EP2683486A1

EP2683486A1 - Device for closing a sample receptacle with a spherical closure element

Info

Publication number: EP2683486A1
Application number: EP12712600.1A
Authority: EP
Inventors: Daniel SIMONS; Dirk LEBER; Harald Quintel; Bruno Walder; Andreas Bretscher
Original assignee: Qiagen Instruments AG
Current assignee: Qiagen Instruments AG
Priority date: 2011-03-11
Filing date: 2012-03-09
Publication date: 2014-01-15
Also published as: CA2829706A1; CN103476500A; BR112013023046A2; CN103476500B; WO2012123376A1; AU2012228413A1; AU2012228413B2; JP2014509731A

Abstract

The invention relates to a device for closing a sample receptacle with a spherical closure element, said device comprising a storage container for a plurality of spherical closure elements, expelling means for expelling one of the closure elements through an outlet opening of a housing of the device and means for limiting the force exerted by the expelling means on the closure element.

Description

Device for closing a sample container with a spherical

Closing element "

The invention relates to a device for closing a sample container with a spherical closure element and a system of such a device and a corresponding sample container.

Specimen containers are used, in particular, in the context of biotechnological methods to process a biological sample or a biological material, for example a sample containing nucleic acids. They can be used, for example, in the context of amplification reactions, such as, for example, a polymerase chain reaction (PCR), to amplify nucleic acids in vitro, in which case the sample containers serve to take up the sample comprising the nucleic acids.

A large number of different sample containers are known from the prior art which are regularly used as disposable products in the context of corresponding biotechnological methods such as, for example, PCR. The sample containers are first filled with the sample, then sealed airtight and finally fed to the PCR process. At the closure of the sample containers high demands are made. On the one hand, the sample containers must be sealed reliably in order not to impair the result of the PCR process by the inlet and outlet of sample material or by unwanted pressure change. On the other hand, as part of a PCR process, a large number of samples and thus sample containers are regularly collected used, which must be filled and sealed. This should therefore be done as automated as possible. Furthermore, the sample containers must be inexpensive to produce, especially because they are needed in large numbers and are used as disposable products.

From EP 0 449 425 A2 a sample container is known in which one end of a cylindrical housing forming a sample space is provided with a circular opening which extends channel-shaped into the sample space. The opening channel tapers shortly before the transition into the sample space and thereby forms a seal seat for a spherical closure element. After placing the closure element on the seal seat this is fixed by means of a sealing plug.

The sample container known from EP 0 449 425 A2, as a three-part system, is not only relatively complicated and thus expensive, but can also be automatically closed with relatively little effort.

Based on this prior art, the present invention seeks to provide a system consisting of a sample container and a device that ensures a secure automated closure of the sample container.

This object is achieved by a device according to independent claim 1 and by a system comprising such a device and a sample container according to independent claim 12. The subject of independent claim 16 is a reservoir, which is to be used in conjunction with the device according to the invention according to claim 1. Advantageous development of the device according to the invention, the system according to the invention and the storage container according to the invention are the subject of the respective dependent claims and will become apparent from the following description of the invention.

The system according to the invention comprises a sample container which has a housing which forms a sample space for receiving a sample and has at least one circular opening which extends channel-shaped into the sample space. The sample container can be closed by means of a spherical closure element, wherein the diameter of the closure element exceeds the diameter of the opening channel in at least one (closure) section only so far that one of the closure elements with its largest circumference in the closure portion is non-positively fixable. The non-positive fixing of the closure element by contact of a grö ßten circumference of the spherical closure element comprehensive range with the wall of the opening channel is important to achieve a secure fixation. The resulting forces in this type of frictional fixation namely have 5 no or only a relatively small (and thus negligible)

Force component in the longitudinal axial direction of the opening channel, but are directed (largely) radially towards the center of the spherical closure element. As a result, with only a relatively small (preferably elastic) deformation of the closure element and the wall of the opening channel, sufficient fixation and at the same time a good sealing effect can be produced. A small deformation then requires only relatively small forces for introducing the closure element in the opening channel. This can not only simplify the automation of the closure of the sample container, but also allow a manual closure of the sample container. In addition, the requirements L 5 are reduced to the materials used for the closure element and the housing, whereby the manufacturing cost of the sample container can be kept low.

In the sample container of the system according to the invention causes the spherical

Closure element in connection with the housing of the sample container thus not only the seal but it is also fixed without additional holding means, such as a sealing plug, as it is known from the sample container of EP 0 449 425 A2, process reliable. Such a sample container can therefore be automatically closed in a simple manner by the

2 5 locking element is driven only in a suitable manner in the opening channel of the housing.

