WO2018043459A1 - Bag-like container for cells - Google Patents

Abstract

A container 1 is provided with an accommodation unit 2, wherein a gas enclosure unit 3 that is partitioned from the accommodation unit 2 is integrated with the accommodation unit 2 to form a bag, so that the accommodation unit 2 can be supported by the gas enclosure unit 3, which is expanded by the action of a gas enclosed therein, in such a state that the bottom side of the accommodation unit 2 is spaced apart from a mounting surface S on which the container 1 is to be mounted. According to this configuration, in the case where a bag-like container made from a soft packaging material is used for the culturing or storage of cells, it becomes possible to maintain the shape of the accommodation unit 2 provided in the container without the need to separately provide a member for maintaining the above-mentioned shape.

Description

Cell-like container

The present invention relates to a cell-like container for cell culture or storage.

In recent years, in the fields of pharmacology and biochemistry such as pharmaceutical production, gene therapy, regenerative medicine, and immunotherapy, cells (including tissues, microorganisms, viruses, etc.) can be efficiently cultured in large quantities in an artificial environment. It has been demanded.

In order to meet such demands, various proposals have been made in the past. For example, in Patent Document 1, a film material (soft packaging material) for forming a container bottom surface is formed in a concavo-convex shape. A culture bag provided with a recess is proposed. According to this, compared with the culture bag which has a planar bottom face, it is supposed that the proliferation rate of a cell can be raised (refer paragraph [0081] of patent document 1).

JP 2009-11260 A

By the way, a bag-like container made of a soft wrapping material, like the culture bag proposed in Patent Document 1, is suitable for closed culture with a low risk of contamination, and is therefore widely used for cell culture applications. However, such a container is easily deformed due to the nature of the material. Therefore, in patent document 1, it is made possible to hold | maintain a container bottom part in the holding tray prepared separately, and to hold | maintain the shape of the recessed part provided in the container bottom part (paragraph [patent document 1 [ 0070]).

However, the preparation of such a holding tray for each culture bag has not only a disadvantage in cost but also a problem in inventory management such as taking up space during storage. Although it is conceivable to reuse the holding tray, in that case, in order to prevent contamination, treatment such as washing and sterilization is required every time it is used, and there is a problem that complicated labor is required.

Furthermore, in Patent Document 1, air holes are provided in the holding tray so that oxygen permeation into the culture bag is not hindered by the holding tray (see paragraph [0072] of Patent Document 1). In addition, there is a limit, and it is inevitable that oxygen permeation is hindered at the portion in contact with the holding tray.

Therefore, the present inventors have provided a container provided in the container without separately preparing a member for holding the shape of the bag-shaped container made of the soft wrapping material for cell culture or storage. As a result of intensive studies so that the shape can be maintained, the present invention has been completed.

The cell-like bag-like container according to the present invention is a bag-like container made of a soft wrapping material used for cell culture or storage, and includes a storage part and a gas enclosure partitioned from the storage part. The housing portion is supported by the gas-filled portion in which the bottom portion of the housing portion is separated from the placement surface on which the container is placed by the bag-filled portion and the gas-filled portion inflated by being filled with gas. The configuration is made possible.

According to the present invention, it is possible to maintain the shape of the housing portion, and it is also possible to absorb an impact from the outside by the gas sealing portion in which the gas is sealed.

It is a top view which shows the outline of the bag-shaped container for cells which concerns on 1st embodiment of this invention. It is explanatory drawing which shows the use condition of the bag-shaped container for cells which concerns on 1st embodiment of this invention. It is a schematic plan view which shows the modification of the bag-shaped container for cells which concerns on 1st embodiment of this invention. It is explanatory drawing which shows the outline of the bag-shaped container for cells which concerns on 2nd embodiment of this invention. It is explanatory drawing which shows the outline of the modification of the bag-shaped container for cells which concerns on 2nd embodiment of this invention.

Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.

[First embodiment]
In FIG. 1, the outline of the bag-shaped container for cells which concerns on 1st embodiment of this invention is shown.

A container 1 shown in FIG. 1 is an example in which the present invention is applied to a culture bag made of a soft wrapping material suitable for closed culture, and the soft wrapping material forming the container 1 can perform cell culture in a closed system. It is preferable that it has oxygen permeability and carbon dioxide permeability necessary for cell culture so that it can do. Furthermore, in order to realize high cell growth efficiency, it is preferable that it has low cytotoxicity, low elution property, and radiation sterilization suitability, so that the progress of cell culture and the state of cells can be observed. It is preferable to have transparency to the extent that it can be seen through.

