U.S. patent application number 14/003761 was filed with the patent office on 2014-02-27 for device for closing a sample receptacle with a spherical closure element.
The applicant listed for this patent is Andreas Bretscher, Dirk Leber, Harald Quintel, Daniel Simons, Bruno Walder. Invention is credited to Andreas Bretscher, Dirk Leber, Harald Quintel, Daniel Simons, Bruno Walder.
Application Number | 20140053503 14/003761 |
Document ID | / |
Family ID | 50146789 |
Filed Date | 2014-02-27 |
United States Patent
Application |
20140053503 |
Kind Code |
A1 |
Simons; Daniel ; et
al. |
February 27, 2014 |
DEVICE FOR CLOSING A SAMPLE RECEPTACLE WITH A SPHERICAL CLOSURE
ELEMENT
Abstract
The invention relates to a device for closing a sample container
with a spherical closing element, wherein the device has a storage
container for a plurality of spherical closing elements, ejecting
means for ejecting one of the closing elements through a discharge
opening in a housing of the device, and means for limiting the
forces exerted by the ejecting means on the closing element.
Inventors: |
Simons; Daniel; (Aathal,
CH) ; Leber; Dirk; (Schwaig, DE) ; Quintel;
Harald; (Steckborn, CH) ; Walder; Bruno;
(Riedikon, CH) ; Bretscher; Andreas; (Uster,
CH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Simons; Daniel
Leber; Dirk
Quintel; Harald
Walder; Bruno
Bretscher; Andreas |
Aathal
Schwaig
Steckborn
Riedikon
Uster |
|
CH
DE
CH
CH
CH |
|
|
Family ID: |
50146789 |
Appl. No.: |
14/003761 |
Filed: |
March 9, 2012 |
PCT Filed: |
March 9, 2012 |
PCT NO: |
PCT/EP12/54169 |
371 Date: |
November 7, 2013 |
Current U.S.
Class: |
53/287 |
Current CPC
Class: |
B65B 7/28 20130101; B01L
3/50825 20130101; B01L 2400/0616 20130101; B01L 2300/041 20130101;
B65B 7/2821 20130101; B65B 7/161 20130101 |
Class at
Publication: |
53/287 |
International
Class: |
B65B 7/28 20060101
B65B007/28 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 11, 2011 |
EP |
1157911.6 |
Claims
1. A device for closing a sample container with a spherical closing
element, comprising a storage container for a plurality of
spherical closing elements, ejecting means for ejecting one of the
closing elements through a discharge opening in a housing of the
device, and means for limiting the forces exerted by the ejecting
means on the closing element.
2. The device as claimed in claim 1, wherein said ejecting means
comprises a ram.
3. The device as claimed in claim 2, comprising drive means for
periodic movement of the ram.
4. The device as claimed in claim 3, comprising a rotary drive
which is connected to the ram via a gear mechanism.
5. The device as claimed in claim 1, comprising a separating
apparatus for individually positioning the closing elements in a
transfer position in a movement path of the ram.
6. The device as claimed in claim 5, wherein said separating
apparatus comprises a feed channel, via which the closing elements
are transported into a transfer position.
7. The device as claimed in claim 6, comprising a barrier element
for temporarily fixing individual closing elements in a transfer
position.
8. The device as claimed in claim 1, comprising a means, which acts
preferably optionally in a vibrating and/or pneumatic manner, for
transporting or for supporting transport of the closing elements
from the storage container to the ejecting means.
9. The device as claimed in claim 1, wherein said ejecting means
are integrated in an exchangeable manner.
10. The device as claimed in claim 1, wherein said ejecting means
are provided with an exchangeable cover.
11. The device as claimed in claim 1, comprising at least one
sensor for sensing ejection of a closing element, filling level of
the storage container and/or forces exerted by the ejecting means
on the closing elements.
12. A system comprising: a device as claimed in claim 1, and; a
housing of a sample container, wherein the housing forms a sample
space for receiving a sample and has at least one circular opening,
wherein the opening extends in a channel-like manner into the
sample space, and wherein the diameter of the closing elements only
exceeds the diameter of the opening channel in at least one closing
portion to such an extent that one of the closing elements can be
fixed in a force-locked manner by a largest circumference thereof
in the closing portion.
13. The system as claimed in claim 12, wherein a contact area of
the ejecting means that comes into contact with the closing
elements is larger than an external cross-sectional area of an
opening channel of the sample container.
14. The system as claimed in claim 12, comprising a sensor for
detecting presence and/or position of the closing element in the
housing of the sample container.
15. The system as claimed in claim 14, wherein said housing of the
sample container is formed in an optically transparent manner at
least in one portion of the closing portion, and the sensor
comprises means for detecting the refractive index of housing
material in a transparent portion.
16. A storage container having a multiplicity of spherical closing
elements capable of being used in a device as claimed in claim 1,
said container comprising a housing and a guiding and/or bearing
apparatus which is arranged within the housing and in which the
closing elements are arranged alongside one another in a row.
