WO2003068398A1

WO2003068398A1 - Sample preparation device and test device set based thereon

Info

Publication number: WO2003068398A1
Application number: PCT/EP2003/001390
Authority: WO
Inventors: Hans Scheefers
Original assignee: Schebo Biotech Aktiengesellschaft
Priority date: 2002-02-12
Filing date: 2003-02-12
Publication date: 2003-08-21
Also published as: EP1474235A1; DE10205709A1

Abstract

The sample preparation device is particularly suited for stool samples to be analysed enzymatically and immuno-chemically, e.g. according to the ELISA solid phase technique and/or lateral flow system, or to be analysed microbiologically. The inventive device comprises a closeable vessel (3) for receiving a liquid reagent and/or liquid solvent and a sample collection rod (13) which has at least one scoop-type recess (15) located on a peripheral surface of one of the ends thereof and which can be inserted with said end into the vessel (3) via an insertion opening (22) of the vessel (3) provided with a scraper shoulder (23). The vessel has an integrally formed sealing part (7) which can be separated at a predetermined breaking point (9) and which seals an open outlet (5) of the vessel (3) when the sealing part (7) is separated. A predetermined amount of liquid can be directly drained off from the sample preparation device by manually squeezing the vessel (3) or by displacing a piston-type component (19, 21).

Description

Sample preparation device and test device set based thereon

description

The invention relates to a sample preparation device by means of which e.g. Samples to be analyzed enzymatically or immunochemically, in particular stool samples, for the analysis can be prepared, as well as a test device set based thereon.

Stool samples that undergo an enzymatic or immunochemical analysis (enzyme immunoassay, rapid test, laterai flow system) or in particular in the solid-phase technique of the ELISA (enzyme linked immunosorbent assay) or a microbiological analysis (e.g. determination of the number of bacteria or the number of parasite eggs) to be supplied must be prepared for the analysis, for example determined in terms of quantity or weight in a reagent or a solvent, as described for example in WO92 / 02630 for elastase 1 / pancreas tests or in DE 1 99 45 947 A1 for the detection of Tumor M2 pyruvate kinase is described. For these or similar tests, it is customary to dissolve stool samples in predetermined volumes of the solvent in a weight-determined manner and to conduct the analysis (qualitative and / or quantitative determination of an analyte). The preparation of samples for such analyzes is comparatively lengthy.

JP 10 300 642 A and JP 10 300 643 A disclose stool sample tubes with a sleeve-shaped beaker for holding a solvent and with a sample holding rod that can be inserted into the beaker. At its end to be inserted into the beaker, the sample holding rod has a sample well that receives the stool sample and is replaced by a provided with an annular lip, inserted in the cup stopper sleeve inserted into the cup. The ring lip wipes off the protruding stool above the scoop and in this way calibrates the stool volume (or stool mass) introduced into the solvent.

Such sample preparation devices, which are already assembled as disposable items with the reagent and / or the solvent, are charged with the sample mass to be analyzed, for example chair, by filling the scoop recess of the sampling rod and inserting it into the reagent or solvent through the insertion opening of the vessel. The wiping lip running along the circumferential surface of the sampling rod calibrates the content of the scoop. Since the wells are comparatively small, they contain essentially only mucus in stool samples and accordingly it can be assumed with sufficient accuracy that the stool sample is not only determined by volume but also by weight.

Although such stool sample tubes simplify the introduction of a predetermined amount of stool into the solvent, they are comparatively difficult to handle when the analysis is continued. In particular, it has been shown that conventional stool sample tubes are not sufficiently tight, so that a part of the reagent or solvent can leak out and the mixing ratio is changed accordingly and analysis errors accordingly occur. Liquids are lost particularly during transport, especially if the stool sample tube is exposed to a negative pressure during flight transport.

It is an object of the invention to provide a sample preparation device, in particular for stool samples, which allows an exact dosing of the sample in a liquid reagent and / or a liquid solvent and is sealed better than before, in particular can also be exposed to a negative pressure during a possible air transport.

The invention is based on a sample preparation device with a closable vessel for holding a liquid reagent and / or liquid solvent and a sampling rod which has at least one scoop recess in the area of one of its ends on its circumferential surface and with this end through a stripping shoulder The opening of the vessel can be inserted into the vessel.

To achieve the object specified above, it is provided that the vessel has an access opening closed by a removable closure part and that the sampling rod relative to the part of the vessel forming the insertion opening on the one hand and the closure part relative to the part of the vessel forming the access opening on the other hand by a sealing arrangement is sealed, to which, in particular to the side of the reagent or solvent, a throttle section encloses the sampling rod or the closure part. The seal is preferably a press fit seal, which seals the sampling rod against the insertion opening or the closure part against the access opening by means of a radial press fit. The throttling section located on the inside of the vessel reduces the suction effect that a negative pressure possibly present on the outside of the vessel exerts on the interior of the vessel and also reduces the compressive force with which any excess pressure in the interior of the vessel acts on the seal. The throttling section can be a throttling gap which can be very narrow in practice, for example the dimensions of an under-fit, which in itself allows the components to be sealed against one another to be moved slightly, but the sealing effect of which is inherent would be inadequate in practice. In a preferred embodiment, the vessel is designed, in a manner known per se, as an elongated sleeve which receives the sampling rod in the longitudinal direction and is closed at one of its longitudinal ends, the other longitudinal end of which forms the access opening which is closed by the removable closure part, the closure part being the one with the stripping shoulder provided insertion opening for the sampling rod. In this context, it is advantageous if the closure part is designed as a sleeve-shaped or cup-shaped sample collecting part, which, facing the sleeve, forms the stripping shoulder. Any excess wiped off at the wiping shoulder can collect in the sample collecting part in this way and does not contaminate the exterior of the device. The sleeve, the sample collection part and also the section of the sampling rod that can be inserted into the sleeve have a cylindrical contour, which facilitates the sealing.

The closure part engages at least over part of its axial length in the sleeve, with at least two annular bead seals, which form a radial interference fit and are provided between the sleeve and the closure part, which form the throttle section in this engagement area at an axial distance from one another. Since the throttle section is limited axially on both sides by press fit seals, the sealing effect is particularly high.

