Tubing system for precise transfer of liquids

Abstract

The present invention relates to a tubing system intended for the controlled transfer of liquids in a bioprocess. The invention further provides, using the tubing system, a method for transferring a metered amount of a liquid and a method for transferring a bulk amount of a liquid. The invention further provides a tubing cassette containing the tubing system. The invention further provides a bioprocessing method involving the tubing system.

Description

[0001] Tubing system for precise transfer of liquids

[0002] The present invention relates to the field of bioprocessing, in particular to the transfer of liquids, which forms an integral part of most bioprocesses. Specifically, the invention provides a tubing system intended for the controlled transfer of liquids in a bioprocess. The invention further provides, using the tubing system, a method for transferring a metered amount of a liquid and a method for transferring a bulk amount of a liquid. The invention further provides a tubing cassette containing the tubing system. The invention further provides a bioprocessing method involving the tubing system.

[0003] In the field of bioprocessing, the controlled transfer of liquids is a critical operation that impacts the efficiency and effectiveness of various processes. Traditional tubing systems used for liquid transfer often face challenges such as high dead volume, which can lead to significant product loss and can create deviations in the processing of the product, for example if more or less of a reagent was added at a particular time compared with the expectation. Additionally, these systems may lack the flexibility to perform both bulk and metered transfers efficiently, requiring complex setups and multiple components.

[0004] Bioprocesses of particular relevance for the present invention are in the area of cell and gene therapy, for example to manufacture autologous T cells that are modified to express a chimeric antigen receptor (CAR). These cells might be used for the treatment of various types of cancer, including different types of leukemia (blood cancer). Other cell therapies based on naive cells, in particular stem cells and their derivatives, are also of interest. Sterile and precise transfer of liquids is of utmost importance for the success of most bioprocesses, but often causes a number of technical problems. One issue arises when multiple pumps are involved, as each pump may have slight calibration differences, leading to flow variability and pressure differences at different points in the system, which ultimately leads to inaccurate volume transfers. Additionally, certain pump types can introduce pulsatile flow, making it difficult to achieve precise dosing. Backflow and siphoning effects may also occur if the system lacks proper control mechanisms, while shear forces generated by some pumps, particularly centrifugal ones, can damage shear-sensitive cells or proteins.

[0005] A significant challenge underlying the present invention is the presence of dead volume within the tubing and fittings. Complex geometries, such as T-junctions or valve bodies, can trap liquid, leading to inaccurate dosing or loss of valuable product. In some cases, liquid may remain in sections of tubing that are not properly drained, while adsorption of proteins or other media components onto tubing surfaces can further reduce the effective volume transferred.

[0006] Maintaining sterility throughout the transfer process is also critical but difficult to ensure. Any break in sterility at connection points, such as sampling ports or sterile connectors, can introduce contamination risks. Small defects in tubing welds or connections may allow microbial ingress, while residual moisture within the system can promote biofilm formation. Furthermore, condensation inside the tubing may create an environment conducive to microbial growth if not properly managed. These are particularly relevant problems to be overcome in the context of the present invention.

[0007] Sterile liquid transfer becomes even more complex when a bioprocessing tubing system is designed to connect multiple ports, allowing for flexible fluid routing between different process steps. In such systems, the coordination of liquid movement introduces additional technical challenges related to flow control, sterility maintenance, and volume accuracy. Together, these factors make sterile liquid transfer a complex challenge, requiring careful system design, material selection, and monitoring strategies to ensure accuracy, sterility, and process efficiency. Although known tubing systems aim at addressing some of these issues, further improvement is necessary.

[0008] Against this background, it is an object of the present invention to provide an improved tubing system that overcomes at least some of the issues associated with known tubing systems.

[0009] The present invention addresses the issues outlined above by providing a novel tubing system designed for the controlled transfer of liquids in bioprocess applications. This tubing system offers the advantage of enabling both bulk transfer and metered transfer between two ports, thereby enhancing operational flexibility. Furthermore, the design of the tubing set significantly reduces the amount of dead volume, minimizing product loss and contamination risks.

[0010] Another key benefit of the tubing system is its ease of implementation. The design allows for straightforward integration into existing bioprocess systems without the need for extensive modifications or specialized equipment. This simplicity not only reduces setup time and costs but also ensures reliable and consistent performance across various applications.

[0011] The tubing system according to the invention is particularly advantageous due to its one-size-fits-all design approach, allowing for a significant reduction in manufacturing costs compared to tubing systems tailored to a specific use case.

[0012] Overall, the innovative tubing set described herein represents a significant advancement in bioprocess liquid transfer technology, offering improved efficiency, reduced product loss, and enhanced operational flexibility. SUMMARY OF THE INVENTION

[0013] Specifically, the invention in a first aspect provides a tubing system, comprising: a first port and a second port configured for connection to external elements; a main conduit fluidically connecting the first port and the second port; a valve associated with each port, each valve being operable independently to open or close the respective port, thereby regulating fluid flow along the main conduit; a metering vessel fluidically connected to the main conduit via a first channel, a valve being operable to open or close the metering vessel, thereby regulating fluid flow along the first channel; an air access point fluidically connected to the main conduit via a second channel, a valve being operable to open or close the air access point, thereby regulating fluid flow along the second channel; a bidirectional pump operatively connected to the main conduit; and pressure sensors located on opposite sides of the bidirectional pump.

[0014] The tubing system is preferably designed to be a pre-sterilized consumable in a bioprocess. Other modules of the bioprocess (e.g., bioreactors, media containers or the like ] can be reversibly connected to the tubing system in a sterile manner, e.g. by welding and sealing / cutting. After performing a bioprocess using the tubing system, the tubing system may be discarded as a whole, or may be stored for further use, e.g. following washing and drying.

[0015] It is generally appreciated that the tubing system according to the present invention can be used for metered transfer, i.e., the precise transfer of defined amounts of liquid, preferably without any dead volume. In this respect, the invention provides, in a second aspect, a method for transferring a metered amount of a liquid using a tubing system according to the first aspect, the method comprising: transferring a first amount of the liquid from a first port into a metering vessel, preferably through a bidirectional pump, clearing the tubing section between the first port and the metering vessel from the liquid by transferring the remaining liquid to the first port using the air inlet, pumping a metered amount of the liquid from the metering vessel to a second port, preferably through the bidirectional pump, and clearing the tubing section between the metering vessel and the second port from the liquid by transferring the remaining liquid to the second port using the air access point.

[0016] It is further appreciated that the tubing system according to the present invention can be used for bulk transfer, i.e., the accelerated transfer of (preferably large) amounts of liquid without necessarily monitoring the exact amount of liquid that is transferred. In this respect, the present invention provides, in a third aspect, a method for transferring a bulk amount of a liquid using the tubing system according to the first aspect, the method comprising transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port, e.g. using air drawn through the air inlet.

[0017] The tubing system according to the first aspect may, according to a fourth aspect of the present invention, be present in a tubing cassette configured such that the tubing system contained therein can be fluidically connected to an external element in a reversible fashion.

[0018] Finally, in a fifth aspect, the invention provides a method for performing a bioprocess (also referred to as a bioprocessing method). The method comprises: providing a bioprocessing station, providing a tubing system according to the first aspect, fluidically connecting the tubing system, which may be present in the form of a tubing cassette, to the bioprocessing station, preferably by welding, performing a method according to the second or third aspect, and disconnecting the tubing system from the bioprocessing station, preferably by sealing and cutting. BRIEF DESCRIPTION OF THE FIGURES

[0019] Further features and advantages of the aspects of the present invention emerge from the following description of exemplary embodiments where reference is made to the attached figures. The figures show in

[0020] Fig. 1 a schematic representation of a first embodiment of a tubing system according to the first aspect of the invention,

[0021] Fig. 2 a schematic representation of a second embodiment of a tubing system according to the first aspect of the invention,

[0022] Fig. 3 a schematic representation of a third embodiment of a tubing system according to the first aspect of the invention,

[0023] Fig. 4 a schematic representation of a fourth embodiment of a tubing system according to the first aspect of the invention,

[0024] Fig. 5 a different schematic representation of the embodiment of Fig. 4,

[0025] Fig. 6 an exploded view of a first embodiment of the cassette according to the fourth aspect of the invention,

[0026] Fig. 7 an exploded view of a second embodiment of the cassette according to the fourth aspect of the invention,

[0027] Fig. 8 a schematic illustration of a method for metered transfer of liquid, and Fig. 9 a schematic illustration of a method for bulk transfer of liquid.

[0028] DETAILED DESCRIPTION

[0029] The following description serves to deepen the understanding of the present disclosure and shall be understood to complement and be read together with the description of exemplary embodiments of the present disclosure as provided in the above section of this description. It is to be understood that this invention is not limited to the particular embodiments, methodologies, protocols and reagents described herein as these may vary within the scope set by the claims. It is also to be understood that terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention which is defined by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0030] In the following description, certain elements of the present invention will be described. These elements may be discussed with respect to specific embodiments; however, it should be understood that they may be combined in any manner and in any number to create additional embodiments. The variously described examples, features and particular embodiments should not be construed to limit the present invention to only the explicitly described embodiments or to the explicitly described combination of features. This description should be understood to disclose and encompass embodiments which combine the explicitly described embodiments with any number of the disclosed and / or preferred elements. Furthermore, any permutations and combinations of all described elements in this application should be considered disclosed by this description unless the context indicates otherwise.

