JP2883294B2 - Biological tissue processing device and reagent processing unit - 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 biological tissue processing apparatus for performing a reagent treatment on a biological tissue sample attached to a sample plate such as a slide glass.

[0002]

2. Description of the Related Art When observing and analyzing tissues and fungi of animals and plants, a sample such as a tissue section or a sample of the fungus is attached to a sample plate such as a slide glass, and the attached sample is dehydrated. Various pretreatments such as staining and hybridization are performed to prepare a desired preparation.

Usually, in these processes, about 20 slide glasses are set upright and aligned on a metal rack (basket), and the slide glasses are immersed together with the rack in a glass reagent tank containing a reagent. It is done by doing. And 1
After processing for one reagent, if necessary,
Immerse the rack in the reagent tank containing the next reagent. In such a process, by preparing the sample with various reagents, a prepared sample for the desired sample can be prepared.

[0004]

However, the conventional method described above has a problem that a large amount of reagent is required first.

In particular, immunostaining and ISH (in situ hybrid)
), the reagents used for such treatment are very expensive, and there is a demand that the treatment be carried out with as little reagent as possible in order to meet the economic conditions of the treatment. In addition, since an increase in the amount of reagent used leads to an increase in the amount of waste liquid, it is desirable to reduce the amount of reagent used from the viewpoint of environmental protection. However, since the above-mentioned conventional method has a configuration in which the entire metal rack is immersed in the reagent tank, it is necessary to fill the reagent tank with a certain amount of reagent, and it has been difficult to reduce the amount of reagent.

[0006] Further, since some of the reagents are very expensive and difficult to prepare in large quantities, conventionally, such reagents are conventionally prepared on the surface of a sample slice on a slide glass. Several to several tens μl of the reagent is dropped into
The work of spreading the reagent over the entire sample using a cover glass or a paraffin film was performed. However, the operation of spreading the reagent must be performed without introducing bubbles, but such an operation requires skill, and there is a limit in improving the operation efficiency.

Further, conventionally, when it is necessary to treat some samples with different types of reagents in a series of processing steps, it is necessary to remove some slide glasses from the rack, which causes a problem of poor work efficiency. was there.

Further, if the time during which the sample is not immersed in the reagent during the transition from the treatment with a certain reagent to the treatment with the next reagent becomes long, the surface of the sample tissue dries, and the next reagent reaches the inside of the tissue. It cannot be sufficiently penetrated. For this reason, conventionally, it has been necessary to inject predetermined reagents into a large number of reagent tanks in advance and to prepare the processing by maintaining the reagent tanks at a predetermined processing temperature.

[0009] The amount of samples to be processed and the types of reagents to be processed have been remarkably increasing year by year due to the development of research and tests in the field of genetic diagnosis. Indeed, the above problems have become larger, and a fundamental solution is desired.

SUMMARY OF THE INVENTION The present invention has been made to solve such a problem. The present invention has been made to reduce the amount of reagents for processing a sample, and to hold a plurality of sample plates (slide glasses) in a rack while holding them. It is an object of the present invention to enable a process using a different type of reagent for each sample plate, and to automatically perform a process of spreading a small amount of reagent on a sample surface, which has been conventionally performed manually using a cover glass or the like.

[0011]

In order to achieve the above object, a biological tissue processing apparatus according to the present invention comprises a holding means for holding a plurality of sample plates to which samples are attached in an upright state; A reagent processing unit having a plurality of storage sections for individually storing the held sample plates, wherein each of the storage sections is such that a sample attachment surface of a sample plate is a capillary gap with respect to a predetermined inner wall surface of the storage section. A first guide member for guiding the sample plate so as to face the predetermined inner wall surface at a distant capillary position, and a predetermined surface of the sample plate on which the sample is adhered is larger than the capillary gap with respect to the predetermined inner wall surface of the housing portion. A reagent processing unit having a second guide member for guiding the sample plate so as to face the predetermined inner wall surface at a normal position separated by a distance; And adjustable reagent injection means in two steps of a predetermined normal amount and a predetermined small amount of reagent injection amount for each housing part a reagent injection means for injecting the reagent within,
A reagent sucking unit for sucking a reagent in each of the storage units, and a relative movement of the holding unit and the reagent processing unit for inserting and extracting the plurality of sample plates into and from each of the storage units of the reagent processing unit. Moving means for setting the sample plate at the normal position of the storage section when the reagent injection amount into each of the storage sections is the normal amount; And a relative moving means for setting the sample plate at the capillary position of the container.

