System for automatic opening of reagent vessels

ES 2 556 969 T3

DESCRIPTION

Automatic reagent container opening system

The invention relates to the technical field of automatic analysis devices in which a large number of reagents can often be accommodated and processed simultaneously. In this regard, it is desirable to allow, as far as possible, fully automatic handling of samples and reagents in the analysis devices, so that no manual handling step is necessary. This enables the simplification and acceleration of many analysis procedures and errors due to human error during the analysis procedure can be minimized.

Automatic analysis devices are subject to high demands, especially in large laboratories, where a high sampling rate must be possible. In them the analysis devices must be able to handle a large number of reagent containers with different samples and must be able to assign them to different reagent containers. In this aspect, pipetting devices are used, among others, to allow the analysis of a sample, by adding the corresponding reagents, in addition to additional sample processing steps. In this way, with fully automatic reagent and sample handling, even time-consuming analysis procedures can be carried out reliably and quickly, without the need for specialized personnel for specialized analysis procedures. A requirement of a fully or partially automated analysis procedure is, for example, the handling of different amounts, which requires a corresponding amount of reagents. A fully automatic analysis system must satisfy a wide variety of requirements. There are high-throughput analysis systems and others with low throughput, as outlined briefly below:

In low-yield reagent assay systems, the cycle time for liquid extraction is approximately 4 to 10 seconds, with the pipetting needle piercing the cap of the container at each extraction. The reagent cartridge has a relatively long residence time in the device, due to low throughput. The residence time is further extended if the reagent cartridge contains little-used reagents that are not frequently requested and the reagent cartridge contains little-used reagents that are not frequently requested and therefore may remain up to 4 weeks in the analysis system with low yields. In such reagent cartridges there is a need for a high level of protection against evaporation.

In assay systems characterized by high reagent yield, the cycle time is generally short, 1 to 4 seconds, for pipetting and positioning of the reagent rotor and pipetting needle. Due to the short cycle time, it is not possible to pierce the funnels with the pipetting needle. Due to the high throughput of the reagents, the residence time of the respective reagent cartridges in such test systems is only one to two days, so in this case evaporation from an open flask can be tolerated.

The handling of very small volumes is described in, for example, patent no. EP 0 504 967. Said document discloses reagent containers that allow the extraction of small volumes and in which evaporation or aging of the liquid is avoided. remaining in the container during subsequent processing steps.

To this end, the reagent container has a suitably designed lid which, on the one hand, is suitable for the extraction of liquid and, on the other hand, suppresses the evaporation of the contents of the container. The lid has, in the center of its base, a circular opening directed to the inside of the lid and opens to the outside at a conical tip. To extract a sample, the tip of the cone is first pierced, so that a pipetting needle, which is provided to extract very small amounts of sample, can be inserted into the container. After removing the reagent from the container, a small opening remains exclusively at the tip of the cylinder. After the sample is drawn, the small opening at the tip of the cap barrel also ensures that virtually no liquid evaporates from the reagent container and that the contents of the container do not change due to contact with, for example, atmospheric moisture or moisture. oxygen in between. You can get more information on such a container closure from the prior art.

However, if higher throughput and shorter processing times are to be achieved, the pipetting device, if it is to allow efficient handling of samples, must be provided with correspondingly large pipetting tips for aspirating liquid. In order to ensure that in this case also the larger pipetting tips can still be inserted into the reagent container, a larger opening in the lid would be necessary.

In the prior art, many possible ways are described to generate openings in a closure of a reagent container. As described in US Patent Nos. 6,255,101 and 3,991,896, this can be accomplished by pushing a bag through a shaft of a reagent container lid with the aid of a pin. The ball is pushed into the reagent container so that the reagent can then be removed.

ES 2 556 969 T3 liquid through the shaft. Similarly, other possibilities are conceivable, for example piercing a closure cap by means of a cannula, such as in WO 83/01912. The diameter of the opening can be selected according to the size of the shaft or the cannula.

An alternative to an enlarged opening in a reagent closure involves removing the cap from the reagent containers before use.

In the prior art, such type of sample handling is used for example in analysis systems in the field of clinical-chemical analysis of biological samples. To extract a desired amount of liquid reagent, the reagent is withdrawn from the open reagent container and transferred via an automatic pipetting device into a reagent cuvette. For each pipetting procedure, an arm of the electromechanically controlled pipetting device is guided into an open reagent container so that sample handling can take place in the desired manner. The content of a standard reagent container in this case is sufficient for a large number of pipetting procedures. In this regard, it has been found that the liquid evaporates during the analysis method before it can be completely consumed, on the one hand due to the removal of the reagent closure and, on the other hand, due to the creation of a large opening in the closing cap. Especially in rooms with low atmospheric humidity, considerable amounts of the reagent solution are often lost through evaporation. One consequence of the above is that evaporation causes an increase in the concentration of the reagent in the liquid. In contrast, the volume of the reagent solution is increased by using open reagent containers in rooms with relatively high atmospheric humidity, or by condensation water that forms when using cold reagents, so that the reagent concentration is reduced. over time. In addition, when using open reagent containers, gas exchange occurs with the surrounding air, which among other things causes the reagent to age. Said effects on the reagent, in particular on the concentration of the reagent, result in deterioration of the precision of the analysis. It has further been found that removal of the reagent cap often must be done manually. Under these circumstances, laboratory personnel must remove new reagent containers from their packaging and first remove the closure in order to insert the open reagent container into the analysis system instead of an empty reagent container. Because it often happens that many different reagents are required at different times in the same analytical system, manual handling by laboratory personnel requires considerable work. When reclosing the containers, it must additionally be ensured that the closures are not intermingled. In procedures that are carried out manually, the possible confusion of the closures represents a source of uncertainty.

Therefore, methods that allow automatic removal of a reagent container closure are described in the prior art. Document No. EP 0 930 504 discloses a lid gripping device which is intended for the automatic handling of a lid on sample containers. The lid of the sample containers in this case has a projection to which the lid gripping device can grip. By means of a claw the lid is held so firmly that lifting the lid gripping device completely disengages the lid from the container, while a holding sleeve keeps the container pressed in such a way as to prevent the container from lifting .

US 5,846,48 similarly discloses an automatic system for opening reagent containers. In this system, a pin of a gripping device is inserted into a groove provided for this purpose in the lid. At one end, the spike has a bead that allows the spike to be trapped in the groove of the lid. The lid can then be removed from the reagent container by lifting the spike.

