JP2020005579A - Graft storage device with sample collection mechanism - Google Patents

Abstract

To provide devices that can efficiently achieve a liquid-tight state with simple work and can easily collect the liquid in a container as a test sample.SOLUTION: Provided is a device 1C for receiving a graft, comprising a container 2C having an edge, and a lid member 3C for sealing the container, the container having an opening 22 on a side, the lid member having a top plate 31, a dome-shaped convex 38, and an opening 32 provided at the top of the convex, and the height of the peripheral of the top plate being configured to be lower than the height of the edge of the container.SELECTED DRAWING: Figure 5

Description

  The present invention relates to a graft accommodation device including a specimen collection mechanism.

  In recent years, development of new regenerative medicine has been promoted as a solution for the treatment of severe heart failure. As an example, a method of applying a sheet-shaped cell culture prepared using a temperature-responsive culture dish to which tissue engineering is applied in severe myocardial infarction or the like to the heart surface has been attempted. The method using a sheet-shaped cell culture allows a large amount of cells to be transplanted safely over a wide area, such as myocardial infarction (including chronic heart failure associated with myocardial infarction), dilated cardiomyopathy, ischemic cardiomyopathy It is particularly useful for the treatment of heart diseases associated with systolic dysfunction (eg, left ventricular systolic dysfunction) (eg, heart failure, especially chronic heart failure).

  In order to apply such a sheet-shaped cell culture to clinical application, for example, it is necessary to store the prepared sheet-shaped cell culture together with a preservation solution in a container and transfer it to an intensive care unit where transplantation is performed. However, sheet cell cultures have low absolute physical strength, and wrinkles, tears, breakage, etc. occur due to vibrations generated when transferring containers, etc. You need to be very careful.

  Various methods and containers have been developed to meet such needs. For example, the container for storing and transporting a membrane-like tissue described in Patent Document 1 below fills the storage portion with a storage solution to such an extent that a gas layer is not formed, thereby causing the storage solution to undulate or flow. As a result, vibration is not transmitted to the film-like tissue, and damage to the film-like tissue can be prevented.

  Patent Document 2 below describes a package for transporting a cultured cell sheet. Such a package eliminates air with some liquid medium when sealing with a lid, so that even if the cultured cell sheet package shakes during transportation, bubbles do not move in the liquid medium, It is designed to prevent displacement and loss of the cultured cell sheet.

JP 2012-130311 A JP 2009-89715 A

  As described above, containers for safely transferring fragile cell sheets have been developed. Further, such a container is devised so that the inside of the container is liquid-tight so that the movement of air bubbles does not occur.

  However, in order to achieve a liquid-tight state by completely removing air bubbles from the inside of the container, advanced technology is required, and strong force is required to remove the lid from the liquid-tight container. In such a case, the liquid may undulate and damage the cell sheet. In addition, it was difficult to collect a liquid in contact with the cell sheet as a test specimen while the container was covered.

  The present invention has been made in view of such points, and a device capable of efficiently achieving a liquid-tight state with a simple operation and capable of easily collecting a liquid in a container as a test sample. The purpose is to provide.

That is, the present invention relates to the following.
[1] A device used detachably mounted on a container for accommodating an implant, including a lid member for sealing the container, the lid member having a top plate portion covering an opening of the container. The device, wherein the top plate has a dome-shaped projection, an opening for discharging liquid, and an opening for injecting liquid, and the opening for discharging liquid is arranged at the top of the projection.
[2] The device according to [1], wherein the opening projects in a port shape so as to enable tube connection.
[3] The device according to [2], wherein the upper end of the opening is configured to be horizontal.

[4] The device according to any one of [1] to [3], wherein at least one opening is disposed near a peripheral edge of the top panel, and projects downward in a port shape.
[5] The device according to any one of [1] to [4], further including a tube connectable to the opening and a sample bag connectable to the tube.
[6] The device according to any one of [1] to [5], wherein the implant is a sheet-shaped cell culture.
[7] The device according to [6], wherein the sheet-shaped cell culture is a laminate.

[8] A device used detachably mounted on a container for accommodating an implant, including a lid member for sealing the container, the lid member having a top plate portion for covering an opening of the container. The device, wherein the top plate has an opening for liquid discharge and an opening for liquid injection, and the opening for liquid injection is arranged near a periphery of the top plate.
[9] The device according to [8], wherein the lid is attached to the container, and the height of the top plate is configured to be lower than the height of the edge of the container.
[10] The device according to [8] or [9], wherein the lid member has a dome-shaped convex portion on the top plate portion, and the opening for discharging the liquid is arranged at the top of the convex portion.

[11] The device according to any one of [8] to [10], further including a cylindrical wall extending from a peripheral portion of the top plate, and an annular member engaged with a lower end of the cylindrical wall.
[12] A seal member that can be interposed between the top plate portion and the end portion of the container is further included, and an anhydrous space surrounded by the seal member, the cylindrical wall, the annular member, and the container can be formed. Device according to [11].
[13] The device according to any one of [8] to [12], further including a tube connectable to the opening and a sample bag connectable to the tube.
[14] The device according to any one of [8] to [13], wherein the implant is a sheet-shaped cell culture.
[15] The device according to [14], wherein the sheet-shaped cell culture is a laminate.

