Perfusion module for a bioreactor, and system comprising a perfusion module and a bioreactor

Abstract

The invention relates to a perfusion module (10, 40, 70) for a bioreactor, comprising a main body (12, 42, 72) having a fluid passage (18, 48, 78) and a recess (20, 50, 80) inclined toward said fluid passage (18, 48, 78), a filter element (14, 44, 74), and at least one fastening element (16, 46, 76, 76a, 76b), wherein the at least one fastening element (16, 46, 76, 76a, 76b) is designed to fasten the filter element (14, 44, 74) to the main body (12, 42, 72), wherein, when the perfusion module (10, 40, 70) is in an assembled condition, the fluid passage (18, 48, 78), the recess (20, 50, 80) of the main body (12, 42, 72) and the filter element (14, 44, 74) together form a flow-permeable cavity (28, 58, 83).

Description

[0001] December 17, 2025

[0002] Perfusion module for a bioreactor and system with a perfusion module and a bioreactor

[0003] The present invention relates to a perfusion module for a bioreactor and to a system comprising such a perfusion module and a bioreactor.

[0004] In chemistry or biology, for example for microbiological investigations or cell cultures, it is common to introduce or remove a reagent or medium from a vessel. This is the case, for instance, when a nutrient medium is added for a cell culture. A challenge here is to keep the objects of investigation, such as biological material (e.g., human or animal cells, bacteria, archaea, fungi, plants, enzyme reactions), within the vessel and to remove only a fluid (e.g., a nutrient medium), waste products, or similar substances without damaging the remaining biological material, impairing its function, or negatively affecting its development (growth or developmental biology).

[0005] It is known from the prior art to fix biological material onto a solid support material while a nourishing fluid is exchanged for the biological material or flows past the fixed biological material. A disadvantage of this method is that the biological material is fixed, which is undesirable in certain investigations or cultivations and complicates further processing. Another known approach involves using a filter or membrane element to retain the biological material when used medium, waste products of the biological material, or other fluids are removed. However, a common problem arises here: due to the pressure differential or suction used to remove the medium, the biological material adheres to the filter or membrane element and may clog pores or openings of the filter or membrane element.Due to the biological properties of the filtrate, organisms can actively adhere to and within the filter medium, leading to so-called "bio-fouling".

[0006] Against this background, the present invention aims to overcome the disadvantages of the prior art and, in particular, to provide improved means for introducing or removing a fluid into or from a biological system.

[0007] The aforementioned problem is solved by a perfusion module for a bioreactor, comprising a base body having a fluid passage and a recess converging towards the fluid passage, a filter element and at least one fastening element, wherein the at least one fastening element is designed to fasten the filter element to the base body, wherein, in an assembled state of the perfusion module, the fluid passage, the recess of the base body and the filter element together form a flow-permeable cavity.

[0008] The aforementioned task is also solved by a system with a perfusion module as disclosed and with a bioreactor having a fluid container, in that the perfusion module forms the bottom of the fluid container.

[0009] The interaction of the base body and the filter element, and their specific design, allows for improved flow during the introduction or discharge of a fluid into or out of a biological system. In particular, the disclosed solution enables, on the one hand, a more homogeneous flow field at the filter element. On the other hand, a relatively large filter area is provided at the filter element or at the bottom of the reactor chamber. This allows, for example, a more favorable ratio between reactor volume and

[0010] GO 241130W02 December 17, 2025 A filter surface area is offered that is larger relative to the volume-to-filter surface area ratio of known so-called "dip tubes" or spargers for cell retention. Both aspects together result in the synergistic effect of a relatively low filtration rate per filter area in the perfusion module or system proposed here, which slows down clogging or blockage of the filter element. Furthermore, biological material, especially cells, is treated more gently due to the lower flow forces at the filter element. At the same time, the filter surface in the reactor can be almost continuously overflowed during mixing, which further reduces clogging. This also allows for better control of fouling.

[0011] Due to the suitability of the perfusion module as a base for a fluid container, the system can be used to expand the functionality for bioreactors, especially for shear-sensitive organisms such as stem or immune cells, or their assemblages such as organoids, sperhoids, cell factories.

[0012] As disclosed, the fluid passage, the recess of the base body, and the filter element together form a flow-permeable cavity. The recess of the base body tapers towards the fluid passage. Thus, the cavity is designed to guide a fluid entering the cavity through the filter element to the fluid passage in a flow-optimized manner when a first main flow direction is present. Fluid flow in the first main direction can occur, for example, in the application of filtration, where suction is applied at the fluid passage. This suction can be generated, for example, by a pump connected to the fluid passage or by hydrostatics. With a flow in the first main direction, a fluid can be distributed across the surface of the filter element and drawn towards the fluid passage by a narrowing stream within the cavity.Thanks to the suction effect distributed across the entire surface of the filter element, otherwise flow-induced accumulation or deposition of biological material and locally intensified currents in the bioreactor are reduced. In other words, the high filter surface area to reactor volume ratio allows for the removal of biological material.

[0013] GO 241130W02 December 17, 2025, can be filtered with little suction or pressure differential, which makes potentially irreversible clogging of the filter medium more difficult. Deposits on the filter surface can then be backwashed essentially evenly.

[0014] The design of the cavity as disclosed also allows for the fluid entering through the fluid passage to be distributed within the cavity in a second main flow direction, or for the incoming flow to be broadened within the cavity and guided in a broadened flow direction across the surface of the filter element. The uniform inflow of the liquid through a large cross-section reduces strong or rapid flow movements at the filter surface. This enables, in particular, a uniform and controllable backwashing or slurry formation at the filter element, which is advantageous for shear-sensitive cells.

[0015] Designing the perfusion module as the base for the fluid reservoir of a bioreactor enables media exchange during the bioreactor's operation, or so-called "in-situ" media exchange. This allows nutrients to be introduced and metabolic waste products flushed out during processes such as cell culture. This results in a higher concentration of biological material in the system and / or a higher process yield in so-called "biology productions," i.e., in cases where cells are not the product but rather produce and expel the desired product. Furthermore, the components retained in the bioreactor or by the filter element can be rapidly concentrated, thus facilitating the harvesting of biological material and intensifying downstream processing. Overall, the perfusion model described above enables process intensification.

