JP3005480B2 - Biological tissue processing equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biological tissue processing apparatus, and more particularly to a structure for supplying a minimum necessary amount of reagent to a biological tissue sample.

[0002]

2. Description of the Related Art Along with recent advances in biotechnology, various treatments for biological tissues are actively performed in research facilities and universities, and there is a strong demand for efficient and rapid treatment. ing. For example, immunostaining and ISH (in
When performing a treatment such as in situ hybridization, a thin slice of biological tissue (hereinafter simply referred to as a sample) is attached to a slide glass as a transparent sample plate, and the sample on the slide glass is dehydrated, stained, and stained. Many processes such as hybridization are performed.

In the case of performing such a process, conventionally, generally, a large number (for example, 20) of slide glasses to which a sample is attached is aligned and held in a metal basket at a predetermined interval. Then, the basket was immersed in a large-sized reagent tank made of glass, and such processing was performed on various reagents.

[0004]

However, in the above-mentioned conventional processing method, there is a problem that the injection of the reagent into the reagent tank and the removal of the reagent after the processing are performed manually, which is complicated. However, since it is necessary to use a large reagent tank capable of immersing the entirety of a large number of slide glasses separated from each other, the amount of each reagent must be uniformly large. there were. That is, a large amount of reagents must be used in the processing such as deparaffinization, but on the other hand, many small and sufficient expensive reagents were used, and the cost of the entire processing could not be reduced, resulting in poor economic efficiency. Then, for the same reason, there is a problem that the drainage is increased more than necessary.

Conventionally, since the same reagent processing is performed on each sample on a slide glass in a basket at once, different reagent processing is required for some of the samples during the processing process. In such a case, it was necessary to remove a part of the slide glass from the basket and perform the above-described processing separately.

Incidentally, conventionally, in order to reduce the amount of reagent and realize individual reagent treatment, a slide glass sample is covered with a cover glass, and a reagent is dropped between the slide glass and the cover glass. The reagent was taken in between the glasses by using the surface tension of the reagent, and the reagent treatment was performed by this.However, bubbles are easily generated between the glasses due to dirt and the like, so skill is required. In addition, there was a problem that work efficiency was poor.

Conventionally, a slide glass and another plate are brought into close proximity to each other to form a minute gap therebetween,
It has also been proposed to perform reagent treatment on a sample by supplying a reagent from above or below the minute gap, but it is difficult to accurately form such a uniform minute gap, and There is a problem that the control and the mechanism for supplying the reagent are complicated.

The present invention has been made in view of the above-mentioned conventional problems, and an object of the present invention is to provide a biological tissue processing apparatus capable of performing processing using a minimum necessary amount of reagent and preventing waste of the reagent. To provide.

Another object of the present invention is to supply a reagent smoothly and efficiently over the entire area of a sample on a sample plate (eg, a slide glass).

Another object of the present invention is to improve the processing efficiency by simultaneously processing a plurality of sample plates.

[0011]

In order to achieve the above object, the present invention provides a sample plate to which a sample of biological tissue is attached, a reagent plate joined to a sample attachment surface of the sample plate, A driving means for joining a plate and the reagent plate to form a capillary gap between the two plates , wherein the reagent plate has a reagent injection path for injecting a reagent between the two plates, The injection hole, which forms the outlet opening of the reagent injection path, is formed at a position facing between the two plates, and the reagent is used only when both plates are joined.
Is formed so as to flow out .

In the above configuration, when the sample plate and the reagent plate are joined together, the surface tension of the reagent acts to cause the reagent to flow out of the injection hole between the two plates, as seen by the so-called capillary phenomenon. , It spreads across the plate. That is, the joining of the two plates has two significances: formation of a capillary gap size between the plates, and thereby, injection of the reagent between the plates.

When the reagent is injected between the two plates,
The sample will be immersed in the reagent, and the sample will be treated with the reagent. In this case, since the sample becomes an inclusion between the two plates, it is desirable that the sample is thin enough that the spread of the sample due to surface tension can be expected. The amount of the reagent to be injected between the two plates is very small and sufficient, so that the amount of the reagent can be reduced, so that the cost for reagent processing can be reduced. According to the present invention, the sample is always immersed in the reagent during the reagent processing, so that there is no danger of drying.

