WO2024024345A1 - Cell culture device - Google Patents

Cell culture device Download PDF

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Publication number
WO2024024345A1
WO2024024345A1 PCT/JP2023/023014 JP2023023014W WO2024024345A1 WO 2024024345 A1 WO2024024345 A1 WO 2024024345A1 JP 2023023014 W JP2023023014 W JP 2023023014W WO 2024024345 A1 WO2024024345 A1 WO 2024024345A1
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WO
WIPO (PCT)
Prior art keywords
lid
rubber sheet
cell culture
culture container
culture device
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PCT/JP2023/023014
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French (fr)
Japanese (ja)
Inventor
慎治 杉浦
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国立研究開発法人産業技術総合研究所
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Publication of WO2024024345A1 publication Critical patent/WO2024024345A1/en

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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
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus

Definitions

  • the present invention relates to a cell culture device.
  • This application claims priority based on Japanese Patent Application No. 2022-121990 filed in Japan on July 29, 2022, the contents of which are incorporated herein.
  • Patent Document 1 discloses a cell culture device.
  • This cell culture device includes a storage tank and a pressure pump.
  • the storage tank includes a container-shaped tank body and a lid.
  • the lid part can open and close the opening of the tank body and can airtightly close the opening.
  • the lid portion is capable of airtightly closing the upper openings of the first culture solution storage chamber and the second culture solution storage chamber of the tank body.
  • the lid portion is in contact with the upper surface of the tank body through packing provided so as to surround each of the upper openings.
  • the cell culture device When culturing cells using a cell culture device such as the one described above, it is necessary to periodically replace the culture medium. When replacing the culture solution, open and close the lid of the cell culture device. At this time, there is a possibility that the sealing material such as the packing may fall off. Further, a large number of conventional sealing materials are arranged so as to surround the upper openings of each of the plurality of storage sections. Therefore, the cell culture device has a large number of parts and is complicated to assemble. Furthermore, if the dimensional error between the culture container and the lid is large, the dimensional error may not be absorbed by the elastic deformation of the individual sealing materials, which may cause problems in maintaining airtightness.
  • the present invention has been made in view of the above problems, and aims to facilitate airtightness in a cell culture device in which the lid is opened and closed.
  • a cell culture device includes a culture container including a plurality of storage sections each having an opening, a lid that is detachably attached to the culture container and covers the openings of the plurality of storage sections, and a lid that covers the openings of the plurality of storage sections. and a pneumatic pipe connected to either one of the lids, and a rubber sheet disposed between the culture container and the lid to ensure airtightness between the culture container and the lid, Either the culture container or the lid is provided with a linear seal protrusion that surrounds the openings of the plurality of reservoirs and projects toward the rubber sheet.
  • the seal protrusion may be provided on the culture container.
  • the lid may have a smooth surface to which the rubber sheet is in close contact.
  • the lid may have a plurality of positioning protrusions that position the rubber sheet on the smooth surface.
  • the plurality of positioning convex portions may be provided on both sides of the rubber sheet in the lateral direction and on one side of the rubber sheet in the longitudinal direction.
  • the culture container may include a plurality of positioning recesses into which the plurality of positioning convex parts are inserted.
  • the pneumatic piping may be connected to the lid.
  • the lid includes a plurality of grooves communicating with the pneumatic piping, and the rubber sheet communicates the plurality of grooves with the plurality of storage sections.
  • a plurality of communication holes may be provided.
  • the seal protrusion may be provided along an opening edge of each of the plurality of storage sections.
  • At least some of the seal protrusions provided along the opening edges of mutually adjacent storage parts among the plurality of storage parts may be shared. good.
  • the height/width ratio of the seal protrusion may be within a range of 0.5 to 10.
  • the rubber sheet may be made of silicone rubber.
  • the durometer hardness of the rubber sheet may be 50 or less.
  • airtightness can be easily maintained in a cell culture device in which the lid is opened and closed.
  • FIG. 2 is an exploded perspective view of the cell culture device shown in FIG. 1.
  • FIG. FIG. 2 is an exploded perspective view of the lid side of the cell culture device shown in FIG. 1.
  • FIG. 3 is an enlarged view of area A shown in FIG. 2.
  • FIG. FIG. 2 is a sectional view taken along the line VV shown in FIG. 1; It is a perspective view of the cell culture device concerning a 2nd embodiment.
  • FIG. 7 is an exploded perspective view of the cell culture device shown in FIG. 6. It is a top view of the culture container with which the cell culture apparatus shown in FIG. 7 is equipped. 9 is a sectional view taken along arrow IX-IX shown in FIG. 8.
  • FIG. 8 is a sectional view taken along arrow IX-IX shown in FIG. 8.
  • FIG. 1 is a perspective view of a cell culture device 1 according to the first embodiment.
  • FIG. 2 is an exploded perspective view of the cell culture device 1 shown in FIG. 1.
  • FIG. 3 is an exploded perspective view of the lid side of the cell culture apparatus 1 shown in FIG. 1.
  • FIG. 4 is an enlarged view of area A shown in FIG.
  • FIG. 5 is a sectional view taken along arrow VV shown in FIG.
  • the cell culture device 1 includes a culture container 2, a lid 3, a pneumatic pipe 4, and a rubber sheet 5.
  • the X-axis direction in the first embodiment is the first horizontal direction, and is the lateral direction of the cell culture device 1.
  • the Y-axis direction in the first embodiment is a second horizontal direction orthogonal to the first horizontal direction, and is the longitudinal direction of the cell culture device 1.
  • the Z-axis direction in the first embodiment is a vertical direction perpendicular to the first horizontal direction and the second horizontal direction, and is the height direction (thickness direction) of the cell culture device 1.
  • the culture container 2 includes a plurality of storage sections 21.
  • the storage section 21 stores a liquid, for example, a culture solution for culturing cells.
  • the storage section 21 is open to the top surface 20A of the culture container 2.
  • the storage portion 21 has a substantially rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the storage portions 21 are arranged in four rows and four columns on the XY plane. Note that the shape, number, and arrangement of the storage portions 21 are not limited to the above embodiments.
  • the culture container 2 includes an upper plate 2a and a bottom plate 2b.
  • the upper plate 2a can be manufactured, for example, by cutting polycarbonate.
  • the bottom plate 2b can be manufactured by cutting stainless steel, for example.
  • the upper plate 2a and the bottom plate 2b can also be manufactured by injection molding of thermoplastic resin such as polystyrene.
  • First fixing parts 6 for fixing the upper plate 2a to the upper part of the bottom plate 2b are provided on both sides of the bottom plate 2b in the X-axis direction.
  • the first fixing part 6 has a substantially C-shape extending in the Y-axis direction, and both ends thereof are fixed to the bottom plate 2b so as to be rotatable about an axis extending in the Y-axis direction.
  • First locking portions 8 that lock the first fixing portion 6 in the Z-axis direction are provided on both sides of the upper plate 2a in the X-axis direction.
  • the upper plate 2a and the bottom plate 2b are fixed by rotating the first fixing part 6 around the Y-axis and engaging the first locking part 8 located above.
  • the first locking portions 8 are provided as a pair at intervals in the Y-axis direction.
  • a gap 9 is formed between the pair of first locking parts 8 in which the lower edge of the lid 3 can be inserted. Thereby, the lid 3 can be removed and the cell culture device 1 can be easily transported.
  • second fixing parts 7 for fixing the lid 3 to the upper part of the upper plate 2a are provided on both sides of the bottom plate 2b in the X-axis direction.
  • the second fixing part 7 has a substantially C-shape extending in the Y-axis direction, and both ends thereof are fixed to the bottom plate 2b so as to be rotatable about an axis extending in the Y-axis direction.
  • the second fixing part 7 is slightly larger than the first fixing part 6.
  • Second locking portions 10 are provided on both sides of the lid 3 in the X-axis direction, with which the second fixing portion 7 locks in the Z-axis direction.
  • the lid 3 and the bottom plate 2b (culture container 2) are fixed by the second fixing part 7 rotating around the Y-axis and being engaged with the second engagement part 10 located above. Note that when removing the lid 3 from the culture container 2, the pair of second fixing parts 7 are rotated so as to open on both sides in the X-axis direction.
  • a channel plate 2c and a transparent plate 2d are sandwiched between the upper plate 2a and the bottom plate 2b.
  • the channel plate 2c can be manufactured, for example, by silicone resin replica molding, polystyrene injection molding, or the like.
  • the channel plate 2c is arranged under the upper plate 2a, and the transparent plate 2d is arranged below the channel plate 2c.
  • a through hole 14, a discharge channel 15, and an introduction channel 16 are formed in the channel plate 2c.
  • the transparent plate 2d is a transparent plate material such as a glass plate, an acrylic plate, a polystyrene plate, a silicone resin plate, or the like.
  • the through hole 14 is arranged at a position corresponding to the bottom surface of the storage section 21 formed in the upper plate 2a.
  • the lower end of the through hole 14 is closed by a transparent plate 2d.
  • a window 13 (opening) is formed in the bottom plate 2b at a position corresponding to the through hole 14. Thereby, the inside of the storage section 21 can be observed from the bottom side of the cell culture device 1 through the window section 13, the transparent plate 2d, and the through hole 14.
  • the discharge channel 15 is located near the through hole 14 and communicates with the bottom surface of the storage section 21 .
  • the introduction channel 16 communicates with a stepped portion higher than the bottom surface of the storage portion 21 .
  • the discharge channel 15 provided in any one of the reservoirs 21a to 21d arranged in the X-axis direction communicates with the introduction channel 16 of the other reservoir 21. ing.
  • two sets of storage parts 21a to 21d may be communicated with each other. All of the storage parts 21a to 21d may communicate in one cycle.
  • the pneumatic piping 4 includes pneumatic piping 4a to 4d that apply pneumatic pressure to the reservoirs 21a to 21d.
  • pneumatic piping 4a to 4d that apply pneumatic pressure to the reservoirs 21a to 21d.
  • a pneumatic pressure difference is created between the reservoirs 21, and the liquid stored in the reservoir 21 is supplied to the other reservoirs 21.
  • the fluid can then be circulated (perfused).
  • a thin Laplace valve 151 with a flow passage cross-sectional area of 0.1 [mm 2 ] or less is provided near the discharge passage 15, and the introduction passage 16 is one step higher than the bottom surface of the storage section 21. Since it communicates with the opening 70, backflow of liquid can be prevented when air pressure is applied.
  • the lid 3 includes a lid main body 3a and a cover 3b.
  • the cover 3b is a transparent plate material such as a glass plate or an acrylic plate.
  • the cover 3b is fixed to the upper part of the lid body 3a via a plurality of bolts 11.
  • the bolt 11 passes through any one of the plurality of through holes 12 formed in the cover 3b and is screwed into the lid body 3a.
  • the number of through holes 12 is greater than the number of bolts 11, but the number may be the same. Note that the lower end of the through hole 12 communicates with a bottomed screw hole (not shown) formed in the lid body 3a.
  • a connection hole 30a to which the pneumatic pipe 4 is connected is formed on one side (+Y side) in the longitudinal direction of the lid body 3a.
  • the lid body 3a includes a plurality of grooves 31 that communicate with the pneumatic piping 4.
  • the groove portion 31 opens to a smooth surface 30B on the lower surface of the lid main body 3a.
  • the upper surface 30A side of the lid main body 3a of the groove portion 31 is closed by the cover 3b.
  • a rubber sheet 3c similar to the rubber sheet 5 described later is sandwiched between the lid body 3a and the cover 3b to maintain airtightness.
  • the groove portion 31 has a substantially rectangular shape when viewed from the bottom, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the groove portions 31 are provided in four rows and four columns, the same number as the storage portions 21, on the XY plane. Note that the shape, number, and arrangement of the groove portions 31 are not limited to the above embodiments as long as they correspond to the shape, number, and arrangement of the storage portion 21.
  • grooves 31 that are adjacent to each other in the longitudinal direction (Y-axis direction) of the lid body 3a communicate with each other through a through hole 32 formed in the lid body 3a.
  • the through holes 32 penetrate in the Y-axis direction through the side walls of the groove portions 31 that are adjacent to each other in the Y-axis direction.
  • the pneumatic pipes 4a to 4d are capable of applying pneumatic pressure to each row of the grooves 31a to 31d.
  • the rubber sheet 5 is interposed between the culture container 2 and the lid 3 to ensure airtightness between the culture container 2 and the lid 3.
  • the rubber sheet 5 has a rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the upper surface 50A and lower surface 50B of the rubber sheet 5 are both smooth surfaces.
