JP6689047B2 - Cooling unit - Google Patents

Description

  The present invention relates to a device for transporting a container containing contents while keeping it cool. More specifically, the present invention relates to an apparatus for transporting a container containing contents such as microorganisms whose activity greatly depends on temperature when the chamber is moved between chambers where the ambient temperature fluctuates greatly, while keeping it cool.

In a facility for producing a biological product, the biological product is often produced through a step of culturing using a target microorganism strain, a raw material such as a culture medium and cultured cells, and then taking out and purifying a crude stock solution. For viruses that enter the human body and cause infections and antibiotics are not very effective, vaccines that use the function of "immunity" to prevent infection by "antibody" that is created when the virus (antigen) enters the human body once , Manufactured as a biologic.
For example, in the production of influenza vaccines, a virus (vaccine strain) selected based on the prediction of the epidemic is prepared, and because of its high proliferative ability and easy availability, chickens are bred in a breeding environment under strict hygiene control. Using fertilized eggs (developed chicken eggs) laid by the hens, the vaccine strain is inoculated into the allantoic cavity of the embryonated chicken eggs, and then cultured at about 37 ° C for 2 to 3 days. Then, when the culture is completed, the embryos of embryonated chicken eggs are cooled for about half a day to stop the growth of the embryos and put into a state of asphyxia, and the chorioallantoic fluid (the allantoic fluid / virus is propagated) of the embryos in the eggs is collected. Collect the allantoic fluid and use it as a crude vaccine solution in a stainless steel container, store it in a cold room in the temperature range of 8 ℃ ± 2 ℃, avoiding freezing and avoiding freezing. Then, the sucrose density gradient centrifugation using a centrifuge is concentrated and purified to remove most of the culture medium components and buffer components unnecessary for the vaccine, thereby eliminating vaccine side reactions. The purified virus is inactivated by degrading it with chemicals such as ether, formalin and β-propiolactone to eliminate infectivity, and then adjusted to a prescribed concentration to prepare a vaccine stock solution.
If good growth is possible, a vaccine (1 mL) for one adult can be made from the soy liquor of two embryonated chicken eggs, so several thousand crude vaccine concentrates will be introduced into 10 to 20 L stainless crude vaccine concentrate. Since the amount is about 10,000, it is important to control the activity of the crude stock solution of the vaccine (including death and mutation occurrence due to uncontrolled growth). Thorough temperature control is required to maintain the effectiveness and safety of viruses that have not been inactivated. In order to ensure at least the activity of not killing the virus, it is necessary to keep the temperature at which the temperature does not freeze and does not reach the temperature at which the growth is activated above 10 ° C., depending on the virus type.
Vaccines are aseptic preparations (sterile injections), and vaccine manufacturing facilities are required to have requirements for manufacturing aseptic preparations and biological preparations. In particular, in the step before the inactivation treatment for eliminating the infectious property, leakage of the target vaccine strain becomes a serious problem while avoiding contamination of various bacteria into the culture environment of the target vaccine strain.
The manufacturing process of the vaccine manufacturing facility consists of a "microorganism culture area" where live microorganisms that proliferate microorganisms exist, a "purification area" for extracting vaccine active ingredients from the microorganisms, a "manufacturing area" after the inactivation step, and a "formulation". The "area" must be clearly demarcated. There are changing rooms and pass rooms dedicated to each area to prevent cross contamination. For example, although a centrifuge is used in the above purification, accidents in the purification area such as dispersion of crude vaccine concentrate due to failure of the centrifuge will not affect the "microorganism culture area" and "production area" by partitioning. It will be possible to recover with minimal cleaning. In addition, most of the time, a clean room is used to prevent contaminants such as bacteria in the air, but the cleanliness is generally made higher as the process proceeds from the "microbial culture area" to the downstream process.
In the production of influenza vaccine, when the crude vaccine stock solution is purified by a centrifuge, the crude vaccine stock solution needs to be maintained in a temperature range of 8 ° C ± 2 ° C.
This is also the case when passing through the above-mentioned “microorganism culture area” and “purification area”. However, in the "purification area", the purified liquid can be maintained in the temperature range of 8 ° C ± 2 ° C depending on the specifications of the centrifuge, but the centrifuge installation environment requires a room temperature of about 20 ° C, which is close to the temperature of a normal living room There is also. As a result, the temperature of the compartment (passroom) is maintained at a temperature range of 8 ° C ± 2 ° C, and the intermediate temperature between the "cooling room" and the "purification area" is maintained. The room temperature cannot be maintained within the range.
For this reason, in the "purification area" and the "compartment" in front of it that are clean rooms, put the crude vaccine stock solution storage container in a cooler box soaked in ice water and maintain the temperature range while adding ice. It was being moved.

  Further, as a device that uses a Peltier element for keeping cold, the device of the following Patent Documents 1, 2, and 3 and a device of Patent Documents 4 and 6 that keeps vaccines cold, and a refrigerator that uses a Peltier device as a device of Patent Document 5 The device is known.

