EP2671034A2 - Installation frigorifique accessible à une personne debout et destinée notamment à la cryoconservation d'échantillons biologiques, et procédé pour faire fonctionner une telle installation - Google Patents

Installation frigorifique accessible à une personne debout et destinée notamment à la cryoconservation d'échantillons biologiques, et procédé pour faire fonctionner une telle installation

Info

Publication number
EP2671034A2
EP2671034A2 EP12702189.7A EP12702189A EP2671034A2 EP 2671034 A2 EP2671034 A2 EP 2671034A2 EP 12702189 A EP12702189 A EP 12702189A EP 2671034 A2 EP2671034 A2 EP 2671034A2
Authority
EP
European Patent Office
Prior art keywords
cooling
cooling system
space
operator
refrigerator
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12702189.7A
Other languages
German (de)
English (en)
Inventor
Günter R. FUHR
Heiko Zimmermann
Bernd KRANZ
Tomm Schmidt
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Helmholtz Zentrum Muenchen Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Helmholtz Zentrum Muenchen Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV, Helmholtz Zentrum Muenchen Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH filed Critical Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Publication of EP2671034A2 publication Critical patent/EP2671034A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02Preservation of living parts
    • A01N1/0236Mechanical aspects
    • A01N1/0242Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
    • A01N1/0252Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
    • A01N1/0257Stationary or portable vessels generating cryogenic temperatures
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25DREFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D3/00Devices using other cold materials; Devices using cold-storage bodies
    • F25D3/10Devices using other cold materials; Devices using cold-storage bodies using liquefied gases, e.g. liquid air
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25DREFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D13/00Stationary devices, e.g. cold-rooms
    • F25D13/02Stationary devices, e.g. cold-rooms with several cooling compartments, e.g. refrigerated locker systems
    • F25D13/04Stationary devices, e.g. cold-rooms with several cooling compartments, e.g. refrigerated locker systems the compartments being at different temperatures
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25DREFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D3/00Devices using other cold materials; Devices using cold-storage bodies
    • F25D3/10Devices using other cold materials; Devices using cold-storage bodies using liquefied gases, e.g. liquid air
    • F25D3/102Stationary cabinets
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25DREFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D25/00Charging, supporting, and discharging the articles to be cooled
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25DREFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D29/00Arrangement or mounting of control or safety devices
    • F25D29/001Arrangement or mounting of control or safety devices for cryogenic fluid systems

Definitions

  • Walk-in cooling system in particular for the cryopreservation of biological samples, and method for their operation
  • the invention relates to a cooling system, in particular for the cryopreservation of biological samples, which has a refrigerated space cooled with liquid nitrogen (LN 2 ).
  • the invention further relates to methods for operating the cooling plant.
  • Applications of the invention are in the long term storage of samples in the cooled state, especially in the cryopreservation of biological samples given.
  • 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 coolant reservoir with liquid nitrogen (temperature: about 195 ° C.) and a large number of individual tanks (so-called cryogenic tanks, mostly double wall steel Dewar vessels, see, for example, EP 1 223 393 A2, WO 2008 / 009840 AI, GB 812 210) from the size of a few liters up to approx. 2 or 3 cubic meters.
  • the cryotanks stand in rooms at normal temperature (room temperature) and are supplied from the coolant reservoir with the liquid nitrogen.
  • the cryotank boxes are arranged on shelves in which tubes, bags or other closed containers with the samples (eg., Liquids, cells, cell components, serums, blood, cell suspensions, pieces of tissue, etc.) are stored.
  • the samples can be arranged completely in liquid nitrogen.
  • the samples are usually in a cool gas phase in the vapor of the liquid Nitrogen stored at less than about -145 ° C. This gas ⁇ phase is formed above a nitrogen lake at the bottom of cryogenic tanks.
  • the cooling in the cryotanks it would be beneficial if they were kept permanently closed. In practical operation, however, they must, for. B. when accessing the samples to be opened repeatedly.
  • the object of the invention is to provide an improved cooling system, in particular for the cryopreservation of biological samples, with which the disadvantages and limitations of conventional cooling systems are overcome.
  • the cooling system should enable effective cooling operation even with high numbers of samples and / or improve automation of access to samples.
  • the object of the invention is also to provide an improved method for operating a refrigeration system, in particular for the cryopreservation of biological samples, with which the disadvantages and limitations of conventional methods are overcome.
  • a refrigeration system in particular for cryopreserving biological samples, having a cooling space and first cooling means arranged to cool the cooling space using liquid nitrogen.
  • the refrigerated space is generally a space enclosed by a floor area, sidewalls, and a ceiling area, which is cooled in its entirety with the first cooling device and is arranged to receive the samples to be preserved.
  • the cooling of the entire refrigerator is provided in a directional manner at least from the bottom thereof.
  • the bottom portion of the refrigerator is set up for direct cooling with the liquid nitrogen.
  • a uniform cooling of the cooling space is thus supported.
  • the cooling space is dimensioned so that at least one operator can stay and move in the cooling space.
  • the interior volume of the cold room is chosen so that the at least one operator completely fits into the cold room and can stand and / or walk in the cold room.
  • the internal volume is at least 10 m 3, in particular at least 100 m 3 , such as. At least 500 m 3 , or even 1000 m 3 or more.
  • the refrigerator is a small cryochamber, withdrawn with z. B. 100 m 3 a cryogenic space, with z. B. 500 m 3 a Kryoraum- Ensemble, and with more than z. B. 1000 m 3 a cryogenic hall, possibly with multiple rooms, is given.
  • the cooling space of the cooling system is set up for receiving a sample receiving device.
  • samples ⁇ receiving means each holding structure is used which is suitable for receiving samples, in particular sample vessels with biological samples.
  • Sample containers include z.
  • the sample receiving device can be permanently arranged in the cold room (in particular fixed) or at least partially detachably arranged.
  • the cooling space is preferably dimensioned so that the operator be present within the equipped with the Pro ⁇ benfactafter worn refrigerator and can move.
  • the bottom area of the cooling space has a platform comprising, for example, at least one perforated plate, grate and / or grid. The platform has a multiple function.
  • the platform is formed so that vapor from the liquid nitrogen can rise through the platform into the cold room.
  • the platform is vapor permeable.
  • a cooling surface is created at the bottom of the refrigerator, with the direct steam, direct cooling of the interior of the refrigerator is made possible by exiting steam, which has an advantageous effect on the effective and uniform cooling of the refrigerator.
  • the platform provides a support area for the operator, and typically also for a sample receiving device in the cold room.
  • the platform is configured as a footprint and / or walkway for the operator. For this purpose, the platform with such a me- that it remains stable and in particular undeformed when loaded with the operator.
  • the mechanical capacity of the platform is at least 100 kg / m 2 (especially suitable for light shelves and an operator), in particular at least 500 kg / m 2 (especially suitable for multiple shelves and operators), such.
