JP2015209995A - Over-cooling freezing device and over-cooling freezing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an over-cooling freezing device and an over-cooling freezing method capable of making sufficient fast cooling speed in over-cooling freezing operation and further capable of improving quality of frozen items.SOLUTION: This invention comprises: a cooling case 13 installed in a refrigerator 12; a low temperature fluid feeding-in part for feeding-in low temperature fluid into the refrigerator 12 and an atmospheric gas feeding-out part for feeding out the atmospheric gas in the refrigerator; atmospheric gas feeding-out means 17 for feeding-out the low temperature atmospheric gas in the cooling case to an atmospheric gas circulation flow passage and atmospheric gas feeding-in means 18 for feeding-in low temperature atmospheric gas in the atmospheric gas circulation flow passage into the cooling case; a cooling container 19 for storing the freezing container storing the liquid-like frozen items; and temperature control means for controlling a feeding-in amount of the low temperature fluid into the refrigerator. The cooling container is contacted with the freezing container to cool the liquid-like frozen items in the freezing container through thermal conduction.

Description

  The present invention relates to a supercooled freezing apparatus and method, and more particularly to a supercooled freezing apparatus and method for freezing biological products such as vaccines and blood used for humans and animals.

  When freezing biological products such as vaccines and blood (liquid pharmaceutical preparations and their raw materials and intermediates), ice crystals generated in the cells or in the intercellular spaces may damage the cell tissue, The concentration may be non-uniform. As a method for avoiding these problems, a supercooling freezing method is known in which freezing is performed through a supercooling state where freezing is not performed even below the freezing point (see, for example, Patent Document 1).

Japanese Patent No. 4253775

  However, in the method described in Patent Document 1, since the supercooled state is released and then the amount of cold air and the air speed are increased and frozen, the cooling rate after the release of the supercooled state is applied to the food. Even if it is sufficient, when freezing a vaccine, blood, etc., there was a risk that the ice crystals would be enlarged and the quality could be lowered.

  Therefore, an object of the present invention is to provide a supercooling freezing apparatus and method that can sufficiently increase the cooling rate of supercooling freezing and can improve the quality of frozen products.

  In order to achieve the above object, the supercooling freezing apparatus of the present invention is a cooling system provided inside a refrigerator in a supercooling freezing apparatus that freezes a liquid object to be frozen stored in a freezing container after it is supercooled. A box, an atmosphere gas circulation channel provided between the outer surface of the cooling box and the inner surface of the cooling chamber, a low-temperature fluid introducing portion for introducing a low-temperature fluid into the cooling chamber, and an excess atmosphere in the cooling chamber Atmospheric gas deriving section for deriving gas to the outside, atmospheric gas deriving means for deriving the low temperature atmospheric gas in the cooling box to the atmospheric gas circulation channel, and low temperature atmospheric gas in the atmospheric gas circulation channel are introduced into the cooling box Atmosphere gas introducing means, a cooling container for storing the freezing container containing the liquid object to be frozen, and a cooling container and a cooling box provided in and out of the cooling box, respectively. Open And an opening / closing member that opens and closes at least the opening of the refrigerator, and a temperature control means that controls the amount of low-temperature fluid introduced into the refrigerator, and the cooling container and the freezing container are brought into contact with each other to generate heat. The liquid object to be frozen in the freezing container is cooled by conduction.

  Furthermore, in the supercooling freezing apparatus of the present invention, the freezing container is a synthetic resin bag body that can store the liquid object to be frozen, and the liquid object to be frozen is stored inside the synthetic resin bag body, The synthetic resin bag body is housed in the cooling container in a state of being housed in a metal freezing container, and the atmosphere gas introducing means is configured to bring the atmosphere gas into contact with the cooling container in a turbulent state. It is a feature.

  Further, the cooling box and the cooling box have the opening and the opening / closing member on a side surface, and a cooling container mounting part for mounting the cooling container is provided on the inner surface of the cooling box, Alternatively, the cooling box and the cooling box have the opening and the opening / closing member on a side surface, and the cooling container is put into and out of the cooling box in a state of being mounted on a cart that can be advanced and retracted in the cooling box. Alternatively, the cooling box and the cooling box have the opening and the opening / closing member on an upper surface, and the cooling container is suspended from above and taken in and out of the cooling box.

