WO2022106006A1 - Fumigation d'un appareil de manipulation de cultures cellulaires - Google Patents

Fumigation d'un appareil de manipulation de cultures cellulaires Download PDF

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Publication number
WO2022106006A1
WO2022106006A1 PCT/EP2020/082725 EP2020082725W WO2022106006A1 WO 2022106006 A1 WO2022106006 A1 WO 2022106006A1 EP 2020082725 W EP2020082725 W EP 2020082725W WO 2022106006 A1 WO2022106006 A1 WO 2022106006A1
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WO
WIPO (PCT)
Prior art keywords
flow
chamber
gas flow
fumigant
generator
Prior art date
Application number
PCT/EP2020/082725
Other languages
English (en)
Inventor
Patrick Clemente GILLIGAN
Kenneth B. K. Teo
David Anthony BULLINARIA
Neil David WALCUCH
Original Assignee
Aixinno Ltd.
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 Aixinno Ltd. filed Critical Aixinno Ltd.
Priority to PCT/EP2020/082725 priority Critical patent/WO2022106006A1/fr
Publication of WO2022106006A1 publication Critical patent/WO2022106006A1/fr

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M37/00Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M39/00Means for cleaning the apparatus or avoiding unwanted deposits of microorganisms

Definitions

  • the invention relates to an apparatus for handling cell cultures.
  • Such an apparatus comprises at least one chamber, wherein the chamber may be part of a module, which is sealed from an external environment. Modules can be store modules for storing cell cultures or a lab ware.
  • the chamber is arranged inside of a container.
  • the apparatus comprises means for providing a flow of a fumigant through at least one region of said chamber. The fumigant is generated by a fumigant generator connected with an inlet conduit to an inlet section of the chamber.
  • the invention further relates to a method for fumigation of at least one region of a chamber preferably of an apparatus as mentioned above.
  • CN 104498359 A discloses an integrated cell culture machine comprising means for sterilisation of at least parts of a chamber of the device.
  • US 8,741,228 B2 discloses an apparatus for decontamination of a region of a chamber, wherein a sterilisation gas is fed into the chamber forming a first flow through the chamber and leaving the chamber through an outlet section.
  • DE 19954 550 Al discloses a device for sterilisation of a chamber of a container.
  • a flow generator generates a turbular gas flow inside the chamber.
  • US 7,132,083 B2 discloses a mobile device for removing a sterilant from a room containing a sterilant atmosphere.
  • WO 2009/ 037231 Al discloses hydrogen peroxide for sterilisation of a cabinet.
  • WO 2020/098960 Al discloses a system for processing biological material comprising several modules, wherein one of the modules is a process module, and other modules forming storage devices for cell cultures, liquids, microplates or lab ware.
  • the modules are sealed from the external environment and from adjacent modules. Lab ware or other material can be passed from one module to another without being exposed to contamination from the external atmosphere.
  • the process module contains equipment, such as a liquid handling apparatus, pipettes, delidders, grippers and decaper.
  • material for a workflow is loaded from one of the stores into the process module to be processed. After processing, the material is transported to a storage module. The process module is ready for the next process.
  • the process module may have a working volume of about half a cubic meter.
  • Devices of the state-of-the-art may use a laminar flow of fumigant.
  • a laminar flow generates boundary layer at surfaces.
  • the fumigant has to diffuse through such a boundary layer.
  • a laminar flow further comprises the disadvantage of producing stationary vortices trapping gas or not reaching each part of the volume.
  • An object of the invention is to accelerate a fumigation of a chamber of a container.
  • a further object of the invention is to improve an apparatus for handling cell cultures or a method for handling cell cultures or a method for fumigation of a chamber.
  • An essential feature of the invention is providing a second flow of fumigant or air through the at least one region of the chamber of the container.
  • the apparatus of the invention comprises a first gas flow generator, wherein the first gas flow generator generates a first gas flow inside the chamber.
  • the first gas flow is preferably a laminar gas flow through the chamber from an inlet section to an outlet section.
  • the outlet section may form a plenum.
  • a fumigant generator which may be a gas generator providing the fumigant which may be hydrogen peroxide.