  • the upper surface 50A of the rubber sheet 5 is in close contact with the smooth surface 30B of the lid 3 shown in FIG. In other words, the rubber sheet 5 is brought into close contact with the lid 3 due to van der Waals force.
  • the rubber sheet 5 is made of silicone rubber, for example. Note that the rubber sheet 5 may be made of rubber other than silicone rubber.
  • the durometer hardness of the rubber sheet 5 is preferably 50 or less. Here, the durometer hardness of the rubber sheet 5 is based on durometer type A of K6253 of the JIS standard.
  • the thickness T (see FIG. 2) of the rubber sheet 5 is preferably larger than the height H (see FIG. 4) of the seal protrusion 60, which will be described later. On the other hand, if the thickness T of the rubber sheet 5 is too large, the operability of the cell culture device will be impaired. Specifically, the thickness T of the rubber sheet 5 is preferably within the range of 1 to 10 [mm].
  • the rubber sheet 5 includes a plurality of communication holes 51 that allow the plurality of grooves 31 provided in the lid 3 and the plurality of reservoirs 21 provided in the culture container 2 to communicate with each other.
  • the communication hole 51 penetrates the rubber sheet 5 in the Z-axis direction.
  • the communication hole 51 has a substantially rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the communication holes 51 are provided in four rows and four columns, the same number as the groove portions 31 and storage portions 21, on the XY plane. Note that the shape, number, and arrangement of the communicating holes 51 are not limited to the above embodiments as long as they correspond to the shape, number, and arrangement of the groove portion 31 and the storage portion 21.
  • the lid 3 has a plurality of positioning protrusions 33 that position the rubber sheet 5 on the smooth surface 30B. This allows the grooves 31a to 31d and the communication holes 51a to 51d to be aligned.
  • the positioning convex portions 33 are provided at three locations in total: on both sides of the rubber sheet 5 in the transverse direction (X-axis direction) and on one side (+Y side) of the rubber sheet 5 in the longitudinal direction.
  • the positioning convex portions 33 are adjacent to both sides in the transverse direction (X-axis direction) and one side in the longitudinal direction (+Y side) with respect to the outer shape of the rubber sheet 5.
  • the positioning convex portion 33 protrudes downward from the smooth surface 30B.
  • the length from the smooth surface 30B to the lower end of the positioning convex portion 33 is greater than the thickness T of the rubber sheet 5.
  • the culture container 2 includes a plurality of positioning recesses 22 into which a plurality of positioning protrusions 33 are inserted.
  • the positioning recesses 22 are provided at three locations in total: on both sides of the culture container 2 in the transverse direction (X-axis direction) and on one side (+Y side) of the culture container 2 in the longitudinal direction.
  • the culture container 2 is provided with a linear seal protrusion 60 that surrounds the openings of the plurality of reservoirs 21 and projects from the top surface 20A toward the rubber sheet 5.
  • the seal protrusion 60 is provided along the opening edge of each of the plurality of reservoirs 21 .
  • the seal protrusion 60 has a generally rectangular ring shape that is one size larger than the storage portion 21 in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the seal protrusion 60 has a pair of short sides 61 extending parallel to the X-axis direction, a pair of long sides 62 extending parallel to the Y-axis direction, and an end of the pair of short sides 61 and a pair of long sides. 62, and four corner portions 63 connecting the ends of the four corners.
  • the corner portion 63 is curved in an arc shape when viewed from above.
  • the tip of the seal protrusion 60 is formed into a flat shape. Note that the tip of the seal protrusion 60 may be upwardly convex and formed into a substantially semicircular shape when viewed in cross section as shown in FIG. 5 . As shown in FIG. 4, at least some of the seal protrusions 60 provided along the opening edges of adjacent reservoirs 21 among the plurality of reservoirs 21 are shared. Specifically, in FIG. 4, the seal protrusion 60 of the reservoir 21d located at the corner of the culture container 2 has a short side 61 on the +Y side and a long side 62 on the -X side, which are the seals of the adjacent reservoir 21. The short side 61 or the long side 62 of the protrusion 60 is shared.
  • the height/width ratio of the seal protrusion 60 is preferably within the range of 0.5 to 10. Specifically, when the width W of the seal projection 60 is 1.0 [mm], the height H of the seal projection 60 is preferably within the range of 0.5 to 10 [mm]. Note that the height/width ratio of the seal protrusion 60 is preferably the same even in the common portion. Thereby, the amount of elastic deformation of the rubber sheet 5 becomes uniform in each storage section 21, and the airtightness is improved. Furthermore, a substantially diamond-shaped space 64 is formed in the culture container 2 and surrounded by the corners 63 of the seal protrusions 60 of the four adjacent storage sections 21 . The space 64 has a spatial volume such that the amount of elastic deformation of the rubber sheet 5 in the inner region and the outer region of each of the four seal protrusions 60 where the corner portions 63 are adjacent to each other is the same.
  • the culture container 2 including the plurality of storage parts 21 is provided with the culture container 2 and a lid 3 covering the culture container 2.
  • a rubber sheet 5 is arranged between the culture container 2 and the lid 3 to ensure airtightness of the plurality of reservoirs 21.
  • the airtightness of the plurality of storage parts 21 can be ensured with one member, so assembly is easy, and by adjusting the thickness T of the rubber sheet 5 and the height H of the seal protrusion 60, It is possible to easily ensure airtightness by absorbing dimensional errors in the culture container 2 and lid 3.
  • the cell culture device 1 includes a culture container 2 including a plurality of storage sections 21 having openings, and a culture container 2 that is removably attached to the culture container 2 and has a plurality of storage sections 21 having openings.
  • a covering lid 3 a pneumatic pipe 4 connected to either one of the culture container 2 or the lid 3 (the lid 3 in this embodiment), and a pneumatic pipe 4 that is arranged between the culture container 2 and the lid 3 and is connected to the culture container 2 and the lid 3.
  • a rubber sheet 5 that secures airtightness between the culture container 2 and the lid 3 is provided, and a linear shape that surrounds the openings of the plurality of reservoirs 21 and protrudes toward the rubber sheet 5 is provided on either the culture container 2 or the lid 3.
  • a seal protrusion 60 is provided. According to this configuration, airtightness can be easily maintained in the cell culture apparatus 1 that opens and closes the lid 3.
  • the seal protrusion 60 is provided on the culture container 2, and the lid 3 has a smooth surface 30B to which the rubber sheet 5 is in close contact.
  • the rubber sheet 5 comes into close contact with the lid 3 side instead of the culture container 2.
  • the rubber sheet 5 can be removed together with the lid 3, and the rubber sheet 5 can be prevented from falling off due to its close contact with the lid 3.
  • the rubber sheet 5 is in close contact with the upper surface 20A of the culture container 2 when replenishing the liquid into the reservoir 21 after removing the lid 3, the liquid may leak into the gap between the rubber sheet 5 and the culture container 2. It is undesirable if it gets into the water because it can cause contamination. Furthermore, the liquid that has entered the gap may deteriorate and affect cell culture. According to this configuration, the above concerns can be eliminated.
  • the lid 3 has a plurality of positioning protrusions 33 that position the rubber sheet 5 on the smooth surface 30B. According to this configuration, it becomes easy to position the rubber sheet 5 on the smooth surface 30B of the lid 3.
  • the plurality of positioning convex portions 33 are provided on both sides of the rubber sheet 5 in the lateral direction and on one side of the rubber sheet 5 in the longitudinal direction.
  • the culture container 2 includes a plurality of positioning recesses 22 into which a plurality of positioning convex parts 33 are inserted. According to this configuration, by utilizing the positioning structure of the rubber sheet 5, it is possible to prevent the lid 3 from being assembled in the opposite direction to the culture container 2 (for example, the assembly where the pneumatic piping 4 is oriented in the opposite direction in the Y-axis direction). can. Thereby, air pressure can be applied to the storage section 21 as designed under predetermined conditions.
  • the pneumatic pipe 4 is connected to the lid 3. Further, the lid 3 includes a plurality of grooves 31 that communicate with the pneumatic piping 4, and the rubber sheet 5 includes a plurality of communication holes 51 that allow the plurality of grooves 31 and the plurality of storage sections 21 to communicate with each other.
  • the pneumatic piping 4 is arranged at a higher position than the storage section 21, even if air bubbles are mixed in during circulation (perfusion) of the culture solution and the liquid in the storage section 21 becomes foamy. Also, it is possible to suppress the bubbles from entering the pneumatic piping 4. Thereby, air pressure can be applied to the storage section 21 as designed under predetermined conditions.
  • the pneumatic pipe 4 may be connected to the culture container 2.
  • the seal protrusion 60 is provided along the opening edge of each of the plurality of storage parts 21. Further, among the plurality of storage sections 21, at least some of the seal protrusions 60 provided along the opening edges of mutually adjacent storage sections 21 are shared. According to this configuration, the storage sections 21 can be arranged in the culture container 2 in a space-saving manner, and the airtightness in each storage section 21 can be ensured uniformly.
  • the height/width ratio of the seal protrusion 60 is within the range of 0.5 to 10. According to this configuration, the effect of ensuring airtightness and preventing the rubber sheet 5 from falling off is high, and sufficient physical strength of the seal protrusion can be ensured.
  • the height H of the seal protrusion 60 is set to 0.3 [mm] or more, dimensional errors in the lid 3 and the culture container 2 can be absorbed to ensure better airtightness.
  • the width W of the seal protrusion 60 is set to 2.0 [mm] or less, the effect of ensuring airtightness and preventing the rubber sheet from falling off is high.
  • the rubber sheet 5 is made of silicone rubber, and when its durometer hardness is 50 or less, the effect of ensuring airtightness and preventing the rubber sheet from falling off becomes higher.
  • FIG. 6 is a perspective view of the cell culture device 1 according to the second embodiment.
  • FIG. 7 is an exploded perspective view of the cell culture device 1 shown in FIG. 6.
  • FIG. 8 is a plan view of the culture container 2 included in the cell culture apparatus 1 shown in FIG. 7.
  • FIG. 9 is a sectional view taken along arrow IX-IX shown in FIG.
  • the cell culture device 1 of the second embodiment differs from the above embodiments in that a hydrogel chamber 110 is provided between the pair of reservoirs 21a and 21b of the culture container 2.
  • the X-axis direction is the first horizontal direction in which the storage section 21a, the hydrogel chamber 110, and the storage section 21b are lined up.
  • the Y-axis direction is a second horizontal direction orthogonal to the X-axis direction.
  • the Z-axis direction is a vertical direction orthogonal to the X-axis direction and the Y-axis direction.
  • FIG. 6 in order to improve the visibility of the internal structure of the cell culture device 1, the external shapes of the culture container 2, lid 3, and rubber sheet 5 are shown with two-dot chain lines, and the internal structure is seen through.
  • the culture container 2 and lid 3 are preferably made of a highly translucent transparent material for purposes such as cell observation.
  • the culture container 2 and the lid 3 may be formed of a material with low translucency or no translucency. In that case, a glass window or the like may be provided at a position where the cells can be visually recognized.
  • the cell culture device 1 of the second embodiment can be manufactured, for example, by injection molding of polystyrene and heat fusion.
  • the hydrogel chamber 110 has a flat internal space.
  • the height (dimension in the Z-axis direction) of the internal space of the hydrogel 101 is, for example, within the range of 100 [ ⁇ m] to 500 [ ⁇ m].
  • the internal space of the hydrogel chamber 110 is filled with hydrogel 101.
  • the hydrogel 101 has a three-dimensional polymeric network structure and retains water, embeds or adheres cells, and cultivates the cells.
  • the hydrogel chamber 110 is formed into a hexagonal shape in plan view.
  • the shape of the hydrogel chamber 110 in plan view is not particularly limited, but the length (dimension in the Y-axis direction) adjacent to the storage part 21a and the storage part 21b is preferably larger than the width (dimension in the X-axis direction).
  • the dimension of the hydrogel chamber 110 in the Y-axis direction is, for example, within a range of 1 [mm] to 20 [mm].
  • the dimension of the hydrogel chamber 110 in the X-axis direction is, for example, within a range of 0.5 [mm] to 10 [mm].
  • the hydrogel chamber 110 has a first surface that communicates with the storage section 21a and a second surface that communicates with the storage section 21b.
  • the first surface and the second surface face each other in the X-axis direction and extend parallel to each other in the Y-axis direction. Both ends of the hydrogel chamber 110 in the Y-axis direction communicate with the introduction hole 114.
  • a hydrogel storage tank 116 into which the hydrogel 101 is introduced is formed directly above the hydrogel chamber 110.
  • the introduction hole 114 communicates both ends of the hydrogel chamber 110 in the Y-axis direction with the bottom surface of the hydrogel storage tank 116.
