EP3653304A1 - Récipient d'échantillon - Google Patents

Récipient d'échantillon Download PDF

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Publication number
EP3653304A1
EP3653304A1 EP19212880.9A EP19212880A EP3653304A1 EP 3653304 A1 EP3653304 A1 EP 3653304A1 EP 19212880 A EP19212880 A EP 19212880A EP 3653304 A1 EP3653304 A1 EP 3653304A1
Authority
EP
European Patent Office
Prior art keywords
section
closure
sample container
closure element
housing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP19212880.9A
Other languages
German (de)
English (en)
Other versions
EP3653304B1 (fr
Inventor
Daniel SIMONS
Dirk LEBER
Harald Quintel
Sasa Lazevski
Bruno Walder
Andreas Bretscher
Thomas Voit
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hombrechtikon Systems Engineering AG
Original Assignee
Hombrechtikon Systems Engineering AG
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Publication date
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Publication of EP3653304A1 publication Critical patent/EP3653304A1/fr
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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
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D39/00—Closures arranged within necks or pouring openings or in discharge apertures, e.g. stoppers
    • B65D39/06—Balls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/045—Connecting closures to device or container whereby the whole cover is slidable

Definitions

  • the invention relates to a sample container with a housing, which forms a sample space for receiving a sample and has at least one circular opening, and with a spherical closure element.
  • sample containers are used in particular in the context of biotechnological methods to process a biological sample or a biological material such as a sample containing nucleic acids. They are used, for example, to amplify nucleic acids in vitro in the context of amplification reactions such as, for example, a polymerase chain reaction ("polymerase chain reaction", PCR).
  • the sample containers serve to hold the sample comprising the nucleic acid.
  • sample containers are known from the prior art and are regularly used as disposable products in the context of corresponding biotechnological processes, 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 placed on the closing of the sample containers.
  • the sample containers must be sealed tightly so that the result of the PCR process is not impaired by the unwanted entry or exit of sample material.
  • a large number of sample containers are regularly used as part of a PCR process, which have to be filled and closed for this purpose. This should therefore be done as automatically as possible.
  • the sample containers must be inexpensive to manufacture, especially because they are required in large numbers and are used as disposable products.
  • a generic sample container in which one end of a cylindrical housing, which forms a sample space, is provided with a circular opening which extends into the sample space in a channel-like manner.
  • the opening channel tapers shortly before the transition into the sample space and thereby forms a sealing seat for a spherical closure element. After the closure element has been placed on the seal seat, it is fixed in place by means of a closure plug.
  • the object of the invention was to provide an improved sample container.
  • the sample container according to the invention should be inexpensive to produce and lockable automatically with relatively little effort.
  • the sample container according to the invention should have a reliable sealing effect.
  • the essence of the invention is that in the sample container according to the EP 0 449 425 A2 functions of sealing and fixing of the closure element effected by two different functional elements by only one functional element, namely the closure element itself.
  • This is achieved in that a spherical closure element is clamped in an opening channel of a housing of the sample container according to the invention that not only a good sealing effect but also a process-reliable fixation can be achieved.
  • This can - unlike that from the EP 0 449 425 A2 known sample container - an additional sealing plug for fixing the closure body can be dispensed with.
  • a sample container according to the invention accordingly has a housing which forms a sample space for receiving a sample and a circular opening which extends in the form of a channel into the sample space. Furthermore, the sample container according to the invention has a spherical closure element.
  • the (largest) diameter of the closure element is selected such that it exceeds the diameter of the opening channel in at least one (closure) section of the opening channel, but only to an extent that allows the closure element to extend so far to be introduced into the closure section of the opening channel in such a way that the non-positive fixing is achieved by contact of an area comprising the largest circumference of the closure element with the closure section.
  • the spherical closure element is in contact with the housing.
  • the opening channel between the closing section and the inside opening forms a (first) projection which reduces the opening cross section of the opening channel compared to the opening cross section in the closing section. Due to the direct contact of the closure element with the housing, a one-piece closure can be formed.
  • the formation of a one-piece closure element and the configuration of the opening channel with the (first) projection make it possible to produce the sample container with the closure element inexpensively, which can be automatically closed with relatively little effort, with a reliable sealing effect being present.
  • the (first) projection can serve as an end stop, which prevents the closure element from being pressed into the sample space beyond the closure section during insertion.
  • the non-positive fixing of the closure element by contact of an area comprising the largest circumference of the spherical closure element with the wall of the opening channel is important in order to achieve a secure fixation.
  • the resulting forces in this type of frictional fixation have no or only a relatively small (and therefore negligible) force component in the longitudinal axial direction of the opening channel; rather, they are (largely) directed radially towards the center of the spherical closure element.
