EP2249966B1 - Container for the preparation, preservation and storage of biological samples using a drying agent - Google Patents

Description

The invention relates to a device for obtaining, preserving and storing sample material in which a sample container for biological sample material is used.

Generic devices are for example from the EP 1 088 212 known. The device described therein is integrated into an ear tag for animals and has a sample extraction means and a sample container.

Usually, biological sample material is not processed directly after its recovery. In some cases, the sample material should be stored after its recovery only for a possible later work-up. In other cases, routine downstream processing is routinely performed, with the interval between recovery and processing being dependent on a number of logistical and other factors.

It should be noted that eg biological tissue samples use decomposition processes immediately after extraction, the degree of which depends, inter alia, on the moisture content of the sample. If, for example, a large number of samples are initially collected from animals and these are sent to the laboratory only after a certain period of time, storage of the sample material obtained without preservation in the form of drying, cooling, etc. can lead to a considerable percentage of the sample material obtained no longer usable for further processing.

In this context is from the DE 199 57 861 a sample container has become known, in which a hygroscopic substance is contained as a drying agent. This known sample container allows a direct preservation of the sample material at the extraction site, in particular, the protein and nucleic acid components are stabilized. Further sample containers are from the US 4865813 , of the US 4073693 and the US 2007/0297939 known.

A problem with the known sample containers is that sample material received in the sample container, e.g. in the context of an automated removal of the sample material from the sample container, can mix with the desiccant, which can be particularly disturbing in the subsequent workup.

The object of the invention is therefore, starting from the state of the art, to provide a device with a sample container which avoids the mentioned disadvantages and which can be obtained in a particularly simple manner in e.g. integrate an ear tag.

The problem is solved with a device having the characterizing features of claim 1.

• einen Probenbehälter für biologisches Probenmaterial auf, der einen durchdringbaren Deckel aufweist und
• ein Probengewinnungsmittel, das mit seinem einen unteren Ende durch den durchdringbaren Deckel des Probenbehälters hindurch in diesen führbar ist, wobei das untere Ende dann in dem Probenbehälter in definierter Position oberhalb und im Abstand zu der oberen Öffnung des Probenkompartiments angeordnet ist, und an dem unteren Ende des Probengewinnungsmittels eine Schneid- oder Stanzeinrichtung vorgesehen ist, mit der sich insbesondere bei Durchführen des unteren Endes durch Gewebe eine Probe gewinnen lässt und wobei

die Position der Schneid- oder Stanzeinrichtung an dem unteren Ende des Probengewinnungsmittels und die obere Öffnung des Probenkompartimentes in dem Probenbehälter so aufeinander abgestimmt sind, dass sich eine mit der Schneid- oder Stanzeinrichtung gewonnene Probe nach Einsetzen des Probengewinnungsmittels in dem Probenbehälter oberhalb des Probenkompartiments befindet bzw. in jenen fällt.The inventive device for the recovery and storage of biological sample material has

• a sample container for biological sample material, which has a penetrable lid and
• a sample extraction means, which is feasible with its one lower end through the penetrable lid of the sample container into this, the lower end then in the sample container in defined Position is arranged above and at a distance from the upper opening of the sample compartment, and at the lower end of the sample collection means a cutting or punching means is provided, with which in particular when passing the lower end through tissue, a sample can be obtained and

the position of the cutting or punching device at the lower end of the sample collection means and the upper opening of the sample compartment in the sample container are coordinated so that a sample obtained with the cutting or punching device is located above the sample compartment after insertion of the sample extraction means in the sample container; in those falls.

The sample container provided in the device according to the invention has an upper opening, which can be closed by a lid, as well as a lateral wall area and a floor. The inside of the sample container contains a hygroscopic substance for drying sample material. Furthermore, the sample container is divided into at least two compartments, one of which (sample compartment) can receive the sample, for example, and the other is a drying compartment containing the hygroscopic substance. The hygroscopic substance is in vapor exchange connection to the interior of the sample container and possibly of the sample compartment.

