WO2020085423A1 - Cell holding device - Google Patents

Cell holding device Download PDF

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Publication number
WO2020085423A1
WO2020085423A1 PCT/JP2019/041679 JP2019041679W WO2020085423A1 WO 2020085423 A1 WO2020085423 A1 WO 2020085423A1 JP 2019041679 W JP2019041679 W JP 2019041679W WO 2020085423 A1 WO2020085423 A1 WO 2020085423A1
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WO
WIPO (PCT)
Prior art keywords
cell
holding device
cell culture
cells
holding member
Prior art date
Application number
PCT/JP2019/041679
Other languages
French (fr)
Japanese (ja)
Inventor
晃輔 堀
紀之 河原
Original Assignee
株式会社幹細胞＆デバイス研究所
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by 株式会社幹細胞＆デバイス研究所 filed Critical 株式会社幹細胞＆デバイス研究所
Priority to JP2020552586A priority Critical patent/JPWO2020085423A1/en
Publication of WO2020085423A1 publication Critical patent/WO2020085423A1/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
    • C12M1/00—Apparatus for enzymology or microbiology
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • 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 holding device, and more particularly to a device capable of measuring contractility of cultured cells.
  • a holder 20 having a holding surface 20a and a plurality of shaft portions 21 is prepared.
  • a base material 10 having a pair of fitting portions 16 and an engagement wall 12 is prepared.
  • a gel Forming a pair of first gel bodies to gel a liquid containing cells and extending in a predetermined direction to form a second gel body of a predetermined shape connecting the pair of first gel bodies to each other, Culturing at least the second gel body to form a cell tissue MS extending in a predetermined direction; fitting a pair of holders provided with the cell tissue to a pair of fitting portions of the base material; Measuring the contractile force of the cellular tissue in response to the elastic deformation of the engagement wall due to the force associated with the contraction of.
  • the above-mentioned method for measuring the contractile force of cellular tissue has the following points to be improved.
  • the above-described method for measuring the contractile force of a cell tissue it is necessary to carry out a plurality of complicated steps over time when culturing cells for measuring the contractile force. Therefore, there is a point to be improved that it takes time to prepare before measuring the contraction force.
  • the structure is different from the cells as the actual tissue, so the contractive force of the cells as the actual tissue may not be measured, There is a point to be improved.
  • an object of the present invention is to provide a cell holding device capable of culturing cells close to an actual tissue and easily measuring the contractility of the cultivated cells. That is, the present invention has solved the above problems by providing the inventions described below.
  • a cell culture part formed of a predetermined fibrous material for culturing and holding cells, a first end and a second end located at both ends of the cell culture part, and the first end And a rim located between the second end and the cell culture holding member, A first fixing portion for directly fixing the first end portion, A second fixing portion for fixing the second end portion, A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion; And a cell holding device.
  • the second fixing portion is Being positioned to face the first fixing portion along the predetermined direction, A cell holding device characterized by: (3) In the cell holding device according to (1), The second fixing portion is Being located along a direction intersecting with the predetermined direction, A cell holding device characterized by: (4) In the cell holding device according to any one of (1) to (3), The cell culture section, Formed by the fibrous material arranged along a predetermined orientation direction, The edge is Having at least a portion along the alignment direction, A cell holding device characterized by: (5) In the cell holding device according to any one of (1) to (4), The first fixing portion and the second fixing portion are Each is at least a part of a flat base, The cell culture holding member arrangement space, A through hole formed so as to penetrate the base, A cell holding device characterized by: (6) In the cell holding device according to (5), The cell culture holding member, Having an opening at a position corresponding to the through hole, A cell holding device characterized by: (7) In the cell holding device according to any one
  • a cell holding device characterized by: (11) In the cell holding device according to any one of (1) to (9), The cell culture holding member, As the cells, cardiomyocytes are cultured and maintained, The contraction rate of the cell culture holding member in which the cardiomyocytes are cultured is 2.5% or more, A cell holding device characterized by: (12) In the cell holding device according to any one of (1) to (11), The cell holding device, Used to measure the contractility of the cells, A cell holding device characterized by: (13) A cell holding device for measuring the contractility of cells, which comprises a cell culture section for culturing and holding cells formed by fibrous substances arranged along a predetermined orientation direction, and the orientation.
  • a cell holding device having a cell culture holding member having an edge portion having at least a part, A first fixing portion for fixing the first end portion, A second fixing portion for fixing the second end portion, A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion; And a cell holding device.
  • a cell culture holding member used in a cell holding device for measuring contractility of cells comprising: A cell culture unit that cultures and holds cells formed by fibrous substances arranged along a predetermined orientation direction, A first end and a second end facing each other along a direction intersecting the alignment direction; An edge portion located between the first end portion and the second end portion and having at least a portion along the alignment direction, A cell culture holding member having.
  • a cell holding device is formed of a predetermined fibrous material, cultivates and holds cells, and a cell culturing section, and a first end and a second end located at both ends of the cell culturing section, And a cell culture holding member having an edge portion located between the first end portion and the second end portion, a first fixing portion for directly fixing the first end portion, the second end A second fixing portion for fixing the portion, and a cell culture holding member arrangement space which is located between the first fixing portion and the second fixing portion and does not fix the edge portion.
  • the cultured cells were restrained in all directions. Since the cells can be beat more freely than before, cells can be beat more than before.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly.
  • cells cultured using the cell holding device can be used for measuring the contraction rate.
  • the cell holding device is characterized in that the second fixing portion is located facing the first fixing portion along the predetermined direction.
  • the cultured cells are kept in all directions.
  • the cells can be beat more freely than in the conventional method, which allows the cells to be beaten more freely than in the conventional method.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly.
  • cells cultured using the cell holding device can be used for measuring the contraction rate.
  • the cell holding device according to the present invention is characterized in that the second fixing portion is located along a direction intersecting with the predetermined direction.
  • the cell culture portion was cultivated by placing it in the cell culture holding member placement space formed in the base and not constraining the cell culture portion in a predetermined direction and in a direction intersecting the predetermined direction. Since cells can be beat more freely than in the conventional method in which the cells are restrained in all directions, the cells can be beat more greatly than in the conventional method.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly.
  • cells cultured using the cell holding device can be used for measuring the contraction rate.
  • the cell culture portion is formed by the fibrous material arranged along a predetermined orientation direction, and the edge portion is at least part of a portion along the orientation direction. It is characterized by having.
  • the cell culture section is placed in the cell culture holding member placement space formed in the base, and the cell culture section is cultivated by constraining it only in the orientation direction of the cell culture holding member and not in the intersecting direction.
  • the cells can be beat more freely than in the conventional method in which the cells are restrained in all directions, so that the cells can be beat more greatly than in the conventional method.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • each of the first fixing portion and the second fixing portion is at least a part of a plate-shaped base portion, and the cell culture holding member placement space penetrates the base portion. It is a through hole formed so that
  • the cell holding device is characterized in that the cell culture holding member has an opening at a position corresponding to the through hole.
  • the cell holding device according to the present invention is characterized in that the edge portion has a portion linearly formed along the orientation direction.
  • the cell holding device according to the present invention is characterized in that the cell culture holding member has an elastic modulus of 2000 MPa or less.
  • the cell holding device further includes an operation unit that can be held by a predetermined holding tool.
  • the cell holding device can be easily moved.
  • the cell holding device is characterized in that the cell culture holding member cultures and holds cardiomyocytes or skeletal muscle cells as the cells.
  • the cell culture holding member is one in which cardiomyocytes are cultured and held as the cells, and the contraction rate of the cell culture holding member obtained by culturing the cardiomyocytes is 2.5% or more. There is a feature.
  • the cell holding device according to the present invention is characterized in that the cell holding device is used for measuring the contractility of the cells.
  • the cell retention device is a cell retention device for measuring the contractility of cells, and is a cell for culturing and retaining cells formed by fibrous substances arranged along a predetermined orientation direction.
  • the cell culture holding member formed on the base portion of the cell culture portion.
  • the cell culture holding member according to the present invention is a cell culture holding member used in a cell holding device for measuring contractility of cells, and cells formed by fibrous substances arranged along a predetermined orientation direction.
  • a cell culture part for culturing and holding cells a first end part and a second end part facing each other in a direction intersecting with the orientation direction, and a position between the first end part and the second end part And an edge portion having at least a portion along the alignment direction.
  • the cells having the same structure as the actual tissue cells are restrained only in the orientation direction of the cell culture holding member.
  • the cultured cells can be beat more freely than in the conventional method in which the cells were constrained in all directions, so that the cells can be beat more than before.
  • the cells can be cultured.
  • FIG. 1 is a perspective view of a cell holding device 100, which is an embodiment of the cell holding device according to the present invention, viewed obliquely from above.
  • FIG. 3 is a perspective view of the cell holding device 100 from an obliquely lower direction.
  • FIG. 3 is a perspective view of the base portion 101 from an obliquely upper direction.
  • FIG. 3 is a perspective view of the base portion 101 from an obliquely lower direction. It is an enlarged view of the cell culture holding member 105. It is a perspective view of the cell culture holding member 105 from an obliquely upper direction.
  • FIG. 1 is a perspective view of a cell holding device 100, which is an embodiment of the cell holding device according to the present invention, viewed obliquely from above.
  • FIG. 3 is a perspective view of the cell holding device 100 from an obliquely lower direction.
  • FIG. 3 is a perspective view of the base portion 101 from an obliquely upper direction.
  • It is
  • FIG. 7 is a diagram showing an operating state of cardiomyocytes cultured in the cell culture holding member 105, where A is a state at the time of contraction and B is a state before the contraction.
  • FIG. 7 is a perspective view of a cell holding device 200, which is another embodiment of the cell holding device according to the present invention, viewed from obliquely above. It is a perspective view of the cell holding device 200 from an obliquely lower direction.
  • FIG. 7 is a perspective view of a cell holding device 300, which is another embodiment of the cell holding device according to the present invention, seen from obliquely above. It is a perspective view of the cell holding device 300 from an oblique lower direction.
  • FIG. 7 is a diagram showing an operating state of cardiomyocytes cultured in the cell culture holding member 105, where A is a state at the time of contraction and B is a state before the contraction.
  • FIG. 7 is a perspective view of a cell holding device 200, which is another embodiment of the cell holding device according
  • FIG. 7 is a perspective view of a cell holding device 400, which is another embodiment of the cell holding device according to the present invention, seen from diagonally above. It is a perspective view of the cell holding device 400 from an obliquely lower direction.
  • FIG. 6 is a perspective view of a cell holding device 500, which is another embodiment of the cell holding device according to the present invention, viewed from obliquely above. It is a perspective view of the cell holding device 500 from an obliquely downward direction.
  • FIG. 7 is a perspective view of a cell holding device 700, which is another embodiment of the cell holding device according to the present invention, viewed from diagonally above. It is a figure which shows the cross section of the cell holding device 700.
  • FIG. 8 is a perspective view of a cell holding device 800, which is another embodiment of the cell holding device according to the present invention, seen from obliquely below. It is a figure which shows the prior art regarding the contractility measurement of a cell.
  • the cell holding device 100 is a device for evaluating the contractility of pulsating cells.
  • FIG. 1 shows a perspective view of the cell holding device 100 from diagonally above
  • FIG. 2 shows a perspective view of the cell holding device 100 from diagonally below.
  • the cell holding device 100 has a base portion 101, a cell culture holding member 105, and an operating portion 107.
  • FIG. 3 shows a perspective view of the base 101 obliquely from above
  • FIG. 4 shows a perspective view of the base 101 obliquely from below
  • the base 101 has a thin disc shape.
  • the base portion 101 has a through hole 101a having a circular cross section in the center.
  • the base 101 has an upper surface P101a (see FIG. 3) and a lower surface P101b (see FIG. 4).
  • the through hole 101a is formed so as to penetrate the base 101 from the upper surface P101a to the lower surface P101b of the base 101.
  • the through hole 101a is formed in a cylindrical shape.
  • the through hole 101a functions as a cell culture holding member placement space.
  • a part of the lower surface P101b of the base 101 functions as a first fixing portion 101b and a second fixing portion 101c.
  • the first fixing portion 101b corresponds to a portion of the lower surface P101b that fixes a first end portion 105b (described later) of the cell culture holding member 105.
  • the second fixing portion 101c corresponds to a portion that fixes the second end portion 105c (described later).
  • the base 101 is formed of, for example, polycarbonate.
  • the cell culture holding member 105 has a thin disc shape and is arranged along the lower surface P101b of the base 101. The cell culture holding member 105 will be described later.
  • the operation portion 107 is formed so as to project from the upper surface P101a (see FIG. 3) of the base portion 101.
  • a plurality of operation portions 107 are radially formed on the upper surface P101a of the base portion 101 with the through hole 101a as the center.
  • Each operation unit 107 has a rectangular shape of a semicircle in the lateral direction in a cross section along the upper surface P101a of the base 101.
  • the operation unit 107 is formed integrally with the base 101 by using a predetermined resin material such as polycarbonate. By disposing the operation unit 107, the operation unit 107 can be held by tweezers or the like, so that the user can easily operate the cell holding device 100.
  • the cell culture holding member 105 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material.
  • the fibrous material forming the cell culture holding member 105 will be described. Even if cells are cultivated in a conventional fiber sheet for cell culture, the elasticity of the fiber itself is small and the rigidity is high compared to the force accompanying the movement of the cell itself such as the contraction force accompanying the pulsation The cells cannot move, that is, the cells are restrained by the fiber sheet, and the movement of the cells is small. Therefore, as the fibrous material forming the cell culture holding member 105, a fibrous material having an elastic force that does not hinder the movement of the cells to be cultured is used.
  • the cell culture holding member 105 is formed by using a fiber made of a thermoplastic polyester elastomer having a predetermined elastic modulus.
  • the thermoplastic polyester elastomer is a block copolymer of PBT (polybutylene terephthalate) and polyether.
  • FIG. 5 is an enlarged view of the cell culture holding member 105.
  • a fiber F105 using a thermoplastic polyester elastomer as a fibrous material is arranged along a predetermined orientation direction A105. Further, the fiber F105 is arranged at a predetermined interval from the other fiber F105 located adjacent thereto.
  • the cell culture holding member 105 is formed by stacking a plurality of layers with a plurality of fibers F105 arranged in a predetermined direction at a predetermined interval as shown in FIG.
  • the fibers F105 forming the cell culture holding member 105 are not necessarily arranged in parallel.
  • the orientation direction A105 in the cell culture holding member 105 does not mean the orientation direction of the individual fibers F105, but the orientation direction that appears as the entire fiber F105 forming the cell culture holding member 105.
  • FIG. 6 shows a perspective view of the cell culture holding member 105 from diagonally above.
  • the cell culture holding member 105 has two openings 105a.
  • the opening 105a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 105 is arranged in the base 101.
  • the opening 105a has an edge portion 105a1 and an arc portion 105a2.
  • the edge portion 105a1 is formed in a straight line along the alignment direction A105. Therefore, it can be said that the edge portion 105a1 has at least a portion along the alignment direction A105.
  • the arcuate portion 105a2 has an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the edge portion 105a1.
  • the cell culture holding unit 105 has a first end 105b, a second end 105c, and a cell culture unit 105d.
  • the first end 105b and the second end 105c are located opposite to each other at both ends of the cell culture unit 105d.
  • the first end portion 105b and the second end portion 105c correspond to portions of the hollow cylindrical portion of the cell culture holding member 105 excluding the cell culture portion 105d, which are located linearly with the cell culture portion 105d.
  • the first end 105b and the second end 105c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like.
  • the end-to-end portion 105e except the first end portion 105b and the second end portion 105c from the hollow cylindrical portion of the cell culture holding member 105 excluding the cell culture portion 105d is also fixed to the base portion 101 by a predetermined adhesive material or the like. It is fixed to the lower surface P101b.
  • the adhesive is absorbed in the gap between the fibers F105 of the cell culture holding member 105 at the stage where the cell culture holding member 105 is pressure-bonded to the lower surface P101b of the base 101, and becomes integrated with the cell culture holding member 105.
  • the adhesive for example, KE45 is used.
  • the cell culture portion 105d is formed between the edge portion 105a1 of the opening 105a.
  • the cell culture part 105d is fixed to the base part 101 along the alignment direction A101 by the first end part 105b and the second end part 105c.
  • the cell culture unit 105d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
  • a cell suspension is dropped through the through hole 101a to the cell culture section 105d exposed from the through hole 101a using a pipette or the like. And culture.
  • a cell having a structure similar to that of an actual tissue cell can be cultured.
  • the cell culture section 105d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture section 105d is constrained only in the orientation direction A105 of the cell culture holding member 105 to intersect.
  • the cultured cells can be beat more freely as compared with the conventional method in which the cells were constrained in all directions, so that the cardiomyocytes can be more greatly beat than in the past. .
  • the state when the cell contracts most and the state before the contraction are photographed by the image capturing device, and the two are compared.
  • the contraction rate of cultured cells can be easily measured. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • FIG. 7 shows an operating state of cardiomyocytes cultured in the cell culture holding member 105 formed by using a fiber made of a thermoplastic polyester elastomer (elastic modulus: 10 to 232 MPa) as a fibrous material.
  • the cell holding device 100 was used in which the cell culture holding member 105 was seeded with cardiomyocytes cultured for 7 days or more.