Furthermore, in US Patent No. 5,064,059, a device is described which allows a lid to be removed from the reagent container. However, the described prior art discloses only an automatic opening of reagent containers closed with a stopper. Usually only stoppers are used to close test tubes in which, for example, blood or other liquid from the human or animal body is received, but not reagent containers. A disadvantage of the prior art is in this case that the mechanisms described do not allow the opening of a screw-type closure of a reagent container. However, in practice it has been found that, for reagent containers that often contain a volatile liquid, a screw-on closure is particularly suitable since this screw-on-type closure ensures a reliable sealing of the container.

In the prior art, US Patent No. 6,216,340 describes the removal of a reagent closure that is attached to the container by screwing on. In this case, the opener and reagent cap interact in a bayonet-type closure. Through a guide groove formed in the reagent closure, the automatic opener can insert a pin along the guide groove by rotation into the cap until it is mounted against a limit stop of the guide groove. In the event that the rotational movement is continued in this direction, it is possible to rotate and uncover the reagent container. By rotating the opener in the opposite direction the connection between the cap and the opener is released again. A disadvantage of the prior art is the fact that it is an essential requirement that the bayonet-type closure on the lid be precisely produced in order to ensure the functional reliability of the system. The screwing operation, after filling the container, should ensure a close tolerance angle position of the bayonet type closure and also have a good sealing effect.

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In addition, the opener must be precisely guided to the respective reagent container to allow engagement of the opener shank with the bayonet-type closure. This requires precise positioning of the reagent containers in the analysis system or detection of the position by the analysis system of the respective reagent container. In addition, complex reagent cap production tools are required, with the result that production costs are increased. In particular in the case of reagent containers managed as disposable items, this is a considerable disadvantage. Before the opener, after removing a first lid, can be used again to open reagent containers, the lid must additionally be removed from the opener. In the example indicated, additional measures are required for this, which allow rotation of the cap in the opposite direction so that the cap can be removed from the opener.

Document No. EP 0 383 564 A1 discloses a cap extractor apparatus for automatically removing caps from liquid containers. The apparatus comprises a holder with a gripping element that can be securely locked against rotation in the cap of the liquid container.

In US Patent No. 3,830,390, a safety closure for medicine bottles or the like is described. The closure comprises an internally threaded cap and an external adapter. The lid of the container is removed by pressing the adapter down and unscrewing the lid.

Document No. JAP 05 228379 A shows an extraction device for test tube caps. The extraction device contains arms that grip the cap of the tube. The cap can be removed by a combined rotation and removal movement.

In US 5,297,599 A, a closure device for sealing reagent containers in an automatic pipetting system is disclosed.

Document No. DE 44 21 220 C1 discloses a closure for bottles or cans. The closure contains a screw cap covered with a cap cover to form a safety closure.

Document No. DE 295 09 760 U1 shows a container having a screw closure and a device for automatically closing the container.

A universal cap that can be used to close containers of various sizes, such as those used in healthcare, is disclosed in document No. WO 98/21109 A1.

And in document No. WO 99/12475 A1 a method and a device for extracting biological samples is disclosed.

The object of the invention is to eliminate the disadvantages of the prior art. This is accomplished by providing automatic reagent container opening in a testing device by unscrewing, without the need to place undue demands on the method steps on the testing device and the system itself. Therefore, the invention has the object of providing a system for opening reagent containers as defined in claim 1.

The invention further includes a method for opening reagent containers according to claim 13. The system features a carrier configured to rotate about an axis and a centering unit that is essentially guided within the carrier. At the lower end of the holder is a latching element which has been configured so that it can be securely locked against rotation in a cover provided for this purpose. The system further comprises a drive unit configured to move the centering unit and with it the carrier along the axis that is perpendicular to the plane of rotational movement of the hooking element. In this way the centering unit is connected to the carrier by springs, so that the centering unit can move inside the carrier along the axis. In the event that the carrier latch is rotated, the displacement of the latch will cause a rotational movement of the cap, so that a threaded connection can be released. In contrast, the centering unit has, at the lower end, a snap-fit ​​element which can be engaged in a snap-fit ​​connection with a cap provided for this purpose. Before locking the latching elements in a lid to be opened, the centering unit advantageously first engages in a snap-fit ​​connection. By connecting the centering unit to the lid in this way, the existing snap-fit ​​connection indirectly allows a relative position of the carrier with respect to the container lid and thus easy mutual guidance of the hooking elements. The carrier latch can now be correspondingly locked in a latch on the lid. In the case where the centering of the system is advantageously carried out in the manner indicated, the steps of the method of opening the reagent containers in the analysis system can be simplified, since it is possible to some extent to dispense with a precise guide from the opener to the reagent container, in particular from the respective hooking elements relative to each other. The indicated preliminary centering of the system consequently also makes it possible to use small-size hooking elements, without it being necessary to require more in particular of the steps of the method. When connecting the cap to the 4

ES 2 556 969 T3 snap-in element and unscrew the latter from the reagent container by rotational movement, the disengaged lid can be moved away from the reagent container by displacement of the snap-in element, which is essentially perpendicular to the plane of movement rotational, wherein during the procedure the cap remains hanging from the snap-fit ​​element.

Also, reagent containers with a screw cap are disclosed, which are not part of the invention. Said reagent containers can be opened with a system according to the invention. To this end, the reagent containers comprise a container with a container neck having a thread. The reagent containers can be screwed onto a lid and closed with the lid. The lid comprises a sleeve in the shape of a hollow cylinder which, on its internal face, has a thread that interacts with the rose on the neck of the container so as to allow a snap-fit ​​connection between the lid and the reagent container. . The sealing of the lid and the reagent container is achieved with the aid of a sealing lip.

The hollow cylinder formed by the sleeve is closed by a cover plate on the upper face of the hollow cylinder, so that the lid remains open towards its lower face and can be rotated around the neck of the container. The cap further has a snap-fit ​​element and a latch element. The elements have been configured so that they can be engaged in a snap-fit ​​connection with a system to open reagent containers and allow secure locking against rotation in the system.

The reagent container opening system is advantageously used in an analysis system. In this, the analysis system has at least one drive unit that drives the carrier's engagement element so that it rotates. With the aid of the same drive unit or another drive unit, a linear movement of the centering unit is carried out which is essentially perpendicular to the plane of rotational movement. One or more control units in the analysis system adjust the displacement of the carrier and the centering unit so that the closure of the reagent container can be unscrewed and the lid can be separated from the reagent container.

