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WO2018123663A1 - Substrat de culture cellulaire et son procédé de production - Google Patents

Substrat de culture cellulaire et son procédé de production Download PDF

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Publication number
WO2018123663A1
WO2018123663A1 PCT/JP2017/045153 JP2017045153W WO2018123663A1 WO 2018123663 A1 WO2018123663 A1 WO 2018123663A1 JP 2017045153 W JP2017045153 W JP 2017045153W WO 2018123663 A1 WO2018123663 A1 WO 2018123663A1
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WO
WIPO (PCT)
Prior art keywords
well
culture
culture substrate
opening
diameter
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Application number
PCT/JP2017/045153
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English (en)
Japanese (ja)
Inventor
増田　秀樹
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Ａｇｃテクノグラス株式会社
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Publication date
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Publication of WO2018123663A1 publication Critical patent/WO2018123663A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/12—Well or multiwell plates

Definitions

  • the present invention relates to a cell culture substrate for culturing a culture object such as a cell to obtain a spheroid (cell aggregate) and a method for producing the same.
  • Spheroid culture in which cells derived from humans or animals are artificially cultured in a culture vessel or the like and aggregated three-dimensionally is well known.
  • the cell population forms a three-dimensional structure, and the cells interact with each other, so it is thought that it can be cultured or maintained in a state that is closer to the three-dimensional structure in vivo. It is known to show superior properties compared to planar adhesion culture.
  • spheroid culture is often used for anticancer drug screening using cancer cells and proliferation and differentiation of pluripotent stem cells.
  • a recess for containing cells and culture solution is provided at the bottom of the container body.
  • the side surface of the concave portion is formed by an inclined surface so that the opening area is expanded as it approaches the open end (see Patent Document 1).
  • a cell culture container in which spheroids and cells are difficult to move to other wells during medium replacement by providing an inclination in a plurality of microwells provided on the culture surface and increasing the depth thereof ( Patent Document 2).
  • Patent Document 2 in order to solve the movement of spheroids from within the well, an inclination (1 to 20 °) is formed, or the depth of the well is made deeper than before (Examples and comparisons in Patent Document 2) See example).
  • the well is formed deeply with respect to the thickness of the bottom, so that the strength of the bottom is reduced, and there is a risk of breakage, cracking, etc. is there.
  • the migration of spheroids from the microwells is suppressed without increasing the depth of the microwells, and the size is uniform.
  • a cell culture substrate capable of forming a spheroid and a method for producing the same are provided.
  • the present invention is a culture substrate having a culture surface for culturing cells, wherein the culture surface has a plurality of microwells, and the microwell has a first well having an inclined surface and the first well.
  • a second well existing in the well, and a protrusion at a boundary between the first well and the second well, and the culture surface is a low cell adhesion surface It is characterized by being.
  • the culture surface preferably has an inclined wall on its outer peripheral surface.
  • the first well is preferably arranged densely on the culture surface.
  • the diameter of the opening of the second well is preferably 0.05 mm to 3 mm.
  • the first well has an inclined surface inside, and the inclination angle of the inclined surface is more than 0 ° and less than 90 °.
  • the depth of the second well is preferably 0.1 to 2 times the diameter of the opening.
  • the diameter of the opening of the first well is preferably 1.5 to 5 times the diameter of the opening of the second well.
  • the depth of the first well is preferably 0.1 to 3 times the diameter of the opening.
  • the combined depth of the first well and the second well is preferably 0.1 to 0.9 times the thickness of the culture surface.
  • the method for producing a culture substrate of the present invention is a method for producing a culture substrate having a culture surface for culturing cells, the first well having an inclined surface, and being present in the first well.