  • the flow generator being realised by a fan may be located in the inlet section of the chamber.
  • the flow generator produces the first flow which is a laminar flow.
  • a filter like a HEPA filter may be located downstream of the flow generator.
  • One or more fans of the first flow generator drive a gas flow of a mixture of sterilisation gas e.g. hydrogen peroxide and a carrier gas, for example air, through the filter.
  • the filter may have a function of a diffusor forming a gas flow with a homogeneous flow velocity.
  • the second flow generator comprising at least one fan generates a second gas flow. During a purge step air is flowed through the volume of the chamber.
  • the second flow generator can modify the laminar gas flow or disturb the laminar gas flow to generate a turbulent gas flow.
  • the second flow generator generates a second gas flow, which is an independent gas flow with respect to the first gas flow.
  • the second flow generator produces a gas flow, which may be perpendicular to the first gas flow.
  • the angle between first gas flow direction and second gas flow direction may be between 60 and 120°.
  • the first laminar gas flow may define an axis, wherein the axis runs between an inlet section or an upper section of the chamber to an outlet section or a lower section of the chamber.
  • the axis can be a vertical axis.
  • the second flow generator generates a flow around the axis.
  • the flow generated by the second flow generator may be a circular flow or a vortex.
  • the first laminar gas flow may be a slow flow.
  • the flow velocity of the laminar gas flow may have values less than 0.3 to 0.5 m/s.
  • the flow velocity of the turbulent flow may be at least two times, five times or ten times as high.
  • There may be a heat generator for heating the fumigant.
  • the heat generator may be located downstream of the fumigant generator and upstream of the inlet section or in the inlet conduit.
  • the heat generator forms a heater for heating the fumigant, which is preferably a mixture of a sterilisation gas with air to an elevated temperature.
  • the outlet section of the chamber is connected to an outlet conduit.
  • the outlet section may be connected via a conduit to the inlet section to generate a circular flow of the fumigant.
  • the circular flow may pass the heater and an optional pump or fan to convey the gas mixture.
  • the before mentioned two flow generators are used to generate a laminar and a turbulent fumigant flow.
  • the flow generators may further be used for purging the chamber after a fumigation step. During the purge step a laminar flow of air and a turbulent flow of air is generated.
  • a further feature of the invention is alternating the flow pattern inside the chamber or at least inside one region of the chamber during the fumigation step and/ or during the purge step.
  • a first step the fumigant and preferably the heated fumigant is flowed in a laminar manner through the chamber or said region of the chamber.
  • the first step may have a duration of 5 to 30 seconds.
  • a second step which preferably immediately follows the first step the fumigant and preferably the heated fumigant is flowed in a turbulent manner through the chamber or said region of the chamber.
  • the second step may have a duration of 5 to 30 seconds.
  • a sequence each of a first step and a second step may be repeated for several times.
  • the sequence can be repeated for the time required for the fumigation, for example 5 to 10 minutes.
  • the fumigant can be passed through a catalytic scrubber.
  • the catalytic scrubber degenerates the sterilisation gas. Hydrogen peroxide react into oxygen and water. Ultraviolet light can be used to degenerate the fumigation gas.
  • the volume of the container is purged after the fumigation step.
  • a laminar flow and a turbulent flow of air can be generated and flowed through the chamber.
  • An apparatus or a method of the invention comprises especially one of the following features:
  • fumigation is accelerated by a combination of heating, and alternating between laminar flow for efficient gas exchange, and turbulent mixing.
  • Heating the chamber, or the incoming gas mixture, which contains the H2O2 vapour, will accelerate H2O2 destruction or neutralisation of biological material in the process module.
  • the chamber is provided with fans for driving air flow, an inlet HEPA filter, and a plenum for receiving the air.
  • the chamber may further be provided with a duct to recirculate air from the plenum to the inlet HEPA filter. If the airflow driven by the fans is relatively slow (less than 0.3 to 0.5 meters per second (m/ s)), then the air flow can be laminar, which gives efficient air exchange.
  • the chamber is further provided with an H2O2 vapour generator, and e.g. an outlet or catalytic scrubber for H2O2.