[16] A device for accommodating an implant, comprising: a container having an edge; and a lid member for sealing the container, wherein the container has an opening on a side surface, and the lid member has a ceiling. It has a plate portion and a dome-shaped convex portion and an opening provided at the top of the convex portion, and is configured such that the height of the peripheral portion of the top plate portion is lower than the height of the edge portion of the container, The device.
[17] The device according to [16], wherein the opening projects in a port shape so as to enable tube connection.
[18] The device according to [16] or [17], wherein the container has a cylindrical rib protruding from a bottom surface of the container.

[19] The device according to any one of [16] to [18], wherein a slit is provided in the cylindrical rib.
[20] A cylindrical wall extending from a peripheral portion of the top plate portion, and first and second seal members interposed between the cylindrical wall and the container, further comprising a first seal member, a second seal member, The device according to any one of [16] to [19], which is capable of forming an anhydrous space surrounded by the cylindrical wall and the container. [21] The device according to any one of [16] to [20], further including a tube connectable to the opening and a sample bag connectable to the tube.
[22] The device according to any one of [16] to [21], wherein the implant is a sheet-shaped cell culture.
[23] The device according to [22], wherein the sheet-shaped cell culture is a laminate.

  ADVANTAGE OF THE INVENTION According to the device of this invention, since a liquid-tight state can be efficiently achieved by a simple mechanism and simple work, there exists a big merit in the point of workability and manufacturing cost. And since the inside of a container can be made into a completely liquid-tight state, air bubbles (gas) do not enter in a container and bubbles do not move in a container due to shaking of the container during transfer, and the fragile object is not damaged. In particular, when the fragile material is a laminate of sheet-shaped cell cultures, bubbles do not move, and the laminate does not shift or lose. Therefore, it can be stored for a long time while maintaining the shape of the fragile object in the liquid to prevent deformation.

  Since the device of the present invention can easily release the liquid-tight state, for example, it is possible to suppress the occurrence of vibration of the container and the flow of the liquid due to forcible removal of the lid member of the operator, and to reduce the fragile object. No damage. In addition, since work can be performed without contaminating the surroundings, cleanliness is strictly controlled, such as in a bio-clean room used for producing sheet-shaped cell cultures and in intensive care rooms where sheet-shaped cell cultures are used. Suitable for use in controlled locations. Further, the liquid in contact with the cell sheet can be collected as a test sample in a state where the container is covered, and can be shipped after inspection for the presence or absence of bacterial contamination.

FIG. 1 is a conceptual diagram illustrating a device 1 according to the first embodiment. FIG. 2 is a conceptual diagram showing a modification of the device 1 of FIG. FIG. 3 is a conceptual diagram illustrating a device 1A according to the second embodiment. FIG. 4 is a conceptual diagram showing a modification of the device 1A of FIG. FIG. 5 is a conceptual diagram illustrating a device 1C according to the third embodiment.

  The fragile object in the present invention refers to an object that has a low physical strength and can be broken, broken, deformed, or the like due to the shaking of the liquid. Examples of the shape of such an object include an object having a thin portion, an object having a band shape, an object having a sheet shape, and the like. Examples of the object having such a sheet shape include, but are not particularly limited to, a sheet-like structure, for example, a sheet-like cell culture, a flat membrane-like membrane tissue made of a biological material, plastic, paper, woven fabric, and nonwoven fabric. And films of various materials such as metals, polymers, and lipids. Among them, those which are hardly decomposable in liquid and those which are hardly disintegratable in liquid are preferred. The sheet-like structure may be polygonal or circular, and may or may not be uniform in width, thickness, diameter, and the like. The sheet-like structure in the present invention may be used alone in a single layer state, or may be used in a laminated state in which two or more sheets are stacked. In the latter case, each layer of the laminate may be connected to each other, or may not be connected.If connected, all the overlapping portions may be connected or partially connected. Is also good. Further, in the present invention, the term "fragile" means that, for example, evaluation of tensile properties with a conventional tensile tester (for example, one described in JIS K 7161) in which an object is fixed to a gripper outside a liquid is performed. Difficult or virtually impossible due to vulnerability. As such a fragile object, for example, an object having a small value of each of the tensile properties and difficult to accurately measure with a conventional tensile tester can be cited. Examples of such brittle materials include those that exhibit a breaking load of less than 10 N (Newton), less than 5 N, less than 2 N, less than 1 N, less than 0.5 N, less than 0.1 N, and less than 0.05 N in a tensile test. . In addition, since the measurement limit of the conventional tensile test is generally about 1 N as a breaking load, in one embodiment of the present invention, a material showing a breaking load lower than this (for example, less than 0.5 N) is preferable as a brittle substance. .