To close such a sample container, the system according to the invention comprises a device which has a reservoir for a plurality of

3 0 spherical closure elements and Aussto ßmittel for ejecting one of

Includes closure elements through an outlet opening of a housing of the device. For closing the sample container thus one of the spherical closure elements is driven by means of the ejection means of the device in the opening channel of the housing of the sample container and there

3 5 fixed non-positively.

In the device according to the invention means are provided which limit the ßst of the Aussto (preferably Sto ßel) forces exerted on the closure element forces. These can serve to limit the loading of the closure element or 10 of the housing of a sample container loaded therewith.

In particular, this can lower requirements for the feed control be set of the plunger, as a too large stroke of the plunger compensated by the force limitation and thus too far driving the closure element into the opening channel of the sample container can be avoided.

5

The force limiting means may preferably be formed as (at least one) spring, for example, between the plunger and the drive means, which cause the periodic movement of the plunger, is arranged. Too large a stroke of the plunger can then be compensated by an elastic deformation of the spring

L O become. Of course, it is also possible to arrange the spring at any point of the power flow between the drive means and the support of the sample container. For example, the sample container may be resiliently mounted in a receptacle or the receptacle is mounted resiliently. The spring is preferably biased integrated into the device to a

L 5 responses only when a defined force is exceeded.

On the other hand, of course, it is also possible to control the introduction of force from the ejection means to the closure element by an electronic control of the ejection movement.

1 0

In a preferred embodiment of the device for closing it can be provided that the ejection means comprise a plunger. This allows a constructive simple way of driving one of the closure elements in the opening channel of the sample container.

1 5

Since it is preferably provided to use the device according to the invention for closing a plurality of sample containers in a short cycle, it can preferably be provided to drive the plunger by means of suitable drive means in a periodic (back-and-forth) movement. The device should then be used in combination with a device that is in one of the periodic

Movement of the plunger corresponding timing either the device according to the invention, the individual sample containers to be closed feeds or the device according to the invention can successively drive off the individual sample containers.

35

The drive means for periodically moving the plunger may preferably comprise a rotary drive, which is connected via a gear with the plunger to translate the rotational movement of the rotary drive in the periodic translational movement of the plunger.

10 In a preferred embodiment, the rotary drive for this purpose have a drive disc on which a decentralized bolt is arranged, which is guided in a slot of the Stö tappet or a guide member connected to the plunger, the orientation of the slot non-parallel (also non-coaxial ) is to the 5 direction of movement. This can be in a structurally simple way the

Rotational movement of the drive pulley are translated into a periodic translational movement of the tappet Stel. For a drive of Stö teller in a periodic translational motion can be used on inexpensive commercially available on the market rotation drives (especially electric motors). Of course it is also possible to have any other connection between the

Provide drive pulley and the plunger or the guide element of the tappet Stel.

The drive means can of course also in any other way, for example by a toggle gear or a (arbitrary) linear motor, L 5, for example in the form of a solenoid in an electrically charged coil guided plunger ("solenoid") are formed

In order to achieve a smooth operation of the device according to the invention and in particular to ensure that only one closure element is taken from the tappet and driven into the opening channel of the housing of a sample container, the device according to the invention may preferably comprise a separating device. This can preferably comprise a feed channel, in which the closure elements are arranged one behind the other and via which these one after the other in the trajectory of the

1 5 ram lying transfer position to be supplied. The movement of

Closure elements in the feed channel can be effected by gravity. Alternatively or additionally, any other means of transport, for example means for exerting vibrations or compressed air transport means can also be used.

3 0

The device according to the invention can furthermore have a blocking element which temporarily fixes the separated closure elements in the transfer position. The fixation of the respective closure element by the blocking element is then preferably released only when the tappet causes this to take. This can be achieved in a simple manner by means of a spring-loaded or resiliently suspended blocking element, which is displaced laterally when a force exerted by the plunger on the closure element force is exceeded, so that the movement path of the closure element is released.

1 0 In a further preferred embodiment of the device according to the invention, this support means for supporting the transport of the Closure element from the reservoir to the ejection means. These can preferably act vibrating and / or pneumatic. The support means can effect the transport alone or only support, for example, exercise in conjunction with a gravitational transport.

Preferably, it can be provided to integrate the plunger interchangeable in the device. Such a configuration is particularly useful when used for sealing of sample containers for a biotechnological process, such as, for example, a PCR process, since there are special requirements placed on the sterility. The replaceable integration of the plunger into the device thus allows easy and inexpensive maintenance to meet the sterility requirements in such applications. Alternatively or additionally, the plunger may also be provided with a replaceable (surface) cover. This embodiment may make it possible to meet the sterility requirement of the system with lower costs compared to a replaceable plunger.

