Patent Application
20230167394
Various embodiments relate to an aeration device for a bioprocessing installation, in particular a bioreactor, and to a bioprocessing installation with such an aeration device.
A bioprocessing installation is generally understood to be an apparatus with which biotechnological processes, e.g. biopharmaceutical processes, can be carried out or supported. Bioreactors, in which microorganisms or mammalian cells are cultivated under given conditions, are only mentioned here as examples. Another example of bioprocessing installations are process mixing systems that can be used to mix liquid biological mediums such as suspensions, solutions, emulsions or the like, that are used in biotechnological processes. Such bioprocessing installations regularly have a container, in which a liquid biological medium consisting of the substances intended for the biotechnological process, for example microorganisms or tissue cells on the one hand, and a corresponding nutrient medium on the other hand, is accommodated in order to be able to carry out the respective biotechnological process step, for example fermentation or cultivation and/or mixing. The product, in case of a bioreactor for example the fermentation broth, is then usually further treated in a so-called downstream process to obtain a product from the cells or the culture supernatant.
A container for such a bioprocessing installation can be a dimensionally stable vessel on the one hand, but on the other hand also a flexible, i.e. bendable and slack, bag, also known as bioprocess bag.
Provision of an oxygen supply is one key factor in cellular metabolic processes. Although tissue cell cultures consume substantially less oxygen than bacteria and yeast cultures, ensuring an efficient supply is the greatest challenge facing the operation of a bioprocessing installation, in particular bioreactor. In addition to supplying the cells with oxygen, i.a. the concentration of dissolved carbon dioxide also plays a part as a controlled variable.
There are two conventional aeration methods: Aerating the headspace of the bioreactor and direct injection of gases through aeration devices such as aeration rings or discs. For the latter purpose, use is made not only of aeration rings or discs (“ring spargers”) comprising gas outlet ports having a discharge opening with a diameter larger than 0.2 mm, for example 0.8 mm, but also of “microspargers”, which are aeration devices with gas outlet ports having a discharge opening with a smaller diameter, for example 0.15 mm. Both types of aeration devices have specific advantages and drawbacks. It is therefore also known to combine both types of gas outlet ports in a common housing (“combined sparger”).
The aeration device (U.S. Pat. No. 10,427,112 B2), which is the starting point of the disclosure, comprises a housing with two aeration channels in its interior. The housing further comprises two gas inlet ports via each of which a gas can be introduced into an assigned aeration channel of the housing. Moreover, the housing comprises a plurality of gas outlet ports provided in the form of a first type of gas outlet ports having larger openings and a second type of gas outlet ports having smaller openings. Each type of gas outlet ports is assigned to a respective one of the aeration channels.
The known aeration device can be used as ring sparger, making use of the larger openings, and as microsparger, making use of the smaller openings. This aeration device can be used for two different applications. Nevertheless, an aeration device would be desirable which could still be used for a wider range of applications. Also an aeration device would be desirable which as much as possible prevents an aeration device from unintentional filling up with the liquid biological medium and/or which prevents unintentional clogging (blocking of the discharge openings).
It is therefore an object of various embodiments to provide an aeration device for a bioprocessing installation, in particular a bioreactor, which can be used for a wider range of applications.
The above noted problem can be solved by an aeration device for a bioprocessing installation, in particular a bioreactor, with the features as described herein.
The idea underlying various embodiments is to have an aeration device which can be adapted to different situations. It is a basic consideration that by manually or automatically configurating an aeration device of a bioprocessing installation, in particular a bioreactor, certain characteristics of the gas discharged from the aeration device into for example a liquid biological medium can be influenced. Such characteristics are, just as an example, the discharge velocity of the gas, the discharge locations of the gas, the discharge direction of the gas, the gas composition and/or the gas bubble size and/or gas bubble shape at the opening of the respective gas outlet port. By influencing certain characteristics of the gas, the behavior of the aeration device can be adapted to different requirements, especially to different biotechnological processes and/or to different stages within a biotechnological process. Moreover, such an aeration device can prevent unintentional filling up with liquid biological medium and/or unintentional clogging as will be explained later.
In detail, it is proposed that the aeration device is configurable with respect to a predetermined discharge of gas via the gas outlet ports. The device is therefore designed to allow certain changes to it, manually or automatically, in order to reach and/or maintain a predetermined discharge of gas via the gas outlet ports.
Various embodiments define different types of gas outlet ports of the housing of the aeration device. The gas outlet ports of a first type have openings with the typical diameter or cross-sectional area of openings of a standard ring sparger. The gas outlet ports of a second type have openings with the typical diameter or cross-sectional area of openings of a standard microsparger. The proposed aeration device may comprise only one of the first and second type of gas outlet ports or both types of gas outlet ports.
Various embodiments relate to an aeration device which is configurable by adjustment using an adjusting mechanism, whereas some embodiments relate to an aeration device which is configurable by replacement of one or more housing parts of the aeration device housing. It is to be noted that both embodiments may also be combined in one aeration device.
Regarding the embodiment of an aeration device which is configurable by adjustment using an adjusting mechanism, according to some embodiments a movable closing element for releasing and for blocking a fluid communication between one or more aeration channels and the outside of the aeration device may be provided. Such a closing element may form an upper cover of the housing. Various embodiments specify designs and functionalities of the clothing element.
In another embodiment, additionally or alternatively a movable closing element for releasing and for blocking a fluid communication of one or more gas inlet ports to one or more aeration channels may be provided. Such a closing element may form a lower cover of the housing. Various embodiments specify designs and functionalities of the clothing element.
According to various embodiments, the adjusting mechanism is configured to be controlled by an electronic control unit of the bioprocessing installation. This makes it particularly easy to adapt the aeration device to different biotechnological processes, or to adapt the aeration device to different stages and/or to changing conditions in a biotechnological process, even during the course of the biotechnological process.
Regarding the embodiment of an aeration device which is configurable by replacement of one or more housing parts of the aeration device housing, according to various embodiments housing parts, which have properties influencing the discharge of gas via the gas outlet ports, are mutually replaceable.