Patent Document 1 discloses a temperature processing device using a Peltier device that also serves as freezing, refrigerating, thawing, and warming of food and the like.
On the cooling side, the device has a heat transfer surface that is installed in a casing formed of a heat insulating layer, faces the storage space, and is in thermal communication with the Peltier element.
On the other hand, the apparatus includes, on the heat radiation side, a heat exchange base body joined to the Peltier element, and a frame body that covers the heat exchange base body and circulates a liquid heat transfer medium inside.
The frame body includes a dispersion member in which a plurality of dispersion holes for ejecting a heat transfer medium are formed on the heat exchange substrate. The dispersion member partitions the frame into a first space and a second space. Then, the heat transfer medium supplied to the frame is diffused in the first space, sprayed vertically from the respective dispersion holes to the heat exchange substrate, and the heat transfer medium colliding with the heat exchange substrate diffuses in the second space. It is designed to be discharged. This device uses pure water or brine antifreeze as the heat transfer medium so that it can be used by switching between a freezer and a refrigerator. In the case of a freezer, the built-in items are frozen.

  Patent Document 2 discloses a temperature control / heat retention device for drinking water. In this device, the cooling surface of the Peltier element is joined to a concave plate dish, and a container containing drinking water is placed on the plate dish. Cooling the drinking water by heat transfer (heat transfer) through the container. is doing. On the other hand, a heat sink is bonded to the heat radiation side of the Peltier element and is air-cooled by a blower.

  Patent Document 3 discloses an apparatus in which a gel-like heat transfer substance that fits the outer shape of a drink container is interposed between the drink container and the Peltier element to improve heat transfer performance. This one also has a heat sink on the heat radiation side and is air-cooled.

  Patent Document 4 discloses a cooling device mainly used for storage and transportation of vaccines. In this product, the container for storing the vaccine is submerged in a casing filled with water, and the water at the top of the casing is cooled so that dense water at 4 ° C gathers near the bottom of the casing. . As a result, the container in the refrigerator is maintained at around 4 ° C, which is optimal for storing vaccines. It is said that freezing of the filled water, which is a refrigerant, is prevented by stopping the refrigerating cycle composed of the cooling unit by the freezing detection sensor.

  Patent Document 5 discloses a storage room for catering foods. In this device, the inside of the storage is divided by a partition plate, one room is cooled by a Peltier element, and the other room is heated by a heater to keep cold food and hot food in parallel. The Peltier element is provided on the ceiling in the refrigerator, and a heat absorbing fin is provided below the Peltier element. The inside of the refrigerator is cooled through the fins. On the other hand, the heat radiation side of the Peltier element is air-cooled by a fan. The heat balance on the hot side and the heat side on the cold side must be the same, and either of them is a device in which the temperature varies.

Japanese Patent No. 3202604 JP, 9-61032, A JP, 2004-212029, A Special table 2012-533050 gazette Utility model registration No. 3026834

Conventionally, in a facility that manufactures biological products, when moving a container that stores contents (culture) in which the activity greatly depends on temperature, such as a target microorganism, in two divided areas, keep it cool. For cooling the container as it is, the water jacket-like heat insulating container may be cooled with ice water, and the sterilization of water and ice used for the cooling and the disposal process are complicated. In addition, cooling work such as ice throwing and cooling temperature control were performed manually.
Such water or ice is not running water, but is a free water that collects a certain amount of water and comes into contact with the air, and free chlorine in the clean water is also released, which becomes a hotbed for various bacteria and causes contamination to the culture. obtain. In addition, it may be prohibited to directly dispose of the water used for keeping a particular culture cold. For example, in the case of influenza vaccine, crude crude solution is not inactivated to eliminate the infectivity of the virus, and if it leaks into the water used for cold storage without accidentally understanding it, there is a risk of infection to workers. Therefore, such disposal prohibition measures may be taken.
Therefore, in the field of biotechnology, in the work inside the building, such as clean rooms, where the entry of germs is disliked, sterilized water can be used as the water brought into the interior, or even the discarded sterilized water can be discarded. May be sterilized.
Along with the difficulty of controlling the cooling temperature with ice water, these treatments are labor-intensive for workers, increase the attention load on workers who must be aware of infection from cultures stored in containers, and It will cause an accident.
In addition, in the technique of Patent Documents 2, 3, and 5 in which the container is directly cooled, the temperature of the cooling mechanism is directly transmitted to the container due to the heat transfer, and the temperature change becomes severe because there is no buffer. I will end up. When the Peltier element is rapidly cooled by the temperature control, the liquid temperature in the container may vary.
In Patent Documents 1 and 4, there is little consideration for freezing of water, and it easily freezes due to a malfunction of the freezing sensor, and influenza virus vaccine, etc., inactivated vaccines other than Japanese encephalitis, rabies, hepatitis A, and rotavirus are produced. Causes killing of the vaccine, which loses the activity of the crude vaccine stock solution.

  Accordingly, the present invention relates to a cold stock solution of a vaccine, a stock solution of a vaccine, a cold storage of a container containing a liquid containing cultured microorganisms such as virus strains, and an object thereof is to provide a cold storage unit capable of reducing the complexity of the work related thereto. And

(1) The cold preservation unit of the present invention is a cold preservation unit that heats and conveys a container containing a liquid containing cultured microorganisms and the like, and the cultured microorganisms and the like are predetermined for cultivation for the purpose of medical use. , Bacteria, cells, and viruses, which are present alone or together with other microorganisms, and cover the whole of the container or the whole other than the upper lid and retain a space around the container. A wagon having a storage chamber, a cooling unit that is adjacent to the storage chamber with a part of the wagon and cools the space air in the storage chamber, and a temperature detection unit that detects temperature information including the space air temperature of the storage chamber. And a control unit that controls the cooling unit to keep the temperature in the storage chamber at a predetermined temperature based on the temperature information obtained from the temperature detection unit, and the cooling unit is a boundary wall with the storage chamber. Installed along Provided on the heat dissipation side of the Peltier element, a Peltier element having a heat transfer surface that is in thermal communication with the Peltier element and extends to the storage chamber side or a heat transfer surface of the Peltier element itself. And a suction fan and a blower fan provided on a boundary wall between the cooling unit and the outside of the wagon.