Preferably, the device has at least one sensor for detecting the ejection of a closure element, the fill level of the reservoir and / or the force exerted by the plunger on the respective closure element force. Such a sensor allows monitoring and documentation of the closing process.

In a preferred embodiment of the system according to the invention can be provided, the contact surface of the plunger, which comes into contact with the closure element during ejection, larger than the outside cross-sectional area of the opening channel of the housing of the sample container. Thereby, the portion of the housing surrounding the opening channel can serve as a (maximum) stop for the plunger, whereby it can be prevented that the closing element is driven further than intended in the opening channel of the housing. In addition, it can be ensured by the relatively large surface of the plunger that a secure closing can be achieved even with a relatively inaccurate positioning of the device relative to the housing of the sample container. This embodiment should preferably be combined with means for limiting the forces exerted by the ejection means on the closure member to avoid damaging the sample container.

The system according to the invention may further comprise a sensor, which determine the position of the closure element in the housing of the sample container can. Again, this may be useful or necessary for checking and documenting the capping process. One possibility for this may be to make the housing of the sample container optically transparent at least in a section of the closure section, wherein the sensor comprises means for detecting the refractive index of the housing material in the transparent

Section includes. Accordingly, the function of the sensor may be based on detecting a change in the refractive index resulting from a transition of the light from a first solid (wall of the orifice channel at the position where the closure element is positioned) to a second solid LO (shutter member) does not set total internal reflection on the inner wall of the orifice passage, while a transition from a solid (wall of the orifice passage) to air (or other gas) on the inner wall is partially mirrored.

Preferably, it can be provided that the housing of the sample container forms a shoulder for forming a support surface. About this support surface, the forces that are applied for the introduction of the closure element (typically 60 N to 130 N, 250 N maximum), are supported on a sample container supporting the holder. In particular, the bearing surface on a

2 0 location of the housing may be formed, which is located in the vicinity of the closing portion of the opening channel. This can be avoided that the forces on other sections of the housing, which are optionally formed with lower wall thicknesses and thus more sensitive (in particular, the surrounding the sample chamber wall of the housing) are transmitted.

2 5

A storage container for use in a device according to the invention comprises a housing and a guide and / or bearing device arranged within the housing, in which a plurality of spherical closure elements are arranged in a row.

Preferably, the guiding and bearing means may comprise a helically extending guide and bearing channel.

Further preferably, it may be provided that the housing of the reservoir 3 5 has a filling opening, which after filling the reservoir with the

Closing elements is permanently closed. According to the invention, such a storage container is therefore preferably provided as a disposable product, which may be advantageous in particular for sterility reasons. From this point of view it can also be provided that the ejection means (in particular the tappet) is integrated into the reservoir provided as a disposable product. The invention will be explained in more detail with reference to embodiments shown in the drawings.

In the drawings shows:

Fig. 1: a sample container of a system according to the invention;

5 shows a section of the sample container of FIG. 1 in a sectional side view; FIG.

FIG. 3 shows a further detail of the sample container of FIG. 1 in a sectional side view; FIG.

Fig. 4: the introduction of the closure element in the sample container

L O according to FIGS. 1 to 3 by means of a tappet in a first

embodiment;

Figures 5 and 6: the introduction of a closure element in a sample container of Figure 1 by means of a plunger in a second embodiment ..; 7a shows the force curve during the introduction of closure elements in FIG

L 5 sample containers according to FIGS. 1 to 3 using a

Stö tels according to FIG. 4;

Fig. 7b: the force curve during the introduction of closure elements in

Sample containers according to FIGS. 1 to 3 using a

Stö tels according to FIGS. 5 and 6;

Fig. 8a and 8b: a sample container of a system according to the invention in a second embodiment in two different

Sectional views;

9a and 9b: a sample container of a system according to the invention in a third embodiment;

FIG. 10 shows a sample container of a system according to the invention in a fourth embodiment; FIG.

Fig. 1 1: a storage container of a device according to the invention for the automatic closure of sample containers in a first embodiment;

3 0 Fig. 12: a closing unit of an apparatus for automated

Closing of sample containers according to the invention;

FIG. 13 shows a principle drawing for the functioning of the closing unit according to FIG. 12; FIG.