According to various embodiments at least one housing part may be detachably connected to the remainder of the housing by a positive connection and/or non-positive connection. Various embodiments specify designs and functionalities of the mutually replaceable housing parts and the respective aeration device.
Various embodiments are directed to an aeration device for a bioprocessing installation, in particular the aeration device according to the first teaching. In that aeration device the surface on the inside of one or more gas outlet ports of the housing and/or of at least a section of one or more aeration channels of the housing is provided with a coating or insert. The coating or insert can be made of a hydrophobic material, or a silicone material. All explanations given for the aeration device described herein are fully applicable to this teaching.
Various embodiments are directed to an aeration device for a bioprocessing installation, in particular the aeration device according to the first or second teaching. In that aeration device for one or more aeration channels of the housing a membrane and/or a filter material is arranged between the respective aeration channel and one or more gas outlet ports of the housing, such that the gas can be discharged from the respective aeration channel through the membrane and/or filter material to the outside of the aeration device. Additionally or alternatively, for one or more aeration channels of the housing a membrane and/or a filter material is arranged inside one or more gas outlet ports of the housing, such that the gas can be discharged from the respective aeration channel through the membrane and/or filter material to the outside of the aeration device. All explanations given for the aeration device described herein are fully applicable to this teaching.
Various embodiments are directed to an aeration device for a bioprocessing installation, in particular the aeration device according to one of the first to third teaching. In that aeration device one or more aeration channels of the housing are bordered at the top by a membrane made of a flexible material, in some embodiments a silicone material, wherein the membrane forms one or more gas outlet ports of the housing. In some embodiments, due to the flexibility of the material of the membrane, the size of the cross-sectional area of the gas outlet ports formed by the membrane changes depending on the gas pressure in the respective aeration channel. All explanations given for the aeration device described herein are fully applicable to this teaching.
Various embodiments directed to an aeration device for a bioprocessing installation, in particular the aeration device according to one of the first to fourth teaching. In that aeration device at least some of the gas outlet ports of a respective one of the aeration channels are non-uniform, or at least one group of gas outlet ports of a respective one of the aeration channels is non-uniform. In some embodiments, the size of the cross-sectional area of the gas outlet ports of at least one of the aeration channels varies along the aeration channel. Additionally or alternatively, the shape of the cross-sectional area of at least some of the gas outlet ports of at least one of the aeration channels may not be circular. All explanations given for the aeration device described herein are fully applicable to this teaching.
Various embodiments are directed to a bioprocessing installation, in particular a bioreactor, comprising a container, in some embodiments a dimensionally stable vessel or flexible bag, in which a liquid biological medium consisting of the substances intended for a biotechnological process can be accommodated, further comprising a proposed aeration device according to one of the first to fifth teaching. All explanations given for the aeration device described herein are fully applicable to this teaching.
Various embodiments provide an aeration device for a bioprocessing installation, in particular a bioreactor, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device, wherein the aeration device is configurable with respect to a predetermined discharge of gas via the gas outlet ports.
In various embodiments, the gas outlet ports are provided in the form of a first type of gas outlet ports which consists of gas outlet ports having an discharge opening with a diameter larger than 0.2 mm, of 0.25 to 4 mm, or 0.5 to 1.0 mm, and/or a cross-sectional area larger than 0.03 mm2, of 0.05 to 12.0 mm2, or of 0.2 to 0.8 mm2, and/or in the form of a second type of gas outlet ports which consists of gas outlet ports having an discharge opening with a diameter of at most 0.2 mm, of 0.005 to 0.2 mm, or of 0.02 to 0.18 mm, and/or a cross-sectional area of at most 0.03 mm2, of 0.00002 to 0.03 mm2, or of 0.0003 to 0.025 mm2.
In various embodiments, the aeration device has an adjusting mechanism, in particular a manually or automatically operable adjusting mechanism, and is configurable with respect to a predetermined discharge of gas via the gas outlet ports in that, by the adjusting mechanism, the discharge of gas via the gas outlet ports is adjustable.
In various embodiments, the adjusting mechanism comprises a movable closing element for releasing and for blocking, at least partly, especially completely, a fluid communication of one or more aeration channels of the housing to the outside of the aeration device.
In various embodiments, the closing element forms an upper cover of the housing and/or is arranged, in relation to the flow direction of the gas, downstream of the respective one or more aeration channels and/or gas outlet ports, and/or, in that the closing element is a rotary slider or linear slider, and/or, in that the closing element is movable around or along a geometrical axis which runs parallel or transversely to the rising direction of the gas bubbles, and/or, in that the closing element is disk shaped.
In various embodiments, the closing element comprises one or more closing element openings which, for releasing, at least partly, especially completely, the fluid communication of one or more aeration channels of the housing to the outside of the aeration device, can each be brought at least in partial, especially in complete, overlap with at least one discharge opening, and/or, which, for completely blocking the fluid communication of one or more aeration channels of the housing to the outside of the aeration device, can each be positioned completely offset to at least one discharge opening.
In various embodiments, the closing element is arranged to release and to block, at least partly, especially completely, a fluid communication of one or more, but not all, aeration channels of the housing to the outside of the aeration device, and to not affect a fluid communication of one or more other aeration channels of the housing to the outside of the aeration device.
In various embodiments, the one or more aeration channels, the fluid communication of which to the outside of the aeration device can be released and blocked by the closing element, are in fluid communication with and/or can be brought into fluid communication with only one type of gas outlet ports, in some embodiments only the second type of gas outlet ports, or with both the first type and the second type of gas outlet ports, in some embodiments in that these gas outlet ports point in and/or transverse to and/or against the rising direction of the gas bubbles, and/or, in that the one or more other aeration channels, the fluid communication of which to the outside of the aeration device cannot be affected by the closing element, are in permanent fluid communication with only one type of gas outlet ports, in some embodiments only the first type of gas outlet ports, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point in a different, in particular opposite, direction than the gas outlet ports assigned to the aeration channel or channels, the fluid communication of which to the outside of the aeration device can be released and blocked by the closing element, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point against and/or transverse to and/or in the rising direction of the gas bubbles.
