WO2012104080A2 - Accessible cooling system, especially for cryopreserving biological samples, and method for the operation thereof - Google Patents

Abstract

A cooling system (1), especially for cryopreserving biological samples (2), comprises a cooling chamber (100) delimited by a bottom area (110), side walls (120), and a top area (130), and a cooling device (200) for cooling the cooling chamber (100) using liquid nitrogen (220). The bottom area (110) is designed for direct cooling using the liquid nitrogen, and the cooling chamber (100) is dimensioned such that an operator (3) can access and move around in the cooling chamber (100). The bottom area (110) has a platform (111) which is permeable to vapor of the liquid nitrogen (220) and forms a support zone for the operator (3). Methods for operating the cooling system are also described.

Description

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.

It is known biological samples for preservation purposes in the frozen state in a refrigeration system, for. B. in a cryobank to store (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 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. In 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. However, in order to avoid sample contamination by the 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. For 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. In practice, Pro ^¬ ben-deposits or withdrawals from inventories or are required borrowed what at cryobanks for example, 10,000 to 1

Millions or more of samples become a critical constraint to the effectiveness of cryotank operation and to providing constant cooling conditions. With such large numbers of samples is a further automation ^¬ tion of all processes, in particular the sample handling is required. Previous automation approaches (see, for example, DE 10 2005 031 648 A1, US 2006/0156753 A1, US 2006/0283197 A1, US 2007/0267419 A1) are limited to the individual cryotanks and entail considerable costs. In cryobanks with more than twenty cryotanks automation Zvi ^¬ rule is the cryotanks extremely costly, as it would require cross-vending machines, however, are not currently available.

It is also known to store food in cold storage. An effective storage and automation he ^{¬ is} sufficient if the cold rooms a walk-in large storage bil ^¬ the. However, this technique is not applicable to refrigerators for cryopreservation of biological samples. Even the slightest ge ^¬, provided in the cooling of food temperatures are too high for the long-term cryopreservation of biological samples. However, operating the conventional refrigerators at lower temperatures is not easy possible. Below -30 ° C, conventional automation techniques fail due to functional and material limitations, especially of motors, bearings, lubricants and the fit of moving parts. In the event of a malfunction or a component failure in the cold room, it would have to be completely warmed up as operators can not safely enter rooms with a temperature below -80 ° C in conventional protective clothing. A deep breath would damage the air sac by freezing and subsequently lead to life-threatening conditions. Add to that the fast tires and icing when opening and entering the rooms. Furthermore, there are problems with the thermal insulation of conventional refrigerated cold rooms and their security in case of accidents. Since cryobanks must be kept cold for decades, in the future probably centuries, in the future, the accident problem is particularly critical. So far, there is a lack of techniques to keep large halls at least - 80 ° C in case of total failure of the cooling system until a repair has taken place.

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. In particular, 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.

These objects are achieved by refrigeration systems and methods for their operation with the features of the independent claims. solves. Advantageous embodiments and applications emerge from the dependent claims.

According to a first aspect of the invention, there is provided 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. For this purpose, the bottom portion of the refrigerator is set up for direct cooling with the liquid nitrogen. Advantageously, a uniform cooling of the cooling space is thus supported. By cooling the cooling space from bottom to top by vapor of the liquid nitrogen can form a gas stratification with a temperature gradient in the cold room. The temperature can rise in a stable and reproducible manner from bottom to top. Advantageously, it thus supports the provision of reproducible storage conditions, in particular a reproducible storage temperature at the location of sample placement.

According to the invention, 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. Preferably, 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. For an internal volume of z. B. 10 m ³ , the refrigerator is a small cryochamber, währned 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 according to the invention is set up for receiving a sample receiving device. As 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. As test tubes, tubes, capillaries, so-called "straws", bags or other closed containers. The sample receiving device can be permanently arranged in the cold room (in particular fixed) or at least partially detachably arranged. According to the invention, the cooling space is preferably dimensioned so that the operator be present within the equipped with the Pro ^¬ benaufnahmeeinrichtung refrigerator and can move. According to the invention, 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. First, 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. Thus, 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. Second, 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. Preferably, 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. Furthermore, 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

Platform over the entire surface of the bottom of the refrigerator.