17. The storage container as claimed in claim 16, wherein said
guiding and bearing apparatus has a guiding and bearing channel
which extends in a spiral shape.
18. The storage container as claimed in claim 16, wherein said
housing has a filling opening which can be closed non-releasably
with the closing elements after the storage container has been
filled.
19. The storage container as claimed in claim 16, comprising an
integrated ejecting means for ejecting one of the closing elements
through a discharge opening in the housing.
Description
[0001] The invention relates to a device for closing a sample
container with a spherical closing element, and also a system
comprising such a device and a corresponding sample container.
[0002] Sample containers are used in particular within the scope of
biotechnological methods in order to process a biological sample or
a biological material, such as a sample containing nucleic acids.
These sample containers can be used for example to duplicate
nucleic acids in vitro within the scope of amplification reactions,
such as a polymerase chain reaction (PCR). Here, the sample
containers are used to receive the sample comprising the nucleic
acids.
[0003] A large number of different sample containers that are
routinely used as disposable products within the scope of
appropriate biotechnological methods, such as PCR, are known from
the prior art. Here, the sample containers are firstly filled with
the sample, then closed in an airtight manner, and lastly supplied
to the PCR process. Here, high demands are placed on the closure of
the sample containers. On the one hand, the sample containers have
to be reliably tightly sealed so as not to compromise the result of
the PCR process by the entry and exit of sample material or by an
undesired pressure change. On the other hand, a large number of
samples and therefore of sample containers are routinely used
within the scope of a PCR process and have to be filled and closed.
This should therefore be performed in an automated manner where
possible. Furthermore, it must be possible to produce the sample
containers cost-effectively, in particular because they are
required in high number and are used as disposable products.
[0004] A sample container is known from EP 0 449 425 A2, wherein
one end of a cylindrical housing, which forms a sample space, is
provided with a circular opening that extends in a channel-shaped
manner into the sample space. The opening channel tapers shortly
before the transition into the sample space and thus forms a seal
seat for a spherical closing element. Once the closing element has
been fitted onto the seal seat, it is fixed by means of a closing
plug.
[0005] As a three-part system, the sample container known from EP 0
449 425 A2 is not only relatively complex and therefore expensive,
but can also only be closed in an automated manner with relatively
high effort.
[0006] Proceeding from this prior art, the object of the invention
was to specify a system comprising a sample container and a device,
said system ensuring reliable automated closure of the sample
container.
[0007] 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. Independent claim 16
relates to a storage container which is to be used in conjunction
with the device according to the invention according to claim 1.
Advantageous developments of the device according to the invention,
of the system according to the invention and of the storage
container according to the invention are disclosed in the
respective dependent claims and will emerge from the following
description of the invention.
[0008] 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 spherical opening, which
extends in a channel-shaped manner into the sample space. The
sample container can be closed by means of a spherical closing
element, the diameter of the closing element exceeding the diameter
of the opening channel in at least one (closing) portion only to an
extent that one of the closing elements can be fixed in a
force-locked manner by its largest circumference in the closing
portion.
[0009] The force-locked fixing of the closing element by contact
between a region comprising the largest circumference of the
spherical closing element and the wall of the opening channel is
important in order to achieve a secure fixing. The resultant forces
with this type of force-locked fixing specifically comprise no, or
only a relatively small (and therefore negligible), force
components in the longitudinal axial direction of the opening
channel, but these are directed (largely) radially in the direction
of the centre of the spherical closing element. Sufficient fixing
and, at the same time, a good sealing effect can thus be produced
with only a relatively small (preferably elastic) deformation of
the closing element and of the wall of the opening channel. A small
deformation then also requires only relatively small forces in
order to introduce the closing element into the opening channel.
This can not only simplify the automation of the closing of the
sample container but also enable manual closing of the sample
container. In addition, the requirements of the materials used for
the closing element and the housing are reduced, whereby the
production costs for the sample container can be kept low.
[0010] In the case of the sample container of the system according
to the invention, the spherical closing element not only effects
sealing in conjunction with the housing of the sample container,
but it is reliably fixed without additional retaining means, for
example a closing plug, as is known from the sample container in EP
0 449 425 A2. Such a sample container can accordingly be closed
easily in an automated manner in that the closing element is merely
driven in a suitable manner into the opening channel of the
housing.
[0011] In order to close such a sample container, the system
according to the invention has a device which comprises a storage
container for a plurality of spherical closing elements and also
ejecting means for ejecting one of the closing elements through a
discharge opening in a housing of the device. Thus, in order to
close the sample container, one of the spherical closing elements
is driven by means of the ejecting means of the device into the
opening channel of the housing of the sample container and is fixed
in a force-locked manner there.