  • An inverted stereomicroscope (OLYMPUS, IX73) was used to acquire the image in FIG. 7.
  • the software (OLYMPUS cellSens standard) attached to the inverted stereomicroscope was used for image acquisition and mutation measurement.
  • the displacement in cultured cardiomyocytes was defined as the distance between the most contracted state at the point where the displacement was greatest and the state before contraction.
  • FIG. 7A shows a state when the cardiomyocytes contract most
  • FIG. 7B shows a state before the cardiomyocytes contract.
  • the dotted line in FIG. 7B shows the outline of the state of the cardiomyocyte shown in FIG. 7A.
  • the maximum displacement X at one end is approximately 54 ⁇ m between the most contracted state (FIG. 7A) and the state before contraction (FIG. 7B).
  • Meters, and thus about 108 micrometers can be observed at both ends.
  • the width W of the cell culture holding member 105 before contraction (FIG. 7B) is about 1225 micrometers. Therefore, the rate of change of the cell culture holding member 105 during contraction is 8.8%.
  • cardiomyocytes were cultured on a cell culture sheet formed of conventional polystyrene (elastic modulus: 2300 to 3300 MPa), the cardiomyocytes could only be observed to have a maximum displacement of several microns.
  • the device 100 it is possible to easily observe the displacement of the cultured cardiomyocytes, and it can be useful for measuring the contraction rate of the cultured cardiomyocytes.
  • Example 1 described above the cell culture holding member 105 had the opening 105a having the linear edge portion 105a1 along the orientation direction A105.
  • the cell culture holding member 205 has an arc-shaped edge portion 205a1.
  • the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
  • FIGS. 8 and 9 show a perspective view of the cell holding device 200 from diagonally above
  • FIG. 9 shows a perspective view of the cell holding device 200 from diagonally below.
  • the cell holding device 200 has a base 101, a cell culture holding member 205, and an operation unit 107.
  • the cell culture holding member 205 has a thin disc shape and is arranged along the lower surface P101b of the base 101.
  • the cell culture holding member 205 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 205 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
  • the cell culture holding member 205 has two openings 205a.
  • the opening 205a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 205 is arranged in the base 101.
  • the opening 205a has an edge portion 205a1 and an arc portion 205a2.
  • the edge portion 205a1 is formed in an arc shape.
  • the edge portion 205a1 has at least a portion R205a1 along the alignment direction A105.
  • the arcuate portion 205a2 has an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the edge portion 205a1.
  • the cell culture holding unit 205 has a first end 205b, a second end 205c, and a cell culture unit 205d.
  • the first end 205b and the second end 205c are located opposite to each other at both ends of the cell culture unit 205d.
  • the first end portion 205b and the second end portion 205c correspond to portions of the hollow cylindrical portion of the cell culture holding member 205 excluding the cell culture portion 205d, which are located linearly with the cell culture portion 205d.
  • the first end 205b and the second end 205c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like.
  • the end portion 205e of the cell culture holding member 205 excluding the first end portion 205b and the second end portion 205c from the hollow cylindrical portion excluding the cell culture portion 205d is also fixed to the base portion 101 by a predetermined adhesive material or the like. It is fixed to the lower surface P101b.
  • the cell culture portion 205d is formed between the edge portion 205a1 of the opening 205a.
  • the cell culture part 205d is fixed to the base part 101 along the alignment direction A101 by the first end part 205b and the second end part 205c.
  • the cell culture unit 205d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
  • a cell having a structure similar to an actual tissue cell can be cultured.
  • the cell culture portion 205d is arranged in the through hole 101a which is the cell culture holding member arrangement space formed in the base 101, and the cell culture portion 205d is constrained only in the orientation direction A105 of the cell culture holding member 205 so that the cell culture holding member 205 intersects.
  • the cultured cells can be beat more freely as compared with the conventional method in which the cells were constrained in all directions, so that the cardiomyocytes can be more greatly beat than in the past. .
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • Example 1 described above the cell culture holding member 105 had the opening 105 having the linear edge portion 105a1 along the orientation direction A105.
  • the cell culture holding member 305 has a flat plate shape having a linear edge portion 305a1 along the orientation direction A105.
  • the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
  • FIG. 10 shows a perspective view of the cell holding device 300 from diagonally above
  • FIG. 10 shows a perspective view of the cell holding device 300 from diagonally below.
  • the cell holding device 300 has a base portion 101, a cell culture holding member 305, and an operating portion 107.
  • the cell culture holding member 305 has a thin flat plate shape and is arranged along the lower surface P101b of the base 101.
  • the cell culture holding member 305 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 305 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
  • the cell culture holding member 305 has an edge portion 305a1.
  • the edge portion 305a1 is formed along the alignment direction A105.
  • the cell culture holding unit 305 has a first end 305b, a second end 305c, and a cell culture unit 305d.
  • the first end 305b and the second end 305c are located opposite to each other at both ends of the cell culture unit 305d.
  • the first end portion 305b and the second end portion 305c correspond to portions that are located linearly with the cell culture portion 305d.
  • the first end 305b and the second end 305c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like.
  • the cell culture portion 305d is formed between the edge portions 305a1.
  • the cell culture part 305d is fixed to the base part 101 along the orientation direction A101 by the first end part 305b and the second end part 305c.
  • the cell culture unit 305d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
  • a cell having a structure similar to that of an actual tissue cell can be cultured.
  • the cell culture portion 305d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture portion 305d is restricted only in the orientation direction A105 of the cell culture holding member 305 and intersects.
  • the cultured cells can be beat more freely than in the conventional method in which the cells are constrained in all directions, and thus the cardiomyocytes can be beat more than before. .
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • the base 101 had a hollow cylindrical shape.
  • the base 401 has two flat plate shapes.
  • the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
  • FIGS. 12 and 13 shows a perspective view of the cell holding device 400 from diagonally above
  • FIG. 13 shows a perspective view of the cell holding device 400 from diagonally below.
  • the cell holding device 400 has a base portion 401, a cell culture holding member 405, and an operating portion 407.
  • the base 401 has a thin flat plate shape.
  • the bases 401 are arranged at predetermined intervals.
  • the base portion 401 has an upper surface P401a (see FIG. 3) and a lower surface P401b (see FIG. 4).
  • the space between the bases 401 arranged at predetermined intervals functions as a cell culture holding member arrangement space.
  • a part of the lower surface P401b of the base portion 401 functions as the first fixing portion 401b and the second fixing portion 401c.
  • the first fixing portion 401b corresponds to a portion of the lower surface P401b that fixes a first end portion 405b (described later) of the cell culture holding member 405.
  • the second fixing portion 401c corresponds to a portion that fixes the second end portion 405c (described later).
  • the base 401 is formed of polycarbonate, for example.
  • the cell culture holding member 405 has a thin flat plate shape, and is arranged along the lower surface P401b of the base 401.
  • the operation unit 407 is formed so as to protrude from the upper surface P401a (see FIG. 3) of the base 401.
  • the operation portion 407 is formed so as to suspend the two base portions 401 on the upper surface P401a of the base portion 101.
  • the operation unit 407 is made of a predetermined resin material, for example, polycarbonate, and is integrally formed with the base 401. By disposing the operation unit 407, the operation unit 407 can be held by tweezers or the like, and thus the user can easily operate the cell holding device 400.
  • the cell culture holding member 405 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Like the cell culture holding member 105, the cell culture holding member 405 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
  • the cell culture holding member 405 has an edge portion 405a1.
  • the edge portion 405a1 is formed along the alignment direction A105.
  • the cell culture holding unit 405 has a first end 405b, a second end 405c, and a cell culture unit 405d.
  • the first end 405b and the second end 405c are located opposite to each other at both ends of the cell culture unit 405d.
  • the first end portion 405b and the second end portion 405c correspond to portions that are located linearly with the cell culture portion 405d.
  • the first end 405b and the second end 405c are fixed to the lower surface P401b of each of the two bases 401 by a predetermined adhesive material or the like.
  • the cell culture part 405d is formed between the edge parts 405a1.
  • the cell culture part 405d is fixed to the base part 101 by the first end part 405b and the second end part 405c along the alignment direction A101.
  • the cell culture unit 405d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
  • a cell having a structure similar to that of an actual tissue cell can be cultured.
  • the cell culture section 405d is arranged in the cell culture holding member arrangement space formed by the two bases 401, the cell culture section 405d is restricted only in the orientation direction A105 of the cell culture holding member 405, and in the intersecting direction.
  • the cultured cells can be beat more freely as compared with the conventional technique in which the cultured cells are restrained in all directions, so that the cardiomyocytes can be beaten more than before.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • Example 1 described above the cell culture holding member 105 had the first end 105b and the second end 105c fixed to the base 101.
  • the cell culture holding member 505 has a first end 105b fixed to the base 101 and a second end not fixed to the base 101. And 505b.
  • the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
  • FIG. 14 shows a perspective view of the cell holding device 500 from diagonally above
  • FIG. 14 shows a perspective view of the cell holding device 500 from diagonally below.
  • the cell holding device 500 has a base portion 101, a cell culture holding member 505, and an operating portion 107.
  • the cell culture holding member 505 has a thin flat plate shape, and is arranged along the lower surface P101b of the base 101.
  • the cell culture holding member 505 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 505 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
  • the cell culture holding member 505 has three openings 505a.
  • the opening 505a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 505 is arranged in the base 101.
  • the opening 505a is divided into two types, two openings 505aX and one opening 505aY.
  • the two openings 505aX are arranged in a mirror image relationship so that respective alignment direction edge portions 505aX1 (described later) face each other.
  • the opening 505aY is arranged such that its own intersecting direction edge portion 505aY1 (described later) and each intersecting direction edge portion 505aX3 (described later) of the two openings 505aX face each other.
  • the opening 505aX has an orientation direction edge portion 505aX1, a circular arc portion 505aX2, and a cross direction edge portion 505aX3.
  • the alignment direction edge portion 505aX1 is formed in a straight line along the alignment direction A105. Therefore, it can be said that the alignment direction edge portion 505aX1 has at least a portion along the alignment direction A105.
  • the arcuate portion 505aX2 is formed in an arcuate shape along the through hole 101a formed in the base 101, and is connected to one end of the alignment direction edge portion 505aX1.
  • the cross direction edge portion 505aX3 is linearly formed in a direction crossing the alignment direction A105.
  • the arcuate portion 505aX3 is connected to one end of the alignment direction edge portion 505aX1 and one end of the arcuate portion 505aX2.
  • the opening 505aY has a cross direction edge portion 505aY1 and an arc portion 505aY2.
  • the cross direction edge portion 505aY1 is formed in a straight line along a direction crossing the alignment direction A105.
  • the cross direction edge 505aY1 of the opening 505aY1 is arranged to face the cross direction edge 505aX3 of the opening 505aX.
  • the arcuate portion 505aY2 is formed in an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the cross direction edge portion 505aY1.
  • the cell culture holding unit 505 has a first end 505b, a second end 505c, a cell culture unit 505d, and a connecting unit 505e.
  • the first end 505b and the second end 505c are located opposite to each other at both ends of the cell culture unit 505d.
  • the first end portion 505b corresponds to a portion of the hollow cylindrical portion of the cell culture holding member 505 excluding the cell culture portion 505d, which is located linearly with the cell culture portion 505d.
  • the first end 505b is directly fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like.
  • the second end portion 505c is not directly fixed to the base portion 101, but is connected to the base portion 101 via the connection portion 505e. Therefore, the cell culture portion 505d can be formed similarly to the cantilever.
  • the second end portion 505c of the cell culture unit 505d is not directly fixed, and the degree of fixing is weak, so that the cell culture unit 505d can contract in the alignment direction A101. That is, the cell culture section 505d can be brought into a state in which it is substantially unrestrained in any direction.
  • the cell culture portion 505d is formed between two edge portions 505aX1 located opposite to each other.
  • Predetermined cells for example, beating cardiomyocytes or skeletal muscle cells are three-dimensionally cultured in the cell culture unit 505d.
  • the cell culture unit 505d holds the cultured cells.
  • the connecting portion 505e is formed between the two intersecting direction edge portions 505aX3 of the opening 505aX and the intersecting direction edge portion 505aY1 of the opening 505aY located opposite thereto.
  • the connection portion 505e is formed to connect the second end portion 505c located at one end of the cell culture portion 505d and the base portion 101. That is, one end of the connecting portion 505e is connected to the second end 505c, and the other end, the connecting end 505e1, is connected to the lower surface P101b of the base 101.
  • the connection end portion 505e1 corresponds to a portion of the connection member 505e that is located in the through hole 101a of the base portion 101 and extends toward the base portion 101 side opposite to the second end portion 505c.
  • the first end portion 505b, the second end portion 505c, the cell culture portion 505d, and the connection portion 505e are integrated by forming an opening 505aX and an opening 505aY in a sheet of a predetermined shape formed of a fibrous material. Formed.
  • the first fixing portion 101b corresponds to a portion of the lower surface P101b that fixes the first end portion 505b of the cell culture holding member 105.
  • the second fixing portion 501c corresponds to the portion that fixes the connection end portion 505e1.
  • a cell having a structure similar to an actual tissue cell can be cultured.
  • the cell culture section 505d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture section 505d is also oriented in the orientation direction A105 of the cell culture holding member 305.
  • the cultured cells can be beat more freely than in the conventional method in which the cells are constrained in all directions. Therefore, the cultured cardiomyocytes can be beaten more than before.
  • the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
  • the cell holding device 700 has a through hole 701c in which cells can be easily cultured, in contrast to the through hole 101c included in the base portion 101 of the cell holding device 100 according to the first embodiment.
  • the same components as those in the first embodiment are designated by the same reference numerals, and detailed description will be omitted.
  • FIG. 16 shows a perspective view of the cell holding device 700 from diagonally above.
  • the cell holding device 700 has a base portion 701, a cell culture holding member 105, an operating portion 707, and an air vent portion 711.
  • the base 701 has a thin disc shape.
  • the base portion 701 has a through hole 701a in the center.
  • the base portion 701 also has an upper surface P701a and a lower surface P701b (see FIG. 17).
  • the through hole 701a is formed so as to penetrate the base 701 from the upper surface P701a to the lower surface P701b of the base 701.
  • the through hole 701a functions as a cell culture holding member placement space.
  • the through hole 701a has a truncated cone shape that narrows from the upper surface P701a where the operation portion 707 is formed toward the lower surface P701b. Accordingly, the opening on the upper surface P701a side of the base portion 701 can be increased, and thus the cell suspension can be easily dropped from the upper side into the through hole 701a. Further, since the capacity of the through hole 701a can be increased, a larger amount of cell suspension can be retained in the through hole 701a.
  • the through hole 701a has an inclined portion S701a at a predetermined distance from the lower surface P701b of the base 701 toward the upper surface P701a.
  • the inclined portion S701a is formed as a surface inclined by a predetermined angle from the axial direction.
  • the axial section of the inclined portion S701a is an inclined straight line.
  • a part of the lower surface P701b of the base portion 701 functions as a first fixing portion and a second fixing portion.
  • the base 701 is formed of, for example, polycarbonate.
  • the operation portion 707 is formed so as to project from the upper surface P701a of the base portion 701.
  • the operation portion 707 is formed on the upper surface P701a of the base portion 701 in parallel with the through hole 701a therebetween.
  • the operating portion 707 can be formed at a distance from the through hole 701a. Therefore, when the cells are cultured, the cell culture solution stored in the through hole 701a exceeds the surface tension of itself and the through hole 701a is formed. Can be prevented from flowing out.
  • the length of the operating portion 707 can be made longer, so that it can be easily pinched with tweezers or the like, and the cell holding device 700 can be easily operated.
  • the cell culture holding member 705 is arranged so that the orientation direction A705 of the fibrous material is oriented in a direction intersecting with the operation portion. Accordingly, the orientation direction A705 of the fibrous material of the cell culture holding member 705 can be easily grasped only by confirming the formation direction of the operation portion 707.
  • the operation unit 707 is formed integrally with the base 701 by using a predetermined resin material such as polycarbonate. By disposing the operation unit 707, the operation unit 707 can be held by tweezers or the like, and thus the user can easily operate the cell holding device 700.
  • the air vent 711 is formed as a region in which a part of the outer peripheral portion of the base 701 is cut off.
  • the small cell culture holding member 701 located below the base 701 is also formed in the same shape as the base 701. Thereby, when the cell holding device 700 is put into a cell content container such as one well of a multi-well plate, the air that has entered the lower part of the cell holding device 700 can be easily discharged.
  • Shape of the opening 105a of the cell culture holding member 105 In the above-described Example 1, the opening 105a of the cell culture holding member 105 has a linear edge portion 105a1 along the orientation direction A101 of the fibrous member, and , The arc-shaped portion 105a2, and the opening 205a of the cell culture holding member 205 has the arc-shaped edge portion 205a1 and the arc-shaped portion 205a2 in the second embodiment described above. It is not limited to the example as long as it has an edge portion having at least a part along the alignment direction.
  • the opening may be circular, elliptical, or rectangular. The same applies to the other examples.
  • an opening not including a portion along the orientation direction of the fibrous material may be formed in each cell culture holding member.
  • cardiomyocytes were shown as cells to be cultured, but the cells are not limited to the exemplified ones.
  • it may be a skeletal muscle cell. It may also be a cardiomyocyte or skeletal muscle cell derived from pluripotent stem cells.