  • a plurality of microwells are formed on the culture surface so as to have a protrusion at the boundary between the first well and the second well.
  • the method for producing a culture substrate it is preferable to form the second well after forming the first well.
  • the first well is preferably formed simultaneously with the culture substrate.
  • a second well is formed in the first well by a laser.
  • the protrusions are preferably formed by a laser.
  • a low cell adhesion treatment is performed on the culture surface after the formation of the microwell.
  • the present invention even if a plurality of microwells for forming spheroids are formed on the culture surface of a conventional culture substrate, the movement of cells and spheroids between wells due to the flow of the culture medium (culture solution) is reduced.
  • the culture medium culture solution
  • An example of the top view of the culture substrate of the present invention is shown.
  • An example of the AA ′ cross-sectional view of the culture substrate of the present invention is shown.
  • An example of the top view of the microwell in the culture base material of this invention is shown.
  • An example of the sectional view of the microwell in the culture substrate of the present invention is shown.
  • An example of the enlarged view of the microprotrusion in the microwell in the culture base material of this invention is shown.
  • An example of the variation of the opening shape of the 1st well in the culture base material of this invention is shown.
  • An example of sectional drawing of the 1st well (before 2nd well formation) in the culture substrate of the present invention is shown.
  • An example of the variation of the opening shape of the 2nd well in the culture base material of this invention is shown.
  • An example of a variation of the BB ′ cross-sectional view of the second well in the culture substrate of the present invention is shown.
  • the culture substrate 1 of the present invention has a culture surface on which at least one surface of the substrate can obtain spheroids in which cells are three-dimensionally aggregated during the culture process, and the culture surface has a plurality of microwells.
  • Examples of the shape of the culture substrate 1 include petri dishes, flasks, multilayer flasks, microplates, sheets, inserts, and the like, but the shape is not particularly limited. After forming a microwell on a sheet-like member, it may be used by placing it on a container such as a petri dish. In the present specification and drawings, an example in which a microwell 3 is provided on a culture surface 2 of a petri dish will be described.
  • one culture substrate 1 of the embodiment of the present invention mainly includes a bottom portion and a peripheral wall portion.
  • the bottom is configured in a disc shape and has a culture surface 2 with a plurality of microwells 3.
  • the culture surface 2 is formed at the bottom.
  • the peripheral wall rises from the peripheral edge of the bottom.
  • the shape of the peripheral wall portion is a state in which the peripheral edge portion is erected.
  • the disk-shaped bottom part is formed with a diameter of, for example, 85 mm and a thickness of, for example, 1 mm.
  • the height of the peripheral wall portion is, for example, 20 mm with respect to the bottom portion.
  • the bottom part and the surrounding wall part are comprised by the integral component.
  • the cell culture substrate 1 may include a lid for covering the opening.
  • the culture surface 2 in the culture substrate 1 of the present invention is preferably a surface to which cells do not adhere or are difficult to adhere (hereinafter referred to as cell low adhesion surface) in order to form spheroids.
  • cell low adhesion surface a surface to which cells do not adhere or are difficult to adhere
  • the culture surface 2 is treated with low cell adhesion (hereinafter referred to as cell low adhesion treatment), or the container itself is formed of a low cell adhesion resin. May be.
  • Examples of the low cell adhesion treatment include coating with a phospholipid polymer (polymer such as 2-methacryloyloxyethyl phosphorylcholine), poly (hydroxyethyl methacrylate), a fluorine-containing compound, or polyethylene glycol, plasma treatment, Surface treatment such as corona discharge and UV ozone treatment may be performed.
  • Examples of the low cell adhesion resin include silicone resin and resin mixed with a cell low adhesion coating component. Note that the low cell adhesion treatment is not limited to the culture surface 2, and the same treatment may be applied to the peripheral wall portion of the culture surface and the like.