  • UV LEDs may further be provided to further accelerate H2O2 destruction.
  • H2O2 sensor provided to monitor H2O2 concentration in the outlet, and a valve provided to isolate the sensor from the initial, high concentrations of H2O2, which may be damaging to the sensor. Valves are provided as necessary to efficiently control the flow of gas.
  • Laminar flow enables efficient gas exchange, however, during laminar flow, a 'boundary layer 7 of air tends to get trapped on surfaces (e.g. of equipment), and the exposure of the surfaces, e.g., to H2O2 during disinfection or air during purging, therefore relies on diffusion through the boundary layer, which is relatively slow. Also, while "dead spots" can be minimised in a laminar flow regime, air or fumigant may be trapped in cavities in and around equipment (similar to parasitic drag on an aircraft), and this air will also be exchanged slowly in laminar flow regimes.
  • a first fan which can be switched on intermittently, to create a fast turbulent flow, orthogonal to the laminar flow.
  • the fan may be positioned to create a vortex about the vertical axis of the process module.
  • the fast, turbulent flow will favor mixing, and will tend to disrupt the boundary layer of air or fumigant on various surfaces, thereby greatly increasing the exposure of those surfaces to H2O2 vapour or air.
  • the direction of fast, turbulent airflow is orthogonal to the direction of the laminar flow, it will tend to mix pockets of air or fumigant that are shielded from the laminar flow.
  • H2O2 vapour When it is desired to fumigate the chamber, H2O2 vapour is heated and pumped into the chamber.
  • the H2O2 vapour can be recirculated in order to increase the efficiency of gas exchange, and also to fumigate the HEPA filter, plenum (outlet section), and recirculation duct.
  • the air flow is alternated between laminar flow, and fast turbulent mixing.
  • the air may be circulated in a laminar flow regime, less than 0.3 - 0.5 m/s, using the large fans above the HEPA filter. This is alternated with fast, turbulent flow, by turning on the other fan, in the chamber.
  • the flow may be maintained as laminar for 30 seconds, then switched to fast turbulent mixing, for 10 seconds. This is repeated for the time required for fumigation, e.g. 5 to 10 minutes.
  • H2O2 is purged from the chamber.
  • the H2O2 may be purged via an external vent, or may be purged by recirculating it through e.g. a catalytic scrubber. While the air is being recirculated, the airflow is once again alternated between laminar flow (e.g. for 5 to 30 seconds per cycle) and fast turbulent mixing (e.g. for 10 seconds per cycle), until the H2O2 is purged down to a desired limit.
  • the H2O2 concentration may be monitored on the outlet.
  • the H2O2 sensor may be sensitive to damage resulting from high concentrations of H2O2, so the sensor may be protected by a valve, until the H2O2 concentration has reduced far enough not to damage the sensor. Once the H2O2 concentration has fallen to the predetermined limit in the outlet, the purge may be completed, and the next process begun.
  • a second fan for generating the turbulent flow of fumigant or air may be located inside the chamber or may be located outside the chamber in a separate housing. There is a flow connection between the separate housing and the chamber wall, which may form a nozzle or a baffle.
  • the fan can be used to create a slight negative pressure in the chamber to drag air or fumigant out of the chamber.
  • Valves can be provided in a duct between the chamber and the fan.
  • a filter in particular an HEPA filter, can be located in flow direction upstream of an outlet fan.
  • the second fan generates a gas flow through a channel, which is connected to a chamber by a number of nozzles.
  • nozzles There may be several nozzles displaced from each other in a vertical direction feeding air or fumigant at different levels into the chamber to form a turbulent flow pattern in the chamber. It is further possi- ble to realise the fumigant generator and/ or the scrubber by a separate module, which can be connected with a detachable pipe connection to a gas supply system, if needed.
