JP7000767B2 - Reagent cartridge, liquid discharge mechanism, and pathological specimen preparation device - Google Patents

Description

The present invention relates to a reagent cartridge, a liquid ejection mechanism, and a pathological specimen preparation device.

Conventionally, a processing device has been known in which a chemical solution containing an antibody or the like is applied to a tissue specimen (biological sample) to automatically perform immunostaining or the like. In the work of preparing a pathological specimen such as immunostaining, it is necessary to change the type of the drug solution and adjust the amount of the drug solution to be applied according to the type and size of the tissue sample. Therefore, since it takes time to prepare a pathological specimen, automation of the processing device is being considered.

For example, Patent Document 1 discloses an automatic dyeing device that transports a slide tray holding a plurality of microscope slides by a transport device including an elevator. Further, Patent Document 2 discloses an automatic analyzer provided with a 3-axis robot or the like for transporting a sample tray provided with a plurality of reaction wells.

Japanese Unexamined Patent Publication No. 2013-92532 Japanese Unexamined Patent Publication No. 6-507498

However, the devices described in Patent Document 1 and Patent Document 2 have a problem that the device tends to be large in size. Specifically, when using a tray on which about 100 slides or reaction wells are placed, it has been difficult to avoid increasing the size of the tray and complicating the transport mechanism. Further, in pathological diagnosis during surgery, it is required to process a small number of tissue specimens more quickly than to automatically process a large number of slides (tissue specimens). For rapid processing of the tissue specimen, it was necessary to shorten the application time of the chemical solution to the tissue specimen while adjusting the amount of the chemical solution to be used to a desired amount according to the type of the tissue specimen and the like. That is, with a small and simple configuration,
There has been a demand for reagent cartridges for devices capable of rapid pathological specimen preparation.

The present invention has been made to solve at least a part of the above-mentioned problems, and can be realized as the following form or application example.

[Application Example] The reagent cartridge according to the present invention includes a drug solution storage section capable of storing the drug solution, a case section capable of accommodating the drug solution storage section so as to be movable in the first direction, and a case section having a nozzle section.
A knocking motion conversion mechanism that converts a knocking motion in a second direction that intersects the knocking section and the first direction of the knocking section into a moving motion in a predetermined range in the first direction of the chemical solution storage section, and a chemical solution. It is provided with an urging means for urging the storage unit in the direction opposite to the first direction, and a discharge control unit for discharging a predetermined amount of the chemical liquid stored in the chemical liquid storage unit from the nozzle unit by one knock operation. ..

According to this application example, it is possible to provide a reagent cartridge for a pathological specimen preparation apparatus capable of rapid pathological specimen preparation with a smaller and simpler configuration than the conventional one. For more information,
The knocking motion conversion mechanism converts the knocking motion in the second direction into the moving motion of the chemical solution storage unit in the first direction, and the chemical liquid in the chemical liquid storage unit is discharged. That is, since the direction of the knocking operation (second direction) is different from the moving direction (first direction) of the chemical liquid storage portion, the second direction.
It is possible to set the direction of to any direction that intersects with the first direction. As a result, the bulkiness of the liquid discharge mechanism in the first direction and the direction opposite to the first direction is reduced, and the pathological specimen preparation device can be made smaller than before.

Since the reagent cartridge is relatively small, it becomes easy to transport the reagent cartridge by a conveyor or the like in the pathological specimen preparation device. Therefore, the reagent cartridge can be moved to the position of the tissue specimen and the chemical solution can be discharged (dropped) without transporting the tray on which the tissue specimen is placed. As a result, the pathological specimen preparation device can be made to have a simple configuration without using a drug solution suction device, a 3-axis robot for transporting trays, or the like, and can be made smaller and cheaper than the conventional one.

Since a predetermined amount of the chemical solution is ejected in a fixed amount by one knocking operation, the labor is saved as compared with the case where the chemical solution is applied while measuring with a pipette or the like. Further, by performing the knocking operation a plurality of times, the chemical solution in a multiple of a predetermined amount can be applied relatively quickly. Therefore, the pathological specimen can be prepared more quickly.

In the reagent cartridge described in the above application example, the knocking motion conversion mechanism includes a slider portion provided in the knock portion and a slope portion provided in the chemical solution storage portion, and by sliding the slider portion and the slope portion. It is preferable to convert the knocking operation of the knocking portion in the second direction into the moving operation of the chemical liquid storage portion in the first direction.

According to this, the knocking motion is converted into the moving motion of the chemical liquid storage unit with a relatively simple configuration. Therefore, the number of parts constituting the knock operation conversion mechanism is reduced, and the occurrence of defects such as malfunction during conversion is suppressed. Therefore, the operational reliability of the reagent cartridge can be improved.

In the reagent cartridge described in the above application example, the case portion has a translucent window portion between the chemical liquid storage portion and the nozzle portion, and the chemical liquid storage portion is transparent to the tip side in the first direction. It has a light chemical flow path, the window portion is provided on the side surface of the case portion facing the chemical liquid flow path from the third direction intersecting the first direction, and the chemical liquid flow path and the window portion are the third. It is preferable that the optical path is formed along the direction of.

According to this, it is possible to check the presence or absence of the chemical solution in the chemical solution flow path through the translucent window portion. That is, it becomes easy to confirm the presence or absence of the chemical solution contained in the reagent cartridge.

In the reagent cartridge described in the above application example, the chemical solution is a primary antibody reagent, a secondary antibody reagent, a coloring reagent, a tissue staining reagent, a nuclear staining reagent, an endogenous Peroxydase block reagent, hematoxillin, a coloring reagent, and a deparaffinizing treatment. It is preferably one selected from the group consisting of reagents, activation reagents, and cleaning solutions.

According to this, the antigen-antibody reaction treatment, the color-developing reaction treatment, the depafrafin treatment, the activation treatment, the blocking treatment of endogenous PO (Peroxidase), the cleaning treatment and the like can be performed by the chemical solution discharged from the reagent cartridge.

In the reagent cartridge described in the above application example, the predetermined amount is preferably 10 μL or more and 1 mL or less.

According to this, it is possible to apply a chemical solution having a volume corresponding to the type and size of the tissue specimen (pathological specimen), the type of the chemical solution, and the like to the tissue specimen.

In the reagent cartridge described in the above application example, the chemical solution storage portion is 500 μL or more, 20
It is preferable that a chemical solution of mL or less can be stored.

According to this, a maximum of about 100 for a treatment using 200 μL of a drug solution at a time.
It is possible to secure the capacity for each batch and suppress the increase in size of the reagent cartridge.

In the reagent cartridge described in the above application example, it is preferable that the chemical liquid storage portion can seal the chemical liquid storage portion and has a lid portion including a communication hole.

According to this, the lid portion can prevent foreign matter from entering or contaminating the stored chemical solution from the outside. Further, since the inside and the outside of the chemical liquid storage portion are communicated with each other by the communication hole, the increase of the negative pressure in the chemical liquid storage portion can be suppressed even if the amount of the chemical liquid to be discharged and stored is reduced. Therefore, the chemical solution can be quickly discharged.

It is preferable that the reagent cartridge described in the above application example is provided with a barcode relating to information on the chemical solution to be stored.

According to this, it is possible to know information such as type, content, date of manufacture, precautions, etc. regarding the stored chemical solution by the barcode.

[Application Example] In the liquid discharge mechanism according to the present invention, the reagent cartridge described in the above application example has a removable holding portion, a stage on which a substrate on which a tissue specimen is fixed can be placed, and a knock portion of the reagent cartridge. Is provided in the second direction, and a cartridge operation unit capable of supplying the chemical solution stored in the reagent cartridge to the substrate placed on the stage is provided.

According to this application example, the chemical solution of the reagent cartridge can be discharged to the tissue specimen fixed on the substrate on the stage. That is, it is possible to provide a liquid discharge mechanism that enables rapid preparation of a pathological specimen with a smaller and simpler structure than before.

In the liquid discharge mechanism described in the above application example, the cartridge operating unit has a pusher capable of reciprocating in a third direction intersecting the second direction, and the pusher reciprocates in the third direction. Therefore, it is preferable to have a convex portion that abuts on the knock portion and causes a knock operation.

According to this, the reciprocating motion of the pusher in the third direction is converted into a knocking motion in the second direction by the contact between the convex portion of the pusher and the knock portion. That is, the driving force for the knocking operation is supplied from the third direction. Therefore, it is possible to set the third direction to any direction that intersects with the second direction. As a result, the bulkiness of the liquid discharge mechanism in the second direction and the direction opposite to the second direction is reduced, and the pathological specimen preparation device can be made smaller than before.

