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WO2019163452A1 - Dispositif de traitement - Google Patents

Dispositif de traitement Download PDF

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Publication number
WO2019163452A1
WO2019163452A1 PCT/JP2019/003208 JP2019003208W WO2019163452A1 WO 2019163452 A1 WO2019163452 A1 WO 2019163452A1 JP 2019003208 W JP2019003208 W JP 2019003208W WO 2019163452 A1 WO2019163452 A1 WO 2019163452A1
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WO
WIPO (PCT)
Prior art keywords
container
processing
flow path
liquid
gas
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2019/003208
Other languages
English (en)
Japanese (ja)
Inventor
守 西谷
隆 光安
高雄 男澤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujifilm Corp
Original Assignee
Fujifilm Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujifilm Corp filed Critical Fujifilm Corp
Priority to JP2020501623A priority Critical patent/JP6986129B2/ja
Publication of WO2019163452A1 publication Critical patent/WO2019163452A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/26—Inoculator or sampler

Definitions

  • the disclosed technology relates to a processing apparatus.
  • JP 2010-524498 A discloses a medium reservoir, a cell treatment device having at least one inlet, at least one outlet, a first lobe and a second lobe, at least one pump, and a fluid flow direction.
  • a cell separation device is described, comprising at least one valve that changes or stops the fluid, which are in communication with each other.
  • JP-T-2009-540868 discloses at least one intake port for taking in fluid, at least one exhaust port for discharging fluid, and at least two for binding a target substance such as nucleic acid.
  • a device for purifying a material of interest that creates a circuit to a port is described. The device also describes flowing air through the conduit to remove fluid remaining in the conduit.
  • the living tissue is composed of cells and an extracellular matrix existing around the cells.
  • the separation process for separating (or isolating) cells from a biological tissue is a process for extracting a cell by decomposing an extracellular matrix using a treatment liquid such as an enzyme agent.
  • a treatment liquid such as an enzyme agent.
  • the processing apparatus includes a first container for housing a biological tissue to be processed, a second container for enclosing a processing liquid used for processing the biological tissue, a first container, and a second container. And a processing liquid transfer means for transferring the processing liquid from the plurality of second containers to the first container.
  • the processing apparatus having the above-described configuration, if the processing liquid remains in the flow path, the amount of the processing liquid added to the living tissue is insufficient, and processing failure may occur.
  • Patent Document 2 Japanese Patent Publication No. 2009-540868
  • a contamination source such as bacteria and viruses
  • living tissue and cells separated from the living tissue are exposed to the contamination source.
  • the disclosed technology aims to suppress the remaining of the treatment liquid in the flow path while suppressing the risk of the living tissue and the cells separated from the living tissue being exposed to the contamination source.
  • a processing apparatus includes a first container for containing a biological tissue to be processed, a plurality of second containers for sealing a processing liquid used for processing the biological tissue, and a first container At least one of the flow paths, a flow path that connects each of the plurality of second containers, a treatment liquid transfer means that sequentially transfers the treatment liquid from each of the plurality of second containers to the first container, and Gas transfer means for transferring aseptic gas to the first container via the section.
  • the gas transfer means transfers the sterile gas to the first container via the flow path, so that the living tissue and the cells separated from the living tissue are exposed to the contamination source. It is possible to suppress the remaining of the processing liquid in the flow path while suppressing the risk of occurrence.
  • the flow path includes a plurality of individual flow paths individually connected to each of the plurality of second containers, and a common flow path that connects each of the plurality of individual flow paths and the first container. Also good. According to this aspect, the total length of the flow path can be shortened as compared with the case where all the flow paths are set as individual flow paths.
  • the sterilized gas may be sealed together with the treatment liquid in each of the plurality of second containers.
  • the gas transfer means converts the sterilized gas sealed in the second container into the second container. You may transfer to a 1st container via the separate flow path connected to this container, and a common flow path.
  • the processing liquid remaining in the flow path can be transferred to the first container by the aseptic gas sealed in each of the second containers. Furthermore, not only the processing liquid remaining in the common flow path but also the processing liquid remaining in the individual flow path can be transferred to the first container.