  • Fig. 1 schematically show a first embodiment in a longitudinal section
  • FIG. 2 schematically section along line II-II in Figure 1
  • FIG. 3 schematically a second embodiment in longitudinal section
  • FIG. 4 a perspective view demonstrate a circular flow pattern
  • Fig. 5 schematically an embodiment in a longitudinal section
  • FIG. 6 schematically a fourth embodiment in a longitudinal section
  • Fig. 7 to Fig. 10 schematically a device of the invention wherein closed valves are represented by an unfilled double triangle, and open valves are represented by a filled double triangle to demonstrate the method
  • Fig. 11 a device of any embodiment of the invention as part of a system of a number of modules.
  • the container 1 comprises a chamber 2 which is sealed to the environment.
  • the chamber 2 comprises an upper section forming an inlet section 7 and a lower section forming an outlet section 8 or plenum.
  • Inlet conduit 4 is connected with the inlet section 7.
  • the inlet section 7 comprises a first gas flow generator 3 which may comprise one or more fans, nozzles or baffles. Downstream with respect to the inlet conduit 4 for a filter 5 is located.
  • the filter 5 may be an HEPA-filter and may fill the full section of the chamber 2.
  • the filter 5 may act as a diffuser.
  • the first gas flow generator 3 generates a laminar gas flow through the chamber 2.
  • the flow pattern is indicated as 9.
  • An axis A is defined by the flow direction of the laminar gas flow.
  • a second gas flow generator 6 comprising at least one fan and optionally comprising nozzles or baffles is located inside or outside the chamber 2.
  • the second gas flow generator 6 may be located inside the chamber 2 in that way that the second gas flow generator 6 can deviate or disturb the laminar gas flow (figure 1).
  • the laminar gas flow may have flow velocities less than 0.3 to 0.5 m/s.
  • the second gas flow generator 6 accelerates the gas flow and changes the direction of the gas flow.
  • the second flow generator 6 can generate a gas flow with a flow direction having an angle between 60 and 120° to the first flow direction or the direction of the axis A.
  • the second gas flow generator 6 is preferably located beside the chamber as shown in figures 3 to 6.
  • the second gas flow generator generates an independent gas flow with respect to the first gas flow.
  • the second gas flow generator may have a fan to accelerate an airflow into the chamber 2.
  • the drawings show a second flow generator 6, which produces a gas flow being perpendicular to the axis A.
  • the second flow generator 6 produces a circular flow pattern 10.
  • the second flow generator 6 produces a turbulent flow pattern like a vortex.
  • a fumigant generator 14 generates a fumigant, which is a sterilisation gas, preferably hydrogen peroxide.
  • the fumigant is heated by a heater 13 being located downstream of the fumigant generator 14.
  • Pump or fan 17 conveys the fumigant through the inlet conduit 4 into the inlet section 7.
  • the fumigant passes through the chamber 2 alternating as a laminar flow or as a turbulent flow.
  • First steps wherein a laminar flow is provided, change with second steps, wherein a turbulent flow is provided.
  • the fumigant leaves the outlet section 8 through an outlet conduit 11.
  • the fumigant may pass through a conduit 19 to the heater 13 and back to the inlet conduit 4 to be fed into the inlet section 7 again.
  • the fumigant passes into a scrubber 15, where the fumigant is decomposed.
  • the scrubber 15 may be a catalytic scrubber.
  • a controller 20 is provided for controlling the fans of the gas flow generators 3, 6, 18, 31 as well as the heater 13, the fumigant generator 14 and the valves.
  • the controller 20 may have a control program for alternating the flow inside the chamber 2 between a laminar flow and turbulent flow and for heating the fumigant.
  • Figure 3 shows a process module of a cell culture system as shown in figure 11.
  • the device shown in figure 3 differs from the device shown in figure 1 by a different arrangement of the second gas flow generator 6 which is a fan generating a gas flow through a wall of the container 1.
  • An opening of the chamber wall forms the nozzle 34, which forms a flow connection between a housing in which the fan 6 is located and the chamber 2.
  • the opening 34 or the fan 6 is located close to a corner of the chamber wall for generating a circular flow around the axis A as shown in figure 4 schematically.
  • An outer fan 31 which may be inside a separate housing together with an additional HEPA-filter 32 is connected via a conduit and two valves 23, 24 with the housing containing the fan 6.
  • the outer fan 31 can generate a negative pressure to suck air or fumigant out of the chamber 2.