In various embodiments, in one adjusting position of the closing element it releases other gas outlet ports than in another adjusting position of the closing element, and/or, in that in one adjusting position of the closing element it blocks other gas outlet ports than in another adjusting position of the closing element.
In various embodiments, in one adjusting position of the closing element it releases the respective gas outlet ports each to another extent than in another adjusting position of the closing element.
In various embodiments, in one adjusting position of the closing element, it releases discharge openings which are associated with one or more other aeration channels than in another adjusting position of the closing element.
In various embodiments, the adjusting mechanism comprises a movable closing element for releasing and for blocking, at least partly, especially completely, a fluid communication of one or more gas inlet ports of the housing to one or more aeration channels of the housing.
In various embodiments, the closing element forms a lower cover of the housing and/or is arranged, in relation to the flow direction of the gas, upstream of the respective one or more aeration channels, and/or, in that the closing element is a rotary slider or linear slider, and/or, in that the closing element is movable around or along a geometrical axis which runs parallel or transversely to the rising direction of the gas bubbles, and/or, in that the closing element is disk shaped.
In various embodiments, the closing element comprises one or more closing element openings which, for releasing, at least partly, especially completely, the fluid communication of one or more gas inlet ports of the housing to one or more aeration channels of the housing, can each be brought at least in partial, especially in complete, overlap with at least one inlet opening of at least one aeration channel, and/or, which, for completely blocking the fluid communication of one or more gas inlet ports of the housing to one or more aeration channels of the housing, can each be positioned completely offset to at least one inlet opening of at least one aeration channel.
In various embodiments, the closing element is arranged to release and to block, at least partly, especially completely, a fluid communication to one or more, but not all, aeration channels of the housing, and to not affect a fluid communication to one or more other aeration channels of the housing, and/or, in that the closing element is arranged to release and to block, at least partly, especially completely, a fluid communication of one or more, but not all, gas inlet ports of the housing to one or more aeration channels of the housing, and to not affect a fluid communication of one or more other gas inlet ports of the housing to one or more aeration channels of the housing.
In various embodiments, the one or more aeration channels, the fluid communication to which can be released and blocked by the closing element, are in fluid communication with and/or can be brought into fluid communication with only one type of gas outlet ports, in some embodiments only the second type of gas outlet ports, or with both the first type and the second type of gas outlet ports, in some embodiments in that these gas outlet ports point in and/or transverse to and/or against the rising direction of the gas bubbles, and/or, in that the one or more other aeration channels, the fluid communication to which cannot be affected by the closing element, are in permanent fluid communication with only one type of gas outlet ports, in some embodiments only the first type of gas outlet ports, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point in a different, in particular opposite, direction than the gas outlet ports assigned to the aeration channel or channels, the fluid communication to which can be released and blocked by the closing element, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point against and/or transverse to and/or in the rising direction of the gas bubbles.
In various embodiments, in one adjusting position of the closing element it releases other inlet openings than in another adjusting position of the closing element, and/or, in that in one adjusting position of the closing element it blocks other inlet openings than in another adjusting position of the closing element.
In various embodiments, in one adjusting position of the closing element it releases the respective inlet openings each to another extent than in another adjusting position of the closing element.
In various embodiments, the gas inlet ports, from which a fluid communication to one or more aeration channels of the housing can be released and blocked, are arranged, in some embodiments integrally, on the closing element and are movable with it relative to the aeration channel or channels and/or inlet openings of the aeration channel or channels.
In various embodiments, for configuration of the aeration device with respect to a predetermined discharge of gas via the gas outlet ports, the adjusting mechanism is configured to be controlled by an electronic control unit of the bioprocessing installation provided for at least partial control of the bioprocessing installation.
In various embodiments, the aeration device is configurable in that at least one housing part of the housing, which has properties influencing the discharge of gas via the gas outlet ports, is detachably connected to the remainder of the housing in such a way that the housing part can be replaced by another housing part which has different properties influencing the discharge of gas via the gas outlet ports.
In various embodiments, the at least one housing part is detachably connected to the remainder of the housing by a positive connection and/or non-positive connection, in particular a snap connection or plug connection.
In various embodiments, the at least one housing part which is detachably connected to the remainder of the housing, forms one or more gas outlet ports of the housing and/or at least a section of one or more aeration channels of the housing, in some embodiments a section defining at least the upper boundary and optionally one or both lateral boundaries of the respective aeration channel.
In various embodiments, one or more other aeration channels of the housing are formed in its entirety by the remainder of the housing.
In various embodiments, a respective one of the gas inlet ports of the housing is assigned to each housing part which is detachably connected to the remainder of the housing, in some embodiments in that the respective gas inlet port of the housing, in some embodiments each gas inlet port of the housing, is arranged, in some embodiments integrally, on the remainder of the housing.
In various embodiments, the at least one housing part forms an upper part of the housing and is arranged, in relation to the flow direction of the gas, downstream of the respective one or more aeration channels and/or inlet openings of the one or more aeration channels.
In various embodiments, the at least one housing part establishes a permanent fluid communication of the respective aeration channel to the outside of the aeration device.
In various embodiments, the gas outlet ports formed by the at least one housing part are gas outlet ports of only one type of gas outlet ports, in some embodiments only the second type of gas outlet ports, or of both the first type and the second type of gas outlet ports, in some embodiments in that these gas outlet ports point in and/or transverse to and/or against the rising direction of the gas bubbles, and/or, in that the one or more other aeration channels which are formed in its entirety by the remainder of the housing, are in permanent fluid communication with only one type of gas outlet ports, in some embodiments only the first type of gas outlet ports, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point in a different, in particular opposite, direction than the gas outlet ports formed by the at least one housing part, in some embodiments in that these gas outlet ports assigned to the one or more other aeration channels point against and/or transverse to and/or in the rising direction of the gas bubbles.
