Microtube and kit

Abstract

Provided is a microtube which includes a container body with an open upper end side and a closed lower end side. The container body includes: a bottom part which includes a bottom surface; a linear part which is arranged on an upper side of the bottom part and has an inner peripheral surface that is continuous with the bottom surface and linearly extends along a vertical direction in a cross section orthogonal to a radial direction; and a reduced-diameter part which is arranged on an upper side of the linear part and is formed so that an inner peripheral surface is continuous with the inner peripheral surface of the linear part and the inner diameter is tapered downward. The inner diameter of the linear part is 2.5 mm or less.

Description

Microtubes and kits CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from Japanese Patent Application No. 2024-125625, the disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a microtube and a kit.

[0003] Conventionally, microtubes have been used to separate, purify, and store contents such as cells. When removing the contents from the microtubes, tools such as syringes and micropipettes are usually used.

[0004] Since the contents may include very expensive items, it is preferable that the microtube be configured so that the contents can be easily retrieved by the device. For example, Patent Document 1 proposes such a microtube, which includes a container body that is open at its upper end and closed at its lower end, the container body having a bottom portion that includes a bottom surface, and the bottom surface is formed in an arc shape with a radius of 0.8 mm or less in a cross section perpendicular to the radial direction.

[0005] Japanese Patent Application Publication No. 2017-35079

[0006] However, the microtube of Patent Document 1 may make it difficult to recover the contents. For example, when the contents are cells, the cells may aggregate to form aggregates, and depending on the size of the aggregates, it may be difficult to recover the cells. Therefore, there is a need for a microtube that makes it even easier to recover the contents.

[0007] In view of the above circumstances, an object of the present invention is to provide a microtube from which the contents can be easily retrieved.

[0008] A microtube according to the present invention comprises a container body having an open upper end and a closed lower end, the container body having a bottom including a bottom surface, a linear portion disposed above the bottom and extending linearly in the up-down direction in a cross section perpendicular to the radial direction, the inner peripheral surface of which is continuous with the bottom surface, and a tapered portion, i.e., an inclined portion, disposed above the linear portion and whose inner peripheral surface is continuous with the inner peripheral surface of the linear portion and whose inner diameter tapers downward, the inner diameter of the linear portion being 2.5 mm or less. Preferably, the inner diameter of the linear portion is 0.5 mm or more.

[0009] In the microtube according to the present invention, the inner circumferential surface of the reduced diameter portion is preferably linear in the cross section and forms an angle of 30° or less with the vertical direction, the angle being preferably 10 to 30°.

[0010] In the microtube according to the present invention, the bottom surface preferably has an inclined surface whose diameter decreases downward.

[0011] In the microtube according to the present invention, the bottom surface is preferably conical or truncated conical.

[0012] In the microtube according to the present invention, the inclined surface is preferably linear in the cross section and forms an angle of 10 to 45 degrees with the vertical direction.

[0013] In the microtube according to the present invention, the container body preferably has a transparency that allows the contents to be visually observed from the outside.

[0014] Furthermore, the microtube according to the present invention preferably further comprises legs that enable it to stand on its own.

[0015] In the microtube according to the present invention, the container body preferably has a storage space for storing an object, and the volume of the storage space is 500 to 5000 μL.

[0016] In the microtube according to the present invention, the container body is preferably filled with cells.

[0017] The microtube according to the present invention preferably includes a lid.

[0018] Furthermore, the microtube according to the present invention is preferably used to contain a content containing a solid to be extracted by a syringe needle.

[0019] Next, a kit according to the present invention includes any of the microtubes described above and a syringe having a needle with an outer diameter smaller than the inner diameter of the straight portion.

[0020] As described above, the present invention can provide a microtube from which the contents can be easily retrieved.

[0021] FIG. 1 is a front view of a microtube according to one embodiment. FIG. 2 is an exploded view showing the state in which the container body and the lid of the microtube in FIG. 1 are separated. FIG. 3 is a vertical central cross-sectional view of FIG. 1. FIG. 4 is a diagram for explaining angles related to the microtube in FIG. 1. FIG. 5 is a diagram for explaining dimensions of the microtube in FIG. 1. FIG. 6 is a diagram showing another embodiment of the elastic member of the lid. FIG. 7 is a diagram showing a modified example of the bottom surface. FIG. 8 is a diagram showing a modified example of the bottom surface. FIG. 9 is a diagram showing a modified example of the bottom surface. FIG. 10 is a diagram showing a modified example of the bottom surface. FIG. 11 is a photograph showing the appearance of Test Examples 1 to 6 in the Examples.

[0022] Hereinafter, a microtube according to one embodiment of the present invention and a kit including the microtube will be described with reference to the drawings.

[0023] The kit according to this embodiment includes the microtube and an instrument for sucking and recovering the contents contained in the microtube.

