WO2012147787A1 - Thin section sample preparation device - Google Patents

Thin section sample preparation device Download PDF

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Publication number
WO2012147787A1
WO2012147787A1 PCT/JP2012/061080 JP2012061080W WO2012147787A1 WO 2012147787 A1 WO2012147787 A1 WO 2012147787A1 JP 2012061080 W JP2012061080 W JP 2012061080W WO 2012147787 A1 WO2012147787 A1 WO 2012147787A1
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WIPO (PCT)
Prior art keywords
sample block
sample
subject
thin
cutting
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PCT/JP2012/061080
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French (fr)
Japanese (ja)
Inventor
大介 中島
祐子 南條
博文 谷口
弘明 飯田
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倉敷紡績株式会社
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Publication of WO2012147787A1 publication Critical patent/WO2012147787A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
    • G01N1/06—Devices for withdrawing samples in the solid state, e.g. by cutting providing a thin slice, e.g. microtome

Definitions

  • the present invention relates to a thin-section sample preparation apparatus for preparing a thin-section sample used for physicochemical sample analysis or microscopic observation of biological samples.
  • a microtome is known as this type of device.
  • a microtome is an apparatus for producing a thin slice sample by slicing a specimen embedded with paraffin or the like with a cutter.
  • a thin slice sample prepared by a microtome is attached to a slide glass and used as a thin slice sample for tissue observation.
  • the preparation work of a thin section sample using a microtome has been conventionally performed manually by an operator, and requires a lot of labor and labor. Further, the thickness required for the thin slice sample is very thin (for example, 3 ⁇ m to 10 ⁇ m, although it varies depending on the sample), and high uniformity is also required. For this reason, even an operator skilled in the use of a microtome usually takes several days to process dozens of sample blocks. Further, since the same work is repeated, an excessive burden is imposed on the worker physically and mentally.
  • Patent Document 1 Japanese Patent Laid-Open No. 2007-212276
  • a surface portion of a sample block is roughly cut by a predetermined amount by a cutter, and the quality of the cutting surface is judged each time the roughing is performed, and the cutting is performed.
  • An apparatus is disclosed that is configured to perform a main cut to produce a thin slice sample when the surface is determined to be “good”. According to the apparatus of Patent Document 1, it is possible to automatically expose the subject in the sample block by an area suitable for observation, so that the burden on the operator can be reduced.
  • thin-section sample preparation time the time required to obtain a desired number of thin-section samples. It has been demanded. From this point of view, there is still room for improvement in the device of Patent Document 1.
  • an object of the present invention is to provide a thin-section sample preparation apparatus that can further reduce the preparation time of a thin-section sample by solving the above-described problems.
  • a thin-section sample preparation device for preparing a thin-section sample by slicing a surface layer portion of a sample block embedding a subject with a cutter, A sample block cutting section comprising the cutter; A sample block transport unit for transporting the sample block; An imaging unit for imaging the surface of the sample block; A control unit for controlling the sample block cutting unit, the sample block transport unit, and the imaging unit; With The control unit performs the slicing operation by relatively moving the sample block cutting unit and the sample block transport unit, causing the imaging unit to image the cutting surface, and Until the exposed area is equal to or larger than a preset area, the amount of thinning of the surface portion of the sample block is varied according to the exposed area of the subject, and rough cutting is performed to perform the thinning operation, thereby exposing the subject.
  • a thin-section sample preparation apparatus that performs the main cutting for performing the slicing operation by setting the amount of slic
  • the time for preparing the thin slice sample is further shortened. be able to.
  • FIG. 1 is a block diagram showing a schematic configuration of a thin-section sample preparation device according to an embodiment of the present invention.
  • FIG. 2 is a flowchart showing a flow relating to switching between the roughing operation and the main cutting operation
  • FIG. 3 is a graph showing the relationship between the amount of additional rough cutting and the exposed area ratio of the subject on the cutting surface of the sample block when the sample block in which the spherical subject is embedded is roughly cut
  • FIG. 4 is a cross-sectional view showing a sample block in which a spherical subject is embedded
  • FIG. 1 is a block diagram showing a schematic configuration of a thin-section sample preparation device according to an embodiment of the present invention.
  • FIG. 2 is a flowchart showing a flow relating to switching between the roughing operation and the main cutting operation
  • FIG. 3 is a graph showing the relationship between the amount of additional rough cutting and the exposed area ratio of the subject on the cutting surface of the sample block when the sample block in which the spherical subject is
  • 5A is a cross-sectional view when the sample block of FIG.
  • FIG. 5B is a top view when the sample block of FIG. 4 is rough-cut by 500 ⁇ m
  • 6A is a cross-sectional view when the sample block of FIG. 5A is further roughened by 500 ⁇ m
  • FIG. 6B is a top view when the sample block of FIG. 5B is further roughened by 500 ⁇ m
  • FIG. 7A is a cross-sectional view when the sample block of FIG. 6A is further roughened by 500 ⁇ m
  • FIG. 7B is a top view when the sample block of FIG. 6B is further roughened by 500 ⁇ m.
  • the inventors of the present invention have obtained the following knowledge as a result of intensive studies to solve the problems of the prior art.
  • FIGS. 5A to 7B are cross-sectional views showing a state when the sample block 120 is roughly cut by 500 ⁇ m
  • FIGS. 5B, 6B, and 7B are top views thereof.
  • the specimen 120a embedded in the sample block 120 is often difficult to collect again, such as human or animal tissue. For this reason, it is absolutely necessary to avoid excessively roughing the subject 120a.
  • the amount of roughing per time may be reduced.
  • the preparation time of the thin slice sample becomes long.
  • paraffin is usually used as the embedding material, but the surface may be slightly concave, and in this case, rough cutting time is very long. Therefore, as a result of intensive studies, the inventors of the present invention have changed the amount of thinning of the surface layer portion of the sample block 120 in accordance with the exposed area of the subject 120a, thereby further reducing the preparation time of the thin slice sample. It has been found that it can be further shortened and it is possible to prevent the subject 120a from being excessively roughened. Based on these findings, the inventors of the present invention have reached the following present invention.
  • a thin-section sample preparation device for preparing a thin-section sample by slicing a surface layer portion of a sample block embedding a subject with a cutter,
  • a sample block cutting section comprising the cutter, a sample block transport section for transporting the sample block,
  • An imaging unit for imaging the surface of the sample block;
  • a control unit for controlling the sample block cutting unit, the sample block transport unit, and the imaging unit; With The control unit performs the slicing operation by relatively moving the sample block cutting unit and the sample block transport unit, causing the imaging unit to image the cutting surface, and Until the exposed area is equal to or larger than a preset area, the amount of thinning of the surface portion of the sample block is varied according to the exposed area of the subject, and rough cutting is performed to perform the thinning operation, thereby exposing the subject.
  • a thin-section sample preparation apparatus that performs the main cutting for performing the slicing operation by setting the amount of slicing the surface layer portion of the sample
  • the control unit when the ratio of the exposed area of the subject with respect to the preset area is smaller than the preset ratio, the control unit performs the subject with respect to the preset area.
  • the thin-section sample preparation device according to the first aspect is provided in which the amount of slicing the surface layer portion of the sample block is made larger than when the ratio of the exposed area of the specimen is larger than a preset ratio.
  • control unit decreases the amount of slicing the surface layer portion of the sample block as the exposed area of the subject approaches the preset area.
  • the control unit when the increase amount of the exposed area of the subject is smaller than a preset increase amount, the control unit ends the rough cutting and starts the main cutting.
  • the thin-section sample preparation device according to any one of the first to third aspects is provided.
  • FIG. 1 is a block diagram showing a schematic configuration of a thin-section sample preparation apparatus according to an embodiment of the present invention.
  • a thin-section sample preparation apparatus 100 is an apparatus that automatically and continuously performs a thin-cut operation for thin-cutting a surface layer portion of a sample block 20 with a cutter 41 to prepare a thin-section sample 24.
  • the sample block 20 is obtained by embedding the subject 20a in an embedding material such as paraffin.
  • Examples of the subject 20a include biological samples such as human and animal tissues.
  • the thin-section sample preparation apparatus 100 includes a sample block storage unit 30 that stores a plurality of sample blocks 20.
  • One sample block selected from the plurality of sample blocks 20 stored in the sample block storage unit 30 is transported by the sample block transport unit 1 to the sample block cutting unit 4 including the cutter 41.
  • the sample block transport unit 1 is configured such that after the sample block 20 to be sliced next is taken out from the sample block storage unit 30 and transported onto the position A, the sample block 20 can be transported back and forth between the positions A to C. Has been.
  • the positions A to C are linearly aligned in the horizontal direction ( ⁇ X axis direction).
  • the sample block transport unit 1 is configured such that the height position ( ⁇ Z-axis direction) of the sample block 20 can be adjusted so that the surface layer portion of the sample block 20 is positioned at a height that can be sliced by the cutter 41. Yes.
  • a height detection unit 2 for detecting the height position of the sample block 20 is arranged above the position A.
  • the imaging unit 3 that images the sample block 20 sliced and exposed by the cutter 41 is disposed above the position B.
  • the imaging unit 3 is configured to have a portion that irradiates the surface of the sample block, such as a white light source or a monochromatic LED light source, and a photographing portion for obtaining image data such as a CCD camera.
  • the sample block cutting section 4 is disposed that can hold the cutter 41 and slice the surface layer portion of the sample block 20.
  • a carrier tape 21 that holds a thin slice sample 24 obtained by slicing the surface layer portion of the sample block 20 with a cutter 41 is supplied.
  • the carrier tape 21 is fed out from the supply reel 5, guided by the guide rollers 81 and 82, and supplied above the position C.
  • the carrier tape 21 holding the sliced piece sample 24 above the position C is guided by the guide rollers 83 and 84 and taken up on the take-up reel 6.
  • a feeding motor 51 is provided on the supply reel 5. By driving the feeding motor 51, the carrier tape 21 is fed from the supply reel 5.
  • the take-up reel 6 is provided with a take-up motor 61.
  • a constant torque is always applied to the take-up reel 6 by always driving the take-up motor 61.
  • the carrier tape 21 fed out from the supply reel 5 by the driving of the feeding motor 51 is taken up on the take-up reel 6 simultaneously with the feeding out.
