Biological tissue processing device

Abstract

To provide a technique that facilitates processing of a biological tissue.SOLUTION: A biological tissue processing device comprises: a first syringe device comprising a first outer cylinder having a first space therein, and a first pusher inserted into the first space from a rear end opening of the first outer cylinder and held so as to move back and forth along the first space; a second syringe device comprising a second outer cylinder having a second space extending in one direction inside and having a connection structure which is connected to a tip of the first outer cylinder and communicates the first space and the second space, on the tip side thereof, and a second pusher inserted into the second space from a rear end opening of the second outer cylinder and held so as to move back and forth along the second space; a chopping portion provided at a position that divides a connecting space into at least the first space side and the second space side in the connecting space composed of a communication path formed between the first space and the second space by connecting the first space and the second space, the first space, and the second space, and for chopping a biological tissue moving between the first space and the second space via the communication path.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a biological tissue processing apparatus. [Background technology]

[0002] With the advancement of technologies such as immunotherapy and regenerative medicine, there are increasing opportunities to extract tissue from living organisms and culture its cells. However, when culturing cells from extracted tissue, the extracted tissue has traditionally been manually cut into small pieces as a pre-processing step. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2019-503793 [Patent Document 2] Re-tabled publication 2005 / 037984 Summary of the Invention [Problem to be solved by the invention]

[0004] Manually cutting the extracted tissue into a state suitable for cell culture can be extremely time-consuming and labor-intensive. For example, the longer the processing time, the greater the risk of contamination during processing, which is undesirable. Furthermore, different operators with different levels of expertise may produce different tissue mincing conditions, potentially affecting the results of culture. Furthermore, because the required size of the minced tissue varies depending on the desired culture conditions, it can be difficult to cut the tissue into the appropriate size. Therefore, an object of the present invention is to provide a technique that makes it possible to easily process biological tissue. [Means for solving the problem]

[0005] In order to solve the above problems, the biological tissue processing device of the present invention comprises: a connecting portion that connects a tip opening portion of a first syringe device including a first outer cylinder having a first space extending in one direction therein and a first pusher that is inserted into the first space from a rear end opening of the first outer cylinder and held so as to be movable back and forth along the extension direction of the first space, to a tip opening portion of a second syringe device including a second outer cylinder having a second space extending in one direction therein and a second pusher that is inserted into the second space from a rear end opening of the second outer cylinder and held so as to be movable back and forth along the extension direction of the second space, and that connects the first space with the second space; a shredding unit that is provided in a communication passage formed between the first space and the second space by communicating the first space and the second space, and that shreds the biological tissue moving between the first space and the second space via the communication passage; Equipped with.

[0006] In order to solve the above problems, the biological tissue processing device of the present invention comprises: a first syringe device including: a first outer cylinder having a first space therein extending in one direction; and a first pusher inserted into the first space from a rear end opening of the first outer cylinder and held so as to be movable forward and backward along the extension direction of the first space; a second syringe device including: a second outer cylinder having a second space therein extending in one direction; and a second plunger inserted into the second space from a rear end opening of the second outer cylinder and held so as to be movable forward and backward along the extension direction of the second space; a connecting portion that connects a tip opening of the first syringe device and a tip opening of the second syringe device and communicates the first space with the second space; In a connecting space formed by a communication passage between the first space and the second space and the first space and the second space, the connecting space is a shredding unit that is provided at a position that divides the space into at least two spaces, the first space side and the second space side, and that shreds the living tissue that moves between the first space and the second space through the communication passage; Equipped with.

[0007] The morcellating portion may be a mesh having a plurality of openings in a plane perpendicular to the moving direction of the biological tissue.

[0008] The biological tissue processing device may have a liquid in at least one of the first space and the second space, and by moving the first plunger or the second plunger back and forth, the liquid may be moved between the first space and the second space, and the biological tissue may be moved in conjunction with the movement of the liquid.

[0009] The biological tissue processing device may further include a fixing member that fixes the relative position of the first plunger when the first plunger is moved back and forth with respect to the first outer cylinder while the liquid is contained in the first space.

[0010] In the biological tissue processing device, the fixing member is an outer cylinder side engaging portion that engages with a part of the first outer cylinder; a pusher-side engaging portion that engages with a part of the first pusher; a connecting rod that connects the outer tube side engaging portion and the plunger side engaging portion so as to fix the relative positions of the outer tube side engaging portion and the plunger side engaging portion; may also be provided.

[0011] The biological tissue processing device includes: an injection port connected to the tip of the first outer cylinder or the tip of the second outer cylinder, through which a liquid containing the shredded biological tissue is injected; an inclined surface that forms at least a part of a flow-down path that allows the liquid injected from the injection port to flow down in a predetermined direction; a first depression disposed downstream of the inclined surface and into which the liquid that has flowed down along the inclined surface flows; an upstream mesh portion that constitutes a part of the flow path, is arranged upstream of the first recess, and has a mesh size of a predetermined size; a second recess into which the liquid that has passed through the mesh of the upstream mesh portion and deviated from the flow-down path flows; The separator may further include a separator having:

[0012] The separation unit may further include an external housing having an internal space in which the inclined surface, the first depression having the upstream mesh portion, the upstream mesh portion, and the second depression are provided, and which closes the internal space at a portion other than the inlet, the first discharge port for discharging the liquid in the first depression, and the second discharge port for discharging the liquid in the second depression.

[0013] In order to solve the above problems, the biological tissue processing device of the present invention comprises: an injection port into which a liquid containing minced biological tissue is injected; an inclined surface that forms at least a part of a flow-down path that allows the liquid injected from the injection port to flow down in a predetermined direction; a first depression disposed downstream of the inclined surface and into which the liquid that has flowed down along the inclined surface flows; an upstream mesh portion that constitutes a part of the flow path, is arranged upstream of the first recess, and has a mesh size of a predetermined size; a second flow path into which the liquid that has passed through the mesh of the upstream mesh portion and deviated from the flow-down path flows; A depression and Equipped with.