  • a slight deformation then requires only relatively small forces to introduce the closure element into the opening channel. This can simplify the automation of the closing of the sample container and also enable manual closing of the sample container.
  • the requirements for the materials used for the closure element and the housing are reduced, as a result of which the manufacturing costs for the sample container can be kept low.
  • the diameter of the closure element also exceeds the smallest diameter of the opening channel, but deliberately so far that a sealing seat is formed on which the closure element is seated.
  • a sealing seat is well known in terms of its good sealing effect, but requires an additional closure element which generates sufficiently high forces in the longitudinal axial direction of the opening channel to press the spherical closure element into the seal seat and thus the to achieve the desired sealing effect.
  • the sample container according to FIG EP 0 449 425 A2 Even if to a small extent - a non-positive fixation can be achieved, but since it does not act on the largest circumference of the spherical closure element, it always has a component in the longitudinal axial direction of the opening channel.
  • This longitudinal axial force component is also directed so that - if it exceeds the frictional forces of the closure element with the opening channel in the region of the ball seat, for example due to an additional effect of an excess pressure within the sample space - the closure element lifts off the seal seat, the sample container is thus unwanted opens.
  • An increase in the frictional forces without a simultaneous increase in the longitudinal axial force component is not possible, so that from the EP 0 449 425 A2 known sample container cannot be securely closed without the additional sealing plug.
  • a ball that is soft compared to the housing (which therefore deforms significantly more than the housing) can have advantages in terms of the sealing effect. However, this advantage may be offset by disadvantages in positioning (checking) and material selection.
  • a ball that is hard compared to the housing is easy to handle during insertion and enables easier positioning and checking of the position, but can entail the risk of the housing being overstretched (right down to the plastic area).
  • the opening channel between the closing section and the outside opening forms a (second or further) projection which reduces the opening cross section of the opening channel compared to the opening cross section in the closing section.
  • a projection which can be formed, for example, (closed) in a ring shape or also by one or more, preferably ring-shaped, individual projections arranged next to one another, can serve in particular as a safety stop to prevent the closure element from being unintentionally released from the closure section of the opening channel, for example as a result of an unexpectedly high level
  • To prevent pressure increase in the sample space which can be caused, for example, by heating as part of the PCR process.
  • the closure element Since the (second or further) protrusion must be passed by the closure element when the sample container is closed, it can be provided that it is dimensioned such that the closure element is introduced into the closure section while exerting a defined press-in force which is not so high should that the closure element or the housing of the sample container is damaged as a result of excessive deformation, but greater than the maximum force to be expected, which is due to an increase in pressure in the sample space.
  • the opening cross section of the opening channel is larger in the region of the (second) projection than in the region of the first projection. It can thereby be achieved that the force that is applied to press the closure element into the opening channel is sufficiently high that the closure element passes the second projection, but is not so high that it can also pass the first projection.
  • the distance between the first and the second closure element is dimensioned as a function of the dimensions of the closure element in such a way that a positioning tolerance of the closure element within the closure section of at most 5 mm and in particular of at most 0.7 mm is given.
  • a displacement of the closure element over this maximum distance in particular due to an increase in pressure within the sample space, generally still leads to a tolerable change in the process conditions, for example of a PCR process.
  • the opening channel is cylindrical in the area of the closure section.
  • the opening channel (also) in the closure section is slightly conical (for example with an inclination angle of 0.1 to 0.5 °), which can facilitate demolding during casting and in particular injection molding of the housing.
  • the angle of inclination can be chosen so small that it has no significant (negative) influence on the fixation and sealing effect of the clamped closure element.
  • the housing of the sample container according to the invention can preferably be tubular (also stepped), the opening being arranged at one (longitudinally axial) end of the housing. Furthermore, the housing can preferably be tapered at the second end, as a result of which even very small sample amounts can be concentrated well in the sample space, which can facilitate the implementation of the biotechnological method, such as a PCR process.
  • the housing of the sample container is at least partially made of an optically transparent material.
  • the tapered end can be made optically transparent, since this is preferably used to hold the sample.
  • the housing in the region that serves to hold the sample has a smaller wall thickness than (at least) a second region of the housing that forms the sample space.
  • the thinnest possible wall thickness can simplify the examination of the sample by means of optical methods, while a thicker wall thickness, in particular in a dead space of the sample space that is not filled with the sample, can avoid or reduce evaporation through the housing, which is preferably made of plastic.