  • the pluripotent stem cells include, for example, embryonic stem cells (ES cells) and iPS cells.
  • the base 101 and the operation unit 107 are formed as one body, but they are formed as separate bodies, and an adhesive or the like is used. You may make it join
  • connection part 505e is formed integrally with the cell culture part 505d and the like, but it may be formed as a separate body.
  • a cell culture holding member 605 is formed with a U-shaped opening 605a in which an opening 505aX and an opening 505aY (see FIG. 15) are integrated, and both are connected.
  • the second end 605c which is not formed is formed, and as shown in FIG. 18B, the formed second end 605c and the base 101 are thin so that both ends of the second end 605c and the base 101 are suspended.
  • the connection member 609 is fixed to the cell culture holding member 605 with a predetermined adhesive material or the like.
  • the cell holding device 600 that connects the second end portion 605c and the base portion 101 by using the thin linear connecting member 609 so as to suspend both ends of the second end portion 605c and the base portion 101
  • the second end portion 605c and the base portion 101 are suspended from one end of the second end portion 605c and the base portion 101, that is, of the cantilever.
  • the connection may be performed using the thin linear connecting member 809.
  • Fibrous material of cell culture holding member In the above-mentioned Examples 1 to 5, thermoplastic polyester elastomer (elastic modulus: 10 to 232 MPa) was exemplified as the fibrous material. It is not limited to the exemplified one as long as it does not restrain the cells cultured in 1. and does not impede movement such as pulsation. As the fibrous material, at least 2000 MPa or less, particularly 500 MPa or less, which is lower than the elastic modulus of conventional polystyrene, is suitable.
  • the cell holding device according to the present invention can be used, for example, for measuring contractility of cardiomyocytes.

Abstract

[Problem] To provide a cell holding device, in which cells each having a structure close to an actual structure can be cultured and the contractile property of cultured cells can be measured easily. [Solution] A cell holding device 100 is provided with a substrate 101, a cell culturing/holding member 105, and an operation section 107. Specific cells, e.g., cardiomyocytes, are cultured in a cell culturing section 105d having a specific orientation direction A105. In this manner, cells each having the same structure as those of actual tissue cells can be cultured. The cell culturing section 105d is placed in a through-hole 101a that is a cell culturing/holding member placing space formed in the substrate 101, and the cell culturing section 105d is constrained only in the orientation direction A105 of the cell culturing/holding member 105 and is not constrained in a direction orthogonal to the orientation direction A105. As a result, cultured cells can beat more freely compared with the conventional methods in which the cell culturing section 105d is constrained in all directions. Accordingly, it becomes possible to beat cardiomyocytes greatly compared with the conventional methods.

Description

細胞保持装置Cell retention device
　本発明は、細胞保持装置に関し、特に、培養した細胞の収縮性を計測できるものに関する。 The present invention relates to a cell holding device, and more particularly to a device capable of measuring contractility of cultured cells.
　細胞の収縮性計測に関する従来技術ついて、図２０に示す細胞組織の収縮力測定方法を用いて説明する。保持面２０ａと複数の軸部２１とを有する保持具２０を準備する。一対の嵌合部１６と、係合壁１２とを有する基材１０を準備する。少なくとも所定方向に間隔をあけて配置した一対の保持具のそれぞれに対して、軸部と当接させて保持面に細胞を含有する液体を載せるステップと、保持面のそれぞれに載せた液体をゲル化して第１ゲル体を対で形成するとともに、細胞を含有する液体をゲル化して所定方向に延び対をなす第１ゲル体同士を接続する所定形状の第２ゲル体を形成するステップと、少なくとも第２ゲル体を培養して所定方向に延びる細胞組織ＭＳを形成するステップと、細胞組織が設けられた一対の保持具を基材の一対の嵌合部に嵌合させるステップと、細胞組織の収縮に伴う力による係合壁の弾性変形に応じて細胞組織の収縮力を測定するステップと、を含む。 The conventional technique relating to the measurement of contractility of cells will be described using the method for measuring the contractile force of cell tissues shown in FIG. A holder 20 having a holding surface 20a and a plurality of shaft portions 21 is prepared. A base material 10 having a pair of fitting portions 16 and an engagement wall 12 is prepared. At least a pair of holders arranged at intervals in a predetermined direction, a step of contacting the shaft portion with a liquid containing cells on the holding surface, and a step of placing the liquid on each of the holding surfaces into a gel Forming a pair of first gel bodies to gel a liquid containing cells and extending in a predetermined direction to form a second gel body of a predetermined shape connecting the pair of first gel bodies to each other, Culturing at least the second gel body to form a cell tissue MS extending in a predetermined direction; fitting a pair of holders provided with the cell tissue to a pair of fitting portions of the base material; Measuring the contractile force of the cellular tissue in response to the elastic deformation of the engagement wall due to the force associated with the contraction of.
　これにより、細胞組織の収縮力を高精度に測定できる（以上、特許文献１参照）。 With this, it is possible to measure the contractile force of the cell tissue with high accuracy (see Patent Document 1 above).
特開２０１６－０４１０５９号公報JP, 2016-041059, A
　前述の細胞組織の収縮力測定方法には、以下に示すような改善すべき点がある。前述の細胞組織の収縮力測定方法では、収縮力を計測する細胞を培養に際して、複数の複雑なステップを、時間掛けて実施する必要がある。このため、収縮力を測定するまでの準備に時間を要する、という改善すべき点がある。 The above-mentioned method for measuring the contractile force of cellular tissue has the following points to be improved. In the above-described method for measuring the contractile force of a cell tissue, it is necessary to carry out a plurality of complicated steps over time when culturing cells for measuring the contractile force. Therefore, there is a point to be improved that it takes time to prepare before measuring the contraction force.
　また、収縮力を計測する細胞を培養に際して、複数の複雑なステップを、時間掛けて実施する必要があるため、培養した細胞の品質が一定しない可能性がある、という改善すべき点がある。 Also, when culturing cells for measuring contractile force, it is necessary to perform multiple complicated steps over time, so the quality of the cultivated cells may not be constant.
　さらに、収縮力を計測する細胞を培養をゲル化して培養するため、実際の組織としての細胞とは構造が異なるため、実際の組織としての細胞の収縮力を計測できていない可能性がある、という改善すべき点がある。 Furthermore, since the cells for measuring contractile force are cultured by gelling and culturing, the structure is different from the cells as the actual tissue, so the contractive force of the cells as the actual tissue may not be measured, There is a point to be improved.
　そこで、本発明は、実際の組織に近い細胞を培養し、培養した細胞の収縮性を容易に計測できる細胞保持装置を提供することを目的とする。
　すなわち、本発明は、下記記載の発明を提供することにより上記課題を解決したものである。
（１）　所定の繊維状物によって形成され、細胞を培養し、保持する細胞培養部と、前記細胞培養部の両端に位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置する縁部と、を有する細胞培養保持部材、
　前記第１端部を直接的に固定する第１固定部、
　前記第２端部を固定する第２固定部、
　前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、
　を有する細胞保持装置。
（２）　（１）に係る細胞保持装置において、
　前記第２固定部は、
　前記所定方向に沿って前記第１固定部に対向して位置すること、
　を特徴とする細胞保持装置。
（３）　（１）に係る細胞保持装置において、
　前記第２固定部は、
　前記所定方向に交差する方向に沿って位置すること、
　を特徴とする細胞保持装置。
（４）　（１）～（３）のいずれかに係る細胞保持装置において、
　前記細胞培養部は、
　所定の配向方向に沿って配置された前記繊維状物によって形成され、
　前記縁部は、
　前記配向方向に沿った部分を少なくとも一部に有すること、
　を特徴とする細胞保持装置。
（５）　（１）～（４）のいずれかに係る細胞保持装置において、
　前記第１固定部、及び、前記第２固定部は、
　それぞれ、平板状の基部の少なくとも一部であり、
　前記細胞培養保持部材配置空間は、
　前記基部を貫通するように形成される貫通孔であること、
　を特徴とする細胞保持装置。
（６）　（５）に係る細胞保持装置において、
　前記細胞培養保持部材は、
　前記貫通孔に対応する位置に開口を有すること、
　を特徴とする細胞保持装置。
（７）　（４）～（６）のいずれかに係る細胞保持装置おいて、
　前記縁部は、
　前記配向方向に沿って直線状に形成されている部分を有すること、
　を特徴とする細胞保持装置。
（８）　（１）～（７）のいずれかに係る細胞保持装置において、
　前記細胞培養保持部材は、
　前記繊維状物の弾性率が、２０００ＭＰａ以下であること、
　を特徴とする細胞保持装置。
（９）　（１）～（８）のいずれかに係る細胞保持装置において、さらに、
　所定の保持具によって挟持できる操作部、
　を有する細胞保持装置。
（１０）　（１）～（９）のいずれかに係る細胞保持装置において、
　前記細胞培養保持部材は、
　前記細胞として、心筋細胞、または、骨格筋細胞を培養し、保持していること、
　を特徴とする細胞保持装置。
（１１）　（１）～（９）のいずれかに係る細胞保持装置において、
　前記細胞培養保持部材は、
　前記細胞として、心筋細胞を培養、保持し、
　前記心筋細胞を培養した前記細胞培養保持部材の収縮率が、２．５パーセント以上であること、
　を特徴とする細胞保持装置。
（１２）　（１）～（１１）のいずれかに係る細胞保持装置において、
　前記細胞保持装置は、
　前記細胞の収縮性の計測に用いられること、
　を特徴とする細胞保持装置。
（１３）　細胞の収縮性を計測するための細胞保持装置であって、所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部と、前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部と、を有する細胞培養保持部材を有する細胞保持装置において、
　前記第１端部を固定する第１固定部、
　前記第２端部を固定する第２固定部、
　前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、
　を有する細胞保持装置。
（１４）　細胞の収縮性を計測するための細胞保持装置に用いる細胞培養保持部材であって、
　所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部、
　前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部、
　前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部、
　を有する細胞培養保持部材。
  Therefore, an object of the present invention is to provide a cell holding device capable of culturing cells close to an actual tissue and easily measuring the contractility of the cultivated cells.
That is, the present invention has solved the above problems by providing the inventions described below.
(1) A cell culture part formed of a predetermined fibrous material for culturing and holding cells, a first end and a second end located at both ends of the cell culture part, and the first end And a rim located between the second end and the cell culture holding member,
A first fixing portion for directly fixing the first end portion,
A second fixing portion for fixing the second end portion,
A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion;
And a cell holding device.
(2) In the cell holding device according to (1),
The second fixing portion is
Being positioned to face the first fixing portion along the predetermined direction,
A cell holding device characterized by:
(3) In the cell holding device according to (1),
The second fixing portion is
Being located along a direction intersecting with the predetermined direction,
A cell holding device characterized by:
(4) In the cell holding device according to any one of (1) to (3),
The cell culture section,
Formed by the fibrous material arranged along a predetermined orientation direction,
The edge is
Having at least a portion along the alignment direction,
A cell holding device characterized by:
(5) In the cell holding device according to any one of (1) to (4),
The first fixing portion and the second fixing portion are
Each is at least a part of a flat base,
The cell culture holding member arrangement space,
A through hole formed so as to penetrate the base,
A cell holding device characterized by:
(6) In the cell holding device according to (5),
The cell culture holding member,
Having an opening at a position corresponding to the through hole,
A cell holding device characterized by:
(7) In the cell holding device according to any one of (4) to (6),
The edge is
Having a portion formed in a straight line along the alignment direction,
A cell holding device characterized by:
(8) In the cell holding device according to any one of (1) to (7),
The cell culture holding member,
The elastic modulus of the fibrous material is 2000 MPa or less,
A cell holding device characterized by:
(9) In the cell holding device according to any one of (1) to (8),
An operation part that can be held by a predetermined holder,
And a cell holding device.
(10) In the cell holding device according to any one of (1) to (9),
The cell culture holding member,
As the cells, culturing and holding cardiomyocytes or skeletal muscle cells,
A cell holding device characterized by:
(11) In the cell holding device according to any one of (1) to (9),
The cell culture holding member,
As the cells, cardiomyocytes are cultured and maintained,
The contraction rate of the cell culture holding member in which the cardiomyocytes are cultured is 2.5% or more,
A cell holding device characterized by:
(12) In the cell holding device according to any one of (1) to (11),
The cell holding device,
Used to measure the contractility of the cells,
A cell holding device characterized by:
(13) A cell holding device for measuring the contractility of cells, which comprises a cell culture section for culturing and holding cells formed by fibrous substances arranged along a predetermined orientation direction, and the orientation. A first end portion and a second end portion facing each other along a direction intersecting the direction, and a portion located between the first end portion and the second end portion and extending along the alignment direction. In a cell holding device having a cell culture holding member having an edge portion having at least a part,
A first fixing portion for fixing the first end portion,
A second fixing portion for fixing the second end portion,
A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion;
And a cell holding device.
(14) A cell culture holding member used in a cell holding device for measuring contractility of cells, comprising:
A cell culture unit that cultures and holds cells formed by fibrous substances arranged along a predetermined orientation direction,
A first end and a second end facing each other along a direction intersecting the alignment direction;
An edge portion located between the first end portion and the second end portion and having at least a portion along the alignment direction,
A cell culture holding member having.
　本発明における課題を解決するための手段及び発明の効果を以下に示す。 The means for solving the problems in the present invention and the effects of the invention are shown below.
　本発明に係る細胞保持装置は、所定の繊維状物によって形成され、細胞を培養し、保持する細胞培養部と、前記細胞培養部の両端に位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置する縁部と、を有する細胞培養保持部材、前記第１端部を直接的に固定する第１固定部、前記第２端部を固定する第２固定部、前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、を有する。 A cell holding device according to the present invention is formed of a predetermined fibrous material, cultivates and holds cells, and a cell culturing section, and a first end and a second end located at both ends of the cell culturing section, And a cell culture holding member having an edge portion located between the first end portion and the second end portion, a first fixing portion for directly fixing the first end portion, the second end A second fixing portion for fixing the portion, and a cell culture holding member arrangement space which is located between the first fixing portion and the second fixing portion and does not fix the edge portion.
　これにより、細胞培養部を、基部に形成される細胞培養保持部材配置空間に配置し、少なくとも縁部では細胞培養部を拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動させることができる。 Thereby, by arranging the cell culture portion in the cell culture holding member arrangement space formed in the base portion and not constraining the cell culture portion at least at the edge portion, the cultured cells were restrained in all directions. Since the cells can be beat more freely than before, cells can be beat more than before.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置を用いて培養した細胞を収縮率の計測に役立てることができる。 In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. In other words, cells cultured using the cell holding device can be used for measuring the contraction rate.
　本発明に係る細胞保持装置では、前記第２固定部は、前記所定方向に沿って前記第１固定部に対向して位置すること、を特徴とする。 The cell holding device according to the present invention is characterized in that the second fixing portion is located facing the first fixing portion along the predetermined direction.
　これにより、細胞培養部を、基部に形成される細胞培養保持部材配置空間に配置し、所定の方向に交差する方向には細胞培養部を拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動させることができる。 Thus, by arranging the cell culture section in the cell culture holding member arrangement space formed in the base and not constraining the cell culture section in a direction intersecting with the predetermined direction, the cultured cells are kept in all directions. The cells can be beat more freely than in the conventional method, which allows the cells to be beaten more freely than in the conventional method.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置を用いて培養した細胞を収縮率の計測に役立てることができる。 In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. In other words, cells cultured using the cell holding device can be used for measuring the contraction rate.
　本発明に係る細胞保持装置では、前記第２固定部は、前記所定方向に交差する方向に沿って位置すること、を特徴とする。 The cell holding device according to the present invention is characterized in that the second fixing portion is located along a direction intersecting with the predetermined direction.
　これにより、細胞培養部を、基部に形成される細胞培養保持部材配置空間に配置し、所定の方向、及び、所定の方向に交差する方向には細胞培養部を拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動させることができる。 As a result, the cell culture portion was cultivated by placing it in the cell culture holding member placement space formed in the base and not constraining the cell culture portion in a predetermined direction and in a direction intersecting the predetermined direction. Since cells can be beat more freely than in the conventional method in which the cells are restrained in all directions, the cells can be beat more greatly than in the conventional method.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置を用いて培養した細胞を収縮率の計測に役立てることができる。 In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. In other words, cells cultured using the cell holding device can be used for measuring the contraction rate.
　本発明に係る細胞保持装置では、前記細胞培養部は、所定の配向方向に沿って配置された前記繊維状物によって形成され、前記縁部は、前記配向方向に沿った部分を少なくとも一部に有すること、を特徴とする。 In the cell holding device according to the present invention, the cell culture portion is formed by the fibrous material arranged along a predetermined orientation direction, and the edge portion is at least part of a portion along the orientation direction. It is characterized by having.
　これにより、配向方向を有する細胞培養部に、所定の細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。 With this, by culturing a predetermined cell in the cell culture section having an orientation direction, a cell having a structure similar to an actual tissue cell can be cultured.
