Device for staining biological sample attached to slide

Abstract

The invention relates to a device (1) for staining a biological sample attached to a slide (2), comprising at least one staining chamber (3) having an opening (4) for receiving the slide (2) in a fixed position, at least one staining agent container (5), at least one staining agent line (6), at least one staining agent pump (7) and a control device (8). Wherein, by means of the dye pump (7), dye can be conveyed from the dye container (5) via the dye line (6) into the dye chamber (3).

Description

Technical Field

[0001] The present invention relates to a device for staining biological samples attached to a specimen slide, comprising at least one staining chamber, at least one staining agent container, at least one staining agent pipeline, at least one staining agent pump and a control device. Background Art

[0002] Such devices can be seen in US Patent US 6,387,326 B1. In the field of histology (i.e., the examination of biological tissues), staining methods are used to better distinguish tissue structures during optical examinations. In this context, various staining methods are known, for example, hematoxylin-eosin staining (HE staining). Using this staining, for example, the cell nuclei of the tissue to be examined can be made to appear blue-violet, and the cytoplasm can be made to appear pink. Intracellular substances can also be stained, for example, cartilage appears purple or fibers appear pink. Staining techniques are also applied in the field of hematology (i.e., the examination of blood and bone marrow).

[0003] The biological sample to be examined is placed on a specimen slide and then stained using different staining agents or staining methods according to the detection method. To achieve the best staining effect, it is crucial to strictly follow the staining method, especially the staining duration and the amount of staining agent applied. For this purpose, it is known in the prior art to automatically stain the specimen slide with the attached biological sample through a device. During this process, the specimen slide is usually transported by the device and undergoes a staining procedure.

[0004] Since the specimen slide is transported by the device, continuous automatic processing of multiple specimen slides can be achieved. However, the disadvantage is that the transport mechanism and the staining process adapted for transportation make such devices complex and expensive. In addition, such devices only make sense in the case of a large number of specimen slides to be stained; for the staining requirements of a small number of specimen slides, the preparation and post-processing work of the device (such as cleaning and rinsing) are too heavy compared to the amount of stained samples. Summary of the Invention

[0005] The object of the present invention is to provide a device for staining biological samples attached to a specimen slide, which can flexibly adjust the staining method even when the number of specimen slides is small.

[0006] The above object is achieved by the features of claim 1. The dependent claims relate to advantageous embodiments.

[0007] The device for staining biological samples attached to a specimen slide according to the present invention comprises at least one staining chamber, at least one staining agent container, at least one staining agent pipeline, at least one staining agent pump and a control device, wherein the staining chamber has an opening for receiving the specimen slide in a fixed position. Through the staining agent pump, the staining agent can be transported from the staining agent container to the staining chamber via the staining agent pipeline.

[0008] In the device according to the present invention, it is advantageous that within the device, the glass slide is held in a fixed position in the staining chamber and the staining process is carried out therein. When staining, the staining agent in the staining agent container is transported to the staining chamber by a staining agent pump, and the glass slide placed in the staining chamber is wetted by the staining agent. The device does not require any moving parts for transporting the glass slide, so it has a simple structure and high cost-effectiveness. Therefore, the device is particularly suitable for staining a small number of glass slides.

[0009] In addition to the staining agent container, the device may also have a rinsing agent container and a collection container. After staining is completed, the rinsing agent can be applied from the rinsing agent container to the glass slide to rinse the glass slide and remove the excess staining agent. The rinsing solution (composed of the staining agent and the rinsing liquid) can be collected in the collection container.

[0010] The staining chamber can be accommodated in a staining chamber housing, and openings are also provided on the staining chamber housing. In addition to the said openings, the staining chamber housing is preferably enclosed on all sides and only provided with inlets and outlets for the staining agent and the rinsing solution. The staining chamber is designed to be compact and relatively small in volume, making the overall device space-saving.

[0011] The staining chamber housing may have a plurality of staining chambers, which are separated from each other by partitions. The staining chambers can be arranged adjacent to and / or above and below each other. Each staining chamber is designed to receive one glass slide, so that each glass slide can be stained individually in one staining chamber. In principle, this enables multiple glass slides to be stained synchronously, and different staining methods can be executed synchronously to meet different expected staining results.