In the present invention, the term “graft” refers to a fragile substance derived from a living body having relatively low physical strength. Grafts include cultured cells (eg, cell cultures) and harvested cells. Implants may also contain products produced by the cells. The graft may contain, in addition to the cells and / or the products of the cells, a material (supplementary material or support material) for supplementing and / or supporting a predetermined part (for example, an affected part) of the living body. The implant can take various shapes such as a sheet, a film, a block, and a column. The graft is used for transplantation into a living body or the like. Examples of the transplant include a three-dimensional cell tissue (organoid, spheroid, etc.) and a two-dimensional cell tissue (sheet-shaped cell culture, etc.).
In the present invention, the sheet-shaped cell culture refers to a cell in which cells are connected to each other to form a sheet. The cells may be connected to each other directly (including via a cell element such as an adhesion molecule) and / or via an intermediary substance. The intervening substance is not particularly limited as long as it is a substance capable of at least physically (mechanically) connecting cells to each other, and examples thereof include an extracellular matrix. The intervening substance is preferably derived from cells, particularly from cells constituting a sheet-shaped cell culture. Cells are at least physically (mechanically) linked, but may be further functionally linked, for example, chemically or electrically. The sheet-shaped cell culture may be composed of one cell layer (single layer) or composed of two or more cell layers (multilayer body). Further, the sheet-shaped cell culture may have a three-dimensional structure having a thickness exceeding the thickness of one cell without the cells showing a clear layer structure. For example, in the vertical cross section of the sheet-shaped cell culture, the cells may exist in a non-uniform (eg, mosaic) state without being uniformly arranged in the horizontal direction. The sheet cell culture may exist as a single, independently formed sheet cell culture, or an independent single sheet cell culture may be present. It may exist as a laminate formed by laminating two or more layers. The layered product is, for example, a layered structure obtained by laminating two (2), three (3), four (4), five (5), or six (6) sheet-shaped cell cultures. It can be a body.

  The sheet-shaped cell culture in the present invention is composed of any cells capable of forming the above-mentioned structure. Examples of such cells include, but are not limited to, adherent cells (adherent cells). Adherent cells include, for example, adherent somatic cells (eg, cardiomyocytes, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, kidney cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, skin Cells, synovial cells, chondrocytes, etc.) and stem cells (eg, tissue stem cells such as myoblasts, cardiac stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.) Including. The somatic cells may be those differentiated from stem cells, especially iPS cells. Non-limiting examples of cells that can form sheet-shaped cell cultures include, for example, myoblasts (eg, skeletal myoblasts), mesenchymal stem cells (eg, bone marrow, adipose tissue, peripheral blood, skin, hair roots) , Muscle tissue, endometrium, placenta, cord blood, etc.), cardiomyocytes, fibroblasts, cardiac stem cells, embryonic stem cells, iPS cells, synovial cells, chondrocytes, epithelial cells (eg, oral mucosal epithelium) Cells, retinal pigment epithelial cells, nasal mucosal epithelial cells, etc.), endothelial cells (eg, vascular endothelial cells, etc.), hepatocytes (eg, hepatic parenchymal cells, etc.), pancreatic cells (eg, pancreatic islet cells, etc.), kidney cells, adrenal glands Cells, periodontal ligament cells, gingival cells, periosteal cells, skin cells and the like. In the present specification, those forming a monolayer cell culture, such as myoblasts or cardiomyocytes, are preferred, and skeletal myoblasts or iPS cell-derived cardiomyocytes are particularly preferred.

  The cells can be from any organism that can be treated with cell culture. Such organisms include, but are not limited to, for example, humans, non-human primates, dogs, cats, pigs, horses, goats, sheep, and the like. Further, only one type of cells may be used for forming the sheet-shaped cell culture, but two or more types of cells may be used. In a preferred embodiment of the present invention, when there are two or more types of cells forming a cell culture, the ratio (purity) of the most abundant cells is 65% or more at the end of cell culture production, for example, for skeletal myoblasts , Preferably 70% or more, more preferably 75% or more.

The sheet-shaped cell culture in the present invention may be a sheet-shaped cultured tissue obtained by disseminating and culturing cells in a scaffold (a scaffold for cell culture), but preferably constitutes a cell culture. Consists of only cell-derived substances and contains no other substances.
The sheet cell culture may be produced by any known technique.

  In one embodiment of the present invention, the sheet-shaped cell culture is a sheet-shaped skeletal myoblast cell culture. This is because the sheet-shaped skeletal myoblast culture is so fragile that it breaks under its own weight when a part of it is grasped, so it cannot be transported alone by itself, nor can it return to its original shape once folded. This is because it is extremely difficult to maintain the shape of the sheet in the liquid.

In the present invention, the container is not particularly limited as long as it can store a fragile substance, a liquid, or the like and does not leak the liquid, and any container including a commercially available container can be used. Examples of the material of the container include polyethylene, polypropylene, Teflon (registered trademark), polyethylene terephthalate, polymethyl methacrylate, nylon 6,6, polyvinyl alcohol, cellulose, silicon, polystyrene, glass, polyacrylamide, polydimethylacrylamide, and metal ( Examples thereof include, but are not limited to, iron, stainless steel, aluminum, copper, and brass). In addition, the container preferably has at least one flat bottom surface for maintaining the shape of the fragile object, and examples thereof include, but are not limited to, a petri dish, a cell culture dish, a cell culture bottle, and the like. Although the area of the flat bottom surface is not particularly limited, it is typically 9.1 to 78.5 cm ² , 1.13 to 78.5 cm ² , preferably 12.6 to 78.5 cm ² , and more preferably 9 to 98.5 cm ² . 0.1 to 60.8 cm ² .