  • the thin slice sample 24 held on the carrier tape 21 is stuck to the slide glass 22 by the thin slice sticking portion 7 disposed between the guide rollers 83 and 84.
  • the thin-section pasting portion 7 is a pair of guide rollers 71 disposed on the upstream side ( ⁇ X axis direction side) of the traveling path of the carrier tape 21 and the downstream side (+ X axis direction side) of the traveling path of the carrier tape 21. And a pair of guide rollers 72 arranged.
  • the thin slice pasting portion 7 is bent downward with the carrier tape 21 sandwiched between the pair of guide rollers 71 and 71 and the pair of guide rollers 72 and 72, and the thin slice sample 24 held on the carrier tape 21. Is brought into contact with the slide glass 22 supplied with an adhesive liquid 23 such as water. As a result, the thin slice sample 24 is attached to the slide glass 22.
  • the slide glass to which the thin section sample 24 is attached is referred to as a slide glass with a thin section.
  • the slide glass 22 with a thin section is transported to the extension unit 9 by the slide glass transport unit 8.
  • the slide glass transport unit 8 transports the slide glass 22 with a thin section to the extension unit 9, and takes out the slide glass 22 to which the thin section sample 24 has not been pasted from the slide glass storage unit (not shown), and a thin section pasting unit. 7 is conveyed below.
  • the extension unit 9 includes a heating plate (not shown), extends the folds of the thin slice sample 24, and completely evaporates the moisture on the slide glass 22, thereby closely attaching the thin slice sample 24 to the slide glass 22. Fix it.
  • each component such as the sample block transport unit 1 is controlled by the control unit 10.
  • the control unit 10 controls the operation of each component based on information input to an input unit (not shown).
  • the input unit is configured to be able to input, for example, the number of manufactured slide glasses with thin sections, the number of thin section samples attached per slide glass, and the like.
  • the manufacturing operation of the thin slice sample 24 will be described.
  • the production operation of the thin slice sample 24 is performed under the control of the control unit 10.
  • the subject 20a is embedded in the embedding material so as not to be exposed to the outside (or slightly exposed).
  • the surface layer portion of the sample block 20 is roughened until the exposed area of the subject 20a is equal to or larger than a preset area, and then a thin slice sample 24 of about 3 to 10 ⁇ m is produced. I try to sharpen.
  • the basic operation of roughing will be described.
  • the sample block transport unit 1 takes out the sample block 20 to be sliced next from the sample block storage unit 30 and transports it to the position A.
  • the height detector 2 detects the height position of the sample block 20.
  • the sample block transport unit 1 determines that the surface layer portion of the sample block 20 is in the extending direction ( ⁇ Y axis direction) of the cutter 41 and the transport direction ( ⁇ X The height position of the sample block 20 is adjusted so that the surface of the sample block 20 is roughened by the cutter 41 while being flattened so as to be parallel to the axial direction.
  • the sample block transport unit 1 transports the sample block 20 to the position B.
  • the imaging unit 3 images the surface of the sample block 20. Thereby, the maximum projection area (maximum projection area) of the subject 20a in the sample block 20 is recognized.
  • the sample block transport unit 1 transports the sample block 20 to the position C. Thereby, the surface layer portion of the sample block 20 is roughly cut by the cutter 41.
  • the sample block transport unit 1 transports the sample block 20 to the position B.
  • the imaging unit 3 captures an image of the cut surface of the sample block 20 that is exposed by being sliced by the cutter 41.
  • the sample block transport unit 1 uses the cutter 41 as the surface layer portion.
  • the height position of the sample block 20 is adjusted so that it is roughly cut. The adjustment of the height position at this time will be described in detail later.
  • the sample block transport unit 1 transports the sample block 20 to the position C.
  • the surface layer portion of the sample block 20 is roughed again by the cutter 41.
  • the sample block transport unit 1 transports the sample block 20 to the position B, and the imaging unit 3 captures the cutting surface of the sample block 20 again.
  • the rough cutting of the sample block 20 and the imaging operation of the cutting surface are repeated until the exposed area of the subject 20a on the cutting surface of the sample block 20 is equal to or larger than a preset area.
  • the rough cutting operation is terminated and the main cutting operation is started.
  • the position of the cutting edge 41a of different cutter 41 or different cutter 41 for rough cutting and main cutting or when the thickness of rough cutting differs from the thickness of main cutting, the thickness accuracy of the section to be manufactured is improved. Therefore, at the position of the cutter 41 used for the main cutting or the cutting edge 41a of the cutter 41, a so-called discarding operation is performed in which the thin cutting sample 24 is thinly cut several times with the main cutting thickness before the thin section sample 24 is manufactured (before the main cutting). Is preferably performed.
  • the sample block transport unit 1 adjusts the height position of the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41 (about 3 ⁇ m to 10 ⁇ m). Thereafter, the sample block transport unit 1 transports the sample block 20 to the position C. Thereby, the surface layer part of the sample block 20 is sliced by the cutter 41, and the thin slice sample 24 is produced. Thereafter, the sample block transport unit 1 retracts the sample block 20 from the position C to the position B or the like, and adjusts the height position of the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41.
  • the operations of adjusting the height position of the sample block 20, slicing, and retracting are automatically and continuously repeated an arbitrary number of times based on information input to the input unit (not shown), and an arbitrary number of sheets A thin slice sample 24 is prepared.
  • the thin slice sample 24 produced by the main cutting operation is affixed to the carrier tape 21.
  • the surface of the carrier tape 21 is subjected to treatments such as humidification, cooling, and charging so that the thin slice sample 24 is securely attached to the carrier tape 21.
  • the thin slice sample 24 affixed to the carrier tape 21 is conveyed to the thin slice affixing unit 7 by driving of the feeding motor 51 and the take-up motor 61 and affixed to the slide glass 22 by the thin segment affixing unit 7. Thereafter, the slide glass 22 with a thin section is conveyed to the extension unit 9 by the slide glass conveyance unit 8. Thereafter, the extension section 9 extends the folds of the thin slice sample 24 and closely fixes the thin slice sample 24 to the slide glass 22.
  • FIG. 2 is a flowchart showing a flow relating to switching between rough cutting operation and main cutting operation. These operations are performed under the control of the control unit 10. In addition, it demonstrates, abbreviate
  • step S1 the surface layer portion of the sample block 20 is roughly cut by the cutter 41.
  • step S ⁇ b> 2 the imaging unit 3 captures an image of the cut surface of the sample block 20 that is exposed by being sliced by the cutter 41.
  • step S3 it is determined whether or not the exposed area of the subject 20a on the cutting surface of the sample block 20 is equal to or larger than a preset area (for example, 80% of the maximum projection area).
  • a preset area for example, 80% of the maximum projection area.
  • step S4 the height position of the sample block 20 is adjusted so that the amount of slice is variable according to the exposed area of the subject 20a.
  • step S4 ends, the process returns to step S1.
  • step S5 the surface layer portion of the sample block 20 is ground by the cutter 41.
  • FIG. 3 shows the amount of additional roughing and the specimen on the cutting surface of the sample block 20 when the specimen block 20 in which a spherical specimen 20a having a radius of 800 ⁇ m is embedded (similar to the specimen block 120 shown in FIG. 4) is roughened. It is a graph which shows the relationship with the exposed area rate of 20a.
  • the additional rough cutting amount refers to the rough cutting amount necessary to make the exposed area ratio of the subject 20a 100%.
  • the rough cutting amount is the amount of thin cutting during the rough cutting operation.
  • the exposed area ratio of the subject 20a indicates the ratio (%) of the exposed area of the subject 20a to the maximum projection area of the subject 20a. Table 1 below shows a setting example of the additional rough cutting amount of the surface layer portion of the sample block 20 with respect to the exposed area ratio of the subject 20a.
  • the control unit 10 controls the sample block transport unit 1 so as to vary the amount of additional rough cutting of the surface layer portion of the sample block 20 in accordance with the exposed area ratio of the subject 20a, and performs a slicing operation to produce the thin slice sample 24. .
  • the control unit 10 causes the sample block transport unit 1 to cut the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41 with an additional roughing amount of 669 ⁇ m. Adjust the height position.
  • the control unit 10 causes the sample block transport unit 1 to sample the surface layer portion of the sample block 20 so that the cutter 41 cuts the surface layer portion with an additional rough cutting amount of 252 ⁇ m.
  • the height position of the block 20 is adjusted.
  • the exposed area ratio of the subject 20a can be made close to 100% by one roughing operation, and the preparation time of the thin slice sample 24 can be greatly shortened.
  • the preparation time of the thin slice sample 24 can be further shortened.
  • the exposed area (rate) of the subject 20a When the exposed area (rate) of the subject 20a is small, there is a low possibility that the subject 20a is excessively cut even if the rough cutting amount is increased. On the other hand, when the exposed area (rate) of the subject 20a is large, if the rough cutting amount remains large, there is a high possibility that the subject 20a will be cut too much. For this reason, when the exposed area (rate) of the subject 20a is smaller than a preset value (for example, 50%), the sample is larger than when the exposed area rate of the subject 20a is larger than a preset value. It is preferable to increase the amount by which the surface layer portion of the block 20 is sliced. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
  • a preset value for example, 50%
  • the exposed area of the subject 20a approaches the preset area, it is preferable to reduce the amount by which the surface layer portion of the sample block 20 is sliced. Even in this case, it is possible to further reduce the preparation time of the thin-section sample 24 while preventing the subject 20a from being excessively roughened.
  • the thickness of the slice is changed for each roughing operation, and the exposed area of the subject 2a is confirmed by the imaging unit 3 for each roughing operation.
  • the thin slice thickness of one roughing operation is made constant, continuous thin slices are performed according to the exposed area ratio of the subject 20a, and the thin slice amount is varied by changing the number of continuous thin slices. good.
  • the continuous slicing means that the exposed area is not checked in the imaging unit 3 between the slicing operation and the slicing operation.
  • the amount of additional rough cutting according to the exposed area ratio of the subject 20a is 50 ⁇ m
  • five rough cutting operations are continuously performed with a thin thickness of 10 ⁇ m per one rough cutting operation (in the imaging unit 3 in the meantime).