The invention allows automatic opening of the reagent container closed with a screw-type closure. In this respect the invention differs from a simple operating procedure that involves the use of latching elements and snap fit elements in the system. By assigning the movement patterns, ie a rotational movement and a linear movement essentially perpendicular thereto, to separate elements of the opener (carrier and centering unit), considerable simplifications of the opener structure and the operating procedure are possible. According to the invention, a snap-fit ​​connection, which allows the lid to be hung from the centering unit and thus enables the lid to be transported, is made separately from the rotationally secure connection of the lid to the carrier. In this way it is possible, for example, to use simple and robust hooking elements and snap-fit ​​elements which allow, particularly as used in the container lid, economical production of the container closure.

In the context of the invention, the term "lock" is to be understood as any form of rotationally secure connection between the latches of the holder and the reagent container lid. For example, a rotationally secure connection can be ensured by coupling, bumping, etc. of the coupling elements to each other.

In a preferred embodiment, in the operating procedure for opening reagent containers in the manner indicated, the opener is first centered relative to the reagent container, wherein the centering unit engages a press-fit member of the plate. cover of the reagent container closure, before the rotationally secure block occurs between the opener and the reagent container. In the case where a push-fit element is provided for the centering unit in the center of the cover plate, and in the case where the carrier is arranged concentrically around the centering unit, the carrier, and in this way the hooking element arranged on the holder is automatically positioned with respect to the center of the lid. The latching elements of the carrier and the lid can thus be easily engaged one within the other, without requiring exact control of the carrier.

The hooking elements and the snap fit elements can take various forms. Quite simple configurations have been found to allow for a rotationally secure locking and secure connection of the respective elements. In an advantageous embodiment, the cover plate of the closure is provided with a press-fit element in the form of a depression that ends in a tapered cone directed towards the interior of the cover. A depression formed in this way, as already described in the prior art, in EP 0 504 967, facilitates the insertion of a corresponding snap-fit ​​element of the centering unit into the lid of the container. reagent.

In order to further adapt a depression, as described, to a press-fit element of an opener, it has proven to be advantageous if the depression, in its upper area, has a protrusion, for example in the form of a ring, which is project into the hollow space formed by the depression. A corresponding snap-fit ​​element of the opener has a corresponding notch in which it can

ES 2 556 969 T3 adjusting the ring of the depression. It is of course also conceivable that notches are present inside the depression and that the press-fit element of the opener has a correspondingly convex shape. However, in practice it has been found that a concave shape of the opener snap-fit ​​member and a corresponding convex shape of the lid snap-fit ​​member are easier to manipulate, since in this way it is possible to achieve a more favorable distribution of stresses in the lid material. Given the stresses that arise in the material, the stress distribution that is achieved allows for a press fit connection.

A corresponding snap-fit ​​element of the opener advantageously has a conical shape. This facilitates insertion of the snap-fit ​​member into a depression, as noted. As the opener is lowered onto the cover plate, the tapered conical shape of the depression allows automatic preliminary centering of the latch towards the center of the depression. In this way, imprecisely controlled operating procedures can be compensated for.

Furthermore, it is also conceivable that the press fit element is inserted into the depression without the depression having special protrusions or recesses. In this case, the snap-fit ​​member is simply trapped within the depression, so that within the meaning of the invention, the connections where the snap-fit ​​member is securely trapped in the cap are also understood as push-fit connections. This entrapment can be accomplished by shaping the snap-fit ​​member, as indicated. To facilitate a snap-fit ​​connection, it additionally proves to be advantageous if the cap is made of at least two different plastics with different degrees of hardness. In the present invention, for example, the depression is made in a softer plastic than the rest of the lid. The lower hardness of the plastic facilitates, at this point, the adaptation of the depression to the press-fit element of the centering unit in order to achieve a press-fit connection with the opener, since the material has the required elasticity for it. Due to the elasticity of the depression, repeated insertion of the press fit member into the depression is also possible, without causing material fatigue leading to breakage or other damage to the stage. The hard outer area of ​​the cap, on the other hand, must withstand the incident torque during the screwing and unscrewing of the cap and must do so without deformation, particularly of the latching elements. This enables repeated screwing and unscrewing of the cap.

For the hooking elements on the opener and on the lid of the reagent container, various mutually adapted structures are similarly conceivable. In this way, for example, possible channels or ribs become possible both in the hooking element of the opener as well as in the outer wall of the cap sleeve, which guarantee the rotationally secure coupling and locking of the snap-fit ​​elements one within. from another and allow the lid to rotate. It is also possible that each of the opener and lid engaging element have toothed structures that engage each other. The toothed structure of the lid is advantageously formed on the cover plate, so that the hooking element of the opener can engage, directly on the cover plate, within the toothed structure of the lid. In a preferred embodiment, the teeth of the respective hooking element have a bevel so as to facilitate the insertion of one tooth into another. In the event that the lid latch is integrated into the cover plate, it is possible to open the reagent containers without the opener having to engage around the sleeve of the container closure. This minimizes the amount of space taken up by the opener during unscrewing in the analysis system. This proves to be advantageous, especially in analysis systems using reagent kits within a cartridge, since in this case there is often no space for an opener to be attached to the cartridge. In this case the system depends on the opener occupying no space, or only minimal space, within the cartridge in order to achieve rotationally secure locking. Integration of the opener into conventional analysis systems demonstrates that such an advantageous embodiment fulfills important conditions and satisfies the strict demands for spatial adaptation of the reagent cartridge, reagent container and analysis system. To meet the space requirements of an analysis system, the size of the reagent container and closure can also be adapted to match the available space. For example, embodiments are conceivable in which sufficient adaptation is provided by reducing the diameter of the container neck or reducing the depth of the thread of the container neck and the cap sleeve. Advantageously, a reliable sealing of the contents of the reagent container must also be ensured.

