Biological tissue cutting device and method of producing tissue fragments using same

Abstract

Provided is a miniaturizable biological tissue cutting device enabling simple and efficient production of minute tissue fragments from biological tissue.　This biological tissue cutting device (1) comprises: first and second cutting units (20, 30) that are interchangeable; and a device body (10). The device body (10) comprises a sample stage (13), a stage holder (12), a mounting unit (14), and a movement unit (15). The sample stage (13) rotates about the Z-axis of the device body (10), and the movement unit (15) causes the mounting unit (14) to move in the X-axis direction. In a state of having been mounted on the mounting unit (14), the first cutting unit (20) comprises a first blade (22) opposing the XZ-plane, and the second cutting unit (30) comprises a second blade (32) opposing the XZ-plane and a third blade (33) opposing the XY-plane. The mounting unit (14), onto which the first cutting unit (20) has been mounted, is moved by the movement unit (15) in the X-axis direction to cut biological tissue. Replacement with the second cutting unit (30) is performed and the sample stage (13) is rotated, the mounting unit (14) is moved by the movement unit in the X-axis direction, and biological tissue is cut again. Tissue fragments are thereby cut out of the biological tissue.

Description

Biological tissue cutting device and method for producing tissue pieces using the same

[0001] The present invention relates to a biological tissue cutting device for cutting biological tissue to produce tissue pieces, and to uses thereof.

[0002] In the field of regenerative medicine, a method has been proposed in which tissue is harvested from a living body, a tissue fragment is excised from the tissue, and then transplanted back into the living body. This method allows the tissue to be harvested from a patient, a tissue fragment is excised from the tissue, and the tissue fragment is transplanted back into the patient as a series of processes, all in one surgical procedure. In other words, regenerative medicine can be performed entirely within the operating room. This method also enables treatment to be performed at low cost and with minimal burden on patients and physicians.

[0003] In this method, if the size of the tissue fragment is large, there is a risk that the supply of nutrients to the inside of the tissue fragment in the living body after transplantation and the engraftment of the tissue fragment may be insufficient. Furthermore, it is important to obtain as many tissue fragments as possible that serve as the source of regeneration from a limited amount of tissue. For these reasons, there is a demand for a technology that can reliably cut out a large amount of fine, uniform-sized tissue fragments.

[0004] Therefore, the present applicant has developed a cutting device capable of cutting out minute tissue pieces (Patent Document 1). The cutting device is an apparatus in which a first cutting unit and a second cutting unit are respectively arranged to cut out hexahedral tissue pieces. The first unit has a blade that cuts out a first cutting surface, and the second cutting unit has a blade that simultaneously cuts out second and third cutting surfaces that intersect with the first cutting surface. This cutting device cuts out multiple first cutting surfaces by repeatedly moving the first cutting unit in the same direction relative to the tissue. Subsequently, it cuts out multiple second and third cutting surfaces by repeatedly moving the second cutting unit in the same direction relative to the tissue. This allows for the production of a large number of hexahedral tissue pieces cut out using a pair of first cutting surfaces, a pair of second cutting surfaces, and a pair of third cutting surfaces.

[0005] International Publication WO2015 / 052225

[0006] In the case of regenerative medicine, as mentioned above, the cutting device can be used in the surgical field, and therefore, in view of the importance of pre-operative maintenance, cleaning to prevent contamination, etc., it is desirable for the device to be small and easily portable.

[0007] Therefore, an object of the present invention is to provide a biological tissue cutting device that can easily and efficiently produce minute tissue pieces from biological tissue and that can be made compact.

[0008] In order to achieve the above object, the biological tissue cutting device of the present invention comprises an exchangeable cutting set for cutting biological tissue and an apparatus main body; the cutting set comprises: a first cutting unit and a second cutting unit; the apparatus main body comprises: a sample stage on which the biological tissue is placed, a stage holder to which the sample stage is detachably attached, a mounting unit to which the cutting units are detachably attached, and a movement unit for moving the mounting unit; based on the coordinate axes of the apparatus main body, the sample stage is rotatable about the Z axis of the sample stage, and the movement unit moves the mounting unit in the X axis direction; the mounting unit is an attachment unit common to the first cutting unit and the second cutting unit and is exchangeable between them; the first cutting unit comprises a first blade, and the first blade faces the XZ plane when the first cutting unit is attached to the mounting unit, and the second cutting unit comprises a second blade and a third blade, When the second cutting unit is attached to the attachment unit, the second blade faces the XZ plane and the third blade faces the XY plane; the attachment unit to which the first cutting unit is attached is moved in the X-axis direction by the moving unit, thereby cutting the biological tissue with the first cutting unit; the first cutting unit is replaced with the second cutting unit and the sample stage is rotated; the attachment unit to which the second cutting unit is attached is moved in the X-axis direction by the moving unit, thereby cutting the biological tissue with the second cutting unit, thereby cutting out tissue pieces from the biological tissue.

[0009] The method for producing tissue pieces from biological tissue of the present invention uses the biological tissue cutting device of the present invention, and includes the steps of: placing the biological tissue on the sample stage; a first cutting step of cutting the biological tissue by moving the mounting unit, to which the first cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a first cut surface by the first blade of the first cutting unit; a replacement step of detaching the first cutting unit from the mounting unit and replacing it with the second cutting unit; a rotation step of rotating the sample stage; and a second cutting step of cutting the biological tissue by moving the mounting unit, to which the second cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a second cut surface by the second blade of the second cutting unit and a third cut surface by the third blade, wherein the method is characterized in that the first cut surface and the second cut surface intersect, and the first cut surface and the second cut surface intersect with the third cut surface, to obtain a tissue piece.

[0010] The main body of the biological tissue cutting device of the present invention has a sample stage on which the biological tissue is placed, a stage holder to which the sample stage can be attached and detached, an attachment unit to which the cutting unit can be attached and detached, and a moving unit that moves the attachment unit; based on the coordinate axes of the main body of the device, the sample stage can rotate around the Z axis of the sample stage, the moving unit moves the attachment unit in the X axis direction, and the attachment unit is an attachment unit common to multiple cutting units, and is characterized by being used in the biological tissue cutting device of the present invention.

[0011] The sample stage of the present invention includes a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray; the sample stage is a convex body protruding upward, the upper surface of the convex body is an area for placing the sample, the outer periphery of the lower end of the sample stage is connected to the tray, the upper surface of the tray is inclined downward from the sample stage side toward the outer periphery of the tray, and has at least one outlet through-hole for outletting the cut piece of the sample from the tray, and has a side wall protruding upward on the outer periphery, the rim is connected to the upper end side of the side wall of the tray and has a portion to be attached to a stage holder of a biological tissue cutting device; at least one of the sample stage, tray, and rim has at least one mark indicating a direction on its upper surface; and is characterized by being used with the biological tissue cutting device of the present invention.

[0012] The biological tissue cutting device of the present invention can be made compact, and can easily and efficiently produce a large amount of fine tissue pieces.

[0013] FIG. 1A is a perspective view showing an outline of the device main body. FIG. 1B is a perspective view showing an outline of a moving unit in the device main body. FIG. 2A is a perspective view showing an outline of a first cutting unit among the cutting units. FIG. 2B is a plan view of a first blade of the first cutting unit. FIG. 3A is a perspective view showing an outline of a second cutting unit among the cutting sets. FIG. 3B is a plan view of a second blade of the second cutting unit. FIG. 3C is a plan view of a third blade of the second cutting unit. FIG. 3D is a side view of the third blade as viewed from the X direction. FIG. 4 is a perspective view showing an outline of a cutting device in which the first cutting unit or the second cutting unit is attached to the device main body. FIG. 5A is a perspective view of biological tissue, specifically, a biological tissue before cutting by the first cutting unit. FIG. 5B is a perspective view of biological tissue cut by the first cutting unit. FIG. 6A is a perspective view of biological tissue, specifically, a biological tissue after cutting by the first cutting unit and before cutting by the second cutting unit. FIG. 6B is a perspective view of biological tissue cut by the second cutting unit. Fig. 7 is a perspective view of a cut tissue piece. Fig. 8A is a schematic diagram of a sample stage, specifically a top view. Fig. 8B is a cross-sectional view taken along the II direction in Fig. 8A. Fig. 9A is a schematic diagram showing an example of attachment of the cutting unit to the attachment unit, specifically a schematic diagram showing an example of the attachment unit 14 in the device body 10 of the cutting device 1. Fig. 9B is a schematic diagram showing an example of the first cutting unit 20. Fig. 10 is a schematic diagram showing an example of the attachment unit 14 to which the first cutting unit 20 is attached.

[0014] [1] An apparatus comprising: an exchangeable cutting set for cutting biological tissue; and an apparatus main body; the cutting set having: a first cutting unit and a second cutting unit; the apparatus main body having: a sample stage on which the biological tissue is placed; a stage holder to which the sample stage is detachably attached; a mounting unit to which the cutting units are detachably attached; and a movement unit for moving the mounting unit; based on the coordinate axes of the apparatus main body, the sample stage is rotatable around the Z axis of the sample stage, and the movement unit moves the mounting unit in the X axis direction; the mounting unit is an attachment unit common to the first cutting unit and the second cutting unit and exchangeable between them; the first cutting unit has a first blade, and the first blade faces the XZ plane when the first cutting unit is attached to the mounting unit; the second cutting unit has a second blade and a third blade, and when the second cutting unit is attached to the mounting unit, the second blade faces the XZ plane and the third blade faces the XY plane; A biological tissue cutting device characterized by: moving the mounting unit to which the first cutting unit is attached in the X-axis direction with the moving unit, thereby cutting the biological tissue with the first cutting unit; replacing the first cutting unit with the second cutting unit and rotating the specimen stage; and moving the mounting unit to which the second cutting unit is attached in the X-axis direction with the moving unit, thereby cutting the biological tissue with the second cutting unit, thereby cutting out tissue pieces from the biological tissue. [2] The biological tissue cutting device described in [1], wherein the moving unit moves the mounting unit back and forth in the X-axis direction. [3] The biological tissue cutting device described in [2], wherein the moving unit repeatedly moves the mounting unit in a forward direction along the X-axis, upward along the Z-axis, backward along the X-axis, and downward along the Z-axis relative to the mounting unit. [4] The biological tissue cutting device described in any one of [1] to [3], wherein the moving unit repeatedly moves back and forth in the X-axis direction and in the Y-axis direction relative to the mounting unit.[5] The biological tissue cutting device according to any one of [1] to [4], wherein the sample stage is further movable in at least one of the XY plane direction and the Z-axis direction. [6] The biological tissue cutting device according to any one of [1] to [5], wherein, when the second cutting unit is attached to the attachment unit, the second blade is approximately parallel to the XZ plane, and the edge side of the third blade is inclined downward with respect to the XY plane. [7] The biological tissue cutting device according to any one of [1] to [6], wherein the sample stage includes a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray, the sample stage is a convex body protruding upward, the upper surface of the convex body is an area for placing the sample, the outer periphery of the lower end of the sample stage is connected to the tray, the upper surface of the tray is inclined downward from the sample stage side toward the outer periphery of the tray, the tray has at least one lead-out through-hole for leading out cut pieces of the sample from the tray, and has a side wall protruding upward on the outer periphery, the rim is connected to the upper end side of the side wall of the tray, and has a portion to be attached to a stage holder of the biological tissue cutting device, and at least one of the sample stage, the tray, and the rim has at least one mark indicating a direction on its upper surface. [8] The biological tissue cutting device according to [7], wherein the stage holder has a convex portion for mounting the sample stage, and the mounting portion on the rim of the sample stage is a through-hole into which the convex portion fits. [9] The biological tissue cutting device according to [7] or [8], wherein the sample stage further has a discharge port, and the discharge port is connected to the outlet through-hole of the tray on the back side of the tray of the sample stage.

