JP7108295B2 - Positive pressure control method for incubator and culture work system using this method - Google Patents

Description

The present invention relates to an incubator, particularly a mobile incubator that can appropriately control the temperature and humidity suitable for culturing, while stably maintaining a sterile state and a positive pressure state inside the culture chamber. of the positive pressure control method. The present invention also relates to a culture work system using a positive pressure control method for an incubator.

With recent developments in the field of regenerative medicine, culturing cells using an incubator is widely practiced. For cell culture, it is necessary to prepare a culture environment suitable for each cell, and the temperature and humidity conditions inside the incubator, or if necessary, carbon dioxide gas concentration, nitrogen gas concentration, etc. are adjusted. .

In order to adjust the temperature conditions inside the incubator, generally, a hot water heater or an electric heater is built in the room of the incubator, the door, the wall such as the shelf plate, and the room temperature is adjusted by the radiant heat from the wall surface. In addition, in order to adjust the humidity condition inside the incubator, generally a humidifying tray is provided inside the incubator to store water, and the room humidity is adjusted by natural evaporation of the stored water. On the other hand, in order to adjust the carbon dioxide gas concentration and nitrogen gas concentration inside the incubator, generally, a carbon dioxide gas concentration sensor, a nitrogen gas concentration sensor, and a supply route from the carbon dioxide gas cylinder or nitrogen gas cylinder are provided. is being adjusted. Moreover, in addition to these, there are cases where air is stirred by an indoor fan in combination to achieve uniformity.

However, indoor temperature and humidity control by radiant heat from walls and air agitation tends to cause uneven temperature and humidity in the room. In particular, since the humidity inside the incubator is high, when the temperature and humidity are not uniform, there is a problem that dew condensation is likely to occur partially.

Therefore, in the incubator of Patent Document 1 below, general temperature adjustment is performed by turning on and off the indoor heater, the door heater, and the stage heater, and when the internal humidity rises and condensation tends to occur, the humidifying tray is exposed. It has been proposed to fine-tune the area of the water surface to improve the accuracy of humidity regulation.

On the other hand, conventional incubators could not guarantee grade A (Ministry of Health, Labor and Welfare, aseptic drug manufacturing guidelines) in line with GMP (Good Manufacturing Practice). This is because the air pressure could not be maintained higher than the external environment to maintain grade A sterilization on the inside. Furthermore, water is supplied from the outside as the water stored inside the incubator evaporates.

Therefore, in the incubator of Patent Document 2 below, it is proposed to provide a filter on the water supply path from the outside of the incubator to the humidifying tray. On the other hand, in Patent Document 3, the inventors of the present invention can supply high-temperature sterilized steam from the outside and control the air supply device and the exhaust device to maintain the air pressure inside the culture chamber higher than the external environment. Suggested an incubator.

JP 2008-005759 A JP 2011-160672 A Japanese Patent Application No. 2017-096398

By the way, in the incubator of Patent Document 1, although the occurrence of dew condensation can be reduced, there is a problem that the temperature and humidity in the room tend to be non-uniform. Further, in the incubator of Patent Document 2, although sterilization of the water stored in the humidifying tray can be ensured, there is also the problem that the temperature and humidity in the room tend to be non-uniform. Furthermore, neither of the patent documents 1 and 2 described above can maintain the air pressure inside the culture chamber higher than the external environment.

On the other hand, the incubator of Patent Document 3 is superior in that the water vapor supplied from the outside can be sterilized and the air pressure inside the culture chamber can be made higher than the external environment. In this incubator, a microcomputer linked with a pressure sensor controls an air supply device and an exhaust device.

On the other hand, a cell culture system in the field of regenerative medicine consists of an isolator that performs operations such as pretreatment of the cultured material, and a plurality of incubators that are connected to this isolator and accommodate the treated cultured material. The incubator containing the object to be cultured is separated from the isolator, moved to the culture station, and cultured for a predetermined time.