By vapor exchange compound is meant that the moisture exiting the sample material can be taken up by the hygroscopic substance. The properties and amount of the hygroscopic substance are matched to the desired drying effect or the sample material to be dried. The selection of suitable substances and their dosage is not a problem for the skilled person and will not be explained further here.

According to the invention, it is provided that the sample compartment has an upper opening provided in its upper end, which faces the opening of the sample container. The sample compartment extends downwardly from its upper end longitudinally of the opening to the bottom of the sample container, where, as described below, the bottom of the sample container may have an opening in the region of the sample compartment. The opening in the upper end of the sample compartment may then be e.g. be closed by a penetrable lid or wall area.

The terms sample compartment and drying compartment are to be understood broadly.

The sample compartment may e.g. include an area where sample material is stored for storage. Covered but is also an area with term, which only serves to guide the sample material during its removal from the sample container for further processing. Finally, the sample compartment may already contain reagents that allow the sample material to be worked up. These different possibilities are explained in detail below.

The term drying compartment is also very broad. It may be a by z. B. separated by a wall area in the interior of the sample container act, is arranged in the hygroscopic substance. Enclosed by the term drying compartment but also in the interior of the sample container arranged or formed moldings with hygroscopic properties.

Of course, it is also conceivable that, in particular, the drying compartment is subdivided into further compartments. You could, for example, introduce compartments with different hygroscopic substances or properties that may be better adapted to specific drying requirements.

In contrast to the prior art, according to the invention, a region extending in the longitudinal direction through the sample container, that is to say from its opening to its base opposite the opening, is provided which is free of hygroscopic substance. This is particularly advantageous in the automated removal of the sample by means of a punch passed through the sample container from above, as will be described below (see, for example, US Pat Fig. 3 ). In particular, in such a removal, the sample material can be removed from the sample container for processing largely without entrainment of possibly contained in the sample container hygroscopic substance.

As will be explained in detail below, it is not absolutely necessary that the sample material be taken up in the sample compartment after its recovery. Depending on the techniques used, it is also possible for the sample material initially to remain above the sample compartment in the region of the opening of the sample container and to be pushed out of the sample container only later when the sample is removed from the sample compartment by means of the punch , This is only one possibility. It goes without saying, too It is conceivable that the sample is obtained in another way and is introduced, for example, by means of tweezers or another suitable instrument directly into the sample compartment.

It is understood that the upper end of a sample compartment separated by a wall is positioned in the sample container so that a vapor exchange connection between e.g. the hygroscopic substance contained in the drying compartment and the sample can be carried out, regardless of whether the sample material is fixed above the sample compartment or arranged in the compartment. In the variant with a drying compartment in the form of a hygroscopic molded part, in contrast, there is a direct vapor exchange connection to the interior of the sample compartment. In this variant, the upper end of the sample compartment can therefore be arranged as desired.

Preferred embodiments of the invention are addressed in the subclaims.

In an advantageous embodiment, it is provided that the drying compartment is a molded part containing the hygroscopic substance. It is conceivable, for example, that the hygroscopic substance is embedded in a plastic from which z. B. a film material can be produced which represents the drying compartment there after insertion or insertion into the sample container. In the prior art are such, for. B. produced by injection molding plastic materials, which may have up to 70% of hygroscopic substance (eg molecular sieve). It is of course also conceivable to spray from such plastics drying devices with other suitable forms and then use them. Of course, it is within the scope of the invention also possible by means of an adapted injection molding process, the drying compartment during the production of the sample container already to train in this. In addition to the mentioned injection molding process, of course, other methods such as extruding or rolling are possible.

In a further advantageous embodiment, it can be provided that a molding component forming a drying compartment is produced by pressing, sintering or extruding hygroscopic substance. Also in this embodiment, it is possible to give the drying compartment a desired shape. In this embodiment, it is usually a molding that is manufactured separately and then used as a drying compartment in a sample container.

In a further embodiment of the invention, it is provided that the sample compartment is delimited by at least one wall formed in the sample container, in particular in relation to a drying compartment in which hygroscopic substance is accommodated.