Examples of such soft packaging materials include thermoplastics such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyester, silicone elastomer, polystyrene elastomer, tetrafluoroethylene-hexafluoropropylene copolymer (FEP), and the like. A resin film made of a resin can be used. These resins may be used in a single layer or may be used by laminating the same or different resins.

The container 1 is bag-made using such a soft wrapping material, is provided with a housing portion 2, and a gas sealing portion 3 partitioned from the housing portion 2 is integrally bag-made. For example, by stacking two pieces of soft packaging material and heat-sealing a predetermined part, as shown in FIG. 1, a square-shaped storage part 2 whose periphery is heat-sealed, and the storage part 2 is partitioned by heat sealing It is possible to form a bag integrally with the gas sealing portion 3 formed.
In addition, in FIG. 1, the site | part in which the soft-packing materials were heat-sealed is shown with a halftone dot.

The storage unit 2 is a place where cells are stored together with a culture solution and the like, and the cells are stored before and after culture. The housing portion 2 can be formed into a predetermined shape by molding means such as vacuum forming, pressure forming, press forming or the like simultaneously with heat sealing or prior to heat sealing. In the illustrated example, the housing portion 2 is formed on the bottom surface of the housing portion 2. A plurality of recesses 20 serving as cell culture parts are provided.

The concave portion 20 provided on the bottom surface of the accommodating portion 2 suppresses the movement of the cells in the accommodating portion 2, allows the cells being cultured to remain in the single concave portion 20, and collects the cells at the bottom of the concave portion 20 for efficient culture. In order to achieve this, for example, it can be formed in a spherical crown shape having an opening diameter (diameter) of 1.5 to 10 mm and a depth of 0.1 mm or more.

In addition, the container 2 is provided with an inlet / outlet port 21 to which a liquid feeding tube can be connected. By providing such an inlet / outlet port 21, for example, the medium is supplied from the medium bag in which the medium is stored, or the cultured cells are collected into the collection bag after the culture is completed. This operation can be performed while maintaining the closed system via the liquid feeding tube connected to the injection port 21.

The injection port 21 is formed of a tubular member through which a culture medium, cells, and the like can circulate. For example, injection molding, extrusion molding, or the like using a thermoplastic resin such as polyethylene, polypropylene, vinyl chloride, polystyrene elastomer, or FEP. Thus, it can be formed into a predetermined shape having a feed hole penetrating in the axial direction. Although not particularly illustrated, in order to prevent the inlet port 21 from adhering the inner surfaces of the top surface side and the bottom surface side of the storage portion 2 to block the flow hole, the storage portion is formed from the base end thereof. 2 can be provided with a port blocking prevention piece projecting into 2.

A gas such as nitrogen gas or air having low permeability with respect to the soft packaging material (resin film) used for the container 1 is sealed in the gas sealing portion 3, and the gas sealing portion 3 expands by sealing the gas. It has become. In order to suppress the permeation of the gas sealed in the gas sealing part 3 while ensuring the oxygen permeability and carbon dioxide permeability of the housing part 2, the container 1 is made using the soft packaging material as described above. At that time, a gas barrier layer may be provided as necessary at a site where the gas sealing portion 3 of the soft packaging material is formed.

The gas enclosure portion 3 may be filled with gas when the container 1 is made, but if the gas enclosure portion 3 is in an inflated state, it will be bulky during storage and during storage. There is also a concern that the gas sealed in the gas escapes and the gas sealing part 3 is deflated. For this reason, it is preferable that the gas sealing part 3 is provided with a gas sealing port 31 so that the gas can be sealed in the gas sealing part 3 when the container 1 is used.
The gas sealing port 31 is not particularly limited as long as the gas sealing port 31 can be opened and closed when the gas is sealed in the gas sealing part 3, but the check is made to facilitate the gas sealing operation. It preferably has a valve structure.

In the container 1 shown in FIG. 1, the gas sealing portion 3 is formed on the peripheral side of the housing portion 2 so as to surround the housing portion 2 except for a portion where the injection port 21 is provided. When gas is enclosed in such a gas enclosure part 3, as shown in FIG.2 (b), the expanded gas enclosure part 3 functions as a support | pillar, and with respect to the mounting surface S on which the container 1 is mounted Thus, the accommodating portion 2 can be supported in a state where the bottom surface side of the accommodating portion 2 is separated.
2A shows the AA end face of FIG. 1, and FIG. 2B shows a state in which the container 1 inflated by enclosing the gas in the gas enclosure 3 is placed on the placement surface S. Is shown.