(2) In such a refrigerating unit, the liquid containing the cultured microorganisms is influenza HA, four kinds of mixture (DPT-IPV), three kinds of mixture (DPT), two kinds of mixture (DT), adult D, tetanus. , A crude vaccine solution of the inactivated vaccine which is hepatitis B, and a vaccine stock solution, and it is preferable that the cold preservation temperature of the air in the storage chamber be in the range of 8 ° C. ± 2 ° C.
(3) The inactivated vaccine containing the cultured microorganisms is HPV, inactivated polio (IPV), hib, Streptococcus pneumoniae-binding type (7-valent, 13-valent), Streptococcus pneumoniae (23-valent) And a crude crude solution of a rotavirus live vaccine, and a vaccine stock solution, and the one in which the space air cold temperature of the storage chamber is in the range of 6 ° C. ± 2 ° C. is preferable.
(4) Further, there are a plurality of the containers, and the inside of the wagon is partitioned into a plurality of storage chambers by partition plates so as to individually store the containers, and each of the storage chambers is provided with a cooling unit. Those that are preferable.

(5) Further, it is preferable that the cooling units are provided near both ends of the wagon so as to sandwich the container.

(6) Further, it is preferable that an opening / closing ceiling door is provided in order to open the upper side of the wagon storage chamber, and the ceiling door is provided with a lid for accessing the inside of the container.

(1) In the cold insulation unit of the present invention, the cold insulation jacket of the container is air and does not require any water for cooling. Therefore, it is not necessary to treat the cooling water used for cooling and contacting the container. In addition, by taking into account dew condensation, etc., and eliminating free water in which various bacteria easily propagate, contamination can be prevented to the maximum. Further, since no water is used, the total weight can be reduced and the transportation becomes easy.

(2) In such a refrigeration unit, when passing through the compartments of “microorganism culture area” and “purification area”, if the centrifuge installation environment in the “purification area” requires a room temperature of about 20 ° C., influenza HA , 4 kinds of mixture (DPT-IPV), 3 kinds of mixture (DPT), 2 kinds of mixture (DT), adult D, tetanus, crude vaccine of inactivated vaccine of hepatitis B, cold container for cold stock solution The keeping temperature of air in the storage room can be kept in the range of 8 ℃ ± 2 ℃. As a result, it is possible to keep the temperature at which the activity of not killing the virus is secured at a minimum, the temperature at which the virus does not freeze, and the temperature at which the growth does not reach the activation temperature above 10 ° C. can be maintained.
(3) When passing through the compartments of the “microorganism culture area” and the “purification area”, if the centrifuge installation environment in the “purification area” requires room temperature of about 20 ° C., HPV, inactivated polio (IPV) ), Hib, pneumococcal binding type (7-valent, 13-valent), pneumococcal (23-valent) inactivated vaccine and rotavirus live vaccine vaccine crude stock solution, storage room for keeping containers containing cold stock solution cold The space air cooling temperature can be kept within the range of 6 ℃ ± 2 ℃. As a result, it is possible to keep the temperature at which the virus is not killed at a minimum, the temperature is not frozen, and the temperature is not higher than 8 ° C. at which the growth is activated.
(4) Further, there are a plurality of the containers, and the inside of the wagon is partitioned into a plurality of storage chambers by partition plates so as to individually store the containers, and each of the storage chambers is provided with a cooling unit. In this case, it is easy to control the temperature inside the storage chamber.

(5) When the cooling units are provided near both ends of the wagon so as to sandwich the container, it is easier to control the temperature in the storage chamber.

(6) Further, an opening-and-closing type ceiling door is provided to open the upper side of the storage room of the wagon,
When the ceiling door is formed with a lid for accessing the inside of the container, the inside can be easily cleaned.

FIG. 1 is a functional block diagram showing an embodiment of a cold insulation unit of the present invention. FIG. 2 is a schematic diagram showing an embodiment of the hardware configuration. FIG. 3 is a front view showing an embodiment of the cold insulation unit. FIG. 4a is a plan view of FIG. 3 and FIG. 4b is a side view of FIG. 4a, but with the door open. FIG. 5 is a diagram showing details of the cooling unit. FIG. 6a is a flowchart showing an example of the flow of processing of the control unit executed in the cooling unit, and FIG. 6b is an example of the database used in the cooling unit. 7a is a schematic plan view of a building including a clean room, and FIG. 7b is a schematic front view of the clean room. Fig. 8a is a front view showing another embodiment of the cold insulation unit, and Fig. 8b is a view corresponding to the side view of Fig. 8a and showing a state where the ceiling door is opened.

