Liquid storage bag, container with liquid, centrifugation method, and method for producing cell preparation

Abstract

To provide a liquid storage bag for storing a liquid containing cells, with suppressed damage to the cells.SOLUTION: A liquid storage bag 10 includes a container body 20 having a storage space S, an introduction section 50, and a discharge section 60. The storage space S includes an accumulation section 25. The introduction section has a first tubular section 51 attached to the container body, and the discharge section 60 has a second tubular section 61 attached to the container body. A central axis X1 of the first tubular section extends along a first direction D1. A central axis X2 of the second tubular section extends along a direction different from the first direction D1. An angle α between a first line segment LS1 on the central axis X1 and a second line segment LS2 on the central axis X2 is 90° or less. An inner wall point 25a of the accumulation section 25 of the storage space S is located farthest from the first tubular section in the first direction D1, and is located at a position that does not overlap with the central axis X2 of the second tubular section when viewed from a direction in which the central axis X2 of the second tubular section extends.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] The present disclosure relates to a liquid-containing bag, a liquid-containing container, a centrifugation method, and a method for producing a cell preparation. [Background technology]

[0002] Conventionally, containers for concentrating cells from a liquid containing cells have been known (for example, Patent Documents 1 and 2). Patent Document 1 discloses a cell concentration container that has a discharge portion at one end of a flexible container body, and that stores a cell suspension containing target cells in a sealed state and is centrifuged to cause the target cells to settle at the one end, producing a cell concentrate. The cell concentration container described in Patent Document 1 has the advantage of being able to concentrate cells while maintaining a closed system with a simple structure, and also being able to easily and efficiently extract the cell concentrate.

[0003] Furthermore, Patent Document 2 discloses a centrifugal separation vessel that contains a liquid to be separated, has a vessel body that can be rotated with its bottom facing radially outward, and has an outlet near the bottom of the vessel body that penetrates the vessel wall and allows the substances inside to be removed.The centrifugal separation vessel described in Patent Document 2 makes it possible to easily and reliably remove the substances that have been centrifuged from the liquid, and in this process, it is possible to avoid contamination of the substances and maintain the integrity of the substances. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2020-162447 [Patent Document 2] Japanese Patent Application Laid-Open No. 2009-189280 Summary of the Invention [Problem to be solved by the invention]

[0005] Such containers are required to minimize damage to cells while allowing for easy and efficient removal of cell concentrate.Furthermore, such containers are required to minimize the load on the discharge section that removes cells from the container when concentrating cells by centrifugation.

[0006] The present disclosure has been made taking these points into consideration, and aims to provide a liquid storage bag, a liquid-filled container, a centrifugation method, and a method for producing a cell preparation that can reduce damage to cells and reduce the load on the discharge section. [Means for solving the problem]

[0007] The embodiments of the present disclosure relate to the following [1] to

[12] .

[0008] [1] A liquid containing bag for containing a liquid containing cells, a container body having a storage space for storing the liquid; an introduction portion that introduces the liquid into the container body; a discharge part that discharges the liquid from the container body, The storage space includes an accumulation portion, the introduction section has a first cylindrical section attached to the container body, the discharge portion has a second cylindrical portion attached to the container body, The central axis of the first cylindrical portion extends along a first direction, a central axis of the second cylindrical portion extends along a direction different from the first direction, a first line segment is a line segment on the central axis of the first cylindrical portion that extends from the first cylindrical portion to an intersection point between the central axis of the first cylindrical portion and the central axis of the second cylindrical portion, and a second line segment is a line segment on the central axis of the second cylindrical portion that extends from the second cylindrical portion to the intersection point, the angle between the first line segment and the second line segment is 90° or less, A liquid storage bag, wherein the accumulation portion of the storage space includes an inner wall point that is part of the inner wall that constitutes the storage space, and the inner wall point is located farthest from the first tubular portion in the first direction and is located at a position that does not overlap with the central axis of the second tubular portion when viewed from the direction in which the central axis of the second tubular portion extends.

[0009] [2] The storage space is surrounded by a seal portion, The seal portion has an inclined seal portion whose inner edge is inclined with respect to the first direction, an inner edge of the inclined seal portion extends such that a length of the storage space in a second direction perpendicular to the first direction in a front view decreases from the first cylindrical portion side toward the accumulation portion side; The liquid containing bag according to [1], wherein the positive and negative inclinations of the inner edges of the inclined seal portions do not change from the first tubular portion side to the collecting portion side.

[0010] [3] The liquid containing bag according to [2], wherein the width of the sealed portion is constant.

[0011] [4] The liquid storage bag according to [1] or [2], wherein the storage space includes a first storage space located on the first tubular portion side and a second storage space located on the second tubular portion side, the accumulation portion is provided in the second storage space, and the discharge portion discharges the liquid in the second storage space.

[0012] [5] The liquid containing bag according to any one of [1], [2] and [4], wherein the capacity of the first containing space is larger than the capacity of the second containing space.

[0013] [6] The storage space is surrounded by a seal portion, A liquid storage bag according to any one of [1], [2], [4] and [5], wherein the length of the sealing portion located around the accumulation portion along the first direction gradually increases as the sealing portion moves away from the accumulation portion in a second direction perpendicular to the first direction in a front view.

[0014] [7] The storage space is surrounded by a seal portion, the sealing portion includes a first sealing portion and a second sealing portion that constitute the collecting portion, a third sealing portion connected to the first sealing portion, and a fourth sealing portion connected to the second sealing portion; an inner edge of the first seal portion and an inner edge of the second seal portion are inclined with respect to the first direction so that a length of the storage space in a second direction perpendicular to the first direction in a front view becomes shorter from the first cylindrical portion side toward the accumulation portion side; an inner edge of the third seal portion extends along the first direction or is inclined with respect to the first direction such that an inclination angle with respect to the first direction is smaller than an inclination angle of the inner edge of the first seal portion with respect to the first direction; The liquid containing bag according to any one of [1] to [6], wherein an inner edge of the fourth seal portion extends along the first direction.

[0015] [8] The liquid containing bag according to [7], wherein the width of the sealed portion is constant.

[0016] [9] The liquid containing bag according to any one of [1] to [8], wherein the second cylindrical portion is heat-sealed to the container body.

[0017]

[10] [1] to [9], and a liquid containing bag according to any one of [1] to [9]. a liquid contained in the liquid containing bag, A liquid-filled container in which the inlet and outlet are sealed.

[0018]

[11]

[10] A step of preparing a liquid-filled container according to the present invention; and rotating the liquid-containing container around a rotation axis perpendicular to the first direction.

[0019]

[12]

[11] A step of collecting the cells in the liquid by the centrifugation method described in

[11] ; a step of separating the storage space of the container body into a first storage space and a second storage space in which the cells are accumulated; Discharging the liquid other than the cells in the second storage space; and introducing an administration liquid into the second storage space. [Effects of the Invention]

[0020] According to the present disclosure, damage to cells can be suppressed, and the load on the discharge part can be suppressed. [Brief explanation of the drawings]