The annular bead seals are expediently integrally formed on one of the two parts - the inner jacket of the sleeve and the outer jacket of the closure part, which facilitates the manufacture and assembly of the sample preparation device. The insertion of the closure part into the sleeve is facilitated if the diameter of the other of the two parts is stepped between the bead seals and decreases in the direction of insertion of the closure part. In this way, the closure part can be inserted into the sleeve with relatively little force before being in an end section of the insertion path the radial force of the bead seals is built up.

In an expedient embodiment, it is provided that the sampling rod has a ring-shaped, thickened second portion which is enlarged in diameter with respect to its first portion which can be inserted into the vessel through the insertion opening and which is sealed in the insertion opening in a radial press fit when the sampling rod is inserted. The insertion opening has in the area of the first section of the sampling rod to form a throttle gap an opening section with a reduced inside diameter. This opening section expediently has an inside diameter which is matched to the outside diameter of the first section of the sampling rod. A gap width on the order of a tenth of a millimeter is also tolerable.

The sealing arrangements explained above ensure that the liquid chamber of the vessel is sealed in a transport-safe manner when the sampling rod is inserted, both before and after sampling. If the sampling rod is immersed in the liquid chamber of the vessel before the sample is taken, it drags out part of the calibrated amount of the liquid when it is drawn out for sampling, which on the one hand can impair the accuracy of the analysis, and on the other hand, the carelessly carried out liquid can damage the environment contaminate.

In a preferred embodiment, which also has independent inventive significance, ie can also be used with sample preparation devices other than the type explained above, it is provided that the insertion opening of the closure part is sealed by a membrane which can be pierced by means of the sampling rod. In this embodiment, the sampling rod is used for the first time after scooping the sample through the membrane, ie introduced into the liquid chamber with destruction of the membrane, whereby the discharge of liquid is prevented. The membrane is expediently integrally formed on the closure part and has a thickness of one hundredth of a millimeter, for example.

Conventional sample preparation devices, as explained at the beginning, are often difficult to handle when the analysis is continued.

In a second aspect, it is the object of the invention to provide a sample preparation device, in particular for stool samples, which allows an exact dosing of the sample in a liquid reagent and / or a liquid solvent and at the same time facilitates the continuation of the analysis on the basis of a sample prepared in this way ,

The invention is also based here on a sample preparation device, with a closable vessel for holding a liquid reagent and / or liquid solvent and a sampling rod which has at least one scoop recess in the area of one of its ends on its circumferential surface and with this end through one with a scraper shoulder provided insertion opening of the vessel is insertable into the vessel. To achieve the object specified above, it is provided that the vessel has an integrally molded closure part which can be separated at a predetermined predetermined breaking point and which closes a drop outlet opening of the vessel which is open when the closure part is removed.

When the analysis is continued, the closure part is broken off or possibly cut off at the predetermined predetermined breaking point and, accordingly, the liquid content mixed with the sample can be used directly by the devices, the further analysis, for example a sand wichassay or a microtiter plate, for example by draining.

In a preferred embodiment, at least the area of the vessel that receives the reagent and / or the solvent consists of a flexible, manually deformable material, such as e.g. soft flexible plastic. The liquid can be drip-dosed by squeezing the container. The closure part and the outlet opening are expediently integrally formed on the vessel, and the outlet opening expediently ends when the closure part is broken off in a pipetting channel which facilitates the formation of metered drops.

In a preferred embodiment, the vessel is again designed as an elongated sleeve which receives the sampling rod in the longitudinal direction. At one of its longitudinal ends, such a sleeve carries the closure part and, in the longitudinal direction, opposite the stripping shoulder. It can also be provided here that the sleeve, opposite the closure part, is closed by means of, for example, a cup-shaped sample collecting part provided with a push-through opening for the sampling rod, which, facing the sleeve, forms the stripping shoulder in the form of an annular lip. The sample collection part can be non-detachably connected to the sleeve or integrally formed thereon, but preferably engages in the sleeve in a tightly but longitudinally displaceable manner with a pin attachment. Such a sample collecting part expediently protrudes outward beyond the sleeve and, if necessary, can be removed from the sleeve together with the sampling rod. The contents of the sleeve are then accessible for removing the sample liquid, for example with the aid of a pipette or the like, without breaking off the closure part.

Since the spigot closes the sleeve tightly, it can be used as a piston to dose the sample liquid when the closure part is broken to be able to deliver. The sample collecting part and the sleeve expediently comprise locking elements which are assigned to one another and which, however, releasably fix the sample collecting part and the sleeve in a position relative to one another from which these components can be moved towards and / or away from one another in the longitudinal direction of the sleeve and accordingly have a defined stroke of the as Specify the piston-effective pin approach. The locking members fix the pin extension here, expediently in two positions relative to the sleeve. In the variants explained above, the sleeve can consist of rigid material. Expediently, however, the sleeve also consists of a flexible material here, so that it can also be manually squeezed for drip dosing.

For mass analyzes or simultaneous analyzes of several parameters, several vessels with parallel sampling rods and outlet openings lying on a line are preferably connected to form a single unit, so that they can be used particularly easily in a grid arrangement of sandwich assays or microtiter plates. The vessels can be integrally connected to one another, but are preferably detachably held on a common, possibly reusable connecting rail.

In the second variant of the sample preparation device explained above, the drip outlet opening is integrally formed on the vessel and is opened at the predetermined predetermined breaking point by breaking off the closure part which is also integrally formed on the vessel. In a variant of the sample preparation device explained above, it is provided that the vessel, similar to the sample preparation device explained under the first-mentioned aspect, has an access opening closed by a removable closure part, to which an outlet tube part ending at one end in a drop outlet opening with its outlet part is removed the other end can be attached sealed. In this variant, an additional element is in shape of the outlet pipe part, but the drop outlet opening can be formed more precisely than in the variant explained at the beginning, which benefits the accuracy of the drop formation. However, both variants have the common advantage that the sample prepared in the vessel can be dispensed directly from the vessel. An intermediate pipetting step, as is required with conventional preparation devices, can be omitted in this way.

In this variant, too, the vessel can be designed as an elongated sleeve, which receives the sampling rod in the longitudinal direction and is closed at one of its longitudinal ends, the other longitudinal end of which forms the access opening closed by the removable closure part. The closure part here has the insertion opening provided with the stripping shoulder for the sampling rod, so that this is simultaneously removed when the closure part is removed. In the second variant, the closure part is also expediently designed as a sample collection part, so that stripped sample residues are also removed when the closure part is removed.