  • the culture substrate 1 of the present invention includes a plurality of microwells 3 on a culture surface 2. Spheroids are cultured in each microwell 3. It is preferable that the microwells 3 are densely arranged on the culture surface 2 and that there is no flat surface between the microwells 3 (a non-flat surface). For example, by setting a non-flat surface between the microwells 3, the seeded cells always fall into the microwell 3, so that the cells can be prevented from staying outside the microwell 3. Thereby, it becomes possible to suppress that a cell does not become a spheroid.
  • “non-flat” in the present specification refers to not being horizontal with respect to the bottom surface of the culture surface 2 (the bottom surface of the culture substrate).
  • “Dense” means that the microwells 3 are formed densely and there is no flat surface between the wells.
  • “cells do not become spheroids” means that the cultured cells are spheroid-like in monolayer culture, single cell suspension culture, non-spherical layered culture, or adhesion culture in which cells adhere to the culture surface 2 and are cultured. It means not to be.
  • the microwell 3 includes a first well 31 and a second well 32.
  • the first well 31 and the second well 32 may be formed integrally, or the second well 32 may be formed after the first well 31 is formed.
  • the case where the second well 32 is formed after the first well 31 is formed will be described.
  • the first well 31 is indicated by the opening diameter 311 and the depth 312
  • the second well 32 is indicated by the opening diameter 321 and the depth 322
  • the microwell 3 is indicated by the depth 30.
  • the second well 32 is formed at the bottom of the first well 31.
  • the second well 32 is formed by opening the bottom of the first well 31 and has the bottom of the opening (hereinafter referred to as the second opening).
  • the second opening refers to the point where the tilt angle of the first well has changed.
  • As the opening shape of the second well 32 as in the example shown in FIG. 8, there are a plurality of openings (circle (a), polygons (b) (c) (e) (f), donut shape (d)). It can be suitably selected from the shape (g) and the like.
  • the shape of the second well 32 can be appropriately selected from a conical shape, a prismatic shape, a U-bottom shape, a V-bottom shape, and the like.
  • the shape does not have a flat portion, for example, a U-bottom shape. It is preferable because cells that have fallen into the well are easily collected and a uniform sphere is easily formed.
  • An example of the cross-sectional shape of the second well is shown in FIG.
  • the diameter 321 of the second opening is preferably 0.05 mm to 3 mm. If the diameter 321 of the second opening is less than 0.05 mm, it may be difficult to take out the spheroids. Moreover, when the diameter 321 of the second opening is more than 3 mm, the spheroids may be likely to jump out of the well.
  • the diameter 321 of the second opening is more preferably 0.1 mm to 2.5 mm, and still more preferably 0.15 mm to 2.0 mm.
  • the depth 322 of the second well is preferably 0.1 to 2 times the diameter 321 of the second opening. If the depth 322 of the second well is less than 0.1 times the diameter of the second opening, there is a problem that spheroids are easily spilled. In addition, if the depth 322 of the second well is more than twice the diameter 321 of the second opening, it becomes difficult to take out spheroids and the bottom surface strength is lowered.
  • the depth 322 of the second well is more preferably 0.2 to 1.8 times the diameter 321 of the second well, and still more preferably 0.3 to 1.7 times. Note that the depth 322 of the second well indicates the value of the longest portion of the height from the second opening to the bottom.
  • the first well 31 has an opening (hereinafter referred to as a first opening) and an inclined surface toward the bottom.
  • the shape seen from the upper surface of the 1st opening part can be suitably selected from a honeycomb type, a lattice type
  • the honeycomb type is preferable because the distance between adjacent wells becomes equal, so that the same amount of medium can easily enter each well and spheroids can be formed under more uniform conditions.
  • the diameter 311 of the first opening is preferably 1.5 to 5 times the diameter 321 of the second well.
  • the diameter 311 of the first opening is more preferably 1.8 to 4.5 times the diameter 321 of the second opening, and even more preferably 2 to 3.5 times.