  • the imaging unit 3 confirms the exposed area of the subject 2a. In this way, depending on the exposed area ratio of the subject 20a, the number of rough cutting operations until the next time the sample block 20 is imaged by the imaging unit 3 is varied to expose the subject 20a in the imaging unit 3. The amount of slicing from the detection of the area to the detection of the exposed area of the next subject 20a may be varied. In this case, the number of roughing operations itself increases as compared with the case where the set additional roughing amount is processed by one roughing operation, but the imaging operation of the imaging unit 3, that is, the exposure area of the subject 20a.
  • the exposed area (rate) of the subject 20a when the exposed area (rate) of the subject 20a is small, it is unlikely that the subject 20a will be cut too much even if the number of continuous slices is increased.
  • the exposed area (rate) of the subject 20a when the exposed area (rate) of the subject 20a is large, there is a high possibility that the subject 20a will be cut too much if the number of continuous slices remains large.
  • the exposed area (rate) of the subject 20a is small, the number of continuous slices of the surface layer portion of the sample block 20 may be increased more than when the exposed area rate of the subject 20a is large. preferable. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
  • the exposed area of the subject 20a approaches the preset area, it is preferable to reduce the amount by which the surface layer portion of the sample block 20 is sliced. That is, it is preferable to reduce the number of continuous slicing. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
  • the thin-section sample preparation apparatus often handles a biological sample as the subject 20a, increasing the thin thickness of one roughing operation may damage the subject 20a in the sample block. Therefore, it is preferable to vary the amount of slicing by making the slicing thickness substantially constant and changing the number of continuous slicing. In the case of a biological sample block using paraffin, it is preferable to set the thin slice thickness per rough cutting operation to about 5 to 30 ⁇ m.
  • the subject 20a has a spherical shape, but the actual subject 20a has various shapes.
  • the rough cutting amount corresponding to the exposed area of the subject 20a may be set as appropriate based on empirical rules.
  • the exposed area of the subject 20a may not exceed a preset area (for example, 80% of the maximum projection region). In this case, the subject 20a is excessively roughened.
  • a small increase in the exposed area of the subject 20a is considered to mean that the point where an area suitable for observation of the subject 20a is exposed is close.
  • the increase rate when the exposed area rate of the subject 20a is 90 to 100%, compared to the increase rate when the exposed area rate of the subject 20a is 0 to 90%. Is getting smaller. For this reason, when the increase amount of the exposed area of the subject 20a becomes smaller than the preset increase amount, it is preferable to finish the rough cutting and start the main cutting. Thereby, it is possible to further prevent the subject 20a from being excessively roughened.
  • the sample block 20 is transported to the sample block cutting unit 4 by the sample block transport unit 1 to produce the thin slice sample 24.
  • the thin section sample 24 may be produced by moving the cutter 41 of the sample block cutting unit 4 to the sample block 20 held by the sample block transport unit 1. That is, the thin slice sample 24 may be manufactured by relatively moving the sample block cutting unit 4 and the sample block transport unit 1.
  • the thin-section sample preparation apparatus can further reduce the preparation time of a thin-section sample, and is therefore useful as a thin-section sample preparation apparatus used for physicochemical sample analysis and microscopic observation of biological samples. is there.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

In order to considerably further shorten preparation time of thin section samples, this thin section sample preparation device is configured to perform: rough cutting in which thin slicing operations are performed on a surface layer part of a sample block by means of a cutter, the cut surface is imaged with an imaging unit, and, until the exposed surface area of the subject in said cutting surface is at least a predetermined surface area, thin cutting operations are performed varying the amount of fine cutting of the surface layer part of the sample block depending on the exposed surface area of the subject; and primary cutting in which, when the exposed surface area of the subject is greater than or equal to the predetermined surface area, fine cutting operations are performed with the amount of thin cutting of the surface layer area of the sample block set to a preset amount.

Description

薄切片試料作製装置Thin section sample preparation equipment
　本発明は、理化学試料分析や生体試料等の顕微鏡観察などに利用される薄切片試料を作製する薄切片試料作製装置に関する。 The present invention relates to a thin-section sample preparation apparatus for preparing a thin-section sample used for physicochemical sample analysis or microscopic observation of biological samples.
　従来、この種の装置としては、ミクロトームが知られている。ミクロトームは、パラフィン等で包埋された被検体をカッターによって薄切りすることにより、薄切片試料を作製する装置である。ミクロトームにより作製された薄切片試料は、スライドガラスに貼付けられ、組織観察用の薄切片試料として利用される。 Conventionally, a microtome is known as this type of device. A microtome is an apparatus for producing a thin slice sample by slicing a specimen embedded with paraffin or the like with a cutter. A thin slice sample prepared by a microtome is attached to a slide glass and used as a thin slice sample for tissue observation.
　ミクロトームを用いた薄切片試料の作製作業は、従来、作業者によって手動で行われており、多大な手間と労力を要するものである。また、薄切片試料に求められる厚さは、非常に薄く（試料によって異なるが例えば３μｍ～１０μｍ）、高い均一性も求められる。このため、ミクロトームの使用に熟練した作業者であっても、数十個の試料ブロックを処理するのには、通常、数日かかる。また、同様の作業の繰り返しであるため、肉体的にも精神的にも作業者に過度の負担がかかる。 The preparation work of a thin section sample using a microtome has been conventionally performed manually by an operator, and requires a lot of labor and labor. Further, the thickness required for the thin slice sample is very thin (for example, 3 μm to 10 μm, although it varies depending on the sample), and high uniformity is also required. For this reason, even an operator skilled in the use of a microtome usually takes several days to process dozens of sample blocks. Further, since the same work is repeated, an excessive burden is imposed on the worker physically and mentally.
　そこで、近年、前記薄切片試料の作製作業を自動化して作業者の負担を軽減する装置が種々提案されている。特許文献１（特開２００７－２１２２７６号公報）には、試料ブロックの表層部分をカッターにより予め決められた量ずつ粗削りし、当該粗削りを１回行う毎に切削面の良否を判断し、当該切削面を「良」と判断したとき、薄切片試料を作製する本削りを行うように構成された装置が開示されている。特許文献１の装置によれば、試料ブロック中の被検体を観察に好適な面積だけ露出させることを自動的に行うことができるので、作業者の負担を軽減することができる。 Therefore, in recent years, various devices for reducing the burden on the operator by automating the preparation of the thin section sample have been proposed. In Patent Document 1 (Japanese Patent Laid-Open No. 2007-212276), a surface portion of a sample block is roughly cut by a predetermined amount by a cutter, and the quality of the cutting surface is judged each time the roughing is performed, and the cutting is performed. An apparatus is disclosed that is configured to perform a main cut to produce a thin slice sample when the surface is determined to be “good”. According to the apparatus of Patent Document 1, it is possible to automatically expose the subject in the sample block by an area suitable for observation, so that the burden on the operator can be reduced.
特開２００７－２１２２７６号公報JP 2007-212276 A
　しかしながら、薄切り動作を自動的に且つ連続的に行う薄切片試料作製装置においては、所望の枚数の薄切片試料を得るための時間（以下、薄切片試料の作製時間という）のより一層の短縮が求められている。この観点において、特許文献１の装置は未だ改良の余地がある。 However, in a thin-section sample preparation device that automatically and continuously performs a thin-slicing operation, the time required to obtain a desired number of thin-section samples (hereinafter referred to as thin-section sample preparation time) can be further reduced. It has been demanded. From this point of view, there is still room for improvement in the device of Patent Document 1.
　従って、本発明の目的は、前記課題を解決することにあって、薄切片試料の作製時間をより一層短縮することができる薄切片試料作製装置を提供することにある。 Therefore, an object of the present invention is to provide a thin-section sample preparation apparatus that can further reduce the preparation time of a thin-section sample by solving the above-described problems.
　前記目的を達成するために、本発明は以下のように構成する。
　本発明によれば、被検体を包埋する試料ブロックの表層部分をカッターにより薄切りして薄切片試料を作製する薄切片試料作製装置であって、
　前記カッターを備える試料ブロック切削部と、
　前記試料ブロックを搬送する試料ブロック搬送部と、
　前記試料ブロックの表面を撮像する撮像部と、
　前記試料ブロック切削部、前記試料ブロック搬送部、及び前記撮像部を制御する制御部と、
　を備え、
　前記制御部は、前記試料ブロック切削部と前記試料ブロック搬送部とを相対的に移動させることにより前記薄切り動作を行い、前記撮像部に前記切削面を撮像させ、当該切削面における前記被検体の露出面積が予め設定された面積以上になるまで、前記被検体の露出面積に応じて前記試料ブロックの表層部分を薄切りする量を可変して前記薄切り動作を行う粗削りをし、前記被検体の露出面積が予め設定された面積以上になったとき、前記試料ブロックの表層部分を薄切りする量を予め設定された量にして前記薄切り動作を行う本削りをする、薄切片試料作製装置を提供する。 In order to achieve the above object, the present invention is configured as follows.
According to the present invention, a thin-section sample preparation device for preparing a thin-section sample by slicing a surface layer portion of a sample block embedding a subject with a cutter,
A sample block cutting section comprising the cutter;
A sample block transport unit for transporting the sample block;
An imaging unit for imaging the surface of the sample block;
A control unit for controlling the sample block cutting unit, the sample block transport unit, and the imaging unit;
With
The control unit performs the slicing operation by relatively moving the sample block cutting unit and the sample block transport unit, causing the imaging unit to image the cutting surface, and Until the exposed area is equal to or larger than a preset area, the amount of thinning of the surface portion of the sample block is varied according to the exposed area of the subject, and rough cutting is performed to perform the thinning operation, thereby exposing the subject. Provided is a thin-section sample preparation apparatus that performs the main cutting for performing the slicing operation by setting the amount of slicing the surface layer portion of the sample block to a preset amount when the area becomes equal to or larger than a preset area.
　本発明によれば、前記被検体の露出面積に応じて前記試料ブロックの表層部分を薄切りする量を可変して前記粗削りをするようにしているので、薄切片試料の作製時間をより一層短縮することができる。 According to the present invention, since the rough cutting is performed by changing the amount of thinning of the surface layer portion of the sample block according to the exposed area of the subject, the time for preparing the thin slice sample is further shortened. be able to.