In the liquid discharge mechanism described in the above application example, the pusher preferably has a plurality of protrusions provided side by side in the third direction.

According to this, one reciprocating operation of the pusher increases the number of times the convex portion and the knock portion come into contact with each other, and the number of knocking operations caused by the contact increases. Therefore, it is possible to increase the supply amount of the chemical solution in each reciprocating operation of the pusher. Further, it is possible to limit the movement distance of the reciprocating motion of the pusher in the third direction so that only a part of the plurality of convex portions is brought into contact with the knock portion to limit the number of knock operations. Become. Thereby, the supply amount of the chemical solution can be adjusted.

[Application Example] The pathological specimen preparation apparatus according to the present invention includes the liquid discharge mechanism described in the above application example.

According to this application example, it is possible to provide a pathological specimen preparation apparatus capable of rapid preparation of a pathological specimen with a smaller and simpler configuration than the conventional one.

In the pathological specimen preparation apparatus described in the above application example, the case portion has a translucent window portion between the chemical liquid storage portion and the nozzle portion, and the chemical liquid storage portion is located on the tip side in the first direction. The chemical liquid flow path and the window portion are provided on the side surface of the case portion facing the chemical liquid flow path from the third direction intersecting the first direction, and the chemical liquid flow path and the window portion are provided. An optical path is formed along a third direction, a holding portion to which a reagent cartridge can be attached and detached, an exit portion capable of emitting light rays with respect to the optical path, a light receiving unit, and the amount of light received by the light receiving unit are calculated. Therefore, it is preferable that the calculation unit for converting into an electric signal is provided, and the emitting unit and the light receiving unit are arranged so that the light receiving unit can receive the light rays emitted from the emitting unit.

According to this, it is possible to detect the presence or absence of the chemical solution in the portion in the chemical solution flow path through which the light beam has passed through the window portion of the reagent cartridge.

The pathological specimen preparation apparatus described in the above application example preferably includes a barcode reader that reads a barcode related to information on the drug solution given to the reagent cartridge.

According to this, by reading the barcode, the type of the stored chemical solution,
Information such as contents, date of manufacture, and precautions can be collected and managed.

The pathological specimen preparation apparatus described in the above application example has a cleaning unit capable of supplying a cleaning solution to a substrate mounted on a stage, and a chemical solution or a cleaning solution supplied to the substrate mounted on the stage.
An electric field agitation unit that can agitate by applying an electric field, a cleaning unit, a liquid discharge mechanism, and an electric field agitation unit
It is preferable to provide a stage moving mechanism capable of moving the stage in the arranged fourth direction.

According to this, the tissue specimen fixed on the substrate can be washed with a washing liquid. In addition, the efficiency of stirring is improved by electric field stirring, and the time required for preparing pathological specimens such as various reaction treatments and cleaning operations is shortened. Further, the substrate is rapidly moved to the electric field stirring unit, the cleaning unit, and the liquid discharge mechanism by the stage moving mechanism. As a result, the tissue specimen can be processed more quickly.

The perspective view which shows the appearance of the reagent cartridge which concerns on Embodiment 1. FIG. Front view showing the appearance of the reagent cartridge. The rear view which shows the appearance of a reagent cartridge. Right side view showing the appearance of the reagent cartridge. Left side view showing the appearance of the reagent cartridge. Top view showing the appearance of the reagent cartridge. Bottom view showing the appearance of the reagent cartridge. FIG. 4 is a cross-sectional view taken along the line AA in FIG. The schematic diagram which shows the path of a chemical solution around a cap. The schematic diagram which shows the path of a chemical solution around a cap. The schematic diagram which shows the parts which make up a knock part. The schematic diagram which shows the slope part of the chemical liquid storage part. The schematic diagram which shows the arrangement of a knock part and a case part. The schematic diagram which shows the knocking motion conversion mechanism. A perspective view showing a substrate on which a tissue specimen is fixed. The side view which shows the liquid discharge mechanism and the cartridge operation part. The schematic diagram which shows the contact state between the convex part of a pusher and a knock part. The schematic diagram which shows the contact state between the convex part of a pusher and a knock part. The schematic diagram which shows the contact state between the convex part of a pusher and a knock part. The schematic diagram which shows the structure of the pathological specimen preparation apparatus.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. In each of the following figures, the scale of each layer and each member is different from the actual scale in order to make each layer and each member recognizable.

<Reagent cartridge>
[exterior]
The schematic configuration of the reagent cartridge of this embodiment will be described with reference to FIGS. 1 to 7. FIG. 1 is a perspective view showing the appearance of the reagent cartridge according to the first embodiment. FIG. 2, FIG.
4, FIG. 5, FIG. 6, and FIG. 7 are a front view, a rear view, a right side view, a left side view, a top view, and a bottom view showing the appearance of the reagent cartridge, respectively.

FIG. 1 is provided with an XYZ axis, which is a coordinate axis orthogonal to each other. In the figures shown below, the XYZ axes will be attached as necessary. In that case, the XYZ axes in each figure are
Corresponds to the XYZ axis in FIG. In the XYZ axis in the present specification, the XY plane coincides with the substantially horizontal plane, the positive direction of the Z axis is the direction opposite to the direction of gravity, and the state shown in FIG. 1 is each member, each part, and the device. It shall indicate the posture (use posture) in the use state of. Unless otherwise specified, the following description is based on the usage posture, and for convenience of explanation, the positive direction of the Z axis may be referred to as upward and the negative direction of the Z axis may be referred to as downward.

The reagent cartridge 100 according to the present embodiment shown in FIG. 1 accommodates a drug solution storage unit 130 capable of storing a drug solution and a state in which the drug solution storage unit 130 can be moved in the negative direction of the Z axis as the first direction. It is possible to knock the case portion 110 having the nozzle portion 111, the knock portion 150, and the Y-axis as a second direction intersecting the Z axis of the knock portion 150 in the negative direction of the chemical solution storage unit. A knocking motion conversion mechanism that converts the 130 into a movement motion in a predetermined range in the negative direction of the Z axis, an urging means that urges the drug solution storage unit 130 in the positive direction of the Z axis, and a single knocking motion. A discharge control unit for discharging a predetermined amount of the chemical solution stored in the chemical solution storage unit 130 from the nozzle unit 111 is provided. The knocking motion conversion mechanism, urging means, and discharge control unit will be described later.

The reagent cartridge 100 is a substantially rectangular parallelepiped, and the case portion 110, which is the main exterior component of the reagent cartridge 100, is also a substantially rectangular parallelepiped. Of the six substantially rectangular surfaces constituting the reagent cartridge 100, the surfaces facing the Z-axis direction are the upper surface (upper surface) and the bottom surface (lower surface), and Y
The side surfaces facing in the axial direction are the front surface and the back surface, and the surfaces facing the X-axis direction are the right side surface and the left side surface. Therefore, in the reagent cartridge 100, the area of the substantially rectangular shape constituting the front surface and the back surface is the largest, the left and right side surfaces are the largest, and the areas of the upper surface and the bottom surface are the smallest. Here, of the six substantially rectangular surfaces described above, the upper surface is the chemical liquid storage portion 130 protruding from the case portion 110, and the other faces are formed by the case portion 110. That is, a part of the upper part of the chemical liquid storage portion 130 housed in the case portion 110 is exposed from the case portion 110.

In the case portion 110 (reagent cartridge 100), the surface on which the knock portion 150 is exposed is the front surface. On the front of the case portion 110, an opening 122 is located above the middle in the Z-axis direction.
Is provided. The opening 122 is rectangular, with the long side of the opening 122 opening along the X-axis direction and the short side opening along the Z-axis direction. The long side is formed with a size about twice that of the short side. A nozzle portion 111 is provided on the bottom surface of the case portion 110 (reagent cartridge 100). Ribs 114 are provided on the outer edge of the bottom surface of the case portion 110 in a substantially frame shape. The base of the nozzle portion 111 and the base of the rib 114 are on the same surface, and the nozzle portion 111 has the rib 114.
Surrounded by. Therefore, the rib 114 protects the nozzle portion 111 from collisions and the like. Further, since the nozzle portion 111 is formed so as to protrude from the bottom surface of the case portion 110, the liquid drainage is improved when the chemical liquid is discharged, and the chemical liquid is prevented from wrapping around and adhering to the periphery of the nozzle portion 111. Be done.