　また、細胞培養部を、基部に形成される細胞培養保持部材配置空間に配置し、細胞培養部を細胞培養保持部材の配向方向にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動させることができる。 In addition, the cell culture section is placed in the cell culture holding member placement space formed in the base, and the cell culture section is cultivated by constraining it only in the orientation direction of the cell culture holding member and not in the intersecting direction. The cells can be beat more freely than in the conventional method in which the cells are restrained in all directions, so that the cells can be beat more greatly than in the conventional method.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。 In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
　本発明に係る細胞保持装置では、前記第１固定部、及び、前記第２固定部は、それぞれ、平板状の基部の少なくとも一部であり、前記細胞培養保持部材配置空間は、前記基部を貫通するように形成される貫通孔であること、を特徴とする。 In the cell holding device according to the present invention, each of the first fixing portion and the second fixing portion is at least a part of a plate-shaped base portion, and the cell culture holding member placement space penetrates the base portion. It is a through hole formed so that
　これにより、貫通孔を有する基部を形成するだけで、容易に、従来よりも、細胞を大きく拍動させることができる細胞保持装置を形成できる。 By doing so, it is possible to easily form a cell holding device that can make cells pulsate larger than in the past by simply forming a base portion having a through hole.
　本発明に係る細胞保持装置では、前記細胞培養保持部材は、前記貫通孔に対応する位置に開口を有すること、を特徴とする。 The cell holding device according to the present invention is characterized in that the cell culture holding member has an opening at a position corresponding to the through hole.
　これにより、容易に、細胞を大きく拍動させることができる細胞培養保持部材を形成できる。 By doing this, it is possible to easily form a cell culture holding member that can cause large pulsation of cells.
　本発明に係る細胞保持装置では、前記縁部は、前記配向方向に沿って直線状に形成されている部分を有すること、を特徴とする。 The cell holding device according to the present invention is characterized in that the edge portion has a portion linearly formed along the orientation direction.
　これにより、容易に、細胞を大きく拍動させることができる細胞培養保持部材を形成できる。 By doing this, it is possible to easily form a cell culture holding member that can cause large pulsation of cells.
　本発明に係る細胞保持装置では、前記細胞培養保持部材は、前記繊維状物の弾性率が、２０００ＭＰａ以下であること、を特徴とする。 The cell holding device according to the present invention is characterized in that the cell culture holding member has an elastic modulus of 2000 MPa or less.
　これにより、容易に、細胞を大きく拍動させることができる細胞培養保持部材を形成できる。 By doing this, it is possible to easily form a cell culture holding member that can cause large pulsation of cells.
　本発明に係る細胞保持装置では、さらに、所定の保持具によって挟持できる操作部、を有する。 The cell holding device according to the present invention further includes an operation unit that can be held by a predetermined holding tool.
　これにより、容易に、細胞保持装置を移動させることができる。 By doing this, the cell holding device can be easily moved.
　本発明に係る細胞保持装置では、前記細胞培養保持部材は、前記細胞として、心筋細胞、または、骨格筋細胞を培養し、保持していること、を特徴とする。 The cell holding device according to the present invention is characterized in that the cell culture holding member cultures and holds cardiomyocytes or skeletal muscle cells as the cells.
　これにより、心筋細胞や骨格筋細胞の収縮性を計測できる。 With this, contractility of cardiomyocytes and skeletal muscle cells can be measured.
　本発明に係る細胞保持装置では、前記細胞培養保持部材は、前記細胞として、心筋細胞を培養、保持し、前記心筋細胞を培養した前記細胞培養保持部材の収縮率が、２．５パーセント以上であること、を特徴とする。 In the cell holding device according to the present invention, the cell culture holding member is one in which cardiomyocytes are cultured and held as the cells, and the contraction rate of the cell culture holding member obtained by culturing the cardiomyocytes is 2.5% or more. There is a feature.
　これにより、培養した心筋細胞の収縮の変化を容易に観察できる。 This makes it possible to easily observe changes in contraction of cultured cardiomyocytes.
　本発明に係る細胞保持装置では、前記細胞保持装置は、前記細胞の収縮性の計測に用いられること、を特徴とする。 The cell holding device according to the present invention is characterized in that the cell holding device is used for measuring the contractility of the cells.
　これにより、細胞保持装置を用いて、容細胞の収縮性を容易に計測できる。 This will allow you to easily measure the contractility of the cells using the cell retention device.
　本発明に係る細胞保持装置は、細胞の収縮性を計測するための細胞保持装置であって、所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部と、前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部と、を有する細胞培養保持部材を有する細胞保持装置において、前記第１端部を固定する第１固定部、前記第２端部を固定する第２固定部、前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、を有する。 The cell retention device according to the present invention is a cell retention device for measuring the contractility of cells, and is a cell for culturing and retaining cells formed by fibrous substances arranged along a predetermined orientation direction. A culturing part, a first end and a second end facing each other along a direction crossing the alignment direction, and located between the first end and the second end, and In a cell holding device having a cell culture holding member having an edge portion having at least a portion along the orientation direction, a first fixing portion that fixes the first end portion, and the second end portion is fixed. It has a 2nd fixing | fixed part, the cell culture holding member arrangement | positioning space which is located between the said 1st fixing | fixed part and the said 2nd fixed part, and does not fix the said edge part.
　これにより、配向方向を有する細胞培養部に、所定の細胞を培養し、実際の組織細胞と同様の構造を有する細胞を培養した上で、細胞培養部を、基部に形成される細胞培養保持部材配置空間に配置し、細胞培養部を細胞培養保持部材の配向方向にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動させることができる。 As a result, after culturing the predetermined cells in the cell culture portion having the orientation direction and culturing the cells having the same structure as the actual tissue cells, the cell culture holding member formed on the base portion of the cell culture portion. By placing the cells in the arrangement space and constraining the cell culture portion only in the orientation direction of the cell culture holding member and not in the intersecting direction, the cultured cells are restrained in all directions as compared with the conventional method. Since the cells can be beat more freely, the cells can be beat larger than before.
　本発明に係る細胞培養保持部材は、細胞の収縮性を計測するための細胞保持装置に用いる細胞培養保持部材であって、所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部、前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部、前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部、を有する。 The cell culture holding member according to the present invention is a cell culture holding member used in a cell holding device for measuring contractility of cells, and cells formed by fibrous substances arranged along a predetermined orientation direction. A cell culture part for culturing and holding cells, a first end part and a second end part facing each other in a direction intersecting with the orientation direction, and a position between the first end part and the second end part And an edge portion having at least a portion along the alignment direction.
　これにより、配向方向を有する細胞培養部に、所定の細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞であって、細胞培養部を細胞培養保持部材の配向方向にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、細胞を大きく拍動できる細胞を培養できる。
  As a result, by culturing the predetermined cells in the cell culture section having the orientation direction, the cells having the same structure as the actual tissue cells are restrained only in the orientation direction of the cell culture holding member. However, by not constraining in the intersecting direction, the cultured cells can be beat more freely than in the conventional method in which the cells were constrained in all directions, so that the cells can be beat more than before. The cells can be cultured.
本発明に係る細胞保持装置の一実施例である細胞保持装置１００の斜め上方向からの斜視図である。FIG. 1 is a perspective view of a cell holding device 100, which is an embodiment of the cell holding device according to the present invention, viewed obliquely from above. 細胞保持装置１００の斜め下方向からの斜視図である。FIG. 3 is a perspective view of the cell holding device 100 from an obliquely lower direction. 基部部１０１の斜め上方向からの斜視図である。FIG. 3 is a perspective view of the base portion 101 from an obliquely upper direction. 基部部１０１の斜め下方向からの斜視図である。FIG. 3 is a perspective view of the base portion 101 from an obliquely lower direction. 細胞培養保持部材１０５の拡大図である。It is an enlarged view of the cell culture holding member 105. 細胞培養保持部材１０５の斜め上方向からの斜視図である。It is a perspective view of the cell culture holding member 105 from an obliquely upper direction. 細胞培養保持部材１０５に培養した心筋細胞の動作状態を示す図であり、Ａは収縮時の状態を、Ｂは収縮前の状態を、それぞれ示す。FIG. 7 is a diagram showing an operating state of cardiomyocytes cultured in the cell culture holding member 105, where A is a state at the time of contraction and B is a state before the contraction. 本発明に係る細胞保持装置の他の実施例である細胞保持装置２００の斜め上方向からの斜視図である。FIG. 7 is a perspective view of a cell holding device 200, which is another embodiment of the cell holding device according to the present invention, viewed from obliquely above. 細胞保持装置２００の斜め下方向からの斜視図である。It is a perspective view of the cell holding device 200 from an obliquely lower direction. 本発明に係る細胞保持装置の他の実施例である細胞保持装置３００の斜め上方向からの斜視図である。FIG. 7 is a perspective view of a cell holding device 300, which is another embodiment of the cell holding device according to the present invention, seen from obliquely above. 細胞保持装置３００の斜め下方向からの斜視図である。It is a perspective view of the cell holding device 300 from an oblique lower direction. 本発明に係る細胞保持装置の他の実施例である細胞保持装置４００の斜め上方向からの斜視図である。FIG. 7 is a perspective view of a cell holding device 400, which is another embodiment of the cell holding device according to the present invention, seen from diagonally above. 細胞保持装置４００の斜め下方向からの斜視図である。It is a perspective view of the cell holding device 400 from an obliquely lower direction. 本発明に係る細胞保持装置の他の実施例である細胞保持装置５００の斜め上方向からの斜視図である。FIG. 6 is a perspective view of a cell holding device 500, which is another embodiment of the cell holding device according to the present invention, viewed from obliquely above. 細胞保持装置５００の斜め下方向からの斜視図である。It is a perspective view of the cell holding device 500 from an obliquely downward direction. 本発明に係る細胞保持装置の他の実施例である細胞保持装置７００の斜め上方向からの斜視図である。FIG. 7 is a perspective view of a cell holding device 700, which is another embodiment of the cell holding device according to the present invention, viewed from diagonally above. 細胞保持装置７００の断面を示す図である。It is a figure which shows the cross section of the cell holding device 700. 本発明に係る細胞保持装置の他の実施例である細胞保持装置６００を示す図であり、Ａは斜め上方向からの斜視図であり、Ｂは斜め下方からの斜視図である。It is a figure which shows the cell holding | maintenance apparatus 600 which is another Example of the cell holding | maintenance apparatus which concerns on this invention, A is a perspective view from diagonally upward direction, B is a perspective view from diagonally downward. 本発明に係る細胞保持装置の他の実施例である細胞保持装置８００の斜め下方からの斜視図である。FIG. 8 is a perspective view of a cell holding device 800, which is another embodiment of the cell holding device according to the present invention, seen from obliquely below. 細胞の収縮性計測に関する従来技術を示す図である。It is a figure which shows the prior art regarding the contractility measurement of a cell.
　以下、本発明の実施例について、図面を参照しながら詳細に説明していく。 Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
　本発明に係る細胞保持装置について、一実施例である細胞保持装置１００を用いて説明する。細胞保持装置１００は、拍動する細胞の収縮性を評価するための装置である。 The cell holding device according to the present invention will be described using the cell holding device 100 which is one embodiment. The cell holding device 100 is a device for evaluating the contractility of pulsating cells.
第１　構成
　細胞保持装置１００の構成について、図１、図２を用いて説明する。図１は、細胞保持装置１００の斜め上方からの斜視図を、図２は、細胞保持装置１００の斜め下方からの斜視図を、それぞれ示す。 1st structure The structure of the cell holding device 100 is demonstrated using FIG. 1, FIG. FIG. 1 shows a perspective view of the cell holding device 100 from diagonally above, and FIG. 2 shows a perspective view of the cell holding device 100 from diagonally below.
　図１に示すように、細胞保持装置１００は、基部１０１、細胞培養保持部材１０５、及び、操作部１０７を有している。 As shown in FIG. 1, the cell holding device 100 has a base portion 101, a cell culture holding member 105, and an operating portion 107.
　図３に基部１０１の斜め上方からの斜視図を、図４に基部１０１の斜め下方からの斜視図を、それぞれ示す。図３に示すように、基部１０１は、薄い円盤形状を有している。基部１０１は、中央に断面円形の貫通孔１０１ａを有している。また、基部１０１は、上面Ｐ１０１ａ（図３参照）、及び、下面Ｐ１０１ｂ（図４参照）を有している。 FIG. 3 shows a perspective view of the base 101 obliquely from above, and FIG. 4 shows a perspective view of the base 101 obliquely from below. As shown in FIG. 3, the base 101 has a thin disc shape. The base portion 101 has a through hole 101a having a circular cross section in the center. Further, the base 101 has an upper surface P101a (see FIG. 3) and a lower surface P101b (see FIG. 4).
　貫通孔１０１ａは、基部１０１の上面Ｐ１０１ａから下面Ｐ１０１ｂまで、基部１０１を貫通するように形成される。貫通孔１０１ａは、円筒形状として形成される。貫通孔１０１ａは、細胞培養保持部材配置空間として機能する。 The through hole 101a is formed so as to penetrate the base 101 from the upper surface P101a to the lower surface P101b of the base 101. The through hole 101a is formed in a cylindrical shape. The through hole 101a functions as a cell culture holding member placement space.
　図４に示すように、基部１０１の下面Ｐ１０１ｂの一部は、第１固定部１０１ｂ、及び、第２固定部１０１ｃとして機能する。第１固定部１０１ｂは、下面Ｐ１０１ｂのうち、細胞培養保持部材１０５の第１端部１０５ｂ（後述）を固定する部分に対応する。同様に、第２固定部１０１ｃは、第２端部１０５ｃ（後述）を固定する部分に対応する。基部１０１は、例えば、ポリカーボネートにより形成される。 As shown in FIG. 4, a part of the lower surface P101b of the base 101 functions as a first fixing portion 101b and a second fixing portion 101c. The first fixing portion 101b corresponds to a portion of the lower surface P101b that fixes a first end portion 105b (described later) of the cell culture holding member 105. Similarly, the second fixing portion 101c corresponds to a portion that fixes the second end portion 105c (described later). The base 101 is formed of, for example, polycarbonate.
　細胞培養保持部材１０５は、薄い円盤形状を有しており、基部１０１の下面Ｐ１０１ｂに沿って配置される。細胞培養保持部材１０５については、後述する。 The cell culture holding member 105 has a thin disc shape and is arranged along the lower surface P101b of the base 101. The cell culture holding member 105 will be described later.
　図１に示すように、操作部１０７は、基部１０１の上面Ｐ１０１ａ（図３参照）から突出するように形成される。操作部１０７は、基部１０１の上面Ｐ１０１ａに、貫通孔１０１ａを中心に、放射状に、複数、形成される。各操作部１０７は、基部１０１の上面Ｐ１０１ａに沿った断面において短手方向半円の長方形形状を有している。操作部１０７は、基部１０１と同様、所定の樹脂素材、例えば、ポリカーボネートにより、基部１０１と一体に形成される。操作部１０７を配置することによって、操作部１０７をピンセット等で保持できるので、使用者は、容易に、細胞保持装置１００を操作することができる。 As shown in FIG. 1, the operation portion 107 is formed so as to project from the upper surface P101a (see FIG. 3) of the base portion 101. A plurality of operation portions 107 are radially formed on the upper surface P101a of the base portion 101 with the through hole 101a as the center. Each operation unit 107 has a rectangular shape of a semicircle in the lateral direction in a cross section along the upper surface P101a of the base 101. Like the base 101, the operation unit 107 is formed integrally with the base 101 by using a predetermined resin material such as polycarbonate. By disposing the operation unit 107, the operation unit 107 can be held by tweezers or the like, so that the user can easily operate the cell holding device 100.
２．細胞培養保持部材１０５
　細胞培養保持部材１０５は、所定の配向方向に沿って配置された繊維状物、例えば、高分子材料で形成されたファイバーによって形成される。 2. Cell culture holding member 105
The cell culture holding member 105 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material.
ここで、細胞培養保持部材１０５を形成する繊維状物について説明する。従来の細胞培養用のファイバーシートに細胞を培養したとしても、拍動にともなう収縮力といった細胞自身の運動にともなう力に比して、ファイバー自体の弾性が小さく、剛性が大きいため、細胞が自由に運動できない状態、つまり、細胞がファイバーシートに拘束された状態となり、細胞の運動が小さくなっている。このため、細胞培養保持部材１０５を形成する繊維状物として、培養する細胞の運動を妨げない程度の弾性力を有するものを使用する。 Here, the fibrous material forming the cell culture holding member 105 will be described. Even if cells are cultivated in a conventional fiber sheet for cell culture, the elasticity of the fiber itself is small and the rigidity is high compared to the force accompanying the movement of the cell itself such as the contraction force accompanying the pulsation The cells cannot move, that is, the cells are restrained by the fiber sheet, and the movement of the cells is small. Therefore, as the fibrous material forming the cell culture holding member 105, a fibrous material having an elastic force that does not hinder the movement of the cells to be cultured is used.
従来の細胞培養用のファイバーシートは、ポリスチレンによるファイバーを用いて形成されたものが多い。一方、細胞培養保持部材１０５は、所定の弾性率を有する熱可塑性ポリエステルエラストマーによるファイバーを用いて形成している。熱可塑性ポリエステルエラストマーは、ＰＢＴ（ポリブチレンテレフタレート）とポリエーテルとのブロック共重合体である。 Many conventional fiber sheets for cell culture are formed by using polystyrene fibers. On the other hand, the cell culture holding member 105 is formed by using a fiber made of a thermoplastic polyester elastomer having a predetermined elastic modulus. The thermoplastic polyester elastomer is a block copolymer of PBT (polybutylene terephthalate) and polyether.