Fig. 14: an isometric view of a reservoir of a

3 5 device according to the invention for the automatic closure of sample containers in a second embodiment;

Fig. 15: the reservoir of FIG. 14 in combination with a

Closing unit in a longitudinal section;

Fig. 16: the reservoir of FIG. 14 in combination with a

1 0 alternative closing unit in a longitudinal section; 17 shows the integration of the components according to FIGS. 11 and 12 into an automated closing device;

FIG. 18 shows the integration of the automated closing device according to FIG.

1 7 in a device for carrying out a PCR;

Fig. 18 is a schematic representation of an alternative supply of

Closure elements to a device for automated

Closing of sample containers according to the invention; and Figs. 20a to 20f are comparisons of a "normal" to deviant one

Force courses, caused by various causes.

L O

FIG. 1 shows a sample container 1 according to the invention in a first embodiment. The sample container 1 has a housing 2, which is formed in a first (head section 3) and a second (middle section 4) section with a substantially cylindrical lateral surface. The lateral surface has only a small

L 5 conical taper, which serves to demold the existing plastic housing 2 after injection molding easier. At the opposite end of the head section 3 of the central portion 4, an end portion 5 connects, in which the housing 2 tapers and thus formed tapering in the broader sense. In the end section 5, the housing 2 is made of one (optical)

2 0 transparent material formed, which is the use of optical measuring elements in

Framework of a biotechnological process, such as, for example, a PCR process in which the sample container 1 is to be used, allows.

On the Au ßenseite between the head 3 and the central portion 4 forms the

2 housing 2 a paragraph 6, which serves as a support surface over which the housing 2 is supported on a Probenbehältnisträger 7 (see Fig .. 2).

Within the central portion 4 and the end portion 5 of the housing 2, a sample space is formed, wherein the wall thickness of the housing 2 in these two

3 0 sections is largely constant, so that in turn is largely cylindrical

Sample space portion within the central portion 4 and a conically tapered, formed with a rounded tip sample space portion in the end portion 5 of the housing 2 is formed.

3 5 In the head portion 3 of the housing 2, an opening channel is formed, which makes it possible to fill the sample container 1 with the sample to be examined. After filling, the sample space is closed by the introduction of a spherical closure element 8 in the manner according to the invention. The closure effect, i. both the sealing and the fixing of the

Closing element 8 in the opening channel is caused by the largest

Au ßendurchmesser of the closure element 8 is slightly larger than that Opening channel in a defined portion (closure portion 1 1) (see Fig. 2) and the closure member 8 is thus fixed by clamping in the opening channel. , Starting from the upper (free) end of the head portion 3 of the opening channel is initially provided with a inlet chamfer 9, the (relative to the 5 Au ßendurchmesser of the closure element 8) large opening cross-section (largest

Diameter: 4.5 mm). The inlet chamfer 9 facilitates the centric attachment of the closure element 8 (largest diameter: 4, 1 mm to 4.2 mm). The inlet land 9 merges into a first annular projection 10, which reduces the opening area (diameter: 3.7 mm) of the opening channel in relation to the opening area L O in the closing portion of the opening channel (diameter: about 4.0 mm). For introducing the closure element 8 in the opening channel, this is loaded with a force (component), which is directed coaxially or parallel to the longitudinal axis of the housing 2 in the direction of the end portion of the housing 2.

L 5

The force is so high that it comes to a deformation of both the housing 2 in the region of the head portion 3 and the closure member 8 itself, which allows the closure member 8 passes the first projection 1 0 and into the closure portion 1 1 of Opening channel is pushed. There it will be

2 0 closure element 8 by its larger (maximum) diameter compared to the diameter of the opening channel in the closure portion 1 1 fixed non-positively, i. clamped. The forces are achieved by a (largely elastic) deformation of the housing 2 in the region of the closure portion 11 and the closure element 8. Due to the symmetrical frictional

2 5 fixation of the spherical closure element 8 in the region of its largest

Cross-section, the reaction forces acting from the wall of the opening channel on the ball - and vice versa - no component in the longitudinal axial direction of the housing. As a result, the closure element 8 is held securely after insertion into the closure portion 1 1, unless significant external forces in

3 0 longitudinal axial direction of the housing 2 act on it.

The first projection 10, which must be passed by the closure element 8 during insertion into the closure section 11, serves firstly as an end stop, which prevents the closure element 8 from generating an overpressure 3 5 within the sealed sample space, for example due to heating in the

Framework of a biotechnological process, such as, for example, a PCR process, is pushed out of the opening channel and the sample container 1 thus opens unintentionally.

1 0 Furthermore, this projection 10 is used to a during insertion of the

Shutter 8 to generate characteristic force curve, based on which Actual introduction of the closure element 8 can be detected in the closure portion 1 1 (in the manner of a snap).