  • the two introduction holes 114 facilitate removing air from the hydrogel chamber 110 and filling the hydrogel chamber 110 with the hydrogel 101 from the hydrogel storage tank 116.
  • the storage section 21a stores the culture solution 102.
  • the storage portion 21a is formed in the shape of a long hole or an ellipse extending in the Y-axis direction when viewed from above. Note that the shape of the storage portion 21a in plan view is not particularly limited. It is preferable that the storage section 21a has a larger internal space (volume) than the hydrogel chamber 110. A side surface on the hydrogel chamber 110 side (+X side) at the bottom of the storage section 21a communicates with the hydrogel chamber 110.
  • the storage section 21b stores the culture solution 102.
  • the storage portion 21b is formed in the shape of a long hole or an ellipse extending in the Y-axis direction when viewed from above. Note that the planar shape of the storage portion 21b is not particularly limited. It is preferable that the storage section 21b also has a larger internal space (volume) than the hydrogel chamber 110.
  • the side surface of the bottom of the storage portion 21b on the hydrogel chamber 110 side (-X side) communicates with the hydrogel chamber 110.
  • the culture container 2 is equipped with strut rows 122 and 132 as a mechanism for retaining the hydrogel 101 in the hydrogel chamber 110 even when a pressure difference is generated between the reservoirs 21a and 21b.
  • the column array 122 forms a micro-sized fluid channel that communicates the hydrogel chamber 110 with the reservoir 21a.
  • the column row 132 forms a micro-sized fluid channel that communicates the hydrogel chamber 110 with the storage section 21b.
  • the rubber sheet 5 is interposed between the culture container 2 and the lid 3 to ensure airtightness between the culture container 2 and the lid 3.
  • the rubber sheet 5 has a rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction.
  • the upper surface 50A and lower surface 50B of the rubber sheet 5 are both smooth surfaces.
  • the upper surface 50A of the rubber sheet 5 is in close contact with the smooth surface 30B of the lid 3. In other words, the rubber sheet 5 is brought into close contact with the lid 3 due to van der Waals force.
  • the rubber sheet 5 includes communication holes 51a, 51b that allow the grooves 31a, 31b provided in the lid 3 to communicate with the reservoirs 21a, 21b provided in the culture container 2. Note that the rubber sheet 5 includes a second communication hole 53 that communicates with the hydrogel storage tank 116 between the communication holes 51a and 51b.
  • the culture container 2 is provided with a linear seal protrusion 60 that surrounds the openings of the plurality of reservoirs 21 and projects from the top surface 20A toward the rubber sheet 5.
  • the seal protrusion 60 is provided along the opening edge of each of the storage parts 21a, 21b and the hydrogel storage tank 116. At least some of the adjacent seal protrusions 60 of the storage parts 21a, 21b and the hydrogel storage tank 116 are shared.
  • the culture container 2 including the storage portions 21a and 21b is provided with the culture container 2 and a lid 3 covering the culture container 2 in order to simultaneously ensure airtightness of the storage portions 21a and 21b.
  • a rubber sheet 5 is arranged between the culture container 2 and the lid 3 to ensure airtightness of the plurality of reservoirs 21.
  • the airtightness of the plurality of storage parts 21 can be ensured with one member, so assembly is easy, and by adjusting the thickness T of the rubber sheet 5 and the height H of the seal protrusion 60, It is possible to easily ensure airtightness by absorbing dimensional errors in the culture container 2 and lid 3.
  • the culture solution 102 is stored in the storage section 21a and the storage section 21b adjacent to the hydrogel chamber 110, and by applying air pressure to the stored culture solution 102.
  • cells can be cultured by infiltrating the hydrogel 101 with a culture solution 102.
  • the lid 3 connected to the pneumatic piping 4 is fixed to the culture container 2, and cells (e.g., vascular endothelial cells) are cultured while the culture solution 102 is infiltrated into the hydrogel 101 using air pressure. Formation of cellular tissue within the gel 101 can be promoted.

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Abstract

This cell culture device comprises: a culture container equipped with a plurality of reservoirs having openings; a lid detachably attached to the culture container to cover the openings of the plurality of reservoirs; a pneumatic piping connected to either the culture container or the lid; and a rubber sheet placed between the culture container and the lid to ensure airtightness between the culture container and the lid. A linear sealing projection, which surrounds the openings of the plurality of reservoirs and projects toward the rubber sheet, is provided in either the culture container or the lid.

Description

細胞培養装置Cell culture device
　本発明は、細胞培養装置に関するものである。
　本願は、２０２２年７月２９日に、日本に出願された特願２０２２－１２１９９０号に基づき優先権を主張し、その内容をここに援用する。 The present invention relates to a cell culture device.
This application claims priority based on Japanese Patent Application No. 2022-121990 filed in Japan on July 29, 2022, the contents of which are incorporated herein.
　下記特許文献１には、細胞培養装置が開示されている。この細胞培養装置は、貯留槽と、加圧ポンプと、を備えている。貯留槽は、容器状の槽本体と、蓋部と、を備えている。蓋部は、槽本体の開口を開閉自在かつ気密に閉止可能である。蓋部は、槽本体の第１培養液貯留室および第２培養液貯留室の上部開口をそれぞれ気密に閉止可能である。蓋部は、上部開口のそれぞれを包囲するように与えられたパッキンを介して槽本体の上面に当接している。 Patent Document 1 below discloses a cell culture device. This cell culture device includes a storage tank and a pressure pump. The storage tank includes a container-shaped tank body and a lid. The lid part can open and close the opening of the tank body and can airtightly close the opening. The lid portion is capable of airtightly closing the upper openings of the first culture solution storage chamber and the second culture solution storage chamber of the tank body. The lid portion is in contact with the upper surface of the tank body through packing provided so as to surround each of the upper openings.
特許第６８２３７９２号公報Patent No. 6823792
　上記のような細胞培養装置を用いて細胞を培養する際には、定期的な培養液の交換が必要となる。培養液の交換を行う際には、細胞培養装置の蓋を開閉する。この際に、上記パッキン等のシール材が脱落する虞がある。また、従来のシール材は、複数の貯留部のそれぞれの上部開口を包囲するように多数配置されている。このため、細胞培養装置は、部品点数が多く、組み立てが煩雑である。さらに、培養容器と蓋との寸法誤差が大きいと、個々のシール材の弾性変形でその寸法誤差を吸収できない場合があり、気密の保持に問題が生じることがある。 When culturing cells using a cell culture device such as the one described above, it is necessary to periodically replace the culture medium. When replacing the culture solution, open and close the lid of the cell culture device. At this time, there is a possibility that the sealing material such as the packing may fall off. Further, a large number of conventional sealing materials are arranged so as to surround the upper openings of each of the plurality of storage sections. Therefore, the cell culture device has a large number of parts and is complicated to assemble. Furthermore, if the dimensional error between the culture container and the lid is large, the dimensional error may not be absorbed by the elastic deformation of the individual sealing materials, which may cause problems in maintaining airtightness.
　本発明は、上記問題点に鑑みてなされたものであり、蓋を開閉する細胞培養装置において気密保持を容易にすることを目的とする。 The present invention has been made in view of the above problems, and aims to facilitate airtightness in a cell culture device in which the lid is opened and closed.
　本発明の一態様に係る細胞培養装置は、開口を有する複数の貯留部を備える培養容器と、前記培養容器に着脱可能に装着され、前記複数の貯留部の開口を覆う蓋と、前記培養容器及び前記蓋のいずれか一方に接続された空圧配管と、前記培養容器と前記蓋との間に配置され、前記培養容器と前記蓋との間の気密を確保するラバーシートと、を備え、前記培養容器及び前記蓋のいずれか一方に、前記複数の貯留部の開口を囲い、前記ラバーシートに向かって突出する線状のシール突起が設けられている。 A cell culture device according to one aspect of the present invention includes a culture container including a plurality of storage sections each having an opening, a lid that is detachably attached to the culture container and covers the openings of the plurality of storage sections, and a lid that covers the openings of the plurality of storage sections. and a pneumatic pipe connected to either one of the lids, and a rubber sheet disposed between the culture container and the lid to ensure airtightness between the culture container and the lid, Either the culture container or the lid is provided with a linear seal protrusion that surrounds the openings of the plurality of reservoirs and projects toward the rubber sheet.
　また、本発明の一態様に係る細胞培養装置において、前記シール突起は、前記培養容器に設けられていてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the seal protrusion may be provided on the culture container.
　また、本発明の一態様に係る細胞培養装置において、前記蓋は、前記ラバーシートが密着する平滑面を有してもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the lid may have a smooth surface to which the rubber sheet is in close contact.
　また、本発明の一態様に係る細胞培養装置において、前記蓋は、前記ラバーシートを前記平滑面に位置決めする複数の位置決め凸部を有してもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the lid may have a plurality of positioning protrusions that position the rubber sheet on the smooth surface.
　また、本発明の一態様に係る細胞培養装置において、前記複数の位置決め凸部は、前記ラバーシートの短手方向の両側と、前記ラバーシートの長手方向の片側に設けられていてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the plurality of positioning convex portions may be provided on both sides of the rubber sheet in the lateral direction and on one side of the rubber sheet in the longitudinal direction.
　また、本発明の一態様に係る細胞培養装置において、前記培養容器は、前記複数の位置決め凸部が挿入される複数の位置決め凹部を備えてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the culture container may include a plurality of positioning recesses into which the plurality of positioning convex parts are inserted.
　また、本発明の一態様に係る細胞培養装置において、前記空圧配管は、前記蓋に接続されていてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the pneumatic piping may be connected to the lid.
　また、本発明の一態様に係る細胞培養装置において、前記蓋は、前記空圧配管と連通する複数の溝部を備え、前記ラバーシートは、前記複数の溝部と前記複数の貯留部とを連通させる複数の連通孔を備えてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the lid includes a plurality of grooves communicating with the pneumatic piping, and the rubber sheet communicates the plurality of grooves with the plurality of storage sections. A plurality of communication holes may be provided.
　また、本発明の一態様に係る細胞培養装置において、前記シール突起は、前記複数の貯留部のそれぞれの開口縁に沿って設けられていてもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the seal protrusion may be provided along an opening edge of each of the plurality of storage sections.
　また、本発明の一態様に係る細胞培養装置において、前記複数の貯留部のうち、互いに隣接する貯留部の開口縁に沿って設けられる前記シール突起の少なくとも一部は、共通化されていてもよい。 Further, in the cell culture device according to one aspect of the present invention, at least some of the seal protrusions provided along the opening edges of mutually adjacent storage parts among the plurality of storage parts may be shared. good.
　また、本発明の一態様に係る細胞培養装置において、前記シール突起の高さ／幅の比率が、０．５～１０の範囲内であってもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the height/width ratio of the seal protrusion may be within a range of 0.5 to 10.
　また、本発明の一態様に係る細胞培養装置において、前記ラバーシートは、シリコーンゴム製であってもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the rubber sheet may be made of silicone rubber.
　また、本発明の一態様に係る細胞培養装置において、前記ラバーシートのデュロメータ硬さは、５０以下であってもよい。 Furthermore, in the cell culture device according to one aspect of the present invention, the durometer hardness of the rubber sheet may be 50 or less.
　上記本発明の一態様によれば、蓋を開閉する細胞培養装置において気密保持を容易にすることができる。 According to one aspect of the present invention, airtightness can be easily maintained in a cell culture device in which the lid is opened and closed.
第１実施形態に係る細胞培養装置を示す斜視図である。It is a perspective view showing a cell culture device concerning a 1st embodiment. 図１に示す細胞培養装置の分解斜視図である。FIG. 2 is an exploded perspective view of the cell culture device shown in FIG. 1. FIG. 図１に示す細胞培養装置が備える蓋側の分解斜視図である。FIG. 2 is an exploded perspective view of the lid side of the cell culture device shown in FIG. 1. FIG. 図２に示す領域Ａの拡大図である。3 is an enlarged view of area A shown in FIG. 2. FIG. 図１に示す矢視Ｖ－Ｖ断面図である。FIG. 2 is a sectional view taken along the line VV shown in FIG. 1; 第２実施形態に係る細胞培養装置の斜視図である。It is a perspective view of the cell culture device concerning a 2nd embodiment. 図６に示す細胞培養装置の分解斜視図である。FIG. 7 is an exploded perspective view of the cell culture device shown in FIG. 6. 図７に示す細胞培養装置が備える培養容器の平面図である。It is a top view of the culture container with which the cell culture apparatus shown in FIG. 7 is equipped. 図８に示す矢視ＩＸ－ＩＸ断面図である。9 is a sectional view taken along arrow IX-IX shown in FIG. 8. FIG.