[0031] Throughout the description, where methods, compositions or uses are described as having, including, or comprising specific components or steps, it is contemplated that, additionally, there are methods, compositions or uses of the present invention that consist essentially of, or consist of, the recited components or steps.

[0032] In the application, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components.

[0033] Terms “a” and “an” and “the” and similar reference used in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0034] The use of the term "include," "includes," "including," "have," "has," "having," "contain," "contains," or "containing," including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0035] Where the use of the term "about" or “approximately” is before a quantitative value, the present invention also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term "about" refers to a ±10% variation from the nominal value unless otherwise indicated or inferred.

[0036] Also as used herein, “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”). The use of the alternative (e.g., “or”) should be understood to mean either one, both, or any combination thereof of the alternatives.

[0037] All citations are hereby incorporated by reference.

[0038] Tubing system according to the first aspect of the invention

[0039] The object named above is solved in accordance with a first aspect of the present invention by a tubing system, comprising: a first port and a second port configured for connection to external elements; a main conduit fluidically connecting the first port and the second port; a valve associated with each port, each valve being operable independently to open or close the respective port, thereby regulating fluid flow along the main conduit; a metering vessel fluidically connected to the main conduit via a first channel, a valve being operable to open or close the metering vessel, thereby regulating fluid flow along the first channel; an air access point fluidically connected to the main conduit via a second channel, a valve being operable to open or close the air access point, thereby regulating fluid flow along the second channel; a bidirectional pump operatively connected to the main conduit; and pressure sensors located on opposite sides of the bidirectional pump.

[0040] The tubing system according to the first aspect comprises at least two ports for connecting other elements of a bioprocess, such as tubing, reservoirs, bioreactors, media containers, waste vessels, additional tubing segments or the like. Typically, the ports are implemented as standardized connectors that allow secure and sterile attachment of external elements. These ports can take various forms depending on the specific requirements of the bioprocess, including sterility, ease of use, and compatibility with existing equipment. Exemplary implementations of the ports are barbed connectors, Luer connectors, clamp fittings, flange connectors. Preferred ports comprise a weldable first piece of sealed sterile tubing, such that another piece of weldable tubing can be welded to the first piece of tubing without breaking the sterile environment of the connector, particularly in cases where sterility must be maintained throughout a process. Alternatively or additionally, ports may incorporate valved connectors, such as pinch valves, diaphragm seals, or quick-disconnect couplings with integrated shutoff features to prevent leaks when attaching or detaching components. In high-integrity sterile processes, ports can also be designed for aseptic docking, where connections are made within sterile enclosures or using sterile welding techniques. The tubing system is generally set up for sterile transfer of fluid between the ports or between pairs of ports.

[0041] The section of the tubing system between two ports is referred to as a “main conduit” in the present disclosure. The transfer of fluid between the two ports generally ensues along the main conduit, although the fluid may be pumped at least intermittently along other parts of the tubing system, e.g. towards the metering vessel or away from it. Apart from the main conduit, the tubing system comprises first and second channels, each sometimes referred to as a “side channel”, together “side channels”, throughout the present disclosure. These side channels fulfil important functions in the tubing system. For example, the first channel connecting the main conduit with the metering vessel enables use of the tubing system to perform precise metered transfer of liquids, as will be described elsewhere herein. The second channel connecting the main conduit to the air access point serves as means for purging the tubing system of liquid. Fluidical connections between any side channel(s) and / or main conduit(s) are referred to as “branching point” throughout the present disclosure. Main conduit and side channels are together referred to as “channels” throughout the present disclosure.

[0042] Apart from the two ports, the tubing system may comprise further ports for connecting additional external elements. The maximum total number of ports a tubing system according to the present invention can accommodate is not limited, e.g. 3, 4, 5, 6, or even 10 or 15 ports or more are possible. In an exemplary embodiment, the tubing system further comprises at least one further port configured for connection to external elements, wherein each port is fluidically connected to every other port via a main conduit, wherein the main conduits can, independently from one another, be entirely separate or share a section of their length, and wherein at least one second channel opens into the main conduit at a location between each pair of ports, wherein preferably, a first channel leading to a metering vessel opens into the main conduit at a location between each pair of ports. In this embodiment, the tubing system is configured to facilitate more complex bioprocesses, such as, for example, a cell culture medium exchange procedure involving a cell culture medium vessel connected to a first port, a vessel for cultivating cells connected to a second port, and a waste vessel connected to a third port, wherein in a first step, spent cell culture medium may be moved from the second port to the third port, and in a subsequent second step, fresh cell culture medium may be moved from the first port to the second port. More examples will be outlined throughout the present disclosure. It is generally preferred that the two ports - or, in case of a tubing system with additional ports, at least two of the ports, preferably each pair of ports - is / are connected by at least two alternative channels which can be accessed by opening and closing a certain combination of valves. For example, the first port may be connected to the second port by a first conduit, wherein the liquid flow along the first conduit is regulated by a first set of valves, one being associated with the first port and one with the second port. In addition, the first and second port may be connected by a second conduit, wherein the liquid flow along the second conduit is regulated by a second set of valves, one being associated with each of the ports. By opening the first set of valves and closing the second set of valves, the first conduit becomes the main conduit and liquid can flow though the first (main) conduit between the two ports. Alternatively, by opening the second set of valves and closing the first set of valves, the second conduit becomes the main conduit and liquid can flowthrough the second (main) conduit between the ports. This design of the tubing system allows for switching between bulk and metered transfer between the same ports, which will be elaborated on elsewhere herein.

[0043] Of course, the tubing system according to the present disclosure achieves a liquid- tight connection between the external elements connected to the ports of the tubing system. Therein, the term “fluidically connected” is intended to mean that one element of the tubing system is connected to another element of the tubing system so that fluid (i.e., liquid or gas) may flow between them without leaking; it is generally preferred that the only points of entry or discharge of fluids to / from the tubing system are the ports (for liquid and gas), and the air access point and optionally the metering vessel (each only for entry and discharge of gas). In this way, the tubing system ensures that a sterile environment is maintained within it.

[0044] The air access point (also referred to as “air inlet” throughout the present disclosure) may generally be designed as an open-ended piece of tubing, the end of which is covered by an air filter, such as a sterile filter having an average pore size of 220 nm or lower.

[0045] For example, a single air access point may be connected by more than one second channel to other parts of the tubing system, wherein a valve is arranged in each second channel to regulate fluid flow along the respective second channel. In this way, the air access point may act on different parts of the tubing system by selectively opening and closing the respective valves.

[0046] For example, at least one second channel may comprise a plurality of branch conduits adjacent to the main conduit, each branch conduit being in fluid communication with the main conduit at a distinct connection point, wherein each branch conduit comprises a valve being operable to open or close the respective branch conduit so as to allow fluid to flow independently through each branch conduit. For example, the connection points between the branch conduits and the main conduit may be placed on both sides of a pump located in the main conduit or in a first channel connecting to the main conduit between the connection points of the branch conduits. In this arrangement, the entire tubing system can be effectively purged of liquid without leaving any dead volume in the system, which is advantageous when pumping high- value liquid or, e.g., when aiming for precise metered transfer of liquid.

[0047] The tubing may be produced from any material known to be compatible with bioprocessing, including but not limited to silicone, thermoplastic elastomers (TPEs), polyvinyl chloride (PVC), fluoropolymers such as PTFE, polyethylene (PE), polypropylene (PP) or ethylene vinyl acetate (EVA). The material choice may depend on factors like fluid type, sterility requirements, biocompatibility, and resistance to pressure, temperature, and gas exchange. The skilled person is capable of choosing the material to achieve a balance of chemical compatibility, flexibility, durability, and sterility. Each of the valves included in the tubing system according to the present invention is generally configured to be able to occlude fluid flow through the tubing system at a defined point, thereby influencing fluid flow along a respective conduit or channel within the tubing system. Although the exact type of valve is not critical for achieving the advantages of the present invention, the valves may preferably be pinch valves or diaphragm valves, wherein each valve may be individually and independently chosen to be of any particular type. It is generally preferred that each valve within the tubing system is individually actuatable to open or close.

[0048] The tubing system according to the present invention comprises a metering vessel. The metering vessel is configured to define a controllable volume within the tubing system, allowing for precise measurement and transfer of liquid. Its structure is tailored to ensure compatibility with the overall fluid pathway while maintaining sterility and minimizing dead volume. Typically, the metering vessel is integrated into the tubing system in such a way that it can be filled and emptied in a controlled manner, e.g. by the action of a pump. The metering vessel may incorporate flexible or rigid walls, depending on the intended mode of operation. A flexible-walled vessel, for instance, can be compressed to expel liquid or expanded to draw liquid in, functioning similarly to a diaphragm-based dosing chamber. Alternatively, a rigid-walled metering vessel may rely on precisely controlled inflow and outflow through associated valve mechanisms. The vessel may also feature volume markings or be paired with external sensors to facilitate monitoring of the liquid level.