  • B. at least 1000 kg / m 2 (in particular ge ⁇ suitable for multiple shelves, machines and operators), or even 5000 kg / m 2 (especially suitable for safety shelves, machines and operators) or more.
  • the platform is preferably formed to extend over at least half of the area of the bottom of the cold room. Particularly preferably, the extends
  • a method for operating the cooling system according to the above first aspect of the invention, in which cooling of the cooling space with the first cooling device and positioning of samples, in particular biological samples, are provided in the cooling space.
  • the first cooling device for filling with liquid nitrogen can be adapted such that a free surface of the liquid nitrogen is formed below the bottom region.
  • the first cooling device has, for example, an upwardly open to the bottom portion and the refrigerator compartment open vessel, for. B. a trough (bottom pan) for receiving ⁇ liquid nitrogen.
  • the floor area platform may include a grid extending over the vessel.
  • a tray with a shallow bowl shape can be used because no requirements are placed on the volume of liquid nitrogen disposed in the first cooler. So In particular, provision is made for the volume of liquid nitrogen arranged in the first cooling device to be smaller than the volume of the vaporous nitrogen present in the interior of the cooling space.
  • the bottom area and the first cooling device are laterally and downwardly equipped with a thermal insulation.
  • a new refrigeration system is created which overcomes the disadvantages and limitations of conventional techniques.
  • the invention overcomes the conventional individual tank principle for cryobanks.
  • the cooling system represents a freely scalable cryobank architecture. Compared with conventional cryotanks, there is the advantage that permanently constant storage conditions are provided for an increased number of samples.
  • the samples can be stored in the refrigerator in sample vessels without requiring tanks, thermal insulation or the like inside the refrigerator. Access to individual samples is possible without affecting the cooling of the remaining samples.
  • the internal volume of conventional cryogenic tanks is far exceeded.
  • the dimensioning not only provides sufficient space for automation technology and / or one or more operators, but also a high heat capacity of the cooled system.
  • the supply of a sample or the introduction of a tool represents only a negligible heat input, so that the totality of the samples is hardly disturbed.
  • the refrigerator compartment can be filled with liquid nitrogen.
  • Material is cooled to temperatures that is sufficiently low for a cryopreservation of biological samples.
  • Liquid nitrogen has advantages as a coolant because it is cheap, easy to handle and in its liquid form with a boiling point at normal pressure of about -195.8 ° C corresponds to all requirements for the cryopreservation of biological samples .
  • the provision of the platform makes it possible for the refrigerator, regardless of its size, to be entered by the operator in order to remedy any failures or malfunctions.
  • the cooling system according to the invention is further characterized by the following advantages.
  • the cryobank architecture can be formed with large, automatable spaces provided with sample receiving devices.
  • the cooling system is scalable from small banks (a few hundred samples) to industrial hall systems (millions of samples). It is a temperature in the refrigerator below -130 ° C targeted adjustable.
  • the cooling system enables partially or fully automated sample storage and withdrawal. Another advantage is the long-term operability and maintenance without a change in the temperature in the refrigerator.
  • the cooling system is equipped with at least one further cooling device (hereinafter: second cooling device) which is operable independently of the first cooling device.
  • the second cooling device is also provided for cooling the cooling space.
  • the second cooling device is arranged for cooling at least one of the side walls of the cooling space. Cooling elements of the second cooling device are z. B. embedded as a hollow wall structure in at least one of the side walls or positioned on the inside of the refrigerator compartment facing side.
  • the second cooling device is alternatively or additionally configured for an electric cooling operation and / or a cooling using liquid helium (LHe).
  • the second cooling device enables a hybrid operation of the cooling system.
  • at least two different cooling principles can be switched serially in time (eg 8 h electrical cooling, 10 h cooling with LN 2 ) or in parallel and / or with different cooling capacities.
  • a full hybrid system or a partial hybrid system can be realized.
  • each of the cooling devices allows a permanent cooling of the cooling chamber to temperatures ⁇ -130 ° C.
  • one of the cooling devices main cooling system, eg LN 2
  • the other of the cooling devices auxiliary system
  • the second cooling device can, in particular, form an emergency cooling system which, if all the other cooling devices, in particular the first cooling device fail, ensures that the temperature does not rise above -138 ° C. in the entire cooling chamber where samples are located.
  • the ceiling region of the cooling space has at least one ceiling opening.
  • the ceiling opening is particularly preferably a permanently free passage opening, through which cool gas exits from the refrigerator compartment always upwards through the ceiling.
  • the ceiling opening constitutes an access opening for samples and / or an input and output opening for the operator.
  • the cooling space does not have any further openings, for example an opening. B. on the side walls or in the floor area, so that the at least one ceiling opening is the only suitable for a passage of the samples, the operator or other mechanical components connection of the interior of the refrigerator with an environment.
  • particularly preferred entry and exit of the operator is provided only above the refrigerator through the ceiling area.
  • the at least one ceiling opening advantageously offers the possibility réelleset ⁇ on the refrigerator a hood chamber zen, in the z.
  • the sample receiving device or at least the cryopreserved samples can be taken up.
  • At least one operating room is provided above the ceiling opening.
  • the tempera ⁇ ture of the operating room can be increased relative to the temperature of the refrigerator compartment.
  • the operating space is preferably thermally isolated from the outer in order ⁇ nosti the cooling system.
  • the operating room contains technical equipment that interact with the refrigerator.
  • a drive device with mechanical adjusting elements, such as robot arms for access to samples, and / or a conveyor for installing or executing the operator in or out of the cold room are provided in the operating room.
  • the operating room can be connected to at least one lock device (person lock device and / or sample lock device).
  • the mechanical adjusting elements such as. As gripping arms, levers or Be ⁇ herungsiana, inserted into the refrigerator. If at least parts of the adjusting elements, in particular connecting regions between relatively movable parts of the actuating elements are heatable, the operability of the drive device in the cooling chamber is improved.
  • the connection areas can be equipped with locally acting heaters.
  • the conveying device in the operating room comprises a cable pull and / or a stepping device. The cable is set up for transporting the operator into and / or out of the cold room. The operator is transported in this variant hanging on a rope or a chain.
  • the tapping device comprises, for example, a ladder or staircase which extends between the interior of the cold room, in particular its floor area, and the operating room above the ceiling area.
  • Supply connections include media lines, in particular coolant or breathing air lines, electrical lines, in particular for power supply or for signal transmission, and / or optical cables, in particular for signal transmission.
  • At least one of the side walls can be constructed in multiple layers with at least two wall layers.
  • the inventors have found that the structure with the at least two thermally insulating wall layers an effective insulation of the cooling space in relation to an environment at room temperature with moderate coolant consumption is possible. Furthermore, the functionality of the cooling system, in particular in case of failure of the cooling, at least over several days can be achieved.
  • the use of several wall layers has the particular advantage that they can be optimally designed in terms of space utilization and the dense filling of the side wall. NEN.