To allow automatic handling of a large number of reagent containers, the closing cap must be removed from the opener again after unscrewing. In this regard it is conceivable that the reagent container is closed again after removing the liquid. In the event that the locked connection between cap and opener is maintained during the operating procedure, the cap hanging from the opener can be placed back into the container after the sample is drawn so that, by a corresponding rotational movement of the holder, it can close the reagent container again. The snap-fit ​​connection is then released by a displacement of the snap-fit ​​member away from the reagent container, this displacement being essentially perpendicular to the plane of rotational motion. The snap-fit ​​element of the centering unit is removed from the lid and the lid remains on the container thanks to the threaded connection. In this way the opener is released again and the system can be used again to open

ES 2 556 969 T3 additional containers. To release the snap-fit ​​element from the opener, the reagent container or lid is held tight.

This operating procedure proves to be particularly advantageous in the case where the reagent container contains liquids which, when in contact with the surrounding air, rapidly experience aging effects, or in which the reagent concentration is critically impaired by condensation, for example from atmospheric humidity, or by evaporation of the liquid. The resealing of these containers consequently avoids excessive alteration of the reagents and can be easily carried out with the device / method according to the invention.

However, on the other hand, there is also the possibility of discarding the lid after opening the container. For this, the lid must be removed from the holder and in this case advantageously the opener first places the lid directly on a disposal station provided for this purpose. In a preferred embodiment, the centering unit is movably guided within the holder, so that the cap can be easily pulled out of the opener, as discussed in greater detail below. To this end, the centering unit is moved along its longitudinal axis, while the carrier remains fixed in position in the system. With the cap now hanging from the centering unit it is moved within the holder, by the movement of the centering unit, until bringing the cap against, for example, a projection provided on the holder. A continuation of the displacement of the centering unit in this case has the effect that the cap is pressed against the projection until the cap disengages from the snap-fit ​​element. In this way the cover of the centering unit can be removed without the need for additional movements or devices in the system.

Furthermore, a displaceably guided centering unit within the holder allows for improved positioning of the opener relative to the closure of the reagent container, making such positioning particularly easy in this manner. In this way it is easy to carry out a preliminary centering of the holder by means of a press fit connection of the centering unit with the cap, as indicated.

Furthermore, preliminary centering of the holder can be achieved in the case that the holder is designed in the form of an outer sheath that can be pushed over a partial area of ​​the container closure.

To this end the sheath is initially pushed over a first area of ​​the container lid so that a partial area of ​​the container closure is surrounded by the carrier sheath. Inside the sheath, the carrier advantageously has latching elements that initially rest on the latching elements of the lid when the sheath is encircling the first area of ​​the lid of the container. Now the lid of the container and the holder are located relative to each other in this way, without the hooking elements being mutually locked at this point. By rotational movement of the sheath, the carrier latch members and the lid latch members can now move relative to each other, maintaining mutual preliminary centering of opener and cap. A displacement of the sheath with respect to the lid takes place until the hooking elements engage and lock within each other. So that pushing the pod onto the lid does not require additional space in the analysis system for the opener, an advantageous embodiment of the reagent container features a lid having a reduced diameter in the area where the pod is pushed onto the top. This is often accomplished by reducing the thickness of the cap sleeve, which typically has grooves / notches due to manufacturing procedures. Such channels or notches are generally necessary for the production process, to facilitate mechanized closure of the reagent containers. In the event that the outer radius of the cap is to be reduced, the formation of said channels in the upper area is advantageously omitted, so that the surface of the cap sleeve in this area is smooth. In this way the radius of the lid in this area is reduced by the depth of the channels. In this way, the present advantageous embodiment also satisfies the strict space requirements of commercially standard analysis systems, as noted above.

In one example, the reagent containers are connected to a cartridge to form a reagent kit. For example, said cartridge is made by a holding element, such as has been described in the prior art, for example in document No. US 5,862,934. Said document discloses a large number of reagent containers which, in the neck of the reagent container and in the closure area, are positioned relative to each other by means of a plate with corresponding cavities. The cavities provided for the reagent container necks and the closure areas are in this case closely matched to the circumference of the reagent container lid, so that there is essentially no clearance between the lids and the plate. The result is that it is not possible to unscrew the cap using an opener that must engage around the edge of the cap during unscrewing. Advantageously, said reagent kits can be opened using an opener according to the invention in which the hooking element has a toothed structure, closing the reagent containers according to the invention with a lid that, as hooking elements, has a toothed structure complemented on cover plate. In this way the coupling of the opener around the lid can be avoided.

The invention is explained in more detail with reference to the following examples, describing the embodiments by way of illustration.

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In the drawings:

<td>Figure 1a Figure 1b Figure 1c</td><td>Shows an opening module of an analysis system in perspective view. It shows a side view of the opening module of figure 1a. Displays the area of ​​the push-fit element of the aperture module on an enlarged scale.</td>

<td>Figures 2a, 2b and 2c</td><td>It shows alternative embodiments of a centering unit centrally disposed within a carrier.</td>

<td>Figures 2d and 2e</td><td>It shows a ball-shaped snap-fit ​​member connected to the holder, in a position outside a closure cap and in an insert position in the closure cap.</td>

<td>Figures 3a, 3b and 3c 3d figure</td><td>They show alternative examples of a reagent container lid. It shows an alternative embodiment of a snap-fit ​​member formed on the underside of the holder.</td>

<td>Figures 4a and 4b</td><td>It shows external views of the closure cap according to the representation in Figures 3a, 3b and 3c.</td>

<td>Figure 5a Figure 5b Figure 6 Figure 7 Figures 8 and 9</td><td>Shows the components of a reagent cartridge with three reagent containers, and shows the reagent cartridge in the assembled state. It shows an alternative embodiment of a slotted snap-fit ​​element. It shows another alternative embodiment of a press fit element. It shows a ball-shaped snap-fit ​​member and a cone-shaped snap-fit ​​member, respectively, interacting with a depression in a reagent container lid.</td>

<td>Figure 10.1</td><td>It shows a first alternative embodiment of a snap-fit ​​element designed in the form of a laminated spring.</td>

<td>Figure 10.2</td><td>It shows a second alternative embodiment of a snap-fit ​​element designed in the form of a laminated spring.</td>

<td>Figure 10.3 Figure 10.4</td><td>Shows a slotted design of a push-fit element. It shows another alternative embodiment of a snap-fit ​​element with a cross groove.</td>

<td>Figure 10.5</td><td>It shows an alternative embodiment of a snap-fit ​​element designed as a clip, and the</td>

<td>Figure 10.6</td><td>It shows an alternative embodiment of a snap-fit ​​element in the form of a pin.</td>

Alternative realizations:

Figures 1a, 1b and 1c show different views of an analysis system with a reagent cartridge opening module.