[0016] Furthermore, the suitability of the perfusion module as the base of the fluid tank reduces the need for separate components. This also enables a

[0017] GO 241130W02 December 17, 2025 space-saving design of the system and reduces the probability of contamination compared to external perfusion systems.

[0018] Furthermore, by simplifying the design of the perfusion module with a limited number of components, and in particular by dispensing with additional flow guidance elements, adsorption effects can be reduced, which can occur, for example, through the adhesion of media components to flow guidance elements.

[0019] For the purposes of this disclosure, bioreactors can be fluid containers in embodiments commonly used in chemistry and bioprocess engineering, whether intended for single or multiple use. A non-exhaustive list of examples includes: stirred tank reactors, bubble column reactors, fixed-bed reactors, fluidized bed reactors, membrane bioreactors, photobioreactors, reactors for tissue engineering, roller bottles, flasks, and wave bags.

[0020] The bioreactor preferably comprises a fluid vessel with a wall comprising a bottom and a side, and a lid compatible with the fluid vessel. The fluid vessel and the lid can form a housing that includes a cavity for holding at least one fluid. This cavity can be called the reactor chamber and can be of any size. The bioreactor can thus have a working volume in the range of 0 to 2000 L, particularly in one of the following ranges: 0.1 to 0.3 L, 0.3 to 2 L, 2 to 10 L, 10 to 50 L, 50 to 200 L, or 200 to 2000 L. Particularly preferred values ​​for the working volume of the bioreactor are: 0.3 L, 2 L, 10 L, 50 L, 200 L, and 2000 L. Working volumes up to approximately 2 L are particularly suitable for research and development purposes for therapeutic agents. Working volumes in the range of approximately 2 to approximately 10 L are particularly suitable for chemistry studies as preparation for production processes.Working volumes from approximately 10 L are particularly suitable for production processes.

[0021] GO 241130W02 December 17, 2025 Optionally, the bioreactor may have a gassing and stirring unit located within the reactor chamber. This gassing and stirring unit may include at least one membrane element and be designed for both fluid transfer, such as gas transfer, and power transmission to drive the gassing and stirring unit. Alternatively or additionally, the bioreactor may have an impeller, such as a Rushton impeller or a skewed blade impeller.

[0022] The perfusion module is preferably designed to serve as the base of the fluid vessel of a bioreactor. For this purpose, the perfusion module can have a connection area for a fluid-tight seal with the wall of the fluid vessel. A sealing element, such as a sealing ring or an adhesive compound, can be provided at this connection area. The connection area can be located on the base body, the filter element, or the mounting element. Alternatively, at least two elements consisting of the base body, the filter element, or the mounting element can form the connection area. Alternatively, the wall of the fluid vessel can have a section designed as a mounting element.

[0023] The fluid passage can be designed for flow in a first main flow direction and in a second main flow direction opposite to the first. This allows the perfusion module to be used both for introducing a fluid into the reactor chamber of the bioreactor, for example for backflushing, and for removing a fluid from the reactor chamber, for example for filtration.

[0024] The fluid passage can be designed to introduce a fluid into or out of the cavity. The fluid may be subject to suction or a pressure differential created by a pump.

[0025] GO 241130WO2 December 17, 2025 According to the disclosure, the recess of the base body tapers towards the fluid passage. The recess can have a funnel-shaped profile when viewed in cross-section, with the funnel-shaped profile tapering towards the fluid passage.

[0026] The filter element can be characterized or selected by its separation efficiency. The separation efficiency (T) describes the effectiveness of a separation process. Specifically, the separation efficiency corresponds to the ratio of the amount or concentration of the substance to be separated (e.g., biological material) that is separated by the filter element to the concentration of the medium from which the substance is separated by the filter element. At least one element from the following list can contribute to the permeability of the filter element, although this list is not exhaustive: pore size, porosity, tortuosity, pore distribution, opening size (e.g., opening diameter), distribution of penetrating openings, pore density or density of penetrating openings, and permeability.

[0027] The filter element can have pores with an average pore size ranging from 0.2 to 200 pm, although this range is not restrictive. Alternatively or additionally, the filter element can have penetrating openings, where the penetrating openings are smaller than the size of the components of a biological material or than the size of carriers for the biological material to be retained in the reactor space. This allows the biological material to be filtered from a fluid; the penetrating openings can, for example, have an average size ranging from 0.2 to 200 pm.

[0028] Depending on the selected initial permeability, pore size, or opening size of the filter element, the perfusion module can be used for various applications. For example, depending on the pore size or the size of the penetrating openings, the perfusion module can be used for carrier separation or so-called "carriers".

[0029] G0241130W02 December 17, 2025 Separation" or for the separation of cells, cell aggregates, and microcarriers. Further application examples include the separation of dissolved components of the medium, such as in dialysis, of large proteins such as antibodies and enzymes, of small proteins, and of individual salts such as urea. Separation can be achieved based on charge differences.

[0030] The filter element can, for example, have a membrane of one of the following types: dense membrane for diffusive entry, porous membrane, woven membrane, spun membrane. The membrane can be made of at least one of the following materials: plastic, ceramic, metal, or natural materials such as cellulose.

[0031] The at least one fastening element is designed, as disclosed, to attach the filter element to the base body. For this purpose, the at least one fastening element may have a connecting section that can be joined to the base body and a receiving area for receiving the filter element. Alternatively or additionally, the base body may have a counter-fastening element that can be joined to the at least one fastening element. Examples of a counter-fastening element are a thread or a clamping mechanism, an element for receiving an adhesive, an adhesive, or a welded joint, without these being limiting.

[0032] Multiple fastening elements can be provided, or the single fastening element can be multi-part. The fastening elements can be distributed across the filter element in sections or at specific points to secure the filter element to the base body. A large filter element can be attached using multiple fastening elements or the multi-part fastening element. In this way, the perfusion module can be adapted to large bioreactors.

