EP3625540A1 - Device for preparing a tissue sample and particularly for producing a wax block containing a tissue sample - Google Patents

Abstract

The invention relates to an arrangement (1) for producing a wax block containing a tissue sample (1), comprising a container (4) in which the tissue sample (1) is deposited and a dosing arrangement ( 10) for dosing different substances in the container (4). The arrangement (1) according to the invention is characterized in that it comprises a emptying device (23) for emptying the container (4) and a control unit (22) is present, which is designed to control the metering arrangement (10) and the emptying device (23) such that in several successive steps at least one of the substances is respectively metered into the container (4) and the container (4) is again emptied after a predefined time.

Description

 Device for preparing a tissue sample and in particular for producing a wax block containing a tissue sample

The invention relates to a device for processing a tissue sample and in particular for producing a tissue sample containing

Wax blocks, which inter alia cross-contamination between

prevented various tissue samples.

BACKGROUND OF THE INVENTION

In the case of a suspected tissue or cell disease, a tissue sample is usually taken from the patient by biopsy. For subsequent microscopic examination, the tissue sample is chemically pretreated, then embedded in a wax block and then cut into thin slices by means of a microtome. The individual slices of the

 Tissue specimens can be color coded to reveal specific cell types. The discs are finally examined with the help of a microscope for possible anomalies or diseases. Likewise, sample material can also be taken from the wax block for further investigations such as PCR, sequencing, Maldi-TOF, etc.

The basic procedure of embedding tissue samples in wax blocks has been used for more than 100 years. Today will be for the

Manufacture of such wax blocks usually machines, such as such as those of the companies Sakura, Leica, Thermo, etc., used.

To fabricate a tissue wax block, we usually perform the following procedure: First, a tissue sample is removed by biopsy and then the tissue sample is placed in a sample vial containing a fixative solution that will prevent the tissue from decaying. The sample vessel is then sent to a laboratory, the tissue sample taken there from the sample vessel, in a cassette, such as. As a so-called Paraform® cassette, and then placed in a dewatering machine (eg the company Sakura). The

Drainage machine includes several baths with different chemicals for drainage and preparation of the tissue sample.

In the dehydrator, the tissue sample cassette is sequentially immersed in the various baths until drainage of the tissue sample is complete. Alternatively, there is also

Automatic drainage systems, where the cassettes remain in one chamber and the liquids in the chamber are exchanged via an inflow and outflow system. Thereafter, the cassette with the tissue sample is placed in a pouring mold and filled with hot, liquid wax. This step of the

Pouring or "blocking" can either be done manually or in a device provided therefor, for example by Sakura with the aid of cuttable biopsy holders, which are known from the patents of Warren P. Williamson et al., US Pat. No. 7,158,814B1, US Pat Sakura company under the name "Tissue-Tek® Paraform® cassette system" sold. The resulting after cooling wax block is then cut with a microtome into thin slices, which are then examined microscopically.

This prior art method of making a wax block containing a tissue sample requires that the tissue sample be first sent to a laboratory, dewatered and processed in a dehydrator, and finally wax impregnated in a pouring mold to produce the wax block. A major disadvantage of the dewatering machine used in this case is that when successively immersing the tissue samples in the individual baths to a

Tissue carryover or cross contamination between different

Tissue samples may come, namely, when tissue parts detach when immersed in a treatment bath from a tissue sample and then attach to the next tissue sample when immersing the next tissue sample in the bathroom again. Besides, it is not possible for each sample process individual drainage protocol, although this would be beneficial for different tissue and sample types. In addition, it is necessary to remove the dewatered tissue sample from the dewatering machine and place it in a pouring mold around the wax block

manufacture. This is relatively expensive.

OBJECT OF THE INVENTION

It is therefore an object of the present invention to provide an apparatus and a method for preparing a tissue sample and in particular for producing a wax block containing a tissue sample, in which a cross contamination between different tissue samples is substantially excluded and which is easy and safe to handle.

This object is achieved according to the invention by the features specified in the independent claims. Further embodiments of the invention will become apparent from the dependent claims.