  • the housing can also be made for the housing to be formed in the closure section of the opening channel from an (optically) transparent material. This enables the position of the closure element in the closure section and also the sealing effect to be checked by means of optical means (also purely visual inspection).
  • a change in the refractive index can be used for a mechanical check, for example, due to the fact that there is no total reflection of the light on the inner wall during the transition from a first solid (wall of the opening channel) to a second solid (closing element) from a solid (wall of the opening channel) to air, on the other hand, partially reflects the inside of the opening channel.
  • the housing can preferably form a shoulder to form a support surface.
  • the forces that are applied to press in the closure element (typically up to 60 N to 130 N and a maximum of 250 N), are supported on a holder carrying the sample container.
  • the support surface can be formed at a location on the housing that is in the vicinity of the closure section of the opening channel. In this way it can be avoided that the forces are transmitted via other sections of the housing, which may be made with smaller wall thicknesses and thus more sensitive (in particular the wall of the housing surrounding the sample space).
  • the housing of the sample container is formed at least in the closure section of the opening channel and / or the closure element itself from a material with a thermal expansion coefficient that is as low as possible and particularly preferably with an expansion coefficient that is as large as possible. This can prevent the pressure in the contact area between the closure element and the wall of the opening channel from changing as a result of heating, for example during a PCR process, which would possibly not only change the fixation of the closure element but also its sealing effect to the same extent .
  • the closure element can be formed from an electrically conductive material. This not only prevents the ball from being electrostatically charged, which could make handling the sample container more difficult, but the conductivity can also allow contact-based or contactless, for example capacitive or inductive, detection of the position of the closure element within the opening channel and / or the sealing effects perform.
  • the closure element of the sample container according to the invention is preferably formed from a material which has no or only a small (in particular technically not relevant) intrinsic fluorescence. This can prevent a monitoring of the biotechnological method, such as the PCR process, based on the measurement of the fluorescence of the sample, from being adversely affected.
  • a predetermined breaking point at which the housing is divided by a defined force.
  • Such a type of opening is particularly suitable for sample containers that are to be used only once (single-use sample container).
  • An advantage of this embodiment of the sample container according to the invention can be, in particular, that the The process of opening can be less complex than removing the closure element fixed in the closure section of the opening channel, but this is also possible.
  • a predetermined breaking point there is also the possibility of designing the housing in two parts, the two parts being connectable to one another, for example, via a plug-in or snap-in connection. To open the closed sample container, the housing can then be opened again at this connection point.
  • the sample container can also be opened by pushing the closure element into the sample space.
  • the sample space should have a larger cross-sectional area than the closure element, at least in one section, in order to be able to empty the sample space.
  • sample containers that are used in the context of the respective biotechnological process should not be reopened.
  • it can further be provided according to the invention to additionally secure the closure element in the closure section, for example by welding it to the wall of the housing with a suitable choice of material (for example by ultrasonic welding or thermal welding) or by flanging one upper edge of the housing is positively fixed.
  • a suitable choice of material for example by ultrasonic welding or thermal welding
  • flanging one upper edge of the housing is positively fixed.
  • any other types of additional positive, non-positive or material fixation are possible.
  • sample container in a preferred embodiment, it can further be provided to provide a second closure section for a second closure element, a second sample space being formed between the two closure elements. All of the developments that were previously shown with respect to the first closure section and / or the first closure element can also be provided for the second closure section and / or the second closure element.
  • a bypass channel can preferably (at least) be provided in the wall of the housing between the two closure sections of the sample container. This can serve to avoid an overpressure which otherwise arises in the lower sample space as a result of the introduction of the one closure element into the lower closure section and to transfer the upper sample material into the lower sample space by pressing down the upper closure element.
  • the present invention further relates to a method for the preparation or processing of a biological sample or a biological material such as a sample containing in particular nucleic acids, in which the sample container according to the invention is used.
  • the sample container according to the invention is described in detail in the description and the claims. Reference is made to the corresponding disclosure.
  • the method can in particular be a biotechnological method such as an amplification method, in particular a PCR method.
  • the 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 largely cylindrical outer surface.
  • the lateral surface has only a slight conical taper, which serves to make it easier to demold the plastic housing 2 after the injection molding.
  • the housing 2 is formed from an (optically) transparent material which enables the use of optical measuring elements in the context of a biotechnological method, such as a PCR process in which the sample container 1 is to be used.