The transition of the opening channel in the sample space of the housing 2 is formed as a 5 annular shoulder. This paragraph represents a second projection 1 2, which serves as an end stop for the closure element 8 and thus limits the closure portion 1 1 of the opening channel on the side of the sample space.

The length of the closure portion 1 1 of the opening channel is dimensioned such that L O the closure element 8 can be displaced therein over a certain distance x before it strikes one of the two projections 1 1, 1 2 (see Fig. 3). In the present case, this distance is limited to a maximum of 0.7 mm, since, according to experience, with such a displacement of the closure element 8, the process parameters (in particular pressure, temperature) within the sample space only change so little that L 5 has no significant (negative) effects the biotechnological

Procedures, such as the PCR process are to be feared. This positioning tolerance of the closure element 8 within the closure portion 1 1 further has the advantage that relatively large tolerances in the manufacture of the housing 2 and the closure member 8 can be specified, whereby

2 0 lower demands on the appropriate tools can be made.

Figures 4 to 6 show the use of a tappet Stels 13 (in two embodiments) to push the closure member 8 in the opening channel. In the embodiment according to the figure 4, the plunger 13 has a 2 5 Au ßendurchmesser of 3.6 mm (or smaller), which is thus lower than that

Inner diameter of the opening channel in the region of the first projection 1 1. The tappet 13 can thus dip into the opening channel. For this purpose, the movement of the tappet should be able to be controlled precisely in order to prevent it from pushing the closure element 8 with a force against the second end serving as the end stop

3 0 projection presses, resulting in damage to the housing 2 or the

Could cause closure element 8. In the embodiment of a Stö ßels 13 according to FIGS. 5 and 6 is therefore provided, the Au ßendurchmesser of Stö ßels 3 significantly larger than the inner diameter of the opening channel in the region of the inlet chamfer 9 form. The movement of the plunger 1 3 is thus at the latest

3 5 limited by that it abuts the free end of the housing 2. One

Pressing the closure element 8 by means of the Stö tappet against serving as an end stop second projection 1 2 can thus be avoided in a simple manner. A further advantage of the large contact surface of the tappet Stel 13 is that a press-in even with a not exactly central arrangement of the plunger 1 3 above the

1 0 closure element 8 is regularly possible without problems (see Fig. 6). FIG. 7a shows an exemplary force progression (force F over the plunger path I) for a closing process using a plunger according to FIG. 4. In a first section (a) of the force curve, the force is almost zero; this section defines the displacement of the plunger 13 until it engages the closure element 5 8. This is followed in a second section by a strong increase in force up to a first maximum value (b) (first extreme point of the curves) required for the closure element let pass the first projection 10. This force then drops to a second extreme point (c), which then (due to the slightly conical design of the opening channel only slightly increasing, cf.

L o section (d)) defines force required to move the ball in the

Closure section 1 1 is required. This force corresponds essentially to the force which results from the friction between the wall of the opening channel in the closure section 11 and the section of the closure element 8 in contact therewith. For a correctly performed closing process

L 5, the application of force ends somewhere in the section (d) of FIG. 7.

However, if the plunger 13 dips too deep into the opening channel, the closure element can be pressed by this against the second projection 12, which is again noticeable by a strong increase in force (section (e)). 2 0 This increase is possibly (ie depending on the immersion of Stö ßels 13) by the breaking load of the sample container 1 (possibly also the closure element 8 or the tappet ßels 1 3) limited (f)), whereby the force a significantly lower level (section (g)) drops.

Fig. 7b shows a corresponding exemplary force curve for the use of a plunger according to FIGS. 5 and 6. The force curve corresponds in the sections (a) and (d) and between them still that of Fig. 7a. After the section (d) then there is an increase in force (h), which is even stronger than in the course of FIG. 7a. This results from the impact of the plunger 1 3 on the edge of

3 0 Sample container 1. The plunger 13 should then only a relatively small way to be moved to avoid overloading the sample container 1 (or the plunger 1 3). In order to control the stroke of the tappet, the force curve can be evaluated so that, for example, when reaching the end of the section (h), a (force) limit value is reached which, for example, shuts off a

3 can lead 5 ram drive. In FIG. 7b, the further course of force is shown in dashed lines, which leads to a rupture of the sample container due to overloading. This is characterized by a continuation of section (h) (section (i)), at the end of which the fracture occurs. This is characterized by a direct decrease of the force to a level near zero (section (k)).

