Modular system for providing bioprocessing equipment assemblies - Patent Application 20070123633

Abstract

A modular system for providing a bioprocessing equipment assembly includes a rigid skid (10) and a plurality of grid modules (12). The skid (10) includes a plurality of identical plug-in structures (14) arranged in a regular two-dimensional grid. The grid arrangement of the plug-in structures (14) defines a two-dimensional plug-in field of identical standard shapes and sizes. At least some of the grid modules (12) have a mating plug-in structure (22) adapted for fastening the respective grid module (12) to one of the plug-in structures (14) of the skid (10). At least some of the grid modules (12), in an installed state fastened to the plug-in structures (14) of the skid (10) and / or adjacent grid modules (12), have a two-dimensional extension in the plane of the grid that is no greater than the standard size of the plug-in field (20). At least some of the grid modules (12) include at least one connection port (30) adapted to receive a rigid universal flow connector (26; 34) of standard shapes and sizes in a standard position and orientation. A universal flow connector (26; 34) establishes a flow connection between two adjacent grid modules (12). The connection port (30) of each grid module (12) defines a standard position and orientation of the universal flow connector (26; 34) so ​​that the grid module (12) in its installed state can be connected via the universal flow connector (26; 34) either directly to the connection port (30) or to another universal flow connector (34) received in the connection port (30) of an opposing grid module (12) fixed to the grid module (12) and / or to an adjacent plug-in structure (14). At least some of the grid modules (12) have at least one integral fluid line (32) through which a medium to be treated or analyzed flows. The integral fluid line (32) is in fluid communication with the connection port (30) of the grid module (12).The plurality of grid modules (12) includes at least one flow control grid module having means for actively changing the flow characteristics of the medium and / or at least one interactive grid module having means for sensing, detecting or measuring the characteristics of the medium.

Description

[Technical field]

[0001] The present invention relates to a modular system for providing bioprocessing equipment assemblies. The present invention further relates to a computer program comprising an algorithm for creating a digital simulation of a bioprocessing equipment assembly configured by a user based on such a modular system. [Background technology]

[0002] In general, processes using single-use devices are becoming more and more popular in the pharmaceutical production of high-quality active substances, as they offer high flexibility and save time, investment and operational costs such as cleaning and testing. Furthermore, it is becoming increasingly important for developers and manufacturers of biopharmaceuticals to be able to rapidly adapt their manufacturing processes.

[0003] Prefabricated and standardized device arrangements, which can be configured in various ways, are often used to perform specific unit operations. An example of such a solution is the FlexAct® system from Sartorius Stedim Biotech GmbH, which is a work platform that connects different biomanufacturing operations. The FlexAct® system is flexibly adaptable and can be used, among other things, for buffer preparation, cell harvesting, virus inactivation, medium preparation, virus clearance, line testing, bag testing, etc. The core of this device arrangement is a compact central multifunctional operating module in the form of a stainless steel trolley with a control unit and an operating panel. The FlexAct® system allows specific unit operations with selected single-use process components (bags, hose lines, connectors, filter capsules, etc.) to be performed in an at least partially automated manner.

[0004] Equipment arrangements known from the prior art have certain limitations. Usually, an equipment arrangement is designed for a specific process step for a specific volume. The installation or conversion of the equipment arrangement on the user side is laborious and consequently error-prone. In particular the fast and correct connection of single-use process parts is a challenge in this regard. Furthermore, coordination between the basic parts of the equipment arrangement (e.g. pumps) connected to the single-use process parts and the further used single-use process parts ("wetware") and the control software (several process steps, basic conditions) needs to be carried out.

[0005] WO2019 / 185356 A1 shows a configurable device for flexible provision of connections and / or functions in a biopharmaceutical process. The configurable device comprises a body in which predefined pipe sections and plug-in positions are formed by recesses in the material of the body. The configurable device further comprises a plurality of functional elements adapted to be inserted into the plug-in positions.

[0006] From WO2020 / 099382 A1, another type of configurable equipment arrangement for carrying out at least one unit operation in a biopharmaceutical process is known. The equipment arrangement comprises a base rack and a number of holders for removably mounting process parts for the unit operation, in particular single-use process parts, directly or indirectly. The holders are then adapted to be removably mounted directly or indirectly to the base rack. The equipment arrangement further comprises a positioning system for defining a specific position of the holders relative to the base rack.

[0007] WO2022 / 012981 A1 discloses an apparatus assembly for producing bioconjugates, comprising a conjugation unit for carrying out a bioconjugation reaction in a culture medium, a first filtration unit for separating precipitates and / or aggregates, and a second filtration unit for carrying out an ultrafiltration and / or diafiltration process. The first filtration unit is arranged in a flow path between the conjugation unit and the second filtration unit. The second filtration unit comprises a single-use loop assembly for recirculating the culture medium in the ultrafiltration and / or diafiltration process, which loop assembly is preferably attached to and / or detached from the basic structure of the apparatus assembly as a whole together with a single-use conjugation bag and a single-use recirculation bag as well as other single-use parts of the apparatus assembly. The apparatus assembly further comprises a single control unit for controlling the transfer of culture medium from the conjugation unit through the first filtration unit to the second filtration unit and for controlling the ultrafiltration and / or diafiltration process.

