Cell preservation container

Abstract

To provide a cell storage container that can suitably keep sterility when housed cells are removed, and from which the cells and cell clusters can be removed without damage.SOLUTION: A cell storage container 1 comprises a cell housing part 10 formed in such a manner that peripheral edge parts of two sheet-like members 61 and 62 are joined, a cell introduction part 20, a cell discharge part 30, a needleless port 40 arranged in the cell discharge part 30, and a needleless port housing part 50 comprising a needleless port housing space 51 formed in such a manner that the two sheet-like members 61 and 62 constituting the cell housing part 10 are extended to the side of the cell discharge part 30, and the peripheral edge parts of the two extended sheet-like members 61 and 62 are joined so as to surround the needleless port 40.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a cell storage container equipped with a needleless port. [Background technology]

[0002] Products used in regenerative medicine require sterility throughout the entire process of using these products. In particular, cell preparations manufactured from cells collected from biological samples are often administered directly to patients, and contamination from the outside world can be a major risk in treatment. Therefore, sterility must be maintained throughout all processes from the storage of the cell preparation in a cell storage container until just before administration to the patient. In addition, when removing the cell preparation from the cell storage container, sterility must also be maintained for areas that may come into contact with instruments used to remove the cell preparation, such as syringes.

[0003] For example, Patent Document 1 proposes a cell storage container formed into a bag shape using a sheet-like resin member. A tubular port member having a diaphragm is disposed at the cell removal port of such a bag-shaped cell storage container. When cells are to be removed, a needle is inserted into the diaphragm of the port member to make a hole in the diaphragm, and the cells are aspirated and removed using a syringe or the like. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2019-005388 A Summary of the Invention [Problem to be solved by the invention]

[0005] Conventionally, when removing cells from a cell storage container, a needle was inserted into a removal port that was exposed to the outside world, making it difficult to maintain sterility and resulting in the risk of contamination when removing the cells. In addition, cells used in regenerative medicine may be stored in a state in which they form clumps. In such cases, if cells are extracted using a needle with a small inner diameter, the formed cell clumps may be damaged. Therefore, there is a demand for a technology that allows cells to be extracted using a tool with a larger inner diameter while maintaining sterility when extracting cells.

[0006] Therefore, an object of the present invention is to provide a cell storage container that can appropriately maintain sterility when the stored cells are removed, and that allows the cells and cell clumps to be removed without damage. [Means for solving the problem]

[0007] The present invention relates to a cell storage container comprising a cell storage section formed by joining the peripheral portions of two sheet-like members, a cell introduction section for introducing cells into the cell storage section, a cell extraction section for extracting cells stored in the cell storage section, a needle-less port disposed in the cell extraction section, and a needle-less port storage section having a needle-less port storage space formed by the two sheet-like members constituting the cell storage section extending toward the cell extraction section and joining the peripheral portions of the two extended sheet-like members so as to surround the needle-less port.

[0008] Furthermore, it is preferable that the length of the needle-less port accommodating space along the surface direction of the sheet-like member and along the radial direction of the needle-less port is 120% to 1200% of the radial length of the needle-less port.

[0009] Moreover, it is preferable that the needle-less port comprises a tubular connecting portion that is placed in the cell withdrawal portion, and a main body portion that is formed with a larger diameter than the connecting portion and that is placed in the needle-less port accommodation space.

[0010] It is also preferable that the edge of the needle-less port accommodating space be formed in a curved shape without corners in the vicinity of the needle-less port. Effect of the Invention