[0012] The opening can be formed as a slit. The width and height of the slit are based on the size of the glass slide to be stained and are preferably matched with the glass slide. Therefore, the opening area is small, and the interior of the staining chamber is largely isolated from the surrounding environment, especially preventing the staining agent or rinsing solution in the staining chamber from drying out. In addition, odor pollution or health hazards caused by the evaporation of liquids (such as the staining agent or rinsing solution) in the device can be reduced.

[0013] A seal can be provided on the circumferential edge of the opening. The seal is preferably formed such that it abuts against the glass slide placed in the staining chamber. This can further reduce odor pollution and / or health hazards caused by the leakage of the staining agent from the device. The seal can be formed as a lip seal, and when the glass slide is inserted, the lip seal seals the glass slide on all sides.

[0014] The staining chamber may be provided with at least one inlet and at least one outlet, wherein the inlet is connected to a stain pipeline. The stain is injected into the staining chamber through the inlet, where the stain wets the glass slides disposed therein. The stain may flow out of the staining chamber through the outlet. After staining is completed, the glass slides may be rinsed with a rinsing solution. The rinsing solution may be injected through this inlet, or another inlet may be provided for supplying the rinsing solution. The rinsing solution flows out through the outlet.

[0015] The staining chamber housing includes a plate-shaped bottom member that is connected to a plate-shaped top member, wherein at least one groove is provided in the bottom member and / or the top member for forming the staining chamber. Such a staining chamber housing is easy to manufacture and cost-effective. Preferably, the staining chamber housing is made of a metallic material.

[0016] A seal (such as a gasket) may be arranged between the bottom member and the top member. The inlet and / or the outlet is preferably provided in the bottom member. For staining a sample glass slide, the glass slide is disposed in the staining chamber such that the biological sample attached to the glass slide faces the bottom member. Thus, the glass slide can be placed flat on the bottom member or placed in the groove of the bottom member. When the stain enters the staining chamber through the inlet, due to capillary action, the stain automatically wets the entire surface of the glass slide, and the excess stain flows out through the outlet.

[0017] Within the device, the staining chamber housing may be arranged inclined relative to the horizontal plane (e.g., 10°). The staining chamber housing is preferably arranged such that the staining chamber is inclined relative to the horizontal plane. Thus, the end of the staining chamber facing the opening is higher than the end of the staining chamber away from the opening. On the one hand, this prevents the stain and / or the rinsing solution from leaking out through the opening. On the other hand, especially when the inlet is located in the opening area and the outlet is associated with the end of the staining chamber away from this opening, a particularly good distribution of the stain on the surface of the glass slide can be achieved.

[0018] The outlet may be connected to a suction pump, wherein the suction pump may be connected to the outlet through a liquid outlet pipeline. The stain and / or the rinsing solution may be actively removed from the staining chamber through the suction pump. The control device is preferably configured to control the stain pump to transport the stain from the stain container to the staining chamber. Thus, the control device controls the stain pump to stain the biological sample attached to the glass slide.

[0019] The staining chamber may have a contact area for supporting the glass slide and a recess defined by the contact area. The contact area is preferably circumferentially arranged in the edge area of the staining chamber so that the glass slide can be supported at its edge area. The recess is preferably formed in a bowl shape, and the bottom member of the recess is spaced apart from the glass slide placed in the contact area. The recess may be designed to form a capillary effect therein, through which a liquid (such as a stain and a rinsing solution) is automatically distributed in the recess and on the surface of the glass slide. However, it is also conceivable that the liquid is actively pumped into and out of the recess.

[0020] The at least one inlet and the at least one outlet can be arranged in the recess. This enables the liquid to come into contact with the slide particularly easily and quickly.

[0021] By means of a suction pump, a vacuum can be generated in the recess, and the slide can be fixed in the staining chamber by means of this vacuum. This achieves the fixing of the slide in the staining chamber. The liquid can moisten the slide and does not leak from the staining chamber during this process.

[0022] The stain pump can be configured to generate a pulsed stain flow. This can be achieved in particular by a peristaltic pump, which usually has a pulsed flow due to its function. The pulsed flow ensures a particularly rapid and thorough wetting of the slide, thereby achieving an improved staining result and shortening the processing time. The effect of the pulsed flow is particularly good if there is a vacuum in the recess when the slide is in place and the pulsed flow enters and exits the recess again. Further improvement can be achieved if the recess is designed such that the liquid is also distributed in the recess by capillary action.