Such a mobile incubator preferably has facilities that can operate with a minimal amount of rechargeable batteries or the like without connecting power lines or the like. Therefore, in order to maintain the air pressure inside the culture chamber higher than that of the external environment, it is desired to control by a simpler mechanism instead of a large-scale combination of an air supply device and an exhaust device.

Therefore, the present invention addresses the above-mentioned problems, can maintain uniform temperature and humidity inside the culture chamber, and even when the inside of the culture chamber is sterilized to grade A, this sterile environment To provide a positive pressure control method for an incubator capable of always maintaining the internal air pressure higher than the external environment by a simple mechanism and a culture work system using this method.

In order to solve the above problems, the inventors of the present invention, as a result of intensive research, found that by combining the opening areas of the air supply port and the air exhaust port and the air supply fan, the air supply fan can respond to the static pressure fluctuation inside the culture chamber. The present invention was completed by utilizing the fact that the air volume fluctuates.

That is, according to the description of claim 1, the positive pressure control method for an incubator according to the present invention is as follows:
A culture chamber (22) having an air supply port (24) and an exhaust port (25), temperature control means for adjusting the temperature of the air inside the culture chamber, and humidifying the air inside the culture chamber. In an incubator (20) comprising humidifying means (50),
The air supply port includes an air supply means (30) for supplying air from the external environment to the interior of the culture chamber, and the air supply means includes an air supply fan (32) and a storage battery for driving the air supply fan (32),
Since the opening area of the air supply port is larger than the opening area of the exhaust port, the fan motor of the air supply fan autonomously operates along the air volume-static pressure curve to reduce the air pressure inside the culture chamber from that of the external environment. can be maintained at a high predetermined static pressure,
When the air pressure in the culture chamber rises due to the humidification of the culture chamber by the humidifying means, the air volume of the air supply fan decreases along the air volume-static pressure curve, resulting in a positive pressure state inside the culture chamber. is maintained at the predetermined static pressure,
When the humidification of the culture chamber by the humidifying means is stopped and the air pressure in the culture chamber decreases, the air volume of the air supply fan increases along the air volume-static pressure curve, and the air volume inside the culture chamber increases. The pressure state is maintained at the predetermined static pressure.

Further, according to the description of claim 2, the present invention provides a positive pressure control method for an incubator according to claim 1,
Fluctuations in the air pressure in the culture chamber are characterized by adjustment in response to variations in carbon dioxide concentration and nitrogen gas concentration in the culture chamber, in addition to humidification or suspension of humidification in the culture chamber by the humidifying means.

Further, according to the description of claim 3, the present invention provides a positive pressure control method for an incubator according to claim 1 or 2,
The humidifying means includes compressed gas generating means for generating compressed gas, water supply means for supplying water, a mixed gas/liquid regulator for adjusting a mixed gas/liquid mixture of the compressed air and the water, and a vaporizer equipped with a heating element for vaporizing gas-liquid to generate water vapor,
The vapor generated by the vaporizer is directly supplied to the air circulated by the circulation means in a sterilized state without passing through an air filter.

In addition, according to the description of claim 4, the culture work system according to the present invention is:
An isolator (10) capable of maintaining a sterile state, and a plurality of incubators (20, 20a to 20h) connectable to the isolator and capable of maintaining a sterile state and transportable,
An operation necessary for culture is performed inside the isolator to prepare an object to be cultured, the object to be cultured is accommodated inside the incubator connected to the isolator, the incubator is separated from the isolator, and the separated incubator is transported to a culture station (110) located away from the isolator, and a plurality of incubators are stored at the culture station to culture the culture object,
The plurality of incubators are controlled by the positive pressure control method for an incubator according to any one of claims 1 to 3 in the moving stage to the culture station and/or the culturing stage.

