Note: Descriptions are shown in the official language in which they were submitted.
CA 02825234 2013-07-19
ACCESSIBLE COOLING SYSTEM, ESPECIALLY FOR CRYOPRESERVING
BIOLOGICAL SAMPLES, AND METHOD FOR THE OPERATION THEREOF
The invention concerns a cooling system, in particular for
cryopreservation of biological samples, which has a cooling
chamber (cold room) cooled with liquid nitrogen (LN2). The
invention furthermore concerns methods for operating the
cooling system. Applications of the invention are given in
long-term storage of samples in the cooled state, in
particular for cryopreservation of biological samples.
It is known to store biological samples for the purpose of
preservation in the frozen state in a cooling system, e.g. in
a cryobank (cryopreservation). Cryobanks are typically
operated at temperatures below -80 C, in particular at a
temperature below the recrystallization temperature of water
ice (-138 C). They contain a cooling agent reservoir with
liquid nitrogen (temperature: about -195 C) and a plurality
of individual tanks (so-called cryotanks, mostly Dewar flasks
made of double-walled steel, see e.g. EP 1 223 393 A2, WO
2008/009840 Al, GB 812 210) with the size ranging from a few
liters up to about 2 or 3 cubic meters. The cryotanks stand
in rooms at normal temperature (room temperature) and are
supplied with the liquid nitrogen from the cooling agent
reservoir. In the cryotanks, boxes in which tubes, bags or
other closed receptacles with the samples (e.g. liquids,
cells, cell constituents, serums, blood, cell suspensions,
pieces of tissue or the like) are stored are arranged in
shelves. The samples can be fully arranged in the liquid
nitrogen. To prevent contamination of samples by the liquid
nitrogen, the samples are, however, mostly stored in a cool
gaseous phase in the vapor of the liquid nitrogen at less
than about -145 C. This gaseous phase is formed above a
nitrogen lake at the bottom of the cryotank.
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For cooling in the cryotanks, it would be advantageous if
they would be maintained permanently closed. In practice,
they must, however, be opened repeatedly, e.g. when accessing
the samples. In practice, sample storing or taking or
Inventories are required, which, for cryobanks with e.g.
10,000 up to 1 million or more samples, leads to a critical
limitation for the effectiveness of the cryotank operation
and for the provision of constant cooling conditions.
In addition, automation of all operations, in particular of
the sample handling, is required for such a large number of
samples. Previous automation approaches (see e.g. DE 10 2005
031 648 Al, US 2006/0156753 Al, US 2006/0283197 Al, US
2007/0267419 Al) are restricted to the individual cryotanks
and entail considerable costs. For cryobanks with more than
twenty cryotanks, automation between the cryotanks is
extremely complicated, because it would require overlaying
automatic machines, which, however, are currently not
available.
It is further known to store food in cooling chambers.
Effective storage and automation are achieved when the
cooling chambers form a walkable large-capacity warehouse.
This technique is, however, not applicable to cooling systems
for the cryopreservation of biological samples. Even the
lowest temperatures provided for cooling of food are too high
for the long-term cryopreservation of biological samples.
Operation of conventional cooling chambers at lower
temperatures is, however, not readily possible. Below -30 C,
the conventional automation techniques fail due to functional
and material limitations, mainly of motors, bearings,
lubricants and the fits of moving parts. In the case of an
incident or failure of a component in the cooling chamber,
the latter would have to be heated completely, because
operators can not safely enter rooms with a temperature below
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-80 C wearing conventional protectional clothing. A deep
breath would cause damage to pulmonary alveoli through freezing
and then lead to life-threatening conditions. The quick
frosting-up and freezing when opening and entering the rooms
is also to be taken into account. Furthermore, there are
problems with the thermal insulation of conventional deep-
cooled cooling chambers and their safeguarding in case of an
accident. Since cryobanks must be kept uninterruptedly cold
for decades, probably in future for centuries, the accident
problem is particularly critical. So far, there is a lack of
techniques to keep large hails at temperatures of at least -
80 C in case of total failure of the cooling system until
appropriate repair has been effected.
The objective of the invention is to provide an improved
cooling system, in particular for cryopreservation of
biological samples, which allows to overcome disadvantages and
limitations of conventional cooling systems. The cooling
system should in particular provide effective cooling
operation even with a high number of samples and/or improve
automation of access to samples. The objective of the invention
is also to provide an improved method for operation of a
cooling system, in particular for cryopreservation of
biological samples, with which disadvantages and limitations
of conventional methods are overcome.
These objectives are solved by cooling systems and methods for
operating the same having the features of the invention.
According to a first aspect of the invention, a cooling system,
in particular for cryopreservation of biological samples, is
provided, which has a cooling chamber and a first cooling
device, which are adapted for cooling of the cooling
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chamber using liquid nitrogen. The cooling chamber is
generally a room delimited by a floor area, side walls and a
ceiling area, which is cooled in its entirety with the first
cooling device and is adapted for accommodating the samples
to be preserved. Cooling of the entire cooling chamber is
provided in a targeted way at least from its floor. To this
effect, the floor area of the cooling chamber is adapted for
direct cooling with the liquid nitrogen. This advantageously
supports uniform cooling of the cooling chamber. Due to the
cooling of the cooling chamber from the bottom up through the
vapor of the liquid nitrogen, a gas layering with a
temperature gradient can be formed in the cooling chamber.
The temperature may rise in a stable and reproducible way
from the bottom upward. This advantageously supports the
provision of reproducible storage conditions, in particular
of a reproducible storage temperature at the location of the
sample deposition.
According to the invention, the cooling chamber is
dimensioned such that at least one operator can stay and move
in the cooling chamber. The internal volume of the cooling
chamber is selected such that the at least one operator
completely fits in the cooling chamber and can stand and/or
walk therein. Preferably, the internal volume is equal to at
least 10 m3, in particular at least 100 m3, such as at least
500 m3, or even 1000 m3 or more. For an internal volume of
e.g. 10 m3, the cooling chamber forms a small cryo chamber,
while with e.g. 100 m3 a cryo room, with e.g. 500 m3 a cryo
room array, and with more than 1000 m3 a cryo hall, possibly
with several rooms, is given.
The cooling chamber of the cooling system according to the
invention is adapted for accommodating a sample receiving
device. Any holding structure, which is suitable for
accommodating samples, in particular of sample containers
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with biological samples, can be used as the sample receiving
device. Sample containers comprise e.g. test tubes, tubelets,
capillaries, so-called "straws", bags or other closed
receptacles. The sample receiving device may be arranged
permanently in the cooling chamber (in particular fixed) or
is at least in parts releasable. According to the invention,
the cooling chamber is preferably dimensioned such that the
operator can stay and move in the cooling chamber equipped
with the sample receiving device.
In accordance with the invention, the floor area of the
cooling chamber has a platform that comprises, for instance,
at least a perforated plate, rust, and/or grating. The
platform has a multiple function. First, the platform is
formed in such a way that vapor of the liquid nitrogen can
ascend through the platform into the cooling chamber. The
platform is permeable to vapor. Thus, a cooling surface is
created on the floor of the cooling chamber, which enables
immediate, direct cooling of the interior of the cooling
chamber through outflowing vapor, which has an advantageous
effect on the effective and uniform cooling of the cooling
chamber. Secondly, the platform forms a support area for the
operator and typically also for a sample receiving device in
the cooling chamber. The platform is configured as a stand
area and/or walking surface for the operator. For this
purpose, the platform is formed with such mechanical load-
carrying capacity that it remains stable and in particular
undeformed under load with the operator. Preferably, the
mechanical load-carrying capacity of the platform is at least
100 kg/m2 (particularly suitable for light shelves and an
operator), in particular at least 500 kg/m2 (particularly
suitable for multiple shelves and operators), such as at
least 1000 kg/m2 (particularly suitable for multiple shelves,
machines and operators), or even 5000 kg/m2 (especially
suitable for security shelves, machines and operators), or
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more. Furthermore, the platform is preferably formed in such
a way that it extends at least over half of the surface of
the floor of the cooling chamber. Particularly preferably,
the platform extends over the entire surface of the floor of
the cooling chamber.