[0008] US2015 / 000777 A1 shows a modular fluid control system made up of a plurality of fluid control modules, each including a manifold portion. The modules are mechanically fixed to a support element. Each module is in close proximity to, but not mechanically fixed to, an adjacent module. The proximity between the modules causes a seal at a first open end of a manifold passage to seal against a second open end of the adjacent module, forming a through passage between the modules. Modules can be removed from within the array without disturbing the adjacent units. Summary of the Invention

[0009] The aim of the present invention is to overcome the limitations of equipment layout known from the prior art and to be able to easily provide individually configured bioprocessing equipment assemblies with great flexibility.

[0010] The above problem is solved by a modular system as claimed in claim 1. Advantageous and advantageous embodiments of the invention are evident from the dependent claims.

[0011] The present invention provides a modular system for providing a bioprocessing equipment assembly, comprising a rigid skid and a number of grid modules. The skid includes a number of identical plug-in structures arranged in a regular two-dimensional grid. The grid arrangement of the plug-in structures defines a two-dimensional plug-in field of identical standard shape and size. At least some of the grid modules have a mating plug-in structure adapted to fasten the respective grid module to one of the plug-in structures of the skid. At least some of the grid modules, in an installed state fastened to the plug-in structure of the skid and / or to an adjacent grid module, have a two-dimensional extension in the plane of the grid that is no greater than the standard size of the plug-in field. At least some of the grid modules include at least one connection port adapted to receive a rigid universal flow connector of a standard shape and size in a standard position and orientation. The connection port of each grid module defines a standard position and orientation of the universal flow connector, such that in its installed state the grid module can be directly connected via the universal flow connector to a connection port of the grid module or of a counter grid module fastened to an adjacent plug-in structure. Alternatively, the grid modules can be connected via a universal flow connector to another universal flow connector received in a connection port of an opposing grid module fixed to an adjacent plug-in structure. At least some of the grid modules have at least one integrated fluid line through which a medium to be treated or analyzed flows. The integrated fluid line is in fluid communication with the connection port of the grid module. The plurality of grid modules includes at least one flow control grid module having means for actively changing a flow characteristic of the medium and / or at least one interacting grid module having means for sensing, detecting or measuring a characteristic of the medium.

[0012] This modular system allows multiple interacting grid modules to be removably fixed in one of several defined positions on the skid to create individually configured bioprocessing equipment assemblies. Direct flow connections between adjacent grid modules allow a compact tubeless setup. Grid modules can be easily exchanged, allowing great flexibility. On the one hand, the invention allows the creation of flexible trial kits in process development and, on the other hand, the creation of fully self-contained, GMP (Good Manufacturing Practice) compliant pre-assembled production assemblies.

[0013] In this context, a rigid skid is understood as a rigid frame, plate, or other support structure that provides, preferably on a generally flat surface, a number of regularly-spaced plug-in structures for mounting a number of grid modules. The skid can be part of a work platform, a control tower, or a similar system for assisting in the execution of unit operations.

[0014] According to the invention, the plug-in structures of the skid are arranged in a regular two-dimensional grid. This means that the plug-in fields defined by the positions of the regularly arranged plug-in structures are all of the same shape and size. In particular, their shape is a rectangle (such as a square) or a regular polygon (equilateral or equilateral), resulting in a regular tessellation of the skid. For example, the regular two-dimensional grid can be a Cartesian plane coordinate grid or a honeycomb grid.

[0015] Grid modules are individual units that provide functions typically required for a bioprocessing equipment assembly. Various types of grid modules can be assigned to different groups or categories. According to the invention, the plurality of grid modules includes at least one flow control grid module having means for actively changing the flow characteristics of a medium and / or at least one interacting grid module having means for sensing, detecting or measuring a property of the medium. The control grid module can include, for example, a valve or a pump, while the interacting grid module can include, for example, a sensor or a probe head. Of course, other types of grid modules can also be employed, as will be explained later.

[0016] The grid modules typically have a mating plug-in structure that mates with the plug-in structure of the skid. However, it should be noted that not all grid modules need to have such a plug-in structure. Some of the grid modules may be held by one or more adjacent grid modules, which are secured to the skid via the mating plug-in structure.

[0017] Furthermore, some of the grid modules may have a two-dimensional extension larger than the standard size of a normal plug-in field. In particular, a dimension of a grid module in one direction in the plane of the grid may be larger than the corresponding dimension of a standard size plug-in field. However, according to the invention, the dimension of such a large grid module is such that it is guaranteed that the large grid module can be connected to a neighboring grid module of standard size via a universal flow connector. In simple terms, the dimension of the larger grid module may be an integer multiple of the corresponding dimension of the plug-in field.

[0018] The fluid connection between adjacent grid modules having fluid-related functions is made via a universal flow connector having a standard shape and size, i.e. the connector is not specific to each grid module (type) but is common to all grid modules. All grid modules requiring a fluid connection are adapted to receive such a universal flow connector in a standard position and orientation, so that only one type of flow connector is required for the entire modular system. According to the invention, the connection port of each grid module defines a standard position and orientation (with respect to the plane of the grid) of the universal flow connector, so that each grid module, in its installed state, can be connected via the universal flow connector to the connection port or to the universal flow connector of the opposing grid module fixed to the adjacent plug-in structure, regardless of the actual type of the grid module (as long as it has a fluid connection).

[0019] It should be noted that the universal flow connector also provides a mechanical connection between two adjacent grid modules, ensuring that the grid modules cannot be displaced relative to one another. This mechanical connection concept can also be used independent of a flow connection. That is, the universal flow connector can be used to provide only a mechanical connection between two adjacent grid modules, without establishing a flow connection.

