Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
  • B01L3/5082—Test tubes per se
  • B01L3/50825—Closing or opening means, corks, bungs
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
  • B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
  • B65B7/00—Closing containers or receptacles after filling
  • B65B7/16—Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons
  • B65B7/28—Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons by applying separate preformed closures, e.g. lids, covers
  • B65B7/2807—Feeding closures
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
  • G01N2035/0403—Sample carriers with closing or sealing means
  • G01N2035/0405—Sample carriers with closing or sealing means manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers

Definitions

• 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.
• PCR polymerase chain reaction
• 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.
• high demands are made.
• 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.
• 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.
• the sample containers must be inexpensive to produce, especially because they are needed in large numbers and are used as disposable products.
• a sample container 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.
• 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.
• 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.
• 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)
• 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
• the system comprises a device which has a reservoir for a plurality of
• closure elements through an outlet opening of a housing of the device.
• 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
• 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.
• 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.
• 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
• the spring at any point of the power flow between the drive means and the support of the sample container.
• 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
• 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.
• the device according to the invention 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
• 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.
• 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.
• 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).
• rotation drives especially electric motors.
• 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
• 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
• Closure elements in the feed channel can be effected by gravity.
• any other means of transport for example means for exerting vibrations or compressed air transport means can also be used.
• 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.
• 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.
• the plunger interchangeable in the device 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.
• 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.
• 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.
• a sensor allows monitoring and documentation of the closing process.
• 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.
• 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.
• 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.
• a sensor which determines the position of the closure element in the housing of the sample container can.
• the sensor comprises means for detecting the refractive index of the housing material in the transparent
• 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.
• the housing of the sample container forms a shoulder for forming a support surface.
• the forces that are applied for the introduction of the closure element are supported on a sample container supporting the holder.
• 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.
• 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.
• the guiding and bearing means may comprise a helically extending guide and bearing channel.
• the housing of the reservoir 3 5 has a filling opening, which after filling the reservoir with the
• Closing elements is permanently closed.
• a storage container is therefore preferably provided as a disposable product, which may be advantageous in particular for sterility reasons.
• the ejection means in particular the tappet
• the reservoir is integrated into a disposable product.
• Fig. 1 a sample container of a system according to the invention
• FIG. 5 shows a section of the sample container of FIG. 1 in a sectional side view
• FIG. 3 shows a further detail of the sample container of FIG. 1 in a sectional side view
• Fig. 4 the introduction of the closure element in the sample container
• 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
• Fig. 7b the force curve during the introduction of closure elements in
• Fig. 8a and 8b a sample container of a system according to the invention in a second embodiment in two different
• 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. 1 1 a storage container of a device according to the invention for the automatic closure of sample containers in a first embodiment
• Fig. 12 a closing unit of an apparatus for automated
• FIG. 13 shows a principle drawing for the functioning of the closing unit according to FIG. 12;
• Fig. 14 an isometric view of a reservoir of a
• Fig. 15 the reservoir of FIG. 14 in combination with a
• Fig. 16 the reservoir of FIG. 14 in combination with a
• FIG. 18 shows the integration of the automated closing device according to FIG.
• Fig. 18 is a schematic representation of an alternative supply of
• 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.
• an end portion 5 connects, in which the housing 2 tapers and thus formed tapering in the broader sense.
• the housing 2 is made of one (optical)
• Framework of a biotechnological process such as, for example, a PCR process in which the sample container 1 is to be used, allows.
• 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.
• an opening channel is formed, which makes it possible to fill the sample container 1 with the sample to be examined.
• 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
• 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).
• a force component
• 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
• 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.
• 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
• 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
• 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.
• the plunger 13 has a 2 5 Au dated prepare for injection.
• the tappet 13 can thus dip into the opening channel.
• 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
• 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
• 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.
• force F force over the plunger path I
• 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.
• 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.
• 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
• 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
• 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)).
• 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
• FIG. 20d shows a deviating force course which occurs in the absence of the
• FIG. 20e shows a deviating course of force which occurs at
• 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
• closure elements 8 a second sample space formed.
• 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
• 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, is intended to
• 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
• 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
• 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),
• 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
• the figure 1 1 shows a reservoir 15, in which an elongated spiral-shaped guide 16 is arranged, the recording and leadership
• 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 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
• Opening channel of an underlying housing 2 of a sample container. 1 (Not shown in Fig. 1 3) pressed.
• interposed closure elements 8 (gravitational) roll into the transfer position, where this is held by a spring-mounted locking element 24 5.
• the locking element 24 is displaced laterally to release the outlet opening.
• 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.
• a stepper motor with a (cyclic) change of direction to realize the movement of the plunger 13.
• 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
• 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
• Fig. 14 shows a storage container 15a for a plurality of closure elements 8 in an alternative embodiment. The main differences to that
• the bottom and wall surfaces of the reservoir 15a are formed so that the bottom
• 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 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.
• L O 13 is resiliently mounted, in a corresponding opening in 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
• 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
• 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.
• 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
• 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.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Hematology (AREA)
• Clinical Laboratory Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Sampling And Sample Adjustment (AREA)
• Closing Of Containers (AREA)
• Automatic Analysis And Handling Materials Therefor (AREA)

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• 2012
  • 2012-03-09 JP JP2013557124A patent/JP2014509731A/ja active Pending
  • 2012-03-09 CA CA2829706A patent/CA2829706A1/en not_active Abandoned
  • 2012-03-09 AU AU2012228413A patent/AU2012228413B2/en not_active Ceased
  • 2012-03-09 EP EP12712600.1A patent/EP2683486A1/de not_active Withdrawn
  • 2012-03-09 CN CN201280012884.1A patent/CN103476500B/zh not_active Expired - Fee Related
  • 2012-03-09 WO PCT/EP2012/054169 patent/WO2012123376A1/de active Application Filing
  • 2012-03-09 BR BR112013023046A patent/BR112013023046A2/pt not_active IP Right Cessation

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