  Further, the cooling box constituent member constituting the cooling box is provided with a low-temperature fluid pipe through which a low-temperature fluid for cooling the cooling box flows, the low-temperature fluid includes liquid nitrogen, liquefied argon, liquid air, It is one of low-temperature nitrogen gas, low-temperature argon gas, low-temperature air, or a mixed fluid thereof.

  The supercooling freezing method of the present invention is a supercooling freezing method in which a liquid frozen object stored in a freezing container is frozen using the supercooled freezing apparatus, and then frozen. The frozen container stored is placed in the cooling box in a state accommodated in the cooling container, and the low-temperature fluid introduced from the low-temperature fluid introduction part into the cooling box is placed in the cooling box through the atmospheric gas circulation channel. The cooling container is cooled by circulating it, the cooling container and the freezing container are brought into contact with each other, and the liquid object to be frozen is cooled by heat conduction to be in a supercooled state. The cooling heat necessary for the freezing of the object to be completed is given by the cooling heat of the cooling container, and the cooling rate of the liquid object to be frozen is -5 ° C / h to -30 ° C / h. It is a feature.

  According to the present invention, after releasing the supercooled state of the liquid object to be frozen, the cooling heat of the cooling container is transferred to the liquid object to be frozen by the heat conduction between the solids and cooled. Can be frozen. As a result, it is possible to suppress the enlargement of ice crystals and to avoid quality deterioration factors other than ice crystals, so that a frozen product with excellent quality can be obtained.

It is explanatory drawing which shows the 1st example of a supercooling freezing apparatus of this invention. It is a cross-sectional side view of a supercooling freezing apparatus similarly. It is III-III sectional drawing of FIG. It is IV-IV sectional drawing of FIG. It is a top view which shows an example of the liquid to-be-frozen object to be frozen. It is a side view similarly. It is explanatory drawing which shows the 2nd form example of the supercooling freezing apparatus of this invention.

  1 to 4 show a first embodiment of the supercooling freezing apparatus of the present invention. The supercooling freezing device 11 shown in the present embodiment includes a box-shaped refrigerator 12, a cooling box 13 disposed inside the refrigerator 12, an outer surface of the cooling box 13, and an inner surface of the refrigerator 12. An atmospheric gas circulation passage 14 provided therebetween, a low-temperature fluid introduction section 15 for introducing a low-temperature fluid into the cooling box 12, and an atmospheric gas deriving section 16 for deriving excess atmospheric gas in the cooling box 12 to the outside The low temperature ambient gas in the cooling box 13 is introduced into the cooling box 13 as a plurality of outlet fans 17 and the atmosphere gas circulation passage 14 serving as the atmosphere gas deriving means for deriving the low temperature atmosphere gas in the cooling box 13 to the atmosphere gas circulation passage 14. A plurality of introduction fans 18 serving as atmospheric gas introduction means, a cooling container 19 containing a freezing container containing the liquid object to be frozen, and the cooling box 19 for taking the cooling container 19 into and out of the cooling box 13. 12 And openings 12a and 13a provided in the cooling box 13, a door 12b as an opening / closing member for opening and closing the opening 12a of the refrigerator 12, and a temperature detecting means 20 for measuring the temperature of the cooling container 19, respectively. The temperature control unit 21 controls the flow rate control unit 15F provided in the low-temperature fluid introduction unit 15 based on the temperature measured by the temperature detection unit 20 to control the amount of low-temperature fluid introduced into the refrigerator 12. And.

  Each component such as the cooling box 13 and the cooling container 19 has excellent corrosion resistance, good cleaning properties, high thermal conductivity, and does not embrittle at low temperatures, such as stainless steel, nickel steel, and oxide film. Aluminum alloy, magnesium alloy, or synthetic resin mixed with carbon nanotubes.