[0012] Provided in the device according to the invention are means
which limit the forces exerted by the ejecting means (preferably
ram) on the closing element. These can serve to limit the loading
of the closing element or of the housing, loaded thereby, of a
sample container. In particular, the advancement control of the ram
can be subjected to less stringent requirements as a result, since
an excessive stroke of the ram can be compensated by the force
limitation and thus excessive driving of the closing element into
the opening channel of the sample container can be avoided.
[0013] The means for force limitation can be formed preferably as
(at least one) spring which is arranged for example between the ram
and the drive means which effect the periodic movement of the ram.
An excessive stroke of the ram can then be compensated by an
elastic deformation of the spring. Of course, it is also possible
to arrange the spring at any desired point in the force flow
between the drive means and the support of the sample container.
For example, the sample container can be spring-mounted in a
receptacle or the receptacle is spring-mounted in a corresponding
manner. The spring is preferably integrated into the device in a
preloaded manner in order to allow it to respond only when a
defined force is exceeded.
[0014] On the other hand, it is of course also possible to control
the introduction of force by the ejecting means onto the closing
element by electronic control of the ejecting movement.
[0015] In a preferred embodiment of the device for closing, the
ejecting means may comprise a ram. This makes it possible to drive
one of the closing elements into the opening channel of the sample
container in a structurally simple manner.
[0016] Since the device according to the invention for closing a
multiplicity of sample containers is preferably used with a short
cycle, the ram may preferably be driven by means of suitable drive
means in a periodic (to-and-fro) movement. The device should then
be used in combination with an apparatus which, in a cycle
corresponding to the periodic movement of the ram, either supplies
the individual sample containers to be closed to the device
according to the invention or allows the device according to the
invention to discharge the individual sample containers in
succession.
[0017] The drive means for the periodic movement of the ram may
preferably have a rotary drive which is connected to the ram via a
gear mechanism in order to convert the rotary movement of the
rotary drive into the periodic translation movement of the ram.
[0018] In a preferred embodiment, the rotary drive may for this
purpose have a drive disc on which a bolt is decentrally arranged,
which is guided in a slot of the ram or of a guide element
connected to the ram, wherein the alignment of the slot is not
parallel to (also not coaxial with) the direction of movement. As a
result, the rotary movement of the drive disc can be converted into
a periodic translation movement of the ram in a structurally simple
manner. In order to drive the ram in a periodic translation
movement, use can be made for this purpose of rotary drives (in
particular electric rotational motors) which are available
cost-effectively on the market. Of course, it is also possible to
provide any other desired connection between the drive disc and the
ram or the guide element of the ram.
[0019] The drive means can of course also be formed in any other
desired manner, for example by way of a toggle lever mechanism or
(any desired) linear motor, for example in the form of a
plunger-type armature ("solenoid") which is movably guided in an
electrically loaded coil.
[0020] In order to achieve smooth operation of the device according
to the invention and in particular to ensure that in each case only
one closing element is entrained by the ram and driven into the
opening channel of the housing of a sample container, the device
according to the invention can preferably comprise a separating
apparatus. This can preferably comprise a feed channel in which the
closing elements are arranged in succession and via which these are
fed in succession to a transfer position located in the movement
path of the ram. The movement of the closing elements in the feed
channel can in this case take place as a result of the force of
gravity. Alternatively or in addition, any other desired transport
means, for example means for exerting vibrations or compressed-air
transport means, can also be used.
[0021] The device according to the invention can furthermore have a
barrier element which temporarily fixes the individual closing
elements in the transfer position. The fixing of the respective
closing element by the barrier element is preferably only released
when the ram entrains it. This can be achieved in a simple manner
by means of a spring-loaded or spring-mounted barrier element which
is laterally displaced when the force exerted by the ram on the
closing element is exceeded, such that the movement path of the
closing element is released.
[0022] In a further preferred embodiment of the device according to
the invention, the latter has supporting means for supporting the
transport of the closing element from the storage container to the
ejecting means. These may act preferably in a vibrating and/or
pneumatic manner. The supporting means can effect transport in
isolation or only support transport, for example exert transport in
conjunction with transport as a result of the force of gravity.
[0023] Preferably, the ram may be integrated in an exchangeable
manner in the device. Such a configuration is expedient in
particular in the case of a use for closing sample containers for a
biotechnological method, for example a PCR process, since
particular requirements are placed on sterility there. The
exchangeable integration of the ram into the device thus allows
simple and cost-effective maintenance in order to meet the
sterility requirements for such applications. Alternatively or in
addition thereto, the ram may also be provided with an exchangeable
(surface) cover. This embodiment can make it possible to meet the
requirement of sterility of the system with--compared with an
exchangeable ram--lower costs.
[0024] Preferably, the device has at least one sensor for sensing
the ejection of a closing element, the filling level of the storage
container and/or the force exerted by the ram on the respective
closing element. Such a sensor makes it possible to monitor and
document the closing process.