[0033] GO 241130W02 December 17, 2025 The following describes various embodiments of the perfusion module and the system, with each embodiment applying independently to the perfusion module and the system. Furthermore, the individual embodiments can be combined with one another as desired.

[0034] In one embodiment of the perfusion module, it is provided that at least one support element is provided in the recess of the base body, and that the at least one support element is designed to support the filter element in an assembled state of the perfusion module and under negative or positive pressure in the cavity.

[0035] The at least one support element can be integrated into the base body. Alternatively, the support element can be designed as a separate component and for placement within the cavity.

[0036] The filter element can be held or supported at a distance from the base surface of the recess of the base body, in particular from the base surface of the recess of the base body, by means of at least one support element. This contributes to forming the cavity. In addition, the at least one support element can contribute to the distribution of a fluid flow.

[0037] In particular, if the at least one support element is designed with a curved base profile, the filter element can be supported in a correspondingly curved position and simultaneously spaced away from the base of the recess.

[0038] The inclusion of at least one support element enables three-dimensional lateral structuring of the base body and corresponding three-dimensional positioning of the filter element. This allows the filter element to be adapted to the flow conditions in the reactor, resulting in rapid [unclear - possibly "processing" or "application"].

[0039] GO 241130W02 December 17, 2025 and gentle resuspension of sedimented biological material such as microcarriers, organoids, cells or other deposits (fouling) or

[0040] Fouling control can be achieved in the reactor room.

[0041] The at least one support element can, for example, be designed as a grid. Alternatively or additionally, the at least one support element can have knobs or spherical elements. Alternatively or additionally, the at least one support element can have pores and / or penetrating openings. An example of this is a support element made of a foamed material. This allows the filter element to be supported while simultaneously permitting fluid flow through to the opening. Depending on the design of the at least one support element, the flow of the fluid through it can be directed, segmented, accelerated, or decelerated.

[0042] In one embodiment of the perfusion module, the at least one support element comprises at least two support elements, wherein the at least two support elements are of essentially the same height relative to a base profile of the base body. Alternatively, the at least one support element may comprise at least two support elements, wherein the at least two support elements are of different heights relative to a base profile of the base body.

[0043] When the base body has a flat profile, the filter element can be supported in a curved position by means of support elements of varying heights. Conversely, when the base body has a curved profile, the filter element can be supported in a curved position corresponding to the curvature of the base profile by means of support elements of essentially the same height. The curvature can be concave or convex. Multiple curvatures can be incorporated. For example, at least one support element can be undulating. If multiple support elements are incorporated, they can have different curvatures.

[0044] GO 241130W02 December 17, 2025 The filter element can have heights such that it is covered with an undulating base surface over the base body. Alternatively, at least one support element can be designed with a height that compensates for the height difference formed by the recess. In this way, the filter element can be covered with a flat base surface (in cross-section) over the base body.

[0045] In one embodiment of the perfusion module, the at least one support element is designed to form a rotationally symmetrical pattern.

[0046] This allows for an optimized distribution of the flow across the surface of the filter element. Additionally, the clogging or blockage of pores or penetrating openings in the filter element can be reduced. The rotational symmetry, or a rotation parameter that characterizes the rotationally symmetrical pattern, can be adapted to a stirred flow intended for the reactor chamber of a bioreactor connected to the perfusion module. Such a stirred flow can be generated, for example, by a gassing and stirring unit.

[0047] Alternatively or additionally, at least one support element can be arranged approximately rotationally symmetrically across the base of the depression.

[0048] Alternatively or additionally, the at least one support element can be designed or positioned as ribs, knobs, or columns, in a spiral, net-like, honeycomb, and / or undulating manner. A spiral design or positioning of the at least one support element enables targeted flow guidance towards the fluid passage. A net-like or honeycomb-like design or positioning of the at least one support element enables the distribution of flow throughout the volume of the cavity.

[0049] In one embodiment of the perfusion module, it is provided that the at least one support element is used for segmentation, in particular for the essentially isovolumetric segmentation of a fluid flow across the volume of the

[0050] GO 241130W02 December 17, 2025 is formed in the cavity and positioned within the recess. Alternatively, it may be provided that the at least one support element comprises at least two support elements and that the at least two support elements are designed and positioned for segmentation, in particular for the essentially isovolumetric segmentation of a fluid flow across the volume of the cavity.

[0051] The inclusion of at least one support element enables fluid flow segmentation of the fluid flowing through the cavity. Furthermore, local blockage of the pores or penetrating openings of the filter element caused by heterologous pressure differences can be reduced.

[0052] Isovolumetric segmentation of the cavity can be understood as a division of the cavity into partial volumes of equal size.

[0053] Preferably, the at least one support element is formed by protrusions in the depression of the base body.

[0054] In one embodiment of the perfusion module, it is provided that the at least one support element comprises at least two support elements and that the at least two support elements are distributed over an area of ​​the recess according to a mathematical function, wherein the mathematical function is based on a trigonometric function based on multiples of the golden angle and on a radial distribution function.

[0055] The radial distribution function, combined with the angle function based on the golden angle, creates a non-periodic yet uniform arrangement of the at least two support elements across the surface of the recess. This novel approach improves the flow distribution. Furthermore, the support of the filter element by the at least one support element can be maintained across different system scales, thus enabling comparability between systems.

[0056] GO 241130W02 December 17, 2025 enables different sizes. Furthermore, compared to, for example, a grid-like distribution at the edge of the recess, this avoids certain issues. Additionally, it allows for complete rotational symmetry in the arrangement of the support elements.

[0057] In a particular embodiment, the mathematical function can be based on phyllotaxis. This distribution method uses the golden angle g to determine the angular position yi of a pore i. The angular position can be expressed as follows:

[0058] Yi = 9 'i

[0059] It can be assumed that the golden angle is approximately 137.5°.