For a reproducible, quantitative analysis, the vessel contains a predetermined volume of reagent or / and solvent. Usually, the sample quantity scooped into the vessel by means of the sampling rod is dissolved in the liquid by shaking or the like. It has proven advantageous here if the chamber of the vessel containing the liquid has essentially no constriction areas in which parts of the liquid or the sample get trapped and can be prevented from mixing. In the case of a vessel designed as a sleeve, the closure part preferably engages in the sleeve and ends in the sleeve on an end surface of a piston section of the closure part which is sealed toward the sleeve and carries the scraper shoulder and extends essentially axially normal to the longitudinal direction to the sleeve. The piston section is expediently enclosed in a ring shape as the scraper shoulder. ßenden piston disc, while the closure part tapers towards the piston disc to form an insertion cone for the sampling rod.

In order to be able to deliver a desired number of liquid drops in a defined manner when the outlet tube part is attached, the sleeve and / or the outlet tube part expediently consists of a flexible, manually deformable material, so that the liquid drops can be squeezed out by squeezing the sleeve or the outlet tube part. The outlet pipe part preferably consists of the flexible material, while the sleeve, for better sealing, consists of plastic material that is stiff compared to the outlet pipe part material.

It facilitates handling when dripping when the outlet pipe part tapers at least approximately conically towards the drop outlet opening.

In principle, it is sufficient if the drop outlet opening ends at an edge of the mouth, which keeps the drop forming at the mouth against gravity due to the cohesive forces and surface tension forces inherent in the drop until a certain drop size is reached. For quantitative analytical measurements, especially if the drops are to be dripped into a dilution solution for further defined dilution, the reproducibly defined drop volume is important. In a preferred embodiment, which allows the production of uniformly large droplets, it is provided that the droplet outlet opening ends at one end of the outlet tube part in a droplet-forming chamber and the other end of the outlet tube part ends in a throttle channel section with smaller ones in relation to the diameter of the droplet-forming chamber Diameter passes. The drop-forming chamber has, at least in the region of its mouth that emits the drop, cylindrical or, at most, weakly conically widening towards the mouth. cut. In such a drop forming chamber, the drop of a predetermined diameter can accumulate before it is released. The smaller diameter cross section of the throttle channel not only slows down the growth of the drop, but also facilitates the tearing off of the liquid thread feeding the drop, in particular if the throttle channel has a muzzle ring cutting edge toward the sleeve.

With the sampling rod, it is also possible, under certain circumstances, to insert solid parts of the sample into the sleeve. In order to prevent such solid particles from interfering with the dripping process, it is provided in a preferred embodiment that the outlet pipe part has a filter body that retains solids, in particular a filter body made of a porous solid material that is permeable to liquids, between its two ends. Such a filter body can be, for example, a ball that is non-positively, e.g. clamped or positive, e.g. behind a locking rib in which the outlet pipe part is held. In this way, the filter body can also be pressed into the outlet pipe part later if necessary.

The sample preparation device consisting of the vessel, the closure part and the sampling rod is usually sold ready-made with the liquid reagent and / or liquid solvent in order to be able to introduce a currently taken sample into the liquid in a fresh, non-dried state. In this way of handling, comparatively high demands are placed on the tightness and the mechanical strength of the closures between the closure part and the vessel on the one hand and the sampling rod and the closure part on the other hand. In conventional sample preparation devices, as explained at the outset, mechanical clamp closures are provided which hold the components to be connected to one another in the clamp fit. In a preferred embodiment of the invention, the locking part on the vessel and / or the sampling rod on the closure part by means of a bayonet coupling, so that the interlocked parts must first be rotated against each other before they can be pulled apart. It goes without saying that the bayonet couplings, but in particular the bayonet coupling holding the closure part on the vessel, can comprise additional latching elements which oppose latching forces from the opening rotation. Sample preparation devices with bayonet couplings between the closure part and the vessel as well as between the sampling rod and the closure part can be exposed to higher transport loads on the shipping route, e.g. in the case of air transport, not least because of the sealing forces that can be achieved as a result of the improved closure security. Such bayonet couplings can be provided in all of the sampling devices explained above.

It is also advantageous if the bayonet coupling which locks the closure part to the vessel has inclined surfaces which pull the closure part away from the vessel during the rotational unlocking movement. Near its sealing surface assigned to the closure part, the vessel has an inner jacket step which expands the diameter toward the access opening and which detach the sealing surfaces of the closure part from the sealing surfaces of the vessel during the pulling movement exerted by the inclined surfaces. In this way, the closure part is screwed out of its sealing position into a position during the unlocking rotary movement, from which it can be removed without great effort. In particular, in this way, when the closure part is removed, there is no sudden change in force, which entails the risk that the liquid contained in the vessel is spilled. The bayonet coupling with inclined surfaces explained above has independent inventive significance. Instead of bayonet couplings, screw connections can alternatively be used. The invention further relates to a test device set for sample preparation, in particular in the form of a commercial packaging with the following components:

A sample preparation device comprising a liquid ^'reagent and / or liquid solvent in a predetermined amount containing, by means of the closure member sealed vessel and with an inserted into the insertion or even inserted sampling wand and an outlet pipe, as explained headed. The retail pack thus has all the device components required for one-time use and allows flexible use, in particular for stool samples, partly in the patient's area and partly at the treating doctor or his laboratory.

Depending on the type of analysis to be carried out, the liquid of the sample preparation device can be fed dropwise to the analysis device, for example, operating according to the lateral flow system, by means of the outlet pipe part included in the test device set. In many cases, however, it is necessary to additionally dilute the concentrate of the sample preparation device in a defined manner before the actual analysis by dropping the concentrate of the sample preparation device into a predetermined amount of a liquid solvent with a defined number of drops before the dilution is fed to the analysis device. In a preferred embodiment, the devices required for the dilution are also part of the test device set. The test device set then further comprises a second container containing liquid solvent in a predetermined amount with an access opening closed by a removable lid and, moreover, a closure cap which can be attached to the access opening in a sealed manner and forms a drop outlet opening. The drop outlet opening can be designed for the formation of defined drop sizes in the manner explained above with reference to the outlet tube part. These are expediently The cap and the outlet pipe part are identical in shape to reduce injection molding costs.

