EP2249966A1

EP2249966A1 - Container for the preparation, preservation and storage of biological samples using a drying agent

Info

Publication number: EP2249966A1
Application number: EP09705434A
Authority: EP
Inventors: Alexander Berner; Bernhard Hostettler
Original assignee: Prionics AG
Current assignee: Prionics AG
Priority date: 2008-01-28
Filing date: 2009-01-22
Publication date: 2010-11-17
Anticipated expiration: 2029-01-22
Also published as: US8361416B2; EP2249966B1; WO2009095178A1; HUE033647T2; CA2710372C; CA2710372A1; CY1118745T1; DE102008007352B4; ES2619832T3; US20100291662A1; PL2249966T3; DE102008007352A1

Abstract

The invention relates to a sample container (10, 100, 500, 700) for biological sample material (23, 230), comprising an upper opening (11) that can be closed by a lid (14, 140, 540), a lateral wall region (12) and a base (13) and a hygroscopic substance (19, 190, 590, 790) contained in the interior of the sample container for drying sample material (23, 230) in the sample container, wherein the sample container is partitioned into at least two compartments, of which one is a sample compartment (16, 160, 560), and the other is a drying compartment (18, 180, 580) containing the hygroscopic substance, wherein the hygroscopic substance is connected to the interior of the sample container in a steam exchange connection, and wherein the sample compartment extends from an upper end, particularly equipped with an opening (40, 400), in the longitudinal direction to the opening in a flush manner to the base (13) of the sample container.

Description

CONTAINER FOR OBTAINING, PRESERVING AND STORING BIOLOGICAL SAMPLES WITH DRYING AGENT

The invention relates to a sample container for biological sample material and a device for the recovery, preservation and storage of sample material, in which such a sample container is used.

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, DE 199 57 861 discloses a sample container in which a hygroscopic substance is contained as drying agent. This known sample container enables a direct preservation of the sample material at the place of extraction, in which, in particular, the protein and nucleic acid fractions are stabilized.

A problem with the generic sample container is that the 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 prior art, to provide a sample container which avoids the mentioned disadvantages and which can be converted in a particularly simple manner into a e.g. integrates sample collection equipment used in conjunction with an ear tag.

The object is achieved with a sample container having the characterizing features of claim 1 and an apparatus for obtaining and storing sample material according to claim 8.

As known from the prior art, the sample container according to the invention also 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 having 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. a wall separated area inside the pro- benbehälters act, in which hygroscopic substance is arranged. 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, 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 for the sample material to be taken up in the sample compartment after it has been obtained. 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 introduced, for example, by means of tweezers or another suitable instrument directly into the Probenkornpar- timent.

It will be understood that the top of a sample compartment separated by a wall is positioned in the sample container such 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, however, 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 each of the above-mentioned embodiments of the Trockenkungskom- partiment.

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, especially 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 according to the invention 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 according to the invention 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.

In the case of conventional sampling, it is provided that the lid can be removed in the course of sampling and can be replaced after the sample material has been arranged in the container. It is also conceivable that the lid, as provided in a preferred embodiment, is penetrable. For this purpose, for example, a protective area can be provided in the lid. This embodiment makes sense, in particular, when using a sample extraction means known, for example, from EP 1 088 212. 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 in connection with the also covered by the invention apparatus for sample extraction.

Of course, the described sample collection means can also be used with a sample container whose lid is not penetrable. In this case, the lid must be removed manually, and then the sample extraction means is introduced into the container as described above. Also in this case it can be provided that the lower end of the sample extraction means then closes the container instead of the originally provided lid.

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. As just mentioned, the invention also relates to a device for the recovery and storage of sample material, with

a sample container according to the invention, which in particular has a penetrable lid and

a sample extraction means which can be guided with its one lower end through the penetrable lid of the sample container into it, the lower end then being arranged in the sample container in a defined position above and at a distance from the upper opening of the sample compartment, and wherein a cutting or punching device is provided at the lower end of the sample-collecting means, with which a sample can be obtained in particular when passing through the lower end through tissue, and wherein

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 matched to one another such that a sample obtained with the cutting or punching device is in the sample container above the sample compartment after insertion of the sample collection means is or falls in those.

The described sample recovery means 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 described in detail in EP 1 088 212. In the case of the ear tag described there, the sample collection 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. The dome and sample collection means are releasably connected to each other such 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, for example as the drying progresses into 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 sample extraction means 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.

Showing:

1 shows a sample container before introducing the sample,

FIG. 2 shows the container from FIG. 1 after insertion of a sample, FIG.

3 shows the sample container from FIG. 2 prior to the removal of the sample material for its processing,

Figs. 4-6 further embodiments of the sample container.

1 shows a sample container 10 having an upper opening 11, a lateral wall region 12 and a bottom 13. The sample container 10 is closed by a lid 14 which is permeable at its central region 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 can be seen from FIG. 1, is in vapor exchange communication with the interior of the sample container 10 and the interior of the sample compartment 16.

In order to prevent the hygroscopic substance 19 from spreading in the sample container 10, the substance may be e.g. be pressed into the compartment 18. It is also conceivable, e.g. the top layer is provided with a screen 70, shown only in Fig. 1, or other means, e.g. cover a semipermeable membrane that 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.

Furthermore, FIG. 1 shows a sample extraction means 20 schematically indicated above the sample container 10, with a lower end 21 in which a stamping 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 shown in Fig. 2. In Fig. 2, the sample extraction means 20 with its lower end 21 has now penetrated the lid 14 of the sample container 10 in its central weakened region 15 and now in turn closes the upper opening 11. It can be seen that the punching device 22 and the sample compartment 16 aligned in such a way are that the sample material 23 is located directly above the opening 40.