[0021] [Figure 1A] FIG. 1A is a front view showing a liquid containing bag according to one embodiment. [Figure 1B] FIG. 1B is an enlarged front view showing a second seal portion of a liquid containing bag as a comparative example. [Figure 2] FIG. 2 is a front view showing another example of the liquid containing bag according to the embodiment. [Figure 3A] FIG. 3A is a front view showing a discharge portion of a liquid containing bag according to one embodiment. [Figure 3B] FIG. 3B is a side view showing the discharge portion of the liquid containing bag according to one embodiment. [Figure 3C] FIG. 3C is a cross-sectional view (a cross-sectional view taken along line IIIC-IIIC in FIG. 3B) showing the discharge portion of the liquid containing bag according to one embodiment. [Figure 4A] FIG. 4A is a perspective view showing another example of the discharge portion of the liquid containing bag according to the embodiment. [Figure 4B]FIG. 4B is a cross-sectional view (cross-sectional view taken along line IVB-IVB in FIG. 1A) showing another example of the discharge portion of the liquid containing bag according to one embodiment. [Figure 5] FIG. 5 is a front view showing a liquid-filled container according to one embodiment. [Figure 6] FIG. 6 is a flow chart illustrating a centrifugation method according to one embodiment. [Figure 7] 7(a)-(d) are diagrams showing a centrifugation method and a method for producing a cell preparation according to one embodiment. [Figure 8] FIG. 8 is a flowchart showing a method for producing a cell preparation according to one embodiment. [Figure 9] FIG. 9 is a front view showing a liquid containing bag according to a first modified example. [Figure 10] FIG. 10 is a front view showing a liquid containing bag according to a second modified example. [Figure 11] FIG. 11 is a front view showing a liquid containing bag according to a third modified example. DETAILED DESCRIPTION OF THE INVENTION

[0022] The present embodiment will be described below with reference to the drawings. FIGS. 1A to 8 are diagrams illustrating the present embodiment. The following figures are schematic diagrams. Therefore, the size and shape of each part are appropriately exaggerated for ease of understanding. Furthermore, appropriate modifications can be made within the scope of the technical concept. In the following figures, identical parts are denoted by the same reference numerals, and some detailed descriptions may be omitted. Furthermore, the numerical values, such as dimensions, and material names of each member described in this specification are examples of embodiments, and are not limited to these and can be selected and used as appropriate. In this specification, terms specifying shapes or geometric conditions, such as parallel, orthogonal, and perpendicular, are interpreted not only to mean their strict meanings but also to include substantially the same state.

[0023] [Liquid Containment Bag] First, the configuration of a liquid containing bag according to this embodiment will be described with reference to Figures 1A to 4B. This liquid containing bag 10 is a container for containing a liquid containing cells.

[0024] As shown in FIG. 1A, the liquid storage bag 10 includes a container body 20 having a storage space S for storing liquid, an introduction section 50 for introducing liquid into the container body 20, and a discharge section 60 for discharging liquid from the container body 20.

[0025] Of these, the container body 20 has a front surface 21 and a back surface 22 that are arranged to face each other. The container body 20 is a flat pouch-type bag formed by a film 21A that forms the front surface 21 and a film 22A that forms the back surface 22.

[0026] The container body 20 has a first edge 31 to an eighth edge 38 that form the outer contour of the container body 20 in a front view. The first edge 31 to the eighth edge 38 are arranged in the following order, starting from the first edge 31 and going clockwise in a front view: the second edge 32, the fourth edge 34, the eighth edge 38, the seventh edge 37, the sixth edge 36, the fifth edge 35, and the third edge 33.

[0027] In this embodiment, the first edge 31 and the second edge 32 extend in a direction inclined in the first direction D1 and the second direction D2. The first edge 31 and the second edge 32 extend toward one side of the first direction D1 (the lower side in FIG. 1A), and the first edge 31 and the second edge 32 are connected to each other at the end on one side of the first direction D1. The second direction D2 is perpendicular to the first direction D1 in a front view.

[0028] The third edge 33 is connected to the first edge 31 and extends in a direction inclined in the first direction D1 and the second direction D2. The third edge 33 extends between the first edge 31 and the fifth edge 35. The third edge 33 may also extend in the first direction D1.

[0029] The fourth edge 34 is connected to the second edge 32 and extends along the first direction D1. The fourth edge 34 extends between the second edge 32 and the eighth edge 38.

[0030] The fifth edge 35 is connected to the third edge 33 and extends in a direction inclined toward the first direction D1 and the second direction D2. The fifth edge 35 also extends parallel to the second edge 32. The fifth edge 35 extends between the third edge 33 and the sixth edge 36.

[0031] The sixth edge 36 is connected to the fifth edge 35 and extends in a direction inclined in the first direction D1 and the second direction D2. The sixth edge 36 may be symmetrical to the third edge 33 with respect to the central axis X2 of a second cylindrical portion 61 (described later) of the discharge portion 60. The sixth edge 36 extends between the fifth edge 35 and the seventh edge 37.

[0032] The seventh edge 37 is connected to the sixth edge 36 and extends along the first direction D1. The seventh edge 37 extends between the sixth edge 36 and the eighth edge 38.

[0033] The eighth edge 38 extends along the second direction D2. The eighth edge 38 extends between the fourth edge 34 and the seventh edge 37.

[0034] The storage space S of the container body 20 is surrounded by a sealed portion 40. The sealed portion 40 is a portion where the film 21A constituting the front surface 21 and the film 22A constituting the back surface 22 are welded together. In this embodiment, the width of the sealed portion 40 is substantially constant (constant) around the entire circumference. In addition, in this embodiment, the sealed portion 40 has a first sealed portion 41 to an eighth sealed portion 48. In this case, the first sealed portion 41 to the eighth sealed portion 48 are provided along the first edge 31 to the eighth edge 38 as the sealed portion 40. Therefore, the first sealed portion 41 to the eighth sealed portion 48 are arranged starting from the first sealed portion 41 in the following order in a clockwise direction when viewed from the front: the second sealed portion 42, the fourth sealed portion 44, the eighth sealed portion 48, the seventh sealed portion 47, the sixth sealed portion 46, the fifth sealed portion 45, and the third sealed portion 43. The width of the seal portion 40 described above refers to the length in a direction perpendicular to the direction in which the inner edge of the seal portion 40 extends. For example, in the first seal portion 41, the width of the seal portion 40 is the length in a direction perpendicular to the direction in which the inner edge of the first seal portion 41 extends.

[0035] In this embodiment, the first seal portion 41 and the second seal portion 42 extend in a direction inclined in the first direction D1 and the second direction D2. The first seal portion 41 and the second seal portion 42 extend toward each other toward one side of the first direction D1 (the lower side in FIG. 1A), and the first seal portion 41 and the second seal portion 42 are connected to each other at their ends on the one side of the first direction D1. In this case, the inner edges of the first seal portion 41 and the second seal portion 42 are inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 decreases from the first tubular portion 51 toward the accumulating portion 25 (the lower side in FIG. 1A), which will be described later.

[0036] The third seal portion 43 is connected to the first seal portion 41 and extends in a direction inclined in the first direction D1 and the second direction D2. The third seal portion 43 extends between the first seal portion 41 and the fifth seal portion 45. Alternatively, the third seal portion 43 may extend in the first direction D1. The inner edge of the third seal portion 43 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 decreases from the first tubular portion 51 side toward the later-described accumulating portion 25 side (the lower side in FIG. 1A ). The inner edge of the third seal portion 43 is inclined with respect to the first direction D1 so that the inclination angle θ3 with respect to the first direction D1 is smaller than the inclination angle θ1 of the inner edge of the first seal portion 41 with respect to the first direction D1. Alternatively, the inner edge of the third seal portion 43 may extend in the first direction D1. By providing the seal portion 40 with the third seal portion 43, when liquid is discharged from the discharge portion 60, the liquid can be more easily collected in the second tubular portion 61 of the discharge portion 60, which will be described later.

[0037] The fourth seal portion 44 is connected to the second seal portion 42 and extends along the first direction D1. The fourth seal portion 44 extends between the second seal portion 42 and the eighth seal portion 48. The inner edge of the fourth seal portion 44 extends along the first direction D1.

[0038] The fifth seal portion 45 is connected to the third seal portion 43 and extends in a direction inclined in the first direction D1 and the second direction D2. The fifth seal portion 45 also extends parallel to the second seal portion 42. The fifth seal portion 45 extends between the third seal portion 43 and the sixth seal portion 46. The inner edge of the fifth seal portion 45 extends parallel to the inner edge of the second seal portion 42.