In a preferred aspect of the present invention, a mesh sheet is interposed between the reagent plate and the sample plate. That is, a thin mesh sheet is interposed between the two plates, and the permeation of the reagent into the mesh sheet and the promotion of the capillary phenomenon thereby facilitate the smooth and reliable spread of the reagent between the plates. Even if a part of the surface of the reagent plate is dirty and the part obstructs the development of the reagent, the reagent can be reliably spread by the mesh sheet. This mesh sheet is used repeatedly or exchanged for each sample as needed. The mesh sheet is desirably attached to a reagent plate in advance.

[0015] In a preferred aspect of the present invention, the mesh sheet is provided with a separation hole which is separated from and surrounds the injection hole. In other words, in a state where the two plates are not joined, if the outflow of the reagent is prevented by the surface tension of the reagent exposed from the injection hole, when the mesh sheet touches the injection hole, the reagent permeates the mesh sheet. In addition, a separation hole is provided in the mesh sheet to prevent the reagent from flowing out from the injection hole. Of course, if the two plates are joined, the reagent will flow out of the injection hole due to the suction of the reagent by the capillary gap between the plates, and the reagent will permeate the entire mesh sheet.

In a preferred aspect of the present invention, the opening area of the injection hole is set to a size such that the reagent flows out only when the two plates are joined. According to this configuration, in a state where the two plates are not joined, the surface tension of the reagent exposed from the injection hole is larger than the outflow action of the reagent from the injection hole, so that the reagent flows out of the injection hole. Instead, it is held in the reagent injection path. This eliminates the need to provide a controlled mechanism such as a valve in the injection hole. When the two plates are joined, the reagent exposed from the injection hole comes into contact with the sample plate surface or the sample itself, so that the reagent flows between the plates as if sucked.

According to another aspect of the present invention, there is provided a sample plate to which a sample of biological tissue is attached, a reagent plate joined to a sample attachment surface of the sample plate, the sample plate and the reagent A driving means for joining the plate and a sponge sheet interposed between the reagent plate and the sample plate, wherein the reagent plate has a reagent injection passage for injecting a reagent into the sponge sheet. It is characterized by being formed.

In the above configuration, the reagent permeates the sponge sheet from the reagent injection hole of the reagent plate, and spreads and is held on the sponge sheet. That is, even if a part of the reagent plate surface is soiled due to the infiltration of the reagent in the sponge sheet, for example, and that part may hinder the reagent development, the reagent can be reliably transferred along the reagent plate surface. Can be spread. Thereafter, when the reagent plate and the sample plate are joined, the sample attached to the sample plate is immersed in the reagent permeated and held by the sponge, and the treatment with the reagent is performed.

In this case, the sample is desirably in the form of a flake so that the surface of the sample comes into contact with the sponge sheet as widely as possible. However, the sponge sheet has elasticity and depends on the shape of the sample to be contacted. Therefore, the requirements regarding the thickness and shape of the sample and the requirement for the accuracy with respect to the distance between the two plates are alleviated in securing the adhesion between the sponge sheet and the sample. In addition, since the reagent has already spread on the sponge sheet when the two plates are joined, there is no need to spread the reagent by capillary action. In other words, in this sense,
The requirements for the control accuracy of the distance between the two plates are moderate. The joining of the two plates, together with the function of supplying the reagent to the sample, the evaporation of the reagent during the reagent processing of the sample,
It has the function of preventing the sample from drying.

The amount of the reagent injected into the sponge sheet is
Since a very small amount is sufficient and the amount of the reagent can be reduced, the cost for the reagent treatment can be reduced. This sponge sheet is used repeatedly or replaced for each sample as needed. The sponge sheet is desirably attached to a reagent plate in advance.