The knock portion 150 is arranged so as to project from the opening 122 in the positive direction of the Y axis. The protruding portion of the knock portion 150 has a substantially square columnar shape with a trapezoid having a top side at the tip side as a bottom surface in a cross-sectional shape along the Z-axis direction. The knock portion 150 is not fixed to the case portion 110, and is in the internal direction of the case portion 110 (negative direction of the Y axis) from the protruding state.
It is possible to move to immerse yourself in. The movement of the knock portion 150 in the negative direction of the Y-axis and the subsequent movement in the positive direction of the Y-axis are collectively referred to as a knock operation. The shape of the portion of the knock portion 150 protruding from the opening 122 is not limited to a square columnar shape, and the shape of the bottom surface may be, for example, a triangle, a polygon, or a semicircle, and their cross sections may be formed. Shape is X
It may change in the middle of the axial direction.

As shown in the front view of FIG. 2, a substantially rectangular window portion 123 is provided below the opening portion 122 of the case portion 110. Since the window portion 123 is made of a light-transmitting forming material, the inside of the case portion 110 can be observed through the window portion 123. The window unit 123
It suffices as long as it has translucency, and may have an opening or a thinned form.

As shown in the rear views of FIGS. 2 and 3, a locking portion 129 is provided from substantially the center to the bottom of the left side surface of the case portion 110. Further, a step 110b is provided downward on the right side surface (right side surface) of the case portion 110 when facing the front surface, and the thickness of the case portion 110 in the X-axis direction is such that the lower side (bottom side) is higher (upper surface side). ) Is shorter than. The step 110b is the case portion 1.
It is preferable to provide it on at least one of the left and right side surfaces of 10. Reagent cartridge 10
0 is stably attached to the pathological specimen preparation device 200 (holding portion 24) described later by the locking portion 129 and the step 110b.

As shown in the right side view of FIG. 4 and the left side view of FIG. 5, one substantially rectangular opening 124 is provided above the left and right side surfaces of the case portion 110. On the inner surface of each opening 124, a claw-shaped locking portion 125 projecting in the negative direction of the Z axis is provided. Further, one convex locking portion 135 protruding in the X-axis direction is provided on each of the left and right side surfaces of the chemical liquid storage portion 130. When the chemical storage portion 130 is housed in the case portion 110, the locking portion 135 opens the opening 1.
By fitting into the 24, the chemical liquid storage unit 130 is arranged with respect to the case unit 110. As a result, the locking portion 135 is locked to the locking portion 125, and the chemical liquid storage portion 130 becomes the case portion 110.
It is prevented from being detached from.

A substantially rectangular opening 127 is provided below the opening 124 of the case 110.
Two openings 127 are arranged side by side in the Z-axis direction on each of the left and right side surfaces. On the inner surface of each opening 127, a claw-shaped support portion 128 projecting in the negative direction of the Z axis is provided. The function of the support portion 128 will be described later.

As shown in the left side view of FIG. 5, the locking portion 129 is provided with a barcode 126 related to information on the chemical solution stored in the reagent cartridge 100. As a result, the reagent cartridge 100 can hold information such as the type, content, date of manufacture, and precautions of the chemical solution. The form of the barcode 126 is not particularly limited, and any one-dimensional code or a two-dimensional code such as a data matrix or a QR code (registered trademark) can be applied. Further, the position where the barcode 126 is assigned is not limited to the above.

As shown in the top view of FIG. 6, the chemical liquid storage unit 130 can seal the chemical liquid storage unit 130 and has a lid portion 131 including a communication hole 132. A pair of communication holes 132 are provided on the upper surface of the lid portion 131 side by side in the X-axis direction. The communication hole 132 is a substantially circular opening and communicates the inside and the outside of the chemical liquid storage portion 130. Therefore, the lid 131 can prevent foreign matter from entering or contaminating the stored chemical solution from the outside. Further, since the communication hole 132 communicates between the inside and the outside of the chemical liquid storage unit 130, even if the amount of the chemical liquid discharged and stored is reduced, the increase in the negative pressure in the chemical liquid storage unit 130 is suppressed. .. Therefore, the chemical solution can be quickly discharged. The opening shape, number, and arrangement of the communication holes 132 are not particularly limited. Further, a breathable waterproof film may be provided at the opening of the communication hole 132 to prevent the mixing of moisture (liquid). Alternatively, when the chemical solution stored in the chemical solution storage portion 130 is in an unused state, the upper surface (cover portion 131) may be covered with a film or the like to close the communication hole 132.

As shown in the bottom view of FIG. 7, the nozzle portion 111 is formed on the bottom surface of the case portion 110 so as to face the negative direction of the Z axis. On the bottom surface of the case portion 110, the nozzle portion 111 is arranged on the central side in the Y-axis direction and on the side closer to the right side surface in the X-axis direction. The tip of the nozzle portion 111 is provided with an opening 111a having a cylindrical inner surface and an inner diameter of about 2.0 mm in order to discharge the chemical solution stored in the reagent cartridge 100.

[Internal structure]
The internal structure of the reagent cartridge 100 will be described with reference to FIG. FIG. 8 is FIG. 4
It is sectional drawing along the AA line inside. The AA line is a line segment extending in the Z-axis direction.

As shown in FIG. 8, the reagent cartridge 100 is configured by inserting (accommodating) the drug solution accommodating portion 130 into the accommodating portion 119 of the case portion 110. The chemical liquid storage unit 130 is provided with a chemical liquid chamber 136 that communicates with the communication hole 132 above the inside. Chemical solution chamber 136 (chemical solution storage unit 130)
) Is preferably capable of storing a chemical solution of 500 μL (microliter) or more and 20 mL (milliliter) or less. According to this, for example, for a process using 200 μL of a chemical solution at a time, a maximum capacity of about 100 times is secured, and the reagent cartridge 1 is used.
It is possible to suppress the increase in size of 00. In the reagent cartridge 100 of the present embodiment, a maximum of 14 mL of a chemical solution can be stored in the chemical solution chamber 136. Chemical chamber 136 (reagent cartridge 10)
The drug solution stored in 0) is not particularly limited, but is, for example, immunohistochemical staining (IH).
A reagent used in the method of C) or the method of preparing a tissue specimen (pathological specimen) by the In situ hybridization (ISH) method for observing the expression level of a gene in a living tissue or cell, which is a primary antibody reagent, 2 It is one selected from the group consisting of the following antibody reagent, color-developing reagent, tissue staining reagent, nuclear staining reagent, endogenous Peroxydase block reagent, hematoxillin, color-developing reagent, deparaffinizing reagent, activation reagent, and cleaning solution.

Such a reagent (chemical solution) is not particularly limited, and is, for example, a primary antibody reagent such as Hep-par1, a secondary antibody reagent such as Envision + Dual Link (DAKO), and an HQ linker (Roche Diagnostics). ) And other linker reagents, 3,
Coloring reagents such as 3'-Diaminobenzidine (DAB), tissue staining reagents, nuclear staining (counterstain) reagents such as hematoxylin, and endogenous PO (Peroxida) such as hydrogen peroxide solution.
se) Blocking reagent, blocking reagent for substrates such as bovine albumin, skim milk, gelatin, deparaffinizing reagent, activating reagent, pure water, phosphate buffered saline (P)
BS: Phosphate Buffered Saline), PBS (PBS-T) containing a nonionic surfactant Tween20 having a blocking action, Tris-Buffered-Saline)
Examples thereof include a cleaning solution such as e (TBS), and it is preferable that the cleaning solution is one selected from these groups. By accommodating these chemicals, the reagent cartridge 100 is used for various treatments for preparing pathological specimens such as antigen-antibody reaction treatment, color development reaction treatment, endogenous PO blocking treatment, depafrafin treatment, activation treatment, and washing. be able to.

In addition to the above-mentioned reagents, the chemical solution chamber 136 (reagent cartridge 100) may contain a liquid used for preparing a tissue specimen. Examples of such a liquid include a liquid for processing liquid paraffin, ethanol, xylene and the like.

The case portion 110 has a ball chamber 112 having a cylindrical inner surface above the opening 111a having a cylindrical inner surface. The upper surface of the ball chamber 112 communicates with the opening of the perforated portion 117, which will be described later. In the ball chamber 112, two balls 113 having a diameter of about 2.0 mm are inserted vertically side by side in the Z-axis direction. The height of the ball chamber 112 (dimensions in the Z-axis direction) is the ball 11
Formed slightly larger than twice the diameter of 3 and inside the ball chamber 112, the two balls 113
Can move up and down. The inner diameter of the ball chamber 112 is slightly larger than the diameter of the ball 113. Since the diameter of the ball 113 is larger than the inner diameter of the opening 111a of the nozzle portion 111,
The entire ball 113 does not immerse in the opening 111a. As the forming material of the ball 113, a forming material having a density smaller than the density of the chemical solution stored in the reagent cartridge 100, not being attacked by the chemical solution, and not contaminating the chemical solution is used. Examples of such a forming material include resins such as polyethylene and polypropylene. As a result, the ball 113 floats upward (in the positive direction of the Z axis) in the chemical solution. The number of balls 113 inserted into the ball chamber 112 is not limited to two, and may be one or three or more.