<First Embodiment>
"1. Outline of the cooling unit"
An outline of a cold storage unit according to an embodiment of the present invention will be described with reference to FIG. The cold preservation unit 1 is a vaccine crude of an inactivated vaccine which is a predetermined influenza HA, four kinds of mixture (DPT-IPV), three kinds of mixture (DPT), two kinds of mixture (DT), adult D, tetanus, and hepatitis B. It is used to convey a stainless steel container 30 containing a stock solution and a vaccine stock solution in a clean room 31 (see FIG. 7b). What is stored in this stainless steel container 30 is a cultivated microorganism, and the cultivated microorganism and the like include predetermined bacteria, cells, and viruses that are cultivated for the purpose of medical use, and they exist alone. Or it is a liquid that is present with other microbes.
The cold insulation unit 1 includes a wagon 2 that has a storage chamber 20 that covers the entire container 30 except the upper lid and has a space around it, and a part of the wagon 2 is adjacent to the storage chamber 20 and the storage chamber 20. Based on the cooling unit 3 that cools the space air, the temperature detection unit 4 that detects temperature information including the space air temperature of the storage chamber, and the temperature information 4a acquired from the temperature detection unit, the temperature inside the storage chamber is determined. The cooling unit 3 is provided with a control unit 5 that performs PID control, for example, in order to keep the cooling unit at a predetermined temperature.
In FIG. 1, a block diagram showing the function of the control unit 5 on the right side is illustrated, and the description of the control unit 5 on the left side is omitted.

Here, Table 1 (Source: Biken Vaccine News, General Incorporated Foundation Osaka University Microbial Diseases Research Group / Mitsubishi Tanabe Pharma Corporation, January 2014) shows the types of vaccines and whether they are live vaccines or inactivated vaccines. Whether they show the storage of those vaccines. In addition, Table 1 also lists vaccines outside the scope of the present invention as reference examples.

  The cooling unit 3 includes a Peltier element 3a installed along a boundary wall (opposing plate 27b) with the storage chamber, a heat transfer surface that is electrically connected to the Peltier element 3a, and extends to the storage chamber side. A heat conductor 3b having a heat transfer surface facing the storage chamber 20 at the heat transfer surface of the Peltier element itself, an air-cooled exhaust heat section 6 provided on the heat radiation side of the Peltier element, and a wagon of the cooling section 3. It is composed of suction louvers 23a and 23b provided on a boundary wall (side wall 23c) with the outside and an outlet fan 6b.

Further, the control unit 5 obtains the temperature information detected by the temperature detection unit 4 as a measured temperature signal 4a which the temperature detection unit allocates to a current value of 4 to 20 mA and sends the temperature information, for example. Cooling obtained by calculating the applied DC current value 8a of the Peltier element based on the deviation between the target set temperature 8b input via the input part of the temperature indicator (hereinafter, input part 11) and the acquired measured temperature signal 4a The condition calculating means 8 and the operating means 9 for operating the Peltier element based on the applied DC current value 8a (cooling condition) obtained from the cooling condition calculating means. Here, the applied DC current value 8a of the Peltier element may be a variable value of the current value as the proportional control, or ON-OFF or the step value is controlled by the length of time as the proportional control over time. It may be a time value of the cooling operation time proportional control.
In the present embodiment, the left and right independent control is performed using the temperature detection units 4 and 4 and the left and right control units 5 and 5 corresponding to the left and right cooling units 3 and 3, but one temperature information 4a is used. The left and right control units 5 and 5 may be controlled based on the above.
Here, the "temperature information" is a concept including a value obtained by allocating and converting the temperature value detected by the temperature detection unit into a current value of 4 to 20 mA, a voltage value of 1 to 5 V, or the like.
The "cooling condition" is the amount of time for cooling operation of the Peltier element in a predetermined time, a value converted from the time, an amount indicating the degree of cooling including the temperature for cooling, and converted from that amount. It is a concept that includes values.
Further, in the present embodiment, the “temperature acquisition means” corresponds to step S1 of FIG. 6a described later, the “cooling condition calculation means” corresponds to step S2 of FIG. 6a, and the “operating means” corresponds to the step of FIG. 6a. S3 corresponds.

"2. Hardware configuration"
As shown in FIG. 2, the control unit 5 of this embodiment is realized almost entirely by a control circuit including a board device and wiring.
The control unit 5 allocates, for example, a 1-5V signal as an analog signal to send a temperature measurement signal, temperature information 4a (see FIG. 1) from the temperature detection unit 4 and a target set temperature 8b obtained from the input unit 11. The temperature acquisition means 7 for acquiring (see FIG. 1) is provided. The temperature acquisition means 7 is a circuit for inputting the temperature information 4a and the like.
Further, the control unit 5 controls the PID circuit corresponding to the temperature indicating controller, the proportional band of the PID circuit, and the time when the output by the proportional operation and the output by the integrating operation are equal to integrate the offset with time to eliminate the offset. : Integration time, time when the output by the proportional operation and the output by the differential operation related to the response speed to the fluctuation become equal: Proportion is set by the PID calculation condition input unit 17a (see FIG. 1) that accepts the setting of the three values of the differential time The cooling condition calculating means 8 is provided for calculating the cooling condition by calculating the band, the integral operation, and the differential operation.
Specified influenza HA, mixed four (DPT-IPV), mixed three (DPT), mixed two (DT), adult D, tetanus, crude vaccine concentrate of inactivated vaccine that is hepatitis B, vaccine concentrate In the case of the container 30, the P operation may be performed by setting the set temperature to 8 ° C. and the proportional band to 4 ° C.
Further, the control unit 5 modulates the pulse width of a pulse having a predetermined cycle based on the set value of the PID calculation condition input unit 17a, and the Peltier element 3a (see FIG. 1) receives a voltage with the modulated pulse width. It is provided with an operating means 9 as a so-called PWM control circuit for applying the voltage. The operating means 9 is a known one that digitally controls an analog signal from the temperature thermistor by a switching power supply so as to reach a set temperature.