According to the above configuration, the incubator used in the positive pressure control method for an incubator according to the present invention has the incubation chamber, the temperature control means, and the humidification means. The culture chamber has an air supply port and an air exhaust port. The temperature control means controls the temperature of the air inside the culture chamber. The humidifying means humidifies the air inside the culture chamber. The air inlet has air supply means for supplying air from the external environment to the interior of the culture chamber. The air supply means includes an air supply fan and a storage battery for driving the air supply fan.

In such an incubator, the opening area of the air supply port is larger than the opening area of the exhaust port, so that the air pressure inside the culture chamber is adjusted by autonomous operation along the air volume-static pressure curve of the fan motor of the air supply fan. A predetermined static pressure higher than the external environment (positive pressure state) can be maintained. While the air pressure inside the culture chamber is maintained at a predetermined static pressure in this way, the air pressure inside the culture chamber may fluctuate.

For example, the air pressure in the culture chamber rises due to humidification of the culture chamber by the humidifying means. In this case, the air volume decreases along the air volume-static pressure curve of the fan motor of the air supply fan, and the amount of air supplied to the culture chamber decreases. As a result, the air pressure in the culture chamber is reduced and the positive pressure state is maintained at a predetermined static pressure. On the other hand, the air pressure inside the culture chamber drops due to another factor. In this case, the air volume increases along the air volume-static pressure curve of the fan motor of the air supply fan, and the volume of air supplied to the culture chamber increases. As a result, the air pressure in the culture chamber increases and the positive pressure state is maintained at a predetermined static pressure.

Therefore, according to the above configuration, the temperature and humidity inside the culture chamber can be maintained uniform, and even when the inside of the culture chamber is sterilized to grade A, it is possible to easily maintain this sterile environment. It is possible to provide a positive pressure control method for an incubator that can always maintain the internal air pressure higher than the external environment by such a mechanism.

Further, according to the above configuration, fluctuations in the air pressure in the culture chamber may be caused by changes in the concentration of carbon dioxide gas or nitrogen gas in the culture chamber, in addition to the humidification or suspension of humidification of the chamber by the humidifying means. Even in this case, it can be dealt with by changing the air volume along the air volume-static pressure curve of the fan motor of the air supply fan in the same manner as described above.

Further, according to the above configuration, the humidifying means includes the compressed gas generating means, the water supplying means, the mixed gas-liquid regulator, and the vaporizer. The gas-liquid mixture adjuster mixes the compressed gas generated by the compressed gas generating means and the water supplied by the water supply means to generate a gas-liquid mixture. The vaporizer has a heating element and vaporizes the generated gas-liquid mixture to generate steam. In this way, the water vapor generated in the vaporizer is supplied directly into the air circulated by the circulation means without passing through an air filter and in a sterile state .

According to such a humidifying means, the temperature and humidity inside the culture chamber can be kept uniform, and dew condensation does not occur inside the culture chamber. Also, the steam generated by the vaporizer does not adversely affect the sterile environment inside. On the other hand, the water vapor supplied to the inside of the culture chamber by such a humidifying means is a mixed gas of compressed gas and vaporized water, and changes the static pressure inside the culture chamber. Even in such a case, according to the above configuration, the positive pressure state in the culture chamber can be maintained at a predetermined static pressure.

Moreover, according to the above configuration, the culture work system according to the present invention includes an isolator and a plurality of incubators. The isolator can be kept sterile. A plurality of incubators can be connected to the isolator to maintain a sterile state, and can be separated from the isolator and transported to the culture station. These incubators are controlled by the positive pressure control method for the incubators according to the above configuration during both the transfer stage to the culture station and the culture stage, or during the transfer stage or the culture stage.

This culture work system is operated as follows. First, an object to be cultured is prepared by performing necessary operations for culture inside the isolator. Next, the object to be cultured is placed inside an incubator connected to an isolator. Then disconnect the incubator from the isolator. Next, the separated incubator is transported to a culture station located away from the isolator. Next, a culture station stores a plurality of incubators and cultures the object to be cultured.

