JP4817320B2 - Thin section specimen preparation device and thin section specimen preparation method - Google Patents

Description

  The present invention cuts a thin section from an embedding block in which a biological sample taken from a human body or a laboratory animal is embedded, and places the thin section on a slide glass to prepare a thin section specimen. The present invention relates to an apparatus and a method for producing a thin-section specimen.

  Conventionally, as one method for inspecting and observing a biological sample taken from a human body or a laboratory animal, a thin section is prepared from an embedding block in which the biological sample is embedded with an embedding agent, and the biological sample is observed. The method is known. More specifically, a thin section prepared from an embedding block is placed on a slide glass to prepare a thin section specimen, and the biological sample contained in the thin section is subjected to a staining process on the slide glass. Observations are made.

  Here, for example, in a preclinical test, several hundred embedded blocks are prepared per test, and several thin slice specimens are prepared per embedded block. For this reason, since it is necessary for an operator to prepare an enormous number of thin-section specimens, a thin-section specimen preparation apparatus capable of performing a series of steps from the embedding block to the preparation of a thin-section specimen in recent years has been developed. It is being developed. Such a sliced piece preparation apparatus includes a cutting means for cutting a sliced piece from an embedded block, a sliced piece carrying means for carrying the cut sliced piece, and a sliced piece transferred from the sliced piece carrying means to a slide glass. There has been proposed one provided with a transfer means (see, for example, Patent Document 1). According to such a thin-section specimen preparation device, the embedding block is cut at a predetermined thin-section thickness by the cutting means to produce a thin section, and the prepared thin section is transported to the slide glass by the thin-section transport means. However, it is said that a thin slice specimen can be produced by transferring a thin slice to a slide glass by a transfer means.

By the way, when cutting the embedding block, a thin slice of a good cut surface can be obtained by adjusting the direction of the embedding block with respect to the cutting direction according to the type and direction of the biological sample. . For this reason, on the stage for cutting the embedded block, the operator may adjust the orientation of the embedded block placed on the stage for each embedded block, depending on the type and orientation of the biological sample. . On the other hand, in the preclinical tests as described above, there is a case where the direction of the biological sample contained in the thin slice on the slide glass is determined to be a fixed direction by a standard work manual or the like. For this reason, the operator prepares a thin slice with the embedding block as a suitable orientation, and then confirms the orientation of the biological sample contained in the thin slice and adjusts the relative orientation of the biological sample with respect to the slide glass. It was necessary to place a thin section on a slide glass.
JP 2004-28910 A

  However, in the apparatus according to Patent Document 1, for example, if the orientation of the embedding block is changed to obtain a thin section of a suitable cut surface, it was produced, transported, and included in the thin section placed on the slide glass. The direction of the biological sample also changes. For this reason, the relative orientation of the biological sample with respect to the slide glass cannot be made constant, and it has not been possible to obtain a thin slice specimen of a constant quality.

  The present invention has been made in view of the above-described circumstances, and is capable of producing a thin-section specimen in which the relative direction of the biological sample with respect to the slide glass is a fixed direction regardless of the direction of the embedding block. A thin slice specimen preparation apparatus and a thin slice specimen preparation method are provided.

In order to solve the above problems, the present invention proposes the following means.
The present invention is a thin-section specimen preparation device that cuts a thin section from an embedding block in which a biological sample is embedded with an embedding agent, and places the thin section on a slide glass to prepare a thin-section specimen. A cutting mechanism for cutting the embedded block to produce the thin slice, and a mounting surface on which the slide glass is placed, and the slide glass is placed within a plane substantially parallel to the placement surface. A slide glass rotary stage that can be rotated, and the thin slice produced by the cutting mechanism is received and conveyed, and the slide glass is placed on the slide glass placed on the placement surface of the slide glass rotary stage. A transport mechanism capable of delivering a thin slice, and detecting direction data representing the orientation of the biological sample contained in the thin slice produced by the cutting mechanism, and based on the direction data, Control for rotating the slide glass by the slide glass rotation stage so that the relative direction between the biological sample contained in the thin section delivered from the feeding mechanism and the slide glass is a preset direction. It is characterized by providing a part.

  The present invention also provides a method for producing a thin-section specimen in which a thin section is cut from an embedding block in which a biological sample is embedded with an embedding agent, and the thin section is placed on a slide glass. The method includes a cutting step of cutting the embedded block to produce the thin section, a transporting step of receiving and transporting the thin section prepared in the cutting step, and the thin section A detection step for detecting direction data representing the direction of the biological sample, and a relative direction between the biological sample and the slide glass included in the thin section based on the direction data detected in the detection step A slide glass rotation step for rotating the slide glass so that the orientation is set in advance, and on the slide glass whose orientation has been adjusted by the slide glass rotation step, The is characterized in that it comprises a delivery step of transferring the thin section.