[0023] The inlet and the outlet can be equipped with quick-release fasteners, allowing for a quick and tool-free replacement of the hoses of the stain line and the liquid outlet line.

[0024] The types of stain, the amount of stain, and the stain exposure time suitable for different biological samples and / or different evaluation methods can be stored in the control device. For this purpose, the control device preferably includes a memory in which various evaluation methods and staining methods and their associated staining programs are stored. In particular, it is conceivable to store the programs of the following staining methods in the control device:

[0025] · Hematoxylin-eosin staining (for histology)

[0026] · Pappenheim staining (for hematology)

[0027] · Wright-Giemsa staining (for cytology)

[0028] · Gram staining (for bacterial analysis)

[0029] · Ziehl-Neelsen staining (for tuberculosis analysis)

[0030] · Papanicolau staining (for gynecological examinations)

[0031] Different staining methods use different staining agents and rinsing solutions, and the exposure time of the staining agent as well as the need for rinsing and / or drying also vary depending on the different staining methods. Therefore, the relevant programs for these different staining methods are stored or storable in the control device, so that different staining methods can be switched particularly easily. In addition, it is conceivable to modify individual process parameters of the staining program, such as the amount of staining agent and / or rinsing agent delivered to the inlet, and even the possible temperature control of the staining chamber. This enables individual parameters to be adjusted to obtain better staining results.

[0032] The staining chamber can be temperature-controlled. For this purpose, the bottom part and / or the top part can be equipped with heating elements. Alternatively, it is also conceivable to arrange the heating element between the bottom part and the top part. The heating element is preferably formed as a resistance heater. Temperature control can accelerate the staining process, especially since the drying time can be shortened. By increasing the processing temperature by only 20 °C, the processing time can be almost doubled. Another advantage is that temperature control can ensure particularly consistent processing conditions.

[0033] The control device can be configured to record the staining methods that have been executed and store them. This enables the method and process parameters used for staining the slides to be traced later. In particular, it is also conceivable to output the stored staining methods to an external storage medium through an interface.

[0034] The input device is preferably associated with the control device. Preferably, the input device is designed as a touch display. The input device makes it particularly easy to select the staining method and modify the process parameters associated with each method. In addition, the control device can have an interface through which alternative staining programs can be read into the control device. Description of the Drawings

[0035] Some embodiments of the present invention will be explained in more detail below with reference to the accompanying drawings. These drawings each schematically show:

[0036] Figure 1 : the device when the slide-in part is open;

[0037] Figure 2 : the device according to Figure 1 with the slide-in part closed;

[0038] Figure 3 : the device according to Figure 1 and Figure 2 with the slide-in part open and no input device;

[0039] Figure 4 : a detailed top view of the slide-in part;

[0040] Figure 5 : a side view of the slide-in part;

[0041] Figure 6 : Detailed bottom view of the staining chamber housing in the device;

[0042] Figure 7 : Top view of the staining chamber housing;

[0043] Figure 8 : Flow chart. Detailed implementation

[0044] Figure 1 The device 1 for staining a biological sample attached to a slide 2 is shown. The biological sample attached to the slide 2 is treated with one or more staining agents in the device 1 in order to differentially stain the structure of the biological sample so that they can be better distinguished during subsequent optical inspection (e.g., microscopy).

[0045] The device 1 includes a plurality of staining chambers 3, each staining chamber 3 having an opening 4 for receiving the slide 2 in a fixed position. The staining chambers 3 are accommodated in a staining chamber housing 9, where the opening 4 is provided in the staining chamber housing 9. In this embodiment, the staining chamber housing 9 has a plurality of staining chambers 3 arranged adjacent to each other, and these staining chambers 3 are separated from each other by a partition 10. Each opening 4 is designed as a slit, and the cross-sectional area of the slit substantially corresponds to the cross-section of the slide 2 to be inspected. Each opening 4 is provided with a seal 14 in the form of a lip seal, where the seal 14 is connected to the circumferential edge of the opening 4 and protrudes inwardly so that when the slide 2 is inserted, the seal 14 makes sealing contact with all sides of the slide 2.

[0046] In this embodiment, a slide-in member 21 in the form of a drawer is associated with the staining chamber 3. Figure 1 The slide-in member 21 is shown in the open position. Figure 2 The device 1 according to Figure 1 is shown, where the slide-in member 21 is in the inserted and closed state.