[0011] According to the cell preservation container of the present invention, sterility can be appropriately maintained when the stored cells are removed, and the cells and cell clumps can be removed without being damaged. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a plan view showing a cell storage container according to a first embodiment of the present invention. [Diagram 2] FIG. 1 is an exploded perspective view showing a cell preservation container according to a first embodiment. [Diagram 3] 2 is a cross-sectional view taken along line AA in FIG. 1. [Figure 4A] FIG. 13 is a diagram showing a manufacturing process for a cell preservation container, illustrating a step of overlapping two sheet-like members having three-dimensional shapes with tubes placed in the grooves. [Figure 4B] FIG. 4B is a diagram showing a process of welding the vicinity of the cell extraction portion from the state shown in FIG. 4A. [Figure 4C] FIG. 4C shows a process of placing a needle-less port at the cell outlet portion and placing a cell introduction tube at the cell introduction portion, from the state shown in FIG. 4B. [Figure 4D] FIG. 13 is a diagram showing a state in which a needle-less port is placed in a cell outlet section and a cell introduction tube is placed in a cell introduction section. [Figure 4E] FIG. 4C is a diagram showing a process for producing a cell preservation container having a cell storage portion and a needle-less port storage portion by high-frequency welding (thermal welding) the outer peripheries of two sheet-like members 61, 62 from the state shown in FIG. 4D. [Diagram 5] FIG. 2 is a diagram showing a procedure for using the cell preservation container of the first embodiment, showing a state in which cells are stored in the cell preservation container. [Figure 6] FIG. 6 is a diagram showing a state in which cells are accommodated in the cell accommodation section, following the state shown in FIG. 5. [Figure 7] FIG. 7 is a diagram showing the state in which the cell introduction tube has been fused, following the state shown in FIG. 6. [Figure 8]FIG. 13 is a diagram showing a state in which cells accommodated in a cell accommodation section are removed, and a diagram showing a state in which the needle-less port accommodation section is opened (cut). [Figure 9] 9 is a view of the opened portion of the cell storage container as viewed in the direction of arrow B in FIG. 8. [Figure 10] 9 is a view of the opened portion of the cell storage container as viewed in the direction of arrow D in FIG. 8. [Figure 11] FIG. 4 is a plan view showing a cell preservation container according to a second embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Hereinafter, preferred embodiments of the cell storage container of the present invention will be described with reference to the drawings. The cell storage container is mainly composed of a sheet-shaped member made of a flexible thermoplastic resin, and is used for storing cells such as stem cells collected from a biological sample, and cell preparations produced by culturing and processing these cells (hereinafter, cells and cell preparations are collectively referred to as cells).

[0014] First, a cell storage container 1 of the first embodiment will be described with reference to Figures 1 to 3. As shown in Figure 1, the cell storage container 1 of the first embodiment includes a cell storage section 10, a cell introduction section 20, a cell extraction section 30, a needle-less port 40 disposed in the cell extraction section 30, and a needle-less port storage section 50.

[0015] 1 to 3, the cell-holding section 10 is constructed by overlapping two sheet-like members 61, 62 and joining most of their peripheral portions together. The cell-holding section 10 has a cell-holding space 11, which is a space surrounded by the sheet-like members 61, 62 whose peripheral portions are joined together. In the first embodiment, the sheet-like members 61, 62 are formed with recesses of the same shape by three-dimensional molding, and the sheet-like members 61, 62 are overlapped so that these recesses face each other to form the cell-containing space 11. The cell-containing section 10 is formed in an elliptical shape in a plan view, as shown in Fig. 1.

[0016] The cell introduction section 20 is used when introducing cells, etc., collected from a biological sample into the cell storage section 10. The cell introduction section 20 includes a cell introduction path 21 and a cell introduction tube 22 disposed in the cell introduction path 21. The cell introduction path 21 is disposed at one end side in the longitudinal direction of the elliptical cell holding section 10. The cell introduction path 21 is formed in each of the sheet-shaped members 61, 62 and is composed of a cell introduction groove 211 extending along the longitudinal direction of the cell holding section 10. One end of the cell introduction groove 211 is continuous with the cell holding space 11. The other end of the cell introduction groove 211 extends to the edge of the sheet-shaped members 61, 62.