The wall defining the sample compartment and the wall portion and bottom of the sample container may be made from any materials known in the art. Particularly suitable are plastics but also glass.

The following further embodiments of the sample container can be realized in conjunction with any of the above-discussed embodiments of the drying compartment.

In order to ensure the most uniform possible drying of the sample, it can be provided according to a preferred embodiment that the sample compartment is surrounded by the drying compartment.

The easiest way to construct this is to realize this in the case of usually round sample containers, if, as provided in a further preferred embodiment, the sample compartment is a hollow cylinder formed at a distance from the side wall of the sample container whose lower end is closed by the bottom of the sample container.

According to a further preferred embodiment, the sample container has a sample compartment whose opening provided in the region of its upper end is closed by a penetrable wall region and in which an opening is provided in a region of the bottom of the sample container covered by the cross section of the drying compartment. Such a sample container can be particularly easily, e.g. by injection molding. At the same time, it is ensured that no hygroscopic substance can enter the sample compartment.

According to a further preferred embodiment, the sample container has a sample compartment in which a separate region is formed by means of a penetrable transverse wall. In the separate area, suitable reagents, in particular in liquid form, can be presented for the treatment of the sample material.

According to the invention it is provided that the sample container is closed by a lid. The lid prevents leakage of the hygroscopic substance and moisture. In addition, contamination of the interior of the sample container can thus be avoided.

As mentioned above, the lid of the sample container is penetrable. For this purpose, for example, a weakened area can be provided in the lid. This feature makes in particular when using a example of the EP 1 088 212 known sample collection means sense. This sample extraction means has at its lower end a punching device and is dimensioned so that it can close the sample container after passing through the lid of a sample container in turn. This will be discussed further below.

Furthermore, it can be provided that the bottom area of the sample container has a weakened area in the cross-section covered by the sample compartment. This weakened area would facilitate pushing out the sample with the above-mentioned punch through the bottom of the sample container.

The hygroscopic substance provided according to the invention in the drying compartment may preferably be zeolite, silica gel or molecular sieve. The fine-grained or pulverulent form of such substances is preferably used.

The sample extraction means provided in the device according to the invention can be used alone for sampling and thereby e.g. be moved manually or automatically.

However, it is also conceivable that the sample collection means and the sample container are components of an ear tag used for the simultaneous marking and sampling of animals.

Such an ear tag is in the EP 1 088 212 described in detail. In the case of the ear tag described there, the sample extraction means is located at the free end of a dome arranged on a male part of the ear tag. The ear tag further includes a female part, on which the sample container is arranged. When marking / sampling, the female and male parts of the ear tag are each placed on different sides of the animal's ear with a suitable device, such as a pair of pliers. Then, with the forceps, the mandrel is advanced through the ear with the sample extraction means, whereby a sample is punched out. After passing the ear, the sample collection means pushed by the mandrel enters and closes the sample container provided on the female part of the ear tag while an adjacent portion of the dome is simultaneously locked in the female part of the ear tag. Mandrel and sample collection means are releasably connected to each other so that the sample container now sealed with the recovery agent can be removed from the female part while the tag remains on the ear.

This, as stated, is a variant that can be used in particular in the marking and sampling of animals in the ear area. Of course, the invention is not limited to such tuned systems. It is also conceivable that the system comprises only the sample collection means and the sample container.

Essential to this system is that the sample collection means is positioned after penetrating the lid so that its cutting or punching device is located centrally above the opening of the sample compartment. In this way, the sample is either kept above the sample compartment or can fall out of it eg in the course of progressive drying in the compartment. It is conceivable that, as in a preferred embodiment, the lower end of the sample collection means closes the sample container. It is but also conceivable that a separate lid is provided, with which the sample container is closed after a Prohengewinnungsmittel has been used, which is not able to close the container.

As already mentioned above, a further preferred embodiment provides that the device is part of an ear tag for the identification of animals.

In the following, the invention will be explained in more detail with reference to figures which illustrate several embodiments.