In order to quickly spread the reagent between the plates, it is desirable that the injection hole be provided as close to the center of the plate surface as possible. On the other hand, if the effect of gravity is considered, it is desirable to provide the injection hole at the upper side if possible.
On the other hand, if a reagent tank communicating with the reagent injection path is formed inside the reagent plate, it is necessary to secure that space. In view of the above circumstances, the injection hole is desirably formed at a position above the center of the reagent plate.

Note that the injection hole is a minute hole, and no particular problem occurs even if it directly hits the sample. At least one injection hole is formed on the sample plate joining surface of the reagent plate, but a plurality of injection holes may be provided if smoother spread of the reagent is expected.

In a preferred aspect of the present invention, the reagent treatment is performed by sandwiching the two sample plates joined back to back with the sample attachment surfaces facing outward from the two reagent plates from both sides thereof.

In a preferred aspect of the present invention, the injection hole is formed on both sides of the reagent plate, and the reagent processing is performed by joining the sample plate from both sides of the reagent plate.

In a preferred aspect of the present invention, a spacer means for forming a predetermined gap between the sample plate and the reagent plate is provided, and the spacer protects the sample at the time of plate joining.

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION

Embodiment 1 Hereinafter, a preferred embodiment of the present invention will be described with reference to the drawings.

FIG. 1 shows a main configuration of a biological tissue processing apparatus according to the present invention. The sample plate 10 made of a slide glass is held by a holding mechanism 14 with its longitudinal direction being vertical. A sample 12 of a biological tissue is attached to one surface 10A of the sample plate 10. This sample 12 is formed in a flake shape. On the other hand, the reagent plate 16 to which the sample plate 10 is joined is
In FIG. 1, it is formed in a plate shape, and its plate joining surface 16A is a flat surface. On the reagent plate 16, a reagent tank 18 is formed in a well shape slightly above the center. The reagent is injected by a dispensing nozzle or the like through the upper opening of the reagent tank 18. A reagent supply path 21 is formed below the reagent tank 18, and an injection hole 20 is formed as an opening on the outlet side.

As shown in FIG.
Is formed at a position slightly above the center of the plate joining surface 16A. When the two plates are not joined, the diameter of the injection hole 20 is set to the reagent tank 18.
The size is set such that the reagent does not flow out from the injection hole 20 when the reagent is placed in the injection hole 20. That is,
The injection hole 20 is a minute hole. FIG. 3 is a sectional view showing the lower part of the reagent tank 18. The diameter D of the injection hole 20 is, for example, 1 mm. Also, the reagent tank 1 is inserted through the injection hole 20.
The length up to 8, that is, the length of the reagent supply path 21 is, for example, 1 mm, and its shape is cylindrical.

As shown in FIG. 3, by providing such a small injection hole 20, it is possible to prevent the reagent from flowing out from the injection hole 20 when the plate is not joined by utilizing the surface tension of the reagent. . Of course, for example, the closing or opening of the injection hole 20 may be controlled by using a valve structure or the like. However, according to this embodiment, the reagent can be controlled by a very simple configuration without employing such a valve structure. Can control outflow. That is, it is possible to introduce a reagent from the injection hole 20 between the two plates by joining the two plates.

In FIG. 2, the height of the reagent plate 16 is, for example, 60 mm, its width is, for example, 30 mm, and its thickness is, for example, 4 mm. Reagent plate 16
Is configured as a resin-formed product, for example. The reagent tank 18
For example, it has a volume of about 100 μl.

FIG. 4 shows a state in which the sample plate 10 and the reagent plate 16 as shown in FIG. 1 are joined together from a state where they are separated from each other. In FIG. 4, when the sample plate 10 is joined to the reagent plate 16, a minute gap 23 is generated between the two plates to the extent that a capillary phenomenon occurs. As a result, the reagent permeates into the gap 23 from the injection hole 20. The reagent then spreads across the plate. As a result, the reagent is supplied to the entire sample 12, and the reagent processing on the sample 12 is performed for a predetermined time in such a plate-joined state. As described above, since the reagent processing can be performed on the sample 12 in the plate-joined state, the problem that the sample 12 is dried or the reagent evaporates unnecessarily can be avoided. As shown in FIG. 4, depending on the position of the sample 12 on the sample plate 10, the injection hole 20 comes into contact with the sample 12, but the reagent is also present inside the injection hole 20, and no particular problem occurs. . In the configuration shown in FIG. 1, one injection hole 20 is provided in one reagent plate 16, but a plurality of injection holes 2 may be formed in the reagent plate 16 as needed.
0 can also be provided. If a plurality of injection holes 20 are provided, the reagent can be more quickly spread between the plates.