[0015]

[10] A method for producing a tissue piece from biological tissue, using the biological tissue cutting device described in any one of [1] to [9], comprising: a positioning step of positioning the biological tissue on the sample stage, a first cutting step of moving the attachment unit, to which the first cutting unit is attached, in the X-axis direction with the movement unit to cut the biological tissue and form a first cut surface with the first blade of the first cutting unit, a replacement step of detaching the first cutting unit from the attachment unit and replacing it with the second cutting unit, a rotation step of rotating the sample stage, and a second cutting step of moving the attachment unit, to which the second cutting unit is attached, in the X-axis direction with the movement unit to cut the biological tissue and form a second cut surface with the second blade of the second cutting unit and a third cut surface with a third blade, wherein the first cut surface intersects with the second cut surface and the second cut surface intersect with the third cut surface to obtain a tissue piece.

[11] A method for producing a tissue piece from biological tissue, using the biological tissue cutting device described in

[10] , wherein the first cutting step is continuously repeated.

[12] The manufacturing method according to

[11] , in which, after performing the first cutting step once, the mounting unit to which the first cutting unit is attached is moved in the Y-axis direction, and then a new first cutting step is performed.

[13] The manufacturing method according to any one of

[10] to

[12] , in which the second cutting step is continuously repeated.

[14] The manufacturing method according to

[13] , in which, after performing the second cutting step once, the mounting unit to which the second cutting unit is attached is moved in the Y-axis direction, and then a new second cutting step is performed.

[15] The manufacturing method according to any one of

[10] to

[14] , in which, after performing the first cutting step and the second cutting step, the mounting unit is moved downward in the Z-axis direction, and then the first cutting step and the second cutting step are newly performed.

[16] The biological tissue cutting device is the biological tissue cutting device described in any one of [7] to [9]; the sample stage further has a discharge port, and the discharge port is connected to the outlet through-hole of the tray on the back side of the tray of the sample stage; a recovery tube is connected to the discharge port; and the method further includes a recovery step of recovering the tissue piece cut from the biological tissue, in which the tissue piece cut from the biological tissue of the sample stage is recovered from the recovery tube via the outlet through-hole of the tray of the sample stage and the discharge port.

[0016]

[17] A device body of a biological tissue cutting device, comprising: a sample stage on which biological tissue is placed; a stage holder to which the sample stage can be detachably attached; an attachment unit to which a cutting unit can be detachably attached; and a movement unit that moves the attachment unit; wherein, based on the coordinate axes of the device body, the sample stage is rotatable around the Z axis of the sample stage, and the movement unit moves the attachment unit in the X axis direction; the attachment unit is a attachment unit common to a plurality of cutting units; and wherein the device body is used for the biological tissue cutting device described in any one of [1] to [9].

[18] A sample stage comprising a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray; the sample stage is a convex body protruding upward, the upper surface of the convex body is an area for placing a sample, the outer periphery of the lower end of the sample stage is connected to the tray, the upper surface of the tray is inclined downward from the sample stage side towards the outer periphery of the tray, and has at least one outlet through-hole for outletting cut pieces of the sample from the tray, and has a side wall protruding upward on the outer periphery, the rim is connected to the upper end side of the side wall of the tray and has a portion to be attached to a stage holder of a biological tissue cutting device; at least one of the sample stage, tray, and rim has at least one mark indicating a direction on its upper surface; A sample stage characterized by being used in the biological tissue cutting device described in any one of [1] to [9].

[19] The specimen stage according to

[18] , wherein the stage holder of the biological tissue cutting device has a protrusion for mounting the specimen stage, and the mounting portion of the rim is a through-hole into which the protrusion fits.

[20] The specimen stage according to

[18] or

[19] , wherein the capacity of the tray is 10 to 100 mL.

[0017] (A) Biological tissue cutting device As described above, the biological tissue cutting device of the present invention comprises an exchangeable cutting set for cutting biological tissue and an apparatus main body; the cutting set comprises a first cutting unit and a second cutting unit; the apparatus main body comprises a sample stage on which the biological tissue is placed, a stage holder to which the sample stage is detachably attached, an attachment unit to which the cutting unit is detachably attached, and a movement unit for moving the attachment unit; based on the coordinate axes of the apparatus main body, the sample stage is rotatable around the Z axis of the sample stage, and the movement unit moves the attachment unit in the X axis direction; the attachment unit is an attachment unit common to both the first cutting unit and the second cutting unit and is exchangeable between them, the first cutting unit comprises a first blade, and the first blade faces the XZ plane when the first cutting unit is attached to the attachment unit, and the second cutting unit comprises a second blade and a third blade, When the second cutting unit is attached to the attachment unit, the second blade faces the XZ plane and the third blade faces the XY plane; the attachment unit to which the first cutting unit is attached is moved in the X-axis direction by the moving unit, thereby cutting the biological tissue with the first cutting unit; the first cutting unit is replaced with the second cutting unit and the sample stage is rotated; the attachment unit to which the second cutting unit is attached is moved in the X-axis direction by the moving unit, thereby cutting the biological tissue with the second cutting unit, thereby cutting out tissue pieces from the biological tissue.

[0018] In the present invention, the term "means" can be read as, for example, a "mechanism." The biological tissue cutting device of the present invention will hereinafter also be referred to as a cutting device.

[0019] In the tissue cutting device of the present invention, the first cutting unit or the second cutting unit can be attached to the attachment unit. Specifically, when the first cutting unit is attached to the attachment unit, the first cutting unit can be used, then removed, and the second cutting unit can be attached again. Furthermore, when the second cutting unit is attached to the attachment unit, the second cutting unit can be used, then removed, and the first cutting unit can be attached again. The cutting device of the present invention uses both the first cutting unit and the second cutting unit to cut biological tissue, but the two can be interchangeable in the attachment unit. Therefore, the cutting device of the present invention can be made smaller than a device in which the first cutting unit and the second cutting unit are located in separate positions.

[0020] As described above, the cutting device of the present invention has a sample stage on which a biological tissue is placed. The three-dimensional coordinate axes (X, Y, Z) of the cutting device of the present invention can be defined based on the central axis of the sample stage. The Z axis of the cutting device of the present invention is an axis parallel to the central axis of the sample stage and is also referred to as a perpendicular axis relative to the surface on the sample stage on which the biological tissue is placed. The Z axis can also be referred to as an up-down axis, for example. The X and Y axes of the cutting device of the present invention are each perpendicular to the Z axis and are perpendicular to each other. Hereinafter, the plane defined by the X and Y axes will be referred to as the XY plane, the plane defined by the X and Z axes will be referred to as the XZ plane, and the plane defined by the Y and Z axes will be referred to as the YZ plane. In the present invention, the directions of the X and Y axes in the XY plane are not particularly limited, and the movement direction of the mounting unit (i.e., the movement direction of the cutting unit attached thereto) can be defined as the X axis direction. Hereinafter, in the present invention, the X-axis, Y-axis, and Z-axis refer to the X-axis, Y-axis, and Z-axis of the cutting device of the present invention, unless otherwise specified.

[0021] In the cutting device of the present invention, the mounting unit is movable in the X-axis direction by the moving unit. In the present invention, movement in the X-axis direction includes both the positive (+) direction and the negative (-) direction on the X-axis. When the first cutting unit is mounted on the mounting unit, the first cutting unit can similarly move in the X-axis direction via the mounting unit. Furthermore, when the second cutting unit is mounted on the mounting unit, the second cutting unit can similarly move in the X-axis direction via the mounting unit.

[0022] The cutting device of the present invention will be described below with reference to specific examples using the drawings. The present invention is not limited to these embodiments. Unless otherwise specified, the description of each embodiment can be applied to other embodiments. In the following drawings, the same parts are designated by the same reference numerals.

[0023] (Embodiment A1) The cutting device of this embodiment can be used to cut biological tissue by attaching the cutting units to the device main body. Fig. 1 is a schematic diagram of the device main body 10, Fig. 1A is a perspective view showing the device main body 10, and Fig. 1B is a perspective view showing the moving unit 15 in the device main body 10. Fig. 2 is a schematic diagram showing a first cutting unit 20 of the cutting units, Fig. 2A is a perspective view of the first cutting unit 20, and Fig. 2B is a plan view of the first blade 22 of the first cutting unit 20. Fig. 3 is a perspective view showing a second cutting unit 30 of the cutting set, Fig. 3A is a perspective view of the second cutting unit 30, Fig. 3B is a plan view of the second blade 32 of the second cutting unit 30, Fig. 3C is a plan view of the third blade 33 of the second cutting unit 30, and Fig. 3D is a side view of the third blade 33 as viewed from the X direction. FIG. 4 is a perspective view showing an outline of the cutting device 1 (20 / 30) in which the first cutting unit 20 or the second cutting unit 30 is attached to the device main body 10. As shown in FIG.

[0024] In the embodiments, when the term "cutting unit" is simply used, it includes the meaning of either the first cutting unit 20 or the second cutting unit 30, and can be read as either the first cutting unit 20 or the second cutting unit 30. In addition, in the drawings, "20 / 30" indicates that the cutting unit may be either the first cutting unit 20 or the second cutting unit 30.

[0025] In each figure, the X-axis, Y-axis, and Z-axis are coordinate axes of the cutting device 1, and the Z-axis is an axial direction parallel to the central axis of the sample stage 13. In this embodiment, the X-axis is an axis perpendicular to the Z-axis and is the direction in which the mounting unit 14 is moved by the moving unit 15. The Y-axis is an axis perpendicular to the Z-axis and X-axis. In each figure, the plus (+) and minus (-) directions of each axis are shown, but this is just an example, and the directions may be opposite.

[0026] (1) Main Unit of the Apparatus As shown in FIG. 1AB, the main unit of the apparatus 10 has a stage holder 12, a sample stage 13, an attachment unit 14 to which the cutting unit can be attached and detached, and a moving unit 15 that moves the attachment unit 14, arranged on a substrate 11.

[0027] The sample stage 13 is a sample stage on which biological tissue is placed. It is preferable that the biological tissue is immobilized on the sample stage 13, for example. The surface on which the biological tissue is placed on the sample stage 13 is referred to as the sample placement surface, and the area where the biological tissue is placed is also referred to as the sample placement area. On the sample placement surface, the sample placement area may have, for example, a thin groove formed therein. By having the groove in the sample placement area, for example, the biological tissue can be fixed in the placement area and movement due to slippage or the like can be prevented. The shape of the groove is not particularly limited, and may be, for example, a plurality of parallel lines or a lattice pattern.

