BACKGROUND

Field of the Invention

The invention relates to a device and a method for receiving a disposable vessel.

Description of the Related Art

Bioreactors and pallet tanks serve as devices for receiving, storing and/or cultivating biological media such as for example fluids and/or cell cultures. Biological media may be provided in disposable vessels which may enclose a volume from a few liters up to several hundred liters. The biological media are inserted, within a disposable vessel, into the bioreactor, in which they are temperature-controlled to a predeterminable temperature over a predetermined time period, normally several hours in duration. Various tests on the biological medium may also be performed in a bioreactor of said type.

The handling of a bioreactor may be performed under clean room conditions, such that particularly high demands are placed on the quality control for the bioreactor.

In so-called single-use processes, it is possible in particular for disposable pouches to be used as disposable vessels. Both upstream and downstream, the use of disposable vessels has proven to save time and costs and to be reliable in terms of process technology. Whereas experience with cell culture processes and some microbial cultures has already been gained, it has hitherto scarcely been possible to realize processes with phototrophic organisms such as algae and/or plant cell cultures, in particular for a production scale of over 50 liters.

The invention is based on the object of realizing a facility of the type mentioned in the introduction for receiving a disposable vessel with phototrophic organisms, which is suitable in particular for a production scale of over 50 liters.

SUMMARY

A first aspect relates to a device for receiving a disposable vessel, having a receiving vessel with at least one receiving vessel wall which delimits a vessel interior space of the receiving vessel for receiving the disposable vessel. The device furthermore has a temperature-control unit for controlling the temperature of the receiving vessel wall. On an inner side, facing toward the vessel interior space, of the receiving vessel wall which is temperature-controlled by the temperature-control unit, there is arranged an illumination device which is designed to radiate light into the vessel interior space of the receiving vessel.

The device may be formed as a bioreactor and/or pallet tank, which may be designed for receiving disposable vessels with a volume from approximately 1 liter to approximately 2000 liters, preferably with a volume from approximately 200 liters to approximately 1000 liters. The device may be formed as a system with multiple components, in particular with or without a disposable vessel as an associated component. The device may be designed in particular for receiving disposable vessels containing a biological medium such as a fluid which is to be stored, temperature-controlled, cultivated and/or tested in some other way in the system over a predetermined time period. The biological medium may be in the form of a cell culture, and/or may have phototrophic organisms.

The disposable vessel may be in the form of a disposable pouch with flexible pouch walls, in particular with transparent plastics walls. The disposable vessel may, in its interior, have agitation components which can be coupled to an agitation device of the device in order to thereby permit mixing of the content of the disposable vessel.

The receiving vessel of the device provides the vessel interior space that is designed for receiving the disposable vessel. Here, the vessel interior space may be designed for receiving a predeterminable type of disposable vessel, that is to say for example a disposable vessel from a predeterminable manufacturer and/or with a predeterminable fill volume. Here, the receiving vessel wall or walls define the vessel interior space. Here, the receiving vessel walls need not fully surround and/or border the vessel interior space. Accordingly, the receiving vessel may for example have an agitation opening through which an agitation device can be connected to the disposable vessel arranged in the vessel interior space. An agitation device of said type is preferably formed on the upper end of the receiving vessel. The receiving vessel may thus be formed in particular without a cover, and/or so as to be open at the top.

In the context of this invention, the expressions “top”, “bottom”, “laterally”, “vertically”, “horizontally”, “height”, “lateral” etc. relate to the reference system of the earth, in which the system or the device is arranged in an operational position.

The disposable vessel is preferably inserted into the receiving vessel so as to lie on a base of the receiving vessel and so as to be in direct physical contact with the receiving vessel walls of the receiving vessel, in particular in contact with the base of the receiving vessel and/or with the receiving vessel walls that adjoin the base.

The at least one receiving vessel wall can be temperature-controlled by means of the temperature-control unit. The temperature-control unit can control the temperature of the receiving vessel wall to a predeterminable, in particular settable temperature. The temperature-control unit may be designed in particular for cooling the receiving vessel wall. Here, the temperature-control unit may either be arranged directly on an outer side, averted from the vessel interior space, of the receiving vessel wall or so as to be at least in direct heat-exchanging contact with the receiving vessel wall. Here, the receiving vessel wall may exhibit high thermal conductance, that is to say may for example be metallic.