According to the invention, a device for preparing a tissue sample is proposed, which comprises one or more chambers or containers (hereinafter "container"), in each of which exactly one tissue sample is inserted, and which further comprises a metering device for metering various substances into the containers The device may comprise a plurality of such containers, the container (s) preferably being designed to receive only one single tissue sample, and the device according to the invention is further characterized in that it comprises an emptying device for emptying the container and a control unit is provided. which controls the metering device and the emptying device in such a way that at least one of the substances is metered into the container in several successive cycles and the container is emptied again after a certain period of time the steps: "Dosing Meanwhile, the tissue sample preferably remains in the container or at least is not ported to another container.The capacity of the device can be increased by arranging several of these containers side by side but separately from each other

Cross contamination between different tissue samples is thus in the

Essentially excluded.

The tissue sample can either be inserted directly into the container, or it can first be inserted into a cassette, which is then inserted into the container. In embodiments in which the tissue sample is inserted directly into the container, a lid or intermediate bottom is preferably provided, which covers a chamber in which the tissue sample is located. In addition, a fixing element can be provided with which the tissue sample can be fixed in the chamber. The fixing element is preferably made of an elastic material and may be e.g. a sponge that presses on the tissue sample from above.

According to a special embodiment, the device according to the invention for preparing a tissue sample may contain a camera which is mounted on the

Cassette located data, in particular barcodes, read and this passes on to the control unit. From the control unit can then individual depending on the sample information contained on the barcodes

Processing protocols are processed. Furthermore, these can

Process data to a higher level IT system e.g. Be passed to the laboratory information system.

According to one embodiment of the invention, the emptying z. B. be implemented as a tilting device for automatically tilting the container. In this case, the container (s) are preferably tiltably mounted. The tilting device for the container (s) is preferably controlled in such a way that the container (s) is emptied after each treatment bath. Thereafter, each container is filled with the next substance. Alternatively, the emptying device can also be realized as a closing device for automatically opening or closing the container. In the simplest case, an opening may be provided in the bottom of the container which is automatically opened or closed by means of a closure. According to another embodiment of the invention, a part of the container may also be designed to be movable in order to open or close the container.

According to a further embodiment of the invention, the emptying device can also be used as a suction device for the automatic suction in the

Be realized container contained substance. The emptying device can for this purpose z. B. a proboscis or the like., Which is immersed in the container or from above.

The emptying of a container can be achieved in principle by evaporation of the liquid contained in the container. In a corresponding embodiment in which the liquid contained in the container evaporates, a heating device is preferably provided. The heater in this case acts as the emptying device and is preferably designed so that the liquid contained in the container partially or completely evaporates within a desired time. The heater can, for. B. may be located directly on the container or in the vicinity of the container. You can z. B. arranged under the container or integrated in the container. The heater may be any known in the art, such as, for. B. an electric heater with a heating coil. The heating device can basically be assigned to a single or several containers. Under the above-mentioned emptying device would be understood in this case, the heater with the associated control unit.

Insofar as the process conditions allow, could also on a

Heating device can be dispensed with. In this case, the substance in the container at a given Verdungstungsrate, the lower depends on the temperature and boiling point of the liquid, evaporate by itself. One would then only have to wait a little longer until the next substance can be added. Under the above-mentioned

Emptying would be understood in this case, a control unit, which is able to calculate the evaporation process or to determine the remaining amount of the substance in the container and to determine accordingly a time for refilling the next substance.

In the manufacture of a wax block using the

Evaporation technique, a substance contained in the container can be either completely or partially evaporated until the next substance is added. According to a preferred embodiment, the next substance is already added when there is still a residue of the previous liquid in the container. This remainder of the previous liquid will at least partially continue to evaporate in the following process. The correct time of refilling the new substance can either be calculated or by means of a sensor, eg. B. by weighing, are measured.

According to another embodiment of the invention, it is also possible to empty a container by adding a new liquid by overfilling the container. If enough new liquid is added, the container overflows, and the liquid previously contained in the container is displaced by the newly added liquid or at least sufficiently diluted. According to a corresponding further embodiment of the invention, the emptying device in this case comprises a metering device with a control unit which doses a new liquid into the container until the previous liquid has been substantially completely rinsed out. The overflowing liquid is preferably collected in a container and may possibly be evaporated or otherwise disposed of. The metering device is preferably the same device as described at the beginning. The tissue sample preferably remains in the same container during the entire dewatering process, possibly until completion of the tissue wax block.

The device according to the invention preferably comprises a waste container which receives the substances flowing out of the container. The

Waste container is preferably arranged directly below the container or containers, so that the substances flowing out of the container directly into the

Waste containers fall into it.