[0025] In a preferred embodiment of the system according to the
invention, the contact area of the ram which comes into contact
with the closing element during ejection may be configured in a
larger manner than the external cross-sectional area of the opening
channel of the housing of the sample container. As a result, the
portion of the housing that surrounds the opening channel can serve
as a (maximum) stop for the ram, as a result of which it is
possible to prevent the closing element from being driven further
than intended into the opening channel of the housing. In addition,
the relatively large area of the ram can ensure that reliable
closing can be achieved even in the case of relatively imprecise
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 ejecting means on the
closing element, in order to avoid damage to the sample
container.
[0026] The system according to the invention can furthermore have a
sensor which can determine the position of the closing element in
the housing of the sample container. This too may be expedient or
necessary to check and document the closing process.
[0027] One possibility for this purpose may be to form the housing
of the sample container in an optically transparent manner at least
in one portion of the closing portion, with the sensor comprising
means for detecting the refractive index of the housing material in
the transparent portion. The operation of the sensor can
accordingly be based on determining a change to the refractive
index, this change being caused by the fact that, during the
transition of the light from a first solid (wall of the opening
channel at the location at which the closing element is positioned)
to a second solid (closing element), there is no total reflection
at the inner wall of the opening channel, whereas, in the event of
a transition from a solid (wall of the opening channel) to air (or
another gas), there is partial reflection at the inner wall.
[0028] Preferably the housing may form a shoulder for forming a
bearing surface. The forces that are to be applied to introduce the
closing element (typically from 60 N to 130 N, at most 250 N) can
be supported at a holder supporting the sample container via said
bearing surface. In particular, the bearing surface can be formed
at a point of the housing that is located in the vicinity of the
closing portion of the opening channel. It is thus possible to
prevent the forces from being transmitted via other portions of the
housing, which may be formed with thinner wall thicknesses and may
therefore be more sensitive (in particular the wall of the housing
surrounding the sample space).
[0029] A storage container for use in a device according to the
invention has a housing and a guiding and/or bearing apparatus
arranged within the housing, a plurality of spherical closing
elements being arranged alongside one another in a row therein.
[0030] Preferably, the guiding and bearing apparatus can have a
guiding and bearing channel that extends in a spiral shape.
[0031] Further preferably, the housing of the storage container may
have a filling opening which is closed non-releasably with the
closing elements after the storage container has been filled.
Accordingly, such a storage container is preferably provided
according to the invention as a single use product, which can be
advantageous in particular for sterility reasons. From this point
of view, it is also possible for the ejecting means (in particular
the ram) to be integrated in the storage container provided as a
single use product.
[0032] The invention will be explained in greater detail
hereinafter on the basis of exemplary embodiments illustrated in
the drawings.
[0033] In the drawings:
[0034] FIG. 1: shows a sample container of a system according to
the invention;
[0035] FIG. 2: shows a detail of the sample container of FIG. 1 in
a sectional side view;
[0036] FIG. 3: shows a further detail of the sample container of
FIG. 1 in a sectional side view;
[0037] FIG. 4: shows the introduction of the closing element into
the sample container according to FIGS. 1 to 3 by means of a ram in
a first embodiment;
[0038] FIGS. 5 and 6: show the introduction of a closing element
into a sample container according to FIG. 1 by means of a ram in a
second embodiment;
[0039] FIG. 7a: shows the force curve when introducing closing
elements into sample containers according to FIGS. 1 to 3 with use
of a ram according to FIG. 4;
[0040] FIG. 7b: shows the force curve when introducing closing
elements into sample containers according to FIGS. 1 to 3 with use
of a ram according to FIGS. 5 and 6;
[0041] FIGS. 8a and 8b: show a sample container of a system
according to the invention in a second embodiment in two different
sectional illustrations;
[0042] FIGS. 9a and 9b: show a sample container of a system
according to the invention in a third embodiment;
[0043] FIG. 10: shows a sample container of a system according to
the invention in a fourth embodiment;
[0044] FIG. 11: shows a storage container of a device according to
the invention for automatically closing sample containers in a
first embodiment;
[0045] FIG. 12: shows a closing unit of a device for the automated
closing of sample containers according to the invention;
[0046] FIG. 13: shows a basic illustration of the operating
principle of the closing unit according to FIG. 12;
[0047] FIG. 14: shows an isometric view of a storage container of a
device according to the invention for automatically closing sample
containers in a second embodiment;
[0048] FIG. 15: shows the storage container according to FIG. 14 in
combination with a closing unit in a longitudinal section;
[0049] FIG. 16: shows the storage container according to FIG. 14 in
combination with an alternative closing unit in a longitudinal
section;
[0050] FIG. 17: shows the integration of the components according
to FIGS. 11 and 12 in an automated closing device;
[0051] FIG. 18: shows the integration of the automated closing
device according to FIG. 17 in a device for carrying out a PCR;
[0052] FIG. 18: shows a schematic illustration of an alternative
supply of closing elements to a device for the automated closing of
sample containers according to the invention; and
[0053] FIGS. 20a to 20f: show comparisons of a "normal" force curve
to deviating force curves, produced by various causes.