[0024] The instrument is preferably a syringe. The syringe includes a cylindrical syringe body that contains the contents therein, a plunger that is inserted from one end of the syringe body and is slidable along the axial direction inside the syringe body, and a needle disposed at the other end of the syringe body. Syringes used in combination with microtubes typically have a capacity of 1 to 1000 μL. The syringe needle is hollow and has an outer diameter of 400 to 1800 μm and an inner diameter of 200 to 1400 μm.

[0025] As shown in Figures 1 to 3, the microtube 1 according to this embodiment comprises a container body 10 that is open at the upper end and closed at the lower end, a lid body 20 for sealing the opening of the container body 10, and legs 30 for enabling the container body 10 to stand on its own.

[0026] The container body 10 includes a bottom 11 including a bottom surface 110. In a cross section C perpendicular to the radial direction and passing through the central axis of the container body 10, the container body 10 includes a linear portion 12 whose inner circumferential surface is continuous with the bottom surface 110 and extends linearly in the vertical direction; a tapered portion 13 disposed above the linear portion 12, whose inner circumferential surface is continuous with the inner circumferential surface of the linear portion 12 and whose inner diameter tapers downward; and a cylindrical portion 14 disposed above the tapered portion 13 and whose inner circumferential surface is continuous with the inner circumferential surface of the tapered portion 13. The tapered portion 13 is, in other words, an inclined portion having an inclined surface whose inner diameter tapers downward. The vertical direction refers to a direction perpendicular to the radial direction of the container body 10. The phrase "along the vertical direction" also includes "along a direction inclined within a range of ±2° from the vertical direction."

[0027] The container body 10 has an internal storage space S for storing the contents. The volume of the storage space S is preferably 500 to 5000 μL, and more preferably 1000 to 2500 μL. The height of the storage space S is preferably 20 to 100 mm, more preferably 20 to 70 mm, and even more preferably 20 to 50 mm. The thickness of the container body 10 is usually 200 to 2000 μm, and preferably 500 to 1500 μm.

[0028] The material constituting the container body 10 is not particularly limited, but examples thereof include polyolefin resins such as polycarbonate resin, polyethylene resin, and polypropylene resin, cycloolefin resin [cycloolefin polymer (COP), cycloolefin copolymer (COC)], polyester resin such as polyethylene terephthalate resin, polymethylpentene resin, methacrylic resin, ABS resin (acrylonitrile-butadiene-styrene copolymer), polyvinyl chloride resin, polyimide resin, and fluororesin [polytetrafluoroethylene (PTFE), perfluoroalkoxyalkane (PFA), perfluoroethylenepropene copolymer (FEP), ethylenetetrafluoroethylene copolymer (ETFE), polyvinylidene fluoride (PVDF), polychlorotrifluoroethylene (PCTFE), ethylenechlorotrifluoroethylene copolymer (ECTFE)].

[0029] The container body 10 preferably has a transparency that allows a user to visually check the contents from the outside. From this viewpoint, the material constituting the container body 10 is preferably a cycloolefin resin.

[0030] The contents are not particularly limited and may be liquid, solid, or a mixture of solid and liquid. Examples of the contents include pharmaceutical compositions (drugs) that require complete recovery with a syringe needle or the like. The contents may be in the form of liquid, solid (insoluble matter), or a mixture of solid and liquid. The microtube of the present invention is particularly suitable when the contents contain solids and require recovery with a syringe needle or the like. Specific examples of the contents include cells, cell aggregates (also known as spheres), cell-derived aggregates, cell-derived insoluble components, nucleic acids (DNA, RNA), nucleic acid-containing vectors (plasmids, viral vectors, episomal vectors, etc.), and proteins (secreted proteins, antibodies, etc.). The microtube of the present invention is useful for containing pharmaceutical compositions containing insoluble components. Even when components aggregate to form aggregates and these aggregates assemble to form the contents, little or no residual material remains in the container when the contents are recovered with a syringe needle or the like. That is, the microtube 1 of this embodiment preferably contains aggregates as active ingredients of pharmaceuticals. The size of the aggregate is not particularly limited, as long as it can be aspirated using a syringe needle or the like. Furthermore, if the aggregate is a solid with an equivalent circle diameter of 100 to 2000 μm, preferably 150 to 1000 μm, and more preferably 200 to 800 μm or 300 to 600 μm, the aggregate will be easier to recover from the microtube 1. The equivalent circle diameter can be measured by capturing an image generated by parallel transmitted illumination from a direction perpendicular to the observation surface in a microscope or digital microscope, and analyzing the resulting figure (i.e., the figure formed when the aggregate is projected onto a plane). Here, the equivalent circle diameter refers to the diameter of a circle having the same area as the figure. The contents preferably include cells, cell populations, cell aggregates, and collections of cell aggregates.