Thereby, it is possible to hold the shape of the accommodating portion 2, particularly the shape of the recess 20 provided on the bottom surface of the accommodating portion 2, without separately preparing a member for holding the shape. As a result, the intended purpose of providing the concave portion 20 on the bottom surface of the accommodating portion 2 is not hindered, and the cells can be collected and cultured efficiently at the bottom portion of the concave portion 20. In addition, since the bottom surface of the housing portion 2 can be brought into non-contact with the mounting surface S, there is no possibility of impeding permeation of oxygen and carbon dioxide necessary for cell culture.

As described above, in the present embodiment, the gas enclosure 3 is disposed so as to be formed on the peripheral edge side of the accommodating portion 2, and the container 1 is placed by the gas enclosure 3 that is expanded by being encapsulated with the gas. Although the housing part 2 can be supported in a state where the bottom surface side of the housing part 2 is separated from the placement surface S, the arrangement of the gas sealing part 3 is not limited to the example shown in FIG. When the container 1 is placed on the placement surface S, the accommodation portion 2 is suspended by the expanded gas sealing portion 3 without the accommodation portion 2 hanging down, and the bottom surface side of the accommodation portion 2 is separated from the placement surface S. If the housing part 2 can be supported in this state, the arrangement of the gas sealing part 3 can be appropriately changed.

FIG. 3 shows another example in which the gas enclosing part 3 is arranged on the peripheral side of the accommodating part 2. As shown in FIG. 3A, one gas enclosing part 3 is arranged along the three sides of the accommodating part 2. As shown in FIG. 2 (b), two gas sealing portions 3 that are bent at both ends and formed in a U shape are opposed to each other with the accommodating portion 2 therebetween. As shown in FIG. 2 (c), two gas sealing portions 3 that are bent at one end side and formed in an L shape are arranged so as to face each other with the accommodating portion 2 therebetween. May be. When the size of the container 1 is large, it can be arranged as shown in FIG.

When the arrangement shown in FIGS. 2 (b) and 2 (c) is adopted, the end of one gas enclosure 3 and the end of the other gas enclosure 3 arranged so as to oppose each other via the housing 2. If the part is separated, the accommodating part 2 may hang down. In such a case, the reinforcing member 30 made of a rigid body can be disposed between both end portions to prevent the housing portion 2 from drooping.

Further, the container 1 can be placed on the mounting table by locking the holes 32 drilled at the four corners thereof with fixing pins standing on the mounting table. In this case, as shown in FIG. 2 (e), by disposing the gas sealing portion 3 along at least two opposing sides of the housing portion 2, the bottom surface side of the housing portion 2 is placed with respect to the placement surface S. The accommodating part 2 can be supported in the separated state.

In this embodiment, an example in which the present invention is applied to a culture bag made of a soft wrapping material suitable for closed culture is described, but the usage mode of the container 1 is not limited to this. The gas sealing portion 3 that is expanded by being filled with gas can also be expected to have a function as a buffer material that absorbs an impact when the container 1 drops. From this, the container 1 is used as a storage container excellent in impact resistance used for the preservation of cells, utilizing the fact that the gas sealing part 3 in which the gas is sealed can absorb the impact from the outside. Is also possible.

For example, when cryopreserving cells, the container is generally frozen with liquid nitrogen at -196 ° C, but the impact resistance of the container is extremely reduced due to freezing, and it is accidentally dropped when the container is removed. Then, the container may be damaged.
If the container 1 of the present embodiment is used as a cryopreservation container and gas is enclosed in the gas enclosure 3 and frozen, when the container 1 is taken out, the gas enclosure 3 swells and functions as a buffer material, and the container 2 Can be protected. After thawing, cell culture can be performed as it is.

[Second Embodiment]
Next, a second embodiment of the present invention will be described.
In the first embodiment described above, the gas sealing part 3 is formed on the peripheral edge side of the housing part 2, but in this embodiment, as shown in FIG. The gas enclosure 3a is formed.

The container 1 shown in FIG. 4 includes, for example, a soft packaging material that forms the top surface side of the housing portion 2, a soft packaging material that forms the bottom surface side of the housing portion 2, and a soft packaging material that forms the gas sealing portion 3a. In addition, the injection port 21 and the gas sealing port 31 are sandwiched at predetermined positions, and the periphery of these soft wrapping materials is heat-sealed, so that it is partitioned from the accommodating portion 2 and overlapped below it. The formed gas sealing part 3a can be made into a bag integrally with the accommodating part 2.