[0054] FIG. 1 shows a sample container 1 according to the invention
in a first embodiment. The sample container 1 comprises a housing
2, which is formed in a first portion (head portion 3) and a second
portion (middle portion 4) with a largely cylindrical lateral
surface. The lateral surface has just a small conical tapering,
which is used in order to more easily demold the housing 2
consisting of plastic after injection molding. The end of the
middle portion 4 opposite the head portion 3 is adjoined by an end
portion 5, in which the housing 2 tapers and is therefore formed in
a tapering manner in the broader sense. In the end portion 5, the
housing 2 is formed from an (optically) transparent material, which
enables the use of optical measuring elements within the scope of a
biotechnological method, such as a PCR process, in which the sample
container 1 is to be used.
[0055] On the outer face between the head portion 3 and the middle
portion 4, the housing 2 forms a shoulder 6, which is used as a
bearing surface, via which the housing 2 is supported on a sample
container support 7 (see FIG. 2).
[0056] Within the middle 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 portions is largely constant, such that
a sample space portion which is again largely cylindrical is formed
within the middle portion 4, and a conically tapering sample space
portion formed with a rounded tip is formed in the end portion 5 of
the housing 2.
[0057] 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 closing element 8 in the
manner according to the invention. The closing effect, that is to
say both the sealing and the fixing of the closing element 8 in the
opening channel, is achieved in that the largest outer diameter of
the closing element 8 is slightly larger than the opening channel
in a defined portion (closing portion 11) (see FIG. 2) and the
closing element 8 is therefore fixed in a wedged manner in the
opening channel.
[0058] Starting from the upper (free) end of the head portion 3,
the opening channel is first provided with an entry chamfer 9,
which defines a relatively (based on the outer diameter of the
closing element 8) large opening cross section (largest diameter:
4.5 mm). The entry chamfer 9 facilitates the central positioning of
the closing element 8 (largest diameter 4.1 mm to 4.2 mm). The
entry chamfer 9 transitions into a first annular protrusion 10,
which reduces the opening cross section (diameter: 3.7 mm) of the
opening channel compared to the opening cross section in the
closing portion of the opening channel (diameter: approximately 4.0
mm). In order to introduce the closing element 8 into the opening
channel, it is loaded by a force (component) which is directed
coaxially with or parallel to the longitudinal axis of the housing
2, specifically in the direction of the end portion of the housing
2.
[0059] The force is so great that it leads to a deformation both of
the housing 2 in the region of the head portion 3 and of the
closing element 8 itself, which makes it possible for the closing
element 8 to pass the first protrusion 10 and to be inserted as far
as the closing portion 11 of the opening channel. There, the
closing element 8 is fixed in a force-locked manner, that is to say
wedged, by means of its larger (maximum) diameter compared to the
diameter of the opening channel in the closing portion 11. Here,
the forces are achieved by a (largely elastic) deformation of the
housing 2 in the region of the closing portion 11 and also of the
closing element 8. Due to the symmetrical force-locked fixing of
the spherical closing element 8 in the region of its largest cross
section, the reaction forces that act from the wall of the opening
channel onto the ball (and vice versa) do not have any component in
the longitudinal axial direction of the housing. Once introduced
into the closing portion 11, the closing element 8 is thus securely
held, provided no significant external forces act thereon in the
longitudinal direction of the housing 2.
[0060] The first protrusion 10, which has to be passed by the
closing element 8 when introduced into the closing portion 11, is
used on the one hand as an end stop that prevents the closing
element 8 from being slid out from the opening channel in the event
of the creation of an overpressure within the closed sample space,
for example caused by heating within the scope of a
biotechnological method, such as a PCR process, and thus prevents
the sample container 1 from being opened undesirably.
[0061] Furthermore, this protrusion 10 is used to produce a force
curve which is characteristic as the closing element 8 is
introduced and on the basis of which an actual introduction of the
closing element 8 as far as the closing portion 11 can be detected
(in the manner of a locking into place).
[0062] The transition of the opening channel into the sample space
of the housing 2 is formed as an annular shoulder. This shoulder
constitutes a second protrusion 12, which is used as an end stop
for the closing element 8 and therefore delimits the closing
portion 11 of the opening channel on the side of the sample
space.
[0063] The length of the closing portion 11 of the opening channel
is dimensioned such that the closing element 8 can be displaced
therein over a specific distance x before it contacts one of the
two protrusions 11, 12 (see FIG. 3). This distance is limited in
the present case to 0.7 mm at most, since experience has
demonstrated that, with a displacement of this type of the closing
element 8, the process parameters (in particular pressure,
temperature) within the sample space only change to such a small
extent that no significant (negative) effects on the
biotechnological method, such as the PCR process, are to be feared.