In this configuration, the plurality of sample plates to which the sample is attached move together with the holding means for holding the sample plate.
Each sample plate is individually accommodated in each accommodation section of the reagent processing unit. As described above, in the present invention, instead of immersing a plurality of sample plates in a large-volume reagent tank at a time, the processing is performed in a relatively small-volume storage unit for each sample plate, thereby Thus, the amount of reagent used for each storage section can be reduced, and further, processing with different reagents can be performed for each storage section.

[0013] In this configuration, when each sample plate is stored in each storage section of the reagent processing unit, it is set to one of two positions, a capillary position and a normal position. The capillary position is defined by the first guide member. When the sample plate is set at the capillary position, the sample attachment surface of the sample plate faces the predetermined inner wall surface of the storage unit via the capillary gap. Therefore, since the reagent rises in the capillary gap due to the capillary phenomenon and spreads on the sample attachment surface, it becomes possible to automatically spread a small amount of reagent on the sample surface. On the other hand, the normal position is defined by the second guide member. For ordinary reagents whose cost does not matter, fill each container with a normal amount of reagent (that is, the amount of sample that is sufficiently immersed in the reagent when the sample plate is set), and set the sample plate in the normal position. To process the sample. When the sample plate is set at the normal position, the distance between the sample sticking surface of the sample plate and the predetermined inner wall surface of the storage section is a predetermined distance larger than the capillary gap, so that the sample plate is set at the capillary position. As compared with the case, a large amount of reagent can be supplied to the sample surface. Therefore, when a certain amount of reagent is required for processing, a sample plate is set at this normal position to perform reagent processing. In this case, by stirring the reagent by the stirring means, the reaction between the sample and the reagent can be promoted, and the processing efficiency can be increased. In this configuration, the sample plate group is set (inserted) into the sample unit by relatively moving the holding unit and the reagent processing unit by the relative moving unit.
At this time, if the amount of the reagent to be injected into the container is the small amount, the sample plate is set at the capillary position with the sample attachment surface facing the predetermined inner wall surface of the container, and the amount of the reagent is set. Is the normal amount, the sample plate is set to the normal position with the sample attachment surface facing the predetermined inner wall surface of the storage unit. As described above, in this configuration, the set position of each sample plate can be switched between the capillary position and the normal position only by the parallel movement in the direction perpendicular to the surface of the sample plate. Then, when the reagent processing in each storage section is completed, the sample plate group is extracted from the reagent processing unit by the operation of the relative moving means, and
Thereafter, the reagent remaining in the storage section is sucked and discharged by the sample suction means.

As a development of the above configuration, the number of sample units is set to two, and furthermore, a temperature adjusting means for individually controlling the reagent temperature of each of the reagent processing units is provided.
While setting the sample plate group held by the holding means in one of the reagent processing units and performing the reagent processing while maintaining the reagent temperature at the set temperature by the temperature adjusting means,
In parallel, the remaining reagent is aspirated, the reagent is injected for the next processing, and the temperature of the reagent is adjusted for the next processing to prepare for the next processing, and the reagent processing in one reagent processing unit is completed. Then, the sample plate group is set in the other reagent processing unit to perform the reagent processing, and at the same time, the preparation for the next processing is performed for the one reagent processing unit, and the two reagent processing units prepare the reagent processing and the next processing preparation. May be alternately repeated.

According to this configuration, while the processing of the sample plate group is performed in one of the reagent processing units, the preparation for the next processing can be performed in the other reagent processing unit simultaneously and in parallel. When the processing in the reagent processing unit is completed, the process can immediately proceed to the processing in the other reagent processing unit for which preparation for the next processing is completed.
Therefore, it is possible to continuously and efficiently proceed with the processing using a plurality of reagents without drying the sample surface of each sample plate.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the biological tissue processing apparatus according to the present invention will be described below with reference to the drawings.