According to a second aspect of the invention, a method for
operating the cooling system according to the preceding first
aspect of the invention is provided, for which cooling of the
cooling chamber with the first cooling device and positioning
of samples, in particular biological samples, in the cooling
chamber is provided for.
Advantageously, the first cooling device can be adapted for
filling with liquid nitrogen in such a way that a free
surface of the liquid nitrogen is formed below the floor
area. The first cooling device has, for example, a vessel,
which is open upwards to the floor area and to the cooling
chamber, such as a trough (floor trough) for receiving liquid
nitrogen. The platform of the floor area may include for
example a grating, which extends over the vessel. Further
advantageous is that a trough with a flat bowl shape can be
used since no demands are made on the volume of the liquid
nitrogen arranged in the first cooling device. Thus, it is in
particular provided for that the volume of the liquid
nitrogen arranged in the first cooling device is less than
the volume of the vaporous nitrogen existing inside the
cooling chamber. Preferably, the floor area and the first
cooling device are equipped laterally and downwardly with
thermal insulation.
Advantageously, with the inventive combination of nitrogen
cooling, cooling chamber sizing and provision of the
platform, a new cooling system is created which overcomes the
disadvantages and limitations of conventional techniques. The
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conventional individual tank principle for cryobanks is
overcome with the invention. The cooling system represents a
freely scalable cryobank architecture. Compared to the
conventional cryotanks, the advantage results that
permanently constant storage conditions are provided for a
larger number of samples. The samples can be stored in sample
containers in the cooling chamber without requiring tanks,
thermal insulation or the like within the cooling chamber.
Access to individual samples is possible without compromising
the cooling of the remaining samples.
With the sizing of the cooling chamber, the internal volume
of conventional cryotanks is far exceeded. The sizing
provides not only sufficient space for automation and/or one
or also more operators, but also high heat capacity of the
cooled system. Thus, the supply of a sample or the insertion
of a tool represents only a negligibly low heat input, so
that the whole of the samples is hardly disturbed.
Compared with the cooling of food in large stores, there is
the advantage that the cooling chamber is cooled with the
liquid nitrogen to a temperature that is sufficiently low for
cryopreservation of biological samples. Liquid nitrogen as a
coolant is advantageous, for it is cheap, easy to handle and
complies in its liquid form with a boiling temperature at
atmospheric pressure of about -195.8 C with all requirements
for cryopreservation of biological samples. At the same time,
providing the platform allows that the cooling chamber can be
accessed independently of its size by the operator in order
to resolve eventual failures or errors.
In addition, the cooling system according to the invention is
characterized by the following advantages. The cryobank
architecture can be formed with large, automatable rooms with
sample receiving devices. The cooling system is scalable from
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small banks (a few hundred samples) up to industrial hall
systems (millions of samples). A temperature below -130 C can
be targetedly adjusted in the cooling chamber. The cooling
system allows a semi- or fully-automated storing and taking
of samples. Another advantage consists is in the long-term
operation capacity and maintenance without any change in
temperature in the cooling chamber.
Further advantages of the invention consist in the complete
freedom from moisture and icing-of the cooling chamber, the
rapid cooling ability of the cooling system without frost
formation, high access speed to all samples in the cooling
chamber, the same access ability for all stocks in the
cooling chamber, the optionally provided electronic
responsiveness of the samples and storage systems, the
controllability of the temperature in predeterminable areas
of the cooling chamber, and the rapid storing and destocking
of samples at a documented sample temperature. In particular,
the freedom from moisture and icing (freedom from water,
storage in dry gas) of the cooling chamber is supported by
the production according to the invention of cooling nitrogen
vapor from the floor area of the cooling chamber. The
invention can be used to implement alternative energy
concepts (use of hydrogen for cooling and power generation).
Furthermore, a strongly redundant design of the safety-
relevant systems and keeping constant the temperature through
controlled cooling in the cooling chamber or its parts is
possible.
According to a preferred embodiment of the invention, the
cooling system is equipped with at least one further cooling
device (hereinafter: second cooling device), which is
operational independently of the first cooling device. The
second cooling device is also provided for cooling of the
cooling chamber. According to a first variant, the second
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cooling device is arranged for cooling of at least one of the
side walls of the cooling chamber. Cooling elements of the
second cooling device are embedded, for example, as a hollow
wall structure in at least one of the side walls, or
positioned on the side pointing towards the interior of the
cooling chamber. According to another variant, the second
cooling device is alternatively or additionally configured
for electric cooling and/or cooling using liquid helium
(LHe).
The second cooling device advantageously allows a hybrid
operation of the cooling system. For example, at least two
different cooling principles can be switched temporally in
series (e.g., 8 h of electrical cooling, 10 h of cooling with
LN2) or in parallel and/or with different cooling capacities.
According to another example, electrical cooling to -150 C
and in addition cooling with LN2, or LN2 cooling and
operator-selectable cooling with LH, or electric cooling to
-80 C of an anteroom, then electrical cooling to -150 C and
cooling with LN2 can be provided for. A full hybrid system or
a semi-hybrid system can be realized with the hybrid
operation. In the full hybrid system, both cooling devices
are each alone fully efficient, i.e. each of the cooling
devices allows permanent cooling of the cooling chamber down
to temperatures < -130 C. In the semi-hybrid system, one of
the cooling devices (main cooling system, e.g. LN2) is
permanently in operation, while the other one of the cooling
devices (auxiliary system) is switched on only if required.
The second cooling device can in particular form an emergency
cooling system, which ensures, in case of failure of all
other cooling devices, in particular of the first cooling
device, that the temperature does not rise above -138 C in
the entire cooling chamber where the samples are located.
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According to a preferred embodiment of the invention, the
ceiling area of the cooling chamber has at least one ceiling
opening. The ceiling opening is particularly preferably a
permanently free through-hole through which cool gas flows
out of the cooling chamber, always upwards, through the
ceiling. Furthermore, the ceiling opening represents an
access opening for samples and/or an entry and exit opening
for the operator. It can advantageously be provided for that
the cooling chamber has no further openings, e. g. on the
side walls or in the floor area, so that the at least one
ceiling opening represents the single connection of the
interior of the cooling chamber with an environment, which is
suitable for the passage of the samples, the operator or
further mechanical components. Thus, it is particularly
preferably provided for that the entry and exit of the
operator take place exclusively above the cooling chamber
through the ceiling area. However, the entry and exit the
operator through a side wall can be provided alternatively or
additionally.
The at least one ceiling opening advantageously offers the
option to place a hood chamber onto the cooling chamber, in
which the sample receiving device or at least the
cryopreservation samples can be accommodated e. g. in the
case of an accident.
In addition, according to a further variant of the invention,
it has proved advantageous if at least one operation room is
provided for above the ceiling opening. The temperature of
the operation room can be increased compared with the
temperature of the cooling chamber. To minimize thermal
losses, the operation room is, however, preferably thermally
insulated from the external environment of the cooling
system. The operation room contains technical systems, which
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have an effect on the cooling chamber. Preferably, a drive
device with mechanical control elements, such as robot arms
for access to samples, and/or a conveying device for driving
the operator into or out of the cooling chamber are provided
for in the operation room. Alternatively or additionally, the
operation room can be connected with at least one lock device
(person lock device and/or sample lock device).
According to a preferred variant of the invention, the
mechanical control elements, such as gripping arms, levers or
actuation elements, can be introduced into the cooling
chamber. If at least parts of the control elements, in
particular connection areas between parts of the control
element, which are movable relative to one another, are
heatable, the operability of the drive device in the cooling
chamber is improved. The connection areas can be equipped
with locally acting heaters.
According to further preferred variants of the invention, the
conveying device comprises in the operation room a rope hoist
and/or a step device. The rope hoist is adapted for
transporting the operator into and/or out of the cooling
chamber. For this variant, the operator is transported
suspended on a rope or a chain. This advantageously increases
in particular the safety during evacuation of the operator
out of the cooling chamber. The step device comprises, for
example, a step ladder or stairs, which extends between the
interior of the cooling chamber, in particular its floor
area, and the operation room above the ceiling area.
