DEVICE FOR PREPARING A TISSUE SAMPLE AND PARTICULARLY FOR PRODUCING A WAX BLOCK CONTAINING A TISSUE SAMPLE

Abstract

The invention relates to an apparatus (1) for producing a wax block containing a tissue sample (1), comprising: a container (4) into which the tissue sample (1) is placed; and a dispensing apparatus (10) for dispensing different substances (8) into the container (4). The apparatus (1) according to the present invention is notable for the fact that it comprises an emptying device (23) for emptying the container (4); and a control unit (22) is provided, which is designed to apply control to the dispensing apparatus (10) and to the emptying device (23) in such a way that in several successive cycles, at least one of the substances is respectively dispensed into the container (4) and the container (4) is emptied again after a specific time period.

Claims

1. An apparatus for processing a tissue sample (1), comprising: a container (4) into which a tissue sample (1) is placed; and a dispensing apparatus (10) for dispensing chemical substances (8) into the container (4), wherein the container (4) is designed to receive a single tissue sample (1); the apparatus comprises an emptying device (23) for emptying the container (4); and a control unit (22) is provided, which is designed to apply control to the dispensing apparatus (10) and to the emptying device (23) in such a way that in several successive cycles, at least one of the substances (8) is respectively dispensed into the container (4) and the container (4) is emptied again after a specific time period.

2. The apparatus according to claim 1, wherein the emptying device (23) is implemented as a tilting device (24) for automatically tilting the container (4).

3. The apparatus according to claim 1, wherein the emptying device (23) is implemented as a closure device (25) for automatically opening or closing the container (4).

4. The apparatus according to claim 1, wherein the emptying device (23) is implemented as an aspiration device (18) for automatic aspiration of the substance contained in the container (4).

5. The apparatus according to claim 1, wherein a waste container (11), which receives the substances flowing out of the container (4), is provided.

6. The apparatus according to claim 5, wherein the waste container (11) comprises a closable cover (13).

7. The apparatus according to claim 6, wherein a closing apparatus for automatically opening and closing the cover (13) is provided.

8. The apparatus according to claim 1, wherein a heating apparatus (31), with which the substances (8) present in the container can be evaporated, is provided.

9. The apparatus according to claim 1, wherein the container (4) is designed to receive a tissue sample or a cassette (20) together with the tissue sample (1), and further comprises holding means that are configured so that the tissue sample, or the cassette (20) having the tissue sample, does not fall out of the container (4) when the container (4) is emptied.

10. The apparatus according to claim 9, wherein the holding means comprise a latching device (7).

11. The apparatus according to claim 1, wherein the dispensing apparatus (10) comprises several dispensing vessels (10a to 10d) that each contain a specific substance.

12. The apparatus according to claim 1, wherein the dispensing apparatus (10) comprises several dispensing vessels (10a to 10d), of which at least one dispensing vessel is filled with a substance for dehydrating the tissue sample (1) and at least one other dispensing vessel is filled with wax.

13. The apparatus according to claim 1, wherein the dispensing apparatus (10) comprises several dispensing vessels (10a to 10d), the dispensing vessels (10a to 10b) being integrated into one common cartridge.

14. The apparatus according to claim 1, wherein the dispensing apparatus (10) comprises several dispensing vessels (10a to 10d); and a heating apparatus (21) for heating at least one of the dispensing vessels (10a to 10d) is provided.

15. The apparatus according to claim 9, wherein the apparatus comprises a camera that can read codes present on the cassettes (20); and the control unit (22) is configured so that the control unit (22) executes an individual dehydration protocol as a function of information contained in the codes.

16. The apparatus according to claim 1, wherein the apparatus comprises several containers (4) into each of which a single tissue sample (1) is placed.

17. The apparatus according to claim 16, wherein the dispensing apparatus (10) is arranged movably, so that the dispensing apparatus (10) can be moved successively from one container (4) to another container (4).