In the above-described embodiment, the function shown in FIG. 1 is realized by forming a control circuit in an on-board device such as a relay or a temperature indicating controller, but a part or all of it is formed by a microcomputer-like circuit such as a sequencer. It may be realized by executing a program.
For example, the sequencer 10 which is a programmable logic controller PLC is a PLC in which a power supply circuit, a noise removal circuit, an analog output unit, etc. are packaged as a set component, and one circuit of equipment delivered by each customer or the whole facility is one. In the construction equipment to be produced, the sequencer 10 that can easily construct the equipment circuit of the dedicated machine is convenient, and the timer circuit and the temperature instruction adjustment can be performed as the ladder circuit by the predetermined application from the external terminal 12 such as the PC connected when the circuit is created. A PID control circuit or the like corresponding to the total can be freely set.
Further, the sequencer is a known one including a memory for storing the program 18, such as a ladder circuit, and an arithmetic unit that is connected to the memory via a bus line and executes the stored program.

"3. Cooling unit details"
As shown in FIG. 3, the wagon 2 is composed of a box body including a bottom plate 21, front and rear plates 22 and 22, and left and right side plates 23 and 23. The inner space of the wagon has a left and right partition plates 13 and 13 provided in the vicinity of a separation distance from the container 30 toward the left and right ends according to a distance between the center partition plate 15 and the container 30 which will be described later. Is provided upright as a diffusion plate, and is further divided into the room 14 of the cooling section and the storage room 20 by the opposing plate 27b of the box 27 forming the rooms 14 of the left and right cooling sections. Further, the storage chamber 20 is divided into left and right storage chambers 16, 16 by a central partition plate 15.
A large number of openings are formed in the left and right partition plates 13 for the passage of air between the cooling unit 3 and the storage chamber 20. For the left and right partition plates 13, for example, punching metal having many holes is used.
As shown in FIG. 4a, the chambers 14, 14 of those cooling sections are closed by top plates 24a, 24a. On the other hand, a ceiling door 24 is provided at the upper opening of the storage chamber 20 and can be opened and closed. One end of the ceiling door 24 is rotatably connected to the upper end of the front plate 22 by hinges 22a, 22a, and the other end is engageable on the rear plate 22 (see FIG. 3) side. Therefore, the cleaning work inside the storage chamber 20 is easy.
As shown in FIG. 3, the bottom plate 21, the front plate 22, the back plate 22, and the like are made of, for example, a heat insulating material such as a foaming resin having a stainless steel plate attached to the front and back. .
Further, on the lower surface of the bottom plate 21, for example, casters 21a are provided near the four corners thereof.

As shown in FIG. 4a, the ceiling door 24 is formed with two openings 24b and 24b, which communicate with the storage chambers 16 and 16, respectively. When the containers 30 and 30 are not put in the openings 24a and 24a, the lids 25 and 25 are covered. On the other hand, when the containers 30 and 30 are put in, the lid 25 removed from the opening can be placed on the lid holder 26 provided on the front plate 22 (see FIG. 3).
Further, a thermometer 19 is provided near the center of the ceiling door 24 near the center so that a worker can monitor the temperature near the center of the storage chamber 20. It is preferable that one thermometer 19 is provided for each of the left and right storage chambers 16, 16 partitioned by the central partition plate 15.
As shown in FIG. 4b, the left and right side plates 23, 23 are respectively formed with openings 23a, 23a which are suction gallery for taking in outside air, and these openings 23a, 23a are punching metal forming the gallery itself. It is closed by 23b and 23b, respectively. Boxes 27 and 27 (see FIG. 3) for housing the cooling units 3 and 3 are provided inside the openings 23a and 23a, respectively.
Further, an exhaust port 23c for exhausting gas is formed above the openings 23a. A blow-out fan 6b (see FIG. 3) for exhaust is provided at the exhaust port 23c.

  In the present embodiment, the diameter of the body of the container 30 (see FIG. 3) is, for example, 250 mm. As shown in FIG. 4a, the diameter of the opening 24b of the ceiling door 24 is larger than 250 mm, and the rubber packing 24c is provided on the inner surface of the opening. The container 30 can be inserted through the opening 24b. The outer peripheral surface of the body is in contact with the rubber packing 24c, and is made airtight or somewhat airtight so that cold air does not leak from the storage chamber 20. As a result, after cooling for about half a day after culturing, the growth of embryos of embryonated eggs is stopped and the animals are put into a state of asphyxia, and the allantoic fluid (allantoic fluid / virus is growing) of the embryos in the eggs is collected and used for vaccine. The crude undiluted solution is placed in a stainless steel container, and the container 30 divides the compartment between the “microorganism culture area” and the “purification area” in which it is stored in a cold room at a temperature range of 8 ° C ± 2 ° C while avoiding freezing and freezing. When passing through, even if the centrifuge installation environment in the “purification area” is about 20 ° C. at room temperature, the container 30 is stored in the storage room 20 in the “cold room” at the most downstream side of the “microorganism culture area”. At this time, the air in the cold room is filled around the body of the container to make it airtight. The air in this cold room has a temperature of 8 ° C ± 2 ° C and the absolute humidity is very low. Condensation on the wall can be prevented.