[0060] To position the support elements at different radii, a radial distribution function can be used. For this purpose, each pore can be assigned a radius r. t The proportion of the circular area spanned by a specific pore radius, relative to the depression area, can correspond to the proportion of the respective support element index relative to the total number of support elements. This proportion can be expressed as follows:

[0061] Ai nr 2 i

[0062] A

[0063]

[0064] S tr. ~ X Vstr 2 " n

[0065] where A i the area of ​​the support element with index i; where A str . corresponds to the area of ​​the depression; where r i the radial position of the support elements with the index i on the surface of the recess; where r str - corresponds to the radius of the depression; and where n corresponds to the number of support elements. From this, the following expression can be derived:

[0066] I i

[0067] r i = √ ― (i / n) · r str .

[0068]

[0069] J n

[0070] In practice, with l / nThe support elements are placed at the boundary of their radial ring section, meaning that the support elements are aligned with the edges of these concentric areas. To achieve a more balanced distribution, where the individual support elements are positioned more towards the center of their respective sections,

[0071] G0241130W02 December 17, 2025 If the radial section lies at its boundary, the index can be shifted by half a step. Overall, the radial distribution function can be expressed as follows:

[0072] i - 0.5

[0073]

[0074] In combination with the trigonometric function based on a multiple of the golden angle, this radial distribution function can achieve a non-periodic yet uniform distribution of support elements across the depression, inspired by natural phyllotaxis. In particular, this allows for an approximately equal distribution of support elements across the surface of the depression.

[0075] In one embodiment of the perfusion module, the base body, viewed in a radial cross-sectional view, has a base profile which is essentially flat. Alternatively, the base body, viewed in a radial cross-sectional view, may have a base profile which is curved.

[0076] The curvature allows the filter element to be positioned and held in such a way that the flow at the perfusion module or at the filter element in the reactor chamber can be adapted to a stirring flow in the reactor chamber.

[0077] The filter element can be attached to the base body by at least one fastening element in such a way that the filter element is tensioned according to the curvature of the base body. An example of this is clamping the edge of the filter element between the fastening element and the base body. In another example, the fastening element is designed with a mesh-like area which, in an assembled state of the perfusion module, presses the filter element against the base body or against the at least one support element.

[0078] GO 241130W02 December 17, 2025 Alternatively or additionally, the filter element can be connected to the base body by bonding, welding, or electrostatic adhesion, with the filter element essentially assuming the shape of the at least one support element. In this way, the filter element can assume a convex shape, even in the absence of a pressure gradient. The filter element can be locally bonded or welded to the support element, in particular to individual support elements.

[0079] Alternatively or additionally, the filter element can assume a curved position corresponding to the curvature of the at least one support element or the base profile of the base body due to an applied suction or pressure difference between the reactor space and the cavity.

[0080] A basic profile can be understood as a profile that characterizes a main extent surface of the depression. In a specific example, if support elements are provided in the depression, for example in the form of knobs or elevations, then the profile of the depression surface without the support elements can be considered the basic profile.

[0081] The base body can be designed such that the curvature is directed towards the fluid outlet. This allows a local low point to be formed on the surface of the filter element, which is clamped onto the at least one support element.

[0082] This allows the fluid to be removed from the reactor chamber as completely as possible.

[0083] Alternatively, the base body or the recess can be designed such that the curvature is directed in the opposite direction to the fluid outlet of the base body. This allows the flow at the surface of the filter element to be adapted to the flow conditions in the reactor chamber. For example, the curvature can be tailored to the arrangement of a gassing and stirring unit to achieve the most homogeneous flow possible in the reactor chamber.

[0084] GO 241130W02 December 17, 2025 Preferably, in an assembled state of the perfusion module, the filter element is clamped by the fastening element on the at least one support element.

[0085] In one embodiment of the perfusion module, the at least one support element, viewed in a radial cross-sectional view, has a curved or corrugated profile. This allows the filter element to be held in a curved position, thereby achieving the same advantages as with a curved or corrugated base profile of the base body.

[0086] In one embodiment of the perfusion module, it is provided that, in an assembled state of the perfusion module, the filter element and the at least one fastening element together form a surface with a medium collection area.

[0087] The medium collection area facilitates the emptying of the bioreactor or its fluid container. Furthermore, it helps to collect components separated during cultivation by the rotation of the aeration and stirring unit.

[0088] The medium collection area can be formed as a local low point in the direction of the gravitational force. This allows collection to be achieved through centripetal acceleration and / or due to the gravitational force.

[0089] Alternatively or additionally, the medium collection area can be designed as the section of the fluid container that is furthest from the rotational axis of the aeration and stirring unit. This allows for the fluidic collection of components separated during the rotation of the aeration and stirring unit along its axis.

[0090] GO 241130W02 17 December 2025 Examples of the design of the medium collection area are: circumferential channel in the bottom of the fluid container, conical area in the bottom of the fluid container, valleys in the bottom of the fluid container, although this list is not exhaustive.

[0091] In one embodiment of the perfusion module, it is provided that, in an assembled state of the perfusion module and viewed in a radial cross-sectional view, the filter element and the at least one fastening element together have a curved profile with a bulge formed towards the center of the filter element, and that the flanks of the bulge form a medium collection channel around the filter element.

[0092] The curvature allows for the optimization of flow patterns in the reactor space, especially in combination with a rotational movement of the gassing and stirring unit.

[0093] The curvature can be oriented towards the reactor chamber. In this way, the medium collection area can, for example, be designed as a circumferential trough.

[0094] Alternatively, the bulge can be directed in the opposite direction to the reactor chamber. This allows a medium collection area to be formed as a local low point.

[0095] The curvature of the bottom sections can correspond to a curve with a radius of curvature. Additionally, the bottom section of the fluid container can have a diameter corresponding to the inner diameter of the fluid container. In one embodiment of the bioreactor, the curvature is designed such that the radius of curvature is equal to or greater than half the diameter of the bottom section, in particular that the radius of curvature is equal to or greater than the diameter of the bottom section, preferably that the radius of curvature is in the range of the diameter of the bottom section up to five times the diameter of the bottom section.

[0096] GO 241130W02 December 17, 2025 The specified curvature areas allow the medium to flow into the medium collection area while minimizing any negative impact on the flow. If the ratio of the radius of curvature to the diameter of the base area is greater than specified, the base is too flat to form a medium collection area. If the ratio is smaller than specified, the increased curvature can negatively affect the flow pattern in the reactor chamber and the flow into the membrane module.