次に、細胞培養保持部材１０５の構造について、細胞培養保持部材１０５の拡大図である図５を用いて説明する。細胞培養保持部材１０５は、繊維状物として熱可塑性ポリエステルエラストマーを用いたファイバーＦ１０５が、所定の配向方向Ａ１０５に沿って配置されている。また、ファイバーＦ１０５は、隣接して位置する他のファイバーＦ１０５とは、所定の間隔で配置されている。なお、細胞培養保持部材１０５は、図５に示すような所定間隔で、所定方向に沿って配置される複数のファイバーＦ１０５を１層として、複数層、重ねられて形成されている。 Next, the structure of the cell culture holding member 105 will be described with reference to FIG. 5, which is an enlarged view of the cell culture holding member 105. In the cell culture holding member 105, a fiber F105 using a thermoplastic polyester elastomer as a fibrous material is arranged along a predetermined orientation direction A105. Further, the fiber F105 is arranged at a predetermined interval from the other fiber F105 located adjacent thereto. The cell culture holding member 105 is formed by stacking a plurality of layers with a plurality of fibers F105 arranged in a predetermined direction at a predetermined interval as shown in FIG.
　ここで、細胞培養保持部材１０５を形成するファイバーＦ１０５は、必ずしも平行に配置されるものではない。細胞培養保持部材１０５における配向方向Ａ１０５は、個別のファイバーＦ１０５の配向方向を意とするものではなく、細胞培養保持部材１０５を形成するファイバーＦ１０５全体として現れる配向方向を意とする。 Here, the fibers F105 forming the cell culture holding member 105 are not necessarily arranged in parallel. The orientation direction A105 in the cell culture holding member 105 does not mean the orientation direction of the individual fibers F105, but the orientation direction that appears as the entire fiber F105 forming the cell culture holding member 105.
　図６に細胞培養保持部材１０５の斜め上方からの斜視図を示す。細胞培養保持部材１０５は、２つの開口１０５ａを有している。開口１０５ａは、細胞培養保持部材１０５を基部１０１に配置した時に、基部１０１に形成される貫通孔１０１ａ内に位置するように形成される。開口１０５ａは、縁部１０５ａ１、及び、円弧部１０５ａ２を有している。縁部１０５ａ１は、配向方向Ａ１０５に沿った直線状に形成されている。したがって、縁部１０５ａ１は、配向方向Ａ１０５に沿った部分を少なくとも一部に有しているといえる。円弧状部１０５ａ２は、基部１０１に形成される貫通孔１０１ａに沿った円弧形状を有し、縁部１０５ａ１の両端に接続する。 FIG. 6 shows a perspective view of the cell culture holding member 105 from diagonally above. The cell culture holding member 105 has two openings 105a. The opening 105a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 105 is arranged in the base 101. The opening 105a has an edge portion 105a1 and an arc portion 105a2. The edge portion 105a1 is formed in a straight line along the alignment direction A105. Therefore, it can be said that the edge portion 105a1 has at least a portion along the alignment direction A105. The arcuate portion 105a2 has an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the edge portion 105a1.
　また、細胞培養保持部１０５は、第１端部１０５ｂ、第２端部１０５ｃ、及び、細胞培養部１０５ｄ有している。第１端部１０５ｂ、第２端部１０５ｃは、細胞培養部１０５ｄの両端に互いに対向して位置する。第１端部１０５ｂ、第２端部１０５ｃは、細胞培養保持部材１０５の細胞培養部１０５ｄを除いた中空円筒部のうち、細胞培養部１０５ｄと直線状に位置する部分に対応する。 Further, the cell culture holding unit 105 has a first end 105b, a second end 105c, and a cell culture unit 105d. The first end 105b and the second end 105c are located opposite to each other at both ends of the cell culture unit 105d. The first end portion 105b and the second end portion 105c correspond to portions of the hollow cylindrical portion of the cell culture holding member 105 excluding the cell culture portion 105d, which are located linearly with the cell culture portion 105d.
　第１端部１０５ｂ、第２端部１０５ｃは、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに固定される。なお、細胞培養保持部材１０５の細胞培養部１０５ｄを除いた中空円筒部から、第１端部１０５ｂ、第２端部１０５ｃを除いた端部間部分１０５ｅも、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに固定される。 The first end 105b and the second end 105c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like. In addition, the end-to-end portion 105e except the first end portion 105b and the second end portion 105c from the hollow cylindrical portion of the cell culture holding member 105 excluding the cell culture portion 105d is also fixed to the base portion 101 by a predetermined adhesive material or the like. It is fixed to the lower surface P101b.
　接着剤は、細胞培養保持部材１０５を基部１０１の下面Ｐ１０１ｂに圧着した段階で、細胞培養保持部材１０５のファイバーＦ１０５の隙間に吸収され、細胞培養保持部材１０５と一体となる。なお、接着剤としては、例えば、ＫＥ４５を使用する。 The adhesive is absorbed in the gap between the fibers F105 of the cell culture holding member 105 at the stage where the cell culture holding member 105 is pressure-bonded to the lower surface P101b of the base 101, and becomes integrated with the cell culture holding member 105. As the adhesive, for example, KE45 is used.
　細胞培養部１０５ｄは、開口１０５ａの縁部１０５ａ１の間に形成される。細胞培養部１０５ｄは、第１端部１０５ｂ、第２端部１０５ｃによって、配向方向Ａ１０１に沿って、基部１０１に固定される。細胞培養部１０５ｄは、所定の細胞、例えば、拍動する心筋細胞や骨格筋細胞が３次元培養され、保持される。なお、細胞培養保持部材１０５に所定の細胞を保持させる際には、ピペット等を用いて、貫通孔１０１ａから露出する細胞培養部１０５ｄに対して、貫通孔１０１ａを介して細胞懸濁液を滴下し、培養する。 The cell culture portion 105d is formed between the edge portion 105a1 of the opening 105a. The cell culture part 105d is fixed to the base part 101 along the alignment direction A101 by the first end part 105b and the second end part 105c. The cell culture unit 105d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells. When holding a predetermined cell in the cell culture holding member 105, a cell suspension is dropped through the through hole 101a to the cell culture section 105d exposed from the through hole 101a using a pipette or the like. And culture.
　所定の配向方向Ａ１０５を有する細胞培養部１０５ｄに、所定の細胞、例えば、心筋細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。また、細胞培養部１０５ｄを、基部１０１に形成される細胞培養保持部材配置空間である貫通孔１０１ａに配置し、細胞培養部１０５ｄを細胞培養保持部材１０５の配向方向Ａ１０５にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、心筋細胞を大きく拍動させることができる。 By culturing a predetermined cell, for example, a cardiomyocyte, in the cell culture section 105d having a predetermined orientation direction A105, a cell having a structure similar to that of an actual tissue cell can be cultured. Further, the cell culture section 105d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture section 105d is constrained only in the orientation direction A105 of the cell culture holding member 105 to intersect. By not constraining in the direction, the cultured cells can be beat more freely as compared with the conventional method in which the cells were constrained in all directions, so that the cardiomyocytes can be more greatly beat than in the past. .
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、収縮する前の状態とを画像撮影装置により撮影し、両者を比較することによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。 In this way, by increasing the pulsation of cells, for example, in the pulsation, the state when the cell contracts most and the state before the contraction are photographed by the image capturing device, and the two are compared. The contraction rate of cultured cells can be easily measured. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
図７に、繊維状物として熱可塑性ポリエステルエラストマー（弾性率：１０～２３２ＭＰａ）によるファイバーを用いて形成した細胞培養保持部材１０５に培養した心筋細胞の動作状態を示す。なお、図７においては、細胞培養保持部材１０５に７日間以上培養を行った心筋細胞が播種された細胞保持装置１００を用いた。図７の画像の取得には、倒立実体顕微鏡（ＯＬＹＭＰＵＳ、ＩＸ７３）を用いた。画像取得及び変異の測定には、倒立実体顕微鏡に付属のソフトウェア（ＯＬＹＭＰＵＳ　ｃｅｌｌＳｅｎｓ　ｓｔａｎｄａｒｄ）を用いた。培養した心筋細胞における変位は、変位が最も大きかった点の最も収縮した状態と収縮する前の状態との距離とした。 FIG. 7 shows an operating state of cardiomyocytes cultured in the cell culture holding member 105 formed by using a fiber made of a thermoplastic polyester elastomer (elastic modulus: 10 to 232 MPa) as a fibrous material. In FIG. 7, the cell holding device 100 was used in which the cell culture holding member 105 was seeded with cardiomyocytes cultured for 7 days or more. An inverted stereomicroscope (OLYMPUS, IX73) was used to acquire the image in FIG. 7. The software (OLYMPUS cellSens standard) attached to the inverted stereomicroscope was used for image acquisition and mutation measurement. The displacement in cultured cardiomyocytes was defined as the distance between the most contracted state at the point where the displacement was greatest and the state before contraction.
　図７Ａは、心筋細胞が最も収縮した時の状態を示し、図７Ｂは、心筋細胞が収縮する前の状態を、それぞれ示す。なお、図７Ｂにおける点線は、図７Ａに示す心筋細胞の状態の外形を示すものである。細胞培養保持部材１０５に培養した心筋細胞では、最も収縮した時の状態（図７Ａ）と収縮する前の状態（図７Ｂ）との間で、片側の端部での最大変位Ｘ＝約５４マイクロメートル、よって、両側の端部では約１０８マイクロメートルを観察できる。収縮する前の状態（図７Ｂ）の細胞培養保持部材１０５の幅Ｗは、約１２２５マイクロメートルである。よって、収縮時の細胞培養保持部材１０５の変化率は、８．８％となる。なお、従来のポリスチレン（弾性率：２３００～３３００ＭＰａ）により形成した細胞培養シートに心筋細胞を培養した場合には、心筋細胞は、数ミクロン程度の最大変位しか観察できなかったことからも、細胞保持装置１００を用いることによって、容易に、培養した心筋細胞の変位を観察でき、ひいては、培養した心筋細胞の収縮率の計測に役立てることができる。
  FIG. 7A shows a state when the cardiomyocytes contract most, and FIG. 7B shows a state before the cardiomyocytes contract. The dotted line in FIG. 7B shows the outline of the state of the cardiomyocyte shown in FIG. 7A. In the cardiomyocytes cultured in the cell culture holding member 105, the maximum displacement X at one end is approximately 54 μm between the most contracted state (FIG. 7A) and the state before contraction (FIG. 7B). Meters, and thus about 108 micrometers can be observed at both ends. The width W of the cell culture holding member 105 before contraction (FIG. 7B) is about 1225 micrometers. Therefore, the rate of change of the cell culture holding member 105 during contraction is 8.8%. In addition, when cardiomyocytes were cultured on a cell culture sheet formed of conventional polystyrene (elastic modulus: 2300 to 3300 MPa), the cardiomyocytes could only be observed to have a maximum displacement of several microns. By using the device 100, it is possible to easily observe the displacement of the cultured cardiomyocytes, and it can be useful for measuring the contraction rate of the cultured cardiomyocytes.
　前述の実施例１においては、細胞培養保持部材１０５は、配向方向Ａ１０５に沿った直線状の縁部１０５ａ１を有する開口１０５ａを有していた。一方、本発明に係る細胞保持装置の一実施例である細胞保持装置２００では、細胞培養保持部材２０５は、円弧状の縁部２０５ａ１を有するものである。以下においては、実施例１と同様の構成については、同様の符号を付し、詳細な説明を省略する。 In Example 1 described above, the cell culture holding member 105 had the opening 105a having the linear edge portion 105a1 along the orientation direction A105. On the other hand, in the cell holding device 200 which is an example of the cell holding device according to the present invention, the cell culture holding member 205 has an arc-shaped edge portion 205a1. In the following, the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
第１　構成
　細胞保持装置２００の構成について、図８、図９を用いて説明する。図８は、細胞保持装置２００の斜め上方からの斜視図を、図９は、細胞保持装置２００の斜め下方からの斜視図を、それぞれ示す。 First Configuration The configuration of the cell holding device 200 will be described with reference to FIGS. 8 and 9. 8 shows a perspective view of the cell holding device 200 from diagonally above, and FIG. 9 shows a perspective view of the cell holding device 200 from diagonally below.
　図８に示すように、細胞保持装置２００は、基部１０１、細胞培養保持部材２０５、及び、操作部１０７を有している。細胞培養保持部材２０５は、薄い円盤形状を有しており、基部１０１の下面Ｐ１０１ｂに沿って配置される。 As shown in FIG. 8, the cell holding device 200 has a base 101, a cell culture holding member 205, and an operation unit 107. The cell culture holding member 205 has a thin disc shape and is arranged along the lower surface P101b of the base 101.
２．細胞培養保持部材２０５
　細胞培養保持部材２０５は、所定の配向方向に沿って配置された繊維状物、例えば、高分子材料で形成されたファイバーによって形成される。細胞培養保持部材２０５は、細胞培養保持部材１０５と同様に、所定の繊維状物であるファイバーＦ１０５が、所定の配向方向Ａ１０５に沿って配置されている（図５参照）。 2. Cell culture holding member 205
The cell culture holding member 205 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 205 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
　図９に示すように、細胞培養保持部材２０５は、２つの開口２０５ａを有している。開口２０５ａは、細胞培養保持部材２０５を基部１０１に配置した時に、基部１０１に形成される貫通孔１０１ａ内に位置するように形成される。開口２０５ａは、縁部２０５ａ１、及び、円弧部２０５ａ２を有している。縁部２０５ａ１は、円弧状の形成されている。ただし、縁部２０５ａ１は、配向方向Ａ１０５に沿った部分Ｒ２０５ａ１を少なくとも一部に有している。円弧状部２０５ａ２は、基部１０１に形成される貫通孔１０１ａに沿った円弧形状を有し、縁部２０５ａ１の両端に接続する。 As shown in FIG. 9, the cell culture holding member 205 has two openings 205a. The opening 205a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 205 is arranged in the base 101. The opening 205a has an edge portion 205a1 and an arc portion 205a2. The edge portion 205a1 is formed in an arc shape. However, the edge portion 205a1 has at least a portion R205a1 along the alignment direction A105. The arcuate portion 205a2 has an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the edge portion 205a1.
　また、細胞培養保持部２０５は、第１端部２０５ｂ、第２端部２０５ｃ、及び、細胞培養部２０５ｄ有している。第１端部２０５ｂ、第２端部２０５ｃは、細胞培養部２０５ｄの両端に互いに対向して位置する。第１端部２０５ｂ、第２端部２０５ｃは、細胞培養保持部材２０５の細胞培養部２０５ｄを除いた中空円筒部のうち、細胞培養部２０５ｄと直線状に位置する部分に対応する。 Further, the cell culture holding unit 205 has a first end 205b, a second end 205c, and a cell culture unit 205d. The first end 205b and the second end 205c are located opposite to each other at both ends of the cell culture unit 205d. The first end portion 205b and the second end portion 205c correspond to portions of the hollow cylindrical portion of the cell culture holding member 205 excluding the cell culture portion 205d, which are located linearly with the cell culture portion 205d.
　第１端部２０５ｂ、第２端部２０５ｃは、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに固定される。なお、細胞培養保持部材２０５の細胞培養部２０５ｄを除いた中空円筒部から、第１端部２０５ｂ、第２端部２０５ｃを除いた端部間部分２０５ｅも、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに固定される。 The first end 205b and the second end 205c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like. The end portion 205e of the cell culture holding member 205 excluding the first end portion 205b and the second end portion 205c from the hollow cylindrical portion excluding the cell culture portion 205d is also fixed to the base portion 101 by a predetermined adhesive material or the like. It is fixed to the lower surface P101b.
　細胞培養部２０５ｄは、開口２０５ａの縁部２０５ａ１の間に形成される。細胞培養部２０５ｄは、第１端部２０５ｂ、第２端部２０５ｃによって、配向方向Ａ１０１に沿って、基部１０１に固定される。細胞培養部２０５ｄは、所定の細胞、例えば、拍動する心筋細胞や骨格筋細胞が３次元培養され、保持される。 The cell culture portion 205d is formed between the edge portion 205a1 of the opening 205a. The cell culture part 205d is fixed to the base part 101 along the alignment direction A101 by the first end part 205b and the second end part 205c. The cell culture unit 205d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
　所定の配向方向Ａ１０５を有する細胞培養部２０５ｄに、所定の細胞、例えば、心筋細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。また、細胞培養部２０５ｄを、基部１０１に形成される細胞培養保持部材配置空間である貫通孔１０１ａに配置し、細胞培養部２０５ｄを細胞培養保持部材２０５の配向方向Ａ１０５にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、心筋細胞を大きく拍動させることができる。 By culturing a predetermined cell, for example, a cardiomyocyte, in the cell culturing unit 205d having a predetermined orientation direction A105, a cell having a structure similar to an actual tissue cell can be cultured. Further, the cell culture portion 205d is arranged in the through hole 101a which is the cell culture holding member arrangement space formed in the base 101, and the cell culture portion 205d is constrained only in the orientation direction A105 of the cell culture holding member 205 so that the cell culture holding member 205 intersects. By not constraining in the direction, the cultured cells can be beat more freely as compared with the conventional method in which the cells were constrained in all directions, so that the cardiomyocytes can be more greatly beat than in the past. .