Various embodiments provide an aeration device for a bioprocessing installation, in particular a bioreactor, in particular the aeration device according to the disclosure, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device, wherein the surface on the inside of one or more gas outlet ports of the housing and/or of at least a section of one or more aeration channels of the housing, in some embodiments of a section defining at least the upper boundary and optionally one or both lateral boundaries of the respective aeration channel, is provided, at least partly, especially completely, with a coating or insert, in some embodiments made of a hydrophobic material, in some embodiments a silicone material, in some embodiments in that the coating or insert protrudes from the housing to form a projection, in some embodiments a cylindrical, conical or funnel-shaped projection.
Various embodiments provide an aeration device for a bioprocessing installation, in particular a bioreactor, in particular the aeration device according to the disclosure, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device, wherein for one or more aeration channels of the housing a membrane and/or a filter material, in some embodiments made of a hydrophobic material, is arranged between the respective aeration channel and one or more gas outlet ports of the housing and/or is arranged inside one or more gas outlet ports of the housing, such that the gas can be discharged from the respective aeration channel through the membrane and/or filter material to the outside of the aeration device.
Various embodiments provide an aeration device for a bioprocessing installation, in particular a bioreactor, in particular the aeration device according to the disclosure, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device, wherein one or more aeration channels of the housing are bordered at the top by a membrane made of a flexible material, in some embodiments a silicone material, and in that the membrane forms one or more gas outlet ports of the housing, in some embodiments in that, due to the flexibility of the material of the membrane, the size of the cross-sectional area of the gas outlet ports formed by the membrane changes depending on the gas pressure in the respective aeration channel, in some embodiments in that the size of the cross-sectional area of the gas outlet ports formed by the membrane is smaller, when the gas pressure in the respective aeration channel is low, and is larger, when the gas pressure in the respective aeration channel is high, in some embodiments in that one or more of the gas outlet ports formed by the membrane are closed, when the gas pressure in the respective aeration channel is low, and are opened, when the gas pressure in the respective aeration channel is high.
Various embodiments provide an aeration device for a bioprocessing installation, in particular a bioreactor, in particular the aeration device according to the disclosure, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device, wherein at least some, in particular all, of the gas outlet ports of a respective one of the aeration channels are non-uniform, or the group of gas outlet ports of a respective one of the aeration channels is non-uniform, wherein the size of the cross-sectional area of the gas outlet ports of at least one, in particular each, of the aeration channels varies along the aeration channel, in some embodiments, increases from the gas inlet port along the aeration channel, and/or in that the shape of the cross-sectional area of at least some, in particular all, of the gas outlet ports of at least one, in particular all, of the aeration channels is not circular.
Various embodiments provide a bioprocessing installation, in particular a bioreactor, comprising a container, such as a dimensionally stable vessel or flexible bag, in which a liquid biological medium consisting of the substances intended for a biotechnological process can be accommodated, further comprising an aeration device according to the disclosure.
In the following, embodiments are explained with respect to the drawing. In the drawing
An exemplary embodiment of a proposed bioprocessing installation 1 in the form of a bioreactor 2 is schematically shown in
In order to form a microbial or cellular product, the microorganisms or tissue cells are cultivated in the container 3 under specified conditions. In addition to the microorganisms or tissue cells on the one hand and the nutrient medium on the other hand, the container 3 allows further liquid or gaseous media, such as oxygen, pH correcting agent or the like, to be added, and the fermentation broth produced by the cultivation and any gases which may have collected in the headspace of the container 3 to be discharged. This discharged fermentation broth can then be fed to, among other things, a filter or centrifuge to obtain the final product.
Another example of a proposed bioprocessing installation 1 not shown here is a process mixing system that is used for mixing suspensions, solutions or emulsions that can be used in biotechnological processes, for example in a downstream or upstream process.
The proposed bioprocessing installation 1, here in the form of the bioreactor 2, also comprises a holder 5, here in the form of a stainless steel housing, in which the container 3 is installed. In the installed state, the container 3 extends in axial direction X, here in the vertical or gravitational direction, from an upper container end to a lower container end.
Here, the bioprocessing installation 1 comprises a stirrer 6, which is installed inside of the container 3. The stirrer 6 has here a stirrer shaft 6a extending in axial direction X from the upper container end towards the lower container end. The stirrer shaft 6a is equipped with at least one stirring element 6b, here in the form of a propeller stirrer. Here, two stirring elements 6b are provided at the stirrer shaft 6a. The stirrer 6 is rotatably driven by a drive motor 7 installed outside of the container 3 at the holder 5. The stirrer 6 here is used for mixing the biological medium during cultivation.
As also shown in
The aeration device 8 is located here below the at least one stirring element 6b. However, it is also conceivable to locate the aeration device 8 or a further aeration device 8 between two stirring elements 6b. Moreover, it is also conceivable to locate the aeration device 8 or a further aeration device 8 above the at least one stirring element 6b. The aeration device 8 or a further aeration device 8 may also be located at the bottom of the container 3 and/or the aeration device 8 or a further aeration device 8 may be located at a side wall of the container 3. Here, the aeration device 8 is arranged around the stirrer shaft 6a and coaxially thereto. However, the aeration device 8 may also be arranged with an offset to the stirrer shaft 6a. Moreover, the aeration device 8 can be oriented at different angles relative to the axial direction X within the container 3 and does not necessarily have to be oriented horizontally, as in the case shown in
As can be seen in
Furthermore, the housing 9 comprises one or more gas inlet ports 11, via each of which a gas can be introduced into at least one aeration channel 10a, 10b of the housing 9. As shown in
Furthermore, the housing 9 comprises a plurality of gas outlet ports 12a, 12b, via each of which the gas can be discharged from the respective aeration channel 10a, 10b to the outside of the aeration device 8 and in particular into the liquid biological medium inside of the container 3. Accordingly, the respective aeration channel 10a, 10b of the housing 9 is or can be brought in fluid communication with the outside of the aeration device 8 and in particular with the liquid biological medium inside of the container 3 via the gas outlet ports 12a, 12b assigned to the respective aeration channel 10a, 10b.