A cartridge 120 located in an analysis system 100 contains three reagent containers 110, 111, with two of the reagent containers 110 being closed, while a reagent container 111 is in the open state. An opening module of the analysis system 100 in Figures 1a and 1b is identified by reference numeral 1.

The reagent cartridge opening module 1 of the analysis system 100 has a holder 2 which, at its lower end, has a latch 4 in the form of a sheath which is pushed onto a lid 20. In the position shown, the latch 4 locks into a reagent container lid 20. The reagent container lid 20 has a depression 22 into which the snap-fit ​​element of the reagent cartridge opening module 1 is inserted. The snap fit elements 5 of the reagent cartridge opening module 1 and the reagent container lid 20 are designed to complement each other, so that the reagent container lid 20 and the cartridge opening module 1 of reagent can be connected to each other and the reagent container lid 20 hangs from the reagent cartridge opening module, that is, on the holder 2 of the latter. A detailed description of the snap-fit ​​elements 5, designed on the holder 2 and on the top of the reagent container lid 20, as shown in Figures 1a, 1b and 1c, is provided below, and is show detailed alternative embodiments of the press fit elements in Figures 2d, 2e, 3a, 3b, 3c and 3d and also in Figures 6, 7, 8 and 9.

In the illustrated position of the reagent cartridge opening module 1 it is possible in principle that the reagent cartridge opening module 1 is also used to reseal the reagent containers 110, 111 or that the reagent cartridge opening module 1 reagent first discards the reagent container cap before the reagent cartridge opening module 1 can then be used to act on the remaining reagent containers 110, 111.

ES 2 556 969 T3

To discard the reagent container lid 20, the reagent cartridge module can be positioned, for example, directly above a discard station (not shown) where the reagent container lid 20 is separated from the opening module 1 reagent cartridge. However, in the event that the reagent container 110, 111 needs to be closed again, the reagent cartridge opening module is first moved by a power unit 112 in the Z direction to the reagent container 110, 111 until Reagent container 20 cap to fit over container neck 130. By a rotational movement of the carrier 2 in the XY plane, the reagent container cap 20 is screwed onto the reagent container 110, 111, simultaneously continuing the movement in the Z direction by an amount corresponding to the rotational movement.

Figure 2 shows details of a reagent cartridge opening module 1 for opening reagent containers 110, 111, with a carrier in which a centering unit 3 is displaceably guided. The centering unit 3 is centrally arranged in carrier 2 and extends along carrier 2 within a guide 12. Centering unit 3 is also connected to carrier 2 via springs 8 and 9. At its lower end, the centering unit 3 has a snap-fit ​​element 5 which in the present invention has been designed in the shape of a ball. The snap-fit ​​element 5 is surrounded by a latch 4 of the holder 4. As in Figure 1, the latch 4 is designed in the form of a sheath, the interior of the sheath being provided with longitudinal ribs / longitudinal channels (not shown) that allow locking into a designed reagent container lid 20. correspondingly. The springs 8 and 9 of the reagent cartridge opening module 1 are mounted in each case by means of the supports 11 and 7 of the centering unit 3 and of the holder 2, respectively. The reagent cartridge opening module 1 is connected by a traction shaft 12 that can produce both a rotational movement of the centering unit 3 as well as, perpendicular to it, a linear movement of the centering unit 3. In its upper area, the centering unit 3 can be designed in the shape of a hexagon. A corresponding formation of the guide 12 of the carrier 2 ensures that the centering unit 3 is fixed in terms of rotation of the carrier 2.

A rotational movement of the centering unit 3 thus automatically produces a rotation of the holder 2. Obviously, embodiments are also conceivable in which the centering unit 3 is received without rotation in the holder 2. To produce a rotational movement of the holder 2 , the carrier 2 is acted upon directly in this case.

To open a reagent container 110, 111, a drive unit (not shown) is used to move the centering unit 3, and with it, the carrier 2, in the Z direction along an axis 16 of the opening module. 1 reagent cartridge. As the lower end of the holder 2 meets with a cover plate of the reagent container lid 20, or the latches 43 provided therein (see the view in Figure 4a), the holder 2 generally first rests first. on the cover plate of the reagent container lid 20. In this position, there is no exact positioning of the latches 4 of the holder 2 with respect to the latches 43 of the reagent container lid 20, so that the latches 43 of the container lid 20 of reagent and the engaging elements 4 of the carrier 2 initially may not engage within each other. When the carrier 2 rests on the lid 20 of the reagent container, the continuous movement of the carrier 2 in the Z direction is blocked. The continuous movement of the centering unit 3 in the Z direction has the effect that the centering unit 3 moves forward inside the carrier 2 in the Z direction. In this way, the spring 8, which presents less resistance than the spring 9, is initially compressed, as shown in figure 2b. Simultaneously, the snap-fit ​​member 5 moves in the Z direction and exits the sheath 4 of the holder 2. Upon exiting, the snap-fit ​​member 5 engages the corresponding snap-fit ​​member of the cap 20 of reagent container. By a slight rotational movement of the traction shaft 6, the snap-fit ​​element 5 fixed in the centering unit 3 is rotated inside the lid 20 of the reagent container, the rotational movement following the holder 2 and thus , also hook element 4. The rotational movement takes place until the latches 4 of the holder 2 and the latches 43 of the lid 20 of the reagent container are correctly positioned relative to each other and can be locked into each other. The outer sheath 13 of the holder 2 can now be engaged with the latches 43 of the lid 20 of the reagent container, the sheath 13 of the holder 2 with the latches 4 being pushed onto the lid 20 of the reagent container. A further rotational movement of the traction shaft 6 has the effect that the lid 20 of the reagent container follows the rotational movement because the latches 4 and 43 are securely locked in terms of rotation and thus the reagent container 110, 111 can be opened by unscrewing. It should be noted that the latching elements of the reagent container lids 20 may be designed in the form of longitudinal ribs 43, as in Figure 4a, and also as longitudinal channels 21, as in Figure 2e.

The slight reverse movement of the reagent cartridge opening module 1 in the Z direction is carried out in order not to prevent the unscrewing of the cap 20 from the reagent container.