[0017] The cell introduction tube 22 is disposed in the cell introduction path 21. The cell introduction tube 22 guides cells, etc., collected from a biological sample to the cell accommodation section 10 in a sterile and airtight state. This cell introduction tube 22 is made of a thermoplastic resin such as EVA resin. In the first embodiment, the cell introduction tube 22 is disposed in a cell introduction groove 211 formed in the sheet-like members 61, 62 so that one end side communicates with the cell accommodation space 11. A tube clip 23 that opens and closes the flow path of the cell introduction tube 22 is attached to the cell introduction tube 22. In addition, a connection port 24 is attached to the tip of the cell introduction tube 22 to which a device such as a syringe used for introducing cells into the cell preservation container 1 can be connected.

[0018] The cell extraction section 30 is used when extracting cells etc. contained in the cell storage section 10. The cell extraction section 30 is disposed at the end (the other end) of the elliptical cell storage section 10 in the longitudinal direction opposite to the side where the cell introduction section 20 is disposed. The cell extraction section 30 comprises a groove 31 and a tube 32 disposed in this groove 31. The groove 31 is formed in each of the sheet-like members 61, 62, and extends along the longitudinal direction of the cell storage section 10. The tube 32 is made of a thermoplastic resin such as EVA resin. One end of the cell extraction section 30 is continuous with the cell storage space 11.

[0019] The needle-less port 40 is disposed in the cell extraction section 30. The needle-less port 40 includes a cylindrical connection section 41 and a main body section 42 having a larger diameter than the connection section 41. The needle-less port 40 is disposed in the cell extraction section 30 with the connection section 41 inserted into the tube 32, and the main body section 42 protrudes from the cell extraction section 30. The connection section 41 and the main body section 42 of the needle-less port 40 are formed from a hard synthetic resin such as polycarbonate or polypropylene. The needleless port 40 (main body 42) has an elastic partition member (not shown) with a slit formed therein, and is an injection port that enables the injection or collection of liquid without using a puncture needle or the like while maintaining airtightness by inserting the tip (cylindrical tip) of a syringe into this slit.

[0020] The needle-less port accommodating section 50 is constituted by a portion where the sheet-like members 61, 62 constituting the cell accommodating section 10 extend towards the cell withdrawal section 30. The sheet-like members 61, 62 extend beyond the tip of the main body section 42 of the needle-less port 40. The extended portions of the sheet-like members 61, 62 are joined on the outside of a portion spaced a predetermined distance from the needle-less port 40 in a plan view, thereby forming the needle-less port accommodating section 50 having the needle-less port accommodating space 51 surrounded by the sheet-like members 61, 62.

[0021] A length W1 in a direction X (hereinafter also referred to as a width direction X) along the surface direction of the sheet-like members 61, 62 in the needle-less port accommodating space 51 and along the radial direction of the needle-less port 40 is preferably set to 120% to 1200% of a radial length W2 (diameter of the main body portion 42) of the needle-less port 40, and more preferably, the length W1 is set to 300% to 600% of the length W2. In the first embodiment, the length W1 is set to 500% of the length W2. Also, the length W1 is preferably set to 25 mm to 250 mm. By setting the length W1 in the width direction X of the needle-less port accommodating space 51 in the range of 120% to 1200% of the radial length W2 of the needle-less port 40 (the diameter of the main body portion 42), as described below, when the needle-less port accommodating portion 50 is opened (cut in the width direction X) and an instrument such as a syringe is connected to the needle-less port 40, the opened portion of the needle-less port accommodating portion 50 can be opened widely, making it difficult for the tip of the syringe to come into contact with the sheet-like members 61, 62. Similarly, by setting the length W1 to 25 mm to 250 mm, it is possible to make it difficult for the tip of the syringe to come into contact with the sheet-like members 61, 62 when the needle-less port accommodating portion 50 is opened (cut in the width direction X) and an instrument such as a syringe is connected to the needle-less port 40.

[0022] Furthermore, the length L1 in the longitudinal direction Y perpendicular to the width direction X from the tip of the main body portion 42 of the needle-less port 40 in the needle-less port accommodating space 51 is set to 5 mm or more. From the viewpoint of maintaining the strength of the cell preservation container 1 and suitably opening the unsealable portion of the needle-less port housing portion 50, it is preferable to use a flexible and elastic EVA resin (ethylene-vinyl acetate copolymer resin) as the sheet-like members 61, 62. Moreover, the thickness of the sheet-like members 61, 62 is preferably 0.2 mm to 0.7 mm, and more preferably 0.35 mm to 0.5 mm.