　本発明のこれらと他の目的と特徴は、添付された図面についての好ましい実施の形態に関連した次の記述から明らかになる。この図面においては、
図１は、本発明の実施形態にかかる薄切片試料作製装置の概略構成を示すブロック図であり、 図２は、粗削りの動作と本削りの動作の切り換えに関する流れを示すフローチャートであり、 図３は、球形の被検体が包埋された試料ブロックを粗削りしたときの、追加粗削り量と試料ブロックの切削面における被検体の露出面積率とを関係を示すグラフであり、 図４は、球形の被検体が包埋された試料ブロックを示す断面図であり、 図５Ａは、図４の試料ブロックを５００μｍ粗削りしたときの断面図であり、 図５Ｂは、図４の試料ブロックを５００μｍ粗削りしたときの上面図であり、 図６Ａは、図５Ａの試料ブロックを更に５００μｍ粗削りしたときの断面図であり、 図６Ｂは、図５Ｂの試料ブロックを更に５００μｍ粗削りしたときの上面図であり、 図７Ａは、図６Ａの試料ブロックを更に５００μｍ粗削りしたときの断面図であり、 図７Ｂは、図６Ｂの試料ブロックを更に５００μｍ粗削りしたときの上面図である。 These and other objects and features of the invention will become apparent from the following description taken in conjunction with the preferred embodiments with reference to the accompanying drawings. In this drawing,
FIG. 1 is a block diagram showing a schematic configuration of a thin-section sample preparation device according to an embodiment of the present invention. FIG. 2 is a flowchart showing a flow relating to switching between the roughing operation and the main cutting operation, FIG. 3 is a graph showing the relationship between the amount of additional rough cutting and the exposed area ratio of the subject on the cutting surface of the sample block when the sample block in which the spherical subject is embedded is roughly cut; FIG. 4 is a cross-sectional view showing a sample block in which a spherical subject is embedded, FIG. 5A is a cross-sectional view when the sample block of FIG. FIG. 5B is a top view when the sample block of FIG. 4 is rough-cut by 500 μm, 6A is a cross-sectional view when the sample block of FIG. 5A is further roughened by 500 μm, FIG. 6B is a top view when the sample block of FIG. 5B is further roughened by 500 μm, FIG. 7A is a cross-sectional view when the sample block of FIG. 6A is further roughened by 500 μm; FIG. 7B is a top view when the sample block of FIG. 6B is further roughened by 500 μm.
　本発明の発明者らは、前記従来技術の課題を解決するために鋭意検討を重ねた結果、以下の知見を得た。 The inventors of the present invention have obtained the following knowledge as a result of intensive studies to solve the problems of the prior art.
　例えば、図４に示すような半径８００μｍの球形の被検体１２０ａが包埋された試料ブロック１２０を５００μｍずつ粗削りした場合には、試料ブロック１２０は、図５Ａ～図７Ｂに示すように変化する。図５Ａ，図６Ａ，図７Ａは、試料ブロック１２０を５００μｍずつ粗削りしたときの状態を示す断面図であり、図５Ｂ，図６Ｂ，図７Ｂは、それらの上面図である。 For example, when the sample block 120 in which the spherical specimen 120a having a radius of 800 μm as shown in FIG. 4 is embedded by 500 μm, the sample block 120 changes as shown in FIGS. 5A to 7B. 5A, FIG. 6A, and FIG. 7A are cross-sectional views showing a state when the sample block 120 is roughly cut by 500 μm, and FIGS. 5B, 6B, and 7B are top views thereof.
　図６Ａ，図６Ｂに示す状態及び図７Ａ，図７Ｂに示す状態では、既に被検体１２０ａの半分以上が粗削りされている。これらの状態で本削りを開始した場合、当該本削りにより作製される薄切片試料における被検体１２０の面積は、次第に小さくなる。このため、被検体１２０ａの面積が観察に好適な面積以上である薄切片試料を所望の枚数得ることができないおそれがある。 In the state shown in FIGS. 6A and 6B and the state shown in FIGS. 7A and 7B, more than half of the subject 120a has already been roughed. When the main cutting is started in these states, the area of the subject 120 in the thin slice sample produced by the main cutting gradually decreases. For this reason, there is a possibility that a desired number of thin slice samples in which the area of the subject 120a is equal to or larger than an area suitable for observation cannot be obtained.
　試料ブロック１２０の包埋される被検体１２０ａは、人間や動物の組織など再度採取することが困難なものが多い。このため、被検体１２０ａを粗削りしすぎることは、絶対に避けなければならない。 The specimen 120a embedded in the sample block 120 is often difficult to collect again, such as human or animal tissue. For this reason, it is absolutely necessary to avoid excessively roughing the subject 120a.
　被検体１２０ａを粗削りしすぎることを防ぐには、１回当たりの粗削り量を小さくすればよい。しかしながら、この場合、当然ながら、薄切片試料の作製時間が長くなる。また、包理材としてはパラフィンが通常使用されるが、その表面は若干の凹状になることがあり、その場合、粗削り時間が非常にかかることになる。そこで、本発明の発明者らは、鋭意検討を重ねた結果、被検体１２０ａの露出面積に応じて試料ブロック１２０の表層部分を薄切りする量を可変することで、薄切片試料の作製時間をより一層短縮でき且つ被検体１２０ａを粗削りしすぎることも防止できることを知見した。これらの知見に基づき、本発明の発明者らは、以下の本発明に想到した。 In order to prevent the subject 120a from being excessively roughed, the amount of roughing per time may be reduced. However, in this case, as a matter of course, the preparation time of the thin slice sample becomes long. In addition, paraffin is usually used as the embedding material, but the surface may be slightly concave, and in this case, rough cutting time is very long. Therefore, as a result of intensive studies, the inventors of the present invention have changed the amount of thinning of the surface layer portion of the sample block 120 in accordance with the exposed area of the subject 120a, thereby further reducing the preparation time of the thin slice sample. It has been found that it can be further shortened and it is possible to prevent the subject 120a from being excessively roughened. Based on these findings, the inventors of the present invention have reached the following present invention.
　本発明の第１態様によれば、被検体を包埋する試料ブロックの表層部分をカッターにより薄切りして薄切片試料を作製する薄切片試料作製装置であって、
　前記カッターを備える試料ブロック切削部と
　前記試料ブロックを搬送する試料ブロック搬送部と、
　前記試料ブロックの表面を撮像する撮像部と、
　前記試料ブロック切削部、前記試料ブロック搬送部、及び前記撮像部を制御する制御部と、
　を備え、
　前記制御部は、前記試料ブロック切削部と前記試料ブロック搬送部とを相対的に移動させることにより前記薄切り動作を行い、前記撮像部に前記切削面を撮像させ、当該切削面における前記被検体の露出面積が予め設定された面積以上になるまで、前記被検体の露出面積に応じて前記試料ブロックの表層部分を薄切りする量を可変して前記薄切り動作を行う粗削りをし、前記被検体の露出面積が予め設定された面積以上になったとき、前記試料ブロックの表層部分を薄切りする量を予め設定された量にして前記薄切り動作を行う本削りをする、薄切片試料作製装置を提供する。 According to the first aspect of the present invention, there is provided a thin-section sample preparation device for preparing a thin-section sample by slicing a surface layer portion of a sample block embedding a subject with a cutter,
A sample block cutting section comprising the cutter, a sample block transport section for transporting the sample block,
An imaging unit for imaging the surface of the sample block;
A control unit for controlling the sample block cutting unit, the sample block transport unit, and the imaging unit;
With
The control unit performs the slicing operation by relatively moving the sample block cutting unit and the sample block transport unit, causing the imaging unit to image the cutting surface, and Until the exposed area is equal to or larger than a preset area, the amount of thinning of the surface portion of the sample block is varied according to the exposed area of the subject, and rough cutting is performed to perform the thinning operation, thereby exposing the subject. Provided is a thin-section sample preparation apparatus that performs the main cutting for performing the slicing operation by setting the amount of slicing the surface layer portion of the sample block to a preset amount when the area becomes equal to or larger than a preset area.
　本発明の第２態様によれば、前記制御部は、前記予め設定された面積に対する前記被検体の露出面積の割合が予め設定された割合よりも小さいとき、前記予め設定された面積に対する前記被検体の露出面積の割合が予め設定された割合よりも大きいときよりも、前記試料ブロックの表層部分を薄切りする量を大きくする、第１態様に記載の薄切片試料作製装置を提供する。 According to the second aspect of the present invention, when the ratio of the exposed area of the subject with respect to the preset area is smaller than the preset ratio, the control unit performs the subject with respect to the preset area. The thin-section sample preparation device according to the first aspect is provided in which the amount of slicing the surface layer portion of the sample block is made larger than when the ratio of the exposed area of the specimen is larger than a preset ratio.
　本発明の第３態様によれば、前記制御部は、前記被検体の露出面積が前記予め設定された面積に近づくに従い、前記試料ブロックの表層部分を薄切りする量を小さくする、第１又は２態様に記載の薄切片試料作製装置を提供する。 According to the third aspect of the present invention, the control unit decreases the amount of slicing the surface layer portion of the sample block as the exposed area of the subject approaches the preset area. A thin-section sample preparation device according to an aspect is provided.
　本発明の第４態様によれば、前記制御部は、前記被検体の露出面積の増加量が予め設定された増加量よりも小さくなったとき、前記粗削りを終了して前記本削りを開始する、第１～３態様のいずれか１つに記載の薄切片試料作製装置を提供する。 According to the fourth aspect of the present invention, when the increase amount of the exposed area of the subject is smaller than a preset increase amount, the control unit ends the rough cutting and starts the main cutting. The thin-section sample preparation device according to any one of the first to third aspects is provided.
　本発明の記述を続ける前に、添付図面において同じ部品については同じ参照符号を付している。
　以下、本発明の実施形態について、図面を参照しながら説明する。 Before continuing the description of the present invention, the same parts are denoted by the same reference numerals in the accompanying drawings.
Hereinafter, embodiments of the present invention will be described with reference to the drawings.
　《実施形態》
　本発明の実施形態にかかる薄切片試料作製装置の概略構成について説明する。図１は、本発明の実施形態にかかる薄切片試料作製装置の概略構成を示すブロック図である。 <Embodiment>
A schematic configuration of a thin-section sample preparation device according to an embodiment of the present invention will be described. FIG. 1 is a block diagram showing a schematic configuration of a thin-section sample preparation apparatus according to an embodiment of the present invention.
