INCUBATOR SHAKER WITH OZONE DECONTAMINATION AND METHOD FOR DECONTAMINATING AN INCUBATOR SHAKER

20220228099 ยท 2022-07-21

    Inventors

    Cpc classification

    International classification

    Abstract

    Disclosed is an incubator shaker (1) for cell cultivation, which comprises an incubation chamber (10), a shaking table (21) disposed in the incubation chamber (10), and an ozone distributing device (100) for distributing ozone in the incubation chamber (10) including a space underneath the shaking table (21). The shaking table (21) is configured to place a cultivation container thereon during a cultivation process. This incubator shaker (1) can be used for a further disclosed method for decontaminating the incubator shaker (1), including the steps of placing the ozone distributing device (100) into the incubation chamber (10), guiding ozone into the incubation chamber (10), and conveying the ozone inside the incubation chamber (10) including a space underneath the shaking table (21).

    Claims

    1. Incubator shaker for cell cultivation, comprising: an incubation chamber; a shaking table disposed in the incubation chamber, wherein the shaking table is configured to place a cultivation container thereon; and an ozone distributing device for distributing ozone in the incubation chamber including a space underneath the shaking table.

    2. Incubator shaker according to claim 1, wherein the ozone distributing device comprises: a side panel having a plurality of openings and being arranged adjacent to a sidewall of the incubation chamber; and a conveying device configured to convey ozone into a first space between the side panel (102) and the sidewall of the incubation chamber.

    3. Incubator shaker according to claim 2, wherein at least one of the plurality of openings is arranged in the side panel at a height being below the shaking table.

    4. Incubator shaker according to claim 2, wherein the ozone distributing device further comprises: a top panel having an opening and being arranged adjacent to a ceiling of the incubation chamber, wherein the conveying device is configured to convey ozone through the opening into a second space between the top panel and the ceiling of the incubation chamber, and wherein the side panel is coupled to the top panel, so that the first space is fluidly connected to the second space.

    5. Incubator shaker according to claim 2, wherein the ozone distributing device further comprises: a filter arranged upstream of a conveying direction of the conveying device and configured to filter a gas before entering the conveying device.

    6. Incubator shaker according to claim 2, wherein the conveying device comprises a motor, wherein the motor is arranged outside of the incubation chamber.

    7. Incubator shaker according to claim 2, further comprising: a UV light source arranged in a region of the incubation chamber to which the conveying device conveys the ozone.

    8. Incubator shaker according to claim 1, wherein the table comprises at least one opening.

    9. Incubator shaker according to claim 1, further comprising: a shaking device configured to move the shaking table.

    10. Incubator shaker according to claim 9, wherein the shaking device comprises an eccentric coupled to the shaking table, and wherein paddles are connected to the eccentric.

    11. Incubator shaker according to claim 1, further comprising: an inlet port configured to guide a gas into the incubation chamber, wherein the inlet port is in fluid communication with an ozone source and a carbon dioxide source.

    12. Incubator shaker according to claim 1, further comprising: an ozone generator arranged inside the incubation chamber.

    13. Incubator shaker according to claim 1, further comprising: a door closing an opening of the incubation chamber to the ambient environment; and a locking mechanism configured to lock the door in a closed position.

    14. Method for decontaminating an incubator shaker, according to claim 1, the method comprising: providing the ozone distributing device; guiding ozone into the incubation chamber; and conveying the ozone inside the incubation chamber, wherein conveying comprises guiding the ozone into a space underneath the table.

    15. Method according to claim 14, wherein the method comprises, before guiding ozone into the incubation chamber: locking a door of the incubation chamber; guiding carbon dioxide into the incubation chamber; determining a carbon dioxide level in the incubation chamber after a predefined time span; and if the carbon dioxide level is below a threshold value, aborting the method.

    Description

    [0056] Preferred embodiments of the invention are now explained in greater detail with reference to the enclosed schematic drawings, in which

    [0057] FIG. 1 schematically illustrates a front view or section through an incubator shaker;

    [0058] FIG. 2 schematically illustrates a side view or cross-section through the incubator shaker;

    [0059] FIG. 3 schematically illustrates a perspective view of a shaking table with openings for optimized ozone circulation;

    [0060] FIG. 4 schematically illustrates a front view or section through a bottom portion of an incubator with a built-in shaking device; and

    [0061] FIG. 5 schematically illustrates a flow diagram of a decontamination method.

    [0062] FIG. 1 schematically illustrates a front view or section through an incubator shaker 1 for cell cultivation. The incubator shaker 1 includes an incubation chamber 10, which is defined by an outer housing 5 and an inner chamber 10. The inner chamber 10 is preferably made from stainless steel, wherein sidewalls, back wall, bottom and ceiling form a closed surface with rounded edges with a radius of 20 mm or more. This allows easy wipe cleaning of the surface of the inner chamber 10.