According to a second aspect of the invention, a ^{method is provided} 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.

Advantageously, 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. For example, the floor area platform may include a grid extending over the vessel. Another advantage is that 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. Preferably, the bottom area and the first cooling device are laterally and downwardly equipped with a thermal insulation.

Advantageously, with the inventive combination of nitrogen cooling, refrigerator dimensioning and provision of the platform platform, 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.

With the dimensioning of the cold room, 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. Thus, 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.

Compared to the cooling of foodstuffs in large-scale warehouses, there is the advantage that 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 . At the same time, 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.

Further advantages of the invention are the complete absence of moisture and icing freedom of the refrigerator, the rapid cooling capacity of the refrigerator without frosting, the high access speed to all samples in the refrigerator, an equal accessibility for all inventories in the refrigerator, the optional electronic responsiveness of the samples and Storage systems, the controllability of the temperature in predefined areas of the cold room, and the rapid storage and removal of samples at a documented sample temperature. In particular, the absence of moisture and freedom from icing (freedom from water, tion in dry gas) of the refrigerator is supported by the inventive generation of the cooling nitrogen vapor from the bottom of the refrigerator ago. With the invention, alternative energy concepts (use of hydrogen for cooling and energy generation) can be implemented. Wei ^¬ direct is a highly redundant design of sicherheitsre ^¬-relevant systems and a stabilization of the temperature controlled cooling in the fridge or its parts 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 operable independently of the first cooling device. The second cooling device is also provided for cooling the cooling space. According to a first variant, 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. According to a further variant, the second cooling device is alternatively or additionally configured for an electric cooling operation and / or a cooling using liquid helium (LHe).

Advantageously, the second cooling device enables a hybrid operation of the cooling system. For example, 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. According to another example, an electrical cooling to -150 ° C and in addition a cooling with LN ₂ , or an LN ₂ cooling and a switchable cooling with LH, or an electric cooling to -80 ° C an antechamber, then an electric cooling to -150 ° C and cooling with LN _{2 be} provided. With the hybrid operation, a full hybrid system or a partial hybrid system can be realized. In the full hybrid system, both cooling devices are in each case fully efficient, ie each of the cooling devices allows a permanent cooling of the cooling chamber to temperatures <-130 ° C. In the partial hybrid system, one of the cooling devices (main cooling system, eg LN ₂ ) is permanently in operation, while the other of the cooling devices (auxiliary system) is switched on only when needed. 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.

According to a preferred embodiment of the invention, 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. Furthermore, the ceiling opening constitutes an access opening for samples and / or an input and output opening for the operator. Advantageously, it can be provided that 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. Thus, particularly preferred entry and exit of the operator is provided only above the refrigerator through the ceiling area. An entry and exit of the operator through a side wall, however, can be provided alternatively or additionally. The at least one ceiling opening advantageously offers the possibility aufzuset ^¬ on the refrigerator a hood ^chamber zen, in the z. In the event of an accident, for example, the sample receiving device or at least the cryopreserved samples can be taken up.

Furthermore, it has proved to be advantageous if, according to a further variant of the invention, 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. In order to minimize thermal losses, however, the operating space is preferably thermally isolated from the outer in order ^¬ gebung the cooling system. The operating room contains technical equipment that interact with the refrigerator. Preferably, 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. Alternatively or additionally, the operating room can be connected to at least one lock device (person lock device and / or sample lock device). According to a preferred variant of the invention, the mechanical adjusting elements, such as. As gripping arms, levers or Be ^¬ tätigungselemente, 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. According to further preferred variants of the invention, 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. Advantageously, in particular the safety during the evacuation of the operator from the cold room is increased. 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.

Further advantages for reducing thermal losses may arise when supply connections between the refrigerator compartment and its surroundings extend through the ceiling region. 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.

According to a further preferred embodiment of the invention, 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. B. a plate made of foamed plastic, in particular a rigid foam plate. 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. 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.

Furthermore, according to the invention, 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. Alternatively or additionally, 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. Advantageously, 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.