  • the depth 312 of the first well is preferably 0.1 to 3 times the diameter 311 of the first opening. If it is less than 0.1 times, depending on the viscosity of the medium, the surface tension of the medium may be lost and the slope may be insufficient. If it exceeds 3 times, the second well cannot be deepened depending on the thickness 21 of the culture surface.
  • the depth 312 of the first well is more preferably 0.13 to 2.5 times the diameter 311 of the first opening, and even more preferably 0.15 to 2 times.
  • the diameter 311 and depth 312 of the first opening can be appropriately adjusted according to the size of the cells to be cultured and the desired spheroid.
  • the inclined surface of the first well preferably has an inclination angle 313 ( ⁇ ) of more than 0 ° and less than 90 °.
  • ⁇ 0 ° (flat surface)
  • the medium does not flow to the second well due to the influence of the surface tension, and the spheroid size tends to vary.
  • the inclination angle 313 ( ⁇ ) is 90 ° or more, the spheroids are likely to be difficult to take out because the shape tends to be deep.
  • the inclination angle 313 ( ⁇ ) is more preferably 5 ° to 80 °, and still more preferably 8 ° to 70 °. Since the optimum angle varies depending on the viscosity of the medium, it can be adjusted as appropriate within the above range.
  • the first well 31 and the second well 32 are connected to each other.
  • the combined depth 30 of the first well and the second well (that is, the depth of the microwell 3) is 0.1 to 0.9 times the thickness 21 of the culture surface of the culture substrate 1. preferable. If the ratio is less than 0.1 times, a well having a sufficient depth cannot be formed. If the ratio exceeds 0.9 times, the strength of the culture surface 2 of the culture substrate 1 may decrease. It is preferably 0.3 to 0.8 times, and more preferably 0.4 to 0.7 times.
  • a protrusion 5 as shown in FIG. 3 and FIG. 4 between the first well 31 and the second well 32 (bonded portion, hereinafter referred to as a boundary portion).
  • the protrusion 5 is for suppressing the cells that have fallen into the second well 32 and the spheroids formed in the second well 32 from moving outside the second well 32. Due to the presence of the protrusions 5, when the culture substrate 1 is tilted at the time of medium exchange or the like, spheroids and cells are blocked by the protrusions 5 and can be retained in the second well 32. It is preferable that the protrusion 5 has a shape protruding at the boundary portion into the second opening.
  • the protrusion 5 protrudes into the second opening as long as the cells fall into the second well 32 through the second opening and the spheroids formed in the second well 43 can be taken out. May be.
  • the protrusion 5 is preferably about 2 ⁇ m to 5 ⁇ m.
  • the shape of the protrusion 5 is not particularly limited, but the point where the cell or spheroid contacts has a sharp corner so as not to damage the cell or spheroid or leave the cell on the protrusion 5. It is preferable that it is a non-flat surface which does not have.
  • Microwell 3 in culture substrate 1 of the present invention per unit area of the culture surface 2, 10 pieces / cm 2 ⁇ 10000 pieces / cm 2, is preferably formed.
  • the number of microwells 3 is less than 10 / cm 2 , the number of microwells 3 decreases, and the number of spheroids that can be formed at one time decreases, so that the culture efficiency may decrease.
  • microwell 3 is 10,000 / cm 2, greater than that greater number of microwells 3, since the increase in the number of spheroids formed at one time, medium exchange frequency is increased by a medium consumption increases There is a risk that labor may occur during the culture, or the cells may not be sufficiently fed with nutrients.
  • the number of microwells 3 can be appropriately adjusted depending on the size of the culture substrate 1 to be used and the size and number of desired spheroids.
  • the microwell 3 preferably has a uniform well size in order to make the size of the obtained spheroid uniform. Since the size of the spheroid depends on the size of the well, if the size of the well is different, the size of the formed spheroid is not uniform, which is not preferable.
  • the culture substrate 1 for example, in the case of a petri dish, there may be a surface that is not wide enough to form a microwell 3 having the same size as the other microwells 3 in the vicinity of the peripheral wall.
  • the surface on which the microwell 3 cannot be formed is left as a flat surface, the cells may fall, and the cells may not become spheroids. Therefore, when the surface where the microwell 3 cannot be formed remains, it is preferable to make the surface non-flat.