  • the volume of the sterile gas sealed in each of the plurality of second containers is the volume of the common flow path section in the flow path from the individual second container to the first container of the plurality of second containers. It is preferably larger than the sum. Thereby, the processing liquid remaining in the individual flow path and the common flow path can be more reliably transferred to the processing container.
  • the processing apparatus may further include an airtight container in which aseptic gas is sealed and connected to a connection portion between the common flow path and the individual flow path.
  • the aseptic gas sealed in the sealed container may be transferred to the first container via the common channel.
  • the processing liquid remaining in the flow path can be transferred to the first container by the aseptic gas sealed in the sealed container.
  • the volume of the sterile gas sealed in the sealed container is preferably larger than the volume of the flow path section through which the sterile gas passes in transferring the sterile gas to the first container. Thereby, the processing liquid remaining in the common flow path can be more reliably transferred to the processing container.
  • the processing apparatus may further include a valve provided in each individual flow path. According to this aspect, the transfer timing of the processing liquid sealed in each of the plurality of second containers to the first container can be controlled.
  • the gas transfer means may transfer aseptic gas to the first container every time the processing liquid is transferred from at least one of the plurality of second containers to the first container. According to this aspect, each time the processing liquid is transferred, the processing liquid remaining in the flow path can be transferred to the first container.
  • the processing apparatus may further include a vibration mechanism that applies vibration to the first container.
  • the treatment liquid stored in the first container can be agitated, and the treatment of the biological tissue with the treatment liquid can be promoted.
  • the processing apparatus may further include temperature control means for controlling the ambient temperature of the first container.
  • temperature control means for controlling the ambient temperature of the first container.
  • FIG. 1 is a front view illustrating an example of a configuration of a processing apparatus 1 according to the first embodiment of the disclosed technique.
  • the processing apparatus 1 includes a processing container 20 for storing a biological tissue to be processed and a plurality of processing liquid enclosures 10 for enclosing a processing liquid used for a biological tissue separation process. Further, the processing apparatus 1 includes an individual flow path 31 and a common flow path 32 as flow paths that connect the processing container 20 and each of the plurality of processing liquid enclosures 10. Further, the processing apparatus 1 includes a liquid feed pump 51 as a processing liquid transfer unit that transfers the processing liquid from the processing liquid enclosure 10 to the processing container 20. The processing apparatus 1 decomposes the extracellular matrix constituting the biological tissue by adding the processing liquid enclosed in the processing liquid enclosure 10 to the biological tissue accommodated in the processing container 20, and removes cells from the biological tissue. The separation process to separate is performed automatically.
  • a disinfecting solution for disinfecting a living tissue for example, a disinfecting solution for disinfecting a living tissue, a washing solution for washing off the disinfecting solution, at least one enzyme solution for decomposing the living tissue, and an enzyme washing solution for washing off the enzyme solution are used as the treating solution.
  • a culture solution is used as the enzyme cleaning solution.
  • the disinfecting liquid, the cleaning liquid, the enzyme liquid, and the enzyme cleaning liquid are sealed in different processing liquid sealing containers 10.
  • different types of treatment liquids are enclosed in the plurality of treatment liquid enclosures 10. Different types of treatment liquids enclosed in the plurality of treatment liquid enclosures 10 are transferred to the treatment container 20 in a predetermined order. It is preferable that different types of processing liquids are not mixed in the processing liquid enclosure 10, the processing container 20, and the flow path.
  • Each of the treatment liquid enclosures 10 is preferably a disposable sealed container in order to suppress the risk of contamination by external contamination sources such as bacteria and viruses. Further, a syringe or bag having a variable volume can be suitably used as the processing liquid enclosure 10.
  • FIG. 1 illustrates a case where a syringe is used as the treatment liquid enclosure 10.
  • Each of the plurality of individual flow paths 31 is provided corresponding to each of the plurality of treatment liquid enclosures 10.
  • Each of the individual channels 31 has one end connected to the corresponding processing liquid enclosure 10 and the other end connected to the common channel 32.
  • a joint 35 is provided at each connection portion between each individual flow path 31 and the common flow path 32.
  • the individual flow path 31 means a flow path section from the processing liquid enclosure 10 to the joint 35.