  Support members 13b for mounting the cooling container 19 are provided in a plurality of stages at predetermined vertical intervals on the inner surfaces of the opposing side wall and rear wall of the cooling box 13. The vertical distance between the support members 13b is set to be larger than the height of the cooling container 19. When the cooling containers 19 are supported by the support members 13b, the space between the upper and lower cooling containers 19 is within the cooling box 13. A space in which a low-temperature atmosphere gas can flow is formed.

  The introduction fan 18 and the lead-out fan 17 are for circulating the low-temperature atmosphere gas in the cooling box 13 through the atmosphere gas circulation passage 14, and in particular, by flowing and circulating in a turbulent state, the cooling box The temperature of the atmospheric gas in the inside 13 and the cooler 12 is made uniform quickly, and the influence of the boundary film on the surface of the cooling object such as the cooling container 19 is eliminated to improve the cooling efficiency. The number of installation of the introduction fan 18 and the extraction fan 17 can be appropriately set according to conditions such as the size of the cooling box 13 and the vertical spacing between the cooling containers 19, and only the introduction fan 18 is provided and the introduction side is ventilated. It is also possible to provide a mouth or provide only the outlet fan 17 to make the introduction side a vent. Furthermore, the flow state of the low-temperature atmosphere gas in the cooling box 13 can be appropriately set by controlling the rotation direction and the rotation speed of the fans 17 and 18.

  As the low-temperature fluid introduced from the low-temperature fluid introduction unit 15, a fluid having fluidity in a desired low-temperature state can be arbitrarily used. For example, liquid nitrogen, liquefied argon, liquid air, low-temperature nitrogen gas, low-temperature argon gas, low temperature Any one of air or a mixed fluid thereof can be used. Usually, in consideration of cost, it is preferable to use liquid nitrogen or low-temperature nitrogen gas obtained by vaporizing liquid nitrogen. When a liquid, for example, liquid nitrogen, is introduced from the low-temperature fluid introduction unit 15, it is preferable to provide an atomization nozzle at the leading end of the introduction unit and introduce the atomized state. Moreover, you may make it provide low temperature fluid piping through which the low temperature fluid for cooling a cooling box distribute | circulates to cooling box structural members, such as the side wall of a cooling box 13, and a rear wall.

  As shown in FIGS. 5 and 6, the liquid object to be frozen in the supercooling freezing apparatus 11 is a synthetic resin that is a freezing container made of a single layer film or sheet or a laminated film or sheet having a predetermined low temperature characteristic. The cooling container 19 may be housed in the cooling container 19 in a state of being housed in the bag-making body 31, or in a state in which the synthetic resin bag body 31 is housed in the metal freezing container 32 as indicated by an imaginary line. It may be housed inside. The cooling container 19 and the metal freezing container 32 are formed in such a size that the synthetic resin bag 31 is in contact with not only the bottom plate but also the top plate, so that the liquid to-be-frozen object can be effectively applied from both the upper and lower sides. Can be cooled.

  Next, the procedure for freezing the liquid object to be frozen using the supercooled freezing apparatus 11 formed in this way will be described. First, a liquid object to be processed is filled and accommodated in a synthetic resin bag 31 corresponding to the type of the liquid object, and the synthetic resin bag 31 is placed in a metal freezing container 32 as necessary. In the state accommodated in the inside, it accommodates in the said cooling container 19, and the cooling container 19 is inserted in the cooling box 13. After closing the door 12b, the introduction fan 18 and the outlet fan 17 are operated, and the low-temperature fluid is introduced into the cooling chamber 12 from the low-temperature fluid introduction unit 15. The amount of the cryogenic fluid introduced is the temperature detection means 21 corresponding to the object to be measured, for example, a liquid object to be frozen detected by the temperature detection means 21 such as a non-contact type or a resistance temperature detector, a synthetic resin bag body 31, a metal container. 32, the temperature control means 22 controls the flow rate control unit 15F according to the temperature of the low-temperature atmosphere gas in the cooling container 19 and the cooling box 13, and adjusts so that the liquid object to be frozen can be cooled at a preset cooling rate. To do.