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。
  In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
　前述の実施例１においては、細胞培養保持部材１０５は、配向方向Ａ１０５に沿った直線状の縁部１０５ａ１を有する開口１０５を有していた。一方、本発明に係る細胞保持装置の一実施例である細胞保持装置３００では、細胞培養保持部材３０５は、配向方向Ａ１０５に沿った直線状の縁部３０５ａ１を有する平板形状を有するものである。以下においては、実施例１と同様の構成については、同様の符号を付し、詳細な説明を省略する。 In Example 1 described above, the cell culture holding member 105 had the opening 105 having the linear edge portion 105a1 along the orientation direction A105. On the other hand, in the cell holding device 300 which is an example of the cell holding device according to the present invention, the cell culture holding member 305 has a flat plate shape having a linear edge portion 305a1 along the orientation direction A105. In the following, the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
第１　構成
　細胞保持装置３００の構成について、図１０、図１１を用いて説明する。図１０は、細胞保持装置３００の斜め上方からの斜視図を、図１０は、細胞保持装置３００の斜め下方からの斜視図を、それぞれ示す。 1st structure The structure of the cell holding device 300 is demonstrated using FIG. 10, FIG. 10 shows a perspective view of the cell holding device 300 from diagonally above, and FIG. 10 shows a perspective view of the cell holding device 300 from diagonally below.
　図１０に示すように、細胞保持装置３００は、基部１０１、細胞培養保持部材３０５、及び、操作部１０７を有している。細胞培養保持部材３０５は、薄い平板形状を有しており、基部１０１の下面Ｐ１０１ｂに沿って配置される。 As shown in FIG. 10, the cell holding device 300 has a base portion 101, a cell culture holding member 305, and an operating portion 107. The cell culture holding member 305 has a thin flat plate shape and is arranged along the lower surface P101b of the base 101.
２．細胞培養保持部材３０５
　細胞培養保持部材３０５は、所定の配向方向に沿って配置された繊維状物、例えば、高分子材料で形成されたファイバーによって形成される。細胞培養保持部材３０５は、細胞培養保持部材１０５と同様に、所定の繊維状物であるファイバーＦ１０５が、所定の配向方向Ａ１０５に沿って配置されている（図５参照）。 2. Cell culture holding member 305
The cell culture holding member 305 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 305 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
　図１１に示すように、細胞培養保持部材３０５は、縁部３０５ａ１を有している。縁部３０５ａ１は、配向方向Ａ１０５に沿って形成されている。 As shown in FIG. 11, the cell culture holding member 305 has an edge portion 305a1. The edge portion 305a1 is formed along the alignment direction A105.
　また、細胞培養保持部３０５は、第１端部３０５ｂ、第２端部３０５ｃ、及び、細胞培養部３０５ｄ有している。第１端部３０５ｂ、第２端部３０５ｃは、細胞培養部３０５ｄの両端に互いに対向して位置する。第１端部３０５ｂ、第２端部３０５ｃは、細胞培養部３０５ｄと直線状に位置する部分に対応する。 Further, the cell culture holding unit 305 has a first end 305b, a second end 305c, and a cell culture unit 305d. The first end 305b and the second end 305c are located opposite to each other at both ends of the cell culture unit 305d. The first end portion 305b and the second end portion 305c correspond to portions that are located linearly with the cell culture portion 305d.
　第１端部３０５ｂ、第２端部３０５ｃは、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに固定される。 The first end 305b and the second end 305c are fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like.
　細胞培養部３０５ｄは、縁部３０５ａ１の間に形成される。細胞培養部３０５ｄは、第１端部３０５ｂ、第２端部３０５ｃによって、配向方向Ａ１０１に沿って、基部１０１に固定される。細胞培養部３０５ｄは、所定の細胞、例えば、拍動する心筋細胞や骨格筋細胞が３次元培養され、保持される。 The cell culture portion 305d is formed between the edge portions 305a1. The cell culture part 305d is fixed to the base part 101 along the orientation direction A101 by the first end part 305b and the second end part 305c. The cell culture unit 305d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
　所定の配向方向Ａ１０５を有する細胞培養部３０５ｄに、所定の細胞、例えば、心筋細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。また、細胞培養部３０５ｄを、基部１０１に形成される細胞培養保持部材配置空間である貫通孔１０１ａに配置し、細胞培養部３０５ｄを細胞培養保持部材３０５の配向方向Ａ１０５にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、心筋細胞を大きく拍動させることができる。 By culturing a predetermined cell, for example, a cardiomyocyte, in the cell culture section 305d having a predetermined orientation direction A105, a cell having a structure similar to that of an actual tissue cell can be cultured. Further, the cell culture portion 305d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture portion 305d is restricted only in the orientation direction A105 of the cell culture holding member 305 and intersects. By not constraining in the direction, the cultured cells can be beat more freely than in the conventional method in which the cells are constrained in all directions, and thus the cardiomyocytes can be beat more than before. .
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。
  In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
　前述の実施例３においては、基部１０１は中空円筒形状を有していた。一方、本発明に係る細胞保持装置の一実施例である細胞保持装置４００では、基部４０１は、２つの平板形状を有するものである。以下においては、実施例１と同様の構成については、同様の符号を付し、詳細な説明を省略する。 In the above-mentioned Example 3, the base 101 had a hollow cylindrical shape. On the other hand, in the cell holding device 400 which is an example of the cell holding device according to the present invention, the base 401 has two flat plate shapes. In the following, the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
第１　構成
　細胞保持装置４００の構成について、図１２、図１３を用いて説明する。図１２は、細胞保持装置４００の斜め上方からの斜視図を、図１３は、細胞保持装置４００の斜め下方からの斜視図を、それぞれ示す。 First Configuration The configuration of the cell holding device 400 will be described with reference to FIGS. 12 and 13. 12 shows a perspective view of the cell holding device 400 from diagonally above, and FIG. 13 shows a perspective view of the cell holding device 400 from diagonally below.
　図１２に示すように、細胞保持装置４００は、基部４０１、細胞培養保持部材４０５、及び、操作部４０７を有している。 As shown in FIG. 12, the cell holding device 400 has a base portion 401, a cell culture holding member 405, and an operating portion 407.
　図１２に示すように、基部４０１は、薄い平板形状を有している。基部４０１は、所定間隔で配置される。また、基部４０１は、上面Ｐ４０１ａ（図３参照）、及び、下面Ｐ４０１ｂ（図４参照）を有している。所定間隔で配置された基部４０１の間の空間が、細胞培養保持部材配置空間として機能する。また、基部４０１の下面Ｐ４０１ｂの一部は、第１固定部４０１ｂ、及び、第２固定部４０１ｃとして機能する。第１固定部４０１ｂは、下面Ｐ４０１ｂのうち、細胞培養保持部材４０５の第１端部４０５ｂ（後述）を固定する部分に対応する。同様に、第２固定部４０１ｃは、第２端部４０５ｃ（後述）を固定する部分に対応する。基部４０１は、例えば、ポリカーボネートにより形成される。 As shown in FIG. 12, the base 401 has a thin flat plate shape. The bases 401 are arranged at predetermined intervals. Further, the base portion 401 has an upper surface P401a (see FIG. 3) and a lower surface P401b (see FIG. 4). The space between the bases 401 arranged at predetermined intervals functions as a cell culture holding member arrangement space. Further, a part of the lower surface P401b of the base portion 401 functions as the first fixing portion 401b and the second fixing portion 401c. The first fixing portion 401b corresponds to a portion of the lower surface P401b that fixes a first end portion 405b (described later) of the cell culture holding member 405. Similarly, the second fixing portion 401c corresponds to a portion that fixes the second end portion 405c (described later). The base 401 is formed of polycarbonate, for example.
　細胞培養保持部材４０５は、薄い平板形状を有しており、基部４０１の下面Ｐ４０１ｂに沿って配置される。 The cell culture holding member 405 has a thin flat plate shape, and is arranged along the lower surface P401b of the base 401.
　図１２に示すように、操作部４０７は、基部４０１の上面Ｐ４０１ａ（図３参照）から突出するように形成される。操作部４０７は、基部１０１の上面Ｐ４０１ａに、２つの基部４０１を懸架するように、形成される。操作部４０７は、基部４０１と同様、所定の樹脂素材、例えば、ポリカーボネートにより、基部４０１と一体に形成される。操作部４０７を配置することによって、操作部４０７をピンセット等で保持できるので、使用者は、容易に、細胞保持装置４００を操作することができる。 As shown in FIG. 12, the operation unit 407 is formed so as to protrude from the upper surface P401a (see FIG. 3) of the base 401. The operation portion 407 is formed so as to suspend the two base portions 401 on the upper surface P401a of the base portion 101. Like the base 401, the operation unit 407 is made of a predetermined resin material, for example, polycarbonate, and is integrally formed with the base 401. By disposing the operation unit 407, the operation unit 407 can be held by tweezers or the like, and thus the user can easily operate the cell holding device 400.
２．細胞培養保持部材４０５
　細胞培養保持部材４０５は、所定の配向方向に沿って配置された繊維状物、例えば、高分子材料で形成されたファイバーによって形成される。細胞培養保持部材４０５は、細胞培養保持部材１０５と同様に、所定の繊維状物であるファイバーＦ１０５が、所定の配向方向Ａ１０５に沿って配置されている（図５参照）。 2. Cell culture holding member 405
The cell culture holding member 405 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Like the cell culture holding member 105, the cell culture holding member 405 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
　図１３に示すように、細胞培養保持部材４０５は、縁部４０５ａ１を有している。縁部４０５ａ１は、配向方向Ａ１０５に沿って形成されている。 As shown in FIG. 13, the cell culture holding member 405 has an edge portion 405a1. The edge portion 405a1 is formed along the alignment direction A105.
　また、細胞培養保持部４０５は、第１端部４０５ｂ、第２端部４０５ｃ、及び、細胞培養部４０５ｄ有している。第１端部４０５ｂ、第２端部４０５ｃは、細胞培養部４０５ｄの両端に互いに対向して位置する。第１端部４０５ｂ、第２端部４０５ｃは、細胞培養部４０５ｄと直線状に位置する部分に対応する。 Also, the cell culture holding unit 405 has a first end 405b, a second end 405c, and a cell culture unit 405d. The first end 405b and the second end 405c are located opposite to each other at both ends of the cell culture unit 405d. The first end portion 405b and the second end portion 405c correspond to portions that are located linearly with the cell culture portion 405d.
　第１端部４０５ｂ、第２端部４０５ｃは、所定の接着材等によって２つの基部４０１のそれぞれ下面Ｐ４０１ｂに固定される。 The first end 405b and the second end 405c are fixed to the lower surface P401b of each of the two bases 401 by a predetermined adhesive material or the like.
　細胞培養部４０５ｄは、縁部４０５ａ１の間に形成される。細胞培養部４０５ｄは、第１端部４０５ｂ、第２端部４０５ｃによって、配向方向Ａ１０１に沿って、基部１０１に固定される。細胞培養部４０５ｄは、所定の細胞、例えば、拍動する心筋細胞や骨格筋細胞が３次元培養され、保持される。 The cell culture part 405d is formed between the edge parts 405a1. The cell culture part 405d is fixed to the base part 101 by the first end part 405b and the second end part 405c along the alignment direction A101. The cell culture unit 405d three-dimensionally cultures and holds predetermined cells, for example, beating cardiomyocytes and skeletal muscle cells.
　所定の配向方向Ａ１０５を有する細胞培養部４０５ｄに、所定の細胞、例えば、心筋細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。また、細胞培養部４０５ｄを、２つの基部４０１によって形成される細胞培養保持部材配置空間に配置し、細胞培養部４０５ｄを細胞培養保持部材４０５の配向方向Ａ１０５にのみ拘束し、交差する方向には拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できるため、従来よりも、心筋細胞を大きく拍動させることができる。 By culturing a predetermined cell, for example, a cardiomyocyte, in the cell culture unit 405d having a predetermined orientation direction A105, a cell having a structure similar to that of an actual tissue cell can be cultured. Further, the cell culture section 405d is arranged in the cell culture holding member arrangement space formed by the two bases 401, the cell culture section 405d is restricted only in the orientation direction A105 of the cell culture holding member 405, and in the intersecting direction. By not restraining, the cultured cells can be beat more freely as compared with the conventional technique in which the cultured cells are restrained in all directions, so that the cardiomyocytes can be beaten more than before.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。
  In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
　前述の実施例１においては、細胞培養保持部材１０５は、基部１０１に固定される第１端部１０５ｂ、第２端部１０５ｃを有していた。一方、本発明に係る細胞保持装置の一実施例である細胞保持装置５００では、細胞培養保持部材５０５は、基部１０１に固定される第１端部１０５ｂと、基部１０１に固定されない第２端部５０５ｂとを有するものである。以下においては、実施例１と同様の構成については、同様の符号を付し、詳細な説明を省略する。 In Example 1 described above, the cell culture holding member 105 had the first end 105b and the second end 105c fixed to the base 101. On the other hand, in the cell holding device 500, which is an example of the cell holding device according to the present invention, the cell culture holding member 505 has a first end 105b fixed to the base 101 and a second end not fixed to the base 101. And 505b. In the following, the same components as those in the first embodiment will be designated by the same reference numerals and detailed description thereof will be omitted.
第１　構成
　細胞保持装置５００の構成について、図１４、図１５を用いて説明する。図１４は、細胞保持装置５００の斜め上方からの斜視図を、図１４は、細胞保持装置５００の斜め下方からの斜視図を、それぞれ示す。 First Configuration The configuration of the cell holding device 500 will be described with reference to FIGS. 14 and 15. FIG. 14 shows a perspective view of the cell holding device 500 from diagonally above, and FIG. 14 shows a perspective view of the cell holding device 500 from diagonally below.
　図１４に示すように、細胞保持装置５００は、基部１０１、細胞培養保持部材５０５、及び、操作部１０７を有している。細胞培養保持部材５０５は、薄い平板形状を有しており、基部１０１の下面Ｐ１０１ｂに沿って配置される。 As shown in FIG. 14, the cell holding device 500 has a base portion 101, a cell culture holding member 505, and an operating portion 107. The cell culture holding member 505 has a thin flat plate shape, and is arranged along the lower surface P101b of the base 101.
２．細胞培養保持部材５０５
　細胞培養保持部材５０５は、所定の配向方向に沿って配置された繊維状物、例えば、高分子材料で形成されたファイバーによって形成される。細胞培養保持部材５０５は、細胞培養保持部材１０５と同様に、所定の繊維状物であるファイバーＦ１０５が、所定の配向方向Ａ１０５に沿って配置されている（図５参照）。 2. Cell culture holding member 505
The cell culture holding member 505 is formed of a fibrous material arranged along a predetermined orientation direction, for example, a fiber formed of a polymer material. Similar to the cell culture holding member 105, the cell culture holding member 505 has fibers F105, which are predetermined fibrous substances, arranged along a predetermined orientation direction A105 (see FIG. 5).
　細胞培養保持部材５０５は、３つの開口５０５ａを有している。開口５０５ａは、細胞培養保持部材５０５を基部１０１に配置した時に、基部１０１に形成される貫通孔１０１ａ内に位置するように形成される。開口５０５ａは、２つの開口５０５ａＸ、及び、１つの開口５０５ａＹの２種類に分けられる。２つの開口５０５ａＸは、それぞれの配向方向縁部５０５ａＸ１（後述）が対向するように、鏡像関係で配置される。開口５０５ａＹは、自身の交差方向縁部５０５ａＹ１（後述）と２つの開口５０５ａＸのそれぞれの交差方向縁部５０５ａＸ３（後述）とが対向するように配置される。 The cell culture holding member 505 has three openings 505a. The opening 505a is formed so as to be located in the through hole 101a formed in the base 101 when the cell culture holding member 505 is arranged in the base 101. The opening 505a is divided into two types, two openings 505aX and one opening 505aY. The two openings 505aX are arranged in a mirror image relationship so that respective alignment direction edge portions 505aX1 (described later) face each other. The opening 505aY is arranged such that its own intersecting direction edge portion 505aY1 (described later) and each intersecting direction edge portion 505aX3 (described later) of the two openings 505aX face each other.
　開口５０５ａＸは、配向方向縁部５０５ａＸ１、円弧部５０５ａＸ２、及び、交差方向縁部５０５ａＸ３を有している。配向方向縁部５０５ａＸ１は、配向方向Ａ１０５に沿った直線状に形成される。したがって、配向方向縁部５０５ａＸ１は、配向方向Ａ１０５に沿った部分を少なくとも一部に有しているといえる。円弧状部５０５ａＸ２は、基部１０１に形成される貫通孔１０１ａに沿った円弧形状に形成され、配向方向縁部５０５ａＸ１の一端に接続する。交差方向縁部５０５ａＸ３は、配向方向Ａ１０５に交差する方向に直線状に形成されている。円弧状部５０５ａＸ３は、配向方向縁部５０５ａＸ１の一端、及び、円弧状部５０５ａＸ２の一端に接続する。 The opening 505aX has an orientation direction edge portion 505aX1, a circular arc portion 505aX2, and a cross direction edge portion 505aX3. The alignment direction edge portion 505aX1 is formed in a straight line along the alignment direction A105. Therefore, it can be said that the alignment direction edge portion 505aX1 has at least a portion along the alignment direction A105. The arcuate portion 505aX2 is formed in an arcuate shape along the through hole 101a formed in the base 101, and is connected to one end of the alignment direction edge portion 505aX1. The cross direction edge portion 505aX3 is linearly formed in a direction crossing the alignment direction A105. The arcuate portion 505aX3 is connected to one end of the alignment direction edge portion 505aX1 and one end of the arcuate portion 505aX2.