A perforated portion 117 is arranged on the upper surface of the ball chamber 112. The perforated portion 117 has a disk shape with a bulge in the central portion, and is provided with an opening serving as a flow path for the chemical solution in the center. The perforated portion 117 is made of, for example, a rubber member having elasticity. A stroke chamber 118 having a cylindrical inner surface is provided above the perforated portion 117.

The chemical liquid storage portion 130 is provided with a protruding portion 137 as a chemical liquid flow path facing downward. The inner surface 137a of the protrusion 137 has a cylindrical shape and communicates with the chemical chamber 136 via the valve 133. A cap 142 is inserted inside the tip of the protrusion 137. Cap 142
The protruding portion 137 including the above is inserted into the stroke chamber 118 of the case portion 110.

The inner surface 137a of the protruding portion 137 of the chemical liquid storage portion 130, the stroke chamber 11 of the case portion 110
8. The ball chamber 112 and the nozzle portion 111 have different inner diameters, but their center lines are arranged so as to substantially coincide with the center line of the opening 111a. From the inner surface of the protrusion 137, the stroke chamber 118, the ball chamber 112, and the opening 111a form a path of the chemical solution from the chemical solution chamber 136 to the nozzle portion 111.

A coiled spring 145 is arranged along the cylindrical outer surface 137b of the protrusion 137. One end of the spring 145 is in contact with the periphery into which the protruding portion 137 of the case portion 110 is inserted, and the other end is in contact with the base of the protruding portion 137.

On the bottom surface of the chemical liquid storage portion 130, a columnar convex portion 138 is provided on the bottom surface of the chemical liquid storage portion 130 so as to be aligned with the protruding portion 137 in the X-axis direction. The accommodating portion 119 in which the drug solution accommodating portion 130 is accommodated is provided with a columnar convex portion 116 per degree so as to face the convex portion 138 per degree. The diameters of the cross-sectional circles of the convex portion 138 per degree and the convex portion 116 per degree are substantially equal. Convex part 13 per degree
A coiled spring 146 is arranged along the outer surface of the cylinder of the 8 and the convex portion 116 per degree. One end of the spring 146 is in contact with the base of the convex portion 116 per degree, and the other end is in contact with the base of the convex portion 138 per degree.

The spring 145 and the spring 146 are urging means for urging the chemical liquid storage unit 130 in the positive direction (upward) of the Z axis. Therefore, the chemical liquid storage unit 130 is urged upward in the storage unit 119, but the chemical liquid storage unit 130 is detached from the case unit 110 by locking the locking unit 125 and the locking unit 135. Is suppressed. FIG. 8 shows a state in which the chemical liquid storage unit 130 is not pressed downward. Such a state is called an initial state. Further, when the chemical liquid storage unit 130 is pressed in the negative direction (downward) of the Z axis against the urging of the springs 145 and 146, the chemical liquid storage unit 130 moves downward in the storage unit 119. In conjunction with this, the protrusion 137 moves downward in the stroke chamber 118.

The chemical liquid storage portion 130 can be moved downward until the hit portion 131a on the outer edge of the lid portion 131 and the hit portion 110a on the upper surface of the case portion 110 come into contact with each other. In other words, due to the contact between the prescription portion 131a and the prescription portion 110a, the chemical liquid storage portion 130
The downward movement of is restricted. With these configurations, the chemical liquid storage unit 130 becomes the storage unit 119.
In, the reciprocating motion is possible in the positive and negative directions of the Z-axis between the locking positions of the locking portion 125 and the locking portion 135 and the contact position between the hit portion 131a and the hit portion 110a. The moving distance of the chemical storage unit 130 in the positive and negative directions of the Z axis is called a stroke.

The window portion 123 provided on the front surface of the case portion 110 is shown by a dotted line. Case part 11
0 has a translucent window portion 123 between the chemical liquid storage portion 130 and the nozzle portion 111.
The window portion 123 faces the protruding portion 137 from the direction of the Y axis that intersects the direction of the Z axis.
The protrusion 137 and the window 123 are provided on the front surface as the side surface of 0, and form an optical path along the direction of the Y axis. Thereby, by observing the reagent cartridge 100 from the outside, the presence or absence of a liquid such as a chemical solution in the protrusion 137 can be visually confirmed. Further, the optical path may be irradiated with a light beam transmitted through the window portion 123 and the protruding portion 137 to optically detect the presence or absence of a chemical solution or the like. The material for forming the window portion 123 and the protruding portion 137 is not particularly limited as long as it has translucency, and examples thereof include resins such as polyethylene and polypropylene. These forming materials may be visually translucent.

A reflection portion (not shown) is provided on the inner surface 137a of the protrusion 137 in a region facing the window portion 123 and facing the positive direction of the Y axis. Reflective part is 570 nm or more, 750 nm
It is preferable to have a reflectance of 30% or more to reflect light rays having the following wavelengths. note that,
When the material for forming the inner surface 137a (protruding portion 137) has the above-mentioned reflectance with respect to a predetermined wavelength, it is not necessary to provide the reflecting portion. Also, to increase the reflection of light rays,
The region irradiated with the light beam on the inner surface 137a may be a flat surface. From the above, the window unit 123,
The protrusion 137, the inside of the protrusion 137, and the inner surface 137a are arranged along the direction of the Y axis to form an optical path.

[Chemical solution route]
The path of the chemical solution when the chemical solution is discharged will be described with reference to FIGS. 9A and 9B.
9A and 9B are schematic views showing the path of the drug solution around the cap.

In FIG. 9A, the periphery of the cap 142 in the same initial state as in FIG. 8 is enlarged and displayed. As shown in FIG. 9A, a gap is provided between the inner surface 137a of the protrusion 137 and the cap 142 inserted into the protrusion 137. This gap communicates with the supply port 143 at the end of the protrusion 137.

An O-ring 141 is arranged above the stroke chamber 118 into which the protrusion 137 is inserted. The O-ring 141 is in close contact with the outer surface 137b of the protruding portion 137, and the case portion 11
It has a function of preventing the chemical solution from leaking from between 0 and the outer surface 137b. Further, in the initial state, the supply port 143 is sealed by the O-ring 141. As a result, the chemical chamber 13
Since the path of the chemical solution from 6 to the opening 111a is blocked by the supply port 143, the chemical solution does not flow out from the chemical solution chamber 136 to the stroke chamber 118 via the supply port 143 in the initial state.

The ball chamber 112 has an opening 112a on the upper surface that communicates with the opening of the perforated portion 117. Since the diameter of the ball 113 is larger than the inner diameter of the opening 112a, the ball 113 has a function of closing the opening 112a when a part of the ball 113 is immersed in the opening 112a. As described above, since the ball 113 floats in the chemical solution, the opening 111 is opened from the ball chamber 112.
In the state where the chemical solution is present and stationary up to a, a part of the upper ball 113 closes the opening 112a, so that the chemical solution is suppressed from dripping from the nozzle portion 111.

The distance h between the lower surface 142a of the cap 142 and the upper surface 117a of the perforation portion 117 is equal to the above-mentioned stroke (distance of movement of the chemical liquid storage portion 130 in the positive and negative directions of the Z axis). That is, when the chemical liquid storage portion 130 is pressed downward once, a chemical liquid equal to the volume obtained by multiplying the cross-sectional area inside the stroke chamber 118 by the distance h (predetermined amount) is discharged from the nozzle portion 111. The predetermined amount can be adjusted mainly by changing the stroke, and is preferably 10 μL or more and 1 mL or less. According to this, it is possible to discharge a chemical solution having a volume corresponding to the type and size of the tissue specimen (pathological specimen), the type of the chemical solution, and the like. In the present embodiment, the predetermined amount of discharge per one pressing is 50 μL.

FIG. 9B shows a state in which the chemical liquid storage unit 130 is pressed downward. Such a state is called a discharge state. As shown in FIG. 9B, when the chemical storage portion 130 is pushed downward with respect to the case portion 110, the protruding portion 137 moves downward in the stroke chamber 118 as compared with the initial state.