The gas outlet ports 12a, 12b assigned to a respective aeration channel 10a, 10b may have different shapes in longitudinal section, e.g. a cylindrical, conical or funnel-shaped shape. The sidewalls of the gas outlet ports 12a, 12b, e.g. the conical gas outlet ports 12a, 12b, may be oriented with an angle between 15° and 40° to the middle axis in flowing direction of the gas outlet port 12a, 12b.
In a plan view parallel to the rising direction of the gas bubbles, according to one variant the gas outlet ports 12a, 12b of one or more aeration channels 10a, 10b are arranged in at least one row, in particular in at least one row running circumferentially over a circumferential section (
One or more, in particular all, aeration channels 10a, 10b and/or rows of gas outlet ports 12a, 12b may be arranged, in the rising direction of the gas bubbles, with the stirring element or elements 6b aligned and/or circumferentially outside.
Each row may comprise one or more, e.g. up to 25 or even more gas outlet ports 12a, 12b.
It is now essential that the aeration device 8 is configurable with respect to a predetermined discharge of gas via the gas outlet ports 12a, 12b. This means that certain characteristics of the aeration device 8 can be changed, manually or automatically, in order to reach and/or maintain a predetermined discharge of gas via the gas outlet ports 12a, 12b.
The term “predetermined discharge” means that the discharge is intended for a specific biotechnological process and/or stage within a biotechnological process, i.e. a discharge which is necessary to allow the biotechnological process and/or stage to run as intended.
As indicated before, the configuration of the aeration device 8 may be carried out manually or automatically.
“Manually” means that a user changes the characteristics of the aeration device 8 by user intervention.
“Automatically” means that the changes of the characteristics of the aeration device 8 are effected, without user intervention, by an electronic control unit 13 of the bioprocessing installation 1, which control unit 13 is provided as shown in
The proposed aeration device 8 may comprise different types of gas outlet ports 12a, 12b. For example, gas outlet ports 12a can be provided in the form of a first type of gas outlet ports 12a. Said first type consists of gas outlet ports 12a having an discharge opening 17 with a diameter larger than 0.2 mm, of 0.25 to 4 mm, or of 0.5 to 1.0 mm, and/or a cross-sectional area larger than 0,03 mm2, of 0.05 to 12.0 mm2, or of 0.2 to 0.8 mm2. Additionally or alternatively, gas outlet ports 12b can be provided in the form of a second type of gas outlet ports 12b. Said second type consists of gas outlet ports 12b having an discharge opening 17 with a diameter of at most 0.2 mm, of 0.005 to 0.2 mm, or of 0.02 to 0.18 mm, and/or a cross-sectional area of at most 0.03 mm2, of 0.00002 to 0.03 mm2, or of 0.0003 to 0.025 mm2. According to the exemplary embodiments shown in
The downward facing gas outlet ports 12a are assigned to a separate aeration channel 10b, which is positioned concentrically to and here radially outside of the aeration channel 10a, whereby gas introduced into the aeration device 8 via a gas inlet port 11, which is here in permanent fluid communication with this aeration channel 10b, can be directed through the aeration channel 10b into the gas outlet ports 12a of this aeration channel 10b and from there to the outside of the aeration device 8. The gas is discharged here at the bottom of the aeration device 8.
It should be noted that, in addition or alternatively to the upward facing and/or to the downward facing gas outlet ports 12a, 12b, there also may be lateral gas outlet ports 12a, 12b, i.e. with openings facing to the side (in the radial direction), which may be of the first and/or second type, these gas outlet ports 12a, 12b in an optional embodiment also being used to configure the aeration device 8.
The term “adjustable” means, that for a specific biotechnological process and/or specific stage within a biotechnological process, it is possible, to set a specific state of the gas discharge once, here manually, and/or to adjust it repeatedly during the biotechnological process and/or stage by control (open-loop-control) or by regulation (closed-loop-control), the latter not being shown here.
Setting and/or repeatedly adjusting the state of the gas discharge allows to reach and/or maintain specific conditions in the biotechnological process and/or stage, e.g. to reach and/or maintain a specific gas composition or distribution and/or a specific cell growth etc.
The term “setting a specific state” means that the specific state is established with a choice between several states. In particular, it is possible to, e.g. manually, choose between three or more selectable states or between any number of selectable states. Thereby, a specific discharge of gas can be individually selected depending on the gas discharge requirements of the biotechnological process and/or stage.
As already indicated before, “manually” means that the adjusting mechanism 14 is operated by user intervention, e.g. a closing element 15, 16 such as a slider or flap is manually moved by a user.
The term “automatically” means that the adjusting mechanism 14 is operated, without user intervention, by an electronic control unit 13 of the bioprocessing installation 1, the electronic control unit 13 being provided for at least partial control of the bioprocessing installation 1. For example, an actuator assigned to the adjusting mechanism 14 is operated based on control signals generated by the electric control unit 13, and moves a closing element 15, 16 such as a slider or flap.
In the exemplary embodiment shown in
A “movable” closing element 15 means that the respective closing element 15 is movable relative to the remainder of the housing 9, in particular movable relative to the aeration channel or channels 10a, 10b and/or gas outlet ports 12a, 12b.
The term “for releasing and for blocking” means that in one adjusting position of the closing element 15, when releasing a fluid communication, it allows a fluid communication of one or more aeration channels 10a of the housing 9 to the outside of the aeration device 8, and in another adjusting position of the closing element 15, when blocking a fluid communication, it does not allow a fluid communication of one or more aeration channels 10a of the housing 9 to the outside of the aeration device 8. In particular, the closing element 15 may be adjusted in such a way as to allow complete blocking and/or complete release and/or, in one or more between positions, partial release.
By means of said adjusting mechanism 14 certain characteristics of the discharged gas can be set or repeatedly adjusted, for example characteristics as the discharge velocity of the gas, the discharge locations of the gas (the locations of the discharge openings 17 of the gas outlet ports 12a, 12b in the housing 9), the discharge direction of the gas (discharge from the top, bottom and/or lateral side of the housing 9), the gas composition and/or the gas bubble size and/or gas bubble shape of the discharged gas at the respective discharge opening 17.