[0031] The bottom portion 11 is a portion disposed below the linear portion 12, and is formed so that the bottom surface 110 is continuous with the inner peripheral surface of the linear portion 12. The bottom surface 110 preferably has an inclined surface that narrows in diameter downward. In this embodiment, the bottom surface 110 is a conical surface that tapers downward, and is formed so that the lengths of the two line segments represented in cross section C are equal. That is, the bottom surface 110 in this embodiment is a right circular cone.

[0032] As shown in FIG. 4 , the inclination angle θa formed by the inclined surface 112 with respect to the vertical direction in cross section C is preferably 45° or less, more preferably 42.5° or less, even more preferably 40° or less, and particularly preferably 35° or less. The inclination angle θa is typically 10° or greater. In one embodiment, the inclination angle θa is preferably 10 to 45°, 10 to 30°, or 10 to 20°. When the bottom surface 110 is a right circular cone or a truncated cone, the cone angle of the right circular cone or truncated cone is preferably 90° or less, more preferably 85° or less, even more preferably 80° or less, and particularly preferably 70° or less. The cone angle is typically 20° or greater. Because the bottom 11 has the inclined surface 112, the distance between the outer circumferential surface of the needle and the inclined surface 112 narrows toward the needle tip, allowing multiple solids, such as aggregates, to be smoothly drawn into the syringe needle. That is, as the inclination angle θa increases, cells accumulated at the bottom spread radially, making it difficult to aspirate the cells in the linear passage formed between the outer circumferential surface of the needle and the inner circumferential surface of the linear portion. However, the inclination angle θa in this specification avoids such a problem, allowing the contents to be uniformly distributed at the bottom during operation. Furthermore, a microtube 1 having such an inclination angle θa facilitates the collection of solids. Specifically, when the needle attempts to simultaneously aspirate multiple solids of a certain size or larger (e.g., approximately 0.8 to 2 times the inner diameter of the syringe needle), the solids interfere with each other, resulting in no solids being aspirated. In contrast, when the inclination angle θa is set as described above, the solids can be aspirated without interference. The inclination angle θa and the cone angle can be determined by preparing a test specimen by laser cutting the container body 10 in two so that the cross section C is exposed, and then measuring the inclination angle θa or the cone angle by magnifying and observing the cross section C of the test specimen under a microscope. Furthermore, by using a technique such as X-ray CT scanning, it is possible to measure the tilt angle θa or the cone angle non-destructively.

[0033] The height h1 of the bottom 11 shown in FIG. 5 (not including the thickness of the container itself) is preferably 1 to 5 mm.

[0034] It is important that the inner diameter of the straight portion 12 is 2.5 mm or less. In this case, the outer diameter of the syringe needle is preferably 0.4 to 1.8 mm. This combination allows the multiple aggregates to be smoothly sucked into the syringe needle through a linear passage formed between the outer circumferential surface of the syringe needle and the inner circumferential surface of the straight portion 12 during aspiration. That is, a microtube 1 equipped with such a straight portion 12 facilitates the recovery of the contents. More specifically, if a needle attempts to simultaneously suck up multiple solids, such as aggregates, each of which is equal to or larger than a certain size (e.g., approximately 0.8 to 2 times the inner diameter of the syringe needle), the solids will interfere with each other, resulting in no solids being sucked in. In contrast, if the inner diameter of the straight portion 12 is set as described above, the solids can be sucked in without interference. The inner diameter of the straight portion 12 is not particularly limited as long as it can aspirate the contents and is larger than the outer diameter of the syringe needle, but is preferably 0.5 mm or more, more preferably 0.7 mm or more, even more preferably 0.9 mm or more, even more preferably 1.0 mm or more, particularly preferably 1.2 mm or more, and particularly preferably 1.4 mm or more. Furthermore, the inner diameter of the straight portion 12 may be 1.6 mm or more. This makes it easier for the syringe needle to be inserted into the straight portion 12 when the contents are aspirated with the syringe. The inner diameter refers to the average inner diameter. The average inner diameter can be determined by magnifying the cross section C of the test specimen with a microscope, measuring the inner diameters at 10 locations selected so as to be equally spaced in the vertical direction, and calculating the arithmetic average of these measurements.

[0035] The height h2 of the straight portion 12 shown in Fig. 5 is preferably 1 to 30 mm, 1 to 20 mm, 1.5 to 15 mm, 2 to 15 mm, or 3 to 10 mm, which makes it easier to form the passage for smooth suction of a plurality of aggregates.

[0036] In the present embodiment, the reduced diameter portion 13 has an inner circumferential surface 131 that is formed in a straight line in the cross section C. The reduced diameter portion 13 is also formed so that the lengths of the two line segments that represent the inner circumferential surface 131 are equal in the cross section C. That is, the inner circumferential surface 131 of the reduced diameter portion 13 in the present embodiment is shaped like a truncated cone whose central axis is aligned along the up-down direction.