1 0 20a to 20f show by way of example deviations from the "normal" force profiles described above: The deviating force curve is shown with a continuous line, while the "normal" force curve is shown in dashed lines 5 , FIG. 20a shows two deviating force profiles in which the dimensioning or the material properties of the sample container in the region of the opening channel and / or of the closure element are incorrect. FIG. 20b shows two deviating force profiles in which the vertical orientation of the closure element, ie the distance between the closure element and the closure element, is shown

L 0 ram is too small or too big. In the deviating force curve according to FIG.

20c, the horizontal orientation is incorrect, i. there is no sufficient agreement between the longitudinal axes of the sample container and the plunger. This can lead to a hindrance of the movement of the closure element. FIG. 20d shows a deviating force course which occurs in the absence of the

L 5 closure element results and the movement of the plunger without substantial

Force is applied to a collision with the sample container. The deviating force profile shown in FIG. 20e can result if the contact surfaces of the closure element and / or of the sample container do not meet the requirements. On the other hand, FIG. 20f shows a deviating course of force which occurs at

2 0 may result in the breakage of a sample container.

8a and 8b show a second embodiment of a sample container 1, in which two closure elements 8 are fixed in a common closure portion 1 1 of the housing 2 frictionally. This will between the two

2 5 closure elements 8 a second sample space formed. The corresponding

Embodiment of the opening channel may - unlike the illustration in FIG. 8 - be arbitrary according to the embodiment according to Figures 1 to 3, i. in particular be provided with one or more projections. Between the lower sample space and the closure portion 1 1 and between the

3 0 closure sections 1 1 and the upper, open end of the sample container 1, a bypass channel 14 is further introduced into the wall of the housing. The upper bypass channel 14 serves to compensate for an overpressure in the two sample chambers, which would otherwise result from the relatively deep introduction of the closure elements. The lower bypass channel 14, on the other hand, is intended to

3 5, for example, as part of the PCR process to transfer a sample contained in the upper sample chamber in the lower sample chamber, as shown in Fig. 8a. For this purpose, the lower closure element 8 is pushed by means of the upper closure element 8 in the portion of the opening channel / sample space having the lower bypass channel 14, so that the sample from the upper

1 0 sample chamber via the lower bypass channel 14 at the lower closure element

8 can flow past in the lower sample chamber. FIGS. 9a to 9b show a sample container 1 in a further embodiment in which it is intended to reopen it by pushing the closure element 8 completely into the sample space by means of a tappet 13 up to the closed end. The sample liquid displaced thereby can flow off via a bypass channel 14 introduced on one side into the wall of the housing 2 and thus removed from the sample container 1.

FIG. 10 shows a sample container 1, in which the housing 2 is provided with a varying wall thickness in the area of the sample space. In the area of

L o sample space, which receives the sample, the housing 2 has the lowest possible

Wall thickness of e.g. 0.2 to 0.3 mm. A small wall thickness simplifies the examination of the sample by optical methods. In contrast, in a portion of the sample space which forms a dead space (i.e., without a sample contained therein), the wall thickness is made stronger (e.g., twice as strong, e.g., 0.4 to 0.6 mm),

L 5 which not only the mechanical stability of the housing 2 can be increased, but in particular, a evaporation of the sample through the housing 2 can be reduced.

Figures 1 1 and 1 2 show individual components of an automated closure device (see Figure 1 7), which in an apparatus for carrying out a

PCR process to be used (see Figure 18).

In this case, the figure 1 1 shows a reservoir 15, in which an elongated spiral-shaped guide 16 is arranged, the recording and leadership

2 5 a plurality of closure elements 13 of a sample container 1 is used. The lower end of the guide 16 terminates in an outlet opening, via which the closure elements of a closure unit 17, as shown partially in FIG. 1 2, can be transferred. The reservoir 1 5, which can be sold as a filled disposable container, this can at the front end of the

3 0 closing unit 17 are attached.

The closing unit 17 comprises an electric motor arranged in a housing 18, via which a drive disk 19 can be driven in rotation. The drive pulley 19 is provided decentrally with a bolt 20 which is in a slot

3 5 21 a ram guide 22 is guided. The leadership of the bolt 20 in the slot 21 translates the rotational movement of the drive pulley 1 9 in a cyclical upward and downward movement of the tappet guide rel 22 including an attached tappet Stel 13, as shown in principle in the figure 13. With each downward movement of the plunger 13 is a held in a transfer position closure element. 8

1 0 carried along and via an outlet opening of the closing in the

Opening channel of an underlying housing 2 of a sample container. 1 (Not shown in Fig. 1 3) pressed. After re-booting the tappet Stel 13 then another of the intermediate in a feed channel 23 interposed closure elements 8 (gravitational) roll into the transfer position, where this is held by a spring-mounted locking element 24 5. In the subsequent downward movement of the Stö tapple 1 3 then the next closure element 8 is taken, the locking element 24 is displaced laterally to release the outlet opening.