Therefore, according to the above configuration, the temperature and humidity inside the culture chamber can be maintained uniform, and even when the inside of the culture chamber is sterilized to grade A, it is possible to easily maintain this sterile environment. It is possible to provide a culture work system that utilizes a positive pressure control method for an incubator that can always maintain the internal air pressure higher than the external environment by such a mechanism.

It should be noted that the reference numerals in parentheses of the respective means above indicate the correspondence with specific means described in the embodiments to be described later.

1 is a plan view showing the overall configuration of an embodiment of a culture work system according to the present invention; FIG. FIG. 2 is a schematic side view showing the configuration of an incubator used in the culture work system of FIG. 1; 3 is an air volume-static pressure curve of a fan motor used in the incubator of FIG. 2. FIG. FIG. 3 is a cross-sectional view showing an embodiment of a vaporizer included in the humidifying device of FIG. 2;

A positive pressure control method for an incubator and a culture work system according to the present invention will be described below by way of embodiments. FIG. 1 is a plan view showing the overall configuration of one embodiment of a culture work system according to the present invention. In FIG. 1, an isolator 10 is installed inside a clean room 100 (on the left side in the figure), and an incubator 20 is connected thereto. The inside of the clean room 100, the inside of the isolator 10 (inside the chamber), and the inside of the incubator 20 (inside the culture room) are sterilized in advance to ensure a sterile state. In particular, the inside of the chamber of the isolator 10 and the inside of the culture room of the incubator 20 are sterilized to grade A conforming to GMP.

In addition, a culture station 110 that stores a plurality of incubators is provided inside the clean room 100 at a position away from the isolator 10 (on the right side in the figure). This culture station 110 stores a plurality of incubators 20a to 20h containing culture objects. The incubator 20 connected to the isolator 10 in FIG. 1 is separated from the isolator 10 and transported to the culture station for storage (broken line arrow in the figure) when the operation of accommodating the culture material is completed.

In such a configuration, an operator (not shown) inside the clean room 100 performs operations necessary for culturing from the outside of the isolator 10 through working gloves, and a culture solution for culturing cells is poured into a Petri dish or the like. filling. A petri dish filled with a culture solution is accommodated inside the incubator 20 from inside the isolator 10 .

The incubator 20 containing petri dishes filled with the culture solution is separated from the isolator 10 and transported to the culture station 110 by an operator (not shown) inside the clean room 100 . The positive pressure state inside the incubator 20 is maintained during this transfer as well. Next, the plurality of incubators 20a to 20h transported to the culture station 110 are stored in the culture station 110, and the cells in the petri dishes housed therein are cultured. During this culture, the positive pressure state inside the incubator 20 is maintained. Also in this embodiment, the incubator 20 after being transported from the isolator 10 to the culture station 110 may be equipped with necessary equipment such as distribution lines and air supply/exhaust pipes.

Next, the configuration of the incubator used in the present invention will be described. As described above, the inside of the chamber of the isolator 10 and the inside of the culture room of the incubator 20 are sterilized to grade A conforming to GMP. Therefore, in order to maintain the grade A state, the air pressure inside the isolator 10 and the incubator 20 is preferably maintained at a higher air pressure (positive pressure state) than the air pressure in the clean room 100 (which is defined as the external environment).

Maintaining a positive pressure within the chamber of isolator 10 is done in a conventional manner. That is, it can be easily performed by controlling the air supply device and the exhaust device by means of a microcomputer interlocked with the pressure sensor. On the other hand, a positive pressure state can be maintained in the culture chamber of the incubator 20 by providing equipment similar to the isolator 10 . However, in a mobile incubator, it is preferable to use equipment that can operate with a minimal amount of rechargeable batteries without connecting power lines or the like.