The receiving vessel may have at least one openable and closable door through which the disposable vessel can be inserted into the vessel interior space.

The illumination device is arranged in the vessel interior space, which illumination device is, in an operational position of the device, arranged between the receiving vessel wall and the disposable vessel. In the operational position of the device, a disposable vessel is inserted into the device. The disposable vessel need not be a constituent part of the device. The disposable vessel may however be formed as a constituent part of the device.

The illumination device may be arranged in the vessel interior space so as to be in heat-exchanging contact with the temperature-controlled receiving vessel wall. Here, it is the case in particular that the illumination device is temperature-controlled, for example cooled, by means of the temperature-control unit. This permits a removal of the illumination-induced heat that can be generated during operation of the illumination device. Here, the illumination device requires no dedicated cooling arrangement, but can be temperature-controlled or cooled by means of the temperature-control unit of the device.

The device is suitable in particular for receiving disposable vessels with phototrophic organisms or cell cultures. The medium situated in the disposable vessel can be irradiated by means of the light radiated by the illumination device. Here, the walls of the disposable vessel are preferably transparent for at least the light wavelength(s) at which the illumination device radiates light into the vessel interior space.

In the context of this invention, the expression “light” does not necessarily mean visible light, but may rather relate to electromagnetic radiation with a wavelength from approximately 50 nm to approximately 50 μm. The expression thus also encompasses in particular ultraviolet and infrared light. The wavelength or the wavelength range of the light radiated by the illumination device may be adapted to particular requirements of the medium in the disposable vessel. The illumination device may have one or more light sources which are oriented such that they radiate light in the direction away from the receiving vessel wall toward the vessel interior space, in particular in a direction away from the receiving vessel wall toward the spatial region in which the disposable pouch is arranged in the operational position, for example toward a central point and/or a central axis of the vessel interior space.

The illumination device may, in the operational position, both directly adjoin the receiving vessel wall and directly adjoin the disposable vessel. Owing to this proximity between disposable vessel and illumination source, particularly efficient radiation of light into the interior of the disposable vessel with greatly reduced losses is made possible. At the same time, by means of the temperature control using the temperature-control unit, an adverse, overly intense generation of heat by the illumination device can be avoided, such as could otherwise lead both to damage of the cell cultures and to damage of a wall, formed from plastic, of the disposable vessel.

The device is thus particularly suitable for receiving disposable vessels which have a culture volume for a microbial culture, a cell culture, a culture of cell and/or tissue conglomerates of plant and/or animal cells and/or hybrid forms.

The device may furthermore have a controller which serves for controlling the light output by the illumination device. The illumination device may for example radiate modulated and/or non-modulated electromagnetic radiation, or else coherent electromagnetic radiation, such as for example laser light. The illumination device may be actuated so as to radiate a controllable quantity of light during controllable time periods. Here, the illumination device can in particular also be deactivated.

In one embodiment, the illumination device has at least one light source which is arranged at a position of the inner side of the receiving vessel wall which is temperature-controlled by the temperature-control unit directly at an outer side, averted from the vessel interior space, of the receiving vessel wall. Here, it is possible in particular for all light sources of the illumination device to be arranged at positions of the inner side of the receiving vessel wall which are temperature-controlled at the outer side. Since, in this embodiment, heat generated at the one or more light sources can be removed in a very efficient manner, this embodiment is particularly efficient. Thus, in this embodiment, the light source of the illumination device is arranged on one side of the receiving vessel wall, whereas the temperature-control unit is arranged at the opposite side of the receiving vessel wall. Here, the temperature control through the receiving vessel wall may act on the light source, which is arranged either so as to be in direct physical contact with the receiving vessel wall or so as to be spaced apart from the receiving vessel wall only by a carrier. As a carrier, use may be made of a substrate, in particular a substrate which is thermally conductive at least at certain points. The temperature control on the outer side of the receiving vessel wall may be performed for example by means of a temperature-control medium, which controls the temperature of the receiving vessel wall at the outer side.