In the present invention, the liquid in the container is composed of at least one kind of component, and the component is not particularly limited. For example, it is composed of liquid such as water, aqueous solution, non-aqueous solution, suspension, and emulsion.
The liquid or liquid in the present specification may be a fluid having fluidity as a whole, and may include other non-liquid components such as a solid substance such as a cell scaffold and bubbles.

  The components constituting the liquid in the container are not particularly limited as long as they have little effect on the fragile substance. When the fragile substance is a membrane made of a bio-derived material, the components constituting the liquid in the container are biocompatible from the viewpoint of biological stability and long-term storability, i.e. On the other hand, those which do not cause unwanted effects such as inflammatory response, immune response, and poisoning response or at least have small effects are preferable. For example, water, saline, physiological buffer (eg, HBSS, PBS, EBSS, Hepes) , Sodium bicarbonate, etc.), medium (eg, DMEM, MEM, F12, DMEM / F12, DME, RPMI1640, MCDB, L15, SkBM, RITC80-7, IMDM, etc.), sugar solution (sucrose solution, Ficoll-paque (registered)) Trademark) PLUS), seawater, serum-containing solution, renographin (registered trademark) solution, metrizamide solution, meg Min solution, glycerin, ethylene glycol, ammonia, benzene, toluene, acetone, ethyl alcohol, benzol, oil, mineral oil, animal fat, vegetable oil, olive oil, colloid solution, liquid paraffin, turpentine oil, linseed oil, castor oil, etc. Can be

  When the fragile material is a sheet-shaped cell culture, the components constituting the liquid in the container can stably store the cells, contain the minimum oxygen and nutrients necessary for cell survival, and Those that do not break down due to osmotic pressure or the like are preferable. For example, physiological saline, physiological buffers (eg, HBSS, PBS, EBSS, Hepes, sodium bicarbonate, etc.), culture media (eg, DMEM, MEM, F12, DMEM / F12, Examples include, but are not limited to, DME, RPMI 1640, MCDB, L15, SkBM, RITC80-7, IMDM, and the like, and sugar solutions (sucrose solution, Ficoll-paque PLUS (registered trademark), and the like).

The amount of liquid in the container is such that the fragile object can be held with the lid member attached to the container, and the bulk of the liquid formed between the bottom of the container and the top of the lid member causes the fragile object to oscillate. The height is not particularly limited as long as it does not move. In one embodiment of the present invention, the diameter of the sheet cell culture is about 35 to 55 mm and the area is 6 cm ² or more, or 10 cm ² or more. The liquid volume can be, for example, 1.0 mm to 20.0 mm regardless of the diameter of the sheet-shaped cell culture.

  In the present invention, the lid member is not particularly limited as long as it can seal the container. Examples of the material of the lid member include polyethylene, polypropylene, Teflon (registered trademark), polyethylene terephthalate, polymethyl methacrylate, nylon 6,6, polyvinyl alcohol, cellulose, silicon, polystyrene, glass, polyacrylamide, polydimethylacrylamide, and metal. (Eg, iron, stainless steel, aluminum, copper, brass) and the like, but are not limited thereto.

  In the present invention, the shapes of the lid member and the container are not particularly limited, as long as the lid member and the container can be engaged with each other and a closed space can be formed by such engagement. For example, when the container is a general-purpose petri dish, the shape of the lid member is preferably circular. The lid member and / or the container may be made of a light-transmitting material so that the state of the fragile object contained in the container and the presence or absence of bubbles in the liquid may be confirmed.

  In the present invention, the fragile material is held in the liquid in the container containing the liquid. The position of the fragile substance in the liquid is not particularly limited, but is arranged at a position where the lid member does not come into contact with the fragile substance in a state where the lid member is attached to the container to form a closed space (or even if the fragile substance is in contact with the container). Good). Preferably, the frangible is located in the liquid of the container, on the bottom surface of the container, near the bottom surface, or the like.

  In the present invention, an annular member refers to a member having a space inside a ring formed by rotating a rectangle around an axis parallel to one side thereof. In addition, the height of the annular member is not particularly limited so that the liquid and the fragile substance can be accommodated in such a space, but is typically 1 to 20 mm, preferably 3 to 15 mm, more preferably 5 to 10 mm. . The inner diameter of the annular member is not particularly limited, but is typically 1 to 15 cm, preferably 3 to 15 cm, and more preferably 3 to 10 cm.

In the present invention, the seal member refers to a member interposed between the container and the lid member to enhance the hermeticity of the container, such as a packing ring.
The annular member and / or the sealing member can be made of an elastic material in order to absorb manufacturing tolerances of the container and the lid member and to enhance the hermeticity of the container. Examples of the elastic material include, but are not limited to, natural rubber, elastomer, nitrile rubber, silicon rubber, and the like.

