with cells, there is a contact area with the cells. Therefore, if a material that causes adverse effects such as infiltration / elution on cells is used, accurate cell information cannot be obtained, which hinders cell detection. In addition, when a technique such as Patent Document 2 is used, a metal material such as a reflective film is formed on the disk-shaped substrate. Therefore, if a material that corrodes the metal material is used, an accurate cell is also obtained. Information cannot be obtained. In addition, if peeling or warping occurs between the base substrate on which the well is formed and the cover member during detection, accurate cell information cannot be detected in the same manner, and peeling may occur even in various temperature and humidity environments. It has also been required for the well forming member and the adhesive between the base substrate on which the well is formed and the cover member that the warp does not change.

International Publication No. 2010/027003 JP 2006-322819 A

  The present invention is a member that forms a sample holding carrier or an ultraviolet curable resin composition for laminating the member, as well as preventing adverse effects such as infiltration and elution of cells, and under various cell information detection environments, An object of the present invention is to realize a sample holding carrier capable of reading accurate cell information.

The present inventors have completed the present invention as a result of intensive studies in order to solve the above problems. That is, the present invention relates to the following (1) to (7).
(1) An ultraviolet curable resin composition for a biosensor substrate, comprising a (meth) acrylate compound (A), a softening component (B), and a photopolymerization initiator (C).
(2) The ultraviolet ray for a biosensor substrate according to (1), comprising (meth) acrylate oligomer (A1) and (meth) acrylate monomer (A2) as the (meth) acrylate compound (A). A curable resin composition.
(3) The (meth) acrylate oligomer (A1) has at least one skeleton selected from the group consisting of urethane (meth) acrylate, polypropylene, polybutadiene, hydrogenated polybutadiene, polyisoprene and hydrogenated polyisoprene (meth) The ultraviolet curable resin composition for a biosensor substrate according to (1) or (2), which is an acrylate.
(4) The softening component (B) includes at least one selected from the group consisting of a hydroxyl group-containing polymer, a terpene resin, a hydrogenated terpene resin, a rosin resin, and a hydrogenated rosin resin. The ultraviolet curable resin composition for a biosensor substrate according to any one of (1) to (3).
(5) The ultraviolet curable resin composition for a biosensor substrate according to any one of (1) to (4), wherein the resin composition has a surface tension of 20 mN / m or more.
(6) Hardened | cured material obtained by irradiating an active energy ray to the ultraviolet curable resin composition as described in any one of (1)-(5).
(7) A biosensor substrate comprising the ultraviolet curable resin composition according to any one of (1) to (6).

It is a principal part expansion schematic of the biosensor board | substrate of this invention. It is an upper top view schematic diagram of the biosensor board | substrate of this invention. It is a cross-sectional schematic diagram of the biosensor substrate of the present invention. It is a schematic diagram of the well formation process of a biosensor board | substrate in this invention.

First, a biosensor substrate to which the ultraviolet curable resin composition of the present invention is applied will be described with reference to FIGS.
Referring to FIG. 1, a substrate 1 has a well formation layer 11 formed on a base substrate 10. The minute well 15 partitioned by the well forming layer functions as a reaction chamber 3 that serves as an interaction field between substances described later.
Examples of the material of the base substrate 10 include resins such as PET, COC, COP, and plastic (acrylic resin, etc.), polystyrene, polyethylene, polypropylene, polyamide, polycarbonate, polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), Cyclic olefin copolymers (COC), polymers such as amorphous polyolefins, metals such as silicon, glass, quartz glass, and combinations of multiple materials such as polymers and glass or metal bonded together (eg PDMS and glass) Etc. are applicable.

On the upper surface of the base substrate 10, there are information pits 12 processed into a fine uneven shape. The pitch width d of the information pits 12 can be adjusted according to the size of the detection target of the fluorescently labeled cells. Here, the pitch width d is usually set smaller than the width of the detection target.
The information pit 12 can be read by irradiating a laser beam or the like. Using this information pit 12, the position information of each reaction region of the biosensor substrate 1 is optically read to identify in which reaction region the fluorescence detection operation is being performed in which reaction chamber. Is possible. Then, by associating the information content recorded in the information pit 12 with the reaction region directly above, the detection operation can be performed by irradiating only a specific reaction region with laser light.
Here, the case where the information pit 12 is used has been described above, but information may be held by meandering the groove in the radial direction of the biosensor substrate using the inner groove of the pit. In this case, information is held by the meandering waveform of the groove. Further, the meandering shape of the groove can be reproduced based on the tracking error signal as in the technique applied to the existing optical disc. Information may be held by a combination of pits and grooves.

A reflective film 13 may be formed on the upper surface of the information pit 12. Usually, the reflective film is formed in a thickness of several μm (for example, 1 to 10 μm) by (vacuum) deposition on the information pits 12. When the reflective film 13 is formed, the reflective film 13 plays a role of selectively reflecting laser light or the like irradiated to the information pits 12. The reflective film 13 is made of a metal such as aluminum, a gold alloy, or a silver alloy.
Here, instead of the reflective film 13, a dielectric film 14 formed of a translucent dielectric material may be applied. In this case, reflection can be generated by making the refractive index of the base substrate 10 and that of the dielectric material different. As such a dielectric material, for example, titanium oxide or the like can be used.
In addition to the case where only one of the reflective film 13 and the dielectric film 14 is used, both the reflective film 13 and the dielectric film 14 may be laminated.

On the base substrate, the well 15 is formed of the well forming material 11 in a state where the reflective film 13 or the dielectric film 14 is laminated or in the absence of these films. As the well forming material, the well 15 can be formed by the ultraviolet curable resin composition of the present invention described later. As will be described later, the ultraviolet curable resin composition of the present invention has little influence on the cells, and it is difficult for the resin to infiltrate into the cells and elution of the cells. Retained. In addition, as a material other than the resin composition of the present invention, it may be composed of silicone, polycarbonate, polymethyl methacrylate and the like.
The shape of the well 15 is shown in FIG. 1 as a cylindrical shape, but is not limited to such a shape. Cylindrical, inverted hemispherical, inverted cone, inverted pyramid (inverted triangular pyramid, inverted quadrangular pyramid, inverted pentagonal pyramid, inverted hexagonal pyramid, inverted polygonal pyramid of heptagon or more), rectangular parallelepiped, etc. The shape which combined two or more of these shapes is illustrated. In the case of the cylindrical shape or the rectangular parallelepiped, the bottom of the well is usually flat, but may be curved, convex, or concave. In the case of the inverted cone shape or the inverted pyramid shape, the bottom surface serves as an opening of the well. However, a shape obtained by cutting a part from the top of the inverted cone shape or inverted pyramid shape (the bottom portion of the well is flat) can be exemplified. . Furthermore, in the case of a shape obtained by cutting a part from the top of an inverted cone or inverted pyramid, the bottom of the well 15 can be a curved surface or the like, as described above. The shape of the well is preferably a cylindrical shape, an inverted hemispherical shape, an inverted conical shape, or an inverted pyramid shape, more preferably a cylindrical shape, an inverted hemispherical shape, and most preferably a cylindrical shape. Further, the well 15 preferably has one type of shape in one biosensor substrate.

As long as cells can be stored in each well 15 in this way, the dimensions of each well 15 are not limited. The dimensions of the wells 15 are preferably determined so that the same number of cells are stored in each well 15. For this reason, it is more preferable that the dimensions of each well 15 are the same. If the opening of the well 15 is circular, the “inner diameter” means the diameter of the opening in the well 15. When the opening of the well 15 is not circular, the “inner diameter” means the length of one side of the opening of the well 15. “Depth” means the distance between the opening of the well 15 and the deepest location of the well 15.
The well 15 is set to such a depth and size that the liquid such as the sample solution can be retained when the liquid is dropped. As long as the object can be held, the depth and size are not particularly limited. For example, the object can be formed with a diameter of 20 to 800 μm and a depth of about 2 to 10 μm. More specifically, the inner diameter of the well is preferably 20 to 500 μm, more preferably 20 to 400 μm, still more preferably 20 to 300 μm, still more preferably 30 to 250 μm, and particularly preferably 30 to 200 μm. Further, the depth is preferably 2 to 200 μm, more preferably 2 to 100 μm, further preferably 2 to 80 μm, still more preferably 2 to 70 μm, and particularly preferably 3 to 70 μm, although it depends on the value of the inner diameter. is there.
It is preferable that the inner diameter and depth of the well 15 have a certain ratio. Specifically, the ratio of (inner diameter: depth) is preferably (1: 0.35-1), more preferably (1: 0.35-0.85), (1: 0 .4 to 0.85), more preferably (1: 0.45 to 0.8).
Note that if the value of the inner diameter is determined by the above-described preferable ratio (inner diameter: depth), the preferable value of the well depth can be determined. However, the well preferably has a depth of 2 μm or more in order to store cells. That is, it is particularly preferable that the well has an inner diameter and a depth in the above-described ratio, the inner diameter has the above-described value, and the depth is 2 μm or more.

The upper surface of the well forming layer 11 can be appropriately subjected to surface treatment or a solid phase layer 16 can be provided.
The surface treatment method is not limited, and examples thereof include plasma treatment and corona discharge treatment. Preferable is plasma treatment, and oxygen plasma treatment is exemplified. For example, when the base substrate 10 is a hydrophobic material (polymer such as polystyrene or PMMA), it is preferable to perform a hydrophilic treatment such as an oxygen plasma treatment. Further, when the base substrate 10 is a hydrophilic material (silicon, glass, or the like), it is not necessary to perform such treatment. Further, it may be prepared by coating with protein, lipid or the like and performing surface treatment.
The solid phase layer 16 is formed of a material suitable for fixing an object. For example, SiO ₂ that can be surface-modified with a silane compound is formed to a thickness of about 50 nm. The solid phase layer 16 formed of SiO ₂ or the like is exposed on the bottom surface of the well 15, and the exposed surface portion is surface-treated with, for example, a silane coupling agent. The functional group at the modified end of the probe substance can be chemically bonded directly or indirectly to the free amino group of the silane coupling agent. That is, the probe substance can be immobilized. Alternatively, the probe substance may be immobilized using a diazo coupling reaction.
If necessary, a transparent electrode layer made of ITO or the like may be provided between the solid phase layer 16 and the base substrate 10. Such a transparent electrode layer is formed to a thickness of about 100 to 200 μm, for example.

The base substrate 10 on which the well forming layer is formed and the cover member 20 are bonded together by an ultraviolet curable resin composition 50 described later.
The cover member 20 can be entirely formed of a metal substrate or sheet. Or resin such as PET, COC, COP, plastic (acrylic resin, etc.), polystyrene, polyethylene, polypropylene, polyamide, polycarbonate, polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), etc. It can also be formed of a metal such as a polymer or silicon, glass, quartz glass, or a substrate or sheet made of polymer and glass or synthetic resin. Here, an electrode layer such as an ITO film may be formed on a part of the synthetic resin substrate or sheet. The cover member 20 can form a hole for injecting the cell solution into the well. It is preferable that the size (diameter) of the hole is smaller than the size of the opening of the well, and the cell solution can be accurately introduced into the well.