Last but not least, if the test device set is intended for the preparation of stool samples, it comprises at least one sheet with a layer of floatable, water-soluble material for settling stool in order to facilitate the patient-side handling of the sample preparation device. The sheet may consist entirely of floatable, water-soluble material, such as e.g. from a film made of PEG (polyethylene glycol), PVP (polyvinylpyrolydone) or from sugar polymers. However, since such materials are often transparent, the sheet preferably consists of a multilayer composite, in which a aforementioned film with a layer of opaque, decomposable material, such as e.g. Paper, cellulose, laminated on one or both sides.

The invention is explained in more detail below with reference to a drawing. Here shows:

1 shows an axial longitudinal section through a sample preparation device according to the invention;

Fig. 2 shows an axial longitudinal section through a detail of a variant of the sample preparation device; 3 shows a schematic illustration of a further variant of a sample preparation device; 4 shows a side view of a variant of a sample preparation device according to the invention, partially shown in axial longitudinal section; Fig. 5a, 5b and 5c the components of the sample preparation device from FIG. 4 each in a perspective representation; 6 shows an axial longitudinal section through the vessel of the sample preparation device with the outlet pipe part attached; 7 shows a detailed illustration of the outlet end of the outlet pipe part; 8a and 8b the components of a dilution vessel and Fig. 9 shows an axial longitudinal section through the sealing area of a variant of the

4 and 5a to 5c.

1 shows a sample preparation device in the form of a stool sample tube 1, but also for example for a pancreas elastase 1 analysis according to WO 92/02 630 or the detection of the pyruvate kinase isozyme according to DE 199 45 947 A1 for other enzymatic or immunochemical analyzes (eg lateral flow system), in particular in the solid phase technique of the ELISA. The stool sample tube, generally designated 1, comprises an elongate, tubular cylindrical sleeve 3, which is tapered at one end to an outlet opening 5 in the form of a pipetting channel. The outlet opening 5 is closed by a closure piece 7 integrally formed on the sleeve 3. The closure piece 7 is connected to the sleeve 3 via a predetermined breaking point 9 and opens the outlet opening 5 when the sleeve 3 breaks or cuts it off.

From the end opposite the closing part 7 in the longitudinal direction, an elongated, cylindrical, sampling rod 1 3 provided with a handle 11 is inserted into the sleeve 3. The sampling rod 13 is provided in the area of its end located in the sleeve 3 on its rod circumferential surface with one or more scoops 1 5 for the stool sample to be analyzed. The sampling rod 1 3 passes through a chamber 17 of a sample collecting sleeve 19 which is held on the sleeve 3 in a sealed manner with a pin extension 21 which extends into the sleeve 3. The pin extension 21 has at its end which extends into the sleeve 3 in the area of a passage opening 22 a stripping shoulder in the form of an annular stripping lip 23 which tightly surrounds the sampling rod 1 3 and sample material which protrudes beyond the scoop depressions 15 when the sampling rod 1 3 is inserted scrapes. While the excess sample material collects in the chamber 1 7, the content of the wells 1 5 is smoothed out and calibrated. The handle 1 1 is designed such that it closes the outer end of the chamber 1 7 along the circumference of the sample collecting sleeve 1 9 when the sampling rod 1 3 is inserted. The sample collecting sleeve 1 9 can be attached to the sleeve 3, for example glued on; it can also be integrally formed on the sleeve 3, whereby the pin extension 21 can then possibly be omitted or the sample collecting sleeve 19 is, however, detachably held on the sleeve 3 in the press fit.

The interior of the sleeve 3, which is sealed off from the outside, contains liquid reagent and / or liquid solvent in a predetermined volume, in which the stool sample introduced into the wells 15 dissolves for the subsequent analysis. It goes without saying that part of the analysis reaction or adsorption reaction can already take place in the liquid and that only the completion of the analysis takes place outside the stool sample tube 1, for example in a sandwich assay or a microtiter plate. The entire analysis process can also take place outside of the stool sample tube. For the analysis, first, as explained above, a stool sample is scooped by piercing with the aid of the sampling rod 13 and introduced into the sleeve 3 while stripping off excess sample material. After the introduced stool sample is dissolved in the liquid, the closure part 7 is broken off and a predetermined amount of the liquid containing the stool sample is applied to the sandwich assay or the microtiter plate. The amount or volume of the liquid to be applied is determined by a predetermined number of drops of liquid dripping from the outlet opening 5. In order to simplify or accelerate the draining process, the sleeve 3 consists of a flexible material, in particular plastic material, so that the drops to be dispensed can be expelled by squeezing the sleeve 3 in the desired number. In embodiments in which the sample collecting sleeve 1 9 with its Pin projection 21 is displaceable in the sleeve 3 like a piston, the displacement effect can also be used to expel the desired amount of liquid.

Fig. 2 shows a variant of the stool sample tube, in which the piston stroke is predetermined by locking elements. Components having the same effect are designated by the reference numerals of FIG. 1 and provided with the letter a to distinguish them. Components of the stool sample tube 1 from FIG. 1 that are not shown in FIG. 2 are present. To explain the structure and the mode of operation, reference is made to the description of FIG. 1.

In the stool sample tube 1 a of FIG. 2, the spigot 21 a of the sample receiving sleeve 19 a is guided in the sleeve 3 a in a sealed, longitudinally displaceable manner. An annular latching projection 25 is provided on the pin projection 21a, to which two ring-shaped circumferential latching grooves 27 and 29 are assigned on the inner circumference of the sleeve 3a, into which the latching projection 25 engages alternately depending on the displacement position of the sample receiving sleeve 1 9a relative to the sleeve 3a. The distance between the annular grooves 27, 29 defines a predetermined piston stroke of the pin projection 21 a and thus a predetermined volume of liquid which can be expelled from the sleeve 3. The locking projection can of course also be provided on the sleeve and engage in grooves of the pin grid.

The stool sample tubes explained above can be used individually for the analysis. If a large number of stool samples are examined, it can be expedient, as shown in FIG. 3, to combine several of the stool sample tubes 1b, each of which can have the structure explained above, for example by means of a connecting rail 31 to form a unit in which the sleeves 3b Test sample tubes 1b or the sampling rods contained therein run parallel to one another and in particular also the outlet openings 5b on a straight line. are ordered. The distances between the outlet openings are chosen to be the same size and correspond to the distances between the analysis wells of the sandwich assay or the microtiter plate. The liquid of the individual stool sample tubes 1 b loaded with stool samples can, as explained above, be drained off individually by squeezing the individual sleeves 3 b; mechanized or motor-driven pipetting arrangements, such as those used for multi-channel pipetting devices, can also be used to advantage. The stool sample tubes 3b can be detachably held on the connecting line; they can also be connected integrally to the structural unit.