  • a mobile device 30, comprising a fumigant generator 14 and a scrubber 15, can be connected to the pipe system of the module via detachable pipe connections 29.
  • the fumigant generated by the fumigant generator flows via a conduit and through valve 23 into the housing of the fan 6 to generate a turbulent flow of fumigant inside the chamber 2.
  • a fan 18 is located downstream of the outlet conduit 11 to accelerate an outlet gas flow via the detachable pipe connection 29 into the scrubber 15 via valve 27.
  • the outlet gas flow can flow through a valve 21 and a valve 22 to the inlet section 7 or through a valve 23 to the chamber comprising the fan 6.
  • the outlet conduit 11 has a flow connection to a sensor 16 in which a valve 28 is arranged.
  • the arrangement shown in figure 3 comprises a process module, and H2O2 source and H2O2 sink, and a pneumatic circuit required for fumigation.
  • Suitable apparatuses are known for the H2O2 source and sink, such as a product of the company Bioquell.
  • An air inlet 37 is connected via a valve 25 with the inlet conduit 4 for feeding air into the chamber 2.
  • the air is distributed by the filter 5 homogeneously into the chamber 2 with a relatively slow velocity of 0.5 m/s or below.
  • the chamber 2 may have an array of appropriated holes. Such an array 12 can be located upstream of the outlet section being formed by a plenum 8. The laminar flow can be established in the chamber 2 which allows efficient gas exchange.
  • the chamber 2 may be further be provided with a duct to recirculate air from the outlet section 8.
  • the fan 18 is in line between the outlet section 8 and the fan 3.
  • the fan 18 conveys the gas from a plenum which is formed by the outlet section 8 and which has the same footprint as the chamber 2 above the array and the footprint of the filter 5.
  • the device shown in figure 5 differs from the device shown in figure 3 in the way that the fumigant generator 14 and the scrubber 15 are fixedly joined with the device.
  • the device shown in figure 6 differs from the device shown in figure 3 or 5 by a flow channel 35 distributing the gas flow generated by fan 6 into three flow paths which may be formed by nozzles 34.
  • the gas, in particular air, flowed through the nozzles 34 into the chamber 2 forms turbulent flow pattern 10 as shown in figure 4.
  • Laminar flow enables efficient gas exchange, however, during laminar flow, a "boundary layer" of air tends to get trapped on surfaces (e.g. of equipment), and exposure of the surfaces, e.g., to H2O2, or removal of H2O2 from the surfaces, therefore relies on diffusion through the boundary layer, which is relatively slow. Also, while “dead spots" can be minimised in a laminar flow regime, air may be trapped in cavities in and around equipment, and this air will also be exchanged slowly in laminar flow regimes.
  • Figure 5 showing air flowing through nozzles 34 or apertures, e.g. spaced down one or two corners, so as to generate a flow that rotates around the central vertical axis A of the process module chamber.
  • a means for generating faster, turbulent, airflow, preferably an orthogonal flow, to mix air out of dead spots, and disrupt boundary layers In a preferred implementation, there is provided an apparatus to generate a second airflow, which is orthogonal to the laminar air flow, to favor sweeping air from pockets that are dead spots with respect to the laminar flow, and is also faster, so as to favor turbulent mixing.
  • the means may include e.g. a series of holes or nozzles 34 in a duct that is routed up one corner of the chamber 2, arranged to drive an airflow rotationally about the central vertical axis A of the chamber 2.
  • There is further a means for driving airflow such as a fan or pump.
  • the fans above the HEP A filter may be driven faster, or reversed, or ramped up and down in speed, to generate turbu- lent airflow.
  • H2O2 sensor 16 provided, to monitor H2O2 concentration on the outlet, and a valve 28 provided to isolate the sensor 16 from the initial, high concentrations of H2O2, which may be damaging to the sensor.
  • valves 21 to 28 In order to increase efficiency and convenience, some means may be provided to direct airflow through the ducts, such as valves 21 to 28, but other means are known in the art, and other pneumatic circuits are possible.
  • Closed valves are represented by an unfilled double triangle, and open valves by a filled double triangle.