The waste container preferably comprises a closable lid, which serves mainly to keep out unpleasant odors. The lid will

preferably automatically operated. For this purpose, for example, a closing device for automatically opening and closing the lid may be provided. The locking device can, for. B. have an electromagnet, which is controlled by the control unit.

The container is preferably dimensioned so large that the tissue sample can be accommodated therein together with a cassette in which the tissue sample is located. To prevent the cassette with the

Tissue sample when emptying the container falls out - for example, if the container is tilted upside down - the container preferably comprises suitable retaining means which prevent falling out of the cassette. In the simplest case, suitable holding means may be a depression at the bottom of the container into which the cassette can be at least partially inserted. Alternatively or additionally, it is also possible to provide latching means, positive-locking holding means or other holding means known from the prior art. According to a preferred embodiment of the invention, the device for preparing a tissue sample is designed both for dewatering the tissue sample and for producing a tissue wax block (hereinafter "wax block"), in which case the wax block is preferably incorporated therein Container prepared in which the tissue sample was previously dehydrated. This offers the advantage that the tissue sample does not have to be converted into any other vessel and the complete manufacturing process can take place within one device.

According to a preferred embodiment of the invention, the container comprises a heating device. The wax in the container can thus be kept liquid until it has completely penetrated into the tissue sample. The heating device is preferably integrated in a bottom of the container, but may also be provided elsewhere. The heater is preferably turned on prior to introduction of wax into the container and turned off after a predetermined time, whereby the wax cools and forms a wax block in which the tissue sample is located.

The metering device according to the invention preferably comprises several

Dosage containers, each containing a specific substance for the chemical

Treatment of the tissue sample and possibly wax for the

 Production of the wax block included. The metering device further comprises one or more drive units for actuating the metering containers. As a result, can each be a small amount of those in the Dosierbehältnissen

Substance be dosed into the container.

To direct the individual substances from the dosing into the container, for example, supply lines, such. As hoses. According to a preferred embodiment of the invention is the

Dosing device but designed so that the ejected from the dosing containers fall directly into the container below. The metering device is in this case directly above the container

arranged or brought into a corresponding position.

The individual dosing containers are preferably in a common

Cartridge integrated. The cartridge can thus as a structural unit in the Device used or removed therefrom.

At least one of the dosing containers preferably comprises wax for the production of the wax block. In order to prevent the wax from hardening, this dosing container preferably comprises a heating device. When

 Heating device can be provided in the simplest case, a heating coil.

Other heating devices are well known in the art.

According to a preferred embodiment of the invention, the device comprises a plurality of containers for receiving tissue samples, whereby it is possible to treat several tissue samples simultaneously. All containers are preferably integrated in a common container unit.

The individual containers can successively or optionally also

be filled simultaneously with the required chemical substances. In the first case, the metering device may comprise a metering unit, which is arranged to be movable and is moved successively from one to the next container. In the second case, each container can also be assigned its own dosing unit, so that the containers can be filled at the same time.

The emptying device is preferably designed such that all containers can be emptied simultaneously or substantially simultaneously. According to a first embodiment, all containers are integrated in a container unit, which is arranged tiltable as a whole. According to a second

Embodiment, each container may include a closing device for opening or closing an opening through which the liquid in the container can be drained. The individual closure devices are preferably activated simultaneously. The container or containers can be dimensioned so that a cassette can only be used edgewise, but not horizontal in the container. For controlling the metering device, the emptying device and optionally the lid of the waste container, a control unit is preferably provided, as is well known from the prior art.

The individual process steps can be accelerated by methods known from the prior art. These include u.a. Vacuum, microwave, ultrasound, agitation, pressure, etc.

The present invention also relates to a method for preparing a tissue sample, wherein the tissue sample is inserted either directly into a container or first in a cassette, and then the cassette is placed in the container in which the tissue sample is treated. According to the invention, only a single tissue sample is inserted per container to a

 To avoid cross-contamination between different tissue samples. After inserting the tissue sample, the following steps are then carried out in successive cycles in order to treat the tissue sample:

 - Dosing at least one chemical substance in the container (4); and - emptying the container (4).

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described by way of example with reference to the accompanying drawings. Show it:

1 shows a side view of a paraform cassette with a tissue sample inserted therein; Fig. 2 is a side view of a container with a heated floor to

Receiving the cassette of Figure 1;

Fig. 3 is a schematic view of an apparatus for processing a

Tissue sample according to an embodiment of the invention; Fig. 4 is a view of the container of Figure 2 in a tilted upside down

Condition and a container disposed under the waste container;

Figure 5 is a side view of a container unit with a plurality of containers, which are pivotally mounted together about an axis.