  • the common flow path 32 means a flow path section from each joint 35 to the processing container 20. Accordingly, the flow path section between the joints 35 adjacent to each other belongs to the common flow path 32.
  • the processing container 20 is connected to one end of the common flow path 32.
  • a liquid feed valve 41 is provided in the middle of each individual flow path 31. That is, each of the plurality of liquid supply valves 41 is provided corresponding to each of the plurality of processing liquid enclosures 10.
  • Each of the liquid supply valves 41 is used for selectively transferring the processing liquid from the processing liquid enclosure 10 to the processing container 20. That is, when the selected liquid feeding valve 41 is opened and the liquid feeding pump 51 is operated, the processing liquid sealed in the processing liquid enclosure 10 corresponding to the liquid feeding valve 41 is transferred to the corresponding individual flow. It is transferred to the processing container 20 via the channel 31 and the common channel 32.
  • a pinch valve can be suitably used as the liquid feeding valve 41. By using a pinch valve as the liquid feed valve 41, it is possible to open and close the flow channel without contacting the fluid passing through the individual flow channel 31.
  • the individual flow path 31 and the common flow path 32 are configured by tubular members. It is preferable that the tubular members constituting the individual flow path 31 and the common flow path 32 can be sterilized, have less eluate, and have corrosion resistance to the processing liquid. Moreover, it is preferable that the tubular member which comprises the individual flow path 31 and the common flow path 32 has thermoplasticity. Since the tubular member has thermoplasticity, the tubular member can be sealed by heat welding after use, so that, for example, when a biological tissue or cell is infected with a contamination source such as a cell and a virus, the contamination source is external. The risk of leaking out can be suppressed. As a tubular member constituting the individual flow path 31 and the common flow path 32, for example, a silicon tube can be used.
  • the joint 35 preferably has corrosion resistance to the processing liquid.
  • Teflon registered trademark
  • polypropylene or polyvinylidene fluoride
  • the joint 35 is preferably capable of heat sterilization treatment and gamma ray sterilization treatment, and polyvinylidene fluoride is suitable as a material for the joint 35.
  • the liquid feed pump 51 is provided in the middle of the common flow path 32.
  • a tube pump can be suitably used as the liquid feed pump 51.
  • the fluid can be transferred without contacting the fluid passing through the common flow path 32.
  • FIG. 2 is a diagram illustrating an example of the configuration of the processing container 20.
  • the processing container 20 includes a first air chamber 21 and a second air chamber 22 that are separated from each other by a filter 23.
  • the processing container 20 has a first circulation port 24 and a second circulation port 25 that respectively communicate with the first air chamber 21, and a third air chamber 22 that communicates with the second air chamber 22 via a conduit 27.
  • a circulation port 26 One end of the pipe line 27 is connected to the third flow port 26, passes through the first air chamber 21 and the filter 23, and the other end reaches the second air chamber 22.
  • the first circulation port 24 is connected to one end of the common flow path 32. That is, the processing liquid sealed in each of the processing liquid sealing containers 10 flows into the first air chamber 21 of the processing container 20 from the first circulation port 24.
  • the first air chamber 21 is a space in which a biological tissue to be processed and cells separated from the biological tissue by separation processing are accommodated.
  • the second air chamber 22 is a space for storing used processing liquid.
  • the filter 23 has, for example, a filter hole having a size smaller than the size of the cell separated from the living tissue.
  • An exhaust valve 42 is provided in the middle of the exhaust passage 33.
  • the exhaust valve 42 is opened when the processing liquid is transferred to the processing container 20.
  • the gas in the processing container 20 is discharged via the exhaust passage 33, and the atmospheric pressure of the first air chamber 21 is maintained at atmospheric pressure.
  • the atmospheric pressure in the second air chamber 22 becomes higher than the atmospheric pressure. Therefore, the pressure in the first air chamber 21 is maintained lower than the pressure in the second air chamber 22.
  • the other end of the exhaust channel 33 can be opened to the atmosphere, but the living tissue stored in the processing container 20 and the cells separated from the living tissue are suppressed from being exposed to a contamination source. It is preferable to take the following measures.
  • a sterile filter may be attached to the other end of the exhaust passage 33.