In particular, such a closing element 15 prevents the housing 9 and respective gas supply lines connecting a gas source with the respective gas inlet port 11 from filling up with the liquid biological medium if no gas exits through the discharge openings 17 of the gas outlet ports 12a, 12b. The closing element 15 therefore can block the fluid communication of the respective aeration channel or channels 10a of the housing 9 to the outside of the aeration device 8 until the beginning of an aeration sequence in a biotechnological process, and then releases the fluid communication until the end of the aeration sequence. This can be done automatically via the control unit 13. In this context it is also emphasized, that also aligning discharge openings 17, here of the aeration channel 10b, downwards prevents the housing 9 and respective gas supply lines from filling up.
As shown in
The term “upper” means that in the intended installed use state the closing element 15 or cover is arranged on the side of the housing 9 facing in the rising direction of the gas bubbles, that is in the vertical direction and parallel to direction of gravity.
The “respective” one or more aeration channels 10a are those aeration channels 10a, the fluid communication of which to the outside of the aeration device 8 can be blocked by the closing element 15. Accordingly, the “respective” gas outlet ports 12a, 12b are those gas outlet ports 12a, 12b, the fluid communication through which to the outside of the aeration device 8 can be blocked by the closing element 15.
Additionally or alternatively, and as also shown in
The closing element 15 here is movable around the geometrical axis X which runs parallel to the rising direction of the gas bubbles. It is also conceivable, in different embodiments (not shown), that the closing element 15 is movable along the geometrical axis X which runs parallel to the rising direction of the gas bubbles, and/or that the closing element 15 is movable around or along a geometrical axis which runs transversely to the rising direction of the gas bubbles.
Here, the closing element 15 shown in
As can be seen in
Here, the closing element 15 is arranged to release and to block, at least partly, especially completely, a fluid communication of one or more, but not all, aeration channels 10a, 10b of the housing 9 to the outside of the aeration device 8, and to not affect a fluid communication of one or more other aeration channels 10b, here one single other aeration channel 10b, of the housing 9 to the outside of the aeration device 8.
According to the exemplary embodiment in
However, it is also conceivable, in a different embodiment (not shown), that the one or more aeration channels 10a, the fluid communication of which to the outside of the aeration device 8 can be released and blocked by the closing element 15, are in fluid communication with and/or can be brought into fluid communication with only one type of gas outlet ports 12a, 12b, in some embodiments only the second type of gas outlet ports 12b.
Here, the gas outlet ports 12a, 12b of the one or more aeration channels 10a, the fluid communication of which to the outside of the aeration device 8 can be released and blocked by the closing element 15, point in the rising direction of the gas bubbles. Additionally or alternatively, said gas outlet ports 12a, 12b or some of said gas outlet ports 12a, 12b may point transverse to and/or against the rising direction of the gas bubbles.
Additionally or alternatively, and as also shown in
Here, the gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point in a different, in particular opposite, direction than the gas outlet ports 12a, 12b assigned to the aeration channel or channels 10a, the fluid communication of which to the outside of the aeration device 8 can be released and blocked by the closing element 15. In various embodiments, these gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point against the rising direction of the gas bubbles. Additionally or alternatively, said gas outlet ports 12a or some of said gas outlet ports 12a may point transverse to and/or in the rising direction of the gas bubbles.
Moreover, as can also be seen in
Additionally or alternatively, and as also shown in
It is also conceivable, in a different embodiment (not shown), that in one adjusting position of the closing element 15 it releases discharge openings 17 which are associated with one or more other aeration channels 10a, 10b than in another adjusting position of the closing element 15. Depending on its adjusting position the closing element 15 can thus cause different aeration channels 10a, 10b to be in fluid communication with the outside of the aeration device 8.
The downward facing gas outlet ports 12a are assigned to a separate aeration channel 10b, which is positioned concentrically to and here radially outside of the aeration channels 10a, whereby gas introduced into the aeration device 8 via a gas inlet port 11, which is here in permanent fluid communication with this aeration channel 10b, can be directed through the aeration channel 10b into the gas outlet ports 12a of this aeration channel 10b and from there to the outside of the aeration device 8. The gas is discharged here at the bottom of the aeration device 8.
It should be noted that, in addition or alternatively to the upward facing and/or to the downward facing gas outlet ports 12a, 12b, there also may be lateral gas outlet ports 12a, 12b, i.e. with openings facing to the side (in the radial direction), which may be of the first and/or second type, these gas outlet ports 12a, 12b in an optional embodiment also being used to configure the aeration device 8.
Also in this case the adjusting mechanism 14 comprises a movable closing element 16. Here the movable closing element 16 is for releasing and for blocking, at least partly, especially completely, a fluid communication of one or more gas inlet ports 11 of the housing 9 to one or more aeration channels 10a of the housing 9.
A “movable” closing element 16 means that the respective closing element 16 is movable relative to the remainder of the housing 9, in particular movable relative to the aeration channel or channels 10a, 10b and/or gas outlet ports 12a, 12b.
In this case the term “for releasing and for blocking” means that in one adjusting position of the closing element 16, when releasing a fluid communication, it allows a fluid communication of one or more gas inlet ports 11 of the housing 9 to one or more aeration channels 10a of the housing 9, and in another adjusting position if the closing element 16, when blocking a fluid communication, it does not allow a fluid communication of one or more gas inlet ports 11 of the housing 9 to one or more aeration channels 10a of a housing 9. In particular, the closing element 16 may be adjusted in such a way as to allow complete blocking and/or complete release and/or, in one or more between positions, partial release.
Additionally or alternatively the adjusting mechanism may comprise one or more control valves (not shown), in particular check valves, e.g. single use valves, each in a respective gas supply line connecting a gas source with the respective gas inlet port 11. Such control valves are for releasing and for blocking, at least partly, especially completely, a fluid communication of an assigned gas inlet port 11 of the housing 9 to one or more aeration channels 10a of the housing 9.