  According to the thin-slice manufacturing device and the method for manufacturing a thin-slice according to the present invention, if the embedded block is placed in the cutting mechanism and cut in the cutting process with the orientation of the embedded biological sample as an arbitrary orientation, Thin slices are produced in the same direction as the biological sample when embedded in the buried block. Next, the prepared thin section is received and transported by a transport mechanism as a transport process, and direction data indicating the direction of the biological sample contained in the thin section is detected by the control unit as a detection process. Is called. Then, as the slide glass rotation step, the control unit slides based on the detected direction data so that the relative direction between the biological sample contained in the thin section and the slide glass is a preset direction. The slide glass is rotated and adjusted by the glass rotation stage. For this reason, as a delivery process, a thin section sample is placed on a slide glass placed on the placement surface of the slide glass rotation stage by placing a thin section with the relative orientation of the biological sample constant. Can be produced.

  In the thin-section specimen preparation apparatus, the cutting mechanism includes an embedding block rotation stage capable of rotating the embedding block in a plane substantially parallel to a surface for cutting the embedding block. An operation unit capable of inputting the rotation angle for rotating the embedded block by the embedded block rotation stage, and the control unit detects the rotation angle input by the operation unit as the direction data, It is more preferable to rotate the slide glass based on the rotation angle.

  Further, in the above method for preparing a thin-section specimen, a cutting direction adjusting step of adjusting the orientation by rotating the embedded block in a plane substantially parallel to the surface of cutting the embedded block before the cutting step. The detecting step detects a rotation angle of the embedded block rotated in the cutting direction adjusting step as the direction data, and the slide glass rotating step rotates the slide glass based on the rotation angle. It is said that it is more preferable.

  According to the thin-slice manufacturing apparatus and the thin-slice manufacturing method according to the present invention, as the cutting direction adjustment step, the embedded block is rotated by the embedded block rotation stage in the cutting mechanism by the rotation angle input by the operation unit. be able to. For this reason, in the cutting process, the embedded block can be cut with a suitable orientation of the biological sample embedded by the cutting mechanism to produce a thin slice. Further, the control unit detects the rotation angle input as the direction data in the detection step, and rotates the slide glass based on the rotation angle in the slide glass rotation step, so that the embedding block in the cutting direction adjustment step The thin slice specimen can be prepared by placing the thin slice on the slide glass with the relative orientation of the biological sample being substantially constant even if the specimen is rotated.

  Further, in the above-described thin-section sample preparation device, the thin-section specimen preparation apparatus includes an imaging unit that captures an image of the thin section transported by the transport mechanism and can acquire an image of the thin section. The direction of the mark formed in the thin section with a directivity corresponding to the direction of the thin section and projected on the image is detected in advance, and the direction of the mark is set to a preset direction. The slide glass may be rotated.

  Further, in the above method for preparing a sliced piece sample, mark formation is performed on the surface to be cut of the embedding block before the cutting step so as to form a directional mark corresponding to the orientation of the sliced piece to be formed. The detection step includes photographing the thin section to obtain an image, detecting the direction of the mark displayed on the image as the direction data, and the slide glass rotation step including the slide glass The slide glass may be rotated so that the relative orientation of the mark with respect to is a preset orientation.

  According to the thin-slice manufacturing apparatus and thin-slice manufacturing method according to the present invention, the mark having a direction corresponding to the orientation of the thin slice is formed on the surface to be cut of the embedding block in the cutting step as the mark forming step. Is formed. In the detection step, the control unit acquires an image of the thin section by the imaging unit, and detects the direction of the mark displayed on the image as the direction data. In general, the biological sample is embedded in an orientation corresponding to the orientation of the embedding block, that is, the orientation of the biological sample and the orientation of the thin section are constant. For this reason, in the slide glass rotation step, the slide glass is rotated so that the direction of the detected mark becomes a preset direction by the control unit, so that the relative direction of the biological sample is made substantially constant. A thin slice specimen can be prepared by placing a thin slice on the plate.

  Further, in the above-described thin-section sample preparation device, the thin-section specimen preparation apparatus includes an imaging unit that captures an image of the thin section transported by the transport mechanism and can acquire an image of the thin section. The range of the biological sample contained in the thin section displayed in the image is detected, and the pattern matching element is compared with the detected range of the biological sample and a preset range so as to be approximately equal to each other. The slide glass may be rotated.

  Further, in the above method for preparing a thin-section specimen, the detecting step captures the thin section to acquire an image, and as the direction data, the biological sample included in the thin section displayed on the image. The range may be detected, and the slide glass rotation step may rotate the slide glass so that pattern matching elements are compared with each other in a range of the biological sample and a preset range.

  According to the thin-section preparation apparatus and the thin-section preparation method according to the present invention, in the detection step, the control unit acquires an image of the thin section by the imaging unit, and determines the range of the biological sample displayed on the image as direction data. To detect. Then, in the slide glass rotation step, the control unit rotates the slide glass so that the pattern matching elements are compared with each other in the range of the detected biological sample and the preset range. Therefore, regardless of the relative orientation of the embedded block and the thin slice and the biological tissue, the thin slice is prepared by placing the thin slice on the slide glass with the relative orientation of the biological sample being substantially constant. can do.