Fig. 1

einen Probenbehälter vor dem Einführen der Probe,

Fig. 2

den Behälter aus Fig. 1 nach dem Einführen einer Probe,

Fig. 3

den Probenbehälter aus Fig. 2 vor der Entnahme des Probenmaterials zu seiner Aufarbeitung,

Figs. 4-6

weiteren Ausführungsformen des Probenbehälters.

Showing:

Fig. 1

a sample container before inserting the sample,

Fig. 2

the container off Fig. 1 after inserting a sample,

Fig. 3

the sample container off Fig. 2 before taking the sample material for its work-up,

Figs. 4-6

further embodiments of the sample container.

Fig. 1 shows a sample container 10 with an upper opening 11, a lateral wall portion 12 and a bottom 13. Closed is the sample container 10 with a lid 14 which is formed penetrable at its central portion 15. In the sample container 10, a sample compartment 16 in the form of a hollow cylinder having an upper opening 40 is formed. In alignment with this opening 40, the sample compartment 16 extends downwards in the longitudinal direction as far as the bottom 13. The sample compartment is bounded by a circumferential wall 17.

Furthermore, a drying compartment 18 surrounding the sample compartment 16 is formed in the sample container 10. The drying compartment 18 is open at the top and is limited to its sides by the side wall portion 12 and the wall 17 and down through the bottom 13 of the sample container 10. In the drying compartment 18, a hygroscopic substance 19 is provided, which, as is apparent from Fig. 1 is in vapor exchange with the interior of the sample container 10 and the interior of the sample compartment 16 stands.

In order to prevent the hygroscopic substance 19 from being distributed in the sample container 10, the substance may, for example, be pressed into the compartment 18. It is also conceivable, for example, the upper layer with a only in Fig. 1 Screen 70 shown or other device, such as a semipermeable membrane cover, which holds the substance in place. Of course, it is also possible to fix the hygroscopic substance 19 by gluing etc. It is crucial, however, that such measures do not affect the vapor exchange rate so much that the desired drying of sample material in the sample container 10 is not or no longer effective.

Further shows Fig. 1 a sample extraction means 20 schematically indicated above the sample container 10, with a lower end 21 in which a punching device 22 is arranged.

In the case shown, biological sample material 23 has already been obtained with the sample extraction means 20, which was pressed into the punching device 22 during production and initially remains there. In the further course of the sample extraction and processing, the sample extraction means 20 is moved in the direction of the arrow 25. The then adjusting state is in Fig. 2 shown.

In Fig. 2 the sample extraction means 20 now penetrates the lid 14 of the sample container 10 in its central weakened region 15 with its lower end 21 and now in turn closes the upper opening 11. It can be seen that the punching device 22 and the sample compartment 16 are aligned with each other in such a way that the sample material 23 is located directly above the opening 40.

In Fig. 3 is the sample container in the in Fig. 2 shown state in a vessel 50 of an otherwise only schematically illustrated microtiter plate 51 used. From above, in the direction of an arrow 52, a punch 53 moves toward the sample container 10 and the sample extraction means 20 placed thereon. In the further course of its movement, the lower end of the punch 53 will penetrate the sample extraction means 20, the biological sample material 23 from the cutting and punching device 22 into the sample compartment 17 and push through it and the bottom 13 of the sample container 10 into the vessel 50 ,

Out Fig. 3 As a result, the sample material 23 moving with the punch 53 through the sample container 10 does not come into contact with the hygroscopic substance 19. To ensure that no hygroscopic substance escapes even after piercing the bottom 13, eg in the bottom area of the drying compartment, an annular reinforcement or other type of device can be provided which prevents leakage of hygroscopic substance even if the bottom 13 is in the area of the drying compartment 18 is destroyed.

As already mentioned above, the task of the sample compartment provided in the sample container according to the invention can consist, for example, in the taking up of biological sample material but also in its guidance during the removal from the container and / or the preparation.

The FIGS. 4 and 5 relate to embodiments of the sample container according to the invention, in which ( Fig. 4 ) the guidance of the sample material or ( Fig. 5 ) His work is in the foreground.