FIG. 1 is a schematic perspective view showing an example of the overall configuration of a biological tissue processing apparatus according to the present invention. The biological tissue processing apparatus illustrated in FIG. 1 includes a plate holder 10 that holds a plurality of sample plates (for example, slide glasses) 100 to which samples are attached in an upright state while being aligned in a predetermined arrangement.
Each sample plate 100 is individually accommodated and reagent processing is performed 2
Temperature control devices 22a and 22b mounted below the two reagent processing units 20a and 20b, the reagent processing units 20a and 20b to individually control the reagent temperatures of the respective reagent processing units, and a reagent dispensing nozzle 3 for dispensing reagents
0, a reagent table section 40 in which a reagent tube 42 for storing a plurality of reagents used for the processing is arranged, and a reagent suction device 50 for sucking and discharging the reagent after the processing is completed.

The lower surface of the plate holder 10 is provided with a plurality of plate holders (not shown) in a predetermined arrangement (3 rows and 6 columns in this example). When processing the sample, the operator mounts and fixes the sample plate 100 on which the sample is attached one by one to the plate holder of the plate holder 10. The plate holder 10 is fitted into the moving bar 12, and the moving bar 12 is configured to move up and down in the z direction (up and down) by an elevating mechanism 14. Therefore, in a state where one of the reagent processing units 20 is arranged at a predetermined sample setting position below the plate holder 10, the plate holder 10 mounted on the moving bar 12 is moved up and down by the elevating mechanism 14.
The reagent processing unit 20
Each sample plate 100 can be inserted into and set in each of the storage sections 200.

In this example, the reagent processing units 20a and 20b are mounted on a table 80 integrally with the temperature controllers 22a and 22b, respectively, and are attached to a unit moving mechanism 60. The reagent processing unit 20 and the temperature controller 22 can be moved in the x direction by the unit moving mechanism 60. For example, when the reagent in the reagent processing unit 20 is sucked and discharged by the reagent suction device 50, the reagent processing unit 20 is moved rightward by the unit moving mechanism 60 and moved to the suction position immediately below the reagent suction device 50. Let it. Then, by lowering the reagent suction device 50 by the suction device moving mechanism 54 in this state, each reagent suction nozzle 52 is inserted into each storage section 200, and the reagent is sucked.

The sample dispensing nozzle 30 includes an x-axis moving mechanism 32
The a, y-axis moving mechanism 32b and the z-axis moving mechanism 32c can move in three axial directions. The reagent is dispensed from a desired one of the reagent tubes 42 of the reagent table section 40 by the reagent dispensing nozzle 30, and the reagent processing unit 2
0 is dispensed into each of the storage units 200. The same reagent may be dispensed into each storage unit 200, but it is also possible to individually dispense different types of reagents, and it is also possible to inject a plurality of types of reagents into the same storage unit 200. It is also possible to use a mixture. In this example, since the reagent dispensing nozzle is movable in three axial directions, there is no particular need to determine the position of the reagent processing unit when dispensing, but a specific dispensing position is determined, and A configuration in which dispensing is performed at a position is also possible.

Next, the structure of the reagent processing unit 20 will be described with reference to FIG.

The reagent processing unit 20 is made of a material that does not cause erosion or corrosion of the reagent, for example, hard resin, Teflon, TPX, glass or the like. As already described with reference to FIG. 1, the reagent processing unit 20 includes:
A plurality of storage units 200 are provided in a predetermined arrangement, and each storage unit 200 functions as an individual reagent tank for one sample plate. FIG. 2 is a perspective view showing the shape of the storage section 200 as these individual reagent tanks.
As shown in the figure, the outer dimensions of the storage unit 200 are, for example, about 50 mm in height, slightly more than 26 mm in width, and about 3.5 mm in depth. A projection 210 projecting 2 mm is formed. The size of the reagent plate is, for example, a length of 76
mm, width 26 mm, and thickness 1 mm. This projection 210
Extends from the lower end to the upper end of the housing portion 200, and these guide portions 210 and the inner walls 220 and 222 in the width direction form two guide grooves 250a and 250b. That is, the accommodation section 200 has a maximum width (more than 26 mm).
Is slightly larger than the width of the sample plate, and
Since the interval between zeros is smaller than the width of the sample plate, the sample plate 100 can be inserted only into the guide grooves 250a and 250b. The width of the guide grooves 250a and 250b is slightly more than 1 mm, and this width is a value slightly larger than the thickness of the sample plate.
A partition spacer 230 is provided at the center of the bottom surface of the housing portion 200 so as to connect the two convex portions 210. Then, at the four corners of the inner wall surface 220, a thickness of about 0.05 mm
A 0.1 mm positioning spacer 240 is provided. These positioning spacers 240 are provided at the end of the inner wall surface 220 so as not to come into contact with the attached sample flakes when the sample plate is inserted (the thickness of the sample attached to the sample plate is 5 to 10 μm). . Such a structure of the storage section 200 can be formed by integral molding of, for example, resin.