This positional tolerance of the closing element 8 within the
closing portion 11 also has the advantage that relatively large
tolerances in the production of the housing 2 and of the closing
element 8 can be specified, whereby the corresponding tools can be
subject to less stringent requirements.
[0064] FIGS. 4 to 6 show the use of a ram 13 (in two embodiments)
in order to slide the closing element 8 into the opening channel.
In the embodiment according to FIG. 4, the ram 13 has an outer
diameter of 3.6 mm (or smaller), which is therefore smaller than
the inner diameter of the opening channel in the region of the
first protrusion 11. The ram 13 can therefore dip into the opening
channel. To this end, the movement of the ram should be
controllable in a precise manner in order to prevent said ram from
pressing the closing element 8 with force against the second
protrusion serving as an end stop, which could lead to damage of
the housing 2 or of the closing element 8. In the embodiment of a
ram 13 according to FIGS. 5 and 6, the outer diameter of the ram 3
is therefore considerably larger than the inner diameter of the
opening channel in the region of the entry chamfer 9. The movement
of the ram 13 is therefore delimited at the latest by the fact that
it contacts the free end of the housing 2. A pressing of the
closing element 8 by means of the ram against the second protrusion
12 serving as an end stop can therefore be easily avoided. A
further advantage of the large contact area of the ram 13 is that
the closing element 8 can be pressed in steadily without
difficulty, even if the ram 13 is not arranged exactly centrally
above the closing element 8 (see FIG. 6).
[0065] FIG. 7a shows an exemplary force curve (force F over the ram
path I) for a closing process with use of a ram according to FIG.
4. In a first portion (a) of the force curve, the force is
practically zero; this portion defines the displacement of the ram
13 until it contacts the closing element 8. This is followed in a
second portion by a sharp rise of the force as far as a first
maximum value (b) (first extreme point of the curves), which is
necessary in order to allow the closing element to pass the first
protrusion 10. This force then falls as far as a second extreme
point (c), which defines the force (which is then only slightly
rising due to the slightly conical design of the opening channel,
see portion (d)) which is necessary to displace the ball in the
closing portion 11. This force corresponds substantially to the
force that is produced from the friction between the wall of the
opening channel in the closing portion 11 and the contacting
portion of the closing element 8. If a closing process is carried
out correctly, the exertion of force ends anywhere in portion (d)
of FIG. 7.
[0066] If the ram 13 dips too deeply into the opening channel
however, the closing element may be pressed thereby against the
second protrusion 12, which is again evidenced by a sharp rise in
force (portion (e)). This rise may be limited (that is to say in
accordance with the depth of dip of the ram 13) by the breaking
load of the sample container 1 (and, where appropriate, also of the
closing element 8 or of the ram 13) ((f)), whereby the force falls
to a considerably lower level (portion (g)).
[0067] FIG. 7b shows a corresponding exemplary force curve for the
use of a ram according to FIGS. 5 and 6. The force curve in
portions (a) and (d) as well as therebetween corresponds to that in
FIG. 7a. After portion (d), there is then a rise in force (h),
which is sharper than that with the curve according to FIG. 7a.
This is produced as a result of the contact between the ram 13 and
the edge of the sample container 1. The ram 13 should then only be
moved further over a relatively short path in order to avoid
overloading the sample container 1 (or the ram 13). To control the
stroke of the ram, the force curve can be evaluated such that, for
example once the end of the portion (h) has been reached, a (force)
limit value is reached, which for example may lead to a
deactivation of a ram drive. In FIG. 7b, the further force curve
that leads to a rupture of the sample container due to overload is
also illustrated with a dashed line arrangement. This is
characterized by a continuation of portion (h) (portion (i)), at
the end of which the rupture occurs. This is characterized by a
direct fall in force to a level close to zero (portion (k)).
[0068] FIGS. 20a to 20f show exemplary deviations from the "normal"
force curves described previously. It is possible to determine the
appropriate fault source from these deviations. Here, the deviating
force curve is illustrated by a continuous line, whereas the
"normal" force curve is shown in a dashed manner. FIG. 20a shows
two deviating force curves, wherein the dimensioning or the
material properties of the sample container in the region of the
opening channel and/or of the closing element are not correct. FIG.
20b shows two deviating force curves, wherein the vertical
alignment of the closing element, that is to say the distance
between the closing element and the ram, is too little or too
large. In the case of the deviating force curve according to FIG.
20c, the horizontal alignment is not correct, that is to say there
is insufficient conformity between the longitudinal axes of the
sample container and of the ram. This may lead to an impairment of
the movement of the closing element. FIG. 20d shows a deviating
force curve which is produced if there is a fault concerning the
closing element and the ram moves without substantial application
of force until colliding with the sample container. The deviating
force curve illustrated in FIG. 20e can be produced if the contact
surfaces of the closing element and/or of the sample container do
not correspond to the requirements. By contrast, FIG. 20f shows a
deviating force curve which can be produced in the event of the
rupture of a sample container.