[0037] In the reduced diameter portion 13, the angle θb formed by the inner circumferential surface 131 shown in FIG. 4 and the vertical direction in cross section C is preferably 30° or less, and more preferably 25° or less. Furthermore, the angle θb is preferably 10° or more, more preferably 12.5° or more, and even more preferably 20° or more. In one embodiment, the angle θb is 10 to 30°, preferably 20 to 30°, more preferably 20 to 27°, and even more preferably 22 to 25°. The angle θb can be measured in the same manner as the cone angle of the bottom portion 11.

[0038] The height h3 of the reduced diameter portion 13 shown in FIG. 5 is preferably 2 to 20 mm, or 5 to 15 mm.

[0039] The cylindrical portion 14 forms an opening of the container body 10 at the upper end. The inner peripheral surface of the cylindrical portion 14 is cylindrical. The height h4 of the cylindrical portion 14 shown in FIG. 5 can be adjusted appropriately depending on the volume of the contents to be contained and the length of the needle of the syringe to be used, but is preferably 5 to 100 mm, 5 to 50 mm, or 10 to 50 mm, for example. The inner diameter of the cylindrical portion 14 is preferably 5 to 20 mm or 5 to 15 mm.

[0040] The cylindrical portion 14 is configured so that its upper end can engage with the lid 20. In this embodiment, the cylindrical portion 14 has a male thread portion 151 formed on its outer peripheral surface so that the upper end can be screwed onto the lid 20. The cylindrical portion 14 also has a rib portion 152 disposed below the male thread portion 151, protruding from the outer peripheral surface and formed circumferentially. The rib portion 152 improves the moldability of the container body 10.

[0041] The lid 20 is configured to engage with the upper end of the cylindrical portion 14. The lid 20 of this embodiment has a disk-shaped upper surface 21 and a cylindrical side surface 22 extending downward from the periphery of the upper surface 21. The lid 20 also has a female thread 221 formed on the inner wall of the side surface 22 so as to threadably engage with the male thread 151 of the cylindrical portion 14. The lid 20 further includes an elastic member 23 having a disk-shaped top plate 231 arranged along the inner wall surface of the upper surface 21. As a result, when the microtube 1 is in the closed state, the elastic member 23 is sandwiched between the inner wall surface of the upper surface 21 and the upper end of the cylindrical portion 14, thereby improving the sealing performance of the microtube 1. It is desirable that the lid 20 have excellent sealing performance. The elastic member 23 of this embodiment is made of rubber. As another embodiment of the elastic member 23, as shown in FIG. 6, the elastic member 23 may have a cylindrical protrusion 232 that protrudes downward from the center of a top plate portion 231.

[0042] The leg portion 30 is formed to extend downward from the upper end of the reduced diameter portion 13, and its outer wall surface is continuous with the outer circumferential surface of the cylindrical portion 14. In this embodiment, the leg portion 30 has a first leg portion 301 and a second leg portion 302, which are arranged with a gap between them in the circumferential direction of the container body 10. The gap makes it easier for the user to see the inside of the bottom portion 11, the straight portion 12, and the reduced diameter portion 13.

[0043] Furthermore, the lower ends of the legs 30 are usually disposed lower than the lower end of the container body 10. In this case, the difference in height between the lower ends of the legs 30 and the lower end of the container body 10 (the extension length d of the legs 30 relative to the lower end of the container body 10 shown in FIG. 5) is preferably 0.5 to 20 mm, 1 to 20 mm, 1 to 10 mm, or 1 to 5 mm.

[0044] The height H of the microtube 1 shown in FIG. 5 is, for example, 40 to 50 mm.

[0045] The microtube and kit according to the present invention are not limited to the configurations of the above-described embodiments. Furthermore, the microtube and kit according to the present invention are not limited by the above-described effects. Various modifications of the microtube and kit according to the present invention are possible without departing from the spirit and scope of the present invention.

[0046] For example, in the above embodiment, a syringe is used as an example of the tool for retrieving the contents, but the present invention is not limited to this, and the tool may be a micropipette.

[0047] Furthermore, in the above embodiment, the bottom surface 110 constituting the bottom portion 11 is a conical surface. However, the microtube of the present invention is not limited to this and may have an embodiment shown in FIG. 7 . Regarding the embodiment shown in FIG. 7 , the same components as those in the above embodiment are designated by the same reference numerals and their description will be omitted. As shown in FIG. 7 , the bottom surface 110 may have a truncated cone shape whose central axis is aligned along the vertical direction and tapers downward. In other words, the bottom surface 110 may have a circular horizontal surface 111 disposed at the lower end so as to extend horizontally, and a linear inclined surface 112 in cross section C formed so as to narrow from the lower end of the inner circumferential surface of the linear portion 12 toward the horizontal surface 111. In this case, the inclination angle of the inclined surface 112 with respect to the vertical direction in cross section C is preferably 45° or less, more preferably 42.5° or less, even more preferably 40° or less, and particularly preferably 35° or less. In one embodiment, the inclination angle is preferably 10 to 45°, 10 to 30°, or 10 to 20°. The inclination angle is usually 10° or greater. That is, the inclination angle corresponds to the inclination angle θa of the microtube 1 according to the above embodiment. In this case, the height of the bottom 11 (not including the thickness of the container itself) is preferably 1 to 5 mm.