With the above configuration, the guide groove 250
The storage section 200 functions as two types of reagent tanks, depending on which of the sample plate is set and the guide groove 250b.

That is, the sample plate 100 with the sample sticking surface facing the inner wall surface 220 with respect to the guide groove 250a.
As shown in FIG. 3A, between the sample attaching surface 100a of the sample plate 100 and the inner wall surface 220, about 0.1 mm defined by the positioning spacer 240 is inserted.
A gap of between 0.05 mm and 0.1 mm is formed. This gap is thin enough to cause capillary action, and this gap is hereinafter referred to as a capillary gap. Therefore, the accommodation section 20
Even if the amount of the reagent to be dispensed to 0 is very small, the reagent rises in the gap between the capillaries due to the capillary phenomenon and the sample attaching surface 100
a, and covers the attached sample 110. Hereinafter, the guide groove 250a is referred to as a minute amount guide groove. Note that FIG.
(A) and FIG.
FIG. 3 is a schematic cross-sectional view showing a positional relationship between the sample plate and the sample plate 100, and the dimensions of each member are not necessarily represented in a strict proportional relationship.

On the other hand, when the sample plate 100 is inserted and set in the guide groove 250b with the sample sticking surface facing the inner wall surface 220 side, as shown in FIG. 3B, the sample sticking surface 100a of the sample plate 100 A gap much larger than the capillary gap is formed between the gap and the inner wall surface 220. Therefore, when the sample plate 100 is set in the guide groove 250b, the sample 1 is
It is necessary to inject an amount of the reagent enough to immerse 10 (this amount is called a normal amount). In the state shown in FIG. 3B, the front side of the sample 110 is covered with a reagent layer of about 2 to 3 mm, so that a relatively large amount of reagent can react with the sample 110. . In this state, if the plate holder 10 is slightly moved up and down or vibrated, the reagent is agitated in the sample plate 100, and the reagent can more effectively act on the sample 110. This reagent agitation can also be performed by vibrating the reagent processing unit 20 by the unit moving mechanism 60.

In this example, the injection of the reagent into the storage section 200 is performed before the sample plate 100 is inserted. That is, in the case of processing with a very small amount of reagent, a very small amount of the reagent is previously injected into the bottom portion of the small amount guide groove 250a, and then the sample plate 100 is slowly moved along the small amount guide groove 250a. By lowering, the lower end of the sample plate 100 comes into contact with the reagent, and at the same time, the reagent is gradually moved by the capillary phenomenon to the sample attaching surface 10.
0a. That is, in this example,
The sample plate 100
Is slowly approached, so that the reagent can be surely spread on the sample attaching surface 100a. Also,
If necessary, the lifting force of the reagent can be increased by moving the sample plate 100 up and down while the sample plate 100 is in contact with the reagent. By such an insertion operation, the reagent can be spread on the sample attaching surface 100a of the sample plate 100 without bubbles.

Note that the sample plate 100 is
If the lower end of the sample plate is floated from the bottom surface of the storage section via a minute gap when the sample plate is set in the inside, the capillary phenomenon can be further efficiently promoted. This is because, for example, the sample plate 100 is
This can be achieved by adjusting the length of the protrusion. That is, in a state where the lower surface of the plate holder 10 is in contact with (mounted on) the upper surface of the reagent processing unit 20, a small gap is formed between the lower end of the sample plate 100 and the bottom surface of the storage unit 200. The protrusion length may be adjusted.

When a normal amount of reagent is used, the amount of reagent is previously injected into the container 200 in the same manner as described above, and then the sample plate 100 is inserted into the container 200. However, in this case, since the capillary phenomenon is not used, the injection time of the reagent is set to the sample plate 1.
It may be performed after 00 is inserted.