According to the thin-section sample preparation apparatus of the present invention, the relative orientation of the biological sample with respect to the slide glass based on the direction data regardless of the orientation of the embedded block by including the slide glass rotation stage and the control unit. A thin slice specimen of a certain quality can be produced with a certain orientation.
In addition, according to the method for producing a sliced piece specimen of the present invention, by providing the detection step and the slide glass rotation step, the biological sample relative to the slide glass is obtained based on the direction data regardless of the direction of the embedded block. It is possible to produce a thin slice specimen of a certain quality with a specific orientation as a certain direction.

(First embodiment)
1 to 4 show a first embodiment according to the present invention. The thin-section specimen preparation apparatus 1 shown in FIG. 1 prepares an ultrathin thin section B1 having a thickness of about 3 to 5 μm from an embedding block B in which a biological sample S is embedded, and the biological specimen included in the thin section B1 In the process of inspecting and observing S, the thin section B1 is automatically cut from the embedded block B and placed on the slide glass P to produce a thin section specimen. The biological sample S is, for example, a sample excised from a tissue such as an organ taken out of a human body or a laboratory animal, and is appropriately selected in the medical field, pharmaceutical field, food field, biological field, and the like. The embedding block B is the above-described biological sample S embedded with the embedding agent B2, that is, the periphery is covered and solidified. The biological sample S is usually unified in the direction for each type. Embedded. The embedding block B is handled by being mounted on an embedding cassette C formed of a resin or the like with a uniform orientation. In more detail, such an embedding block B is produced as follows. First, the mass of the biological sample S is immersed in formalin, and the protein constituting the biological sample S is fixed. And after making a structure | tissue solid, it cut | disconnects to a suitable magnitude | size. Finally, it is produced by embedding in solidified embedding agent B2 the thing which replaced the water | moisture content inside the cut | disconnected biological sample S by embedding agent B2, and making it. Here, the embedding agent B2 is a material that can be easily liquefied and cooled and solidified as described above, and is dissolved by being immersed in an organic solvent, such as resin or paraffin. Hereinafter, the configuration of the thin-section specimen preparation device 1 will be described.

  As shown in FIG. 1, the thin-section specimen preparation device 1 includes a cutting mechanism 2 that cuts the embedding block B to prepare the thin section B1, a mounting table 3 on which the slide glass P is placed, and a thin section B1. A transport mechanism 4 that transports from the cutting mechanism 2 to the mounting table 3 and a control unit 5 that controls each component are provided. The cutting mechanism 2 includes a placement surface 10 on which an embedding cassette C on which the embedding block B is mounted can be placed, and an embedding block rotation stage 11 that moves the embedding block B placed on the placement surface 10. And an embedded block Z stage 12, a cutter 13 capable of cutting the embedded block B placed on the placement surface 10, a cutter driving unit 14 for moving the cutter 13, and an operation unit 15.

  An embedding cassette C on which the embedding block B is mounted can be mounted on the mounting surface 10 in a substantially same direction by a transfer robot (not shown). Moreover, the cutter 13 is being fixed to the cutter drive part 14 so that the embedding block B can be cut within the cutting surface B3. Moreover, the cutter drive unit 14 can move the cutter 13 forward and backward in the X direction toward the embedding block B placed on the placement surface 10 within the cutting surface B3. Cutting can be performed at the cutting surface B3. In addition, it is good also as a structure which changes to the cutter drive part 14 and moves the embedding block B to the X direction with respect to the cutter 13. FIG. Moreover, the embedding block rotating stage 11 can rotate the embedding block B placed on the placement surface 10 within the cutting surface B3, and thereby the embedding block B can be rotated from any direction by the cutter 13. Can be cut. Further, the embedded block Z stage 12 can advance and retract the embedded block B placed on the placement surface 10 in the Z direction substantially orthogonal to the cutting surface B3. Now, the embedded block B can be cut.

  The operation unit 15 can manually set the rotation angle by the embedding block rotary stage 11 and the amount of movement in the Z direction by the embedding block Z stage 12, and can manually drive the cutter driving unit 14. Cutting with the cutter 13 is possible. On the other hand, the control unit 5 sets and drives the movement amount of the embedding block Z stage 12 according to the preset thin section thickness regardless of the operation by the operation unit 15, and also performs the cutter at a preset cutting speed. It is possible to cut by the cutter 13 by driving the drive unit 14. When each manual operation is performed by the operation unit 15, an operation result by the operation unit 15 is output, and the control unit 5 rotates the rotation angle by the embedding block rotation stage 11 or the Z direction by the embedding block Z stage 12. It is possible to detect the amount of movement.

  Moreover, the mounting table 3 has a mounting surface 20a on which the slide glass P can be mounted on the upper part, a slide glass rotating stage 20 capable of rotating the slide glass P within the mounting surface 20a, and a slide glass A slide glass triaxial stage 21 capable of moving P in three axes in the X direction, the Y direction, and the Z direction is provided. The slide glass rotation stage 20 and the slide glass triaxial stage 21 are connected to the control unit 5 and are transported by a transport robot (not shown) and placed on the placement surface 20a under the control of the control unit 5. The slide glass P can be moved. Details of the control by the control unit 5 will be described later. Further, the slide glass P is placed on the placement surface 20a with a substantially constant orientation in a state where the droplet P2 for adsorbing the thin slice B1 adheres to the placement surface P1 by the above-described transport robot (not shown). The mounting table 3 may also have an operation unit, and the slide glass rotary stage 20 and the slide glass triaxial stage 21 may be driven manually.