　開口５０５ａＹは、交差方向縁部５０５ａＹ１、及び、円弧部５０５ａＹ２を有している。交差方向縁部５０５ａＹ１は、配向方向Ａ１０５に交差する方向に沿って直線状に形成される。なお、開口５０５ａＹ１の交差方向縁部５０５ａＹ１は、開口５０５ａＸの交差方向縁部５０５ａＸ３と対向して配置される。円弧状部５０５ａＹ２は、基部１０１に形成される貫通孔１０１ａに沿った円弧形状に形成され、交差方向縁部５０５ａＹ１の両端のそれぞれに接続する。 The opening 505aY has a cross direction edge portion 505aY1 and an arc portion 505aY2. The cross direction edge portion 505aY1 is formed in a straight line along a direction crossing the alignment direction A105. The cross direction edge 505aY1 of the opening 505aY1 is arranged to face the cross direction edge 505aX3 of the opening 505aX. The arcuate portion 505aY2 is formed in an arcuate shape along the through hole 101a formed in the base portion 101, and is connected to both ends of the cross direction edge portion 505aY1.
　また、細胞培養保持部５０５は、第１端部５０５ｂ、第２端部５０５ｃ、細胞培養部５０５ｄ、及び、接続部５０５ｅを有している。第１端部５０５ｂ、第２端部５０５ｃは、細胞培養部５０５ｄの両端に互いに対向して位置する。なお、第１端部５０５ｂは、細胞培養保持部材５０５の細胞培養部５０５ｄを除いた中空円筒部のうち、細胞培養部５０５ｄと直線状に位置する部分に対応する。 Further, the cell culture holding unit 505 has a first end 505b, a second end 505c, a cell culture unit 505d, and a connecting unit 505e. The first end 505b and the second end 505c are located opposite to each other at both ends of the cell culture unit 505d. The first end portion 505b corresponds to a portion of the hollow cylindrical portion of the cell culture holding member 505 excluding the cell culture portion 505d, which is located linearly with the cell culture portion 505d.
　第１端部５０５ｂは、所定の接着材等によって基部１０１の下面Ｐ１０１ｂに直接的に固定される。一方、第２端部５０５ｃは、基部１０１に直接的に固定されず、接続部５０５ｅを介して、基部１０１に接続される。よって、細胞培養部５０５ｄを片持ち梁と同様に形成できる。細胞培養部５０５ｄは、第２端部５０５ｃが直接的に固定されておらず、固定の度合いが弱いため、配向方向Ａ１０１にも収縮できる。つまり、細胞培養部５０５ｄを、いずれの方向にも拘束されないに等しい状態にできる。 The first end 505b is directly fixed to the lower surface P101b of the base 101 by a predetermined adhesive material or the like. On the other hand, the second end portion 505c is not directly fixed to the base portion 101, but is connected to the base portion 101 via the connection portion 505e. Therefore, the cell culture portion 505d can be formed similarly to the cantilever. The second end portion 505c of the cell culture unit 505d is not directly fixed, and the degree of fixing is weak, so that the cell culture unit 505d can contract in the alignment direction A101. That is, the cell culture section 505d can be brought into a state in which it is substantially unrestrained in any direction.
　細胞培養部５０５ｄは、対向して位置する２つの縁部５０５ａＸ１の間に形成される。細胞培養部５０５ｄには、所定の細胞、例えば、拍動する心筋細胞や骨格筋細胞が３次元培養される。細胞培養部５０５ｄは、培養された細胞を保持する。 The cell culture portion 505d is formed between two edge portions 505aX1 located opposite to each other. Predetermined cells, for example, beating cardiomyocytes or skeletal muscle cells are three-dimensionally cultured in the cell culture unit 505d. The cell culture unit 505d holds the cultured cells.
　接続部５０５ｅは、開口５０５ａＸの２つの交差方向縁部５０５ａＸ３、及び、それらに対向して位置する開口５０５ａＹの交差方向縁部５０５ａＹ１の間に形成される。接続部５０５ｅは、細胞培養部５０５ｄの一端部に位置する第２端部５０５ｃと基部１０１とを接続するように形成される。つまり、接続部５０５ｅの一端は第２端部５０５ｃに接続され、他の一端である接続端部５０５ｅ１は基部１０１の下面Ｐ１０１ｂに接続される。なお、接続端部５０５ｅ１は、接続部材５０５ｅのうち基部１０１の貫通孔１０１ａ内に位置する部部を第２端部５０５ｃとは反対の基部１０１側に延長した部分に対応する。また、第１端部５０５ｂ、第２端部５０５ｃ、細胞培養部５０５ｄ、及び、接続部５０５ｅは、繊維状物で形成された所定形状のシートに開口５０５ａＸ、開口５０５ａＹを形成することによって、一体的に形成される。 The connecting portion 505e is formed between the two intersecting direction edge portions 505aX3 of the opening 505aX and the intersecting direction edge portion 505aY1 of the opening 505aY located opposite thereto. The connection portion 505e is formed to connect the second end portion 505c located at one end of the cell culture portion 505d and the base portion 101. That is, one end of the connecting portion 505e is connected to the second end 505c, and the other end, the connecting end 505e1, is connected to the lower surface P101b of the base 101. The connection end portion 505e1 corresponds to a portion of the connection member 505e that is located in the through hole 101a of the base portion 101 and extends toward the base portion 101 side opposite to the second end portion 505c. The first end portion 505b, the second end portion 505c, the cell culture portion 505d, and the connection portion 505e are integrated by forming an opening 505aX and an opening 505aY in a sheet of a predetermined shape formed of a fibrous material. Formed.
　なお、基部１０１の下面Ｐ１０１ｂの一部は、第１固定部１０１ｂ（図４参照）、及び、第２固定部５０１ｃ（図示せず）として機能する。第１固定部１０１ｂは、下面Ｐ１０１ｂのうち、細胞培養保持部材１０５の第１端部５０５ｂを固定する部分に対応する。一方、第２固定部５０１ｃは、接続端部５０５ｅ１を固定する部分に対応する。 Note that part of the lower surface P101b of the base 101 functions as the first fixing portion 101b (see FIG. 4) and the second fixing portion 501c (not shown). The first fixing portion 101b corresponds to a portion of the lower surface P101b that fixes the first end portion 505b of the cell culture holding member 105. On the other hand, the second fixing portion 501c corresponds to the portion that fixes the connection end portion 505e1.
　所定の配向方向Ａ１０５を有する細胞培養部５０５ｄに、所定の細胞、例えば、心筋細胞を培養することによって、実際の組織細胞と同様の構造を有する細胞を培養できる。また、細胞培養部５０５ｄを、基部１０１に形成される細胞培養保持部材配置空間である貫通孔１０１ａに配置し、また、細胞培養部５０５ｄを細胞培養保持部材３０５の配向方向Ａ１０５にも、配向方向Ａ１０５に交差する方向にも拘束しないことによって、培養された細胞が、全ての方向に拘束されていた従来に比して、より自由に拍動できる。よって、従来よりも、培養した心筋細胞を大きく拍動させることができる。 By culturing a predetermined cell, for example, a cardiomyocyte, in the cell culture unit 505d having a predetermined orientation direction A105, a cell having a structure similar to an actual tissue cell can be cultured. Further, the cell culture section 505d is arranged in the through hole 101a which is a cell culture holding member arrangement space formed in the base 101, and the cell culture section 505d is also oriented in the orientation direction A105 of the cell culture holding member 305. By not constraining in the direction intersecting with A105, the cultured cells can be beat more freely than in the conventional method in which the cells are constrained in all directions. Therefore, the cultured cardiomyocytes can be beaten more than before.
　このように、細胞の拍動を大きくすることによって、例えば、拍動において、細胞が最も収縮した時の状態と、細胞が収縮する前の状態とを画像撮影装置により撮影し、両者を比較したり、大きく拍動する細胞に対して直接的に圧力を計測したりすることによって、容易に、培養した細胞の収縮率を計測することができる。つまり、細胞保持装置１００を用いて培養した細胞を収縮率の計測に役立てることができる。
  In this way, by increasing the pulsation of the cells, for example, in the pulsation, the state where the cells contract most and the state before the cells contract are photographed by the image capturing device, and the both are compared. Alternatively, the contraction rate of the cultured cells can be easily measured by directly measuring the pressure on the cells that beating greatly. That is, cells cultured using the cell holding device 100 can be used for measuring the contraction rate.
　本実施例に係る細胞保持装置７００は、前述の実施例１における細胞保持装置１００の基部１０１が有する貫通孔１０１ｃに対して、より細胞を培養しやすい貫通孔７０１ｃを有するものである。以下においては、実施例１と同様の構成については同様の符号を付し、詳細な説明を省略する。
  The cell holding device 700 according to the present embodiment has a through hole 701c in which cells can be easily cultured, in contrast to the through hole 101c included in the base portion 101 of the cell holding device 100 according to the first embodiment. In the following, the same components as those in the first embodiment are designated by the same reference numerals, and detailed description will be omitted.
第１　構成
　細胞保持装置７００の構成について、図１６を用いて説明する。図１６は、細胞保持装置７００の斜め上方からの斜視図を示す。 First Configuration The configuration of the cell holding device 700 will be described with reference to FIG. FIG. 16 shows a perspective view of the cell holding device 700 from diagonally above.
　図１６に示すように、細胞保持装置７００は、基部７０１、細胞培養保持部材１０５、操作部７０７、及び、空気抜き部７１１を有している。 As shown in FIG. 16, the cell holding device 700 has a base portion 701, a cell culture holding member 105, an operating portion 707, and an air vent portion 711.
　基部７０１は、薄い円盤形状を有している。基部７０１は、中央に貫通孔７０１ａを有している。また、基部７０１は、上面Ｐ７０１ａ、及び、下面Ｐ７０１ｂ（図１７参照）を有している。 The base 701 has a thin disc shape. The base portion 701 has a through hole 701a in the center. The base portion 701 also has an upper surface P701a and a lower surface P701b (see FIG. 17).
　貫通孔７０１ａは、基部７０１の上面Ｐ７０１ａから下面Ｐ７０１ｂまで、基部７０１を貫通するように形成される。貫通孔７０１ａは、細胞培養保持部材配置空間として機能する。貫通孔７０１ａは、操作部７０７が形成される上面Ｐ７０１ａから下面Ｐ７０１ｂに向かって狭まるような円錐台形状を有している。これにより、基部７０１の上面Ｐ７０１ａ側の開口を大きくできるため、貫通孔７０１ａに対して、上側から容易に細胞懸濁液を滴下することができる。また、貫通孔７０１ａの容量を多くできるため、より多くの細胞懸濁液を貫通孔７０１ａに保持させることができる。 The through hole 701a is formed so as to penetrate the base 701 from the upper surface P701a to the lower surface P701b of the base 701. The through hole 701a functions as a cell culture holding member placement space. The through hole 701a has a truncated cone shape that narrows from the upper surface P701a where the operation portion 707 is formed toward the lower surface P701b. Accordingly, the opening on the upper surface P701a side of the base portion 701 can be increased, and thus the cell suspension can be easily dropped from the upper side into the through hole 701a. Further, since the capacity of the through hole 701a can be increased, a larger amount of cell suspension can be retained in the through hole 701a.
　ここで、貫通孔７０１ａの形状について、図１７を用いて説明する。図１７は、基部７０１、及び、操作部７０７の軸方向断面を示す。貫通孔７０１ａは、基部７０１の下面Ｐ７０１ｂから上面Ｐ７０１ａに向かって所定距離の位置に傾斜部Ｓ７０１ａを有している。傾斜部Ｓ７０１ａは、軸方向から所定角度だけ傾斜する面として形成される。なお、傾斜部Ｓ７０１ａの軸方向断面は、傾斜直線となる。このように、貫通孔７０１に傾斜部Ｓ７０１ａを形成することによって、細胞培養時の細胞播種の歩留まりを向上させることができる。 Here, the shape of the through hole 701a will be described with reference to FIG. FIG. 17 shows an axial cross section of the base portion 701 and the operation portion 707. The through hole 701a has an inclined portion S701a at a predetermined distance from the lower surface P701b of the base 701 toward the upper surface P701a. The inclined portion S701a is formed as a surface inclined by a predetermined angle from the axial direction. The axial section of the inclined portion S701a is an inclined straight line. By forming the inclined portion S701a in the through hole 701 in this manner, the yield of cell seeding during cell culture can be improved.
　図１６に戻って、実施例１における基部１０１と同様に、基部７０１の下面Ｐ７０１ｂの一部は、第１固定部、及び、第２固定部として機能する。基部７０１は、例えば、ポリカーボネートにより形成される。 Returning to FIG. 16, similarly to the base portion 101 in the first embodiment, a part of the lower surface P701b of the base portion 701 functions as a first fixing portion and a second fixing portion. The base 701 is formed of, for example, polycarbonate.
　操作部７０７は、基部７０１の上面Ｐ７０１ａから突出するように形成される。操作部７０７は、基部７０１の上面Ｐ７０１ａに、貫通孔７０１ａを間に、平行に、形成される。これにより、貫通孔７０１ａと距離をおいて操作部７０７を形成することができるので、細胞を培養する際に、貫通孔７０１ａに貯留した細胞培養液が自身の表面張力を越えて、貫通孔７０１ａから流れ出ることを防止できる。 The operation portion 707 is formed so as to project from the upper surface P701a of the base portion 701. The operation portion 707 is formed on the upper surface P701a of the base portion 701 in parallel with the through hole 701a therebetween. As a result, the operating portion 707 can be formed at a distance from the through hole 701a. Therefore, when the cells are cultured, the cell culture solution stored in the through hole 701a exceeds the surface tension of itself and the through hole 701a is formed. Can be prevented from flowing out.
　また、貫通孔７０１ａを中心に放射状に形成する場合に比して、操作部７０７の長さを永できるため、ピンセット等で挟持しやすく、細胞保持装置７００を容易に操作できる。 Further, as compared with the case where the through hole 701a is formed in a radial shape as a center, the length of the operating portion 707 can be made longer, so that it can be easily pinched with tweezers or the like, and the cell holding device 700 can be easily operated.
　なお、細胞培養保持部材７０５は、繊維状物の配向方向Ａ７０５が操作部に対して交差する方向に向くように配置される。これにより、操作部７０７の形成方向を確認するだけ、細胞培養保持部材７０５の繊維状物の配向方向Ａ７０５を容易に把握することができる。操作部７０７は、基部７０１と同様、所定の樹脂素材、例えば、ポリカーボネートにより、基部７０１と一体に形成される。操作部７０７を配置することによって、操作部７０７をピンセット等で保持できるので、使用者は、容易に、細胞保持装置７００を操作することができる。 Note that the cell culture holding member 705 is arranged so that the orientation direction A705 of the fibrous material is oriented in a direction intersecting with the operation portion. Accordingly, the orientation direction A705 of the fibrous material of the cell culture holding member 705 can be easily grasped only by confirming the formation direction of the operation portion 707. Like the base 701, the operation unit 707 is formed integrally with the base 701 by using a predetermined resin material such as polycarbonate. By disposing the operation unit 707, the operation unit 707 can be held by tweezers or the like, and thus the user can easily operate the cell holding device 700.
　空気抜き部７１１は、基部７０１の外周部の一部を切除した領域として形成される。なお、基部７０１下に位置する細細胞培養保持部材７０１についても、基部７０１と同形状として形成される。これにより、細胞保持装置７００を、マルチウェルプレートの１つのウェル等の細胞内容容器に投入した際に、細胞保持装置７００の下部に入り込んだ空気を容易に排出することができる。
  The air vent 711 is formed as a region in which a part of the outer peripheral portion of the base 701 is cut off. The small cell culture holding member 701 located below the base 701 is also formed in the same shape as the base 701. Thereby, when the cell holding device 700 is put into a cell content container such as one well of a multi-well plate, the air that has entered the lower part of the cell holding device 700 can be easily discharged.
［その他の実施形態］
　（１）細胞培養保持部材１０５の開口１０５ａの形状：前述の実施例１においては、細胞培養保持部材１０５の開口１０５ａは、繊維状部材の配向方向Ａ１０１に沿った直線状の縁部１０５ａ１、及び、円弧状部１０５ａ２を有し、前述の実施例２においては、細胞培養保持部材２０５の開口２０５ａは、円弧状の縁部２０５ａ１、及び、円弧状部２０５ａ２を有するとしたが、繊維状部材の配向方向に沿った部分を少なくとも一部に有する縁部を有するものであれば、例示のものに限定されない。例えば、円形状、楕円形状、矩形状の開口であってもよい。他の実施例についても同様である。 [Other Embodiments]
(1) Shape of the opening 105a of the cell culture holding member 105: In the above-described Example 1, the opening 105a of the cell culture holding member 105 has a linear edge portion 105a1 along the orientation direction A101 of the fibrous member, and , The arc-shaped portion 105a2, and the opening 205a of the cell culture holding member 205 has the arc-shaped edge portion 205a1 and the arc-shaped portion 205a2 in the second embodiment described above. It is not limited to the example as long as it has an edge portion having at least a part along the alignment direction. For example, the opening may be circular, elliptical, or rectangular. The same applies to the other examples.