Although the sample plate 10 is joined to the reagent plate 16 in the configuration shown in FIG. 1, the reagent plate 16 can be joined to the sample plate 10. After the reagent processing, the sample plate 10 and the reagent plate 16 are separated from each other, and the reagent plate 16 is washed if necessary.

The reagent plate 16 shown in FIG.
Although formed in a plate shape, various structures can be configured as long as the plate joining surface 16A is a flat surface. In addition, if the volume of the reagent tank 18 can be reduced, the position of the injection hole 20 can be set higher. On the contrary, if the volume of the reagent tank 18 needs to be relatively large, the depth of the And the injection hole 20 is provided at a position corresponding thereto. In any case, at least 2
The injection hole 20 needs to face the space where the two plates are joined. The position of the injection hole 20 can be raised near the upper end of the sample plate 10 by extending the reagent plate 16 in the vertical direction and making the reagent tank 18 higher than the upper end of the sample plate 10.

[Embodiment 2] FIG. 5 shows another embodiment. In the figure, the same components as those in the above embodiment are denoted by the same reference numerals, and description thereof will be omitted. In this embodiment, a mesh sheet 24 is joined to the plate joining surface 16A of the reagent plate 16. The reagent plate 16 itself shown in FIG. 5 has the same structure as that shown in FIG. The mesh sheet 24 has a thickness of, for example, 10
It is a sheet having a mesh structure of 0 μm or less, and its size is, for example, 45 mm × 25 mm. The mesh sheet 24 is formed with a separation opening 24A which is separated from the injection hole 20 and surrounds the injection hole 20. That is, in a state where the mesh sheet 24 is not directly in contact with the injection hole 20 and the two plates are not joined, the reagent in the injection hole 20 is caused by the surface tension of the reagent as shown in FIG. The outflow prevention is maintained. If the separation opening 24A is not formed in the mesh sheet 24, the injection hole 2 is formed when the reagent is poured into the reagent tank 18.
The reagent spreads through the mesh sheet 24 through the “0”. Of course, in such a state, if the sample plate 10 is joined, the reagent spreads over the whole, and the sample 1
2 can be performed, but if the reagent is infiltrated into the mesh sheet 24 in advance, the evaporation or drying of the reagent may become a problem, so the separation opening 24A is provided as described above. I have. The mesh sheet is made of, for example, nylon, and the thickness of the sheet is desirably 40 μm, and the thickness of the nylon fiber is, for example, 40 μm. The aperture ratio is 50%.

FIG. 6 shows a state where the sample plate 10 is joined to the reagent plate 16 in the embodiment shown in FIG. By joining the two plates, the reagent flows out of the injection hole 20 into the gap 23 between the plates. In this case, the action of the mesh sheet 24 can promote the development of the reagent. For example, when the sample plate 10 is partially stained, the mesh sheet 24 is extremely effective.

In this embodiment, it is desirable that the mesh sheet 24 be detachable from the reagent plate 16. Then, if necessary, the mesh sheet 24 is replaced for each reagent treatment.

[Embodiment 3] FIG. 7 shows another embodiment. In the figure, the same components as those in the above embodiment are denoted by the same reference numerals, and description thereof will be omitted. In FIG. 7, the holding mechanism 14 has two sample plates 10- with the surface on which the sample 12 is attached facing outward, that is, back to back.
1, 10-2 are held. A pair of reagent plates 16-1 and 16-2 are provided on both sides of the sample plate pair. If the sample plate pair is sandwiched between the pair of reagent plates 16-1 and 16-2 by the drive mechanism 25, the sample 12 can be moved in the same manner as in the embodiment shown in FIG.
Can be treated with a reagent. The embodiment shown in FIG. 7 has an advantage that the reagent processing can be performed on two samples 12 at the same time.