[0023] In the first embodiment, as shown in FIG. 1, the edge of the needle-less port accommodating space 51 is formed in a curved shape without corners in the vicinity of the needle-less port 40. By forming the edge of the needle-less port accommodating space 51 in a curved shape without corners in the vicinity of the needle-less port 40, when ethylene oxide gas (EOG) is used to sterilize the cell storage container 1, it is possible to suppress concentration of force at one point on the edge of the needle-less port accommodating space 51 in a state in which EOG has permeated into the needle-less port accommodating space 51 and the needle-less port accommodating space 51 has expanded. Here, "the vicinity of the needle-less port 40" refers to an edge (a range 511 shown in FIG. 1 ) extending in the width direction X from a base portion (a boundary portion between the main body portion 42 and the connecting portion 41) of the needle-less port 40 where the needle-less port 40 and the sheet-like members 61, 62 are joined at the edge of the needle-less port accommodating space 51. In the first embodiment, the edge of the needle-less port accommodating space is formed in a curved shape without corners all around.

[0024] Next, a method for manufacturing the cell storage container 1 of the first embodiment will be described with reference to FIGS. 4A to 4E.

[0025] 4A, a recess corresponding to the shape of the cell storage section 10, a cell introduction groove 211, and a recessed groove 31 corresponding to the shape of the cell withdrawal section 30 are formed by three-dimensional molding in sheet-like members 61 and 62. In the first embodiment, the sheet-like members 61 and 62 are each formed with a three-dimensional shape of the same shape. Next, a tube 32 is placed in the groove 31 of one of the sheet-shaped members (sheet-shaped member 62), and then the other sheet-shaped member (sheet-shaped member 61) is superimposed so that the positions of the cell storage section 10, the cell introduction groove 211, and the cell withdrawal section 30 are aligned.

[0026] Next, as shown in Fig. 4B, the overlapped sheet-like members 61, 62 and the tube 32 disposed between the sheet-like members 61, 62 are sandwiched and welded by tube welding dies 110, 110 at and near the cell extraction section 30. This causes the sheet-like members 61, 62 and the tube 32 disposed between the sheet-like members 61, 62 to be welded at and near the cell extraction section 30 (see Fig. 4C).

[0027] 4C, the connection part 41 of the needle-less port 40 is inserted into the tube 32. Furthermore, the cell introduction tube 22 is placed in the portion of the sheet-shaped members 61, 62 where the cell introduction groove 211 is formed.

[0028] Next, as shown in FIG. 4D, the other sheet-shaped member (sheet-shaped member 61) is laid over it so that the positions of the cell storage section 10, cell introduction groove 211, and cell withdrawal section 30 coincide, and the cell introduction tube 22 is welded to the sheet-shaped member.

[0029] 4E, the two sheet-like members 61, 62 are joined by high-frequency welding (thermal welding) outside the cell-accommodating section 10 and outside the portion forming the needle-less port accommodation space 51. At this time, a region R where high-frequency welding (thermal welding) is not performed may be provided in a part of the portion outside the cell-accommodating section 10.

[0030] This produces a cell storage container 1 having a cell accommodating section 10 and a needle-less port accommodating section 50. Here, in the first embodiment, the portion of the sheet-like members 61, 62 corresponding to the needle-less port accommodating section 50 is not three-dimensionally molded, but the sheet-like members 61 and 62 are joined together with the needle-less port 40 having a predetermined diameter (thickness) sandwiched therebetween, so that a needle-less port accommodating space 51 having a predetermined thickness is formed between the sheet-like members 61 and 62.

[0031] The cell storage container 1 is then subjected to an EOG sterilization process. In the EOG sterilization process, while the cell storage container 1 is placed inside a sterilizer, EOG is introduced into the sterilizer at a predetermined pressure to sterilize the outer surface of the cell storage container 1, and the EOG is also allowed to penetrate into the cell accommodating space 11 and the needle-less port accommodating space 51, thereby sterilizing the inside of the cell accommodating section 10 and the inside of the needle-less port accommodating section 50.