    [0063] A shaking table 21 is placed inside the incubation chamber 10, which is separately illustrated in FIG. 3. The shaking table 21 allows for placing a cultivation container 28 (FIG. 4) thereon. For instance, a cultivation container 28 may be an Erlenmeyer flask or microtiter plate or a special cell culture flask, which contains a cell culture. The cultivation container 28 may directly be placed on the table 21, or alternatively, a tray (not illustrated) is placed on top of the shaking table 21, on which the cultivation container 28 is fixed.

    [0064] The incubator shaker 1 may further comprise an ozone distributing device 100 for distributing ozone in the incubation chamber 10, including distributing ozone underneath the shaking table 21. With reference to FIGS. 1 and 2, the latter of which schematically illustrates a side view or cross-section through the incubator shaker 1, the ozone distributing device 100 will be explained.

    [0065] The most basic form of an ozone distributing device 100 is a side panel 102 having a plurality of openings 104 and being arranged adjacent to a sidewall of the incubation chamber 10. Two side panels 102 are illustrated in FIG. 1 arranged adjacent to a respective sidewall of incubation chamber 10. In addition, a conveying device 110 conveys ozone into a first space between the side panel 102 and the sidewall of the incubation chamber. Although FIG. 1 illustrates the conveying device 110 as being spaced apart from side panel 102, the conveying device 110 may be arranged inside of the incubation chamber 10 such that ozone conveyed by the conveying device 110 is directly conveyed into the first space. The conveyed ozone is then able to leave the first space via the openings 104 and towards the centre of the incubation chamber 10.

    [0066] At least one of the plurality of openings 104 in the side panel 102 is arranged at a height being below the shaking table 21. As is illustrated with the plurality of arrows indicating the airflow through each of the plurality of openings 104 in FIG. 1, at least a portion of the ozone streaming through the openings 104 is guided into the space of the incubation chamber 10 underneath the shaking table 21. Thus, efficient decontamination underneath the table is achieved by the ozone distributing device 100.

    [0067] The ozone distributing device 100 may further comprise a top panel 106 arranged adjacent to the ceiling of the incubation chamber 10. The top panel 106 may also have an opening 108. The conveying device 110 can be configured to convey ozone through the opening 108 in the top panel 106 into a second space between the top panel 106 and the ceiling of the incubation chamber 10. For example, the conveying device 110 may transport ozone (e.g. air with a predefined ozone concentration) from an interior space of the incubation chamber 10 into the second space. The side panel 102 can be coupled to the top panel 106 in such a manner, that the first space is fluidly connected to the second space. Thus, any gas/ozone conveyed by the conveying device 110 into the second space has to stream towards the first space and the openings 104 in the side panel 102.

    [0068] A filter 118 can be arranged upstream of the conveying device 110, in order to filter any particles from the ozone before entering the conveying device 110, the second space and the first space. As can be derived from the arrows depicted in FIGS. 1 and 2, a forced airflow is achieved through the incubation chamber 10. In order to increase efficiency of the decontamination, the incubator shaker 1 may include more than one conveying device 110, two of which are illustrated in FIG. 1. In combination with a second side panel 102, a symmetric forced airflow, and hence ozone flow, can be achieved for efficient decontamination.

    [0069] In addition to the side panel(s) 102, a back panel 103 may further be arranged adjacent to a back wall of the incubation chamber 10, thereby forming a third space between the back panel 103 and the back wall of the incubation chamber 10. As with the side panel(s) 102, ozone may be conveyed by the conveying device 110 from the second space into the third space, from which the ozone may enter the interior space of the incubation chamber 10 again via corresponding openings 105 provided in the back panel 103.

    [0070] In an optional configuration the back panel 103 may also have an opening (not illustrated), such as opening 108 in top panel 106. The or a conveying device 110 can be configured to convey ozone through the opening in the back panel 103 into a third space between the back panel 103 and the back wall of the incubation chamber 10. For example, the conveying device 110 may transport ozone (e.g. air with a predefined ozone concentration) from an interior space of the incubation chamber 10 into the third space. The side panel 102 can be coupled to the back panel 103 in such a manner, that the first space is fluidly connected to the third space. Thus, any gas/ozone conveyed by the conveying device 110 into the third space has to stream towards the first space and the openings 104 in the side panel 102.

    [0071] Likewise, a filter (not illustrated), such as filter 118 at top panel 106, can be arranged upstream of the conveying device 110 arranged at the back panel 103, in order to filter any particles from the ozone before entering the conveying device 110, the third space and the first space. As can be derived from the arrows depicted in FIGS. 1 and 2, a forced airflow is achieved through the incubation chamber 10. In order to increase efficiency of the decontamination, the incubator shaker 1 may include more than one conveying device 110, preferably two, left and right at the back panel. In combination with a second side panel 102, a symmetric forced airflow, and hence ozone flow, can be achieved for efficient decontamination.