[Embodiment 4] FIG. 8 shows still another embodiment. In the figure, the same components as those in the above embodiment are denoted by the same reference numerals, and description thereof will be omitted. In this embodiment, the reagent plate 26 has two injection holes 20.
Is provided. That is, the injection hole 20 is provided on each of the one surface 26A and the other surface 26B of the reagent plate 26. All of these injection holes 20 are provided in the reagent tank 18.
Is in communication with A pair of sample plates 1 is placed on both sides of such a reagent plate 26 with the sample 12 adhering surfaces facing each other.
0, and by joining two sample plates 10 from both sides to the center reagent plate 26,
Reagent treatment can be performed on two samples 12 simultaneously using the same reagent plate. The embodiment shown in FIG. 8 has an advantage that the physical quantity can be reduced. However, it is limited to the case where the same reagent processing is performed on the two samples 12.

[Fifth Embodiment] FIG. 9 shows another embodiment. FIG. 9 used for describing this embodiment.
In FIG. 11 to FIG. 11, the same components as those in the above embodiment are denoted by the same reference numerals, and the description may be omitted. Although the reagent plate 16 itself shown in FIG. 9 has the same structure as those of the first and second embodiments, the plate joining surface 16A of the reagent plate 16 of the present embodiment has the second embodiment. Is replaced with a sponge plate 70 with an adhesive or the like. This sponge plate 70 is peelable and replaceable.

FIG. 10 is a side sectional view of a main part of the embodiment shown in FIG. The sponge plate 70 includes a substrate 72
Has a structure in which a sponge sheet 74 is attached.
The substrate 72 is, for example, a resin film having an opening 76 in a portion corresponding to the injection hole 20 and having a size approximately equal to or larger than that. The sponge sheet 74 is made of, for example, nylon and has elasticity, and usually has a thickness of 2 mm. Its size is, for example, 45 mm × 25 mm. The sponge sheet 74 has no opening at a portion corresponding to the opening 76 of the substrate 72. Since the sponge sheet 74 is thin and has low strength, if the sponge sheet 74 is directly attached to the reagent plate 16 with an adhesive or the like,
It is inconvenient because it is easy to tear when replacing. However, in the present embodiment, the sponge sheet 74 is handled integrally with the substrate 72, and at the time of replacement, the sponge sheet 74 is pinched by
The sponge sheet 74 can be easily removed by peeling off the sponge sheet 6A. In addition, the sponge plate 70 has an appropriate strength against bending due to the substrate 72. Therefore,
By attaching the sponge plate 70 to the plate joining surface 16A, the sponge sheet 74 can be easily mounted flat, that is, without sprinkling or distortion, on the plate joining surface 16A. Thus, the sponge plate 70 is effective in making the sponge sheet 74 disposable. In addition, the sponge sheet 7
If you do not exchange 4 or do not exchange much,
The sponge sheet 74 may be directly attached to the plate joining surface 16A.

The reagent that has reached the opening of the injection hole 20 on the side of the plate joining surface 16 A contacts the sponge sheet 74. The sponge sheet 74 sucks the reagent, and the sucked reagent penetrates through the sponge sheet 74 from the injection hole 20 to the surroundings, in particular, downwards due to gravity. Therefore, in this embodiment, the reagent is spread in a plane on the sponge sheet 74 before the sample plate 10 and the reagent plate 16 are joined. In this way, the two plates are joined together with the reagent spread on the sponge sheet 74. In the present embodiment, since the reagent may exude from the injection hole 20 before the two plates are joined, the diameter may be slightly larger than that in the above-described embodiment, and may be, for example, 2 mm.