Figures 2b and c show the procedure described for opening a reagent container 110, 111. Obviously it is also possible to position the reagent cartridge opening module 1 relative to the reagent container lid 20 directly so that the hooking elements 4 and 43 can be immediately coupled one inside the other and a sheath 13 of the carrier 2 is already pushed over parts of the lid 20 of the 9

ES 2 556 969 T3 reagent container before the snap-in element 5 engages the lid 20 of the reagent container.

The described procedure allows the preliminary centering of the centering unit 3 and, thus, of the carrier 2, with respect to the lid 20 of the reagent container, allowing the simplification of the control procedures in the analysis system 100. By releasing the screw connection between the reagent container 110, 111 and the reagent container cap 20 by rotational movement of the reagent cartridge opening module 1, the reagent cartridge is separated from the reagent container 110, 111 in the Z direction The reagent container lid 20 can now be disposed of in a waste container. To release the lid 20 of the reagent container from the opening module 1 of the reagent cartridge, the projections 14 of the holder 2 are guided against a clamping device 15. In the event that the reagent cartridge opening module 1 moves in the Z direction, so that the holder 2 in the analysis device rests on the clamping device 15, only the centering unit 3 moves within of the carrier 2, and the lid 20 of the reagent container connected to the centering unit 3 follows the movement, as shown in FIG. 2c. In this way the spring 9 is compressed and the spring 8 is relaxed. The reagent container lid 20 follows the movement of the snap-fit ​​element 5 until the reagent container lid 20 within the holder 2 is guided against the end face 10 of the knockout. Through the vertical movement of the centering unit 3 with respect to the holder 2, which is retained by the clamping device 15, the centering unit 3 is pulled back with respect to the holder 2 until the lid 20 of the reagent container rests against the face. terminal 10 of the knockout hole, and in a further movement the snap-fit ​​connection between the cap 20 of the reagent container and the opening module 1 of the reagent cartridge is released, and the reagent container lid 20 falls from the holder 2 sheath. The reagent container lid 20 is no longer attached to the reagent cartridge opening module 2 and the reagent cartridge can be used for additional reagent containers 110, 111 .

Figures 2d and 2e illustrate in detail the snap-fit ​​connection, shown in Figures 2a and 2c, between the reagent cartridge opening module 1 and the reagent container lid 20. The snap-fit ​​element 5 of the centering unit 3 is designed in the shape of a ball 5, as already shown. A correspondingly adapted reagent container lid 20 has a depression 22 which projects into the lid and ends in a conical tip 23. Thus, in addition to its function according to the invention, a reagent container lid 20 designed in this way also presents the possibility of being used in a method with low sample throughput, as described in the prior art. The reagent container lid 20 also has sealing lips 25 that ensure reliable sealing of the reagent container 110, 111 in the closed state. The outer jacket of the lid 20 of the reagent container has hooking elements 43 in the form of longitudinal ribs, as already described in relation to figure 1. In the upper area 24, the depression 22 is formed of concave recesses 24 , so that a reliable snap-fit ​​connection with the ball 5 of the centering unit is facilitated.

Figure 2e shows the procedure already described in which the carrier 2, in its lower area, is pushed onto the lid 20 of the reagent container, the locking elements of the carrier 2 and the lid 20 of the reagent container, blocking one within the other. Simultaneously, the ball 5 fits into the depression 22 of the lid 20 of the reagent container. The conveniently concave shape of the depression 22 in the upper area 24 of the reagent container lid 20 not only ensures a reliable snap-fit ​​connection but also ensures that the plastic of the reagent container lid 20 is not exposed to no excessive tension when snapping the ball-shaped latch 5, thereby avoiding damage to the lid 20 of the reagent container. This is particularly important in the event that the lid 20 of the reagent container is not discarded after opening, but is instead intended to be used to close the reagent container 110, 111 later during the course of the operating procedure. .

Figures 3a, 3b, 3c and 3d show different examples of the reagent container cap and snap-fit ​​element.

Figure 3a shows a cross section of a reagent container cap 20 which is contacted by a thread 31 to a container neck of a reagent container 30. The reagent container cap 20 has a thread 31 and, in use , is connected in this threaded area to the neck of the container 130 and its threaded portion 31 (not shown).

The lid 20 of the reagent container has a conical shaped depression 22. The snap-fit ​​element 5 complementary to the centering unit 3 has a conical shape which is convex in its upper area 32a. Due to the conical shape of the snap-in element 5, a preliminary centering of the reagent cartridge opening module 1 relative to the reagent container 111 is possible, as already indicated. The convex shaped area 32a further allows for a secure press fit connection.

In order to lock the lid 20 of the reagent container on the opening module 1 of the reagent cartridge, the lid 20 of the reagent container has, in an upper area, latching elements 33 which are integrated in the cover plate of the lid of the reagent. reagent container. As already shown in Figure 2, the lid 20 of the reagent container also has sealing lips 25 that ensure reliable sealing of the contents of the container. Without 10

ES 2 556 969 T3, however, if the hooking elements 43 of the lid 20 of the reagent container are not integrated into the cover plate of the lid 20 of the reagent container, but instead are designed as longitudinal channels 21, such as in Figure 2d, this will require the reagent cartridge to satisfy the space requirements of the reagent cartridge opening module 1.

In the event that the reagent cartridge opening module 1 is used accordingly in an analysis system 100 where only little or no space is available for the integration of the reagent cartridge opening module 1, the reagent container 110, 111 may be made smaller. To this end, it is possible, for example, to reduce the thread depth 39 of the thread 31 so that the diameter of the cap is minimized. However, any reduction in thread depth 39 should only be made to the extent that it ensures reliable sealing of reagent container 110, 111 and sufficient stability of reagent container lid 20 and sealing lips 25.

Figure 3b shows an embodiment of the snap fit elements 5 that are complementary to those of Figure 3a. The snap-fit ​​element 5 according to figure 3b is conical in shape so that, again, the insertion of the snap-fit ​​element 5 into the depression 22 of the lid 20 of the reagent container is facilitated by applying the opening module 1 from the reagent cartridge. The snap-fit ​​member 5 has a snap-fit ​​groove 32b in the shape of a concave ring. As shown in detail in FIG. 3c, the lid 20 of the reagent container has a corresponding protrusion 34 into which the snap-fit ​​element 5 can be snapped. A concave-shaped embodiment of the snap-fit ​​element 5, as shown in figure 3d, is obviously also possible without the snap-fit ​​element 5 being tapered at the top of the snap-fit ​​groove 32b; In the alternative embodiment of the snap-fit ​​element 5 in the view of Figure 3d, it extends in a cylindrical shape at the top of the snap-fit ​​groove 32b. Figures 4a and 4b show alternative examples of a reagent container lid 20.