  • a closed container such as a bag for allowing the gas discharged from the processing container 20 to flow in may be connected to the other end of the exhaust passage 33.
  • One end of the drainage flow path 34 is connected to the third circulation port 26.
  • a waste liquid tank 60 is connected to the other end of the drainage flow path 34.
  • a drainage pump 52 and a drainage valve 43 are provided in the middle of the drainage flow path 34.
  • the drainage valve 43 is opened and the drainage pump 52 is operated, the first air chamber 21 and the second air chamber 22 are air-treated by the processing liquid staying in the first air chamber 21. Since the pressure in the second air chamber is lower than the pressure in the first air chamber, the processing liquid staying in the first air chamber 21 is While falling (moving) to the second air chamber 22 side, it is transferred to the waste liquid tank 60 via the third circulation port 26 and the drainage flow path 34.
  • a gas-liquid discrimination sensor 50 ⁇ / b> A is provided in a portion of the common flow path 32 between the liquid feed pump 51 and the processing container 20. Further, a gas-liquid discrimination sensor 50 ⁇ / b> B is provided in a portion of the drainage flow path 34 between the processing container 20 and the drainage pump 52.
  • Each of the gas-liquid discrimination sensors 50A and 50B discriminates whether the fluid flowing through the flow path is liquid or gas, and supplies a discrimination signal indicating the discrimination result to the control unit 80 (see FIG. 3) described later. To do.
  • the gas-liquid discrimination sensors 50A and 50B determine whether the fluid flowing through the flow path is liquid or gas based on, for example, the refraction angle of the laser light irradiated in the flow path. Also good.
  • the closed container 11 is connected to the end of the common flow path 32 opposite to the end on the processing container 20 side via an air supply flow path 36. That is, the sealed container 11 is connected to a connection portion between the individual flow path 31 and the common flow path 32.
  • the sealed container 11 is filled with aseptic gas.
  • FIG. 1 illustrates the case where a syringe is used as the sealed container 11.
  • the gas sealed in the sealed container 11 is preferably a gas having no cytotoxicity, and may be, for example, a mixed gas containing oxygen or air.
  • An air supply valve 44 is provided in the middle of the air supply flow path 36.
  • the aseptic gas sealed in the sealed container 11 is transferred to the processing container 20 via the air supply flow path 36 and the common flow path 32. Is done.
  • the gas flowing through the common flow path 32 passes through each connection portion between the common flow path 32 and the individual flow path 31. In this manner, by transferring the sterile gas sealed in the sealed container 11 to the processing container 20, the processing liquid remaining in the common flow path 32 is transferred to the processing container 20 together with the sterile gas.
  • the volume of the gas sealed in the sealed container 11 is preferably larger than the sum of the volumes of the common flow path sections in the flow paths from the individual processing liquid sealed containers 10 to the processing containers 20.
  • the volume of the gas sealed in the sealed container 11 is preferably larger than the sum of the volumes of the flow paths from the individual joints 35 to the processing container 20 in each of the processing liquid sealing containers 10. Thereby, the processing liquid remaining in the common flow channel 32 can be more reliably transferred to the processing container 20.
  • FIG. 3 is a side view showing an example of the configuration of the processing apparatus 1.
  • the processing apparatus 1 includes a vibration mechanism 70 that applies vibration to the processing container 20.
  • the vibration mechanism 70 is connected to the motor 71, the cam 73 connected to the rotation shaft 72 of the motor 71, the cam follower 74 disposed so as to contact the cam 73, and the cam follower 74.
  • a vibration stage 75 that performs a linear reciprocating motion is included.
  • the drive control of the motor 71 is performed by the control unit 80.
  • a holding unit 76 that holds the processing container 20 is mounted on the vibration stage 75.
  • the vibration stage 75 performs a linear reciprocating motion, whereby vibration is applied to the processing container 20 held by the holding unit 76.
  • the control unit 80, the motor 71, the cam 73, and the cam follower 74 are accommodated in the housing 81.
  • a heater 77 and a temperature sensor 78 are embedded in the holding unit 76.
  • the holding unit 76 is made of a material having a relatively high thermal conductivity such as metal, and also functions as a heat block that transfers heat generated from the heater 77 to the processing container 20.