[0049] In a preferred embodiment, the metering vessel comprises an air inlet connected to it to allow for inflow and outflow of sterile air, thus avoiding overpressurisation or creation of a vacuum. The air inlet may be in the form of an open-ended piece of tubing having a sterile air filter attached at its end. The air inlet may be arranged in a top part of the metering vessel, such that it is not contacted by liquid flowing into the metering vessel. The metering vessel is generally arranged inline within a first channel of the tubing system, which connects the metering vessel to the main conduit. The metering vessel is accessed by opening / closing a valve, which is preferably one that has no dead volume. It is further preferred that the metering vessel is positioned at the end of the first channel within the tubing system, such that it has a single connection point through which liquid is both received and dispensed. Unlike other components of the tubing system, which may feature multiple connection points to accommodate different flow paths, the metering vessel interfaces with the system through a single inlet, ensuring controlled fluid transfer. In systems requiring highly accurate dosing, the vessel may be designed to accommodate a defined liquid volume with minimal expansion or contraction, ensuring repeatability in metered transfers. Regardless of its specific geometry, the metering vessel serves as a critical element in achieving controlled liquid handling while maintaining sterility and compatibility with the single-use nature of the tubing system.

[0050] In an exemplary embodiment of the tubing system according to the first aspect, the metering vessel is configured for measurement of the liquid volume present therein. This is preferably achieved by the metering vessel being connected to a weighing system. Therein, the measurement is preferred to be a continuous and / or real-time measurement.

[0051] In an exemplary embodiment of the tubing system according to the first aspect, the metering vessel (MV) is configured for being reversibly sealed and unsealed, wherein preferably, reversible sealing is achieved through welding. The ability to weld and seal / cutthe metering vessel for reversibly connecting to the tubing system enables secure and sterile integration of the metering vessel into the system while allowing for its removal without compromising system integrity. Welding ensures a seamless and leak-free connection, reducing the risk of contamination and maintaining sterility throughout operation. The option to seal and cut the vessel further allows for controlled disconnection, enabling the option to replace the metering vessel as a consumable component without exposing the tubing system to environmental contaminants and without having to replace the entire tubing system when performing multiple consecutive metered transfers. For example, in this exemplary embodiment the metering vessel may be used to acquire an aliquot of the pumped liquid without compromising the sterile environment within the tubing system by pumping a metered amount of liquid into the metering vessel, performing sealing and cutting, and removing the metering vessel from the tubing system, e.g. for further analysis or storage of the aliquot.

[0052] The tubing system comprises a bidirectional pump for pumping fluid through the channels and conduits of the tubing system. The term “bidirectional” is intended to infer the usual meaning of the term, which is that the pump can be controlled / actuated to pump fluid into a first direction, and the same pump can alternatively be controlled / actuated to pump the fluid into a second direction opposite the first direction. Although the tubing system is generally compatible with encompassing more than one pump, arrangements including multiple pumps have certain disadvantages as alluded to above. It is therefore generally preferred that the tubing system comprises exactly one pump.

[0053] In an exemplary embodiment of the tubing system according to the first aspect, the bidirectional pump is a peristaltic pump. As is commonly known, peristaltic pumps consist of a pump head comprising a central rotating mechanism with multiple rollers or shoes for sequentially compressing the adjacent tubing. Usually, peristaltic pumps further comprise an occlusion track, which is typically a curved surface against which the tubing is compressed by the rollers. To pump fluid, the rotating rollers squeeze the tubing against the occlusion track, pinching it completely closed at the point of contact. This prevents backflow and isolates discrete segments of fluid. As the rotor continues to turn, each roller moves along the tubing, pushing the fluid trapped between successive points of occlusion forward. After the roller passes, the tubing relaxes back to its natural shape, creating a slight vacuum that helps draw in more fluid from the upstream side, ensuring continuous flow. In the context of the present invention, peristaltic pumps have the advantage that the pump head can be provided as a reusable pre-installed component of, for example, a bioprocessing station, and can be used in combination with a consumable tube set which is fitted to the pump head when arranged on the bioprocessing station, e.g. in the form of a millifluidic module.

[0054] The pump is operatively connected to the main conduit. This means that the pump is functionally integrated with the conduit in such a way that it can actively influence fluid flow within the main conduit. This does not necessarily mean a direct physical attachment to the main conduit - rather, it signifies that the pump interacts with the tubing system to move, regulate, or control the fluid inside the main conduit.

[0055] The location of the pump within the tubing system is important for the pumping functionality of the tubing system. For example, if bulk liquid transfer is intended, it is necessary to arrange the pump within the main conduit. In this configuration, the pump can directly act onto the main conduit to pump fluid from one port through the main conduit directly to another port, i.e. without pumping into the metering vessel. Alternatively, for example, if metered transfer is intended, the pump may be arranged along a side channel, e.g. along the first channel, i.e. between the branching point and the metering vessel, or between the main conduit and the metering vessel.

[0056] In an exemplary embodiment of the tubing system according to the first aspect, a bidirectional pump is located between two branch conduits of a second channel leading to an air access point. This configuration allows air to be introduced from both sides of the pump, effectively displacing any remaining liquid and eliminating dead volume within the system. By ensuring that no residual liquid remains in the pump or adjacent tubing sections, this design optimizes liquid recovery, which is particularly advantageous when handling high-value liquids or when precise metered transfer is required. The ability to fully purge the system further enhances accuracy and reproducibility, while also minimizing product loss and preventing crosscontamination between process steps. In an exemplary embodiment of the tubing system according to the first aspect (alternative 1), the first and second channels are configured to connect to the main conduit at separate connection points, wherein preferably each of the first and second channels comprises a separate bidirectional pump. In this embodiment, fluid flow in the tubing system can be controlled independently in each channel. This allows for precise modulation of liquid and air introduction, optimizing purging efficiency and ensuring complete evacuation of the system. The separation of the channels also provides greater flexibility in system operation, particularly when different flow rates or pressures are required for liquid and air transfer.

[0057] In an alternative embodiment of the tubing system according to the first aspect (alternative 2), the first channel and the second channel are configured to connect to the main conduit via a unified connection by sharing at least a section of their length, preferably adjacent to the main conduit. In this embodiment, it is preferred that the bidirectional pump is located in the shared section of the first channel and the second channel. This arrangement simplifies the tubing system by reducing the number of pumps required, minimizing mechanical complexity and potential failure points. With both liquid and air traveling through the same pump, transitions between liquid transfer and system purging can be managed efficiently without the need for additional valving. This design is particularly advantageous in compact setups where space constraints or system simplification are priorities, while still ensuring effective purging and controlled metered transfer.

[0058] In an exemplary embodiment of the tubing system according to the first aspect, in addition to the second channel, a first channel opens into the main conduit at a location between each pair of ports. This configuration is particularly advantageous in tubing systems comprising more than two ports, as it provides for metered transfer of liquids between each pair of ports.

[0059] The tubing system according to the invention incorporates two pressure sensors which are positioned on either side of the bidirectional pump, enabling differential pressure monitoring across the pumping mechanism. This arrangement allows for a more precise assessment of pump performance by detecting pressure drops, ensuring consistent flow rates, and identifying variations that may result from system irregularities such as filter clogging, tubing deformation, or air bubble formation. By continuously measuring pressure both upstream and downstream of the pump, the system can dynamically adjust operating parameters to maintain optimal liquid transfer conditions. The use of two pressure sensors further enhances process control by enabling closed-loop feedback regulation, where real-time pressure data can be used to adjust pump speed or valve operation in response to changing conditions. This is particularly advantageous in applications requiring highly controlled transfer, where pressure stability is critical for maintaining accurate liquid dosing, for example during high-precision bulk transfer of liquid through the tubing system according to the present invention. Additionally, dual-sensor configurations improve system diagnostics, facilitating early detection of leaks or pump malfunctions and reducing the risk of process deviations.

[0060] In embodiments of the tubing system comprising more than one pump, it is preferred that the tubing system comprises at least one pressure sensor associated with each further pump, ideally two pressure sensors located on either side of each further pump.

[0061] In some particularly preferred embodiments, the main conduits between all ports of the tubing system share a section of their length. This section of tubing is also referred to herein as the “shared main conduit”. Therein, it is generally preferred that the bidirectional pump is located in the shared main conduit, thereby enabling the system to perform bulk transfer between each pair of ports. Moreover, the first channel leading to the metering vessel may open into the shared main conduit, enabling the possibility of metered transfer between each pair of ports. It is particularly preferred that at least one second channel, preferably all second channels, most preferably all first and second channels open(s) into the shared main conduit. For example, the shared main conduit may comprise the following branching points in succession: a second channel leading to an air access point, the bidirectional pump, a first channel leading to the metering vessel, and another second channel leading to the same or a different air access point.