When gas is sealed in the gas sealing portion 3a formed to overlap the lower portion of the housing portion 2, the housing portion 2 is lifted by the expanded gas sealing portion 3a, and the placement surface S on which the container 1 is placed is placed. The accommodating part 2 can be supported in a state where the bottom surface side of the accommodating part 2 is separated. Thereby, it becomes possible to hold | maintain the shape of the accommodating part 2 similarly to 1st embodiment.

Moreover, in this embodiment, as shown in FIG. 5, the gas enclosure part 3b can be formed also on the upper part of the accommodating part 2, and can be formed.
The container 1 shown in FIG. 5 includes, for example, a soft packaging material that forms the gas sealing portion 3b, a soft packaging material that forms the top surface side of the housing portion 2, and a soft packaging material that forms the bottom surface side of the housing portion 2. In addition to overlapping the soft wrapping material forming the gas sealing portion 3a and sandwiching the injection port 21 and the gas sealing port 31 at a predetermined position, the peripheral edges of these soft wrapping materials are heat-sealed, thereby The gas sealing portions 3 a and 3 b that are partitioned from each other and overlapped with the upper and lower portions thereof can be formed integrally with the housing portion 2.

When the gas sealing part 3a is overlapped and formed only on one side below the housing part 2, when the gas sealing part 3a is filled with gas and inflated, the container 1 may be warped in a bow. The warping of the container 1 can be suppressed by forming the gas sealing portions 3a and 3b so as to overlap the upper and lower sides of the housing portion 2.

The present embodiment is different from the first embodiment described above in that the gas sealing portions 3a and 3b are formed below the storage portion 2 or stacked one above the other. Since the configuration other than this is common to the above-described first embodiment, a duplicate description is omitted.

In addition, as in the first embodiment described above, this embodiment can also be used as a storage container with excellent impact resistance used for storage of cells. In particular, when the gas enclosures 3a and 3b are formed so as to overlap the upper and lower sides of the housing part 2, the entire surface of the housing part 2 is covered by the gas enclosures 3a and 3b that can absorb external impacts on the surface. Higher shock absorbing performance can be exhibited.

Although the present invention has been described with reference to the preferred embodiment, the present invention is not limited to the above-described embodiment, and it goes without saying that various modifications can be made within the scope of the present invention.

That is, the cell-like bag-like container according to the present invention includes the accommodating portion 2 and the gas enclosing portion 3 partitioned from the accommodating portion 2 is integrally formed, and the gas enclosing portion 3 inflated by enclosing the gas. If the container 2 can be supported in a state where the bottom surface side of the container 2 is separated from the placement surface S on which the container 1 is placed, the other detailed configuration is the same as that of the above-described embodiment. It can change suitably, without being limited to. Further, the detailed configurations described in the above-described embodiments can be appropriately selected and combined.

All the contents of the documents described in this specification and the content of the Japanese application that forms the basis of the Paris priority of the present application are incorporated herein.

The present invention can be widely used as a bag-like container for cells used for cell culture or storage in the fields of pharmaceutics and biochemistry.

DESCRIPTION OF SYMBOLS 1 Container 2 Storage part 20 Recessed part 21 Port for injection | pouring 3, 3a, 3b Gas enclosure part 31 Gas enclosure port S Mounting surface

Claims (7)

1. A bag-like container made of a soft packaging material used for cell culture or storage,
   The container is provided with a container, and the gas enclosure part partitioned from the container is integrally formed,
   The gas encapsulating part swelled by enclosing gas allows the accommodating part to be supported in a state where the bottom surface side of the accommodating part is separated from the placement surface on which the container is placed. Cell-like container.
2. 2. The bag-like container for cells according to claim 1, wherein the soft packaging material has oxygen permeability or carbon dioxide permeability.
3. The cell-shaped bag-like container according to claim 1 or 2, wherein the gas sealing part is provided with a gas sealing port.
4. The cell-shaped bag-like container according to any one of claims 1 to 3, wherein a recess serving as a cell culture part is provided on a bottom surface of the housing part.
5. The cell-shaped bag-like container according to any one of claims 1 to 4, wherein the gas sealing portion is formed on a peripheral side of the housing portion.
6. The cell-shaped bag-like container according to any one of claims 1 to 4, wherein the gas sealing portion is formed so as to overlap at least below the storage portion.
7. The cell-shaped bag-like container according to claim 6, wherein the gas sealing part is formed so as to overlap the top and bottom of the housing part.

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