FIG. 2 is a schematic side view showing the configuration of an incubator used in the culture work system. In FIG. 2, an incubator 20 includes a pedestal 21 with casters 21a placed on the floor, a culture chamber 22 mounted on the pedestal 21, and an air temperature inside the culture chamber 22. A temperature control device (not shown) to adjust, a humidification device 50 to humidify the air inside the culture chamber 22, a carbon dioxide gas concentration control device 60 to adjust the carbon dioxide gas concentration inside the culture chamber 22, and the culture chamber 22. and a circulation device (not shown) for circulating the air inside the culture chamber 22 . These apparatuses are also provided with various sensors for detecting the pressure, temperature, humidity, carbon dioxide gas concentration, nitrogen gas concentration, etc. inside the culture chamber 22 (none of them are shown). The carbon dioxide gas concentration control device 60, the nitrogen gas concentration control device 70, the circulation device, etc. may be installed as necessary.

The culture chamber 22 has an outer wall and an inner wall covered with a stainless metal plate, and a heat insulating material is filled between the outer wall and the inner wall to form a heat insulating wall. A heater (a part of the temperature control device) for heating the inside of the culture chamber 22 may be built in the heat insulating wall. A connection door 23 is provided on the front wall portion 22a (left side in the drawing) of the culture chamber 22 to airtightly connect with the isolator 10 and communicate with the inside. The structure of the connection door 23 is not particularly limited as long as airtight connection with the isolator 10 is possible.

An air supply port 24 for supplying air to the inside of the culture chamber 22 is opened in the upper wall portion 22b of the culture chamber 22, and an air supply device 30 is connected to the air supply port 24. As shown in FIG. An air supply duct 31 is connected to the air supply device 30, and a fan motor 32 and a HEPA filter 33 are provided in the conduit. On the other hand, an exhaust port 25 for exhausting the air inside the culture chamber 22 is opened in the bottom wall portion 22c of the culture chamber 22, and an exhaust duct 41 is connected to the exhaust port 25. As shown in FIG. In this embodiment, the opening area of the air supply port 24 is designed to be larger than the opening area of the exhaust port 25 (the reason will be described later).

The fan motor 32 of the air supply device 30 supplies the air inside the clean room 100 to the culture room 22 of the incubator 20 . At that time, the supplied air is further cleaned by the HEPA filter 33 . The capacity of the fan motor 32 is selected to have a predetermined maximum air volume and maximum static pressure in order to maintain the positive pressure inside the culture chamber 22 of the incubator 20 . The type of the fan motor 32 is not particularly limited, and may be of any type such as a propeller fan that is an axial flow fan, a sirocco fan that is a centrifugal fan, a turbo fan, or the like. It should be noted that in this embodiment, the incubator 20 does not use a distribution line to drive the fan motor 32 during both the movement stage and the culture stage from the isolator 10 to the culture station 110, or during the movement stage or the culture stage. It is supposed to be based on a storage battery (not shown) provided.

Although not shown in FIG. 2, the pipelines of the air supply duct 31 and the exhaust duct 41 may be provided with electromagnetic valves and catalyst layers, respectively. The catalyst layer is used to decompose the hydrogen peroxide gas released from the culture chamber 22 during aeration after the interior of the culture chamber 22 of the incubator 20 is decontaminated with hydrogen peroxide gas.

Next, using the incubator 20 having such a configuration, a positive pressure control method inside the culture chamber 22 will be described. As described above, the opening area of the air supply port 24 of the culture chamber 22 (corresponding to the pipe diameter of the air supply duct 31) is designed to be larger than the opening area of the exhaust port 25 (corresponding to the pipe diameter of the exhaust duct 41). ing. In such a state, the fan motor 32 is driven. FIG. 3 is an air volume-static pressure curve of the fan motor 32 used in the incubator 22. FIG.