[0039] The sixth seal portion 46 is connected to the fifth seal portion 45 and extends in a direction inclined in the first direction D1 and the second direction D2. The sixth seal portion 46 may be line-symmetric with the third seal portion 43 about the central axis X2 of a second cylindrical portion 61 (described later) of the discharge portion 60. The sixth seal portion 46 extends between the fifth seal portion 45 and the seventh seal portion 47. The inner edge of the sixth seal portion 46 is line-symmetric with the inner edge of the third seal portion 43 about the central axis X2 (described later). By including the sixth seal portion 46 in the seal portion 40, liquid can be more easily collected in the second cylindrical portion 61 (described later) of the discharge portion 60 when it is discharged from the discharge portion 60.

[0040] The seventh seal portion 47 is connected to the sixth seal portion 46 and extends along the first direction D1. The seventh seal portion 47 extends between the sixth seal portion 46 and the eighth seal portion 48. The inner edge of the seventh seal portion 47 extends along the first direction D1.

[0041] The eighth seal portion 48 extends along the second direction D2. The eighth seal portion 48 extends between the fourth seal portion 44 and the seventh seal portion 47. The inner edge of the eighth seal portion 48 extends along the second direction D2.

[0042] The seal portion 40 also has an inclined seal portion 49 whose inner edge is inclined with respect to the first direction D1. The inner edge of this inclined seal portion 49 extends such that the length of the storage space S in the second direction D2 decreases as it moves from the first tubular portion 51 side toward the later-described accumulating portion 25 side (the lower side in FIG. 1A). In this embodiment, the first seal portion 41 and the second seal portion 42 are the inclined seal portion 49.

[0043] In this embodiment, the positive and negative slopes of the inner edge of the inclined seal portion 49 do not change from the first cylindrical portion 51 side toward the later-described accumulation portion 25 side (the lower side in FIG. 1A). This prevents cells from being trapped at the inner edge of the inclined seal portion 49. Here, in this specification, the positive and negative slopes of the inner edge refer to the positive and negative slopes in an XY coordinate system formed by the X axis extending along the second direction D2 and the Y axis extending along the first direction D1 in a front view. In the example shown in FIG. 1A, the slope of the inner edge of the first seal portion 41, which is the inclined seal portion 49, is positive. On the other hand, the slope of the inner edge of the second seal portion 42, which is the inclined seal portion 49, is negative.

[0044] Here, as shown in FIG. 1B, for example, when the inclination of the inner edge of the second seal portion 42, which is the inclined seal portion 49, changes from positive to negative, a recess 49a in which cells are trapped is formed at the inner edge of the second seal portion 42. In contrast, by not changing the positive or negative of the inclination of the inner edge of the inclined seal portion 49, the formation of a recess 49a in which cells are trapped can be prevented. Therefore, cells can be prevented from being trapped at the inner edge of the inclined seal portion 49. The inner edge of the inclined seal portion 49 may include a portion where the inclination is 0. In other words, the inner edge of the inclined seal portion 49 may include a portion extending parallel to the second direction D2. It is preferable that the length along the second direction D2 of the portion where the inclination is 0 is 10 mm or less. This allows the amount of cells (e.g., 1×10) used in the cell pharmaceutical to be reduced. 6 This effectively prevents the trapping of cell-enriched products (cells or more).

[0045] The storage space S also includes an accumulation section 25. This accumulation section 25 accumulates concentrated products such as cells in the liquid by centrifugation. Therefore, the accumulation section 25 is also a section that is heavily loaded by centrifugal force during centrifugation. In this embodiment, the accumulation section 25 is composed of a first sealed section 41 and a second sealed section 42. In this case, the accumulation section 25 is formed in a region near the intersection of the first sealed section 41 and the second sealed section 42. Here, as described above, the sealed section 40 is a section where the films 21A and 22A are welded to each other. Therefore, in the region near the intersection of the first sealed section 41 and the second sealed section 42, the distance between the films 21A and 22A is narrow in the direction perpendicular to the first direction D1 and the second direction D2. In this case, even in the liquid-filled container 10A described below, in the region near the intersection of the first sealed portion 41 and the second sealed portion 42, the distance between the films 21A and 22A becomes narrower in the direction perpendicular to the first direction D1 and the second direction D2. Therefore, by forming the accumulation portion 25 in the region near the intersection of the first sealed portion 41 and the second sealed portion 42, the concentrated product can be easily accumulated in the accumulation portion 25. Furthermore, when the accumulation portion 25 is formed by the sealed portion 40, the accumulation portion 25 can be formed in a desired shape and at a desired position based on the shape of the sealed portion 40, etc. This makes it easy to manufacture a container body 20 in which the storage space S includes the accumulation portion 25. In this embodiment, the accumulation portion 25 refers to a range of the storage space S within 10 mm of an inner wall point 25a described below as the center.

[0046] As described above, the first seal portion 41 and the second seal portion 42 extend toward one side in the first direction D1 (the lower side in FIG. 1A ), and the first seal portion 41 and the second seal portion 42 are connected to one end of the first direction D1. Therefore, the accumulation portion 25 has a V-shape when viewed from the front. This makes it easier for the concentrated product to accumulate at one point (the corner of the V) in the accumulation portion 25, making it easier to visually check the concentrated product. In this case, the curvature radius of the V-shaped corner may be, for example, 5 μm or more, preferably 10 μm or more, more preferably 100 μm or more, even more preferably 200 μm or more, and even more preferably 1 mm or more. The curvature radius of the V-shaped corner is preferably equal to or greater than the size of a cell (e.g., a diameter of approximately 10 μm). The curvature radius of the V-shaped corner is, for example, preferably 20 mm or less, more preferably 10 mm or less. By setting the radius of curvature to 20 mm or less, cells can be accumulated in a narrow area. This makes it easier to visually check the concentrated product. Furthermore, by setting the radius of curvature to 10 mm or less, cells can be accumulated in an even narrower area, making it even easier to visually check the concentrated product. Although not shown, the accumulation section 25 may have other shapes, such as a U-shape when viewed from the front.

[0047] The accumulation portion 25 of the storage space S includes an inner wall point 25a that is a part of the inner wall that constitutes the storage space S. Furthermore, the inner wall point 25a is located farthest from the first cylindrical portion 51 in the first direction D1. As a result, the inner wall point 25a of the accumulation portion 25 is the part in the storage space S that receives the greatest load due to centrifugal force during centrifugation. Furthermore, the inner wall point 25a of the accumulation portion 25 of the storage space S is located at a position that does not overlap with the central axis X2 of the second cylindrical portion 61, which will be described later, when viewed from the direction in which the central axis X2 of the second cylindrical portion 61 of the discharge portion 60 extends.

[0048] Furthermore, the storage space S includes a first storage space S1 located on the first tubular portion 51 side and a second storage space S2 located on the second tubular portion 61 side. The above-mentioned accumulation portion 25 is provided in the second storage space S2, and the discharge portion 60 is configured to discharge liquid from the second storage space S2. In this embodiment, the boundary between the first storage space S1 and the second storage space S2 is formed by a straight line X3 that is perpendicular to the second seal portion 42 and passes through the intersection of the inner edge of the sixth seal portion 46 and the inner edge of the seventh seal portion 47. In this case, as described below, the storage space S can be separated into the first storage space S1 and the second storage space S2 by clamping the container body 20 along the straight line X3 with, for example, a clip or the like. The second housing space S2 is surrounded by the inner edge of the sixth seal portion 46, the inner edge of the fifth seal portion 45, the inner edge of the third seal portion 43, the inner edge of the first seal portion 41, part of the inner edge of the second seal portion 42, and the straight line X3. In other words, the outer edge of the second housing space S2 is defined by the inner edge of the sixth seal portion 46, etc. In this way, by the inner edge of the sixth seal portion 46 defining part of the outer edge of the second housing space S2, when liquid is discharged from the discharge portion 60, it is possible to make it easier for the liquid to collect in the second tubular portion 61 of the discharge portion 60, which will be described later. This makes it easier for the liquid to be discharged from the discharge portion 60.