At this time, since the internal volume of the stroke chamber 118 is compressed, positive pressure is generated. The positive pressure pushes the ball 113 downward, releasing the blockage between the ball 113 and the opening 112a. At the same time, the downward movement of the protrusion 137 also releases the obstruction of the supply port 143 by the O-ring 141. Therefore, the path of the chemical solution from the chemical solution chamber 136 to the opening 111a (nozzle portion 111) is connected, and the chemical liquid is discharged from the nozzle portion 111.

Since the gap between the inner surface 137a of the protrusion 137 and the cap 142 and the supply port 143 are narrower than the path of the chemical solution after the stroke chamber 118, negative pressure is not generated in the stroke chamber 118 in the discharge state. Functions as a communication hole. Further, even in the discharge state, the O-ring 141 and the outer surface 137b of the protruding portion 137 are in close contact with each other to maintain airtightness, and it is possible to prevent the chemical solution from leaking to the accommodating portion 119 along the outer surface 137b.

When the lower surface 142a of the cap 142 and the upper surface 117a of the perforated portion 117 come into contact with each other and the downward pressing of the chemical liquid storage portion 130 is completed, the springs 145 and 146 (see FIG. 8) urge the chemical liquid storage portion 130. Moves upwards. In conjunction with this, the protrusion 137 also moves upward in the stroke chamber 118. At this time, a negative pressure is generated in the stroke chamber 118, so that
The ball 113 is sucked up and closes the opening 112a again. As a result, the discharge of the chemical solution from the nozzle portion 111 is stopped. On the other hand, since the supply port 143 is open, the chemical solution in the chemical solution chamber 136 is supplied to the stroke chamber 118 through the supply port 143. In this way, the transition from the discharge state to the initial state is made.

In the above-mentioned path of the chemical solution, the portion from the gap between the inner surface 137a of the protruding portion 137 and the cap 142 to the opening 111a corresponds to the discharge control unit. By the discharge control unit, the chemical solution stored in the chemical solution storage unit 130 is pressed once from the nozzle unit 111 to a predetermined amount (5).
0 μL) Discharged.

[Knock motion conversion mechanism]
The knocking motion conversion mechanism will be described with reference to FIGS. 10, 11, 12, and 13.
FIG. 10 is a schematic view showing parts constituting the knock portion. FIG. 11 is a schematic view showing a slope portion of the chemical liquid storage portion. FIG. 12 is a schematic view showing the arrangement of the knock portion and the case portion. FIG. 13 is a schematic diagram showing a knocking motion conversion mechanism.

The knock portion 150 shown in FIG. 10 is a substantially U-shaped (substantially U-shaped) part in an XY plan view having an opening portion on the negative direction side of the Y axis. Two sliders 151 on each side at both ends in the X-axis direction
Is provided so as to protrude. The slider portion 151 has an elevation angle of about 30 degrees with respect to the negative direction of the Y axis. A rib 152 is provided on the outward side surface of the slider portion 151.

The chemical liquid storage portion 130 shown in FIG. 11 includes the lid portion 131, the locking portion 135, and the protruding portion 13 described above.
In addition to No. 7, two slope portions 139 on each side are provided side by side in the Z-axis direction on the left and right side surfaces. Of the two slopes 139, the upper side has a trapezoidal square columnar bottom when viewed from the X-axis direction, and the lower side has a triangular columnar shape. The slope portion 139 has a depression angle of about 30 degrees with respect to the direction of the Y axis. The elevation angle of the slider portion 151 and the depression angle of the slope portion 139 are not limited as long as they are substantially the same and the slider portion 151 and the slope portion 139 are slidable.

The knocking motion conversion mechanism includes a slider portion 151 provided in the knocking portion 150 and a slope portion 139 provided in the chemical liquid storage portion 130, and the knocking portion 150 is caused by sliding between the slider portion 151 and the slope portion 139. The knocking motion of the Y-axis in the negative direction is converted into the moving motion of the drug solution storage unit 130 in the negative direction of the Z-axis.

As shown in FIG. 12, each of the four ribs 152 of the knock portion 150 has a case portion 110.
It is arranged in contact with the support portion 128 of. By the contact between the rib 152 and the support portion 128, the knocking operation of the knock portion 150 is guided by the support portion 128. Therefore, during the knock operation, the movement of the knock portion 150 is restricted so that the knock portion 150 can move only in the positive and negative directions of the Y axis relative to the case portion 110.

In FIG. 13, in the reagent cartridge 100, the knock portion 150 and the chemical liquid storage portion 13
0 is shown by a solid line, and other parts such as the case portion 110 are shown by a dotted line. As shown in FIG.
The open portion of the knock portion 150 is assembled so as to fit into the chemical liquid storage portion 130. Since the elevation angle of the slider portion 151 and the depression angle of the slope portion 139 match, the slider portion 15
1 and the slope portion 139 are in contact with each other. Since the slider portion 151 and the chemical liquid storage portion 130 are not fixed, the knock portion 150 (slider portion 151) slides while maintaining contact with the slope portion 139, and is relatively relative to the chemical liquid storage portion 130. It is possible to move. In addition, FIG.
In 3, the slider portion 151 and the slope portion 139 on the right side surface side are numbered, and the numbering is omitted on the left side surface side, but the above-mentioned operation is the same on the left and right sides, and the left and right operations proceed at the same time.

In the reagent cartridge 100, when the knocking operation is performed with the case portion 110 fixed, the knocking portion 150 moves so as to be immersed in the internal direction (negative direction of the Y axis) of the case portion 110. At this time, the slider portion 151 abuts on the slope portion 139 and slides so as to ride on the slope, but as described above, movement other than the direction of the Y axis is restricted. Therefore, the knocking motion of the knocking section 150 is converted into a relative moving motion of the drug solution storage section 130 downward (in the negative direction of the Z axis) with respect to the case section 110. That is, when the knock operation is performed while the case portion 110 of the reagent cartridge 100 is held, the chemical liquid storage portion 130 housed in the case portion 110 is pressed downward by the knock operation conversion mechanism. As a result, as described above, the chemical solution stored in the chemical solution storage unit 130 is discharged from the nozzle unit 111.

Knock section 150, drug solution storage section 130, case section 1 constituting the reagent cartridge 100
10. And the material for forming the components constituting these are not particularly limited, and are not easily attacked by liquids such as the stored chemicals, and the components, additives, impurities and the like contained in the forming materials are not easily eluted into the chemicals. It is preferable to use a resin, metal or the like. As a result, it is possible to suppress the occurrence of deterioration and deterioration of the stored liquid and improve the reliability of the pathological diagnosis result. In particular, as a material for forming a component constituting a path of a chemical solution, it is preferable to use a resin because of the ease of molding the component. Examples of such resins include polyethylene, polypropylene, polyphenylene ether, polyphenylene sulfide, polystyrene, polyamide, polyacetal, ABS (acrylonitrile-butadiene-styrene copolymer), urethane, acrylic, polycarbonate, PBT (polybutylene terephthalate), and EPM (polybutylene terephthalate). Polymer compounds such as ethylene-propylene rubber), EPDM (ethylene-propylene-diene rubber), butyl rubber, and silicone rubber can be mentioned, and one or more selected from these groups can be applied. The forming material used for the case portion 110 and the forming material used for the chemical solution storage portion 130 may be the same or different.

<Tissue specimen>
Next, the tissue specimen will be described with reference to FIG. FIG. 14 is a perspective view showing a substrate on which a tissue specimen is fixed.

Pathological specimens produced by the pathology department provide important information regarding the patient's diagnosis, prognosis and medical procedure selection. As a method for preparing a pathological specimen, immunohistochemical staining (IHC) is used to observe the expression level of proteins in the tissue or cell while observing the shape of the tissue or cell as a tissue specimen.
) Method and In situ hybridization (ISH) method for observing the expression level of genes in tissues and cells.

As shown in FIG. 14, the tissue specimen 5 used for preparing the pathological specimen is fixed to the substrate 1. The substrate 1 has a width of 26 mm and a length of 7 as standardized by JIS R 3703: 1998.
A colorless and transparent glass slide for a microscope having a thickness of 6 mm and a thickness of 1.1 mm is used. A water-repellent ring 2 is formed on the substrate 1 in order to hold a liquid such as a chemical solution supplied (discharged) to the fixed tissue specimen 5 within a predetermined range. The tissue specimen 5 is fixed to the inside of the water-repellent ring 2 in a sliced state, for example. The water-repellent ring 2 may be formed by applying a water-repellent agent to the substrate 1 in a ring shape, or may have a water-repellent ring-shaped seal attached to the substrate 1. The water-repellent ring 2 surrounds the tissue specimen 5 with respect to the substrate 1 on which the tissue specimen 5 is fixed.
May be formed. The shape of the water-repellent portion of the water-repellent ring 2 is not limited to a circular shape, and may be a polygon such as a rectangle.