[0020] The universal flow connector may be permanently fixed to the grid module or may be integral with the grid module, in which case the connection port and the universal flow connector are formed as one piece. From a logical standpoint, the connection port is understood as a structure that immediately surrounds the universal flow connector and complements the flow paths to and from the integral fluid lines of the grid module.

[0021] The connection ports of the grid modules are in fluid communication with an integral fluid line. In some applications, it is sufficient for this fluid line to be a dead-end fluid line into which the medium to be analyzed flows. Such a dead-end can be used as a common measurement location for many different parameters, and only one dead-end fluid line is needed to measure the various parameters.

[0022] The actual shape and size of the grid modules and the corresponding standard shape and size of the two-dimensional plug-in fields on the skid can be chosen accordingly. For low-volume experimental setups (laboratory scale), the grid modules and plug-in fields can be small compared to grid modules used in high-volume commercial production assemblies (factory scale). The same applies to the diameter of the connection ports.

[0023] Apart from the flow control and interaction grid modules, the modular system according to the invention may include other types of grid modules. In particular, the plurality of grid modules may further include at least one connector grid module or at least one manifold-type grid module. A connector grid module provides a simple fluid path for connecting separate grid modules, whereas a manifold-type grid module distributes fluid to or collects fluid from multiple grid modules. For example, the fluid lines in a manifold-type grid module may have a Y-shaped, T-shaped, or X-shaped configuration.

[0024] The modular concept of the invention is most effective in practice with grid modules whose maximum extension in the plane of the grid is equal to the corresponding extension of the plug-in field, regardless of the actual shape of the plug-in field (square, regular hexagon, etc.), which allows maximum flexibility for setting up well-defined individual configurations that can be easily assembled by the user and modified as needed.

[0025] According to a preferred embodiment of the invention, at least one of the grid modules includes four connection ports in an orthogonal arrangement, which allows such a grid module to establish flow connections in all orthogonal directions within the plane of the grid, thus providing maximum flexibility.

[0026] The array of grid modules can also be expanded in further directions, thus enabling even more complex three-dimensional configurations. To this end, at least one of the grid modules includes an additional plug-in structure to allow another grid module to be connected in a direction perpendicular to the plane of the grid. According to this concept, grid modules can be stacked on top of each other, overcoming the limitations of two-dimensional grid module patterns.

[0027] To provide flow connections between stacked grid modules, at least one grid module includes a universal flow connector oriented perpendicular to the plane of the grid in the installed state of the grid modules.

[0028] Apart from the flow connections, it is also useful to standardize the electrical and / or optical connections required in the final bioprocessing equipment assembly. Thus, at least some of the grid modules can include at least one electrical and / or optical universal connector adapted to be connected to an electrical and / or optical universal connector of an adjacent grid module or to an electrical and / or optical interface of an adjacent grid module.

[0029] According to a further development of the invention, the modular system is not limited to fluid-related grid modules but further comprises at least one non-fluidic grid module which does not have a fluidic connection with an adjacent grid module but has at least one mechanical and / or electrical and / or optical universal connector adapted to be connected to a universal mechanical and / or electrical and / or optical connector of an adjacent grid module.

[0030] Some of the grid modules typically used in a particular arrangement may be pre-assembled to form a structural unit before being secured to the skid.

[0031] In particular, a group of pre-assembled grid modules can be held together in an installation box or frame for ease of shipping and installation. According to a variant, the box or frame itself includes flow and / or electrical and / or optical connectors.

[0032] The mounting box or mounting frame itself can also be considered as a skid within the meaning of the present invention. This means that the mounting box or mounting frame serves as a support structure and provides a number of regularly arranged plug-in structures for carrying a corresponding number of grid modules. In this case, the mounting box or mounting frame and the grid modules fixed therein can constitute an autarchic bioprocessing equipment assembly within the meaning of the present invention.

[0033] To assist the user in setting up the configuration in the modular system and to avoid confusion, at least some of the grid modules may be provided with a schematic graphical representation on their exterior surface of the functionality associated with the respective grid module, allowing the user to easily identify the functionality of the grid module at any time.

[0034] At least some of the plug-in fields of the skid can also be provided with schematic graphic representations. In particular, if certain plug-in fields are reserved for certain grid modules, such schematic graphic representations of the functions related to those grid modules show the user where to place them. According to a further development of the invention, the schematic graphic representations can be visualized in the plug-in fields according to (some of) predefined configuration schemes or according to digital configuration schemes created in a computer program. Permanent graphic representations can be realised as printed, etched structures etc., whereas variable graphic representations require that the skid includes one or more displays or lighting means, or that the graphic representations are projected onto the skid by a projector or that the graphic representations are presented to the user via AR (Augmented Reality).

[0035] To avoid the clutter of cables associated with power supply and data / signal transfer, the grid modules may include wireless communication modules and / or wireless power receivers.

[0036] A key aspect of the invention is the incorporation of functional components, particularly sensors, in some of the grid modules. Such sensors are used to monitor certain characteristics of the media flowing through the respective modules. To facilitate the placement and installation of such functional components, universal receptacles can be used that are adapted to accept universal functional components. "Universal" means that the different types of functional components have designs that fit into the standard design of the receptacle, and the receptacle can accept different types of functional components.

[0037] Preferably, the universal receptacle is incorporated into a fluid line or flow connector of the grid module, it being understood that the fluid line or flow connector itself can be designed such that no additional parts are required to receive the functional parts, i.e., the fluid line or flow connector itself is the universal receptacle.