18. A method for processing a tissue sample (1), comprising the following steps: placing several tissue samples (1) into several containers (4), each one of the tissue samples (1) being respectively placed into one of the containers (4); after which, in several successive cycles, the following steps are respectively performed: dispensing at least one chemical substance (8) into the individual containers (4); and emptying the containers (4).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The invention will be explained in further detail below, by way of example, with reference to the attached drawings, in which:

[0040] FIG. 1 is a side view of a Paraform cassette having a tissue sample placed therein;

[0041] FIG. 2 is a side view of a container having a heated base, for receiving the cassette of FIG. 1;

[0042] FIG. 3 is a schematic view of an apparatus for processing a tissue sample, in accordance with an embodiment of the invention;

[0043] FIG. 4 is a view of the container of FIG. 2 in an upside-down tilted state, and of a waste container arranged below the container;

[0044] FIG. 5 is a side view of a container unit having several containers that are mounted tiltably collectively around an axis;

[0045] FIG. 6 is a side view of a container unit having several containers, and of a dispensing apparatus arranged thereabove which is displaceable in a horizontal and a vertical direction;

[0046] FIGS. 7a, 7b are various views of a container having a movable container base that can be opened or closed;

[0047] FIGS. 8a, 8b are various views of a container having an aspiration device for aspirating the liquid present in the container;

[0048] FIG. 9 is a schematic view of the electronic controller pertaining to the apparatus according to the present invention;

[0049] FIG. 10 schematically depicts a tissue wax block;

[0050] FIG. 11a is a simplified side view of the container having tissue sample 1 wherein the container is filled with a chemical liquid;

[0051] FIG. 11b shows the same container as FIG. 11a, wherein the liquid level of the chemical liquid is lower than in FIG. 11a;

[0052] FIG. 11c shows the same container as FIG. 11a, wherein a further liquid is being introduced into the container;

[0053] FIG. 12a shows the same container as FIG. 11a, wherein the container is being filled with a chemical liquid;

[0054] FIG. 12b shows the same container as FIG. 12a, wherein a further liquid is being introduced and the container is overflowing; and

[0055] FIG. 12c shows the same container as FIG. 12b; the second liquid has very largely displaced or replaced the first liquid via overflow.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0056] FIG. 1 is a side view of a cassette 20 having a tissue sample 1 placed thereinto. Cassette 20 can be, for example, a so-called Paraform cassette that substantially comprises a cassette frame 2 and a replaceable base inlay or tissue holder 3 in which tissue sample 1 is arranged. Optionally, however, any other commercially usual cassette 20 can be used. In the method described below, cassette 20 is embedded into a wax block and sectioned into thin slices together with tissue sample 1 present therein. Lastly, the slices can be investigated with the aid of a microscope for possible anomalies or diseases.

[0057] FIG. 2 is a side view of a container 4 having a heated base 5 for receiving cassette 20 of FIG. 1. In this embodiment, container 4 comprises a shaft 6 around which it can be pivoted. A liquid present in container 4 can thus easily be tipped out.

[0058] In order to prevent cassette 20 having tissue sample 1 from falling out when container 4 is emptied, for example if the container is tipped upside down, container 4 comprises holding means that prevent the cassette from falling out. In the exemplifying embodiment depicted, the holding means are embodied as latching means 7, in particular as latching protrusions. Alternatively or additionally, other holding means known from the existing art can also be provided.

[0059] FIG. 3 is a schematic view of an apparatus for processing a tissue sample 1, in accordance with an embodiment of the invention. The apparatus that is depicted serves to dehydrate tissue sample 1 and, if applicable, also to produce a tissue wax block 27 that is depicted by way of example in FIG. 10. Dehydration of tissue sample 1 is accomplished as a rule in several successive steps. Once tissue sample 1 has been dehydrated, wax block 27 is then produced in a final working step.

[0060] Visible at the center of FIG. 3 is a container 4 having, inserted thereinto, a cassette 20 in which tissue sample 1 is located. Container 4 is mounted pivotably around a shaft 6. Located above container 4 is a dispensing apparatus 10 that comprises several dispensing vessels 10a to 10d. In the exemplifying embodiment depicted, only the exit nozzles of dispensing vessels 10a to 10d are visible.