[0048] The microtube of the present invention may also have the configurations shown in Figures 8 to 10. Regarding the configurations of Figures 8 to 10, the same components as those in the above-described embodiment are designated by the same reference numerals and their description will be omitted. As shown in Figures 8 to 10, the bottom surface 110 may be composed of only a horizontal surface 111 extending horizontally in cross section C (Figure 8), may be a convex surface projecting upward from the lower end of the inner circumferential surface of the straight portion 12 (Figure 9), or may be a concave surface projecting downward from the lower end of the inner circumferential surface of the straight portion 12 (Figure 10).

[0049] In addition, in the above embodiment, the reduced diameter portion is shown as the reduced diameter portion 13 whose inner circumferential surface in cross section C is linear. However, the present invention is not limited to this. For example, the inner circumferential surface of the reduced diameter portion may be formed in a spherical shape that is concave outward in cross section C, or may be formed in a spherical shape that bulges inward.

[0050] The present disclosure includes the following: [1] A microtube comprising a container body that is open at its upper end and closed at its lower end, the container body having a bottom including a bottom surface, a linear portion disposed above the bottom and extending linearly in the up-down direction with its inner circumferential surface continuing from the bottom surface in a cross section perpendicular to the radial direction, and a tapered portion disposed above the linear portion with its inner circumferential surface continuing from the inner circumferential surface of the linear portion and formed so that its inner diameter tapers downward, and the inner diameter of the linear portion is 2.5 mm or less.

[0051] According to this configuration, the inner circumferential surface is continuous with the straight portion, and the tapered portion has an inner diameter tapering downward, which makes it easier for the contents to be guided into the straight portion during centrifugation or when allowed to settle naturally. Furthermore, contents placed in the straight portion with an inner diameter of 2.5 mm or less can be easily retrieved using a commonly used tool such as a syringe.

[0052] [2] The microtube according to [1] above, wherein the straight portion has an inner diameter of 0.5 mm or more.

[0053] Such a straight portion allows the needle of a syringe to be easily inserted.

[0054] [3] The microtube according to [1] or [2] above, wherein the inner circumferential surface of the reduced diameter portion is linear in the cross section and forms an angle of 30° or less with the up-down direction.

[0055] According to this configuration, the inner circumferential surface of the reduced diameter portion is linear in the cross section and forms an angle of 30° or less with the vertical direction, so that the contents can easily move downward along the inner circumferential surface of the reduced diameter portion, and the contents can easily be guided into the linear portion. In other words, because the reduced diameter portion has a relatively steep inner circumferential surface, clogging of the reduced diameter portion by the contents is suppressed, and the contents can easily be guided into the linear portion.

[0056] [4] The microtube according to the above [3], wherein the angle is 10 to 30°, preferably 20 to 30°, more preferably 20 to 27°, and even more preferably 22 to 25°.

[0057] With this configuration, the contents are more easily guided into the straight section.

[0058] [5] The microtube according to any one of the above [1] to [4], wherein the bottom surface has an inclined surface whose diameter decreases downward.

[0059] According to this configuration, the bottom surface has an inclined surface that narrows in diameter downward, making it easier to retrieve the contents.

[0060] [6] The microtube according to any one of the above [1] to [5], wherein the bottom surface is conical or truncated conical.

[0061] According to this configuration, the bottom surface is conical or truncated conical, which makes it even easier to retrieve the contents.

[0062] [7] The microtube according to [5] above or [6] citing [5] above, wherein the inclined surface is linear in the cross section and forms an angle of 10 to 45 degrees with the vertical direction, preferably 10 to 30 degrees, and more preferably 10 to 20 degrees.

[0063] With this configuration, the inclined surface is linear in cross section and forms an angle of 10 to 45 degrees with the vertical direction, making it easier to retrieve solid contents in particular and making it easier to manufacture.

[0064] [8] The microtube according to any one of the above [1] to [7], wherein the container body has a transparency that allows the contents to be visually observed from the outside.

[0065] According to this configuration, the container body has a transparency that allows the contents to be seen from the outside, which allows the user to see the contents from the outside, thereby improving operability when retrieving the contents.

[0066] [9] The microtube according to any one of the above [1] to [8], further comprising legs for enabling the microtube to stand on its own.

[0067] According to this configuration, the provision of legs that enable the container to stand on its own further improves operability for the user. More specifically, as will be described later, when removing insoluble matter that has settled to the bottom, i.e., solid contents, the operation must be carried out carefully so as not to cause the contents to float due to the microtube tipping over. With this configuration, the container can stand on its own in a minimum amount of space without using a container holder or the like, and the user can handle the microtube smoothly.