[0049] The capacity of the first storage space S1 may be larger than the capacity of the second storage space S2. This allows for a higher cell concentration rate when concentrating cells in a liquid. The capacity of the first storage space S1 may be at least twice, preferably at least three times, and more preferably at least four times, the capacity of the second storage space S2. By making the capacity of the first storage space S1 at least twice the capacity of the second storage space S2, the cell concentration rate of the cells stored in the second storage space S2 can be increased by three times or more. Furthermore, by making the capacity of the first storage space S1 at least three times the capacity of the second storage space S2, the cell concentration rate of the cells stored in the second storage space S2 can be increased by four times or more. Furthermore, by making the capacity of the first storage space S1 at least four times the capacity of the second storage space S2, the cell concentration rate of the cells stored in the second storage space S2 can be increased by five times or more. Increasing the cell concentration in a cell suspension may increase the cell viability due to the paracrine effect, etc. Therefore, by increasing the concentration rate of the cells accommodated in the second accommodation space S2, the survival rate of the cells can be increased. Here, the concentration rate can be expressed by the following formula (1). Concentration rate = (cell concentration in the second storage space S2 after centrifugation) ÷ (cell concentration in the entire storage space S before centrifugation) Equation (1) The "cell concentration in the second storage space S2 after centrifugation" refers to the cell concentration in the second storage space S2 separated from the first storage space S1 by clamping the container body 20 along the line X3, for example, with a clip or the like. The capacity of the first storage space S1 may be less than twice the capacity of the second storage space S2, and the capacity of the second storage space S2 can be designed according to the desired volume of concentration. Furthermore, the "cell concentration" refers to the number of cells per unit volume of liquid. The cell concentration is expressed in units of cells / mL, for example.

[0050] As shown in FIG. 2 , a marking portion M may be formed on the container body 20. This marking portion M serves as a mark for positioning a clip, for example, when dividing the storage space S into the first storage space S1 and the second storage space S2 with a clip or the like. For example, the marking portion M may be formed at the intersection of the line X3 and the seal portion 40. Specifically, the marking portion M may be formed at the intersection of the inner edge of the sixth seal portion 46 and the inner edge of the seventh seal portion 47, and at the intersection of the line X3 and the second seal portion 42. By forming the marking portion M on the container body 20 in this manner, the clip can be easily positioned when dividing the storage space S into the first storage space S1 and the second storage space S2 with a clip or the like. This improves work efficiency. The marking portion M may have any shape that is visible. For example, the mark portion M may be formed by changing the pattern or width of a part of the seal portion 40, or may be formed by embossing, cutting, holes, a seal member, or the like.

[0051] The material constituting such a container body 20 may be any thermoplastic resin that can be heat-sealed by heat sealing, etc. For example, suitable materials for the container body 20 include polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer, ethylene-propylene copolymer resin, polybutadiene resin, styrene-butadiene copolymer resin, and hydrogenated resins thereof, polyurethane resin, and mixtures of these resins.

[0052] The characteristics of the container body 20, such as thickness, strength, light transmittance, heat resistance, and gas barrier properties, can be adjusted appropriately depending on the use of the liquid storage bag 10 or the type of liquid stored in the storage space S, so they will not be described here.

[0053] The films 21A and 22A that constitute the container body 20 may have a single-layer structure or a multi-layer structure. When the films 21A and 22A have a multi-layer structure, only the inner surfaces of the films 21A and 22A may be made of the resin material described above, and the other layers may have aluminum layers containing aluminum. Furthermore, the outer surfaces of the films 21A and 22A may be coated with a material such as silica, as necessary. In this case, barrier properties can be imparted to the liquid containing bag 10. Furthermore, when the films 21A and 22A have a multi-layer structure, each layer may be made of the thermoplastic resin described above. For example, the layer that constitutes the inner surface may be polyethylene (PE), and the layer that constitutes the outer surface may be polyethylene terephthalate (PET).

[0054] Although an example in which the container body 20 is made up of films 21A and 22A has been described, the present invention is not limited to this. For example, the container body 20 may be formed by folding a single film to make them face each other, and then welding the portions other than the folded portions. The size of the container body 20 is preferably such that it can fit into a holder of an existing centrifugal separator. More preferably, the size of the container body 20 is such that the container body 20 can be set in the holder of the centrifugal separator without folding the container body 20. For example, if the width (length in the second direction D2) of the container body 20 is equal to or smaller than the inner dimensions of the holder, the container body 20 (liquid-filled container 10A described below) can be easily set in the holder of an existing centrifugal separator.

[0055] Next, the introduction section 50 will be described with reference to FIG. 1A. The introduction section 50 is a section for introducing a liquid into the storage space S of the container body 20. The introduction section 50 is configured separately from the films 21A and 22A that form the front surface 21 and the back surface 22. As shown in FIG. 1A, the introduction section 50 has a first cylindrical section 51 attached to the container body 20. The first cylindrical section 51 is attached to the eighth seal section 48. That is, the first cylindrical section 51 is heat-sealed to the films 21A and 22A at the eighth seal section 48. In this case, the central axis X1 of the first cylindrical section 51 extends along the first direction D1. This prevents cells from being trapped in the first cylindrical section 51 after the liquid is introduced into the storage space S (particularly during centrifugation, which will be described later). Here, if cells are trapped in the first cylindrical section 51, there is a possibility that the trapped cells may remain near the first cylindrical section 51 due to a meniscus phenomenon or the like. In response to this, by preventing cells from being trapped in the first cylindrical portion 51, it is possible to prevent cells from remaining near the first cylindrical portion 51.

[0056] The first cylindrical portion 51 is a tubular member, and may have both longitudinal ends open before the liquid is introduced into the storage space S. The tubular member may be sealed after the liquid is introduced into the storage space S. In this case, the sealing performance of the liquid-filled container 10A, which will be described later, can be improved. The introduction portion 50 may be closed before the liquid is introduced, or may be configured so that both longitudinal ends are open when the liquid is introduced. The first cylindrical portion 51 may have a configuration similar to that of the second cylindrical portion 61 shown in FIGS. 4A and 4B, which will be described later. That is, although not shown, the first cylindrical portion 51 may include an attachment portion (see attachment portion 65 shown in FIGS. 4A and 4B) for facilitating attachment to the container body 20. In this case, a flow path portion (see flow path portion 66 shown in FIG. 4A) disposed within the storage space S of the container body 20 may be provided on one side of the attachment portion. The flow path portion may also have a notch (see notch 67 shown in FIG. 4A). The other side of the mounting portion may be formed with a threaded portion (see threaded portion 68 shown in Figures 4A and 4B) to which a cap (not shown) is attached, and a flange portion (see flange portion 69 shown in Figures 4A and 4B) used when discharging liquid may be provided between the mounting portion and the threaded portion.

[0057] The material constituting the introduction section 50 may be any thermoplastic resin that can be heat-sealed to the films 21A and 22A by heat sealing or the like. For example, polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer, ethylene-propylene copolymer resin, polybutadiene resin, styrene-butadiene copolymer resin, and hydrogenated resins thereof, polyurethane resin, and mixtures of these resins may be suitably used as the material constituting the introduction section 50. The first cylindrical portion 51 of the introduction section 50 and the container body 20 may be made of the same material. This improves adhesion between the container body 20 and the first cylindrical portion 51 and prevents damage to the welded portion between the container body 20 and the first cylindrical portion 51 during centrifugation. The introduction section 50 may be manufactured by, for example, injection molding or the like.