　また、各実施例において、繊維状物の配向方向に沿った部分を含まない開口をそれぞれの細胞培養保持部材に形成するようにしてもよい。 Also, in each embodiment, an opening not including a portion along the orientation direction of the fibrous material may be formed in each cell culture holding member.
　（２）培養する細胞：前述の実施例１～実施例４においては、培養する細胞として心筋細胞を示したが、例示のものに限定されない。例えば、骨格筋細胞であってもよい。また、多能性幹細胞由来の心筋細胞や骨格筋細胞であってもよい。なお、多能性幹細胞としては、例えば、胚性幹細胞（ＥＳ細胞）やｉＰＳ細胞がある。 (2) Cells to be cultured: In the above-mentioned Examples 1 to 4, cardiomyocytes were shown as cells to be cultured, but the cells are not limited to the exemplified ones. For example, it may be a skeletal muscle cell. It may also be a cardiomyocyte or skeletal muscle cell derived from pluripotent stem cells. The pluripotent stem cells include, for example, embryonic stem cells (ES cells) and iPS cells.
　（３）基部１０１と操作部１０７との一体性：前述の実施例１においては、基部１０１と操作部１０７とは一体として形成されるとしたが、別体としてそれぞれ形成し、接着材等の接着部材を用いて、両者を接合するようにしてもよい。実施例１を除く他の実施例についても同様である。 (3) Integrality between the base 101 and the operation unit 107: In the first embodiment described above, the base 101 and the operation unit 107 are formed as one body, but they are formed as separate bodies, and an adhesive or the like is used. You may make it join | bond together both using an adhesive member. The same applies to other embodiments except the first embodiment.
　（４）培養細胞：前述の実施例１～実施例４においては、基部１０１の貫通孔１０１ａ内において、細胞培養保持部材１０５の細胞培養部１０５ｄに細胞を３次元培養するとしたが、２次元培養するようにしもよい。 (4) Cultured cells: In the above-described Examples 1 to 4, cells were three-dimensionally cultured in the cell culture portion 105d of the cell culture holding member 105 in the through hole 101a of the base 101, but two-dimensional culture was performed. You may do this.
　（５）接続部５０５ｅ：前述の実施例５においては、接続部５０５ｅは、細胞培養部５０５ｄ等と一体的に形成されるとしたが、別体として形成するようにしてもよい。例えば、図１８Ａに示す細胞保持装置６００のように、細胞培養保持部材６０５に、開口５０５ａＸ、開口５０５ａＹ（図１５参照）を一体としたコの字状の開口６０５ａを形成して、いずれも接続していない第２端部６０５cを形成し、図１８Ｂに示すように、形成した第２端部６０５cと基部１０１とを、第２端部６０５ｃの両端と基部１０１とを懸架するように、細い線状の接続部材６０９を用いて接続するようにしてもよい。この場合、接続部材６０９の太さ、形状等については、培養する細胞の運動を十分に確認できるように、適宜、決定すればよい。なお、接続部材６０９は、所定の接着材等によって、細胞培養保持部材６０５に固定する。 (5) Connection part 505e: In the above-mentioned fifth embodiment, the connection part 505e is formed integrally with the cell culture part 505d and the like, but it may be formed as a separate body. For example, as in the cell holding device 600 shown in FIG. 18A, a cell culture holding member 605 is formed with a U-shaped opening 605a in which an opening 505aX and an opening 505aY (see FIG. 15) are integrated, and both are connected. The second end 605c which is not formed is formed, and as shown in FIG. 18B, the formed second end 605c and the base 101 are thin so that both ends of the second end 605c and the base 101 are suspended. You may make it connect using the linear connecting member 609. In this case, the thickness and shape of the connecting member 609 may be appropriately determined so that the movement of the cells to be cultured can be sufficiently confirmed. The connection member 609 is fixed to the cell culture holding member 605 with a predetermined adhesive material or the like.
　また、第２端部６０５cと基部１０１とを、第２端部６０５ｃの両端と基部１０１とを懸架するように、細い線状の接続部材６０９を用いて接続する細胞保持装置６００に対して、図１９に示す細胞保持装置８００のように、第２端部６０５cと基部１０１とを、第２端部６０５ｃのいずれか一方の端と基部１０１とを懸架するように、つまり、片持ち梁のように、細い線状の接続部材８０９を用いて接続するようにしてもよい。 Further, to the cell holding device 600 that connects the second end portion 605c and the base portion 101 by using the thin linear connecting member 609 so as to suspend both ends of the second end portion 605c and the base portion 101, As in the cell holding device 800 shown in FIG. 19, the second end portion 605c and the base portion 101 are suspended from one end of the second end portion 605c and the base portion 101, that is, of the cantilever. As described above, the connection may be performed using the thin linear connecting member 809.
　（６）細胞培養保持部材の繊維状物：前述の実施例１～実施例５においては、繊維状物として、熱可塑性ポリエステルエラストマー（弾性率：１０～２３２ＭＰａ）を例示したが、細胞培養保持部材に培養した細胞を拘束せず、拍動等の運動を妨げるものであなければ、例示のものに限定されない。繊維状物としては、少なくとも従来のポリスチレンの弾性率よりも低い２０００ＭＰａ以下、特に、５００ＭＰａ以下のものが適当である。
 
  (6) Fibrous material of cell culture holding member: In the above-mentioned Examples 1 to 5, thermoplastic polyester elastomer (elastic modulus: 10 to 232 MPa) was exemplified as the fibrous material. It is not limited to the exemplified one as long as it does not restrain the cells cultured in 1. and does not impede movement such as pulsation. As the fibrous material, at least 2000 MPa or less, particularly 500 MPa or less, which is lower than the elastic modulus of conventional polystyrene, is suitable.

　本発明に係る細胞保持装置は、例えば、心筋細胞の収縮性の計測に用いることができる。
  The cell holding device according to the present invention can be used, for example, for measuring contractility of cardiomyocytes.
１００　　　細胞保持装置
　１０１　　　基部
　　Ｐ１０１ａ　　　上面
　　Ｐ１０１ｂ　　　下面
　　１０１ａ　　　貫通孔
　　１０１ｂ　　　第１固定部
　　１０１ｃ　　　第２固定部
　１０５　　　細胞培養保持部材
　　１０５ａ　　　開口
　　　１０５ａ１　　　縁部
　　１０５ｂ　　　第１端部
　　１０５ｃ　　　第２端部
　　１０５ｄ　　　細胞培養部
　１０７　　　操作部
２００　　　細胞保持装置
　２０５　　　細胞培養保持部材
　　２０５ａ　　　開口
　　　２０５ａ１　　　縁部
　　２０５ｂ　　　第１端部
　　２０５ｃ　　　第２端部
　　２０５ｄ　　　細胞培養部
３００　　　細胞保持装置
　３０５　　　細胞培養保持部材
　　３０５ａ１　　　縁部
　　３０５ｂ　　　第１端部
　　３０５ｃ　　　第２端部
　　３０５ｄ　　　細胞培養部
４００　　　細胞保持装置
　４０１　　　基部
　　Ｐ４０１ａ　　　上面
　　Ｐ４０１ｂ　　　下面
　　４０１ａ　　　貫通孔
　　４０１ｂ　　　第１固定部
　　４０１ｃ　　　第２固定部
　４０５　　　細胞培養保持部材
　　４０５ａ１　　　縁部
　　４０５ｂ　　　第１端部
　　４０５ｃ　　　第２端部
　　４０５ｄ　　　細胞培養部
　４０７　　　操作部
５００　　　細胞保持装置
　５０５　　　細胞培養保持部材
　　５０５ａ　　　開口
　　　５０５ａＸ　　　開口
　　　　５０５ａＸ１　　　配向方向縁部
　　　　５０５ａＸ３　　　交差方向縁部
　　　５０５ａＹ　　　開口
　　　　５０５ａＹ１　　　交差方向縁部
　　５０５ｂ　　　第１端部
　　５０５ｃ　　　第２端部
　　５０５ｄ　　　細胞培養部
　　５０５ｅ　　　接続部
６００　　　細胞保持装置
　６０５　　　細胞培養保持部材
　　６０５ａ　　　開口
　　５０５ｂ　　　第１端部
　　６０５ｃ　　　第２端部
　　６０５ｄ　　　細胞培養部
　６０９　　　接続部材
７００　　　細胞保持装置
　７０１　　　基部
　　Ｐ７０１ａ　　　上面
　　Ｐ７０１ｂ　　　下面
　　７０１ａ　　　貫通孔
　７０５　　　細胞培養保持部材
　１０７　　　操作部
　７１１　　　空気抜き部
８００　　　細胞保持装置
　８０９　　　接続部材
 

  100 cell holding device 101 base P101a upper surface P101b lower surface 101a through hole 101b first fixing portion 101c second fixing portion 105 cell culture holding member 105a opening 105a1 edge portion 105b first end portion 105c second end portion 105d cell culture portion 107 operation portion 200 Cell Holding Device 205 Cell Culture Holding Member 205a Opening 205a1 Edge 205b First End 205c Second End 205d Cell Culture Section 300 Cell Holding Device 305 Cell Culture Holding Member 305a1 Edge 305b First End 305c Second End 305d Cell culture unit 400 Cell holding device 401 Base P401a Upper surface P401b Lower surface 401a Through hole 401b First fixing portion 401c Second fixing portion 405 Cell culture preservation Member 405a1 Edge portion 405b First end portion 405c Second end portion 405d Cell culture portion 407 Operation portion 500 Cell holding device 505 Cell culture holding member 505a Opening 505aX opening 505aX1 Orientation edge 505aX3 Crossing edge 505aY Opening edge 505a Part 505b First end part 505c Second end part 505d Cell culture part 505e Connection part 600 Cell holding device 605 Cell culture holding member 605a Opening 505b First end part 605c Second end part 605d Cell culture part 609 Connection member 700 Cell holding device 701 Base part P701a Upper surface P701b Lower surface 701a Through hole 705 Cell culture holding member 107 Operation part 711 Air vent part 800 Cell holding device 809 Contact Continuation member

Claims (14)

  1. 　所定の繊維状物によって形成され、細胞を培養し、保持する細胞培養部と、前記細胞培養部の両端に位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置する縁部と、を有する細胞培養保持部材、
    　前記第１端部を直接的に固定する第１固定部、
    　前記第２端部を固定する第２固定部、
    　前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、
    　を有する細胞保持装置。     A cell culture part formed of a predetermined fibrous material for culturing and holding cells, a first end part and a second end part located at both ends of the cell culture part, and the first end part and the A cell culture holding member having an edge portion located between the second end portion,
    A first fixing portion for directly fixing the first end portion,
    A second fixing portion for fixing the second end portion,
    A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion;
    And a cell holding device.
  2. 　請求項１に係る細胞保持装置において、
    　前記第２固定部は、
    　前記所定方向に沿って前記第１固定部に対向して位置すること、
    　を特徴とする細胞保持装置。     The cell holding device according to claim 1,
    The second fixing portion is
    Being positioned to face the first fixing portion along the predetermined direction,
    A cell holding device characterized by:
  3. 　請求項１に係る細胞保持装置において、
    　前記第２固定部は、
    　前記所定方向に交差する方向に沿って位置すること、
    　を特徴とする細胞保持装置。     The cell holding device according to claim 1,
    The second fixing portion is
    Being located along a direction intersecting with the predetermined direction,
    A cell holding device characterized by:
  4. 　請求項１～請求項３のいずれかに係る細胞保持装置において、
    　前記細胞培養部は、
    　所定の配向方向に沿って配置された前記繊維状物によって形成され、
    　前記縁部は、
    　前記配向方向に沿った部分を少なくとも一部に有すること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 3,
    The cell culture section,
    Formed by the fibrous material arranged along a predetermined orientation direction,
    The edge is
    Having at least a portion along the alignment direction,
    A cell holding device characterized by:
  5. 　請求項１～請求項４のいずれかに係る細胞保持装置において、
    　前記第１固定部、及び、前記第２固定部は、
    　それぞれ、平板状の基部の少なくとも一部であり、
    　前記細胞培養保持部材配置空間は、
    　前記基部を貫通するように形成される貫通孔であること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 4,
    The first fixing portion and the second fixing portion are
    Each is at least a part of a flat base,
    The cell culture holding member arrangement space,
    A through hole formed so as to penetrate the base,
    A cell holding device characterized by:
  6. 　請求項５に係る細胞保持装置において、
    　前記細胞培養保持部材は、
    　前記貫通孔に対応する位置に開口を有すること、
    　を特徴とする細胞保持装置。     The cell holding device according to claim 5,
    The cell culture holding member,
    Having an opening at a position corresponding to the through hole,
    A cell holding device characterized by:
  7. 　請求項４～請求項６のいずれかに係る細胞保持装置おいて、
    　前記縁部は、
    　前記配向方向に沿って直線状に形成されている部分を有すること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 4 to 6,
    The edge is
    Having a portion formed in a straight line along the alignment direction,
    A cell holding device characterized by:
  8. 　請求項１～請求項７のいずれかに係る細胞保持装置において、
    　前記細胞培養保持部材は、
    　前記繊維状物の弾性率が、２０００ＭＰａ以下であること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 7,
    The cell culture holding member,
    The elastic modulus of the fibrous material is 2000 MPa or less,
    A cell holding device characterized by:
  9. 　請求項１～請求項８のいずれかに係る細胞保持装置において、さらに、
    　所定の保持具によって挟持できる操作部、
    　を有する細胞保持装置。     The cell holding device according to any one of claims 1 to 8, further comprising:
    An operation part that can be held by a predetermined holder,
    And a cell holding device.
  10. 　請求項１～請求項９のいずれかに係る細胞保持装置において、
    　前記細胞培養保持部材は、
    　前記細胞として、心筋細胞、または、骨格筋細胞を培養し、保持していること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 9,
    The cell culture holding member,
    As the cells, culturing and holding cardiomyocytes or skeletal muscle cells,
    A cell holding device characterized by:
  11. 　請求項１～請求項９のいずれかに係る細胞保持装置において、
    　前記細胞培養保持部材は、
    　前記細胞として、心筋細胞を培養、保持し、
    　前記心筋細胞を培養した前記細胞培養保持部材の収縮率が、２．５パーセント以上であること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 9,
    The cell culture holding member,
    As the cells, cardiomyocytes are cultured and maintained,
    The contraction rate of the cell culture holding member in which the cardiomyocytes are cultured is 2.5% or more,
    A cell holding device characterized by:
  12. 　請求項１～請求項１１のいずれかに係る細胞保持装置において、
    　前記細胞保持装置は、
    　前記細胞の収縮性の計測に用いられること、
    　を特徴とする細胞保持装置。     The cell holding device according to any one of claims 1 to 11,
    The cell holding device,
    Used to measure the contractility of the cells,
    A cell holding device characterized by:
  13. 　細胞の収縮性を計測するための細胞保持装置であって、所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部と、前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部と、及び、前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部と、を有する細胞培養保持部材を有する細胞保持装置において、
    　前記第１端部を固定する第１固定部、
    　前記第２端部を固定する第２固定部、
    　前記第１固定部と前記第２固定部との間に位置し、前記縁部を固定しない細胞培養保持部材配置空間、
    　を有する細胞保持装置。     A cell holding device for measuring the contractility of cells, which is a cell culture unit for culturing and holding cells formed by fibrous substances arranged along a predetermined orientation direction, and a crossing portion with the orientation direction. A first end portion and a second end portion that are opposed to each other in the direction of the direction, and a portion that is located between the first end portion and the second end portion and that extends along the alignment direction. In a cell holding device having a cell culture holding member having an edge portion having a
    A first fixing portion for fixing the first end portion,
    A second fixing portion for fixing the second end portion,
    A cell culture holding member placement space that is located between the first fixing portion and the second fixing portion and does not fix the edge portion;
    And a cell holding device.
  14. 　細胞の収縮性を計測するための細胞保持装置に用いる細胞培養保持部材であって、
    　所定の配向方向に沿って配置された繊維状物によって形成される細胞を培養し、保持する細胞培養部、
    　前記配向方向と交差する方向沿って対向して位置する第１端部及び第２端部、
    　前記第１端部と前記第２端部との間に位置し、前記配向方向に沿った部分を少なくとも一部に有する縁部、
    　を有する細胞培養保持部材。
          A cell culture holding member used in a cell holding device for measuring contractility of cells,
    A cell culture unit that cultures and holds cells formed by fibrous substances arranged along a predetermined orientation direction,
    A first end and a second end facing each other along a direction intersecting the alignment direction;
    An edge portion located between the first end portion and the second end portion and having at least a portion along the alignment direction,
    A cell culture holding member having.
PCT/JP2019/041679 2018-10-25 2019-10-24 Cell holding device WO2020085423A1 (en)

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JP6739028B2 (en) * 2016-07-13 2020-08-12 パナソニックＩｐマネジメント株式会社 Medium and potential measuring device for biological tissue or microorganism

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WO2016060260A1 (en) * 2014-10-16 2016-04-21 国立大学法人京都大学 Tissue fragment
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