[0097] In one embodiment of the perfusion module, the recess of the base body has an outer circumference and the fluid passage is essentially centered relative to this outer circumference. Alternatively, the recess of the base body can have an outer circumference and the fluid passage is essentially decentered relative to this outer circumference.

[0098] A key advantage of a centrally positioned fluid passage is that the perfusion module can be designed with rotational symmetry. This allows for a more uniform distribution of pressure and flow within the reactor chamber.

[0099] A decentralized arrangement is particularly suitable when designing the perfusion module for a bioreactor with a relatively large reactor space, for example approximately 2 L or approximately 10 L, in order to improve the accessibility of the fluid passage.

[0100] The arrangement of the fluid passage can be selected, in particular, depending on the flow within the reactor chamber. Specifically, a centered or decentralized arrangement can be chosen depending on whether the flow is directed towards the reactor chamber (i.e., for introducing a fluid into the reactor chamber) or whether the flow is directed out of the reactor chamber (i.e., for expelling a fluid from the reactor chamber). This selection can be based on the possible occurrence of

[0101] GO 241130WO2 December 17, 2025 may be caused by backflow, although backflow should generally be avoided.

[0102] An off-center arrangement of the fluid passage is particularly advantageous when a bearing element is provided to accommodate an axle, with the bearing element being essentially centered relative to the outer circumference of the recess. This allows an axle, for example, the axle of an agitator for a bioreactor, to be mounted centrally. In this way, a uniform flow within the reactor chamber can be achieved with the centrally mounted agitator, and any inflow or outflow from the reactor chamber through the off-center fluid passage has little impact on the agitator's movement or the flow within the reactor chamber.

[0103] In one embodiment of the perfusion module, it is provided that the fastening element and the base body can be connected via a material-bonded connection and / or a form-fit connection.

[0104] A material-bonded connection allows for the simple and cost-effective creation of the perfusion module. Examples of material-bonded connections include adhesive bonding and welding. A form-fit connection allows for a reusable and stable perfusion module. A screw connection is an example of a form-fit connection.

[0105] In one embodiment of the perfusion module, the at least one fastening element is designed to attach the filter element to the base body via a material-bonded connection and / or a form-fit connection.

[0106] Thus, the filter element can also be held in place on the base body by the connection that links the mounting element to the base body. In other words, the base body, the mounting element, and the filter element can be fastened together with a single connection.

[0107] GO 241130WO2 December 17, 2025 For example, the filter element can be clamped, welded, glued, pressed, potted or cast between the fastening element and the base body.

[0108] In a particular embodiment, the filter element can be connected to the base body by a plurality of connections. For example, in addition to being fastened to the base body by the fastening element, the filter element can also be directly attached to the base body. In a particular example, the filter element can be clamped to the base body by the fastening element and additionally connected to individual support elements of the base body by welding or bonding.

[0109] In one embodiment of the perfusion module, a bearing element is provided for receiving an axis.

[0110] As the size or volume of a bioreactor increases, mechanical requirements can change. Stirring the fluid can be advantageous for certain reactions, which is why a movable stirring element can be inserted into the reactor chamber. However, in a relatively large reactor chamber with a correspondingly large fluid volume, moving the stirrer can become difficult. In such cases, mounting the stirrer through the bottom of the bioreactor can be particularly helpful. With the disclosed embodiment, such mounting can also be ensured when a perfusion module as described in the disclosure is used.

[0111] The bearing element can have a material composition that exhibits a low friction ratio with the material of the axle to be mounted.

[0112] In addition, the bearing element can have a shape that is adapted to the shape of the axle to be accommodated.

[0113] G0241130W02 December 17, 2025 In one embodiment of the system, the bioreactor has a stirrer arranged in the fluid container with an axis of movement, and the axis of movement is received by the bearing element of the mounting element of the perfusion module.

[0114] This allows for a particularly stable system design. In particular, the system can be scaled for larger bioreactor intake volumes. This enables adequate stirring of the fluid or biological system within the reactor chamber, as well as the introduction or removal of components from the fluid into or out of the biological system.

[0115] In one embodiment of the perfusion module, the bearing element is formed on the fastening element. Alternatively, the bearing element can be formed on the base body.

[0116] Integrating the bearing element into the mounting element is particularly suitable when the mounting element is part of the reactor chamber wall. This allows the agitator to be stably held by the bearing element while the main body is removed, for example, to replace the filter element.

[0117] An example of how the bearing element can be integrated into the mounting element is a mounting element with an annular section and a platform. The annular section can be designed to secure the edge of the filter element to the base body. The platform can be arranged concentrically relative to the annular section and incorporate the bearing element. The annular section and the platform can be connected by webs. The webs can be designed and / or arranged according to the support elements of the base body. Such a design and / or arrangement of the webs minimizes flow disturbance.

[0118] GO 241130W02 December 17, 2025 Training on the base body allows for a simplified design of the fastening element.

[0119] In one embodiment of the perfusion module, the fastening element comprises a first fastening part and a second fastening part, wherein the first fastening part is designed for fastening the filter element to the base body, and wherein the second fastening part is designed for fastening the filter element to the base body and comprises the bearing element.

[0120] The two-part mounting element allows the filter element to be held to the base body on the one hand, and on the other hand, an axle, in particular the axle of a bioreactor stirrer, to be accommodated. In a specific example, the first and second mounting parts can be designed as connecting pieces. Alternatively or additionally, the first and second mounting parts can be connected to each other by a positive-locking connection. Alternatively or additionally, the first mounting part can be designed to attach the filter element to an edge region of the base body. The second mounting part can be designed to attach the filter element to a central region of the base body. In this example, the second mounting part enables a centered position of the bearing element on the base body.This design is particularly advantageous when the filter element is ring-shaped.

[0121] In one embodiment of the perfusion module, the fastening element may comprise a first fastening part and a second fastening part, wherein the first fastening part is designed to fasten the filter element to the base body when a fluid flows through the filter element in a first direction, and wherein the second fastening part is designed to fasten the filter element to the base body when a fluid flows through the filter element in a second direction.