[0032] In the first embodiment, by forming the edge of the needle-less port accommodating space 51 in a curved shape without corners near the needle-less port 40, it is possible to suppress concentration of force at one point on the edge of the needle-less port accommodating space 51 in a state in which EOG has permeated into the needle-less port accommodating space 51 and the needle-less port accommodating space 51 has expanded during the EOG sterilization process. This makes it possible to prevent the needle-less port accommodating portion 50 from being damaged during the EOG sterilization process.

[0033] Next, a method of using the cell preservation container 1 of the first embodiment will be described with reference to FIGS.

[0034] When storing cells in the cell preservation container 1, a specific cell C collected from a biological sample storage container is introduced into the cell storage section 10 via a cell introduction tube 22 by an instrument 100 such as a syringe, as shown in Fig. 5. After the cells are stored in the cell storage section 10, the flow path of the cell introduction tube 22 is closed by a tube clip 23, as shown in Fig. 6. Next, as shown in Fig. 7, the cell introduction tube 22 is fused on the cell storage section 10 side of the tube clip 23, thereby sealing the cell preservation container 1. The cell preservation container 1 is stored in this state.

[0035] When the cells contained in the preserved cell storage container 1 are to be used, the end side in the longitudinal direction Y of the needle-less port accommodating section 50 is cut in the width direction X with scissors or the like, as shown in Fig. 8. Then, as shown in Fig. 9 and Fig. 10, due to the elasticity of the flexible sheet-like members 61, 62, the cut portion of the needle-less port accommodating section 50 opens widely in the thickness direction of the sheet-like members 61, 62. In this state, the tip (cylinder tip) of a syringe (not shown) is inserted into the needle-less port 40, and the cells contained in the cell accommodating section 10 are collected.

[0036] The cell preservation container 1 of the first embodiment described above provides the following advantages.

[0037] (1) The cell storage container 1 is configured to include a cell storage section 10 formed of two sheet-like members 61, 62, a needle-less port 40, and a needle-less port storage section 50 having a needle-less port storage space 51 formed by the two sheet-like members 61, 62 extending toward the cell extraction section 30 and bonding the peripheral portions of the two extended sheet-like members 61, 62 to surround the needle-less port 40. As a result, the needle-less port 40 can be kept sealed by the needle-less port accommodating section 50, so that the sterility of the needle-less port 40 can be maintained until immediately before the cells are collected. In addition, since the cells can be collected without using a puncture needle or the like, the cells can be taken out without being damaged. In addition, when the needle-less port accommodating section 50 is opened (cut in the width direction X), the opened portion of the needle-less port accommodating section 50 can be opened widely in the thickness direction of the sheet-like members 61, 62. Therefore, when an instrument such as a syringe is connected to the needle-less port 40, the tip of the syringe is unlikely to come into contact with the sheet-like members 61, 62, so that the cells can be taken out with an instrument having a larger inner diameter while favorably maintaining sterility when taking out the accommodated cells.

[0038] (2) The length W1 in the width direction X of the needle-less port accommodating space 51 is set to 120% to 1200%, preferably 300% to 600%, of the radial length W2 of the main body 42 of the needle-less port 40. This makes it possible to more suitably open the opened portion of the needle-less port accommodating portion 50 widely in the thickness direction of the sheet-like members 61, 62 when the needle-less port accommodating portion 50 is opened (cut in the width direction X).

[0039] (3) The needle-less port 40 is configured to include a cylindrical connecting portion 41 and a main body portion 42 formed with a diameter larger than that of the connecting portion 41, with the connecting portion 41 disposed in the cell withdrawal portion 30 and the main body portion 42 disposed in the needle-less port accommodation space 51. This allows the sheet-like members 61 and 62 to be joined in a state in which the needle-less port 40 having a predetermined diameter (thickness) is sandwiched between them, so that the needle-less port accommodation space 51 having a predetermined thickness can be formed without three-dimensionally forming the sheet-like members 61 and 62.