Further advantages can result for reducing thermal losses if
supply connections run between the cooling chamber and its
environment through the ceiling area. Supply connections
comprise medium lines, in particular coolant or breathing air
lines, electric cables, in particular for power supply or for
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signal transmission, and/or optical cables, in particular for
signal transmission.
According to a further preferred embodiment of the invention,
at least one of the side walls can have a multi-layer
structure with at least two wall layers. The inventors have
found that the structure with the at least two thermally
insulated wall layers allow effective insulation of the
cooling chamber with respect to an environment at room
temperature and with a moderate coolant consumption.
Furthermore, the operability of the cooling system can be
achieved, in particular in case of failure of the cooling, at
least over a plurality of days. The use of multiple wall
layers has the particular advantage that they can be
optimally designed with respect to the use of space and the
dense filling of the side wall. Each wall layer is a wall
layer, which extends along the extension of the side wall.
Each of the wall layers has thermally insulating effect, i.e.
a thermal conductivity, which is lower than 0.05 W/m2 (simple
insulating foam materials), in particular lower than 0.004
W/m2 (vacuum pads), in particular lower than 0.001 W/m2
(vacuum insulation), and/or a moisture-repellent effect. A
plurality of wall layers are stacked vertical to the
extension of the side wall. A wall layer comprises at least
one plastic layer, at least one vacuum component layer and/or
at least one vapor-blocking layer. The plastic layer
comprises e.g. a board made of foamed plastics, in particular
a rigid foam board. With the plastic layer, the cubature can
be advantageously optimized with respect to a further wall
layer. The vacuum component layer comprises e.g. vacuum
insulation panels, which are advantageous due to their low
thermal conductivity. The vapor-blocking layer comprises, for
example, a foil, which is impermeable for water vapor. In
particular, a plurality of vapor locks can be available
within the side wall to prevent failure due to moisture.
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At least one of the wall layers can be formed in particular
from a material (composite material, e.g. foam, liquid;
inflatable body, e.g. with suitable sealing material), which
is suitable to close autonomously any interruption, such as
cracks or holes. At least one of the side walls can thus be a
self-healing wall.
At least one of the wall layers can furthermore have a
switchable thermal conductivity. The thermal conductivity can
be switched e.g. by means of evacuation from a vacuum
component layer or supply of a gas or a liquid into a vacuum
component layer.
At least one of the side walls can be covered according to
the invention on the inner side facing toward the cooling
chamber with a metallic material in order to, for example,
form a cooling layer and/or in order to accommodate cooling
elements of the second (electric) cooling device.
Furthermore, according to the invention, at least one of the
side walls can be constructed in a modular manner with at
least one wall element, which, with a vertical movement with
respect to the respective side wall, can be released from its
compound. The at least one wall element is shiftable and can
be separated from the side wall. The at least one wall
element advantageously allows a structure of the side wall
with individually interchangeable insulation media without
risks for the samples. Alternatively or additionally, the at
least one wall element allows an emergency opening of the
cooling chamber for rapid removal of samples from the cooling
chamber in case of an accident (evacuation). The wall element
can be instantaneously shiftable off the side wall, for
example by means of blowing-up. Advantageously, for the case
of accident, a docking device for a mobile evacuation
container can be provided for on an external side of the side
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wall, corresponding to the position of the at least one
shiftable wall element.
According to a further preferred embodiment of the invention,
at least one of the side walls can have a door opening, which
is closed by a movable door leaf. The door leaf is, such as
the surrounding side wall, designed in a thermally insulating
manner. The lateral door opening can be advantageous for
sidewards access by the operator to the cooling chamber.
Preferably, the door opening is arranged with a predetermined
distance above the floor area. The distance is preferably
equal to at least 10 cm, in particular at least 50 cm, up to
several meters. The door opening is connected via stairs with
the floor area. In this case, a downwardly closed space is
formed up to a level below the door opening and above the
floor area to receive the vaporous nitrogen. At least part of
the vaporous nitrogen cannot escape from the cooling chamber
even if the door opening is open. Alternatively or
additionally, it can be provided for that the door leaf is
arranged shiftable parallel to the respective side wall. In
this case, a wall surface (bulkhead), which can be drawn e.g.
in the height or to the side, is created. A docking device
for an evacuation container or a lock device can be provided
for on an external side of the side wall, corresponding to
the position of the door opening.
Advantageously, a sample receiving device in the cooling
chamber can comprise shelves (so-called "racks"), which form
the support structure for the biological samples. In this
case, advantages result for automated access to samples, e.g.
with the mechanical control elements. Shelves comprise
carrier plates (racks) on which the containers with the
biological samples are freely located. Particularly
preferably, the shelves are formed from a material with
increased thermal conductivity, e. g. metal. This
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advantageously allows a homogeneous temperature distribution
in the sample receiving device.
The sample receiving device can be designed for an electric
and/or optical connection with a control device (operational
control). This advantageously allows an electronic
responsiveness of the shelves and, if necessary, of the
samples on the shelves.
According to a variant of the invention, the sample receiving
device can be equipped with thermal bridges, which protrude
into the floor area. The thermal bridges consist of materials
with an increased thermal conductivity, e.g. of metal. This
advantageously creates a thermally well conductive connection
to the LN2-lake of the first cooling device. According to a
further variant the invention, the sample receiving device
can alternatively or additionally form a rigid component. For
example, the shelves are connected to a rigid structure. In
this case, advantages result for the position accuracy and
the reproducibility of the weight load of the platform.
According to a further variant of the invention, the cooling
chamber can be subdivided by partition walls into subrooms.
The partition walls can extend in the vertical and/or
horizontal direction in the cooling chamber. This
advantageously achieves a segmentation into pre- and main
cooling chambers and, if necessary, into secondary cooling
chambers. For example, samples can be cooled targetedly
according to the storage capacity used and the access
frequency and/or storage temperature demand. For example, the
temperature can be targetedly decreased or increased in
certain parts of the cooling chamber, such as in a front,
central, upper, rear and/or below part. Furthermore, heat
corridors can be formed, through which an increased
temperature is provided in the case of an accident for rapid
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evacuation of the samples.
With the partition walls, a structure can be created, which
is characterized by mutually surrounding subrooms with
different temperatures. For example, a subroom can have the
lowest temperature in the middle of the cooling chamber and
offer the highest safety for maintaining the cryopreservation
temperature. This allows a storage strategy for which the
most valuable frozen live samples are stored in the subroom
in the middle of the cooling chamber, frozen dead material in
the surrounding subrooms, and liquid, genetic material,
serines etc. in an external subroom.
According to general features of the invention, the cooling
system can be equipped with at least one of the following
components:
- ventilators for thorough mixing of the cool gaseous phase
in the interior of particular rooms,
- gas sensors, e.g. oxygen sensors,
- temperature sensors, in particular for a spatially
distributed temperature measurement in the cooling chamber,
- alarm devices, e. g. alarm lamps,
- lighting equipment with minimized entry of infrared or
thermal radiation, e.g. using light-emitting diodes (LED) or
other cold light sources, glass fibers for light coupling in
the ceiling area, in the floor area or in at least one of the
side walls (glass fibers can be supplied into the cooling
chamber in particular via thermal insulation, e.g. via
coupling-in via an evacuated vacuum component),
- contactless energy and signal entry (inductive or optical
coupling),
- monitoring devices, e.g. a camera monitoring system, a
movement detector and/or a heat detector,
- emergency power supply with self-connection, bridging-free
voltage supply,
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- coolant sprinkler system in the upper area of the cooling
chamber, e.g. for supply of liquid nitrogen or helium for
rapid cooling of the cooling chamber, and
- connecting device for external liquid gas supply, e.g.
from a tanker, in the case of an accident,
- a nitrogen liquefaction system,
- a coolant container, which is provided for receiving a
reserve volume of liquid nitrogen, and/or
- condensate collection elements, which protrude from the
floor area into the cooling chamber.