4 and 5a to 5c show a variant of a stool sample tube from FIGS. 1 to 3, which differs from the stool sample tube of these figures in that the drop outlet opening and the closure part closing the drop outlet opening are not integrally formed on the vessel of the stool sample tube, but rather is provided by separate components that can be separated from the vessel. Components having the same effect are identified by the reference numbers in FIG. 1 and 2 designated and provided with a letter to distinguish them. To explain the structure and the mode of operation, reference is made to the description of FIGS. 1 to 3.

The stool sample tube 1c shown in FIGS. 4 and 5a to 5c in turn comprises a circular cylindrical sleeve 3c for receiving a predetermined volume (level 33) of a liquid reagent and / or liquid solvent. The sleeve 3c has an integral bottom 35 at one longitudinal end. At its other longitudinal end, the sample collecting sleeve 1 9c serving as a closure piece seals an access opening 37 (FIG. 5c) of the sleeve 3c in a manner which will be explained in more detail below. The sampling rod 1 3c provided with scooping recesses 1 5c in turn passes through a central passage opening 22c of the sample collecting sleeve 1 9c provided with an annular stripping shoulder 23c. The Wiping shoulder 23c in turn seals the sample collecting sleeve 19c against the sampling rod 13c.

The sample collecting sleeve 19c engages with a pin boss 21c with less radial play in the sleeve 3c, the pin boss 21c merging to form an insertion bevel for the sampling rod 13c in a conical neck 39 which narrows towards the wiper shoulder or wiper lip 23c. For the sealing of the sample collecting sleeve 1 9c with respect to the sleeve 3c, the pin extension 21 c is provided with an annular bead 41 and at the tapered end the conical extension 39 carries a piston disk 43 which surrounds the stripping shoulder 23c and seals against the sleeve 3c. The piston disk 43 has the conical extension 39 facing away from an axially normal end face and separates the annular bag space remaining between the conical extension 39 and the sleeve 3c from the chamber of the sleeve 3c containing the liquid. The area of the sleeve 3c which absorbs the liquid is thus essentially free of sack space, which benefits the reproducibility of the mixing process of the sample introduced into the liquid.

The sample collecting sleeve 19c is locked on the sleeve 3c by means of a bayonet coupling against unintentional loosening. The bayonet coupling comprises radially projecting, diametrically opposite pins 45 from the pin extension 21 c, which can be inserted into the assigned bayonet slots 47 and locked against the sleeve 3 c by rotating the sample collecting sleeve 19 c.

On the side of both the sealing bead 41 and the piston disk 43 facing the access opening 37, the inner jacket of the sleeve 3c is closely adjacent to the sealing bead 41 or the piston disk 43 with an inner jacket step slightly increasing the diameter toward the access opening 37, for example by 0.05 mm 49 or 51 provided. The bayonet slots 47 have inclined surfaces 53 which during the unlocking rotational movement of the Specimen collecting sleeve 1 9c, relative to sleeve 3c, forcibly pull the annular bead 41 over the inner jacket step 51 and the piston disc 43 over the inner jacket step 49 and thus cancel the sealing clamping action. The sample collecting sleeve 19c can then be removed completely with comparatively little force. A jerk of detachment when removing the sample collecting sleeve 1 9c with the risk of spilling the liquid contained in the sleeve 3c is avoided.

The sampling rod 13c is also locked in relation to the sample collecting sleeve 19c against unintentional loosening by means of a bayonet coupling. The handle 1 1 c merges with the sample collecting sleeve 1 9c into a closure disk 55, which has radially projecting pins 57 on its outer circumference. The sample collecting sleeve 1 9c in turn has at its end facing away from the sleeve 3c the pin 57 associated bayonet slots 59, in which the pins 57 engage when the sample receiving rod 1 3c is inserted and can be locked by twisting. Between the bayonet slots 59, the sample collecting sleeve carries handling projections 61 which facilitate the unlocking rotation of the sample collecting sleeve 1 9c relative to the sleeve 3c.

In order to facilitate the insertion of the grip area and in particular the closure plate 55 into the sample collecting sleeve 19c, the closure plate 55 continues towards the sampling rod 13c with a plurality of reinforcing ribs 62 which are distributed in the circumferential direction and have insertion edges 64 which run obliquely towards the sampling rod 13c.

Since both the sample collection sleeve 19c relative to the sleeve 3c and the sampling rod 1 3c on the sample collection sleeve 1 9c are locked by bayonet couplings and the handle 1 1 c closes the sample collection sleeve 1 9c with its closure plate 55, the stool sample tube 1 c is extremely transport-safe and also safe when a stool sample has already been introduced. According to the variant of the stool sample tube shown in FIG. 1, the sampling rod 1 3c is first unlocked by turning the handle 11 c and then pulled out axially. After taking up the stool sample, the rod is inserted through the stripping shoulders 23c and the handle 11 c is locked again on the sample collecting sleeve 19c by twisting. By shaking the stool sample tube, which has been resealed in this way, the sample introduced into the wells 15 c is dissolved in the liquid and distributed evenly.

In order to be able to supply the liquid of the stool sample tube 1 c mixed with the stool sample in a defined quantity to the further analysis procedures, the sample collecting sleeve 1 9c can be unlocked from the sleeve 3c and, including the sampling rod 1 3c still connected to it, can be removed from the sleeve 3c. 6, an essentially conical outlet pipe part 63 is sealingly placed on the then free access opening 37, which has at its larger diameter end the pin 65 associated with the bayonet slots 53, with which it can be locked on the sleeve 3c. The outlet pipe part 63 is made of flexible, manually deformable plastic material and has a drop outlet opening 67 at its smaller-diameter longitudinal end, through which 63 drops of a defined size can be dispensed from the liquid contained in the sleeve 3c by squeezing the outlet pipe part. As shown in FIG. 6, the connecting pipe part 63 can engage in the sleeve 3c, or else overlap the sleeve 3c from the outside.