  Moreover, the conveyance mechanism 4 is comprised by the conveyance tape 25 arrange | positioned along the X direction from the cutting mechanism 2 to the mounting base 3, and is a tape delivery part in order toward the mounting base 3 from the cutting mechanism 2 side. 26, a first roller 27, a second roller 28, and a tape winding unit 29. The tape delivery unit 26 is a unit in which the transport tape 25 is wound in a roll shape and supplies the transport tape 25 toward the sample stage 3 of the cutting mechanism 2, and a shaft body 26 a around which the transport tape 25 is wound. And a drive unit (not shown) for rotating the shaft body 26a. A drive unit (not shown) is connected to the control unit 5, and can rotate the shaft body 26 a at a predetermined rotation speed under the control of the control unit 5. Similarly, the tape take-up unit 29 collects the transport tape 25 that has been wound around the transport tape 25 and has passed through the mounting table 3, and a shaft body 29 a around which the transport tape 25 is wound. And a drive unit (not shown) for rotating the shaft body 29a. A drive unit (not shown) is connected to the control unit 5, and can rotate the shaft body 29 a at a predetermined rotation speed under the control of the control unit 5. The first roller 27 and the second roller 28 are provided to face the tape delivery unit 26 or the tape take-up unit 29 with the cutting mechanism 2 or the mounting table 3 interposed therebetween, respectively, and guide the transport tape 25. Is. The first roller 27 and the second roller 28 are also provided with a drive unit (not shown) and rotate independently of the tape feeding unit 26 and the tape winding unit 29 under the control of the control unit 5. It is possible.

  Then, by independently rotating the tape delivery unit 26 and the first roller 27, the transport tape 25 is disposed above the embedding block B placed on the placement surface 10 of the cutting mechanism 2. From the state, the lower surface 25a can be brought into contact with the cut surface B4 of the embedding block B by loosening. Further, by independently rotating the second roller 28 and the tape winding unit 29, the transport tape 25 is disposed above the slide glass P placed on the placement surface 20 a of the placement table 3. From the state, the lower surface 25a can be brought into contact with the mounting surface P1 of the slide glass P by being slackened. Further, a negative charge is applied to the upper surface 25b of the transport tape 25 delivered from the tape delivery unit 26 by a charging device (not shown). On the other hand, a positive charge is given to the cut surface B4 of the embedding block B placed on the placement surface 10 by another charging device (not shown). For this reason, the thin slice B1 cut from the embedding block B to which a positive charge is applied can be attached to the lower surface 25a of the transport tape 25, and the tape feeding portion 26, the first roller 27, and the second The thin section B1 can be transported in the X direction by driving the roller 28 and the tape winding unit 29 in conjunction with each other.

  Next, a method for producing a thin-section specimen by the thin-section specimen production apparatus 1 and details of control by the control unit 5 will be described. FIG. 2 shows a flow chart of thin section specimen preparation. First, as the preparation step S1, an embedding cassette C on which a predetermined embedding block B is mounted is selected by a transfer robot (not shown), and the embedding block B is determined in advance on the mounting surface 10 of the cutting mechanism 2. Place and fix according to the direction. In addition, the slide glass P with the droplets P2 attached to the placement surface P1 is placed on the placement surface 20a of the placement table 3 in a predetermined direction by another transport robot (not shown).

  Next, as the cutting direction adjustment step S2, the operator rotates the embedded block rotation stage 11 while confirming the biological sample S embedded in the embedded block B under the operation of the operation unit 15. The biological sample S is adjusted so as to be in an optimum direction with respect to the X direction to be cut. At this time, as the detection step S3, the rotation angle required for the adjustment is input from the operation unit 15 to the control unit 5, and the control unit 5 detects the rotation angle as direction data. Further, as the slide glass rotation step S4, the control unit 5 adjusts the direction of the slide glass P based on the rotation angle that is the detected direction data. That is, the control unit 5 rotates the slide glass P by the slide glass rotation stage 20 by the same rotation angle as the detected rotation angle. For example, as shown in FIG. 3, when the embedding block B is not rotated in the cutting direction adjustment step S <b> 2, the detected rotation angle is 0 degree, and the control unit 5 drives the slide glass rotation stage 11. I won't let you. On the other hand, as shown in FIG. 4, when the embedded block B is rotated 90 degrees counterclockwise in the cutting direction adjustment step S2, if the counterclockwise direction is positive, the detected rotation angle is +90 degrees, The control unit 5 rotates the slide glass rotation stage 11 by +90 degrees. For this reason, the relative orientation of the biological sample S and the slide glass P embedded in the embedded block B is always constant. 3 and 4, a frost portion P4 is provided on one end side of the placement surface P1 of the slide glass P. The frost portion P4 is, for example, a surface roughened and can be written with identification characters. In this embodiment, the orientation of the slide glass P is determined by this. Further, the slide glass triaxial stage 21 may be driven together with the slide glass rotation step S4 to move the slide glass P in the X direction, the Y direction, and the Z direction. By moving in the X direction and the Y direction, it is possible to adjust the position of the slide glass P in the XY plane (the length direction and the width direction of the slide glass P), and by moving in the Z direction, The separation distance between the slide glass P and the transport tape 25 can be adjusted.