  • the system will be connected, e.g. by means of tubing and fittings, such as camlock fittings, to an apparatus that can generate H2O2, and after fumigation is complete, can destroy residual H2O2.
  • tubing and fittings such as camlock fittings
  • FIG. 7 shows the start of the fumigation.
  • H2O2 vapour is injected, by opening valves 26 and 22, and running fans 3 (and optionally fan 18). This results in air from the system being recirculated through the H2O2 generator 14, which injects H2O2 vapour.
  • HEPA filter 5 acts as a diffuser, and if the air flow in the chamber 2 is below about 0.5m/s, then conditions are generally favourable for laminar flow.
  • Injection of H2O2 vapour under laminar flow may be conveniently continued for 5 to 30 seconds, or longer, to allow time for stable laminar flow to develop, and air exchange, but in typical conditions, e.g. at 0.5 m/s, with less than two linear meters height for the air to travel in the chamber 2, the system air should be exchanged in seconds.
  • the conditions required to achieve turbulent flow will depend to some extent on the chamber 2, and on the size and shape of the nozzles or apertures. Flowing air through an aperture or nozzle, rather than across the whole area of a wall, will tend to create a jet, and the shear region between the air jet and surrounding air can generate turbulence, depending of the relative velocities. Importantly, further turbulence will be generated as the moving air passes by obstructions, such as equipment. Constricting the airflow at the nozzle will speed the airflow up, and the shape of the nozzles will also affect how well surrounding air is entrained. Suitable conditions are usually found by injecting smoke into the airflow, and increasing the airspeed until suitable conditions are found.
  • the air containing H2O2 vapour can be recirculated through the system.
  • valves 21 and 22 are opened, and fans 3 (and optionally Fan 18) are run.
  • Valves 21 and 23 are opened, and fan 6 (and optionally fan 18) are run.
  • fumigation may further be accelerated by other means, such as heating the vapour.
  • valve 27 is opened to allow recirculation through the catalytic scrubber 15, or some other means to remove the H2O2.
  • the air containing the H2O2 vapour may be exhausted through a vent.
  • valve 22 is opened, and fans 3 are run. It may be advantageous to also run fan 18 and close valve 21. As described previously, when fans 3 are run slowly enough for airflow in the chamber to be below ⁇ 0.5 m/s, this will usually result in substantially laminar flow, which may leave dead pockets of air, and leave boundary layers of air undisturbed on surfaces.
  • the laminar flow is alternated with fast, orthogonal turbulent flow, by closing valve 22, turning off fans 3, opening valve 23, and running fan 6. Airflow should be above 1 m/s (see figure 10).
  • purging is achieved by recirculating the air from the system through the catalytic scrubber, while alternating between laminar flow and turbulent, mixing in the chamber with laminar flow for 5 to 30 seconds or more at less than 0.5 m/s, and turbulent mixing flow for 5 to 30 seconds or more at 0.5 to 1 m/s or greater. Multiple cycles of alternating laminar flow and turbulent mixing are run, while recirculating air from the system through the catalytic scrubber 15. Once the H2O2 levels are predicted to be low enough not to harm the H2O2 sensor, valve 28 can be opened to expose the H2O2 sensor to levels of H2O2 vapour coming from the system. This allows the purging to continue until measured H2O2 vapour levels reach, or are below, a pre-defined threshold level.
  • purging may further be accelerated by other means, such as heating the vapour, and exposing the vapour to UV light, e.g. from UV LEDs.
  • FIG 11 schematically shows a system comprising several modules of a cell culture system for handling, maintaining or storing biological cells in microplates.
  • a process module 1 may be realised as shown in figures 1 to 5.
  • the processor module contains equipment as mentioned above.
  • material for a workflow is loaded from storage modules 36 into the process module, the process is run, and material is unloaded from the process module, leaving the process module ready for the next process.
  • the above explanations serve to explain the inventions covered by the application as a whole, which further develop the state-of-the-art at least through the following combinations of features, each of which may also be dependent, whereby two, several or all of these combinations of features may also be combined, mainly:
  • An apparatus characterised by at least one second gas flow generator 6 for generating a turbulent gas flow in said at least one region.