  The cooling rate is appropriately set according to the type and amount of the liquid to be frozen. For example, in the case of a human-derived liquid preparation, in the range of −5 ° C./h to −30 ° C./h, in the case of an albumin solution or a vaccine, A range of 5 ° C / h to -15 ° C / h is preferred. In the case of distilled water, the cooling rate can be set to −120 ° C./h or more. The liquid object to be frozen is efficiently cooled from the cooling container 19 cooled by the circulating low-temperature atmospheric gas through the metal freezing container 32 and the synthetic resin bag 31 by heat conduction between the solid-solid-liquid. Can do.

  After the freezing point of the liquid object to be frozen has been cooled to the supercooled state, and when the supercooled state is released naturally or forcibly, the temperature of the liquid object to be frozen rises to the freezing point. 19 is cooled to the temperature when the supercooled state is released by the low-temperature atmosphere gas circulating and flowing in the cooling box 13, so that the liquid to-be-frozen object whose temperature has increased is solid-liquid due to the cold heat capacity of the cooling container 19. It is possible to rapidly cool to a predetermined freezing temperature by heat conduction between (solid).

  Thus, by cooling the liquid object to be frozen by heat conduction from the cooling container 19 which is a solid, it can be efficiently cooled without being affected by the boundary film, and a cooling rate of −5 ° C./h or more. And can be cooled efficiently in a stable state. In addition, after the supercooled state is released, the liquid object to be frozen can be instantly frozen by rapidly cooling the liquid object to be frozen by the heat capacity of the cooling container 19.

  As a result, the generation of needle-like crystals can be prevented, the cell structure is not destroyed, and protein denaturation, drip generation, freezing damage, and the like do not occur. Therefore, the present invention can be suitably used for freezing biological products (liquid pharmaceutical preparations and raw materials and intermediates thereof) such as vaccines and blood used for humans and animals, and improving their quality and recovery rate. Can be improved.

  FIG. 7 is an explanatory view showing a second embodiment of the supercooling freezing apparatus of the present invention. In the following description, the same components as those of the supercooling freezing apparatus shown in the first embodiment are denoted by the same reference numerals, and detailed description thereof is omitted.

  The supercooling freezing apparatus shown in FIG. 7 is arranged so that the bottom surface 13c of the cooling box 13 is flush with the floor surface on which the supercooling freezing apparatus 11 is installed, and can be taken in and out by a carriage 26 on which a plurality of cooling containers 19 are mounted. An example formed is shown. In this manner, by mounting the plurality of cooling containers 19 on the carriage 26 and forming them in and out of the cooling box 13, workability when supercooling and freezing a large amount of liquid object to be frozen can be improved. .

  Although not shown, it is also possible to form openings on the top surfaces of the cooling cabinet 12 and the cooling box 13 so that the cooling container 19 is suspended by a crane or the like and taken in and out of the cooling box 13. .

  In the case of supercooling freezing, the temperature of the low-temperature atmosphere gas in the box-shaped body 13, the surface temperature of the liquid object to be frozen, and the center temperature of the liquid object to be frozen are measured in advance using a resistance temperature detector. In addition, the optimum cooling temperature is specified, and the temperature of the low-temperature atmosphere gas in the box-like body 13 is set as the control temperature during mass production operation, and the temperature of the supercooling freezing considering the correlation of each temperature It is preferable to create a program and activate the temperature control means 22.