[0028] The biological tissue may be fixed to the sample placement area using, for example, an adhesive. The adhesive is not particularly limited, and is preferably a medical adhesive, specifically, an α-cyanoacrylate adhesive.

[0029] The material of the surface of the sample stage 13 (for example, the sample placement surface) is not particularly limited, and examples include polymers such as polycarbonate, glass, and stainless steel.

[0030] The apparatus main body 10 has, for example, a stage holder (also called a stage base) 12 on a substrate 11, on which a sample stage 13 is detachably attached. By making the sample stage 13 detachable, for example, the sample stage 13 can be removed from the apparatus main body 10 and easily cleaned. The sample stage 13 attached to the stage holder 12 is preferably fixed to the stage holder 12 during use. There are no particular limitations on the method for fixing the sample stage 13, and it can be fixed, for example, by a mounting portion on the sample stage 13 and a mounting portion on the stage holder 12. Examples of fixing methods include fitting. Furthermore, a locking device such as a screw or a plunger may be used to fix the sample stage 13.

[0031] In the main body 10 of the apparatus, the sample stage 13 is rotatable around the Z axis of the sample stage 13. The sample stage 13 can be rotated, for example, by a desired rotation angle D° and fixed at that position. In addition, in the main body 10 of the apparatus, the sample stage 13 can also be moved, for example, in the Z axis direction (also referred to as the height direction). Movement in the Z axis direction is, for example, movement upward (positive direction of the Z axis) and downward (negative direction of the Z axis).

[0032] For example, the stage holder 12 may also rotate and / or move the sample stage 13. In this case, the stage holder 12 is also referred to as a stage adjustment unit that adjusts the position of the sample stage 13.

[0033] The movement of the sample stage 13 in the Z direction can be performed by, for example, a height adjustment mechanism, and it is preferable that the stage holder 12 has the height adjustment mechanism. The height adjustment mechanism is not particularly limited, and examples thereof include bolt-type, dial-type, screw-type, and ratchet-type adjusters.

[0034] As described above, the device main body 10 has the mounting unit 14 and the moving unit 15 that moves the mounting unit 14. In the device main body 10, the moving unit 15 is disposed on the base plate 11, and the moving unit 15 and the mounting unit 14 are linked together.

[0035] The first cutting unit 20 and the second cutting unit 30 are each detachably attached to the mounting unit 14. That is, the first cutting unit 20 and the second cutting unit 30 are interchangeable with respect to the mounting unit 14. When the first cutting unit 20 is attached to the mounting unit 14, it is preferable that the first cutting unit 20 is fixed to the mounting unit 14, and when the second cutting unit 30 is attached to the mounting unit 14, it is preferable that the second cutting unit 30 is fixed to the mounting unit 14. There are no particular limitations on the method for fixing the first cutting unit 20 or the second cutting unit 30 to the mounting unit 14, and examples include fixing with screws or the like.

[0036] The mounting unit 14 is attached with the first cutting unit 20 or the second cutting unit 30, and each cutting unit cuts the biological tissue placed on the specimen stage 13. For this reason, the mounting unit 14 is located, for example, above the specimen stage 13.

[0037] The moving unit 15 can move the attachment unit 14 in the X-axis direction. This allows the cutting unit 20 / 30 attached to the attachment unit 14 to move in the X-axis direction. In this way, by moving the attachment unit 14 in the X-axis direction, the biological tissue can be cut by the cutting unit 20 / 30.

[0038] In the biological tissue, for example, a position where cutting of the biological tissue starts is referred to as a cutting start position, and a position where cutting of the biological tissue ends is referred to as a cutting end position. Since the cutting unit 20 / 30 moves in the X-axis direction, in the biological tissue, a direction connecting the cutting start position and the cutting end position is, for example, parallel to the X-axis.

[0039] The moving unit 15 has, for example, a sliding plate 151 and a handle 152 as a mechanism for moving the mounting unit 14 in the X-axis direction, as shown in FIG. 1AB . The sliding plate 151 is, for example, a plate extending in the X-axis direction, and the mounting unit 14 is connected to one end of the sliding plate 151 in the X-axis direction. In this embodiment, the end of the sliding plate 151 extending in the X-axis direction to which the mounting unit 14 is connected is referred to as the positive direction of the X-axis, and the other end is referred to as the negative direction of the X-axis. A handle 152 is connected to the sliding plate 151. For example, a user can grasp the handle 152 and move the handle 152 in the X-axis direction, thereby moving the sliding plate 151 in the X-axis direction in conjunction with the movement of the sliding plate 151. Then, in conjunction with the movement of the sliding plate 151, the mounting unit 14 connected to the sliding plate 151 also moves in the X-axis direction.

[0040] The moving unit 15 may also include, for example, a mechanism for changing the height of the sliding plate 151. The mechanism can change the height of the mounting unit 14 by, for example, reciprocating the sliding plate 151 along the X-axis, i.e., by moving the sliding plate 151 in one direction along the X-axis and then in the opposite direction along the X-axis. This change in height, which is a mechanism for changing the height, also changes the height of the mounting unit 14. In this way, the following is possible, for example, by moving the sliding plate 151 in one direction along the X-axis (e.g., the positive direction) (forward movement). On the other hand, by moving the sliding plate 151 in the opposite direction along the X-axis (e.g., the negative direction) (return movement), cutting is not performed, and the cutting unit 20 / 30 can be returned to its original position, i.e., the set position of the cutting unit 20 / 30, from which cutting of the living tissue begins.

[0041] The mechanism for changing the height may be, for example, a cam mechanism such as a grooved cam, and the sliding plate 151 is preferably moved along the cam mechanism. In this case, for example, when the sliding plate 151 is moved in one direction along the X axis (e.g., the positive direction), the sliding plate 151 is raised upward by the cam mechanism at the end point. Then, while maintaining this height, the sliding plate 151 can be moved in the opposite direction along the X axis (e.g., the negative direction). This allows the mounting unit 14 and the cutting unit 20 / 30 to be returned to, for example, the set position. In this way, movement in one direction along the X axis causes the cutting unit 20 / 30 to cut the biological tissue, and movement in the opposite direction along the X axis moves the cutting unit 20 / 30 away from the biological tissue, returning the cutting unit 20 / 30 to the set position.

[0042] Preferably, the moving unit 15 further includes a mechanism for moving the mounting unit 14 in the Y-axis direction. By moving the mounting unit 14 in the Y-axis direction using the moving unit 15, the cutting units 20 / 30 can be moved in the Y-axis direction. By moving the mounting unit 14 in the Y-axis direction in this manner, the set positions of the mounting unit 14 and the cutting units 20 / 30 can be moved in the Y-axis direction, for example.

[0043] In this embodiment, the moving unit 15 has, as shown in FIG. 1AB , a mechanism for moving the mounting unit 14 in the Y-axis direction, for example, a ratchet 155, a lead screw 154, and a lead nut 153. The lead screw 154 has a spiral groove. The ratchet 155 includes a ratchet gear 155a having multiple teeth and a ratchet pawl 155b. The ratchet pawl 155b is fixed to the sliding plate 151. The ratchet gear 155a is fixed to the lead screw 154. The lead nut 153 and the lead screw 154 are threadedly engaged so that the lead screw 154 can rotate. The direction perpendicular to the X-axis along which the sliding plate 151 extends is the Y-axis, and the lead screw 154 is disposed along the Y-axis. In this embodiment, one end of the lead screw 154 is referred to as the positive direction of the Y-axis, and the other end is referred to as the negative direction of the Y-axis. For example, when a user grips the handle 152 and moves the handle 152 in the negative direction of the X axis, the ratchet 155, the feed nut 153, and the feed screw 154 can move the sliding plate 151 in the Y axis direction. Details of the movement in the Y axis direction will be described later.

[0044] Each component of the device body 10 is preferably made of, for example, a sterilizable material, specifically, a sanitary specification that is resistant to high temperatures and pressures and allows autoclave sterilization. The sample stage 13 is preferably disposable and replaceable for each patient, since this further reduces the possibility of contamination and infection between individuals.

[0045] (2) Cutting Unit In this embodiment, the cutting units are the first cutting unit 20 and the second cutting unit 30. The first cutting unit 20 and the second cutting unit 30 each have a blade. The type of blade is not particularly limited as long as it can cut biological tissue, and specific examples include blades such as a cutter and a knife.

[0046] As shown in FIG. 2AB , the first cutting unit 20 has a first blade 22 fixed to the main body 31. The first blade 22 has a blade 221 and an edge (also referred to as a cutting edge) 222, with the lower part of the blade 221 being the edge 222. Specifically, the first cutting unit 20 is attached to the mounting unit 14 of the device main body 10 in the following manner. That is, for example, the first blade 221 faces the XZ plane, has the edge 222 on the lower side of the Z axis, and the edge 222 is aligned with the X axis. The edge 222 is, for example, inclined, specifically, inclined upward toward the movement direction (the positive direction of the X axis). The end of the edge 222 facing the movement direction is the tip (also referred to as a cutting edge) 223 of the edge 222, and preferably comes into contact with the object to be cut first.

[0047] In this specification, the expression "the first blade 22 faces the XZ plane" means, for example, that the blade 221 of the first blade 22 faces the XZ plane. Facing the XZ plane can also mean, for example, that it is aligned along the XZ plane. The blade 221 of the first blade 22 may be completely parallel to the XZ plane as a whole, or may be tilted relative to the XZ plane. In the latter case, the edge 222 side of the first blade 22 (specifically, the blade 221 of the first blade 22) may be tilted in either direction relative to the XZ plane. That is, the edge 222 side of the first blade 22 may be tilted, for example, in the negative direction of the Y axis or in the positive direction of the Y axis. It is preferable that the blade 221 of the first blade 22 and the XZ plane are, for example, approximately parallel. The angle between the blade 221 of the first blade 22 and the XZ plane is, for example, 0°±1° to 0°±10°, and preferably 0°±1° to 0°±3°. A negative angle is, for example, the angle when the edge 222 side of the first blade 22 is inclined in the (-) direction of the Y axis, and a positive angle is, for example, the angle when the edge 222 side of the first blade 22 is inclined in the (+) direction of the Y axis.

[0048] When cutting a biological sample using the first cutting unit 20, the biological sample is placed at the positive end of the X-axis, and the first cutting unit 20 is moved in the positive direction, whereby the biological sample is cut by the edge 222 of the first blade 22.

[0049] 2B, the inclination of the edge 222 of the first blade 22 is preferably a predetermined angle θx with respect to the XY plane (horizontal plane). The angle θx is not particularly limited, and when expressed as sin θx, for example, the lower limit is, for example, 1 / 200, 3 / 200, or 5 / 200, and the upper limit is, for example, 30 / 200, 50 / 200, or 80 / 200, and the range is preferably, for example, 1 / 200 to 80 / 200, 3 / 200 to 50 / 200, or 5 / 200 to 30 / 200.

[0050] 3ABCD, the second cutting unit 30 has a second blade 32 and a third blade 33 fixed to a main body 31. The second blade 32 has a blade 321 and an edge 322, and the third blade 33 has a blade 331 and an edge 332. In the second cutting unit 30, the second blade 32 and the third blade 33 are fixed to the main body 31 so that the respective blades 321 and 331 maintain a constant angle.