The operation of inserting the sample plate 100 into the storage section 200 is performed by lowering the plate holder 10 by the elevating mechanism 14 as described with reference to FIG. At this time, in this configuration, since the plate holder 10 can only be moved in the z direction by the elevating mechanism 14, the positioning for accurately inserting the sample plate 100 into each guide groove 250 is performed by the unit moving mechanism 60. This is done by moving the side. That is,
The sample setting position, which is the position of the reagent processing unit when the sample plate 100 is inserted into the reagent processing unit 20, includes a position for setting the sample plate in the small amount guide groove 250a, and a position for the normal amount guide groove 250a.
There are two types of positions when setting to b. The unit moving mechanism 60 sets the reagent processing unit 20 to one of the position for the minute amount and the position for the normal amount in accordance with a command from a control unit (not shown). In this configuration, the reagent processing unit 2 by the unit moving mechanism 60
Only by moving the x-axis direction of 0, the sample plate can be positioned in each of the minute reagent processing and the normal reagent processing.

In the configuration of the housing portion 200, the width (width in the depth direction) of the convex portion 210 is configured to gradually increase in a tapered shape from the upper end to the lower end of the housing portion.
If the width of the guide groove at the upper end is larger than the thickness of the sample plate by a certain degree or more and the width of the guide groove at the lower end is substantially equal to the thickness of the sample plate, the width of the Even if the positioning accuracy of the reagent processing unit 20 is slightly lowered, the sample plate can be reliably set at a predetermined position. Even in this case,
When the sample plate is set in the micro-amount guide groove 250a, it is necessary to make the gap between the accommodating portion 200 and the sample attaching surface a capillary gap from the upper end to the lower end. Such positioning control is performed, for example, such that after the sample plate reaches a certain depth (for example, the position of the positioning spacer 240 at the lower end), the reagent processing unit 20 presses the positioning spacer 240 at the upper end against the sample plate 100. In the x-axis direction. If the positioning accuracy at the time of inserting the sample plate is sufficiently high, it is also possible to omit, for example, the lower two of the four positioning spacers 240.

In the above example, the two guide grooves 250 are formed by the convex portions 210 extending from the upper end to the lower end of the storage section 200, but the configuration for positioning the sample plate is not limited to this. For example, the protrusion 210
Positioning spacer 2 on the inner wall surface 220 without providing
It is possible to position the sample plate only by the partition 40 and the partition spacer 230 on the bottom surface of the storage section 200. That is, in this case, the partition spacer 230 is formed in a tapered shape as shown in FIG.
By setting the distance between the lower end of the sample plate and the positioning spacer 240 substantially equal to the thickness of the sample plate, the lower end of the sample plate can be reliably positioned. Then, at the time of inserting the sample plate, the reagent processing unit 20 is moved in the x-axis direction so that the positioning spacer 240 at the upper end is pressed against the sample plate 100 in the same manner as in the case of the accommodation section having the tapered convex portion 210 described above. By doing so, the positioning of the upper end of the reagent plate is achieved. It should be noted that the processing with a normal amount of reagent does not require strict positioning as compared with the case of a minute amount of reagent, so the above processing is not necessarily required.

In the above example, the positioning spacer 2
40 are provided at the four corners of the inner wall surface 220, but if they are provided continuously from the upper end to the lower end at both left and right end portions of the inner wall surface 220, the inner wall surface 220, the sample attaching surface 100a,
In addition, since one tubular space is formed by the positioning spacer 240, it is possible to further enhance the capillary action.

Further, in the above example, the bottom surface of the housing portion 200 is divided into the minute amount guide groove side and the normal amount guide groove side by the partition spacer 230, but this structure is not essential. Absent. If the bottom of the storage section is divided by the partition spacer 230 and the reagent is injected into one of the divisions (on the guide groove side for minute amount), the amount of the reagent at the time of processing the minute amount reagent can be reduced. At the same time, it is necessary to make the dispensing nozzle thinner to some extent, and to increase the positioning accuracy of the dispensing nozzle during reagent injection. Therefore, when it is necessary to use a dispensing nozzle that is somewhat thick, or when the positioning accuracy of the dispensing nozzle cannot be extremely high,
It is also conceivable to adopt a configuration in which the partition spacer 230 is removed (however, it is impossible to remove both the projection 210 and the partition spacer 230 because the positioning of the sample plate cannot be performed). In this configuration, it is necessary to increase the amount of reagent at the time of processing a very small amount of reagent, but positioning accuracy of the dispensing nozzle is not required.