  • the housing 2 On the outside between the head section 3 and the middle section 4, the housing 2 forms a shoulder 6, which serves as a support surface, via which the housing 2 is attached to a sample container carrier 7 (cf. Fig. 2 ) is supported.
  • a sample space is formed within the central section 4 and the end section 5 of the housing 2, the wall thickness of the housing 2 being largely constant in these two sections, so that a largely cylindrical sample space section within the central section 4 and a conical shape tapering, with rounded tip formed sample space portion is formed in the end portion 5 of the housing 2.
  • An opening channel is formed in the head section 3 of the housing 2, which makes it possible to fill the sample container 1 with the sample to be examined.
  • the sample space is closed by introducing a spherical closure element 8 in the manner according to the invention.
  • the closure effect ie both the sealing and the fixing of the closure element 8 in the opening channel, is brought about by the fact that the largest outer diameter of the closure element 8 is slightly larger than the opening channel in a defined section (closure section 11) (cf. Fig. 2 ) and the closure element 8 is thus clamped in the opening channel.
  • the opening channel is initially provided with an inlet chamfer 9, which defines a relatively large (based on the outer diameter of the closure element 8) opening cross section (largest diameter: 4.5 mm).
  • the inlet chamfer 9 facilitates the central positioning of the closure element 8 (largest diameter: 4.1 mm to 4.2 mm).
  • the inlet chamfer 9 merges into a first annular projection 10, which reduces the opening cross section (diameter: 3.7 mm) of the opening channel in relation to the opening cross section in the closure section of the opening channel (diameter: approx. 4.0 mm).
  • the closure element 8 is loaded with a force (component) which is directed coaxially or parallel to the longitudinal axis of the housing 2, specifically in the direction of the end section of the housing 2.
  • the force is so high that there is a deformation of both the housing 2 in the region of the head section 3 and of the closure element 8 itself, which enables the closure element 8 to pass the first projection 10 and to be pushed into the closure section 11 of the opening channel becomes.
  • the closure element 8 is non-positively fixed, ie clamped, in the closure section 11 due to its larger (maximum) diameter compared to the diameter of the opening channel.
  • the forces are achieved by a (largely elastic) deformation of the housing 2 in the region of the closure section 11 and of the closure element 8.
  • the first projection 10, which has to be passed by the closure element 8 when it is introduced into the closure section 11, serves on the one hand as an end stop, which prevents the closure element 8 from creating an overpressure within the closed sample space, for example by heating in the context of a biotechnological method, such as a PCR process, is pushed out of the opening channel and the sample container 1 thus opens unintentionally.
  • this projection 10 serves to generate a force curve which is characteristic when the closure element 8 is inserted, by means of which an actual insertion of the closure element 8 into the closure section 11 can be detected (in the manner of a snap-in).
  • the transition of the opening channel into the sample space of the housing 2 is designed as an annular shoulder.
  • This paragraph represents a second projection 12, which serves as an end stop for the closure element 8 and thus delimits the closure section 11 of the opening channel on the side of the sample space.
  • the length of the closure section 11 of the opening channel is dimensioned such that the closure element 8 can be displaced therein by a certain distance x before it strikes one of the two projections 11, 12 (cf. Fig. 3 ). In the present case, this distance is limited to a maximum of 0.7 mm, since experience has shown that with such a displacement of the closure element 8, the process parameters (in particular pressure, temperature) change so little within the sample space that there are no significant (negative) effects on the biotechnological process Methods such as the PCR process, for example.
  • This positioning tolerance of the closure element 8 within the closure section 11 also has the advantage that relatively large tolerances can be specified in the manufacture of the housing 2 and the closure element 8, as a result of which lower demands can be placed on the corresponding tools.
  • the Figures 4 to 6 show the use of a plunger 13 (in two embodiments) to push the closure element 8 into the opening channel.
  • the plunger 13 has an outer diameter of 3.6 mm (or smaller), which is thus smaller than the inner diameter of the opening channel in the region of the first projection 11.
  • the plunger 13 can thus dip into the opening channel.
  • the movement of the plunger should be precisely controllable in order to prevent the plunger from pressing the closure element 8 against the second projection serving as an end stop, which could damage the housing 2 or the closure element 8.
  • the outer diameter of the plunger 3 be made considerably larger than the inner diameter of the opening channel in the region of the inlet chamfer 9.
  • the movement of the plunger 13 is thus limited at the latest by the fact that it strikes the free end of the housing 2. Pressing the closure element 8 by means of the plunger against the second projection 12 serving as an end stop can thus be avoided in a simple manner.
  • Another advantage of the large contact surface of the plunger 13 is that it is regularly possible to press it in even if the plunger 13 is not arranged exactly centrally above the closure element 8 (cf. Fig. 6 ).
  • the Figure 7a shows an exemplary force curve (force F over the tappet travel I) for a closing process using a tappet according to Fig. 4 .
  • force F force over the tappet travel 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 comes into contact with the closure element 8.
  • This is followed in a second section by a strong increase in the force up to a first maximum value (b) (first extreme point of the curves) which is required to move the closure element to let the first projection 10 pass.