Further advantages and details of the invention are described
below with reference to the attached drawings. The figures
show as follows:
Figures 1 and 2: schematic cross-sectional views of
preferred embodiments of the cooling system
according to the invention;
Figures 3 and 4: schematic perspective views of further
embodiments of the cooling system according
to the invention;
Figure 5: schematic cross-sectional views of a side
wall of the cooling system according to the
invention;
Figure 6: a schematic overview representation of the
cooling system with additional drive
devices according to the invention;
Figure 7: schematic top and cross sectional views of
a further embodiment of the cooling system
according to the invention having a
segmented cooling chamber and an
illustration of taking a sample off a
shelf;
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Figure 8: a schematic cross-sectional view of a
further embodiment of the cooling system
according to the invention;
Figure 9: a schematic illustration of the adaptation
of a cooling chamber of the cooling system
according to the invention depending on the
conditions of application; and
Figure 10: a schematic illustration of a further
operating mode of the cooling system
according to the invention.
Preferred embodiments of the cooling system according to the
invention and of the methods for operating the same are
described in the following with exemplary reference to a
cooling system with a cooling chamber, which is dimensioned
such that an operator can perform several walking steps in
the cooling chamber. The realization of the invention is not
restricted to the cooling chamber size exemplary shown, but
is rather accordingly possible even with considerably larger
cooling chambers (halls) or also with smaller cooling
chambers. Embodiments are described in the following in
particular with reference to the structure of the cooling
system and the novel operating modes, which are allowed by
the cooling system according to the invention. Details of the
cryopreservation of biological samples, such as the sample
preparation or the realization of certain cooling procedures
or the deposition of the samples together with stored sample
data can be realized with the cooling system according to the
invention as is known per se from the prior art.
Figure 1 shows a first embodiment of the cooling system
according to the invention 1 in a schematic cross-sectional
view with a cooling chamber 100, a first cooling device 200,
a second cooling device 300, an operation room 400 and a
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coolant supply 500.
The cooling chamber 100 is delimited downwards by a floor
area 110, sidewards by side walls 120 and upwards by a
ceiling area 130. The internal volume of the cooling chamber
100 is equal to e.g. 10 m * 5 m * 3 m. A sample receiving
device 140 is arranged in the cooling chamber 100, standing
on the floor area 110 and adjacent to the side walls 120. The
inner surface of the cooling chamber 100 is provided with a
cooling layer 101, which is formed from a material having
high thermal conductivity, e.g. metal. The cooling layer 101
has the advantageous effect that a temperature compensation
in the cooling chamber 100 takes place in the vertical
direction. In particular, the temperature can be adjusted
below -130 C also in the upper area of the cooling chamber
100, which is important for the long-term storage of living
biological samples.
Temperature sensors 103 are arranged in the cooling chamber
100 and in the operation room 400. Several temperature
sensors 103 are provided at different distances from the
floor area 110. This allow the detection of a temperature
distribution in the cooling chamber 100. If required,
additional cooling with the second cooling device 300 and/or
a ventilation device (not shown) in the cooling chamber 100
can take place to achieve compensation of the temperature, in
particular sinking of the temperature in the upper regions of
the cooling chamber 100.
The floor area 110 comprises a platform 111, which extends
over the first cooling device 200 with a trough 210. The
trough 210 has a double-walled trough body with an evacuated
interior and is provided on its outer side with thermal
insulation. The thermal insulation has the same structure as
the side walls 120. Alternatively or additionally, the trough
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is insulated with an infrared mirrored vacuum region. During
operation of the cooling system 1, liquid nitrogen 220 is
contained in the trough 210. The liquid nitrogen 220
preferably has a free surface towards the floor area 110. A
nitrogen lake is formed. Filling of the trough 210 and
maintaining the reservoir of liquid nitrogen 220 during
operation of the cooling system 1 takes place by means of the
coolant supply 500.
The platform 111 comprises a grating, e.g. made of steel,
which extends over the trough 210 and is equipped with step
platforms 112. The step platforms 112 reduce any possible
mechanical contact between an operator 3 and the platform
111, so that any heat flow from the operator 3 to the
platform 111 is minimized. Since the platform 111 forms a
support area for the operator 3 and also the sample receiving
device 140, the platform 111 can be mechanically supported in
the trough 210 by additional components (not represented).
The side walls 120 comprise several stratiform wall layers
with an inner plastic layer 121 and two outer vacuum
component layers 122.1, 122.2. The plastic layer 121
comprises a layer made of a polymer foam, e.g. a polyurethane
foam. The thickness of the plastic layer 121 can e.g. be
selected in the range of 10 cm to 1 m or also above 1 m. The
vacuum component layers comprise an internal layer 122.1 of
evacuated components (so-called "vacuum components") and an
external evacuated hollow wall 122.2. The evacuated
components of the internal vacuum component layer 122.1 are
formed parallelepipedic, in particular like conventional
building stones or bricks for building purposes, and are made
out of plastic with an evacuated or evacuatable interior. The
hollow wall of the external vacuum component layer 122.2 is
evacuated in a normal operation mode or optionally filled
with a cooling liquid. The hollow wall has in particular an
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advantageous function for the case that one of the cooling
devices fails. If one of the cooling devices fails, the
hollow wall of the external vacuum component layer 122.2 can
be filled from a swichtable external auxiliary container 540
(see Figure 6) with a coolant such as liquid nitrogen in
order to prevent undesirable heating of the cooling chamber
100, since heat penetration from the outside is prevented,
even though it occurs with high coolant expenditure. In this
case, this hollow wall should not form the outermost layer.
Deviating from the illustration in Figure 1, the order of the
plastic layer and the vacuum component layer can be reversed.
Furthermore, further plastic and/or vacuum component layers
can be provided for. Further details of the side walls 120
are described below with reference to Figure 5.
The ceiling area 130 comprises a plastic layer 132, formed
e.g. out of polymer foam, in which a ceiling opening 131 is
formed. Above the ceiling opening 131 is provided the
operation room 400 with a drive device 410 and mechanical
control elements 411, which project into the interior of the
cooling chamber 100. Figure 1 shows by way of example a rod
assembly with a vertical (412) and a horizontal (413)
shifting units, which can be actuated with the drive device
410. With the mechanical control elements 411, samples 2 can
be introduced into the sample receiving device 140 or removed
therefrom. The mechanical control elements 411 are driven
from above, i.e. from the operation room 400, e.g. using rope
hoists, chains, toothed belts and the like, whose drive
device 410 is arranged in the operation room 400. If
required, motors, deflection rollers or other mechanical
connection areas can be encapsulated in a thermally
insulating manner or locally heated. To prevent thermal
bridges, thermally insulating elements (not shown) are
contained in the mechanical control elements 411.
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The sample receiving device 140 comprises shelves 141 (so-
called "cryo racks") in which biological samples 2 are stored
in sample containers. The shelves 141 have frames made of
thermally well conductive material, e.g. made of metal, which
have thermal contact to the platform 111 and via thermal
bridges 142 directly to the liquid nitrogen 220 in the first
cooling device 200. This advantageously ensures effective
cooling up to the upper compartments of the shelves 141.
The second cooling device 300 is provided for on the side
walls 120, in particular arranged on its surface facing
inwardly or embedded therein. The second cooling device 300
is configured for electric cooling. It comprises cooling
elements 310, which are connected with cooling aggregates
320. The cooling aggregates 320 are located outside the
cooling chamber 100, preferably above it. With the second
cooling device 300, it is e.g. possible to provide electric
cooling down to a temperature of -150 C. According to
alternative variants of the invention, the second cooling
device 300 can be formed as a substitute by nitrogen cooling
or cooling with liquid helium.
The operation room 400 contains the drive device 410 for the
mechanical control elements 411. In addition, the operations
room 400 can further contain drive devices (see e.g. Figure
2) and/or be connected with a person and/or sample lock
device 450, 460 (see e.g. Figures 3, 6).