　以下、本発明の各実施形態について図面を参照して説明する。なお、数値範囲を示す「～」は、その前後に記載された数値を下限値及び上限値として含むことを意味する。 Hereinafter, each embodiment of the present invention will be described with reference to the drawings. Note that "~" indicating a numerical range means that the numerical values written before and after it are included as the lower limit and upper limit.
　（第１実施形態）
　図１は、第１実施形態に係る細胞培養装置１の斜視図である。図２は、図１に示す細胞培養装置１の分解斜視図である。図３は、図１に示す細胞培養装置１が備える蓋側の分解斜視図である。図４は、図２に示す領域Ａの拡大図である。図５は、図１に示す矢視Ｖ－Ｖ断面図である。
　図１及び図２に示すように、細胞培養装置１は、培養容器２と、蓋３と、空圧配管４と、ラバーシート５と、を備えている。 (First embodiment)
FIG. 1 is a perspective view of a cell culture device 1 according to the first embodiment. FIG. 2 is an exploded perspective view of the cell culture device 1 shown in FIG. 1. FIG. 3 is an exploded perspective view of the lid side of the cell culture apparatus 1 shown in FIG. 1. FIG. 4 is an enlarged view of area A shown in FIG. FIG. 5 is a sectional view taken along arrow VV shown in FIG.
As shown in FIGS. 1 and 2, the cell culture device 1 includes a culture container 2, a lid 3, a pneumatic pipe 4, and a rubber sheet 5.
　なお、以下の説明において、ＸＹＺ直交座標系を設定し、このＸＹＺ直交座標系を参照しつつ各構成の位置関係について説明することがある。第１実施形態のＸ軸方向は、第１の水平方向であって、細胞培養装置１の短手方向である。第１実施形態のＹ軸方向は、第１の水平方向と直交する第２の水平方向であって、細胞培養装置１の長手方向である。第１実施形態のＺ軸方向は、第１の水平方向及び第２の水平方向と直交する鉛直方向であって、細胞培養装置１の高さ方向（厚み方向）である。 In the following description, an XYZ orthogonal coordinate system is set, and the positional relationship of each component may be explained with reference to this XYZ orthogonal coordinate system. The X-axis direction in the first embodiment is the first horizontal direction, and is the lateral direction of the cell culture device 1. The Y-axis direction in the first embodiment is a second horizontal direction orthogonal to the first horizontal direction, and is the longitudinal direction of the cell culture device 1. The Z-axis direction in the first embodiment is a vertical direction perpendicular to the first horizontal direction and the second horizontal direction, and is the height direction (thickness direction) of the cell culture device 1.
　培養容器２は、図２に示すように、複数の貯留部２１を備えている。貯留部２１には、液体として、例えば細胞を培養する培養液が貯留される。貯留部２１は、培養容器２の上面２０Ａに開口している。貯留部２１は、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、平面視で略長方形状を有する。貯留部２１は、Ｘ－Ｙ平面において、４行×４列で設けられている。なお、貯留部２１の形状、個数及び配置は、上記態様に限定されない。 As shown in FIG. 2, the culture container 2 includes a plurality of storage sections 21. The storage section 21 stores a liquid, for example, a culture solution for culturing cells. The storage section 21 is open to the top surface 20A of the culture container 2. The storage portion 21 has a substantially rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction. The storage portions 21 are arranged in four rows and four columns on the XY plane. Note that the shape, number, and arrangement of the storage portions 21 are not limited to the above embodiments.
　培養容器２は、図１に示すように、アッパープレート２ａと、ボトムプレート２ｂと、を備えている。アッパープレート２ａは、例えばポリカーボネートの切削加工によって製造することができる。また、ボトムプレート２ｂは、例えばステンレスの切削加工により製造することができる。なお、アッパープレート２ａおよびボトムプレート２ｂは、ポリスチレン等の熱可塑性樹脂の射出成型によって製造することもできる。ボトムプレート２ｂのＸ軸方向両側には、ボトムプレート２ｂの上部にアッパープレート２ａを固定する第１の固定部６が設けられている。第１の固定部６は、Ｙ軸方向に延びる略Ｃ字状を有し、その両端がボトムプレート２ｂに対しＹ軸方向に延びる軸回りに回転自在に固定されている。 As shown in FIG. 1, the culture container 2 includes an upper plate 2a and a bottom plate 2b. The upper plate 2a can be manufactured, for example, by cutting polycarbonate. Further, the bottom plate 2b can be manufactured by cutting stainless steel, for example. Note that the upper plate 2a and the bottom plate 2b can also be manufactured by injection molding of thermoplastic resin such as polystyrene. First fixing parts 6 for fixing the upper plate 2a to the upper part of the bottom plate 2b are provided on both sides of the bottom plate 2b in the X-axis direction. The first fixing part 6 has a substantially C-shape extending in the Y-axis direction, and both ends thereof are fixed to the bottom plate 2b so as to be rotatable about an axis extending in the Y-axis direction.
　アッパープレート２ａのＸ軸方向両側には、第１の固定部６がＺ軸方向で係止する第１の係止部８が設けられている。第１の固定部６がＹ軸回りに回転し、上方に位置する第１の係止部８に係止することで、アッパープレート２ａとボトムプレート２ｂとが固定される。第１の係止部８は、Ｙ軸方向に間隔をあけて一対で設けられている。一対の第１の係止部８の間には、蓋３の下縁に手先を入れることができる隙間９が形成されている。これにより、蓋３の取り外しができ、また、細胞培養装置１の搬送が容易になる。 First locking portions 8 that lock the first fixing portion 6 in the Z-axis direction are provided on both sides of the upper plate 2a in the X-axis direction. The upper plate 2a and the bottom plate 2b are fixed by rotating the first fixing part 6 around the Y-axis and engaging the first locking part 8 located above. The first locking portions 8 are provided as a pair at intervals in the Y-axis direction. A gap 9 is formed between the pair of first locking parts 8 in which the lower edge of the lid 3 can be inserted. Thereby, the lid 3 can be removed and the cell culture device 1 can be easily transported.
　また、ボトムプレート２ｂのＸ軸方向両側には、アッパープレート２ａの上部に蓋３を固定する第２の固定部７が設けられている。第２の固定部７は、Ｙ軸方向に延びる略Ｃ字状を有し、その両端がボトムプレート２ｂに対しＹ軸方向に延びる軸回りに回転自在に固定されている。第２の固定部７は、第１の固定部６よりも一回り大きい。 Further, second fixing parts 7 for fixing the lid 3 to the upper part of the upper plate 2a are provided on both sides of the bottom plate 2b in the X-axis direction. The second fixing part 7 has a substantially C-shape extending in the Y-axis direction, and both ends thereof are fixed to the bottom plate 2b so as to be rotatable about an axis extending in the Y-axis direction. The second fixing part 7 is slightly larger than the first fixing part 6.
　蓋３のＸ軸方向両側には、第２の固定部７がＺ軸方向で係止する第２の係止部１０が設けられている。第２の固定部７がＹ軸回りに回転し、上方に位置する第２の係止部１０に係止することで、蓋３とボトムプレート２ｂ（培養容器２）とが固定される。なお、培養容器２から蓋３を取り外すときは、一対の第２の固定部７をＸ軸方向両側に開くように回動させる。 Second locking portions 10 are provided on both sides of the lid 3 in the X-axis direction, with which the second fixing portion 7 locks in the Z-axis direction. The lid 3 and the bottom plate 2b (culture container 2) are fixed by the second fixing part 7 rotating around the Y-axis and being engaged with the second engagement part 10 located above. Note that when removing the lid 3 from the culture container 2, the pair of second fixing parts 7 are rotated so as to open on both sides in the X-axis direction.
　図５に示すように、アッパープレート２ａとボトムプレート２ｂとの間には、流路プレート２ｃと、透明プレート２ｄと、が挟持されている。流路プレート２ｃは、例えばシリコーン樹脂のレプリカモールディングやポリスチレンの射出成型等によって製造することができる。流路プレート２ｃは、アッパープレート２ａの下に配置され、透明プレート２ｄは、流路プレート２ｃの下に配置されている。流路プレート２ｃには、貫通孔１４と、排出流路１５と、導入流路１６と、が形成されている。透明プレート２ｄは、ガラス板や、アクリル板、ポリスチレン板、シリコーン樹脂板等の透明な板材である。 As shown in FIG. 5, a channel plate 2c and a transparent plate 2d are sandwiched between the upper plate 2a and the bottom plate 2b. The channel plate 2c can be manufactured, for example, by silicone resin replica molding, polystyrene injection molding, or the like. The channel plate 2c is arranged under the upper plate 2a, and the transparent plate 2d is arranged below the channel plate 2c. A through hole 14, a discharge channel 15, and an introduction channel 16 are formed in the channel plate 2c. The transparent plate 2d is a transparent plate material such as a glass plate, an acrylic plate, a polystyrene plate, a silicone resin plate, or the like.
　貫通孔１４は、アッパープレート２ａに形成された貯留部２１の底面に対応する位置に配置されている。貫通孔１４の下端は、透明プレート２ｄによって閉塞されている。ボトムプレート２ｂには、貫通孔１４に対応する位置に窓部１３（開口部）が形成されている。これにより、細胞培養装置１の底面側から、窓部１３、透明プレート２ｄ、貫通孔１４を介して、貯留部２１の内部の様子を観察することができる。 The through hole 14 is arranged at a position corresponding to the bottom surface of the storage section 21 formed in the upper plate 2a. The lower end of the through hole 14 is closed by a transparent plate 2d. A window 13 (opening) is formed in the bottom plate 2b at a position corresponding to the through hole 14. Thereby, the inside of the storage section 21 can be observed from the bottom side of the cell culture device 1 through the window section 13, the transparent plate 2d, and the through hole 14.
　排出流路１５は、貫通孔１４の近傍であって、貯留部２１の底面に連通している。導入流路１６は、貯留部２１の底面よりも高い段差部分に連通している。図２に示すように、Ｘ軸方向で並ぶ貯留部２１ａ～２１ｄのうち、いずれか一つの貯留部２１に設けられた排出流路１５は、他の貯留部２１の導入流路１６に連通している。例えば、貯留部２１ａ～２１ｄが２組ずつ連通してもよいし。貯留部２１ａ～２１ｄの全てが一巡に連通してもよい。 The discharge channel 15 is located near the through hole 14 and communicates with the bottom surface of the storage section 21 . The introduction channel 16 communicates with a stepped portion higher than the bottom surface of the storage portion 21 . As shown in FIG. 2, the discharge channel 15 provided in any one of the reservoirs 21a to 21d arranged in the X-axis direction communicates with the introduction channel 16 of the other reservoir 21. ing. For example, two sets of storage parts 21a to 21d may be communicated with each other. All of the storage parts 21a to 21d may communicate in one cycle.
　空圧配管４は、貯留部２１ａ～２１ｄに空圧をかける空圧配管４ａ～４ｄを備えている。空圧配管４ａ～４ｄから貯留部２１ａ～２１ｄに選択的に空圧をかけることで、貯留部２１間に空圧差を生じさせ、貯留部２１に貯留された液体を他の貯留部２１に供給し、その液体を循環（灌流）させることができる。なお、排出流路１５の近傍には、流路断面積が０．１［ｍｍ２］以下の細いラプラス弁１５１が設けられており、導入流路１６は、貯留部２１の底面よりも一段高い開口部７０に連通しているため、空圧をかけたときに、液体の逆流を防止できる。 The pneumatic piping 4 includes pneumatic piping 4a to 4d that apply pneumatic pressure to the reservoirs 21a to 21d. By selectively applying pneumatic pressure to the reservoirs 21a to 21d from the pneumatic pipes 4a to 4d, a pneumatic pressure difference is created between the reservoirs 21, and the liquid stored in the reservoir 21 is supplied to the other reservoirs 21. The fluid can then be circulated (perfused). Note that a thin Laplace valve 151 with a flow passage cross-sectional area of 0.1 [mm 2 ] or less is provided near the discharge passage 15, and the introduction passage 16 is one step higher than the bottom surface of the storage section 21. Since it communicates with the opening 70, backflow of liquid can be prevented when air pressure is applied.
