JP5462025B2 - Isolator, automatic cell culture device, and isolator sterilization method - Google Patents

Description

  The present invention relates to an isolator in which a working space that is a sterile environment is formed, and in particular, an automatic cell culture is performed in a sterile environment space as a sterile environment space that has been rendered sterile by a sterilization process. The present invention relates to an automatic cell culture apparatus.

  The work space formed inside the isolator is required to be in an aseptic environment in order to perform work such as cell culture. In order to ensure an aseptic environment in the work space, the isolator supplies clean air to the work space via a particle removal filter such as a HEPA filter, and also supplies air in the work space to the work space via the HEPA filter. A configuration that exhausts air is adopted. In addition, before starting work such as cell culture operation in the work space or after the work is completed, sterilization treatment is performed by supplying a sterilization gas such as hydrogen peroxide gas to the work space. After such a sterilization process is performed, the air containing the sterilization gas remaining in the work space is replaced with the external air supplied through the HEPA filter, thereby forming a sterile environment in the work space ( For example, see Patent Document 1).

JP 2009-226048 A

  In Patent Document 1, after a predetermined sterilization process is performed, a replacement process is performed in which air containing sterilization gas remaining in the work space is replaced with external air supplied through a HEPA filter. The air in the working space passes through the sterilizing substance removing filter 36 to remove the sterilizing substance, and is discharged (released) out of the working space. Therefore, the flow rate of air in the sterilizing substance removal filter 36 is set so that the concentration of the sterilizing substance contained in the air after passing through the sterilizing substance removal filter 36 is less than a predetermined reference value (for example, less than 1 ppm). There is a need to. As described above, since the flow rate of the air discharged to the outside of the work space is limited, there is a problem that the time required for the replacement process cannot be significantly reduced.

  In various devices handling such sterilized materials, specifications complying with various standards regarding safety with respect to the surrounding environment and the like are adopted, but in recent years, it has been required to further improve such safety. .

  Accordingly, an object of the present invention is to solve the above-mentioned problems, and in the work space formed inside the isolator, the isolator capable of shortening the time required for detoxifying the work space after sterilization processing It is an object of the present invention to provide a sterilization method, an isolator, and an automatic cell culture apparatus.

  Another object of the present invention is to provide an isolator sterilization method and isolator, and an automatic cell culture apparatus that can further improve the safety with respect to the surrounding environment in an isolator in which sterilization gas is handled.

  In order to achieve the above object, the present invention is configured as follows.

According to the first aspect of the present invention, the working space, the air supply portion that supplies gas to the working space, and the exhaust portion that exhausts gas from the working space, and circulates the gas in the working space. A sterilizing gas for supplying a sterilizing gas in which the sterilizing mist is vaporized by directly supplying the sterilizing mist into the working space , and a circulation filter and a circulation fan arranged in the middle of the circulation channel A supply device, and the circulation channel is made harmless to the first circulation channel used for gas circulation when sterilizing the work space and the sterilization gas after the sterilization process is performed. A second circulation channel used for gas circulation, and a channel switching unit that switches between the first circulation channel and the second circulation channel when the processing is performed; Harmless to disinfect the sterilization gas contained in the circulating gas placed in the circulation channel A device, and an external communication passage that communicates with the outside of the working space a working space, a filter disposed in the middle of the external communication passage, is disposed in the middle of the external communication passage, the work space through an external communication passage An exhaust fan for exhausting the gas in the outside, a pressure detecting means for detecting the pressure in the working space, and a negative pressure on the working space based on the detection result of the pressure detecting means when performing the sterilization process And an exhaust flow rate adjusting means for adjusting the exhaust flow rate of the gas by the exhaust blower .

According to a second aspect of the present invention, there is provided the isolator according to the first aspect, further comprising a decomposition device that is disposed in the middle of the external communication flow path and decomposes a sterilization gas contained in the exhausted gas.

According to the third aspect of the present invention, the sterilization gas is a gas containing hydrogen peroxide, and the detoxification device includes a catalyst for decomposing hydrogen peroxide into water and oxygen, and is disposed in the work space or in the circulation channel. The isolator according to the first aspect is further provided with a cooling device that cools and condenses the circulating gas.