According to a further preferred embodiment of the invention, 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. Preferably, 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. Alternatively or additionally, it can be provided that the door leaf is arranged to be displaceable parallel to the respective side wall. In this case, a z. B. in the height or side drawable wall surface (bulkhead) created. On an outer side of the side wall to match the position of the door opening, a docking device for an evacuation container or a lock device can advantageously be provided.

Advantageously, a sample receiving device in the refrigerator space racks (so-called "racks") include, which form the support structure for the biological samples. In this case, there are advantages for automated access to samples, eg. B. with the mechanical control elements. Shelves comprise support plates (shelves) on which the containers with the biological samples are exposed. Particularly preferably, the shelves are made of a material with increased thermal conductivity, z. As metal formed. Advantageously, 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. According to a variant of the invention, 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. According to a further variant of the invention, the sample receiving device may alternatively or additionally form a rigid component. For example, 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.

According to a further variant of the invention, 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. Advantageously, a segmentation in pre-and main refrigerators, and possibly auxiliary cooling chambers is achieved. For example, samples may be cooled selectively according to the used storage capacity and access frequency and / or storage temperature requirement. It can, for. For example, 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. Furthermore, heat corridors can be formed which, in the event of an accident, provide an elevated temperature for rapid evacuation of the samples.

With the intermediate walls, a structure can be created, which is characterized by mutually surrounding subspaces with different temperatures. For example, 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.

According to general features of the invention, the cooling system may be equipped with at least one of the following components:

- Fans for mixing the cool gas phase in special rooms inside

 - Gas sensors, z. B. oxygen sensors,

 Temperature sensors, in particular for a spatially resolved temperature measurement in the cold room,

- Alarms, z. B. alarm lamps,

 - Lighting equipment with minimized entry of infrared or thermal radiation, z. B. using light emitting diodes (LED) or other cold light sources, 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),

 - contactless energy and signal input (inductive or optical coupling)

 - Monitoring equipment, eg. B. a camera surveillance, a motion detector and / or a heat detector,

 - emergency generator with automatic connection, bridging-free power supply,

- Coolant sprinkler system in the upper part of the refrigerator, z. B. for feeding liquid nitrogen or helium for rapid cooling of the refrigerator, and

- Connection device for an external LPG feed, z. B. of tankers, for the accident, a nitrogen liquefaction plant,

 - A coolant container, which is provided for receiving a Reservevolu mens liquid nitrogen, and / or

 - Condensate collection elements that protrude from the floor area into the cold room.

Further advantages and details of the invention will become apparent from the following description of the accompanying drawings. Show it:

Figures 1 and 2 are schematic cross-sectional views Favor ter embodiments of the cooling system according to the invention;

Figures 3 and 4: schematic perspective views of others

 Embodiments of the cooling system according to the invention;

FIG. 5: schematic cross-sectional views of a

 Side wall of the cooling system according to the invention

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;

Figure 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; and

FIG. 10: a schematic illustration of a further

Operating mode of the cooling systems 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. 1 shows a first embodiment of the cooling system 1 according to the invention in a schematic cross-sectional view with a cooling space 100, a first cooling device 200, a second cooling device 300, an operating space 400 and a coolant supply 500. 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. In the cooling space 100, 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.

In the cooling chamber 100 and in the operating room 400 temperature sensors 103 are arranged. 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. 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. If one of the cooling devices fails, 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.

Notwithstanding the representation shown in Figure 1, the order of the plastic layer and the vacuum component can be reversed position. Furthermore, further plastic and / or vacuum component layers may be provided. Further details of the side walls 120 are described below with reference to FIG.

The ceiling area 130 comprises a plastic layer 132, formed, for example, from polymer foam, in which a ceiling opening 131 is formed. Above the ceiling opening 131, 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. With the mechanical adjusting elements 411, 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. With the second cooling device 300, e.g. an electric cooling to a temperature of -150 ° C be provided. According to alternative variants of the invention, the second

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. In addition, 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 ^¬ ßerhalb the cooling chamber 100 thermally insulated, for example, formed by a vacuum line. In contrast, inside the cooling chamber 100 (at 521) a thermal insulation of the coolant line 520 is not provided. Thus, the cooling of the interior of the refrigerator 100 is improved. In addition, 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

100 a dry and cold nitrogen atmosphere is formed and avoid further ice deposits.