[0051] The second blade 32 is attached to the mounting unit 14 of the device body 10 in the following manner. That is, for example, the second blade 32 has its blade 321 facing the XZ plane, an edge 322 on the lower side of the Z axis, and the edge 322 is aligned with the X axis. The edge 322 is, for example, inclined, specifically, inclined upward toward the movement direction (the positive direction of the X axis). This inclination, in relation to the third blade 33, can also be said to be inclined so that the distance between the edge 322 and the third blade 33 increases toward the movement direction. The end of the edge 322 facing the movement direction becomes the tip (also called the cutting edge) 323 of the edge 322, and it is preferable that it is the first to come into contact with the object to be cut.

[0052] In the present invention, the expression "the second blade 32 faces the XZ plane" means, for example, that the blade 321 of the second blade 32 faces the XZ plane. Facing the XZ plane can also be, for example, along the XZ plane. The blade 321 of the second blade 32 may be completely parallel to the XZ plane as a whole, or may be tilted relative to the XZ plane. In the latter case, the edge 322 side of the second blade 32 (specifically, the blade 321 of the second blade 32) may be inclined in either direction relative to the XZ plane. That is, the edge 322 side of the second blade 32 may be inclined, for example, in the negative direction of the Y axis or in the positive direction of the Y axis. It is preferable that the blade 321 of the second blade 32 and the XZ plane are, for example, approximately parallel. The angle between the blade 321 of the second blade 32 and the XZ plane is, for example, 0°±1° to 0°±10°, or 0°±1° to 0°±3°. A negative angle is, for example, the angle when the edge 322 side of the second blade 32 is inclined in the (-) direction of the Y axis, and a positive angle is, for example, the angle when the edge 322 side of the second blade 32 is inclined in the (+) direction of the Y axis.

[0053] The third blade 33 is attached to the attachment unit 14 of the device body 10 in the following state. That is, the third blade 33 has, for example, its blade 331 facing the XY plane and an edge 332 on the side of the second blade 32. The edge 332 is, for example, inclined, and this inclination is such that, in relation to the second blade 32, the distance from the second blade 32 increases toward the movement direction (the positive direction of the X axis). The end of the edge 332 on the movement direction side becomes the tip (also called the cutting edge) 333 of the edge 332, and it is preferable that it be the first to come into contact with the object to be cut.

[0054] In the present invention, the expression "the third blade 33 faces the XY plane" means, for example, that the blade 331 of the third blade 33 faces the XY plane. Facing the XY plane can also mean, for example, that it is aligned along the XY plane. The blade 331 of the third blade 33 may be completely parallel to the XY plane as a whole, but is preferably tilted relative to the XY plane. The edge 332 of the third blade 33 (specifically, the blade 331 of the third blade 33) may be tilted in any direction relative to the XY plane, but is preferably tilted downward relative to the XY plane as shown in FIG. 3D . The downward direction refers to the downward direction of the Z axis, e.g., the (-) direction of the Z axis in FIG. 3D . The angle (θw) between the blade 331 of the third blade 33 and the XY plane is, for example, 0° to 10°, and preferably 2° to 7°. In this way, by tilting the third blade 33 in the XY plane, for example, when the third blade 33 cuts tissue, the area of ​​contact between the third blade 33 and the tissue piece can be reduced, and as a result, physical damage to the tissue piece can be further reduced.

[0055] In the second cutting unit 30, the second blade 32 and the third blade 33 are arranged, for example, such that the blade 321 and the blade 331 are substantially perpendicular to each other. The edge 322 of the second blade 32 and the edge 332 of the third blade 33 are perpendicular to each other, for example, with the point of application as the boundary. In the present invention, the angle between the blade 321 of the second blade 32 and the blade 331 of the third blade 33 is, for example, 90°±20°, and preferably 90°±5°.

[0056] When cutting a biological sample using the second cutting unit 30, the biological sample is placed at the positive end of the X-axis, and the second cutting unit 30 is moved in the positive direction, whereby the biological sample is cut by the edge 322 of the second blade 32 and the edge 332 of the third blade 33.

[0057] 3B, the inclination of the edge 322 of the second blade 32 is preferably a predetermined angle θy with respect to the XY plane (horizontal plane). When the angle θy is expressed as sin θy, for example, the lower limit is, for example, 1 / 200, 3 / 200, or 5 / 200, and the upper limit is, for example, 30 / 200, 50 / 200, or 80 / 200, and the range is preferably, for example, 1 / 200 to 80 / 200, 3 / 200 to 50 / 200, or 5 / 200 to 30 / 200.

[0058] Furthermore, it is preferable that the surface of the blade 331 of the third blade 33 is parallel to the XY plane (horizontal plane), and the inclination of the edge 332 of the third blade 33 is at a predetermined angle θz with respect to the XZ plane (vertical plane). When the angle θz is expressed as sin θz, for example, the lower limit is, for example, 1 / 200, 3 / 200, or 5 / 200, and the upper limit is, for example, 30 / 200, 50 / 200, or 80 / 200, and the range is, for example, 1 / 200 to 80 / 200, 3 / 200 to 50 / 200, or 5 / 200 to 30 / 200.

[0059] The first cutting unit 20 and the second cutting unit 30 are preferably made of, for example, a sterilizable material, specifically, a sanitary specification that is resistant to high temperatures and pressures and allows for autoclave sterilization. Furthermore, the first blade 22 of the first cutting unit 20 and the second blade 32 and third blade 33 of the second cutting unit 30 are preferably disposable and replaceable for each patient, since this further reduces the possibility of contamination and infection between individuals.

[0060] Since the cutting unit 20 / 30 moves due to the movement of the mounting unit 14, for example, the movement of the mounting unit 14 can be interpreted as the movement of the cutting unit 20 / 30, and the movement of the cutting unit 20 / 30 can be interpreted as the movement of the mounting unit 14.

[0061] (3) Cutting Device By attaching the first cutting unit 20 or the second cutting unit 30 to the attachment unit 14 of the device body 10, the cutting device 1 can cut biological tissue.

[0062] 4, the first cutting unit 20 or the second cutting unit 30 can be attached to the attachment unit 14 of the device main body 10. Specifically, the first cutting unit 20 and the second cutting unit 30 can be used to cut biological tissue by sequentially replacing and attaching them to the attachment unit 14.

[0063] (4) Method for Cutting Biological Tissue According to the cutting device 1 of this embodiment, for example, by cutting biological tissue with the first cutting unit 20 and the second cutting unit 30, it is possible to produce a large amount of uniformly sized hexahedral tissue pieces, as shown in Figures 5AB and 6AB.

[0064] Figures 5AB and 6AB are schematic diagrams of the biological tissue 40. Figure 5A is a perspective view of the biological tissue 40 before cutting by the first cutting unit 20, and Figure 5B is a perspective view of the biological tissue 40 cut by the first cutting unit 20. Figure 6A is a perspective view of the biological tissue 40 after cutting by the first cutting unit 20 and before cutting by the second cutting unit 30, and Figure 6B is a perspective view of the biological tissue cut by the second cutting unit 30. Figure 7 is a perspective view of a cut tissue piece 50.

[0065] In this embodiment, as shown in Fig. 5A, the first cutting unit 20 attached to the mounting unit 14 repeatedly cuts the biological tissue 40 placed on the sample stage 13 of the cutting device 1 multiple times (1st to nth times, where n is a positive integer) in the positive direction of the X-axis of the cutting device 1. Because the blade 221 of the first blade 22 of the first cutting unit 20 is parallel to the XZ plane, multiple incisions are made parallel to the XZ plane (dotted lines in the figure) as shown in Fig. 5B. This allows multiple cut surfaces parallel to the XZ plane, i.e., first cut surfaces 501, to be formed in the biological tissue 40.

[0066] After multiple cuts are made by the first cutting unit 20, the first cutting unit 20 is removed from the mounting unit 14, and the second cutting unit 30 is attached. Then, the specimen stage 13 of the cutting device 1 is rotated. As a result, as shown in Fig. 6A, the first cutting plane 501 of the biological tissue 40 is positioned so as to intersect with the X-axis of the cutting device 1. Fig. 6A shows an example in which the specimen stage 13 is rotated by 90°.

[0067] As shown in FIG. 6A , the second cutting unit 30 repeatedly cuts the biological tissue 40 multiple times (first to nth times, where n is a positive integer) in the positive direction of the X-axis of the cutting device 1. This results in multiple incisions in two directions. Specifically, the blade 321 of the second blade 32 of the second cutting unit 30 is parallel to the XZ plane, so it makes incisions parallel to the XZ plane. Furthermore, the blade 331 of the third blade 33 of the second cutting unit 30 is parallel to the XY plane, so it simultaneously makes multiple incisions parallel to the XY plane. Therefore, as shown in FIG. 6B , multiple cut surfaces parallel to the XZ plane, i.e., second cut surfaces 502, and multiple cut surfaces parallel to the XY plane, i.e., third cut surfaces 503, can be simultaneously formed.

[0068] As shown in Fig. 6B, multiple cut surfaces (501, 502, 503) in three directions are formed on the biological tissue 40 by cutting using the first cutting unit 20 and the second cutting unit 30. This makes it possible to obtain a large number of hexahedral tissue pieces 50 surrounded by a pair of first cut surfaces 501, a pair of second cut surfaces 502, and a pair of third cut surfaces 503, as shown in Fig. 7.

[0069] In this embodiment, the X-axis, Y-axis, and Z-axis are the coordinate axes of the cutting device 1, as described above. The first cutting unit 20 and the second cutting unit 30 are both attached to the mounting unit 14, which moves along the X-axis, and move in the X-axis direction. After being cut by the first cutting unit 20, the biological tissue 40 on the sample stage 13 rotates in the same manner as the sample stage 13 (rotation angle D°) due to the rotation of the sample stage 13. Therefore, in the tissue piece 50 cut from the biological tissue 40, the first cutting surface 501 and the second cutting surface 502 intersect at an opposing angle of D°, and at an opposing angle of (180-D)°.

[0070] 6B shows an example in which the intersection of the first cut surface 501 and the second cut surface 502, and the intersection of the first cut surface 501 and the second cut surface 502 and the third cut surface 503 are substantially perpendicular (approximately 90°). In the present invention, the intersection is not limited to being perpendicular.

[0071] According to this embodiment, yield can be improved for the following reasons. For example, assume that the formation of the first cut surface, the second cut surface, and the third cut surface are sequentially performed on the biological tissue as separate processes. When the first cut surface is formed and then the second cut surface is formed, a lattice-shaped incision is formed on the upper surface of the biological tissue. Subsequently, when attempting to form the third cut surface, which separates the biological tissue from the biological tissue, the structural instability of the lattice-shaped incision causes the biological tissue to collapse or crumble, making cutting difficult. In contrast, according to this embodiment, after the first cut surface 501 is formed by the first cutting unit 20, the second cut surface 502 and the third cut surface 503 can be simultaneously formed by the second cutting unit 30. This avoids the aforementioned problems and improves yield.