FIG. 11 shows a state where the sample plate 10 is joined to the reagent plate 16 in the embodiment shown in FIG. Sponge sheet 74
Is in contact with the sample 12 and is depressed according to the shape of the sample 12. First, the supply of the reagent to the sample is effectively performed by the elasticity of the sponge sheet 74. Specifically, this is because, in part, the surface of the sponge sheet 74 fits the surface of the sample 12 at the end portion or the uneven portion of the sample 12. Another is a sponge sheet 74.
The reagent retained inside the sample 12 exudes, and the exuded reagent 80 is spread on the sponge sheet 74 of the surface of the sample 12.
This is because it also covers the parts that are not hit. Thus, when the two plates are joined, the surface of the sample 12 is covered with the reagent, and the reagent processing proceeds. Further, the flow of air between the two plates is suppressed by the joining, the evaporation of the reagent and the drying of the sample are suppressed, and the reagent treatment for a long time can be stably performed.

If the sample plate 10 is bonded to the reagent plate 16 too strongly, the sample 12 will be damaged. For example, the driving means is stopped when the thickness of the sponge sheet 74 becomes about 1 mm. Here, due to the fact that it is not necessary to bring the two plates close to each other to cause a capillary phenomenon, and the above-described elasticity of the sponge sheet 74 and the effect of effectively supplying the reagent, the accuracy of the interval between the two plates is reduced. The fact that it is not so required is one of the features of the present embodiment.

Since the reagent spreads through the sponge sheet 74, in the present embodiment, as in the case where the mesh sheet 24 is used, for example, a part of the plate joining surface 16A of the reagent plate is dirty, and the part is dirty. Even in the case where the development of the reagent is hindered, the reagent should
It can be reliably spread along 6A. On the other hand, the sponge sheet 74 is superior in terms of liquid holding power as compared with the case where only the plate bonding surface 16A is used or the mesh sheet, so that even if the sponge sheet 74 is kept vertical, the reagent inside the sponge sheet 74 flows away Hateful.

[Embodiment 6] Next, the overall configuration of a biological tissue processing apparatus according to the present invention will be described with reference to FIG. The apparatus employs the reagent treatment by plate bonding shown in FIG. A plurality of reagent containers 28 are arranged upright on the upper surface of the apparatus main body 27. Different reagents are stored in the respective reagent containers, and the reagent is dispensed by the dispensing nozzle 30. The dispensing nozzle 30 is configured to be freely movable three-dimensionally, that is, in the X, Y, and Z directions by the transport mechanism 32.

On the other hand, a plurality of slide glasses 10 are held by the holding mechanism 14 with the longitudinal direction directed vertically. More specifically, the upper end of the slide glass 10 is held by the holding mechanism 14, and a plurality of slide glass rows composed of a plurality of slide glasses 10 are held in a line. The holding mechanism 14 can be moved up and down by an upper and lower stage 46.

On the other hand, the reagent processing unit 38 and the reagent processing unit 40, which can be moved in the horizontal direction by the horizontal stage 48, have a plurality of well-shaped reagent tanks 42 and 44, respectively. In each of the reagent processing units 38 and 40, a plurality of reagent tanks 42 and 4 are arranged in an array pattern of the plurality of slide glasses 10 held by the holding mechanism 14.
4 are formed, and a plurality of slide glasses 10 can be collectively subjected to a reagent treatment. However, the reagent tanks 42 and 44 are separated from each other, and the reagent processing can be performed by injecting different reagents by the dispensing nozzle 30.

The reagent processing unit 38 and the reagent processing unit 40 have the same structure as one another, and while one of the reagent processing is actually performed, the other is prepared for the next reagent processing, that is, from the reagent tank. Of the next reagent, dispensing of the next reagent, and the like.

The removal of the reagent is performed by a plurality of suction nozzles 50 supported by the upper and lower stages 49 so as to be vertically movable. The suction nozzles 50 are arranged at the arrangement pitch of the reagent tanks, and can perform suction for each row of the reagent tanks.

The reagent tanks 42 and 44 are formed in a well shape having a rectangular cross section. When the slide glass 10 is inserted into each of the reagent tanks 42 and 44, the slide glass 10 is periodically rotated by the upper and lower stages 46. Is performed, thereby improving the reagent processing efficiency.

The temperature control section 52 joined below the reagent processing units 38 and 40 controls the temperature of each of the reagent processing units 38 and 40 at a constant temperature, thereby performing the reagent processing under a constant temperature condition. be able to.