  • This force then drops to a second extreme point (c), which defines the force (which then increases only slightly due to the slightly conical design of the opening channel, see section (d)), which is required to move the ball in the closure section 11 .
  • This force essentially corresponds to the force that results from the friction between the wall of the opening channel in the closure section 11 and the section of the closure element 8 that is in contact with it. If the closing process is carried out correctly, the application of force ends somewhere in section (d) of the Fig. 7 .
  • Section (e) If, however, the plunger 13 dips too deeply into the opening channel, the closure element can be pressed by the latter against the second projection 12, which is again noticeable by a strong increase in force (section (e)).
  • This increase may be limited (ie depending on the immersion of the plunger 13) by the breaking load on the sample container 1 (possibly also the closure element 8 or the plunger 13) ((f)), as a result of which the force is reduced to a significantly lower level ( Section (g)) drops.
  • the Fig. 7b shows a corresponding exemplary force curve for the use of a plunger according to the 5 and 6 .
  • the force curve in sections (a) and (d) and in between corresponds to that of Fig. 7a .
  • the plunger 13 should then only be moved a relatively short distance in order to overload the sample container 1 (or the To avoid tappet 13).
  • the force curve can be evaluated, so that, for example, when the end of section (h) is reached, a (force) limit value is reached which, for example, can cause a tappet drive to be switched off.
  • a (force) limit value is reached which, for example, can cause a tappet drive to be switched off.
  • the further force curve is shown in dashed lines, which leads to a breakage of the sample container due to overload. This is characterized by a continuation of section (h) (section (i)), at the end of which the break occurs. This is characterized by a direct drop in force to a level close to zero (section (k)).
  • the 20a to 20f show examples of deviations from the "normal" force profiles described above. The corresponding source of error can be concluded from these deviations.
  • the deviating force curve is shown with a solid line, while the "normal" force curve is shown in dashed lines.
  • the 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 the closure element are incorrect.
  • the Fig. 20b shows two different force profiles, in which the vertical orientation of the closure element, ie the distance between the closure element and the plunger is too small or too large.
  • the horizontal alignment is not correct, ie there is insufficient correspondence between the longitudinal axes of the sample container and the plunger.
  • the Fig. 20d shows a deviating force curve, which results in the absence of the closure element and the movement of the plunger takes place without significant force until a collision with the sample container.
  • the Indian Fig. 20e Deviating force curve shown can result if the contact surfaces of the closure element and / or the sample container do not meet the requirements.
  • the 20f shows, however, a deviating force curve, which can result from the breakage of a sample container.
  • the 8a and 8b show a second embodiment of a sample container 1, in which two closure elements 8 are non-positively fixed in a common closure section 11 of the housing 2.
  • a second sample space is formed between the two closure elements 8.
  • the corresponding design of the opening channel can - in contrast to the representation in the Fig. 8 - Any according to the embodiment according to the Figures 1 to 3 be, ie in particular be provided with one or more projections.
  • a bypass channel 14 is also introduced into the wall of the housing.
  • the upper bypass channel 14 serves to overpressure in the two sample spaces would otherwise arise due to the relatively deep insertion of the closure elements.
  • the lower bypass channel 14 is intended to transfer a sample contained in the upper sample chamber into the lower sample chamber, for example as part of the PCR process, as is shown in FIG Fig. 8a is shown.
  • the lower closure element 8 is pushed by means of the upper closure element 8 into the section of the opening channel / sample space having the lower bypass channel 14, so that the sample can flow from the upper sample chamber via the lower bypass channel 14 past the lower closure element 8 into the lower sample chamber .
  • the 9a to 9b show a sample container 1 in a further embodiment, in which provision is made to open it again by pushing the closure element 8 completely into the sample space up to the closed end by means of a plunger 13.
  • the displaced sample liquid can flow out via a bypass channel 14 introduced into the wall of the housing 2 on one side and can thus be removed from the sample container 1.
  • the 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.
  • the housing 2 In the area of the sample space that receives the sample, the housing 2 has the smallest possible wall thickness of, for example, 0.2 to 0.3 mm.
  • a small wall thickness simplifies the examination of the sample using optical methods.
  • the wall thickness is made thicker (for example twice as thick, for example 0.4 to 0.6 mm), as a result of which not only the mechanical stability of the housing 2 can be increased, but in particular also an evaporation of the sample through the housing 2 can be reduced.
  • FIGS 11 and 12 show individual components of an automated closing device (cf. Figure 17 ) which are to be used in a device for carrying out a PCR process (cf. Figure 18 ).
  • the shows Figure 11 a storage container 15, in which an elongated spiral guide 16 is arranged, which serves to receive and guide a plurality of closure elements 13 of a sample container 1.
  • the lower end of the guide 16 ends in an outlet opening, through which the closing elements of a closing unit 17, as partially shown in FIG Figure 12 can be transferred.
  • the storage container 15, which can be sold as a filled disposable container can be attached to the front end of the closing unit 17.