[0072] A specific example of a method for cutting biological tissue and obtaining tissue pieces using the cutting device 1 of this embodiment will be described below. In this example, the attachment unit 14 of the cutting device 1 is moved in the positive direction of the X axis to cut the biological tissue with the cutting unit, and then the attachment unit 14 is moved in the positive direction of the Y axis to form multiple parallel cut surfaces. However, the present invention is not limited to this example.

[0073] (First step) First, the first cutting unit 20 is attached to the mounting unit 14 of the device body 10 to form the cutting device 1. The first cutting unit 20 is attached so that the surface of the blade 221 of the first blade 22 is parallel to the XZ plane, the edge 222 of the first blade 22 faces downward, and the tip 223 of the edge 222 faces in the positive direction of the X axis.

[0074] In this example, the biological sample is cut by moving the mounting unit 14 in the positive direction of the X axis. For this reason, before cutting, it is preferable to set the first cutting unit 20 on the negative side of the X axis relative to the sample placement area of ​​the sample stage 13. The position where the cutting unit (the mounting unit 14 to which it is attached) is set to start cutting in this way is referred to as, for example, the set position as described above.

[0075] (Second Step) Next, a biological tissue is placed on the sample stage 13 of the cutting device 1. Specifically, the biological tissue is placed in the sample placement area of ​​the sample stage 13. The order of the first step and the second step is not particularly limited, and may be reversed, for example.

[0076] (Third step) Then, the position of the sample stage 13 relative to the first cutting unit 20 in the Z direction (height direction), i.e., the height of the sample stage 13, is adjusted. The height of the sample stage 13 can be adjusted, for example, by the height adjustment mechanism of the stage holder 12, as described above.

[0077] When the first blade 22 of the first cutting unit 20 moves in the X-axis direction and comes into contact with the side of the biological tissue placed on the sample stage 13, it moves further to make an incision parallel to the XZ plane on the upper surface of the biological tissue. Therefore, by adjusting the height of the sample stage 13, it is possible to adjust the positional relationship so that the biological tissue placed on the sample stage 13 and the first blade 22 of the first cutting unit 20 come into contact.

[0078] Furthermore, by adjusting the height of the sample stage 13, for example, the depth (cut dimension) of the incision made by the first blade 22 in the biological tissue can also be adjusted. By adjusting the height, for example, the incision made by the first cutting unit 20 in the biological sample can be set to a sufficient depth, thereby achieving a sufficient yield. Furthermore, when the biological tissue is fixed to the sample stage 13 with an adhesive or the like, for example, by adjusting the height of the sample stage 13, the first blade 22 of the first cutting unit 20 can be adjusted so as not to come into contact with the adhesive layer interposed between the sample stage 13 and the biological tissue. This, for example, can prevent the adhesive from being mixed into the obtained tissue pieces and also sufficiently prevent the biological tissue fixed to the adhesive layer from collapsing due to cutting of the strong adhesive layer.

[0079] (Step 4) Next, the attachment unit 14 to which the first cutting unit 20 is attached is moved in the X-axis direction by the moving unit 15, thereby cutting the biological tissue with the first cutting unit 20. Specifically, the handle 152 of the moving unit 15 is moved in the positive direction of the X-axis. In the first cutting unit 20, the blade 221 of the first blade 22 is parallel to the XZ plane. Therefore, by moving the first cutting unit 20 in the positive direction of the X-axis, an incision parallel to the XZ plane is made in the biological tissue, and a first cutting surface 501 is formed.

[0080] The attachment unit 14 may be reciprocated in the X-axis direction, for example. That is, the attachment unit 14 may be moved in one direction (positive direction) along the X-axis (forward movement), the biological tissue may be cut by the first cutting unit 20, and then the attachment unit 14 may be moved in the opposite direction (negative direction) along the X-axis (return movement) to return to the set position. In this case, it is preferable that the first cutting unit 20 is moved away from the biological tissue during the return movement.

[0081] In this case, it is preferable that the moving unit 15 has the cam mechanism, for example, as described above. According to this configuration, for example, when cutting by the first cutting unit 20 is completed, the first cutting unit 20 is raised above the biological tissue via the attachment unit 14 along the cam mechanism. Then, when the first cutting unit 20 returns to the set position, the first cutting unit 20 can be lowered below the biological tissue via the attachment unit 14 along the cam mechanism.

[0082] As described above, the cutting device 1 of this embodiment can also move the attachment unit 14 in the Y-axis direction. Therefore, after moving the attachment unit 14 in the positive direction of the X-axis and cutting the biological tissue with the first cutting unit 20, for example, the attachment unit 14 can be returned in the negative direction of the X-axis and moved in the positive direction of the Y-axis. This makes it possible to perform cutting in the X-axis direction from a new set position. In other words, by repeatedly moving in the X-axis direction and the Y-axis direction, it is possible to repeatedly form parallel XZ planes on the biological tissue.

[0083] In this way, by repeating cutting in the X-axis direction and moving in the Y-axis direction, multiple incisions parallel to the XZ plane can be made in the biological tissue. Specifically, as shown in Fig. 5A, by repeatedly cutting the biological tissue 40 multiple times (first to nth times) in the positive direction of the X-axis, multiple first cut surfaces 501 parallel to the XZ plane can be formed as shown in Fig. 5B. The multiple cuts in the X-axis direction are made in the biological tissue with the same incision depth, for example.

[0084] Specifically, the movement of the mounting unit 14 in the X-axis direction and the Y-axis direction by the moving unit 15 is performed, for example, as follows.

[0085] First, when the handle 152 is moved in the positive direction of the X-axis, the first cutting unit 20 moves from the cutting start position of the biological sample to the cutting end position, and an incision is made in the biological sample in the XZ plane along the X-axis. This forms a first cutting surface 501 in the biological tissue. Next, the handle 152 is moved back in the negative direction of the X-axis. This causes the ratchet pawl 155b fixed to the sliding plate 151 to contact the teeth of the ratchet gear 155a, rotating the ratchet gear 155a by one pitch. In the example of FIG. 1B, the ratchet gear 155a rotates toward the front side of the page. This causes the feed screw 154 to which the ratchet gear 155a is fixed to rotate in the same manner. As the feed screw 154 rotates, the feed nut 153 threadedly engaged with the feed screw 154 moves in the positive direction of the Y-axis. The sliding plate 151 is fixed to the feed nut 153. Therefore, this series of movements causes the attachment unit 14 fixed to the sliding plate 151 and the first cutting unit 20 fixed to the attachment unit 14 to move in the positive direction of the Y axis. In this way, by moving the attachment unit 14 back and forth once in the X axis direction, the first cutting unit 20 can cut the biological tissue once, and then move the first cutting unit 20 in the positive direction of the Y axis for the next new cut.

[0086] Here, the "one pitch" refers to, for example, the distance that the attachment unit 14 moves in the Y-axis direction (e.g., the positive direction) when the attachment unit 14 is reciprocated once in the X-axis direction. In other words, it can also be said to be the distance that the first cutting unit 20 moves in the Y-axis direction (e.g., the positive direction). The length of the pitch is, for example, the distance between adjacent first cutting surfaces 501, i.e., the incision distance. In other words, the length of the pitch can be set, for example, based on the desired size of the tissue piece to be cut, specifically, the desired length between opposing first cutting surfaces 501 in the tissue piece.

[0087] The pitch can be adjusted, for example, by the groove structure of the feed screw 154, the number of teeth on the ratchet gear 155a, etc. The rotation of the feed screw 154 for one pitch can be, for example, in increments of a predetermined angle (e.g., 45°), and a rotation of the predetermined angle (e.g., 45°) can result in one pitch of movement. The predetermined angle of the feed screw 154 can be adjusted, for example, by the number of teeth (number of gears) on the ratchet gear 155a and the feed angle. The device main body 10 shown in FIG. 1AB is an example in which, for example, the ratchet gear 155a has 10 teeth arranged at 45° intervals. In this case, one rotation of the ratchet gear 155a due to one reciprocating movement of the mounting unit 14 results in a feed angle of 45°, and the resulting 45° rotation of the feed screw 506 moves the sliding plate 151, which is linked to the feed nut 153, by one pitch. Then, by the movement of the sliding plate 151, the mounting unit 14 and the first cutting unit 20 also move by one pitch.

[0088] The length of one pitch, i.e., the length by which the mounting unit 14 (and the first cutting unit 20) is moved in the Y-axis direction, is not particularly limited, and can be exemplified as follows: The lower limit of one pitch is, for example, 0.03 mm, 0.05 mm, 0.1 mm, or 0.2 mm, and the upper limit is, for example, 1 mm, 2 mm, or 3 mm, and the range is, for example, 0.03 to 3 mm, 0.05 to 3 mm, 0.1 to 2 mm, or 0.2 to 1 mm.

[0089] (Fifth Step) When cutting by the first cutting unit 20 is completed, the first cutting unit 20 is removed from the mounting unit 14. Then, as shown in Figure 4, the second cutting unit 30 is attached to the device body 10 to form the cutting device 1 (30).

[0090] The second cutting unit 30 is attached so that the second blade 32 and the third blade 33 are oriented as follows: That is, the surface of the blade 321 of the second blade 32 is parallel to the XZ plane and the edge 322 faces downward, and the surface of the blade 331 of the third blade 33 is parallel to the XY plane and the edge 322 faces toward the second blade 32 (the negative direction of the Y axis).

[0091] In this example, the biological sample is cut by moving the mounting unit 14 in the positive direction of the X axis. Therefore, similar to the first cutting unit 20, it is preferable that the second cutting unit 30 be set on the negative side of the X axis relative to the sample placement area of ​​the sample stage 13 before cutting.

[0092] (Sixth Step) Next, the sample stage 13 of the cutting device 1 is rotated to a desired angle while the biological tissue cut by the first cutting unit 20 is still positioned thereon. The sixth step may be performed, for example, when cutting by the first cutting unit 20 is completed, i.e., after the fourth step.

[0093] The rotation angle D° of the specimen stage 13 is not particularly limited and may be, for example, 90±45°, 90±30°, or 90±10°. When the specimen stage 13 is rotated by, for example, 90°, the first cut surface of the biological tissue 40 on the specimen stage 13 by the first cutting unit 20 becomes parallel to the YZ plane, as shown in FIG. 6A .

[0094] (Seventh Step) Then, the position of the sample stage 13 relative to the second cutting unit 30 in the Z direction (height direction), that is, the height of the sample stage 13 is adjusted.

[0095] Specifically, the height of the specimen stage 13 is adjusted so that the biological tissue placed on the specimen stage 13 can be cut by the second cutting unit 30. This height adjustment makes it possible to set, for example, the depth of incision (incision dimension) made in the biological tissue by the second blade 32 of the second cutting unit 30 and the position (cutting depth) at which a tissue piece is cut from the biological tissue by the third blade 33 of the second cutting unit 30. The height of the specimen stage 13 can be adjusted, for example, by the height adjustment unit of the stage holder 12, as described above.

[0096] (Step 8) Subsequently, in the same manner as when using the first cutting unit 20, the attachment unit 14 to which the second cutting unit 30 is attached is moved in the X-axis direction by the moving unit 15. Specifically, by moving the handle 152 of the moving unit 15 in the positive direction of the X-axis, the second cutting unit 30 is moved in the positive direction of the X-axis, and the biological tissue is cut.