[0068]

[10] The microtube according to any one of the above [1] to [9], wherein the container body has a storage space for storing an object, and the volume of the storage space is 500 to 5000 μL.

[0069] According to this configuration, the volume of the storage space is 500 to 5000 μL, so that a sufficient amount of contents can be stored.

[0070]

[11] The microtube according to any one of [1] to

[10] above, wherein the container body is filled with cells.

[0071] Such a configuration makes it easier to recover cells, which are valuable and expensive as storage items.

[0072]

[12] The microtube according to any one of [1] to

[11] above, which is provided with a lid.

[0073] With this configuration, it is possible to prevent expensive cells from spilling out when the microtube is accidentally turned over.

[0074]

[13] The microtube according to any one of the above [1] to

[12] , which is used to contain a content including a solid to be extracted by a syringe needle.

[0075]

[14] A kit comprising the microtube according to any one of [1] to

[13] above and a syringe having a needle with an outer diameter smaller than the inner diameter of the straight portion.

[0076] With this configuration, the outer diameter of the syringe needle is smaller than the inner diameter of the straight portion of the microtube, making it possible to reliably insert the tip of the needle into the straight portion, making it easier to retrieve the contents.

[0077] The present invention will be described in more detail below with reference to examples.

[0078] In this example, the shape of the container body constituting the microtube was variously changed using a 3D printer, and the recovery rate of the contents filled in each container body was evaluated. Note that the container body was made of an acrylate-based photocurable resin.

[0079] [Experiment 1] First, an experiment was conducted on the recovery rate of a conventionally widely used type of microtube, and various changes in the shape of the container body were investigated based on the shape of the microtube.

[0080] Test Example 1 A conventional microtube was prepared as shown in Fig. 11(a) . Specifically, the microtube had a container body including a lower portion (height: 16 mm) whose inner peripheral surface was a right circular cone with a cone angle of 30°, and a cylindrical upper portion (height: 24 mm) disposed above the lower portion and whose inner peripheral surface was continuous with that of the lower portion.

[0081] 11(b), a microtube was produced that had an eccentric container body with an eccentric lower part by forming the inner circumferential surface of the lower part in Test Example 1 into an oblique conical shape at cross section C. Specifically, a microtube was produced that had a container body consisting of a lower part (height 16 mm) whose inner circumferential surface was obliquely conical with a cone angle of 30° and an upper part similar to that of Test Example 1.

[0082] Test Example 3 As shown in FIG. 11(c), a microtube was produced that had a container body with a linear groove formed in the lower part of Test Example 1 for aligning the needle of a syringe.

[0083] 11(d) was produced. This microtube was of the type shown in Fig. 8 and included a bottom portion 11 having an inner surface consisting of a circular bottom surface 111 extending horizontally, a straight portion 12 whose inner circumferential surface was continuous with bottom surface 111 and extended linearly in the vertical direction, and a tapered portion 13 whose inner circumferential surface was continuous with the inner circumferential surface of straight portion 12 and whose inner diameter tapered downward, where the angle θb formed between the inner circumferential surface of tapered portion 13 and the vertical direction at cross section C was 30° and the inner diameter of straight portion 12 was 1.5 mm (height H of the microtube: 40 mm, height h2 of straight portion 12: 20 mm, extension length d of leg portion 30: 5 mm).

[0084] 11( e) was produced. This microtube was a capillary-type microtube (height h2 of the straight portion 12: 10 mm) in which the inner diameter of the straight portion 12 in Test Example 4 was changed to 2.0 mm.

[0085] 11(f) was produced. This microtube was the same as in Test Example 5, except that the height h2 of the straight portion 12 was changed to 21 mm.

[0086] [Evaluation Method 1 for Test Examples 1 to 6] Approximately 60 cell aggregates (circular equivalent diameter: average 393 μm) were placed into the container body of each microtube as the contents, and the supernatant was removed to prepare microtubes filled with cell aggregates. Two testers, A and B, used a syringe equipped with a syringe body with a capacity of 5 μL and a needle with an outer diameter of 700 μm and an inner diameter of 400 μm as a tool to recover the contents, and aspirated the cell aggregates from each container body. The recovery rate was calculated according to the following formula. The cell aggregates were deformable and could be aspirated with the syringe. Recovery rate (%) = [Number of packed cell aggregates (60) - Number of cell aggregates remaining in the container body] / [Number of packed cell aggregates (60)] x 100 = [Number of aspirated cell aggregates] / [Number of packed cell aggregates (60)] x 100

[0087] [Evaluation method 2 for Test Examples 1 to 6] The operability during collection was evaluated according to the following evaluation criteria: (Evaluation criteria for operability) ◎: Particularly excellent at preventing the contents from moving upstream along the inner surface of the container body and adhering to the inner surface ○: Excellent at preventing the contents from moving upstream along the inner surface of the container body and adhering to the inner surface △: Poor at preventing the contents from moving upstream along the inner surface of the container body and adhering to the inner surface

[0088] The evaluation results of Test Examples 1 to 6 are shown in Table 1 below. Among these, the recovery rates were relatively high for the capillary-type microtubes of Test Examples 4 to 6. These results suggest that it is preferable to provide an inner circumferential surface (i.e., a linear portion) that extends linearly upward from the bottom surface in the cross section of the container body.