    [0072] The shaking table 21 may comprise at least one opening 22 (FIGS. 1 and 3), which allows a flow of ozone from the space underneath the shaking table 21 towards the centre of the incubation chamber 10, and hence towards the conveying device 110. Thus, the space underneath the shaking table 21 can be ventilated with the optimal ozone concentration as in the remaining regions of the incubation chamber 10, which allows an efficient decontamination underneath the shaking table 21.

    [0073] A motor 112 of the conveying device 110 may be arranged outside of the incubation chamber 10, for example, in a space between outer housing 5 and incubation chamber 10. This prevents any electric component from coming into contact with the ozone during decontamination. Alternatively, the motor 112 may also be arranged outside housing 5.

    [0074] The incubator shaker 1 may further comprise a shaking device 20 configured to shake the table 21. Exemplary shaking devices 20 are illustrated in FIG. 3 (mobile shaking device) and FIG. 4 (built-in shaking device), while another exemplary installation is illustrated in FIGS. 1 and 2. For instance, the shaking table 21 may be installed on an eccentric 25 connected to a motor driven rotor 24, so that the table 21 can be moved in an orbit or circle. This allows shaking of any flask 28 arranged on the table 21.

    [0075] This rotational movement can further be used to convey the ozone in the space underneath the table 21. For example, the motor driven rotor 24 may be equipped with at least one gas conveying means 120, such as a paddle or blade. This gas conveying means 120 moves together with the motor driven rotor 24 and, hence, moves the ozone in the space underneath the shaking table 21, so that a good ventilation is achieved, and the ozone flows substantially equally through every section of the space underneath the shaking table 21.

    [0076] The motor driven rotor 24 is turning around a fixed shaft 26 which functions as a stator as illustrated in FIGS. 1 and 2. This exemplary arrangement of the shaking device 20 inside of the incubation chamber 10 allows having a flat bottom wall of the incubation chamber 10. Thus, the bottom wall of the incubation chamber 10 can easily be cleaned. The space underneath the shaking device 20 can still be efficiently decontaminated due to the good ventilation of ozone underneath the table 21 and underneath the shaking device 20. The motor driven rotor 24 may have a function of a housing around the motor (not separately illustrated) separating the motor, particularly its electric and electronic components, from the atmosphere inside the incubation chamber 10. Such housing, for example made from easy-to-clean stainless steel, prevents humidity and ozone from reaching the motor. The gas conveying means 120 can then additionally or alternatively be mounted on the housing, particularly when the housing is turning around the shaft 26 with high speed during the decontamination process. An optional stand 27 of a mobile shaking device 20 (FIG. 3) can be placed outside of the incubation chamber 10 during the decontamination process or may be placed onto the bottom wall of the incubation chamber 10 (not illustrated).

    [0077] Alternatively, as illustrated in FIG. 4 the bottom wall of the incubation chamber 10 may include a protrusion covering the motor 30, so that the motor 30 is outside of the incubation chamber 10. This allows the motor 30 to be installed without a specific fluid-tight housing. The rotating shaft 31 should at least include a portion extending through the incubation chamber 10 or through the incubation chamber 10 and housing 5 (as illustrated in FIG. 4). In any case, a fluid-tight seal 29 is to be employed to seal the rotating shaft 31 connecting the motor 30 and the table 21. Although the surface of the bottom wall of the incubation chamber 10 has a more complex structure and/or sealing elements are required at the rotating shaft 31 and/or shaking table 21, decontamination is still efficient due to the good ventilation and provision of ozone underneath the shaking table 21. Moreover, a stand 27 for the shaking device 20 (as in FIG. 3) may not be required, since the protrusion of the bottom wall of the incubation chamber 10 can be formed to provide sufficient structural stability for the shaking device 20.

    [0078] The incubator 1 may further comprise an inlet port 130 configured to guide a gas into the incubation chamber 10. This inlet port 130 may be in fluid communication with an ozone source 131, illustrated as a valve. In addition thereto, the inlet port 130 may be in fluid communication with a carbon dioxide source 132, also illustrated as a valve. Thus, the inlet port 130 required for the carbon dioxide introduction for the cultivation process may also be used for the introduction of ozone during the decontamination process. Therefore, no additional inlet port and associated sealing is required.

    [0079] The ozone may be produced in an ozone generator 133. In FIG. 1, the ozone generator 133 is illustrated as a device being located outside of the incubator 1. For instance, the ozone generator 133 may be in fluid communication with the inlet port via valve 131. Alternatively, an ozone source in form of a pressure storage may be used instead of the ozone generator 133.