[0062] Method for metered transfer according to the second aspect of the invention

[0063] The object named above is further solved in accordance with a second aspect of the present invention by a method for transferring a metered amount of a liquid using a tubing system according to the first aspect of the present invention. The method, also referred to as “metered transfer method” throughout the present disclosure, comprises: transferring a first amount of the liquid from a first port into a metering vessel, preferably through a bidirectional pump, clearing the tubing section between the first port and the metering vessel from the liquid by transferring the remaining liquid to the first port using the air access point, pumping a metered amount of the liquid from the metering vessel to a second port, preferably through the bidirectional pump, and clearing the tubing section between the metering vessel and the second port from the liquid by transferring the remaining liquid to the second port using the air access point.

[0064] It is generally understood that the methods described herein, while only referring to the transfer between the first port and the second port, shall not be limited to this specific combination of ports, but shall encompass transfer between any combination of two ports of the tubing system (e.g., from the second port to the first port, or from the first or second port to a further port). The present disclosure only refers to first and second port in order to remain easy to understand.

[0065] In the first step of the method according to the second aspect, a defined amount (first amount) of a liquid is transferred from a first port into a metering vessel. Therein, the liquid passes through the following consecutive elements of the tubing system: a valve associated with the first port, optionally a section of the main conduit connecting the first port with another port, at least a section of the first channel, and the valve associated with the metering vessel. The liquid passes through a pump, preferably through the bidirectional pump, which may be located in the main conduit (e.g., in the shared main conduit) or in the first channel.

[0066] The bidirectional pump is controlled to pump fluid towards the metering vessel until it is determined that the first amount of liquid has been transferred. This may be achieved by any means known in the art, for example by determining the weight of the metering vessel and causing stopping of the pump when a predetermined weight difference of the metering vessel is observed.

[0067] Once the first amount of liquid has been transferred to the metering vessel, the metering vessel is preferably closed off from the tubing system, for example by closing the valve associated with the metering vessel (which is preferred) or by sealing and cutting the metering vessel, thus severing its physical connection with the first channel (which is possible, but less preferred). This ensures that the metered liquid contained in the metering vessel does not leak out during the subsequent clearance of the tubing system.

[0068] Subsequently, the tubing section between the first port and the metering vessel is cleared from the liquid. Generally, the liquid is cleared by transferring the remaining liquid to the first port, whereby unused liquid is preserved and does not need to be discarded or otherwise removed from the system. The clearance is generally achieved using the air inlet, e.g. by opening the valves associated with the air access point and the first port and pumping towards the first port, thereby replacing the liquid with air from the air inlet, preferably until the entire distance between air access port and first port contains only air. The skilled person understands that in order to prevent any remaining liquid from moving through the tubing system in subsequent steps, it is required that the pumping should continue until the remaining liquid has at least passed through the valve associated with the first port.

[0069] The section cleared may be the entire tubing between the first port and the metering vessel, e.g. in case that the metering vessel is directly connected to a main conduit or second channel (i.e. if the first channel has no volume). Alternatively, the section cleared can also be a defined section between first port and metering vessel, e.g. the section between first port and branching point of the first channel. In this alternative embodiment, the metered volume includes the amount of liquid present in the uncleared section of tubing, which can e.g. correspond to the volume of the first channel.

[0070] Once the path has been cleared, a metered amount of the liquid is pumped from the metering vessel to a second port. This is preferably achieved by pumping through the bidirectional pump, e.g. in a tubing system where the bidirectional pump acts on the side channel or main conduit between the metering vessel and the second port. The pumping is generally performed until the entire metered amount has passed a fixed point of reference, which may be close to the metering vessel. The passing of the metered amount can be detected, for example, by continuously determining the weight of the metering vessel and comparing the determined amount with a target weight of the metering vessel which is representative of the metered amount having passed the fixed point of reference. For example, the fixed point of reference may be a branching point of the first channel leading to the metering vessel with a second channel or a main conduit.

[0071] The metered amount can have the same volume as the first amount pumped into the metering vessel (which is possible but less preferred), or can have a lower volume, e.g. the first amount minus a predetermined dead volume which remains as a residue inside the metering vessel or first channel (which is preferred). This is because the latter approach enables rapid filling of the metering vessel, followed by controlled dispensing at a reduced flow rate to achieve precise volumetric delivery. In order to avoid accumulating high vacuum pressure in the tubing system during this pumping step, it is possible to open the valve associated with the air inlet. Thereby, air is introduced into the tubing system and replaces the vacuum left behind during pumping. Alternatively, for example, the metering vessel may have a variable volume (e.g. by being implemented as a flexible container) and / or may preferably have a separate air inlet connected to it, thus also avoiding high vacuum pressure.

[0072] In a subsequent step, the method according to the second aspect involves clearing the tubing section between the metering vessel and the second port from the liquid. Generally, the liquid is cleared by transferring the remaining liquid to the second port, thus ensuring complete transfer of the entire metered volume. The clearance is generally achieved using the air inlet, e.g. by opening the valves associated with the air access point and the second port and pumping towards the second port, thereby replacing the liquid with air from the air inlet, preferably until the entire distance between air access port and second port contains only air.

[0073] The section cleared may be the entire tubing between the metering vessel and the second port, e.g. in case that the metering vessel is directly connected to a main conduit or second channel (i.e. if the first channel has no volume). Alternatively, the section cleared can also be a defined section between metering vessel and second port, e.g. the section between the branching point of the first channel and the second port. In this alternative embodiment, the metered volume does not include the amount of liquid present in the uncleared section of tubing, which can e.g. correspond to the volume of the first channel.

[0074] In an optional but advantageous final step, the method according to the second aspect may involve clearing the metering vessel and the first channel from the remaining liquid. This can be implemented by transferring the remaining liquid to the first port in order to recover non-transferred volume retained there. In this implementation, all liquid is removed from the tubing system, and any liquid not transferred is preserved for later use. Alternatively, the remaining liquid can be transferred to a waste outlet, e.g. to another port connected to a waste container, thereby directly discarding any remaining liquid not intended for recovery, such as a transfection mixture. This step can be achieved, for example, by pumping from the metering vessel to the first port or waste outlet, thereby replacing the liquid with air drawn in through an air inlet of the metering vessel.

[0075] The method according to the second aspect of the present invention is particularly advantageous because it allows for high precision of the transferred volume. This is ensured by having the pump cleared from metered liquid from both sides: once from the side opposite the first port after pumping the liquid to the metering vessel, and once from the side opposite the second port after pumping the liquid towards the second port.

[0076] Method for bulk transfer according to the third aspect of the invention

[0077] The object named above is further solved in accordance with a third aspect of the present invention by a method for transferring a bulk amount of a liquid using a tubing system according to certain embodiments of the first aspect of the invention. This method, also referred to herein as “bulk transfer method”, comprises: transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second portby transferring the remaining liquid to the second port, and / or clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port, e.g. using air drawn through the air inlet.

[0078] The method according to the third aspect is intended to transfer a large amount of liquid directly between two external elements connected to two ports of the tubing system according to the first aspect. It is not necessary to precisely determine or measure the amount transferred; it is, however, possible to do so, e.g. by weighing one or both of the external elements and causing stopping of the transfer once a predetermined weight difference is measured. Another exemplary possibility is measuring the pressure inside the tubing system as described elsewhere herein and causing stopping of the transfer once the pressure exceeds or falls below a limit value.

[0079] The method comprises, in a first step, transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump. During this step, the bulk amount of liquid passes through at least the following consecutive components of the tubing system according to the first aspect: the first port, the valve associated with the first port, a main conduit connecting the first port with the second port, the bidirectional pump, the valve associated with the second port, and the second port. This step ensues until the transfer is caused to stop, e.g. by actuating the bidirectional pump to stop pumping towards the second port.

[0080] In a subsequent step, the method according to the third aspect comprises clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and / or clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port, e.g. using air drawn through the air inlet or through the metering vessel. In this context, the term “remaining liquid” refers to the part of the bulk liquid which is present in the referred-to part of the tubing system, i.e. the liquid which has exited the first port and travelled through the main conduit to the bidirectional pump. For example, this can be achieved by having an air inlet arranged on the side of the bidirectional pump opposite the second port (along the conduits and channels), opening the valves associated with the air inlet and the second port, closing all other valves, and pumping towards the second port. This step ensures that all liquid exits the tubing system, thereby reducing the amount of waste produced by the system. Alternatively or additionally, this can be achieved by having an air inlet arranged on the side of the bidirectional pump opposite the first port (along the conduits and channels), opening the valves associated with the air inlet and the first port, closing all other valves, and pumping towards the second port.

[0081] If the sections of the tubing system on both sides of the bidirectional pump, including the section formed by the bidirectional pump, are cleared from remaining liquid, the method according to the invention allows for complete clearance of the tubing system from liquid. This effect is of particularly advantageous when transferring high-value liquids, as it ensures that no liquid is wasted in the course of transferring through the tubing system according to the invention.