The configuration examples of the biological tissue processing apparatus and the reagent processing unit according to the present invention have been described above. Next, the flow of the reagent processing according to the present configuration will be described.

As shown in FIG. 1, this configuration is provided with two reagent processing units 20a and 20b.
This configuration is characterized in that the reagent processing and the preparation for the next processing are alternately performed in these two reagent processing units, so that the processing with a plurality of types of reagents is continuously performed on the sample plate without waiting time. One. FIG.
Is a flowchart showing the flow of this reagent processing. Hereinafter, this processing will be described in detail with reference to FIGS.

When performing a series of reagent treatments on a sample plate group, the sample plates 100 are first mounted and fixed on the plate holder 10. At this time, the sample plate 100
Are mounted in such a manner that the sample attachment surfaces are all directed in the same direction, that is, in the direction of the inner wall surface provided with the positioning spacer of each storage section 200 of the reagent processing unit 20. The plate holder 10 is detachable from the moving bar 12, and the mounting of the sample plate 100 can be performed with the plate holder 10 removed from the moving bar 12. When the mounting of the sample plate 100 is completed, the plate holder 1
0 is attached to the moving bar 12, and the processing sequence is started according to a preset program.

That is, first, the reagent is dispensed from each reagent tube 42 of the reagent table section 40 by the reagent dispensing nozzle 30, and the first reagent is dispensed into each storage section 200 of the reagent processing unit 20a (S502a). . At this time, the reagent to be dispensed may be the same for all the storage units 200, or may be of a different type for each of the storage units 200. The reagent to be dispensed depends on the program
Dispensed in normal or very small volumes. Then, after dispensing, the temperature of the reagent is adjusted by the temperature controller 22a as necessary.

When the dispensing of the reagent and the adjustment of the reagent temperature are completed, the reagent processing unit 20a is moved to the unit moving mechanism 60.
To the sample setting position immediately below the plate holder 10. At this time, in the case of processing with the normal amount reagent, the reagent processing unit 20a is provided with the normal amount guide groove 25.
The reagent processing unit 20a is moved to the position corresponding to the minute amount guide groove 250a in the case of processing with the minute amount reagent. When the reagent processing unit 20a is disposed at a predetermined position, the plate holder 1 is moved by the elevating mechanism 14.
0 is lowered and each sample plate 100 is
(S504a). With such an operation,
Each sample plate 100 is inserted into a predetermined guide groove of the storage section 200. In this insertion process, when the amount of the reagent is very small, it is desirable to make the descending speed of the sample plate 100 slower than in the case of the normal amount of the reagent in order to effectively cause the capillary phenomenon.

As described above, when the insertion process is completed and each sample plate 100 is set in the predetermined guide groove of each storage section 200, the reagent process starts (506).
a). During the reagent processing, the temperature controller 22a maintains the reagent temperature of the reagent processing unit 20a at the set temperature. In the case of the normal amount reagent processing, for example, the efficiency of the reagent processing can be enhanced by moving the plate holder 10 up and down by the operation of the elevating mechanism 14 to agitate the reagent.

Now, this reagent processing takes about 5 minutes even for short ones, and several hours for long ones. Therefore, in this embodiment, the reagent processing unit 20b is used in parallel with this reagent processing. On the other hand, preparations are made for processing with the next reagent. That is, the reagent is first dispensed to the reagent processing unit 20b by the reagent dispensing nozzle 30, and the temperature of the reagent is adjusted as necessary (S502b).

The reagent processing unit 20 for dispensing reagents
When the position b (dispensing position) is determined separately from the sample setting position (for example, when the movable range of the reagent dispensing nozzle is limited), the reagent processing unit 20b is moved to that position. Therefore, the sample plate 100 is moved to the reagent processing unit 2
With the setting at 0a, the unit moving mechanism 60 is operated to move the reagent processing units 20a and 20b in the x-axis direction. At this time, since the plate holder 10 has a structure in which the movement in the left-right direction (x-axis direction) is not restricted by the moving bar 12, such movement is possible. As a structure which enables such movement, for example, there is the following. That is, the plate holder 10
Slits 16 are provided on the left and right side surfaces of the movable bar 12, and the insertion portion of the moving bar 12 into the plate holder 10 has a thickness substantially equal to the width of the slit 16. Then, the plate holder 10 and the moving bar 12 are fixed by engaging a ratchet ball provided on the inner surface of the slit of the plate holder 10 with the recess of the insertion portion surface of the moving bar 12. With such a configuration, the plate holder 10 is normally fixed to the moving bar 12 with a certain amount of force, and when a certain amount of force is applied in the left-right direction, the ratchet ball comes out of the recess, and the plate holder 10 is moved from the moving bar 12 Come off. When reagent dispensing at the dispensing position is completed,
The reagent processing units 20a and 20b are returned to their original plate setting positions, and the plate holder 10 is mounted on the moving bar 12.