Fig. 6 is a side view of a container unit with a plurality of containers and an overlying metering device which is adjustable in the horizontal and vertical directions.

Fig. 7a, 7b different views of a container with a movable

Container bottom, which can be opened or closed;

8a, 8b different views of a container with a suction device for sucking the liquid in the container;

9 shows a schematic view of the electronic control belonging to the device according to the invention; and Fig. 10 is a schematic representation of a tissue wax block.

FIG. 1 a shows a simplified side view of the container with the tissue sample 1. The container is filled with a chemical liquid. Fig. 1 1 b shows the same container as Fig. 1 1 a, the liquid level of the chemical liquid is lower than in Fig. 1 1 a.

Fig. 1 1 c shows the same container as Fig. 1 1 a, a further liquid is introduced into the container.

Fig. 12a shows the same container as Fig. 1 1 a, the container is filled with a chemical liquid. Fig. 12b shows the same container as Fig. 12a, it is filled with another liquid and the container overflows. Fig. 12c shows the same container of Fig. 12b, the second liquid has displaced the first liquid largely by overflow / replaced.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

1 shows a side view of a cassette 20 with a tissue sample 1 inserted therein. The cassette 20 may be z. B. is a so-called Paraform® cassette, which consists essentially of a cassette frame 2 and a replaceable bottom inlay or tissue holder 3, in which the tissue sample 1 is arranged. Optionally, however, any other commercially available cassette 20 can be used. The cassette 20 is poured into a wax block in the method described below and cut into thin slices together with the tissue sample 1 therein. Finally, the discs can be examined with the aid of a microscope for possible anomalies or diseases.

FIG. 2 shows a side view of a container 4 with a heated bottom 5 for receiving the cassette 20 of FIG. 1. The container 4 includes in this

 Embodiment, an axis 6, around which it can be pivoted. A liquid contained in the container 4 can thus be easily dumped.

In order to prevent the cassette 20 with the tissue sample 1 from falling out when the container 4 is emptied, for example when the container is tilted upside down, the container 4 comprises holding means which prevent the cassette from falling out. In the illustrated embodiment, the holding means are as

Locking means 7, in particular as locking projections executed. Alternatively or additionally, other known from the prior art holding means may be provided.

3 shows a schematic view of an apparatus for processing a tissue sample 1 according to an embodiment of the invention. The device shown serves to drain the tissue sample 1 and optionally also for producing a fabric wax block 27, as shown by way of example in FIG. 10. The draining of the tissue sample 1 is usually carried out in several successive steps. After draining the

Tissue sample 1 then follows the production of the wax block 27 in a final step.

In the center of Fig. 3, a container 4 is seen with a cassette inserted therein 20, in which the tissue sample 1 is located. The container 4 is pivotally mounted about an axis 6. Above the container 4 is a metering device 10, which comprises a plurality of metering containers 10a-10d. In the illustrated embodiment, only the outlet nozzles can be seen from the dosing containers 10a-10d.

The individual containers 10a-10c each contain a chemical substance for dewatering the tissue sample 1; In addition, the dosing container 10d contains liquid wax for producing a wax block 27.

Each metering container 10a-10d may be assigned its own drive unit (not shown) for actuating the respective metering container 10a-10d. The individual drive units are controlled by a control unit 22, either individually or possibly also several dosing containers 10a-10d at the same time, whereby they release a certain amount of the substance contained therein.

In the illustrated embodiment, the dosing container 10a is actuated, whereby the chemical substance 8 contained therein emerges in droplets and falls into the container 4 arranged directly below.

As already mentioned, the dosing containers 10a-10c each contain a chemical liquid for dewatering the tissue sample 1. In contrast, wax for producing the wax block 27 is located in the dosing container 10d. In order to melt the wax contained in the dosing container 10d or in the liquid To maintain state, a heater 21 is provided which heats the wax. As already mentioned, the container 4 for receiving the tissue sample 1 also comprises a heating device 31 integrated in the bottom 5. With the help of the heater 31, the wax contained in the container 4 is kept liquid until it has completely penetrated the tissue sample 1. Thereafter, the heater 31 is turned off, whereby the wax cools and solidifies into a wax block 27, as shown in Fig. 10.