　図１において、薄切片試料作製装置１００は、試料ブロック２０の表層部分をカッター４１により薄切りして薄切片試料２４を作製する薄切り動作を自動的に且つ連続的に行う装置である。試料ブロック２０は、被検体２０ａをパラフィン等の包埋材の中に埋め込んだものである。被検体２０ａとしては、例えば、人間や動物の組織などの生体試料が挙げられる。 1, a thin-section sample preparation apparatus 100 is an apparatus that automatically and continuously performs a thin-cut operation for thin-cutting a surface layer portion of a sample block 20 with a cutter 41 to prepare a thin-section sample 24. The sample block 20 is obtained by embedding the subject 20a in an embedding material such as paraffin. Examples of the subject 20a include biological samples such as human and animal tissues.
　薄切片試料作製装置１００は、複数の試料ブロック２０を収納する試料ブロック収納部３０を備えている。試料ブロック収納部３０に収納された複数の試料ブロック２０から選択された１つの試料ブロックは、試料ブロック搬送部１によりカッター４１を備える試料ブロック切削部４へと搬送される。 The thin-section sample preparation apparatus 100 includes a sample block storage unit 30 that stores a plurality of sample blocks 20. One sample block selected from the plurality of sample blocks 20 stored in the sample block storage unit 30 is transported by the sample block transport unit 1 to the sample block cutting unit 4 including the cutter 41.
　試料ブロック搬送部１は、試料ブロック収納部３０から次に薄切り処理される試料ブロック２０を取り出して位置Ａ上に搬送したのち、当該試料ブロック２０を位置Ａ～Ｃの間で往復搬送可能に構成されている。なお、位置Ａ～Ｃは、横方向（±Ｘ軸方向）に直線的に整列している。また、試料ブロック搬送部１は、試料ブロック２０の表層部分がカッター４１により薄切り可能な高さに位置するように、試料ブロック２０の高さ位置（±Ｚ軸方向）を調整可能に構成されている。 The sample block transport unit 1 is configured such that after the sample block 20 to be sliced next is taken out from the sample block storage unit 30 and transported onto the position A, the sample block 20 can be transported back and forth between the positions A to C. Has been. The positions A to C are linearly aligned in the horizontal direction (± X axis direction). Further, the sample block transport unit 1 is configured such that the height position (± Z-axis direction) of the sample block 20 can be adjusted so that the surface layer portion of the sample block 20 is positioned at a height that can be sliced by the cutter 41. Yes.
　位置Ａの上方には、試料ブロック２０の高さ位置を検出する高さ検出部２が配置されている。位置Ｂの上方には、カッター４１により薄切りされて露出した試料ブロック２０を撮像する撮像部３が配置されている。撮像部３は、例えば、白色光源や単色ＬＥＤ光源のような試料ブロック表面を照射する部分と、ＣＣＤカメラのような画像データを得るための撮影部分とを有するように構成されている。位置Ｃの上方には、カッター４１を保持して試料ブロック２０の表層部分を薄切可能な試料ブロック切削部４が配置されている。 Above the position A, a height detection unit 2 for detecting the height position of the sample block 20 is arranged. Above the position B, the imaging unit 3 that images the sample block 20 sliced and exposed by the cutter 41 is disposed. The imaging unit 3 is configured to have a portion that irradiates the surface of the sample block, such as a white light source or a monochromatic LED light source, and a photographing portion for obtaining image data such as a CCD camera. Above the position C, the sample block cutting section 4 is disposed that can hold the cutter 41 and slice the surface layer portion of the sample block 20.
　また、位置Ｃの上方には、試料ブロック２０の表層部分がカッター４１によって薄切りされることにより得られた薄切片試料２４を保持するキャリアテープ２１が供給される。キャリアテープ２１は、供給リール５から繰り出され、ガイドローラ８１，８２に案内されて位置Ｃの上方に供給される。位置Ｃの上方で薄切片試料２４を保持したキャリアテープ２１は、ガイドローラ８３，８４に案内されて巻取リール６に巻き取られる。 Further, above the position C, a carrier tape 21 that holds a thin slice sample 24 obtained by slicing the surface layer portion of the sample block 20 with a cutter 41 is supplied. The carrier tape 21 is fed out from the supply reel 5, guided by the guide rollers 81 and 82, and supplied above the position C. The carrier tape 21 holding the sliced piece sample 24 above the position C is guided by the guide rollers 83 and 84 and taken up on the take-up reel 6.
　供給リール５には、繰り出しモータ５１が設けられている。繰り出しモータ５１が駆動されることにより、供給リール５からキャリアテープ２１が繰り出される。また、巻取リール６には、巻取モータ６１が設けられている。巻取モータ６１が常に駆動されることにより、巻取リール６には常に一定のトルクがかけられている。これにより、繰り出しモータ５１の駆動により供給リール５から繰り出されたキャリアテープ２１は、当該繰り出しと同時に巻取リール６に巻き取られる。 A feeding motor 51 is provided on the supply reel 5. By driving the feeding motor 51, the carrier tape 21 is fed from the supply reel 5. The take-up reel 6 is provided with a take-up motor 61. A constant torque is always applied to the take-up reel 6 by always driving the take-up motor 61. Thereby, the carrier tape 21 fed out from the supply reel 5 by the driving of the feeding motor 51 is taken up on the take-up reel 6 simultaneously with the feeding out.
　キャリアテープ２１に保持された薄切片試料２４は、ガイドローラ８３，８４の間に配置された薄切片貼付部７によりスライドガラス２２に貼り付けられる。薄切片貼付部７は、キャリアテープ２１の走行経路の上流側（－Ｘ軸方向側）に配置された一対のガイドローラ７１と、キャリアテープ２１の走行経路の下流側（＋Ｘ軸方向側）に配置された一対のガイドローラ７２とを備えている。薄切片貼付部７は、一対のガイドローラ７１，７１の間と一対のガイドローラ７２，７２の間でキャリアテープ２１を挟んで下方に撓ませ、当該キャリアテープ２１に保持された薄切片試料２４を、水などの接着液２３が供給されたスライドガラス２２に接触させる。これにより、薄切片試料２４がスライドガラス２２に貼り付けられる。以下、薄切片試料２４が貼り付けられたスライドガラスを、薄切片付きスライドガラスという。 The thin slice sample 24 held on the carrier tape 21 is stuck to the slide glass 22 by the thin slice sticking portion 7 disposed between the guide rollers 83 and 84. The thin-section pasting portion 7 is a pair of guide rollers 71 disposed on the upstream side (−X axis direction side) of the traveling path of the carrier tape 21 and the downstream side (+ X axis direction side) of the traveling path of the carrier tape 21. And a pair of guide rollers 72 arranged. The thin slice pasting portion 7 is bent downward with the carrier tape 21 sandwiched between the pair of guide rollers 71 and 71 and the pair of guide rollers 72 and 72, and the thin slice sample 24 held on the carrier tape 21. Is brought into contact with the slide glass 22 supplied with an adhesive liquid 23 such as water. As a result, the thin slice sample 24 is attached to the slide glass 22. Hereinafter, the slide glass to which the thin section sample 24 is attached is referred to as a slide glass with a thin section.
　薄切片付きスライドガラス２２は、スライドガラス搬送部８により伸展部９へ搬送される。スライドガラス搬送部８は、薄切片付きスライドガラス２２を伸展部９へ搬送するとともに、スライドガラス収納部（図示せず）から薄切片試料２４を未貼付のスライドガラス２２を取り出して薄切片貼付部７の下方へ搬送する。伸展部９は、加温板（図示せず）を備え、薄切片試料２４の皺の伸展を行うとともに、スライドガラス２２上の水分を完全に蒸発させて薄切片試料２４をスライドガラス２２に密着固定する。 The slide glass 22 with a thin section is transported to the extension unit 9 by the slide glass transport unit 8. The slide glass transport unit 8 transports the slide glass 22 with a thin section to the extension unit 9, and takes out the slide glass 22 to which the thin section sample 24 has not been pasted from the slide glass storage unit (not shown), and a thin section pasting unit. 7 is conveyed below. The extension unit 9 includes a heating plate (not shown), extends the folds of the thin slice sample 24, and completely evaporates the moisture on the slide glass 22, thereby closely attaching the thin slice sample 24 to the slide glass 22. Fix it.
　試料ブロック搬送部１などの各構成要素は、制御部１０により動作を制御される。制御部１０は、入力部（図示せず）に入力された情報に基づいて、各構成要素の動作を制御する。入力部は、例えば、薄切片付きスライドガラスの製作枚数や１枚のスライドガラス当たりの薄切片試料の貼り付け数などを入力可能に構成されている。 The operation of each component such as the sample block transport unit 1 is controlled by the control unit 10. The control unit 10 controls the operation of each component based on information input to an input unit (not shown). The input unit is configured to be able to input, for example, the number of manufactured slide glasses with thin sections, the number of thin section samples attached per slide glass, and the like.
　次に、薄切片試料２４の作製動作について説明する。この薄切片試料２４の作製動作は、制御部１０の制御の下に行われる。なお、通常、試料ブロック２０が試料ブロック収納部３０に収納された状態では、被検体２０ａは外部に露出しない（あるいは僅かに露出する）ように包埋材の中に埋め込まれている。このため、本実施形態においては、被検体２０ａの露出面積が予め設定された面積以上になるまで試料ブロック２０の表層部分を粗削りし、その後、３～１０μｍ程度の薄切片試料２４を作製する本削りを行うようにしている。まず、粗削りの基本的な動作について説明する。 Next, the manufacturing operation of the thin slice sample 24 will be described. The production operation of the thin slice sample 24 is performed under the control of the control unit 10. Normally, when the sample block 20 is stored in the sample block storage unit 30, the subject 20a is embedded in the embedding material so as not to be exposed to the outside (or slightly exposed). For this reason, in this embodiment, the surface layer portion of the sample block 20 is roughened until the exposed area of the subject 20a is equal to or larger than a preset area, and then a thin slice sample 24 of about 3 to 10 μm is produced. I try to sharpen. First, the basic operation of roughing will be described.
　まず、試料ブロック搬送部１が試料ブロック収納部３０から次に薄切り処理される試料ブロック２０を取り出し、位置Ａに搬送する。
　次いで、高さ検出部２が試料ブロック２０の高さ位置を検出する。
　次いで、試料ブロック搬送部１が、高さ検出部２の検出情報に基づいて、試料ブロック２０の表層部分がカッター４１の延在方向（±Ｙ軸方向）及び試料ブロック２０の搬送方向（±Ｘ軸方向）に対して平行になるように平面出しするとともに試料ブロック２０の表層部分がカッター４１に粗削りされるように、試料ブロック２０の高さ位置を調整する。 First, the sample block transport unit 1 takes out the sample block 20 to be sliced next from the sample block storage unit 30 and transports it to the position A.