  The reaction chamber 3 partitioned in this way is defined by the well 15, the cured product layer of the ultraviolet curable resin composition 50, and the cover member 20. The number of cells stored in each well 15 is not limited as long as cells can be held in the well 15 of the reaction chamber 3 and two or more cells can be stored in each well 15. From the viewpoint that specific cells that are detection targets can be detected with higher sensitivity as the number of cells held in the wells 15 increases, it is possible to store 10 or more cells in each well 15. It is preferable that 50-500 cells, more preferably 100-300 cells can be stored.

  Here, the method of contacting the cells with the biosensor substrate 1 is not limited as long as the cells can be brought into contact with the biosensor substrate 1.

  For example, it may be performed by bringing cultured cells or cells themselves collected from a living body into contact with the biosensor substrate 1, mixing these with a solution such as a buffer solution or a culture solution, and using the obtained mixed solution as the biosensor substrate 1. You may carry out by making it contact.

  For example, the blood cells may be brought into contact with the well 15 by bringing the collected blood itself into contact with the well 15 (addition, dropping, etc.), and the collected blood is mixed with a solution such as a buffer solution or a culture solution. Alternatively, the obtained mixed solution may be brought into contact with the well 15. In addition, blood cells are contacted with the well 15 by separating the blood cells from the collected blood, mixing it with a solution such as a buffer solution or a culture solution, and then bringing the mixed solution into contact with the well 15. You may go.

  In addition, contact of cultured cells (for example, mammalian or insect-derived cells and yeast) with the biosensor substrate 1 may be performed by bringing the cultured cells into contact with the biosensor substrate 1 together with the medium (addition, dropping, etc.). Alternatively, the culture medium containing cultured cells may be mixed with a solution such as a buffer solution or a culture solution, and the obtained mixed solution may be brought into contact with the biosensor substrate 1. Alternatively, the cultured cells may be recovered from the culture medium, mixed with a solution such as a buffer solution or a culture solution, and then contacted with the biosensor substrate 1.

  Further, the method of developing the cells on the biosensor substrate 1 is not limited as long as the cells can be expanded on the well 15. The cells may be developed on the well 15 by bringing a plurality of cells (cell group) itself into contact with the well 15, or may be further developed using a developing solution after the contact. Examples of the developing solution include a buffer solution, a culture solution, and a surfactant.

  For example, when the cell to be developed on the well 15 is a blood cell, the blood cell may be developed on the well 15 by bringing the blood cell into contact with the well 15 as described above. The blood cells may be further developed using a developing solution. For example, even if the cell to be developed is a cultured cell, it can be developed on the well 15 in the same manner as the blood cell. At least through such a procedure, cells (for example, blood cells and cultured cells) can be stored in each well 15. If cells are difficult to spread on the chip (especially when air remains at the bottom of the chamber), insert the chip into a medium or buffer solution in advance and perform ultrasonic treatment, or use a brush or the like on the chip surface. There is no problem even if the cells are brought into contact with the biosensor substrate 1 and developed after the solution is developed so that the air does not enter the well 15 by rubbing.

The concentration of the cell when the cell is developed on the well 15 is not particularly limited, and may be, for example, 1 × 10 ¹⁰ to 1 × 10 ⁴ (cells / ml) depending on the cell type. After the cells are expanded, excess cells are removed, so that the cells can be stored almost uniformly as a single layer in each well 15. In addition, the cell concentration to be appropriately developed may be adjusted according to the cell type and well 15 used.

  The method for removing (washing) excess cells from the biosensor substrate 1 is not limited as long as excess cells can be removed from the biosensor substrate 1 (that is, from inside the well 15 and from outside the well 15).

  For example, excess cells may be removed by gently tilting the biosensor substrate 1 using a pipetman or the like and flowing a washing solution such as a buffer solution, a culture solution, a surfactant, or an enzyme. In addition, when removing and washing excess cells adsorbed on portions other than the well 15, an instrument such as a cell scraper may be used.

It should be noted that the concentration of cells to be developed is reduced (for example, 1 × 10 ⁶ cells / ml or less for red blood cells), thereby increasing the concentration of cells to be developed (for example, 1 × 10 ⁸ cells / ml or more for red blood cells). ), The number of cells stored in each well 15 after the removal operation can be reduced. Even in this case, the number of cells stored in each well 15 is substantially the same. Therefore, by setting the concentration of cells to be developed to be thin, it is possible to adjust each well 15 so that one to several cells are uniformly stored as a single layer. Conversely, even if the concentration of cells to be expanded is increased, the number of cells that can be stored in the well 15 is not increased because the cells are uniformly stored in the well 15 after the removal operation. The number of cells stored is limited by the bottom area of the well 15.

  Further, it is preferable that the removal (washing) of excess cells from the well 15 is performed after the cells are brought into contact with and spread in the well 15 and then the cells are appropriately adsorbed in the well 15. The time required for the adsorption is not limited and can be appropriately adjusted by those skilled in the art.

  In confirming the presence or absence of a specific cell as a detection target, the method is not limited as long as the specific cell can be detected.

  For example, when there is a substance that specifically binds to the specific cell, it can be detected by confirming the presence or absence of binding using the substance. Examples of such substances include, but are not limited to, antibodies and aptamers. Alternatively, when a substance that specifically reacts with the specific cell exists, it can be detected by confirming the presence or absence of the reaction using the substance.

  The method for confirming the presence or absence of such a bond or reaction is not particularly limited, but it is preferable to use fluorescence. For example, if a substance that specifically binds to specific cells is used after being fluorescently labeled, only specific cells in the sample can be labeled. Therefore, the presence or absence of the specific cell can be easily confirmed by the presence or absence of fluorescence.

  In particular, before bringing the sample into contact with the well 15, a fluorescent label is applied so that only specific cells in the sample are labeled, and after the cells are held in the well 15, the fluorescent label is detected to detect the specific cells. Can be confirmed. Alternatively, only specific cells may be fluorescently labeled after the cells are retained in the well 15.

  For example, when detecting a blood cell infected with a pathogenic microorganism from blood cells, before contacting the blood cell with the well 15, the nucleus of the pathogenic microorganism in the infected blood cell is fluorescently stained, and a detection device to be described later Can be used to detect infected blood cells based on the fluorescence. Alternatively, after storing blood cells in the wells 15 formed on the biosensor substrate 1, the nuclei of pathogenic microorganisms in the blood cells may be fluorescently stained to similarly detect the infected blood cells. For example, when blood cells infected at the bedside or the like are to be detected, it is better to fluorescently stain the nuclei of pathogenic microorganisms in the infected blood cells before the well 15 is brought into contact with the blood cells and deployed. Since the processing after the deployment becomes simple, infected blood cells can be detected more easily. For example, it is not limited to the nuclei of pathogenic microorganisms in blood cells. For example, a specific protein (specific amino acid sequence) is targeted by using a fluorescently labeled antibody, or specified by using a fluorescently labeled probe. These gene sequences may be targeted.

  In addition, for example, when it is desired to detect a cell expressing a specific marker in cultured cells, an antibody specific to the marker and fluorescently labeled is allowed to act on the cultured cells in advance and held in the well 15. Thereafter, the specific cell can be detected based on the fluorescence using a detection apparatus described later. Alternatively, after storing the cultured cells in the well 15 formed on the biosensor substrate 1, cells expressing a specific marker in the cultured cells are labeled using a fluorescently labeled antibody, and the cells are classified based on the fluorescence. It may be detected.

  A specific example will be described. First, in an erythrocyte cell suspension containing infected erythrocytes, the infected erythrocytes are labeled by fluorescent staining so that the nuclei of infectious microorganisms such as protozoa are stained. Label with a fluorescent substance. The erythrocyte cell suspension containing the labeled infected erythrocytes is developed on the well 15, and after removing and washing excess blood cells, fluorescence detection is performed by a detection device described later. Thus, by examining the fluorescence intensity, the number of labeled cells, etc., it is possible to analyze not only the presence or absence of infectious disease but also the degree and type.

  For example, as shown in FIG. 2, a plurality of wells 15 may be arranged on the biosensor substrate 1, and 100 blood cells may be stored in each well 15. When one infected blood cell is detected per well 15, the infection rate can be determined to be 1%.

  For example, even when a total of 1 million blood cells are held in the well 15 and one of the blood cells is infected, the infected blood cell can be detected. In this case, according to the detection method of the present invention, it can be said that detection is possible even when only 0.0001% of infected blood cells are present in the sample.

  In the detection target of the present invention, specific cells to be detected and a large number of cells including the specific cells (that is, a cell group) are not particularly limited.

  For example, a cell expressing a specific gene or a cell in which biological substances such as nucleic acids, proteins, lipids, and sugars are excessive or deficient than usual is detected as a specific cell from various cell groups. be able to. Such specific cells may be cells that exist in nature or may be cells that have been subjected to artificial treatment. The cells existing in the natural world are not particularly limited, and examples thereof include pathogenic cells, diseased cells, cells infected with pathogenic bacteria or pathogenic organisms, mutated cells, unknown cells having specific properties, and the like. The artificial treatment is not particularly limited, and examples thereof include physical treatment (eg, electromagnetic wave irradiation), chemical treatment (eg: drug treatment), genetic engineering treatment (eg: gene recombination treatment), and the like. .

  Further, among such artificial treatments, a treatment that has a known effect on cells can be applied to the cell group, and a cell that does not show the effect or a cell that shows the effect more strongly can be detected as a specific cell. . For example, cells exhibiting resistance or high sensitivity to drug treatment can be detected as specific cells.

  Further, the cell group is not particularly limited. It may be a group of cells derived from a multicellular organism as well as a group of unicellular organisms. Examples of cells derived from multicellular organisms include cells obtained from normal tissues or pathological tissues of organisms, and cultured cells derived from these cells. Moreover, the organism from which these cells are obtained is not particularly limited. For example, it may be an animal-derived cell or a plant-derived cell, and more specific examples include, but are not limited to, vertebrate (particularly mammals and birds) -derived cells, insect-derived cells, plant cultured cells, and the like. Moreover, even if it is the group of the same cell, the group in which multiple types of cells are mixed may be sufficient.