    [0080] Alternatively or additionally, as is illustrated in FIG. 2, an ozone generator 135 may be included in the incubator 1. Thus, no additional storage for ozone is required and the ozone may be generated directly from oxygen present in the air and atmosphere in and around the incubator 1.

    [0081] As a further exemplary variant, the ozone generator 135 may be arranged inside of the incubation chamber 10 (instead of the position illustrated in FIG. 2 between incubation chamber 10 and outer housing 5). This would even allow avoiding an inlet port for ozone through the incubation chamber 10. For example, ozone generator 135 may be arranged in the second space, i.e. between the top panel 106 and the ceiling of the incubation chamber 10, and/or in the first or third space, i.e. between the side panel 102 and a sidewall of the incubation chamber 10 or the back panel 103 and a back wall of the incubation chamber 10, respectively.

    [0082] The interior space of the incubation chamber 10 may be reached through a door 7 closing an opening of the incubation chamber 10 to the ambient environment. In order to prevent ozone from exiting the incubation chamber 10 during the decontamination process, the door 7 may be locked by a locking mechanism 15. This locking mechanism 15 may be under control of one or more sensors, that measure an ozone concentration inside of the incubation chamber 10.

    [0083] In order to decompose ozone after the decontamination process, and in order to release the locking mechanism 15, so that the door 7 can be opened again, a UV light source 116 can be installed inside of the incubator 1. Particularly, the UV light source 116 can be arranged inside of the incubation chamber 10. Preferably, the ozone conveyed by conveying device 110 passes the UV light source 116, so that the ozone is decomposed while being conveyed through the incubation chamber 10.

    [0084] In addition or alternatively, a catalyst (not illustrated) can be arranged in a similar manner inside the incubator 1 or inside of the incubation chamber 10. If the catalyst is a passive catalyst, it should be sealed from the conveyed ozone during the decontamination process and should be open for the ozone to pass over/through the catalyst after the decontamination process, in order to decompose the ozone. For instance, a bypass (not illustrated) may be provided in the incubator 1, which can be sealed off from the incubation chamber 10 (via valves or doors) and which may be open to the flow of ozone induced by the conveying device 110 for decomposition of ozone.

    [0085] The ozone distributing device 100 may be designed to be at least partially removable from the incubation chamber 10. This allows wipe cleaning of the incubation chamber 10, for example, before a disinfection process using ozone is started. Moreover, at least a part of the ozone distributing device 100 could be removable. In order to reach the UV light source or the ozone generator, both items may require replacement after a certain number of decontamination processes.

    [0086] FIG. 5 schematically illustrates a flow diagram of a decontamination method using the incubator shaker 1. In a first step 201, the ozone distributing devices provided, for example, provided to an incubator. The decontamination process is then started. For example, process parameters may be set and confirmed by a user. Thereafter, the ozone distributing device 110 is capable of providing ozone in the incubation chamber 10 and to produce a forced airflow through the incubation chamber 10, wherein the air can comprise ozone. This provision and conveying of ozone may be fully automated, particularly when process parameters are set upfront.

    [0087] In step 210 ozone is guided into the incubation chamber 10. This may be achieved by opening a valve 131 fluidly connected to an ozone source 133 and an inlet port 130 opening into the interior space of the incubation chamber 10. Alternatively, an ozone generator 135 may be operated to generate ozone directly inside of the incubator 1 and/or inside of the incubation chamber 10.

    [0088] Afterwards, in step 220, the ozone (enriched air) is conveyed throughout the interior space of the incubation chamber 10. This conveying includes distributing ozone even in a space under a shaking table 21 arranged in the incubation chamber 10. During step 220, further ozone may still be guided into or be produced in the incubation chamber 10 (step 210).

    [0089] After a predefined time span, the decontamination process is stopped, i.e. the guiding or generation of ozone in the incubation chamber 10 (step 210) is stopped. The conveying of the ozone and air may be continued (step 220) as long as the ozone is decomposed. This decomposition of the ozone may be accelerated by switching on a UV light source and/or by guiding the ozone through a catalyst.

    [0090] In order to protect the ambient environment around the incubator 1 from the harmful ozone, a test may be run before guiding the ozone into the incubation chamber 10 (step 210). Particularly, the optional steps (see dashed-lined square in FIG. 5) may represent such testing. Firstly, in step 205, the door 7 of the incubation chamber 10 is locked, and in step 206, carbon dioxide is guided into the incubation chamber 10.

    [0091] In step 207, a carbon dioxide level is determined inside the incubation chamber 10 and compared to a threshold. If the carbon dioxide level is above the threshold, it is very likely that the incubation chamber 10 is airtight, i.e. does not leak a gas, such as carbon dioxide or ozone. If the carbon dioxide level, however, is below the threshold, the decontamination process is aborted in step 208, i.e. steps 210 and 220 are not performed, since the low carbon dioxide level is an indication for a leakage.