On the other hand, on the horizontal stage 48, a reagent processing unit 54 for performing the above-described plate joining is held movably in the horizontal direction. This reagent processing unit 5
4 has three well rows corresponding to the three slide glass rows held by the holding mechanism 14. Each well 56 has a depth slightly longer than the entire slide glass row, and the plate joining shown in FIG. 1 is performed. That is, FIG.
As will be understood from FIG. 3, the reagent tank 18 is formed on one wall of each well 56, and the injection hole 20 communicating with the reagent tank 18 is formed on one surface (joining surface of the sample plate) of each well. . The slide glass 10 held by the holding mechanism 14 (see FIG. 12) and inserted into the well 56 is joined to one surface thereof, and the reagent treatment is performed as described above. After the completion of the reagent processing, the slide glass 10 is pulled out of the well 56. Thereafter, if necessary, the inside of the well 56 and the inside of the reagent tank 18 are washed and sucked,
Preparations are made for the next reagent treatment. Each well 56
Since they are separated from each other, reagent treatment can be performed simultaneously on each slide glass 10 using different reagents. A temperature control unit 58 having the same function as the above-described temperature control unit 52 is provided below the reagent processing unit 54.

As described above, when performing reagent processing with a small amount of reagent, the reagent processing unit 54 is used. On the other hand, when the reagent processing is performed with a relatively large amount of reagent, the reagent processing units 38 and 40 are used.
In this case, while the reagent processing is being performed by one of the reagent processing units, the remaining reagent is aspirated and the next reagent is injected in the other reagent processing unit, and such reagent processing and preparation for the same are performed. Are performed alternately to improve the processing efficiency. Of course, similarly, if two sets of the reagent processing units 54 are provided, the reagent processing and preparation for the reagent processing can be performed alternately.

As in the second and fifth embodiments,
In the case where the mesh sheet 24, the sponge plate 70, or the sponge sheet 74 is joined to the plate joining surface, the reagent plate shown in FIGS. Facilitates replacement. That is, an array of wells into which reagent plates can be fitted is formed in the reagent tank. The shape of the opening of each well is rectangular, and one side thereof has a size corresponding to the width of the plate joining surface of the reagent plate. On the side adjacent thereto, a dimension corresponding to the sum of the thickness of the reagent plate, the thickness of the slide glass 10 and the thickness of the sample 12 attached thereto, more precisely, the sum is further added to the slide glass 10 Dimensions that take into account the accuracy of the insertion / removal operation and the margin for the joining operation are given. To make it easier to remove the reagent plate, for example, the depth of the well is smaller than the height of the reagent plate, so that the upper part of the reagent plate protrudes from the well, or a projection is provided on the upper part of the reagent plate,
This can get caught on the edge of the well.

In each of the above embodiments, if a spacer is provided between both plates, the sample can be protected when the plates are joined. As such a spacer means, for example, a convex portion can be provided on the plate joining surface side of the reagent plate.

In the first to fourth embodiments, the height of the convex portion is preferably set to the capillary gap size. In the fifth embodiment, the sponge sheet 74 has a thickness at which the sponge sheet 74 is hardened by compression, for example, about 1 mm. is there. Moreover, the convex part is
It can be configured as protrusions provided at the four corners of the bonding surface of the reagent plate.

[0057]

As described above, according to the present invention,
Reagent treatment can be performed using the minimum necessary amount of reagent,
It is possible to provide a biological tissue processing apparatus capable of preventing waste of a reagent. Further, according to the present invention, it is possible to supply the reagent smoothly and efficiently over the entire area of the sample on the sample plate,
Further, according to the present invention, it is possible to improve the processing efficiency by simultaneously performing the reagent processing on a plurality of sample plates. Further, according to the present invention using the capillary phenomenon, there is an advantage that drying and evaporation of the reagent during the reagent processing can be prevented as much as possible, while according to the present invention using the sponge, the distance between the reagent plate and the sample plate is reduced. Since the required accuracy is relaxed, there is an advantage that the drive system and the control system of the biological tissue processing apparatus can be easily configured.