In FIG. 3, point 4 on the vertical axis represents the maximum static pressure P4 of the fan motor 32, at which the air volume is zero. In this state, air is not supplied even if the fan motor 32 rotates due to the positive pressure inside the culture chamber 22 . On the other hand, point 5 on the horizontal axis represents the maximum air volume L5 of the fan motor 32, at which time the static pressure is zero. In this state, the air pressure inside the incubation chamber 22 is the same as the air pressure inside the clean room 100, and even if the fan motor 32 rotates, the inside of the incubation chamber 22 does not become a positive pressure.

In this embodiment, the inside of the culture room 22 of the incubator 20 must be maintained in a positive pressure state with respect to the inside of the clean room 100 . By making the inside of the culture room 22 sterilized to grade A into a positive pressure state, it is possible to prevent the air inside the clean room 100 lower than grade A from entering the culture room 22 . Here, the degree of positive pressure to be maintained inside the culture chamber 22 is not particularly limited, but +30 Pa may be maintained, for example.

In this embodiment, the positive pressure state can be maintained only by driving the fan motor 32 . Therefore, in this embodiment, the internal structure of the culture chamber 22, the number of objects (packing density), the opening area of the air supply port 24 and the opening area of the exhaust port 25 of the culture chamber 22, and the target positive pressure state can be used to determine the model and performance of the fan motor 32, or the set output.

In FIG. 3, point 1 is that the inside of the culture chamber 22 is maintained in a positive pressure state, the static pressure P1 is a target positive pressure (for example, +30 Pa), and the air volume L1 is increased from the air supply port 24 to the culture chamber. 22 , and the same amount of L1 is exhausted from the exhaust port 25 . In this state, if there is no internal change, a stable positive pressure state is maintained. However, cells are actually cultured inside the culture chamber 22, and changes in humidity, carbon dioxide gas concentration, nitrogen gas concentration, and the like occur.

Of these, the change in humidity inside the incubation chamber 22 is considered to be the most influential. The humidifier 50 operates to stably maintain the humidity conditions (culture conditions) inside the culture chamber 22 . Of the culture conditions in the culture chamber 22, it is important to maintain the temperature and humidity conditions stably. For example, the temperature condition must be maintained at 37±0.5° C., and the humidity condition must be maintained at a relative humidity of 95 to 100% RH. Therefore, water vapor is supplied from the humidifier 50 to the inside of the incubation chamber 22 under the control of a microcomputer linked with a humidity sensor.

In the present invention, the supply of steam is not particularly limited, and any method may be used as long as the sterile condition can be maintained. For example, as is conventionally practiced, a humidifying tray may be provided inside the incubator to retain water, and the room humidity may be adjusted by natural evaporation of the retained water. However, in this embodiment, as proposed in the above-mentioned Patent Document 3, a humidifying device 50 capable of ensuring sterilization of water vapor supplied from the outside is adopted. The humidifier 50 vaporizes a mixture of compressed air and water to generate and supply water vapor (details will be described later).

In FIG. 3, when the positive pressure state (set static pressure P1) set at point 1 is maintained, the humidity sensor detects a decrease in humidity. In response to this, the humidifying device 50 controlled by the microcomputer operates to generate water vapor and supply it to the interior of the culture chamber 22 . This water vapor is a mixed gas of compressed air and water vapor, and slightly increases the air pressure inside the incubation chamber 22 . In the air volume-static pressure curve of FIG. 3, when the static pressure rises from P1 to P2 (state of point 2), the air volume of the fan motor 32 decreases from L1 to L2.

As a result, the amount of air supplied to the inside of the culture chamber 22 is reduced, and the air pressure inside the culture chamber 22 is lowered. As a result, the air pressure inside the incubation chamber 22 converges to the set static pressure P1. The air pressure inside the culture chamber 22 is increased not only by the operation of the humidifier 50, but also by the supply of carbon dioxide by the carbon dioxide concentration control device 60 or the supply of nitrogen gas by the nitrogen gas concentration control device 70. also occur.