  • the temperature sensor 78 includes, for example, a thermocouple, detects the temperature of the holding unit 76, and supplies a temperature detection signal indicating the detected temperature to the control unit 80.
  • the controller 80 controls the output of the heater 77 based on the temperature detection signal from the temperature sensor 78.
  • the control unit 80 controls the heater 77 so that the temperature of the holding unit 76 is maintained at a predetermined temperature (for example, 37 ° C.). By holding the processing container 20 in the temperature-controlled holding unit 76, the ambient temperature of the processing container 20 is kept constant (for example, 37 ° C.).
  • the control unit 80 controls the opening and closing of the liquid supply valve 41, the air supply valve 44, the exhaust valve 42 and the drainage valve 43, and the drive control of the liquid supply pump 51 and the drainage pump 52 in addition to the control of the motor 71 and the heater 77. Also do.
  • FIG. 4A shows an example of the configuration of the distribution system 2 of the processing apparatus 1, which is configured by connecting a plurality of processing liquid enclosures 10, a sealed container 11, a processing container 20, and a waste liquid tank 60 through a flow path.
  • FIG. 4B is a perspective view illustrating an example of the configuration of the main body 3 of the processing apparatus 1.
  • the distribution system 2 can be attached to and detached from the main body 3 while the plurality of processing liquid enclosures 10, the sealed container 11, the processing container 20, and the waste liquid tank 60 are connected via the flow path. is there.
  • the distribution system 2 can be attached to the main body 3 as it is.
  • the risk that each component of the distribution system 2 is exposed to the contamination source can be suppressed.
  • FIG. 5 is a flowchart illustrating an example of a flow of processing executed by the control unit 80 when the processing device 1 performs separation processing for separating cells from biological tissue.
  • different types of treatment liquids are enclosed in each of the plurality of treatment liquid enclosures 10. It is assumed that biological cells to be processed are accommodated in the first air chamber 21 of the processing container 20.
  • the sealed container 11 is assumed to be filled with aseptic gas.
  • Each of the plurality of liquid supply valves 41 is identified by an identification number N (N is a natural number) in the control unit 80. In the initial state, it is assumed that the liquid supply valve 41, the exhaust valve 42, the drainage valve 43, and the air supply valve 44 are closed, and the liquid supply pump 51 and the drainage pump 52 are respectively stopped.
  • step S1 the control unit 80 sets the set value of the identification number N of the liquid delivery valve 41 to 1. Thereby, the liquid feeding valve 41 corresponding to the identification number 1 is selected.
  • step S2 the control unit 80 controls the exhaust valve 42 to an open state.
  • step S3 the control unit 80 controls the liquid supply valve 41 corresponding to the identification number 1 to be in an open state.
  • step S ⁇ b> 4 the control unit 80 starts the operation of the liquid feed pump 51. Thereby, the processing liquid sealed in the processing liquid sealing container 10 corresponding to the identification number 1 is transferred to the processing container 20 via the corresponding individual flow path 31 and the common flow path 32.
  • the exhaust valve 42 is opened and the drain valve 43 is closed, so that the first air chamber 21 is brought along with the inflow of the processing liquid into the processing container 20.
  • the gas inside is discharged to the outside of the processing container 20 via the exhaust passage 33. Accordingly, a state in which the pressure of the first air chamber 21 is lower than the pressure of the second air chamber 22 can be formed, and the processing liquid that has flowed into the processing container 20 is retained in the first air chamber 21. be able to. That is, the living tissue can be immersed in the treatment liquid in the first air chamber 21.
  • step S4A the control unit 80 detects the liquid feeding state of the processing liquid by monitoring the discrimination signal supplied from the gas-liquid discrimination sensor 50A.
  • step S ⁇ b> 5 the control unit 80 determines whether or not the processing liquid has been fed.
  • the control unit 80 determines that the fluid flowing through the common flow path 32 has changed from liquid to gas based on the determination signal supplied from the gas-liquid determination sensor 50A. To do. If the controller 80 determines that the processing liquid has been supplied, the process proceeds to step S6.
  • step S6 the control unit 80 controls the liquid feeding valve 41 corresponding to the identification number 1 to be closed.