According to the fourth aspect of the present invention, the work space in the isolator according to any one of the first to third aspects is an aseptic environment space sterilized by sterilization treatment, and is disposed in the aseptic environment space, Provided is an automatic cell culture apparatus further comprising a robot for performing cell culture operations in a sterile environment space.

According to the fifth aspect of the present invention, the sterilized gas supply means for supplying the sterilized gas into the sterile environment space and the pressure of the sterile environment space are kept positive when the cell culture is performed. The automatic cell culture apparatus according to the fourth aspect, further comprising: a supply flow rate adjusting means for cell culture processing for adjusting a supply flow rate of the sterilization gas by the sterilization gas supply means.

According to the sixth aspect of the present invention, the sterilization mist is directly supplied into the work space while the gas in the work space of the isolator is circulated through the circulation filter using the first circulation channel. As a result, the sterilization mist is vaporized, the sterilization gas is supplied, the work space is kept at a negative pressure, the work space is sterilized, and the supply of the sterilization gas is stopped after a predetermined time. In addition, the sterilized gas contained in the circulated gas by switching the first circulation channel to the second circulation channel and passing the gas through the detoxification device arranged in the second circulation channel. A method for sterilizing an isolator is provided.

  According to the present invention, the following effects can be obtained.

  First, in the step of supplying sterilization gas into the work space, the sterilization gas is circulated through the first circulation path while supplying the sterilization gas into the work space. Sterilization gas can be spread evenly.

  Further, in the detoxification process of the sterilizing gas remaining in the work space after the sterilization process is completed, the circulation path is switched from the first circulation path to the second circulation path and is provided in the second circulation path. The sterilizing gas detoxifying device can be used to detoxify the gas including the sterilizing gas circulated inside. In that case, in particular, since the detoxification device is arranged in the circulation system, there is no restriction on the concentration of gas remaining in the downstream path, and the circulation flow rate can be increased as much as possible. Therefore, the time required for detoxifying the sterilization gas remaining in the work space and the circulation path can be greatly reduced.

  Such detoxification treatment is performed in a system in which the work space and the circulation channel are substantially sealed with respect to the outside of the work space (that is, a closed system). Further improvement can be achieved.

The schematic diagram of the isolator concerning 1st Embodiment of this invention. Flowchart of sterilization process and detoxification process in the isolator of the first embodiment Model explanatory drawing of the state in which sterilization processing is performed in the isolator of the first embodiment Model explanatory drawing of the state in which the detoxification process is performed in the isolator of 1st Embodiment The schematic diagram of the isolator concerning 2nd Embodiment of this invention. Schematic diagram of an isolator according to a modification of the second embodiment Schematic diagram of an automatic cell culture device according to a third embodiment of the present invention.

  Embodiments according to the present invention will be described below in detail with reference to the drawings.

(First embodiment)
The main configuration of the isolator 10 according to the first embodiment of the present invention is shown in the schematic diagram of FIG. FIG. 1 shows a main configuration related to the sterilization process and the detoxification process of the sterilized gas after the sterilization process in the isolator 10 of the first embodiment, and the work arranged in the work space inside the isolator 10. The configuration of the device or the like is not shown.

  As shown in FIG. 1, the isolator 10 communicates with a substantially sealed work space 11, an air supply part 12 provided on the ceiling surface of the work space 11, and an exhaust part 13 provided on the floor surface. The circulation channel 14 for circulating the atmospheric gas in the work space 11 (hereinafter simply referred to as “gas”), and the gas in the work space 11 are arranged in the middle of the circulation channel 14. A circulation fan (circulation blower) 15 and a HEPA filter (circulation filter) 16 provided in the air supply section 12 in the circulation flow path 14 are provided.