Next, the height detector 2 detects the height position of the sample block 20.
Next, based on the detection information of the height detection unit 2, the sample block transport unit 1 determines that the surface layer portion of the sample block 20 is in the extending direction (± Y axis direction) of the cutter 41 and the transport direction (± X The height position of the sample block 20 is adjusted so that the surface of the sample block 20 is roughened by the cutter 41 while being flattened so as to be parallel to the axial direction.
　次いで、試料ブロック搬送部１が試料ブロック２０を位置Ｂに搬送する。
　次いで、撮像部３が試料ブロック２０の表面を撮像する。これにより、試料ブロック２０中の被検体２０ａの最大投影領域（最大投影面積）を認識する。
　次いで、試料ブロック搬送部１が試料ブロック２０を位置Ｃに搬送する。これにより、試料ブロック２０の表層部分がカッター４１により粗削りされる。 Next, the sample block transport unit 1 transports the sample block 20 to the position B.
Next, the imaging unit 3 images the surface of the sample block 20. Thereby, the maximum projection area (maximum projection area) of the subject 20a in the sample block 20 is recognized.
Next, the sample block transport unit 1 transports the sample block 20 to the position C. Thereby, the surface layer portion of the sample block 20 is roughly cut by the cutter 41.
　次いで、試料ブロック搬送部１が試料ブロック２０を位置Ｂに搬送する。
　次いで、撮像部３が、カッター４１により薄切りされて露出した試料ブロック２０の切削面を撮像する。 Next, the sample block transport unit 1 transports the sample block 20 to the position B.
Next, the imaging unit 3 captures an image of the cut surface of the sample block 20 that is exposed by being sliced by the cutter 41.
　試料ブロック２０の切削面における被検体２０ａの露出面積が予め設定された面積（例えば前記最大投影領域の８０％）未満であるとき、試料ブロック搬送部１が、試料ブロック２０の表層部分がカッター４１に粗削りされるように試料ブロック２０の高さ位置を調整する。なお、このときの高さ位置の調整については後で詳しく説明する。その後、試料ブロック搬送部１が、試料ブロック２０を位置Ｃに搬送する。これにより、試料ブロック２０の表層部分がカッター４１により再度粗削りされる。その後、試料ブロック搬送部１が試料ブロック２０を位置Ｂに搬送し、撮像部３が再度試料ブロック２０の切削面を撮像する。この試料ブロック２０の粗削り及び切削面の撮像動作は、試料ブロック２０の切削面における被検体２０ａの露出面積が予め設定された面積以上になるまで繰り返される。 When the exposed area of the subject 20a on the cutting surface of the sample block 20 is less than a preset area (for example, 80% of the maximum projection region), the sample block transport unit 1 uses the cutter 41 as the surface layer portion. The height position of the sample block 20 is adjusted so that it is roughly cut. The adjustment of the height position at this time will be described in detail later. Thereafter, the sample block transport unit 1 transports the sample block 20 to the position C. Thereby, the surface layer portion of the sample block 20 is roughed again by the cutter 41. Thereafter, the sample block transport unit 1 transports the sample block 20 to the position B, and the imaging unit 3 captures the cutting surface of the sample block 20 again. The rough cutting of the sample block 20 and the imaging operation of the cutting surface are repeated until the exposed area of the subject 20a on the cutting surface of the sample block 20 is equal to or larger than a preset area.
　試料ブロック２０の切削面における被検体２０ａの露出面積が予め設定された面積以上になると、粗削りの動作を終了し、本削りの動作に移行する。なお、粗削りと本削りとで異なるカッター４１又は異なるカッター４１の刃先４１ａの位置を使用する場合、あるいは粗削りの厚さと本削りの厚さが異なる場合は、作製される切片の厚さ精度を良くするため、本削りに使用されるカッター４１又はカッター４１の刃先４１ａの位置で、薄切片試料２４の作製前（本削り前）に本削り厚さで数回薄切りのみを行う、いわゆる捨て切り動作を行うのが好ましい。 When the exposed area of the subject 20a on the cutting surface of the sample block 20 is equal to or larger than a preset area, the rough cutting operation is terminated and the main cutting operation is started. In addition, when using the position of the cutting edge 41a of different cutter 41 or different cutter 41 for rough cutting and main cutting, or when the thickness of rough cutting differs from the thickness of main cutting, the thickness accuracy of the section to be manufactured is improved. Therefore, at the position of the cutter 41 used for the main cutting or the cutting edge 41a of the cutter 41, a so-called discarding operation is performed in which the thin cutting sample 24 is thinly cut several times with the main cutting thickness before the thin section sample 24 is manufactured (before the main cutting). Is preferably performed.
　本削り動作においては、試料ブロック搬送部１が、試料ブロック２０の表層部分がカッター４１に薄切り（３μｍ～１０μｍ程度）されるように試料ブロック２０の高さ位置を調整する。その後、試料ブロック搬送部１が、試料ブロック２０を位置Ｃへ搬送する。これにより、試料ブロック２０の表層部分がカッター４１により薄切りされ、薄切片試料２４が作製される。その後、試料ブロック搬送部１が、試料ブロック２０を位置Ｃから位置Ｂなどへ退避させ、試料ブロック２０の表層部分がカッター４１に薄切りされるように試料ブロック２０の高さ位置を調整する。この試料ブロック２０の高さ位置の調整、薄切り、及び退避の動作が、前記入力部（図示せず）に入力された情報に基づく任意の回数、自動的且つ連続的に繰り返され、任意の枚数の薄切片試料２４が作製される。 In the main cutting operation, the sample block transport unit 1 adjusts the height position of the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41 (about 3 μm to 10 μm). Thereafter, the sample block transport unit 1 transports the sample block 20 to the position C. Thereby, the surface layer part of the sample block 20 is sliced by the cutter 41, and the thin slice sample 24 is produced. Thereafter, the sample block transport unit 1 retracts the sample block 20 from the position C to the position B or the like, and adjusts the height position of the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41. The operations of adjusting the height position of the sample block 20, slicing, and retracting are automatically and continuously repeated an arbitrary number of times based on information input to the input unit (not shown), and an arbitrary number of sheets A thin slice sample 24 is prepared.
　前記本削りの動作により作製された薄切片試料２４は、キャリアテープ２１に貼り付けられる。なお、このとき、薄切片試料２４がキャリアテープ２１により確実に貼り付くように、キャリアテープ２１の表面に加湿、冷却及び帯電などの処理をしておくことが好ましい。キャリアテープ２１に貼り付けられた薄切片試料２４は、繰り出しモータ５１及び巻取モータ６１の駆動により薄切片貼付部７に搬送され、薄切片貼付部７によりスライドガラス２２に貼り付けられる。その後、薄切片付きスライドガラス２２は、スライドガラス搬送部８により伸展部９へ搬送される。その後、伸展部９が、薄切片試料２４の皺を伸展するとともに、薄切片試料２４をスライドガラス２２に密着固定させる。 The thin slice sample 24 produced by the main cutting operation is affixed to the carrier tape 21. At this time, it is preferable that the surface of the carrier tape 21 is subjected to treatments such as humidification, cooling, and charging so that the thin slice sample 24 is securely attached to the carrier tape 21. The thin slice sample 24 affixed to the carrier tape 21 is conveyed to the thin slice affixing unit 7 by driving of the feeding motor 51 and the take-up motor 61 and affixed to the slide glass 22 by the thin segment affixing unit 7. Thereafter, the slide glass 22 with a thin section is conveyed to the extension unit 9 by the slide glass conveyance unit 8. Thereafter, the extension section 9 extends the folds of the thin slice sample 24 and closely fixes the thin slice sample 24 to the slide glass 22.
　図２は、粗削りの動作と本削りの動作の切り換えに関する流れを示すフローチャートである。これらの動作は、制御部１０の制御の下に行われる。なお、前記と重複する部分については省略しながら説明する。 FIG. 2 is a flowchart showing a flow relating to switching between rough cutting operation and main cutting operation. These operations are performed under the control of the control unit 10. In addition, it demonstrates, abbreviate | omitting about the part which overlaps with the above.
　ステップＳ１では、試料ブロック２０の表層部分をカッター４１により粗削りする。 In step S1, the surface layer portion of the sample block 20 is roughly cut by the cutter 41.
　ステップＳ２では、カッター４１により薄切りされて露出した試料ブロック２０の切削面を撮像部３により撮像する。 In step S <b> 2, the imaging unit 3 captures an image of the cut surface of the sample block 20 that is exposed by being sliced by the cutter 41.
　ステップＳ３では、試料ブロック２０の切削面における被検体２０ａの露出面積が予め設定された面積（例えば前記最大投影領域の８０％）以上であるか否か判定する。被検体２０ａの露出面積が予め設定された面積未満であるとき、ステップＳ４に移行し、被検体２０ａの露出面積が予め設定された面積以上であるとき、ステップＳ５に移行する。 In step S3, it is determined whether or not the exposed area of the subject 20a on the cutting surface of the sample block 20 is equal to or larger than a preset area (for example, 80% of the maximum projection area). When the exposed area of the subject 20a is less than the preset area, the process proceeds to step S4, and when the exposed area of the subject 20a is equal to or larger than the preset area, the process proceeds to step S5.
　ステップＳ４では、被検体２０ａの露出面積に応じて薄切り量を可変するように、試料ブロック２０の高さ位置を調整する。ステップＳ４が終了すると、ステップＳ１に戻る。 In step S4, the height position of the sample block 20 is adjusted so that the amount of slice is variable according to the exposed area of the subject 20a. When step S4 ends, the process returns to step S1.
　ステップＳ５では、試料ブロック２０の表層部分をカッター４１により本削りする。 In step S5, the surface layer portion of the sample block 20 is ground by the cutter 41.