  • step S7 the control unit 80 controls the air supply valve 44 to an open state.
  • the liquid feed pump 51 maintains the operating state.
  • the aseptic gas enclosed in the sealed container 11 is transferred to the processing container 20 via the common flow path 32.
  • the aseptic gas sealed in the hermetic container 11 passes through each connection part of the common flow path 32 and the individual flow path 31 and reaches the processing container 20.
  • the aseptic gas sealed in the sealed container 11 is transferred to the processing container 20, so that the processing liquid remaining in the common flow path 32 in step S ⁇ b> 7 ⁇ / b> A. Is swept away by the aseptic gas discharged from the sealed container 11 and flows into the processing container 20 together with the aseptic gas.
  • the control unit 80 controls the air supply valve 44 to be closed in step S8 when a predetermined time has elapsed since the control of the air supply valve 44 to the open state. Thereby, the transfer of the aseptic gas enclosed in the sealed container 11 to the processing container 20 is stopped.
  • the predetermined time is set to a time required for the aseptic gas discharged from the sealed container 11 to reach the processing container 20.
  • the control unit 80 stops the operation of the liquid feed pump 51.
  • the control unit 80 controls the exhaust valve 42 to be closed. At this time, the state in which the biological tissue and the processing liquid are accommodated in the first air chamber 21 is maintained.
  • step S ⁇ b> 11 the control unit 80 starts the operation of the vibration mechanism 70 by starting the driving of the motor 71. Thereby, the processing liquid accommodated in the processing container 20 is stirred, and the process with respect to the biological tissue by the said processing liquid is accelerated
  • step S12 the control unit 80 determines whether or not a predetermined time has elapsed since the operation of the vibration mechanism 70 was started. If it is determined that the predetermined time has elapsed, the process proceeds to step S13. In step S ⁇ b> 13, the control unit 80 stops the operation of the vibration mechanism 70 by stopping the driving of the motor 71. Thereby, the stirring process of the process liquid accommodated in the process container 20 is complete
  • step S14 the control unit 80 controls the exhaust valve 42 to be in an open state.
  • step S15 the control unit 80 controls the drain valve 43 to be in an open state.
  • step S ⁇ b> 16 the control unit 80 starts the operation of the drainage pump 52.
  • the atmospheric pressure of the second air chamber 22 becomes lower than the atmospheric pressure of the first air chamber 21, and the processing liquid staying in the first air chamber 21 passes through the filter. Then, it is transferred to the second air chamber 22. Thereafter, the processing liquid is transferred to the waste liquid tank 60 via the drainage flow path 34.
  • step S16A the control unit 80 detects the liquid feeding state of the processing liquid by monitoring the discrimination signal supplied from the gas-liquid discrimination sensor 50B.
  • step S ⁇ b> 17 the control unit 80 determines whether or not the liquid supply of the processing liquid from the processing container 20 to the waste liquid tank 60 has been completed.
  • the control unit 80 determines that the fluid flowing through the drainage flow path 34 has changed from liquid to gas based on the determination signal supplied from the gas-liquid determination sensor 50B, the processing liquid has been supplied. Is determined. If the controller 80 determines that the processing liquid has been supplied, the process proceeds to step S18.
  • step S18 the control unit 80 controls the drain valve 43 to be closed.
  • step S19 the control unit 80 stops the operation of the drainage pump 52.
  • step S20 the control unit 80 determines whether or not the processing from step S2 to step S19 has been completed for all the processing liquids sealed in each of the processing liquid enclosures 10. For example, the control unit 80 performs the above determination by determining whether or not the set value of the current identification number N of the liquid supply valve 41 is the maximum value corresponding to the number of processing liquid enclosures 10. Also good. When it is determined that the processing from step S2 to step S19 has been completed for all the processing liquids, the control unit 80 ends this routine. On the other hand, if it is determined that the processing from step S2 to step S19 is not completed for all the processing liquids, the control unit 80 shifts the processing to step S21.
  • step S21 the control unit 80 increases the set value of the identification number N of the liquid feeding valve 41 by one, and returns the process to step S2.
  • the liquid supply valve 41 corresponding to the identification number 2 is selected, and the processing from step S2 to step S19 is performed on the processing liquid sealed in the processing liquid enclosure 10 corresponding to the identification number 2.