The coolant supply 500 comprises a coolant-storage container
510 and a coolant line 520. The coolant line 520 leads from
the coolant storage container 510 through the ceiling area
130 and through the cooling chamber 100 into the first
cooling device 200. The coolant line 520 is thermally
insulated outside the cooling chamber 100, e.g. formed by a
vacuum line. In contrast, inside the cooling chamber 100 (at
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521), a thermal insulation of the coolant line 520 is not
provided for. This improves cooling of the interior of the
cooling chamber 100. In addition, the coolant line 520
represents in the cooling chamber 100 a condensate collection
element (moisture trap). Any residual moisture in the cooling
chamber 100 settles on the coldest place, i.e. on the surface
of the coolant line 520, until a dry and cold nitrogen
atmosphere is formed in the whole cooling chamber 100 and
there are no further ice deposits.
The function of the coolant line 520 as condensate collection
element is advantageous in particular during the initial
cooling of the cooling chamber. Moisture is bound by means of
the condensate collection element, so that a dry storage is
guaranteed during operation the cooling system 1. The dry
storage (storage preventing ice deposition) is not
advantageous only for the shelf-life of the samples, but also
for the automation of the sample handling. In this way,
movable parts of the mechanical control elements 411 can be
moved easier.
Figure 1 illustrates an important design principle of the
cooling system according to the invention. All supply
connections, in particular supply lines and openings, into
the interior of the cooling chamber 100 exclusively occur
through the ceiling area 130, i.e. from above. This leads to
minimization of the heat supply. Furthermore, warmer top
attachments can be arranged in the operations room 400 or
above it (see Figure 2) for devices, which cannot operate at
low temperatures. In particular, chambers with higher
temperature or even with an internal heater for operation of
movable parts, such as motors, can be put on top. A plurality
of chambers of this type can be constructed tower-like one
above the other (see Figure 2). Since gas is formed
continuously from the first cooling device 200 with clear
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increase of volume and the cooling system 1 is designed
pressure-free, i.e. not gas-tight, nitrogen continuously
flows through the cooling chamber 100 from below. For
discharge of the nitrogen, an outlet 102, e.g. in the form of
a siphon, is arranged in the uppermost part of the cooling
system. Also significant for the reliable operation of the
cooling system 1 is heating in the case of an incident, which
is as delayed as possible, in particular in case of failure
of cooling devices. This is in particular achieved with the
thermally insulating structure of the side walls 120.
For operation of the cooling system 1, the cooling chamber
100 with the first cooling device 200, eventually supported
by the second cooling device 300, is cooled down to the
desired cryopreservation temperature. Subsequently, using the
mechanical control elements 411, the biological samples 2 are
arranged in the sample receiving device 140 in the cooling
chamber 100. In the case of an incident or for the purpose of
maintenance, control or operating work, the operator 3 can
step into the cooling chamber 100 through the ceiling opening
131 or through a lateral door (see Figure 4). The operator 3
wears a protective suit with thermal insulation and a head
protection, which guarantees protection of the operator
against thermal loss.
Figure 2 illustrates in a schematic cross-sectional view of a
modified embodiment of the cooling system 1 according to the
invention, which is constructed with respect to the cooling
chamber 100, the first cooling device 200, the second cooling
device 300 and the coolant supply 500, as was described above
with reference to Figure 1. With respect to the operation
room 400, following differences arise. According to Figure 2,
the operation room 400 comprises a first chamber 420, which
is essentially constructed like the operation room 400
according to Figure 1, a second chamber 430 and a third
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chamber 440. In the second and third chambers 430, 440,
further operating equipment 431, 441, such as measurement
and/or control devices or further drives, are arranged. The
chambers of the operation room 400 are each arranged
thermally insulated. A specific temperature can be adjusted
in each of the chambers. Typically, the temperature rises
from the first (420) up to third (440) chamber. For conveying
the gas atmosphere formed in the cooling chamber 100, the
chambers of the operations room 400 are connected via tube
connections 401 (or other through-holes). On the upper side
of the third chamber 440, an outlet 102 with a siphon is
provided for.
Between the chambers 420, 430 and 440, partition walls with
each at least one chamber door 402 are provided for. This
facilitates the setting of different temperatures in the
chambers 420, 430 and 440. If, for example, a temperature in
the range of -196 C to -140 C is adjusted in the cooling
chamber 100, a temperature of round -80 C could be adjusted
in the second chamber 430 and a temperature in the range of
-40 C to -20 C adjusted in the third chamber 440.
Accordingly, different operating devices, which have
different operating temperatures, can be accommodated in the
chambers 420, 430 and 440. For monitoring of the
temperatures, a temperature sensor 403 is arranged in each
one of the chambers 420, 430 and 440.
Deviating from Figure 2, the chambers 420, 430 and 440 could
be open relative to one another. In this case, too, in case
of undisturbed cooling, a sequence of horizontally arranged
gas layers with upwardly increasing temperatures can be
formed. Furthermore, a local heater, in particular with a
resistance heating or an infrared lamp, can be arranged in at
least one of the chambers 420, 430 and 440 in order to heat
temperature sensitive components for the operation at least
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in certain operation phases. This is advantageously possible
without having to accept influencing the temperature in the
cooling chamber 100.
Figure 3 illustrates features of the walk-in access by the
operator 3 to the cooling chamber 100 by means of a further
embodiment of the cooling system 1 according to the
invention. The illustration of the cooling chamber 100 with
the floor area 110, the side walls 120 and the ceiling area
130 is represented in a simplified manner in a schematic
perspective view. In a practical implementation, the cooling
system 1 can be constructed with respect to these components,
as is described above with reference to Figures 1 and 2.
In the ceiling area 130 is a ceiling opening 131 provided
for, which can be closed with a cover 132. The temperature
stratification in the cooling chamber 100 is advantageously
hardly affected due to providing the opening for the access
by the operator 3 on the top side of the cooling chamber 100
when the operator 3 accesses it. Alternatively, the opening
can be provided for the access by the operator 3 in one of
the side walls (see Figure 4).
The operation room 400 is arranged above the ceiling opening
131. There is a conveying device 150 arranged in the
operation room 400, which is configured for introducing the
operator 3 into the cooling chamber 100 and/or for removing
the operator 3 from the cooling chamber 100. The conveying
device is exemplarily illustrated with a rope hoist 151
having a hoist and a step device 152 (ladder). The components
151, 152 can be provided for individually. For safety
reasons, it is, however, preferred to provide both components
in order to be able to remove the operator 3 rapidly and
securely from the cooling chamber 100 if this is required.
The rope hoist 151 can also be used for the transport of
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samples 2 and/or shelves 141.
The operation room 400 is connected with a person lock device
450, which can be accessed to from the outside via a
thermally insulated external lock door 451. The person lock
device 450 is separated from the operation room 400 by a
thermally insulating, internal lock door 453. Between the
operation room 400 and the person lock device 450, a tube
connection 452 is provided for pressure equalization, so that
no pressure difference can arise between both rooms and
nitrogen gas can escape from the cooling chamber 100 via the
operation room 400 into the person lock device 450 and from
the latter outwardly via an outlet 102.
The walk-in access to the cooling chamber 100 via the person
lock device 450 is done such that the operator 3 first wears
a protective suit 4 with a breathing air supply 5 outside the
person lock device 450. In the person lock device 450, a
preliminary cooling to a medium temperature range, e.g. -
80 C, then takes place. For this purpose, the person lock
device 450 is equipped with a cooling device (not shown).
Alternatively, the person lock device 450 can be cooled with
a part of the vapor flowing out of the cooling chamber 100.
If the operator 3 is sufficiently cooled down, he is
transferred into the operation room 400 and from there, using
the rope hoist 151 and/or by means of the step device 152,
transferred into the cooling chamber 100. In the cooling
chamber 100, the operator 3 can move, for example in order to
carry out maintenance work on the sample receiving device
140.
The lock door 451 of the person lock device 450, the internal
lock door 453 and the cover 132 are provided with electric
contacts and a closing control system, which is adapted for
at least one of the following procedures.