[0058] Next, the discharge portion 60 will be described with reference to Fig. 1A and Figs. 3A to 4B. The discharge portion 60 is a portion for discharging liquid from the storage space S of the container body 20. The discharge portion 60 is configured as a separate body from the films 21A and 22A that form the front and back surfaces 21 and 22. As shown in Fig. 1A, the discharge portion 60 has a second tubular portion 61 attached to the container body 20. The second tubular portion 61 is attached to the fifth seal portion 45. That is, the second tubular portion 61 is heat-sealed to the films 21A and 22A (container body 20) at the fifth seal portion 45. In this case, the central axis X2 of the second tubular portion 61 extends in a direction different from the first direction D1. Specifically, the central axis X2 of the second tubular portion 61 extends in a direction inclined toward the first direction D1 and the second direction D2.

[0059] In this embodiment, the end of the second cylindrical portion 61 on the storage space S side does not face the first cylindrical portion 51 side (upper side in FIG. 1A ). Here, as shown in FIG. 1A , a line segment on the central axis X1 of the first cylindrical portion 51, which extends from the first cylindrical portion 51 to an intersection P between the central axis X1 of the first cylindrical portion 51 and the central axis X2 of the second cylindrical portion 61, is defined as a first line segment LS1. Furthermore, a line segment on the central axis X2 of the second cylindrical portion 61, which extends from the second cylindrical portion 61 to the intersection P, is defined as a second line segment LS2. In this case, the angle α between the first line segment LS1 and the second line segment LS2 is 90° or less. This makes it possible to prevent cells from being trapped in the second cylindrical portion 61 after introducing a liquid into the storage space S (particularly during centrifugation, which will be described later). This makes it possible to prevent cells from remaining near the second cylindrical portion 61. Here, after discharging the liquid from the discharge portion 60, the accumulated cells may be suspended by pipetting. In this case, if cells are trapped in the second cylindrical portion 61, the cells may be damaged when the administration liquid for suspension is discharged onto the cells or when the cells are sucked up. In contrast, damage to the cells can be reduced by preventing the cells from being trapped in the second cylindrical portion 61. The angle α between the first line segment LS1 and the second line segment LS2 may be greater than 0°.

[0060] As described above, the second cylindrical portion 61 is attached to the fifth seal portion 45. That is, the second cylindrical portion 61 is attached at a position different from that of the accumulation portion 25. Specifically, the second cylindrical portion 61 is attached closer to the first cylindrical portion 51 than the accumulation portion 25 in the first direction D1. As described above, the accumulation portion 25 is a portion that accumulates concentrated products such as cells by centrifugation. Therefore, the accumulation portion 25 is also a portion that is subjected to a large load due to centrifugal force during centrifugation. In contrast, by attaching the second cylindrical portion 61 at a position different from that of the accumulation portion 25, it is possible to prevent the second cylindrical portion 61 from being subjected to a large load due to centrifugal force during centrifugation. Therefore, it is possible to prevent damage to the second cylindrical portion 61. Furthermore, by attaching the second cylindrical portion 61 at a position different from that of the accumulation portion 25, it is possible to prevent the administration liquid for suspension from being discharged onto the cells when performing a pipetting operation on the accumulated cells. Furthermore, since the second cylindrical portion 61 is attached at a position different from that of the accumulation portion 25, it is possible to prevent the accumulated cells from being sucked in when performing a pipetting operation on the accumulated cells, thereby reducing damage to the cells.

[0061] The second cylindrical portion 61 may be a tubular member and may be closed in a manner that allows the liquid in the storage space S to be removed. In this case, the second cylindrical portion 61 may be closed, for example, by a screw cap, a member having an insertion surface through which a needle can be pierced, a member that can be opened by screwing, or a connector with a stopper. When the second cylindrical portion 61 is closed by a member having an insertion surface through which a needle can be pierced, the insertion surface is preferably capable of accepting an 18-gauge injection needle or a bottle needle. When the insertion surface is capable of accepting a bottle needle, as shown in FIGS. 3A to 3C , the second cylindrical portion 61 may include a main body portion 62 attached to the container body 20 and a protrusion 63 disposed within the storage space S of the container body 20. Furthermore, as shown in FIG. 3C , the main body portion 62 may be provided with an insertion surface 64 through which a bottle needle is inserted.

[0062] 4A and 4B, the second cylindrical portion 61 may include an attachment portion 65 for facilitating attachment to the container body 20. In this case, a flow path portion 66 to be disposed within the storage space S of the container body 20 may be provided on one side of the attachment portion 65. A notch 67 may be formed in this flow path portion 66. A threaded portion 68 to which a cap (not shown) is attached may be formed on the other side of the attachment portion 65, and a flange portion 69 to be used when discharging liquid may be provided between the attachment portion 65 and the threaded portion 68.

[0063] The material constituting the discharge portion 60 may be any thermoplastic resin that can be heat-sealed to the films 21A and 22A by heat sealing or the like. For example, suitable materials for the discharge portion 60 include polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer, ethylene-propylene copolymer resin, polybutadiene resin, styrene-butadiene copolymer resin, and hydrogenated resins thereof, polyurethane resin, and mixtures of these resins. The second tubular portion 61 of the discharge portion 60 and the container body 20 may be made of the same material. This improves adhesion between the container body 20 and the second tubular portion 61 and prevents damage to the welded portion between the container body 20 and the second tubular portion 61 during centrifugation. In the case of the discharge portion 60 shown in FIGS. 3A to 3C , the main body portion 62, the protruding portion 63, and the insertion surface 64 are preferably made of the same material, and more preferably, are molded integrally. This prevents damage to the insertion surface 64 during centrifugation. 4A and 4B, the attachment portion 65, the flow path portion 66, the threaded portion 68, and the flange portion 69 are preferably made of the same material, and more preferably molded integrally. The discharge portion 60 can be produced by, for example, injection molding.

[0064] The liquid contained in the liquid containing bag 10 according to the present embodiment is not particularly limited, and may be, for example, a medicinal liquid such as a pharmaceutical product. Specific examples of such medicinal liquids include biological cells such as bone marrow cells and lymphocytes. Furthermore, the medicinal liquid may be, for example, a cell preparation, and specific examples include hepatoma cells, hepatocytes (liver parenchymal cells), Kupffer cells, endothelial cells such as vascular endothelial cells and corneal endothelial cells, fibroblasts, osteoblasts, osteoclasts, periodontal ligament-derived cells, epidermal cells such as epidermal keratinocytes, epithelial cells such as tracheal epithelial cells, digestive tract epithelial cells, cervical epithelial cells, and corneal epithelial cells, mammary gland cells, pericytes, muscle cells such as smooth muscle cells and cardiac muscle cells, kidney cells, pancreatic islet cells of Langerhans, nerve cells such as peripheral nerve cells and optic nerve cells, chondrocytes, bone cells, stem cells, embryonic stem cells (ES cells), and induced pluripotent stem cells (iPS cells). Examples of stem cells include bone marrow undifferentiated mesenchymal stem cells, hematopoietic stem cells, vascular stem cells, neural stem cells, small intestinal stem cells, adipose stem cells, skin stem cells, periodontal tissue stem cells, ciliary body stem cells, corneal limbal stem cells, and visceral stem cells.