　次に、被検体２０ａの露出面積に応じて薄切り量を可変する際の具体例について述べる。図３は、半径８００μｍの球形の被検体２０ａが包埋された試料ブロック２０（図４に示す試料ブロック１２０と同様）を粗削りしたときの、追加粗削り量と試料ブロック２０の切削面における被検体２０ａの露出面積率との関係を示すグラフである。ここで、追加粗削り量とは、被検体２０ａの露出面積率を１００％にするのに必要な粗削り量をいう。また、粗削り量とは、粗削り動作時における薄切り量をいう。被検体２０ａの露出面積率は、被検体２０ａの最大投影領域に対する被検体２０ａの露出面積の割合（％）を示している。下記表１は、被検体２０ａの露出面積率に対する試料ブロック２０の表層部分の追加粗削り量の設定例を示している。 Next, a specific example will be described in which the amount of slice is varied according to the exposed area of the subject 20a. FIG. 3 shows the amount of additional roughing and the specimen on the cutting surface of the sample block 20 when the specimen block 20 in which a spherical specimen 20a having a radius of 800 μm is embedded (similar to the specimen block 120 shown in FIG. 4) is roughened. It is a graph which shows the relationship with the exposed area rate of 20a. Here, the additional rough cutting amount refers to the rough cutting amount necessary to make the exposed area ratio of the subject 20a 100%. The rough cutting amount is the amount of thin cutting during the rough cutting operation. The exposed area ratio of the subject 20a indicates the ratio (%) of the exposed area of the subject 20a to the maximum projection area of the subject 20a. Table 1 below shows a setting example of the additional rough cutting amount of the surface layer portion of the sample block 20 with respect to the exposed area ratio of the subject 20a.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　制御部１０は、試料ブロック２０の表層部分の追加粗削り量を被検体２０ａの露出面積率に応じて可変するように試料ブロック搬送部１を制御し、薄切片試料２４を作製する薄切り動作を行う。例えば、被検体２０ａの露出面積率が２５％のとき、制御部１０は、試料ブロック２０の表層部分がカッター４１により６６９μｍの追加粗削り量で薄切りされるように試料ブロック搬送部１に試料ブロック２０の高さ位置を調整させる。また、例えば、被検体２０ａの露出面積率が９０％のとき、制御部１０は、試料ブロック２０の表層部分がカッター４１により２５２μｍの追加粗削り量で薄切りされるように試料ブロック搬送部１に試料ブロック２０の高さ位置を調整させる。これにより、１回の粗削り動作で被検体２０ａの露出面積率を１００％近くにすることができ、薄切片試料２４の作製時間を大幅に短縮することができる。 The control unit 10 controls the sample block transport unit 1 so as to vary the amount of additional rough cutting of the surface layer portion of the sample block 20 in accordance with the exposed area ratio of the subject 20a, and performs a slicing operation to produce the thin slice sample 24. . For example, when the exposed area ratio of the subject 20a is 25%, the control unit 10 causes the sample block transport unit 1 to cut the sample block 20 so that the surface layer portion of the sample block 20 is sliced by the cutter 41 with an additional roughing amount of 669 μm. Adjust the height position. For example, when the exposed area ratio of the subject 20a is 90%, the control unit 10 causes the sample block transport unit 1 to sample the surface layer portion of the sample block 20 so that the cutter 41 cuts the surface layer portion with an additional rough cutting amount of 252 μm. The height position of the block 20 is adjusted. Thereby, the exposed area ratio of the subject 20a can be made close to 100% by one roughing operation, and the preparation time of the thin slice sample 24 can be greatly shortened.
　以上、本実施形態によれば、被検体２０ａの露出面積率に応じて試料ブロック２０の表層部分を薄切りする量を可変して前記粗削りをするようにしているので、薄切片試料２４の作製時間をより一層短縮することができる。 As described above, according to the present embodiment, since the rough cutting is performed by varying the amount of slice of the surface layer portion of the sample block 20 in accordance with the exposed area ratio of the subject 20a, the preparation time of the thin slice sample 24 Can be further shortened.
　なお、被検体２０ａの露出面積（率）が小さいときは、粗削り量を大きくしても被検体２０ａを切削しすぎる可能性は低い。一方、被検体２０ａの露出面積（率）が大きいときは、粗削り量が大きいままであると、被検体２０ａを切削しすぎる可能性が高い。このため、被検体２０ａの露出面積（率）が予め設定された値（例えば５０％）よりも小さいときは、被検体２０ａの露出面積率が予め設定された値よりも大きいときよりも、試料ブロック２０の表層部分を薄切りする量を大きくするようにすることが好ましい。これにより、被検体２０ａを粗削りしすぎることを防止しつつ、薄切片試料２４の作製時間をより一層短縮することができる。 When the exposed area (rate) of the subject 20a is small, there is a low possibility that the subject 20a is excessively cut even if the rough cutting amount is increased. On the other hand, when the exposed area (rate) of the subject 20a is large, if the rough cutting amount remains large, there is a high possibility that the subject 20a will be cut too much. For this reason, when the exposed area (rate) of the subject 20a is smaller than a preset value (for example, 50%), the sample is larger than when the exposed area rate of the subject 20a is larger than a preset value. It is preferable to increase the amount by which the surface layer portion of the block 20 is sliced. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
　また、被検体２０ａの露出面積が予め設定された面積に近づくに従い、試料ブロック２０の表層部分を薄切りする量を小さくすることが好ましい。この場合であっても、被検体２０ａを粗削りしすぎることを防止しつつ、薄切片試料２４の作製時間をより一層短縮することができる。 In addition, as the exposed area of the subject 20a approaches the preset area, it is preferable to reduce the amount by which the surface layer portion of the sample block 20 is sliced. Even in this case, it is possible to further reduce the preparation time of the thin-section sample 24 while preventing the subject 20a from being excessively roughened.
　なお、前記実施態様では、１回の粗削り動作毎に薄切り厚みを可変し、１回の粗削り動作毎に撮像部３で被検体２ａの露出面積を確認するようにしたが、本発明はこれに限定されない。例えば、１回の粗削り動作の薄切り厚みは一定にし、被検体２０ａの露出面積率に応じて、連続した薄切りを行い、その連続した薄切り回数を可変させることで薄切り量を可変させるようにしても良い。なお、連続した薄切りとは、薄切り動作と薄切り動作との間に撮像部３での露出面積の確認を行わないことをいう。例えば、被検体２０ａの露出面積率に応じた追加粗削り量が５０μｍである場合、１回の粗削り動作当たり１０μｍの薄切り厚みで５回の粗削り動作を連続して行い（その間の撮像部３での露出面積確認は省略）、５回の粗削り動作の終了後、撮像部３で被検体２ａの露出面積を確認する。このように、被検体２０ａの露出面積率に応じて、次に撮像部３で試料ブロック２０を撮像するまでの粗削り動作の回数を可変するようにして、撮像部３での被検体２０ａの露出面積の検出から次の被検体２０ａの露出面積の検出までの薄切り量を可変してもよい。この場合、粗削り動作の回数自体は、設定された追加粗削り量を１回の粗削り動作で処理する前記の場合と比べて増加するが、撮像部３の撮像動作、すなわち被検体２０ａの露出面積の確認（検出）回数は、従来までの１回の粗切り動作毎に撮像する場合と比べて、大幅に減少する。その結果、薄切片試料の作製時間を従来より大幅に短縮することができる。また、この場合、カッター４１の高さ位置の調整を一定ピッチにすることができるので、当該調整を容易にすることができるという利点がある。 In the above embodiment, the thickness of the slice is changed for each roughing operation, and the exposed area of the subject 2a is confirmed by the imaging unit 3 for each roughing operation. It is not limited. For example, the thin slice thickness of one roughing operation is made constant, continuous thin slices are performed according to the exposed area ratio of the subject 20a, and the thin slice amount is varied by changing the number of continuous thin slices. good. Note that the continuous slicing means that the exposed area is not checked in the imaging unit 3 between the slicing operation and the slicing operation. For example, when the amount of additional rough cutting according to the exposed area ratio of the subject 20a is 50 μm, five rough cutting operations are continuously performed with a thin thickness of 10 μm per one rough cutting operation (in the imaging unit 3 in the meantime). (Exposed area confirmation is omitted) After the five roughing operations are completed, the imaging unit 3 confirms the exposed area of the subject 2a. In this way, depending on the exposed area ratio of the subject 20a, the number of rough cutting operations until the next time the sample block 20 is imaged by the imaging unit 3 is varied to expose the subject 20a in the imaging unit 3. The amount of slicing from the detection of the area to the detection of the exposed area of the next subject 20a may be varied. In this case, the number of roughing operations itself increases as compared with the case where the set additional roughing amount is processed by one roughing operation, but the imaging operation of the imaging unit 3, that is, the exposure area of the subject 20a. The number of times of confirmation (detection) is greatly reduced as compared with the case where imaging is performed for each rough cutting operation until now. As a result, the production time of the thin slice sample can be significantly shortened compared to the conventional case. In this case, since the height position of the cutter 41 can be adjusted to a constant pitch, there is an advantage that the adjustment can be facilitated.
　なお、前記の場合、被検体２０ａの露出面積（率）が小さいときは、連続薄切り回数を多くしても被検体２０ａを切削しすぎる可能性は低い。一方、被検体２０ａの露出面積（率）が大きいときは、連続薄切り回数が多いままであると、被検体２０ａを切削しすぎる可能性が高い。このため、被検体２０ａの露出面積（率）が小さいときは、被検体２０ａの露出面積率が大きいときよりも、試料ブロック２０の表層部分を連続した薄切りする回数を多くするようにすることが好ましい。これにより、被検体２０ａを粗削りしすぎることを防止しつつ、薄切片試料２４の作製時間をより一層短縮することができる。 In the above case, when the exposed area (rate) of the subject 20a is small, it is unlikely that the subject 20a will be cut too much even if the number of continuous slices is increased. On the other hand, when the exposed area (rate) of the subject 20a is large, there is a high possibility that the subject 20a will be cut too much if the number of continuous slices remains large. For this reason, when the exposed area (rate) of the subject 20a is small, the number of continuous slices of the surface layer portion of the sample block 20 may be increased more than when the exposed area rate of the subject 20a is large. preferable. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
　また、被検体２０ａの露出面積が予め設定された面積に近づくに従い、試料ブロック２０の表層部分を薄切りする量を小さくすることが好ましい。すなわち、連続した薄切り回数を少なくすることが好ましい。これにより、被検体２０ａを粗削りしすぎることを防止しつつ、薄切片試料２４の作製時間をより一層短縮することができる。 In addition, as the exposed area of the subject 20a approaches the preset area, it is preferable to reduce the amount by which the surface layer portion of the sample block 20 is sliced. That is, it is preferable to reduce the number of continuous slicing. Thereby, the preparation time of the thin slice sample 24 can be further shortened while preventing the subject 20a from being excessively roughened.