  • the processing from step S2 to step S19 is repeatedly performed until the processing is completed for all the processing liquids sealed in each of the processing liquid sealing containers 10.
  • the processing liquids of different types are sequentially transferred from the processing liquid sealing container 10 to the processing container 20 and used.
  • This processing liquid can be automatically transferred from the processing container 20 to the waste liquid tank 60.
  • the flow path through which the treatment liquid passes forms a closed system, so that the risk of exposure of biological tissues and cells separated from biological tissues to sources of contamination such as bacteria and viruses is suppressed. Can do.
  • the sealed container 11 connected to the connection portion between the individual flow path 31 and the common flow path 32 is filled with aseptic gas, and the processing liquid is transferred from the processing liquid sealing container 10 to the processing container 20.
  • the aseptic gas sealed in the sealed container 11 is transferred to the processing container 20.
  • the processing liquid remaining in the common channel 32 is pushed away by the aseptic gas discharged from the sealed container 11 and flows into the processing container 20 together with the aseptic gas.
  • the processing liquid remaining in the flow path to the processing container 20
  • the risk of occurrence of defects can be suppressed.
  • the processing liquid remaining in the flow path is transferred by a sterile gas sealed in the hermetic container 11, the living tissue and the cells separated from the living tissue are contaminated by contamination sources such as bacteria and viruses. Risk can be suppressed.
  • processing liquids are sequentially transferred from the processing liquid enclosure 10 to the processing container 20, and further, the processing liquid remaining in the common flow path 32 is also transferred to the processing container 20, thereby The risk that a plurality of different types of treatment liquids sealed in each of the treatment liquid enclosures 10 are mixed can be suppressed.
  • the treatment liquid remains in the flow path while suppressing the risk of the living tissue and the cells separated from the living tissue being exposed to the contamination source. It becomes possible to suppress.
  • each of the processing liquid enclosures 10 is filled with an extra amount of processing liquid corresponding to the amount of the processing liquid remaining in the corresponding individual flow path 31.
  • FIG. 6 is a front view illustrating an example of a configuration of a processing apparatus 1A according to the second embodiment of the disclosed technique.
  • the processing apparatus 1 ⁇ / b> A has a sterile filter 90 connected to the air supply channel 36. That is, the aseptic filter 90 is used as an alternative to the sealed container 11 (see FIG. 1) in the processing apparatus 1 according to the first embodiment.
  • the processing apparatus 1A when the liquid supply pump 51 is operated while the air supply valve 44 is opened, gas is introduced from the outside into the common flow path 32 through the aseptic filter 90 and transferred to the processing container 20. As a result, the processing liquid remaining in the common flow path 32 is pushed away by the sterilized gas introduced through the sterilizing filter 90 and flows into the processing container 20 together with the sterilized gas.
  • the same effect as that of the processing apparatus 1 according to the first embodiment can be obtained.
  • FIG. 7 is a front view illustrating an example of a configuration of a processing apparatus 1B according to the third embodiment of the disclosed technique.
  • the processing apparatus 1B does not include the air supply flow path 36, the air supply valve 44, and the sealed container 11 included in the processing apparatus 1 (see FIG. 1) according to the first embodiment. 1 (see FIG. 1).
  • a sterile gas 101 is sealed together with the processing liquid 100 in each of the processing liquid sealing containers 10 as shown in FIG.
  • the aseptic gas 101 sealed in the processing liquid sealing container 10 corresponds to the corresponding individual. It is transferred to the processing container 20 via the flow path 31 and the common flow path 32. As a result, the treatment liquid remaining in the individual flow path 31 and the common flow path 32 corresponding to the treatment liquid enclosure 10 is pushed away by the aseptic gas discharged from the treatment liquid enclosure 10, and the aseptic condition is obtained. It flows into the processing container 20 together with the gas.
  • the volume of the aseptic gas 101 enclosed in each of the plurality of treatment liquid enclosures 10 is larger than the volume of the flow path section through which the gas 101 passes in transferring the gas 101 to the treatment container 20. That is, the volume of the gas 101 enclosed in each processing liquid enclosure 10 is in the section from the connecting portion of the corresponding individual channel 31 and the common channel 32 to the processing vessel 20. The volume is preferably larger than the total volume of the common flow path 32.