7 shows details of the drop outlet opening 67. This comprises an essentially circular cylindrical drop formation chamber 71, which may widen slightly conically towards the mouth edge 69 of the outlet pipe part 63 and which, towards the other end of the outlet pipe part 63, flows into a throttle channel 73 with the opposite Diameter of the drop formation chamber 71 passes to a reduced diameter. The throttle channel 73 ends on its side distant from the mouth edge 69 in a mouth ring cutter 75. The throttle channel 73 limits the filling speed of the drop formation chamber 71, which in turn ensures drops of uniform size.

In order to prevent solid particles, which were introduced into the liquid by means of the sampling rod 13c despite the wiping shoulder 23c, from the drop outlet opening 67, the outlet pipe part 63 contains a filter body 77, here in the form of a ball made of porous plastic material which, although permitting liquid constituents, contains solid constituents however holds back. The filter body 77 is seated in a press fit or, as shown in FIG. 6, in a positive fit behind retaining ribs 79 or the like and can therefore be installed in the outlet pipe part 63 if necessary, and also subsequently.

In a preferred embodiment, the bottom 35 of the sleeve 3c contains on its inner and / or outer side a central, annular material weakening 80, which allows the bottom 35 to be pierced, for example by a sampling needle of an automatic analysis system. Since the interior of the annular material weakening 80 is thickened compared to the thickness of the material weakening 80, the sleeve 3c can be produced with more uniform properties in an injection molding process.

Depending on the analysis method, the liquid of the stool sample tube 1 c loaded with the sample can be fed directly to the further analysis procedure with the help of the outlet tube part 63, for example by dripping onto a sandwich assay or a microtiter plate or another lateral flow analysis system. In many cases, however, the concentrate contained in the stool sample tube has to be diluted before the actual analysis process. 8a and 8b show a dilution device which can be prefabricated with the dilution liquid and which comprises a predetermined amount (level 77) of dilution liquid-containing, tubular cylindrical cup 79, the access opening 81 of which is sealed off by means of a removable cover indicated at 83. The cup 79 with the lid 83 can be pre-assembled with the predetermined amount of dilution liquid. For the dilution process, the cover 83 is removed and the concentrate contained in the sleeve 3c is dripped into the dilution liquid in a predetermined number of drops via the outlet pipe part 63. The cover 83 is then replaced and the dilution liquid is mixed, for example by shaking. Finally, instead of the cover 83, a drip cap 85 (FIG. 8a) is placed in a sealed manner on the access opening 81. The drip cap 85 has a tube extension 87 which engages in the cup 79 and opens in a tapering manner into a drop outlet opening 89. The drop outlet opening 89 can be implemented similarly to the drop outlet opening 67 shown in FIG. 7 and comprise a throttle channel with an adjoining drop forming chamber ,

In the illustrated embodiment, the lid 83 and the drip cap 85 are attached to the cup 79 by a snap connection. It goes without saying that a bayonet coupling or a screw connection or the like can be provided in the same way. The drip cap 85 and the outlet pipe part 63 are expediently identical in shape in order to keep injection molding costs low.

With the help of the drip cap 85 placed on the cup 79, the diluted test liquid can be fed to the further analysis procedures. It goes without saying that when shaking the cup 79 it may not be necessary to close the lid 83 separately, but that in individual cases the drip cap 85 is sufficient as a closure.

FIG. 9 shows a variant of the sampling device explained with reference to FIGS. 4 and 5a to 5c, which is characterized by particularly high tightness. In particular, the stool sample tube 1 c of this variant can also be subjected to a negative pressure, for example the negative pressure during an aircraft transport, without there being any loss of liquid in the reagent or solvent. Components corresponding to the exemplary embodiment in FIGS. 4 and 5a to 5c are identified by the reference numbers of these figures. To explain the construction and the mode of operation, including the entire construction of the stool sample tube 1 c, reference is made to FIGS. 4 and 5a to 5c.

In this variant, too, the approximately cup-shaped sample collecting sleeve 19c engages with its pin extension 21c with a slight radial play in the sleeve 3c and the pin extension 21c merges to form an insertion bevel for the sampling rod 13c in a conical extension 39 narrowing towards the stripping shoulder 23c. For the sealing of the sample collecting sleeve 1 9c with respect to the sleeve 3c, the pin shoulder 21 c carries the annular bead 41 and the circumference of the piston disk 43 is also provided with an annular bead 91. In order to make it easier to insert the sample collecting sleeve 1 9c into the sleeve 3c and still allow radial press-fit forces to act between the ring beads 41, 91 and the inner jacket 93 of the sleeve 3c when the sample collecting sleeve 1 9c is inserted, the inner jacket 93 is approximately at the axial spacing of the ring beads 41 , 91 are provided with inclined steps 95, 97, which reduce the inside diameter of the inner casing 93 step-wise, so that the inner casing 93 exerts radial constraining forces on the annular beads 41, 91 when the inclined steps 95, 97 assigned to the annular beads 41, 91 are overcome. Corresponding to the gradually reduced inner diameter of the inner casing 93, the outer diameters of the annular beads 41, 91 also decrease in the direction of insertion. The annular beads 41, 91 form a double seal which, owing to the throttling action of successive sealing points, reliably prevents liquid losses between the sleeve 3c and the sample collecting sleeve 1 9c even under reduced pressure.

The sampling rod 1 3c is different from the exemplary embodiment in FIGS. 4 and 5a to 5c in the region of the passage opening 22c receiving it the sample collecting sleeve 1 9c also stepped in its outer diameter. The sampling rod 1 3c has a first section 99 which carries the scooping recesses 1 5c and dips into the sleeve 3c and a closure section 101 which engages in the passage opening 22c when the sampling rod 1 3c is inserted and whose diameter is larger than that of section 99. The inside diameter is also corresponding the passage opening 22c to the liquid chamber of the sleeve 3c stepped. An inner circumferential step 103 narrows the passage opening from a first opening section encompassing the closure section 101 with a radial press fit to a diameter of a section 107 allowing passage of the section 99 essentially without press-fit forces. While the section 105 for generating the radial press-fit forces can optionally have a flat annular bead , The inner diameter of section 107 is approximately equal to the outer diameter of section 99. The diameters of the sections 99, 107 are preferably the same, but with a slight tolerance of the sub-tolerance ensuring the sampling rod 1 3c in the passage opening 22c. In this way, a throttle gap is created between the opposing surfaces of the sections 99, 107, which relieves the seal between the sections 101 and 105. This seal also seals securely against external negative pressure without it being difficult to insert the sampling rod 1 3c due to excessive radial pressing forces.