Further, the substrate 1 has a marking region 3 for identifying the fixed tissue specimen 5.
It is provided on one end side in the longitudinal direction of the. For example, a sticker on which the name and control number of the fixed tissue sample 5 are described may be attached to the marking area 3, or the name and control number of the fixed tissue sample 5 can be described. A coating surface may be formed.

The water repellent ring 2 is not limited to being formed once with respect to the substrate 1, and may be formed, for example, two. The active tissue specimen may be fixed in one water-repellent ring 2 and the negative tissue specimen for comparison may be fixed in the other water-repellent ring 2. After that, the substrate 1 to which the tissue specimen 5 is fixed
Will be referred to as a substrate 10.

<Liquid discharge mechanism>
The liquid discharge mechanism according to the present embodiment for the pathological specimen preparation apparatus will be described with reference to FIG. FIG. 15 is a side view showing the liquid discharge mechanism and the cartridge operation unit.

The liquid discharge mechanism 20 shown in FIG. 15 causes a knock operation while holding the reagent cartridge 100, and discharges a liquid such as a chemical solution stored in the reagent cartridge 100 to the substrate 10.

The liquid discharge mechanism 20 holds the reagent cartridge 100 in a detachable holding portion 24 and a substrate 10.
The stage 25 on which the reagent cartridge 100 can be placed and the knock portion 150 of the reagent cartridge 100 are moved in the negative direction of the Y-axis, and the chemical solution stored in the reagent cartridge 100 is supplied to the substrate 10 mounted on the stage 25. It is provided with a possible cartridge operation unit 21. Liquid discharge mechanism 2
At 0, the discharge direction of the chemical solution is downward (negative direction of the Z axis).

The cartridge operating unit 21 has a pusher 22 capable of reciprocating in the negative direction of the Z axis as a third direction intersecting the negative direction of the Y axis. The pusher 22 has a plurality of convex portions 23a and 23b provided side by side in the negative direction of the Z-axis at the end of the rod, and hits the knock portion 150 by reciprocating in the negative direction of the Z-axis. It touches and causes a knocking motion. The driving force for the reciprocating operation of the pusher 22 is not particularly limited, and may be, for example, an electric pusher using a linear motion stepping motor.

The convex portions 23a and 23b have a substantially square columnar shape having a trapezoidal cross-sectional shape in the X-axis direction, and the upper side of the trapezoid is oriented in the negative direction of the Y-axis so as to abut the knock portion 150 during the reciprocating operation. It is provided in. The convex portion 23a and the convex portion 23b have similar shapes, and both have a knock portion 150.
Each can cause a knocking motion. Further, even if the convex portions 23a and 23b come into contact with the knock portion 150 from the lower side (negative direction of the Z axis) of the knock portion 150, a knock operation can be generated. Here, the shapes of the convex portions 23a and 23b are not limited to the square columnar shape, and the cross-sectional shape in the X-axis direction may be, for example, a triangle, a polygon, or a semicircle. Pusher 22
The number of convex portions of the is not limited to two, and may be one or three or more.

When the reagent cartridge 100 is mounted, the holding portion 24 abuts and holds the locking portion 129 (see FIG. 2) and the step 110b (see FIG. 2), so that the reagent cartridge 100 is in a ejection state including a knock operation. It has a function to suppress the shake. That is, in order to exhibit the knocking operation, when the knocking portion 150 is pressed by the pusher 22, the occurrence of blurring is suppressed. Therefore, the pressing force of the pusher 22 is less likely to be attenuated, and the play of contact between the pusher 22 and the knock portion 150 is reduced. As a result, the knocking operation is stably performed. At the same time, the positions of the substrate 10 and the reagent cartridge 100 are less likely to shift, and droplets of the chemical solution can be ejected to a desired position on the substrate 10. The holding unit 24
Is connected to a transfer mechanism (not shown) using a conveyor, and moves the position of the reagent cartridge 100 while holding the reagent cartridge 100.

Next, the manifestation of the knocking motion by the pusher 22 will be described with reference to FIGS. 16A to 16C. 16A, 16B, and 16C are schematic views showing a contact state between the convex portion of the pusher and the knock portion. 16A to 16C show the reagent cartridge 100 held by the end portion of the pusher 22 and the holding portion 24 (not shown) from the right side, and the end portion of the pusher 22, the knock portion 150, and the drug solution storage portion. 130 is a solid line, reagent cartridge 100
Other parts are shown by dotted lines.

FIG. 16A shows the above-mentioned initial state. In this state, the pusher 22 has not moved downward (in the negative direction of the Z axis) and has not come into contact with the knock portion 150. The position of the pusher 22 at this time is set as the initial position.

FIG. 16B shows a state in which the pusher 22 has moved downward and the convex portion 23a and the knock portion 150 have begun to come into contact with each other. When the convex portion 23a (pusher 22) and the knock portion 150 start to come into contact with each other, the knock portion 150 is pushed in the negative direction of the Y axis, and a knock operation occurs. Further, the knocking motion conversion mechanism causes the chemical liquid storage unit 130 to start moving downward in the case unit 110.

FIG. 16C shows a state in which the contact between the convex portion 23a and the knock portion 150 is completed, and the movement of the knock portion 150 in the negative direction in the Y-axis is completed. At this time, when the downward pressing of the chemical solution storage unit 130 is completed, the reagent 7 as the chemical solution is discharged from the reagent cartridge 100 in a predetermined amount (50 μL).

Here, when the pusher 22 is pulled upward from the state shown in FIG. 16C and returned to the initial position,
The contact with the knock portion 150 is released. Therefore, due to the urging of the springs 145 and 146 (not shown), the chemical liquid storage portion 130 moves upward, and the knock portion 150 is pushed out to return to the initial state. This completes one knock operation. In this case, the discharge amount of the reagent 7 is 50 μ.
It becomes L.

Further, from the state of FIG. 16C, the pusher 22 is further moved downward so that the knock portion 150 is located between the convex portion 23a and the convex portion 23b, and the contact between the convex portion 23a and the knock portion 150 is released. Will be done. As a result, the knock portion 150 is pushed out to return to the initial state, and the first knock operation is completed. Subsequently, when the pusher 22 is pulled upward from this state, the convex portion 23a begins to come into contact with the knock portion 150 from below the knock portion 150, a second knock operation occurs, and the reagent 7 is discharged. Then, when the pusher 22 is pulled up and returned to the initial position, the second knocking operation is completed, and a total of two knocking operations are performed. In this case, the total discharge amount of the reagent 7 is 100 μL.

Further, when the pusher 22 is moved further downward from the state where the knock portion 150 is located between the convex portion 23a and the convex portion 23b after the first knocking operation is completed, the convex portion 23b
And the knock portion 150 start to come into contact with each other. Therefore, the knocking operation by the convex portion 23b is exhibited. Next, when the pusher 22 is moved upward and returned to the initial position from the state where the downward pressing of the drug solution storage portion 130 is completed by the knocking operation by the convex portion 23b, the convex portion 23 is again used.
The knocking action by a is expressed. As a result, a total of three knock operations are performed. In this case, the total discharge amount of the reagent 7 is 150 μL.

As described above, by adjusting the downward movement distance of the pusher 22, the convex portion 2
The number of times the knock portions 150 come into contact with the 3a and 23b changes, and a plurality of knock operations are exhibited. As a result, the reagent 7 which is an integral multiple of a predetermined amount (50 μL) can be quickly discharged without using a syringe or a suction device. That is, the reagent 7 can be quickly discharged with a smaller and simpler structure than the conventional one. Further, the knock operation is a so-called side knock method, and the cartridge operation unit 21 (pusher 22) is directly above the reagent cartridge 100.
Is not arranged, so that the height (dimension in the Z-axis direction) of the liquid discharge mechanism 20 can be reduced as compared with the case where the liquid discharge mechanism 20 is not a side knock type.

<Pathological specimen preparation device>
The pathological specimen preparation apparatus according to this embodiment will be described with reference to FIG. FIG. 17 shows
It is a schematic schematic diagram which shows the structure of the pathological specimen preparation apparatus.