When the reagent processing in the reagent processing unit 20a is completed (that is, when a time specified by a program or the like has elapsed), the plate holder 10 is raised and the sample plate 100 is extracted from the reagent processing unit 20a (S508a).

When the first reagent processing in the reagent processing unit 20a is completed in this way, the reagent processing unit 20b, which has undergone reagent dispensing and temperature adjustment and is ready for the next processing, is moved to the sample setting position immediately below the plate holder 10. Go to Then, the plate holder 10 is lowered again, and the sample plate 100 is moved to the reagent processing unit 20.
b (S504b) and perform reagent processing (S506).
b).

In parallel with the reagent processing, the reagent processing unit 20a prepares for the next processing.

That is, first, the reagent remaining liquid in each storage section 200 is sucked and discharged (S500a). More specifically,
With the sample plate 100 set in the reagent processing unit 20b, the reagent processing units 20a and 20b are moved in the x-axis direction, and the respective accommodation sections 20 of the reagent processing unit 20a are moved.
The position is adjusted so that 0 is directly below each suction nozzle 52 of the reagent suction device 50, and the reagent suction device 50 is lowered by the suction device moving mechanism 54 to suck the reagent in each storage section 200.

Next, the reagent for the next process is dispensed to the reagent processing unit 20a by the reagent dispensing nozzle 30 (S502a). When the dispensing is completed, the reagent processing units 20a and 20b are moved and the plate holder 1
0 is attached to the moving bar 12 again, and the management of the reagent temperature is performed until the next processing is started.

In the preparation for the next processing, if necessary, each accommodating portion of the reagent processing unit 20a can be washed after the suction of the reagent. In the cleaning process, a cleaning liquid is injected into each of the storage sections by the dispensing nozzle 30, and for example, a reagent suction nozzle 52 is inserted thereinto and stirred to enhance the cleaning effect. After the completion of the cleaning, the cleaning liquid is sucked by the reagent suction nozzle 52.

When the reagent processing in the reagent processing unit 20b is completed in this way, the sample plate 100 is extracted from the reagent processing unit 20b and
Set to a, and perform the next reagent treatment. Then, in parallel with the reagent processing, the next processing preparation similar to that described above is performed for the reagent processing unit 20b.

The above-described cycle is repeated according to the program, and the reagent processing units 20a and 20a
By alternately performing the reagent processing and the preparation for the next processing in b,
A series of processing proceeds.

According to the present configuration, the reagent processing and the preparation for the next processing are performed in parallel by the two reagent processing units, whereby the sample plate can be processed continuously without waiting time.

In the above example, two reagent processing units are used. However, more reagent processing units can be used. For example, it is conceivable that the next processing is set to an extremely short time and preparation for the next processing is not temporally possible during the next processing. However, if three or more reagent processing units are used, such a case is possible. Even in this case, the preparation for the next processing and the preparation for the next processing can be simultaneously performed in advance during the current processing, and the processing can be shifted to the next processing without waiting time after the next processing.

In the example of FIG. 1 described above, the moving bar 12 is movable in the z-axis direction, the reagent dispensing nozzle 30 is movable in the three-axis direction, the reagent suction device 50 is movable in the z-axis direction, and the reagent processing unit is the x-axis. The configuration is movable in the direction, but another configuration can be adopted. For example, the reagent suction device 50 is
If the plate holder 10 is configured to be movable in the axial and x-axis directions, the plate holder 10 does not need to have a structure that is displaced from the moving bar 12 in the x-axis direction.

[0053]

As described above, according to the present invention,
Since the reagent processing is automated and the reagent processing unit is divided for each storage section, the amount of reagent used can be reduced as compared with the conventional method in which the sample plate is immersed in the reagent tank together with the metal rack.