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. Furthermore warmer attachments for devices are arranged, which can not ar ^¬ BEITEN at low temperatures in the operating room 400 or about this (see Figure 2). In particular, 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. Of importance for the reliable operation of the cooling system 1 is also possible delayed heating in case of failure, especially in case of failure of cooling equipment. This is achieved in particular by the thermally insulating structure of the side walls 120. For operation of the cooling system 1, the cooling space 100 with the first cooling device 200, possibly assisted by the second cooling device 300, is cooled down to the desired cryoconservation temperature. Subsequently, using the mechanical adjusting elements 411, the biological samples 2 are arranged in the sample receiving device 140 in the cooling chamber 100. In the event of a fault or for maintenance, inspection or operating purposes, 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

Protective suit with a thermal insulation and a head protection, which ensure protection of the operator against heat loss. 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. With respect to the operating room 400, the following differences arise. According to FIG. 2, 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. In 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.

Between the chambers 420, 430 and 440 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.

Notwithstanding Figure 2, 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 derstandsheizung 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. In a practical implementation, the cooling system 1 can be constructed with respect to these components, as described above with reference to FIGS. 1 and 2.

In the ceiling area 130, a ceiling opening 131 is provided, which is closable with a lid 132. Advantageously, by providing the opening for the access of the operator 3 at the top of the refrigerator 100, the

Temperature stratification in this at the entrance of the operator 3 hardly affected. Alternatively, 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. In the operating room 400, 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 conveyor

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. The cable

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. Between the operating room 400 and the passenger lock device 450, 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. In the personal lock device 450, a pre-cooling to a medium temperature range, for example -80 ° C. For this is the Personal lock device 450 equipped with a cooling device (not shown). Alternatively, 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. In 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.

First, 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. In this case, 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. This is followed by a further cooling the operator 3 to a predetermined temperature. Once the operator 3 has cooled sufficiently and the atmosphere in the service room 400 has reached predetermined normal values, the lid 132 is opened so that the operator 3 can enter the refrigerator compartment 100. In the refrigerator 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.

Secondly, in an emergency situation it is provided that the cover 132 and the inner and outer lock doors 451, 453 are simultaneously opened via emergency switches (not shown). In this situation, a quick access to the interior of the refrigerator 100, in particular to rescue the

Operator 3 and / or to secure stored samples enabled. In the emergency situation, 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

Oxygen sensors (not shown) are monitored. As a result, further assistants may act without protective suit and without their own oxygen supply in the refrigerator compartment 100. FIG. 4 schematically illustrates characteristics of the inspection of the

Cooling chamber 100 and the supply or removal of the sample receiving device 140 in or out of the cooling chamber 100 with reference to a further embodiment of the cooling system according to the invention 1. As in Figure 3, 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.

For feeding or removal of the sample receiving device 140, 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. In the operating room 400 there is 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.

Notwithstanding Figure 3, 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. Between the door opening 125 and the floor area 110, 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. In the outer chamber 455, for example, a temperature of -20 ° C is provided, while in the inner chamber 456 a temperature of -80 ° C is provided.

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.

Since a permanent work stay (> 15 minutes) may be required in the refrigerator compartment 100, 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

(see Figure 1) may be provided below the bottom portion of the refrigerator. In the schematic cross-sectional views of FIGS. 5A to 5C, 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.

According to FIG. 5A, 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. This is followed by a first vacuum component capable 122.1 which an evacuated, along the side wall 120 includes erstre ^¬ 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. Advantageously, this is reflected from the outside kom ^¬ ing thermal radiation.

This is followed by another 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. Within the vacuum component location 122.2 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). On the outside of the plastic layer 121, 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 (see FIG. 1) are arranged.

In particular, 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. In contrast, the thickness of the side wall 120 of the cooling system according to the invention does not play a critical role.