  Returning to FIG. 3, the box 27 includes a peripheral wall 27a that extends inward from the vicinity of the edge of the opening 23a, and an opposing plate 27b that is continuous from the inner end of the peripheral wall 27a and that faces the left and right partition plates 13. Become. The box 27 takes in outside air and entrains exhaust heat with the internal space (the storage chamber 20 including the partition plate 13 that is a diffusion plate) in which the cooled air of the wagon 2 circulates, so that the air in the box is sucked in. It separates from the space (room 14 of the cooling section) that is sucked from the louvers 23a 23b and led out to the outside by the blow-out fan 6b.

  As shown in FIG. 5, an opening is formed in the facing plate 27b, and the cooling surface of the Peltier element 3a is airtightly fitted in the opening and is arranged so as to face the storage chamber side. The cooling surface is provided with a heat conductor 3b such as a fin heat sink that is thermally conductive, and exposes the heat transfer surface toward the storage chamber 20 (see FIG. 3) through the opening. The cooling surface of the Peltier element 3a may be directly exposed through the opening without using the heat conductor 3b.

On the heat radiation side of the Peltier element 3a, an air-cooled heat exhaust unit 6 is provided. The heat dissipation portion 6 is coated with, for example, silicone-based grease on the heat radiation side surface of the Peltier element 3a, and is brought into close contact with the heat sink 6a without a gap. The heat released from the heat sink is discharged to the outside by the fan 6b for exhaust heat.
As shown in FIG. 3, the blow-out fan 6b exhausts the air in the box, so that the outside air enters the box from the punching metal 23b, which is a suction gallery. As a result, the air whose heat has been exchanged by the heat sink 6a is exhausted from the exhaust port 23c.
As the Peltier device 3a, the fan 3c, and the heat exhausting unit 6 of the cooling unit 3, known ones can be used.

Returning to FIG. 3, the temperature detection unit 4 is provided below the partition plate 13 on the right side of the drawing on the storage chamber 20 side. As the temperature detector 4, for example, a conventionally known one such as a thermocouple or a thermistor can be used.
It is also possible to arrange it above the partition plate 13 or in front of the center of the partition plate 13.

"4. Flowchart"
Next, a flowchart showing an example of the flow of processing of the control unit 5 will be described with reference to FIG. 6a.

(S1) The control unit 5 uses the temperature acquisition unit 7 to acquire the measured temperature signal 4a sent by the temperature detection unit 4 at a predetermined timing based on a clock signal generated in the device.
(S2) Then, the cooling operation time of the Peltier element is included based on the deviation between the measured temperature signal 4a obtained from the temperature acquisition means 7 and the target set temperature 8b previously input from the input unit 11 (see FIG. 1). The cooling condition 8a is obtained.
In this step S2, for example, the proportional band, the integration time, and the differential time input from the PID calculation condition input unit 17a are calculated at predetermined time intervals based on the deviation between the target set temperature 8b and the detected temperature signal 4a. The corrected cooling condition 8a for the operating means 9 is calculated and output.
In the case of P operation in which only the proportional band is set, the correction value based on the temperature difference may be stored in the data table 17 in advance. FIG. 6b shows an example of the data structure of the data table 17. In the data table 17, for example, a correction value based on the temperature difference 8c between the temperature information 4a and the target temperature 8b is stored for each target temperature 8b. For these parameters, an operator can input a target temperature or the like using a touch panel or an operation panel as the input unit 11.

(S3) Based on the obtained cooling condition 8a, the pulse width of the pulse having a predetermined period is modulated in the inverter circuit that outputs the DC current on the Peltier element side. A so-called PWM control is performed in which a voltage is applied to the Peltier element 3a with the pulse width.
For example, when the temperature difference is large, the value as the cooling condition 8a is large, and the voltage application time to the Peltier element is long. On the other hand, when the temperature difference is small, the value as the cooling condition 8a is small, and the voltage application time to the Peltier element is short. As a result, the temperature can be brought close to the target temperature early, and the temperature can be stabilized when the temperature approaches the target temperature.

  In the memory built in the control unit 5, the start timer time of the cooling operation start and the stop timer time of the operation stop can be input via the input unit 11 (see FIG. 1). The control unit 5 acquires time information from the built-in clock, and when it matches the input time, starts or stops cooling.

Next, the clean room will be described with reference to FIGS. 7a and 7b. The clean room 31 shown in FIG. 7a is a room that is dustproof to the same level as a clean room used in, for example, a chemical manufacturing factory, a semiconductor device manufacturing factory, a food factory, etc., and a HEPA filter is used to obtain highly clean air. Are used. The temperature in the clean room is set to 22 ° C ± 3 ° C. The clean room 31 is divided into a working room 34a and a cold room 34b which are partitioned by a wall.
In the clean room 31, as shown in FIG. 7b, the HEPA filter 33 provided on the ceiling 32 enables the cleanliness of, for example, about class 1000 to be obtained. Further, a uniform downflow is adopted in which clean air is uniformly blown from the entire surface of the ceiling 32 of the clean room 31 and the blown clean air is blown vertically from the grating floor 31a as it is with a downward flow. In order to maintain high strength, etc., where there is a large load on the equipment, a grating floor is not used, but a normal non-perforated panel floor is used.
The equipment indicated by reference numeral 35 in the working chamber 34a is a centrifuge.