  On the other hand, simultaneously with the above-described detection step S3 and slide glass rotation step S4, as a cutting step S5, the embedded block B is cut at a predetermined thickness to produce a thin slice B1. That is, the control unit 5 drives the embedded block Z stage 12 of the cutting mechanism 2 to move the embedded block B in the Z direction so as to have a predetermined thickness. Next, the control unit 5 drives the tape delivery unit 26 and the first roller 27 of the transport mechanism 4 to loosen the transport tape 25 and bring the lower surface 25a into contact with the cut surface B4 of the embedding block B. To. Here, by the charging device (not shown), the embedded block B is charged with a positive charge, and the upper surface 25b of the transport tape 25 is charged with a negative charge. For this reason, the lower surface 25a of the transport tape 25 and the cut surface B4 of the embedding block B are in close contact with each other by electrostatic force. Then, the control unit 5 drives the cutter driving unit 14 and moves the cutter 13 toward the embedded block B at a predetermined cutting speed, thereby cutting the embedded block B, and a thin slice having a predetermined thickness. B1 can be produced. Here, since the direction of the biological sample S embedded in the embedded block B by the embedded block rotation stage 11 can be cut as a suitable direction with respect to the X direction, which is the cutting direction, good cutting is possible. A thin slice B1 can be produced as a surface.

  Next, as the transporting step S6, the produced thin slice B1 is received and transported toward the mounting table 3. That is, the thin slice B1 produced in the cutting step S5 is received by the transport tape 25 by electrostatic force and is in close contact with the lower surface 25a. Then, the control unit 5 drives the tape delivery unit 26 and the first roller 27, so that the transport tape 25 that holds the thin slice B1 in close contact moves above the embedding block B, and the thin slice B1 is embedded. Leave block B. Further, the control unit 5 also drives the second roller 28 and the tape take-up unit 29 and interlocks with the tape feeding unit 26 and the first roller 27, whereby the transport tape 25 is placed along the X direction on the mounting table 3. As a result, the thin section 3 is transported to above the slide glass P of the mounting table 3.

  Next, as a delivery step S7, the thin slice B1 is delivered from the transport tape 25 to the slide glass P, thereby completing the thin slice specimen. That is, the control unit 5 drives the second roller 28 and the tape winding unit 29 in a state where the thin slice B1 is positioned above the slide glass P placed on the placement surface 20a, and the thin slice B1 is The transport tape 25 is lowered until it comes into contact with the placement surface P1 of the slide glass P. When the thin slice B1 comes into contact with the placement surface P1 of the slide glass P, the droplet P2 adheres to the placement surface P1, so that the thin slice B1 is detached from the transport tape 25 due to the surface tension of the droplet P2. It becomes a state adsorbed on the mounting surface P1 of the slide glass P, whereby a thin slice specimen is produced. At this time, the orientation of the slide glass P is adjusted by the slide glass rotation step S4, so that the relative orientation of the biological sample S1 included in the thin slice B1 with respect to the slide glass P is fixed, and the slide glass P is placed. A thin slice specimen can be prepared by placing the thin slice B1 on the surface P1.

  As described above, in the thin-section specimen preparation device 1 of the present embodiment, even if the embedded block B is rotated in the cutting direction adjustment step S2, the control unit 5 performs the slide based on the rotation angle that is direction data. With the relative orientation of the biological sample S relative to the glass P as a constant orientation, a thin slice specimen with a constant quality can be produced. Further, in the cutting direction adjustment step S2, the direction of the biological sample S embedded in the embedded block B can be adjusted with respect to the X direction, which is the cutting direction, by the embedded block rotation stage 11, so that it is optimal. By cutting the embedding block B from the direction, a thin slice B1 having a good cut surface B4 can be produced.

  In the present embodiment, the slide glass P is rotated in the slide glass rotation step S4 by the rotation angle obtained by rotating the embedding block B in the cutting direction adjustment step S2. However, the present invention is not limited to this. For example, the slide glass P may be rotated by an angle corrected by a preset correction amount based on the detected rotation angle. In the cutting direction adjustment step S2, the operator determines the rotation angle of the embedding block B by direct operation by operating the operation unit 15. However, the present invention is not limited to this. For example, when the operator inputs an ID number from the operation unit 15, the rotation angle recorded corresponding to the ID number is called, and the embedded block B is rotated and cut. In other words, the embedding cassette C on which the embedding block B is mounted is assigned an ID number corresponding to the embedding block B mounted on the embedding block B, and a plurality of them are stored in the storage shelf. The control unit 5 records the ID number, the storage position of the storage shelf corresponding to the ID number, the type of the embedded biological sample S, and the rotation angle rotated by the embedded block rotation stage 11. Yes. Moreover, it is set as the structure which can input the ID number of the embedding block B which produces a thin slice sample with the operation part 15. FIG. In such a case, when the operator inputs the ID number in the operation unit 15, the control unit 5 selects the embedding cassette B corresponding to the ID number as the preparation step S <b> 1 and embeds the cassette C up to the cutting mechanism 2. Transport. And the control part 5 calls the rotation angle corresponding to ID number as cutting direction adjustment process S2, and rotates the embedding block B with this rotation angle. Finally, by cutting the embedding block B in the cutting step S5, the embedding block B can be cut in an optimal direction to produce the thin slice B1.