The pathological specimen preparation device 200 shown in FIG. 17 includes a liquid discharge mechanism 20, a cleaning unit 30, an electric field stirring unit 40, a chemical liquid information acquisition unit 50, and a stage moving mechanism 60. Stage movement mechanism 60
Is, for example, a conveyor driven by an electric stepping motor. The stage moving mechanism 60 moves the stage 25 in the fourth direction in which the liquid discharge mechanism 20 (cartridge operating unit 21), the cleaning unit 30, and the electric field stirring unit 40 are arranged. As a result, the substrate 10 (tissue specimen 5) placed on the stage 25 can be subjected to treatments such as application of the reagent 7, cleaning with the cleaning liquid 6, and stirring of the applied reagent 7 and the cleaning liquid 6. Here, the fourth direction is, for example,
The direction is positive or negative on the Y-axis, but the direction is not limited to this. The fourth direction is the positive and negative directions of the Z axis.
It may be in the positive or negative direction of the X-axis, or in any other direction having an inclination with respect to the XYZ axis. In FIG. 17, the power supply device, the control unit, the drive unit, the structure, and the like are omitted.

In the method for preparing pathological specimens such as IHC and ISH, as a common step, the substrate 10 is used.
Examples thereof include a cleaning step of applying a cleaning liquid 6 to the substrate 10 to perform cleaning, and a reaction step of applying (discharging) the reagent 7 to the substrate 10 to react the tissue specimen 5 with the reagent 7. As the reagent 7, as described above,
Examples thereof include primary antibody reagents and secondary antibody reagents used in the antigen-antibody reaction step, and color-developing reagents used in the color-developing reaction step. The washing step is performed not only before these reaction steps, but also after the reaction step in order to remove the residual excess reagent 7. Pathological specimen preparation device 200
Then, in order to efficiently prepare the pathological specimen, the reagent cartridge 100 is placed on the substrate 10.
An electric field agitation step is incorporated in which an electric field is applied to a liquid such as the reagent 7 discharged from the agitator. The substrate 10 goes back and forth between these cleaning steps, reaction steps, and electric field stirring steps by the stage moving mechanism 60.

[Chemical solution information acquisition department]
The reagent cartridge 100 is transported to the chemical solution information acquisition unit 50 by the holding unit 24 and the transport mechanism (not shown). The chemical solution information acquisition unit 50 has a remaining amount sensor 80 and a barcode reader 70, and is connected to a control unit and the like.

The chemical solution information acquisition unit 50 includes a protrusion 137, a window unit 123, and the reagent cartridge 100.
An operation of calculating the amount of light received by the light emitting unit 80a, the light receiving unit 80b, and the light receiving unit 80b for the optical path 81 formed by the reflecting unit (not shown) and converting it into an electric signal. Department (
(Not shown). The light emitting unit 80a and the light receiving unit 80b form a remaining amount sensor 80, and are arranged so that the light receiving unit 80b can receive the light rays emitted from the light emitting unit 80a. That is, the emitting unit 80a and the light receiving unit 80b are the window unit 123 of the reagent cartridge 100.
And are opposed to each other in the direction of the Y axis and are arranged on the optical path 81.

Here, it is preferable that the wavelength of the light beam emitted from the emitting unit 80a and the light receiving unit 80b, for example, a distance measuring reflection type sensor, is 570 nm or more and 750 nm or less. By using light rays having a wavelength in the above range, it is possible to suppress the occurrence of alteration in the components contained in the reagent 7, such as proteins. Further, since it is out of the infrared region, it is possible to prevent the reagent 7 from being excessively heated. Furthermore, the molecular structure of the compound contained in the chemical solution can suppress the absorption and attenuation of light rays. In this embodiment, a red light emitting diode is used as the light source of the emission unit 80a.

With the above configuration, the light beam is directed from the emission unit 80a to the optical path 81 from the reagent cartridge 1.
It is emitted to the window portion 123 of 00, passes through the window portion 123 and the protruding portion 137 (see FIG. 8), and passes through the window portion 123.
It reaches the inside of the protrusion 137. Then, it is reflected by the inner surface 137a (reflecting portion), travels in the optical path 81 in the reverse direction of the above, and is received by the light receiving portion 80b. At this time, if the reagent 7 is present on the optical path 81 inside the protrusion 137, the light beam is absorbed, and the light ray is attenuated as compared with the case where the reagent 7 is not present. Therefore, the presence or absence of the reagent 7 in the optical path 81 of the protrusion 137 can be detected by calculating the voltage value of the distance measuring reflection type sensor (remaining amount sensor 80) by the calculation unit. Information on the presence or absence of the reagent 7 may be displayed on a display device or the like attached to the pathological specimen preparation device 200.

The calculation unit has, for example, a CPU (Central Processing Unit) and a memory, and calculates the presence / absence of the reagent 7 from the voltage value output by the light receiving unit 80b (distance measuring reflection type sensor). Further, the arithmetic unit may have a control function for causing the pathological specimen preparation device 200 to execute various operations.

In the present embodiment, the emitting unit 80a and the light receiving unit 80b are arranged integrally, but the present invention is not limited to this, and the emitting unit 80a and the light receiving unit 80b may be arranged separately.

In the chemical solution information acquisition unit 50, the reagent cartridge 100 is used by the barcode reader 70.
The bar code 126 related to the information of the chemical solution given to the above is read. As a result, information such as the type, content, date of manufacture, and precautions regarding the stored reagent 7 can be collected and managed by the control unit or the like.

[Washing section]
The cleaning unit 30 has a cleaning liquid 6 from the nozzle 31 with respect to the substrate 10 placed on the stage 25.
Supply. The nozzle 31 is connected from a cleaning liquid tank (not shown) in which the cleaning liquid 6 is stored by a pipe via a pump (not shown), and the cleaning liquid 6 is supplied from the cleaning liquid tank. A plurality of cleaning liquid tanks and pumps may be used depending on the type of cleaning liquid 6. for example,
PBS or TB to prevent the tissue specimen 5 from drying out and to maintain the fixed state of the tissue specimen 5.
A cleaning liquid tank in which S and the like are stored, a cleaning liquid tank in which pure water is stored, and the like are individually used. The piping from the plurality of cleaning liquid tanks to the nozzle 31 is switched by opening and closing the valve.
The cleaning liquid may be selectively supplied from the nozzle 31 to the substrate 10.

The cleaning liquid 6 used for cleaning is removed from the substrate 10 as waste liquid. Waste liquid is a gutter (not shown)
Waste liquid tank (not shown) collected by and placed below the pathological specimen preparation device 200.
Is stored in. The mechanism for removing the cleaning liquid from the substrate 10 is not particularly limited, and a known method can be used. The pathological specimen preparation device 200 uses a method in which the substrate 10 is tilted and removed together with the stage 25 by a cam mechanism. In the same way as the cleaning liquid tank,
A plurality of types of waste liquid tanks may be used depending on the type.

[Electric field agitator]
The electric field stirring unit 40 applies an electric field to a liquid such as the reagent 7 or the cleaning liquid 6 supplied to the substrate 10 placed on the stage 25 to stir. Therefore, in the electric field stirring unit 40, the upper electrode 41 as the upper electrode and the stage 25 which also serves as the lower electrode as the lower electrode are moved up and down (
They are arranged at predetermined intervals facing each other (in the Z-axis direction). A rectangular potential whose potential changes between 0 kV and 4 kV is applied between the upper electrode 41 and the stage 25 at a predetermined cycle, and an electric field is generated. The Coulomb force generated with the increase in the electric potential deforms the liquid on the substrate 10 so as to be attracted to the upper electrode 41 side (ceiling direction). The Coulomb force weakens as the potential drops, and the liquid attracted to the upper electrode 41 side is deformed so as to fall due to gravity. Therefore, since the electric potential changes periodically, the liquid is repeatedly deformed and stirred.

[Other configurations]
The pathological specimen preparation device 200 may be equipped with a CCD (Charge-Coupled Device) image sensor that images the marking region 3 of the substrate 10 mounted on the stage moving mechanism 60. The information of the tissue sample such as the name and the control number of the tissue sample 5 displayed in the marking area 3 may be read by the CCD image sensor and managed by the calculation unit. Cartridge operation unit 21 (pusher 22) according to these information and the information of the barcode 126.
The type and discharge amount of the reagent 7 supplied to the substrate 10 can be changed by adjusting the operation of.

A plurality of reagent cartridges 100 may be mounted on the pathological specimen preparation device 200. For example, a plurality of holding portions 24 are provided in the loop-shaped transport mechanism, and the plurality of reagent cartridges 100 are placed on the transport mechanism. The desired reagent cartridge 100 may be selectable according to the type and treatment of the tissue specimen 5 while moving the transport mechanism in a loop.