  More specific examples of detecting specific cells include, for example, detecting malaria parasite-infected erythrocytes from blood cells of malaria parasite infection patients. In the case of a Plasmodium infection, even if there is only one infected blood cell in a large number of blood cells of about 1 million, this infected blood cell can be detected. In addition, for example, it can be preferably used in searching for cancer stem cells present in a cancer cell group. Furthermore, for example, from the group of artificially treated cells, cells that have a specific property by the treatment can be selected. It is also possible to select cells that are particularly strong and have the specific properties. More specifically, for example, cells that produce the substance can be detected particularly efficiently from a plurality of cells transformed to produce a particular substance by genetic recombination treatment. Alternatively, for example, cells that have lost a specific function due to electromagnetic wave irradiation treatment or drug treatment can be detected. In addition, cells having resistance or high sensitivity to these treatments can be detected.

  In addition, the present invention, for example, detects (and thus screens) cells having specific properties (for example, drug resistance, drug sensitivity, expression of specific genes, excessive or insufficient specific biological substances, etc.), and detection of detected cells. It can be used for further analysis.

  In clinical settings, for example, it can be suitably used for diagnosing diseases (particularly cytodiagnosis). It is possible to collect human tissue suspected of illness and detect whether pathogenic cells, lesion cells, pathogenic bacteria, or cells infected with pathogenic organisms are not present in a cell group of the tissue, which can be used for diagnosis. Furthermore, investigation of drug resistance and sensitivity of the various cells thus detected, gene analysis by PCR, FISH, and the like can be performed in the well 15. Further, the various cells can be cultured inside and outside the well 15 to examine their properties in more detail. More specifically, for example, at the bedside or the like, the presence / absence / degree of infected cells can be quickly grasped by a patient who may be infected with an infectious disease. In addition, cancer (eg, blood cancer) tissue collected by surgical operation can be used to examine the proportion of cancer cells that are resistant or sensitive to anticancer agents and can be used for treatment. .

  Further, after storing (holding) a plurality of cells (cell groups) in each well 15 provided in the biosensor substrate 1, a label capable of specifically detecting a specific cell as a detection target in the stored cells. Can be applied. Further, in a sample containing a plurality of cells (cell group), it is possible to label specific cells as detection targets in advance. It is preferable to label specific cells in advance because the labeling efficiency tends to be uniform. The labeling method is not particularly limited, and can be appropriately selected depending on the properties of the specific cell that is the detection target. However, in view of the simplicity of detection and toxicity, a fluorescent label is particularly preferable. is there. The specific cells can be detected based on the presence or absence of the label (for example, the presence or absence of a fluorescent label). Further, based on the number of labels to be detected (for example, the number of fluorescent labels), the cells in the sample can be detected. It is also possible to perform a quantitative analysis as to how many specific cells are present. Furthermore, based on the intensity of the label (for example, the fluorescence intensity of the fluorescent label), the intensity of the property of the detected specific cell can be analyzed. Specifically, for example, when a specific target cell is a cell infected with an infectious disease pathogen, the quantitative data and the intensity of labeling of each cell (for example, fluorescence intensity in the case of a fluorescent label) By paying attention, it is also possible to analyze the severity and stage of infection. In addition, in the case where a specific cell to be targeted is a cell given a specific property by artificial processing, the ratio that can be given the specific property by the specific artificial processing or the specific property of each cell Expression intensity can be determined. Therefore, it is possible to examine how efficiently the nature of the cell can be changed by what kind of artificial processing, and how the nature can be changed.

  Therefore, it is also possible to culture the specific cell in the well 15 after detecting the specific cell that is the detection target by the biosensor substrate 1 of the present invention. As a result, the specific cell can be examined over time in the well 15. For example, the response to the stimulus can be examined by culturing the specific cell with the stimulus. Examples of the stimulation include, but are not limited to, the addition of drugs such as growth factors and vitamins, changes in culture temperature, no addition of essential nutrients, and the like. Further, when differentiation is induced in the specific cell by the stimulation, it is preferable that the specific cell can be detected and induced in the well 15. This is because, when the culture in the well 15 cannot be performed, the differentiation induction stimulus is once applied in the culture petri dish and the culture is returned to the well 15, which is troublesome. In addition, when cells adhere to the petri dish, an operation of peeling the adhesion with an enzyme or the like is required, and the operation may damage the cells and impair the function of the cells.

  Specifically, for example, PC12 cells (Rat adrenal pheochromocytoma cell line) are detected in the well 15, and nerve growth factor (NGF) is added thereto and cultured for several days to differentiate into neuronal cells and synapse. A network can be formed.

  Furthermore, in the screening of drug candidate substances as described below, some drug candidate substances must be screened for several days after addition in addition to substances whose effects on cells can be observed immediately after addition (several minutes to several hours). For example, there may be substances that cannot be observed to affect the cells. Therefore, when screening for drug candidate substances, it may be required to observe the state of the cells after culturing and maintaining the cells for several days after adding the drug candidate substances. For this reason, the biosensor substrate 1 of the present invention can be preferably used for screening drug candidate substances.

  According to the biosensor substrate 1 of the present invention, as described above, various cells can be targeted for detection. For example, it is possible to target cultured cells such as blood cells, human-derived cells and animal cells, yeast cells, microbial cell stem cells, and cancer cells exemplified above. Then, by using the biosensor substrate 1 of the present invention, it is possible to detect, measure, analyze, etc. only specific target cells quickly, simply and with high sensitivity from among the cells present in the sample.

  According to the drug candidate substance screening method, the influence of various drug candidate substances on cells can be measured easily and quickly, and substances exhibiting the desired activity can be efficiently selected.

  In the drug candidate substance screening method of the present invention, a biosensor substrate 1 that includes a plurality of wells 15 and in which cells are held is used.

  In the drug candidate substance screening method of the present invention, first, a drug candidate substance is added to the well 15 in which the cells are held. The same drug candidate substance may be added to all the wells 15 included in the biosensor substrate 1, or the drug candidate substance added by the well 15 may be changed. In addition, it is preferable that a drug candidate substance is not added to some of the wells 15 and the cells held in these wells 15 are used as controls.

  After adding the drug candidate substance, the influence of the drug candidate substance on the cells held in the well 15 is measured. The method for measuring the influence may be appropriately set according to the drug candidate substance to be used, the cell to be used, and the desired activity.

  For example, when screening for a substance that acts as an anticancer agent, cancer cells are held in the well 15 and a drug candidate substance is added to measure the rate and time at which the cancer cells die. That's fine.

  Based on the measurement result, a substance exhibiting a desired activity may be selected from drug candidate substances used in the experiment. For example, in the example of screening a substance that acts as the above-described anticancer agent, a substance that has an effect of killing cancer cells with high efficiency may be selected.

  By doing in this way, many drug candidate substances can be screened easily and rapidly.

  In addition, the biosensor substrate 1 used in the method for screening a drug candidate substance of the present invention is not particularly limited, but is preferably the above-described biosensor substrate 1 of the present invention. With the biosensor substrate 1 of the present invention, cells can be stored in the well 15 as a single layer more uniformly and efficiently.

  As described above, according to the biosensor substrate 1 of the present invention, cells can be cultured in the well 15 for at least several days. Therefore, if the drug candidate substance screening method of the present invention is carried out using the biosensor substrate 1 of the present invention, after adding the drug candidate substance, the cells are cultured and maintained for several days or more, and then the substance is a cell. Can be measured.

  Furthermore, in the biosensor substrate 1 of the present invention, since approximately the same number of cells are held in each well 15, the state of the cells in each well 15 can be made uniform. Therefore, if the drug candidate substance screening method of the present invention is carried out using the biosensor substrate 1 of the present invention, what effect each drug candidate substance has when the different drug candidate substances are added to each well 15. It is easy to compare and evaluate whether to give to cells.

FIG. 2 is a plan view of the biosensor substrate 1 as viewed from above. The biosensor substrate 1 shown in FIG. 2 is used to detect the interaction between substances, and the overall shape is, for example, a flat plate with a main surface being circular, like an optical disk such as a CD or DVD. However, the biosensor substrate 1 according to the present invention is not limited to a disk-like form, but if it is a disk-like form, it is advantageous because an apparatus and technology used for an existing optical disk can be used. .
A center hole 2 is formed at the center of the biosensor substrate 1. The center hole 2 is a portion into which a fitting mechanism for holding and rotating the substrate is inserted when the substrate is mounted on a predetermined analysis device.
The biosensor substrate 1 is obtained by bonding the base substrate 10 on which the wells described above are formed and the cover member 20 with an ultraviolet curable resin composition to be described later. The cover member 20 is formed with a number of holes as many as the wells formed by the well-forming layers existing in the base substrate 10 so as to be aligned radially in a top view (see FIG. 2). In the present embodiment, the cover member 20 may be formed of a conductive material for use as an electrode.

  FIG. 3 is a cross-sectional view of FIG. Referring to FIG. 3, a light transmissive base substrate 1 having a large number of wells and a large number of information pits 12 aligned (not shown) on the surface of the base substrate 1 existing below the well is provided. .

  In the above, when the biosensor substrate is rotated, the hole of the cover member 20 above the well 15 may be further closed with a lid member or the like. By doing so, it is possible to prevent unscheduled outflow, evaporation or movement of the sample from the well 15.

  Here, the mechanism by which the fluorescently labeled specimen emits fluorescence when the target sample is irradiated with laser light will be described. When excitation light (laser light or the like) is irradiated to the specimen on which the fluorescent label placed on the bottom surface of the well 15 is applied, fluorescence is generated from the specimen. The beam diameter of the fluorescence is larger than the beam diameter of the excitation light. The wavelength is also changing. Therefore, the fluorescence state of such fluorescence is detected using an apparatus described in Patent Document 2, International Publication No. 2013/146364, or International Publication No. 2014/069511.

Next, the ultraviolet curable resin composition of the present invention will be described.
The ultraviolet curable resin composition for a biosensor substrate of the present invention is a resin composition used for bonding the well-forming member of the biosensor substrate or each member of the biosensor substrate described above, and is a (meth) acrylate compound (A ), A softening agent (B) and a photopolymerization initiator (C). The (meth) acrylate compound (A) is a (meth) acryloyl group including a (meth) acrylate oligomer (A1) having a weight average molecular weight of 7000 or more and a (meth) acrylate monomer (A2) that does not satisfy the weight average molecular weight. It is a compound that has.
The phrase “can be added to an ultraviolet curable resin composition used for optics” means that an additive that lowers the transparency of the cured product to an extent that it cannot be used for optics is not included.
In the ultraviolet curable resin composition used in the present invention, when a cured sheet having a thickness after curing of 200 μm is prepared, the average transmittance of the sheet with light having a wavelength of 400 to 800 nm is: At least 90%.

The ultraviolet curable resin composition of the present invention contains a (meth) acrylate compound (A) and a softening agent (B). There are various types of UV curable resins, but the combination of the (meth) acrylate compound (A) and the softening agent (B) prevents cell infiltration and elution of the cell sample into the cured resin layer. There is an effect. In general, since cell samples are hydrophilic including physiological saline or the like, it is considered that these compounds do not adversely affect the hydrophilicity of the sample.
Furthermore, since the resin composition of the combination hardly peels when bonded, it effectively prevents peeling between the base substrate 10 on which the well forming material is formed and the cover member 20. And since it has toughness and high peel strength even under high temperature and high humidity, it is possible to prevent peeling even in such an environment. Furthermore, since the transmittance is high, cell detection is not inhibited.
Therefore, the combination can be used as a resin composition that is extremely suitable for the biosensor substrate 10.