[0014] The biological tissue processing device may further include an external housing having an internal space in which the inclined surface, the first recess, the mesh portion, and the second recess are provided, and which closes the internal space at portions other than the inlet, the first outlet for discharging the liquid in the first recess, and the second outlet for discharging the liquid in the second recess.

[0015] The biological tissue processing device includes: 11. The biological tissue processing device according to claim 7, further comprising a downstream mesh section provided in the flow path between the upstream mesh section and the first recess, the downstream mesh section having a mesh size equal to or larger than that of the upstream mesh section, and causing the liquid that has passed through the mesh to flow into the second recess. The mesh sizes of the upstream mesh section and the downstream mesh section can each be set to an appropriate size depending on the use after separation. [Effects of the Invention]

[0016] The present invention can provide a technique that allows for easy processing of biological tissue. [Brief explanation of the drawings]

[0017] [Figure 1] FIG. 1 is a diagram showing a schematic configuration of a biological tissue processing system. [Figure 2] 2A and 2B are diagrams showing the configuration of a first outer cylinder in a first syringe device, in which FIG. 2A is a front view of the first outer cylinder, FIG. 2B is a diagram of the first outer cylinder seen from the tip side, and FIG. 2C is a diagram of the first outer cylinder seen from the rear end side. [Figure 3] 3A and 3B are diagrams showing the configuration of a first plunger used in a first syringe device, in which FIG. 3(A) is a front view of the first plunger, FIG. 3(B) is a view of the first plunger from the tip side, and FIG. 3(C) is a view of the first plunger from the rear end side. [Figure 4] 4A and 4B are diagrams showing the configuration of a second outer cylinder in a second syringe device, in which FIG. 4A is a front view of the second outer cylinder, FIG. 4B is a diagram of the second outer cylinder seen from the tip side, and FIG. 4C is a diagram of the second outer cylinder seen from the rear end side. [Figure 5] FIG. 10 is a diagram showing a modified example of the cutting unit. [Figure 6] FIG. 10 is a diagram showing a modified example of the cutting unit. [Figure 7] FIG. 10 is a diagram showing the configuration of a morcellation device according to a modified example. [Figure 8] 8A and 8B are diagrams showing the configuration of a first outer cylinder in a first syringe device, in which FIG. 8A is a front view of the first outer cylinder, FIG. 8B is a diagram of the first outer cylinder seen from the tip side, and FIG. 8C is a diagram of the first outer cylinder seen from the rear end side. [Figure 9] 9A and 9B are diagrams showing the configuration of the second outer tube 21 in the second syringe device, where FIG. 9A is a front view of the second outer tube 21, FIG. 9B is a diagram of the second outer tube 21 viewed from the tip side, and FIG. 9C is a diagram of the second outer tube 21 viewed from the rear end side. [Figure 10A] FIG. 1 shows steps of a dicing method. [Figure 10B] FIG. 1 shows steps of a dicing method. [Figure 11A] FIG. 2 is a plan view showing the inside of the protective housing with the cover open. [Figure 11B] FIG. 2 is a perspective view showing the external appearance of the protective housing with the cover closed. [Figure 12] FIG. [Figure 13] 10A and 10B are diagrams showing an example in which the first syringe device or the second syringe device to which the stopper is attached is housed in a protective housing. [Figure 14] FIG. 2 is a diagram showing the configuration of a sorting device. [Figure 15] FIG. 1 is an explanatory diagram of a separation method using a separation device. DETAILED DESCRIPTION OF THE INVENTION

[0018] First Embodiment A biological tissue processing system 100 according to a mode for carrying out the present invention (hereinafter referred to as an embodiment) will be described below with reference to the drawings. The configuration of the following embodiment is an example, and the present invention is not limited to the configuration of the embodiment. FIG. 1 is a diagram showing a schematic configuration of the biological tissue processing system 100. The biological tissue processing system 100 includes a pulverizing device 1 for pulverizing the biological tissue, a protective housing 5 used for storing and transporting the biological tissue, a fixing member (stopper) 6, and a sorting device 7 for sorting the pulverized tissue. However, the biological tissue processing system 100 may be configured without some elements or may include other elements. Examples of biological tissue include tumors excised from patients, but are not limited to this and may include other tissues. Furthermore, the living body is not limited to a human. The biological tissue processing system 100 of this embodiment is one form of a biological tissue processing device.

[0019] 《Shredder device》 The slicing device 1 is composed of a first syringe device 10, a second syringe device 20, a connecting part 17, and a slicing part 18. The first syringe device 10 has a first outer cylinder 11 and a first plunger (first pusher) 12, and the second syringe device 20 has a second outer cylinder 21 and a second plunger (second pusher) 22.

[0020] Figure 2 shows the configuration of the first outer cylinder 11 in the first syringe device 10, where Figure 2(A) is a front view of the first outer cylinder 11, Figure 2(B) is a view of the first outer cylinder 11 from the tip side, and Figure 2(C) is a view of the first outer cylinder 11 from the rear end side.

[0021] The first outer cylinder 11 has a generally cylindrical outer cylinder body 114, and a first space 115 extending in one direction (also referred to as the axial direction or the extension direction) from the front end to the rear end is formed inside. The first outer cylinder 11 also has a connecting structure 110 on the front side for connecting to the connecting part 17, and a flange (finger hook) 116 protruding radially from the outer peripheral surface of the cylinder is provided at the rear end. As shown in FIG. 2(C), a rear end opening 117 continuing to the first space 115 is formed at the rear end surface of the first outer cylinder 11.

[0022] In the connecting structure 110, a front tube (front end opening) 111, which has a smaller diameter than the outer tube body 114, and a lock tube 118 are arranged coaxially with the outer tube body 114. A female screw portion 112 for connecting to the connecting portion 17 is formed on the inner circumferential surface of the lock tube 118. The front tube 111 has an internal space 113 that runs from its front end to its rear end, and the internal space 113 communicates with the first space 115.