This in Fig. 4 shown embodiment of a sample container 100 according to the invention in turn has a cover 140, side wall portions 120 and a bottom portion 130. In the sample container 100, a sample compartment 160 is provided, which is bounded by a wall 170. Surrounding the sample compartment 160 is a drying compartment 180 in which hygroscopic substance 190 is disposed. The drying compartment 180 is bounded by the wall 170 or the lateral wall region 120.

The sample compartment 160 has an upper opening 400, which in contrast to the previously in the Figures 1 - 3 embodiment shown by a lid or a wall portion 410 is closed.

Also in this embodiment, the sample compartment extends to the upper opening 400 in an aligned manner down to the bottom 130 of the sample container 100, although in this case the bottom portion 130 in the covered by the sample compartment 160 cross section is not formed, that is open.

A particular advantage of this embodiment is, as explained below, that no hygroscopic substance 190 can enter the sample compartment.

Also in this embodiment, the sample extraction can be performed by means of a sample extraction means 200 having a lower end 210, in FIG which a cutting and punching device 220 is provided. In the case shown, biological sample material 230 was already obtained with the cutting and punching device 220, which was pressed into the cutting and punching tool 220 as in the other exemplary embodiments shown and remains there.

It can further be seen that in the lateral wall region 120 of the sample container, a circumferential projection 240 is formed, into which the sample extraction means 200 has been snapped with a corresponding circumferential recess 250. In this position, the sample extraction means 200 remains for a period between recovery and work-up.

The connection between recess 250 and projection 240 is selected so that by further pressing z. B. with an only schematically indicated annular wide punch 300, the sample extraction means can be pushed further into the sample container 100, in which case the cutting and punching device 220 penetrates the lid or wall portion 310. Once this is done, the biological sample material 230 may be pushed out of the cutting and punching device 220 and through the sample compartment 160 out of the sample container 100 with another narrower punch 510 through the sample collection means 200.

FIG. 5 concerns a further embodiment of a sample container 500 according to the invention.

This embodiment is substantially the same as in FIG Fig. 1 shown embodiment match. Thus, the sample container 500 also has a cover 540, a side wall region 520 and a bottom wall region 530. In the sample container 500, in turn, a sample compartment 560 is provided, the surrounded by a drying compartment 580 containing hygroscopic substance 590.

In contrast to the exemplary embodiments shown so far, a transverse wall region 600 is furthermore provided in the sample compartment 560. The wall region 600 is arranged in the case shown approximately at mid-height in the sample compartment 560. He can easily but in another altitude position z. B. located directly in the region of an opening 40 of the sample compartment 560.

In the now closed by the transverse wall 600 and a side wall 570 of the sample compartment 560 and the bottom 530 of the sample container 500 area 660 suitable reagents, in particular in liquid form 610 for processing, preservation or other treatment of the sample material not shown in this figure be submitted.

It is conceivable, for example, to provide a lysis buffer here, with which sample material is brought into contact in the laboratory for the preparation of the work-up. It is also conceivable to submit reagents for further work-up steps. In this way, time or work steps can be saved, since the in Fig. 5 illustrated sample container 500 both offers the opportunity to dry the sample material after extraction as well as perform in it after piercing the wall 600 first processing steps.

This embodiment furthermore advantageously permits contamination-free working in the laboratory, since the sample material does not have to be transferred to a further laboratory vessel. The contact between the sample material and the reagent can be established without having to intervene in the closed system formed by the sample container and the sample extraction means, or this closed system has to be opened. It would also be conceivable that not only the Initial processing of the sample material in this sample container performs, but that by the design of other compartments in this closed system, for example, a PCR reaction or an Elisa test could be performed.

Fig. 6 shows a sample container 700, in which a trained as a molding 785 drying compartment 780 is provided. The molding 785 is a thick-walled film in which hygroscopic substance 790 is embedded and which lines the sample container 700 in the sidewall region 720 from the inside.