　なお、薄切片試料作製装置では被検体２０ａとして生体試料を扱うことが多いため、１回の粗削り動作の薄切り厚みを厚くすると、試料ブロック中の被検体２０ａにダメージを与える恐れがある。したがって、前記薄切り厚みはほぼ一定にし、連続した薄切り回数を可変させることで、薄切り量を可変させることが好ましい。なお、パラフィンを用いた生体試料ブロックの場合、１回の粗削り動作当たりの薄切り厚みは５～３０μｍ程度に設定することが好ましい。 Note that since the thin-section sample preparation apparatus often handles a biological sample as the subject 20a, increasing the thin thickness of one roughing operation may damage the subject 20a in the sample block. Therefore, it is preferable to vary the amount of slicing by making the slicing thickness substantially constant and changing the number of continuous slicing. In the case of a biological sample block using paraffin, it is preferable to set the thin slice thickness per rough cutting operation to about 5 to 30 μm.
　なお、前記実施形態では、被検体２０ａが球形であるとしたが、実際の被検体２０ａは種々の形状のものがある。この場合、被検体２０ａの露出面積に応じた粗削り量は、経験則に基づき適宜設定すればよい。 In the above embodiment, the subject 20a has a spherical shape, but the actual subject 20a has various shapes. In this case, the rough cutting amount corresponding to the exposed area of the subject 20a may be set as appropriate based on empirical rules.
　また、被検体２０ａの形状や埋込状態によっては、被検体２０ａの露出面積が予め設定された面積（例えば最大投影領域の８０％）以上にならないことが有り得る。この場合、被検体２０ａを粗削りしすぎることになる。一方、被検体２０ａの露出面積の増加量が小さくなることは、被検体２０ａの観察に好適な面積が露出するポイントが近いことを意味すると考えられる。例えば、図３に示す試料ブロック２０の場合、被検体２０ａの露出面積率が０～９０％のときの増加率に比べて、被検体２０ａの露出面積率が９０～１００％のときの増加率は小さくなっている。このため、被検体２０ａの露出面積の増加量が予め設定された増加量よりも小さくなったとき、粗削りを終了して本削りを開始することが好ましい。これにより、被検体２０ａを粗削りしすぎることをより一層防止することができる。 Further, depending on the shape and embedded state of the subject 20a, the exposed area of the subject 20a may not exceed a preset area (for example, 80% of the maximum projection region). In this case, the subject 20a is excessively roughened. On the other hand, a small increase in the exposed area of the subject 20a is considered to mean that the point where an area suitable for observation of the subject 20a is exposed is close. For example, in the case of the sample block 20 shown in FIG. 3, the increase rate when the exposed area rate of the subject 20a is 90 to 100%, compared to the increase rate when the exposed area rate of the subject 20a is 0 to 90%. Is getting smaller. For this reason, when the increase amount of the exposed area of the subject 20a becomes smaller than the preset increase amount, it is preferable to finish the rough cutting and start the main cutting. Thereby, it is possible to further prevent the subject 20a from being excessively roughened.
　また、前記実施形態では、試料ブロック搬送部１により試料ブロック２０を試料ブロック切削部４へ搬送することにより、薄切片試料２４を作製するようにしたが、本発明はこれに限定されない。例えば、試料ブロック切削部４のカッター４１を試料ブロック搬送部１に保持された試料ブロック２０へ移動させて、薄切片試料２４を作製するようにしてもよい。すなわち、試料ブロック切削部４と試料ブロック搬送部１とを相対的に移動させることにより、薄切片試料２４を作製するようにしてもよい。 In the above embodiment, the sample block 20 is transported to the sample block cutting unit 4 by the sample block transport unit 1 to produce the thin slice sample 24. However, the present invention is not limited to this. For example, the thin section sample 24 may be produced by moving the cutter 41 of the sample block cutting unit 4 to the sample block 20 held by the sample block transport unit 1. That is, the thin slice sample 24 may be manufactured by relatively moving the sample block cutting unit 4 and the sample block transport unit 1.
　本発明は、添付図面を参照しながら好ましい実施の形態に関連して充分に記載されているが、この技術に熟練した人々にとっては種々の変形や修正は明白である。そのような変形や修正は、添付した請求の範囲による本発明の範囲から外れない限りにおいて、その中に含まれると理解されるべきである。 Although the present invention has been fully described in connection with preferred embodiments with reference to the accompanying drawings, various changes and modifications will be apparent to those skilled in the art. Such changes and modifications are to be understood as being included therein, so long as they do not depart from the scope of the present invention according to the appended claims.
　２０１１年４月２６日に出願された日本国特許出願Ｎｏ．２０１１－０９８４８８号の明細書、図面、および特許請求の範囲の開示内容は、全体として参照されて本明細書の中に取り入れられるものである。 Japanese patent application No. filed on April 26, 2011. The disclosures in the specification, drawings, and claims of 2011-098488 are hereby incorporated by reference in their entirety.
　本発明にかかる薄切片試料作製装置は、薄切片試料の作製時間をより一層短縮することができるので、理化学試料分析や生体試料等の顕微鏡観察などに利用される薄切片試料作製装置として有用である。 The thin-section sample preparation apparatus according to the present invention can further reduce the preparation time of a thin-section sample, and is therefore useful as a thin-section sample preparation apparatus used for physicochemical sample analysis and microscopic observation of biological samples. is there.
　　１　　試料ブロック搬送部
　　２　　高さ検出部
　　３　　撮像部
　　４　　試料ブロック切削部
　　５　　供給リール
　　６　　巻取リール
　　７　　薄切片貼付部
　　８　　スライドガラス搬送部
　　９　　伸展部
　１０　　制御部
　２０　　試料ブロック
　２１　　キャリアテープ
　２２　　スライドガラス
　２３　　接着液
　２４　　薄切片試料
　３０　　試料ブロック収納部
　４１　　カッター
　５１　　繰り出しモータ
　６１　　巻取モータ
　７１，７２，８１～８４　　ガイドローラ
１００　　薄切片試料作製装置 DESCRIPTION OF SYMBOLS 1 Sample block conveyance part 2 Height detection part 3 Imaging part 4 Sample block cutting part 5 Supply reel 6 Take-up reel 7 Thin section sticking part 8 Slide glass conveyance part 9 Extending part 10 Control part 20 Sample block 21 Carrier tape 22 Slide glass DESCRIPTION OF SYMBOLS 23 Adhesive liquid 24 Thin section sample 30 Sample block storage part 41 Cutter 51 Feeding motor 61 Winding motor 71,72,81-84 Guide roller 100 Thin section sample preparation apparatus

Claims (4)

  1. 　被検体を包埋する試料ブロックの表層部分をカッターにより薄切りして薄切片試料を作製する薄切片試料作製装置であって、
    　前記カッターを備える試料ブロック切削部と、
    　前記試料ブロックを搬送する試料ブロック搬送部と、
    　前記試料ブロックの表面を撮像する撮像部と、
    　前記試料ブロック切削部、前記試料ブロック搬送部、及び前記撮像部を制御する制御部と、
    　を備え、
    　前記制御部は、前記試料ブロック切削部と前記試料ブロック搬送部とを相対的に移動させることにより前記薄切り動作を行い、前記撮像部に前記切削面を撮像させ、当該切削面における前記被検体の露出面積が予め設定された面積以上になるまで、前記被検体の露出面積に応じて前記試料ブロックの表層部分を薄切りする量を可変して前記薄切り動作を行う粗削りをし、前記被検体の露出面積が予め設定された面積以上になったとき、前記試料ブロックの表層部分を薄切りする量を予め設定された量にして前記薄切り動作を行う本削りをする、薄切片試料作製装置。     A thin-section sample preparation device for preparing a thin-section sample by slicing a surface layer portion of a sample block embedding an object with a cutter,
    A sample block cutting section comprising the cutter;
    A sample block transport unit for transporting the sample block;
    An imaging unit for imaging the surface of the sample block;
    A control unit for controlling the sample block cutting unit, the sample block transport unit, and the imaging unit;
    With
    The control unit performs the slicing operation by relatively moving the sample block cutting unit and the sample block transport unit, causing the imaging unit to image the cutting surface, and Until the exposed area is equal to or larger than a preset area, the amount of thinning of the surface portion of the sample block is varied according to the exposed area of the subject, and rough cutting is performed to perform the thinning operation, thereby exposing the subject. A thin-section sample preparation apparatus that performs the main cutting for performing the slicing operation by setting the amount of slicing the surface layer portion of the sample block to a preset amount when the area becomes equal to or larger than a preset area.
  2. 　前記制御部は、前記予め設定された面積に対する前記被検体の露出面積の割合が予め設定された割合よりも小さいとき、前記予め設定された面積に対する前記被検体の露出面積の割合が予め設定された割合よりも大きいときよりも、前記試料ブロックの表層部分を薄切りする量を大きくする、請求項１に記載の薄切片試料作製装置。 When the ratio of the exposed area of the subject with respect to the preset area is smaller than the preset ratio, the ratio of the exposed area of the subject with respect to the preset area is preset. The thin-section sample preparation device according to claim 1, wherein an amount of slicing a surface layer portion of the sample block is made larger than when the ratio is larger than the ratio.
  3. 　前記制御部は、前記被検体の露出面積が前記予め設定された面積に近づくに従い、前記試料ブロックの表層部分を薄切りする量を小さくする、請求項１又は２に記載の薄切片試料作製装置。 3. The thin-section sample preparation device according to claim 1, wherein the control unit reduces an amount of slicing a surface layer portion of the sample block as an exposed area of the subject approaches the preset area.
  4. 　前記制御部は、前記被検体の露出面積の増加量が予め設定された増加量よりも小さくなったとき、前記粗削りを終了して前記本削りを開始する、請求項１～３のいずれか１つに記載の薄切片試料作製装置。 4. The control unit according to claim 1, wherein when the increase amount of the exposed area of the subject is smaller than a preset increase amount, the control unit ends the rough cutting and starts the main cutting. The thin-section sample preparation apparatus described in 1.
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