In the present invention, the convex portion refers to a non-flat portion such as a protruding portion or a bulging portion. The horizontal cross-sectional area of the convex portion refers to, for example, the area of a two-dimensional cross section that appears when the convex portion is cut at the liquid surface while the convex portion is immersed in a liquid.
In one embodiment of the present invention, the projection may be formed in a dome shape having a top, and is preferably designed so that the top of the projection intersects with the center line of the opening. Examples of the shape of the curved surface of the convex portion include, but are not limited to, a hyperboloid, a paraboloid, a hemisphere, a cone, and a pyramid.

[First Embodiment]
One aspect of the present invention is a device used by being detachably attached to a container for accommodating an implant, which includes a lid member for sealing the container, and the lid member covers the opening of the container. The top plate has a dome-shaped protrusion, an opening for liquid discharge, and an opening for liquid injection, and the opening for liquid discharge is disposed at the top of the protrusion. And the device.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings.
First, a first embodiment of the present invention will be described.
FIG. 1 is a conceptual diagram showing a device 1 according to the first embodiment of the present invention, and FIG. 2 is a conceptual diagram showing a modification of the device 1. In each of the drawings in the present application, the size of each member is appropriately emphasized for ease of description, and the illustrated members do not indicate the actual size.

  As shown in FIG. 1A, the device 1 according to the first embodiment of the present invention includes a lid member 3 for sealing a container 2. The container 2 is a commercially available petri dish having an edge 21 surrounding the opening, and constitutes a storage space in which the liquid L, the fragile material S, and the like can be stored. The lid member 3 includes a top plate portion 31, a cylindrical wall 34 hanging down from a peripheral portion of the top plate portion 31, and openings 32 and 33. The lid member 3 has a dome-shaped convex portion 38 on the top plate portion 31, the opening portion 32 is provided at the top of the convex portion 38, and the opening portion 33 is provided near the periphery of the top plate portion 31. I have. The openings 32 and 33 protrude upward in a port shape, and are configured to connect a tube or the like. A ring-shaped seal member R is arranged on the periphery of the top plate portion 31.

  As shown in FIG. 1B, when using the device 1, the lid member 3 is attached to the container 2 containing the liquid L and the fragile object S, and is brought into close contact with the container 2 via the seal member R. At this time, the cylindrical wall 34 functions as a guide mechanism for positioning the lid member 3 with respect to the container 2 and also as a fitting mechanism that can fit the container 2 and the lid member 3. Next, a tube (not shown) is connected to the opening 33, and a syringe (not shown) containing a liquid is connected to the tip of the tube. Also, a tube (not shown) is connected to the opening 32, and a sample collection bag (not shown) is connected to the tip of the tube.

  When the syringe connected to the opening 33 is operated to inject the liquid into the container 2, the liquid falls near the peripheral edge of the container 2, so that a problem such as breakage of the fragile object S does not easily occur. When the liquid in the syringe is further poured into the container 2, the liquid volume in the container 2 increases, and the liquid level of the liquid L reaches the opening 32 and is discharged from the opening 32. At this time, even when bubbles are present in the liquid L, since the convex portion 38 is inclined with respect to the horizontal plane, buoyancy is applied to the bubbles and the bubble is reliably pushed out to the top (opening 32) of the convex portion 38. Can be discharged. The discharged liquid L is collected in a sample collection bag through a tube, and can be sent to the test in a state where the liquid L in contact with the fragile substance S is contained in the bag.

  When the required amount of liquid L as a specimen is collected in the bag, the tubes connected to the openings 32 and 33 are removed, a stopper (not shown) is attached, and the liquid L is transferred while maintaining the liquid-tight space. When the fragile material S is used at the transfer destination, a syringe is attached to the opening 33, and the syringe is operated with the opening 32 opened to collect the liquid L in the container 2 into the syringe. The liquid L collected in the syringe can be sent to the test as a specimen. When a certain amount of liquid L is discharged, the liquid level becomes horizontal, so that the liquid level does not shake even if the lid member 3 is removed. Further, since the lid member 3 does not have a structure to enter the liquid-tight space and the liquid-tight state is released before the lid member 3 is removed, it is difficult for the operator to remove the lid member with an excessive force. Then, the fragile object S stored in the container 2 is taken out and used.

  The present embodiment is not limited to this, and those skilled in the art can suitably change the configuration and shape of the device to design a device having a different configuration and shape. For example, as shown in FIG. 2A, the heights of the upper ends of the port-shaped openings 32 and 33A can be made horizontal. Thereby, in the liquid-tight state, the heights of the liquid surfaces of the openings 32 and 33A are uniform, so that the liquid L does not easily overflow from the openings. Further, as shown in FIG. 2B, the opening 33B can be made to protrude downward in a port shape. This allows the liquid to be injected while the lower end of the opening 33B is immersed in the liquid L, so that bubbling or the like is unlikely to occur. Furthermore, when the liquid L is removed from the opening 33B, the liquid level can be made lower. Therefore, when the lid member 3 is removed, problems such as the liquid L leaking out of the container hardly occur. Three or more openings may be provided in the lid member 3, and the liquid may be injected or discharged from the three or more openings.