  The work space 11 is formed using, for example, a stainless steel panel having excellent corrosion resistance and a clean specification, and a connecting portion is sealed using a seal member or the like in order to ensure the airtightness in the work space 11. The circulation channel 14 is formed as an air duct structure using a part of the ceiling panel, the side wall panel, and the floor panel of the work space 11. The air supply unit 12 is formed in the ceiling portion of the work space 11 according to the size of the HEPA filter 16. The exhaust part 13 is formed, for example, by punching metal disposed on the floor of the work space 11. The circulation fan 15 is arrange | positioned in the circulation flow path 14 in the ceiling part of the working space 11, for example.

  Since the isolator 10 is configured in this way, the gas in the work space 11 exhausted from the exhaust unit 13 is sent to the air supply unit 12 through the circulation flow path 14, and the HEPA filter 16 is supplied to the air supply unit 12. By passing the gas, the gas in the work space 11 can be circulated so as to remove particles such as fine dust and bacteria contained in the gas and supply clean gas into the work space 11. A class 100 level of cleanliness can be obtained, for example, by circulating gas 300 times / hour with respect to the volume of the work space 11. In order to efficiently circulate the gas in the entire work space 11, it is desirable that the air supply unit 12 and the exhaust unit 13 are arranged widely and evenly on the ceiling surface and the floor surface.

  The work space 11 of the isolator 10 of the first embodiment is required to be an aseptic environment. Here, the aseptic environment refers to a state in which substances necessary for work performed in the work space have been removed as much as possible. In addition to a clean environment in which the amount of particles in the gas is kept below a predetermined amount, viruses and An environment where there are no bacteria. In order to realize such an aseptic environment, the work space 11 is sterilized. Here, sterilization refers to the complete killing of not only microorganisms but also viruses and bacteria to the protein level.

  In order to perform such a sterilization process, a sterilization gas supply device for supplying a sterilization gas is disposed in the work space 11. Specifically, as the sterilization gas, for example, hydrogen peroxide gas is used, and by applying ultrasonic vibration to the hydrogen peroxide solution contained therein, the refined hydrogen peroxide solution mist is removed. An ultrasonic mist generator 17 sprayed into the work space 11 is employed as a sterilization gas supply device. Note that the hydrogen peroxide solution stored in the ultrasonic mist generator 17 is, for example, an aqueous solution having a concentration of about 35 wt% in consideration of its handleability. Further, since the size of the mist supplied from the ultrasonic mist generator 17 is fine, it can be vaporized as hydrogen peroxide gas in a short time and accompanied by a significant temperature rise with respect to the gas. There is no such heat.

  As shown in FIG. 1, in the isolator 10, the circulation flow path 14 is divided into two flow paths in the middle, and the branched flow paths are integrated again. Specifically, the circulation channel 14 is provided in the work space 11 when performing a sterilization process (details will be described later) of the work space 11 or when performing work processes such as cell culture in the work space 11. A detoxification process for detoxifying the sterilization gas component contained in the gas in the work space 11 after sterilization of the first circulation flow path 14A used for the circulation of the gas and the work space 11 (details) Is branched into two channels, the second circulation channel 14B used for the circulation of the gas in the work space 11 when performing the following.

In the middle of the first circulation channel 14A, there is no device for processing the passing gas, whereas in the middle of the second circulation channel 14B, there is a gas that passes. A detoxifying device 18 for detoxifying the sterilizing gas contained therein is disposed. In the first embodiment, since hydrogen peroxide gas is used as the sterilization gas, the detoxification device 18 using manganese dioxide is used as a catalyst for detoxifying the hydrogen peroxide gas. That is, in the detoxification device 18, hydrogen peroxide gas (H ₂ O ₂ ) is converted to water (H ₂ O) and oxygen (O ₂ ) by bringing a gas containing hydrogen peroxide gas into contact with manganese dioxide as a catalyst. ) To make the sterilization gas harmless. In this way, detoxification of sterilization gas means that chemical treatment of sterilization gas is performed on the virus, bacteria, and human body against sterilization gas that completely kills viruses and bacteria to the protein level. On the other hand, it means to the extent that does not have a substantial effect.