[0040] (4) The edge of the needle-less port accommodating space 51 is formed in a curved shape without corners near the needle-less port 40. This makes it possible to suppress concentration of force at one point on the edge of the needle-less port accommodating space 51 when EOG permeates into the needle-less port accommodating space 51 and the needle-less port accommodating space 51 expands during the EOG sterilization process. This makes it possible to prevent the needle-less port accommodating portion 50 from being damaged during the EOG sterilization process.

[0041] (5) The cell preservation container 1 is configured to include a needle-less port 40. This allows an infusion line to be easily connected directly to the needle-less port 40, making it possible to inject stem cells directly from the cell preservation container 1 into the patient's body. Conventionally, stem cells contained inside the cell preservation container were transferred to a syringe and then injected into the patient, but this eliminates the need for a syringe, making it possible to carry out more aseptic procedures.

[0042] Next, a cell storage container 1A of a second embodiment will be described with reference to Fig. 11. The cell storage container 1A of the second embodiment differs from the first embodiment in the shape of the needle-less port receiving portion 50A. In describing the second embodiment, the same components are denoted by the same reference numerals, and the description thereof will be omitted or simplified. In the cell storage container 1A of the second embodiment, the needle-less port accommodating section 50A is formed in an elliptical shape that is substantially the same as the cell accommodating section 10 in a plan view. In the second embodiment, the length W1 in the width direction X of the needle-less port accommodating space 51A is set to 120% of the radial length W2 of the needle-less port 40. Here, the length W1 in the width direction X of the needle-less port accommodating space 51A indicates the length at the position where the length in the width direction X is the longest in the elliptical needle-less port accommodating section 50A. In the second embodiment, the tip of the needle-less port 40 is located at the same position in the longitudinal direction Y as the position where the length in the width direction X of the elliptical needle-less port accommodating section 50A is the longest.

[0043] The cell preservation container 1A of the second embodiment described above provides the same effects as the first embodiment.

[0044] Although each of the preferred embodiments of the cell preservation container of the present invention has been described above, the present invention is not limited to the above-mentioned embodiments and can be modified as appropriate. For example, in the first and second embodiments, the needle-less port accommodating sections 50, 50A are configured without forming a three-dimensional shape on the sheet-shaped members 61, 62, but this is not limited thereto. That is, the needle-less port accommodating sections 50, 50A may be configured by forming a three-dimensional shape on the sheet-shaped members 61, 62 in the same manner as the cell accommodating section.

[0045] In the first embodiment, the cell preservation container 1 is subjected to EOG sterilization, but this is not limiting. That is, the cell preservation container may be subjected to radiation sterilization using gamma rays, electron beams, or the like. [Explanation of symbols]

[0046] 1, 1A cell storage container 10 Cell storage section 20 Cell introduction section 30 Cell extraction section 40 Needleless Sport 41 Connection 42 Main body 50, 50A Needleless port housing 51, 51A Needleless port housing space

Claims

1. a cell storage section formed by joining the peripheral portions of two sheet-shaped members; A cell introduction part for introducing cells into the cell storage part; a cell discharge section for discharging the cells accommodated in the cell accommodation section; a needleless port disposed in the cell outlet portion; a needle-less port accommodating section having a needle-less port accommodating space formed by the two sheet-like members constituting the cell accommodation section extending toward the cell extraction section and bonding the peripheral portions of the two extended sheet-like members so as to surround the needle-less port, A cell storage container in which the length of the needle-less port accommodating space along the surface direction of the sheet-like member and along the radial direction of the needle-less port is 120% to 1200% of the radial length of the needle-less port.

2. The cell storage container of claim 1, wherein the needleless port comprises a cylindrical connection portion that is arranged in the cell extraction portion, and a main body portion that is formed with a larger diameter than the connection portion and is arranged in the needleless port accommodating space.

3. 3. The cell storage container according to claim 1, wherein an edge of the needle-less port accommodating space is formed in a curved shape without corners in the vicinity of the needle-less port.

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