The sampling rod 13c can tightly close the insertion opening 22c both before and after scooping a sample. However, if the sampling rod 13c is also in the sleeve 3c before the sample is taken, it carries liquid with it when it is pulled out, which can lead to contamination of the surroundings during the sampling. In a preferred embodiment it is provided that the sampling rod 1 3c is inserted into the liquid chamber of the sleeve 3c for the first time after the sampling. Until then, the push-through opening 22c is indicated by an integral part of the sample collecting sleeve 19c indicated at 109. molded membrane 1 09 tightly sealed. The membrane 109 has a thickness of for example one or two hundredths of a millimeter and is pierced by the tip of the sampling rod 13c when the sampling rod 13c loaded with the sample is inserted into the liquid chamber. In the exemplary embodiment shown, the membrane 109 is arranged flush with the piston disk 43. A membrane of the type described can also be provided in the variants of the sample preparation device explained above.

At least the stool sample tube 1 c shown in FIGS. 4 and 5a to 5c, pre-assembled with the required amount of liquid, and the outlet tube part 63 together form a commercial packaging unit. A component of the commercial packaging unit is preferably also at least one with a layer of floatable, water-soluble material to facilitate the removal of stool. The sheet can be made from a film of the buoyant, water-soluble material, e.g. consist of a film made of PEG (polyethylene glycol), PVP (polyvinylpyrolydone) or a sugar polymer. It is conveniently opaque to facilitate its handling. The sheet advantageously consists of a composite of the water-soluble, floatable material and a layer of rotten, opaque paper (cellulose) in order to delay the dissolution in the water. Also preferred is the dilution device consisting of the pre-assembled cup 79 containing the dilution liquid and sealed by the cover 83, as well as the drip cap 85 as part of the commercial packaging unit. Except for the analysis devices, all devices required for the preparation of prepared test liquids are therefore part of the trading unit. It goes without saying that the analysis devices can also be part of the trading unit. In particular, the lateral flow system can be part of the packaging unit.

Claims

EXPECTATIONS

1 . Sample preparation device, in particular for stool samples, with ε a closable container (3c) for holding a liquid

Reagent or / and solvent and a sampling rod (13c) which has at least one scoop recess (15c) in the area of one of its ends on its peripheral surface. and with this end can be inserted into the vessel (3c) through an insertion opening 0 (22c) of the vessel (3c) provided with a stripping shoulder (23c), characterized in that the vessel (3c) has a closure part (19c) which can be removed by a has closed access opening (37) and that the sampling rod (13c) relative to the part of the vessel (3c) forming the insertion opening (22c) on the one hand and 5 the closure part (19c) relative to the part of the vessel (3c ) on the other hand, is sealed by a sealing arrangement (41, 91 or 1 05, 107), to which, particularly towards the side of the reagent or solvent, a sampling rod (1 3c) or the closure part (1 9c) is enclosed Throttle section connects.

2. Sample preparation device according to claim 1, characterized in that the vessel is designed as an elongated, the sampling rod (13c) in the longitudinal direction, on one of its longitudinal 5 the sealed sleeve (3c), the other longitudinal end of which is that of the removable closure part (1 9c) forms a closed access opening (37) and that the closure part (1 9c) has the insertion opening (22c) for the sampling rod (13c) provided with the stripping shoulder (23c). 0

3. Sample preparation device according to claim 2, characterized in that the closure part (13c) as a cup- or sleeve-shaped A sample collecting part is formed which, facing the sleeve (3c), forms the stripping shoulder (23c), in particular in the form of an annular lip.

4. Sample preparation device according to claim 2 or 3, characterized in that the closure part (1 9c) engages in the sleeve (3c) and in the sleeve (3c) on a jm substantially axially normal to the longitudinal direction of the sleeve (3c) extending end face of a Sealed sleeve (3c), the stripping shoulder (23c) carrying piston portion (43) of the closure part (1 9c) ends.

5. Sample preparation device according to claim 4, characterized in that the piston section is designed as a piston plate (43) coaxial with the wiping shoulder (23c) and the closure part (1 9c) tapers towards the piston plate (43).

6. Sample preparation device according to one of claims 2 to 5, characterized in that the closure part (1 9c) engages at least over part of its axial length in the sleeve (3c) and that in this engagement area to form the throttle section with axial

At least two annular bead seals (41, 91) sealing in a radial interference fit are provided between the sleeve (3c) and the closure part (1 9c) at a distance from one another.

7. Sample preparation device according to claim 6, characterized in that the annular bead seals (41, 91) on one of the two parts - the inner jacket of the sleeve (3c) or the outer jacket of the closure part (1 9c) - are integrally formed.

8. Sample preparation device according to claim 7, characterized in that the diameter of the other of the two parts between the bead seals (41, 91) is stepped and decreases in the direction of insertion of the closure part (1 9c).

9. Sample preparation device according to one of claims 2 to 8, characterized in that the sampling rod (13c) has a first section (99), which can be inserted into the vessel (3c) through the insertion opening (22c) and is provided with the scoop recess (1 5c) ) with an enlarged, ring-shaped, compressed second section (101), which is sealed in the inserted sampling rod (13c) in a radial press fit in the insertion opening (22c) and that the insertion opening (22c) in the region of the first section (99) of the Sampling rod (13c) has an opening section (107) which forms the throttle section and is reduced in inside diameter.

1 0. Sample preparation device according to one of claims 1 to 9 or the preamble of claim 1, characterized in that the insertion opening (22c) of the closure part (1 9c) is sealed by a membrane (1 09) which can be pushed through by means of the sampling rod (1 3c) is.

1 1. Sample preparation device according to claim 10, characterized in that the membrane is integrally formed on the closure part (19c).

1 2. Sample preparation device according to one of claims 1 to 1 1, characterized in that the closure part (1 9c) by means of a bayonet coupling (45, 47) on the vessel (3c) can be locked.

1 3. Sample preparation device according to claim 1 2, characterized in that the vessel (3c) near its sealing surface associated with the closure part (1 9c) at least one to the diameter Has access opening (37) extending inner jacket surface step (49, 51) and that the bayonet coupling (49, 51) pulls the closure part (1 9c) with its sealing surface during the unlocking movement away from the vessel (3c) and over the inner jacket step (49, 51) - has inclined surfaces.