In one embodiment, the illumination device has a multiplicity of light sources which are arranged so as to be distributed over at least 50% of the area of the inner side of all lateral receiving vessel walls. Through the use of a multiplicity of light sources, the luminous power and/or the number of photons that can be radiated into the vessel interior space is increased. The light sources may be arranged such that light sources are arranged on as many receiving vessel walls as possible. One aim here may be to achieve substantially uniform illumination over the outer surfaces of the vessel. In this embodiment, light sources are arranged at least on 50% of the lateral receiving vessel walls. The lateral receiving vessel walls are in this case those walls of the receiving vessel which delimit the vessel interior space in a lateral direction. These are, for example in the case of a substantially cylindrical, upright receiving vessel, all of the walls of the cylinder casing without the cylinder base and without the cylinder cover. It is preferably possible here for the light sources to be arranged on substantially all lateral receiving vessel walls. Here, “substantially” means that those surfaces of the lateral receiving vessel walls on which a door and/or a viewing window is arranged may remain omitted. Here, the light sources may be arranged on the receiving vessel walls substantially from the bottom to the top, in particular from a foot of the receiving vessel up to an intended fill height.

In one embodiment, the illumination device has a multiplicity of actuatable LEDs as light sources. In this way, it is possible for both modulated and non-modulated radiation to be output. LEDs are suitable as particularly efficient light sources, because LEDs generate relatively little heat in relation to the quantity of light output, whereby the heat generation can be reduced and, at the same time, the radiated luminous power can be increased. Furthermore, LEDs can be formed with a small structural height, such that these light sources can be arranged substantially areally on the inner side of the receiving vessel wall, without overly reducing the volume of the vessel interior space and without forming significant projections in the interior of the receiving vessel, which would impede an insertion of the disposable vessel.

In one embodiment, the illumination device radiates at least 90% of the radiated luminous power with a predetermined wavelength or with a predetermined wavelength spectrum of between 50 nm and 50 μm. The illumination device may thus be designed to radiate electromagnetic radiation with the predetermined wavelength or a predetermined wavelength spectrum. This may in particular involve laser light and/or light from LEDs. The predetermined wavelength or the predetermined wavelength spectrum may be adapted to the content of the disposable vessel, in particular to wavelengths that influence the metabolism of the cells situated therein. Here, the illumination device may for example be designed to radiate at least 90% of the radiated luminous power at the predetermined wavelength or in the predetermined wavelength spectrum.

In one embodiment, the illumination device is designed to radiate light by means of exchangeable light sources which have different radiation spectra. Accordingly, the device can be used firstly for a culture medium which requires electromagnetic radiation of a first wavelength and/or of a first wavelength spectrum, which is radiated by a first set of light sources of the illumination device. The light sources can subsequently be exchanged for light sources that radiate predominantly light of a second wavelength and/or of a second wavelength spectrum, which may be suitable for a different type of cells or metabolism influencing. The exchangeable form of the light sources serves firstly for enabling damaged individual light sources to be exchanged if required and for the variation of the radiation spectrum of the illumination device, for example by exchange of all light sources for light sources with different radiation characteristics. In this embodiment, the illumination device may in particular have a holder which is arranged and/or fastened in the interior of the receiving vessel, and may furthermore have at least one exchangeable carrier on which the light sources are arranged. Said carrier may for example be of strip-shaped form, wherein multiple light sources may be arranged on each strip. The carriers, together with the light sources arranged thereon for example as a subassembly, can be dismounted from the holder of the illumination device and exchanged. The carriers of the light sources can in particular be individually exchanged and/or individually fastened to the holder.

In one embodiment, an external shape of an outer side, averted from the vessel interior space, of the illumination device is adapted to an internal shape of the inner side of the receiving vessel wall. Here, the external shape of the illumination device is thus formed as a complementary counterpart to the internal shape of the receiving vessel wall. As a counterpart of said type, the outer wall of the illumination device bears closely against the inner wall of the receiving vessel wall. In this way, the heat conduction between the illumination device and the receiving vessel wall is improved. Here, a further layer, for example a thermally conductive foil and/or an adhesive, may be arranged between the receiving vessel wall and the illumination device.