[0061] The individual vessels 10a to 10d each contain a chemical substance for dehydrating tissue sample 1; dispensing vessel 10d furthermore contains liquid wax for producing a wax block 27.

[0062] Each dispensing vessel 10a to 10d can have a separate drive unit (not shown) associated with it, for actuation of the respective dispensing vessel 10a to 10d. The individual drive units have control applied to them by a control unit 22, either each individually or, as applicable, several dispensing vessels 10a to 10d simultaneously, with the result that they deliver a specific quantity of the substance contained therein.

[0063] In the exemplifying embodiment depicted, dispensing container 10a is being actuated, with the result that chemical substance 8 contained therein emerges dropwise and falls into container 4 arranged directly below.

[0064] As already mentioned, dispensing vessels 10a to 10c each contain a chemical liquid for dehydrating tissue sample 1. Dispensing vessel 10d, conversely, contains wax for producing wax block 27. A heating apparatus 21, which heats the wax, is provided In order to melt the wax contained in dispensing vessel 10d or to keep it in the liquid state.

[0065] As mentioned, container 4 for receiving tissue sample 1 likewise comprises a heating apparatus 31 integrated into base 5. With the aid of heating apparatus 31, the wax present in container 4 is kept liquid until it has completely infiltrated into tissue sample 1. Heating apparatus 31 is then switched off, with the result that the wax cools and solidifies into a wax block 27, as illustrated in FIG. 10.

[0066] A tilting device for tilting container 4 is labeled schematically with the reference character 24. Tilting device 24 is a first variant embodiment of a general emptying device 23 for emptying container 4. It can comprise, for example, an electrical drive system that actuates a lever provided on container 4, with the result that container 4 pivots around shaft 6.

[0067] A waste container 11 having a closable cover 13 is located below container 4. Container 4 is preferably emptied several times, by tilting container 4, during the production of tissue wax block 27. The liquids flowing out of container 4 then land in waste container 11 arranged below, and are collected there. A closing apparatus for cover 13 controls the opening and closing of cover 13. For emptying, container 4 is tilted preferably at least 90 degrees and in particular at least 120 degrees.

[0068] The following method, for example, can be carried out in order to produce a tissue wax block 27 with the aid of an apparatus according to the present invention: Once a tissue sample 1 has been taken, it is placed into a cassette 20 that is then introduced into container 4 of the apparatus. The entire production process for the block can be carried out, if applicable, at the location where the tissue is sampled.

[0069] If necessary, a cartridge having several dispensing vessels 10a to 10d in which the chemicals necessary for production are contained, is placed into dispensing apparatus 10. The apparatus is then started via a start button, with the result that various working steps are executed in succession. In a first step, first dispensing vessel 10a, which is filled e.g. with an aqueous formalin solution (for example, 10% formalin), is actuated. As a result, the formalin solution is expelled from dispensing vessel 10a and runs into container 4, arranged therebelow, having tissue sample 1 present therein. A delay time of, for example, 30 minutes then follows. Container 4 is then tilted, for example, 90 degrees or more with the result that the liquid present therein flows out of container 4 into waste container 11 present therebelow. Cover 13 of waste container 11 is, in this context, automatically opened, for instance with the aid of an electromagnet, and closed again after a predefined period of time.

[0070] In a second step, second dispensing vessel 10b, which is filled e.g. with ethanol, is then actuated, with the result that the liquid ethanol is expelled from dispensing vessel 10b and flows into container 4, arranged therebelow, having tissue sample 1 present therein. A delay time of, for example, 30 minutes, in which the liquid ethanol acts, then follows.

[0071] Once the delay time has elapsed, container 4 is tilted again so that the liquid present therein flows out and drops into waste container 11 present therebelow. Cover 13 of waste container 11 is once again opened by means of the closing apparatus, and closed again after a predefined time.