　蓋３は、図１に示すように、蓋本体３ａと、カバー３ｂと、を備えている。カバー３ｂは、ガラス板や、アクリル板等の透明な板材である。カバー３ｂは、蓋本体３ａの上部に複数のボルト１１を介して固定されている。ボルト１１は、カバー３ｂに形成された複数の貫通孔１２のいずれか一つを通って蓋本体３ａに螺合する。この例では、ボルト１１の数よりも、貫通孔１２の数の方が多いが、同数であってもよい。なお、貫通孔１２の下端は、蓋本体３ａに形成された図示しない有底のねじ孔に連通している。 As shown in FIG. 1, the lid 3 includes a lid main body 3a and a cover 3b. The cover 3b is a transparent plate material such as a glass plate or an acrylic plate. The cover 3b is fixed to the upper part of the lid body 3a via a plurality of bolts 11. The bolt 11 passes through any one of the plurality of through holes 12 formed in the cover 3b and is screwed into the lid body 3a. In this example, the number of through holes 12 is greater than the number of bolts 11, but the number may be the same. Note that the lower end of the through hole 12 communicates with a bottomed screw hole (not shown) formed in the lid body 3a.
　図３に示すように、蓋本体３ａの長手方向の片側（＋Ｙ側）の側面には、空圧配管４が接続される接続孔３０ａが形成されている。蓋本体３ａは、空圧配管４と連通する複数の溝部３１を備えている。溝部３１は、蓋本体３ａの下面の平滑面３０Ｂに開口している。なお、溝部３１の蓋本体３ａの上面３０Ａ側は、カバー３ｂによって閉塞されている。なお、蓋本体３ａとカバー３ｂとの間には、気密保持のため、図５に示すように、後述するラバーシート５と同様のラバーシート３ｃが挟持されている。 As shown in FIG. 3, a connection hole 30a to which the pneumatic pipe 4 is connected is formed on one side (+Y side) in the longitudinal direction of the lid body 3a. The lid body 3a includes a plurality of grooves 31 that communicate with the pneumatic piping 4. The groove portion 31 opens to a smooth surface 30B on the lower surface of the lid main body 3a. Note that the upper surface 30A side of the lid main body 3a of the groove portion 31 is closed by the cover 3b. Note that, as shown in FIG. 5, a rubber sheet 3c similar to the rubber sheet 5 described later is sandwiched between the lid body 3a and the cover 3b to maintain airtightness.
　溝部３１は、図３に示すように、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、底面視で略長方形状を有する。溝部３１は、Ｘ－Ｙ平面において、貯留部２１と同数の４行×４列で設けられている。なお、溝部３１の形状、個数及び配置は、貯留部２１の形状、個数及び配置に対応していれば、上記態様に限定されない。複数の溝部３１のうち、蓋本体３ａの長手方向（Ｙ軸方向）で隣り合う溝部３１同士は、蓋本体３ａに形成された貫通孔３２によって互いに連通している。貫通孔３２は、Ｙ軸方向で隣り合う溝部３１の側壁をＹ軸方向に貫通している。つまり、空圧配管４ａ～４ｄは、溝部３１ａ～３１ｄの列ごとに空圧をかけることができるようになっている。 As shown in FIG. 3, the groove portion 31 has a substantially rectangular shape when viewed from the bottom, with the X-axis direction being the short direction and the Y-axis direction being the long direction. The groove portions 31 are provided in four rows and four columns, the same number as the storage portions 21, on the XY plane. Note that the shape, number, and arrangement of the groove portions 31 are not limited to the above embodiments as long as they correspond to the shape, number, and arrangement of the storage portion 21. Among the plurality of grooves 31, grooves 31 that are adjacent to each other in the longitudinal direction (Y-axis direction) of the lid body 3a communicate with each other through a through hole 32 formed in the lid body 3a. The through holes 32 penetrate in the Y-axis direction through the side walls of the groove portions 31 that are adjacent to each other in the Y-axis direction. In other words, the pneumatic pipes 4a to 4d are capable of applying pneumatic pressure to each row of the grooves 31a to 31d.
　ラバーシート５は、図２に示すように、培養容器２と蓋３との間に介在し、培養容器２と蓋３との間の気密を確保する。ラバーシート５は、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、平面視で長方形状を有する。ラバーシート５の上面５０Ａ及び下面５０Ｂは、それぞれ平滑面となっている。ラバーシート５の上面５０Ａは、図３に示す蓋３の平滑面３０Ｂに密着する。つまり、ラバーシート５は、ファンデルワールス力により蓋３側に密着する。 As shown in FIG. 2, the rubber sheet 5 is interposed between the culture container 2 and the lid 3 to ensure airtightness between the culture container 2 and the lid 3. The rubber sheet 5 has a rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction. The upper surface 50A and lower surface 50B of the rubber sheet 5 are both smooth surfaces. The upper surface 50A of the rubber sheet 5 is in close contact with the smooth surface 30B of the lid 3 shown in FIG. In other words, the rubber sheet 5 is brought into close contact with the lid 3 due to van der Waals force.
　ラバーシート５は、例えば、シリコーンゴムから形成されている。なお、ラバーシート５は、シリコーンゴム以外のゴムであってもよい。ラバーシート５のデュロメータ硬さは、５０以下であるとよい。ここで、ラバーシート５のデュロメータ硬さとは、ＪＩＳ規格のＫ６２５３のデュロメータータイプＡに準拠する。ラバーシート５の厚みＴ（図２参照）は、後述するシール突起６０の高さＨ（図４参照）より大きいとよい。一方、ラバーシート５の厚みＴが大きすぎると細胞培養装置の操作性を損なってしまう。具体的に、ラバーシート５の厚みＴは、１～１０［ｍｍ］の範囲内が好ましい。 The rubber sheet 5 is made of silicone rubber, for example. Note that the rubber sheet 5 may be made of rubber other than silicone rubber. The durometer hardness of the rubber sheet 5 is preferably 50 or less. Here, the durometer hardness of the rubber sheet 5 is based on durometer type A of K6253 of the JIS standard. The thickness T (see FIG. 2) of the rubber sheet 5 is preferably larger than the height H (see FIG. 4) of the seal protrusion 60, which will be described later. On the other hand, if the thickness T of the rubber sheet 5 is too large, the operability of the cell culture device will be impaired. Specifically, the thickness T of the rubber sheet 5 is preferably within the range of 1 to 10 [mm].
　ラバーシート５は、蓋３に設けられた複数の溝部３１と、培養容器２に設けられた複数の貯留部２１と、を連通させる複数の連通孔５１を備えている。連通孔５１は、ラバーシート５をＺ軸方向に貫通している。連通孔５１は、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、平面視で略長方形状を有する。連通孔５１は、Ｘ－Ｙ平面において、溝部３１及び貯留部２１と同数の４行×４列で設けられている。なお、連通孔５１の形状、個数及び配置は、溝部３１及び貯留部２１の形状、個数及び配置に対応していれば、上記態様に限定されない。 The rubber sheet 5 includes a plurality of communication holes 51 that allow the plurality of grooves 31 provided in the lid 3 and the plurality of reservoirs 21 provided in the culture container 2 to communicate with each other. The communication hole 51 penetrates the rubber sheet 5 in the Z-axis direction. The communication hole 51 has a substantially rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction. The communication holes 51 are provided in four rows and four columns, the same number as the groove portions 31 and storage portions 21, on the XY plane. Note that the shape, number, and arrangement of the communicating holes 51 are not limited to the above embodiments as long as they correspond to the shape, number, and arrangement of the groove portion 31 and the storage portion 21.
　図３に示すように、蓋３は、ラバーシート５を平滑面３０Ｂに位置決めする複数の位置決め凸部３３を有する。これにより、溝部３１ａ～３１ｄと連通孔５１ａ～５１ｄとを位置合わせできる。位置決め凸部３３は、ラバーシート５の短手方向（Ｘ軸方向）の両側と、ラバーシート５の長手方向の片側（＋Ｙ側）の合計で３箇所に設けられている。蓋３にラバーシート５を配置する際に、ラバーシート５の外形に対して、位置決め凸部３３が短手方向（Ｘ軸方向）の両側と長手方向の片側（＋Ｙ側）に隣接する形でラバーシート５を配置することで、ラバーシート５のＸＹ平面上の配置を決定できる。位置決め凸部３３は、平滑面３０Ｂから下方に向けて突出している。平滑面３０Ｂから位置決め凸部３３の下端までの長さは、ラバーシート５の厚みＴより大きい。 As shown in FIG. 3, the lid 3 has a plurality of positioning protrusions 33 that position the rubber sheet 5 on the smooth surface 30B. This allows the grooves 31a to 31d and the communication holes 51a to 51d to be aligned. The positioning convex portions 33 are provided at three locations in total: on both sides of the rubber sheet 5 in the transverse direction (X-axis direction) and on one side (+Y side) of the rubber sheet 5 in the longitudinal direction. When placing the rubber sheet 5 on the lid 3, the positioning convex portions 33 are adjacent to both sides in the transverse direction (X-axis direction) and one side in the longitudinal direction (+Y side) with respect to the outer shape of the rubber sheet 5. By arranging the rubber sheet 5, the arrangement of the rubber sheet 5 on the XY plane can be determined. The positioning convex portion 33 protrudes downward from the smooth surface 30B. The length from the smooth surface 30B to the lower end of the positioning convex portion 33 is greater than the thickness T of the rubber sheet 5.
　図２に示すように、培養容器２は、複数の位置決め凸部３３が挿入される複数の位置決め凹部２２を備える。位置決め凹部２２は、培養容器２の短手方向（Ｘ軸方向）の両側と、培養容器２の長手方向の片側（＋Ｙ側）の合計で３箇所に設けられている。蓋３の下部に設けられた３つの位置決め凸部３３を、培養容器２の上部に設けられた３つの位置決め凹部２２に挿入することで、培養容器２に対する蓋３の逆組み（例えばＹ軸方向における空圧配管４の向きが逆となった組み付け）を防止することができる。 As shown in FIG. 2, the culture container 2 includes a plurality of positioning recesses 22 into which a plurality of positioning protrusions 33 are inserted. The positioning recesses 22 are provided at three locations in total: on both sides of the culture container 2 in the transverse direction (X-axis direction) and on one side (+Y side) of the culture container 2 in the longitudinal direction. By inserting the three positioning protrusions 33 provided at the bottom of the lid 3 into the three positioning recesses 22 provided at the top of the culture container 2, the lid 3 can be assembled in the opposite direction to the culture container 2 (for example, in the Y-axis direction). assembly in which the direction of the pneumatic piping 4 is reversed) can be prevented.
　図４に示すように、培養容器２には、複数の貯留部２１の開口を囲い、上面２０Ａからラバーシート５に向かって突出する線状のシール突起６０が設けられている。シール突起６０は、複数の貯留部２１のそれぞれの開口縁に沿って設けられている。シール突起６０は、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、平面視で、貯留部２１よりも一回り大きな略長方形の環形状を有する。具体的に、シール突起６０は、Ｘ軸方向に平行に延びる一対の短辺６１と、Ｙ軸方向に平行に延びる一対の長辺６２と、一対の短辺６１の端部と一対の長辺６２の端部とを接続する４つの角部６３と、を備えている。角部６３は、平面視で、円弧状に湾曲している。 As shown in FIG. 4, the culture container 2 is provided with a linear seal protrusion 60 that surrounds the openings of the plurality of reservoirs 21 and projects from the top surface 20A toward the rubber sheet 5. The seal protrusion 60 is provided along the opening edge of each of the plurality of reservoirs 21 . The seal protrusion 60 has a generally rectangular ring shape that is one size larger than the storage portion 21 in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction. Specifically, the seal protrusion 60 has a pair of short sides 61 extending parallel to the X-axis direction, a pair of long sides 62 extending parallel to the Y-axis direction, and an end of the pair of short sides 61 and a pair of long sides. 62, and four corner portions 63 connecting the ends of the four corners. The corner portion 63 is curved in an arc shape when viewed from above.
　シール突起６０の先端は、平面状に形成されている。なお、シール突起６０の先端は、上方に凸状となり、図５に示す断面視で略半円形状に形成されていてもよい。図４に示すように、複数の貯留部２１のうち、互いに隣接する貯留部２１の開口縁に沿って設けられるシール突起６０の少なくとも一部は、共通化されている。具体的に、図４中、培養容器２の角に位置する貯留部２１ｄのシール突起６０は、＋Ｙ側の短辺６１と、－Ｘ側の長辺６２とが、隣り合う貯留部２１のシール突起６０の短辺６１または長辺６２と共通化されている。 The tip of the seal protrusion 60 is formed into a flat shape. Note that the tip of the seal protrusion 60 may be upwardly convex and formed into a substantially semicircular shape when viewed in cross section as shown in FIG. 5 . As shown in FIG. 4, at least some of the seal protrusions 60 provided along the opening edges of adjacent reservoirs 21 among the plurality of reservoirs 21 are shared. Specifically, in FIG. 4, the seal protrusion 60 of the reservoir 21d located at the corner of the culture container 2 has a short side 61 on the +Y side and a long side 62 on the -X side, which are the seals of the adjacent reservoir 21. The short side 61 or the long side 62 of the protrusion 60 is shared.