In a refinement of this embodiment, the external shape of the illumination device is of convex form, whereas the internal shape of the receiving vessel wall is of concave form. For example, the receiving vessel may be substantially in the form of an upright cylinder which has a substantially circular or oval cross section. The inner side of the receiving vessel is thus concave. Here, the outer side of the illumination device is adapted to said concave shape by virtue of said outer side itself being of convex form in the direction toward the inner side of the outer vessel wall. Here, too, the heat conduction between the illumination device and the receiving vessel wall is increased.

In one embodiment, the illumination device is designed to emit light with a luminous power of up to approximately 3000 μmol/m2s into the vessel interior space. With such high radiation power, intense generation of heat can occur. This heat generation is compensated by means of the temperature-control unit. Particularly efficient cultivation of biological media is possible by means of the high luminous power.

In one embodiment, the illumination device has a multiplicity of light sources arranged on a strip, wherein the strip is arranged substantially vertically along the receiving vessel wall. It is thereby made possible for a multiplicity of light sources to be arranged on the receiving vessel wall simultaneously. This is advantageous in particular in the case of rounded and/or curved receiving vessel walls, on which vertical strips as carriers of the light sources are arranged. The strips may be formed either as carriers of multiple light sources spaced apart vertically from one another, or so as to support in each case one elongate light source, for example one elongate and/or rod-shaped light source. A multiplicity of such strips may be arranged in the receiving vessel along the curvature of the receiving vessel wall. The strips may be arranged at a position in the receiving vessel at which the receiving vessel wall is formed with an only one-dimensional curvature, that is to say has a curvature only in one direction of extent. The receiving vessel wall may be of non-curved form in a direction perpendicular to the direction of curvature. The strips may be arranged in the receiving vessel so as to extend along the receiving vessel wall said non-curved direction of extent, in which the receiving vessel wall is of substantially straight form. The strips may be formed as a carrier and/or substrate for the light sources. Furthermore, the strips may be formed as thermal bridges between the light sources and the receiving vessel wall, and/or may have such thermal bridges. Furthermore, a thermally conductive foil and/or an adhesive layer may be arranged between the receiving vessel wall and the strip.

In one embodiment, in an operational position of the device, the disposable vessel is in physical contact with the illumination device. This means that the illumination device is arranged such that, in the operational position of the device, in which the disposable vessel has been inserted into the receiving vessel, the disposable vessel lies directly against the illumination device. This enables the content of the disposable vessel to be illuminated in a particularly efficient manner or with low losses.

In one embodiment, an in particular transparent resin layer and/or lacquer layer with a thickness of up to approximately 1 mm is arranged over light sources of the illumination device. Sharp edges, which could damage the disposable vessel, of the illumination sources can be smoothed by means of the resin layer and/or lacquer layer. Furthermore, by means of the resin layer and/or lacquer layer, projections can be reduced in order to smooth the receiving vessel walls that are narrowed by the illumination device. An epoxy resin may be used as resin. The resin layer and/or lacquer layer is in particular of transparent form for the one or more wavelengths radiated by the illumination device. The resin layer and/or lacquer layer on the light sources preferably has a maximum thickness of approximately half of one millimeter.

In one embodiment, the illumination device has at least one thermal bridge between light sources of the illumination device and the temperature-controlled receiving vessel wall. Such thermal bridges improve the removal of heat from the light sources via the receiving vessel wall.

In one embodiment, the temperature-control unit is designed to impart a heat removal power of up to at least 8 kW, preferably at least 10 kW, particularly preferably up to at least 20 kW. Such intense heat removal power of the temperature-control unit may permit an approximately equally great generation of heat during the illumination of the content of the disposable vessel. Thus, this embodiment permits particularly bright, intense and highly powerful illumination of a biological medium.

In one embodiment, the receiving vessel wall is formed at least partially as a temperature-control cavity wall. Here, the temperature-control unit is designed to control the temperature of the vessel interior space by means of a temperature-control medium arranged in the temperature-control cavity wall.

The temperature-control cavity wall is formed in the receiving vessel walls of the receiving vessel can be formed as part of a closed temperature-control circuit. The temperature-control cavity wall may be formed as part of the receiving vessel walls. The temperature-control cavity wall may be formed as a double wall with a temperature-control inner wall and a temperature-control outer wall. Here, the temperature-control inner wall may face toward the vessel interior space of the receiving vessel, and the temperature-control outer wall may be averted from the vessel interior space.