The embodiment of FIG. 5A may be modified such that a further hollow wall is inserted, which is part of a further, in particular electrical, cooling device. In the event of a fault (for example, if the first cooling device fails below the bottom area of the cooling space), 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). In addition, the cooling element 310 may be in communication with the liquid ^¬ stick material 220 of the first cooling device 200 (see Figure 1). In normal operation, the cooling of the interior of the cooling chamber 100 is supported by the cooling element 310. In case of failure, 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.

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 In detail, 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. This is followed by 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. Furthermore, 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. Typically, the temperature in the cold room 100 is less than -140 ° C. For this purpose, 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). However, a variant of the invention is preferred in which 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. For electrical supply to the liquefaction plant, 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. With a level sensor, the level of the liquid nitrogen of the first cooling device 200 is detected. When falling below a critical level 520, liquid nitrogen is replenished in the first Kühleinrich ^¬ tung 200 via the Kühlmit ^¬ telleitung.

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).

In addition, 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. More specifically, 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. Furthermore, 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. Finally, 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). In the cooling system 1 according to FIG. 7, 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 Ausfüh 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.

Furthermore, the 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 Zufüh ^¬ 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.

Alternatively, it may be provided that all the cooling chambers 105, 106 and 107 enter exclusively from above and the door openings 161 are reserved for access only in the event of a malfunction. In this case, the door openings 161 can be arranged at the level of the floor area, the stairs 162 are then not required. In the intermediate walls 160 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.

In the innermost cooling chamber 105, 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. In the innermost cooling chamber 105 in particular reserve or backup stocks are housed. In the middle cooling chamber 106 are samples that require frequent access. This area can be used as Workspace of the cryobank can be used. Finally, 107 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. In the operating room 400, 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

Nitrogen loading, so that within the isolation tower 480, a temperature of z. B. -160 ° C is given and only the sample removed for a short time an ambient temperature of z. B. -20 ° C, while all other samples of the shelf 141 remain in a formed by the insulating tower 480, movable range of the low temperature region in the cooling chamber 100.

The use of porous material, eg. B. Silica based airgel, for the storage of coolant, in particular liquid nitrogen, for active cooling of the isolation tower 480 is not mandatory. The isolation tower 480 may also be formed of a thermally insulating material. Furthermore, according to the invention, the use of 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. In normal operation, 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. Although 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.

To inspect the refrigerator 100 enters an operator 3 through the person-lock device 450, the operating room 400. Between the person-lock device 450 and the operating room 400 a lock door is provided by wel che the operator 3 via a staircase 457 in the operating ^¬ space 400th can get. From the operating room 400, the inspection of the cooling chamber 100 takes place through the ceiling opening 131. Above the operating room 400 is the hood chamber 400.1 (Havarieturm), in the sample receiving devices 140, in particular the tower-like shelves 141 can be transferred in the event of an accident. Figure 8 shows as a further advantageous feature of the OF INVENTION ^¬ to the invention cooling system 1 is a nitrogen-sprinkler system

108, which is arranged in the cooling chamber 100. Preferably, the nitrogen-sprinkler system 108 is located at the Untersei ^¬ te of the ceiling portion 130. Advantageously, with the nitrogen sprinkler system 108, a fast cooling at

First use of the refrigerator or in case of accident can be achieved. The nitrogen sprinkler system 108 is supplied via coolant lines from the coolant supply 500 (see Figures 1, 6).

Furthermore, 100 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. One

Ice coating can be done by replacing the condensate collection elements

109, by mechanical scraping, aspiration or by sublimation using locally inflated dry warm gas. Thus, in contrast to conventional cryopreservation techniques, ice formation in the remaining cooling space can be suppressed.

A venting of the cooling chamber 100 and the operating room 400 via a pipe connection with a siphon. In the event of an accident, an external ventilation device can introduce dry, tempered air into the operating room 400. For this purpose, a flexible tube element 128 is provided. Advantageously, in the operating state of the refrigeration system 1, 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. In the case of an immediately required removal of the samples (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 removable or knocked out of this. On the outside of the side wall 120, 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. FIG. 9 illustrates that in the case of a design of the refrigeration plant 1 in the size of an industrial building, the use of variable partitions 160 is advantageous. 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. Preferably, 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. Furthermore, 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.