  • Each wall layer is a wall layer extending along the extent of the side wall.
  • Each of the wall layers has a thermally insulating effect, ie a thermal conductivity which is less than 0.05 W / m 2 (simple insulating foams), in particular less than 0.004 W / m 2 (vacuum pads), in particular less than 0.001 W / m 2 (vacuum insulation), and / or a moisture-repellent effect.
  • Several wall layers are arranged stacked perpendicular 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 barrier layer.
  • the plastic layer comprises z.
  • the plastic layer can advantageously be used to optimize the cubature with respect to a further wall layer.
  • the vacuum component layer comprises z. B. vacuum insulation panels, which are advantageous because of their low thermal conductivity.
  • the vapor barrier layer includes, for example, a water vapor impermeable film. In particular, there may be multiple vapor barriers within the sidewall to prevent moisture loss.
  • At least one of the wall layers may in particular be formed of a material (composite material, eg foam, liquid, inflatable bodies, eg with suitable sealing material) which is suitable for automatically interrupting any interruptions, such as, for example, As cracks or holes to close.
  • a material composite material, eg foam, liquid, inflatable bodies, eg with suitable sealing material
  • At least one of the side walls can thus be a self-healing wall.
  • At least one of the wall layers may also have a switchable thermal conductivity.
  • the thermal conductivity can be switched, for example, by evacuating one or a supply of a gas or a liquid into a vacuum component layer.
  • At least one of the side walls may, according to the invention, be covered with a metallic material on the inner side facing the refrigerator compartment, for example to form a cooling layer and / or to receive cooling elements of the second (electric) cooling device.
  • At least one of the side walls can be modularly constructed with at least one wall element which can be detached from its composite by a movement perpendicular to the respective side wall.
  • the at least one wall element is displaceable and separable from the side wall.
  • the at least one wall element advantageously allows a structure of the side wall with individually exchangeable isolation media without endangering the samples.
  • the at least one wall element allows an emergency opening of the cold room for a rapid removal of samples from the cold room in the event of an accident (evacuation).
  • the wall element may be instantaneously displaceable from the side wall, for example by a blast.
  • a docking device for a mobile evacuation container for a disaster event can be provided on an outer side of the side wall to match the position of the at least one displaceable wall element.
  • At least one of the side walls may have a door opening which is closed by a movable door leaf.
  • the door leaf is constructed as the surrounding side wall thermally insulating.
  • the side door opening may have advantages for lateral access for the operator to the refrigerator.
  • the door opening is arranged at a predetermined distance above the floor area. The distance is preferably at least 10 cm, in particular at least 50 cm, up to several meters.
  • the door opening is connected to the floor area via a staircase. In this case, down to a level below the door opening is formed a downwardly closed space for receiving the vaporous nitrogen above the floor area. At least some of the vaporous nitrogen can not escape from the cold room even with the door open.
  • the door leaf is arranged to be displaceable parallel to the respective side wall.
  • a docking device for an evacuation container or a lock device can advantageously be provided.
  • a sample receiving device in the refrigerator space racks include, which form the support structure for the biological samples.
  • Shelves comprise support plates (shelves) on which the containers with the biological samples are exposed.
  • the shelves are made of a material with increased thermal conductivity, z. As metal formed.
  • this allows a homogeneous temperature distribution in the sample receiving device.
  • the sample receiving device may be designed for electrical and / or optical connection to a control device (loading control). This advantageously allows an electronic responsiveness of the shelves and possibly the samples in the shelves.
  • the sample receiving device may be equipped with thermal bridges which protrude into the bottom region.
  • the thermal bridges are made of materials with increased thermal conductivity, eg. B. of metal. Pre geous enough, so that a good thermal conductivity Ver ⁇ connection to LN created 2 -See the first cooling device.
  • the sample receiving device may alternatively or additionally form a rigid component.
  • the shelves are connected to a rigid structure. In this case, there are advantages for the position accuracy and the reproducibility of the weight load of the platform.
  • the cooling space can be subdivided by partition walls into subspaces.
  • the intermediate walls can extend in the cooling space in the vertical and / or horizontal direction.
  • a segmentation in pre-and main refrigerators, and possibly auxiliary cooling chambers is achieved.
  • samples may be cooled selectively according to the used storage capacity and access frequency and / or storage temperature requirement. It can, for.
  • the temperature in certain parts of the cold room may be deliberately lowered or increased, e.g. in a front, middle, upper, back and / or lower part.
  • heat corridors can be formed which, in the event of an accident, provide an elevated temperature for rapid evacuation of the samples.
  • a structure can be created, which is characterized by mutually surrounding subspaces with different temperatures.
  • a compartment in the middle of the cold room can have the lowest temperature and provide the highest security for maintaining the cryopreservation temperature. This allows a strategy in which the most valuable frozen live samples in the subspace in the middle of the cold room, frozen dead material in the surrounding subspaces, and liquids, genetic material, sera, etc. are stored in an outer subspace.
  • the cooling system may be equipped with at least one of the following components:
  • Temperature sensors in particular for a spatially resolved temperature measurement in the cold room,
  • LED light emitting diodes
  • glass fibers for light coupling in the ceiling area, in the floor or in at least one of the side walls (glass fibers can in the refrigerator in particular via a heat insulation, for example by coupling via an evacuated Vacuum component to be supplied),
  • Monitoring equipment eg. B. a camera surveillance, a motion detector and / or a heat detector
  • a coolant container which is provided for receiving a Reservevolu mens liquid nitrogen, and / or
  • Figures 1 and 2 are schematic cross-sectional views Favor ter embodiments of the cooling system according to the invention.
  • Embodiments of the cooling system according to the invention are Embodiments of the cooling system according to the invention.
  • FIG. 5 schematic cross-sectional views of a
  • FIG. 6 shows a schematic overview of the cooling system according to the invention with additional operating devices
  • Figure 7 is a schematic plan and cross-section views of another embodiment of the cooling system according to the invention with a segmented cooling chamber and an illustration of a sampling from a shelf;
  • FIG. 8 is a schematic cross-sectional view of another embodiment of the inventive Shen cooling system
  • FIG. 9 shows a schematic illustration of the adaptation of a cooling space of the cooling system according to the invention as a function of the conditions of use
  • FIG. 10 a schematic illustration of a further embodiment
  • cooling system according to the invention Preferred embodiments of the cooling system according to the invention and the method for their operation are described below with reference to an exemplary cooling system with a cooling space, which is dimensioned so that an operator in the cold room can run several steps.
  • the realization of the invention is not limited to the refrigerator size shown as an example, but also possible with considerably larger cold rooms (halls) or with smaller cold rooms.
  • Embodiments will be described below with particular reference to the structure of the cooling system and the new modes of operation, which are made possible 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 protocols or the storage of 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.
  • the cooling space 100 is bounded below by a floor area 110, laterally by side walls 120 and upwards by a ceiling area 130.