[0065] The liquid-containing bag 10 according to the present embodiment can be used, for example, as a medical container for containing the liquid described above. In this case, for example, after the liquid Lq containing the cells Ce is filled into the storage space S of the container body 20 through the inlet 50, the inlet 50 and the outlet 60 are sealed. Note that the outlet 60 may be sealed in advance before the storage space S is filled with the liquid Lq. In this manner, as shown in FIG. 5, a liquid-filled container 10A is obtained, which includes the liquid-containing bag 10 and the liquid Lq contained in the liquid-containing bag 10, and in which the inlet 50 and the outlet 60 are sealed. This embodiment also provides such a liquid-filled container 10A. Note that this liquid-filled container 10A may be used to store the liquid Lq in a frozen state. In this case, the liquid-filled container 10A containing the cell-containing liquid Lq may be frozen and stored at −80°C or below, preferably −150°C or below. At the time of use, the liquid Lq may be thawed at a temperature between 30° C. and 40° C., preferably at 37° C., and then the cells may be centrifuged from the liquid Lq. In this case, the container body 20, the inlet part 50, and the outlet part 60 are preferably made of a material with excellent freeze resistance.

[0066] [Operation of this embodiment] Next, the operation of this embodiment configured as described above will be explained. Here, a centrifugation method for centrifuging cells from liquid Lq and a method for producing a cell preparation will be explained. First, the centrifugation method for centrifuging cells from liquid Lq will be explained with reference to Figures 6 and 7(a).

[0067] First, for example, a liquid-filled container 10A as shown in FIG. 5 is prepared (preparation step, reference numeral S1 in FIG. 6). At this time, first, the liquid-containing bag 10 as shown in FIG. 1A is fabricated. Next, a predetermined amount of liquid Lq containing cells Ce is filled into the storage space S of the container body 20 through the introduction part 50, and then the introduction part 50 is sealed. In this way, a liquid-filled container 10A is obtained, which includes the liquid-containing bag 10 and the liquid Lq containing cells Ce stored in the liquid-containing bag 10.

[0068] Next, as shown in Fig. 7(a), the liquid-filled container 10A is rotated about a rotation axis X4 that is perpendicular to the first direction D1 (rotation step, reference symbol S2 in Fig. 6). In the illustrated example, the rotation axis X4 extends in the second direction D2 when viewed from the front. Although not shown, the rotation axis X4 may extend in a direction perpendicular to both the first direction D1 and the second direction D2.

[0069] When rotating the liquid-filled container 10A, first, the liquid-filled container 10A is set in a holder of a centrifugal separator (not shown). Then, the liquid-filled container 10A is rotated around the rotation axis X4. Here, the accumulation portion 25 of the storage space S is located farthest from the first cylindrical portion 51 in the first direction D1. As a result, during centrifugation, the load due to centrifugal force is greatest on the accumulation portion 25 within the storage space S. Therefore, the cells Ce accumulate in the accumulation portion 25. In this way, the cells Ce are centrifuged from the liquid Lq, and the cells Ce accumulate in the accumulation portion 25 (FIG. 7(b)).

[0070] Next, a method for producing a cell preparation will be described with reference to FIGS. 7(b)-(d) and 8. FIG.

[0071] First, the cells Ce in the liquid Lq are accumulated by the centrifugal separation method shown in Figures 6 and 7(a) (accumulation step, symbol S11 in Figure 8).

[0072] Next, as shown in Figure 7(b), the container body 20 is clamped along the line X3 (see Figure 1A) using, for example, a clip CL, thereby separating the storage space S into a first storage space S1 and a second storage space S2 in which the cells Ce are accumulated (separation process, symbol S12 in Figure 8).

[0073] Next, as shown in FIG. 7(c), the accumulated cells Ce are subjected to a pipetting operation.

[0074] At this time, first, the liquid Lq (supernatant) other than the cells Ce in the second storage space S2 is discharged (discharge step, reference numeral S13 in FIG. 8). The liquid Lq other than the cells Ce is discharged from the discharge unit 60. A syringe needle may be used to discharge the liquid Lq from the discharge unit 60. Here, in this embodiment, the inner wall point 25a of the accumulation section 25 of the storage space S is provided at a position that does not overlap with the central axis X2 of the second cylindrical portion 61 when viewed from the direction in which the central axis X2 of the second cylindrical portion 61 extends. This makes it possible to prevent the cells Ce from being sucked in when the liquid Lq (supernatant) other than the cells Ce in the second storage space S2 is discharged. This makes it possible to reduce damage to the cells Ce.

[0075] Next, the administration liquid is introduced into the second storage space S2 (introduction step, reference numeral S14 in FIG. 8). In this way, a suspension (cell preparation) in which cells are suspended is obtained. Here, as described above, in this embodiment, the inner wall point 25a of the accumulation section 25 of the storage space S is located at a position that does not overlap with the central axis X2 of the second cylindrical portion 61 when viewed from the direction in which the central axis X2 of the second cylindrical portion 61 extends. Therefore, when the administration liquid is introduced into the second storage space S2, it is possible to prevent the administration liquid for suspension from being ejected onto the cells Ce. Therefore, damage to the cells Ce can be reduced.

[0076] Thereafter, as shown in FIG. 7(d), the suspension in which the cells are suspended (cell preparation) is collected.

[0077] As described above, according to the present embodiment, the accumulation portion 25 of the storage space S includes the inner wall point 25a, which is a part of the inner wall constituting the storage space S. Furthermore, the inner wall point 25a is located farthest from the first cylindrical portion 51 in the first direction D1 and is provided at a position that does not overlap with the central axis X2 of the second cylindrical portion 61 of the discharge portion 60 when viewed from the direction in which the central axis X2 of the second cylindrical portion 61 extends. This makes it possible to prevent the administration liquid for suspension from being discharged onto the cells Ce when performing a pipetting operation on the accumulated cells Ce. Furthermore, it is possible to prevent the cells Ce from being sucked in when performing a pipetting operation on the accumulated cells Ce. Therefore, it is possible to reduce damage to the cells Ce. Furthermore, in this embodiment, it is possible to prevent a large load due to centrifugal force from being applied to the second cylindrical portion 61 during centrifugation. Therefore, it is possible to prevent the second cylindrical portion 61 from being damaged.

[0078] Furthermore, in this embodiment, unlike conventional methods, the cells Ce in the liquid Lq can be centrifuged without transferring the liquid Lq to a centrifuge tube, which makes it possible to prevent bacteria and the like from getting mixed in with the liquid Lq (contamination).

[0079] Furthermore, according to this embodiment, the angle α between the first line segment LS1 and the second line segment LS2 is equal to or less than 90°, which prevents the cells Ce from being trapped in the second cylindrical portion 61 when the cells Ce are centrifuged from the liquid Lq.

[0080] Furthermore, according to this embodiment, the storage space S is surrounded by the seal portion 40, and the seal portion 40 has an inclined seal portion 49 whose inner edge is inclined with respect to the first direction D1. The inner edge of the inclined seal portion 49 extends such that the length of the storage space S in the second direction D2 decreases as the inner edge moves from the first cylindrical portion 51 toward the collecting portion 25. The positive and negative inclination of the inner edge of the inclined seal portion 49 does not change as the inner edge moves from the first cylindrical portion 51 toward the collecting portion 25. This prevents cells Ce from being trapped at the inner edge of the inclined seal portion 49.

[0081] Furthermore, according to this embodiment, the storage space S includes a first storage space S1 located on the first cylindrical portion 51 side and a second storage space S2 located on the second cylindrical portion 61 side. The accumulation unit 25 is provided in the second storage space S2. Furthermore, the discharge unit 60 discharges the liquid Lq in the second storage space S2. This eliminates the need to discharge unnecessary liquid Lq (supernatant). Furthermore, after discharging the liquid Lq (supernatant) in the second storage space S2, the administration liquid can be introduced into the second storage space S2 to suspend the cells Ce. In this case, the cells Ce can be collected in a washed state.