[0069] FIGS. 8a and 8b show a second embodiment of a sample
container 1, wherein two closing elements 8 are fixed in a
force-locked manner in a common closing portion 11 of the housing
2. A second sample space is thus formed between the two closing
elements 8. The corresponding embodiment of the opening channel, by
contrast with the illustration in FIG. 8, can be selected
arbitrarily in accordance with the exemplary embodiment according
to FIGS. 1 to 3, that is to say in particular can be provided with
one or more protrusions. Furthermore, a bypass channel 14 is formed
in the wall of the housing between the lower sample space and the
closing portion 11 and also between the closing portion 11 and the
upper, open end of the sample container 1. The upper bypass channel
14 is used to balance an overpressure in the two sample spaces,
which would otherwise be produced as a result of the relatively
deep introduction of the closing elements. By contrast, the lower
bypass channel 14 is provided, for example within the scope of the
PCR process, to transfer a sample contained in the upper sample
chamber into the lower sample chamber, as is illustrated in FIG.
8a. To this end, the lower closing element 8 is slid by means of
the upper closing element 8 into the portion of the opening
channel/sample space comprising the lower bypass channel 14, such
that the sample can flow from the upper sample chamber via the
lower bypass channel 14, past the lower closing element 8, and into
the lower sample chamber.
[0070] FIGS. 9a to 9b show a sample container 1 in a further
embodiment, in which said sample container is to be opened again by
pressing the closing element 8 by means of a ram 13 completely into
the sample space as far as the closed end. The sample liquid
displaced during this process can flow off via a bypass channel 14
formed on one side in the wall of the housing 2 and can thus be
removed from the sample container 1.
[0071] FIG. 10 shows a sample container 1, wherein the housing 2 is
provided in the region of the sample space with a varying wall
thickness. In the region of the sample space which receives the
sample, the housing 2 has a minimal wall thickness, for example
from 0.2 to 0.3 mm. A thin wall thickness simplifies the
examination of the sample by means of optical methods. In a portion
of the sample space which forms a dead space (that is to say with
no sample contained therein), the wall thickness is thicker, by
contrast (for example twice as thick, for example 0.4 to 0.6 mm),
whereby not only can the mechanical stability of the housing 2 be
increased, but in particular also an evaporation of the sample
through the housing 2 can be reduced.
[0072] FIGS. 11 and 12 show individual components of an automated
closing device (see FIG. 17) which is to be used in a device for
carrying out a PCR process (see FIG. 18).
[0073] Here, FIG. 11 shows a storage container 15, in which a
drawn-out guide 16 running in a spiraled manner is arranged and is
used to receive and guide a multiplicity of closing elements 13 of
a sample container 1. The lower end of the guide 16 ends in an
outlet opening, via which the closing element can be transferred to
a closing unit 17, as is illustrated in part in FIG. 12. The
storage container 15, which can be sold as a filled disposable
container, can be fastened for this purpose to the front end of the
closing unit 17.
[0074] The closing unit 17 comprises an electric motor arranged in
a housing 18, said electric motor being able to drive a drive disc
19 in rotation. The drive disc 19 is provided decentrally with a
bolt 20, which is guided in a slot 21 of a ram guide 22. The
guidance of the bolt 20 in the slot 21 translates the rotational
movement of the drive disc 19 into a cyclical upward and downward
movement of the ram guide 22, inclusive of a ram 13 fastened
thereto, as is illustrated in principle in FIG. 13. With each
downward movement of the ram 13, a closing element 8 held in a
transfer position is entrained and is pressed via a discharge
opening of the closing unit into the opening channel of a housing 2
of a sample container 1 arranged therebelow (not illustrated in
FIG. 13). Once the ram 13 has been raised again, a further one of
the closing elements 8 stored temporarily in succession in a feed
channel 23 can then roll (as a result of the force of gravity) into
the transfer position, where it is held via a spring-mounted
barrier element 24. With the subsequent downward movement of the
ram 13, the next closing element 8 is then entrained, wherein the
barrier element 24 is displaced to the side in order to release the
discharge opening.
[0075] Alternatively, it is also possible for the movement back and
forth of the ram 13 to be caused not by a unidirectional rotation
(through 360.degree.) of the drive disc 19, but for said drive disc
to also be drivable by means of a stepper motor having a (cyclical)
rotational direction change in order to move the ram 13. Any, and
in particular even changing, displacement paths, speed profiles,
etc. of the ram 13 can thus be implemented. This can be used in
particular to limit the force exerted by the ram 13 onto the
closing element 8 (in conjunction with a measurement process using
sensors) by means of a corresponding control of the stepper motor.
This embodiment can also be developed such that the cyclical
movement of the ram 13 is produced in principle by a continuous
rotation of the drive disc 19, and the drive motor only stops the
movement and reverses its direction of movement if there is a risk
that the permissible force will be exceeded.