As an alternative to the representation in FIG. 9, according to FIG. 10, 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.

The features of the invention disclosed in the foregoing description, claims and drawings may be significant to the realization of the invention in its various forms both individually and in combination.

Claims

 Claims 1. Cooling system (1), in particular for the cryopreservation of biological samples (2), comprising:

 a cooling space (100) delimited by a floor area (110), side walls (120) and a ceiling area (130), and

- A first cooling device (200), which is provided for cooling the cooling space (100) with liquid nitrogen (220), wherein

 the floor area (110) is configured for direct cooling with liquid nitrogen,

characterized in that:

 - The refrigerator compartment (100) is dimensioned so that in the refrigerator compartment (100) an operator (3) can stay and move, and

 - The bottom portion (110) has a platform (111), which is permeable to vapor of the liquid nitrogen (220) and forms a support area for the operator (3).

2. Cooling system according to claim 1, comprising:

 - A second cooling device (300) which is independently of the first cooling device (200) for cooling the cooling space (100) operable.

3. Cooling system according to claim 2, wherein

 - The second cooling device (300) for cooling at least one of the side walls (120) of the cooling space (100) provided and / or is configured for an electric cooling operation.

4. Cooling system according to one of the preceding claims, wherein - The ceiling portion (130) has a ceiling opening (131), wherein above the ceiling opening (131) at least one operating space (400) is provided, the drive means

(410) with mechanical adjusting elements (411), a conveying device (150) for introducing the operator (3) into the cooling space (100) and / or connected to a lock device (450).

5. Cooling system according to claim 4, wherein

 - The mechanical adjusting elements (411) in the cooling chamber (100) are insertable, wherein at least parts of the adjusting elements

(411) are heatable, and / or

 - The conveyor (150) comprises a cable (151) and / or a stepping device (152).

6. Cooling system according to one of the preceding claims, wherein

 - The side walls (120) are multi-layered with several wall layers, the at least one plastic layer (121), at least one vacuum component layer (122.1, 122.2)

and / or at least one vapor barrier layer.

7. Cooling system according to one of the preceding claims, wherein

- At least one of the side walls (120) modular with at least one wall element (123) is constructed, which is perpendicular to the respective side wall (120) displaceable and from the side wall (120) separable.

8. Cooling system according to claim 7, wherein

- On a outside of the side wall (120) with the at least one wall element (123) is provided a docking device (700) for an evacuation container.

9. Cooling system according to one of the preceding claims, wherein

 - At least one of the side walls (120) has a door opening (125) with a door leaf (126).

10. The cooling system according to claim 9, wherein

 - The door opening (125) is arranged at a predetermined distance above the floor area and / or the door leaf (126) is arranged parallel to the respective side wall (120) slidably.

11. Cooling system according to one of the preceding claims, wherein

 - In the cooling chamber (100) a sample receiving device (140) with shelves (141) is provided, which is adapted to receive the samples.

12. The cooling system according to claim 11, wherein

 - The sample receiving device (140) with thermal bridges (142) is provided, which protrude into the bottom region (110).

13. A cooling system according to one of the preceding claims, comprising

 Partition walls (160) which extend in the vertical and / or horizontal direction in the cooling space,

 a coolant auxiliary reservoir (540) provided for receiving a reserve volume of liquid nitrogen,

a nitrogen liquefaction plant (530),

 Condensate collecting elements (109, 521) arranged in the cooling space (100),

 - A nitrogen sprinkler system (108), which is arranged in an upper region of the cooling space (100), and / or

- A helium feed system, which is configured for cooling the refrigerator (100).

14. A method of operating a refrigeration system according to one of the preceding claims, comprising the steps of:

 Cooling the cooling space (100) with the first cooling device (200), and

 - Positioning of biological samples in the cold room (100).

15. The method according to claim 14, wherein

 - An operator (3) in the refrigerator (100) performs control, maintenance and / or operating steps.