A tilting device for tilting the container 4 is schematically with the

Reference numeral 24 denotes. The tilting device 24 is a first one

It may, for example, have an electric drive which actuates a lever provided on the container 4, whereby the container 4 pivots about the axis 6.

Below the container 4 is a waste container 1 1 with a

Closable lid 13. During the manufacture of the tissue wax block 27, the container 4 is preferably emptied several times by tilting the container 4. The effluent from the container 4 liquids then land in the waste container below 1 1 and are collected there. A closing device for the cover 13 controls the opening and closing of the cover 13. For emptying, the container 4 is preferably tilted by at least 90 degrees and in particular by at least 120 degrees.

To produce a tissue wax block 27 by means of a

The apparatus according to the invention can be used, for example, to carry out the following method: After the removal of a tissue sample 1, it is placed in a cassette 20, which is then placed in the container 4 of the device

is entered. The entire production process of the block may optionally be carried out at the site of tissue removal. If necessary, a cartridge with a plurality of metering containers 10a-10d is inserted into the metering device 10, in which the for the production

necessary chemicals are included. The device is then started via a start button, whereby various steps are processed sequentially. In a first step, the first metering container 10a is actuated, which is filled, for example, with an aqueous formalin solution (for example 10% formalin). As a result, the formalin solution is pressed out of the dosing container 10a and runs into the container 4 arranged thereunder with the tissue sample 1 located therein. This is followed by a waiting period of

for example, 30 minutes. The container 4 is then tilted by, for example, 90 degrees or more, causing the liquid therein to flow from the container 4 into the waste container 11 below. The lid 13 of

Waste container 1 1 is doing automatically, for example, with the help of a

Electromagnet opened and closed again after a predetermined period of time.

In a second step, the second dosing container 10b is then actuated, which is filled, for example, with ethanol, whereby the ethanol liquid is pressed out of the dosing container 10b and flows into the container 4 located thereunder with the tissue sample 1 located therein. This is followed by a waiting time of, for example, 30 minutes, in which the ethanol liquid acts.

After the waiting time, the container 4 is tilted again, so that the liquid therein flows out and flows into the underlying waste container 1 1 inside. The lid 13 of the waste container 1 1 is in turn opened by means of the locking device and again after a predetermined time

closed.

In a third working phase, the third dosing container 10c is actuated, which is filled, for example, with xylene or a xylene substitute. This occurs one corresponding amount of the liquid from the metering container 10c and flows into the container 4 disposed thereunder with the tissue sample 1 therein. This is followed by a waiting period of, for example, 30 minutes in which the

Liquid can act on the tissue sample 1.

After the waiting time, the container 4 is tilted again, whereby the liquid runs out of the container 4 and flows into the waste container 1 below 1. The lid 13 of the refuse container 1 1 is in turn opened by means of the closing device and closed again after a predetermined time. The process of dewatering the tissue sample 1 is complete.

Hereinafter, the heating device 21 for heating the

Dosagebehältnisses 10d heated to about 70 ° C. This will do that in the

Dosage container 10d wax contained liquid, so that it can be dosed.

In a fourth working phase then the fourth metering container 10d

controlled, which is filled with liquid wax (paraffin). Thereby, the liquid wax in the correct amount from the dosing container 10d

pushed out and flows into the underlying container 4, in which the tissue sample 1 is located. This is followed by a waiting time of, for example, 30 minutes during which the wax can penetrate into the tissue sample 1. In addition, the arranged in the container 4 heater is heated. The individual steps described here by way of dosing and

 Emptying can also be performed several times in succession, e.g. to obtain a rinsing effect or to supply chemicals.

After the waiting time, the two heaters are turned off and a cooling system (not shown), such as a ventilation, turned on, whereby the wax contained in the container 4 is solidified into a wax block 27. After a predetermined period of time, for example, goes a green LED and signals the user that the tissue wax block 27 is now ready to be removed.

Fig. 4 shows the apparatus for processing a tissue sample 1 of Fig. 3 in a state in which the container 4 is tilted upside down. The liquid contained in the container 4 flows out of the container 4 and falls directly into the underlying waste container 1 1 (see drop 14). To avoid that

Liquid drips next to the waste container 1 1, this has at its upper end a collecting funnel 12. The lid 13 is open and is closed again after the dumping of the liquid. The collected in the waste container 1 1

Liquid is designated by the reference numeral 15. 5 shows a top view of a container unit with a plurality of containers 4, in each of which a cassette 20 with a tissue sample 1 is inserted. The

Container unit is pivotable as a whole about an axis 6. Such

Container unit has the advantage that all containers 4 can be emptied simultaneously.