[0082] It is possible to improve the transfer precision of the method according to the third aspect. This can be achieved, for example, by transferring a priming amount of liquid from the first port to the metering vessel, then transferring the bulk amount of liquid, then clearing the section between the bidirectional pump and the second port from liquid by pumping the remaining liquid to the second port, and then clearing the tubing system from remaining liquid between the metering vessel and the first port by pumping towards the first port, thereby emptying the metering vessel. This sequence of steps mitigates some error introduced by the dead volume of the tubing system between the first port and the metering vessel, resulting in a more precise transfer of bulk liquid. To consolidate, the method according to this exemplary embodiment comprises the following steps: transferring a priming amount of the liquid from a first port to a metering vessel transferring an intended bulk amount of the liquid from the first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and clearing the tubing section between the first port and the metering vessel by transferring the remaining liquid to the first port using the metering vessel. It is preferred that the priming amount of liquid has at least the same volume as the tubing between the first port and the metering vessel.

[0083] In general, the steps of clearing the tubing sections between the pump and the respective ports can be performed in reverse order without having to further adapt the method in any way, i.e. the method according to the third aspect encompasses an embodiment wherein the tubing section between the bidirectional pump and the first port is cleared first, and afterwards the tubing section between the bidirectional pump and the second port is cleared.

[0084] Tubing cassette according to the fourth aspect of the invention

[0085] The object named above is further solved in accordance with a fourth aspect of the present invention by a tubing cassette comprising a tubing system according to the first aspect of the present invention. The tubing cassette is generally configured that the tubing system contained therein can be fluidically connected to an external element in a reversible fashion.

[0086] The term “cassette” is intended to refer to a structured interface for integrating the tubing system into a broader process environment while providing a controlled and organized layout for fluid transfer. The cassette typically defines a firm surface that defines connection points for external elements and other components such as sensors or pumps, enabling secure integration and controlled fluid handling. By providing a standardized interface, the cassette enhances ease of use, facilitates reliable and sterile connections, and contributes to overall process efficiency by reducing setup complexity and ensuring consistent performance.

[0087] In one embodiment, the cassette consists of a rigid structure in which fluid pathways are defined by preformed channels within a first molded body, eliminating the need for flexible tubing while ensuring precise and reproducible fluid routing. For example, the cassette may comprise a sandwich-like structure including a first molded body and a flexible membrane. In this embodiment, the first molded body, formed from a material such as a polymer, contains embedded therein fluid channels and recessed valve regions. The flexible membrane, for example made from silicone, is affixed to the first molded body, covering the channels and valve regions in a sealing manner, such that the conduits and channels of the tubing system are formed by the first molded body and the flexible membrane. The membrane serves as an integral part of the valve mechanism, as it can be selectively deformed into the recessed areas to block fluid flow through the corresponding channels, thereby functioning as a valve. For example, a second molded body may be positioned on the opposite side of the membrane, providing structural support while incorporating through-holes aligned with the valve regions. These through-holes allow actuation elements, such as pistons, to extend through the second molded body and press against the membrane at designated points, selectively controlling fluid passage within the channels. This arrangement enables precise and reliable valve operation while maintaining a compact and enclosed design that facilitates integration into a broader fluid handling system.

[0088] In an alternative embodiment, the cassette may enclose flexible tubing within a defined housing, combining the adaptability of soft-walled conduits with the benefits of a structured arrangement.

[0089] For example, the tubing cassette may be configured to mate with an interface on a bioprocessing station, e.g. forming an adapter module thereof. In this embodiment, the dimensions and port locations of the cassette align with the bioprocessing station. Thereby, the tubing cassette and bioprocessing stations can be easily used in combination to perform bioprocesses, such as outlined below in the context of the fifth aspect.

[0090] Bioprocessing method according to a fifth aspect of the present invention

[0091] The object named above is further solved in accordance with a fifth aspect of the present invention by a bioprocessing method comprising: providing a bioprocessing station, providing a tubing system according to the first aspect of the present invention, fluidically connecting the tubing cassette to the bioprocessing station, preferably by welding, performing a method according to the second or third aspect of the present invention, and disconnecting the tubing system from the bioprocessing station, preferably by sealing and cutting.

[0092] The bioprocessing method comprises the use of the tubing system according to the first aspect of the invention and a bioprocessing station configured to interact with the tubing system during operation. The method includes providing the tubing system in a state suitable for fluid handling, wherein the tubing system comprises a structured arrangement of channels and connection points for interfacing with external elements and components of the bioprocessing station such as valve actuators. The bioprocessing module is arranged to facilitate controlled fluid transfer through the tubing system, enabling the execution of process steps necessary for the intended bioprocessing application.

[0093] In one embodiment, the bidirectional pump of the tubing system may be implemented in that the bioprocessing station comprises a peristaltic pump head and the tubing system comprises a protruding tubing section aligning and mating with the peristaltic pump head. In this way, the consumable part of the tubing system comprises no electronic components and is therefore easier to mass-produce and discard.

[0094] The bioprocessing method according to the fifth aspect further includes performing a bioprocess, wherein fluid is directed through the tubing system in accordance with a defined sequence of operations as laid out above in the context of the second and third aspects. The interaction between the tubing system and the bioprocessing station ensures that process conditions are maintained within predefined parameters, supporting the controlled progression of the bioprocess. Upon completion of the bioprocess, the tubing system is disconnected from the bioprocessing station. Disconnection may involve sealing and detaching fluid connections, removing physical interfaces, and / or deactivating integrated control mechanisms. The disconnection process is preferably performed in a manner that maintains the integrity of both the tubing system and the bioprocessing module, ensuring that any remaining fluid is managed appropriately and that system components remain in a state suitable for subsequent use or disposal.

[0095] Exemplary bioprocesses according to the present invention include, but are not limited to, the following:

[0096] 1) Feeding of a cell culture present in a culture container (e.g. first port) with media from a life support tray (e.g., second port).

[0097] 2) Removal of permeate from a cell expansion bag (e.g., first port) to a life support tray (e.g., second port).

[0098] 3) Emptying of remaining media from a life support media bag (e.g., first port) to a life support permeate bag (e.g., second port).

[0099] 4) Refilling of a life support media bag (e.g., first port) from a container directly connected to a cell expansion transfer line (e.g., third port).

[0100] 5) Emptying a life support permeate bag (e.g., second port) to a container directly connected to the cell expansion transfer line (e.g., third port).

[0101] 6) Purging a line with gas drawn from the headspace of an expansion bag (e.g., first port).

[0102] 7) Removing liquid from a cell expansion bag (e.g., first port) to a container directly connected to the cell expansion transfer line (e.g., third port).

[0103] 8) Adding liquid to the cell expansion bag (e.g., first port) from a container directly connected to the cell expansion transfer line (e.g., third port).

[0104] 9) Removing liquid from the cell expansion bag (e.g., first port) using a tubing cassette connected to the cell expansion transfer line (e.g., third port). 10) Adding liquid to the cell expansion bag (e.g., first port) using a tubing cassette connected to the cell expansion transfer line (e.g., third port).

[0105] 11) Removal of media from the life support media bag (e.g., first port) to a container directly connected to the cell expansion transfer line (e.g., third port) (for use as rinse liquid).

[0106] In one embodiment, the tubing system is present in the form of a cassette according to the fourth aspect of the invention. By employing a cassette-based configuration, the method enables reliable, repeatable, and scalable bioprocessing while allowing for the efficient exchange of system components. The ability to disconnect the cassette upon process completion facilitates ease of operation, supports sterility management, and enhances process flexibility by allowing for rapid system reconfiguration or replacement.

[0107] Further embodiments of the present invention

[0108] The following embodiments provide further advantages of the present disclosure. Embodiments referencing others also refer to previous embodiments numbers containing a letter. For example, “Tubing system according to embodiment 1 to 5” also reverts back to embodiment 4a.

[0109] 1. Tubing system, comprising: a first port (T2) and a second port (T4) configured for connection to external elements; a main conduit fluidically connecting the first port (T2) and the second port (T4); a valve (V10, V8) associated with each port (T2, T4), each valve (V10, V8) being operable independently to open or close the respective port (T2, T4), thereby regulating fluid flow along the main conduit; a metering vessel (MV) fluidically connected to the main conduit via a first channel, a valve (V6) being operable to open or close the metering vessel (MV), thereby regulating fluid flow along the first channel; an air access point (F) fluidically connected to the main conduit via a second channel, a valve (V7) being operable to open or close the air access point (F), thereby regulating fluid flow along the second channel; a bidirectional pump operatively connected to the main conduit; and pressure sensors located on opposite sides of the bidirectional pump. . Tubing system according to embodiment 1, wherein the metering vessel (MV) is configured for measurement of the fluid volume present therein. . Tubing system according to embodiment 2, wherein the metering vessel (MV) is connected to a weighing system. . Tubing system according to embodiment 2 or 3, wherein the measurement is a continuous and / or real-time measurement. a. Tubing system according to any one of the preceding embodiments, wherein the metering vessel comprises an air inlet connected to it. b. Tubing system according to embodiment 4a, wherein the air inlet is in the form of an open-ended piece of tubing having a sterile air filter attached at its end. c. Tubing system according to embodiment 4a or 4b, wherein the air inlet is arranged in a top part of the metering vessel. . Tubing system according to any one of the preceding embodiments, wherein the bidirectional pump is a peristaltic pump. 6. Tubing system according to any one of the preceding embodiments (alternative 1), wherein the first and second channels are configured to connect to the main conduit at separate connection points.