  • the internal volume of the cooling space 100 is for example 10 m ⁇ 5 m 3 m.
  • a sample receiving device 140 is arranged on the floor area 110 and adjoins the side walls 120.
  • the inner ⁇ re surface of the cooling chamber 100 is equipped with a cooling layer 101, which is formed of a material with high thermal conductivity, eg metal.
  • the cooling layer 101 has the advantageous effect that a temperature compensation takes place in the cooling space 100 in the vertical direction. It may in particular ⁇ sondere the tempera ture ⁇ be set below -130 ° C in the upper region of the cooling space 100, which living for long-term storage of biological samples is important.
  • temperature sensors 103 are arranged in the cooling chamber 100 and in the operating room 400. Several temperature sensors 103 are provided at different distances from the bottom area 110. If necessary, compensation of the temperature, in particular a lowering of the temperature in the upper regions of the cooling space, can be achieved by additional cooling with the second cooling device 300 and / or a ventilation device (not shown) in the cooling space 100 100 can be achieved.
  • the floor area 110 comprises a platform 111, which extends above the first cooling device 200 with a trough 210.
  • the tub 210 has a double-walled tub body with an evacuated interior and on its outer side a thermal insulation. The thermal insulation is constructed like the side walls 120. Alternatively or additionally, the trough is insulated with an infrared-mirrored vacuum region. profiled.
  • liquid nitrogen 220 In operation of the refrigerator 1 is located in the well 210, liquid nitrogen 220.
  • the liquid nitrogen 220 preferably has a bottom portion 110 toward the free Oberflä ⁇ surface. A nitrogen lake is formed.
  • the filling of the tub 210 and the maintenance of the reservoir of liquid nitrogen 220 during operation of the cooling system 1 is carried out using the refrigerant supply 500th
  • the platform 111 comprises a grid, eg of steel, which extends over the trough 210 and is equipped with treads 112.
  • the foot platforms 112 reduce a ⁇ even tual mechanical contact between an operator 3, and the platform 111 so that a heat flow is minimized by the operator 3 to the platform 111th 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 tub 210 by additional components (not shown).
  • the side walls 120 comprise a plurality of layered 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 of a polymer foam, for example a polyurethane foam.
  • the thickness of the plastic layer 121 may be selected, for example, in the range of 10 cm to 1 m or even above 1 m.
  • the vacuum component layers initially comprise an inner layer 122.1 of evacuated components (so-called “vacuum components”) and an outer evacuated hollow wall 122.2.
  • the evacuated components of the inner vacuum component layer 122.1 are parallelepiped-shaped, in particular like conventional building blocks or bricks for building purposes, and made of plastic with an evacuated or evacuated interior.
  • the cavity wall of the outer vacuum component layer 122.2 is evacuated during normal operation or optional filled with a cooling liquid.
  • the cavity wall in particular has an advantageous function in case of failure of a cooling device.
  • the hollow wall of the outer vacuum component capable 122.2 may be made of a switchable external auxiliary tank 540 (see FIG ⁇ gur 6) with a coolant such as liquid nitrogen, to be filled in order to avoid undesirable heating of the cooling space 100, since the heat input from the outside, although coolant-consuming but still prevented. In this case, this cavity wall should not form the outermost layer.
  • the ceiling area 130 comprises a plastic layer 132, formed, for example, from polymer foam, in which a ceiling opening 131 is formed.
  • the operating room 400 is provided with a drive device 410 and mechanical adjusting elements 411, which project into the interior of the cooling space 100.
  • FIG. 1 shows by way of example a linkage with a vertical (412) and a horizontal (413) displacement unit, which can be actuated by the drive device 410.
  • samples 2 can be introduced into or removed from the sample receiving device 140.
  • the mechanical adjusting elements 411 are driven from above, ie from the operating room 400, for example by using cables, chains, toothed belts and the like, whose drive device 410 is arranged in the operating room 400. If required, motors, pulleys or other mechanical connection areas thermally insulating encapsulated or locally heated. To avoid thermal bridges 411 thermally insulating elements (not shown) are included in the mechanical control elements.
  • the sample receiving device 140 comprises shelves 141 (so-called "cryo racks") in which biological samples 2 are located in sample containers
  • the shelves 141 have frames of thermally highly conductive material, for example of metal, the thermal contact to the platform 111 and thermal bridges 142 directly to the liquid nitrogen 220 in the first cooling device 200. This advantageously ensures effective cooling down to the upper compartments of the shelves 141.
  • the second cooling device 300 is provided on the side walls 120, in particular arranged on the inwardly facing surface or embedded in this.
  • the second cooling device 300 is configured for electrical cooling. It includes cooling elements 310, which are connected to cooling units 320.
  • the cooling units 320 are located outside of the cooling space 100, preferably above it.
  • an electric cooling to a temperature of -150 ° C be provided.
  • the second cooling device 300 e.g. an electric cooling to a temperature of -150 ° C be provided.
  • the second cooling device 300 e.g. an electric cooling to a temperature of -150 ° C be provided.
  • the second cooling device 300 e.g. an electric cooling to a temperature of -150 ° C be provided.
  • the second cooling device 300 e.g. an electric cooling to a temperature of -150 ° C be provided.
  • Cooling device 300 may alternatively be formed by a nitrogen cooling or cooling with liquid helium.
  • the operating room 400 contains the drive device 410 for the mechanical adjusting elements 411.
  • the operating room 400 can contain further operating devices (see eg FIG. 2) and / or be connected to a passenger and / or sample lock device 450, 460 (see eg FIGS , 6).
  • the coolant supply 500 comprises a coolant reservoir 510 and a coolant line 520.
  • the coolant line 520 leading from the coolant storage tank 510 through the ceiling portion 130 and through the cooling chamber 100 into the first cooling device 200.
  • the coolant line 520 is au ⁇ ßerraum the cooling chamber 100 thermally insulated, for example, formed by a vacuum line.
  • a thermal insulation of the coolant line 520 is not provided.
  • the cooling of the interior of the refrigerator 100 is improved.
  • the coolant ⁇ line 520 in the cooling chamber 100 is a condensate collecting element (moisture trap). Any residual moisture in the refrigerator 100 is reflected in the coldest place, ie down on the surface of the coolant line 520, down to the entire refrigerator
  • the function of the coolant line 520 as condensate collecting element is particularly advantageous in the first cooling of the cooling space. Moisture is bound with the condensate collecting element, so that a dry storage is ensured during operation of the cooling system 1. Dry storage (storage avoiding ice precipitation) is beneficial not only for the shelf life of samples, but also for the automation of sample handling. Moving parts of the mecha ⁇ African actuators 411 can be more easily adjusted.
  • Figure 1 illustrates an important design principle of the cooling system according to the invention. All supply connections, in particular feeders and openings, into the interior of the cooling space 100 take place exclusively through the ceiling area 130, ie from above. This will minimize the Heat supply reached.