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Firstly, an inspection of the cooling chamber 100 can be
provided during normal operation of the cooling system 1. The
operator puts on the protective suit 4 with the breathing air
supply 5 outside. In this case, the outer lock door 451 of
the person lock device 450 can only be opened if the inner
lock door 453 and the cover 132 are closed. If the operator 3
is in the lock device 450, the outer lock door 451 is closed,
and the inner lock door 453 can only be opened if a dry
nitrogen atmosphere with a predetermined temperature has been
formed in the person lock device 450. For this purpose,
gaseous or liquid nitrogen can be blown in from the outside.
As soon as the predetermined temperature and the dryness of
the atmosphere are reached in the person lock device 450, the
inner lock door 453 is opened and the operator 3 can walk
into the operation room 400. Here, there is a further cooling
of the operator 3 to a predetermined temperature. As soon as
the operator 3 is sufficiently cooled down and the atmosphere
in the operations room 400 has reached predetermined standard
values, the cover 132 is opened so that the operator 3 can
enter in the cooling chamber 100. In the cooling chamber 100,
the operator 3 is video-monitored and stays in contact via
wireless audio connection with helpers outside the cooling
system 1. Leaving the cooling system 1 is done during normal
operation in reverse order.
Secondly, it is provided for in an emergency situation that
the cover 132 and the inner and outer lock door 451, 453 can
be opened simultaneously by means of emergency switches (not
shown). In this situation, rapid access to the interior of
the cooling chamber 100, in particular for rescue of the
operator 3 and/or for safeguarding stored samples, is
allowed. In the emergency situation, the operator 3 can leave
the cooling chamber 100 by himself through the ceiling
opening 131 and the person lock device 450 or be drawn out
from there. Simultaneously, it can be provided for that
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heated dry air is blown in from the outside by means of a
blower 460 into the cooling chamber 100 and from there into
the operation room 400 and the person lock device 450. The
temperature can thereby be increased to a value above -50 C
and oxygen can be supplied. This operation can be monitored
by means of oxygen sensors (not shown). As a result, further
helpers can act in the cooling chamber 100, if necessary
without a protective suit and without their own oxygen
supply.
Figure 4 schematically illustrates features of the inspection
of the cooling chamber 100 and the supply or withdrawal of
the sample receiving device 140 into or out of the cooling
chamber 100 by means of a further embodiment of the cooling
system 1 according to the invention. As shown in Figure 3,
the cooling system 1 is illustrated in a simplified schematic
perspective view with the floor area 110, the side walls 120
and the ceiling area 130.
For the supply or withdrawal of the sample receiving device
140, the ceiling opening 131 is provided in the ceiling area
130 with an operation room 400 located above it. The
operation room 400 has a tower-shaped hood chamber 400.1 with
a height, which is such that a shelf 141 of the sample
receiving device 140 can be accommodated completely in the
operation room 400. A drive device 410 with a rope hoist 414,
with which the shelves 141 can be drawn into the operation
room 400 in particular in the case of an accident, is located
in the operation room 400.
Deviating from Figure 3, a door opening 125 having a
shiftable door leaf 126 is arranged in one of the side walls
120 to allow walk-in access by the operator 3. The door
opening 125 is at a predetermined height above the floor area
110. The elevated entrance is preferred so that the cold gas
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filling in the cooling chamber 100 does not flow away to the
outside when the door opening 125 is opened. Between the door
opening 125 and the floor area 110, there are stairs 127 via
which the operator 3 can get into the cooling chamber 100.
The door leaf 126 is configured for shifting parallel to the
even extension of the side wall 120. A vertical or horizontal
movement parallel to the side wall is preferred, since the
horizontal stratification of the cold gas filling would
otherwise be impaired in the cooling chamber 100 in case of
pivoting off the side wall.
Outside the cooling chamber 100, a person lock device 450
with at least two chambers 455, 456 and an outer (451), a
central (454) and an inner (126, 457) lock door is arranged
on the side wall 120. The inner lock door 457 is formed by
the door leaf 126. Tube connections 452 through which cold
gas can flow out from the cooling chamber 100 to the outside
are provided for between the cooling chamber 100 and the
cooling chambers 455, 456. From the outer chamber 455, the
gas flows through the outlet 102 to the environment. In the
outer chamber 455, a temperature of e.g. -20 C is provided
for, whereas a temperature of -80 C is provided for in the
inner chamber 456.
For inspection of the cooling chamber 100, the operator 3
puts on the protective suit 4 with the breathing air supply 5
outside the person lock device 450. The operator 3 is cooled
down step by step in the person lock device 450 until he can
walk through the door opening 125 into the cooling chamber
100. The doors 451, 454, 457 of the person lock device 450
can be controlled for the normal operation or the emergency
situation, as was described above with reference to Figure 3.
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Since it may be required to stay for a longer period of time
(> 15 minutes) in the cooling chamber 100, schematically
shown supply connections 104 are arranged in the cooling
chamber 100. The protective suit 4 and/or the breathing air
supply 5 can temporarily or permanently be connected to the
supply connections 104, e.g. in order to save an energy
source in the protective suit 4 or in order to supply oxygen.
Figures 5A to 5C show further details of a side wall 120 of
the cooling chamber 100 of the cooling system according to
the invention. The features of the side wall 120 can also be
provided accordingly for thermal insulation of the first
cooling device 200 (see Figure 1) below the floor area of the
cooling chamber. In the schematic cross-sectional view of
Figures 5A to 5C, the cooling chamber 100 is arranged
respectively to the right of the side wall 120, i.e. the
external side of the side wall 120 is, in Figures 5A to 5C,
respectively to the left of the side wall 120.
According to Figure 5A, there is first on the inner side of
the side wall 120 a cooling layer 101, which consists of
metal, e.g. aluminium or steel, with a thickness in the range
of a few mm up to 1 cm. The cooling layer 101 is in direct
thermal contact with the first cooling device 200 (see Figure
1), in particular with the liquid nitrogen 220 of the first
cooling device 200, so that cooling of the interior of the
cooling chamber 100 is supported with the cooling layer 101.
Then, there is a first vacuum component layer 122.1, which
comprises an evacuated hollow wall, which extends along the
side wall 120. The outer surface of the evacuated hollow wall
is designed for reflection of infrared radiation (thermal
radiation) and is provided for this purpose with a reflective
surface finish or a reflecting foil 120.1. Thereby, thermal
radiation coming from the outside is advantageously
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reflected.
Then, there is a further vacuum component layer 122.2, which
comprises a brickwork made of brick-shaped insulating
components. The insulating components are hollow plastic
bodies with an evacuated, closed interior. Each insulating
component is a self-contained system. Within the vacuum
component layer 122.2, the insulating components are arranged
in a multi-layered offset manner as in a brickwork, so that
this is advantageous for the suppression of the heat
transport through the side wall 120.
Outwardly, there is then a plastic layer 121 made of a foamed
plastics, e.g. of polyurethane. The thickness of the plastic
layer 121 is equal to e.g. 10 am up to 1 m (for insulation
and stability purposes). On the external side of the plastic
layer 121, a protective layer 121.1 for mechanical protection
of the side wall 120, a further wall expansion and/or a
further vacuum component layer (see Figure 1) are arranged.
An advantage of the invention consists in particular in that
the thickness of the side wall 120 can be increased as needed
without any essential practical limitations. An overall
thickness in the range of 1 m to 6 m or 10 m or above is
possible and recommended depending on the dimension of the
cooling system. For conventional cryotanks, tank walls as
thin as possible are required in order to save store room. In
contrast thereto, the thickness of the side wall 120 of the
cooling system according to the invention plays no critical
role.
The embodiment of Figure 5A can be modified in such a way
that a further hollow wall is inserted, which is part of a
further, in particular electric, cooling device. In the case
of an incident (e.g. in case of failure of the first cooling
device below the floor area of the cooling chamber), cooling
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of the cooling chamber can be carried out completely by the
side wall 120, while the first cooling device is
simultaneously serviced and repaired. Cooling from the side
wall 120 can be provided e.g. when the stock of liquid
nitrogen 220 of the first cooling device 200 is running short
and cannot be filled up rapidly enough. This modification is
shown with further details in Figure 5B.