  • 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 disk 19 is provided decentrally with a bolt 20 which is guided in an elongated hole 21 in a tappet guide 22.
  • the guidance of the bolt 20 in the elongated hole 21 translates the rotary movement of the drive disk 19 into a cyclical upward and downward movement of the tappet guide 22, including a tappet 13 attached to it, as is basically the case in FIG Figure 13 is shown.
  • a closure element 8 held in a transfer position is taken along and via an outlet opening of the closure unit into the opening channel of a housing 2 of a sample container 1 arranged underneath (in the Fig. 13 not shown) pressed.
  • a further one of the closure elements 8 (gravitationally) interposed in a feed channel 23 can roll into the transfer position, where it is held by a spring-loaded locking element 24.
  • the next closure element 8 is then taken along, the locking element 24 being displaced laterally in order to expose the outlet opening.
  • the Fig. 14 shows a storage container 15a for a plurality of closure elements 8 in an alternative embodiment.
  • the main differences to the reservoir 15 according to the Fig. 11 lie in the fact that, on the one hand, the closure elements 8 are unsorted in a storage space of the storage container 15a, ie are stored as a bed, and on the other hand, a plunger 13a is integrated for dispensing the closure elements 8 from the storage container 15a.
  • the bottom and wall surfaces of the storage container 15a are designed in such a way that the closure elements located at the bottom of the bed are fed to an output channel 29, the inside diameter of which is only slightly larger than the outside diameter the closure elements is. This ensures that the closure elements occasionally reach a transfer position, where they can be gripped and taken away by the plunger 13a.
  • the Fig. 15 shows the use of the storage container according to the 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 the plunger 13a integrated in the storage container 15a, which serves for the individual dispensing of the closure elements 8 from the storage container, as a result of which these are placed on a sample container 1 underneath.
  • a second plunger 13 integrated in the closing unit 17a serves to drive the closure element 8 previously placed on a (different) sample container 1 into the closure section of the opening channel of this sample container.
  • the main advantage of using two plungers is improved hygiene when the storage container 17a including the plunger 13a is used as a disposable container, which is thus disposed of after use.
  • the plunger 13 itself is constructed in several parts and comprises a plunger element 31 which is axially displaceably mounted in the lower end of a base body 32 of the plunger 13. Via a central bore with an internal thread, the plunger element 31 is connected to a 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 contact plates 35.
  • the prestressing forces are supported on the corresponding contact surfaces of the base body 32 by means of an abutment of the upper contact plate 35 and an annular projection of the tappet element 31.
  • the prestress of the helical spring can be changed via the screwing depth of the threaded bolt 33 into the plunger element 31 and thus a limit value for the force exerted by the plunger element 31 on the closure element 8 can be set. As soon as this force is exceeded, the tappet stroke is compensated (partially) by retracting the tappet element 13.
  • the Fig. 16 shows a closing unit 17b which is functionally essentially that of FIG Fig. 15 corresponds, but is structurally simpler.
  • a (mechanical) force limiting unit is not provided there, rather it is achieved electronically by a corresponding actuation of a tappet drive.
  • the tappet element 31a is therefore axially immovably integrated in the base body 32a of the tappet 13 and also the bolt 30a for taking the tappet 13a Storage container is not spring loaded.
  • the reservoir 15a 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 Figure 17 is shown. There, the unit comprising the closing unit 17 and the storage container 15 can be moved along a first axis (in the transverse direction) via a linear drive 26.
  • the automatic closing device according to the Figure 17 is in turn in a device for carrying out a PCR process Figure 18 can be integrated such that the entire closing device 25 can be moved via a second linear drive 27 to a second axis (in the longitudinal direction) which is oriented perpendicular to the first axis (the travel axis of the linear drive 26 of the closing device).
  • the movability of the unit comprising the closure unit 17 and the storage container 15 in two axes oriented perpendicular to one another enables a plurality of housings 2 of sample containers 1, which are positioned in several rows in a total of three sample container carriers 7, to be moved and each to be closed with a closure element 8.
  • the correct placement of the closure element 8 in the individual housings 2 is checked with the aid of a laser distance sensor (not shown).
  • the Fig. 19 shows a schematic representation of the possibility of releasably fixing the closure elements 8 in a conveyor belt (blister belt) 28 and positioning them one after the other by means of a movement of the conveyor belt 28 in the transfer position, from which they are then pushed into the opening channel of a sample container by means of a plunger 13 1 can be introduced.
  • the conveyor belt 28 has a base belt 36 which is provided with openings arranged at regular intervals, a closure element 8 abutting one side of the base belt 26 in the region of each of the openings and surrounded there by a holding belt 37 and thus held.
  • the individual closure elements can be released from the conveyor belt 28 through the respective opening by means of the plunger 13 and driven into the opening channel of the sample container 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mechanical Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
EP19212880.9A 2011-03-11 2012-03-09 Récipient d'échantillon Active EP3653304B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11157906 2011-03-11
PCT/EP2012/054165 WO2012123375A1 (fr) 2011-03-11 2012-03-09 Récipient à échantillon
EP12712599.5A EP2683485B1 (fr) 2011-03-11 2012-03-09 Récipient d'échantillon