  • cooler attachments for devices are arranged, which can not ar ⁇ BEITEN at low temperatures in the operating room 400 or about this (see Figure 2).
  • chambers with a higher temperature or even with an internal heating for operating be ⁇ movable parts, such as motors, are placed.
  • Several such chambers can be built tower-like on top of each other (see Figure 2). Since gas is continuously formed from the first cooling device 200 under a significant volume increase and the cooling system 1 is pressure-free, ie not gas-tight, constructed, the cooling space 100 is continuously flowed through by nitrogen from below. To drain the nitrogen, an outlet 102, eg in the form of a siphon, is arranged in the uppermost part of the cooling system.
  • the cooling space 100 with the first cooling device 200 is cooled down to the desired cryoconservation temperature.
  • the biological samples 2 are arranged in the sample receiving device 140 in the cooling chamber 100.
  • the operator 3 can enter the cooling space 100 through the ceiling opening 131 or through a side door (see FIG. 4).
  • the operator 3 carries one
  • FIG. 2 illustrates, in a schematic cross-sectional view, a modified embodiment of the refrigeration system 1 according to the invention, which is constructed with respect to the cooling space 100, the first cooling device 200, the second cooling device 300 and the coolant supply 500, as described above with reference to FIG.
  • the operating room 400 comprises a first chamber 420, which is essentially constructed like the operating room 400 according to FIG. 1, a second chamber 430 and a third chamber 440.
  • the second and third chambers 430, 440 are further operating devices 431 , 441, such as measuring and / or control devices or other drives arranged.
  • the chambers of the operating room 400 are each arranged thermally insulated. In each of the chambers, a specific temperature can be set. Typically, the temperature increases from the first (420) to the third (440) chamber. For passing the gas atmosphere formed in the cooling chamber 100, the chambers of the operating room 400 are connected via pipe connections 401 (or other passage openings). At the top of the third chamber 440, an outlet 102 with a siphon is provided.
  • partition walls are each provided with at least one chamber door 402. This facilitates the setting of various temperatures in the chambers 420, 430 and 440. If, for example, a temperature in the range from -196 ° C. to -140 ° C. is set in the cooling chamber 100, a temperature in the second chamber 430 of around -80 ° C. and in the third chamber 440 could be in the range be set from -40 ° C to -20 ° C. Accordingly, in the chambers 420, 430 and 440 different operating devices can be accommodated, which have different operating temperatures. For monitoring the temperature In each of the chambers 420, 430 and 440, a temperature sensor 403 is arranged.
  • the chambers 420, 430 and 440 could be open relative to each other. In this case too, an undisturbed cooling would result in a sequence of horizontally stored gas layers with an upward temperature. Furthermore, in at least one of the chambers 420, 430 and 440, a local heating, in particular with a Wi derstandsproofung or be disposed an infrared radiator to ⁇ least to heat temperature-sensitive components to operate in certain operating phases. Advantageously, this is possible without any influence on the temperature in the cooling chamber 100 having to be accepted.
  • FIG. 3 illustrates features of the access of the operator 3 to the cooling chamber 100 on a further exemplary 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 in a schematic perspective view is shown in simplified form.
  • the cooling system 1 can be constructed with respect to these components, as described above with reference to FIGS. 1 and 2.
  • a ceiling opening 131 is provided, which is closable with a lid 132.
  • the opening for the access of the operator 3 at the top of the refrigerator 100 the
  • the opening for the access of the operator 3 may be provided in one of the side walls (see figure). Above the ceiling opening 131 of the operating room 400 is arranged.
  • a conveyor 150 is arranged, which is configured to introduce the operator 3 into the refrigerator compartment 100 and / or for the removal of the operator 3 from the refrigerator compartment 100.
  • the 150 is exemplified with a winch 151 with winch and with a kicker 152 (ladder).
  • the components 151, 152 may be provided individually. However, for safety reasons, it is preferred to provide both components in order to be able to quickly and safely remove the operator 3 from the cooling space 100 if necessary.
  • 151 may also be used to transport samples 2 and / or shelves 141.
  • the operating room 400 is connected to a personal lock device 450, which can be entered from outside through a thermally insulating, outer lock door 451.
  • the personal lock device 450 is separated from the service room 400 by a thermally insulating, internal lock door 453.
  • a pipe connection 452 is provided for pressure equalization, so that no pressure difference can arise between the two spaces and nitrogen gas from the cooling chamber 100 via the operating room 400 into the passenger lock device 450 and from there via an outlet 102 to can escape outside.
  • Entering the cooling chamber 100 via the personal lock device 450 takes place in such a way that the operator 3 first applies a protective suit 4 with a breathing air supply 5 outside the personal lock device 450.
  • a pre-cooling to a medium temperature range for example -80 ° C.
  • the personal lock device 450 equipped with a cooling device (not shown).
  • the personal lock device 450 may be cooled with a portion of the steam exiting the cooling chamber 100.
  • With sufficient cooling of the operator 3, their transition into the operating room 400 takes place and from there using the cable 151 and / or the stepping device 152, the transition into the refrigerator 100.
  • the operator 3 can move, for example, for maintenance at the sample receiving device 140.
  • the lock door 451 of the personal lock device 450, the inner lock door 453 and the lid 132 are provided with electrical contacts and a closing control arranged for at least one of the following procedures.
  • a visit of the cooling chamber 100 may be provided during normal operation of the cooling system 1.
  • the operator externally pulls the protective suit 4 with the breathing air supply 5.
  • the outer lock door 451 of the personal lock device 450 can be opened only when the inner lock door 453 and the lid 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 not be opened until a dry nitrogen atmosphere with a predetermined temperature has formed in the personal lock device 450. For this purpose, gaseous or liquid nitrogen can be injected from the outside. Once the predetermined temperature and the dryness of the atmosphere in the personal lock device 450 are reached, the inner lock door 453 is opened and the operator 3 can move into the service room 400.
  • the lid 132 is opened so that the operator 3 can enter the refrigerator compartment 100.
  • the operator 3 is under video surveillance and via a wireless audio connection in contact with assistants outside the cooling system 1.
  • the exit of the cooling system 1 is carried out in normal operation in reverse order.
  • the operator 3 can leave the cooling space 100 by means of the ceiling opening 131 and the person lock device 450 by his own efforts or be pulled out of it. At the same time it can be provided that warm dry air is blown from the outside via a fan 460 into the cooling room 100 and from there into the operating room 400 and the personal lock device 450. This allows the temperature to be raised above -50 ° C and oxygen supplied. This process can be over
  • FIG. 4 schematically illustrates characteristics of the inspection of the
  • the cooling system 1 in schematic simplified perspective view simplified with the bottom portion 110, the side walls 120 and the ceiling portion 130 illustrated.
  • the ceiling opening 131 is provided with a ⁇ is located on operating room 400 in the ceiling area 130th
  • the operating room 400 has a tower-shaped hood chamber 400.1 with a height such that a shelf 141 of the sample-receiving device 140 can be completely accommodated in the operating room 400.