  As the (meth) acrylate compound in the ultraviolet curable resin composition of the present invention, a (meth) acrylate oligomer can be used. The (meth) acrylate oligomer (A1) is not particularly limited. From (meth) acrylate having a urethane (meth) acrylate, polyisoprene or hydrogenated polyisoprene skeleton, polybutadiene or hydrogenated polybutadiene skeleton. It is preferable to use any one selected from the group consisting of Among them, urethane (meth) acrylate is preferable from the viewpoint of adhesive strength, and has at least one skeleton selected from the group consisting of polybutadiene / hydrogenated polybutadiene / polyisoprene / hydrogenated polyisoprene from the viewpoint of moisture resistance. Urethane (meth) acrylate is more preferable.

  The urethane (meth) acrylate is obtained, for example, by reacting polyhydric alcohol, polyisocyanate, and hydroxyl group-containing (meth) acrylate.

  Examples of the polyhydric alcohol include polybutadiene glycol, hydrogenated polybutadiene glycol, polyisoprene glycol, hydrogenated polyisoprene glycol, neopentyl glycol, 3-methyl-1,5-pentanediol, ethylene glycol, propylene glycol, 1,4 A cyclic skeleton such as alkylene glycol having 1 to 10 carbon atoms such as butanediol and 1,6-hexanediol, triol such as trimethylolpropane and pentaerythritol, tricyclodecanedimethylol, and bis- [hydroxymethyl] -cyclohexane; Alcohols, and the like; and polybasic acids such as succinic acid, phthalic acid, hexahydrophthalic anhydride, terephthalic acid, adipic acid, azelaic acid, tetrahydrophthalic anhydride, etc. Polyester polyol obtained by reaction, caprolactone alcohol obtained by reaction of polyhydric alcohol and ε-caprolactone, polycarbonate polyol (for example, polycarbonate diol obtained by reaction of 1,6-hexanediol and diphenyl carbonate, etc.) or polyether polyol (For example, polyethylene glycol, polypropylene glycol, polytetramethylene glycol, ethylene oxide-modified bisphenol A, etc.) and the like. From the viewpoint of adhesive strength and moisture resistance, the polyhydric alcohol is preferably propylene glycol, polybutadiene glycol, hydrogenated polybutadiene glycol, polyisoprene glycol, or hydrogenated polyisoprene glycol, and weight average molecular weight from the viewpoint of transparency and flexibility. Is particularly preferably propylene glycol having a viscosity of 2000 or more, hydrogenated polybutadiene glycol, or hydrogenated polyisoprene glycol. Hydrogenated polybutadiene glycol or polypropylene glycol is preferred from the viewpoint of discoloration such as heat-resistant colorability and compatibility. The upper limit of the weight average molecular weight at this time is not particularly limited, but is preferably 10,000 or less, and more preferably 5000 or less. Moreover, you may use together 2 or more types of polyhydric alcohol as needed.

  Examples of the organic polyisocyanate include isophorone diisocyanate, hexamethylene diisocyanate, tolylene diisocyanate, xylene diisocyanate, diphenylmethane-4,4'-diisocyanate, dicyclopentanyl isocyanate, and the like. Among these, isophorone diisocyanate is preferable from the viewpoint of toughness.

  Examples of the hydroxyl group-containing (meth) acrylate include hydroxy C2-C4 alkyl (meth) acrylates such as hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, hydroxybutyl (meth) acrylate, dimethylol cyclohexyl mono ( A (meth) acrylate, a hydroxycaprolactone (meth) acrylate, a hydroxyl group terminal polyalkylene glycol (meth) acrylate, etc. can be used.

  Reaction for obtaining the said urethane (meth) acrylate is performed as follows, for example. That is, organic polyisocyanate is mixed with polyhydric alcohol per equivalent of hydroxyl group so that the isocyanate group is preferably 1.1 to 2.0 equivalent, more preferably 1.1 to 1.5 equivalent, and the reaction temperature Is preferably reacted at 70 to 90 ° C. to synthesize a urethane oligomer. Next, the hydroxy (meth) acrylate compound is mixed so that the hydroxyl group is preferably 1 to 1.5 equivalents per equivalent of isocyanate group of the urethane oligomer, and reacted at 70 to 90 ° C. to obtain the target urethane (meta ) Acrylate can be obtained.

  As a weight average molecular weight of the said urethane (meth) acrylate, about 7000-100000 are preferable and 10000-60000 are more preferable. When the weight average molecular weight is less than 7000, shrinkage increases, and when the weight average molecular weight is greater than 100,000, curability is poor. Moreover, it is preferable that molecular weight distribution (Mw / Mn) value is 1.5 or more.

  In the ultraviolet curable resin composition of this invention, urethane (meth) acrylate can be used 1 type or in mixture of 2 or more types by arbitrary ratios. The weight ratio of urethane (meth) acrylate in the photocurable transparent adhesive composition of the present invention is usually 5 to 90% by weight, preferably 10 to 50% by weight.

The (meth) acrylate having the polyisoprene skeleton has a (meth) acryloyl group at the terminal or side chain of the polyisoprene molecule. A (meth) acrylate having a polyisoprene skeleton can be obtained as “UC-203” (manufactured by Kuraray Co., Ltd.). The (meth) acrylate having a polyisoprene skeleton preferably has a polystyrene-equivalent number average molecular weight of 1,000 to 50,000, more preferably about 25,000 to 45,000.
The weight ratio of the (meth) acrylate having a polyisoprene skeleton in the photocurable transparent adhesive composition of the present invention is usually 5 to 90% by weight, preferably 10 to 50% by weight.

  In the ultraviolet curable resin composition of this invention, a (meth) acrylate monomer (A2) can be contained as a (meth) acrylate compound. As the (meth) acrylate monomer (A2), a (meth) acrylate having one (meth) acryloyl group in the molecule can be preferably used. Here, the photopolymerizable monomer (C) excludes urethane (meth) acrylate, polyisoprene or (meth) acrylate having a hydrogenated polyisoprene skeleton, polybutadiene or (meth) acrylate having a hydrogenated polybutadiene skeleton ( (Meth) acrylate is shown.

  Specific examples of the (meth) acrylate having one (meth) acryloyl group in the molecule include octyl (meth) acrylate, isooctyl (meth) acrylate, amyl (meth) acrylate, isoamyl (meth) acrylate, lauryl ( Carbon such as (meth) acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, stearyl (meth) acrylate, cetyl (meth) acrylate, isomyristyl (meth) acrylate, isostearyl (meth) acrylate, tridecyl (meth) acrylate 5 to 25 alkyl (meth) acrylate, benzyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, acryloylmorpholine, phenylglycidyl (meth) acrylate, tricyclodecane ( ) Acrylate, dicyclopentenyl acrylate, dicyclopentenyloxyethyl (meth) acrylate, isobornyl (meth) acrylate, dicyclopentanyl (meth) acrylate, 1-adamantyl acrylate, 2-methyl-2-adamantyl acrylate, 2- (Meth) acrylate having a cyclic skeleton such as ethyl-2-adamantyl acrylate, 1-adamantyl methacrylate, polypropylene oxide-modified nonylphenyl (meth) acrylate, dicyclopentadieneoxyethyl (meth) acrylate, etc. 7 alkyl (meth) acrylate, ethoxydiethylene glycol (meth) acrylate, polypropylene glycol (meth) acrylate, polypropylene oxide modified Polyalkylene glycol (meth) acrylates such as nylphenyl (meth) acrylate, ethylene oxide modified phenoxylated phosphoric acid (meth) acrylate, ethylene oxide modified butoxylated phosphoric acid (meth) acrylate and ethylene oxide modified octyloxylated phosphoric acid (meth) acrylate, caprolactone Examples thereof include modified tetrafurfuryl (meth) acrylate.

Above all, from the viewpoint of flexibility and reactivity, the following formula (1)

X-O-R ₂ (1)

(Wherein, X represents an acryloyl group, and R ₂ represents an alkyl group having 8 to 20 carbon atoms)
A monofunctional acrylate represented by formula (1) is preferred from the viewpoint of adhesive strength.

X—O—R ₃ (1 ′)

(In the formula, X represents an acryloyl group, and R ₃ represents an alkyl group having 12 to 18 carbon atoms)
The monofunctional acrylate represented by these is more preferable. Among these, isostearyl acrylate is more preferable from the viewpoints of low volatility, reactivity, and flexibility.
Here, from the viewpoint of improving the compatibility while avoiding white turbidity of the resin composition itself and improving the compatibility, the number of R ₂ alkyl groups in the above formula (1) is defined as MR, and the formula (1) In the compound represented, it is preferable to show a certain ratio when the total number of carbon atoms excluding the acryloyl group is MC and the number of branched carbon chains is MB. Specifically, it is preferably a resin composition containing both compounds such that MR / (MC + MB) (hereinafter referred to as a special ratio) is 5.5 or less, and particularly preferably 5 or less. preferable. Further, from the viewpoint of making the whitening resistance particularly excellent, the resin composition contains both compounds having the low volatility / whitening resistance acrylate and the special ratio of 5.5 or less. It is preferably 5 or less.

The composition of the present invention can contain (a (meth) acrylate other than a (meth) acrylate having one (meth) acryloyl group in the molecule) as long as the characteristics of the present invention are not impaired. For example, tricyclodecane dimethylol di (meth) acrylate, dioxane glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, polytetramethylene glycol di (meth) acrylate, alkylene oxide modified bisphenol A type di (meth) acrylate , Trimethylol C2-C10 alkanes such as caprolactone-modified hydroxypivalic acid neopentyl glycol di (meth) acrylate and ethylene oxide-modified phosphoric acid di (meth) acrylate, trimethylolpropane tri (meth) acrylate, trimethyloloctanetri (meth) acrylate Tri (meth) acrylate, trimethylolpropane polyethoxytri (meth) acrylate, trimethylolpropane polypropoxytri ( Trimethylol C2-C10 alkane polyalkoxy tri (meth) acrylate such as acrylate, trimethylolpropane polyethoxypolypropoxy tri (meth) acrylate, tris [(meth) acryloyloxyethyl] isocyanurate, pentaerythritol tri ( (Meth) acrylate, ethylene oxide modified trimethylolpropane tri (meth) acrylate, propylene oxide modified trimethylolpropane tri (meth) acrylate and other alkylene oxide modified trimethylolpropane tri (meth) acrylate pentaerythritol polyethoxytetra (meth) acrylate, Pentaerythritol polypropoxytetra (meth) acrylate, pentaerythritol tetra (meth) acrylate, ditrime Trimethylolpropane tetra (meth) acrylate, dipentaerythritol tetra (meth) acrylate, dipentaerythritol penta (meth) acrylate, and dipentaerythritol hexa (meth) acrylate.
In this invention, when using together, in order to suppress cure shrinkage, it is preferable to use mono- or bifunctional (meth) acrylate.