[0097] In the second cutting unit 30, the blade 321 of the second blade 32 is parallel to the XZ plane, and the blade 331 of the third blade 33 is parallel to the XY plane. Therefore, by moving the second cutting unit 30 in the X-axis direction, the second blade 32 makes an incision parallel to the XZ plane and the third blade 33 makes an incision parallel to the XY plane in the biological tissue simultaneously. This simultaneously forms a second cut surface 502 and a third cut surface 503. Then, a hexahedral tissue piece is obtained from the biological tissue by the first cut surface 501 formed by the first cutting unit 20 and the second cut surface 502 and third cut surface 503 formed by the second cutting unit, as shown in FIGS. 6B and 7 .

[0098] In this embodiment, the "simultaneous formation" of the second cut surface 502 and the third cut surface 503 means, for example, that they are formed by moving the second cutting unit 30 in one direction (i.e., in one process).

[0099] Similarly to the first cutting unit 20, the second cutting unit 30 can also move back and forth in the X-axis direction and in the Y-axis direction using the mounting unit 14. The description of the first cutting unit 20 can be applied to these. That is, the description of the movement in the X-axis direction and the movement in the Y-axis direction in the fourth step can be applied to this eighth step by replacing the first cutting unit 20 with the second cutting unit 30. The multiple cuts in the Y-axis direction are performed, for example, on the XY plane at the same depth in the biological tissue.

[0100] In this way, by repeatedly cutting in the X-axis direction and moving in the Y-axis direction using the second cutting unit 30, it is possible to simultaneously make multiple incisions parallel to the XZ plane and multiple incisions parallel to the XY plane in the biological tissue. Specifically, as shown in Fig. 6A described above, by repeatedly cutting the biological tissue 40 multiple times (first to nth times) in the positive direction of the X-axis, it is possible to form multiple second cut surfaces 502 parallel to the XZ plane and multiple third cut surfaces 503 parallel to the XY plane as shown in Fig. 6B.

[0101] (Step 9) Cutting by the first cutting unit 20 and cutting by the second cutting unit 30 are performed as a set. As a result, as shown in Fig. 6B, a single layer of tissue fragments is cut out from the upper surface side of the biological tissue 40. The single layer of tissue fragments includes a plurality of tissue fragments 50.

[0102] The number of layers (n, n is a positive integer) cut out from the biological tissue is not particularly limited and can be set appropriately depending on, for example, the type of the biological tissue, the size (for example, thickness) of the biological tissue, etc.

[0103] When performing one set of operations to cut out a tissue piece in the first layer and then cut out a tissue piece in the second layer, for example, the living tissue whose upper surface has been newly exposed by cutting out the first layer may be similarly cut using the cutting unit 20 / 30. The same applies to cutting out the third and subsequent layers.

[0104] As a specific example, when the incision depth in the XZ plane by the first cutting unit 20 is set to the thickness of one layer, n sets of cutting by the first cutting unit 20 and cutting by the second cutting unit 30 are considered as one set, and n layers can be cut out by repeating these n sets. In this case, when one set of cutting to cut out one layer is completed, the attachment unit 14 can be moved one layer in the negative direction of the Z axis, and a new set can be performed. The length of the movement for one layer can be set, for example, depending on the desired thickness of the tissue piece.

[0105] The length by which the mounting unit 14 (and the first cutting unit 20) is moved in the Z-axis direction is not particularly limited, and examples thereof include the following: In the case of movement by one layer, the lower limit is, for example, 0.03 mm, 0.05 mm, 0.1 mm, or 0.2 mm, the upper limit is, for example, 1 mm, 2 mm, or 3 mm, and the range is, for example, 0.03 to 3 mm, 0.05 to 3 mm, 0.1 to 2 mm, or 0.2 to 1 mm.

[0106] As another specific example, the depth of the cut in the XZ plane by the first cutting unit 20 is set to a thickness equivalent to m layers (m is a positive integer equal to or greater than 2). That is, after cutting by the first cutting unit 20, cutting by the second cutting unit 30 is repeatedly performed for m layers, thereby cutting out m layers. In this case, too, for example, after cutting out one layer by the second cutting unit 30, the mounting unit 14 is moved by one layer in the negative direction of the Z axis, and a new layer (second layer) is cut out. If the m layers is three or more, for example, the movement by one layer and the cutting out of a new layer may be repeated in a similar manner.

[0107] The tissue pieces are cut from the biological tissue 40 by, for example, moving the second cutting unit 30 in the X-axis direction, and are deposited between the second blade 32 and the third blade 33 of the second cutting unit 30. Therefore, for example, the deposited tissue pieces can be collected in a sample receiving bucket by washing the second cutting unit 30 with a solvent. The type of solvent is not particularly limited, and a preservative solution for the tissue pieces is preferred, and specific examples include physiological saline, a buffer solution, a physiological buffer solution, water, etc.

[0108] When cutting the same biological tissue, the first cutting unit 20 and the second cutting unit 30 may be new or the same each time they are attached to the attachment unit 14, for example.

[0109] (5) Biological Tissue and Tissue Graft The biological tissue applicable to this embodiment is not particularly limited. Examples of the biological tissue include biological tissue used to produce the tissue fragment. Examples of the biological tissue include biological tissue used in regenerative medicine and biological tissue used in cell preparation. Specific examples include cartilage, skin tissue, vascular tissue, liver tissue, membrane tissues such as periosteum, synovium, mucosa, and periodontal ligament, hormone-producing tissues such as the thyroid gland, adrenal gland, and prostate, as well as nerves, tendons, fat, and muscles. When the tissue fragment is produced from biological tissue used in regenerative medicine, the tissue fragment can also be referred to as, for example, a tissue fragment for regenerative medicine. Furthermore, when the tissue fragment is produced from biological tissue used in cell preparation, the tissue fragment can also be referred to as, for example, a tissue fragment for cell preparation.

[0110] The shape of the biological tissue placed on the sample stage 13 is not particularly limited, and examples thereof include a sheet shape and a block shape. The size of the biological tissue is not particularly limited. The thickness of the biological tissue has a lower limit of, for example, 0.05 mm, 0.1 mm, 0.5 mm, or 1 mm, and an upper limit of, for example, 3 mm, 5 mm, or 10 mm, and ranges of, for example, 0.05 to 10 mm, 0.1 to 10 mm, 0.5 to 10 mm, 1 to 10 mm, 0.5 to 5 mm, 0.5 to 3 mm, or 1 to 3 mm. The area of ​​the biological tissue has a lower limit of, for example, 50 mm. ２ , 100 mm ２ , 200 mm ２ and the upper limit is, for example, 2,500 mm ２ , 5,000 mm ２ , 10,000 mm ２ and the range is, for example, 50 to 10,000 mm ２ , 100-5,000mm ２ , 200-2,500mm ２ is.

[0111] The shape of the tissue piece 50 cut from the biological tissue is not particularly limited, and may be, for example, a hexahedron as described above, and specific examples include a cube, a rectangular parallelepiped, and a parallelepiped. The size of the tissue piece 50 is not particularly limited, and the length of one side may have a lower limit of, for example, 0.03 mm, 0.05 mm, 0.1 mm, or 0.2 mm, and an upper limit of, for example, 1 mm, 2 mm, or 3 mm, and ranges of, for example, 0.03 to 3 mm, 0.05 to 3 mm, 0.1 to 2 mm, or 0.2 to 1 mm. The sides of the hexahedron may have, for example, the same length or different lengths.

[0112] The excised tissue piece 50 can be used, for example, for regenerating biological tissue, surgery in regenerative medicine, treatment, etc. The subject to which the tissue piece is applied is not particularly limited, and examples thereof include humans and non-human animals, and the method of application may be, for example, in vitro or in vivo.

[0113] (Variation 1) In the present embodiment, an example has been given in which the biological tissue is cut when the attachment unit 14 is moved in the positive direction of the X axis, but this is not limiting. As a variation, for example, the biological tissue may be cut when the attachment unit 14 is moved in the negative direction of the X axis. In this case, for example, the cutting start point of the biological tissue may be set on the positive side of the X axis, the cutting end point may be set on the negative side, and the cutting unit 20 / 30 attached to the attachment unit 14 may be positioned on the positive side of the X axis from the biological tissue before starting cutting.

[0114] Alternatively, the mounting unit 14 may be moved in both the positive and negative directions along the X axis to cut the biological tissue. In this case, for example, the mounting unit 14 may be moved in the positive direction along the X axis, then moved in the positive direction along the Y axis, and then moved in the negative direction along the X axis. This allows cutting to be performed by movement in both directions along the X axis. In this case, the first blade 22 of the first cutting unit 20 and the second blade 32 and third blade 33 of the second cutting unit 30 are preferably shaped so that they can cut the biological tissue by movement in both directions along the X axis.

[0115] In addition, in the present embodiment, an example has been given in which multiple parallel cut surfaces are formed by moving the mounting unit 14 in the positive direction of the Y axis, but this is not limiting. As a modified example, for example, multiple parallel cut surfaces may be formed by moving the mounting unit 14 in the negative direction of the Y axis.

[0116] [Embodiment A2] As described above, the cutting units of the cutting device 1 only need to be configured such that the first cutting unit 20 includes the first blade 22 and the second cutting unit 30 includes the second blade 32 and the third blade 33, and other configurations are not particularly limited.

[0117] 2AB and 3ABCD in the first embodiment, the first blade 22 of the first cutting unit 20 and the second blade 32 and third blade 33 of the second cutting unit 30 are illustrated as single-edged blades. However, the present invention is not limited to this, and double-edged blades such as round blades may also be used.

[0118] There are no particular limitations on the thickness of the edge 222 of the first blade 22 of the first cutting unit 20. The thickness of the edge 222 has a lower limit of, for example, 10 μm, 20 μm, or 30 μm and an upper limit of, for example, 500 μm, 600 μm, or 850 μm, and a range of, for example, 10 to 850 μm, 20 to 600 μm, or 30 to 500 μm.

[0119] The thickness of the edge 322 of the second blade 32 of the second cutting unit 30 is not particularly limited. The lower limit of the thickness of the edge 322 is, for example, 10 μm, 20 μm, or 30 μm, and the upper limit is, for example, 500 μm, 600 μm, or 850 μm, and the range is, for example, 10 to 850 μm, 20 to 600 μm, or 30 to 500 μm. Furthermore, the thickness of the edge 332 of the third blade 33 of the second cutting unit 30 is not particularly limited. The thickness of the edge 332 is, for example, 10 μm, 20 μm, or 30 μm, and the upper limit is, for example, 1500 μm, 2000 μm, or 3000 μm, and the range is, for example, 10 to 3000 μm, 20 to 2000 μm, or 30 to 1500 μm. The second blade 32 and the third blade 33 may have, for example, different thicknesses or the same thickness.