[0122] GO 241130W02 17 December 2025 In this way, the fastening of the filter element can be designed to be dependent on the flow direction. In a specific example, the first fastening element can be designed to attach the filter element to the base body when the flow is directed towards the reactor chamber. The second fastening element can be designed to attach the filter element to the base body when the flow is directed away from the reactor chamber.

[0123] In one embodiment of the perfusion module, it is provided that the recess of the base body has an outer circumference, and that, in an assembled state of the perfusion module, the bearing element is essentially centered relative to the outer circumference of the recess.

[0124] A centered positioning of the bearing element allows for the centered mounting of an agitator shaft within the bioreactor chamber, particularly when the perfusion module forms the base of the bioreactor. This ensures a uniform flow within the reactor chamber. This is especially advantageous when combined with a centered fluid outlet on the base body.

[0125] In one embodiment of the perfusion module, the filter element is designed to be multi-part, or the filter element has at least one recess.

[0126] In particular, the filter element can have a design adapted to the design of the fastening element and / or the base body. In a specific example, the fastening element has a first fastening part and a second fastening part, wherein the first fastening part is provided for fastening the filter element to an edge region of the base body, and wherein the second fastening part is provided for fastening the filter element to a central region of the base body. The filter element can be disc-shaped with a central recess.

[0127] G0241130W02 17 December 2025 the filter element can be attached to the base body at the outer edge by the first fastening part, and to the base body at the inner edge, i.e. at the edge of the centered recess, by the second fastening part.

[0128] In another example, the filter element can be segmented.

[0129] For this purpose, the fastening element can have at least one recess, wherein the at least one recess is adapted to the design of the base body. In particular, the design of the at least one recess can be adapted to the shape and / or the arrangement of one or more support elements in the recess of the base body. Adapting the filter element to the shape or design of the base body and / or the fastening element enables improved flow distribution.

[0130] The filter element can be replaceable, particularly as a consumable. For this purpose, the fastening element can be designed to detachably attach the filter element to the base body. Specifically, the base body and the fastening element can be designed to accommodate a standard-sized filter element. This allows for a durable perfusion module and thus extends its overall service life. This embodiment offers the advantage that the filter element can be easily replaced and renewed. Furthermore, a replaceable filter element allows the filter element to be adapted to the intended use of the perfusion module or to a medium contained within the bioreactor chamber.

[0131] The filter element can be made of a permeable material.

[0132] The filter element can be made of a porous material. Examples of porous materials include: woven cellulose or plastic, nonwoven fabric, spun tile, electrospun tile, foamed plastic, metal foam, and wire mesh.

[0133] GO 241130W02 December 17, 2025 Alternatively or additionally, the filter element can have multiple layers. These layers can have different material compositions. Alternatively or additionally, the layers can have different structures. For example, the filter element can have a first layer with a first porosity and a second layer with a second porosity, where the first and second porosities are different. A multi-layered filter element offers increased mechanical stability. Furthermore, a multi-layered filter element can be used for staged filtration of a medium.For example, a multi-layer filter element, in particular a filter element with layers of different porosity or separation efficiencies, can be used to perform an initial filtration of coarse components that would block the pores of the further layers of the filter element or the fluid passage.

[0134] Alternatively or additionally, the filter element can have multiple layers. These layers can have different functionalities. One example of a functionalization is a charge for adjustable adsorption or repulsion of dissolved particles.

[0135] Alternatively or additionally, the filter element can be designed as a composite. An example of a composite design is a composition of at least two different materials, where a first material forms a structure-providing matrix, and a second material fills the matrix formed by the first material. The first material can provide stability to the filter element. The second material can enable the filter element to perform a specific function, such as the targeted filtration of biological cells or components of a mixture from the reactor chamber of the bioreactor.

[0136] In one embodiment of the system, the fluid container comprises a wall with a bottom area and a wall area, and the wall area contains at least one fastening element of the perfusion module.

[0137] G0241130W02 17 December 2025, and that the bottom area is formed by the filter element and the base body of the perfusion module.

[0138] In this embodiment, the fastening element is formed as part or a section of the wall area. This eliminates the need for a separate fastening element from the wall area.

[0139] In one embodiment of the system, the fluid container comprises a one-piece wall with a bottom section and a wall section, the bottom section forming the base body of the perfusion module. Alternatively, the fluid container may comprise a one-piece wall with a bottom section and a wall section, the bottom section forming the filter element of the perfusion module.

[0140] In both alternatives, part of the perfusion module is formed by the bottom section of the fluid container. This reduces the number of separate components of the perfusion module and thus also the effort required to connect the individual components.

[0141] In another embodiment of the system, a check valve is installed upstream of the fluid passage in the base body. This allows the flow to be blocked or allowed to pass depending on its direction. Multiple check valves can be provided, enabling targeted and directed fluid supply and / or discharge. For example, several sources or receiving containers can be connected to the reactor chamber via the perfusion module, allowing multiple fluids to be supplied to or discharged from the reactor chamber.

[0142] In another embodiment of the system, the perfusion module is detachably connected to the fluid reservoir of the biorector. This allows the perfusion module to be replaced and, if necessary, easily cleaned.

[0143] G0241130W02 December 17, 2025 The possible replacement of the fluid vessel's bottom, particularly with a perfusion module as disclosed, increases the bioreactor's range of functionalities. Furthermore, the detachable perfusion module is suitable for single use, thus eliminating the need for complex cleaning or sterilization procedures.

[0144] In another embodiment of the system, the perfusion module is at least partially manufactured using additive manufacturing or forming processes. Other possible manufacturing methods include machining and photopolymerization. This allows for complex designs of the perfusion module, for example, with flow-optimized support elements.

[0145] Further features and advantages of the perfusion module and the system will become apparent from the following description of exemplary embodiments, with reference to the attached drawing.