  In the ultraviolet curable resin composition of this invention, these (meth) acrylate monomer components can be used 1 type or in mixture of 2 or more types by arbitrary ratios. The weight ratio of the (meth) acrylate monomer (A2) in the photocurable transparent adhesive composition of the present invention is usually 5 to 90% by weight, preferably 10 to 50% by weight. When it is less than 5% by weight, the curability is poor, and when it is more than 90% by weight, shrinkage increases.

  The total content of the component (A1) and the component (A2) in the ultraviolet curable resin composition is usually 20 to 90% by weight, preferably 20 to 70% by weight, based on the total amount of the adhesive composition. More preferably, it is 30 to 60% by weight.

  Epoxy (meth) acrylate can be used for the ultraviolet curable resin composition of this invention in the range which does not impair the characteristic of this invention. Epoxy (meth) acrylate has a function of improving curability and improving the hardness and curing speed of a cured product. Any epoxy (meth) acrylate can be used as long as it is obtained by reacting a glycidyl ether type epoxy compound with (meth) acrylic acid, and preferably used epoxy (meth) acrylate. Examples of the glycidyl ether type epoxy compound to be obtained include diglycidyl ether of bisphenol A or its alkylene oxide adduct, diglycidyl ether of bisphenol F or its alkylene oxide adduct, diglycidyl of hydrogenated bisphenol A or its alkylene oxide adduct. Diglycidyl ether, ethylene glycol diglycidyl ether, propylene glycol diglycidyl ether of ether, hydrogenated bisphenol F or its alkylene oxide adduct Neopentyl glycol diglycidyl ether, butanediol diglycidyl ether hexanediol diglycidyl ether to, cyclohexanedimethanol diglycidyl ether, and polypropylene glycol diglycidyl ether.

  Epoxy (meth) acrylate is obtained by reacting these glycidyl ether type epoxy compounds with (meth) acrylic acid under the following conditions.

  (Meth) acrylic acid is reacted at a ratio of 0.9 to 1.5 mol, more preferably 0.95 to 1.1 mol, per 1 equivalent of the epoxy group of the glycidyl ether type epoxy compound. The reaction temperature is preferably 80 to 120 ° C., and the reaction time is about 10 to 35 hours. In order to accelerate the reaction, it is preferable to use a catalyst such as triphenylphosphine, TAP, triethanolamine, or tetraethylammonium chloride. Further, in order to prevent polymerization during the reaction, for example, paramethoxyphenol, methylhydroquinone or the like can be used as a polymerization inhibitor.

An epoxy (meth) acrylate that can be suitably used in the present invention is a bisphenol A type epoxy (meth) acrylate obtained from a bisphenol A type epoxy compound. The weight average molecular weight of the epoxy (meth) acrylate is preferably 500 to 10,000.
The weight ratio of the epoxy (meth) acrylate in the ultraviolet curable resin composition of the present invention is usually 1 to 80% by weight, preferably 5 to 30% by weight.

  The softening component (B) is used in the ultraviolet curable resin composition of the present invention. Specific examples of the softening component that can be used include polymers, oligomers, phthalates, hydrogenated phthalates, phosphates, glycol esters, citrates, fats that are compatible with the composition. Group dibasic acid esters, fatty acid esters, epoxy plasticizers, castor oils, rosin resins, hydrogenated rosin resins, terpene resins, hydrogenated terpene resins, and liquid terpenes. Examples of the oligomer and polymer include a polyisoprene skeleton, a hydrogenated polyisoprene skeleton, a polybutadiene skeleton, a hydrogenated polybutadiene skeleton or an xylene skeleton, an esterified product thereof, polybutene, and the like. From the viewpoint of transparency, hydrogenated rosin resins, hydrogenated terpene resins, hydrogenated polyisoprene, hydrogenated polybutadiene, polybutene, liquid terpenes, and hydrogenated phthalates are preferred. Furthermore, from the viewpoint of adhesive strength and compatibility with other materials, hydrogenated terpene resins containing hydroxyl groups at the ends or side chains, hydrogenated polyisoprenes containing hydroxyl groups at the ends or side chains, hydroxyl groups terminated Alternatively, hydroxyl group-containing polymers such as hydrogenated polybutadiene contained in the side chain, hydrogenated rosin resins, and hydrogenated phthalates are particularly preferable.

  The weight ratio of the softening component in the ultraviolet curable resin composition is usually 5 to 40% by weight, preferably 10 to 35% by weight when a solid softening component is used. When using a liquid softening component, it is 10 to 70 weight% normally, Preferably it is 20 to 60 weight%.

  The photopolymerization initiator (C) contained in the composition of the present invention is not particularly limited. For example, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2,4,6-trimethylbenzoylphenylethoxyphos Fin oxide, bis (2,4,6-trimethylbenzoyl) -phenylphosphine oxide, bis (2,6-dimethoxybenzoyl) -2,4,4-trimethyl-pentylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone ( Irgacure 184; manufactured by BASF), 2-hydroxy-2-methyl- [4- (1-methylvinyl) phenyl] propanol oligomer (Esacure ONE; manufactured by Lambarti), 1- [4- (2-hydroxyethoxy) -phenyl ] -2-Hydroxy-2-methyl 1-propan-1-one (Irgacure 2959; manufactured by BASF), 2-hydroxy-1- {4- [4- (2-hydroxy-2-methyl-propionyl) -benzyl] -phenyl} -2-methyl- Propan-1-one (Irgacure 127; manufactured by BASF), 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651; manufactured by BASF), 2-hydroxy-2-methyl-1-phenyl-propan-1-one (Darocur 1173; manufactured by BASF), 2-methyl-1- [4- (methylthio) phenyl] -2-morpholinopropan-1-one (Irgacure 907; manufactured by BASF), oxy-phenyl-acetic acid 2- [ 2-Oxo-2-phenyl-acetoxy-ethoxy] -ethyl ester and oxy-phenyl-acetic acid 2- [2-hydroxy-ethoxy] -ethyl ester mixture (Irgacure 754; manufactured by BASF), 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -butan-1-one, 2 -Chlorothioxanthone, 2,4-dimethylthioxanthone, 2,4-diisopropylthioxanthone, isopropylthioxanthone and the like can be mentioned.

In the present invention, in the photopolymerization initiator (C), the molar extinction coefficient at 302 nm or 313 nm measured in acetonitrile or methanol is 300 ml / (g · cm) or more, and the molar extinction coefficient at 365 nm is 100 ml. It is preferable to use a photopolymerization initiator that is not more than / (g · cm). By using such a photopolymerization initiator, it is possible to contribute to an improvement in adhesive strength.
Examples of such a photopolymerization initiator (C) include 1-hydroxycyclohexyl phenyl ketone (Irgacure 184; manufactured by BASF), 2-hydroxy-2-methyl-1-phenyl-propan-1-one (Darocur 1173). Manufactured by BASF), 1- [4- (2-hydroxyethoxy) -phenyl-]-2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959; manufactured by BASF), phenylglyoxylic acid And methyl ester (Darocur MBF; manufactured by BASF).

  In the ultraviolet curable resin composition of this invention, these photoinitiators (C) can be used 1 type or in mixture of 2 or more types in arbitrary ratios. The weight ratio of the photopolymerization initiator (C) in the ultraviolet curable adhesive composition of the present invention is usually 0.2 to 5% by weight, preferably 0.3 to 3% by weight. If it is more than 5% by weight, the transparency of the cured resin layer may be deteriorated.

  The ultraviolet curable resin composition of this invention can contain the additive etc. which are mentioned later as another component. The content ratio of the other components with respect to the total amount of the ultraviolet curable resin composition of the present invention is a balance obtained by subtracting the total amount of the components (A) to (C) from the total amount. Specifically, the total amount of the other components is 5 to 75% by weight, preferably 15 to 75% by weight, more preferably about 35 to 65% by weight, based on the total amount of the ultraviolet curable resin composition of the present invention. is there.

  Furthermore, amines that can serve as photopolymerization initiation assistants can be used in combination with the photopolymerization initiator. Examples of amines that can be used include benzoic acid 2-dimethylaminoethyl ester, dimethylaminoacetophenone, p-dimethylaminobenzoic acid ethyl ester, and p-dimethylaminobenzoic acid isoamyl ester. When using photoinitiator auxiliary agents, such as this amine, content in the adhesive composition for adhesion | attachment of this invention is 0.005 to 5 weight% normally, Preferably it is 0.01 to 3 weight%.

  In the ultraviolet curable resin composition of the present invention, an antioxidant, an organic solvent, a silane coupling agent, a polymerization inhibitor, a leveling agent, an antistatic agent, a surface lubricant, a fluorescent whitening agent, and a light stabilizer are optionally added. You may add additives, such as an agent (for example, hindered amine compound etc.) and a filler.

  Specific examples of the organic solvent include alcohols such as methanol, ethanol and isopropyl alcohol, dimethyl sulfone, dimethyl sulfoxide, tetrahydrofuran, dioxane, toluene, xylene and the like.

  Specific examples of the silane coupling agent include, for example, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 2- (3,4-epoxy) (Cyclohexyl) ethyltrimethoxysilane, N- (2-aminoethyl) 3-aminopropylmethyldimethoxysilane, γ-mercapropropyltrimethoxysilane, N- (2-aminoethyl) 3-aminopropylmethyltrimethoxysilane, 3 -Aminopropyltriethoxysilane, 3-mercaptopropyltrimethoxysilane, vinyltrimethoxysilane, N- (2- (vinylbenzylamino) ethyl) 3-aminopropyltrimethoxysilane hydrochloride, 3-methacryloxypropyltrimethoxysilane 3 Silane coupling agents such as chloropropylmethyldimethoxysilane and 3-chloropropyltrimethoxysilane; isopropyl (N-ethylaminoethylamino) titanate, isopropyl triisostearoyl titanate, titanium di (dioctyl pyrophosphate) oxyacetate, tetra Titanium coupling agents such as isopropyldi (dioctylphosphite) titanate and neoalkoxytri (pN- (β-aminoethyl) aminophenyl) titanate; Zr-acetylacetonate, Zr-methacrylate, Zr-propionate, neo Alkoxy zirconate, neoalkoxy trisneodecanoyl zirconate, neoalkoxy tris (dodecanoyl) benzenesulfonyl zirconate, neoalkoxy tris ( Chi range aminoethyl) zirconate, neoalkoxy tris (m-aminophenyl) zirconate, ammonium zirconium carbonate, Al- acetylacetonate, Al- methacrylate, zirconium or the like Al- propionate, or aluminum coupling agent, and the like.