14. Sample preparation device according to one of claims 1 to 1 3, characterized in that the sampling rod (1 3c) can be locked on the closure part (19c) by means of a bayonet coupling (57, 59).

1 5. Sample preparation device, in particular for stool samples, with a closable vessel (3) for receiving a liquid reagent and / or liquid solvent and a sampling rod (13) which has at least one scoop recess (1 5) in the area of one of its ends on its peripheral surface and can be inserted at this end into the vessel (3) through an insertion opening (22) of the vessel (3) provided with a stripping shoulder (23), characterized in that the vessel (3) is an integrally formed, at a predetermined predetermined breaking point (9 ) Detachable closure part (7) which closes a drop outlet opening (5) of the vessel (3) which is open when the closure part (7) is detached.

1 6. Sample preparation device according to claim 1 5, characterized in that at least the area of the vessel (3) receiving the reagent and / or the solvent consists of a flexible, manually deformable material, in particular plastic material.

17. Sample preparation device according to claim 1 6, characterized in that the closure part (7) and the outlet opening (5) are integrally formed in the flexible region of the vessel (3).

1 8. Sample preparation device according to one of claims 1 5 to 1 7, characterized in that the vessel (3) is designed as an elongated, the sampling rod (1 3) in the longitudinal direction receiving sleeve, the closure part (7) and at one of its longitudinal ends in the longitudinal direction opposite the stripping shoulder

(23).

1 9. Sample preparation device according to claim 1 8, characterized in that the sleeve (3) the closure part (7) opposite by means of a through-opening (22) for the sampling rod (1 3) provided sample collection part (1 9) is closed, which the The sleeve (3) faces the stripping shoulder (23) in the form of an annular lip.

20. Sample preparation device according to claim 19, characterized in that the sample collecting part (1 9) engages with a pin extension (21) in the sleeve (3) tightly, but guided in a longitudinally displaceable manner.

21. Sample preparation device according to claim 20, characterized in that the sample collecting part (1 9a) and the sleeve (3a) comprise mutually associated latching members (25, 27, 29) which position the sample collecting part (1 9a) and the sleeve (3a) relatively but releasably fix to each other, from which these components can be moved towards and / or away from each other in the longitudinal direction of the sleeve (3a).

22. Sample preparation device according to claim 21, characterized in that the latching members (25, 27, 29) fix the pin extension (21 a) in two positions relative to the sleeve (3a).

23. Sample preparation device according to one of claims 1 9 to

22, characterized in that the sample collecting part (1 9) including the sampling rod (1 3) can be removed from the sleeve (3).

24. Sample preparation device according to one of claims 1 5 to

23, characterized in that a plurality of vessels (3b) with sampling rods parallel to one another and outlet openings (5b) lying on a line are connected to form a structural unit.

25. Sample preparation device according to claim 24, characterized in that the vessels (3b) are detachably held on a common connecting rail (31).

26. Sample preparation device, in particular for stool samples, with a closable vessel (3c) for holding a liquid reagent and / or liquid solvent and a sampling rod (1 3c) which has at least one scoop recess (1 5c) in the area of one of its ends on its peripheral surface and with this end it can be inserted into the vessel (3c) through an insertion opening (22c) of the vessel (3c) provided with a stripping shoulder (23c), characterized in that the vessel (3c) closed one by means of a removable closure part (1 9c) Has access opening (37) to which, when the closure part (1 9c) has been removed, an outlet pipe part (63) which ends at one end in a drop outlet opening (67) can be attached in a sealed manner with its other end.

27. Sample preparation device according to claim 26, characterized in that the outlet pipe part (63) which can be attached to the access opening (37) consists of a flexible, manually deformable material, in particular plastic material.

28. Sample preparation device according to claim 26 or 27, characterized in that the outlet pipe part (63) tapers approximately conically towards the drop outlet opening (67).

29. Sample preparation device according to one of claims 26 to 28, characterized in that the drop outlet opening (67) at one end of the outlet pipe part (63) ends in a drop-forming chamber (71) which towards the other end of the outlet pipe part (63) a throttle channel section (73) with a smaller diameter in relation to the diameter of the drop-forming chamber (71) merges.

30. Sample preparation device according to claim 29, characterized in that the throttle channel (73) has an orifice ring cutting edge (75) towards the other end of the outlet pipe part (63).

31 Sample preparation device according to one of Claims 26 to 30, characterized in that the outlet pipe part (63) has a filter body (77) which retains solids, in particular a filter body (77) made of a porous solid material which is permeable to liquids, between its two ends.

32. Sample preparation device according to claim 31, characterized in that the filter body (77) is held non-positively or positively in the outlet pipe part (63).

33. Sample preparation device according to claim 31 or 32, characterized in that the filter body (77) has a spherical shape.

34. Sample preparation device according to one of claims 26 to 33, characterized in that the sample preparation device is additionally designed according to one of claims 1 to 1 4.

35. Test device set for a sample preparation, in particular in the form of a commercial package comprising a sample preparation device according to one of claims 1 to 14 or 26 to 34, with a container containing the liquid reagent and / or liquid solvent in a predetermined amount and closed by the closure part (19c) ( 3c) and a sampling rod (13c) inserted or insertable into the insertion opening and further comprising the outlet pipe part (63) in each case according to one of the preceding claims 26 to 34.

36. Test device set according to claim 35, characterized in that it furthermore contains a second liquid solvent in a predetermined amount containing a vessel (79) with an access opening (81) closed by a removable lid (83) and, moreover, one with the lid (83) removed. includes a drip cap (85) which can be sealed against the access opening (81) and forms a drop outlet opening (89).

37. Test device set according to claim 36, characterized in that the drop outlet opening (89) ends in a drop-forming chamber which merges towards the vessel (79) into a throttle channel section with a smaller diameter in relation to the diameter of the drop-forming chamber.

38. Test device set according to any one of claims 35 to 37, characterized in that it comprises at least one sheet with a layer of water-soluble material for settling stool.

39. Test equipment set according to claim 38, characterized in that the sheet is multilayered and on at least one side of the layer made of the floatable, water-soluble material has a further layer made of a decomposable material, in particular an opaque, decomposable material.

40. Test device set according to one of claims 35 to 39, characterized in that it comprises a lateral flow device.