  • a drive device 410 with a cable 414, with which the shelves 141 can be pulled into the operating room 400, in particular in the event of an accident.
  • a door opening 125 is arranged with a sliding door leaf 126 for access of the operator 3 in one of the side walls 120.
  • the door opening 125 has a predetermined height above the floor area 110. The elevated entrance is preferred so that the cold gas filling in the cooling chamber 100 does not flow outwardly upon opening the door opening 125.
  • a staircase 127 is provided, via which the operator 3 can enter the cooling room 100.
  • the door panel 126 is configured to translate parallel to the planar extent of the side wall 120. A vertical or horizontal door movement parallel to the side wall is preferred because otherwise the horizontal layering of the cold gas filling in the cooling chamber 100 would be disturbed when pivoting out of the side wall. Outside the cooling chamber 100 is on the side wall 120 a
  • Personal lock device 450 having at least two chambers 455, 456 and an outer (451), a middle (454) and an inner (126, 457) lock door arranged.
  • the inner lock door 457 is formed by the door panel 126. be- see the cooling chamber 100 and the cooling chambers 455, 456 pipe connections 452 are provided, through which cold gas can flow from the cooling chamber 100 to the outside. From the outer chamber 455, the gas flows through the outlet 102 into the environment.
  • a temperature of -20 ° C is provided, while in the inner chamber 456 a temperature of -80 ° C is provided.
  • the operator 3 To inspect the cooling space 100, the operator 3, outside the personal lock device 450, applies the protective suit 4 to the breathing air supply 5.
  • the operator 3 is gradually cooled in the personal lock device 450 until it can enter the refrigerator 100 through the door opening 125.
  • the doors 451, 454, 457 of the personal lock device 450 may be controllable for normal operation or emergency situation as described above with reference to FIG.
  • supply connections 104 shown schematically in the refrigerator compartment 100 are arranged.
  • the protective suit 4 and / or the breathing air supply 5 can be temporarily or permanently connected to the supply connections 104, e.g. to spare an energy source in the protective suit 4 or to supply oxygen.
  • FIGS. 5A to 5C show further details of a side wall 120 of the cooling space 100 of the cooling system according to the invention.
  • the features of the side wall 120 may accordingly also for the thermal insulation of the first cooling device 200
  • the cooling space 100 is arranged in each case to the right of the side wall 120, ie the outside of the side wall 120 is to the left of the side wall 120 in FIGS. 5A to 5C, respectively.
  • a cooling layer 101 which consists of metal, eg aluminum or steel, with a thickness in the range of a few mm to 1 cm, is initially arranged on the inside of the side wall 120.
  • the cooling layer 101 is in direct thermal contact with the first cooling device 200 (see FIG. 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 assisted with the cooling layer 101.
  • a first vacuum component capable 122.1 which an evacuated, along the side wall 120 includes réellere ⁇ ADORABLE hollow wall.
  • the outer surface of the evacuated hollow wall is designed for a reflection of infrared radiation (heat radiation) and for this purpose is provided with a reflective surface finish or a reflective foil 120.1.
  • this is reflected from the outside kom ⁇ ing thermal radiation.
  • vacuum component layer 122.2 which comprises a masonry of goose-shaped insulation components.
  • the insulation components are hollow plastic bodies with an evacuated, closed interior.
  • Each isolation device is a self-contained system.
  • the isolati ⁇ ons devices are arranged offset of ⁇ multilayered zueinan as in a masonry, so that there are advantages for the suppression of heat transfer through the side wall 120 ben erge-.
  • Outwardly 121 follows a plastic layer of a foamed plastic on ⁇ , for example of polyurethane.
  • the thickness of the plastic layer 121 is, for example, 10 cm to 1 m (made of insulating material). tion and stability reasons).
  • a protective layer 121.1 for the mechanical protection of the side wall 120, a further wall structure and / or a further vacuum component layer are arranged.
  • an advantage of the invention is that the thickness of the sidewall 120 can be increased as needed without significant practical limitations.
  • a total thickness in the range of 1 m to 6 m or 10 m or more is possible and depending on the dimension of the cooling system is recommended.
  • Conventional cryogenic tanks require as thin tank walls as possible to save storage space.
  • the thickness of the side wall 120 of the cooling system according to the invention does not play a critical role.
  • FIG. 5A may be modified such that a further hollow wall is inserted, which is part of a further, in particular electrical, cooling device.
  • a further hollow wall is inserted, which is part of a further, in particular electrical, cooling device.
  • the cooling of the cooling space can be completely taken over by the side wall 120, while at the same time the first cooling device is being repaired.
  • the cooling from the sidewall 120 may be e.g. be provided when the supply of liquid nitrogen 220 of the first cooling device 200 is running low and can not be filled quickly enough. This modification is shown in more detail in Figure 5B.
  • FIG. 5B shows the side wall 120, in which the vacuum component layer 122.1 is arranged with an increased thickness and, in addition, a cooling element 310 of the second cooling device 300 (see FIG. 1) is arranged on the inside of the side wall 120.
  • the cooling element 310 includes another layered, hollow-walled component, such as a variety of hollow pipes made of metal.
  • the hollow wires may be arranged 120 coverage or with mutual spacing on the In ⁇ inner side of the side wall.
  • the cooling element 310 is connected to a cooling unit 320 (see FIG. 1).
  • the cooling element 310 may be in communication with the liquid ⁇ stick material 220 of the first cooling device 200 (see Figure 1).
  • the cooling element 310 can be flowed through from the outside with an additional coolant.
  • the additional refrigerant may by an electrical cooling system or from a coolant tank connected or tankers, for example with liquid nitrogen, be ⁇ be made available.
  • FIG. 5C shows a further modified version of the pages ⁇ wall 120, in which the order of the vacuum component location 122.3 and the plastic sheet is exchanged 121st
  • the metallic cooling layer 101 is initially provided on the inside of the side wall 120, below which the first vacuum component layer 122.1 is arranged.
  • This can be equipped with a reflecting element 120.1 as in FIG. 5A.
  • the plastic layer 121 and the masonry of insulating components of the vacuum component layer 122.2 To the outside, another protective layer 122.3 follows, with which the vacuum component layer 122.2 is stabilized.
  • conventional wall structures may follow outwardly for protection or stabilization purposes.
  • the schematic block diagram in FIG. 6 illustrates the connection of the inventive refrigeration system 1 with the coolant supply 500 and an operating controller 600.
  • 1 is equipped with a cold room 100, which is configured for the long-term storage of biological samples at temperatures below -80 ° C, especially below -130 ° C.
  • the temperature in the cold room 100 is less than -140 ° C.
  • the first cooling device 200 (see FIG. 1) is supplied with liquid nitrogen as follows.
  • the coolant supply 500 comprises a first (510) and a second (511) coolant reservoir (tank).