[0082] Furthermore, according to this embodiment, the capacity of the first storage space S1 is larger than the capacity of the second storage space S2. This allows the concentration rate of the cells Ce to be increased when concentrating the cells Ce in the liquid Lq. In this case, by increasing the concentration rate of the cells Ce contained in the second storage space S2, the survival rate of the cells Ce can be increased.

[0083] Furthermore, according to this embodiment, the inner edges of the first seal portion 41 and the second seal portion 42 constituting the accumulation portion 25 are inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 decreases from the first tubular portion 51 side toward the accumulation portion 25 side. Furthermore, the inner edge of the third seal portion 43 either extends along the first direction D1 or is inclined with respect to the first direction D1 so that the inclination angle θ3 with respect to the first direction D1 is smaller than the inclination angle θ1 of the inner edge of the first seal portion 41 with respect to the first direction D1. Furthermore, the inner edge of the fourth seal portion 44 extends along the first direction D1. This makes it easier for cells Ce to accumulate in the accumulation portion 25.

[0084] Furthermore, according to the present embodiment, the second cylindrical portion 61 is heat-welded to the container body 20. This improves adhesion between the container body 20 and the second cylindrical portion 61, and prevents damage to the welded portion between the container body 20 and the second cylindrical portion 61 during centrifugation.

[0085] [Variations] Next, various modified examples of the present disclosure will be described with reference to Figures 9 to 11. Figures 9 to 11 are views showing liquid containing bags according to various modified examples of the present disclosure. In Figures 9 to 11, the same parts as those shown in Figures 1A to 8 are designated by the same reference numerals, and detailed descriptions thereof will be omitted.

[0086] (First Modification) Fig. 9 shows a liquid containing bag 10 according to a first modified example. In Fig. 9, the sealed portion 40 has a ninth sealed portion 401 to an eighteenth sealed portion 410. In this case, the ninth sealed portion 401 to the eighteenth sealed portion 410 are arranged in the following order, starting from the ninth sealed portion 401 and going clockwise in a front view: the tenth sealed portion 402, the eleventh sealed portion 403, the twelfth sealed portion 404, the thirteenth sealed portion 405, the fourteenth sealed portion 406, the fifteenth sealed portion 407, the sixteenth sealed portion 408, the seventeenth sealed portion 409, and the eighteenth sealed portion 410.

[0087] In this modification, the ninth seal portion 401 extends along the second direction D2. The ninth seal portion 401 extends between the tenth seal portion 402 and the eighteenth seal portion 410. The inner edge of the ninth seal portion 401 extends along the second direction D2.

[0088] The tenth seal portion 402 is connected to the ninth seal portion 401 and extends in a direction inclined in the first direction D1 and the second direction D2. The tenth seal portion 402 extends between the ninth seal portion 401 and the eleventh seal portion 403. The inner edge of the tenth seal portion 402 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 becomes shorter from the first tubular portion 51 side toward the accumulation portion 25 side (the lower side in FIG. 9 ).

[0089] The eleventh seal portion 403 is connected to the tenth seal portion 402 and extends in a direction inclined in the first direction D1 and the second direction D2. The eleventh seal portion 403 extends between the tenth seal portion 402 and the twelfth seal portion 404. The inner edge of the eleventh seal portion 403 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 decreases from the first tubular portion 51 side toward the accumulation portion 25 side (the lower side in FIG. 9 ). The inner edge of the eleventh seal portion 403 is inclined with respect to the first direction D1 so that the inclination angle θ11 with respect to the first direction D1 is greater than the inclination angle θ10 of the inner edge of the tenth seal portion 402 with respect to the first direction D1.

[0090] The twelfth seal portion 404 is connected to the eleventh seal portion 403 and extends along the first direction D1. The twelfth seal portion 404 extends between the eleventh seal portion 403 and the thirteenth seal portion 405. The inner edge of the twelfth seal portion 404 extends along the first direction D1.

[0091] The thirteenth seal portion 405 is connected to the twelfth seal portion 404 and extends along the second direction D2. The thirteenth seal portion 405 extends between the twelfth seal portion 404 and the fourteenth seal portion 406. The inner edge of the thirteenth seal portion 405 extends along the second direction D2.

[0092] The fourteenth seal portion 406 is connected to the thirteenth seal portion 405 and extends along the first direction D1. The fourteenth seal portion 406 extends between the thirteenth seal portion 405 and the fifteenth seal portion 407. The inner edge of the fourteenth seal portion 406 extends along the first direction D1.

[0093] The fifteenth seal portion 407 is connected to the fourteenth seal portion 406 and extends in a direction inclined in the first direction D1 and the second direction D2. The fifteenth seal portion 407 extends between the fourteenth seal portion 406 and the sixteenth seal portion 408. The inner edge of the fifteenth seal portion 407 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 becomes shorter from the first cylindrical portion 51 side toward the accumulation portion 25 side (the lower side in FIG. 9 ).

[0094] The 16th seal portion 408 is connected to the 15th seal portion 407 and extends in a direction inclined in the first direction D1 and the second direction D2. The 16th seal portion 408 extends between the 15th seal portion 407 and the 17th seal portion 409. The inner edge of the 16th seal portion 408 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 increases from the first tubular portion 51 side toward the accumulation portion 25 side (the lower side in FIG. 9 ).

[0095] The seventeenth seal portion 409 is connected to the sixteenth seal portion 408 and extends along the first direction D1. The seventeenth seal portion 409 extends between the sixteenth seal portion 408 and the eighteenth seal portion 410. The inner edge of the seventeenth seal portion 409 extends along the first direction D1.

[0096] The 18th seal portion 410 is connected to the 17th seal portion 409 and extends in a direction inclined in the first direction D1 and the second direction D2. The 18th seal portion 410 may be line-symmetrical to the 16th seal portion 408 with respect to the central axis X2 of the second cylindrical portion 61 of the discharge portion 60. The 18th seal portion 410 extends between the 17th seal portion 409 and the 9th seal portion 401. The inner edge of the 18th seal portion 410 is inclined with respect to the first direction D1 so that the length of the storage space S in the second direction D2 decreases from the first cylindrical portion 51 side toward the accumulation portion 25 side (the lower side in FIG. 9 ). The inner edge of the 18th seal portion 410 is line-symmetrical to the inner edge of the 16th seal portion 408 with respect to the central axis X2.

[0097] In this modification, the tenth seal portion 402, the eleventh seal portion 403, the fifteenth seal portion 407 and the eighteenth seal portion 410 are inclined seal portions 49.

[0098] In this modification, the accumulation section 25 is composed of a ninth seal section 401, a tenth seal section 402, and an eighteenth seal section 410. The inner wall point 25a is formed on the inner edge of the ninth seal section 401. As described above, the inner edge of the ninth seal section 401 extends along the second direction D2. Therefore, in this modification, the inner wall point 25a is an arbitrary point on the inner edge of the ninth seal section 401. In this case, the length of the inner edge of the ninth seal section 401 (the length along the second direction D2) may be, for example, 5 μm or more, preferably 10 μm or more, more preferably 100 μm or more, even more preferably 200 μm or more, and even more preferably 1 mm or more. The length of the inner edge of the ninth seal section 401 is preferably equal to or greater than the size of a cell (e.g., a diameter of approximately 10 μm). Furthermore, the length of the inner edge of the ninth sealing unit 401 is preferably, for example, 40 mm or less, more preferably 20 mm or less, and even more preferably 10 mm or less. By making the length of the inner edge of the ninth sealing unit 401 40 mm or less, cells can be accumulated in a narrow area. This makes it easier to visually check the concentrated product. Also, by making the length of the inner edge of the ninth sealing unit 401 20 mm or less, cells can be accumulated in an even narrower area, making it easier to visually check the concentrated product. Furthermore, by making the length of the inner edge of the ninth sealing unit 401 10 mm or less, cells can be accumulated in an even narrower area, making it even easier to visually check the concentrated product.