[0089]

[0090] [Experiment 2] In Experiment 2, the shape of the container body was varied and evaluated based on Test Example 4, which had yielded favorable results in Experiment 1. The basic shape and size of the container body were as follows: a bottom portion including a bottom surface; a linear portion (height h2: 5 mm) whose inner circumferential surface is continuous with the bottom surface and extends linearly in the vertical direction at cross section C; a tapered portion (height h3: 5 mm) located above the linear portion, whose inner circumferential surface is continuous with the inner circumferential surface of the linear portion and whose inner diameter tapers downward; and a cylindrical portion (inner diameter 8 mm, height h4: 20 mm) located above the tapered portion, whose inner circumferential surface is continuous with the inner circumferential surface of the tapered portion at cross section C, whose inner circumferential surface is linear and whose angle θb with the vertical direction is 22.5°. The container bodies were designed with various changes to the shape of the bottom surface and the inner diameter of the linear portion, as shown in Table 2 below, and the recovery rates were evaluated according to the following evaluation method. The volume of the storage space of the container body was set to 1.1 mL.

[0091] [Evaluation Method for Experiment 2] Approximately 70 cell aggregates (average circle equivalent diameter: 488 μm) were placed into each container body as the contents, and the supernatant was removed to prepare a container body filled with cell aggregates. Next, the recovery rate was determined in the same manner as in Evaluation Method 1 in Experiment 1, except that a syringe with a capacity of 5 μL and a syringe needle with an outer diameter of 700 μm and an inner diameter of 400 μm was used as the device to recover the contents. The results are shown in Table 2.

[0092]

[0093] From the evaluation results shown in Table 2, it was found that in order to improve the recovery rate, it is preferable to set the lower limit of the inner diameter of the straight portion between 0.9 and 1.1 mm. Specifically, it is considered preferable that the inner diameter of the straight portion is 1.0 mm or more.

[0094] [Experiment 3] The results in Table 2 suggest that a right circular cone shape is preferable for the bottom surface, and therefore, in order to further improve the recovery rate, the shapes of Test Examples 15 to 18 (with a right circular cone shape for the bottom surface) were changed and evaluated as shown in the following Table 3. The volume of the storage space in the container body was set to 2 mL.

[0095] [Evaluation Method for Experiment 3] Approximately 70 cell aggregates (average circle equivalent diameter: 403 μm) and approximately 50 cell aggregates (average circle equivalent diameter: 618 μm) were placed into each container body as the contents, and the supernatant was removed to prepare container bodies filled with cell aggregates. Next, the recovery rate was determined in the same manner as Evaluation Method 1 in Experiment 1, except that a syringe with a capacity of 5 μL and a syringe needle with an outer diameter of 700 μm and an inner diameter of 400 μm was used as the device to recover the contents. The results are shown in Table 3.

[0096]

[0097] From the evaluation results in Table 3, it was found that the recovery rate tended to decrease as the inner diameter of the straight portion increased from 2.0 mm to 2.5 mm. Therefore, in order to ensure a high recovery rate of around 80%, it is considered preferable to set the upper limit of the inner diameter of the direct portion to 2.5 mm or less.

[0098] Furthermore, it was found that in order to further improve the recovery rate, it is preferable to set the upper limit of the cone angle between 75 and 90°. Specifically, it is considered that the cone angle is preferably 85° or less, and more preferably 80° or less.

[0099] [Experiment 4] Next, in order to further improve the recovery rate, the shape was changed as shown in Table 4 below and evaluation was carried out.

[0100] [Evaluation Method for Experiment 4] Approximately 60 cell aggregates (average circle equivalent diameter: 417 μm) and approximately 35 cell aggregates (average circle equivalent diameter: 471 μm) were placed into a container body (container material: cycloolefin polymer (COP)) as the contents, and the supernatant was removed to prepare a container body filled with cell aggregates. Next, the recovery rate was determined in the same manner as Evaluation Method 1 in Experiment 1, except that a syringe with a capacity of 5 μL and a needle with an outer diameter of 700 μm and an inner diameter of 400 μm was used as the device to recover the contents. The results are shown in Table 4.

[0101]

[0102] The evaluation results in Tables 3 and 4 reveal that the lower limit of the cone angle may be 30° or less. On the other hand, from the viewpoint of manufacturing microtubes, it is considered preferable that the lower limit of the cone angle is 20° or more.