[0038] As already indicated above, at least one of the grid modules may include multiple functional components, for example, a flow control grid module including a valve may further include a sensor or flow cell, and a grid module including intersecting fluid lines may further include multiple sensors housed in some of the fluid line portions.

[0039] One or more of the grid modules may include a fastening mechanism with an extendable hook for securing the grid module to the skid via the hook.

[0040] The grid module may include a mounting structure for securing a component having a structure that matches the mounting structure, the mounting structure of the grid module acting as an adapter for securing, for example, a probe head or other component.

[0041] As mentioned at the beginning, single-use equipment is increasingly used, especially in pharmaceutical production of high-quality active ingredients, due to its high flexibility, but also due to the time, investment and operating cost savings for cleaning, validation, testing etc. of the equipment. Single-use equipment is no longer only used in the field of product and process development, but also in the field of clinical trial manufacturing (CTM) for approval procedures and also in the field of commercial good manufacturing practice (GMP) in pharmaceutical production. The grid modules of the modular system according to the invention are therefore preferably single-use grid modules made of materials whose properties do not deteriorate significantly when sterilized by ionizing radiation such as gamma, beta or X-rays, chemicals or steam. This means that the fundamental properties of such materials, such as mechanical stability, toughness (opposite of brittleness), etc., as well as the dimensions of parts made from such materials, are not significantly affected by the sterilization process.

[0042] According to a preferred embodiment of the invention, the materials used for the grid module can be further differentiated as follows: the parts in contact with fluids during use are made from a first material group in order to meet the high safety and regulatory requirements for materials in contact with pharmaceuticals and intermediates, and the structural parts that do not come into contact with fluids during use are made from a second material group different from the first material. The first material is certified with respect to at least one of the following criteria: biological safety, chemical compatibility and robustness, extractables and / or leachables, TSE / BSE (spongiform encephalopathy) regulations, and the second material is selected from at least one of the following: recycled plastics, renewable materials. This differentiation of materials allows the use of highly regulated materials only when necessary, reducing CO2 emissions and saving resources and costs.

[0043] Furthermore, according to a particular embodiment of the invention, the distinguishability of the components made from the first and second materials allows the components to be easily separated after use and further processed appropriately. The fluid contacting parts can be separated from the rest of the grid module after use without opening the fluid contacting parts, preventing residual fluids from coming into contact with the rest of the grid module. This allows separation into contaminated / non-contaminated parts, into different types of unmixed / homogeneous plastics (recycling), or into recycled parts (reusable returnable packaging) and disposable parts.

[0044] The present invention also provides a computer program including an algorithm for creating a digital simulation of a bioprocessing equipment assembly configured by a user based on the modular system described above. The computer program provides digital counterparts of the grid modules and a digital interface, allowing the user to configure a digital version of the bioprocessing equipment assembly based on the digital counterparts of the grid modules. The computer program then provides a simulation of the functionality of the bioprocessing equipment assembly configured by the user. In this way, the computer program allows the user to create a digital version of the bioprocessing equipment assembly before it is built in the real world, for example based on the drag-and-drop functionality of the program. The computer program assists the user in setting up the configuration and can test and simulate the functionality of the configuration, thus avoiding costly errors in the real configuration.

[0045] To assist the user in creating a fully functional bioprocessing equipment assembly, the computer program can include standard configuration templates, trouble-solver algorithms, and optimization suggestion algorithms that can be based on artificial intelligence.

[0046] Furthermore, the digital version created by the computer program can serve as a digital twin of the actual bioprocessing equipment assembly for controlling the process performed by the equipment assembly (particularly controlling pumps, valves, etc.) and / or for detecting deviations (via sensors, etc.) and correcting them (adjusting process parameters, etc.).

[0047] Further features and advantages of the present invention will become apparent from the following description and the accompanying drawings which are referenced. [Brief description of the drawings]

[0048] [Figure 1] FIG. 1 is a plan view of a skid of a modular system according to the present invention, comprising a number of plug-in fields arranged as a first type of two-dimensional grid. [Diagram 2] FIG. 2 is a plan view of three plug-in structures on the skid. [Diagram 3] FIG. 3 is a plan view of a skid with a number of plug-in fields arranged as a second type of two-dimensional grid. [Figure 4] FIG. 4 is a bottom perspective view of the grid module. [Diagram 5] FIG. 5 is a top view of three grid modules connected on a skid according to the first connection concept. [Figure 6] FIG. 6 is a side view of the three grid modules of FIG. [Figure 7] FIG. 7 shows a universal flow connector of the first connection concept, where one universal connector connects two grid modules. [Figure 8] FIG. 8 is a top view of two grid modules connected according to the second connection concept, with two universal flow connectors connecting the two grid modules. [Figure 9] FIG. 9 is a perspective view of a grid module with two different universal flow connectors based on a first and a second connection concept, respectively. [Figure 10] FIG. 10 is a top view of a group of pre-assembled grid modules held within an installation box. [Figure 11] FIG. 11 is a plan view of three connected grid modules containing sensor inserts. [Figure 12a] FIG. 12a is a perspective view of a grid module which serves as a holder for the probes. [Figure 12b] FIG. 12b is a side view of the grid module of FIG. 12a. [Figure 13] FIG. 13 shows a computer running a program that creates a digital simulation of a bioprocessing equipment assembly. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] 1 shows a schematic of a rigid skid 10 for a modular system onto which multiple grid modules 12 can be secured to create an individually configured bioprocessing equipment assembly. The skid 10 includes multiple identical plug-in structures 14 disposed on a generally flat surface 16, where each plug-in structure 14 is configured with four mounting holes 18 located at the corners of an imaginary square. However, the plug-in structures 14 may include any means for removably securing the grid modules 12 onto the skid 10, such as screws, threads, magnets, hooks, latches, etc.