  Moreover, although the structure which affixes and conveys to the conveyance tape 25 with an electrostatic force was mentioned as an example as the conveyance mechanism 4, it does not restrict to this. For example, adhesive force may be applied to the transport tape 25 so that the transport tape 25 is adhered and transported, or the transport tape 25 may be placed on the transport tape 25 and transported. It is sufficient that at least the thin slice B1 produced by the cutting mechanism 2 can be transferred to the mounting table 3 without changing its orientation and delivered to the slide glass P.

(Second Embodiment)
5 and 6 show a second embodiment according to the present invention. In this embodiment, members that are the same as those used in the above-described embodiment are assigned the same reference numerals, and descriptions thereof are omitted.

  As shown in FIG. 5, the thin-section specimen preparation device 40 of this embodiment is provided above the transport tape 25 between the cutting mechanism 2 and the mounting table 3 and is transported by the transport tape 25. And a second CCD camera 42 provided above the mounting surface 20a of the mounting table 3 and capable of shooting the slide glass P and the transported thin section B1. With. In addition, the control unit 5 is equipped with an image analyzer 43 and can analyze images taken by the first CCD camera 41 and the second CCD camera 42. Details of image analysis by the image analyzer 43 of the control unit 5 will be described later.

  In the present embodiment, the embedding block B used in the thin-section specimen preparation device 40 has an orientation flat (hereinafter referred to as orientation flat) B5 that is a mark indicating the orientation of the embedding block B and the thin section B1. Is formed. As shown in FIG. 6, the orientation flat B <b> 5 is obtained by chamfering the corners uniformly in the thickness direction at a certain angle in a substantially rectangular outer shape. For this reason, even if the embedded block B is cut at any position to produce the thin slice B1, the same orientation flat B5 is also formed in the thin slice B1. Then, the thin section B1 transported by the transport tape 25 is photographed by the first CCD camera 41, and the orientation of the orientation flat B5 of the thin section B1 displayed in the image is detected by the image analyzer 43 of the control unit 5. Thus, it is possible to detect the orientation of the thin slice B1 using the orientation of the orientation flat B5 as direction data. Further, the slide glass P placed on the placement table 3 is photographed by the second CCD camera 42, and the image analyzer 43 of the control unit 5 displays the image according to the orientation of the frost part P4 of the slide glass P displayed on the image. It is possible to detect the orientation of the slide glass P.

  Next, a method for producing a thin-section specimen by the thin-section specimen preparation apparatus 40 and details of control by the control unit 5 will be described. Details of the same points as in the first embodiment are omitted. In the present embodiment, the orientation flat B5 is formed as a mark forming step when the embedded block B to be a thin slice specimen is manufactured. The orientation flat B5 may be formed by using the shape of the embedding agent B2 forming the embedding block B as a shape having the orientation flat B5, or by cutting the embedding agent B2 after solidification to form the orientation flat B5. It is good as a thing.

  And as the preparatory process S1, the embedding block B is mounted on the cutting mechanism 2, and the slide glass P is mounted on the mounting table 3. Next, as cutting direction adjustment process S2, the direction of the embedding block B is adjusted by the operation part 15, and it cuts by cutting process S5. And as conveyance process S6, the thin slice B1 produced by cutting is conveyed by the conveyance mechanism 4. FIG. Then, in the middle of the conveyance, the thin section B1 is photographed by the first CCD camera 41 in a state of being closely held on the conveyance tape 25 as the detection step S3. The image acquired by photographing is input to the image analyzer 43 of the control unit 5, and the control unit 5 detects the orientation of the orientation flat B5 as direction data.

  Next, as the slide glass rotation step S4, the control unit 5 adjusts the direction by rotating the slide glass P by the slide glass rotation stage 20 based on the orientation of the orientation flat B5 that is the detected direction data. That is, the control unit 5 sets in advance corresponding to the detected orientation of the orientation flat B5 and the orientation of the thin section B1 when the orientation of the biological sample S included in the thin section B1 is optimal with respect to the slide glass P. The necessary orientation correction value is determined by comparing the orientation of the orientation flat B5. Then, the control unit 5 rotates the slide glass P by the slide glass rotation stage 20 by this angle correction value. For this reason, the direction of the biological sample S1 contained in the thin slice B1 and the direction of the slide glass P can be made constant. Here, the control unit 5 further monitors the orientation of the slide glass P by the second CCD camera 43 based on the orientation of the frost portion P1 of the slide glass P. For this reason, even if the slide glass P is not placed in a predetermined direction in the preparation step S1, only the angle correction value corresponding to the deviation of the slide glass P can be further corrected and rotated, and more accurately. The direction of the biological sample S1 and the direction of the slide glass P can be adjusted. Finally, as a delivery step S7, the thin slice B1 is placed on the slide glass P whose orientation has been adjusted to produce a thin slice specimen in which the relative orientation of the biological sample S1 is constant with respect to the slide glass P. be able to.