[0146] The drawing shows

[0147] Fig. 1a shows a first embodiment of a perfusion module in a perspective exploded view;

[0148] Fig. lb shows the basic body from Fig. 1a in a perspective view;

[0149] Fig. 2 shows another embodiment of a perfusion module in a cross-sectional view;

[0150] Fig. 3a shows another embodiment of a perfusion module in a cross-sectional view;

[0151] Fig. 3b shows the perfusion module from Fig. 3a in a cross-sectional view.

[0152] G0241130W02 December 17, 2025 Fig. 1a shows a first embodiment of a perfusion module 10 in a perspective exploded view. The perfusion module 10 comprises a base body 12, a filter element 14, and a mounting element 16.

[0153] The base body 12 is also shown in Fig. 1b. The base body 12 has a fluid passage 18, a recess 20 tapering towards the fluid passage 18, support and bracing elements 22, 24 and a connecting section 26 for connection with the fastening element 14. The fluid passage 18 is centered relative to the recess 20 of the base body 12.

[0154] The fluid passage 18, the recess 20 of the base body 12 and the filter element 14 together form a flow-permeable cavity 28.

[0155] The support and segmentation elements 22, 24 are designed as elongated elevations, each with a principal direction of extension, and are arranged in the recess 20 such that the principal directions of extension converge towards each other.

[0156] Furthermore, the support and segmentation elements 22, 24 have partially different lengths in order to direct and distribute the flow exiting or entering the fluid passage 18. The radial arrangement of the support and segmentation elements 22, 24 enables flow segmentation in the cavity formed by the filter element 14 and the recess 20. When the flow is directed from the filter element 14 towards the base body 12, the arrangement and design of the support and segmentation elements 22, 24 direct the flow towards the fluid passage 18. When the flow is directed from the base body 12 towards the filter element 14, the arrangement of the support and segmentation elements 22, 24 enables the flow to be distributed throughout the volume of the cavity formed by the recess 20 and the filter element 14.

[0157] GO 241130W02 December 17, 2025 The filter element 14 is disc-shaped. The fastening element 16 is ring-shaped. The fastening element 16 is designed to fasten the filter element 14 to the base body 14 at the edge of the filter element 14 by means of a positive connection, in particular by clamping it.

[0158] Fig. 2 shows another embodiment of a perfusion module 40 in a perspective cross-sectional view. The perfusion module 40 comprises a base body 42, a filter element 44, and a mounting element 46.

[0159] The base body 42 has a fluid passage 48, a recess 50 converging towards the fluid passage 48, support and segmentation elements 52, 54 and a connecting section 56 for connection with the fastening element 46.

[0160] The fluid passage 48, the recess 50 of the base body 42 and the filter element 44 together form a flow-permeable cavity 58.

[0161] Filter element 44 is designed as a filter sheet made of a porous material. Furthermore, filter element 44 is disc-shaped with an outer diameter.

[0162] The perfusion module 40 is designed for a bioreactor with a fluid vessel having a wall section 60. The fastening element 46 is formed by an edge region of the wall section 60. The edge region, or fastening element 46, has a connecting section 62 for connection with the connecting section 56 of the base body 402 and an inner diameter. The outer diameter of the filter element 44 is larger than the inner diameter of the fastening element 46. Thus, the perfusion module 40 is designed such that the fastening element 46 serves to fasten the filter element 44 to the base body 402.

[0163] Fig. 3a shows another embodiment of a perfusion module 70 in a perspective cross-sectional view and Fig. 3b shows the perfusion module 70 from the

[0164] GO 241130W02 December 17, 2025 Fig. 3a in a cross-sectional view. The perfusion module 70 has a base body 72, a filter element 74 and a mounting element 76.

[0165] The base body 72 has a fluid passage 78, a recess 80 tapering towards the fluid passage 78, and a connecting section 82 for connection to the fastening element 76. The fluid passage 78 is centered relative to the recess 80 of the base body 72.

[0166] The fluid passage 78, the recess 80 of the base body 72 and the filter element 74 together form a flow-permeable cavity 83.

[0167] The filter element 74 is disc-shaped with a centrally located recess.

[0168] The fastening element 76 comprises a first fastening part 76a and a second fastening part 76b. The first fastening part 76a is designed similarly to the fastening element 46 from Fig. 2. In particular, the first fastening part 76a is designed to fasten the filter element 74 to the base body 72 at its edge. Furthermore, the first fastening part 76a is designed as a wall region 84 of a fluid vessel of a bioreactor.

[0169] The second fastening part 76b is designed to fasten the filter element 74 to the base body 72 in the edge region of the recess of the filter element 74. The second fastening part 76b has a bearing element 86 for receiving an axle 88. The axle 88 can, in particular, be the axle of a stirring element for a bioreactor.

[0170] GO 241130W02 December 17, 2025

Claims

1. GO 241130W02 December 17, 2025 3. Patent claims 1. Perfusion module (10, 40, 70) for a bioreactor, 5. with a base body (12, 42, 72) having a fluid passage (18, 48, 78) and a recess (20, 50, 80) converging towards the fluid passage (18, 48, 78), 6. with a filter element (14, 44, 74) and 7. with at least one fastening element (16, 46, 76, 76a, 76b), wherein the at least one fastening element (16, 46, 76, 76a, 76b) is designed to fasten the filter element (14, 44, 74) to the base body (12, 42, 72), 8. wherein, in an assembled state of the perfusion module (10, 40, 70), the fluid passage (18, 48, 78), the recess (20, 50, 80) of the base body (12, 42, 72) and the filter element (14, 44, 74) together form a flow-permeable cavity (28, 58, 83).

2. Perfusion module (10, 40, 70) according to claim 1, 10. characterized by this, 11. that at least one support element (22, 24, 52, 54) is provided in the recess (20, 50, 80) of the base body (12, 42, 72), and 12. that the at least one support element (22, 24, 52, 54) is designed to support the filter element (14, 44, 74) in an assembled state of the perfusion module (10, 40, 70) and in the case of negative pressure or positive pressure in the cavity (28, 58, 83).