[Brief description of the drawings]

FIG. 1 is a diagram showing a main configuration of a biological tissue processing apparatus according to a first embodiment of the present invention.

FIG. 2 is a perspective view showing a configuration of a reagent plate.

FIG. 3 is a cross-sectional view showing the operation of an injection hole.

FIG. 4 is a cross-sectional view showing a state where a sample plate is joined to a reagent plate in the first embodiment.

FIG. 5 is a perspective view showing a reagent plate having a mesh sheet according to a second embodiment of the present invention.

FIG. 6 is a cross-sectional view showing a state in which a sample plate is joined to a reagent plate having a mesh sheet.

FIG. 7 is a diagram showing a third embodiment of the present invention.

FIG. 8 is a diagram showing a fourth embodiment of the present invention.

FIG. 9 is a perspective view showing a reagent plate having a sponge sheet according to a fifth embodiment of the present invention.

FIG. 10 is a sectional view showing a state before a sample plate is joined to a reagent plate in the fifth embodiment.

FIG. 11 is a cross-sectional view showing a state where a sample plate is joined to a reagent plate in a fifth embodiment.

FIG. 12 is a view showing an entire configuration of a biological tissue processing apparatus according to the present invention.

[Explanation of symbols]

10 sample plates (slide glass), 12 samples,
16 reagent plates, 18 reagent tanks, 20 injection holes, 2
1 reagent supply path, 24 mesh sheet, 70 sponge plate, 74 sponge sheet.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁷ , DB name) G01N 1/30 G01N 1/28 G01N 33/48

Claims (12)

(57) [Claims] 1. A sample plate to which a sample of biological tissue is attached, a reagent plate joined to a sample attachment surface of the sample plate, and the sample plate and the reagent plate joined to each other,
A drive means for forming a capillary gap between the two plates ; and a reagent injection path for injecting a reagent between the two plates is formed in the reagent plate, and an injection hole forming an outlet opening of the reagent injection path. Is formed at a position facing between the two plates so that the reagent flows out only when both plates are joined.
An apparatus for treating biological tissue. 2. The biological tissue processing apparatus according to claim 1, wherein a mesh sheet is interposed between the reagent plate and the sample plate. 3. The biological tissue processing apparatus according to claim 2, wherein the mesh sheet is attached to a reagent plate in advance. 4. The biological tissue processing apparatus according to claim 3, wherein the mesh sheet is provided with a separation hole which is separated from and surrounds the injection hole. 5. The apparatus according to claim 1, wherein the opening area of the injection hole is set to a size such that the reagent flows out only when the two plates are joined. Characteristic biological tissue processing equipment. 6. A sample plate to which a sample of biological tissue is attached, a reagent plate joined to a sample attachment surface of the sample plate, driving means for joining the sample plate and the reagent plate, and the reagent plate And a sponge sheet interposed between the sample plate, and wherein the reagent plate is provided with a reagent injection path for injecting a reagent into the sponge sheet. apparatus. 7. The biological tissue processing apparatus according to claim 6, wherein the sponge sheet is attached to a reagent plate in advance. 8. The biological tissue processing apparatus according to claim 1, wherein the injection hole is formed at a position above a center of the reagent plate. 9. The biological tissue processing apparatus according to claim 1, wherein a reagent tank communicating with the reagent injection path is formed in the reagent plate. apparatus. 10. The apparatus according to claim 1, wherein the two sample plates joined back-to-back with the sample-adhering surface facing outward by the two reagent plates from both sides thereof. An apparatus for treating biological tissue, wherein a reagent treatment is carried out by sandwiching the same. 11. The apparatus according to claim 1, wherein the injection holes are formed on both surfaces of the reagent plate, and the two sample plates are joined from both sides of the reagent plate. An apparatus for treating biological tissue, wherein the reagent treatment is performed. 12. The apparatus according to claim 1, further comprising: spacer means for forming a fixed gap between the sample plate and the reagent plate; and plate joining by the spacer means. An apparatus for treating biological tissue, which sometimes protects a sample.