  Specific examples of the polymerization inhibitor include paramethoxyphenol and methylhydroquinone.

  Specific examples of the light stabilizer include, for example, 1,2,2,6,6-pentamethyl-4-piperidyl alcohol, 2,2,6,6-tetramethyl-4-piperidyl alcohol, 1,2,2, 6,6-pentamethyl-4-piperidyl (meth) acrylate (manufactured by ADEKA Corporation, LA-82), tetrakis (1,2,2,6,6-pentamethyl-4-piperidyl) -1,2,3 4-butanetetracarboxylate, tetrakis (2,2,6,6-totramethyl-4-piperidyl) -1,2,3,4-butanetetracarboxylate, 1,2,3,4-butanetetracarboxylic acid 1,2,2,6,6-pentamethyl-4-piperidinol and 3,9-bis (2-hydroxy-1,1-dimethylethyl) -2,4,8,10-tetraoxaspiro [5.5] Undeka Esterified product with bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, bis (1-undecanoxy-2,2,6,6-tetramethylpiperidin-4-yl) ) Carbonate, 2,2,6,6, -tetramethyl-4-piperidyl methacrylate, bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, bis (1,2,2,6,6) -Pentamethyl-4-piperidyl) sebacate, 4-benzoyloxy-2,2,6,6-tetramethylpiperidine, 1- [2- [3- (3,5-di-t-butyl-4-hydroxyphenyl) Propionyloxy] ethyl] -4- [3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionyloxy] -2,2,6,6-tetramethylpiperidine, 1,2 , 2,6,6-pentamethyl-4-piperidinyl-methacrylate, bis (1,2,2,6,6-pentamethyl-4-piperidinyl) [[3,5-bis (1,1-dimethylethyl)- 4-hydroxyphenyl] methyl] butyl malonate, decanedioic acid bis (2,2,6,6-tetramethyl-1 (octyloxy) -4-piperidinyl) ester, 1,1-dimethylethyl hydroperoxide and octane Reaction product, N, N ′, N ″, N ″ ′-tetrakis- (4,6-bis- (butyl- (N-methyl-2,2,6,6-tetramethylpiperidin-4-yl) amino ) -Triazin-2-yl) -4,7-diazadecane-1,10-diamine, dibutylamine, 1,3,5-triazine, N, N′-bis (2,2,6,6-tetramethyl- 4 A polycondensate of piperidyl-1,6-hexamethylenediamine and N- (2,2,6,6-tetramethyl-4-piperidyl) butylamine, poly [[6- (1,1,3,3-tetramethyl Butyl) amino-1,3,5-triazine-2,4-diyl] [(2,2,6,6-tetramethyl-4-piperidyl) imino] hexamethylene [(2,2,6,6-tetra Methyl-4-piperidyl) imino]], dimethyl succinate and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidineethanol, 2,2,4,4-tetramethyl-20- (Β-Lauryloxycarbonyl) ethyl-7-oxa-3,20-diazadispiro [5 · 1 · 11 · 2] heneicosan-21-one, β-alanine, N,-(2,2,6,6-tetra Methyl-4-pi Lysinyl) -dodecyl ester / tetradecyl ester, N-acetyl-3-dodecyl-1- (2,2,6,6-tetramethyl-4-piperidinyl) pyrrolidine-2,5-dione, 2,2,4, 4-tetramethyl-7-oxa-3,20-diazadispiro [5,1,11,2] heneicosan-21-one, 2,2,4,4-tetramethyl-21-oxa-3,20-diazadicyclo- [5,1,11,2] -Heneicosane-20-propanoic acid dodecyl ester / tetradecyl ester, propanedioic acid, [(4-methoxyphenyl) -methylene] -bis (1,2,2,6,6) -Pentamethyl-4-piperidinyl) ester, 2,2,6,6-tetramethyl-4-piperidinol higher fatty acid ester, 1,3-benzenedicar Hindered amines such as xiamidamide, N, N′-bis (2,2,6,6-tetramethyl-4-piperidinyl), benzophenone compounds such as octabenzone, 2- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol, 2- (2-hydroxy-5-methylphenyl) benzotriazole, 2- [2-hydroxy-3- (3,4,5,6) -Tetrahydrophthalimido-methyl) -5-methylphenyl] benzotriazole, 2- (3-tert-butyl-2-hydroxy-5-methylphenyl) -5-chlorobenzotriazole, 2- (2-hydroxy-3,5 -Di-t-pentylphenyl) benzotriazole, methyl 3- (3- (2H-benzotriazol-2-yl) -5-t-butyl-4-hydro Xoxyphenyl) propionate and polyethylene glycol reaction product, benzotriazole compounds such as 2- (2H-benzotriazol-2-yl) -6-dodecyl-4-methylphenol, 2,4-di-t-butylphenyl- Benzoates such as 3,5-di-tert-butyl-4-hydroxybenzoate, 2- (4,6-diphenyl-1,3,5-triazin-2-yl) -5-[(hexyl) oxy] phenol The hindered amine compound is particularly preferable.

As the hindered amine (B), for example, a compound represented by the structure of the following formula is preferable.

（式中、Ｒ_１は炭素数１〜１２のアルキル基、炭素数１〜１２のアルコキシ基を表し、Ｒ２はカーボネート基、又は、１〜４価の有機カルボン酸のカルボキシル基から水素原子を除いた残基を表し、ｋは１〜４の整数を表す。）
Ｒ_１としては、炭素数１〜３のアルキル基又は、炭素数６〜１２のアルコキシ基が好ましく、炭素数１〜３のアルキル基が特に好ましい。
Ｒ_２としては、カーボネート基、（メタ）アクリロイル基含有を含有しても良い炭素数１〜１０のアルキル基を有するカルボン酸のカルボキシル基から水素原子を除いた有機基が好ましく、カーボネート基又は（メタ）アクリロイル基含有を含有する炭素数１〜１０のアルキル基を有するカルボン酸のカルボキシル基から水素原子を除いた有機基がより好ましい。

(In the formula, R ₁ represents an alkyl group having 1 to 12 carbon atoms and an alkoxy group having 1 to 12 carbon atoms, and R 2 represents a carbonate group or a hydrogen group removed from a carboxyl group of a monovalent to tetravalent organic carboxylic acid. And k represents an integer of 1 to 4.)
The R _1, an alkyl group having 1 to 3 carbon atoms or, preferably an alkoxy group having from 6 to 12 carbon atoms, particularly preferably an alkyl group having 1 to 3 carbon atoms.
R ₂ is preferably an organic group obtained by removing a hydrogen atom from a carboxyl group of a carboxylic acid having a C 1-10 alkyl group which may contain a carbonate group and a (meth) acryloyl group. The organic group which remove | excluded the hydrogen atom from the carboxyl group of the carboxylic acid which has a C1-C10 alkyl group containing meth) acryloyl group content is more preferable.

  Commercially available hindered amines (B) include tetrakis (1,2,2,6,6-pentamethyl-4-piperidyl) 1,2,3,4-butanetetracarboxylate (manufactured by ADEKA, trade name ADK STAB LA- 52), tetrakis (1,2,2,6,6-pentamethyl-4-piperidyl) butane-1,2,3,4-butanetetracarboxylate (manufactured by ADEKA, trade name ADK STAB LA-57), 1, 2,2,6,6-pentamethyl-4-piperidyl and tridecyl-1,2,3,4-butanetetracarboxylate (trade name ADEKA STAB LA-62, manufactured by ADEKA), 2,2,6,6- Condensation product of tetramethyl-piperidinol, tridecyl alcohol and 1,2,3,4-butanetetracarboxylic acid (trade name ADEKA manufactured by ADEKA) Stub LA-67), 1,2,3,4-butanetetracarboxylic acid and 2,2,6,6-tetramethyl-4-piperidinol and β, β, β, β-tetramethyl-3,9- ( Condensate with 2,4,8,10-tetraoxaspiro [5,5] undecane) -diethanol (trade name ADEKA STAB LA-68LD, manufactured by ADEKA), bis (2,2,6,6-) decanedioate Tetramethyl-4-piperidyl) (trade name ADEKA STAB LA-77Y, trade name TINUVIN 123, trade name TINUVIN 123) manufactured by ADEKA, 1,2,2,6,6-pentamethyl-4-piperidyl methacrylate ( ADEKA, trade name ADK STAB LA-82, Hitachi Chemical, trade name FA-711MM), bis (1-undecanoxy-2,2,6,6-tetramethylpi) Lysine-4-yl) carbonate (made by ADEKA, trade name ADK STAB LA-81), 2,2,6,6-tetramethyl-4-piperidyl methacrylate (made by ADEKA, trade name ADK STAB LA-87, Hitachi Chemical Co., Ltd.) Manufactured, trade name FA-712HM), high molecular weight hindered amine light stabilizer (manufactured by Ciba Specialty Chemicals, trade name CHIMASSORB 119FL, CHIMASSORB 2020FDL), poly [{6- (1,1,3,3-tetra Methylbutyl) amino-1,3,5-triazine-2,4-diyl} {(2,2,6,6-tetramethyl-4-piperidyl) imino} hexamethylene {(2,2,6,6- Tetramethyl-4-piperidyl) imino}] (Ciba Specialty Chemicals, trade name CHIMASSORB 944FDL), polymer sterically hindered amine derivative (manufactured by Ciba Specialty Chemicals, trade name TINUVIN 622LD), 2- (3,5-di-t-butyl-4-hydroxybenzyl) -2-n-butylmalon Bis (1,2,2,6,6-pentamethyl-4-piperidyl) (trade name TINUVIN 144, manufactured by Ciba Specialty Chemicals), bis (1,2,2,6,6-pentamethyl-4-piperidinyl) ) Sebacate (Ciba Specialty Chemicals, trade name TINUVIN 765), bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate (Ciba Specialty Chemicals, trade name TINUVIN 770), etc. Is available.

  In the photocurable adhesive composition of the present invention, the hindered amine is preferably 0.01 to 20 parts by weight, more preferably 0.5 to 10 parts by weight, most preferably 100 parts by weight of the (meth) acrylate oligomer. Contains 0.1 to 3 parts by weight.