[0120] As described above, the first blade 22 of the first cutting unit 20 is a blade that cuts biological tissue in the XZ plane. The first blade 22 preferably has a thin thickness, for example. By reducing the thickness of the first blade 22, for example, it becomes easier to insert the first blade 22 into biological tissue and it becomes easier to maintain the overall shape of the biological tissue after cutting by the first blade 22 in its original shape before cutting. From this perspective, the first blade 22 is preferably relatively thinner than, for example, the third blade 33 of the second cutting unit 30. By making the first blade 22 of the first cutting unit 20 relatively thinner than the third blade 33 of the second cutting unit 30, for example, the lines on the first cutting surface 501 (e.g., the cuts indicated by the dotted lines in FIG. 5B ) are more neatly aligned, making the subsequent cutting process by the second cutting unit 30 easier to operate.

[0121] Similarly to the first blade 22, the second blade 32 of the second cutting unit 30 is a blade that cuts biological tissue in the XZ plane. It is preferable that the second blade 32 also has a thin thickness, for example. By reducing the thickness of the second blade 32, it becomes easier to insert the second blade 32 into biological tissue. From this perspective, similar to the first blade 22, it is preferable that the second blade 32 is relatively thin compared to the third blade 33 of the second cutting unit 30.

[0122] As described above, the third blade 33 of the second cutting unit 30 is a blade that cuts biological tissue in the XY plane. Specifically, the third blade 33 can, for example, cut the biological tissue in the XY plane, thereby scraping off and recovering a layer containing multiple tissue fragments from the biological tissue, as described above. The thickness of the third blade 33 is not particularly limited. Furthermore, the third blade 33 may be relatively thicker than the first blade 22 and the second blade 32, for example, by polishing it to make it easier to cut.

[0123] [Embodiment A3] This embodiment illustrates another example of a sample stage that can be attached to the cutting device of the present invention. The sample stage in this embodiment will be described with reference to Figures 8AB and 9AB.

[0124] 8A and 8B are schematic diagrams of the sample stage 60, FIG. 8A being a top view, and FIG. 8B being a cross-sectional view taken along line II of FIG. 8A.

[0125] The sample stage 60 includes a sample stage 61 , a tray 62 surrounding the sample stage 61 , and a rim 63 surrounding the tray 62 .

[0126] The sample stage 61 is a convex body that protrudes upward, and the upper surface of the convex body is a sample placement area 611. The sample stage 61 may have, for example, grooves on its upper surface, i.e., in the placement area 611. The placement area 611 may have, for example, the grooves, which may provide an anti-slip effect for the sample. The shape of the grooves is not particularly limited, and may be formed in a grid pattern, for example. The anti-slip structure is not limited to the grooves, and the placement area 611 may have, for example, dot-shaped protrusions.

[0127] The outer periphery of the lower end of the sample stage 61 is connected to the tray 62. For example, it is preferable that the upper surface of the tray 62 is inclined downward from the sample stage 61 side toward the outer periphery of the tray 62. Furthermore, it is preferable that the tray 62 has, for example, an outlet through-hole 66 for guiding the cut pieces of the sample cut on the sample stage 61 out of the tray 62. The position of the outlet through-hole 66 in the tray 62 is not particularly limited, and it is preferable that it be, for example, close to the outer periphery of the tray 62.

[0128] The tray 62 has a side wall that protrudes upward around its periphery, and the upper end of the side wall of the tray 62 is connected to the rim 63 .

[0129] As described above, the tray 62 is preferably inclined toward the outer periphery of the tray 62, for example, because this makes it easier to recover the cut pieces. When the cut pieces cut on the sample stage 61 are poured onto the tray 62 using the recovery liquid, the inclination of the tray 62 allows the cut pieces to move toward the outer periphery of the tray 62. Furthermore, the outer periphery of the tray 62 has a rim 63 formed by an upwardly protruding side wall, so that the cut pieces that have moved are stopped by the side wall of the tray 62 and accumulated on the outer periphery of the tray 62. Furthermore, as described above, the tray 62 has an outlet through-hole 66, so that the cut pieces can be easily discharged from the tray 62 to the outside through the outlet through-hole 66.

[0130] The number of outlet through holes 66 in the tray 62 is not particularly limited, and may be one as shown in FIG. 8AB, or may be two or more.

[0131] The rim 63 has, for example, a portion to be attached to a stage holder in the cutting apparatus of the present invention. The structure of the portion to be attached is not particularly limited, as long as the portion to be attached of the specimen stage 60 and the portion to be attached to the specimen stage 60 in the stage holder of the cutting apparatus have a corresponding structure.

[0132] As a specific example, the stage holder of the cutting device has a protrusion (the mounting portion) for mounting the sample stage 60, and the mounting portion of the rim 63 of the sample stage 60 is a through-hole into which the protrusion fits. In FIG. 8AB , the mounting portion 65 of the rim 63 is a through-hole. The mounting portion 65 is in the form of a pot-shaped hole and has a release region 651 and a mounting region 652. When the protrusion of the stage holder is, for example, a cylindrical body protruding upward, the release region 651 and the mounting region 652 can have the following sizes: That is, the release region 651 is, for example, circular, and its diameter is larger than the diameter of the protrusion. Furthermore, the mounting region 652 is, for example, a horizontally elongated ellipse aligned along the circumferential direction of the rim 63, and its minor axis is smaller than the diameter of the protrusion. In this configuration, for example, the sample stage 60 can be fixed to the stage holder by passing the convex portion of the stage holder through the release region 651 of the mount portion 65 and then press-fitting the convex portion into the mount region 652 of the mount portion 65. As shown in embodiment A3, for example, since the stage holder is rotatable, if the sample stage 60 is fixed to the stage holder, the sample stage 60 can be rotated by rotating the stage holder. The rotation mechanism of the stage holder is not particularly limited, and a general rotation mechanism can be applied.

[0133] As described above, the sample stage 60 rotates in the circumferential direction when switching between cutting by the first cutting unit and cutting by the second cutting unit. Therefore, it is preferable that the orientation of the sample stage 60 can be easily visually recognized by, for example, an operator. Therefore, it is preferable that at least one of the sample stage 60, for example, the sample table 61, the tray 62, and the rim 63, has at least one mark indicating the direction on its upper surface.

[0134] In this embodiment, as an example, the rim 63 of the sample stage 60 has marks 67 indicating directions. As shown in Fig. 8A, the rim 63 has the letters "X" and "Y" as the marks 67. These marks 67 may be painted on the rim 63 or may be formed by through-holes, for example.

[0135] The sample stage 60 may further include, for example, a discharge port. Specifically, the discharge port may be connected to a discharge through-hole 66 of the tray 62 on the rear side of the tray 62 of the sample stage 60. The discharge port may be, for example, a port that connects the discharge through-hole 66 of the tray 62 to a tube. By connecting one end of the tube to the discharge through-hole 66 via the discharge port, the cut pieces accumulated on the tray 62 of the sample stage 60 can also be collected from the other end of the tube.

[0136] The sample stage 60 may further have, for example, a gripping portion (protrusion) 64 that protrudes in the outer circumferential direction from the rim 63. A user can handle the sample stage 60 by, for example, gripping the gripping portion 64.

[0137] There are no particular limitations on the size of each part of the sample stage 60. Examples are shown below, but the present invention is not limited to these examples. (Sample stage 60) Diameter D0: 100 to 150 mm (Sample stage 61) Diameter D1: 20 to 50 mm Height H1 from tray 62: 5 to 10 mm (Tray 62) Capacity: 10 to 100 mL Tray width L2: 25 to 40 mm Tray tilt angle θ: 1° to 5° (Rim 63) Rim width L3: 10 to 15 mm

[0138] In this embodiment, when one end of the tube is connected to the outlet through-hole 66 of the sample stage 60 via the discharge port, for example, after cutting the biological tissue, the cut tissue pieces can be collected as follows.

[0139] In the recovery step exemplified in Embodiment A1, prior to recovery of the tissue pieces, a recovery liquid for recovering the tissue pieces is added to the sample stage 60. Specifically, the recovery liquid is added to the sample stage 61 of the sample stage 60. As a result, the tissue pieces flow together with the recovery liquid from the sample stage 61 into the tray 62. Because the tray 62 is inclined, the recovery liquid containing the tissue pieces further flows toward the outer periphery of the tray 62. Because the outer periphery of the tray 62 has a discharge through-hole 66, the tissue pieces can be flowed into the discharge through-hole 66 by the flow of the recovery liquid. When the tissue pieces are flowed into the discharge through-hole 66, for example, the recovery solution may further be added.

[0140] Then, the tissue pieces flow into the tube from the outlet through-hole 66 via the discharge port, and the tissue pieces can be collected from the other end of the tube.

[0141] When the tissue pieces are collected by the tube, for example, negative pressure may be created inside the tube from the other end of the tube, thereby forcibly collecting the tissue pieces from the other end of the tube.

[0142] When the biological tissue is cut on the specimen stage 61 of the specimen stage 60, for example, the movement of the cutting unit may cause the tissue piece to automatically drop from the specimen stage 61 onto the tray 62. In such a case, for example, the recovery liquid may be added to the tray 62 to recover the tissue piece.

[0143] [Embodiment A4] In the cutting device of the present invention, the method of attaching the first cutting unit and the second cutting unit to the attachment unit is not particularly limited. That is, it is preferable that the attachment unit of the cutting device has a common attachment portion for the first cutting unit and the second cutting unit, and that the first cutting unit and the second cutting unit have the same attachment portion corresponding to the attachment portion of the attachment unit.

[0144] An example of the attachment of the cutting unit to the attachment unit will be described with reference to Figures 9A, 9B and 10. Unless otherwise specified, the above-described embodiments can be applied.

[0145] Fig. 9A is a schematic diagram showing an example of the attachment unit 14 in the device body 10 of the cutting device 1, and Fig. 9B is a schematic diagram showing an example of the first cutting unit 20. Fig. 10 is a schematic diagram showing an example of the first cutting unit 20 attached to the attachment unit 14.

[0146] 1A, the device body 10 of the cutting device 1 has a mounting unit 14 disposed on the underside of the sliding plate 151. A specific example of this mounting unit 14 is shown in Fig. 9A. As shown in Fig. 9A, the mounting unit 14 has a body 141 and an insertion rod 142, and the insertion rod is fixed to the body 141 in a direction parallel to the X-axis.

[0147] 9B, the first cutting unit 20 has a cylindrical through-hole 202 oriented parallel to the X-axis. This through-hole 202 corresponds to the insertion rod 142 of the mounting unit 14 and is sized to allow the insertion rod 142 to be inserted therein.

[0148] 10 , the first cutting unit 20 is attached to the mounting unit 14 by passing the insertion rod 142 of the mounting unit 14 through the through-hole 202 of the first cutting unit 20. Then, for example, it is preferable to further pass a fastener 70 through the insertion rod 142 to fix the first cutting unit 20 to the mounting unit 14. The type of fastener 70 is not particularly limited, and for example, the insertion rod 142 and the fastener may be a combination of a bolt and a nut.

[0149] The second cutting unit 30 illustrated in Figures 3ABCD also preferably has a through-hole oriented parallel to the X-axis, similar to the first cutting unit 20 in Figure 9B. This allows the second cutting unit 30 to be attached to and fixed to the mounting unit 14, similar to the first cutting unit 20.