[0072] In a third working phase, third dispensing vessel 10c, which is filled e.g. with xylene or a xylene substitute, is actuated. As a result, a corresponding quantity of the liquid emerges from dispensing vessel 10c and flows into container 4, arranged therebelow, having tissue sample 1 present therein. This is then followed by a delay time of, for example, 30 minutes in which the liquid can penetrate into tissue sample 1.

[0073] Once the delay time has elapsed, container 4 is once again tilted, with the result that the liquid runs out of container 4 and flows into waste container 11 located therebelow. Cover 13 of waste container 11 is once again opened with the aid of the closing apparatus, and closed again after a predefined time. The procedure for dehydrating tissue sample 1 is thereby complete.

[0074] Heating apparatus 21 is then heated to approximately 70 C. in order to heat up dispensing vessel 10d. The result is that the wax contained in dispensing vessel 10d becomes liquid so that it can be dispensed.

[0075] In a fourth working phase, control is then applied to fourth dispensing vessel 10d, which is filled with liquid wax (paraffin). The result is that the correct quantity of liquid wax is forced out of dispensing vessel 10d and flows into container 4, arranged therebelow, in which tissue sample 1 is located. A delay time of, for example, 30 minutes, in which the wax can penetrate into tissue sample 1, then follows. The heating apparatus arranged in container 4 is also heated up.

[0076] The individual dispensing and emptying steps described here by way of example can also each be carried out several times in succession, for example in order to obtain a rinsing effect or to deliver chemicals.

[0077] Once the delay time has elapsed, the two heating apparatuses are switched off and a cooling system (not shown), for example a ventilation system, is switched on, with the result that the wax present in container 4 solidifies into a wax block 27. After a predefined period of time has elapsed, for example, a green LED lights up and signals to the user that tissue wax block 27 is now complete and can be removed.

[0078] FIG. 4 shows the apparatus for processing a tissue sample 1 of FIG. 3, in a state in which container 4 is tipped upside down. The liquid contained in container 4 flows out of container 4 and drops directly into waste container 11 located therebelow (see droplets 14). Waste container 11 has a collection funnel 12 at its top end in order to prevent liquid from dripping along said container. Cover 13 is has been opened, and will be closed again after the liquid is tipped out. The liquid collected in waste container 11 is labeled with the reference character 15.

[0079] FIG. 5 is a view from above of a container unit having several containers 4 into each of which a cassette 20 having a tissue sample 1 is placed. The container unit is pivotable as a whole around a shaft 6. The advantage of such a container unit is that all the containers 4 can be emptied simultaneously.

[0080] FIG. 6 is a side view of a container unit having several containers 4 and a dispensing apparatus 10 that is arranged thereabove and is displaceable in a horizontal plane (X, Y directions) and in a vertical direction (Z). A pertinent drive unit for dispensing apparatus 10 is not depicted.

[0081] FIGS. 7a and 7b are different views of a container 4 having a second variant of emptying device 23. In the example depicted, emptying device 23 comprises a movable container base 17 that is mounted pivotably via a pivot joint 16 and can be opened or closed in order to empty container 4. This mechanism is one possible embodiment of a closure device 25 for automatically opening or closing container 4. Container 4 is furthermore designed so that cassette 20 does not fall out when container base 17 is opened. Suitable projections or latching means, for example, can be provided for this purpose.

[0082] FIGS. 8a and 8b are various views of a container 4 having an aspiration device 18 for aspirating the liquid present in container 4. Aspiration device 18 is a further possibility for a general emptying device 23 for emptying container 4. FIG. 8a shows a state in which aspiration device 18 is arranged above container 4, and FIG. 8b a state in which aspiration device 18 is immersed into container 4 and is aspirating liquid. The aspirated liquid is labeled with the reference character 19.