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP12712599.5A Division EP2683485B1 (fr) 2011-03-11 2012-03-09 Récipient d'échantillon
EPPCT/EP2012/712599 Previously-Filed-Application 2012-03-09

Publications (2)

Publication Number Publication Date
EP3653304A1 true EP3653304A1 (fr) 2020-05-20
EP3653304B1 EP3653304B1 (fr) 2024-05-01

Family

ID=44327213

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EP12712599.5A Active EP2683485B1 (fr) 2011-03-11 2012-03-09 Récipient d'échantillon
EP19212880.9A Active EP3653304B1 (fr) 2011-03-11 2012-03-09 Récipient d'échantillon

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP12712599.5A Active EP2683485B1 (fr) 2011-03-11 2012-03-09 Récipient d'échantillon

Country Status (9)

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US (1) US9242246B2 (fr)
EP (2) EP2683485B1 (fr)
JP (1) JP2014513927A (fr)
CN (1) CN103459037B (fr)
AU (1) AU2012228412B2 (fr)
BR (1) BR112013023055A2 (fr)
CA (1) CA2829703A1 (fr)
ES (2) ES2979386T3 (fr)
WO (1) WO2012123375A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI20155107A (fi) 2015-02-19 2016-08-20 Thermo Fisher Scientific Oy Näyteastia
US10537892B2 (en) * 2017-01-03 2020-01-21 Illumina, Inc. Sample tube with integrated mixing plunger head
WO2021213636A1 (fr) 2020-04-21 2021-10-28 Hombrechtikon Systems Engineering Ag Récipient d'échantillon et procédé permettant d'analyser un échantillon
DE102020131098A1 (de) * 2020-11-24 2022-05-25 Syntegon Technology Gmbh Vorrichtung zum Verschließen von pharmazeutischen Behältnissen