[0050] The plug-in structures 14 are arranged in a regular two-dimensional grid extending in orthogonal x and y directions. The regular arrangement of the plug-in structures 14 defines a number of two-dimensional plug-in fields 20 of the same standard shape and the same standard size, as can be derived from FIG.

[0051] The two-dimensional grid according to the embodiment shown in Figures 1 and 2 is a Cartesian plane coordinate grid, i.e. the plug-in fields 20 of the skid 10 represent a tessellation by rectangles, in particular by squares, and each plug-in field 20 can be addressed by a two-dimensional index (x, y).

[0052] 3 shows another embodiment of the skid 10 with plug-in structures 14 that define another kind of regular two-dimensional grid. Here, each plug-in structure 14 is composed of six mounting holes 18 arranged at the vertices of an imaginary regular hexagon. The plug-in field 20 thus forms a honeycomb pattern.

[0053] Regardless of the actual type of plug-in field 20 (rectangular, square, hexagonal, triangular, etc.), all plug-in fields 20 on the skid 10 must be identical in terms of shape and size, and the shape of all plug-in fields 20 must be a regular polygon.

[0054] The plug-in fields 20 and / or their boundaries may be marked on the skid 10. Furthermore, some of the plug-in fields 20 may include markings related to the flow direction and / or the type or function of the grid modules 12 that are fixed to the respective plug-in fields 20 according to a pre-established configuration scheme (establishment of the configuration scheme is described below). The markings may be provided in any suitable manner, e.g. by (color) printing, etched structures, lighting, projection, augmented reality (AR), etc.

[0055] FIG. 4 is a bottom view of an exemplary grid module 12 taken from a plurality of grid modules 12 of different types. The grid module 12 has a mating plug-in structure 22 that fits with any of the plug-in structures 14 of the skid 10. Here, the mating plug-in structure 22 includes four mounting studs 24 arranged at the corners of an imaginary square, similar to the arrangement of the mounting holes 18 of the plug-in field 20. The plug-in and mating plug-in structures 14, 22 are designed to allow the grid module 12 to be securely fixed in any of the plug-in fields 20 of the skid 10. The actual fixing of the plug-in structure and mating plug-in structure 14, 22 can be based on clip connections, latch connections, clamp connections, etc. (including, for example, screws, magnets, hooks, etc.). It should be noted that the secure fixing is not permanent but separable, i.e. the fixed grid module 12 can be removed from the skid 10 as needed, especially after use.

[0056] Some grid modules 12 may also include plug-in and mating plug-in structures on one or more of their lateral sides to allow adjacent grid modules 12 to be secured to one another (within the plane of the grid). For example, the grid module 12 shown in Figure 3 has mounting holes on either side of the connection port 30 on each lateral side of the grid module 12. These mounting holes may correspond to and receive mounting studs on the opposing lateral sides of an adjacent grid module 12.

[0057] In an installed state secured to the plug-in structure 14 of the skid 10 and / or adjacent grid modules 12, the grid modules 12 have a two-dimensional extension in the plane of the grid that is no larger than the standard size of the plug-in field 20. This is true for most of the grid modules 12 employed to create bioprocessing equipment assemblies. However, some grid modules 12 may be larger in the x and / or y directions. The dimensions in the x and / or y directions of such larger grid modules 12 are integer multiples of the corresponding dimensions of the standard size plug-in field 20.

[0058] As already indicated, multiple grid modules 12 of different types can be arranged and fixed on the skid 10. The different types of grid modules 12 can be grouped, for example, as follows: grid modules 12 having means for actively changing the flow characteristics of the medium, such as valves or pumps, are called flow control grid modules; grid modules 12 having means for sensing, detecting or measuring the characteristics of the medium, such as sensors or probe heads, are called interacting grid modules; grid modules 12 that provide straight or angled fluid paths for connecting separate grid modules 12 and grid modules 12 that include manifolds (e.g. T-pieces, Y-pieces, crisscrosses) for distributing fluid to or collecting fluid from multiple grid modules 12 are called connector grid modules and manifold type grid modules, respectively.

[0059] A grid module 12 may serve multiple functions. For example, a flow control grid module that includes valves may also include sensors. In such a case, each grid module 12 may be assigned to a group related to its primary function (here, flow control).

[0060] Although these are the most important, the above grouping is not exhaustive: even grid modules 12 that are not fluid-related but have other functions can be employed to create a bioprocessing equipment assembly.

[0061] However, connections and fluid communication between grid modules 12, such as those shown by way of example in Figures 5, 6 and 8, allow fluid to flow in a defined manner from one grid module 12 to another grid module 12 and are important to the modular concept. In the following, characteristic standardized flow connections between grid modules 12 are described.