Also by means of the adjusting mechanism 14 shown in
In particular, such a closing element 16 prevents respective gas supply lines connecting a gas source with the respective gas inlet port 11 from filling up with the liquid biological medium if no gas is supplied into the aeration channels 10a. The closing element 16 therefore can block the fluid communication of the one or more gas inlet ports 11 of the housing 9 to the one or more aeration channels 10a of the housing 9 until the beginning of an aeration sequence in a biotechnological process, and then releases the fluid communication until the end of the aeration sequence. This can be done automatically via the control unit 13. In this context it is also emphasized, that also aligning discharge openings 17, here of the aeration channel 10b, downwards prevents the respective gas supply lines from filling up.
As shown in
The term “lower” means that in the intended installed use state the closing element 16 or cover is arranged on the side of the housing 9 facing against the rising direction of the gas bubbles.
The “respective” one or more aeration channels 10a are those aeration channels 10a, to which the fluid communication can be blocked by the closing element 16.
Additionally or alternatively, and as also shown in
The closing element 16 here is movable around the geometrical axis X which runs parallel to the rising direction of the gas bubbles. It is also conceivable, in different embodiments (not shown), that the closing element 16 is movable along the geometrical axis X which runs parallel to the rising direction of the gas bubbles, and/or that the closing element 16 is movable around or along a geometrical axis which runs transversely to the rising direction of the gas bubbles.
Here, the closing element 16 shown in
As can be seen in
Additionally or alternatively, the one or more closing element openings 18, for completely blocking the fluid communication of one or more gas inlet ports 11 of the housing 9 to one or more aeration channels 10a of the housing 9, can each be positioned completely offset to at least one inlet opening 19 of at least one aeration channel 10a.
Here, the closing element 16 is arranged to release and to block, at least partly, especially completely, a fluid communication to one or more, but not all, aeration channels 10a, 10b of the housing 9, and to not affect a fluid communication to one or more other aeration channels 10b, here one single other aeration channel 10b, of the housing 9. Moreover, additionally or alternatively, the closing element 16 is arranged to release and to block, at least partly, especially completely, a fluid communication of one or more, but not all, gas inlet ports 11 of the housing 9 to one or more aeration channels 10a, 10b of the housing 9, and to not affect a fluid communication of one or more other gas inlet ports 11 of the housing 9 to one or more aeration channels 10b, here one single other aeration channel 10b, of the housing 9.
According to the exemplary embodiment in
However, it is also conceivable, in a different embodiment (not shown), that the one or more aeration channels 10a, the fluid communication to which can be released and blocked by the closing element 16, are in fluid communication with and/or can be brought into fluid communication with both the first type and the second type of gas outlet ports 12a, 12b.
Here, the gas outlet ports 12b of the one or more aeration channels 10a, the fluid communication to which can be released and blocked by the closing element 16, point in the rising direction of the gas bubbles. Additionally or alternatively, said gas outlet ports 12b or some of said gas outlet ports 12b may point transverse to and/or against the rising direction of the gas bubbles.
Additionally or alternatively, and as also shown in
Here, the gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point in a different, in particular opposite, direction than the gas outlet ports 12b assigned to the aeration channel or channels 10a, the fluid communication to which can be released and blocked by the closing element 16. In various embodiments, these gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point against the rising direction of the gas bubbles. Additionally or alternatively, said gas outlet ports 12a or some of said gas outlet ports 12a may point transverse to and/or in the rising direction of the gas bubbles.
Moreover, as can also be seen in
Additionally or alternatively, in one adjusting position of the closing element 16 it releases the respective inlet openings 19 each to another extent than in another adjusting position of the closing element 16. Depending on its adjusting position the closing element 16 can thus cause the inlet openings 19 of one or more aeration channels 10a to be released to different extents, that is with different sizes of the flowable cross sections.
Moreover, according to the exemplary embodiment in
As explained above, in both exemplary embodiments of
The downward facing gas outlet ports 12a are assigned to a separate aeration channel 10b, which is positioned concentrically to and here radially outside of the aeration channels 10a, whereby gas introduced into the aeration device 8 via a gas inlet port 11, which is here in permanent fluid communication with this aeration channel 10b, can be directed through the aeration channel 10b into the gas outlet ports 12a of this aeration channel 10b and from there to the outside of the aeration device 8. The gas is discharged here at the bottom of the aeration device 8.
It should be noted that, in addition or alternatively to the upward facing and/or to the downward facing gas outlet ports 12a, 12b, there also may be lateral gas outlet ports 12a, 12b, i.e. with openings facing to the side (in the radial direction), which may be of the first and/or second type, these gas outlet ports 12a, 12b in an optional embodiment also being used to configure the aeration device 8.
It should be noted that in
The different designs, in particular the different sizes and/or arrangements of gas outlet ports 12a, 12b, lead to different properties influencing the discharge of gas via the gas outlet ports 12a, 12b. Due to said properties of the housing parts 20a, 20b, 20c, 20d certain characteristics of the discharged gas can be set, e.g. the discharge velocity of the gas, the discharge locations of the gas, the discharge direction of the gas and/or the gas bubble size and/or gas bubble shape at the respective discharge opening.
The term “detachably connected” means that the respective housing part 20a, 20b, 20c, 20d is non-destructively detachable to the remainder of the housing 9. Thereby, the respective housing part 20a, 20b, 20c, 20d can be replaced, such that a non-destructive removal and replacement is possible. In particular the aeration device 8 comprises a set of several functionally identical housing parts of this interchangeable type, each of which can be mounted to the remainder of the housing 9 according to a specific biotechnological process and/or specific stage within a biotechnological process.
Here, the at least one housing part 20a, 20b, 20c, 20d is detachably connected to the remainder of the housing 9 by a positive connection (form-fit connection) and/or non-positive connection (force-locking connection), in particular a snap connection or plug connection.