[0110] 7. Tubing system according to embodiment 6, wherein each of the first and second channels comprises a separate bidirectional pump.

[0111] 8. Tubing system according to any one of embodiments 1 to 5 (alternative 2), wherein the first channel and the second channel are configured to connect to the main conduit via a unified connection by sharing at least a section of their length.

[0112] 9. Tubing system according to embodiment 8, wherein the shared section is located adjacent to the main conduit.

[0113] 10. Tubing system according to embodiment 8 or 9, wherein the bidirectional pump is located in the shared section of the first channel and the second channel.

[0114] 11. Tubing system according to any one of the preceding embodiments, further comprising at least one further port (Tl, T3] configured for connection to external elements.

[0115] 12. Tubing system according to embodiment 11, wherein each port (Tl, T2, T3, T4] is fluidically connected to every other port via a main conduit.

[0116] 13. Tubing system according to embodiment 11 or 12, wherein the main conduits can, independently from one another, be entirely separate or share a section of their length. 14. Tubing system according to any one of embodiments 11 to 13, wherein at least one second channel opens into the main conduit at a location between each pair of ports.

[0117] 15. Tubing system according to any one of embodiments 11 to 14, wherein a first channel leading to a metering vessel opens into the main conduit at a location between each pair of ports.

[0118] 16. Tubing system according to any one of embodiments 11 to 15, wherein all main conduits share a section of their length (shared main conduit).

[0119] 17. Tubing system according to embodiment 16, wherein the bidirectional pump is located in the shared main conduit.

[0120] 18. Tubing system according to embodiment 16 or 17, wherein the first channel opens into the shared main conduit.

[0121] 19. Tubing system according to any one of embodiments 16 to 18, wherein at least one second channel opens into the shared main conduit.

[0122] 20. Tubing system according to any one of embodiments 16 to 19, wherein all second channels open into the shared main conduit.

[0123] 21. Tubing system according to any one of embodiments 16 to 20, wherein all first and second channels open into the shared main conduit.

[0124] 22. Tubing system according to any one of the preceding embodiments, wherein the metering vessel (MV) is configured for being reversibly sealed and unsealed.

[0125] 23. Tubing system according to embodiment 22, wherein reversible sealing is achieved through welding. 23a. Tubing system according to any one of the preceding embodiments, wherein the metering vessel (MV) has a separate air inlet for filtered air.

[0126] 23b. Tubing system according to any one of embodiments 1 to 23, wherein the metering vessel (MV) has a variable volume.

[0127] 24. Tubing system according to any one of the preceding embodiments, wherein the main conduit comprises at least two distinct connection points for a second channel, which can lead to the same or different air access points (F).

[0128] 25. Tubing system according to embodiment 24, wherein each second channel comprises a valve being operable to open or close the respective second channel so as to allow fluid to flow independently through each second channel.

[0129] 26. Tubing system according to embodiment 24 or 25, wherein the bidirectional pump is located between the connection points of the second channels.

[0130] 27. Tubing system according to any one of embodiments 24 to 26, wherein in addition to two second channels, a first channel opens into the main conduit at a location between each pair of ports.

[0131] 28. Method for transferring a metered amount of a liquid using a tubing system according to any one of the preceding embodiments, the method comprising: transferring a first amount of the liquid from a first port into a metering vessel, preferably through a bidirectional pump, clearing the tubing section between the first port and the metering vessel from the liquid by transferring the remaining liquid to the first port using the air access point, pumping a metered amount of the liquid from the metering vessel to a second port, preferably through the bidirectional pump, and clearing the tubing section between the metering vessel and the second port from the liquid by transferring the remaining liquid to the second port using the air access point. a. Method according to embodiment 28, further comprising: clearing the metering vessel and the first channel from remaining liquid. b. Method according to embodiment 28a, wherein the remaining liquid is transferred to the first port. c. Method according to embodiment 28a., wherein the remaining liquid is transferred to a waste outlet. . Method for transferring a bulk amount of a liquid using a tubing system according to any one of embodiments 17 to 21 or 24 to 27, the method comprising: transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and / or clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port, e.g. using air drawn through the air access point. a. Method according to embodiment 29, comprising: transferring a priming amount of the liquid from a first port to a metering vessel transferring an intended bulk amount of the liquid from the first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and clearing the tubing section between the first port and the metering vessel by transferring the remaining liquid to the first port using the metering vessel.

[0132] 30. Tubing cassette comprising a tubing system according to any one of embodiments 1 to 27, wherein the tubing cassette is configured that the tubing system contained therein can be fluidically connected to an external element in a reversible fashion.

[0133] 31. Tubing cassette according to embodiment 30, comprising: a first molded body containing, embedded therein, fluid channels and valve regions, and a flexible membrane covering the channels and valve regions.

[0134] 32. Tubing cassette according to embodiment 30 or 31, wherein the first molded body is formed from a rigid material such as a polymer.

[0135] 33. Tubing cassette according to any one of embodiments 30 to 32, wherein the flexible membrane is made from silicone.

[0136] 34. Tubing cassette according to any one of embodiments 30 to 33, wherein the flexible membrane is affixed to the first molded body, covering the channels and valve regions in a sealing manner.

[0137] 35. Tubing cassette according to any one of embodiments 30 to 34, further comprising a second molded body on the opposite side of the flexible membrane.

[0138] 36. Tubing cassette according to embodiment 35, wherein the second molded body comprises a recess precisely fitted to accommodate the flexible membrane. 37. Tubing cassette according to any one of embodiments 35 to 36, wherein the second molded body comprises through-holes aligned with the valve regions of the first molded body and flexible membrane.

[0139] 38. Tubing cassette according to any one of embodiments 35 to 37, wherein the second molded body comprises sensor openings positioned to correspond with pressure sensor regions of the flexible membrane.

[0140] 39. Tubing cassette according to embodiment 30, comprising a rigid housing enclosing a flexible tubing set.

[0141] 40. Tubing cassette according to any one of embodiments 30 to 39, wherein the tubing cassette is configured to mate with an interface on a bioprocessing station.

[0142] 41. Bioprocessing method comprising: providing a bioprocessing station, providing a tubing system according to any one of embodiments 1 to 27, fluidically connecting the tubing system to the bioprocessing station, preferably by welding, performing a method according to embodiment 28 or 29, and disconnecting the tubing system from the bioprocessing station, preferably by sealing and cutting.

[0143] DETAILED DESCRIPTION OF THE FIGURES

[0144] In the following, several exemplary embodiments of certain aspects of the invention are further elaborated and expanded upon with reference to the figures. Especially where the figures show schematic illustrations and technical drawings, the elements and components of the invention are indicated by reference numerals. In these figures, identical reference numerals indicate functionally identical elements.

[0145] Fig- 1 shows a schematic illustration of a minimal embodiment of a tubing system according to the present invention.

[0146] The tubing system 1 comprises a first port T2 and a second port T4. The ports T2, T4 are configured to connect to external elements. The ports function as entry and exit points of fluid to be transferred through the tubing system 1. Associated with the first and second port T2, T4 are valves V2 and V4, respectively. The valves V2, V4 can be opened and closed independently of one another, e.g. by being independently actuatable to open or close. In the embodiment of Fig. 1, the tubing between the ports T2, T4 is the main conduit 2.

[0147] At the branching point 3, a side channel 4 opens into the main conduit 2. In the part adjacent to the main conduit 2, the side channel 4 is a common section of the first channel 5 leading to the metering vessel MV and the second channel 6 leading to the air access point F. The metering vessel MV and air access point F are operable to open or close by their associated valves V6 and V7, respectively. These valves regulate the flow of fluid along their respective channel.

[0148] As shown in Fig. 1, the bidirectional pump P is located in the common section of the side channel 4, thereby operatively connected to the main conduit 2. The pump P is flanked by two pressure sensors PSI, PS2, which connect to the side channel 4 at branching points on either side of the pump P. It is generally preferred that the pump P is implemented as a section of tubing extending between the connection points Pla and Plb which can interface with a peristaltic pump head able to facilitate bidirectional pumping.

[0149] In order to facilitate metered transfer of liquid between the ports T2 and T4 (described in detail with respect to the second aspect of the present invention), in a first step valves V2 and V6 must be open while valves V4 and V7 are closed, and the pump P is controlled to pump fluid towards the metering vessel MV. Once a first amount of liquid has been transferred, the pump P is controlled to stop pumping. The transfer of the intended amount can be confirmed, e.g., by determining the weight of the metering vessel MV, or by letting the pumping continue for a predetermined amount of time.