In this invention, antioxidant (C) can be contained suitably. By containing the antioxidant (C), it is possible to improve heat resistance and moisture resistance and more effectively prevent deterioration such as discoloration. Antioxidants include BHT, 2,4-bis- (n-octylthio) -6- (4-hydroxy-3,5-di-t-butylanilino) -1,3,5-triazine, pentaerythrityl. Tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate], 2,2-thio-diethylenebis [3- (3,5-di-t-butyl-4-hydroxyphenyl) Propionate], triethylene glycol-bis [3- (3-t-butyl-5-methyl-4-hydroxyphenyl) propionate], 1,6-hexanediol-bis [3- (3,5-di-t- Butyl-4-hydroxyphenyl) propionate], octadecyl-3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate, N, N′-hexamethylene Bis (3,5-di-tert-butyl-4-hydroxy-hydrocinnamamide), 1,3,5-trimethyl-2,4,6-tris (3,5-di-tert-butyl-4- Hydroxybenzyl) benzene, tris- (3,5-di-t-butyl-4-hydroxybenzyl) -isocyanurate, octylated diphenylamine, 2,4, -bis [(octylthio) methyl] -O-cresol, isooctyl- 3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate, dibutylhydroxytoluene, 2,4-bis- (n-octylthio) -6- (4-hydroxy-3,5-di-t -Butylanilino) -1,3,5-triazine, pentaerythrityl tetrakis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate], , 2-thio - diethylene bis [3- (3,5-di -t- butyl-4-hydroxyphenyl) propionate], can be exemplified 2,4-bis (octylthiomethyl) -6-methylphenol and the like.
These antioxidants can be used alone or in combination of two or more. The amount of the antioxidant is preferably 0.1 to 10 parts by weight, more preferably 0.5 to 3 parts by weight with respect to 100 parts by weight of the (meth) acrylate oligomer.

  Specific examples of the filler include, for example, crystalline silica, fused silica, alumina, zircon, calcium silicate, calcium carbonate, silicon carbide, silicon nitride, boron nitride, zirconia, fosterite, steatite, spinel, titania, talc and the like. Examples thereof include powder or beads obtained by spheroidizing these.

  When present in the composition of various additives, the weight ratio of the various additives in the photocurable transparent adhesive composition is 0.01 to 3% by weight, preferably 0.01 to 1% by weight, and more preferably. Is 0.02 to 0.5% by weight.

  The ultraviolet curable resin composition of the present invention can be obtained by mixing and dissolving the aforementioned components at room temperature to 80 ° C., and if necessary, impurities may be removed by an operation such as filtration. In the adhesive composition for bonding of the present invention, it is preferable to appropriately adjust the compounding ratio of the components so that the viscosity at 25 ° C. is in the range of 300 to 50000 mPa · s from the viewpoints of applicability and antifoaming properties.

  The surface tension of the obtained resin composition is preferably within a certain range from the viewpoint of applicability. In the present invention, the surface tension of the resin composition is preferably 20 to 40 mN / m, and particularly preferably 22 to 32 mN / m.

  Next, the preferable form of the manufacturing process of the biosensor board | substrate using the ultraviolet curable resin composition of this invention is demonstrated. The ultraviolet curable resin composition of this invention can be used for bonding of the base substrate 10 provided with the well forming material or the well forming layer and the cover member as described above.

First, as shown in FIG. 4A, the base substrate 10 is formed by injection molding. Here, the information pits 12 described above are formed on the upper surface of the base substrate 10. Subsequently, if necessary, a reflective film or a dielectric layer film is formed on the upper surface of the base substrate 10 by vapor deposition. Thereafter, as shown in FIG. 4B, the bottom surface layer 41a is formed on the base substrate or the reflective film or the dielectric film by using the ultraviolet curable resin composition of the present invention by a slit coater, roll coater, spin coater, screen printing method or the like. Are stacked. Thereafter, the bottom layer 41a is irradiated with ultraviolet rays to form the bottom layer 41a. Next, as shown in FIG. 4C, the upper surface layer 41b is formed on the upper surface of the bottom surface layer 12a by 2P molding. Then, the upper surface layer 41b is irradiated with ultraviolet rays to form a cured product layer. Thereby, a well formation layer in which a plurality of wells are formed is formed.
In this case, the embodiment in which the bottom layer 41a and the top layer 41b are formed in two steps has been described above. However, the ultraviolet curable resin composition of the present invention is injected by placing the bottom layer 41a and the top layer 41b in a mold or the like. Then, the well formation layer may be formed at a time by irradiating ultraviolet rays at a time.

Moreover, the ultraviolet curable resin composition of this invention can be used for bonding of the base substrate 10 provided with the well formation layer and the cover member as described above.
Here, as described above, the well forming layer is composed of the ultraviolet curable resin composition of the present invention, or silicone, polycarbonate, polymethyl methacrylate, or the like. The ultraviolet curable resin composition of the present invention is applied on the well forming layer 11 thus configured by a slit coater, roll coater, spin coater, screen printing method or the like. Then, the biosensor substrate of the present invention can be obtained by laminating the cover member 20 and irradiating the base substrate 10 or the cover member 20 with ultraviolet rays.

The dose of ultraviolet rays about 100~4000mJ / cm ² is preferably in accumulated light amount, particularly preferably about 200~3000mJ / cm ^2. The light source used for curing by irradiation with ultraviolet to near ultraviolet light may be any light source as long as it is a lamp that emits ultraviolet to near ultraviolet light. For example, a low-pressure, high-pressure or ultrahigh-pressure mercury lamp, metal halide lamp, (pulse) xenon lamp, or electrodeless lamp can be used.

The curing shrinkage of the cured product of the ultraviolet curable resin composition of the present invention is preferably 4.0% or less, and particularly preferably 3.0% or less. Thereby, when the ultraviolet curable resin composition is cured, the internal stress accumulated in the cured resin can be reduced, and the interface between the base material and the layer made of the cured product of the ultraviolet curable resin composition can be reduced. It is possible to effectively prevent the distortion.
In addition, when the substrate such as glass is thin, when the curing shrinkage rate is large, since the warpage during curing becomes large, the display performance is greatly adversely affected. Is preferred.

It is preferable that the transmittance | permeability in 400 nm-800 nm of the hardened | cured material of the ultraviolet curable resin composition of this invention is 90% or more. This is because when the transmittance is less than 90%, it is difficult for light to pass therethrough and the visibility is lowered when used in a display device.
Moreover, since the improvement of visibility can be expected further when the transmittance at 400 to 450 nm of the cured product is high, the transmittance at 400 to 450 nm is preferably 90% or more.

  When the optical base material is used as an adhesive, the detection performance is further improved when the refractive index of the cured product is 1.45 to 1.55 in order to improve visibility.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

Ｕ１：ウレタンアクリレート（※修正要：ポリプロピレングリコール（分子量３０００）、イソホロンジイソシアネート、２−ヒドロキシエチルアクリレートの３成分をモル比１：１．３：２の反応物）
Ｕ２：ウレタンアクリレート、１，２−水素化ポリブタジエングリコール（分子量２０００）、イソホロンジイソシアネート、２−ヒドロキシエチルアクリレートの３成分をモル比１：１．２：２の反応物
Ｓ−１８００Ａ：イソステアリルアクリレート、新中村化学(株)社製
ＬＡ：ラウリルアクリレート、日油（株）社製
ＦＡ−５１３ＡＳ：ジシクロペンタニルアクリレ−ト、日立化成（株）社製
４−ＨＢＡ：４−ヒドキシブチルアクリレート、大阪有機化学工業（株）社製
Ｍ−１０５：水添テルペン樹脂、軟化点１０５℃、ヤスハラケミカル（株）社製
ＫＥ−３１１：水添ロジンエステル樹脂、荒川化学（株）社製、商品名パインクリスタルＫＥ−３１１
ＹＳポリスターＮＨ：水添テルペンフェノール樹脂、ヤスハラケミカル（株）社製
ＬＶ−１００：ポリブテン、ＪＸ日鉱日石エネルギー(株)製
ＧＩ−２０００：１，２−水素化ポリブタジエングリコール（分子量２０００）、日本曹達（株）社製
ＰＰＧ３０００：ポリプロピレングリコール（重量平均分子量３２００）、旭硝子（株）社製、商品名エクセノール３０２０
ＰＰＧ１０００：ポリプロピレングリコール（重量平均分子量１０００）、旭硝子（株）（株）社製、商品名エクセノール１０２０
ＵＰ−１１７１：アクリルポリマー（重量平均分子量８０００）、東亞合成（株）社製
Ｉｒｇａｃｕｒｅ １８４Ｄ：１−ヒドロキシシクロヘキシルフェニルケトン、ＢＡＳＦ社製
Ｓｐｅｅｄｃｕｒｅ ＴＰＯ：２，４，６−トリメチルベンゾイルジフェニルフォスフィンオキサイド、ＬＡＭＢＳＯＮ社製
ＬＡ−８２：１，２，２，６，６−ペンタメチル−４−ピペリジルメタクリレート、ＡＤＥＫＡ社製、商品名アデカスタブ ＬＡ−８２
ＬＡ−８１：ビス（１−ウンデカンオキシ−２，２，６，６−テトラメチルピペリジン−４−イル）カルボネート、ＡＤＥＫＡ社製、商品名アデカスタブ ＬＡ−８１
１５２０Ｌ：２，４−ビス(オクチルチオメチル)−６−メチルフェノール、ＢＡＳＦ社製、イルガノックス１５２０Ｌ Preparation of UV-curable resin composition Heat mixing was performed at the blending ratio shown in Table 1 to prepare Examples 1 to 9.

U1: Urethane acrylate (* correction required: reaction product of polypropylene glycol (molecular weight 3000), isophorone diisocyanate, 2-hydroxyethyl acrylate in a molar ratio of 1: 1.3: 2)
U2: Reactant S-1800A: isostearyl acrylate having a molar ratio of 1: 1.2: 2 of three components of urethane acrylate, 1,2-hydrogenated polybutadiene glycol (molecular weight 2000), isophorone diisocyanate and 2-hydroxyethyl acrylate, Shin-Nakamura Chemical Co., Ltd. LA: Lauryl acrylate, NOF Corporation FA-513AS: Dicyclopentanyl acrylate, Hitachi Chemical Co., Ltd. 4-HBA: 4-Hydroxybutyl acrylate , Osaka Organic Chemical Industry Co., Ltd. M-105: Hydrogenated terpene resin, softening point 105 ° C., Yashara Chemical Co., Ltd. KE-311: Hydrogenated rosin ester resin, manufactured by Arakawa Chemical Co., Ltd., trade name Pine Crystal KE-311
YS Polystar NH: hydrogenated terpene phenol resin, LV-100 manufactured by Yashara Chemicals Co., Ltd., polybutene, GI-2000 manufactured by JX Nippon Oil & Energy Corporation, 1,2-hydrogenated polybutadiene glycol (molecular weight 2000), Nippon Soda PPG3000: Polypropylene glycol (weight average molecular weight 3200), manufactured by Asahi Glass Co., Ltd., trade name Exenol 3020
PPG1000: Polypropylene glycol (weight average molecular weight 1000), manufactured by Asahi Glass Co., Ltd., trade name EXCENOL 1020
UP-1171: Acrylic polymer (weight average molecular weight 8000), Irgacure 184D manufactured by Toagosei Co., Ltd .: 1-hydroxycyclohexyl phenyl ketone, Speedcure manufactured by BASF TPO: 2,4,6-trimethylbenzoyldiphenylphosphine oxide, LAMBSON LA-82: 1,2,2,6,6-pentamethyl-4-piperidyl methacrylate, manufactured by ADEKA, trade name ADK STAB LA-82
LA-81: Bis (1-undecanoxy-2,2,6,6-tetramethylpiperidin-4-yl) carbonate, manufactured by ADEKA, trade name ADK STAB LA-81
1520L: 2,4-bis (octylthiomethyl) -6-methylphenol, manufactured by BASF Corp., Irganox 1520L

The following evaluation was performed using the obtained compositions 1 to 9 of the present invention.