On the other hand, the air pressure inside the culture chamber 22 may drop. In this case, in the air volume-static pressure curve of FIG. 3, when the static pressure drops from P1 to P3 (state of point 3), the air volume of the fan motor 32 increases from L1 to L3. As a result, the amount of air supplied to the inside of the culture chamber 22 increases, and the air pressure inside the culture chamber 22 rises. As a result, the air pressure inside the incubation chamber 22 converges to the set static pressure P1.

As described above, in this embodiment, the temperature and humidity inside the culture chamber can be kept uniform, and even when the inside of the culture chamber is sterilized to Grade A, this sterile environment can be maintained. In order to do so, it is possible to provide a positive pressure control method for an incubator that can always maintain the internal air pressure higher than the external environment with a simple mechanism, and a culture work system using this method.

Here, the configuration of the humidifier 50 with which the positive pressure control method for the incubator according to the present embodiment can obtain more effects will be described. This humidifier 50 employs a specific humidification mechanism capable of supplying a very small amount of water vapor to the interior of the culture chamber 22 . The humidifier 50 is composed of a compressed gas generator, a water supply device, a mixed gas-liquid regulator, and a vaporizer. The gas/liquid mixture adjuster mixes water supplied from the water supply device and compressed air supplied from the compressed gas generation device to generate an atomized gas/liquid mixture (mist). A discharge part of the gas-liquid mixture adjuster is connected to the vaporizer to supply atomized gas-liquid mixture (mist) to the vaporizer. The vaporizer vaporizes the atomized gas-liquid mixture (mist) supplied from the gas-liquid mixture regulator to generate water vapor.

Here, the structure of the vaporizer employed in this embodiment will be described. FIG. 4 is a cross-sectional view showing one embodiment of a vaporizer included in the humidifying device. In FIG. 4, the vaporizer 51 includes a cylindrical outer tube 52 extending from one end 51a to the other end 51b, and a heating element 53 incorporated therein in parallel with the longitudinal direction of the outer tube 52. It consists of The outer cylindrical tube 52 is made of stainless steel. The heating element 53 has a heater 54 extending parallel to the longitudinal direction of the outer tube 52 . Between the inner peripheral surface of the outer cylindrical tube 52 and the heating element 53, a gap is provided through which the air-fuel mixture (mist) passes.

The heater 54 is installed at one outer peripheral end of the outer cylindrical tube 52 (on the one end 51a side of the evaporator 51) with a connection terminal 54b made of silicone rubber, and receives power from an electric wire 54a. Fever. The surface of the heater 53 that reaches a high temperature is covered with quartz glass 55 . Further, in this embodiment, the inner peripheral surface of the outer cylindrical tube 52 is also coated with quartz glass. The heater 54 is not particularly limited in its structure, and may be a rod-shaped heater or a coil-shaped heater. In addition, the surface of the heater and the inner peripheral surface of the outer cylindrical tube are not necessarily required to be coated with quartz glass, but in the present embodiment, dust generation is prevented and thermal efficiency is improved.

In such a vaporizer 51, an atomized gas-liquid mixture (mist) supplied from a gas-liquid mixture adjuster (not shown) is introduced from an inlet 56a opening at one end 51a of the vaporizer 51. It is introduced inside the vaporizer 51 . The gas-liquid mixture (mist) introduced into the vaporizer 51 is heated by the heat generating element 53 and passes through the gap between the outer tube 52 and the heat generating element 53 to open at the other end 51b of the vaporizer 51. move toward the exit port 56b. During this time, the water (liquid) in the mixed gas liquid is heated by the heating element 53 and vaporized into water vapor (gas), which is discharged from the discharge port 56b. It should be noted that the temperature of the discharged steam may be controlled while measuring the temperature of the steam at the outlet 56b with a temperature sensor.

By adopting the vaporizer 51 having such a configuration, for example, 1 g/hr. ~60g/hr. From the viewpoint of thermal efficiency, it is effective even for a very small amount of water supply, which is within the range of . As a result, in the present embodiment, the air supply device and the exhaust device can be controlled by the air volume-static pressure curve of the fan motor 32 without being controlled by a microcomputer.