  • the coolant reservoirs 510, 511 can be refilled as needed by external mobile reservoirs (tanker trucks).
  • the coolant supply 500 is equipped with its own liquefaction plant 530.
  • the liquefaction plant 530 continuously supplies liquid nitrogen into the coolant reservoirs 510, 511.
  • the liquefaction plant 530 has the advantage that complete, long-term cooling over long periods of time, months, years or decades, can be ensured.
  • an emergency power generator 531 is provided, which can also serve to supply the second cooling device in the event of a fault.
  • the first coolant reservoir 510 is connected to the first cooling device 200 via the coolant line 520 (see FIG. 1). Furthermore, the first coolant reservoir is connected to a coolable hood chamber 400.1 (see FIG. 4) of the operating room 400 in order to maintain a temperature of e.g. -80 ° C.
  • the second coolant reservoir 511 is connected to the personal lock device 450 for the operator (s) via an evaporator and a second coolant line 521 and a temperature controller 522.
  • the temperature- Controller 522 is actuated to set a temperature of -40 ° C in the personal lock device 450 in a first chamber and a temperature of -80 ° C in a second chamber.
  • the temperature control 522 is additionally used to additionally temper a sample lock device 460 for samples.
  • the subsequent delivery of liquid nitrogen into the first cooling device 200 is carried out using a control loop.
  • a level sensor With a level sensor, the level of the liquid nitrogen of the first cooling device 200 is detected.
  • liquid nitrogen is replenished in the firstdeeinrich ⁇ tung 200 via thedemit ⁇ teltechnisch.
  • the coolant supply 500 is additionally equipped with an external auxiliary reservoir 540 for supplying the cooling system 1 with liquid nitrogen in the event of a malfunction.
  • the auxiliary container 540 is preferably via a blocking element, such. As a valve, with the hollow wall 122.2 in the side wall 120 (see Figure 1).
  • the second cooling device is connected to the cooling system 1, which is an electric cooling unit 320 for setting a temperature of -80 ° C, preferably configured from -150 ° C in the cooling chamber 100.
  • the coolant of the second cooling device 300 is supplied to the cooling elements 310 in the side wall of the cooling space 100 (see, for example, FIGS.
  • FIG. 6 also illustrates the components of the operating controller 600 of the refrigeration system 1 according to the invention.
  • the operating controller 600 includes a first controller 601 for the sample storage and retrieval machine and a second controller Control 602 for system control.
  • the second controller 602 includes, in particular, a temperature control and / or a control of the sensors, the light and the monitoring technology, such as video cameras.
  • the operation control 600 comprises a first database 603, which is coupled to data memories of the samples stored in the cooling system 1. Data from the first database 603 controls electronic components of the sample containers and / or alarm systems to detect critical sample conditions.
  • the second database 604 is adapted for interfacing with the electronic components of the samples.
  • the data connection between the operation control 600 and the cooling system 1 is conducted or wireless.
  • the operation control 600 includes a vacuum system 605 which is arranged to evacuate components of the side walls 120 of the refrigerator compartment 100 and can be supplied with the generator 531 as needed.
  • FIG. 7 shows a further embodiment of the cooling system 1 according to the invention in a schematic cross-sectional view from above (FIG. 7A) and in a schematic cross-sectional view from the side (FIG. 7B). Furthermore, FIG. 7 shows a variant of the sampling provided in the refrigeration system 1 according to the invention from a shelf (FIG. 7C).
  • the cooling space 100 is segmented by intermediate walls 160 into a plurality of cooling chambers 105, 106, 107.
  • the arrangement of the cooling chambers 105, 106 and 107 is limited to the outside by a bottom portion 110, side walls 120 and a ceiling portion 130, as described above with reference to the Ausure tion example, for example according to Figure 1.
  • the cooling space 100 can only be entered from above through the ceiling area 130.
  • the cooling space 100 is free from openings that extend in the horizontal direction through one of the side walls. walls 120 lead. Thus, any disturbances of a horizontal stratification of the gas in the cooling chamber 100 are avoided.
  • cooling system 1 is completely set up for automated operation. In normal operation, no inspection of the cooling chamber 100. Rather, takes place takes place Zuept ⁇ tion or take samples from automated systems solely by the ceiling portion 130 (see, for. Example, Figure 7C).
  • the intermediate walls 160 contain doorways 161, which are arranged with egg ⁇ nem distance above the bottom portion 110 (see also Figure 4).
  • An operator 3 can enter each of the cooling chambers 105, 106 and 107 through the door openings 161 via stairs 162.
  • the door leaves of the door openings 161 can be pulled through shafts 415 into the operating room 400 above the ceiling area 130.
  • the door openings 161 are arranged so that they have the greatest possible mutual distance. As shown in Fig. 7A, the door opening 161 is disposed on a side of the inner cooling chamber 105, which is positioned opposite to the side of the middle cooling chamber 106 in which the second door opening 161 is disposed.
  • the arrangement of the door openings 161 advantageously makes it possible that with simultaneous opening of both door openings no direct gas flows from the outermost into the innermost cooling chamber occur.
  • the door openings 161 can be arranged at the level of the floor area, the stairs 162 are then not required.
  • viewing window (not shown) may be provided. With these advantageously the observation and illumination of the inner cooling chambers is facilitated.
  • the viewing windows preferably have a reduced heat conduction and preferably vacuum composite windows are used.
  • FIG. 7B illustrates how the cooling space 100 can be entered via a personal lock device 450.
  • An operator 3 enters the personal lock device 450 via a staircase. In the protective suit, the operator 3 can rise from the person lock device 450 via the ceiling opening 131 into the outermost cooling chamber 107. From this, the operator 3 can go over the door openings 161 into the inner cooling chambers 106, 105.
  • the cooling system 1 according to FIG. 7 has the advantage that different temperatures can be set in the cooling chambers 105, 106 and 107.
  • the innermost cooling chamber 105 is the safest space due to the enclosed position
  • Cooling System 1 The cooling chamber 105 will heat the slowest in the event of an accident, since it is protected by the outer cooling chambers 106, 107 from heat input. Accordingly, the cooling system 1 according to FIG. 7 is preferably used as follows.
  • the most valuable samples such as living material, eg single cells, cell suspensions, blood or tissue parts are stored. Typically, these are low moving inventories requiring only a few sample accesses.
  • the innermost cooling chamber 105 in particular reserve or backup stocks are housed.
  • the middle cooling chamber 106 are samples that require frequent access. This area can be used as Workspace of the cryobank can be used.
  • samples are stored in the outermost cooling chamber, which tolerate an elevated storage temperature of up to -50 ° C, possibly even down to -20 ° C. The samples include dead matter, sera, plasma, genetic material or the like.
  • FIG. 7C illustrates how shelves 141 of the sample receiving device may be drawn from the refrigerator compartment 100 through an opening in the ceiling section 130 into the upper service compartment 400 to remove individual samples from the shelves 141.