  Further, as shown in FIG. 1, the flow path for switching the flow path through which the circulated gas flows is provided at a branch point between the first circulation path 14 </ b> A and the second circulation path 14 </ b> B in the circulation path 14. A switching valve (flow path switching unit) 19 is provided. The flow path switching valve 19 is between the first circulation flow path selection position (100% open position) shown in FIG. 3A and the second circulation flow path selection position (0% open position) shown in FIG. 3B. It can be operated automatically.

  A cooling device 20 is arranged on the upstream wall surface of the branch portion of the flow path in the circulation flow path 14. The cooling device 20 has a function of dehumidifying the gas by cooling the gas and condensing moisture by contacting with the passing gas when the detoxification process is performed. Further, in combination with such a dehumidifying function, it is also used when cooling is performed to lower the temperature of the gas in the work space 11. In the first embodiment, for example, a Peltier cooling device is employed as such a cooling device 20. Any cooling device may be used as long as it has a function of condensing moisture contained in the gas in contact with the gas. In addition, a heat exchanger or a heat pump type device may be employed. However, it is desirable to adopt the Peltier type from the viewpoint of device space and the like. The water condensed by the cooling device 20 is drained to the outside of the work space 11 through a drain valve 31 provided in the circulation flow path 14 at the lower part of the work space 11.

  Further, as shown in FIG. 1, an exhaust passage (external communication passage) 21 communicated with the outside of the work space 11 is connected to the circulation passage 14. The exhaust passage 21 is provided mainly for releasing a part of the gas in the work space 11 to the outside so that the pressure in the work space 11 does not increase during the sterilization process.

  A HEPA filter 22 (filter) is provided at a connection portion of the exhaust flow path 21 with the circulation flow path 14, and an exhaust fan 23 (exhaust fan) and an exhaust flow path 21 are provided in the exhaust flow path 21. A decomposition device 24 is provided for decomposing sterilization gas components contained in the passing gas. The decomposition device 24 has substantially the same configuration as the detoxification device 18. Further, in the exhaust passage 21 between the decomposition device 24 and the HEPA filter 22, the pressure adjustment for adjusting the pressure in the work space 11 by adjusting the flow rate of the exhaust gas flowing through the exhaust passage 21. A valve 25 and a minute pressure adjusting valve 26 for adjusting a minute pressure difference in the exhaust passage 21 before and after the pressure adjusting valve 25 are provided.

  As shown in FIG. 1, the work space 11 is provided with a pressure gauge 27 (pressure detection means) for detecting pressure. For example, during the sterilization process, the pressure detected by the pressure gauge 27 is detected. Adjusting the pressure by controlling the opening degree of the pressure adjusting valve 25 and the minute pressure adjusting valve 26 so as not to be a positive pressure, that is, to maintain a pressure equal to or lower than the pressure outside the work space 11. Is possible. Further, based on the pressure detected by the pressure gauge 27, control of operation / stop of the exhaust fan 21 and control of the rotational speed of the exhaust fan 21 (inverter control) are also performed. In the first embodiment, the pressure adjusting valve 25, the minute pressure adjusting valve 26, and the exhaust fan 21 are an example of the flow rate adjusting means for the exhaust flow rate.

  Further, as shown in FIG. 1, a temperature / humidity meter 28 and a hydrogen peroxide concentration meter 29 are installed in the work space 11. For example, the cooling device 20 is controlled so that the temperature and humidity of the work space 11 detected by the thermohygrometer 28 satisfy a preset condition. Further, in the sterilization process, the amount of mist generated by the ultrasonic mist generator 17 is reduced so that the hydrogen peroxide concentration in the work space 11 detected by the hydrogen peroxide concentration meter 29 satisfies a preset concentration condition. In the detoxification process that is controlled, it is determined whether or not the detoxification process by the detoxification apparatus 18 can be terminated.

  The isolator 10 is provided with a control device 30 that performs overall control while associating operations of the respective components. The control device 30 controls, for example, the control of the hydrogen peroxide gas concentration in the work space 11 in the sterilization process, the determination of the end of the harmless process in the detoxification process, and the control of the pressure in the work space 11 in the sterilization process. It can be carried out.