The cold room 34b is located on the most downstream side of the "microorganism culture area", in which a plurality of containers 30 are left standing on a shelf or the like, and two of them are transferred to the cold insulation unit 1. Alternatively, the cold room 34b may be the entrance of the "purification area" in the position of the pass room. The worker who has changed clothes in another dressing room picks up the cold insulation unit 1 from the work chamber 34a and moves to the work chamber 34a. Centrifuge 35 Remove the lid of the container 30 of the cold insulation unit 1 that has been moved to the machine side, insert the tube connected to the centrifuge 35 into the container 30, suck out the crude vaccine solution therein, and place it in the centrifuge 35. The solution is quantitatively introduced, the chemicals are mixed, and the mixture is centrifuged, and the treated solution in which the virus has been separated and concentrated and the buffer partial solution of the crude vaccine stock solution after the virus has been separated are separately received in different tanks. During this series of operations, the crude vaccine stock solution is kept cold at a temperature of 10 ° C. or lower as much as possible.
The container 30 that has received the treatment liquid from which the virus has been separated and concentrated from the centrifuge is similarly kept cold, exits the working chamber, and moves to the next inactivation treatment process together with the cold preservation unit.

<Other Embodiments>
The above examples have been described by taking the influenza HA vaccine as an example, but inactivation which is four-type mixture (DPT-IPV), three-type mixture (DPT), two-type mixture (DT), adult D, tetanus, hepatitis B. Also in the case of the vaccine crude stock solution and the container 30 containing the vaccine stock solution, the P operation may be performed by setting the set temperature to 8 ° C. and the proportional band to 4 ° C.
In addition, HPV, inactivated polio (IPV), hib, Streptococcus pneumoniae-binding type (7-valent, 13-valent), inactivated vaccine that is Streptococcus pneumoniae (23-valent) and crude vaccine of live vaccine of rotavirus, vaccine stock solution In order to keep the space air cooling temperature of the storage chamber that cools the container for storing 6 in the range of 6 ° C. ± 2 ° C., the P operation may be set at 6 ° C. and the proportional band at 4 ° C.

<Still Another Embodiment>
FIG. 8a is a plan view showing another embodiment of the cold insulation unit. Since the cold insulation unit 36 has many parts in common with the cold insulation unit 1 described above, the same parts are designated by the same reference numerals and the description thereof will be omitted.
The cold insulation unit 36 shown in FIG. 8a is provided with four openings 24b so that four containers 30 (see FIG. 1) can be stored. The cooling unit 3 is provided near the left and right side plates 22, 22. In addition, you may divide by one pair so that two pieces may be controlled by one pair.
Further, the ceiling door 24 of the cold insulation unit 1a can be separated by a separation line 24d communicating with the opening 24b, and as shown in FIG. 8b, can be opened so as to be united with a portion including the front plate 22 and to fall toward the front. You can Therefore, when the ceiling door 24 is opened, the container 30 can be taken out by pulling out toward the front plate 22 without the bottom portion being lifted up to the ceiling door 24.
In the present embodiment, the height of lifting to take out the container 30 was about 70 cm.

<Still Another Embodiment>
Although not shown, a fan may be provided between the left and right partition plates 13 (see FIG. 5) and the heat conductor 3b. The fan is provided near the center of the partition plate 13, sucks air near the center of the storage chamber 20, and makes the sucked air contact the heat transfer surface of the heat conductor. Then, the air cooled by contacting the heat transfer surface is turned inward while flowing vertically along the facing plate 27b, and flows into the storage chamber 20 from above and below the partition plate 13.
For this reason, the air flow in the storage chamber 20 flows inward in parallel to the bottom plate 21 and the ceiling door 24, then gently turns toward the vicinity of the center in the height direction, and finally along the central axis line. It flows toward the fan of the partition plate 13. Such air convection can be performed by one or both cooling sections 3.
Further, by arranging the cooling units 3 and 3 on the left and right sides so as to be offset from each other on the front side and the back side, an air flow that draws a circle in a plan view may be formed.

<Modification>
In the present embodiment, the opening 24b is formed in the ceiling door 24 (see FIG. 4a), and the upper portion of the container 30 is protruded to facilitate the hose connection of the device such as the centrifuge 35. May be stored. In the case of such a cold storage unit, it is difficult to work with the centrifuge 35 or the like, but it is convenient to simply move between cold rooms or move a long distance.
Further, the ceiling door 24 may be detachable.
Also, an odd number of containers 30 such as one, three or five may be placed. Further, the container may be made of a material other than stainless steel such as aluminum, iron and glass. Examples of the container 30 include a bottomed tubular body, a shoulder portion that smoothly reduces in diameter from an upper end of the body portion, a neck portion that extends upward from an inner end of the shoulder portion, and a neck portion of the neck portion. It consists of an upper lid that closes the opening. It should be noted that both the neck and / or the shoulder may not be formed.
Further, the temperature information 4a and 4a from the two temperature detection units 4 are averaged, and the proportional band, the integration time, and the differential time input from the PID calculation condition input unit 17a are calculated at predetermined time intervals based on the average value. Then, the corrected cooling condition 8a for the operating means 9 may be calculated to obtain the output.
The storage chamber may be kept warm by using the Peltier device 3a.
Further, a rechargeable battery may be mounted so that it can be moved freely beyond the range of the power cord 3c. In that case, if the rechargeable battery is provided on the lower surface of the bottom plate 21 of the wagon 2, the center of gravity is lowered, so that the movement of the wagon 2 is stabilized.