The latter has, in a cover plate 40, a depression 22 serving as a snap-fit ​​element 5. In an upper area 42 of the reagent container lid sleeve, a toothed structure 44 is formed on the pressure plate. cover 40, in which toothed structure 44 can be locked into a corresponding latch on carrier 2. In order to facilitate the insertion of the hooking elements into one another, the toothed structure 44 has an oblique configuration. In its lower area 41, the reagent container lid 20 has longitudinal ribs 43 which are used to screw the reagent container lid 20 onto the reagent container 110, 111 during the production process. However, in the upper area 42 the longitudinal ribs 43 are not continued, so that in this area the diameter of the cap can be reduced. Due to the reduced diameter of the cap, a sheath 13, for example as shown in the previous figures, can be pushed onto the cap 20 of the reagent container. For preliminary centering of the hooking elements, the sleeve 13 is for example pushed over the upper area 42, the centering unit 3 being further snapped into the lid 20 of the reagent container. The latching elements 4 of the holder 2 are arranged in an upper area of ​​the sheath 13 so that they can be locked into the latching elements on the cover plate 40 of the lid 20 of the reagent container when the sheath 13 has already been pushed. on the area 42 of the lid 20 of the reagent container. In this way, the holder 2 can be positioned relative to the lid 20 of the reagent container with the sheath 13, alone or in addition to the snap-fit ​​connection. In this way, the coupling of the hooking elements one within the other can easily be ensured. By these means, the small-sized hooking elements can also be reliably positioned relative to each other and locked within each other, without imposing great demands on precise control of the carrier 2 or on the design of the hooking elements.

Figures 5a and 5b show, by way of example, a plurality of reagent containers 110, 111 which have a closure and which are joined together to form a reagent kit. Figure 5a shows the reagent containers 110 in the open state. The reagent containers 110, 111 have a reagent container neck 130 with an opening for the extraction of a liquid contained in the reagent container 110, 111. The neck 130 of the reagent container also has a thread 31, so that the reagent container 110, 111 can be closed by screwing the lid 20 of the reagent container. The reagent container lids are designed analogously to those of Figure 4 and have a toothed structure 44 that constitutes the hooking element of the closing lid of the reagent container lid 20, and have a depression 22 as an adjusting element. pressure 5 of the lid 20 of the reagent container, as already indicated in relation to figure 4.

In the area 140 of the reagent containers 110, 111, at the bottom of the necks 130 of the reagent containers, the reagent containers 110, 111 have a groove 141 that interacts with a corresponding channel 153 of a cover 150 and fits into a press fit type connection with it. In this way the cover 150 is firmly connected to the reagent container, with mutual positioning of the reagent containers 110, 111. The cover 150 has up to three recesses 151 that are shaped corresponding to the circumference of the lid 20 of the reagent container. In the assembled state of the reagent container 110, 111 and the cover 150, the cover plate 40 of the reagent container cover 20 and the cover plate 154 of the cover 150 form a plane. The cover 150 also has recesses 152 that allow the reagent kit to be transported within the analysis system 100. The analysis system 100 for this purpose has gripping means that engage in the recesses 152 and allow lifting or adjustment of the reagent kit. Reagent containers 110, 111 display, 11

ES 2 556 969 T3 in its lower area, an obliquely shaped container bottom (not shown) tapering towards the center. This is intended to ensure that a pipette needle, which at all times draws liquid from the center of the reagent container 110, 111, can also easily extract small amounts of liquid residue from the reagent container 110, 111. In order to ensure that the reagent containers 110, 111 can be safely inserted and transported into the analysis device 100 despite the oblique bottom plate, the reagent containers 110, 111 have a bottom area 143 wherein the reagent container 110, 111 is inserted and clamped in each case. The bottom area 43 can be divided along partitions 144 into individual bottom portions 145, 146 and 147. Each reagent container 110, 111 has its own clip-on bottom portion 145, 146, 147. The reagent containers 110, 111 are individually filled and screw-closed, each with its bottom portion 145, 146, and 147 in place, and only then are they mounted on a cartridge.

It would also be conceivable to hold reagent containers 110, 111 and bottom area 143 together in order to ensure that reagent containers 110, 111 are firmly secured within bottom area 143. Bottom area 143, which can also be made in One piece, it features a flat bottom plate, which allows reliable placement of reagent containers 110, 111 in analysis system 100. A reagent kit, in which the reagent containers 110, 111 are joined together by a cover 154 forming a reagent kit, is described in, for example, EP Patent No. 0 692 308. The reagent kit it can be made, for example, of three reagent containers 110, 111, as shown in Figure 5a, or of two reagent containers 110, 111, as shown in Figure 5b. In the case where an identical cover 150 is used for the reagent kits with a different number of reagent containers 110, 111, this will mean that, as shown in figure 5b, some of the holes 151 for the covers 20 reagent container are not being used. However, this is not of great importance during the course of the analysis procedure.

Figure 6 shows an alternative embodiment of a slotted press fit member.

A slotted snap-fit ​​member 51 comprises a slot that extends parallel to the axis of symmetry and can be designed in a first slot length 52. Depending on the desired resilience properties of the slotted snap-fit ​​member 51, the slot can have a first length 52.1 and an additional length 52.2. Reference numeral 53 indicates the width of the groove. This can also be modified, as indicated by the larger slot width 53.1 in Figure 6. The longitudinal slot ends at the tip 61 of the slotted snap-fit ​​element 51. On its circumferential face, it has a snap-fit ​​channel 32b which is concave and annular in shape. At the top of the press-fit channel 32b, the slotted press-fit element 51 has a cylindrical contour 59, while the area of ​​the slotted press-fit element 51 which is located at the bottom of the fit channel a pressure 32b is essentially conical.

Figure 7 shows a further alternative embodiment of a press fit element.

The illustration in Figure 7 shows a split snap-fit ​​54 having a first snap-fit ​​half 55 and a second snap-fit ​​half 56. The snap-fit ​​halves 55 and 56 they are connected to each other in a hinged manner at a hinge 58 and a spring 57 is disposed between the inner faces of the snap-fit ​​element halves 55, 56. The sleeve surfaces of the snap-fit ​​halves 55, 56, shown in cross section, also have a concave-shaped snap-fit ​​channel 32b. At the top of the press-fit channel 32b, the press-fit element halves 55, 56 have a cylindrical contour 59. At the bottom of the press-fit channel 32b, the press-fit element halves 55 , 56 are approximately conical, tapering to a point 61.