[0150] In order to clear the tubing section between the metering vessel MV and the first port T2, valve V6 is closed and valve V7 is opened, and the pump P is controlled to pump fluid towards the first port T2 through the valve V2 which remained open. This pumping is continued until the transferred liquid has been replaced by air in the entire section between the metering vessel MV and the first port T2, which can be confirmed visually, or by measuring the pressure e.g. with one or both of the pressure sensors PSI, PS2, or e.g. by reading out signals from a liquid presence sensor.

[0151] Once the tubing system has been cleared of the remaining liquid, valves V2 and V7 are closed, valves V4 and V6 are opened, and the pump P is controlled to pump towards the second port T4. This pumping is continued until the metered amount of liquid has exited the metering vessel MV, which can be confirmed, e.g., by determining the weight of the metering vessel MV.

[0152] Next, the part of the metered amount remaining in the tubing system 1, i.e. the part that has not yet entered the second port T4, must be cleared from the tubing system 1. This is achieved by closing valve V6 and opening valve V7 and continuing to pump fluid towards the second port T4. This pumping may continue, for example, until the transferred liquid has been replaced by air in the entire section between the metering vessel MV and the second port T4, which can be confirmed visually, or by measuring the pressure e.g. with one or both of the pressure sensors PSI, PS2, or e.g. by reading out signals from a liquid presence sensor. In an optional final step, the liquid remaining in the metering vessel MV can be recovered from the tubing system. This is especially useful in cases where the liquid is intended for later use; however, in cases where the liquid shall not be recovered, the metering vessel can be discarded after transferring the metered amount to the second port T4. To recover the liquid remaining in the metering vessel, valves V7 and V4 are closed and valves V2 and V6 are opened. The bidirectional pump P is controlled to pump towards the first port T2, i.e. towards valve V2, thereby replacing the liquid remaining in the metering vessel MV and in the first channel 5 with air entering the metering vessel MV through an air inlet. This pumping may continue, for example, until the transferred liquid has been replaced by air in the entire section between the metering vessel MV and the first port T2, which can be confirmed visually, or by measuring the pressure e.g. with one or both of the pressure sensors PSI, PS2, or e.g. by reading out signals from a liquid presence sensor.

[0153] Fig- 2 shows an illustration of another embodiment of a tubing system 1 according to the present invention. This embodiment differs from the one shown in Fig. 1 by the added valves V10 and V8 which are associated with the first and second ports, respectively. In this embodiment, the tubing system 1 allows for metered transfer according to the second aspect of the present invention as well as for bulk transfer according to the third aspect of the present invention.

[0154] Metered transfer is accomplished as described in relation to Figure 1. For bulk transfer between the ports T2, T4, the following steps may be taken after having connected a source element (e.g., a container filled with a liquid) to the first port T2 and a destination element (e.g., an empty container) to the second port T4:

[0155] In an optional initial step, valves V2 and V6 are opened, and the pump P is controlled to pump towards the metering vessel MV, i.e. towards valve V6. This pumping is continued until a priming amount of liquid has been transferred towards the metering vessel. Including this step has the effect that dead volume effects within the tubing system 1 are reduced and the liquid can be transferred with improved accuracy. Next, valve V6 is closed and valve V8 is opened, with the other valves being closed, and the pump P is controlled to pump towards the second port (i.e., towards valve V8) along the main conduit 2. This pumping is continued until the bulk amount of liquid has been transferred to the second port T4. Once the bulk transfer is finished, valve V8 is closed and valve V7 associated with the air access point is opened. The pump P is controlled to pump towards the first port (i.e., towards valve V2, which remains open). This pumping is continued until no liquid remains between the bidirectional pump and the first port.

[0156] Alternatively, if the remaining liquid is intended to be transferred towards the second port, valves V10 and V4 are opened instead of valves V2 and V8 before initiating the bulk transfer, and the pump P is controlled to pump in the opposite direction (i.e., towards valve V4). After finishing the bulk transfer, valve V10 is closed and valve V7 is opened, and the pump P is controlled to pump towards the second port (i.e., towards valve V4) until the section between the bidirectional pump and the second port is cleared of liquid.

[0157] Fig- 3 shows an illustration of another embodiment of a tubing system 1 according to the first aspect of the present invention. This embodiment differs from the one shown in Fig. 2 by the additional valve V5 which is associated with the air access point and opens into the main conduit between the first port T2 and the second port T4 at a distinct branching point F2 which, compared to the branching point Fl at which the second channel controlled by valve V7 opens into the main conduit, is located on the opposite side of the bidirectional pump. This means that, if the main conduit runs along valves V2 and V8, for example, the second channel controlled by valve V5 opens into the main conduit upstream of the bidirectional pump and the second channel controlled by valve V7 opens into the main conduit downstream of the bidirectional pump. This allows for clearing the entire tubing system 1 of remaining liquid when performing a bulk transfer method according to the third aspect of the invention. This is done as follows. In a first step, valves V2 and V8 are opened, with the other valves being closed, and the pump P is controlled to pump towards the second port (i.e., towards valve V8) along the main conduit 2. This pumping is continued until the bulk amount of liquid has been transferred to the second port T4. Once the bulk transfer is finished, valve V8 is closed and valve V7 associated with the air access point is opened. The pump P is controlled to pump towards the first port (i.e., towards valve V2, which remains open). This pumping is continued until no liquid remains between the bidirectional pump and the first port. Subsequently, valves V2 and V7 are closed, valves V8 and V5 are opened, and the pump P is controlled to pump towards the second port (i.e., towards valve V8). This pumping is continued until no liquid remains between the bidirectional pump and the second port. Because the section between the branching points Fl and F2 is cleared from remaining liquid twice, the entire tubing system is cleared of the transferred liquid.

[0158] Fig. 4 shows another embodiment of the tubing system according to the first aspect of the invention. This embodiment corresponds to the one shown in Fig. 3, except that it contains two additional ports, resulting in a total of four ports (Tl, T2, T3, T4). Each port is associated with at least one valve regulating fluid flow along a respective channel: port Tl is associated with valve VI, port T2 is associated with valves V2 and V10, port T3 is associated with valves V3 and V9, and port T4 is associated with valves V4 and V8.

[0159] In the exemplary embodiment shown in Fig. 4, the tubing system 1 is arranged as follows, which will be illustrated by imagining pumping a liquid from port Tl to port T2 through valves VI and V10: After entering the tubing system through port Tl, the liquid passes through valve VI, passes the branching point leading towards valve V2 and port T2, then passes the branching point leading towards valve V3 and port T3, then passes the branching point leading towards valve V4 and port T4, then passes the branching point leading towards valve V5 and the air access point. Thereafter, the liquid passes the branching point Pla where the pressure can be measured by the pressure sensor PSI, then passes through the bidirectional pump P, and then passes the branching point Plb where the pressure can be measured by the pressure sensor PS2. Thereafter, the liquid passes the branching point leading towards valve V6 and the metering vessel MV, then passes the branching point leading towards valve V7 and the air access point, then passes the branching point leading towards valve V8 and port T4, then passes the branching point leading towards valve V9 and port T3, and finally passes through valve V10 and exits the tubing system through port T2.

[0160] The tubing system 1 as shown in Fig. 4 comprises, at the indicated section, a shared main conduit 10. Any liquid pumped between any pair of ports Tl, T2, T3, T4, must pass through the shared main conduit 10. Moreover, the shared main conduit 10 comprises the branching points towards the side channels, and comprises the pump P.

[0161] The tubing system shown in Fig. 4 allows for metered transfer and bulk transfer between each pair of ports, while also allowing for the entire system to be cleared from remaining liquid and replacing by air.

[0162] Fig- 5 shows an alternative configuration of the tubing system according to the invention, which has essentially the same features as the embodiment shown in Fig. 4. The system allows for metered and bulk transfer between each pair of ports, and also allows for the entire system to be cleared from remaining transported liquid to be replaced by air.

[0163] As outlined above with respect to Fig. 4, the configuration of the tubing system shown in Fig. 5 will be illustrated by following a liquid from port Tl to port T2 through direct pumping. Once the liquid enters the tubing system, it passes through valve VI, then along the branching point leading to valve V2 and port T2, then passes to connection point Pla, which functions as a branching point towards valve V5 and air access point F and towards a channel containing pressure sensor PSI and further downstream branching towards valve V3 and port T3 in the one branch, and towards valve V4 and port T4 in the other branch. Continuing through connection point Pla, the liquid passes through a tube section interfacing with a peristaltic pump head (not shown) and into connection point Plb, which functions as a branching point towards valve V6 and the metering vessel MV and towards valve V7 and the air access point F. Continuing on, the liquid passes along a branching point leading to a channel containing pressure sensor PS2 and, further downstream, a branched section leading, on one side, to valve V8 and port T4 and, on the other side, to valve V9 and port T3. Following the liquid leads now through valve V10 and port T2, where the liquid exits the tubing system.