[0062] According to a first connection concept, the fluid connection between adjacent grid modules 12 is established via a common rigid universal flow connector 26 of a first kind, shown alone in FIG. 7. The universal flow connector 26 is symmetrical and has two identical connection ends 28. The grid module 12 includes at least one connection port 30 in fluid communication with at least one integral fluid line 32 through which the medium to be treated or analyzed can flow. The integral fluid line 32 can also be dead-ended. In any case, the connection port 30 is adapted to receive one connection end 28 of such a symmetrical universal flow connector 26. Each connection port 30 of the grid module 12 is arranged and designed such that when one of the connection ends 28 of the universal flow connector 26 is received therein, the opposite free connection end 28 is necessarily in a standard position and orientation (relative to the plane of the grid) that allows it to be received by the opposing connection port 30 of the adjacent grid module 12, i.e. the grid module 12 fixed to the adjacent plug-in structure 14.

[0063] A plurality of such universal flow connectors 26 all have the same standard shape and size and are used for fluid connection between adjacent grid modules 12 .

[0064] 5 and 6, the right grid module 12 has four connection ports 30 for receiving four universal flow connectors 26 spaced at 90° intervals. The connection ports 30 are oriented to allow flow in four different directions parallel to the x and y directions.

[0065] According to a second connection concept shown in Figure 8, each connection port 30 of a grid module 12 has a second type of universal flow connector 34. In this case, the universal flow connector 34 is designed to cooperate with a universal flow connector 34 provided at the opposite connection port 30 of an adjacent grid module 12 to establish a flow connection between the two grid modules 12. This cooperation can be supported by an additional mechanical connection, such as a tri-clamp connection as shown in Figure 8. As with the first concept, all universal flow connectors 34 used according to this connection concept have the same standard shape and the same standard diameter.

[0066] Figure 9 shows both connection concepts with one grid module. A first type of universal flow connector 26 and a second type of universal flow connector 34 are shown, both of which are received in connection ports 30 of the grid module 12. As already indicated, this also includes solutions in which the universal flow connector 26 or 34 is integrally formed with the connection port 30 (not shown in Figure 9).

[0067] A first type of universal flow connector 26 connects two adjacent grid modules 12 by having its two connection ends 28 received in two opposing connection ports 30 of the adjacent grid modules 12. Alternatively, two second type of universal flow connectors 34 are required to connect two adjacent grid modules 12. The two universal flow connectors 34 are respectively received in opposing connection ports 30 of the adjacent grid modules 12, and their free ends cooperate with each other to establish a flow connection. The connection may be supported by a tri-clamp member or the like to ensure a robust connection between the free ends.

[0068] Either connection concept can be combined with the previously described plug-in concept to allow for easy and flexible creation of complex tubeless bioprocessing device assemblies.

[0069] If necessary, electrical and / or optical connections between adjacent grid modules 12 can be established in a standardized manner as well. For such connections, the grid modules 12 include electrical and / or optical connectors. Such connectors are connected to electrical and / or optical connectors of adjacent grid modules 12 or to electrical and / or optical interfaces of adjacent grid modules 12. The electrical and / or optical connectors can be standard universal connectors.

[0070] Depending on the function of each module, electrical and / or optical connections between adjacent grid modules 12 may be provided in addition to or instead of the flow connections.

[0071] If desired, the skid 10 includes one or more special mounting structures (not shown) at predetermined locations on the skid 10 for mounting special elements that require additional components connected thereto. For example, such predetermined locations may include a pump driver or a valve driver or an optical connector mounted on the rear of the skid 10 to mount, for example, a pump head that requires a pump driver, or a valve that requires a valve driver, or an optical sensor that requires an optical connector, to their counterparts. The special mounting structures provided on the front of the skid 10 may also be used to mount special elements or grid modules 12 that cannot be secured to the skid 10 by (only) the normal plug-in structures 14 due to their large size, weight, or other reasons.

[0072] 5 and 6 show three exemplary grid modules 12 fixed in different ways. The right grid module 12 is fixed to the skid 10 via plug-in structures 14, 22. The middle grid module 12 is arranged above the defined plug-in field 20 of the skid 10, but is fixed only to the adjacent grid modules 12 on the left and right. The left grid module 12 is placed in position as described above. In particular, this grid module houses single-use valves connected to valve actuators (not shown) mounted on the rear of the skid 10. Fixation of the grid modules 12 by plug-in structures 14, 22 may additionally be provided.

[0073] Some of the grid modules 12 have an additional plug-in structure 14 on their top side opposite the mating plug-in structure 22. The additional plug-in structure 14 is similar to the plug-in structure 14 of the skid 10, and thus allows another grid module 12 to be stacked on top. Flow and / or electrical and / or optical connections between the stacked grid modules 12 may be established in the z-direction, as previously described.

[0074] 10 shows a group of grid modules 12 pre-assembled before being secured to the skid 10. The pre-assembled grid modules 12 are held together within a mounting box 36 or mounting frame (not shown) to form a structural unit. The mounting box 36 or mounting frame itself may include flow and / or electrical and / or optical connectors as required.

[0075] The mounting box 36 has an exterior surface that displays a schematic graphical representation 38 of the functionality associated with each grid module 12. Of course, if not mounted in a box 36, the grid module 12 itself can have an exterior surface that displays a schematic graphical representation 38 of its functionality.

[0076] The mounting box 36 itself can be considered a skid if it has regularly-spaced plug-in structures that mate with corresponding plug-in structures on the grid modules 12 .

[0077] FIG. 11 shows how functional components 40, such as sensors and optical flow cells, can be incorporated into different types of grid modules 12.