3. Perfusion module (10, 40, 70) according to claim 2, 14. characterized in that the at least one support element (22, 24, 52, 54) comprises at least two support elements (22, 24, 52, 54), wherein the at least two support elements (22, 24, 52, 54) are of essentially the same height relative to a basic profile of the base body (12, 42, 72), 15. or 16. that the at least one support element (22, 24, 52, 54) comprises at least two support elements (22, 24, 52, 54), wherein the at least two support elements (22, 24, 52, 54) are of different heights relative to a basic profile of the base body (12, 42, 72).

4. Perfusion module (10, 40, 70) according to claim 2 or 3, 18. characterized thereby, 19. that the at least one support element (22, 24, 52, 54) forms a rotationally symmetric pattern.

5. Perfusion module (10, 40, 70) according to one of claims 2 to 4, 21. characterized by this, 22. that the at least one support element (22, 24, 52, 54) is designed for segmentation, in particular for the essentially isovolumetric segmentation of a fluid flow over the volume of the cavity (28, 58, 83) and is arranged in the recess (20, 50, 80), 23. or 24. that the at least one support element (22, 24, 52, 54) comprises at least two support elements (22, 24, 52, 54) and the at least two support elements (22, 24, 52, 54) are designed and arranged for segmentation, in particular for the substantially isovolumetric segmentation of a fluid flow over the volume of the cavity (28, 58, 83).

6. Perfusion module (10, 40, 70) according to one of claims 2 to 5, 26. characterized by this, 27.GO / sw 241130DE 17 December 2025 that the at least one support element (22, 24, 52, 54) comprises at least two support elements (22, 24, 52, 54) and the at least two support elements (22, 24, 52, 54) are distributed over an area of ​​the depression (20, 50, 80) according to a mathematical function, 28.where the mathematical function is based on a trigonometric function based on multiples of the golden angle and on a radial distribution function.

7. Perfusion module (10, 40, 70) according to one of the preceding claims, characterized in that 30.that, viewed in a radial cross-sectional view, the base body (12, 42, 72) has a basic profile, wherein the basic profile is essentially flat, 31. or 32.that, viewed in a radial cross-sectional view, the base body (12, 42, 72) has a basic profile, wherein the basic profile is curved.

8. Perfusion module (10, 40, 70) according to one of the preceding claims, characterized in that 34.that the recess (20, 50, 80) of the base body (12, 42, 72) has an outer circumference and the fluid passage (18, 48, 78) is substantially centered relative to the outer circumference, 35 or 36. that the depression (20, 50, 80) of the base body (12, 42, 72) has an outer perimeter and the fluid passage (18, 48, 78) is substantially decentered relative to the outer perimeter.

9. Perfusion module (10, 40, 70) according to one of the preceding claims, characterized in that 38.GO / sw 241130DE 17 December 2025 that the fastening element (16, 46, 76, 76a, 76b) and the base body (12, 42, 72) can be connected via a material-bonded connection and / or via a form-fit connection.

10. Perfusion module (10, 40, 70) according to claim 9, 40. characterized by this, 41. that the at least one fastening element (16, 46, 76, 76a, 76b) is designed to fasten the filter element (14, 44, 74) to the base body (12, 42, 72) via the material-bonded connection and / or via the form-fit connection with the base body (12, 42, 72).

11. Perfusion module (10, 40, 70) according to one of the preceding claims, characterized in that 43. that a bearing element (86) is provided for receiving an axle (88).

12. Perfusion module (10, 40, 70) according to claim 11, 45. characterized by this, 46.that the bearing element (86) is formed on the fastening element (16, 46, 76, 76a, 76b), 47. or 48.that the bearing element (86) is formed on the base body (12, 42, 72).

13. Perfusion module (10, 40, 70) according to claim 12, 50. characterized by this, 51. that the fastening element (16, 46, 76, 76a, 76b) has a first fastening part (76a) and a second fastening part (76b), wherein the first fastening part (76a) is designed for fastening the filter element (14, 44, 74) to the base body (12, 42, 72), and wherein the second fastening part (76b) is designed for fastening the filter element (14, 44, 74) to the base body (12, 42, 72) and has the bearing element (86). 52.GO / sw 241130DE December 17, 2025 14. Perfusion module (10, 40, 70) according to one of claims 11 to 13, characterized in that, 53. that the depression (20, 50, 80) of the base body (12, 42, 72) has an outer perimeter, and 54. that, in an assembled state of the perfusion module (10, 40, 70), the bearing element (86) is substantially centered relative to the outer circumference of the depression (20, 50, 80).

15. Perfusion module (10, 40, 70) according to one of the preceding claims, characterized in that 56. that the filter element (14, 44, 74) is designed in multiple parts, 57. or 58.that filter element (14, 44, 74) has at least one recess.

16. System 60. with a perfusion module (10, 40, 70) according to one of the preceding claims and 61. with a bioreactor comprising a fluid reservoir, 62. characterized thereby, 63. that the perfusion module (10, 40, 70) forms the bottom of the fluid container 17. System according to claim 16, 65. characterized by this, 66. that the fluid container comprises a wall with a bottom area and a wall area (60, 84), 67. that the wall area (60, 84) has at least one fastening element (16, 46, 76, 76a, 76b) of the perfusion module (10, 40, 70), and 68. that the bottom area is formed by the filter element (14, 44, 74) and the base body (12, 42, 72) of the perfusion module (10, 40, 70). 69.GO / sw 241130DE December 17, 2025 18. System according to claim 16, 70. characterized by this, 71. that the fluid container comprises a one-piece wall with a bottom area and a wall area (60, 84), wherein the bottom area forms the basic body (12, 42, 72) of the perfusion module (10, 40, 70), 72. or 73. that the fluid container comprises a one-piece wall with a bottom area and a wall area (60, 84), wherein the bottom area forms the filter element (14, 44, 74) of the perfusion module (10, 40, 70) 19. System according to any of the preceding claims, 75. characterized by this, 76. that the bioreactor has a stirrer arranged in the fluid vessel with a axis of movement (88), and 77.- that the axis of movement (88) is received by the bearing element (86) of the fastening element (16, 46, 76, 76a, 76b) of the perfusion module (10, 40, 70). 78.GO / sw 241130DE December 17, 2025

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