[0023] The first outer cylinder 11 is made of a transparent plastic. The material of the first outer cylinder 11 is not particularly limited, but may be, for example, metal, glass, or ceramic in addition to plastic. It is desirable that the first outer cylinder 11 be made of a transparent material so that the internal state can be seen during slicing.

[0024] 3A and 3B are diagrams showing the configuration of first plunger 12 used in first syringe device 10, with Fig. 3(A) being a front view of first plunger 12, Fig. 3(B) being a view of first plunger 12 as seen from the tip end side, and Fig. 3(C) being a view of first plunger 12 as seen from the rear end side. First plunger 12 has a rod-shaped rod portion 121, a gasket 122 provided at the tip end of rod portion 121, and a flange 123 provided at the rear end of rod portion 121.

[0025] The front end side of the first plunger 12 is inserted into the first space 115 from the rear end opening 117 of the first outer cylinder 11. The gasket 122 of the first plunger 12 inserted into the first space 115 contacts the inner peripheral surface of the first space 115, and in this state, the first plunger 12 is moved (advanced and retreated) toward the front end side or rear end side along the first space 115. That is, the first plunger 12 is able to advance and retreat while the gasket 122 at the front end contacts the inner peripheral surface of the first space 115 and maintains airtightness with the first space 115. Retained.

[0026] The first syringe device 10 may also have a cap 13 that closes the tip opening of the leading tube 111. The cap 13 of this embodiment is inserted between the leading tube 111 and the locking tube 118 and threadedly engages with a female thread portion 112 inside the locking tube 118 to close the tip opening of the leading tube 111. The cap 13 may be attached to the leading tube 111 by a configuration other than threaded coupling. For example, the cap 13 may have a blind hole into which the leading tube 111 is fitted, and when the leading tube 111 is fitted into this blind hole, the cap 13 may be tightly fitted onto the leading tube 111 by the elastic force of the cap 13. The cap 13 may also be configured to close the tip opening by being fitted into the internal space 113 from the tip opening of the leading tube 111.

[0027] Figure 4 is a diagram showing the configuration of the second outer cylinder 21 in the second syringe device 20, where Figure 4(A) is a front view of the second outer cylinder 21, Figure 4(B) is a view of the second outer cylinder 21 from the tip side, and Figure 4(C) is a view of the second outer cylinder 21 from the rear end side.

[0028] The second outer cylinder 21 has a generally cylindrical outer cylinder body 214, and a second space 215 extending in one direction (also referred to as the axial direction or the extension direction) from the front end to the rear end is formed inside the second outer cylinder 21. The front end of the second space 215 is provided with a connecting structure 210 for connecting to the connecting part 17, and the rear end is provided with a flange (finger hook) 216 provided so as to protrude radially from the outer peripheral surface of the cylinder. As shown in Fig. 4(C), a rear end opening 217 continuing to the second space 215 is formed on the rear end surface of the second outer cylinder 21.

[0029] The second outer cylinder 21 is made of a transparent plastic. The material of the second outer cylinder 21 is not particularly limited, but may be, in addition to plastic, metal, glass, or ceramic, for example. It is desirable that the second outer cylinder 21 be made of a transparent material so that the internal state can be seen during slicing.

[0030] The second outer cylinder 21 has a predetermined volume (1 cm in this example) from the tip of the second space 215. 3 ) along the outer circumferential surface of the second outer cylinder 21, a line is marked as an index (scale) 219 to indicate the rear end of the region.

[0031] The second plunger 22 (FIG. 1) has a rod-shaped rod portion 221, a gasket 222 provided at the tip of the rod portion 221, and a flange 223 provided at the rear end of the rod portion 221. The second plunger 22 has the same configuration as the first plunger 12, and the rod portion 221, gasket 222, and flange 223 of the second plunger 22 are the same as the rod portion 121, gasket 122, and flange 123 of the first plunger 12, so a repeated description will be omitted.

[0032] 5 is a diagram showing the configuration of the connecting portion 17. In the connecting structure 210, a front tube 211, which has a smaller diameter than an outer tube body 214 that surrounds a second space 215, and a lock tube 208 are coaxially connected to the outer tube body 214. The front tube 211 has an internal space 213 that runs through it from its front end to its rear end, and the internal space 213 communicates with the second space 215. A female thread portion 212 for connecting to the connecting portion 17 is formed on the inner circumferential surface of the lock tube 208.

[0033] Connecting portion 17 is a generally cylindrical member, and has connecting structures 171 at both ends for connecting to first syringe device 10 or second syringe device 20. Connecting structures 171 in this embodiment are male threaded portions provided on the outer periphery of both ends of connecting portion 17. Note that connecting structure 171 is not limited to screws, and may be any other structure as long as it can be connected to first syringe device 10 or second syringe device 20. Also, connecting portion 17 has internal space 172 that penetrates from end to end.

[0034] When the first syringe device 10 and the second syringe device 20 are connected, the internal spaces 113, 213, 172 of the front cylinder 111, 211 and the connecting portion 17 become a communication passage that connects the first space 115 and the second space 215. This allows biological tissue or liquid (hereinafter also referred to as tissue preservation solution) placed in the first syringe device 10 or the second syringe device 20 to move in the axial direction (X direction) between the first space 115 and the second space 215 via the communication passage. The tissue preservation solution is a liquid used to suspend and preserve or transport minced tissue or cells obtained by decomposing this tissue, and examples thereof include physiological saline, Ringer's solution, liquid culture medium, serum, and mixtures thereof.

[0035] The finely cutting unit 18 is provided within the internal space of the connecting unit 17 and divides the internal space 172 into a first space side and a second space side. In this embodiment, the finely cutting unit 18 is a mesh having multiple openings (mesh) on a plane perpendicular to the moving direction (X direction) of the biological tissue. The finely cutting unit 218 is not limited to a mesh, and may be any member having multiple openings that divides biological tissue by passing through the openings. FIG. 6 shows a modified example of the finely cutting unit 218. For example, a plurality of thin blades 281, such as razor or cutter blades, are arranged in parallel with slit-like gaps 282 between them, with the blade 28A of each thin blade 281 facing either the first space side or the second space side. In this embodiment, the finely cutting unit 218 is provided only in the second syringe device 20. However, the finely cutting unit 218 may be provided only in the first syringe device 10. The finely cutting unit 218 may also be provided in both the first syringe device 10 and the second syringe device 20. Alternatively, the slitting portion 18 may be provided at either end of the connecting portion 17, i.e., between the first syringe device 10 or the second syringe device 20.