Figure 5B shows the side wall 120, for which the vacuum
component layer 122.1 is arranged with an increased thickness
and, additionally, a cooling element 310 of the second
cooling device 300 (see Figure 1) is arranged on the inner
side of the side wall 120. The cooling element 310 comprises
a further stratiform, hollow-walled component, such as a
plurality of hollow lines made of metal. The hollow lines can
be arranged on the whole surface or with mutual distances on
the inner side of the side wall 120. The cooling element 310
is connected with a cooling aggregate 320 (see Figure 1). In
addition, the cooling element 310 can be in communication
with the liquid nitrogen 220 of the first cooling device 200
(see Figure 1).
During normal operation, cooling of the interior of the
cooling chamber 100 is supported by the cooling element 310.
In the case of an incident, the cooling element 310 can be
flown through from the outside by an additional coolant. The
additional coolant can be provided by an electric cooling
system or from a coolant tank or a connected tanker, e.g.
with liquid nitrogen.
Figure 5C shows a further modified variant of the side wall
120, for which the order of the vacuum component layer 122.3
and the plastic layer 121 is inverted. In detail is, at
first, the metallic cooling layer 101 is provided for on the
inner side of the side wall 120, the first vacuum component
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layer 122.1 being arranged under the metallic cooling layer.
The latter can be equipped with a reflecting element 120.1 as
can be seen in Figure 5A. Then come the plastic layer 121 and
the brickwork made of insulating components of the vacuum
component layer 122.2. Outwardly, there is then a further
protective layer 122.3 with which the vacuum component layer
122.2 is stabilized. Furthermore, conventional wall
structures can follow outwardly for protection or
stabilization purposes.
The schematic representation in Figure 6 illustrates the
connection of the cooling system 1 according to the invention
with the coolant supply 500 and an operational control system
600. The cooling system 1 is equipped with a cooling chamber
100, which is configured for long-term storage of biological
samples at temperatures below -80 C, in particular below
-130 C. Typically, the temperature in the cooling chamber 100
is less than -140 C. For this purpose the first cooling
device 200 (see Figure 1) is supplied with liquid nitrogen as
follows.
The coolant supply 500 comprises a first (510) and a second
(511) coolant storage container (tank). The coolant storage
containers 510, 511 can, if required, be filled up by means
of external mobile reservoirs (tankers). Preferred is,
however, a variant of the invention for which the coolant
supply 500 is equipped with its own liquefaction system 530.
The liquefaction system 530 continuously delivers liquid
nitrogen into the coolant storage container 510, 511. The
liquefaction system 530 has the advantage that uninterrupted
long-term cooling can be ensured over long time periods,
months, years or decades. For electric supply of the
liquefaction system, a current generator 531 is provided for,
which can also serve, in the case of an incident, to supply
the second cooling device.
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The first coolant storage container 510 is connected via the
coolant line 520 with the first cooling device 200 (see
Figure 1). Furthermore, the first coolant storage container
is connected with a coolable hood chamber 400.1 (see Figure
4) of the operation room 400 in order to set therein a
temperature of e.g. -80 C in the case of an incident.
The second coolant storage container 511 is connected via an
evaporation system and a second coolant line 521 and a
temperature control device 522 with the person lock device
450 for the operator(s). The temperature control device 522
is actuated in such a way that a temperature of -40 C is set
in a first chamber and a temperature of -80 C is set in a
second chamber in the person lock device 450. The temperature
control device 522 is furthermore used for additionally
tempering a sample lock device 460 for samples.
The subsequent supply of liquid nitrogen into the first
cooling device 200 is performed using a control loop. The
level of the liquid nitrogen of the first cooling device 200
is recorded with a fill level sensor. In the event of it
falling below a critical level, liquid nitrogen is
additionally supplied to the first cooling device 200 via the
coolant line 520.
The coolant supply 500 is, in addition, provided with an
external auxiliary container 540 for supply of the cooling
system 1 with liquid nitrogen in the case of an incident. The
auxiliary container 540 is preferably connected via a
blocking element, such as a valve, with the hollow wall 122.2
in the side wall 120 (see Figure 1).
In addition, the second cooling device, which comprises an
electric cooling aggregate 320 that is configured for setting
a temperature of -80 C, preferably of -150 C, in the cooling
chamber 100, is connected to the cooling system 1. The
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coolant of the second cooling device 300 is delivered to the
cooling element 310 in the side wall of the cooling chamber
100 (see e.g. Figures 1, 5B).
Figure 6 also illustrates the components of the operational
control device 600 of the cooling system 1 according to the
invention. In particular, the operational control device 600
comprises a first control device 601 for the sample storing
and withdrawal automatic machine and a second control device
602 for system control. The second control device 602
comprises in particular a temperature-setting device and/or
control of the sensors, of the light and the monitoring
system, such as of video cameras. Furthermore, the
operational control device 600 comprises a first database
603, which is coupled with data storage devices of the
samples deposited in the cooling system 1. Electronic
components of the sample containers and/or alarm systems are
controlled with data from the first database 603 for
detecting critical sample states. The second database 604 is
adapted for coupling to the electronic components of the
samples. The data connection between the operational control
system 600 and the cooling system 1 can be wired or wireless.
Finally, the operational control device 600 comprises a
vacuum system 605, which is arranged for evacuation of
components of the side walls 120 of the cooling chamber 100
and, if required, can be supplied with the generator 531.
Figure 7 shows a further embodiment of the cooling system 1
according to the invention in a schematic cross-sectional
view from above (Figure 7A) and in a schematic cross-
sectional view from the side (Figure 7B). Furthermore, Figure
7 shows a variant of the removal of samples from a shelf
provided for in the cooling system 1 according to the
invention (Figure 7C). For the cooling system 1 according to
Figure 7, the cooling chamber 100 is segmented by means of
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partition walls 160 into a plurality of cooling chambers 105,
106, 107. The arrangement of the cooling chambers 105, 106
and 107 is bounded outwardly by a floor area 110, side walls
120 and a ceiling area 130, as is described above with
reference to the exemplary embodiment e.g. according to
Figure 1. The cooling chamber 100 can exclusively be accessed
from above through the ceiling area 130. The cooling chamber
100 is free of openings, which lead in the horizontal
direction through one of the side walls 120. Thus, any
disturbances of a horizontal stratification of the gases in
the cooling chamber 100 are avoided.
Furthermore, the cooling system 1 is completely adapted for
automated operation. During normal operation, there is no
inspection of the cooling chamber 100. Instead, the supply or
removal of samples is performed via automated systems
exclusively through the ceiling area 130 (see e.g. Figure
7C).
The partition walls 160 contain door openings 161, which are
arranged with a distance above the floor area 110 (see also
Figure 4). An operator 3 can access, via stairs 162, each of
the cooling chambers 105, 106 and 107 through the door
openings 161. The door leaves of the door openings 161 can be
drawn through chutes 415 into the operation room 400 via the
ceiling area 130. The door openings 161 are arranged in such
a way that they have a greatest possible mutual distance. As
can be seen in Figure 7A, the door opening 161 is arranged on
a side of the inner cooling chamber 105, which is positioned
opposite the side of the central cooling chamber 106 in which
the second door opening 161 is arranged. The arrangement of
the door openings 161 advantageously allows that there is no
direct gas flow from the outermost cooling chamber to the
innermost cooling chamber when both door openings are
simultaneously opened.
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Alternatively, it can be provided for that all cooling
chambers 105, 106 and 107 are accessed to exclusively from
above and the door openings 161 are kept merely for access in
the case of an incident. In this case, the door openings 161
can be arranged in height of the floor area, wherein the
stairs 162 are then not necessary.
Windows (not represented) can be provided in the partition
walls 160. They advantageously facilitate the observation and
lighting of the interior of the cooling chambers. The windows
preferably have a reduced thermal conductivity, and vacuum
composite windows are preferably used.
Figure 7B illustrates how the cooling chamber 100 can be
accessed to via a person lock device 450. An operator 3
accesses the person lock device 450 via stairs. The operator
3 wearing the protective suit can climb from the person lock
device 450 via the ceiling opening 131 into the outermost
cooling chamber 107. From there, the operator 3 can walk
through the door openings 161 into the inner cooling chambers
106, 105.