[0078] The left grid module 12 is an interacting grid module with four connection ports 30. An integral fluid line 32 extends between two of the opposing connection ports 30. The other two connection ports 30 function as universal receptacles for receiving universal functional components 40. "Universal" in this context means that all connection ports 30 are the same in shape and size, and the shape and size of the functional components 40 match the shape and size of the connection ports 30 such that the functional components 40 are securely retained in the connection ports 30. In the example shown in FIG. 11, the functional components 40 are a combined pressure and temperature sensor and a conductivity sensor, both of which have access to the fluid in the integral fluid line 32.

[0079] The sealing means prevents fluid from leaking through the connection ports 30 in which the functional components 40 are received. Of course, the number and location of the functional components 40 within the interacting grid module may vary.

[0080] According to a variant, a universal adapter is used to hold the functional part 40 , which is adapted to the shape and size (particularly the diameter) of the connection port 30 , so that the adapter together with the functional part 40 is held in the connection port 30 .

[0081] The central grid module 12 in Figure 11 is a connector grid module with an integrated fluid line 32. A functional component 40, such as a flow sensor, is integrated into or inserted into the fluid line 32. Of course, there can be multiple functional components 40 in the grid module 12, especially in the case of manifold type grid modules.

[0082] The grid module 12 on the right is a flow control grid module with a valve block 42. On top of the valve block 42 a functional part 40, here a sensor insert, is arranged. The sensor insert may include an optical flow cell, for example in the bypass line. A probe head can be used in combination with the optical flow cell to perform spectroscopic measurements.

[0083] In general, different kinds of functional components 40, in particular sensors, can be integrated into the grid module 12, such as sensors for measuring pressure, differential pressure, pH, conductivity, temperature, refractive index, or optical sensors for measuring absorbance or transmittance, optical density, or spectroscopic sensors such as NIR, MIR, UV-Vis, fluorescence, or light scattering sensors such as Raman scattering, multi-angle light scattering (MALS) or dynamic light scattering (DLS). Furthermore, a sampling port can be provided and either the connection port 30 or the universal flow connector 26, 34 can be used as a sampling port for sterile sampling.

[0084] Preferably, the functional components 40 are separate units and can be replaced or moved to other grid modules 12. The functional components 40 can be qualified and tested separately from the grid module 12.

[0085] As previously mentioned, electrical and / or optical connections between adjacent grid modules 12 may be established via electrical and / or optical connectors and / or interfaces. These electrical and / or optical connections may be used to transfer power to the grid modules 12 and / or to transfer control and / or measurement signals to and / or from the grid modules 12.

[0086] According to a variant, one or more of the grid modules 12 may include a wireless communication module for data transfer.

[0087] According to another variant, wireless transmission of power to a grid module 12 can be realized by providing a power transmitter below the corresponding plug-in field 20. The grid module 12 includes a power receiver, so that power can be transmitted to the grid module 12 by induction in the "z-direction".

[0088] Preferably, the entire grid module 12 is a single-use grid module 12 made from materials that can be sterilized by ionizing radiation, chemicals, or steam without significant degradation of their properties. If this is not possible, the non-single-use parts of the grid module 12 are removable so that all single-use parts can be disposed of together after the other parts have been removed.

[0089] According to another embodiment, all parts that come into contact with fluids during use of the bioprocessing equipment assembly are made from materials certified with respect to standards for biosafety and / or chemical compatibility and robustness and / or extractables and / or leachables and / or TSE / BSE regulations. The materials of other components can be recycled plastics or renewable materials.

[0090] It should be noted that a grid module assembly on a skid 10 can be connected to another grid module assembly on another skid 10 by any of the connection concepts described above, or via additional sterile connectors, or in combination with tubing lines.

[0091] 12a and 12b are perspective and side views of a grid module 12 that serves as a special holder for a probe 44. The mounting studs 24 of this holder can be inserted into the mounting holes 18 of the skid 10. The grid module 12 has a rotation mechanism that can be manually operated via a rotating wheel 46. By operating the rotation mechanism, a locking mechanism is activated. In particular, a hook 48 extends from the mounting studs 24 and engages rearwardly with the rear face 16 of the skid 10, locking the grid module 12 to the skid 10. Thus, the probe 44, which is fixed to the mounting structure of the grid module 12, is held in a defined position and orientation. Of course, this locking mechanism can be used with any type of grid module 12, and the mounting structure can function as an adapter to hold any part whose structure fits with the mounting structure.

[0092] FIG. 13 symbolically illustrates a computer 50 executing a program for creating a digital simulation of a bioprocessing equipment assembly. The program is intended to simulate the configuration and overall function of a bioprocessing equipment assembly that can later be actually created using the modular system including the skid 10 and grid module 12 described above. The configuration scheme (layout) of the bioprocessing equipment assembly can be directly visualized by the computer program and virtually tested before ordering and building the corresponding real bioprocessing equipment assembly. The computer program includes standard configuration templates, problem solving algorithms, and optimization suggestion algorithms. In another application, the simulation of the configured bioprocessing equipment assembly can be used as a digital twin, for example for process control and / or deviation detection and correction. [Explanation of symbols]

[0093] 10 Skid 12 Grid Module 14 Plugin Structure 16 Surface 18 Mounting holes 20 Plugin Fields 22 Mating plug-in structure 24 Mounting stud 26 Universal Flow Connector (Type 1) 28 Connection end 30 Connection Ports 32 Fluid Lines 34 Universal Flow Connector (Type 2) 36 Installation box 38 Graphic Display 40 Functional parts 42 Valve block 44 Probe 46 Spinning Wheel 48 Hook 50 Computer