　シール突起６０の高さ／幅の比率は、０．５～１０の範囲内であるとよい。具体的に、シール突起６０の幅Ｗが１．０［ｍｍ］の場合、シール突起６０の高さＨは０．５～１０［ｍｍ］の範囲内であるとよい。なお、シール突起６０の高さ／幅の比率は、共通化部分でも同じであるとよい。これにより、各貯留部２１においてラバーシート５の弾性変形量が均一になり、気密性が高まる。また、培養容器２には、隣り合う４つの貯留部２１のシール突起６０の角部６３に囲まれた略菱形の空間６４が形成されている。空間６４は、角部６３が隣接する４つのシール突起６０において、各々の内側領域と外側領域におけるラバーシート５の弾性変形量が同じになるような空間容積を有する。 The height/width ratio of the seal protrusion 60 is preferably within the range of 0.5 to 10. Specifically, when the width W of the seal projection 60 is 1.0 [mm], the height H of the seal projection 60 is preferably within the range of 0.5 to 10 [mm]. Note that the height/width ratio of the seal protrusion 60 is preferably the same even in the common portion. Thereby, the amount of elastic deformation of the rubber sheet 5 becomes uniform in each storage section 21, and the airtightness is improved. Furthermore, a substantially diamond-shaped space 64 is formed in the culture container 2 and surrounded by the corners 63 of the seal protrusions 60 of the four adjacent storage sections 21 . The space 64 has a spatial volume such that the amount of elastic deformation of the rubber sheet 5 in the inner region and the outer region of each of the four seal protrusions 60 where the corner portions 63 are adjacent to each other is the same.
　上記構成の細胞培養装置１では、複数の貯留部２１を備える培養容器２について、複数の貯留部２１の気密を同時に確保するため、培養容器２と当該培養容器２を被覆する蓋３とを備え、培養容器２と蓋３の間にラバーシート５を配置して複数の貯留部２１の気密を確保している。この際に、培養容器２の上面に線状のシール突起６０を備えることで、ラバーシート５を弾性変形させ、当該シール突起６０に沿った部位での気密を確保できる。このラバーシート５によれば、一つの部材で複数の貯留部２１の気密を確保できるため、組み立てが容易、且つ、ラバーシート５の厚みＴやシール突起６０の高さＨを調整することで、培養容器２や蓋３の寸法誤差を吸収して気密を容易に確保できる。 In the cell culture device 1 having the above configuration, in order to simultaneously ensure the airtightness of the plurality of storage parts 21, the culture container 2 including the plurality of storage parts 21 is provided with the culture container 2 and a lid 3 covering the culture container 2. A rubber sheet 5 is arranged between the culture container 2 and the lid 3 to ensure airtightness of the plurality of reservoirs 21. At this time, by providing the linear seal protrusion 60 on the upper surface of the culture container 2, the rubber sheet 5 can be elastically deformed and airtightness can be ensured at the region along the seal protrusion 60. According to this rubber sheet 5, the airtightness of the plurality of storage parts 21 can be ensured with one member, so assembly is easy, and by adjusting the thickness T of the rubber sheet 5 and the height H of the seal protrusion 60, It is possible to easily ensure airtightness by absorbing dimensional errors in the culture container 2 and lid 3.
　このように、上述した本実施形態に係る細胞培養装置１は、開口を有する複数の貯留部２１を備える培養容器２と、培養容器２に着脱可能に装着され、複数の貯留部２１の開口を覆う蓋３と、培養容器２及び蓋３のいずれか一方（本実施形態では蓋３）に接続された空圧配管４と、培養容器２と蓋３との間に配置され、培養容器２と蓋３との間の気密を確保するラバーシート５と、を備え、培養容器２及び蓋３のいずれか一方に、複数の貯留部２１の開口を囲い、ラバーシート５に向かって突出する線状のシール突起６０が設けられている。この構成によれば、蓋３を開閉する細胞培養装置１において気密保持を容易にすることができる。 As described above, the cell culture device 1 according to the present embodiment described above includes a culture container 2 including a plurality of storage sections 21 having openings, and a culture container 2 that is removably attached to the culture container 2 and has a plurality of storage sections 21 having openings. A covering lid 3, a pneumatic pipe 4 connected to either one of the culture container 2 or the lid 3 (the lid 3 in this embodiment), and a pneumatic pipe 4 that is arranged between the culture container 2 and the lid 3 and is connected to the culture container 2 and the lid 3. A rubber sheet 5 that secures airtightness between the culture container 2 and the lid 3 is provided, and a linear shape that surrounds the openings of the plurality of reservoirs 21 and protrudes toward the rubber sheet 5 is provided on either the culture container 2 or the lid 3. A seal protrusion 60 is provided. According to this configuration, airtightness can be easily maintained in the cell culture apparatus 1 that opens and closes the lid 3.
　また、本実施形態では、シール突起６０は培養容器２に設けられており、蓋３はラバーシート５が密着する平滑面３０Ｂを有する。この構成によれば、蓋３を開いた際にラバーシート５が培養容器２ではなく蓋３側に密着する。これにより、蓋３と共にラバーシート５を取り外すことができ、また、蓋３との密着によりラバーシート５の脱落を防止することができる。なお、蓋３を取り外した後、液体を貯留部２１に補充する際に、ラバーシート５が培養容器２の上面２０Ａに密着していると、仮に、液体がラバーシート５と培養容器２の隙間に入り込むと、汚染の原因となりうるため好ましくない。また、隙間に入り込んだ液体が劣化して、細胞の培養に影響を及ぼす場合がある。この構成によれば、上記懸念を排除することができる。 Furthermore, in this embodiment, the seal protrusion 60 is provided on the culture container 2, and the lid 3 has a smooth surface 30B to which the rubber sheet 5 is in close contact. According to this configuration, when the lid 3 is opened, the rubber sheet 5 comes into close contact with the lid 3 side instead of the culture container 2. Thereby, the rubber sheet 5 can be removed together with the lid 3, and the rubber sheet 5 can be prevented from falling off due to its close contact with the lid 3. Note that if the rubber sheet 5 is in close contact with the upper surface 20A of the culture container 2 when replenishing the liquid into the reservoir 21 after removing the lid 3, the liquid may leak into the gap between the rubber sheet 5 and the culture container 2. It is undesirable if it gets into the water because it can cause contamination. Furthermore, the liquid that has entered the gap may deteriorate and affect cell culture. According to this configuration, the above concerns can be eliminated.
　また、本実施形態では、蓋３は、ラバーシート５を平滑面３０Ｂに位置決めする複数の位置決め凸部３３を有する。この構成によれば、蓋３の平滑面３０Ｂにラバーシート５を位置決めすることが容易になる。 Furthermore, in this embodiment, the lid 3 has a plurality of positioning protrusions 33 that position the rubber sheet 5 on the smooth surface 30B. According to this configuration, it becomes easy to position the rubber sheet 5 on the smooth surface 30B of the lid 3.
　また、本実施形態では、複数の位置決め凸部３３は、ラバーシート５の短手方向の両側と、ラバーシート５の長手方向の片側に設けられている。また、培養容器２は、複数の位置決め凸部３３が挿入される複数の位置決め凹部２２を備えている。この構成によれば、ラバーシート５の位置決め構造を利用して、培養容器２に対する蓋３の逆組み（例えばＹ軸方向における空圧配管４の向きが逆となった組み付け）を防止することができる。これにより、所定の条件で設計通りに貯留部２１に空圧をかけることができる。 Furthermore, in this embodiment, the plurality of positioning convex portions 33 are provided on both sides of the rubber sheet 5 in the lateral direction and on one side of the rubber sheet 5 in the longitudinal direction. Furthermore, the culture container 2 includes a plurality of positioning recesses 22 into which a plurality of positioning convex parts 33 are inserted. According to this configuration, by utilizing the positioning structure of the rubber sheet 5, it is possible to prevent the lid 3 from being assembled in the opposite direction to the culture container 2 (for example, the assembly where the pneumatic piping 4 is oriented in the opposite direction in the Y-axis direction). can. Thereby, air pressure can be applied to the storage section 21 as designed under predetermined conditions.
　また、本実施形態では、空圧配管４は、蓋３に接続されている。また、蓋３は、空圧配管４と連通する複数の溝部３１を備え、ラバーシート５は、複数の溝部３１と複数の貯留部２１とを連通させる複数の連通孔５１を備える。この構成によれば、空圧配管４が貯留部２１よりも高い位置に配置されるため、仮に、培養液の循環（灌流）の際に気泡が混入して貯留部２１の液体が泡立ったとしても、当該泡が空圧配管４に侵入することを抑制できる。これにより、所定の条件で設計通りに貯留部２１に空圧をかけることができる。なお、貯留部２１を深くすれば、空圧配管４を培養容器２に接続してもよい。 Furthermore, in this embodiment, the pneumatic pipe 4 is connected to the lid 3. Further, the lid 3 includes a plurality of grooves 31 that communicate with the pneumatic piping 4, and the rubber sheet 5 includes a plurality of communication holes 51 that allow the plurality of grooves 31 and the plurality of storage sections 21 to communicate with each other. According to this configuration, since the pneumatic piping 4 is arranged at a higher position than the storage section 21, even if air bubbles are mixed in during circulation (perfusion) of the culture solution and the liquid in the storage section 21 becomes foamy. Also, it is possible to suppress the bubbles from entering the pneumatic piping 4. Thereby, air pressure can be applied to the storage section 21 as designed under predetermined conditions. In addition, if the storage part 21 is deep, the pneumatic pipe 4 may be connected to the culture container 2.
　また、本実施形態では、シール突起６０は、複数の貯留部２１のそれぞれの開口縁に沿って設けられている。また、複数の貯留部２１のうち、互いに隣接する貯留部２１の開口縁に沿って設けられるシール突起６０の少なくとも一部は、共通化されている。この構成によれば、培養容器２に省スペースで貯留部２１を配置しつつ、各貯留部２１における気密性を均一に確保することができる。 Furthermore, in this embodiment, the seal protrusion 60 is provided along the opening edge of each of the plurality of storage parts 21. Further, among the plurality of storage sections 21, at least some of the seal protrusions 60 provided along the opening edges of mutually adjacent storage sections 21 are shared. According to this configuration, the storage sections 21 can be arranged in the culture container 2 in a space-saving manner, and the airtightness in each storage section 21 can be ensured uniformly.
　また、本実施形態では、シール突起６０の高さ／幅の比率が、０．５～１０の範囲内である。この構成によれば、気密確保とラバーシート５の脱落防止効果が高く、シール突起の十分な物理的強度を確保できる。特に、シール突起６０の高さＨが０．３［ｍｍ］以上とすると、蓋３や培養容器２の寸法誤差を吸収してより気密を確保できる。さらに、シール突起６０の幅Ｗを２．０［ｍｍ］以下とすると、気密確保とラバーシートの脱落防止効果が高い。また、ラバーシート５は、シリコーンゴム製であり、そのデュロメータ硬さが、５０以下であると、気密確保とラバーシートの脱落防止効果がより高くなる。 Furthermore, in this embodiment, the height/width ratio of the seal protrusion 60 is within the range of 0.5 to 10. According to this configuration, the effect of ensuring airtightness and preventing the rubber sheet 5 from falling off is high, and sufficient physical strength of the seal protrusion can be ensured. In particular, when the height H of the seal protrusion 60 is set to 0.3 [mm] or more, dimensional errors in the lid 3 and the culture container 2 can be absorbed to ensure better airtightness. Furthermore, when the width W of the seal protrusion 60 is set to 2.0 [mm] or less, the effect of ensuring airtightness and preventing the rubber sheet from falling off is high. Further, the rubber sheet 5 is made of silicone rubber, and when its durometer hardness is 50 or less, the effect of ensuring airtightness and preventing the rubber sheet from falling off becomes higher.
　（第２実施形態）
　次に、本発明の第２実施形態について説明する。以下の説明において、上述の実施形態と同一又は同等の構成については同一の符号を付し、その説明を簡略若しくは省略する。 (Second embodiment)
Next, a second embodiment of the present invention will be described. In the following description, the same or equivalent configurations as those in the above-described embodiment are given the same reference numerals, and the description thereof will be simplified or omitted.