[0036] <<Variations>> In the above-described embodiment, the first and second syringe devices 10, 20 and the connecting part 17 are configured separately, but at least one of the first and second syringe devices and the connecting part may be configured integrally. Figure 7 shows the configuration of a morcellating device 1A according to a modified example.

[0037] The morcellating device 1A is composed of a first syringe device 10A and a second syringe device 20A. The first syringe device 10A has a first outer cylinder 11 and a first plunger (first pusher) 12, and the second syringe device 20A has a second outer cylinder 21 and a second plunger (second pusher) 22.

[0038] Figure 8 shows the configuration of the first outer cylinder 11A in the first syringe device 10A, where Figure 8(A) is a front view of the first outer cylinder 11A, Figure 8(B) is a view of the first outer cylinder 11A from the tip side, and Figure 8(C) is a view of the first outer cylinder 11A from the rear end side.

[0039] First outer cylinder 11A includes a generally cylindrical outer cylinder body 114, and a first space 115 extending in one direction (also referred to as the axial direction or the extension direction) from the front end to the rear end is formed therein. First outer cylinder 11A also includes a connecting structure 110A on the front side for connecting to second syringe device 20A, and a flange (finger hook) 116 protruding radially from the outer peripheral surface of the cylinder is provided at the rear end. A rear end opening 117 that continues to first space 115 is formed at the rear end surface of first outer cylinder 11A, as shown in FIG. 8(C).

[0040] In connecting structure 110A, leading tube 111, which has a smaller diameter than outer tube body 114, is connected coaxially to outer tube body 114. A male thread portion 112A for connecting to second syringe device 20A is formed on the outer peripheral surface of leading tube 111. That is, leading tube 111 is a bolt type that functions as a male thread when connected. Lead tube 111 has internal space 113 that runs from its front end to its rear end, and internal space 113 communicates with first space 115.

[0041] The first outer cylinder 11A is made of transparent plastic. The material is not particularly limited, and may be, in addition to plastic, metal, glass, ceramic, etc. It is desirable that the first outer cylinder 11A be made of a transparent material so that the inside state can be seen during shredding.

[0042] The first syringe device 10A may also have a cap 13 that closes the tip opening of the leading tube 111. The cap 13 of this embodiment is a screw cap that screws into the male thread portion 112A of the leading tube 111. Note that the cap 13 may be attached to the leading tube 111 by other means than threaded coupling. For example, the cap 13 may have a blind hole into which the leading tube 111 is fitted, and when the leading tube 111 is fitted into this blind hole, the cap 13 may be tightly fitted into the leading tube 111 by the elastic force of the cap 13. The cap 13 may also be configured to be fitted into the internal space 113 from the tip opening of the leading tube 111, thereby closing the tip opening.

[0043] Figure 9 shows the configuration of the second outer cylinder 21 in the second syringe device 20A, where Figure 9(A) is a front view of the second outer cylinder 21, Figure 9(B) is a view of the second outer cylinder 21 from the tip side, and Figure 9(C) is a view of the second outer cylinder 21 from the rear end side.

[0044] Second outer cylinder 21 has a generally cylindrical outer cylinder body 214, and a second space 215 extending in one direction (also referred to as the axial direction or the extension direction) from the front end to the rear end is formed therein, with a slit portion 218 disposed at the front end of second space 215. Second outer cylinder 21 also has a connecting structure 210 on the front side for connecting to first syringe device 10A, and a flange (finger hook) 216 provided at the rear end so as to protrude radially from the outer peripheral surface of the cylinder. As shown in FIG. 9(C), a rear end opening 217 continuing to second space 215 is formed at the rear end surface of second outer cylinder 21.

[0045] In coupling structure 210, leading tube 211, which has a smaller diameter than outer tube body 214 and surrounds second space 215, is connected coaxially to outer tube body 214. Lead tube 211 has internal space 213 that penetrates from its front end to its rear end, and internal space 213 communicates with second space 215. An internal thread portion 212 for coupling to first syringe device 10A is formed on the inner circumferential surface of leading tube 211. That is, leading tube 211 is a nut type that functions as an internal thread portion when coupled.

[0046] When the first syringe device 10A and the second syringe device 20A are connected, the internal spaces 113, 213 of the front cylinders 111, 211 become a communication passage that connects the first space 115 and the second space 215. This allows biological tissue or liquid (hereinafter also referred to as tissue preservation solution) placed in the first syringe device 10A or the second syringe device 20A to move in the axial direction (X direction) between the first space 115 and the second space 215 via the communication passage. The tissue preservation solution is a liquid used to suspend and preserve or transport minced tissue or cells obtained by decomposing this tissue, and examples thereof include physiological saline, Ringer's solution, liquid culture medium, serum, and mixtures thereof.

[0047] The thin-slicing unit 218 is provided at the boundary between the communication passage and the second space 215, and divides the connected space consisting of the first space 115, the second space 215, and the communication passage into two spaces, one on the first space side and the other on the second space side. In this embodiment, the thin-slicing unit 218 is a mesh having multiple openings in a plane perpendicular to the moving direction (X direction) of the biological tissue. The thin-slicing unit 218 is not limited to a mesh, and may be any member having multiple openings that divides biological tissue by passing through these openings. FIG. 5 shows a modified example of the thin-slicing unit 218. For example, a plurality of thin blades 281, such as razor or cutter blades, are arranged in parallel with slit-like gaps 282 between them, with the blade 28A of each thin blade 281 facing either the first space side or the second space side. In this embodiment, the thin-slicing unit 218 is provided only in the second syringe device 20A, but the thin-slicing unit 218 may be provided only in the first syringe device 10A. The cutting portion 218 may be provided in both the first syringe device 10A and the second syringe device 20A. , 213, that is, in the communication passage.