Further, according to the present invention, since the operation of spreading a small amount of reagent on the surface of a sample can be automated, the efficiency of sample preparation can be greatly improved.

Further, according to the present invention, the reagent processing and the preparation for the next processing are performed in parallel by the two reagent processing units, whereby the sample plate can be processed continuously without waiting time. Therefore, a series of processes can be performed without drying the sample.

Further, according to the present invention, the reagent in the container is stirred by the stirring means, whereby the reaction of the reagent is promoted and efficient processing can be performed.

[Brief description of the drawings]

FIG. 1 is a schematic perspective view showing an example of a configuration of a biological tissue processing apparatus according to the present invention.

FIG. 2 is a perspective view showing a structure of a storage section of the reagent processing unit according to the present invention.

FIG. 3 is a cross-sectional view illustrating a state where a sample plate is inserted into a storage unit.

FIG. 4 is a cross-sectional view showing another example of the structure of the storage section.

FIG. 5 is a flowchart showing a flow of a reagent process using the biological tissue processing apparatus according to the present invention.

[Explanation of symbols]

10 plate holder, 14 lifting mechanism, 20a, 20
b Reagent processing unit, 22a, 22b temperature controller, 30 reagent dispensing nozzle, 40 reagent table section, 4
2 reagent tubes, 50 reagent suction devices, 52 reagent suction nozzles, 60 unit moving mechanism, 100 sample plates,
200 compartments.

Claims (4)

(57) [Claims] 1. A reagent processing unit having a holding means for holding a plurality of sample plates to which a sample is attached in an upright state, and a plurality of storage portions for individually storing the respective sample plates held by the holding means. A first guide for guiding the sample plate such that each of the storage sections faces the predetermined inner wall surface at a capillary position in which a sample sticking surface of the sample plate is separated from the predetermined inner wall surface of the storage section by a capillary gap. The guide plate guides the sample plate such that the sample sticking surface of the sample plate faces the predetermined inner wall surface at a normal position separated by a predetermined distance larger than the capillary gap with respect to the predetermined inner wall surface of the storage section. A reagent processing unit having a second guide member, and reagent injecting means for injecting a reagent into each of the storage units, wherein a reagent injection amount into each of the storage units A reagent injecting means that can be adjusted in two stages of a predetermined normal amount and a predetermined minute amount; a reagent suctioning unit that suctions a reagent in each of the storage units; and the holding unit and the reagent processing unit that are relatively moved to move the plurality of samples. Relative moving means for inserting and removing a plate from each storage section of the reagent processing unit,
The sample plate is set at the normal position of the storage section when the reagent injection amount into each of the storage sections is the normal amount, and the reagent plate is set when the reagent injection amount into each of the storage sections is the minute amount. And a relative moving means for setting a sample plate at the capillary position of the storage section. 2. The biological tissue processing apparatus according to claim 1, further comprising two reagent processing units, further comprising a temperature adjusting unit for individually controlling a reagent temperature of each of the reagent processing units. While setting the sample plate group held by the holding means in the reagent processing unit and performing the reagent processing while maintaining the reagent temperature at the set temperature by the temperature adjusting means,
At the same time, the other reagent processing unit performs suction of the remaining reagent, injection of the reagent for the next processing, and adjustment of the reagent temperature for the next processing to prepare for the next processing, and the reagent processing in one reagent processing unit ends. Then, the sample plate group is set in the other reagent processing unit and the reagent processing is performed, and at the same time, the one reagent processing unit is prepared for the next processing, and the two reagent processing units perform the reagent processing and the next processing preparation. A biological tissue processing apparatus, wherein 3. The biological tissue processing apparatus according to claim 1, further comprising a stirring means for stirring a reagent in each of the storage sections of the reagent processing unit. 4. A reagent processing unit having a plurality of storage sections for storing a sample plate to which a sample of biological tissue is attached, and causing a sample on the sample plate to react with a reagent in these storage sections. A first guide for guiding the sample plate such that the sample attachment surface of the sample plate faces the predetermined inner wall surface at a capillary position separated by a capillary gap from the predetermined inner wall surface of the storage unit;
And a guide member for guiding the sample plate such that the sample attachment surface of the sample plate faces the predetermined inner wall surface at a normal position separated by a predetermined distance larger than the capillary gap with respect to the predetermined inner wall surface of the storage section. And a second guide member.