Alternatively, it is also possible, the periodic back-and-forth movement of the LO plunger 13 is not caused by a rectified rotation (360 °) of the drive pulley 19, but this can also be driven by a stepper motor with a (cyclic) change of direction to realize the movement of the plunger 13. As a result, any and, in particular, also changing travel paths, speed profiles, etc. of the tappet 13 can be realized. This L 5 can be used in particular to the ß of the tappet 1 3 on the

Closing element 8 limiting force (in conjunction with a sensory measurement) by a corresponding control of the stepping motor to limit. This embodiment can also be developed so that the cyclic movement of the plunger 13 is basically realized by a continuous rotation of the drive pulley 2 0 19 and the drive motor, the movement only in an impending

Exceeding the permissible force stops and reverses its direction of movement.

Fig. 14 shows a storage container 15a for a plurality of closure elements 8 in an alternative embodiment. The main differences to that

2 5 reservoir 1 5 according to FIG. 1 1 are that on the one hand the

Closure elements 8 in a reservoir of the reservoir 1 5a unsorted, i. are stored as a bed and, on the other hand, a tappet 13 a for the isolated output of the closure elements 8 from the reservoir 15 a is integrated. The bottom and wall surfaces of the reservoir 15a are formed so that the bottom

3 0 lying in the bulk closure elements are fed to an output channel 29, the inner diameter of which is only slightly larger than the Au ßendurchmesser the closure elements. This ensures that the closure elements occasionally reach a transfer position, where they can be detected and taken along by the plunger 13a.

3 5

FIG. 15 shows the use of the storage container according to FIG. 14 in combination with an alternative closing unit 17a (only partially shown). A special feature of this combination is the use of a total of two plungers, on the one hand in the reservoir 15a integrated plunger 1 3a, which serves for 1 0 scattered dispensing the closure elements 8 from the reservoir, whereby they are placed on an underlying sample container 1. One second, in the closing unit 1 7a integrated plunger 13, however, serves to drive the previously placed on a (other) sample container 1 closure element 8 in the closure portion of the opening channel of this sample container. The main advantage of using two plungers lies in improved hygiene when the storage container 1 7a including the tappet 1 3a as

Disposable container is used, which is thus disposed of after use.

As is apparent from Fig. 1 5, the movements of the two plungers 1 3, 13 a coupled together. For this purpose, a bolt 30 engages in a portion of the tappet Stö

L O 13 is resiliently mounted, in a corresponding opening in the plunger 1 3a. The

Movement of the plunger 13 is thus transmitted to the plunger 1 3a. The tappet 13 itself is constructed in several parts and comprises a tappet element 31 Stel, which is mounted axially displaceably in the lower end of a base body 32 of the plunger 1 3. About a central bore with an internal thread, the plunger element 31 with a

L 5 threaded pin 33 which is part of a force limiting unit. The

Force limiting unit also includes a spring 34 (cylindrical coil spring), which is biased by two bearing plates 35. The biasing forces are thereby via a system of the upper contact plate 35 and an annular projection of the plunger element 31 at corresponding contact surfaces of the main body 32nd

2 0 supported. About the depth of thread of the threaded bolt 33 in the plunger element 31, the bias of the coil spring can be changed and thus a limit for the force exerted by the plunger element 31 on the closure element 8 force can be adjusted. As soon as this force is exceeded, a (partial) compensation of the tappet stroke takes place by a retraction of the tappet element 1 3.

1 5

Fig. 16 shows a closing unit 1 7b, which corresponds functionally substantially to that of Fig. 15, but it is constructed structurally simpler. A (mechanical) force limiting unit is not provided there, but this is achieved electronically, by a corresponding control of a plunger drive. Therefore, the tappet element 31 a is axially immovable in the base body 32 a of the

Integrated plunger 13 and also the bolt 30a for driving the plunger 13a of the reservoir is not resiliently mounted. The storage container 1 5a corresponds to that of FIG. 15.

The closing units 17, 17a, 17b and storage containers 15, 15a can be integrated into an automatic closing device 25, as shown in FIG. 17. There, the unit of closing unit 1 7 and reservoir 1 5 via a linear drive 26 along a first axis (in the transverse direction) is movable.