(Viscosity) It was measured at 25 ° C. using an E-type viscometer (TV-200: manufactured by Toki Sangyo Co., Ltd.).

(Refractive index): The refractive index (25 ° C.) of the cured ultraviolet curable resin layer was measured with an Abbe refractometer (DR-M2: manufactured by Atago Co., Ltd.).

(Curing shrinkage ratio): Two slide glasses having a thickness of 1 mm coated with a fluorine-based release agent were prepared, and the composition was applied to one of the release agent application surfaces so that the film thickness was 200 μm. Thereafter, the two slide glasses were bonded so that the respective release agent application surfaces face each other. The resin composition was cured by irradiating the resin composition with ultraviolet rays having an accumulated light amount of 2000 mJ / cm ^{2 through} a glass with a high-pressure mercury lamp (80 W / cm, ozone-less). Thereafter, the two slide glasses were peeled off to produce a cured product for measuring the film specific gravity. Based on JIS K7112 B method, specific gravity (DS) of hardened | cured material was measured. Moreover, the liquid specific gravity (DL) of the resin composition was measured at 25 degreeC. From the measurement results of DS and DL, the cure shrinkage rate was calculated from the following formula, and both were 2.4%.
Curing shrinkage (%) = (DS−DL) ÷ DS × 100

(Rigidity): Two release-treated PET films were prepared, and the obtained ultraviolet curable resin composition was applied to one of the release surfaces so that the film thickness was 200 μm. Thereafter, the two PET films were bonded together such that the release surfaces face each other. The resin composition was cured by irradiating the resin composition with ultraviolet rays having an integrated light quantity of 3000 mJ / cm ^{2 through} a PET film with a high-pressure mercury lamp (80 W / cm, ozone-less). Thereafter, the two PET films were peeled off to prepare a cured product for measuring the rigidity. The rigidity was measured by changing the temperature with ARES (TA Instruments, 1 Hz). The data at 25 ° C. is described below.

(Transmittance): Two slide glasses having a thickness of 1 mm were prepared, and the obtained ultraviolet curable resin composition was applied to one of them so that the film thickness after curing was 200 μm. Then, two slide glasses were bonded together. The resin composition was cured by irradiating ultraviolet rays with an integrated light amount of 3000 mJ / cm ^{2 through} a glass with a high-pressure mercury lamp (80 W / cm, ozone-less) to prepare a cured product for measuring transmittance. About the transmittance | permeability of the obtained hardened | cured material, the transmittance | permeability in the wavelength range of 400-800 nm and 400-450 nm was measured at 25 degreeC using the spectrophotometer (U-3310, Hitachi High-Technologies Corporation).

(Dielectric constant): A sample similar to the above-mentioned rigidity modulus measurement was prepared and measured using a dielectric constant measuring device LCR meter (PRECISION COMPONENT ANALYZER) 6446B Wayne Kerr Electronics. The measurement sample holder measured the dielectric constant at 1 MHz and 25 degreeC using SHZ-2.

(HAZE): A sample similar to the above-described transmittance measurement was prepared, and measurement was performed in a 25 ° C. environment using a fully automatic haze meter (MODEL TC-H3DPK) (manufactured by Tokyo Denshoku).

(YI value measurement) Two slide glasses having a thickness of 1 mm were prepared, and the obtained ultraviolet curable resin composition was applied to one of them so that the film thickness after curing was 200 μm. Then, two slide glasses were bonded together. The resin composition was cured by irradiating ultraviolet rays with an integrated light amount of 3000 mJ / cm ^{2 through} a glass with a high-pressure mercury lamp (80 W / cm, ozone-less) to prepare a cured product for measuring transmittance. Moreover, about the 85 degreeC high temperature test and the measurement of YI value, the sample was measured using the photometer (U-3310, Hitachi High-Technologies Corporation). Table 3 shows the measurement results.

  Furthermore, the following evaluation was performed using the obtained resin compositions 1 to 9 of the present invention.

(Heat and moisture resistant adhesion) 2 pieces of 1 mm thick glass sheet (10 cm × 15 cm) or 1 mm thick polycarbonate sheet piece (manufactured by Teijin Ltd .: Panlite PC-1151) (10 cm × 15 cm) Was prepared, and the ultraviolet curable resin composition obtained on one side was applied so that the film thickness was 200 μm, and then the other was bonded to the application surface. Through the glass, the resin composition was irradiated with ultraviolet rays having an integrated light amount of 5000 mJ / cm ² with a high-pressure mercury lamp (80 W / cm, ozone-less), and the resin composition was cured to prepare a sample for evaluating adhesiveness. In the case of a polycarbonate piece having a high UV shielding ability around 365 nm (manufactured by Teijin: Panlite PC-7129 or Mitsubishi Gas Chemical Co., Ltd .: MR-58U), 405 mJ using 405 nm of a UV-LED light source. The resin composition was irradiated with UV light of / cm ² to cure the resin composition, and an adhesive evaluation sample was prepared. Moreover, the test piece was similarly produced also in the dissimilar base material of a raw glass and a polycarbonate sheet. Using these test pieces, a heat resistance test at 95 ° C., a low temperature test at −40 ° C., and a humidity resistance test at 85 ° C. and 85% RH were performed and left for 100 hours. In the sample for evaluation, peeling of the cured resin from the substrate interface was visually confirmed. The results are shown in Table 4.

〇：剥がれや気泡の発生などの不良が発生しない。
△：一部剥がれや気泡が発生する。（全面積の半分は接着した状態）
×：９割以上剥がれてしまう。

◯: Defects such as peeling and generation of bubbles do not occur.
Δ: Partial peeling or bubbles are generated. (Half of the total area is bonded)
X: It peels off 90% or more.

The high temperature and high humidity test allows the adhesion to be maintained in a state where moisture is retained on the biosensor substrate, and also allows the adhesion to be maintained in an environment of −40 ° C. and 95 ° C. It shows that adhesion can be maintained.

(Metal corrosion test)
(Silver substrate) 2 mm polycarbonate sheet pieces (manufactured by Teijin Ltd .: Panlite PC-1151) (10 cm × 10 cm) are prepared, and silver is sputtered on one side to form a thin film (0.3 μm). After that, the obtained ultraviolet curable resin composition was applied so that the film thickness was 50 μm, and the other was bonded to the coated surface. The resin composition was cured by irradiating the resin composition with ultraviolet light having an integrated light quantity of 3000 mJ / cm ^{2 with} a high-pressure mercury lamp (80 W / cm, ozone-less).
(Copper substrate) One copper-clad laminate (10 cm × 10 cm) of FR4 (Frame Regentant Type 4) and a 1 mm thick polycarbonate sheet piece (manufactured by Teijin Limited: Panlite PC-1151) (10 cm × 10 cm) 1 A sheet was prepared, and the obtained ultraviolet curable resin composition was applied so that the film thickness was 50 μm, and the other was bonded to the application surface. The resin composition was cured by irradiating the resin composition with ultraviolet light having an integrated light quantity of 3000 mJ / cm ^{2 with} a high-pressure mercury lamp (80 W / cm, ozone-less).
When the test piece obtained as described above was placed in a thermostat at 60 ° C. and 80% and the state of the metal surface after 100 hours was confirmed, no change that could be visually confirmed occurred.
From this result, the material of the present invention can be used without problems even for a substrate having a well of a type that reads and reflects laser light, such as an optical disk.

○：金属表面の変化なし（目視確認）
×：金属表面に変色あり（目視確認）

○: No change in metal surface (visual confirmation)
X: Discoloration on the metal surface (visual confirmation)

(Saline dissolution test)
The above-mentioned resin cured film sample similar to the measurement of rigidity is prepared, and immersed in physiological saline (Otsuka raw food injection: manufactured by Otsuka Pharmaceutical Co., Ltd.) for 24 hours as a sodium chloride aqueous solution almost equal to the body fluid. Compared.
As a result, in Example 1 and Example 2, a slight increase in weight was observed. This is probably because the polypropylene glycol component in the component absorbed water.
In Examples 3 to 9, a slight weight reduction is observed, but the amount is extremely small. This is considered due to the fact that the resin composition obtained in the examples is hydrophobic. From this result, it is thought that it is hard to elute with respect to components, such as a physiological saline and blood, and the said resin component has no possibility of affecting the cell etc. in a well.

  As mentioned above, the said embodiment disclosed this time is an illustration in all the points, Comprising: It is not restrictive. The technical scope of the present invention is defined by the terms of the claims, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

DESCRIPTION OF SYMBOLS 1 Biosensor substrate 2 Center hole 3 Reaction chamber 10 Base substrate 11 Well formation material 12 Information pit 15 Well 20 Cover member 50 Ultraviolet curable resin composition

Claims (7)

An ultraviolet curable resin composition for a biosensor substrate, comprising a (meth) acrylate compound (A), a softening component (B), and a photopolymerization initiator (C). 2. The ultraviolet curable resin for a biosensor substrate according to claim 1, comprising (meth) acrylate oligomer (A1) and (meth) acrylate monomer (A2) as the (meth) acrylate compound (A). Composition. The (meth) acrylate oligomer (A1) is a (meth) acrylate having at least one skeleton selected from the group consisting of urethane (meth) acrylate, polypropylene, polybutadiene, hydrogenated polybutadiene, polyisoprene and hydrogenated polyisoprene. The ultraviolet curable resin composition for a biosensor substrate according to claim 1 or 2, wherein   The softening component (B) contains at least one selected from the group consisting of a hydroxyl group-containing polymer, a terpene resin, a hydrogenated terpene resin, a rosin resin, and a hydrogenated rosin resin. Item 4. The ultraviolet curable resin composition for a biosensor substrate according to any one of Items 1 to 3.   The surface tension of the resin composition is 20 mN / m or more, The ultraviolet curable resin composition for a biosensor substrate according to any one of claims 1 to 4.   Hardened | cured material obtained by irradiating an active energy ray to the ultraviolet curable resin composition as described in any one of Claims 1-5.   A biosensor substrate comprising the ultraviolet curable resin composition according to any one of claims 1 to 6.

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