[0150] (B) Method for manufacturing tissue pieces from biological tissue The method for manufacturing tissue pieces from biological tissue of the present invention, as described above, uses the biological tissue cutting device of the present invention, and includes the steps of: placing biological tissue on the sample stage; a first cutting step of cutting the biological tissue by moving the mounting unit, to which the first cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a first cut surface by the first blade of the first cutting unit; a replacement step of detaching the first cutting unit from the mounting unit and replacing it with the second cutting unit; a rotation step of rotating the sample stage; and a second cutting step of cutting the biological tissue by moving the mounting unit, to which the second cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a second cut surface by the second blade of the second cutting unit and a third cut surface by the third blade, wherein the first cut surface and the second cut surface intersect, and a tissue piece is obtained in which the first cut surface and the second cut surface intersect with the third cut surface.

[0151] The manufacturing method of the present invention is characterized by using the biological tissue cutting device of the present invention, and other configurations and conditions are not particularly limited. The manufacturing method of the present invention can be applied to the manufacturing method of the present invention.

[0152] In the manufacturing method of the present invention, it is preferable to repeat the first cutting step and the second cutting step. This makes it possible to easily prepare multiple tissue pieces from the biological tissue immobilized in the biological tissue cutting device. The manufacturing method of the present invention can also be referred to as, for example, a method for cutting biological tissue.

[0153] As described above, the manufacturing method of the present invention may further include, after the second cutting step, a recovery step of recovering the tissue piece cut from the biological tissue. In the manufacturing method of the present invention, the steps after the second cutting step can also be referred to as, for example, the tissue piece recovery method of the present invention.

[0154] (C) Device body The device body of the biological tissue cutting device of the present invention, as described above, has a sample stage on which the biological tissue is placed, a stage holder to which the sample stage can be attached and detached, an attachment unit to which the cutting unit can be attached and detached, and a moving unit that moves the attachment unit; based on the coordinate axes of the device body, the sample stage can rotate around the Z axis of the sample stage, and the moving unit moves the attachment unit in the X axis direction; the attachment unit is an attachment unit common to multiple cutting units, and is characterized by being used in the biological tissue cutting device of the present invention.

[0155] The device main body of the present invention is the device main body of the biological tissue cutting device (A) above, and the above description can be used.

[0156] (D) Sample Stage As described above, the sample stage of the present invention comprises a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray, wherein the sample stage is a convex body protruding upward, the upper surface of the convex body being the sample placement area, the outer periphery of the lower end of the sample stage being connected to the tray, the upper surface of the tray being inclined downward from the sample stage side towards the outer periphery of the tray, and having at least one outlet through-hole for outletting the cut piece of the sample from the tray, and having a side wall protruding upward on the outer periphery, the rim being connected to the upper end of the side wall of the tray and having a portion to be attached to a stage holder of a biological tissue cutting device, and at least one of the sample stage, tray, and rim having at least one mark indicating a direction on its upper surface, and characterized in that the sample stage is used with the biological tissue cutting device of the present invention.

[0157] The specimen stage of the present invention is the specimen stage in the biological tissue cutting device of (A) above, and the above description can be used.

[0158] The above describes the embodiments of the present invention by way of example, but the scope of the present invention is not limited to these, and can be changed or modified according to the purpose within the scope of the claims.

[0159] This application claims priority based on Japanese Patent Application No. 2024-77266, filed May 10, 2024, the disclosure of which is incorporated herein in its entirety by reference.

[0160] As described above, the biological tissue cutting device of the present invention can be made smaller, and can easily and efficiently produce a large amount of fine tissue pieces.

[0161] REFERENCE SIGNS LIST 1 Cutting device 10 Device body 11 Substrate 12 Stage holder 13, 60 Sample stage 14 Mounting unit 141 Body 142 Insertion rod 15 Moving unit 151 Sliding plate 152 Handle 153 Feed nut 154 Feed screw 155 Ratchet 20 First cutting unit 202 Through hole 22 First blade 221, 321, 331 Blade 222, 322, 332 Edge 30 Second cutting unit 31 Body 32 Second blade 33 Third blade 40 Biological tissue 50 Tissue piece 501 First cutting surface 502 Second cutting surface 503 Third cutting surface 61 Sample stage 62 Tray 63 Rim 64 Grip portion 65 Mounting portion 66 Lead-out through hole 67 Mark 70 fastener

Claims

1. An apparatus comprising an exchangeable cutting set for cutting biological tissue and an apparatus main body; the cutting set comprises a first cutting unit and a second cutting unit; the apparatus main body comprises a sample stage on which the biological tissue is placed, a stage holder to which the sample stage is detachably attached, a mounting unit to which the cutting units are detachably attached, and a movement unit for moving the mounting unit; based on the coordinate axes of the apparatus main body, the sample stage is rotatable around the Z axis of the sample stage, and the movement unit moves the mounting unit in the X axis direction; the mounting unit is an attachment unit common to the first cutting unit and the second cutting unit and is exchangeable between them; the first cutting unit comprises a first blade, and when the first cutting unit is attached to the mounting unit, the first blade faces the XZ plane; and the second cutting unit comprises a second blade and a third blade, and when the second cutting unit is attached to the mounting unit, the second blade faces the XZ plane and the third blade faces the XY plane; a moving unit for moving the attachment unit to which the first cutting unit is attached in the X-axis direction, thereby cutting the biological tissue with the first cutting unit; a change from the first cutting unit to the second cutting unit and a rotation of the sample stage; and a moving unit for moving the attachment unit to which the second cutting unit is attached in the X-axis direction, thereby cutting the biological tissue with the second cutting unit, thereby cutting out tissue pieces from the biological tissue.

2. The biological tissue cutting device according to claim 1, wherein the moving unit moves the mounting unit back and forth in the X-axis direction.

3. The biological tissue cutting device of claim 2, wherein the moving unit repeats movement in the forward direction along the X axis, movement upward along the Z axis, movement in the backward direction along the X axis, and movement downward along the Z axis relative to the mounting unit.

4. A biological tissue cutting device according to any one of claims 1 to 3, wherein the moving unit repeats reciprocating movement in the X-axis direction and movement in the Y-axis direction relative to the mounting unit.

5. A biological tissue cutting device according to any one of claims 1 to 4, wherein the sample stage is further movable in at least one of the XY plane direction and the Z axis direction.

6. A biological tissue cutting device according to any one of claims 1 to 5, wherein, when the second cutting unit is attached to the attachment unit, the second blade is approximately parallel to the XZ plane, and the edge side of the third blade is inclined downward relative to the XY plane.

7. A biological tissue cutting device according to any one of claims 1 to 6, wherein the sample stage includes a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray, the sample stage is a convex body protruding upward, the upper surface of the convex body is an area for placing the sample, the outer periphery of the lower end of the sample stage is connected to the tray, the upper surface of the tray is inclined downward from the sample stage side towards the outer periphery of the tray, has at least one outlet through-hole for outletting the cut piece of the sample from the tray, and has a side wall protruding upward on the outer periphery, the rim is connected to the upper end side of the side wall of the tray and has a portion to be attached to a stage holder of the biological tissue cutting device, and at least one of the sample stage, tray, and rim has at least one mark indicating a direction on its upper surface.

8. A biological tissue cutting device as described in claim 7, wherein the stage holder has a protrusion for mounting the sample stage, and the mounting portion on the rim of the sample stage is a through hole into which the protrusion fits.

9. A biological tissue cutting device as described in claim 7 or 8, wherein the sample stage further has an ejection port, and the ejection port is connected to the outlet through-hole of the tray on the back side of the tray of the sample stage.

10. A method for producing tissue pieces from biological tissue, using the biological tissue cutting device described in any one of claims 1 to 9, comprising: a positioning step of positioning the biological tissue on the sample stage; a first cutting step of cutting the biological tissue by moving the mounting unit, to which the first cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a first cut surface with the first blade of the first cutting unit; a replacement step of detaching the first cutting unit from the mounting unit and replacing it with the second cutting unit; a rotation step of rotating the sample stage; and a second cutting step of cutting the biological tissue by moving the mounting unit, to which the second cutting unit is attached, in the X-axis direction with the moving unit, thereby forming a second cut surface with the second blade of the second cutting unit and a third cut surface with a third blade, wherein the method obtains tissue pieces where the first cut surface intersects with the second cut surface and where the first cut surface and the second cut surface intersect with the third cut surface.

11. The manufacturing method according to claim 10, wherein the first cutting step is continuously repeated.

12. The manufacturing method according to claim 11, wherein after one first cutting step is performed, the mounting unit to which the first cutting unit is attached is moved in the Y-axis direction, and then a new first cutting step is performed.

13. A manufacturing method according to any one of claims 10 to 12, wherein the second cutting step is continuously repeated.

14. The manufacturing method according to claim 13, wherein after one second cutting step is performed, the mounting unit to which the second cutting unit is attached is moved in the Y-axis direction, and then a new second cutting step is performed.

15. A manufacturing method described in any one of claims 10 to 14, wherein after the first cutting step and the second cutting step are performed, the mounting unit is moved downward along the Z axis, and then the first cutting step and the second cutting step are performed again.

16. The manufacturing method according to any one of claims 10 to 15, wherein the biological tissue cutting device is the biological tissue cutting device described in any one of claims 7 to 9; the sample stage further has an ejection port, and the ejection port is connected to the outlet through-hole of the tray on the back side of the tray of the sample stage; a recovery tube is connected to the ejection port; and the method further comprises a recovery step of recovering the tissue pieces cut from the biological tissue, and in the recovery step, the tissue pieces cut from the biological tissue of the sample stage are recovered from the recovery tube via the outlet through-hole of the tray of the sample stage and the ejection port.

17. A device body for a biological tissue cutting device, characterized in that it comprises a sample stage for placing biological tissue, a stage holder to which the sample stage can be detached, an attachment unit to which a cutting unit can be detached, and a moving unit for moving the attachment unit; the sample stage is rotatable around the Z axis of the sample stage, and the moving unit moves the attachment unit in the X axis direction, based on the coordinate axes of the device body; the attachment unit is an attachment unit common to multiple cutting units; and is used in a biological tissue cutting device described in any one of claims 1 to 9.

18. A sample stage comprising a sample stage, a tray surrounding the sample stage, and a rim surrounding the tray; the sample stage is a convex body protruding upward, the upper surface of the convex body is an area for placing the sample, the outer periphery of the lower end of the sample stage is connected to the tray, the upper surface of the tray is inclined downward from the sample stage side towards the outer periphery of the tray, and has at least one outlet through-hole for outletting the cut piece of the sample from the tray, and has a side wall protruding upward on the outer periphery, the rim is connected to the upper end side of the side wall of the tray and has a portion to be attached to a stage holder of a biological tissue cutting device; at least one of the sample stage, tray, and rim has at least one mark indicating direction on its upper surface; and 19. A specimen stage according to claim 18, wherein the stage holder of the biological tissue cutting device has a protrusion for mounting the specimen stage, and the mounting portion on the rim is a through hole into which the protrusion fits.

20. The sample stage according to claim 18 or 19, wherein the capacity of the tray is 10 to 100 mL.

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