[0103] [Experiment 5] In Experiment 5, a study was carried out using a container body having a bottom surface shaped like a truncated cone as shown in FIG. The basic shape and size of the container body used were a bottom portion including a bottom surface, a linear portion (inner diameter 2.0 mm, height h2: 3.1 mm) whose inner circumferential surface is continuous with the bottom surface and extends linearly along the vertical direction in cross section C, a tapered portion (height h3: 10 mm) disposed above the linear portion, whose inner circumferential surface is continuous with the inner circumferential surface of the linear portion and whose inner diameter tapers downward, and a cylindrical portion (inner diameter 10.3 mm, height h4: 27 mm) disposed above the tapered portion and whose inner circumferential surface is continuous with the inner circumferential surface of the tapered portion, as shown in FIG. 7 . The shape of the bottom surface was a truncated cone-like bottom surface 110 whose central axis was along the vertical direction and tapered downward, and the tapered portion had a linear inner circumferential surface in cross section C that formed an angle θb of 23° with the vertical direction, and an inclined surface 112 whose inclination angle θa with the vertical direction was 15°. The volume of the storage space of the container body was set to 2 mL.

[0104] [Evaluation Method for Experiment 5] As the contents, approximately 100 cell aggregates (circle equivalent diameter: average 375 μm) were placed in Test Example 36 (n = 7), approximately 46 cell aggregates (circle equivalent diameter: average 471 μm) in Test Example 37 (n = 8), approximately 81 cell aggregates (circle equivalent diameter: average 406 μm) in Test Example 38 (n = 8), and approximately 96 cell aggregates (circle equivalent diameter: average 366 μm) in Test Example 39 (n = 1) were placed in a container body (container material: cycloolefin polymer (COP)). The supernatant was removed to prepare a container body filled with cell aggregates. Next, the recovery rate was determined in the same manner as in Evaluation Method 1 in Experiment 1, except that a syringe with a capacity of 5 μL and a needle with an outer diameter of 700 μm and an inner diameter of 400 μm was used as the instrument for recovering the contents. The results are shown in Table 5.

[0105]

[0106] In Test Examples 36 to 39, the operability during suction was as good as that of Test Example 4. From the evaluation results in Table 5, it was found that good results were obtained when the bottom shape was a truncated cone.

[0107] 1: microtube, 10: container body, 11: bottom, 110: bottom surface, 111: horizontal surface, 112: inclined surface, 12: straight portion, 13: tapered portion, 131: inner peripheral surface, 14: cylindrical portion, 20: lid, 21: upper surface, 22: side surface, 221: female thread portion, 23: elastic member, 231: top plate portion, 232: protrusion, 30: leg portion, 301: first leg portion, 302: second leg portion, S: storage space, θa: inclination angle, θb: angle, h1: height of bottom portion, h2: height of straight portion, h3: height of tapered portion, h4: height of cylindrical portion, H: height of microtube, d: extension length of leg portion

Claims

1. A microtube comprising a container body that is open at its upper end and closed at its lower end, the container body having a bottom including a bottom surface, a linear portion disposed above the bottom and extending in a straight line in the vertical direction, the inner circumferential surface of which is continuous with the bottom surface in a cross section perpendicular to the radial direction, and a tapered portion disposed above the linear portion and whose inner circumferential surface is continuous with the inner circumferential surface of the linear portion and whose inner diameter tapers downward, and the inner diameter of the linear portion is 2.5 mm or less.

2. The microtube according to claim 1, wherein the inner diameter of the straight portion is 0.5 mm or more.

3. The microtube according to claim 1, wherein the inner peripheral surface of said reduced diameter portion is linear in said cross section and forms an angle of 30° or less with said vertical direction.

4. The microtube according to claim 3, wherein the angle is between 10 and 30 degrees.

5. A microtube according to any one of claims 1 to 4, wherein the bottom surface has an inclined surface whose diameter decreases downward.

6. The microtube according to claim 5, wherein the bottom surface is conical or frustoconical.

7. The microtube according to claim 5, wherein the inclined surface is linear in the cross section and forms an angle of 10 to 45 degrees with the vertical direction.

8. A microtube according to any one of claims 1 to 4, wherein the container body has a transparency that allows the contents to be visually observed from the outside.

9. The microtube according to any one of claims 1 to 4, further comprising legs for enabling the microtube to stand on its own.

10. A microtube according to any one of claims 1 to 4, wherein the container body has a storage space for storing an item, and the volume of the storage space is 500 to 5000 μL.

11. The microtube according to any one of claims 1 to 4, wherein the container body is filled with cells.

12. The microtube according to claim 11, which is provided with a lid.

13. A microtube according to any one of claims 1 to 4, which is used to contain a content including a solid to be extracted by a syringe needle.

14. A kit comprising the microtube according to any one of claims 1 to 4 and a syringe having a needle with an outer diameter smaller than the inner diameter of the straight portion.

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