In the illustrated embodiment, the drying compartment 780 surrounds a sample compartment 760 without providing a wall between the two compartments. This is not necessary in the embodiment shown, since due to its embedding in the molded part 785 there is no risk of contamination by the hygroscopic substance 790.

In the exemplary embodiment shown, the molded part 785 forming the drying compartment 780 is a type of film or sleeve insertable into the sample container 700. Naturally, other shapes are also conceivable.

Furthermore, as already mentioned above, it is also conceivable that the drying compartment in this embodiment is manufactured externally and then inserted into the sample container. It is equally possible that sample container and drying compartment are made together, for. B. by successive steps of an injection molding process.

Claims (7)

1. A device for collection and storage of sample material comprising

   - a sample container (10, 100, 500) for biological sample material (23, 230) comprising an upper opening (11) which can be closed by a lid (14, 140, 540), a lateral wall region (12, 120, 520) and a base (13, 130, 530) and a hygroscopic substance (19, 190, 590) contained in the interior of the sample container (10, 100, 500) for drying sample material (23, 230) in the sample container (10, 100, 500), wherein the sample container (10, 100, 500) is divided into at least two compartments (16, 160, 560; 18, 180, 580), of which one is a sample compartment (16, 160, 560) and the other is a drying compartment (18, 180, 580) containing the hygroscopic substance (19, 190, 590), and wherein the hygroscopic substance (19, 190, 590) communicates via a steam exchange connection with the interior of the sample container (10, 100, 500), and wherein the sample compartment (16, 160, 560) extends in a flush manner from an upper end provided with an opening (40, 400) in the longitudinal direction from the opening (40, 400) to the base (13, 130, 530) of the sample container (10, 100, 500) and is delimited by at least one wall (17, 170, 570) formed in the sample container (10, 100, 500), wherein the sample container (10, 100, 500) is closed by means of a penetrable lid (14, 140, 540),

   - a sample collection means (20, 200) which can be inserted with its one lower end (21, 210) into the sample container (10, 100, 500), wherein the lower end (21, 210) is arranged in the sample container (10, 100, 500) in a defined position above and spaced apart from the upper opening (40, 400) of the sample compartment (16, 160, 560), and wherein at the lower end of the sample preparation means (20, 200) a cutting or stamping device (22, 220) is provided, by which biological sample material (23, 230) can be obtained by passage of the lower end (21, 210) through tissue, and wherein

   - the position of the cutting or stamping device (22, 220) on the lower end (21, 210) of the sample collection means (20, 200) and the upper opening (40, 400) of the sample compartment (16, 160, 560) in the sample container (10, 100, 500) are adapted to one another in such a way that the sample material (23, 230) obtained by the cutting or stamping device (22, 220) is located above the sample compartment (16, 160, 560) or falls into the sample compartment after insertion of the sample preparation means (20, 200) into the sample container (10, 100, 500).
2. The device according to claim 1, wherein the lower end (21, 210) of the sample collection means (20, 200) closes the sample container (10, 100, 500) after the insertion.
3. The device according to claim 1 or 2, wherein in the sample container (10, 100, 500) the sample compartment (16, 160, 560) is surrounded by the drying compartment (18, 180, 580).
4. The device according to one of claims 1 to 3, wherein the sample compartment (160) is closed in the region of its upper end (400) by a penetrable wall region (410) and an opening (135) is provided in the base (130) of the sample container in a region covered by the cross-section of the sample compartment (160).
5. The device according to one of claims 1 to 3, wherein a separate region (660) in which reagents (610), in particular in liquid form, which are suitable for the processing of the sample material are received, is formed in the sample compartment (560) by means of a transverse wall (600).
6. The device according to one of claims 1 to 5, wherein the sample compartment (16, 160, 560) is a hollow cylinder which is spaced apart from a side wall region (12, 120, 520) of the sample container (10, 100, 500) and of which the lower end borders the base (13, 130, 530) of the sample container (10, 100, 500).
7. The device according to one of claims 1 to 6, wherein the hygroscopic substance (19, 190, 590) is selected from the group consisting of zeolite, silica gel and molecular sieve.

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