1 Cooling Unit 1a Cooling Unit 2 Wagon 3 Cooling Unit 3a Peltier Element 3b Heat Conductor 3c Power Cord 4 Temperature Detection Unit 4a Temperature Information 5 Control Unit 6 Heat Dissipation Unit 6a Heat Sink 6b Fan 7 Temperature Acquisition Unit 8 Cooling Condition Calculation Unit 8a Cooling Condition 8b Target temperature 9 Operating means 10 Sequencer 11 Input section 12 External terminal 13 Left and right partition plates (diffusion plates)
14 Left / Right Cooling Room 15 Central Partition Plate 16 Left / Right Storage Room 17 Data Table 17a PID Calculation Condition Input Section 18 Program 19 Thermometer 20 Storage Room 21 Bottom Plate 21a Caster 22 Front Plate, Back Plate 22a Hinge 23 Left and Right Side Plates 23a opening (sucking slurries)
23b Punching metal (sucking gully)
23c Exhaust port 24 Ceiling door 24a Top plate 24b Opening 24c Packing 25 Lid 26 Lid holder 27 Box 27a Peripheral wall 27b Opposing plate 30 Container 31 Clean room 31a Grating floor 32 Ceiling 33 HEPA filter 34a Working room 34b Cold room 35 Centrifuge

Claims (7)

A cold storage unit that heats and conveys a container containing a liquid containing cultured microorganisms,
The cultivated microorganisms and the like include predetermined bacteria, cells, and viruses that are cultured for the purpose of medical use, and they exist alone or together with other microorganisms,
A wagon that covers the entire container or the whole other than the upper lid, and has a storage chamber that holds a space around the container,
A cooling unit which is adjacent to the storage chamber in a part of the wagon and cools the space air in the storage chamber,
A temperature detection unit for detecting temperature information including the space air temperature of the storage chamber,
Based on the temperature information obtained from the temperature detection unit, consisting of a control unit for controlling the cooling unit to keep the temperature of the storage chamber at a predetermined temperature,
The cooling unit is a Peltier element installed along a boundary wall between the storage chamber and the cooling unit, and a heat transfer surface that is in thermal communication with the Peltier device and projects toward the storage chamber or a heat transfer surface of the Peltier device itself. Consisting of an air-type heat transfer part having a heat-dissipating part, an air-type heat exhaust part provided on the heat-dissipating side of the Peltier element, and a suction louver and a blower fan provided on the boundary between the cooling part and the outside of the wagon. ,
The inside of the wagon is partitioned into a plurality of storage chambers by a central partition plate so as to individually store the containers,
According to the distance between the central partition plate and the container , the storage chamber is near a distance away from the container toward the left and right ends, away from the boundary wall between the storage chamber and the cooling unit, and air is spread on both sides as a diffusion plate. A cold insulation unit characterized in that a partition plate having a large number of opening and closing openings is erected inside. The liquid containing the cultured microorganisms,
Influenza HA, mixed four (DPT-IPV), mixed three (DPT), mixed two (DT), adult D, tetanus, hepatitis B inactivated vaccine crude stock solution, vaccine stock solution,
The cold insulation unit according to claim 1, wherein the space air cold temperature of the storage chamber is set in a range of 8 ° C ± 2 ° C. The liquid containing the cultured microorganisms,
HPV, inactivated polio (IPV), hib, Streptococcus pneumoniae-binding type (7-valent, 13-valent), inactivated vaccine that is Streptococcus pneumoniae (23-valent) and crude vaccine of live vaccine of rotavirus, vaccine stock solution ,
2. The cold insulation unit according to claim 1, wherein the cold keeping temperature of the space air in the storage chamber is in the range of 6 ° C. ± 2 ° C. 3. In the storage chamber, a fan that causes an air flow to bring air into contact with the pneumatic heat transfer unit is provided between the partition plate having the multiple openings and the heat transfer unit , and near the center of the partition plate. It has been provided, et al.,
The cold insulation unit according to any one of claims 1 to 3. A plurality of the containers,
A cooling unit is provided in each of the plurality of storage chambers,
The cold insulation unit according to any one of claims 1 to 4, wherein the cooling unit is provided near both ends of the wagon so as to sandwich the container. In order to open the upper part of the storage room of the wagon, it is equipped with an openable ceiling door,
The cold insulation unit according to any one of claims 1 to 5, wherein a lid for accessing the inside of the container is formed on the ceiling door. A cold storage unit that heats and conveys a container containing a liquid containing cultured microorganisms,
The cultivated microorganisms and the like include predetermined bacteria, cells, and viruses that are cultured for the purpose of medical use, and they exist alone or together with other microorganisms,
A wagon that covers the entire container or the whole other than the upper lid, and has a storage chamber that holds a space around the container,
A cooling unit which is adjacent to the storage chamber in a part of the wagon and cools the space air in the storage chamber,
A temperature detection unit for detecting temperature information including the space air temperature of the storage chamber,
Based on the temperature information obtained from the temperature detection unit, consisting of a control unit for controlling the cooling unit to keep the temperature of the storage chamber at a predetermined temperature,
The cooling unit is a Peltier element installed along a boundary wall between the storage chamber and the cooling unit, and a heat transfer surface that is in thermal communication with the Peltier device and projects toward the storage chamber or a heat transfer surface of the Peltier device itself. An air-type heat transfer section having, an air-type heat exhaust section provided on the heat dissipation side of the Peltier element, and a cooling gallery and a suction fan and a blower fan provided on the boundary wall outside the wagon,
A plurality of the containers,
The inside of the wagon is partitioned into a plurality of storage chambers by a central partition plate so as to individually store the containers,
A cooling unit is provided in each of these storage chambers,
A cooling unit, wherein the cooling units are provided near both ends of the wagon so as to sandwich the container.

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