[0048] The second outer cylinder 21 is made of a transparent plastic. The material of the second outer cylinder 21 is not particularly limited, but may be, in addition to plastic, metal, glass, or ceramic, for example. It is desirable that the second outer cylinder 21 be made of a transparent material so that the internal state can be seen during slicing.

[0049] The second outer cylinder 21 has lines marked as indicators (scales) 219 along the outer surface of the second outer cylinder 21 so as to indicate the rear end of a region having a predetermined volume (1 cm3 in this example) from the tip of the second space 215.

[0050] ≪Shredded method≫ Next, a method for slicing biological tissue using the slicing device 1 will be described. FIGS. 10A and 10B are diagrams illustrating steps of the slicing method. In step A, the cap 13 is attached to the first syringe device 10 in its initial state, with the tissue preservation solution 80 filled in the first space 115. Meanwhile, the second syringe device 20 in its initial state has the second space 215 empty, and the excised biological tissue 81 is placed into the second space 215 through the rear end opening 217 of the second outer cylinder 21. At this time, by adjusting the amount of biological tissue so that the rear end (upper end in the position shown in the figure) of the biological tissue 81 placed in the tip portion of the second space 215 reaches the indicator 219, a predetermined amount of biological tissue 81 (approximately 1 g in this embodiment) can be placed.

[0051] In step B, second plunger 22 is fitted into second outer cylinder 21 containing biological tissue 81, and second plunger 22 is moved toward the tip end so as to expel excess air. Then, front cylinder 211 of second syringe device 20 is screwed onto front cylinder 111 of first syringe device 10 from which cap 13 has been removed, thereby connecting first syringe device 10 and second syringe device 20, and connecting first space 115 and second space 215.

[0052] In step C, the first plunger 12 on the first syringe device 10 side is moved toward the tip, and the tissue preservation solution 80 in the first space 115 is moved toward the second space 215. In step D, the second plunger 22 on the second syringe device 20 side is moved toward the tip, and the tissue preservation solution 80 in the second space 215 is moved toward the first space 115, and the biological tissue 81 is moved toward the first space 115 together with the tissue preservation solution 80. At this time, the biological tissue 81 is pressed against the mesh-like shredding section 218 by the pressure of the moving tissue preservation solution 80, and is shredded by passing through the openings in the mesh.

[0053] In step E, the first plunger 12 of the first syringe device 10 is moved toward the tip, and the tissue preservation solution 80 in the first space 115 is moved toward the second space 215 together with the biological tissue 81. The biological tissue 81 is again chopped as it passes through the chopping unit 18. Steps D and E are then repeated a predetermined number of times (e.g., more than ten times) to chop the biological tissue 81 into the desired size. When repeating steps D and E, the first syringe device 10 and the second syringe device 20 may be temporarily disconnected, and a drug for treating the biological tissue 81, such as trypsin or polyethylene glycol, or other cells to be fused with the cells of the biological tissue 81, may be added to the tissue preservation solution. Alternatively, the chopping unit 218 may be replaced with one having a smaller opening, or another chopping unit (mesh) having a smaller opening than the chopping unit 18 provided in the connecting unit may be added between the first syringe device 10 or the second syringe device 20 and the connecting unit 17, to further chop the biological tissue 81 into smaller pieces.

[0054] In step F, the second plunger 22 on the second syringe device 20 side is moved to the tip side, and the living tissue 81 after cutting is moved to the first space 115 side together with the tissue preservation solution 80. In this state, the second syringe device 20 is removed from the first syringe device 10, and the cap 13 is attached to the front tube 111 of the first syringe device 10 to complete the cutting process. Although the tissue is contained in the first syringe device 10, it may also be contained in the second syringe device 20.

[0055] As described above, according to this embodiment, biological tissue can be minced by a simple operation such as moving the first plunger 12 or the second plunger 22 back and forth, thereby reducing the operator's workload. Furthermore, according to this embodiment, biological tissue can be quickly minced, thereby reducing contamination and damage to the biological tissue due to mincing. In particular, in this embodiment, the biological tissue is minced in a closed, connected space, effectively reducing the possibility of contamination. Furthermore, the size of the biological tissue after mincing can be set by adjusting the size of the opening in the mincing section and the number of repetitions of steps D and E, etc., thereby reducing variations in processing due to factors such as the operator's level of skill, and achieving consistent processing results.

[0056] <Storage and transportation of minced tissue> The biological tissue processing system 100 is equipped with a protective housing 5 for storing or transporting the biological tissue after it has been minced. Fig. 11A is a plan view showing the inside of the protective housing 5 with the lid open, and Fig. 11B is a perspective view showing the appearance of the protective housing 5 with the lid closed.

[0057] The protective housing 5 has a roughly rectangular parallelepiped outer shape and includes an outer shell 51 that defines six sides of the rectangular parallelepiped, and a buffer material 52 disposed in the internal space of the outer shell 51. The buffer material 52 is provided with a plurality of recesses 521 shaped to fit the first syringe device 10 with the cap 13 attached. At this time, the first syringe device 10 contains the tissue preservation solution and the minced biological tissue in the first space 115, and the first plunger 12 is retracted. The inner surface of the recess 521 is shaped to fit along the outer surface of the first outer cylinder 11 so that, when the first syringe device 10 is housed, there is no unnecessary gap (play) between the outer surface of the first syringe device 10 and the inner surface of the recess 521. In particular, recess 521 in this embodiment has mating recess 522 into which flange 116 of first outer cylinder 11 fits, and also has outer cylinder mating portion 523 into which outer cylinder body 114 and cap 13 fit. Outer cylinder mating portion 523 is a recess that has the same external shape as outer cylinder body 114 with cap 13 attached, and this shape makes it possible to determine the direction in which first syringe device 10 should be fitted.