With the alternative embodiments of press fit elements shown in Figures 6 and 7 and which are connected to a holder 2 (not shown herein), a press fit connection can be obtained with a cap 20 of reagent container that also takes into account small tolerances in production. The resilience of the snap fit elements shown in Figures 6 and 7, provided with a longitudinal slot or designed in two parts, ensures a reliable grip of the lid 20 of the reagent container.

Figures 8 and 9 show how a ball-shaped snap-fit ​​member or a snap-fit ​​member designed with a snap-fit ​​channel, respectively, interact with corresponding depressions within the lid 20 of the reagent container.

Figure 8 shows a ball-shaped snap-fit ​​member 5 formed in a carrier 2 movable in the insertion direction 63 on the lid 20 of the reagent container. The lid 20 of the reagent container has a conical shaped tip 23 which, in the figure 8 illustration, is configured as a smooth conical surface 60. The ball-shaped snap-fit ​​element 5 penetrates into the cone 23 and It is fixed by a peripheral channel 62. Peripheral press-fit channel 62 is located in upper area 24 of tapered tip 23.

ES 2 556 969 T3

Figure 9 shows a snap-fit ​​member 5 that is formed in a holder 2 and in which a snap-fit ​​channel 32b is formed. The snap-fit ​​element 5 has a cylindrical part 59. By moving the snap-fit ​​element 5 designed with the snap-fit ​​channel 32b in the insertion direction 63 towards the conical tip 23 of the reagent container lid 20, the protrusion 34 in the upper area 24 of the conical area 23 it fits into the press-fit channel 32b of the press-fit element 5, so that a secure press-fit connection is established.

The illustrations in Figures 10.1 to 10.6 show various alternative embodiments of a snap-fit ​​element used in a reagent cartridge opening module 1.

For example, the snap-fit ​​element 5 shown in Figure 10.1 can be designed as a leaf spring 64, with a number of spring tabs 65 adjoining a cylindrical portion 59 of the holder 2. The spring tabs 65 of the fit member a resilient pressure 64 can be oriented at a 90 ° angle to each other, although this is not absolutely necessary. In this way, the individual spring tabs 65 could also be arranged at an angle of 120 ° to each other. Each of the spring tabs 65 has a concave shaped recess 32b that interacts with a complementary raised portion in the wall material of the depression 22 of the lid 20 of the reagent container.

Figure 10.2 further shows a snap-fit ​​element 5 which can be designed in the form of a slotted leaf spring 51. In the carrier 2, which meets the resilient snap-fit ​​element 51, the recesses 66 are arranged on both sides. of a longitudinal groove formed in a first length of groove 52. A cylindrical part 59 extends at the bottom of the recesses 66. This cylindrical part 59 is contiguous, in turn, with the concave shape 32b which ends in a tip 61 of the pressure fitting element 51 designed as a leaf spring. By the weakness of the material provided by the recesses 66 in the circumference of the holder 2, a certain elasticity is provided to the halves of the slotted snap-fit ​​element 51 that is separated by the slot 52.

Figure 10.3 also shows a snap-fit ​​5 in which recesses 66 are absent and is designed with only a slot 68. Due to the absence of recesses 66, the elasticity of the two halves of the snap-fit The pressure that is separated by the slot 52 is considerably less than the elasticity of the snap-fit ​​element 51 at the top of the cylindrical part 59 of which the recesses 66 are located. The snap-fit ​​element 5 designed with a groove 68 also has, in the upper part of the tip 61, a concave shape 32b designed in the form of a peripheral groove.

Furthermore, Figure 10.4 shows an alternative embodiment of a snap-fit ​​member 5 that is provided with a cross groove 67. This means that the individual circumferential segments of the snap-fit ​​member 5 that are separated from each other by the cross groove 67 they receive an elasticity that is greater than the elasticity of the snap-fit ​​element 5 having a single groove 68. The individual segments of the snap-fit ​​element that are separated from each other by the cross groove 67 further present, in the upper part of the tip 61, a concave recess 32b that interacts with a depression 22 (not shown in Figure 10) of the housing cover 20, as indicated in detail above.

Furthermore, Figure 10.5 shows an alternative embodiment of a snap-fit ​​element 5 designed in the form of a clip 69. The clip 69 comprises individual legs 71 of the clip that are arranged at an angle of approximately 90 ° to each other. The individual branches 71 of the clip also have a concave shape 32b on their outer circumference. In addition, clip 69 is tubular in design and has a hollow cavity 72 that extends in the axial direction of clip 69.

Furthermore, Figure 10.6 shows a further alternative embodiment of a snap-fit ​​element designed as a simple spine 70, with the holder 2 presenting a cylindrical part in which, in the lower area located at the top of the point 61, it is forms a peripheral groove of concave shape 32b.

Depending on the embodiment and the desired stiffness, possible materials for the resilient snap-fit ​​elements 5 shown in Figures 10.1 and 10.2 include plastics with good sliding and resilience properties (e.g. POM) and metals, such as like steel, or other materials for springs, for example phosphor bronze. Metallic materials are preferably used in the embodiments of the snap-fit ​​element 5 shown in figures 10.1 and 10.2 and also for the snap-fit ​​element 5 designed as a clip in the illustration in figure 10.5

List of reference numbers reagent cartridge opening module 2 carrier 3 centering unit latch element push-fit element pull shaft 1st bearing

ES 2 556 969 T3 first spring second spring first projections second sheath guide support second projections clamping device shaft reagent container lid longitudinal channels depression conical tip upper area sealing lips thread

32a convex shape of snap-fit ​​element 32b concave shape of snap-fit ​​element latch element protrusion thread depth cover plate container lid sleeve longitudinal ribs toothed structures soft part slotted snap-fit ​​element first groove length

52-1 second slot length

52.2 third groove length first groove width

53.1 second slot width split snap-fit ​​element first snap-fit ​​half second snap-fit ​​half half spring element hinge cylindrical part of snap-fit ​​element 23 push-fit sleeve smooth surface peripheral channel insertion direction snap-in spring barb recess cross groove groove clip spigot clip branch hollow cavity