  Next, in the isolator 10 having such a configuration, a procedure for performing sterilization processing and subsequent detoxification processing of sterilization gas will be described. In this description, the procedure of the sterilization process and the detoxification process is shown in the flowchart of FIG. 2, and the operation of each component of the isolator 10 at that time is schematically illustrated in FIGS. 3A (sterilization process) and FIG. 3B (detoxification process). Shown in In addition, each process demonstrated below is performed when the control apparatus 30 controls operation | movement of each structure part.

  First, in step S1 of the flowchart of FIG. 2, the flow path switching valve 19 is operated in the circulation flow path 14 to start the sterilization process inside the work space 11, and the first circulation flow path selection position (100% open). The gas is allowed to pass through the first circulation channel 14A. Thereafter, the circulation fan 15 is operated (step S2), and the gas in the work space 11 passes through the first circulation flow path 14A in the circulation flow path 14 and then returns to the work space 11 through the HEPA filter 16. Thus, gas circulation is performed.

  When the circulation of the gas in the work space 11 is confirmed, as shown in FIG. 3A, the operation of the ultrasonic mist generator 17 is disclosed, and a sterilization gas (hydrogen peroxide gas) is supplied into the work space 11. (Step S3). The amount of sterilization gas supplied by the ultrasonic mist generator 17 or the operation / operation thereof so that the concentration in the work space 11 is constantly detected by the hydrogen peroxide concentration meter 29 and the concentration is kept within a preset concentration range. Stop is controlled. When the hydrogen peroxide concentration is maintained within a preset concentration range, the sterilization process in the work space 11 including the circulation channel 14 is started (step S4), and this state is maintained until the sterilization set time has elapsed. Is maintained (step S5). By this sterilization process, all members in the work space 11 such as a work device arranged in the work space 11 are sterilized.

  While this sterilization process is being performed, the pressure in the work space 11 is constantly detected by the pressure gauge 28, and the operation of the exhaust fan 23, the control of the rotational speed, the pressure are maintained so as to keep the pressure within a preset pressure range. Control of the adjusting valve 25 and the minute pressure adjusting valve 26 is performed. The fine mist generated by the ultrasonic mist generator 17 tends to be easily vaporized as the pressure is kept at a negative pressure. Therefore, it is preferable that the pressure is controlled so as to be maintained in a preset negative pressure range during the sterilization process. In addition, although it may be a case where it is not maintained at a negative pressure, it is desirable to control at least so that a pressure does not become a positive pressure. The sterilized gas component contained in the gas discharged to the outside through the exhaust passage 21 by the operation of the exhaust fan 23 passes through the decomposition device 24 and is discharged to the outside in a state of being decomposed into water and oxygen. Is done.

  Thereafter, when it is determined in step S5 that the sterilization set time has elapsed, the operation of the ultrasonic mist generator 17 is stopped, and the supply of sterilization gas into the work space 11 is stopped (step S6). This completes the sterilization process.

  After the sterilization process is completed, a detoxification process for detoxifying the sterilization gas remaining in the work space 11 and the circulation channel 14 is disclosed. Specifically, as shown in FIG. 3B, in the circulation flow path 14, the flow path switching valve 19 is operated to be positioned at the second circulation flow path selection position (0% open position), and the second circulation flow The gas is allowed to pass through the path 14B (step S7). By this operation, the gas flowing through the circulation channel 14 passes through the second circulation channel 14B, and the sterilized gas component contained in the gas passing through the detoxification device 18 is decomposed into water and oxygen. It is rendered harmless (step S8).

  This detoxification process is performed until the concentration in the work space 11 detected by the hydrogen peroxide concentration meter 29 falls below a preset harmless reference value (step S9). Further, since the humidity in the work space 11 increases during the detoxification process, the circulated gas is cooled by the cooling device 20, and the contained moisture is condensed, that is, dehumidified. The condensed water is discharged to the outside of the work space 11 through the drain valve 31. Further, even during the detoxification process, pressure control is performed so that the pressure in the work space 11 is maintained within a preset pressure range.

  Thereafter, when it is confirmed that the concentration of the sterilizing gas in the work space 11 has reached a preset reference value, the detoxification process is completed.