  • An apparatus characterised in that a heater 13 is provided for heating the fumigant or air prior entering said region.
  • An apparatus characterised by at least one filter 5 being arranged in the flow path of the fumigant or air prior entering said region, wherein the filter 5 is preferably a HEPA filter.
  • An apparatus characterised in that the first gas flow generator 3 produces a gas flow with a first flow direction and the second gas flow generator 6 is located inside said chamber or outside said chamber and produces a gas flow in a second flow direction being different from the first flow direction.
  • An apparatus characterised in that the second flow direction comprises an angle between 60 and 120° to the first flow direction and preferably an angle of 90°.
  • An apparatus characterised in that the second gas flow generator 6 deviates the gas flow produced by the first gas flow generator 3 or generates a gas flow independent from said laminar gas flow.
  • An apparatus characterised in that a conduit 11 connects an outlet section 8 of said chamber 2 with a scrubber in particular 15 with a catalytic scrubber 15.
  • An apparatus characterised by a controller 20 for alternately switching between laminar flow condition and turbular flow condition inside said at least one region.
  • An apparatus characterised by a sensor 16 in particular located downstream of a scrubber 15 being sensitive to the fumigant.
  • An apparatus characterised in that the first and/ or second gas flow generator 3, 6 comprises a fan, a nozzle 34 and/ or a baffle.
  • An apparatus characterised in that said chamber 2 is coupled to at least one storage module 36 for storing microplates, cell cultures, lab ware and/ or handling devices.
  • An apparatus characterised in that the inlet section 7 is located in an upper section of the container 1 and/ or that the outlet section 8 is located in a lower section of the container 1.
  • An apparatus characterised in that the second gas flow generator 6 is located outside the chamber 2 and is in a flow connection to the chamber 2 by an opening 34 in a side wall of the chamber 2.
  • An apparatus characterised by a number of openings 34 in a side wall of the chamber 2 being located in different distances from the inlet section 7, wherein each of said openings 34 is in a flow connection with a flow channel 35 for distributing a gas flow generated by the send gas flow generator to the openings 34.
  • a method characterised by switching alternately between said laminar flow and a turbular flow at least inside said region.
  • a method characterised in that the laminar flow is generated by at least one first flow generator 3 and that the turbular flow is generated by at least one second flow generator 6.
  • a method characterised in that the first gas flow generator 3 generates a laminar flow in a first flow direction and the second gas flow generator disturbs the laminar gas flow or generates an independent gas flow in a second flow direction being different from the first flow direction.
  • a method characterised in that the second flow direction comprises an angle between 60 and 120° to the first flow direction and preferably an angle of 90°.
  • a method characterised in that the fumigant comprises a sterilisation gas, in particular H2O2.
  • a method characterised in that the chamber 2 is purged with a purge gas, in particular air, after applying the fumigant to the chamber 2.
  • a method characterised in that during purging the chamber 2 a purge gas flow is altered between a laminar and a turbulent flow.
  • a method characterised in that UV-light is used for a degradation of the fumigant after exhausting the fumigant out of the chamber.
  • a method characterised in that a gas flow comprising the fumigant is recirculated through the chamber 2 by using a conduit 19 connecting the outlet section 8 with the inlet section 7.
  • a method characterised in that a first step with a laminar flow has a duration of 5 to 30 seconds and in that a second step immediately following the first step with turbular flow has a duration of 5 to 30 seconds.
  • a method characterised in that the flow velocity of the laminar gas flow inside the chamber 2 is less than 0.3 to 0.5 m/s and/ or that the second gas flow generator 6 produces flow velocities at least two times higher than the velocity of the laminar gas flow.