The temperature-control medium is formed and arranged in a cavity between the temperature-control inner wall and the temperature-control outer wall. The temperature-control unit controls the temperature of the vessel interior space, in particular the content of the disposable vessel and/or the illumination device, by means of the temperature-control medium. For this purpose, a controller may be provided, by means of which the temperature and/or the pressure of the temperature-control medium in the temperature-control cavity wall can be controlled and/or set. The controller may be formed as part of the temperature-control unit. The temperature-control unit may thus comprise the controller and/or the temperature-control medium arranged in the temperature-control cavity wall.

The interior of the temperature-control cavity wall may be formed as a free cavity or with at least one flow-guiding element for guiding the flow of the temperature-control medium through the temperature-control cavity wall.

The two walls of the temperature-control cavity wall, that is to say a temperature-control inner wall and a temperature-control outer wall, may have a spacing of a few millimeters to one another, and may be spaced apart from one another for example by between 5 mm and 40 mm.

The inner side of the temperature-control cavity wall, that is to say the temperature-control inner wall facing toward the vessel interior space, may in this case be formed so as to directly join the vessel interior space and/or the illumination device. In other words, it is possible for no further element of the device to be formed between the vessel interior space and the temperature-control cavity wall. In other words, the temperature-control cavity wall may thus at least partially directly surround and/or delimit the vessel interior space and/or the illumination device.

Here, “at least partially surround” means that the temperature-control cavity wall surrounds the vessel interior space at its outer surface over at least 40%, preferably over at least 60%, particularly preferably over at least 70%, particularly preferably over at least 80% thereof. In particular, this may mean that the vessel interior space is fully surrounded and/or bordered and/or temperature-controlled by the temperature-control cavity wall aside from an upper cover region and possible viewing window and/or a door opening.

The temperature-control cavity wall may be formed as a pressure appliance in accordance with the PED guideline (“Pressure Equipment Directive” for the European Economic Area) and/or in accordance with the ASME guideline (“American Society of Mechanical Engineers” for the American Economic Zone), in particular as a pressure appliance with approximately 6 barg.

In general, the temperature-control medium may be formed as a fluid such as for example a liquid or a gas, which is situated in a closed temperature-control circuit. The temperature-control cavity wall of the receiving vessel constitutes at least a part of said temperature-control circuit.

In one embodiment, the receiving vessel is designed to receive disposable vessels with a volume of at least approximately 50 liters, preferably at least 1000 liters, particularly preferably at least approximately 2000 liters. In the case of known devices, it has hitherto not been possible for disposable vessels of such large volumes to be efficiently illuminated and cultivated. The impingement of light required for this purpose is made possible for the first time by the particularly efficient illumination and cooling by means of the device according to the invention. It must be noted here that, although the light emitted by the illumination device under some circumstances does not penetrate fully into the middle of the medium in the disposable vessel, it is nevertheless possible for adequately uniform illumination of the medium to be provided by virtue of the medium being mixed by means of an agitation device.

In one embodiment, the device satisfies the GMP guidelines. The GMP guidelines, which is an abbreviation for “Good Manufacturing Practice”, are guidelines concerning requirements with regard to hygiene, premises, equipment, documentation and inspections in the pharmaceutical sector. The device may be designed so as to satisfy the requirements stated in the GMP guidelines, in particular the requirements with regard to sterility.

A second aspect relates to a method for receiving a disposable vessel, having the steps:

receiving a disposable vessel in a vessel interior space of a receiving vessel with at least one receiving vessel wall which delimits the vessel interior space;

illuminating the disposable vessel arranged in the vessel interior space by means of an illumination device which is arranged on an inner side, facing toward the vessel interior space, of the receiving vessel wall; and

controlling the temperature of the receiving vessel wall.

The method can be performed in particular by means of the device according to the first aspect. Therefore, all of the statements made in the context of the device also apply to the method according to the second aspect, and vice versa.

The invention will be described in more detail below on the basis of exemplary embodiments shown in figures. Identical reference signs are used to denote identical or similar components of the embodiments. Individual features of the embodiments may be combined with other embodiments.