[0058] 11A , when first syringe device 10 is fitted into recess 521, flange 116 engages with mating recess 522, restricting movement of outer barrel body 114 primarily in the X direction, and the outer peripheral surface of outer barrel body 114 abuts against the inner surface of outer barrel mating portion 523, restricting movement of outer barrel body 114 primarily in the Y direction. Fixing first outer barrel 11 to recess 521 in this manner prevents first syringe device 10 from rattling within protective housing 5, so the inner surface of recess 521 located around first plunger 12 does not necessarily need to be aligned with the outer surface of first plunger 12. For example, there may be a gap between first plunger 12 and recess 521 to the extent that it does not compress first plunger 12.

[0059] 11A and 11B , housing the first plunger 12 in the protective housing 5 prevents the first plunger 12 from moving due to unintended external forces or vibrations during transportation. This prevents the first plunger 12 from moving toward the distal end, causing leakage of the tissue preservation solution and biological tissue, or from retracting and becoming detached from the first outer cylinder 11. By storing the syringe in a refrigerator or freezer or transporting it in this state, the syringe can be stored or transported stably. While the above description mainly shows an example in which the first syringe device 10 is housed in the protective housing 5, the second syringe device 20 containing the slicing of biological tissue or the tissue preservation solution can also be housed in the protective housing 5, similar to the first syringe device 10.

[0060] The biological tissue processing system 100 may also include a stopper 6 for fixing the first plunger 12 when storing or transporting the biological tissue after pulp cutting. Fig. 12 is an external perspective view of the stopper 6, and Fig. 13 is a perspective view of the first syringe device 10 or the second syringe device 12 with the stopper 6 attached. 10 is a diagram showing an example in which the device 20 is housed in a protective housing 5. FIG.

[0061] The stopper 6 has an outer tube side engaging portion 61 that engages with a part of the first outer tube 11 (in this example, the flange 116), and a plunger side engaging portion 62 that engages with a part of the first plunger 12 (in this example, the flange 123). The stopper 6 also has a connecting rod 63 that connects the outer tube side engaging portion 61 and the plunger side engaging portion 62 so as to fix the relative positions of the outer tube side engaging portion 61 and the plunger side engaging portion 62.

[0062] The outer tube side engaging portion 61 of the stopper 6 has a slit 611 extending in a direction perpendicular to the longitudinal direction (X direction) of the connecting rod 63, and the outer tube side engaging portion 61 is attached so that the flange 116 is inserted into the slit 611 from the radial outside of the first outer tube 11, thereby engaging the outer tube side engaging portion 61 with the flange 116. In addition, the plunger side engaging portion 62 of the stopper 6 has a slit 621 extending in a direction perpendicular to the longitudinal direction of the connecting rod 63, and the plunger side engaging portion 62 is attached so that the flange 123 is inserted into the slit 621 from the radial outside of the first plunger 12, thereby engaging the plunger side engaging portion 62 with the flange 123.

[0063] When the stopper 6 is attached to the first syringe device 10 in this manner and the outer tube side engaging portion 61 and the plunger side engaging portion 62 engage with the flanges 116, 123 of the first syringe device 10, the first plunger 12 is fixed relatively to the first outer tube 11. This prevents the first plunger 12 from moving due to unintended external forces or vibrations during transportation. That is, it prevents the first plunger 12 from moving toward the tip side, causing leakage of the tissue preservation solution and biological tissue, and the first plunger 12 from retracting and becoming detached from the first outer tube 11. By storing the syringe in a refrigerator or freezer or transporting it in this state, the syringe can be stored or transported stably.

[0064] In the above explanation, an example of attaching the stopper 6 to the first syringe device 10 has been mainly shown, but the stopper 6 can also be attached to the second syringe device 20 containing the sliced ​​biological tissue or tissue preservation solution in the same manner.

[0065] 13, first syringe device 10 or second syringe device 20 equipped with stopper 6 may be housed in protective housing 5. This allows for even more stable storage and transportation. When first syringe device 10 or second syringe device 20 equipped with stopper 6 is housed in protective housing 5, the inner surface of recess 521 may be configured to have the same outer shape as first syringe device 10 or second syringe device 20 equipped with stopper 6, or the shape may be the same as the example in FIG. 810A, and stopper 6 may be fitted by elastically deforming the inner surface of recess 521.

[0066] <Sorting of minced tissue> 14 is a diagram showing the configuration of the separation device 7. The separation device (separation unit) 7 is a device that separates the biological tissue after shredding according to purpose. The separation device 7 may be one form of a biological tissue processing device. The separation device 7 has an external housing 71 having an internal space 70 therein, an injection port 72 provided at the top of the external housing 71, a first discharge port 73 provided at the bottom end of the external housing 71, and a second discharge port 74 provided at the bottom of the external housing 71 at a position higher than the first discharge port 73.

[0067] The external housing 71 defines an internal space 70 and closes the internal space 70 so that outside air does not enter except from specific locations such as the inlet 72, first outlet 73, and second outlet 74. The lower surface of the external housing 71, particularly the inner wall surface defining the lower surface of the internal space 70, forms an inclined surface 711 that is inclined in a predetermined direction.

[0068] Inlet 72 is connected to front tube 111 of first outer tube 11 or front tube 211 of second outer tube 21, and tissue preservation solution containing slicing biological tissue is injected through inlet 72. Inclined surface 711 is formed to be relatively high directly below inlet 72 and to become lower toward first outlet 73, and the liquid injected through inlet 72 flows down from directly below the inlet in a direction (predetermined direction) toward first outlet 73 according to the inclination of inclined surface 711.

[0069] A first recess 712 is formed in the lower part of the external housing 71, downstream of the inclined surface 711. The first recess 712 has a downwardly recessed shape so that the tissue preservation solution that has flowed down along the inclined surface 711 flows into it. A first discharge port 73 is provided at the lower end of the first recess 712, which discharges the tissue preservation solution in the first recess 712 to the outside. The first discharge port 73 is equipped with a one-way valve 731 that can open and close an opening for discharging the tissue preservation solution to the outside.