The cooling system 1 according to Figure 7 has the advantage
that different temperatures can be adjusted in the cooling
chambers 105, 106 and 107. Due to its included position, the
innermost cooling chamber 105 is the safest room of the
cooling system 1. The cooling chamber 105 will warm up the
slowest in the case of an accident on the, since it is
protected against heat penetration by the outer cooling
chambers 106, 107. Accordingly, the cooling system 1
according to Figure 7 is preferably used as follows.
The most valuable samples, such as living material, e.g.
individual cells, cell suspensions, blood or tissue parts are
deposited in the innermost cooling chamber 105. Typically,
these comprise rarely moving stocks that require only a few
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sample accesses. In particular reserve or backup stocks are
accommodated in the innermost cooling chamber 105. The middle
cooling chamber 106 contains samples, which require frequent
access. This area can be used as a workspace of the cryobank.
Finally, samples, which tolerate an increased storage
temperature of up to -50 C, if required even up to -20 C,
are stored in the outermost cooling chamber 107. The samples
comprise dead material, serines, plasma, genetic material or
the like.
Figure 7C illustrates how shelves 141 of the sample receiving
device can be drawn from the cooling chamber 100 through an
opening in the ceiling area 130 into the upper operations
room 400 in order to take individual samples from the shelves
141. In the operation room 400 is arranged a movable
isolation tower 480, which consists at least on its inner
side of a porous material 481, e.g. silicate-based aerogel.
The shelves 141 are drawn up along vertical rails 143 out of
the low temperature area into the isolation tower 480. The
lifting is performed up to a height, which allows removal of
the desired sample from the shelf 141 through a slit 482 in
the isolation tower 480. The isolation tower 480 is connected
with a reservoir of liquid nitrogen (not shown). The porous
material is loaded with liquid nitrogen, so that a
temperature of e.g. -160 C is given within isolation tower
480 and only the removed sample is exposed for a short time
to an ambient temperature of e.g. -20 C, while all other
samples of the shelf 141 remain in a mobile extension of the
low temperature range formed by the isolation tower 480 in
the cooling chamber 100.
The use of porous material, e.g. silicate-based aerogel, for
storage of coolant, in particular liquid nitrogen, is not
mandatory for active cooling of the isolation tower 480. The
isolation tower 480 can also be formed from a thermally
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insulating material. Furthermore, according to the invention,
the use of porous material, e.g. silicate-based aerogel, can
in general be provided for also on other parts of the cooling
chamber 100, in particular of the floor area 110, the side
walls 120 or of the ceiling area 130.
Figure 8 illustrates a further embodiment of the cooling
system 1 according to the invention with additional details.
During normal operation, this cooling system 1 also works
automatically, so that operators do not enter the cooling
chamber. An inspection of the cooling chamber 100 is done
only in special situations, such as in the case of an
accident, for maintenance work, installation works or checks.
Although the normal operation is intended without any
inspection of the cooling chamber 100, the special case of
inspection of the cooling chamber 100 is represented here.
The cooling system 1 is, as described above, constructed with
a cooling chamber 100 and an operation room 400 located above
it. The cooling chamber 100 is delimited by the floor area
110, side walls 120 and the ceiling area 130. The first
cooling device 200 is located under the floor area 110. The
second cooling device 300 is connected with the side wall
120. In the ceiling area 130, there is at least one ceiling
opening 131 through which the conveying device 150 with a
rope hoist 151 and a ladder 152 protrudes from the operation
room 400 into the cooling chamber 100.
For inspection of the cooling chamber 100, an operator 3
steps through the person lock device 450 into the operation
room 400. Between the person lock device 450 and the
operation room 400, there is a lock door through which the
operator 3 can access the operation room 400 via stairs 457.
From the operation room 400, the inspection of the cooling
chamber 100 is done through the ceiling opening 131. Above
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the operation room 400, there is the hood chamber 400.1
(accident tower) into which sample receiving devices 140, in
particular the tower-like shelves 141, can be transferred in
the case of an accident.
Figure 8 shows as a further advantageous feature of the
cooling system 1 according to the invention a nitrogen
sprinkler system 108, which is arranged in the cooling
chamber 100. The nitrogen sprinkler system 108 is preferably
located on the underside of the ceiling area 130.
Advantageously, rapid cooling can be achieved with the
nitrogen sprinkler system 108 at first use of the cooling
chamber or in case of an accident. The nitrogen sprinkler
system 108 is supplied out of the coolant supply apparatus
500 (see Figures 1, 6) via coolant lines.
Furthermore, condensate collection elements 109 are
illustrated in the cooling chamber 100. The condensate
collection elements 109 comprise e.g. sheet metals, which are
in communication with the first cooling device 200, in
particular the liquid nitrogen 220. The condensate collection
elements 109 form an ice trap. Any ice coating can be removed
by replacing the condensate collection elements 109 by means
of mechanical scraping, sucking or by means of sublimation
using locally inflated dry warm gas. Thus, in contrast to
conventional cryopreservation techniques, ice formation can
be suppressed in the remaining cooling chamber.
Ventilation of the cooling chamber 100 and of the operation
room 400 is performed via a tube connection with a siphon. In
the case of an accident, an external ventilation equipment
can supply dry, tempered air to the operation room 400. A
flexible tubular element 128 is provided for this purpose.
Advantageously, a breathable atmosphere with a temperature in
the range of -5 C to -50 C can be supplied so quickly in the
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operating state of the cooling system 1 that the operation
room 400 can be accessed to within less than one minute, in
particular within 20 s. If this is also required for the
cooling chamber 100, a rolled-up pipe can be led through the
ceiling opening 131 along the ladder 152 into the cooling
chamber 100. In the case of active ventilation of the cooling
chamber 100, the latter can likewise be accessed to within 10
to 20 s without a breathing apparatus and a protective suit.
For the case that immediate removal of the samples is
required (evacuation), a wall element 123 is arranged in a
lateral wall region. The wall element 123 is connected via an
opening joint 124 with the side wall 120 and can be removed
from it or knocked out of it. On the external side of the
side wall 120 can be arranged a schematically illustrated
docking device 700 for a mobile evacuation container.
The automatic sample deposition or sample removal is
performed with a sample access automatic machine 470, which
is located in the operation room 400 and contains a drive
device 410 for the mechanical control elements 411. An
horizontal movement of the control elements 411 is performed
in the operations room 400 above a temperature of -80 C. A
vertical arm 416 of the control elements 411 engages through
a slit that opens in the ceiling opening 131 during the
movement into the cooling chamber 100, so that all trays of
the shelves 141 are accessible. A sample is taken out,
transported upwards, arrives in the sample access automatic
machine 470 and is transferred to a tempered lock (-60 to
-80 C) where the sample is conveyed to a place of removal
458, which can be accessed to without any thermal protective
clothing.
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Figure 9 illustrates that, in case the cooling system 1 is
designed with the size of an industrial hall, using variable
partition walls 160 is advantageous. Partition walls 160 can
be inserted in the cooling chamber 100 or removed therefrom
as required. The partition walls 160 run in a transverse
and/or longitudinal direction relative to a longitudinal
extension of the cooling chamber 100. Preferably, the
partition walls 160 can be moved in the vertical direction,
i.e. upwards, so that it is advantageously prevented that
undesirable gas flows or uncontrolled thermal gradients arise
in the cooling chamber 100. Furthermore, the partition walls
160 allow separate cooling in individual chambers of the
cooling chamber 100 wit variable temperatures. In this way,
cryobanks can be realized with a storage capacity of millions
of samples.
Alternative to the representation in Figure 9, according to
Figure 10, a modular structure of the cooling system 1 can be
provided for, wherein all chambers or sample receiving
devices form separate elements in the cooling chamber 100,
which, if necessary, can be supplied in a fully autarkic
manner. Such an approach has the advantage of free
extensibility.
The features of the invention which are disclosed in the
above description, the claims and the drawings may be
important both individually and in any combination for
implementing the invention in its various designs.