[0047] The slide-in member 21 has a plurality of receiving portions, and a plurality of slides 2 can be placed in these receiving portions simultaneously. By inserting the slide-in member 21 into the device 1, each slide 2 is simultaneously guided into an independent staining chamber 3. The insertion of the slide-in member 21 is operated by a stepping motor 22 connected to a gear 23 of the slide-in member 21. The slide-in member 21 is provided with a seal 14 to ensure the seal between the staining chambers 3 and the seal of the staining chambers 3 in the direction of the opening 4.

[0048] The device 1 further includes a plurality of staining agent containers 5, staining agent pipelines 6, a plurality of staining agent pumps 7, and a control device 8.

[0049] The control device 8 is configured to control the stain pump 7 to stain the biological sample attached to the slide 2. The control device 8 stores the stain type, the amount of stain, and the stain exposure time suitable for different biological samples and / or different evaluation methods. The device 1 is configured to perform the following staining methods:

[0050] · Hematoxylin-eosin staining method (for histology)

[0051] · Pappenheim staining method (for hematology)

[0052] · Wright-Giemsa staining method (for cytology)

[0053] · Gram staining method (for bacterial analysis)

[0054] · Ziehl-Neelsen staining method (for tuberculosis analysis)

[0055] · Papanicolau staining method (for gynecological examination)

[0056] An input device 18 in the form of a touch display is associated with the control device 8. The control device 8 is also equipped with a memory for storing staining programs. The memory can also be used to save the performed staining. The saved staining can also be output through an interface, for example, transferred to an external storage medium. In the control device 8, the predetermined programs and process parameters of the above staining methods are stored. The process parameters can be modified through the input device, and the above modifications can also be saved in the control device 8. This makes it possible to change the predetermined program, for example, to change the staining result or to adapt the device 1 to a changing stain. The modified parameters can also be output through the interface.

[0057] Figure 3 Figure 1 shows the device 1 according to Figure 1 wherein in this view, the unit formed by the cover plate consisting of the control device 8 and the input device 18 is removed so that the interior of the device 1 can be seen unobstructed. This unit is firmly fixed in the device 1 and can be disassembled without tools for maintenance. This is particularly advantageous because the pipeline 6 formed by the flexible hose wears out and must be replaced regularly only for hygienic reasons.

[0058] In this embodiment, the apparatus 1 includes the same number of dye pumps 7 as the number of dyeing chambers 3, such that each dyeing chamber 3 is assigned one dye pump 7. The dye pump 7 conveys the dye from the dye container 5 to the dyeing chamber 3 through a dye pipeline 6. The dye pump 7 is designed as a peristaltic pump, where the peristaltic pump is modular and multiple dye pumps 7 are connected together. In this embodiment, each dye pump 7 is assigned a motor 20 in the form of a stepper motor. In an alternative embodiment, the dye pumps 7 are connected in such a way that they are controlled by a single motor 20. The dye pump 7 is configured to generate a pulsed dye flow.

[0059] The dyeing chamber housing 9 is arranged obliquely in the apparatus 1; its inclination angle relative to the horizontal plane is ten degrees. This inclination is designed such that the dyeing chamber housing 9 decreases in the direction of the rear wall of the apparatus 1.

[0060] The dye removed after the dyeing process is conveyed to the reservoir tank 28. Adjacent to the reservoir tank 28, there is a rinsing agent container 29 for containing the rinsing solution.

[0061] The scanner 30 is arranged on one side wall of the apparatus 1. In this embodiment, the scanner 30 is provided for reading QR codes and for reading the QR codes attached to the dye container 5. The read information is forwarded to the control device 8. By scanning the dye container 5 immediately before assembly, operation errors can be avoided, and the scanned information can be used for program selection and quality assurance.

[0062] Figure 4 A detailed top view of the slide-in part 21 is shown. In this view, in particular, the laterally arranged stepper motor 22 together with the gear 23 can be seen. The slide-in part 21 is mounted on the laterally arranged guide rail 24.

[0063] Figure 5 A side view of the slide-in part 21 according to Figure 4 is shown. In this view, the rack 25 can be seen. The rack 25 is connected to the side of the slide-in part and is operatively connected to the gear 23 so as to be able to move the slide-in part 21 relative to the dyeing chamber housing 9.