  • the aseptic gas 101 having the above volume is enclosed in each of the plurality of treatment liquid enclosures 10. Thereby, the processing liquid remaining in the individual flow path 31 and the common flow path 32 can be reliably transferred to the processing container 20.
  • the aseptic gas sealed in each of the processing liquid sealing containers 10 passes not only through the common channel 32 but also through the corresponding individual channel 31. Not only the processing liquid remaining in the common flow path 32 but also the processing liquid remaining in the individual flow path 31 can be transferred to the processing container 20.
  • the processing apparatus 1B according to the third embodiment since the aseptic gas 101 is sealed in each of the processing liquid enclosures 10, the processing apparatus 1 according to the first embodiment (see FIG. 1). ), The air supply flow path 36 and the air supply valve 44 are not required, and the apparatus configuration can be simplified.
  • aseptic gas may be sealed in the sealed container 11 and may be sealed in each of the plurality of processing liquid sealing containers 10.
  • the process liquid is transferred from each of the process liquid enclosures 10 to the process container 20 by the liquid feed pump 51 provided in the middle of the common flow path 32.
  • the liquid feed pump 51 provided in the middle of the common flow path 32.
  • the treatment liquid is transferred from each of the treatment liquid enclosures 10 to the treatment container 20 to each of the plurality of treatment liquid enclosures 10. You may carry out by the syringe pump provided accompanying.
  • connection part of the several separate flow path 31 and the common flow path 32 existed for every separate flow path 31 was illustrated, it is limited to this aspect. It is not something.
  • the number of connection portions between the plurality of individual flow paths 31 and the common flow path 32 may be one.
  • processing container 20 is an example of a first container in the disclosed technology.
  • the treatment liquid enclosure 10 is an example of a second container in the disclosed technology.
  • the liquid feed pump 51 is an example of a processing liquid transfer unit in the disclosed technology, and is an example of a gas transfer unit in the disclosed technology.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Ce dispositif de traitement comprend un premier récipient pour stocker un tissu biologique à traiter, de multiples seconds récipients pour sceller un liquide de traitement à utiliser dans le traitement du tissu biologique, un trajet d'écoulement qui relie le premier récipient et chacun des multiples seconds récipients, un moyen de transfert de liquide de traitement pour transférer séquentiellement le liquide de traitement de chacun des multiples seconds récipients au premier récipient, et un moyen de transfert de gaz pour transférer un gaz aseptique dans le premier récipient à travers au moins une partie du trajet d'écoulement. <u /> <u />
PCT/JP2019/003208 2018-02-20 2019-01-30 Dispositif de traitement Ceased WO2019163452A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021065225A (ja) * 2019-10-18 2021-04-30 株式会社島津製作所 微生物回収方法および微生物回収装置
JP2022165506A (ja) * 2021-04-20 2022-11-01 株式会社島津製作所 前処理装置、前処理方法、およびプログラム
US12070723B2 (en) 2019-10-18 2024-08-27 Shimadzu Corporation Microorganism recovering method and microorganism recovering apparatus

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016013392A1 (fr) * 2014-07-22 2016-01-28 株式会社日立ハイテクノロジーズ Dispositif pour dispersions cellulaires et système de culture repiquée automatique l'utilisant

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016013392A1 (fr) * 2014-07-22 2016-01-28 株式会社日立ハイテクノロジーズ Dispositif pour dispersions cellulaires et système de culture repiquée automatique l'utilisant

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021065225A (ja) * 2019-10-18 2021-04-30 株式会社島津製作所 微生物回収方法および微生物回収装置
US12070723B2 (en) 2019-10-18 2024-08-27 Shimadzu Corporation Microorganism recovering method and microorganism recovering apparatus
JP2022165506A (ja) * 2021-04-20 2022-11-01 株式会社島津製作所 前処理装置、前処理方法、およびプログラム
US11998908B2 (en) 2021-04-20 2024-06-04 Shimadzu Corporation Preprocessing device, preprocessing method, and non-transitory computer readable medium storing program

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