[0070] Additionally, an upstream mesh section 713 having openings (mesh) of a predetermined size is disposed upstream of the first recess 712 in the lower part of the external housing 71, along a path (flow path) along which the tissue preservation solution flows from directly below the injection port to the first recess 712. The upstream mesh section 713 constitutes part of the flow path, and biological tissue larger than the openings flows downstream together with the tissue preservation solution. Additionally, a downstream mesh section 715 is provided in the flow path between the upstream mesh section 713 and the first recess 712, directly above the first recess 712 in this example. The downstream mesh section 715 has meshes (openings) larger than those of the upstream mesh section 713, and allows biological tissue that passes through the meshes to flow into the first recess 712 together with the tissue preservation solution. The mesh sizes of the upstream mesh section 713 and the downstream mesh section 715 can be appropriately adjusted depending on the intended use after separation.

[0071] A second recess 714 is formed below the mesh portion 713, into which the tissue preservation solution that has passed through the openings in the mesh portion 713 and deviated from the flow path flows. The second recess 714 has a downwardly recessed shape so that the tissue preservation solution and living tissue that have passed through the mesh portion 713 flow into it. A second release port 74 is provided at the lower end of the second recess 714, which releases the tissue preservation solution in the second recess 714 to the outside. The second release port 74 is equipped with a one-way valve 741 that can open and close the opening for releasing the tissue preservation solution to the outside.

[0072] Although external housing 71 of the present embodiment closes internal space 70 in areas other than injection port 72, first outlet 73, and second outlet 74, external housing 71 may have an air vent valve that releases to the outside air displaced within internal space 70 by injection of tissue preservation solution into internal space 70 from injection port 72 and blocks the inflow of outside air into internal space 70. However, this is not limiting, and instead of sealing the gap between first syringe device 10 and injection port 72 when first syringe device 10 is connected to injection port 72, a small gap may be provided that allows air within internal space 70 to be pushed out when positive pressure is created within internal space 70 by injection.

[0073] 15 is an explanatory diagram of the separation method using the separation device 7. In step α, the front tube 111 of the first syringe device 10 is connected to the injection port 72, and the first plunger 12 is moved toward the tip side to inject the shredded biological tissue into the internal space 70 together with the tissue preservation solution.

[0074] In step β, the injected tissue preservation solution flows down along the inclination of the inclined surface 711 , passes through the mesh portion 713 and flows into the second recess 714 , and also passes over the mesh portion 713 and flows into the first recess 712 .

[0075] In step γ, the first syringe device 10 is removed from the injection port 72, and the one-way valve 731 of the first discharge port 73 is opened to discharge the tissue preservation solution in the first recess 712 to the outside. The biological tissue contained in the tissue preservation solution discharged from the first discharge port 73 is used for, for example, D culture or S culture.

[0076] In step δ, the one-way valve 741 of the second release port 74 is opened to release the tissue preservation solution in the second recess 714 to the outside. The biological tissue contained in the tissue preservation solution released from this second release port 74 is used for, for example, C culture.

[0077] The biological tissue contained in the tissue preservation solution released from this second release port 74 has a size that allows it to pass through the openings of the mesh portion 713. Therefore, for example, by setting the openings of the mesh portion 713 to match the size of the biological tissue to be used for C culture, it is possible to separate the biological tissue to be used for C culture from other tissue. In other words, the sorting device 7 can sort the biological tissue after shredding according to the purpose. This reduces the effort required to cut the biological tissue according to the desired culture conditions, and makes it easier to process the biological tissue. Furthermore, since the sorting device 7 of this embodiment performs sorting within the closed internal space 70, it is possible to effectively suppress the occurrence of contamination.

[0078] 15 shows an example in which the tissue preservation solution is injected into the separation device 7 using the first syringe device 10, but the tissue preservation solution may also be injected into the separation device 7 using the second syringe device 20. Furthermore, a configuration may be adopted in which tissue preservation solution containing biological tissue that has been minced by a means other than the mincing device 1 is placed in a container such as a beaker, and the tissue preservation solution is injected from this container into the separation device 7. In this embodiment, the storage or release of the tissue preservation solution is performed by opening and closing the one-way valves 731 and 741. However, if the injected tissue preservation solution is not stored in the internal space 70 but is immediately released, the one-way valves 731 and 741 may be omitted. Furthermore, the first release port 73 and the second release port 74 may have a connection portion for connecting the first syringe device 10 or the second syringe device 20, and the tissue preservation solution may be sucked out using the first syringe device 10 or the second syringe device 20.

[0079] As described above, the biological tissue processing system 100 of this embodiment performs processes such as cutting, preserving, transporting, and sorting within the limited space of the first syringe device 10, the second syringe device 20, and the sorting device 7, making it easy to perform the processes and effectively suppressing the occurrence of contamination. [Explanation of symbols]

[0080] 1 Shredding device 5 Protective housing 6 Fixing member (stopper) 7 Sorting device (sorting section) 10 First syringe device (first syringe device) 11 First outer cylinder 12 First plunger 13 Cap 20 Second syringe device (second syringe device) 21 Second outer cylinder 22 Second plunger 51 Outer shell 52 Cushioning material 61 outer cylinder side engagement portion 62 Pusher side engagement portion 63 Connecting rod 70 Interior Space 71 External enclosure 72 Inlet 73 First outlet 74 Second outlet 80 Tissue preservation solution 81 Biological Tissue 100 Biological tissue processing system 110 Connection structure 111,211 Nozzle 112 Male thread 113,213 interior space 114 Outer cylinder body 115 First space 116,123 flanges 117 Rear end opening 121 Rod 122 Gasket 123 flange 210 Connection structure 211 Nozzle 212 Female thread 213 Interior Space 214 Outer cylinder body 215 Second space 216,223 Flanges 217 Rear end opening 218 Shredded section 219 scale) 219 indicators 221 Rod 222 Gasket 281 Thin Blade 282 Gap 521 depression 522 Joint recess 523 Outer tube joint 611 Slit 621 Slit 711 Slope 712 First depression 713 Reticulum 714 Second depression 731,741 One-way valve