6 shows a side view of a container unit with a plurality of containers 4 and a metering device 10 arranged above it, which is adjustable in a horizontal plane (directions x, y) and in a vertical direction (z). An associated drive unit for the metering device 10 is not shown.

FIGS. 7a and 7b show different views of a container 4 with a second variant of the emptying device 23. In the example shown, the emptying device 23 comprises a movable container bottom 17, which is pivotally mounted via a hinge 16 and can be opened or closed to the container 4 to empty. This mechanism is one possible embodiment of a closure device 25 for automatically opening or closing the container 4. The container 4 is also designed so that the cassette 20 does not fall out when the container bottom 17 is opened. For this purpose, z. B. suitable projections or locking means may be provided. Fig. 8a and 8b show different views of a container 4 with a

Suction device 18 for sucking the liquid in the container 4. The suction device 18 is another possibility of a general

In this case, Figure 8a shows a state in which the suction device 18 is disposed above the container 4, and Figure 8b shows a state in which the suction device 18 is immersed in the container 4 and sucks liquid. The aspirated liquid is designated by the reference numeral 19. Fig. 9 is a schematic view of belonging to the device according to the invention electronic control unit 22. As can be seen, is the

Control unit 22 with the metering device 10, the emptying device 23 and the drive of the lid 13 of the waste container 1 1 and possibly also with a

Heating device 31 in conjunction and is able to control the said units according to user specifications. The process sequence for producing a tissue wax block 27 can be effected by means of a software application

be set user-specifically. The user can make the desired settings on an input unit (not shown). 10 shows a schematic representation of a tissue wax block 27 with a cuttable paraform tissue holder 3 enclosed therein and a thin wax layer 28 adjacent thereto. The wax layer 28 is formed between tissue holder 3 and the container 4, which also serves as a pouring mold in the last process step. As can be seen from the stepped course of the wax layer 28, in this case a container 4 with a corresponding stepped bottom contour was used.

FIGS. 11a-11c show various states of a container 4 in a special method for producing a tissue wax block 27, in which the container 4 is heated, so that the liquid contained therein evaporates. For this purpose, a heating device 31 is arranged below the container 4, with which the substance located in the container 4 8 can be heated. The heating device 31 together with an associated control unit 22 forms in this case a variant of the emptying device 23 mentioned above.

The container 4 is trough-shaped in this embodiment and comprises a first chamber 32 which is formed at the bottom of the trough-shaped container 4, and an overlying second chamber 33 which has a larger volume than the first chamber 32. The container 4 further includes an intermediate bottom 35, which spatially separates the first and second chambers 32, 33 from each other, wherein the intermediate bottom has at least one opening through which a fluid exchange between the two chambers 32, 33 can take place. The tissue sample 1 is disposed in the first chamber 32 and is fixed therein by a sponge 34 or the like.

The intermediate bottom 35 may, for. B. be designed as a lid, so that the first chamber 32 can be opened or closed. The intermediate bottom 35 or the opening closable therewith is preferably in this case

dimensioned so that a tissue sample 1 from above, through the second chamber 33 through, can be inserted into the first chamber 32.

In Fig. 11a, the container 4 is almost filled to the upper edge with a substance 8 or liquid. The control unit 22 controls the heating device 31 in such a way that the liquid contained in the container (s) 4 evaporates at the desired speed. The evaporation rate can z. B. be set on the heating power. In Fig. 1 1 b, the liquid level has already dropped to about half.

After a certain waiting time, the next substance 8 is metered into the container 4 or the cassette 20, and preferably in a state in which there is still residual liquid in the container 4 (see Figures 1 1 b, c). The rest of the previous liquid will then continue to evaporate in the following process. Because it is a controlled evaporation process with known parameters the correct time to refill can be calculated quite well. Optionally, the right moment for the addition of the new substance 8 by means of a sensor, for. B. by weighing, are measured.