  As described above, according to the device 1 according to the first embodiment of the present invention, a liquid-tight state can be efficiently achieved with a simple mechanism and a simple operation, so that there are great advantages in terms of workability and manufacturing cost. is there. And since the inside of a container can be made into a completely liquid-tight state, air bubbles (gas) do not enter in a container and bubbles do not move in a container due to shaking of the container during transfer, and the fragile object is not damaged. In particular, when the fragile material is a laminate of sheet-shaped cell cultures, bubbles do not move, and the laminate does not shift or lose. Therefore, it can be stored for a long time while maintaining the shape of the fragile object in the liquid to prevent deformation.

  Further, according to the device 1 according to the first embodiment of the present invention, since the liquid-tight state can be easily released, for example, the vibration of the container or the flow of the liquid due to the forcible removal of the lid member by the operator. Can be suppressed and fragile objects are not damaged. In addition, since work can be performed without contaminating the surroundings, cleanliness is strictly controlled, such as in a bio-clean room used for producing sheet-shaped cell cultures and in intensive care rooms where sheet-shaped cell cultures are used. Suitable for use in controlled locations. Further, the liquid in contact with the cell sheet can be collected as a test sample in a state where the container is covered, and can be shipped after inspection for the presence or absence of bacterial contamination.

[Second embodiment]
One aspect of the present invention is a device used by being detachably attached to a container for accommodating an implant, which includes a lid member for sealing the container, and the lid member covers the opening of the container. Having a plate portion, the top plate portion has an opening for liquid discharge, and an opening for liquid injection, and the opening for liquid injection is arranged near the periphery of the top plate portion, Related to the device.

Next, a second embodiment of the present invention will be described.
FIG. 3 is a conceptual diagram showing a device 1A according to a second embodiment of the present invention, and FIG. 4 is a conceptual diagram showing a modification of the device 1A in FIG. In each of the drawings in the present application, the size of each member is appropriately emphasized for ease of description, and the illustrated members do not indicate the actual size.
In the figure, the same components as those of the device 1 according to the first embodiment are denoted by the same reference numerals, and the differences from the first embodiment will be described in detail below. The description is omitted.

  As shown in FIG. 3A, a device 1A according to a second embodiment of the present invention includes a lid member 3A for sealing a commercially available container 2. The lid member 3 </ b> A includes a top plate 31, a cylindrical wall 34 extending vertically from a peripheral edge of the top plate 31, and openings 32 and 33. The openings 32 and 33 are provided near the center of the top panel 31 and near the periphery of the top panel 31, respectively. The openings 32 and 33 protrude upward in a port shape, and are configured so that the upper ends are horizontal. The outer diameter of the cylindrical wall 34 is substantially the same as the inner diameter of the container 2, and is configured such that when the top plate portion 31 is attached to the container 2, the cylindrical wall 34 comes into close contact with the inner surface of the container 2. The upper end 39 of the cylindrical wall 34 is enlarged in the radial direction, and is configured to be able to be placed on the edge 21.

  As shown in FIG. 3B, when using the device 1 </ b> A, the lid member 3 </ b> A is attached to the container 2 while keeping the cylindrical wall 34 in close contact with the inner side surface of the container 2, and the upper end 39 of the cylindrical wall 34 is attached to the container 2. 3 is engaged with the edge 21. At this time, the cylindrical wall 34 functions as a guide mechanism for positioning the lid member 3A with respect to the container 2 and as a fitting mechanism capable of fitting the lid member 3A to the container 2. In addition, the portion of the cylindrical wall 34 below the top plate 31 serves as a stopper when the top plate 31 is pushed into the container 2. Does not hurt S. In addition, since the height of the top plate portion 31 from the bottom surface of the container 2 is the same as the height of the lower portion of the cylindrical wall 34, the height of the lower portion of the cylindrical wall 34 is adjusted so that the container It is also possible to adjust the position of the top plate part 31 in 2.

  Next, a tube, a syringe, and a sample collection bag are connected to the openings 32 and 33, and a liquid injecting operation, a liquid L discharging operation, a sample (liquid L) collecting operation, and the like are performed. When the tube is attached to or removed from the openings 32 and 33, the liquid or the liquid L in the tube or the liquid L in the port may flow out due to pressure. Also in this case, since the height of the top plate 31 is lower than the edge 21 of the container 2, the outflowing liquid is received in the space A between the top plate 31 and the cylindrical wall 34. Further, by further closing the lid 4 from above, the liquid flowing into the space A can be prevented from leaking out of the container 2 during the transfer. Further, since the upper ends of the openings 32 and 33 are horizontal, the liquid L does not flow out of the container 2 when the plug is removed from the openings 32 and 33. At the transfer destination, the lid member 3A is removed by grasping the upper end portion 39 of the cylindrical wall 34, and the fragile material S stored in the container 2 is taken out and used.

  The present embodiment is not limited to this, and those skilled in the art can suitably change the configuration and shape of the device to design a device having a different configuration and shape. For example, a dome-shaped convex portion may be provided on the top plate portion 31, and an opening 32 may be provided on the top of the convex portion. Accordingly, even when bubbles are present in the liquid L, the liquid L can be pushed out to the top of the projection (the opening 32) and discharged. At this time, the upper ends of the openings 32 and 33 may be configured to be horizontal. Further, the opening 33 can be made to protrude downward in a port shape. This allows the liquid to be injected while the lower end of the opening 33 is immersed in the liquid L, so that bubbling or the like is unlikely to occur.