  • the inclined wall 4 is formed as shown in FIG. 2 (a), the peripheral wall is thickened as shown in FIG. 2 (b), a part forming a non-flat surface is placed, and a partition is attached. Good.
  • the above-mentioned correspondence is not limited to use when the microwell 3 having a uniform size cannot be formed.
  • the microwell 3 is formed only on a part of the culture surface 2 and the number of microwells 3 is specified. It is also possible to use it when desired.
  • a partition may be provided.
  • the partition may be joined to the culture surface 2, may be placed, or may be one that does not contact the culture surface 2 (for example, a drop lid shape).
  • the material of the partition is not particularly limited, but may be the same material as the culture substrate 1 or may be a different material, or may be made of a membrane-like material that passes only the medium without passing through the cells.
  • the center portion of the first well 31 and the center portion of the second well 32 may or may not match. By making them coincide, the length of the inclined surface of the first well 31 becomes uniform, so that the cells easily fall uniformly. Moreover, by not matching, the well opening has a tilted shape, and the cells can be prevented from popping out when the container is tilted.
  • a method for producing the culture substrate 1 of the present invention will be described.
  • a manufacturing method can be suitably changed with the raw material of a base material to be used, a desired shape, a magnitude
  • the culture substrate 1 main body (the state before formation of the microwell) may be manufactured by a method suitable for the material and size of the substrate.
  • the material of the substrate can be appropriately selected from resin, glass, metal, or a combination thereof.
  • resin for example, in addition to acrylic resin, polystyrene resin, polyester resin, polycarbonate resin, polypropylene resin, etc., a mixture of the above-mentioned substances with low cell adhesion, or a colorant (for example, titanium oxide, carbon, etc.)
  • a mixture or the like can be used.
  • the culture substrate can be suitably selected from, for example, injection molding, press molding, vacuum molding, blow molding and the like.
  • the first well 31 and the second well 32 may be formed at a time, and the second well 32 may be formed after the first well 31 is formed.
  • the method for forming the microwell include a mold (molded together when the base body is manufactured), laser (CO 2 laser, YAG laser, excimer laser, etc.), nanoimprint, press and the like.
  • the second well 32 is formed after the first well 31 is formed, the first well 31 is formed in advance with a mold, and then the second well 32 is formed with a laser. It becomes easy to standardize.
  • the resin when the second well is formed on the resin base material with a CO 2 laser, the resin is dissolved and vaporized, so that the surface becomes a smooth surface, so that it becomes easy to form a beautiful spherical spheroid.
  • the smooth protrusion 5 is formed at the boundary portion, the spheroid is hardly damaged and a preferable form is obtained.
  • the intensity of the laser light is preferably 5 to 500 W.
  • the irradiation spot is preferably circular, but the shape is not particularly limited as long as a well capable of aggregating cells can be formed.
  • the diameter of the irradiation spot is suitably 20 ⁇ m to 1500 ⁇ m.
  • the laser irradiation position can also be adjusted as appropriate according to the desired well shape. Further, the strength may be appropriately adjusted depending on the material of the culture substrate 1. For example, 5-30 W is preferable for polystyrene, and 80-200 W is preferable for glass.
  • the culture surface 2 of the culture substrate 1 is not a low cell adhesion surface (not molded from a low cell adhesion material), it is necessary to separately perform a cell low adhesion treatment.
  • a low adhesion treatment method the culture surface 2 is immersed in a liquid containing a low adhesion substance and fixed to the culture surface 2, or the low adhesion substance is mixed with a UV curable resin and fixed by UV irradiation. And a method of attaching a sheet containing a substance that has low adhesion. Even when the culture substrate 1 is formed of a material having low cell adhesion, the low adhesion treatment may be performed together.
  • 1 culture substrate
  • 2 culture surface
  • 21 thickness of culture surface
  • 3 microwell
  • 30 depth of whole microwell
  • 31 first well
  • 311 diameter of first well
  • 312 Depth of first well
  • 313 inclination angle of first well
  • 32 second well
  • 321 diameter of second well
  • 322 depth of second well
  • 4 inclined wall
  • 5 Projection