The pathological specimen preparation device 200 may be provided with a plurality of stages 25. The number of stages 25 is not particularly limited, but for example, 2 to 10 are preferable, and 3 to 8 are more preferable. By setting the number of stages 25 in the above range, the pathological specimen preparation apparatus 200 can be relatively miniaturized while improving the work efficiency of pathological specimen preparation.

As described above, the reagent cartridge 100, the liquid discharge mechanism 20, and the liquid discharge mechanism 20 according to the present embodiment.
According to the pathological specimen preparation device 200, the following effects can be obtained.

It is possible to provide a reagent cartridge 100, a liquid discharge mechanism 20, and a pathological specimen preparation device 200, which are smaller and simpler than conventional ones and enable rapid preparation of pathological specimens. Specifically, the knocking motion conversion mechanism allows the knocking motion in the negative direction of the Y-axis to be performed by the chemical liquid storage unit 13.
It is converted into a movement operation in the negative direction of the Z axis of 0, and the reagent 7 of the chemical liquid storage unit 130 is discharged. That is, the direction of the knocking operation (negative direction of the Y axis) is the moving direction (Z) of the chemical liquid storage unit 130.
Since the direction is different from the negative direction of the axis), the bulkiness of the liquid discharge mechanism 20 is reduced, and the pathological specimen preparation device 200 can be made smaller than before.

Since the relatively small reagent cartridge 100 is used, the reagent cartridge 100 can be easily transported by a transport mechanism such as a conveyor in the pathological specimen preparation device 200. Therefore, the reagent cartridge 100 can be moved to the position of the tissue specimen 5 and the reagent 7 can be discharged without transporting the tray on which many slides or reaction wells are placed as in the conventional case. As a result, the pathological specimen preparation device 200 can have a simple configuration without using a suction device for the reagent 7, a 3-axis robot for transporting trays, or the like, and can be made smaller and cheaper than before. ..

Since a predetermined amount of the reagent 7 is quantitatively discharged by one knocking operation, it is possible to save the trouble of applying the reagent 7 while measuring with a pipette or the like. Further, by performing the knocking operation a plurality of times, the reagent 7 in a multiple of a predetermined amount can be applied relatively quickly. Therefore, the pathological specimen can be prepared more quickly.

The knocking motion is converted into the moving motion of the chemical liquid storage unit 130 by a relatively simple knocking motion conversion mechanism. Therefore, the number of parts constituting the knocking motion conversion mechanism is reduced, and the number of parts is reduced.
Occurrence of malfunctions such as malfunction during conversion is suppressed. Therefore, the reagent cartridge 100
Operation reliability can be improved.

The reciprocating motion of the pusher 22 in the negative direction of the Z axis is converted into a knocking motion in the negative direction of the Y axis by the contact between the convex portion 23a or the convex portion 23b of the pusher 22 and the knock portion 150. Since the driving force for the knocking operation is supplied from the negative direction of the Z axis, the bulkiness of the liquid discharge mechanism 20 in the positive and negative directions of the Y axis is reduced, and the pathological specimen preparation device 200 is made smaller than before. Can be done.

Since the pusher 22 has a plurality of convex portions 23a and 23b, the number of times the convex portions 23a and 23b and the knock portion 150 come into contact with each other increases due to one reciprocating operation of the pusher 22, and the knock operation caused by the contact increases. The number of times increases. Therefore, it is possible to increase the supply amount of the reagent 7 in the reciprocating operation of the pusher 22 once. Also, pusher 22
Limiting the movement distance of the reciprocating motion in the negative direction of the Z axis, and limiting the number of knocking operations by bringing only a part of the plurality of convex portions 23a and 23b into contact with the knocking portion 150. Will be possible. Thereby, the supply amount of the reagent 7 can be adjusted.

Through the translucent window portion 123, the presence or absence of the reagent 7 in the protruding portion 137 facing the window portion 123 can be detected. In addition, the presence or absence of the reagent 7 can be easily optically detected by using the chemical solution information acquisition unit 50. Specifically, the presence or absence of the reagent 7 inside the protrusion 137 can be optically confirmed from the outside of the reagent cartridge 100 by using the remaining amount sensor 80 and the optical path 81. Therefore, it is not necessary to visually check the remaining amount of the reagent 7, and it becomes easy to grasp the replacement time of the reagent cartridge 100. That is, it is possible to provide a reagent cartridge 100 suitable for a pathological specimen preparation device 200 used for intraoperative pathological diagnosis.

The tissue specimen 5 fixed to the substrate 10 can be washed with the washing liquid 6. In addition, the efficiency of stirring is improved by electric field stirring, and the time required for various reactions and cleaning work is shortened. Further, the substrate 10 is subjected to the electric field stirring unit 40 and the cleaning unit 3 by the stage moving mechanism 60.
0, it is quickly moved to the liquid discharge mechanism 20. As a result, the tissue sample 5 can be processed more quickly.

The present invention is not limited to the above-described embodiment, and various changes and improvements can be made to the above-mentioned embodiment.

5 ... Tissue specimen, 6 ... Cleaning liquid, 7 ... Reagent as chemical solution, 10 ... Substrate, 20 ... Liquid discharge mechanism, 21 ... Cartridge operation unit, 22 ... Pusher, 23a, 23b ... Convex part, 24 ... Holding part, 25 ... Stage, 30 ... Cleaning unit, 40 ... Electric field stirring unit, 60 ... Stage moving mechanism, 70 ...
Bar code reader, 80 ... remaining amount sensor, 80a ... emitting part, 80b ... light receiving part, 81 ... optical path, 100 ... reagent cartridge, 110 ... case part, 111 ... nozzle part, 123 ... window part,
126 ... Bar code, 130 ... Chemical storage, 131 ... Lid, 132 ... Communication hole, 137 ... Projection as chemical flow path, 139 ... Slope, 145, 146 ... Spring as urging means, 15
0 ... Knock part, 151 ... Slider part, 200 ... Pathological specimen preparation device.

Claims (9)

A chemical storage unit that can store chemicals and
A case portion that can accommodate the chemical liquid storage portion so as to be movable in the first direction and has a nozzle portion, and a case portion.
Knock part and
A knocking motion conversion mechanism that converts a knocking motion of the knocking portion in a second direction intersecting with the first direction into a moving motion of the chemical liquid storage section in a predetermined range in the first direction.
An urging means for urging the chemical storage portion in a direction opposite to the first direction,
A reagent cartridge including a discharge control unit that discharges a predetermined amount of the chemical solution stored in the chemical solution storage unit from the nozzle unit by one knock operation. The knocking motion conversion mechanism includes a slider portion provided in the knocking portion and a slope portion provided in the chemical liquid storage portion.
A claim that the sliding of the slider portion and the slope portion converts the knocking motion of the knocking portion in the second direction into the moving motion of the chemical liquid storage portion in the first direction. The reagent cartridge according to 1. The case portion has a translucent window portion between the chemical liquid storage portion and the nozzle portion.
The chemical liquid storage portion has a translucent chemical liquid flow path on the tip side in the first direction.
The window portion is provided on the side surface of the case portion facing the chemical liquid flow path from a third direction intersecting with the first direction.
The reagent cartridge according to claim 1 or 2, wherein the chemical flow path and the window portion form an optical path along the third direction. The chemical solution is composed of a primary antibody reagent, a secondary antibody reagent, a coloring reagent, a tissue staining reagent, a nuclear staining reagent, an endogenous Peroxydase blocking reagent, a hematoxillin, a coloring reagent, a deparaffinizing reagent, an activation reagent, and a washing solution. The reagent cartridge according to any one of claims 1 to 3, which is one selected from the group. The reagent cartridge according to any one of claims 1 to 4, wherein the predetermined amount is 10 μL or more and 1 mL or less. The reagent cartridge according to any one of claims 1 to 5, wherein the reagent cartridge can store 500 μL or more and 20 mL or less of the drug solution. The reagent cartridge according to any one of claims 1 to 6, wherein the chemical storage portion can seal the chemical liquid storage portion and has a lid portion including a communication hole. The reagent cartridge according to any one of claims 1 to 7, to which a barcode relating to the information of the chemical solution to be stored is attached. The reagent cartridge according to any one of claims 1 to 8 is provided with a detachable holding portion and a removable holding portion.
A stage on which a substrate on which a tissue specimen is fixed can be placed,
The knock portion of the reagent cartridge is moved in the second direction, and the substrate placed on the stage is provided with a cartridge operating portion capable of supplying the chemical solution stored in the reagent cartridge. Liquid discharge mechanism.

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