Claims

1. 1. A modular system for providing a bioprocessing equipment assembly, comprising: The modular system a rigid skid (10); a plurality of grid modules (12); The skid (10) includes a plurality of identical plug-in structures (14); The plurality of plug-in structures (14) are arranged in a regular two-dimensional grid, the grid arrangement of the plug-in structures (14) defining two-dimensional plug-in fields of the same standard shape and size; At least some of the grid modules (12) have mating plug-in structures (22) adapted to secure the respective grid modules (12) to any of the plug-in structures (14) of the skid (10); At least some of the grid modules (12), when installed in a fixed state relative to the plug-in structure (14) of the skid (10) and / or adjacent grid modules (12), have a two-dimensional extension in the plane of the grid that is no greater than the standard size of the plug-in field (20); At least some of the grid modules (12) include at least one connection port (30) adapted to receive a rigid universal flow connector (26; 34) of a standard shape and size in a standard position and orientation; a universal flow connector (26; 34) for establishing a flow connection between two adjacent grid modules (12); the connection ports (30) of each grid module (12) define standard positions and orientations for universal flow connectors (26; 34), and the grid module (12), in its installed state, can be connected via the universal flow connectors (26; 34) either directly to the connection ports (30) or to another universal flow connector (34) received in the connection ports (30) of an opposing grid module (12) fixed to the grid module (12) and / or fixed to an adjacent plug-in structure (14); At least some of the grid modules (12) have at least one integral fluid line (32) through which a medium to be treated or analyzed flows; the integral fluid line (32) is in fluid communication with the connection port (30) of the grid module (12); The plurality of grid modules (12) includes at least one flow control grid module having means for actively changing a flow characteristic of a medium and / or at least one interactive grid module having means for sensing, detecting or measuring a characteristic of the medium. Modular system.

2. The plurality of grid modules (12) further includes at least one connector grid module or manifold-type grid module. The modular system of claim 1 .

3. The two-dimensional extensions of at least some of the grid modules (12) are identical; 3. A modular system according to claim 1 or 2.

4. At least one grid module (12) includes four universal flow connectors (26; 34) in a right-angle arrangement; The modular system of claim 1 .

5. At least one grid module (12) includes a further plug-in structure (14) that allows another grid module (12) to be connected via a mating plug-in structure (22) in a direction perpendicular to the plane of the grid; The modular system of claim 1 .

6. At least one grid module (12) includes a universal flow connector (26; 34) oriented perpendicular to the plane of the grid in the installed state of the grid module (12); The modular system of claim 1 .

7. At least some of the grid modules (12) include at least one electrical and / or optical connector adapted to be connected to an electrical and / or optical connector of an adjacent grid module (12) or to an electrical and / or optical interface of an adjacent grid module (12); The modular system of claim 1 .

8. and further comprising at least one non-fluidic grid module that does not have a fluid connection with an adjacent grid module but has at least one mechanical and / or electrical and / or optical connector adapted to be connected to a mechanical and / or electrical and / or optical connector of an adjacent grid module. The modular system of claim 1 .

9. A group of grid modules (12) are pre-assembled to form a structural unit before being secured to the skid (10); The modular system of claim 1 .

10. A group of pre-assembled grid modules (12) are held together in an installation box (36) or installation frame; The box (36) or frame optionally contains flow and / or electrical and / or optical connectors; The modular system of claim 9.

11. At least some of the grid modules (12) have an exterior surface that displays a schematic graphical representation of a function associated with the respective grid module (12); The modular system of claim 1 .

12. At least one grid module (12) includes a wireless communication module and / or a wireless power receiver; The modular system of claim 1 .

13. At least one grid module (12) includes a universal receptacle for receiving a universal functional component (40); The modular system of claim 1 .

14. The universal receptacle is incorporated into a fluid line (32) or flow connector of the grid module (12); The modular system of claim 13.

15. At least one grid module (12) includes a plurality of functional components (40); The modular system of claim 1 .

16. At least one grid module (12) includes a fastening mechanism with an extendable hook (48); The modular system of claim 1 .

17. At least one grid module (12) includes a mounting structure for securing a component having a structure compatible with the mounting structure; The modular system of claim 1 .

18. The grid module (12) is a single-use grid module (12) made from a material whose properties do not significantly deteriorate even when sterilized by ionizing radiation, chemicals, or steam. The modular system of claim 1 .

19. Components that come into contact with the fluid during use are made from a first group of materials, and structural components that do not come into contact with the fluid during use are made from a second group of materials that are different from the first group of materials; the first material is certified with respect to at least one of the following standards: biosafety, chemical compatibility and robustness, extractables and / or leachables, and TSE / BSE regulations; The second material is selected from at least one of recycled plastic and renewable materials; The modular system of claim 1 .

20. 10. A computer program including an algorithm for creating a digital simulation of a user-configured bioprocess equipment assembly based on the modular system of claim 1, comprising: the computer program provides a digital counterpart and digital interface of the grid module (12) and allows a user to configure a digital version of a bioprocessing equipment assembly based on the digital counterpart of the grid module (12); The computer program provides a simulation of the function of the bioprocess equipment assembly. Computer program.

21. at least one of a standard configuration template, a trouble-solver algorithm, and an optimization suggestion algorithm; 21. A computer program according to claim 20.

Images