  In the present embodiment, the orientation flat B5 is taken as an example of the mark having the directivity corresponding to the direction of the thin slice, but the present invention is not limited to this. 7 and 8 show modifications. That is, as shown in FIG. 7, notches may be formed uniformly in the thickness direction on any side of the embedded block B. Further, as shown in FIG. 8, when the biological sample S is embedded with the embedding agent B2, a substantially bar-shaped index that can be identified by an image captured by the first CCD camera 41 at a predetermined position as a mark. The object B7 may be embedded in the thickness direction. In this case, it is possible to function as direction data by embedding the index object B7 in at least two predetermined places, but by using three or more places as shown in FIG. Can be identified. Moreover, although all said examples are formed before the embedding block B is mounted in the cutting mechanism 2, it does not restrict to this. For example, the cutting mechanism 2 is provided with a mechanism capable of forming a groove having a certain direction on the cutting surface B4 of the embedded block B, and the cutting of the embedded block B is performed before the cutting direction adjusting step S2. The groove may be formed as a mark on the surface B4. Similarly to the first embodiment, an ID number is assigned to the embedding cassette C, and the rotation angle by the embedding block rotation stage 11 in the cutting direction adjustment step S2 is set based on the input ID number. It is good to do. Moreover, it is good also as what sets direction, such as orientation flat B5, in a different direction in slide glass rotation process S5 for every kind of biological sample based on the input ID number.

(Third embodiment)
5 and 9 show a third embodiment according to the present invention. In this embodiment, members that are the same as those used in the above-described embodiment are assigned the same reference numerals, and descriptions thereof are omitted. The configuration of the thin-section specimen preparation device 50 of this embodiment is the same as that of the second embodiment except for the control method of the control unit 5.

  As shown in FIG. 5, in the thin-section sample preparation device 50 of the present embodiment, the image analyzer 43 of the control unit 5 is included in the thin section B1 from the image captured by the first CCD camera as direction data. It is possible to detect the range of the biological sample S1. In addition, an image when the biological sample S1 is in an optimal orientation with respect to the slide glass P is recorded in the control unit 5 as a standard image, and is set in advance so as to be based on the range of the biological sample in the standard image. Has been. For this reason, in the slide glass rotation step S4, the control unit 5 uses the pattern of the range of the biological sample S included in the thin section B1 in the image detected in the detection step S3 and the range of the biological sample in the standard image. The matching elements are compared and the detected images are rotated to be approximately equal. Then, the slide glass P is rotated by the angle correction value when approximately equal.

  By doing so, for example, as in the first embodiment, as shown in FIG. 5, even if the embedded block B is rotated in the cutting direction adjusting step S2, the slide glass P is correspondingly moved in the slide glass rotating step S4. Can be rotated, and a thin slice specimen can be produced with the relative orientation of the biological sample S with respect to the slide glass P being constant. Here, as shown in FIG. 9, the orientation of the biological sample S with respect to the direction of the embedding block B is embedded differently from the normal direction due to an error of an operator who produces the embedding block B. There is a case. However, in the case of this embodiment, since the direction of the biological sample S can be directly detected as the direction data, the thin slice with the relative direction of the biological sample S1 with respect to the slide glass P is constant in the slide glass rotation step S4. A thin slice specimen can be prepared by placing B1.

  In the present embodiment, an ID number can be input by the operation unit 15, and the standard image is recorded for each type of biological sample and each type of biological sample in association with the ID number in the control unit 5. It is suitable. In this way, the type of the biological sample of the thin-section specimen to be produced by the control unit 5 is specified only by inputting the ID number, and the direction of the biological sample is optimized for each type of biological specimen, A thin slice specimen can be prepared by placing B1 on the slide glass P.

  In the second embodiment and the third embodiment, the first CCD camera 41 is disposed between the cutting mechanism 2 and the mounting table 3 and above the transport belt 25, so that the thin slice B1 in the middle of transport is provided. However, the present invention is not limited to this. For example, the first CCD camera 41 is arranged above the embedding block B placed on the placement surface 10 of the cutting mechanism 2 to photograph the cut surface B4 of the embedding block B after the cutting direction adjustment step S2. It is good to do. Since the orientation of the embedding block B and the orientation of the thin slice B1 are constant unless the orientation of the thin slice B1 is changed during the conveyance, the orientation of the slide glass P can be adjusted in the slide glass rotation step S4 in the same manner. it can.

  As mentioned above, although embodiment of this invention was explained in full detail with reference to drawings, the concrete structure is not restricted to this embodiment, The design change etc. of the range which does not deviate from the summary of this invention are included.