As can be seen in
Furthermore, according to the exemplary embodiment in
Moreover, here a respective one of the gas inlet ports 11 of the housing 9 is assigned to each housing part 20a, 20b, 20c, 20d which is detachably connected to the remainder of the housing 9. Here, the respective gas inlet port 11 of the housing 9, in some embodiments each gas inlet port 11 of the housing 9, is arranged, such as integrally, on the remainder of the housing 9.
As shown in
The term “upper” means that in the intended installed use state the housing part 20a, 20b, 20c, 20d is arranged on the side of the housing 9 facing in the rising direction of the gas bubbles, that is in the vertical direction and parallel to direction of gravity.
The “respective” one or more aeration channels 10a are those aeration channels 10a, the fluid communication of which to the outside of the aeration device 8 is established via the gas outlet ports 12a, 12b of the housing part 20a, 20b, 20c, 20d.
As also can be seen in
Here, the gas outlet ports 12a, 12b formed by the at least one housing part 20a, 20b, 20c, 20d are gas outlet ports 12a, 12b of both the first type and the second type of gas outlet ports 12a, 12b. However, it is also conceivable that the gas outlet ports 12a, 12b are of only one type of gas outlet ports 12a, 12b, in some embodiments only the second type of gas outlet ports 12b. The gas outlet ports 12a, 12b formed by the at least one housing part 20a, 20b, 20c, 20d here point in, but may additionally or alternatively also point transverse to and/or against the rising direction of the gas bubbles.
Additionally or alternatively, and as also shown in
Here, the gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point in a different, in particular opposite, direction than the gas outlet ports 12a, 12b formed by the at least one housing part 20a-20d. In some embodiments, the gas outlet ports 12a assigned to the one or more other aeration channels 10b, here the single other aeration channel 10b, point against the rising direction of the gas bubbles. Additionally or alternatively, said gas outlet ports 12a or some of said gas outlet ports 12a may point transverse to and/or in the rising direction of the gas bubbles.
These embodiments of aeration channels 10a, 10b with gas outlet ports 12a, 12b, which are described below, may be provided in the aeration device 8 described above. However, these can also be used advantageously on their own in an aeration device 8 according to an independent further teaching. All explanations given for the above aeration device 8 according to the first teaching are therefore fully applicable to each further teaching.
Here, the coating or insert 21 is made of a hydrophobic material, or a silicone material. According to the exemplary embodiment in
Additionally or alternatively, the coating or insert 21 may be made of flexible material. In particular the protruding part of the coating or insert 21 may be made of flexible material.
It is also conceivable, in a different embodiment (not shown), that the surface on the inside of one or more gas outlet ports 12a, 12b of the housing 9 and/or of at least a section of one or more aeration channels 10a, 10b of the housing 9, in some embodiments of a section defining at least the upper boundary and optionally one or both lateral boundaries of the respective aeration channel 10a, 10b, is provided partly with a coating or an insert of a hydrophilic material.
Additionally or alternatively, such a membrane 23 and/or a filter material 24, in some embodiments made of a hydrophobic material, is arranged inside one or more gas outlet ports 12a, 12b of the housing 9 (
In some embodiments, as can be seen in
In some embodiments, one or more of the gas outlet ports 12a, 12b formed by the membrane 23 are closed, when the gas pressure in the respective aeration channel 10a, 10b is low, and are opened, when the gas pressure in the respective aeration channel 10a, 10b is high. This means that with no gas pressure and in some embodiments below a certain gas pressure, at least some gas outlet ports 12a, 12b are closed. In particular, thereby it is possible to change the amount of active (released) gas outlet ports 12a, 12b. At higher gas pressure more gas outlet ports 12a, 12b may be active than at low gas pressure.
The downward facing gas outlet ports 12a are assigned to a separate aeration channel 10b, which is positioned concentrically to and here radially outside of the aeration channels 10a, whereby gas introduced into the aeration device 8 via a gas inlet port 11, which is here in permanent fluid communication with this aeration channel 10b, can be directed through the aeration channel 10b into the gas outlet ports 12a of this aeration channel 10b and from there to the outside of the aeration device 8. The gas is discharged here at the bottom of the aeration device 8.
It should be noted that, in addition or alternatively to the upward facing and/or to the downward facing gas outlet ports 12a, 12b, there also may be lateral gas outlet ports 12a, 12b, i.e. with discharge openings facing to the side (in the radial direction), which may be of the first and/or second type, these gas outlet ports 12a, 12b in an optional embodiment also being used to configure the aeration device 8.
The term “non-uniform” means on one hand that some, in particular all, of the gas outlet ports 12a, 12b may each have, in cross-section and/or in longitudinal section, a non-uniform outer contour, e.g. a triangular or square outer contour, and on the other hand that within one group defined by a plurality of gas outlet ports 12a, 12b, in cross-section and/or in longitudinal section, not all gas outlet ports 12a, 12b have the same outer contour. A “group” of gas outlet ports 12a, 12b is defined as all gas outlet ports 12a, 12b that are assigned to the same aeration channel 10a, 10b. A “group” of gas outlet ports 12a, 12b is, additionally or alternatively, defined as all gas outlet ports 12a, 12b of the same type.
In some embodiments, as symbolized in
Additionally or alternatively, as also symbolized in
According to an independent sixth teaching a bioprocessing installation 1, in particular a bioreactor 2, is provided, comprising a container 3, in some embodiments a dimensionally stable vessel or flexible bag 4, in which a liquid biological medium consisting of the substances intended for a biotechnological process can be accommodated, wherein the bioprocessing installation 1 further comprises a proposed aeration device 8. All explanations given for the aeration device 8 according to the first to fifth teaching are fully applicable to this teaching.
| Number | Date | Country | Kind |
|---|---|---|---|
| 20315231.9 | Apr 2020 | EP | regional |
This application is a national stage application under 35 U.S.C. 371 of International Patent Application Serial No. PCT/EP2021/061336, entitled “Aeration Device for a Bioprocessing Installation,” filed Apr. 29, 2021, which claims priority from European Patent Application No. EP 20 315 231.9, filed Apr. 30, 2020, the disclosure of which is incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/061336 | 4/29/2021 | WO |