Claims

1. a connecting portion that connects a tip opening portion of a first syringe device including a first outer cylinder having a first space extending in one direction therein and a first pusher that is inserted into the first space from a rear end opening of the first outer cylinder and held so as to be movable back and forth along the extension direction of the first space, to a tip opening portion of a second syringe device including a second outer cylinder having a second space extending in one direction therein and a second pusher that is inserted into the second space from a rear end opening of the second outer cylinder and held so as to be movable back and forth along the extension direction of the second space, and that connects the first space with the second space; a shredding unit that is provided in a communication passage formed between the first space and the second space by communicating the first space and the second space, and that shreds the biological tissue moving between the first space and the second space via the communication passage; A separating unit that separates the biological tissue after cutting; Equipped with The sorting unit is an injection port connected to the tip of the first outer cylinder or the tip of the second outer cylinder, through which a liquid containing the shredded biological tissue is injected; an inclined surface that forms at least a part of a flow-down path that allows the liquid injected from the injection port to flow down in a predetermined direction; a first depression disposed downstream of the inclined surface and into which the liquid that has flowed down along the inclined surface flows; an upstream mesh portion that constitutes a part of the flow path, is arranged upstream of the first recess, and has a mesh size of a predetermined size; a second recess into which the liquid that has passed through the mesh of the upstream mesh portion and deviated from the flow-down path flows; a downstream mesh section that is provided in the flow path between the upstream mesh section and the first recess, has mesh openings that are larger than or equal to mesh openings of the upstream mesh section, and causes the liquid that has passed through the mesh openings to flow into the first recess; having Biological tissue processing device.

2. a first outer cylinder having a first space therein extending in one direction; and a first pusher inserted into the first space from a rear end opening of the first outer cylinder and held so as to be movable forward and backward along the extension direction of the first space. a first syringe device having a plunger; a second syringe device including: a second outer cylinder having a second space therein extending in one direction; and a second plunger inserted into the second space from a rear end opening of the second outer cylinder and held so as to be movable forward and backward along the extension direction of the second space; a connecting portion that connects a tip opening of the first syringe device and a tip opening of the second syringe device and communicates the first space with the second space; a communication passage formed between the first space and the second space by communicating the first space and the second space, a shredding unit that is provided in a connected space consisting of the first space and the second space at a position that divides the connected space into at least two spaces, one on the side of the first space and the other on the side of the second space, and that shreds the living tissue that moves between the first space and the second space via the communication passage; A separating unit that separates the biological tissue after cutting; Equipped with The sorting unit is an injection port connected to the tip of the first outer cylinder or the tip of the second outer cylinder, through which a liquid containing the shredded biological tissue is injected; an inclined surface that forms at least a part of a flow-down path that allows the liquid injected from the injection port to flow down in a predetermined direction; a first depression disposed downstream of the inclined surface and into which the liquid that has flowed down along the inclined surface flows; an upstream mesh portion that constitutes a part of the flow path, is arranged upstream of the first recess, and has a mesh size of a predetermined size; a second recess into which the liquid that has passed through the mesh of the upstream mesh portion and deviated from the flow-down path flows; a downstream mesh section that is provided in the flow path between the upstream mesh section and the first recess, has mesh openings that are larger than or equal to mesh openings of the upstream mesh section, and causes the liquid that has passed through the mesh openings to flow into the first recess; having Biological tissue processing device.

3. 3. The biological tissue processing device according to claim 1, wherein the shredding unit is a mesh having a plurality of openings in a plane perpendicular to the moving direction of the biological tissue.

4. 4. The biological tissue processing device according to claim 1, wherein a liquid is present in at least one of the first space and the second space, and the liquid is moved between the first space and the second space by moving the first plunger or the second plunger back and forth, and the biological tissue is moved in accordance with the movement of the liquid.

5. The biological tissue processing device according to claim 4 , further comprising a fixing member that fixes a relative position of the first plunger when the first plunger is moved back and forth relative to the first outer cylinder while the liquid is contained in the first space.

6. The fixing member is an outer cylinder side engaging portion that engages with a part of the first outer cylinder; a pusher-side engaging portion that engages with a part of the first pusher; a connecting rod that connects the outer tube side engaging portion and the plunger side engaging portion so as to fix the relative positions of the outer tube side engaging portion and the plunger side engaging portion; The biological tissue processing device according to claim 5 , comprising:

7. the sorting section has an internal space in which the inclined surface, the first recess, the upstream mesh section, and the second recess are provided, and the sorting section has the inlet and a first outlet for discharging the liquid in the first recess.

2. The biological tissue processing device according to claim 1, further comprising an outer casing that closes the internal space except for a second outlet that discharges the liquid in the second recess.

8. an injection port into which a liquid containing minced biological tissue is injected; an inclined surface that forms at least a part of a flow-down path that allows the liquid injected from the injection port to flow down in a predetermined direction; a first depression disposed downstream of the inclined surface and into which the liquid that has flowed down along the inclined surface flows; an upstream mesh portion that constitutes a part of the flow path, is arranged upstream of the first recess, and has a mesh size of a predetermined size; a second recess into which the liquid that has passed through the mesh of the upstream mesh portion and deviated from the flow-down path flows; a downstream mesh section that is provided in the flow path between the upstream mesh section and the first recess, has mesh openings that are larger than or equal to mesh openings of the upstream mesh section, and causes the liquid that has passed through the mesh openings to flow into the first recess; A biological tissue processing device comprising:

9. 9. The biological tissue processing device according to claim 8, further comprising an external housing having an internal space in which the inclined surface, the first recess, the upstream mesh portion, and the second recess are provided, and which closes the internal space at a portion other than the inlet, a first outlet for discharging the liquid in the first recess, and a second outlet for discharging the liquid in the second recess.

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