1 is an overall view of a thin-section specimen preparation device according to a first embodiment of the present invention. It is a flow figure of thin section preparation of a 1st embodiment of this invention. It is explanatory drawing of the slide glass rotation process of 1st Embodiment of this invention. It is explanatory drawing of the slide glass rotation process of 1st Embodiment of this invention. It is a whole figure of the sliced piece preparation apparatus of 2nd Embodiment and 3rd Embodiment of this invention. It is a top view which shows the embedding block used with the sliced piece preparation apparatus of 2nd Embodiment of this invention. It is a top view which shows one modification of the embedding block used with the sliced piece preparation apparatus of 2nd Embodiment of this invention. It is a top view which shows the other modification of the embedding block used with the sliced piece preparation apparatus of 2nd Embodiment of this invention. It is explanatory drawing of the slide glass rotation process of the 3rd Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1, 40, 50 Thin section sample preparation apparatus 2 Cutting mechanism 4 Conveyance mechanism 5 Control part 10 Mounting surface 11 Embedded block rotation stage 13 Cutter 15 Operation part 20 Slide glass rotation stage 20a Mounting surface 41 1st CCD camera ( Imaging means)
B Embedded block B1 Thin section B3 Cutting surface B5 Orient flat (mark)
B6 Notch (mark)
B7 Indicator (mark)
S, S1 biological sample

Claims (8)

A thin-section specimen preparation device that cuts a thin section from an embedding block in which a biological sample is embedded with an embedding agent, and places the thin section on a slide glass to prepare a thin-section specimen.
A cutting mechanism for cutting the embedded block and producing the thin slice;
A slide glass rotation stage having a placement surface on which the slide glass is placed and capable of rotating the slide glass in a plane substantially parallel to the placement surface;
A transport mechanism capable of receiving and transporting the thin section produced by the cutting mechanism and delivering the thin section on the slide glass placed on the placement surface of the slide glass rotation stage; ,
Direction data representing the orientation of the biological sample contained in the thin section produced by the cutting mechanism is detected, and the living body contained in the thin section delivered from the transport mechanism based on the direction data. A thin-section sample preparation apparatus comprising: a control unit that rotates the slide glass by the slide glass rotation stage so that a relative direction between the sample and the slide glass is a preset direction. In the thin-section sample preparation apparatus according to claim 1,
The cutting mechanism includes an embedding block rotation stage capable of rotating the embedding block in a plane substantially parallel to a surface for cutting the embedding block;
An operation unit capable of inputting the rotation angle for rotating the embedded block by the embedded block rotation stage;
The control unit detects the rotation angle input by the operation unit as the direction data, and rotates the slide glass based on the rotation angle. In the thin-section sample preparation apparatus according to claim 1,
Imaging means capable of capturing an image of the thin section by capturing the thin section transported by the transport mechanism,
The control unit detects, as the direction data, a direction of a mark formed in the thin section and having a directivity corresponding to the direction of the thin section and projected on the image, and the direction of the mark The thin-section sample preparation apparatus is characterized in that the slide glass is rotated so as to have a preset orientation. In the thin-section sample preparation apparatus according to claim 1,
Imaging means capable of capturing an image of the thin section by capturing the thin section transported by the transport mechanism,
The control unit detects, as the direction data, a range of the biological sample included in the thin slice displayed in the image, and a pattern matching element based on the detected range of the biological sample and a preset range And the slide glass is rotated so as to be substantially equal to each other. A method for producing a thin-section specimen, in which a thin section is cut from an embedding block in which a biological sample is embedded with an embedding agent, and the thin section is placed on a slide glass,
Cutting the embedded block to produce the thin slice; and
A transporting process for receiving and transporting the thin section produced in the cutting process;
A detection step of detecting direction data representing the orientation of the biological sample contained in the thin section;
Based on the direction data detected in the detection step, the slide glass is rotated so that a relative direction between the biological sample contained in the thin section and the slide glass is a preset direction. Slide glass rotation process,
A method for producing a thin-section specimen, comprising: a delivery step for delivering the thin section received in the transporting step on the slide glass whose orientation has been adjusted by the slide glass rotation step. In the method for producing a thin-section specimen according to claim 5,
A cutting direction adjusting step of adjusting the orientation by rotating the embedded block in a plane substantially parallel to the surface of cutting the embedded block before the cutting step;
The detection step detects a rotation angle of the embedded block rotated in the cutting direction adjustment step as the direction data,
In the slide glass rotating step, the slide glass is rotated based on the rotation angle. In the method for producing a thin-section specimen according to claim 5,
A mark forming step of forming a mark having directionality corresponding to the direction of the thin slice formed on the surface to be cut of the embedding block before the cutting step;
In the detection step, the thin section is photographed to obtain an image, and the direction data is detected as the direction of the mark projected on the image,
In the slide glass rotation step, the slide glass is rotated so that the relative direction of the mark with respect to the slide glass is set in a preset direction. In the method for producing a thin-section specimen according to claim 5,
In the detection step, an image is obtained by photographing the thin section, and as the direction data, a range of the biological sample included in the thin section displayed in the image is detected,
In the slide glass rotating step, the slide glass is rotated so that pattern matching elements are compared in a range of the biological sample and a preset range so as to be substantially equal.

Images