  Next, a device 1B according to a modification of the second embodiment of the present invention will be described. Hereinafter, differences from the second embodiment will be described in detail, and description of similar items will be omitted.

  As shown in FIG. 4A, a device 1B according to a modification of the second embodiment of the present invention includes a lid member 3B for sealing a commercially available container 2. The lid member 3B includes a top plate portion 31, openings 32, 33, a cylindrical wall 34, a top portion 35 extending in a radial direction from an upper end portion of the cylindrical wall 34, and a tubular skirt hanging from a peripheral portion of the top portion 35. It has a wall 36, a sealing member 37 and a projection 38. The height of the peripheral edge of the top plate 31 is lower than the edge 21 of the container 2. The outer diameter of the cylindrical wall 34 is smaller than the inner diameter of the container 2, and a space G (second space) is formed between the outer surface of the cylindrical wall 34 and the inner surface of the container 2. . The top portion 35 is configured to be placed on the edge 21 of the container 2 when the lid member 3B is attached to the container 2. The cylindrical skirt wall 36 has an inner diameter substantially equal to or larger than the outer diameter of the container 2, and guides the position of the cylindrical wall 34 to the center of the container 2 when attaching the lid member 3 </ b> B to the container 2. Functions as a mechanism.

  As shown in FIG. 4B, when using the device 1B, the lid member 3B is attached to the container 2 while the cylindrical skirt wall 36 is along the outer surface of the container 2. At this time, the elastic member 4 may be interposed between the lower end of the cylindrical wall 34 and the bottom surface of the container 2 to enhance the adhesion. The annular member 4 is a member having a space (first space) inside a ring formed by rotating a rectangle around an axis parallel to one side thereof. The cross section of the annular member 4 is rectangular, and is configured such that there is no space into which bubbles or the like enter when the annular member 4 is immersed in a liquid. Further, by installing the annular member 4 on the bottom surface of the container 2, the fragile object S is captured in the first space (see FIG. 4A). The problem that the fragile material is lost at the lower end is hard to occur.

  When attaching the lid member 3B, the liquid volume of the liquid L in the container 2 is adjusted to be lower than the height of the annular member 4 with the annular member 4 installed on the bottom surface of the container 2. Then, the first space and the second space are separated by the lid member 3B, and the liquid is injected into the first space and the space above the first space, whereby the second space can be made an anhydrous space in which the liquid L does not exist. Since the anhydrous space is double-blocked by the annular member 4 and the sealing member 37, even if the liquid L in the liquid-tight space flows out beyond the annular member 4, the sealing member 37 Can be blocked. Further, when removing the lid member 3B, the liquid L in the liquid-tight space is received by the second space, so that the operation of discharging the liquid L can be omitted. By providing a circular groove on the lower surface side of the seal member 37 so that the edge 21 of the container 2 enters the groove, the lid member 3B can be firmly fixed to the container 2.

  As described above, according to the devices 1A and 1B according to the second embodiment of the present invention, a liquid-tight state can be efficiently achieved with a simple mechanism and a simple operation, so that the workability and the manufacturing cost are large. There are benefits. And since the inside of a container can be made into a completely liquid-tight state, air bubbles (gas) do not enter in a container and bubbles do not move in a container due to shaking of the container during transfer, and the fragile object is not damaged. In particular, when the fragile material is a laminate of sheet-shaped cell cultures, bubbles do not move, and the laminate does not shift or lose. Therefore, it can be stored for a long time while maintaining the shape of the fragile object in the liquid to prevent deformation.

  Further, according to the devices 1A and 1B according to the second embodiment of the present invention, the liquid-tight state can be easily released. Of the fragile material can be prevented. In addition, since work can be performed without contaminating the surroundings, cleanliness is strictly controlled, such as in a bio-clean room used for producing sheet-shaped cell cultures and in intensive care rooms where sheet-shaped cell cultures are used. Suitable for use in controlled locations. Further, the liquid in contact with the cell sheet can be collected as a test sample in a state where the container is covered, and can be shipped after inspection for the presence or absence of bacterial contamination.

[Third embodiment]
One aspect of the present invention is a device for receiving an implant, comprising a container having an edge and a lid member for sealing the container, wherein the container has an opening on a side surface, The member has a top plate, a dome-shaped protrusion, and an opening provided at the top of the protrusion, and the height of the peripheral portion of the top plate is lower than the height of the edge of the container. The device.

Next, a third embodiment of the present invention will be described.
FIG. 5 is a conceptual diagram showing a device 1C according to the third embodiment of the present invention. In each of the drawings in the present application, the size of each member is appropriately emphasized for ease of description, and the illustrated members do not indicate the actual size.
In the drawings, the same components as those of the devices according to the first and second embodiments are denoted by the same reference numerals, and the differences will be described in detail below, and the description of the same items will be omitted. I do.