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2367883A (en) * 1942-09-21 1945-01-23 Frankfort Distilleries Inc Bottle closure
EP0264181A2 (fr) * 1986-10-13 1988-04-20 Nihon Taisanbin Kogyo Kabushiki Kaisha Récipient d'emballage
WO1991006483A1 (fr) * 1989-10-27 1991-05-16 Bo Kultti Dispositif de fermeture pour recipients
EP0503867A2 (fr) * 1991-03-08 1992-09-16 Material Engineering Technology Laboratory, Inc. Obturateur pour récipient, et dispositif de stockage et de mélange
WO1997010155A1 (fr) * 1995-09-15 1997-03-20 Egon Erlich Contenant inviolable
EP0954486A1 (fr) * 1997-01-24 1999-11-10 Diagnostica Stago Bouchage pour flacon de reactif utilisable par un automate d'analyse
EP1847461A2 (fr) * 2006-04-18 2007-10-24 Terxo AG Récipient en plastique
DE102008010402B3 (de) * 2008-02-21 2009-04-09 Bruker Biospin Ag System zur Bereitstellung einer Vielzahl von Probengefäßen, insbesondere NMR-Probenröhrchen, und Verwendung des Systems
WO2009047821A1 (fr) * 2007-10-10 2009-04-16 Bisio Progetti S.P.A. Flacon à dose unique apte à être refermé

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5241990Y2 (fr) * 1973-06-29 1977-09-22
JPS6388960U (fr) * 1986-05-30 1988-06-09
US5127895A (en) * 1990-03-30 1992-07-07 Beckman Instruments, Inc. Self-seal centrifuge tube

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2367883A (en) * 1942-09-21 1945-01-23 Frankfort Distilleries Inc Bottle closure
EP0264181A2 (fr) * 1986-10-13 1988-04-20 Nihon Taisanbin Kogyo Kabushiki Kaisha Récipient d'emballage
WO1991006483A1 (fr) * 1989-10-27 1991-05-16 Bo Kultti Dispositif de fermeture pour recipients
EP0503867A2 (fr) * 1991-03-08 1992-09-16 Material Engineering Technology Laboratory, Inc. Obturateur pour récipient, et dispositif de stockage et de mélange
WO1997010155A1 (fr) * 1995-09-15 1997-03-20 Egon Erlich Contenant inviolable
EP0954486A1 (fr) * 1997-01-24 1999-11-10 Diagnostica Stago Bouchage pour flacon de reactif utilisable par un automate d'analyse
EP1847461A2 (fr) * 2006-04-18 2007-10-24 Terxo AG Récipient en plastique
WO2009047821A1 (fr) * 2007-10-10 2009-04-16 Bisio Progetti S.P.A. Flacon à dose unique apte à être refermé
DE102008010402B3 (de) * 2008-02-21 2009-04-09 Bruker Biospin Ag System zur Bereitstellung einer Vielzahl von Probengefäßen, insbesondere NMR-Probenröhrchen, und Verwendung des Systems

Also Published As

Publication number Publication date
ES2769308T3 (es) 2020-06-25
JP2014513927A (ja) 2014-06-19
CA2829703A1 (fr) 2012-09-20
US9242246B2 (en) 2016-01-26
EP2683485A1 (fr) 2014-01-15
AU2012228412B2 (en) 2016-01-07
EP2683485B1 (fr) 2019-12-04
AU2012228412A9 (en) 2015-12-03
AU2012228412A1 (en) 2013-10-03
WO2012123375A1 (fr) 2012-09-20
CN103459037A (zh) 2013-12-18
US20140056784A1 (en) 2014-02-27
ES2979386T3 (es) 2024-09-25
CN103459037B (zh) 2016-11-02
EP3653304B1 (fr) 2024-05-01
BR112013023055A2 (pt) 2016-12-13

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