[0099] In addition, in this modified example, the boundary line between the first storage space S1 and the second storage space S2 is formed by a straight line X5 connecting the intersection of the inner edge of the 10th seal portion 402 and the inner edge of the 11th seal portion 403 and the intersection of the inner edge of the 15th seal portion 407 and the inner edge of the 16th seal portion 408.

[0100] Moreover, in this modification, the first cylindrical portion 51 of the introduction part 50 is attached to the thirteenth seal part 405. In this case as well, it is possible to prevent the cells Ce from being trapped in the first cylindrical portion 51 after the liquid Lq is introduced into the storage space S (especially during centrifugation).

[0101] Furthermore, in this modification, the second cylindrical portion 61 of the discharge part 60 is attached to the seventeenth seal part 409. In this case, the central axis X2 of the second cylindrical portion 61 extends along the second direction D2. Even in this case, it is possible to prevent cells from being trapped in the second cylindrical portion 61 after the liquid Lq is introduced into the storage space S (especially during centrifugation).

[0102] In this modification, the inner wall point 25a of the accumulation section 25 of the storage space S is also located farthest from the first cylindrical portion 51 in the first direction D1, and is located at a position that does not overlap with the central axis X2 of the second cylindrical portion 61 when viewed from the direction in which the central axis X2 of the second cylindrical portion 61 of the discharge section 60 extends. This reduces damage to the cells Ce. Furthermore, it is possible to prevent a large load due to centrifugal force from being applied to the second cylindrical portion 61 during centrifugation. This prevents the second cylindrical portion 61 from being damaged.

[0103] (Second Modification) Fig. 10 shows a liquid containing bag 10 according to a second modification. In Fig. 10, the length in the first direction D1 of the sealed portion 40 located around the collecting portion 25 gradually increases in the second direction D2 as it moves away from the collecting portion 25. In the example shown in Fig. 10, the length L1 in the first direction D1 of the first sealed portion 41 and the length L2 in the first direction D1 of the second sealed portion 42 gradually increase in the second direction D2 as it moves away from the collecting portion 25.

[0104] According to this modification, the length in the first direction D1 of the sealing portion 40 located around the accumulating portion 25 gradually increases in the second direction D2 as it moves away from the accumulating portion 25. This increases the rigidity of the sealing portion 40 that constitutes the accumulating portion 25. Therefore, when the liquid-filled container 10A is set in a holder of a centrifugal separator, the shape of the accumulating portion 25 can be stably maintained.

[0105] (Third Modification) Fig. 11 shows a liquid containing bag 10 according to a third modified example. In Fig. 11 as well, the lengths in the first direction D1 of the sealed portions 40 located around the collecting portion 25 gradually increase in the second direction D2 as they move away from the collecting portion 25. In the example shown in Fig. 11, the length L10 of the tenth sealed portion 402 in the first direction D1, the length L11 of the eleventh sealed portion 403 in the first direction D1, and the length L18 of the eighteenth sealed portion 410 in the first direction D1 gradually increase in the second direction D2 as they move away from the collecting portion 25.

[0106] In this modification as well, when the liquid-filled container 10A is set in the holder of the centrifugal separator, the shape of the accumulation section 25 can be stably maintained.

[0107] It is also possible to combine the multiple components disclosed in the above embodiment and each modification as needed, or to delete some of the components disclosed in the above embodiment and each modification. [Explanation of symbols]

[0108] 10 Liquid storage bag 10A Liquid container 20 Container body 25 Accumulation section 25a Inner wall point 40 Seal part 41 First seal part 42 Second seal part 43 Third seal part 44 4th seal part 49 Inclined seal 50 Introduction 51 First cylinder part 60 Discharge section 61 Second cylinder part Ce cells Lq liquid S Storage space S1 First Storage Space S2 Second storage space

Claims

1. A liquid containing bag for containing a liquid containing cells, a container body having a storage space for storing the liquid; an introduction portion for introducing the liquid into the container body; a discharge part that discharges the liquid from the container body, The storage space includes an accumulation portion, The introduction portion has a first cylindrical portion attached to the container body, The discharge portion has a second cylindrical portion attached to the container body, The central axis of the first cylindrical portion extends along a first direction, A central axis of the second cylindrical portion extends along a direction different from the first direction, a first line segment is a line segment on the central axis of the first cylindrical portion, the line segment extending from the first cylindrical portion to an intersection point between the central axis of the first cylindrical portion and the central axis of the second cylindrical portion, and a second line segment is a line segment on the central axis of the second cylindrical portion, the line segment extending from the second cylindrical portion to the intersection point, an angle between the first line segment and the second line segment is 90° or less, A liquid storage bag, wherein the accumulation portion of the storage space includes an inner wall point which is part of an inner wall constituting the storage space, the inner wall point being located farthest from the first tubular portion in the first direction and being provided at a position which does not overlap with the central axis of the second tubular portion when viewed from the direction in which the central axis of the second tubular portion extends.

2. The storage space is surrounded by a seal portion, The seal portion has an inclined seal portion whose inner edge is inclined with respect to the first direction, an inner edge of the inclined seal portion extends such that a length of the accommodation space in a second direction perpendicular to the first direction in a front view becomes shorter as the length of the accommodation space becomes shorter from the first cylindrical portion side toward the accumulation portion side; The liquid containing bag according to claim 1 , wherein the positive and negative inclinations of the inner edges of the inclined seal portions do not change from the first tubular portion side to the collecting portion side.

3. The liquid containing bag according to claim 2 , wherein the width of the sealed portion is constant.

4. 2. The liquid storage bag according to claim 1, wherein the storage space includes a first storage space located on the first tubular portion side and a second storage space located on the second tubular portion side, the accumulation portion is provided in the second storage space, and the discharge portion discharges the liquid in the second storage space.

5. The liquid containing bag according to claim 4 , wherein the first containing space has a larger capacity than the second containing space.

6. The storage space is surrounded by a seal portion, 2. The liquid storage bag according to claim 1, wherein the length along the first direction of the sealing portion located around the accumulating portion gradually increases as the sealing portion moves away from the accumulating portion in a second direction perpendicular to the first direction in a front view.

7. The storage space is surrounded by a seal portion, the sealing portion includes a first sealing portion and a second sealing portion that configure the accumulation portion, a third sealing portion connected to the first sealing portion, and a fourth sealing portion connected to the second sealing portion; an inner edge of the first seal portion and an inner edge of the second seal portion are inclined with respect to the first direction such that a length of the storage space in a second direction perpendicular to the first direction in a front view becomes shorter from the first cylindrical portion side toward the accumulation portion side; an inner edge of the third seal portion extends along the first direction or is inclined with respect to the first direction such that an inclination angle with respect to the first direction is smaller than an inclination angle of the inner edge of the first seal portion with respect to the first direction; The liquid containing bag according to claim 1 , wherein an inner edge of the fourth seal portion extends along the first direction.

8. The liquid containing bag according to claim 7 , wherein the width of the sealed portion is constant.

9. The liquid containing bag according to claim 7 , wherein the second tubular portion is heat-welded to the container body.

10. A liquid containing bag according to any one of claims 1 to 9; A liquid contained in the liquid containing bag, A liquid-filled container, the inlet and outlet being sealed.

11. A step of preparing a liquid-containing container according to claim 10; and rotating the liquid-containing container about a rotation axis perpendicular to the first direction.

12. A step of collecting the cells in the liquid by the centrifugation method according to claim 11; A step of dividing the storage space of the container body into a first storage space and a second storage space in which the cells are accumulated; Discharging the liquid other than the cells in the second storage space; and introducing an administration liquid into the second storage space.

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