  • a method characterised in that sensing of the sterilisation gas downstream of a scrubber 15 by using a sensor 16.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Disinfection, Sterilisation Or Deodorisation Of Air (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

Appareil pour manipuler des cultures cellulaires comprenant une chambre (2) disposée dans un récipient (1) et des moyens pour fournir un flux d'un fumigant à travers au moins une région de ladite chambre (2), lesdits moyens comprenant un générateur de fumigant (14) relié par un conduit d'entrée (4) à une section d'entrée (7) de ladite chambre (2), au moins un premier générateur de flux gazeux (3) étant prévu pour générer un flux laminaire dudit fumigant ou d'air à travers ladite au moins une région. Un second générateur de flux gazeux (6) est prévu pour générer un flux gazeux turbulent dans la au moins une région. L'invention concerne en outre un procédé de fumigation d'au moins une zone d'une telle chambre. Le flux de gaz laminaire peut être perturbé ou un second flux de gaz turbulaire peut être généré.
PCT/EP2020/082725 2020-11-19 2020-11-19 Fumigation d'un appareil de manipulation de cultures cellulaires WO2022106006A1 (fr)

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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1954550A1 (de) 1969-10-30 1971-07-08 Basf Ag Polymere Thiophen-2,3,4,5-tetracarbonsaeurediimide
US6010400A (en) * 1995-05-25 2000-01-04 Flanders Filters, Inc. Isolation workstation
US7132083B2 (en) 2000-08-04 2006-11-07 Bioquell Uk Limited Apparatus for removing sterilant from a sterilant containing atmosphere
WO2009037231A1 (fr) 2007-09-17 2009-03-26 Aseptix Technologies B.V. Procédé de désinfection à large spectre, générant peu de résidus et faisant appel à un aérosol à base de peroxyde d'hydrogène en petites gouttelettes
JP2010154793A (ja) * 2008-12-26 2010-07-15 Sanyo Electric Co Ltd Co2インキュベータ
US20120083030A1 (en) * 2010-09-30 2012-04-05 Sanyo Electric Co., Ltd. Incubator
US20130084215A1 (en) * 2010-03-31 2013-04-04 Panasonic Healthcare Co., Ltd. Hydrogen peroxide gas generator
US8741228B2 (en) 2011-09-23 2014-06-03 American Sterilizer Company Hydrogen peroxide vaporizer with heated diffuser
CN104498359A (zh) 2014-12-18 2015-04-08 宁波新芝生物科技股份有限公司 一种细胞培养一体机
US20190151488A1 (en) * 2016-04-07 2019-05-23 Metall + Plastic Gmbh Decontamination assembly
WO2020098960A1 (fr) 2018-11-16 2020-05-22 Aixinno Limited Système de traitement de matériel biologique, comprenant une pluralité de modules de stockage de conception uniforme

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1954550A1 (de) 1969-10-30 1971-07-08 Basf Ag Polymere Thiophen-2,3,4,5-tetracarbonsaeurediimide
US6010400A (en) * 1995-05-25 2000-01-04 Flanders Filters, Inc. Isolation workstation
US7132083B2 (en) 2000-08-04 2006-11-07 Bioquell Uk Limited Apparatus for removing sterilant from a sterilant containing atmosphere
WO2009037231A1 (fr) 2007-09-17 2009-03-26 Aseptix Technologies B.V. Procédé de désinfection à large spectre, générant peu de résidus et faisant appel à un aérosol à base de peroxyde d'hydrogène en petites gouttelettes
JP2010154793A (ja) * 2008-12-26 2010-07-15 Sanyo Electric Co Ltd Co2インキュベータ
US20130084215A1 (en) * 2010-03-31 2013-04-04 Panasonic Healthcare Co., Ltd. Hydrogen peroxide gas generator
US20120083030A1 (en) * 2010-09-30 2012-04-05 Sanyo Electric Co., Ltd. Incubator
US8741228B2 (en) 2011-09-23 2014-06-03 American Sterilizer Company Hydrogen peroxide vaporizer with heated diffuser
CN104498359A (zh) 2014-12-18 2015-04-08 宁波新芝生物科技股份有限公司 一种细胞培养一体机
US20190151488A1 (en) * 2016-04-07 2019-05-23 Metall + Plastic Gmbh Decontamination assembly
WO2020098960A1 (fr) 2018-11-16 2020-05-22 Aixinno Limited Système de traitement de matériel biologique, comprenant une pluralité de modules de stockage de conception uniforme

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