  As shown in FIG. 5A, a device 1C according to a modification of the third embodiment of the present invention includes a container 2C having an edge 21 and a lid member 3C for sealing the container 2C. The lid member 3C has a top plate part 31, an opening part 32, a cylindrical wall 34, a top part 35, a cylindrical skirt wall 36, a seal member 37, and a convex part 38. In the present embodiment, the cylindrical wall 34 extends upward from the peripheral edge of the top plate 31 and does not extend downward. The outer diameter of the cylindrical wall 34 is smaller than the inner diameter of the container 2, and the top plate 31 is pushed into the container 2 </ b> C so that the peripheral edge of the top plate 31 can be arranged at a position lower than the edge 21 of the container 2 </ b> C. It is configured.

  The seal members 37 are arranged between the outer surface of the cylindrical wall 34 and the inner surface of the container 2C, and between the top plate 31 and the end 21 of the container 2. In the present embodiment, the openings 32 and 22 are provided on the top of the convex portion 38 of the lid member 3C and on the side surface of the container 2C, respectively. The container 2C has a cylindrical rib 23 protruding from the bottom surface, and is configured to form a space (first space) inside the cylindrical rib 23. In a state where the lid member 3C is attached to the container 2C, a gap is formed between the top plate portion 31 and the cylindrical rib 23. The opening 22 of the container 2C is provided on the side surface of the container 2C so as to be horizontal to the cylindrical rib 23.

  As shown in FIG. 5B, when using the device 1C, the liquid L and the fragile substance S are put inside the cylindrical wall 34 of the container 2C, and the lid member 3C is attached to the container 2C. Next, the syringe connected to the opening 22 is operated to inject the liquid into the container 2C. Since the liquid injected from the opening 22 is blocked by the cylindrical ribs 23, problems such as the fragile object S swinging and being broken by the liquid injection hardly occur. Then, when the liquid is further injected, the liquid flows into the first space beyond the height of the cylindrical rib 23, the container 2C is filled with the liquid L, and is discharged from the opening 32 of the lid member 3C. When the liquid L is discharged at the transfer destination, the opening 32 is opened and the liquid L is discharged from the opening 22. At this time, since the fragile substance S is trapped in the first space, the water L Less susceptible to A slit may be provided in the cylindrical rib 23 so that the liquid injected from the opening 22 and the liquid L in the first space move smoothly. Such a slit may be provided above the cylindrical rib 23 so that the liquid L holding the fragile object S remains.

  As described above, according to the device 1 </ b> C according to the third embodiment of the present invention, a liquid-tight state can be efficiently achieved with a simple mechanism and a simple operation. is there. And since the inside of a container can be made into a completely liquid-tight state, air bubbles (gas) do not enter in a container and bubbles do not move in a container due to shaking of the container during transfer, and the fragile object is not damaged. In particular, when the fragile material is a laminate of sheet-shaped cell cultures, bubbles do not move, and the laminate does not shift or lose. Therefore, it can be stored for a long time while maintaining the shape of the fragile object in the liquid to prevent deformation.

  In addition, according to the device 1C according to the third embodiment of the present invention, since the liquid-tight state can be easily released, for example, the vibration of the container or the flow of the liquid due to the forcible removal of the lid member by the worker Can be suppressed and fragile objects are not damaged. In addition, since work can be performed without contaminating the surroundings, cleanliness is strictly controlled, such as in a bio-clean room used for producing sheet-shaped cell cultures and in intensive care rooms where sheet-shaped cell cultures are used. Suitable for use in controlled locations. Further, the liquid in contact with the cell sheet can be collected as a test sample in a state where the container is covered, and can be shipped after inspection for the presence or absence of bacterial contamination.

Although the present invention has been described with reference to the illustrated embodiment, the present invention is not limited to this. Each configuration of the lid members 3, 3A, 3B, 3C in the first to third embodiments can be freely combined.
In the present invention, each configuration can be replaced with any configuration that can perform the same function, or any configuration can be added.

1, 1A, 1B, 1C Device 2, 2C Container 21 Edge 22 Opening 23 Cylindrical rib 3, 3A, 3B, 3C Lid 31 Top plate 32 Opening 33, 33A, 33B Opening 34 Cylindrical wall 35 Top part 36 Cylindrical skirt wall 37, R seal member 38 Convex part 4 Ring member

Claims (8)

  A device for accommodating an implant, comprising a container having an edge, and a lid member for sealing the container, the container has an opening on a side surface, the lid member is a top plate portion and The said device which has a convex part of a dome shape, and the opening provided in the top part of a convex part, and is comprised so that the height of the periphery of a top plate part may become lower than the height of the edge of a container.   The device of claim 1, wherein the opening projects into a port to allow for tube connection.   The device according to claim 1, wherein the container has a cylindrical rib protruding from a bottom surface of the container.   The device according to any one of claims 1 to 3, wherein the cylindrical rib is provided with a slit.   A first sealing member, a second sealing member, and a cylindrical wall that further include a cylindrical wall extending from a peripheral portion of the top plate portion and first and second seal members interposed between the cylindrical wall and the container; The device according to any one of claims 1 to 4, wherein the device can form an anhydrous space, surrounded by a container.   The device according to any one of claims 1 to 5, further comprising a tube connectable to the opening and a sample bag connectable to the tube.   The device according to claim 1, wherein the implant is a sheet cell culture.   The device according to claim 7, wherein the sheet-shaped cell culture is a laminate.