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Abstract

L'invention concerne un substrat de culture cellulaire présentant une surface de culture sur laquelle sont formés de multiples micropuits, permettant d'empêcher la migration de sphéroïdes depuis les micropuits en vue de former des sphéroïdes présentant des tailles uniformes sans avoir besoin de former les micropuits trop profondément. L'invention concerne un substrat de culture présentant une surface de culture sur laquelle des cellules doivent être cultivées, ledit substrat de culture étant caractérisé en ce que de multiples micropuits sont formés sur la surface de culture, chacun des micropuits présente un premier puits présentant une surface inclinée et un second puits formé dans le premier puits, une saillie est formée sur la limite entre le premier puits et le second puits, et la surface de culture est une surface de faible adhérence cellulaire.
PCT/JP2017/045153 2016-12-28 2017-12-15 Substrat de culture cellulaire et son procédé de production WO2018123663A1 (fr)

Applications Claiming Priority (2)

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JP2016256320A JP2020043764A (ja) 2016-12-28 2016-12-28 細胞培養基材及びその製造方法
JP2016-256320 2016-12-28

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020166452A1 (fr) * 2019-02-13 2020-08-20 古河電気工業株式会社 Récipient de stockage
WO2021024943A1 (fr) 2019-08-02 2021-02-11 積水化学工業株式会社 Matériau d'échafaudage pour culture cellulaire et récipient de culture cellulaire
WO2021034533A1 (fr) * 2019-08-16 2021-02-25 Corning Incorporated Ensembles de culture cellulaire et leurs procédés d'utilisation
WO2021039882A1 (fr) * 2019-08-28 2021-03-04 学校法人東海大学 Procédé de culture d'une population cellulaire contenant des cellules souches/progénitrices positives tie2 à l'aide d'un substrat de culture et utilisation correspondante
WO2021132480A1 (fr) * 2019-12-27 2021-07-01 Ａｇｃ株式会社 Substrat de culture et boîte de culture
WO2022039165A1 (fr) 2020-08-18 2022-02-24 東ソー株式会社 Procédé pour induire la différenciation de cellules souches pluripotentes en cellules ectodermiques, mésodermiques et endodermiques
JP7672219B2 (ja) 2020-12-16 2025-05-07 Ａｇｃテクノグラス株式会社 マイクロプレート

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005069001A1 (fr) * 2003-09-25 2005-07-28 Toyama Prefecture Puce de reseau de micropuits et son procede de fabrication
WO2014196204A1 (fr) * 2013-06-07 2014-12-11 株式会社クラレ Flacon à culture et procédé de culture
WO2016069892A1 (fr) * 2014-10-29 2016-05-06 Corning Incorporated Dispositifs et procédés pour la génération et la culture d'agrégats cellulaires 3d

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005069001A1 (fr) * 2003-09-25 2005-07-28 Toyama Prefecture Puce de reseau de micropuits et son procede de fabrication
WO2014196204A1 (fr) * 2013-06-07 2014-12-11 株式会社クラレ Flacon à culture et procédé de culture
WO2016069892A1 (fr) * 2014-10-29 2016-05-06 Corning Incorporated Dispositifs et procédés pour la génération et la culture d'agrégats cellulaires 3d

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020166452A1 (fr) * 2019-02-13 2020-08-20 古河電気工業株式会社 Récipient de stockage
JP2020129981A (ja) * 2019-02-13 2020-08-31 古河電気工業株式会社 格納容器
JP7019618B2 (ja) 2019-02-13 2022-02-15 古河電気工業株式会社 格納容器
WO2021024943A1 (fr) 2019-08-02 2021-02-11 積水化学工業株式会社 Matériau d'échafaudage pour culture cellulaire et récipient de culture cellulaire
WO2021034533A1 (fr) * 2019-08-16 2021-02-25 Corning Incorporated Ensembles de culture cellulaire et leurs procédés d'utilisation
WO2021039882A1 (fr) * 2019-08-28 2021-03-04 学校法人東海大学 Procédé de culture d'une population cellulaire contenant des cellules souches/progénitrices positives tie2 à l'aide d'un substrat de culture et utilisation correspondante
JP7626993B2 (ja) 2019-08-28 2025-02-05 学校法人東海大学 培養基材を用いたＴｉｅ２陽性幹／前駆細胞を含む細胞集団の培養方法およびその利用
WO2021132480A1 (fr) * 2019-12-27 2021-07-01 Ａｇｃ株式会社 Substrat de culture et boîte de culture
WO2022039165A1 (fr) 2020-08-18 2022-02-24 東ソー株式会社 Procédé pour induire la différenciation de cellules souches pluripotentes en cellules ectodermiques, mésodermiques et endodermiques
JP7672219B2 (ja) 2020-12-16 2025-05-07 Ａｇｃテクノグラス株式会社 マイクロプレート

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