The automatic closing device according to FIG. 17 is again in such a way

Device for performing a PCR process according to FIG 18 integrated, that the entire Verschließvornchtung 25 via a second linear drive 27 to a second axis (in the longitudinal direction), which is aligned perpendicular to the first axis (the travel axis of the linear drive 26 of the closing device), is movable. The mobility of the unit comprising closing unit 17 and storage container 15 in two axes oriented perpendicular to one another allows a plurality of housings 2 of sample containers 1, which are positioned in a plurality of rows in a total of three sample container carriers 7, to be closed by a closure element 8. The correct placement of the closure element 8 in the individual housings 2 is checked by means of a laser distance sensor (not shown).

FIG. 19 shows in a schematic representation the possibility of releasably fixing the closure elements 8 in a conveyor belt (blister belt) 28 and positioning these successively in the transfer position via a movement of the conveyor belt 28, from which they are then moved by means of a plunger 13 the opening channel of a sample container 1 can be introduced. The conveyor belt 28 has a base belt 36 provided with openings arranged in a regular pitch, wherein in the region of each of the openings a closure element 8 bears against one side of the base belt 26 and is surrounded and thus held by a holding belt 37. The individual closure elements can be removed by means of the plunger 13 through the respective opening from the conveyor belt 28 and driven into the opening channel of the sample container 1.

Claims

claims:

1 . Device for closing a sample container (1) with a spherical closure element (8), characterized by a reservoir (15) for a plurality of spherical closure elements (8), ejection means for expelling one of the closure elements (8) through an outlet opening of a housing of the device and Means for limiting the forces exerted by the ejection means on the closure element (8).

2. Device according to claim 1, characterized in that the ejection means comprise a plunger (13).

3. A device according to claim 2, characterized by drive means for periodically moving the plunger (13).

4. Apparatus according to claim 3, characterized by a rotary drive, which is connected via a transmission with the plunger (13).

5. Device according to one of the preceding claims, characterized by a separating means for isolated positioning of the closure elements (8) in a transfer position in the movement path of the plunger.

6. The device according to claim 5, characterized in that the separating device comprises a feed channel (23) via which the closure elements (8) are transported to the transfer position.

7. Apparatus according to claim 6, characterized by a blocking element (24) for temporarily fixing the isolated closure elements (8) in the transfer position.

8. Device according to one of the preceding claims, characterized by preferably vibrating and / or pneumatically acting means for transporting or supporting the transport of the closure elements (8) from the reservoir (15) to the ejection means.

9. Device according to one of the preceding claims, characterized in that the ejection means are interchangeable integrated.

10. Device according to one of the preceding claims, characterized in that the ejection means is provided with an exchangeable cover.

1 1. Device according to one of the preceding claims, characterized by at least one sensor for detecting the ejection of a closure element (8), the level of the reservoir (15) and / or of the Aussto ßmitteln on the closure elements (8) forces exerted.

5 12. System off

a device according to one of the preceding claims and - a housing (2) of a sample container (1), wherein the housing (2) forms a sample space for receiving a sample and having at least one circular opening, wherein the opening extends channel-shaped into the LO sample space and wherein the diameter of the closure elements

(8) the diameter of the opening channel in at least one (closure) section (1 1) only so far exceeds that one of the closure elements (8) with its widest circumference in the closure portion (1 1) is non-positively fixable.

L 5

13. System according to claim 1 2, characterized in that the sealing elements coming into contact with the closure elements (8) contact surface of the ejection means is greater than the au ßenseitige cross-sectional area of the opening channel of the sample container (1).

2 0 14. System according to claim 1 2 or 1 3, characterized by a sensor for

Detecting the presence and / or the position of the closure element (8) in the housing (2) of the sample container (1).

15. System according to claim 14, characterized in that the housing (2) of the sample container (1) at least in a portion of the closure portion

2 5 (1 1) is optically transparent and the sensor means for detecting the

Refractive index of the housing material in the transparent portion comprises.

16. Storage container (15) with a plurality of spherical closure elements (8) for use in a device according to one of the preceding

3 0 claims, characterized by a housing (2) and one within the

Housing (2) arranged guide and / or bearing device, in which the closure elements (8) are arranged juxtaposed.

17. Storage container (1 5) according to claim 1 6, characterized in that the guiding and bearing means a helical guide and

35 bearing channel has.

18, reservoir (15) according to claim 16 or 17, characterized in that the housing (2) has a filling opening, which is inextricably closed after filling of the reservoir (15) with the closure elements (8).

19. Storage container according to one of claims 16 to 18, characterized by integrated ejection means for ejecting one of the closure elements (8) through an outlet opening of the housing (2).