  By providing the exhaust flow path 21 in the isolator 10, the ultrasonic mist generator 17 is released by releasing the pressure in the work space 11 through the exhaust flow path 21 (maintaining within a predetermined range) during the sterilization process. It is possible to suppress an increase in pressure due to evaporation of more generated mist. Furthermore, an increase in pressure associated with the generation of oxygen can be suppressed during the detoxification process. Therefore, the exhaust passage 21 can function as a pressure relief passage. However, in order to positively and reliably control the pressure, the exhaust passage 21 is preferably provided with an exhaust fan 23. .

  In the above description, the case where the flow path switching valve 19 provided in the circulation flow path 14 selectively switches between the 100% open position and the 0% open position has been described. An intermediate position may be selected. For example, a part of the gas may pass through the first circulation channel 14A and the remaining part of the gas may pass through the second circulation channel 14B. For example, since the sterilization gas is absorbed by the members in the work space 11 and the hydrogen peroxide concentration is increased after the detoxification process is completed, it is possible to pass a part of the gas through the detoxification device 18 as described above. It is possible to cope with a subsequent increase in concentration.

  According to the isolator 10 of the first embodiment, the sterilization process and the subsequent detoxification process can be performed in a substantially closed system without replacing the sterilization gas by introducing external air. Therefore, it is possible to form a highly sterile environment and further improve the safety of the isolator 10 with respect to the surrounding environment.

  Further, since the detoxification device 18 is arranged in the circulation system, there is no restriction on the concentration of gas remaining in the downstream path, and the circulation flow rate can be increased as much as possible. Therefore, the time required for the detoxification process of the sterilizing gas remaining in the work space 11 and the circulation path can be greatly shortened.

(Second Embodiment)
In addition, this invention is not limited to the said embodiment, It can implement with another various aspect. For example, FIG. 4 is a schematic diagram showing the main configuration of the isolator 110 according to the second embodiment of the present invention. In the isolator 110 of the second embodiment shown in FIG. 4, the same reference numerals are assigned to the same components as those of the isolator 10 of the first embodiment, and the description thereof is omitted. Hereinafter, only the points different from the first embodiment will be described.

  As shown in FIG. 4, the isolator 110 has a configuration different from the configuration of the first embodiment in that sterilization gas supply means for maintaining the pressure of the work space 11 at a positive pressure is provided. doing.

  Specifically, in the isolator 110, an aseptic gas supply passage 141 is connected to the circulation passage 14. The supply air channel 141 is connected to the aseptic gas cylinder 142, and by opening the manual valve 143 of the aseptic gas cylinder 142, aseptic gas is supplied into the working space 11 through the supply air channel 141 and the circulation channel 14. .

  Furthermore, a pressure adjusting valve 144 and a minute pressure adjusting valve 145 are provided in the middle of the air supply channel 141. For example, the pressure detected by the pressure gauge 27 falls within a preset positive pressure range. The supply amount of the sterilized gas is adjusted so as to be maintained. In the second embodiment, the pressure adjusting valve 144 and the minute pressure adjusting valve 145 are examples of the sterilization gas flow rate adjusting means. It is desirable that the pressure adjusting valve 25 in the exhaust passage 21 be closed while the positive pressure is maintained as described above.

  As the sterilized gas supplied from the sterilized gas cylinder 142 as described above, a gas that exists in nature such as air, nitrogen, and carbon dioxide and that is substantially harmless to cells cultured in the work space 11 is used. The In addition, as a method for generating such a sterilized gas, in the case where it is directly generated by a chemical reaction, a gas obtained by sterilizing the contaminated gas by using means such as ozone, ultraviolet sterilization, or pressurized superheat sterilization is put in the cylinder 142. It may be filled.

  Such positive pressure maintenance in the work space 11 using aseptic gas is performed, for example, when cell culture or the like is performed in the work space 11. By holding the positive pressure in this way, it is possible to suppress the invasion of bacteria and the like that affect cell culture from outside the work space 11.