  • a movable isolation tower 480 is arranged, at least on its inside of a porous material 481, z. B. airgel based on silicate is formed.
  • the shelves 141 are pulled up into the isolation tower 480 along vertical rails 143 from the low temperature range. The lifting takes place to a height which allows removal of the desired sample from the shelf 141 through a slot 482 located at the isolation tower 480.
  • the isolation tower 480 is connected to a reservoir of liquid nitrogen (not shown).
  • the porous material is liquid
  • porous material eg. B. Silica based airgel
  • the isolation tower 480 may also be formed of a thermally insulating material.
  • po- red material eg. B. airgel on silicate, in general also on other parts of the refrigerator compartment 100, in particular the bottom portion 110, the side walls 120 or the ceiling portion 130 may be provided.
  • FIG. 8 illustrates a further embodiment of the cooling system 1 according to the invention with additional details.
  • this cooling system 1 works automatically so that operators do not enter the refrigerator.
  • An inspection of the refrigerator compartment 100 takes place only in special situations, such as e.g. in the event of an accident, during maintenance, installations or controls.
  • the normal operation is provided without the inspections of the refrigerator compartment 100, the special case of the inspection of the refrigerator compartment 100 is shown here.
  • the cooling system 1 is, as described above, constructed with a cooling space 100 and an operating space 400 located above it.
  • the cooling space 100 is limited by the floor area 110, side walls 120 and the ceiling area 130.
  • Below the floor area 110 is the first cooling device 200.
  • the second cooling device 300 is connected to the side wall 120.
  • In the ceiling area 130 is at least one ceiling opening 131, through which the conveyor 150 with a cable 151 and a conductor 152 from the operating room 400 into the cooling chamber 100 protrude.
  • cooling system 1 is a nitrogen-sprinkler system
  • the nitrogen-sprinkler system 108 which is arranged in the cooling chamber 100.
  • the nitrogen-sprinkler system 108 is located at the Untersei ⁇ te of the ceiling portion 130.
  • the nitrogen sprinkler system 108 is supplied via coolant lines from the coolant supply 500 (see Figures 1, 6).
  • condensate collection elements 109 are illustrated in the refrigerator.
  • the condensate collection elements 109 include e.g. Metal sheets, which are in communication with the first cooling device 200, in particular the liquid nitrogen 220.
  • the condensate collecting elements 109 form an ice trap.
  • Ice coating can be done by replacing the condensate collection elements
  • an external ventilation device can introduce dry, tempered air into the operating room 400.
  • a flexible tube element 128 is provided.
  • a breathable gas atmosphere at a temperature in the range of -5 ° C to -50 ° C so be supplied quickly that the operating room 400 can be entered within less than a minute, in particular within 20 s. If this is also required for the cooling space 100, a rolled-up hose can be guided through the ceiling opening 131 along the ladder 152 into the cooling space 100. With active ventilation of the cold room 100 this can also be entered within 10 to 20 s without breathing apparatus and protective suit.
  • 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 removable or knocked out of this.
  • a schematically illustrated docking device 700 may be arranged for a mobile evacuation container.
  • the automatic sample storage or sampling takes place with a sample access automaton 470, which is located in the operating room 400 and contains a drive device 410 for the mechanical actuating elements 411.
  • a horizontal movement of the adjusting elements 411 takes place in the operating room 400 above a temperature of -80 ° C.
  • a vertical arm 416 the adjusting members 411 extends through a opening in the movement ⁇ the slot in the ceiling opening 131 in the refrigerator 100, so that all compartments of the shelves 141 are accessible.
  • a sample is taken out, transported upwards, sampler 470 enters the machine and is transferred to a temperature-controlled lock (-60 to -80 ° C.), where the sample is taken to a removal point 458, which is visited without any thermal protective clothing can be.
  • Partition walls 160 may be inserted into or removed from the cooling compartment 100 as needed.
  • the partitions 160 extend in the transverse and / or longitudinal direction relative to egg ⁇ ner longitudinal extent of the cooling chamber 100.
  • the intermediate walls blank 160 in the vertical direction ie, move upward, so that advantageously prevents the refrigerator compartment uncontrolled 100 undesired gas flows or thermal gradients arise.
  • allow the partition walls 160 has a separate cooling in individual chambers of the cooling chamber 100 with variable temperature ⁇ structures. In this way, cryobanks can be realized with storage capacities of millions of samples.
  • a modular design of the cooling system 1 can be provided, wherein all chambers or sample receiving devices in the cooling space 100 form separate elements, which are possibly supplied completely autonomously.
  • Such a concept has the advantage of free expandability.
EP12702189.7A 2011-02-02 2012-02-01 Installation frigorifique accessible à une personne debout et destinée notamment à la cryoconservation d'échantillons biologiques, et procédé pour faire fonctionner une telle installation Withdrawn EP2671034A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011010121.7A DE102011010121B4 (de) 2011-02-02 2011-02-02 Begehbare Kühlanlage, insbesondere zur Kryokonservierung biologischer Proben, und Verfahren zu deren Betrieb
PCT/EP2012/000451 WO2012104080A2 (fr) 2011-02-02 2012-02-01 Installation frigorifique accessible à une personne debout et destinée notamment à la cryoconservation d'échantillons biologiques, et procédé pour faire fonctionner une telle installation

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EP2671034A2 true EP2671034A2 (fr) 2013-12-11

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US (1) US20140000307A1 (fr)
EP (1) EP2671034A2 (fr)
JP (1) JP2014504716A (fr)
CN (1) CN103459949B (fr)
CA (1) CA2825234C (fr)
DE (1) DE102011010121B4 (fr)
WO (1) WO2012104080A2 (fr)

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DE102011010120A1 (de) * 2011-02-02 2012-08-02 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Kühlanlage, insbesondere zur Kryokonservierung biologischer Proben, mit Einrichtungen für den Fall einer Havarie
WO2017042915A1 (fr) 2015-09-09 2017-03-16 ギガフォトン株式会社 Dispositif de stockage de cible
CN105211050B (zh) * 2015-10-22 2017-12-12 上海原能细胞医学技术有限公司 用于冻存细胞的操作台
FI126430B (fi) * 2015-12-16 2016-11-30 Oy Cryon Ltd Järjestelmä huippukylmähoitoon
CN105737471B (zh) * 2016-02-04 2018-08-31 上海理工大学 速冷便携式生物样品低温保存箱
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CN103459949B (zh) 2016-06-01
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WO2012104080A3 (fr) 2013-01-24
US20140000307A1 (en) 2014-01-02
JP2014504716A (ja) 2014-02-24
WO2012104080A8 (fr) 2012-11-08
CA2825234C (fr) 2018-11-27
DE102011010121B4 (de) 2016-09-01
DE102011010121A1 (de) 2012-08-02
CA2825234A1 (fr) 2012-08-09

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