In FIG. 3, the sample container in the state shown in FIG. 2 is inserted into a vessel 50 of a microtiter plate 51, which is otherwise shown only schematically. 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 ,

From FIG. 3 it follows that the sample material 23 moved 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, e.g. in the bottom region of the drying compartment an annular reinforcement or other type of device are provided which prevents leakage of hygroscopic substance even if the bottom 13 in 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. Figures 4 and 5 relate to embodiments of the sample container according to the invention, in which (Fig. 4) is the leadership of the sample material or (Fig. 5) its processing in the foreground.

The exemplary embodiment of a sample container 100 according to the invention shown in FIG. 4 again has a cover 140, side wall regions 120 and a bottom region 130. Provided in the sample container 100 is a sample compartment 160, which is delimited by a wall 170. Surrounding the sample compartment 160 is a drying compartment 180 in which hygroscopic substance 190 is arranged. 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 exemplary embodiment previously shown in FIGS. 1-3, is closed by a cover or a wall area 410.

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 test 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 in the context of production 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 has been done, the biological sample material 230 can be pushed out of the cutting and punching device 220 and through the sample compart- ment 160 out of the sample container 100 with another narrower punch 510 through the sample extraction means 200.

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

This embodiment is substantially identical to the embodiment shown in Fig. 1. 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, here e.g. to provide a lysis buffer to which sample material is brought into contact in preparation for work-up in the laboratory. It is also conceivable to submit reagents for further work-up steps. In this way, time or work steps can be saved, since the sample container 500 shown in FIG. 5 offers both the possibility to dry the sample material after extraction as well as to carry out first work-up steps in it after piercing the wall 600.

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 drying compartment 780 designed as a molded part 785 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

Sample container for biological sample material, as well as apparatus for obtaining, preserving and storing sample material with such a sample containerPATENTIAL CLAIMS:

1. Sample container for biological sample material, with an upper opening, which is closed by a lid, a lateral wall portion and a bottom and contained inside the sample container hygroscopic substance for drying sample material in the sample container, wherein the sample container in at least two compartments one of which is a sample compartment and the other is a drying compartment comprising the hygroscopic substance, the hygroscopic substance being in vapor exchange communication with the interior of the sample container, characterized in that the sample compartment (16, 160) extends from an upper compartment, especially one Opening (40, 400) longitudinally end to the opening (40, 400) extending to the bottom (13, 130, 530) of the sample container (10, 100, 500) extends.

2. Sample container according to claim 1, characterized in that the sample compartment (16, 160, 560) of the drying compartment (18, 180, 580) is surrounded.

3. Sample container according to claim 1 or 2, characterized in that the drying compartment (780) as a hygroscopic substance (790) containing molding (785) is formed.

4. Sample container according to claim 3, characterized in that the molded part consists of plastic, in which the hygroscopic substance is embedded.

5. Sample container according to claim 3, characterized in that the drying compartment, in particular by pressing, sintering or extrusion into a desired shape brought hygroscopic substance.

6. Sample container according to claim 1 or 2, characterized in that the sample compartment (16, 160) by at least one in the sample container (10, 100, 500) formed wall (17, 170, 570) is limited.

7. Sample container according to one of the preceding claims, characterized by a sample compartment (160) which is closed in the region of its upper end (400) by a penetrable wall region (410) and in a region covered by the cross section of the drying compartment (160) in the Bottom (130) of the sample container an opening (135) is provided.

8. Sample container according to one of the preceding claims, characterized by a Probenkompartiment (560), in which by means of a transverse wall (600), a separate region (660) is formed in the treatment of the sample material suitable reagents (610), in particular in liquid form are included.

9. Sample container according to one of the preceding claims, characterized in that the sample compartment (16, 160, 560) at a distance from the side wall region (12, 120, 520) of the sample container (10, 100, 500) formed hollow cylinder, the lower End adjacent to the bottom (13, 130, 530) of the sample container (10, 100, 500).

10. Sample container according to one of the preceding claims, characterized in that it is closed by a penetrable lid (14, 140, 540).

11. Sample container according to one of the preceding claims, characterized in that the hygroscopic substance (19, 190, 590) is selected from the group comprising zeolite, silica gel or molecular sieve.

12. Apparatus for recovering and storing sample material with

a sample container (10, 100) according to one of the preceding claims and

a sample extraction means (20, 200) which is insertable with its one lower end (21, 210) in the sample container (10, 100), wherein the lower end (21, 210) in the sample container (10, 100) in Position above and spaced from the upper opening (40, 400) of the sample compartment (16, 160) is arranged, and wherein at the lower end of the sample extraction means (20, 200) a cutting or punching device (22, 220) is provided with which can be obtained in particular by passing the lower end (21, 210) through tissue biological sample material (23, 230) and wherein the position of the cutting or punching device (22, 220) at the lower end (2 L 210) of the sample collection means (20, 200) and the upper opening (40, 400) of the sample compartment (16, 160) in the sample container (10, 100) are coordinated with one another in such a way that the sample material (23, 230) obtained with the cutting or punching device (22, 220) is inserted into the sample container (10, 100) after insertion of the sample extraction means (20, 200) above the sample compartment (16 , 160).

13. The apparatus according to claim 12, characterized in that the sample container (10, 100) has a penetrable lid (14, 140).

14. The apparatus of claim 12 or 13, characterized in that the lower end (21, 210) of the sample collection means (20, 200) closes the sample container (10, 100) after insertion.

15. The device according to claim 12, characterized in that it is part of an ear tag for the identification of animals.