[0076] FIG. 14 shows a storage container 15a for a multiplicity of
closing elements 8 in an alternative embodiment. The main
differences from the storage container 15 according to FIG. 11 lie
in the fact that on the one hand the closing elements 8 are stored
in an unsorted manner, that is to say as a packing, in a storage
space of the storage container 15a and on the other hand a ram 13a
for dispensing the closing elements 8 individually from the storage
container 15a is integrated. The base and wall surfaces of the
storage container 15a are formed such that the closing elements
arranged at the bottom in the packing are fed to a dispensing
channel 29, of which the inner diameter is only slightly larger
than the outer diameter of the closing elements. It is thus ensured
that the closing elements reach a transfer position individually,
where they can be caught and entrained by the ram 13a.
[0077] FIG. 15 shows the use of the storage container according to
FIG. 14 in combination with an alternative closing unit 17a (only
illustrated in part). A particular feature of this combination is
for use of a total of two rams, on the one hand the ram 13a
integrated into the storage container 15a for dispensing the
closing elements 8 individually from the storage container, whereby
the closing elements are placed on a sample container 1 arranged
beneath. By contrast, a second ram 13 integrated into the closing
unit 17a is used to drive the closing element 8 placed beforehand
on a (different) sample container 1 into the closing portion of the
opening channel of this sample container. The main advantage of the
use of two rams lies in improved hygiene when the storage container
17a, inclusive of the ram 13a, is to be used as a disposable
container, which is therefore disposed of after use.
[0078] As can be seen from FIG. 15, the movements of the two rams
13, 13a are coupled to one another. To this end, a bolt 30, which
is spring-mounted in a portion of the ram 13, engages in a
corresponding opening in the ram 13a. The movement of the ram 13 is
thus transmitted to the ram 13a. The ram 13 itself is constructed
in a number of parts and comprises a ram element 31, which is
mounted in an axially displaceable manner in the lower end of a
main body 32 of the ram 13. The ram element 31 is connected via a
central bore with an inner thread to a threaded pin 33, which is
part of a force limitation unit. The force limitation unit
additionally comprises a spring 34 (cylindrical helical spring),
which is biased by two contact plates 35. The bias forces are
supported here via an abutment of the upper contact plate 35 and an
annular protrusion of the ram element 31 against corresponding
contact areas of the main body 32. The bias of the helical spring
can be changed via the depth to which the threaded bolt 33 is
screwed into the ram element 31, and a limit value for the force
exerted by the ram element 31 onto the closing element 8 can thus
be adjusted. As soon as this force is exceeded, the ram stroke is
compensated for (partially) by a retreat of the ram element 13.
[0079] FIG. 16 shows a closing unit 17b, which corresponds
substantially to that of FIG. 15 in terms of function, but is of
simpler construction however. A (mechanical) force limitation unit
is not provided here, rather this is achieved electronically by a
corresponding controller of the ram drive. The ram element 31a is
therefore integrated in the main body 32a of the ram 13 in an
axially stationary manner, and the bolt 30a for entrainment of the
ram 13a of the storage container also is not spring-mounted. In
this case, the storage container 15a corresponds to that of FIG.
15.
[0080] The closing units 17, 17a, 17b and storage containers 15,
15a can be integrated into an automatic closing device 25, as is
illustrated in FIG. 17. There, the unit formed from a closing unit
17 and storage container 15 can be displaced by a linear drive 26
along a first axis (in the transverse direction).
[0081] The automatic closing device according to FIG. 17 can in
turn be integrated into a device for carrying out a PCR process
according to FIG. 18, in such a way that the closing device 25 as a
whole is displaceable by a second linear drive 27 along a second
axis (in the longitudinal direction), which is oriented
perpendicularly to the first axis (the axis of displacement of the
linear drive 26 of the closing device). The displaceability of the
unit formed of the closing unit 17 and storage container 15 in two
axes oriented perpendicularly to one another makes it possible to
remove a multiplicity of housings 2 of sample containers 1, which
are positioned in a number of rows in a total of three sample
container supports 7, and to close each of said housings with a
closing element 8. The correct placement of the closing element 8
in the individual housings 2 is checked here with the aid of a
laser distance sensor (not illustrated).
[0082] FIG. 19, in a schematic illustration, shows the possibility
of fixing the closing elements 8 releasably in a conveyor belt
(blister tape) 28 and of positioning said closing elements
successively over a movement of the conveyor belt 28 in the
transfer position, from which they can then be introduced by means
of a ram 13 into the opening channel of a sample container 1. The
conveyor belt 28 has a main belt 36 provided with openings arranged
at regular intervals, wherein, in the region of each of the
openings, a closing element 8 rests on one side of the main belt 26
and is surrounded there by a retaining belt 37 and is thus held in
place. The individual closing elements can be removed from the
conveyor belt 28 through the prospective opening and driven into
the opening channel of the sample container 1 by means of the ram
13.
* * * * *