Since the boiling pots of the chemicals or substances 8 used in the process increase from step to step, it would even be possible to manage without an additional heating device 31. In this case, you would fill the first substance 8 and then wait a while until only so much of the first substance 8 is present that the next substance 8 can be post-dosed. The waiting time depends among other things on the temperature and the

Boiling point of the respective substance 8 from. After the waiting time, there is only so little remaining liquid that it evaporates completely or at least almost completely in the subsequent process. The correct time of refilling can either be calculated or measured by a sensor. FIGS. 12a-12c show various states of a container 4 at a

Method for producing a fabric wax block 27, in which the container 4 is overfilled by the addition of a new liquid. If enough new liquid is added, the container 4 runs over, and so far in the

Container 4 liquid is displaced by the newly added liquid or at least sufficiently diluted. In this case, the control unit 22 controls the metering device 10 such that the latter

Liquid so long in the or the container 4 dosed until the previous

Liquid was rinsed out substantially completely. The overflowing liquid is preferably collected in a container.

The individual embodiments of the emptying device 23 and des

Discharging can be combined in any way, as far as the expert considers appropriate.

Claims

claims 1 . Device (1) for processing a tissue sample (1), comprising a container (4), in which a tissue sample (1) is inserted, and a  Dosing device (10) for dosing chemical substances (8) into the container (4), characterized in that  - The container (4) for receiving a single tissue sample (1) is designed, - The device (1) an emptying device (23) for emptying the container (4);  - And that a control unit (22) is provided which is adapted to the dosing device (10) and the emptying device (23) to control so that in several successive cycles each at least one of Substances (8) are metered into the container (4) and the container (4) is emptied again after a certain period of time. 2. Device (1) according to claim 1, characterized in that the emptying device (23) is realized as a tilting device (24) for automatic tilting of the container (4). 3. Device (1) according to claim 1, characterized in that the emptying device (23) is realized as a closing device (25) for automatically opening or closing the container (4). 4. Device (1) according to claim 1, characterized in that the emptying device (23) is realized as a suction device (18) for automatically sucking off the substance contained in the container (4). 5. Device (1) according to one of the preceding claims, characterized in that at least one waste container (11) is provided which receives the substances flowing out of the container (4). 6. Device (1) according to claim 5, characterized in that the waste container (1 1) has a closable lid (1 3). 7. Device (1) according to claim 6, characterized in that a closing device for automatically opening and closing the lid (13) is provided. 8. Device (1) according to one of the preceding claims, characterized in that a heating device (31) is provided with which the substances (8) located in the container can be evaporated. 9. Device (1) according to one of the preceding claims, characterized in that the container (4) is adapted to receive a tissue sample or a cassette (20) together with the tissue sample (1), and further comprising holding means which are designed so that the tissue sample or the cassette (20) with the Tissue sample does not fall out of the container (4) when the container (4) is emptied. 10. Device (1) according to claim 9, characterized in that the holding means comprise a latching device (7). 1 1. Device (1) according to one of the preceding claims, characterized in that the metering device (10) comprises a plurality of metering containers (10a-10d) each containing a specific substance. 12. Device (1) according to one of the preceding claims, characterized in that the metering device (10) comprises a plurality of metering containers (10a-10d), of which at least one is filled with a substance for draining the tissue sample (1) and at least one other with wax. 13. Device (1) according to one of the preceding claims, characterized in that the metering device (10) comprises a plurality of metering containers (10a-10d), wherein the metering containers (10a-10b) are integrated in a common cartridge. 14. Device (1) according to one of the preceding claims, characterized in that the metering device (10) comprises a plurality of metering containers (10a-10d), and in that a heating device (21) for heating at least one of Dosage containers (10a-10d) is provided. 15. Device (1) according to one of the preceding claims, characterized in that it includes a camera that can read codes located on the cassettes (20) and that the control unit (22) is arranged to process an individual drainage protocol depending on the information contained on the codes. 16. Device (1) according to one of the preceding claims, characterized in that it comprises a plurality of containers (4) into each of which a single tissue sample (1) is inserted, 17. Device (1) according to claim 1 6, characterized in that the metering device (10) is movably arranged so that it can be successively moved from one to the next container (4). 18. A method for preparing a tissue sample (1), characterized by the following steps:  - Inserting a plurality of tissue samples (1) in a plurality of containers (4), wherein in each case one of the tissue samples (1) in each one of the container (4) is inserted;  - after which the following steps are carried out in several consecutive cycles:  Dosing at least one chemical substance (8) into the individual containers (4); and  Emptying the container (4).