　図６は、第２実施形態に係る細胞培養装置１の斜視図である。図７は、図６に示す細胞培養装置１の分解斜視図である。図８は、図７に示す細胞培養装置１が備える培養容器２の平面図である。図９は、図８に示す矢視ＩＸ－ＩＸ断面図である。
　第２実施形態の細胞培養装置１は、培養容器２の一対の貯留部２１ａ，２１ｂの間に、ハイドロゲルチャンバー１１０が設けられている点で、上記実施形態と異なる。 FIG. 6 is a perspective view of the cell culture device 1 according to the second embodiment. FIG. 7 is an exploded perspective view of the cell culture device 1 shown in FIG. 6. FIG. 8 is a plan view of the culture container 2 included in the cell culture apparatus 1 shown in FIG. 7. FIG. 9 is a sectional view taken along arrow IX-IX shown in FIG.
The cell culture device 1 of the second embodiment differs from the above embodiments in that a hydrogel chamber 110 is provided between the pair of reservoirs 21a and 21b of the culture container 2.
　なお、以下の説明において、ＸＹＺ直交座標系を設定し、このＸＹＺ直交座標系を参照しつつ各構成の位置関係について説明することがある。Ｘ軸方向は、貯留部２１ａ、ハイドロゲルチャンバー１１０、及び貯留部２１ｂが並ぶ第１の水平方向である。Ｙ軸方向は、Ｘ軸方向と直交する第２の水平方向である。Ｚ軸方向は、Ｘ軸方向及びＹ軸方向と直交する鉛直方向である。 In the following description, an XYZ orthogonal coordinate system is set, and the positional relationship of each component may be explained with reference to this XYZ orthogonal coordinate system. The X-axis direction is the first horizontal direction in which the storage section 21a, the hydrogel chamber 110, and the storage section 21b are lined up. The Y-axis direction is a second horizontal direction orthogonal to the X-axis direction. The Z-axis direction is a vertical direction orthogonal to the X-axis direction and the Y-axis direction.
　なお、図６においては、細胞培養装置１の内部構造の視認性を向上させるため、培養容器２、蓋３及びラバーシート５の外形を二点鎖線で示し、その内部構造を透視させている。培養容器２及び蓋３は、細胞の観察等のために、透光性の高い透明材料等で形成されることが好ましい。なお、培養容器２及び蓋３は、透光性の低い若しくは透光性の無い材料で形成されてもよい。その場合、細胞を視認できる位置にガラス窓等を設けてもよい。第２実施形態の細胞培養装置１は、例えばポリスチレンの射出成型と熱融着により製造することができる。 In addition, in FIG. 6, in order to improve the visibility of the internal structure of the cell culture device 1, the external shapes of the culture container 2, lid 3, and rubber sheet 5 are shown with two-dot chain lines, and the internal structure is seen through. The culture container 2 and lid 3 are preferably made of a highly translucent transparent material for purposes such as cell observation. In addition, the culture container 2 and the lid 3 may be formed of a material with low translucency or no translucency. In that case, a glass window or the like may be provided at a position where the cells can be visually recognized. The cell culture device 1 of the second embodiment can be manufactured, for example, by injection molding of polystyrene and heat fusion.
　ハイドロゲルチャンバー１１０は、図６に示すように、扁平状の内部空間を有している。ハイドロゲル１０１の内部空間の高さ（Ｚ軸方向の寸法）は、例えば１００［μｍ］～５００［μｍ］の範囲内である。ハイドロゲルチャンバー１１０の内部空間には、ハイドロゲル１０１が充填されている。ハイドロゲル１０１は、高分子の三次元網目構造を有して水分を保持すると共に、細胞を包埋もしくは接着し、細胞を培養する。 As shown in FIG. 6, the hydrogel chamber 110 has a flat internal space. The height (dimension in the Z-axis direction) of the internal space of the hydrogel 101 is, for example, within the range of 100 [μm] to 500 [μm]. The internal space of the hydrogel chamber 110 is filled with hydrogel 101. The hydrogel 101 has a three-dimensional polymeric network structure and retains water, embeds or adheres cells, and cultivates the cells.
　ハイドロゲルチャンバー１１０は、平面視で六角形に形成されている。なお、ハイドロゲルチャンバー１１０の平面視形状は特に限定されないが、貯留部２１ａ及び貯留部２１ｂと隣接する長さ（Ｙ軸方向の寸法）は、幅（Ｘ軸方向の寸法）よりも大きいとよい。ハイドロゲルチャンバー１１０のＹ軸方向の寸法は、例えば１［ｍｍ］～２０［ｍｍ］の範囲内である。ハイドロゲルチャンバー１１０のＸ軸方向の寸法は、例えば０．５［ｍｍ］～１０［ｍｍ］の範囲内である。 The hydrogel chamber 110 is formed into a hexagonal shape in plan view. Note that the shape of the hydrogel chamber 110 in plan view is not particularly limited, but the length (dimension in the Y-axis direction) adjacent to the storage part 21a and the storage part 21b is preferably larger than the width (dimension in the X-axis direction). . The dimension of the hydrogel chamber 110 in the Y-axis direction is, for example, within a range of 1 [mm] to 20 [mm]. The dimension of the hydrogel chamber 110 in the X-axis direction is, for example, within a range of 0.5 [mm] to 10 [mm].
　ハイドロゲルチャンバー１１０は、貯留部２１ａに連通する第１面と、貯留部２１ｂに連通する第２面と、を有している。第１面及び第２面は、Ｘ軸方向で対向し、Ｙ軸方向に互いに平行に延びている。ハイドロゲルチャンバー１１０のＹ軸方向の両端部は、導入孔１１４と連通している。ハイドロゲルチャンバー１１０の直上部には、ハイドロゲル１０１を導入するハイドロゲル貯留槽１１６が形成されている。 The hydrogel chamber 110 has a first surface that communicates with the storage section 21a and a second surface that communicates with the storage section 21b. The first surface and the second surface face each other in the X-axis direction and extend parallel to each other in the Y-axis direction. Both ends of the hydrogel chamber 110 in the Y-axis direction communicate with the introduction hole 114. A hydrogel storage tank 116 into which the hydrogel 101 is introduced is formed directly above the hydrogel chamber 110.
　導入孔１１４は、ハイドロゲルチャンバー１１０のＹ軸方向の両端と、ハイドロゲル貯留槽１１６の底面とを連通させている。２つの導入孔１１４により、ハイドロゲルチャンバー１１０から空気を抜き、ハイドロゲル貯留槽１１６からハイドロゲルチャンバー１１０にハイドロゲル１０１を充填し易くなる。 The introduction hole 114 communicates both ends of the hydrogel chamber 110 in the Y-axis direction with the bottom surface of the hydrogel storage tank 116. The two introduction holes 114 facilitate removing air from the hydrogel chamber 110 and filling the hydrogel chamber 110 with the hydrogel 101 from the hydrogel storage tank 116.
　貯留部２１ａは、培養液１０２を貯留する。貯留部２１ａは、平面視でＹ軸方向に延びる長孔状ないし楕円状に形成されている。なお、貯留部２１ａの平面視形状は特に限定されない。貯留部２１ａは、ハイドロゲルチャンバー１１０よりも内部空間（容積）が大きいとよい。貯留部２１ａの底部のハイドロゲルチャンバー１１０側（＋Ｘ側）の側面は、ハイドロゲルチャンバー１１０に連通している。 The storage section 21a stores the culture solution 102. The storage portion 21a is formed in the shape of a long hole or an ellipse extending in the Y-axis direction when viewed from above. Note that the shape of the storage portion 21a in plan view is not particularly limited. It is preferable that the storage section 21a has a larger internal space (volume) than the hydrogel chamber 110. A side surface on the hydrogel chamber 110 side (+X side) at the bottom of the storage section 21a communicates with the hydrogel chamber 110.
　貯留部２１ｂは、培養液１０２を貯留する。貯留部２１ｂは、平面視でＹ軸方向に延びる長孔状ないし楕円状に形成されている。なお、貯留部２１ｂの平面形状は特に限定されない。貯留部２１ｂも、ハイドロゲルチャンバー１１０よりも内部空間（容積）が大きいとよい。貯留部２１ｂの底部のハイドロゲルチャンバー１１０側（－Ｘ側）の側面は、ハイドロゲルチャンバー１１０に連通している。 The storage section 21b stores the culture solution 102. The storage portion 21b is formed in the shape of a long hole or an ellipse extending in the Y-axis direction when viewed from above. Note that the planar shape of the storage portion 21b is not particularly limited. It is preferable that the storage section 21b also has a larger internal space (volume) than the hydrogel chamber 110. The side surface of the bottom of the storage portion 21b on the hydrogel chamber 110 side (-X side) communicates with the hydrogel chamber 110.
　培養容器２は、貯留部２１ａ，２１ｂに圧力差を生じさせた状態でも、ハイドロゲルチャンバー１１０にハイドロゲル１０１を保持させる機構として、支柱列１２２，１３２を備えている。支柱列１２２は、ハイドロゲルチャンバー１１０と貯留部２１ａと連通させるマイクロサイズの流体チャネルを形成する。また、支柱列１３２は、ハイドロゲルチャンバー１１０と貯留部２１ｂと連通させるマイクロサイズの流体チャネルを形成する。 The culture container 2 is equipped with strut rows 122 and 132 as a mechanism for retaining the hydrogel 101 in the hydrogel chamber 110 even when a pressure difference is generated between the reservoirs 21a and 21b. The column array 122 forms a micro-sized fluid channel that communicates the hydrogel chamber 110 with the reservoir 21a. Moreover, the column row 132 forms a micro-sized fluid channel that communicates the hydrogel chamber 110 with the storage section 21b.
　蓋３の平滑面３０Ｂ（下面）には、貯留部２１ａ，２１ｂに連通する上方に向かって凹状の溝部３１ａ，３１ｂが形成されている。なお、ハイドロゲル貯留槽１１６の上部は、蓋３の平滑面３０Ｂによって閉塞されている。蓋３には、貯留部２１ａ，２１ｂに連通するように空圧配管４ａ，４ｂが接続されている。なお、蓋３に対する空圧配管４ａ，４ｂの接続方向は、Ｙ軸方向に限らず、Ｘ軸方向であっても、Ｚ軸方向であってもよい。 On the smooth surface 30B (lower surface) of the lid 3, upwardly concave grooves 31a and 31b are formed which communicate with the reservoirs 21a and 21b. Note that the upper part of the hydrogel storage tank 116 is closed by the smooth surface 30B of the lid 3. Pneumatic pipes 4a and 4b are connected to the lid 3 so as to communicate with the reservoirs 21a and 21b. Note that the connection direction of the pneumatic pipes 4a, 4b to the lid 3 is not limited to the Y-axis direction, but may be the X-axis direction or the Z-axis direction.
　ラバーシート５は、図６及び図７に示すように、培養容器２と蓋３との間に介在し、培養容器２と蓋３との間の気密を確保する。ラバーシート５は、Ｘ軸方向を短手方向、Ｙ軸方向を長手方向とする、平面視で長方形状を有する。ラバーシート５の上面５０Ａ及び下面５０Ｂは、それぞれ平滑面となっている。ラバーシート５の上面５０Ａは、蓋３の平滑面３０Ｂに密着する。つまり、ラバーシート５は、ファンデルワールス力により蓋３側に密着する。 As shown in FIGS. 6 and 7, the rubber sheet 5 is interposed between the culture container 2 and the lid 3 to ensure airtightness between the culture container 2 and the lid 3. The rubber sheet 5 has a rectangular shape in plan view, with the X-axis direction being the short direction and the Y-axis direction being the long direction. The upper surface 50A and lower surface 50B of the rubber sheet 5 are both smooth surfaces. The upper surface 50A of the rubber sheet 5 is in close contact with the smooth surface 30B of the lid 3. In other words, the rubber sheet 5 is brought into close contact with the lid 3 due to van der Waals force.
　ラバーシート５は、蓋３に設けられた溝部３１ａ，３１ｂと、培養容器２に設けられた貯留部２１ａ，２１ｂと、を連通させる連通孔５１ａ，５１ｂを備えている。なお、ラバーシート５は、連通孔５１ａ，５１ｂの間に、ハイドロゲル貯留槽１１６に連通する第２の連通孔５３を備えている。 The rubber sheet 5 includes communication holes 51a, 51b that allow the grooves 31a, 31b provided in the lid 3 to communicate with the reservoirs 21a, 21b provided in the culture container 2. Note that the rubber sheet 5 includes a second communication hole 53 that communicates with the hydrogel storage tank 116 between the communication holes 51a and 51b.