[0083] FIG. 9 is a schematic view of electronic control unit 22 pertinent to the apparatus according to the present invention. As is evident, control unit 22 is connected to dispensing apparatus 10, to emptying device 23, and to the drive system of cover 13 of waste container 11, and optionally also to a heating apparatus 31, and is capable of applying control to those units according to user stipulations. The process sequence for producing a tissue wax block 27 can be adjusted in user-specific fashion by means of a software application. The user can perform his or her desired settings on an input unit (not shown).

[0084] FIG. 10 schematically depicts a tissue wax block 27 having an enclosed sectionable Paraform tissue holder 3 and a thin wax layer 28 adjacent thereto. Wax layer 28 is produced between tissue holder 3 and container 4, which also serves as a base mold in the last process step. As is evident from the stepped profile of wax layer 28, in this case a container 4 having a corresponding step-shaped base contour was used.

[0085] FIGS. 11a to 11c show various states of a container 4 in the context of a special method for producing a tissue wax block 27 in which container 4 is heated so that the liquid contained therein evaporates. A heating apparatus 31, with which substance 8 present in container 4 can be heated, is provided for this purpose below container 4. Heating apparatus 31, together with a pertinent control unit 22, constitutes in this case a variant of emptying device 23 recited earlier.

[0086] In this exemplifying embodiment, container 4 is embodied in a trough shape and comprises a first chamber 32 that is embodied at the base of trough-shaped container 4, as well as a second chamber 33, located thereabove, which has a larger volume than first chamber 32. Container 4 furthermore contains a partition 35 that physically separates first and second chambers 32, 33 from one another, the partition having at least one opening through which a fluid exchange can take place between the two chambers 32, 33. Tissue sample 1 is arranged in first chamber 32 and is immobilized therein by way of a sponge 34 or the like.

[0087] Partition 35 can be embodied, for example, as a cover, so that first chamber 32 can be opened or closed. Partition 35, or the opening that can be closed off therewith, is in this case preferably dimensioned so that a tissue sample 1 can be placed from above, through second chamber 33, into first chamber 32.

[0088] In FIG. 11a, container 4 is filled almost to the top edge with a substance 8 or liquid. Control unit 22 applies control to heating apparatus 31 in such a way that the liquid contained in container or containers 4 evaporates at the desired speed. The evaporation rate can be adjusted, for example, by way of the heating output. In FIG. 11b the liquid level has already dropped approximately by half.

[0089] After a specific delay time, the next substance 8 is dispensed into container 4 or cassette 20, preferably in a state in which residual liquid is still present in container 4 (see FIGS. 11b, c). The residue of the previous liquid will then be further vaporized in the next process. Because the evaporation process is a controlled one with known parameters, the correct point in time for refilling can be calculated quite well. Optionally, the correct moment for adding the new substance 8 can also be measured by means of a sensor, e.g. by weighing.

[0090] Because the boiling points of the chemicals or substances 8 used in the process increase from one step to the next, it would in fact be possible to do without an additional heating apparatus 31. In this case, first substance 8 would be introduced and there would then be a certain delay until the quantity of the first substance 8 that is present is only so much that the next substance 8 can be dispensed after it. The delay time depends, among other factors, on the temperature and the boiling point of the respective substance 8. After the delay time, the amount of residual liquid that is present is so small that it completely, or at least almost completely, vaporizes in the subsequent process. Once again, the correct point in time for topping up either can be calculated or can be measured by means of a sensor.

[0091] FIGS. 12a to 12c show various states of a container 4 in the context of a method for producing a tissue wax block 27 in which container 4 is overfilled by adding a new liquid. When sufficient new liquid has been dispensed in, container 4 overflows and the liquid hitherto present in container 4 is displaced, or at least sufficiently diluted, by the new liquid dispensed in. In this case control unit 22 applies control to dispensing apparatus 10 in such a way that the latter dispenses the new liquid into container or containers 4 until the previous liquid has been substantially completely rinsed out. The overflowing liquid is preferably collected in a container.

[0092] The individual embodiments of emptying device 23 and of the emptying method can be combined in any manner to the extent deemed useful by one skilled in the art.