[0064] Figure 6 A bottom view of the dyeing chamber housing 9 and the slide-in part 21 is shown, where the dyeing chamber 3 is arranged in the dyeing chamber housing 9. In this view, in particular, the inlet 15 and the outlet 16 provided in the bottom part 11 and the pipelines connected to them can be seen.

[0065] The dyeing chamber housing 9 includes a plate-shaped bottom part 11, which is connected to a plate-shaped top part 12. In this embodiment, the groove 13 forming the dyeing chamber 3 is provided in the bottom part 11. The bottom part 11 and the top part 12 are made of a metal material and are firmly connected together by a threaded connection.

[0066] Each staining chamber 3 is provided with an inlet 15 and an outlet 16, wherein the inlet 15 is connected to the stain line 6. The outlet 16 is connected to the collection container 19. A suction pump 17 is arranged between the outlet 16 and the collection container 19.

[0067] Figure 7 Shows a top view of the staining chamber housing 9 according to Figure 6 . In this view, the recess 27 embedded in the bottom member 11 can be seen particularly easily. The recess 27 is defined by a circumferential contact area 26. The inlet 15 and the outlet 16 are provided in the recess, wherein the inlet is associated with one narrow side of the recess and the outlet 16 is associated with the other narrow side. When the slide 2 is placed in the recess, a vacuum can be generated in the recess 27 by means of the suction pump 17, thereby fixing the slide 2 in the staining chamber 3 by a force fit.

[0068] Figure 8 Shows a flow chart of the device 1 and a schematic diagram of the components of the device 1.

Claims

1. An apparatus (1) for staining a biological sample attached to a slide (2), comprising at least one staining chamber (3), at least one staining agent container (5), at least one staining agent pipeline (6), at least one staining agent pump (7) and a control device (8), wherein the staining chamber (3) has an opening (4) for receiving the slide (2) at a fixed position, where, Via the dye pump (7), the dye can be transported from the dye container (5) to the dyeing chamber (3) via the dye pipeline (6).

2. The apparatus according to claim 1, characterized in that, The dyeing chamber (3) is accommodated in a dyeing chamber housing (9), and the opening (4) is provided in the dyeing chamber housing (9).

3. The apparatus according to claim 1 or 2, characterized in that, The dyeing chamber housing (9) has a plurality of dyeing chambers (3), and the plurality of dyeing chambers (3) are separated from each other by a partition (10).

4. The apparatus according to claim 3, characterized in that, Each dyeing chamber (3) is assigned a dye pump (7).

5. The apparatus according to any one of claims 1 to 4, characterized in that, The opening (4) is formed as a slit.

6. The apparatus according to any one of claims 1 to 5, characterized in that, A seal (14) is provided at the circumferential edge of the opening (4).

7. The apparatus according to any one of claims 1 to 6, characterized in that, The dyeing chamber (3) is provided with at least one inlet (15) and at least one outlet (16), wherein the inlet (15) is connected to the dye pipeline (6).

8. The apparatus according to any one of claims 2 to 7, characterized in that, The dyeing chamber housing (9) has a plate-shaped bottom member (11), and the bottom member (11) is connected to a plate-shaped top member (12), wherein at least one recess (13) is provided in the bottom member (11) and / or the top member (12) for forming the dyeing chamber (3).

9. The apparatus according to any one of claims 2 to 8, characterized in that, The dyeing chamber housing (9) is arranged obliquely in the device (1).

10. The apparatus according to any one of claims 7 to 9, characterized in that, The outlet (16) is connected to a suction pump (17).

11. The apparatus according to any one of claims 1 to 10, characterized in that, The control device (8) controls the dye pump (7) to transport the dye from the dye container (5) to the dyeing chamber (3).

12. The apparatus according to any one of claims 1 to 11, characterized in that, The dyeing chamber (3) has a contact area (26) for supporting the slide (2) and a recess (27) defined by the contact area (26).

13. The apparatus according to claim 12, characterized in that, The at least one inlet (15) and the at least one outlet (16) are arranged in the recess (27).

14. The apparatus according to claim 13, characterized in that, Under the action of the suction pump (17), a vacuum can be generated in the recess (27), so as to fix the slide (2) in the dyeing chamber (3).

15. The apparatus according to any one of claims 4 to 14, characterized in that, The dye pump (7) is configured to generate a pulsed dye flow.

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