　図７及び図８に示すように、培養容器２には、複数の貯留部２１の開口を囲い、上面２０Ａからラバーシート５に向かって突出する線状のシール突起６０が設けられている。シール突起６０は、貯留部２１ａ，２１ｂ及びハイドロゲル貯留槽１１６のそれぞれの開口縁に沿って設けられている。貯留部２１ａ，２１ｂ及びハイドロゲル貯留槽１１６の隣り合うシール突起６０の少なくとも一部は、共通化されている。 As shown in FIGS. 7 and 8, the culture container 2 is provided with a linear seal protrusion 60 that surrounds the openings of the plurality of reservoirs 21 and projects from the top surface 20A toward the rubber sheet 5. The seal protrusion 60 is provided along the opening edge of each of the storage parts 21a, 21b and the hydrogel storage tank 116. At least some of the adjacent seal protrusions 60 of the storage parts 21a, 21b and the hydrogel storage tank 116 are shared.
　上記構成の細胞培養装置１では、貯留部２１ａ，２１ｂを備える培養容器２について、貯留部２１ａ，２１ｂの気密を同時に確保するため、培養容器２と当該培養容器２を被覆する蓋３とを備え、培養容器２と蓋３の間にラバーシート５を配置して複数の貯留部２１の気密を確保する。この際に、培養容器２の上面２０Ａに線状のシール突起６０を備えることで、ラバーシート５を弾性変形させ、当該シール突起６０に沿った部位での気密を確保できる。このラバーシート５によれば、一つの部材で複数の貯留部２１の気密を確保できるため、組み立てが容易、且つ、ラバーシート５の厚みＴやシール突起６０の高さＨを調整することで、培養容器２や蓋３の寸法誤差を吸収して気密を容易に確保できる。 In the cell culture device 1 having the above configuration, the culture container 2 including the storage portions 21a and 21b is provided with the culture container 2 and a lid 3 covering the culture container 2 in order to simultaneously ensure airtightness of the storage portions 21a and 21b. A rubber sheet 5 is arranged between the culture container 2 and the lid 3 to ensure airtightness of the plurality of reservoirs 21. At this time, by providing the linear seal protrusion 60 on the upper surface 20A of the culture container 2, the rubber sheet 5 can be elastically deformed and airtightness can be ensured at the region along the seal protrusion 60. According to this rubber sheet 5, the airtightness of the plurality of storage parts 21 can be ensured with one member, so assembly is easy, and by adjusting the thickness T of the rubber sheet 5 and the height H of the seal protrusion 60, It is possible to easily ensure airtightness by absorbing dimensional errors in the culture container 2 and lid 3.
　また、上記構成の第２実施形態によれば、ハイドロゲルチャンバー１１０に隣接した貯留部２１ａ及び貯留部２１ｂに培養液１０２を貯留し、貯留された培養液１０２に対して空圧をかけることで、ハイドロゲル１０１に培養液１０２を浸透させて細胞を培養できる。このように、培養容器２に空圧配管４を接続された蓋３を固定し、空圧によってハイドロゲル１０１に培養液１０２を浸透させながら細胞（例えば血管内皮細胞）を培養することで、ハイドロゲル１０１中での細胞組織の形成を促進させることができる。 Further, according to the second embodiment having the above configuration, the culture solution 102 is stored in the storage section 21a and the storage section 21b adjacent to the hydrogel chamber 110, and by applying air pressure to the stored culture solution 102. , cells can be cultured by infiltrating the hydrogel 101 with a culture solution 102. In this way, the lid 3 connected to the pneumatic piping 4 is fixed to the culture container 2, and cells (e.g., vascular endothelial cells) are cultured while the culture solution 102 is infiltrated into the hydrogel 101 using air pressure. Formation of cellular tissue within the gel 101 can be promoted.
　以上、本発明の好ましい実施形態及び実施例を記載し説明してきたが、これらは本発明の例示的なものであり、限定するものとして考慮されるべきではないことを理解すべきである。追加、省略、置換、およびその他の変更は、本発明の範囲から逸脱することなく行うことができる。従って、本発明は、前述の説明によって限定されていると見なされるべきではなく、特許請求の範囲によって制限されている。 While preferred embodiments and examples of the invention have been described and illustrated, it is to be understood that these are illustrative of the invention and are not to be considered as limiting. Additions, omissions, substitutions, and other changes may be made without departing from the scope of the invention. Accordingly, the invention should not be considered limited by the foregoing description, but rather by the claims.
１…細胞培養装置
２…培養容器
２ａ…アッパープレート
２ｂ…ボトムプレート
２ｃ…流路プレート
２ｄ…透明プレート
３…蓋
３ａ…蓋本体
３ｂ…カバー
３ｃ…ラバーシート
４…空圧配管
４ａ～４ｄ…空圧配管
５…ラバーシート
６…第１の固定部
７…第２の固定部
８…第１の係止部
９…隙間
１０…第２の係止部
１１…ボルト
１２…貫通孔
１３…窓部
１４…貫通孔
１５…排出流路
１６…導入流路
２０Ａ…上面
２１…貯留部
２１ａ～２１ｄ…貯留部
２２…位置決め凹部
３０ａ…接続孔
３０Ａ…上面
３０Ｂ…平滑面
３１…溝部
３１ａ～３１ｄ…溝部
３２…貫通孔
３３…位置決め凸部
５０Ａ…上面
５０Ｂ…下面
５１…連通孔
５１ａ～５１ｄ…連通孔
５３…第２の連通孔
６０…シール突起
６１…短辺
６２…長辺
６３…角部
６４…空間
７０…開口部
１０１…ハイドロゲル
１０２…培養液
１１０…ハイドロゲルチャンバー
１１４…導入孔
１１６…ハイドロゲル貯留槽
１２２…支柱列
１３２…支柱列
１５１…ラプラス弁 1... Cell culture device 2... Culture container 2a... Upper plate 2b... Bottom plate 2c... Channel plate 2d... Transparent plate 3... Lid 3a... Lid body 3b... Cover 3c... Rubber sheet 4... Pneumatic piping 4a to 4d... Empty Pressure piping 5...Rubber sheet 6...First fixing part 7...Second fixing part 8...First locking part 9...Gap 10...Second locking part 11...Bolt 12...Through hole 13...Window part 14...Through hole 15...Discharge channel 16...Introduction channel 20A...Top surface 21...Storage portions 21a to 21d...Storage portion 22...Positioning recess 30a...Connection hole 30A...Top surface 30B...Smooth surface 31...Groove portions 31a to 31d...Groove portion 32...Through hole 33...Positioning convex portion 50A...Upper surface 50B...Lower surface 51...Communication hole 51a to 51d...Communication hole 53...Second communication hole 60...Seal protrusion 61...Short side 62...Long side 63...Corner section 64... Space 70...Opening 101...Hydrogel 102...Culture solution 110...Hydrogel chamber 114...Introduction hole 116...Hydrogel storage tank 122...Strut row 132...Strut row 151...Laplace valve

Claims (13)

  1. 　開口を有する複数の貯留部を備える培養容器と、
    　前記培養容器に着脱可能に装着され、前記複数の貯留部の開口を覆う蓋と、
    　前記培養容器及び前記蓋のいずれか一方に接続された空圧配管と、
    　前記培養容器と前記蓋との間に配置され、前記培養容器と前記蓋との間の気密を確保するラバーシートと、を備え、
    　前記培養容器及び前記蓋のいずれか一方に、前記複数の貯留部の開口を囲い、前記ラバーシートに向かって突出する線状のシール突起が設けられている、
    　細胞培養装置。     a culture container including a plurality of reservoirs having openings;
    a lid that is removably attached to the culture container and covers the openings of the plurality of reservoirs;
    pneumatic piping connected to either the culture container or the lid;
    a rubber sheet disposed between the culture container and the lid to ensure airtightness between the culture container and the lid;
    Either one of the culture container and the lid is provided with a linear seal protrusion that surrounds the openings of the plurality of reservoirs and projects toward the rubber sheet.
    Cell culture equipment.
  2. 　前記シール突起は、前記培養容器に設けられている、
    　請求項１に記載の細胞培養装置。     The seal protrusion is provided on the culture container,
    The cell culture device according to claim 1.
  3. 　前記蓋は、前記ラバーシートが密着する平滑面を有する、
    　請求項２に記載の細胞培養装置。     The lid has a smooth surface that the rubber sheet adheres to,
    The cell culture device according to claim 2.
  4. 　前記蓋は、前記ラバーシートを前記平滑面に位置決めする複数の位置決め凸部を有する、
    　請求項３に記載の細胞培養装置。     The lid has a plurality of positioning protrusions that position the rubber sheet on the smooth surface.
    The cell culture device according to claim 3.
  5. 　前記複数の位置決め凸部は、前記ラバーシートの短手方向の両側と、前記ラバーシートの長手方向の片側に設けられている、
    　請求項４に記載の細胞培養装置。     The plurality of positioning convex portions are provided on both sides of the rubber sheet in the width direction and on one side of the rubber sheet in the length direction,
    The cell culture device according to claim 4.
  6. 　前記培養容器は、前記複数の位置決め凸部が挿入される複数の位置決め凹部を備える、
    　請求項４または５に記載の細胞培養装置。     The culture container includes a plurality of positioning recesses into which the plurality of positioning convex parts are inserted.
    The cell culture device according to claim 4 or 5.
  7. 　前記空圧配管は、前記蓋に接続されている、
    　請求項１～５のいずれか一項に記載の細胞培養装置。     the pneumatic piping is connected to the lid;
    The cell culture device according to any one of claims 1 to 5.
  8. 　前記蓋は、前記空圧配管と連通する複数の溝部を備え、
    　前記ラバーシートは、前記複数の溝部と前記複数の貯留部とを連通させる複数の連通孔を備える、
    　請求項７に記載の細胞培養装置。     The lid includes a plurality of grooves communicating with the pneumatic piping,
    The rubber sheet includes a plurality of communication holes that communicate the plurality of grooves and the plurality of storage parts,
    The cell culture device according to claim 7.
  9. 　前記シール突起は、前記複数の貯留部のそれぞれの開口縁に沿って設けられている、
    　請求項１～５のいずれか一項に記載の細胞培養装置。     The seal protrusion is provided along an opening edge of each of the plurality of storage parts,
    The cell culture device according to any one of claims 1 to 5.
  10. 　前記複数の貯留部のうち、互いに隣接する貯留部の開口縁に沿って設けられる前記シール突起の少なくとも一部は、共通化されている、
    　請求項９に記載の細胞培養装置。     At least some of the seal protrusions provided along the opening edges of mutually adjacent storage parts among the plurality of storage parts are shared;
    The cell culture device according to claim 9.
  11. 　前記シール突起の高さ／幅の比率が、０．５～１０の範囲内である、
    　請求項１～５のいずれか一項に記載の細胞培養装置。     The height/width ratio of the seal protrusion is within the range of 0.5 to 10.
    The cell culture device according to any one of claims 1 to 5.
  12. 　前記ラバーシートは、シリコーンゴム製である、
    　請求項１～５のいずれか一項に記載の細胞培養装置。     The rubber sheet is made of silicone rubber.
    The cell culture device according to any one of claims 1 to 5.
  13. 　前記ラバーシートのデュロメータ硬さは、５０以下である、
    　請求項１～５のいずれか一項に記載の細胞培養装置。     The durometer hardness of the rubber sheet is 50 or less.
    The cell culture device according to any one of claims 1 to 5.
PCT/JP2023/023014 2022-07-29 2023-06-21 Cell culture device WO2024024345A1 (en)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
WO2013103108A1 (en) * 2012-01-04 2013-07-11 株式会社ジャパン・ティッシュ・エンジニアリング Cell separation container
WO2016158233A1 (en) * 2015-04-03 2016-10-06 国立研究開発法人産業技術総合研究所 Cell culture apparatus and cell culture method
WO2017154880A1 (en) * 2016-03-08 2017-09-14 国立研究開発法人産業技術総合研究所 Cell culture device and cell culture method
JP2020523008A (en) * 2017-06-08 2020-08-06 ヴィトロライフ アー／エス Lid for culture dish

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013103108A1 (en) * 2012-01-04 2013-07-11 株式会社ジャパン・ティッシュ・エンジニアリング Cell separation container
WO2016158233A1 (en) * 2015-04-03 2016-10-06 国立研究開発法人産業技術総合研究所 Cell culture apparatus and cell culture method
WO2017154880A1 (en) * 2016-03-08 2017-09-14 国立研究開発法人産業技術総合研究所 Cell culture device and cell culture method
JP2020523008A (en) * 2017-06-08 2020-08-06 ヴィトロライフ アー／エス Lid for culture dish

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