DESCRIPTION OF SYMBOLS 11 ... Supercooling freezing apparatus, 12 ... Cooling box, 12a ... Opening part, 12b ... Door, 13 ... Cooling box, 13a ... Opening part, 13b ... Support member, 13c ... Bottom surface, 14 ... Atmospheric gas circulation flow path, 15 ... Low-temperature fluid introduction unit, 15F ... flow rate control unit, 16 ... atmospheric gas derivation unit, 17 ... derivation fan, 18 ... introduction fan, 19 ... cooling container, 20 ... temperature detection means, 21 ... temperature control means, 26 ... cart, 31 ... Synthetic resin bags, 32 ... Metal freezing containers

Claims (11)

  In a supercooling freezing apparatus that freezes a liquid object to be frozen stored in a freezing container after being supercooled, a cooling box provided inside the cooling box, an outer surface of the cooling box, and an inner surface of the cooling box An atmosphere gas circulation passage provided between them, a low-temperature fluid introduction portion for introducing a low-temperature fluid into the cooling chamber, an atmosphere gas outlet portion for deriving excess atmosphere gas in the cooling chamber to the outside, and the inside of the cooling box The atmospheric gas deriving means for deriving the low temperature atmospheric gas to the atmospheric gas circulation flow path, the atmospheric gas introduction means for introducing the low temperature atmospheric gas of the atmospheric gas circulation flow path into the cooling box, and the liquid to be frozen stored therein A cooling container for storing the freezing container, an opening provided in each of the cooling box and the cooling box for putting the cooling container into and out of the cooling box, and opening and closing for opening and closing at least the opening of the cooling box And a temperature control means for controlling the amount of low-temperature fluid introduced into the refrigerator, and the liquid container to be frozen in the freezing container is cooled by heat conduction by bringing the cooling container and the freezing container into contact with each other. A supercooling freezing apparatus characterized by that.   The supercooled freezing apparatus according to claim 1, wherein the freezing container is a synthetic resin bag body capable of storing the liquid object to be frozen.   The liquid object to be frozen is housed in a synthetic resin bag body, and the synthetic resin bag body is housed in the cooling container in a state of being housed in a metal freezing container. Item 2. The supercooling freezing apparatus according to item 1.   The supercooling freezing apparatus according to any one of claims 1 to 3, wherein the atmospheric gas introduction means causes the atmospheric gas to contact the cooling vessel in a turbulent state.   The cooling box and the cooling box have the opening and the opening / closing member on a side surface, and a cooling container mounting portion for mounting the cooling container is provided on the inner surface of the cooling box. The supercooling freezing apparatus according to any one of claims 1 to 4.   The cooling box and the cooling box have the opening and the opening / closing member on a side surface, and the cooling container is put into and out of the cooling box in a state of being mounted on a carriage that can be advanced and retracted in the cooling box. The supercooled freezing apparatus according to any one of claims 1 to 4.   The said cooling box and said cooling box have the said opening part and the said opening-and-closing member on the upper surface, and the said cooling container is suspended from upper direction, and is taken in / out of the cooling box of Claim 1 thru | or 4 characterized by the above-mentioned. The supercooling freezing apparatus of any one of Claims.   8. The supercooling freezing apparatus according to claim 7, wherein the cooling box constituting member constituting the cooling box is provided with a low-temperature fluid pipe through which a low-temperature fluid for cooling the cooling box flows.   The said low temperature fluid is any one of liquid nitrogen, liquefied argon, liquid air, low temperature nitrogen gas, low temperature argon gas, low temperature air, or these mixed fluids, The any one of Claim 1 thru | or 8 characterized by the above-mentioned. The supercooling freezing apparatus of description.   A supercooled freezing method for freezing a liquid object to be frozen stored in a freezing container using the supercooled freezing apparatus according to any one of claims 1 to 9, wherein the liquid object is frozen. The cryocontainer containing objects is placed in the cooling box in a state of being accommodated in the cooling container, and the low-temperature fluid introduced from the low-temperature fluid introduction portion into the cooling box is cooled through the atmospheric gas circulation channel. Cooling the cooling container by circulating it in the box, bringing the cooling container and the freezing container into contact with each other, cooling the liquid object to be frozen by heat conduction to bring it into a supercooled state, releasing the supercooled state, A supercooling and freezing method, characterized in that cold heat necessary for freezing the object to be frozen is given by the cold heat of the cooling container.   The cooling rate of the said to-be-frozen thing of liquid is -5 degreeC / h--30 degreeC / h, The supercooling freezing method of Claim 10 characterized by the above-mentioned.

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