  In the isolator 110, the gas supply means for keeping the pressure in the work space 11 at a positive pressure is not limited to the configuration shown in FIG. Instead of such a case, a configuration in which a gas obtained by sterilizing external air is supplied into the work space 11 as in the isolator 210 shown in FIG.

  As shown in FIG. 5, the isolator 210 according to the modification of the second embodiment sterilizes the supply air flow path 251 connected to the circulation flow path 14 and the external air taken in through the supply air flow path 251. An air sterilizer 252 to perform, an air supply fan 253, a pressure adjusting valve 254, and a minute pressure adjusting valve 255 are provided. Further, a HEPA filter 256 is installed at a connection portion of the air supply channel 251 to the circulation channel 14.

  As such an air sterilizer 252, means such as ozone, ultraviolet sterilization, pressurized superheat sterilization, plasma sterilization, etc. can be employed.

  Note that, in the isolators 110 and 210 of the second embodiment, the configuration and the procedure for performing the sterilization process and the detoxification process are the same as those in the first embodiment.

(Third embodiment)
Next, FIG. 6 shows a schematic side view of the main configuration of the automatic cell culture device 310 (hereinafter referred to as “automatic cell culture device 310”) according to the third embodiment of the present invention. In FIG. 6, the internal structure of the apparatus is schematically illustrated in order to facilitate understanding of the apparatus configuration. In addition, since the automatic cell culture device 310 of the third embodiment employs a device configuration that substantially includes the configuration of the isolator 210 of the second embodiment, the same reference numerals are used for common components. A description thereof may be omitted.

  As shown in FIG. 6, the automatic cell culture device 310 includes a work space 11 constituted by a stainless steel panel, various devices for cell automatic culture operation arranged in the work space 11, Air conditioning equipment for maintaining the environment in a sterile environment.

  Inside the work space 11, there are a work table 361 for performing various operations for cell culture, and two robot arms that are arranged in and near the work table 361 and perform various operations for cell culture automatically. 362 and 363 are provided. In addition, although not particularly illustrated, the work space 11 is provided with an incubator (a constant temperature chamber), a pass box, and a glove box. The robot arms 362 and 363 (robots) are, for example, an operation of implanting predetermined cells in a container (such as a petri dish) brought into the work space 11 through a pass box, an operation of accommodating the container in which the cells are implanted in an incubator, A predetermined operation such as inspecting the cells cultured on the work table 361 by taking out the container in which cell culture has been performed in the incubator is performed.

  Further, as shown in FIG. 6, the circulation flow path 14 is configured by a ceiling and a part of the floor of the work space 11 and a duct, and the air supply unit 12 positioned in the ceiling part includes a HEPA filter 16 and Two HEPA filter fan units integrated with the circulation fan 15 are arranged. In addition, a punching metal is disposed in the exhaust portion 13 located in the floor portion, and the gas blown out from the ceiling surface is exhausted from the floor surface, and the gas in the work space 11 passes through the circulation channel 14. Circulated.

  In the circulation flow path 14, a first circulation flow path 14 </ b> A and a second circulation flow path 14 </ b> B are formed in a portion constituted by a duct, and the second circulation flow path 14 </ b> B has a harmless device 18. Is installed. A flow path switching valve 19 is installed in the flow path switching portion. Further, the exhaust passage 21 and the air supply passage 251 are connected to the circulation passage 14. In FIG. 6, the details of the air supply channel 251 are not shown, but a configuration substantially similar to that of the air supply channel 251 shown in FIG. 5 is adopted.

  Furthermore, an ultrasonic mist generator 17 is installed on the wall surface of the work space 11, and the ultrasonic mist generator 17 supplies mist to the gas taken in from the work space 11 to sterilize. The gas is supplied into the work space 11 as a gas.

  Thus, the apparatus configuration for performing the sterilization process and the detoxification process in the present invention can be specifically applied to the automatic cell culture apparatus 310. In the automatic cell culture device 310, the space in the working space 11 can be reliably sterilized, and after sterilizing, external air is not taken in to replace the sterilizing gas. The sterilizing gas can be rendered harmless in a substantially closed space. Therefore, the aseptic environment required for the automatic cell culture device 310 can be realized at a higher level.