Further, in the vaporizer 51, the gas-liquid mixture is heated by the heating element 53 to become high-temperature steam. In this embodiment, the temperature of the steam generated by the vaporizer 51 is controlled to 100° C. or even higher in order to ensure the sterilization of the steam. As a result, the steam generated by the vaporizer 51 is sterilized and can be directly supplied to the culture chamber 22 without passing through an air filter. Thus, a sterile environment inside the culture chamber 22 that maintains a grade A sterile environment is maintained.

10... isolator, 20, 20a to 20h... incubator,
21... Mounting frame, 21a... Caster,
22... Culture chamber, 22a... Front wall part, 22b... Upper wall part, 22c... Lower wall part,
23... Connection door, 24... Air supply port, 25... Exhaust port,
30... Air supply device, 31... Air supply duct, 41... Exhaust duct,
32... fan motor, 33... HEPA filter,
50 Humidifier 51 Vaporizer 51a, 51b End 52 Outer tube
53 Heating element 54 Heater 54a Electric wire 54b Connection terminal
55... Quartz glass, 56a... Inlet, 56b... Outlet,
60... Carbon dioxide gas concentration control device, 70... Nitrogen gas concentration control device,
100... Clean room, 110... Culture station.

Claims (4)

An incubator having a culture chamber having an air supply port and an exhaust port, temperature control means for adjusting the temperature of the air inside the culture chamber, and humidification means for humidifying the air inside the culture chamber,
The air supply port includes air supply means for supplying air from the external environment to the interior of the culture chamber, and the air supply means includes an air supply fan and a storage battery for driving the air supply fan,
Since the opening area of the air supply port is larger than the opening area of the exhaust port, the air supply fanAutonomous operation along the air volume-static pressure curve of the fan motormaintains the air pressure inside the culture chamber at a predetermined static pressure that is higher than the external environmentIt is possible,
When the air pressure in the culture chamber rises due to the humidification of the culture chamber by the humidification means, along the air volume-static pressure curveof the air supply fanWhile the positive pressure state inside the culture chamber is maintained at the predetermined static pressure by reducing the air volume,
Humidification of the culture chamber by the humidification means stops When the air pressure in the culture chamber drops, along the air volume-static pressure curveof the air supply fanA positive pressure control method for an incubator, wherein the positive pressure state inside the culture chamber is maintained at the predetermined static pressure by increasing air volume. A change in the air pressure in the culture chamber is caused by adjustment corresponding to a change in carbon dioxide gas concentration or nitrogen gas concentration in the culture chamber, in addition to humidification or suspension of humidification in the culture chamber by the humidifying means. Item 1. A positive pressure control method for an incubator according to item 1. The humidifying means includes compressed gas generating means for generating compressed gas, water supply means for supplying water, a mixed gas/liquid regulator for adjusting a mixed gas/liquid mixture of the compressed air and the water, and a vaporizer equipped with a heating element for vaporizing gas-liquid to generate water vapor,
3. The positive of the incubator according to claim 1 or 2, wherein the steam generated by the vaporizer is directly supplied to the air circulated by the circulation means in a sterilized state without passing through an air filter. pressure control method. An isolator capable of maintaining a sterile state, and a plurality of incubators connectable to the isolator and capable of maintaining a sterile state and transportable,
An operation necessary for culture is performed inside the isolator to prepare an object to be cultured, the object to be cultured is accommodated inside the incubator connected to the isolator, the incubator is separated from the isolator, and the separated incubator is transported to a culture station located away from the isolator, and a plurality of incubators are stored at the culture station to culture the culture object,
A culture work system characterized in that the plurality of incubators are controlled by the positive pressure control method for an incubator according to any one of claims 1 to 3 in the step of moving to the culture station and/or in the step of culturing. .

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