  In the above description of the embodiment, the case where an ultrasonic mist generator is employed as the sterilization gas supply device has been described as an example. However, as the sterilization gas supply device, hydrogen peroxide water is heated and evaporated. You may employ | adopt apparatuses, such as a heating evaporation type.

  Further, as a detoxification device for detoxifying hydrogen peroxide gas, in addition to using manganese dioxide as a catalyst, even when using catalase which is a kind of enzyme, or using a catalyst in which platinum is atomized, good.

  It is to be noted that, by appropriately combining arbitrary embodiments of the various embodiments described above, the effects possessed by them can be produced.

DESCRIPTION OF SYMBOLS 10 Isolator 11 Working space 12 Air supply part 13 Exhaust part 14 Circulation flow path 14A 1st circulation flow path 14B 2nd circulation flow path 15 Circulation fan 16 HEPA filter 17 Ultrasonic mist generator 18 Detoxification device 19 Flow path switching Valve 20 Cooling device 21 Exhaust flow path 22 HEPA filter 23 Exhaust fan 24 Exhaust detoxification device 25 Pressure adjusting valve 26 Micro pressure adjusting valve

Claims (6)

Working space,
A circulation passage that communicates with an air supply unit that supplies gas to the work space and an exhaust unit that exhausts gas from the work space, and circulates the gas in the work space;
A circulation filter and a circulation fan arranged in the middle of the circulation flow path;
By directly supplying the sterilizing mist in the working space, and a sterilizing gas supply unit for supplying a sterilizing gas sterilization mist is vaporized,
The circulation channel is
A first circulation channel used for gas circulation when performing a sterilization process of the working space;
A second circulation flow path used for gas circulation when performing the detoxification treatment of the sterilization gas after the sterilization treatment,
A flow path switching unit that switches between the first circulation flow path and the second circulation flow path,
A detoxification device disposed in the second circulation channel and detoxifying the sterilization gas contained in the circulated gas ;
An external communication channel that communicates the work space with the outside of the work space;
A filter arranged in the middle of the external communication channel;
An exhaust fan that is disposed in the middle of the external communication channel and exhausts the gas in the work space to the outside through the external communication channel;
Pressure detecting means for detecting the pressure in the work space;
And an exhaust flow rate adjusting means for adjusting the exhaust flow rate of the gas by the exhaust blower so as to keep the pressure in the working space at a negative pressure based on the detection result of the pressure detection means when performing the sterilization process. , Isolators. Disposed in the middle of the external communication passage, further comprising a decomposition apparatus for decomposing a sterilizing gas contained in the gas exhausted, the isolator of claim 1. The sterilization gas is a gas containing hydrogen peroxide, the detoxification device contains a catalyst that decomposes hydrogen peroxide into water and oxygen,
It arranged in the working space or the circulation flow path, further comprising a cooling device for condensing and the circulating gas is cooled, isolator of claim 1. The work space in the isolator according to any one of claims 1 to 3 is an aseptic environment space sterilized by a sterilization process,
An automatic cell culture apparatus further comprising a robot arranged in a sterile environment space and performing a cell culture operation in the sterile environment space. Sterilized gas supply means for supplying sterilized gas into the sterile environment space;
When carrying out cell culture, the apparatus further comprises a supply flow rate adjusting means for cell culture treatment for adjusting the supply flow rate of the sterilization gas by the sterilization gas supply means so as to keep the pressure of the sterile environment space at a positive pressure. The automatic cell culture apparatus according to claim 4 . The sterilization mist is vaporized by supplying the sterilization mist directly into the work space while circulating the gas in the work space of the isolator through the circulation filter using the first circulation channel. Supply the sterilization gas , keep the pressure in the work space at a negative pressure, sterilize the work space,
After a predetermined time has elapsed, the supply of sterilization gas is stopped, the first circulation channel is switched to the second circulation channel, and the gas is passed through the detoxification device disposed in the second circulation channel. A method for sterilizing an isolator, wherein the sterilization gas contained in the circulated gas is rendered harmless.

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