[0164] Fig. 6 shows in A a cassette according to the fourth aspect of the invention in exploded view, and in B in assembled form. The cassette consists of a first molded body 60 in which fluid pathways are defined as preformed channels (not shown), a flexible membrane 70 and a second molded body 80. The layout of the channels preformed in the first molded body 60 aligns with the one of the flexible membrane 70, which in the assembled state of the cassette covers all channels and valve regions 71. The valve regions 71 are designed as Widenings in the channels. The layout of the channels and valves corresponds to the one shown in Fig. 4.

[0165] On the first molded body 60, four port outlets 61 are mounted, which function as entry / exit points of liquid through the ports T1 to T4 as described above in relation to Fig. 4. In each case, an external element can be connected to the cassette by connecting a piece of tubing to one of the port outlets 61 and, on the other end, to the external element (e.g., a medium vessel). This can be done, for example, by welding or by any other means known in the field.

[0166] Moreover, the first molded body 60 has an air inlet port 62 and a metering vessel port 63 mounted thereon, which facilitate access to the air inlet and the metering vessel, respectively. As described above with respect for the port outlets 61, the air inlet and metering vessel can be connected with the inlet port 62 and metering vessel port 63, respectively, by any method known in the field. Suitable air inlets are tubing pieces having, at their end opposite the air inlet port 62, a sterile filter for air. Finally, the first molded body 60 has connection outlets 64 adjacent to a recess 65 which accommodate the pumping means. It is preferred that a tubing section is connected with both connection outlets 64 and engages with a peristaltic pump head arranged in the recess 65, whereby the tubing system inside the cassette is coupled to a bidirectional pump.

[0167] The flexible membrane 70 comprises, beside the channel regions and valve regions 71, pressure sensor regions 72. These are shown to be circular in shape, but may have any shape suitable for measuring the pressure inside the pressure sensor regions 72, which function as deformable interfaces where pressure changes within the fluidic channels are transmitted to an external sensor. During operation, when fluid flows through the cassette, pressure fluctuations cause the flexible membrane to deflect in response to changes in the internal pressure of the pressure sensor region 72 beneath it. The degree of membrane deflection corresponds to the applied pressure, allowing for indirect pressure measurement. This deflection can be detected by an externally positioned pressure transducer or force sensor that is placed in contact with or in proximity to the membrane. The sensor registers the displacement or force exerted by the membrane and converts this mechanical deformation into an electrical signal, which can then be used to monitor pressure in real-time. This approach ensures that the pressure sensor remains physically separate from the fluid path, preventing contamination and enabling sterile, single-use cassette designs. Additionally, the flexibility of the membrane allows for a sensitive and responsive measurement while maintaining the structural integrity of the cassette. The circular shape of the pressure sensor region provides uniform deformation characteristics, ensuring consistent and reproducible pressure readings across different operating conditions.

[0168] The second molded body 80 is configured to be positioned over the flexible membrane 70, providing structural support and facilitating interaction with external control elements. It comprises a recess 81 that is dimensioned to precisely accommodate the flexible membrane 70, ensuring that the membrane remains securely positioned over the channels, valve regions 71, and outlets 61, 62, 63 of the first molded body. This recess 81 establishes a sealed interface around the periphery of the flexible membrane 70, preferably sealed by glueing or the like, preventing unintended liquid escape and maintaining the integrity of the fluidic pathways within the cassette.

[0169] The second molded body 80 further includes a plurality of through-holes 82 strategically arranged to align with the valve regions 71 in the flexible membrane 70. These through-holes 82 allow for the passage of valve actuators, such as pistons or plungers (not shown), which can selectively engage the flexible membrane 70 to control fluid flow through the channels. By pressing the flexible membrane 70 into the underlying valve regions pre-formed within the first molded body 60, these actuators can occlude or regulate flow in a controlled manner.

[0170] Additionally, the second molded body 80 comprises a set of sensor openings 83 positioned to correspond with the pressure sensor regions 72 of the flexible membrane and below the first molded body 60. These sensor openings 83 enable external pressure sensors to be brought into direct contact with the flexible membrane 70, allowing for accurate pressure measurement without breaching the sealed fluidic environment. The membrane’s flexibility ensures that pressure variations within the channels are effectively transmitted to the sensor interface, facilitating precise real-time monitoring.

[0171] By providing a structured interface for valve actuation and pressure sensing, the second molded body 80 enhances the functionality of the tubing system while maintaining a compact and integrated design. The combination of sealing, controlled actuation, and sensor accessibility ensures reliable operation and supports applications requiring precise fluid management within a bioprocessing environment.

[0172] Fig. 7 shows another exemplary embodiment of a cassette according to the fourth aspect of the present invention. Fig. 7A shows the cassette in exploded view, and Fig. 7B in assembled form. This cassette is configured to be used in combination with a bioprocessing station comprising two peristaltic pump heads which are located in the two recesses 65, 81 when the cassette is positioned on the bioprocessing station.

[0173] The general construction of the cassette shown in Fig. 7 is highly similar to the one shown in Fig. 6, comprising a first molded body 60 and a second molded body 80 with a flexible membrane 70 sandwiched in-between. Valves can be actuated by pistons or the like (not shown) which pass through the through-holes 82 and press onto the valve regions 71. The pressure in the tubing can be determined by pressure sensors (not shown) which can be placed in the sensor openings 83 and thereby come into contact with the pressure sensor regions 72 of the flexible membrane 70. The cassette comprises a total of six port outlets 61 for ports T1 to T6 as labeled in Fig. 7B. Moreover, the first molded body 60 contains an air inlet 62, a metering vessel port 63, and four connection outlets 64, two for each peristaltic pump. In an operation-ready state, each port 61, 62, 63 is preferably attached to a sterile piece of tubing, which can be connected to another piece of tubing by welding to form a sterile connection with an external element such as a medium container or a bioreactor, and the connection outlets 64 are pairwise connected by a sterile piece of tubing configured to interact with a peristaltic pump head.

[0174] Fig- 8 shows a schematic illustration of a method 100 according to the second aspect of the invention. The method 100 comprises the following features:

[0175] Method for transferring a metered amount of a liquid using a tubing system according to the first aspect, the method comprising: (101) transferring a first amount of the liquid from a first port into a metering vessel, preferably through a bidirectional pump, (102) clearing the tubing section between the first port and the metering vessel from the liquid by transferring the remaining liquid to the first port using the air access point, (103) pumping a metered amount of the liquid from the metering vessel to a second port, preferably through the bidirectional pump, and (104) clearing the tubing section between the metering vessel and the second port from the liquid by transferring the remaining liquid to the second port using the air access point. (105)

[0176] Fig- 9 shows a schematic illustration of a method 110 according to the third aspect of the invention. The method 110 comprises the following features:

[0177] Method for transferring a bulk amount of a liquid using a tubing system according to some embodiments of the first aspect, the method comprising: (111) transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump, (112) clearing the tubing section between the bidirectional pump and the second portby transferring the remaining liquid to the second port, and / or clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port. (113)

[0178] List of reference numerals

[0179] 1 tubing system

[0180] 2 main conduit

[0181] 3 branching point

[0182] 4 side channel

[0183] 5 first channel

[0184] 6 second channel

[0185] 10 shared main conduit

[0186] 60 first molded body

[0187] 61 port outlet

[0188] 62 air inlet port

[0189] 63 metering vessel port

[0190] 64 connection outlet

[0191] 65 recess 70 flexible membrane

[0192] 71 valve region (thicker parts)

[0193] 72 pressure sensor region

[0194] 80 second molded body 81 recess

[0195] 82 through-hole

[0196] 83 sensor opening

[0197] F air inlet / air access point

[0198] Fl, F2 branching point MV metering vessel

[0199] P pump

[0200] Pla connection point

[0201] Plb connection point

[0202] PSI pressure sensor PS2 pressure sensor

[0203] T1-T4 port

[0204] V1-V10 valve

Claims

C l a i m s1. Tubing system, comprising: a first port (T2) and a second port (T4) configured for connection to external elements; a main conduit fluidically connecting the first port (T2) and the second port (T4); a valve (V10, V8) associated with each port (T2, T4), each valve (V10, V8) being operable independently to open or close the respective port (T2, T4), thereby regulating fluid flow along the main conduit; a metering vessel (MV) fluidically connected to the main conduit via a first channel, a valve (V6) being operable to open or close the metering vessel (MV), thereby regulating fluid flow along the first channel; an air access point (F) fluidically connected to the main conduit via a second channel, a valve (V7) being operable to open or close the air access point (F), thereby regulating fluid flow along the second channel; a bidirectional pump operatively connected to the main conduit; and pressure sensors located on opposite sides of the bidirectional pump.

2. Tubing system according to claim 1, wherein the metering vessel (MV) is configured for measurement of the fluid volume present therein, preferably by being connected to a weighing system, preferably wherein the measurement is a continuous and / or real-time measurement.

3. Tubing system according to any one of the preceding claims, wherein the bidirectional pump is a peristaltic pump.

4. Tubing system according to any one of the preceding claims, wherein the first and second channels are configured to connect to the main conduit at separateconnection points, wherein preferably each of the first and second channels comprises a separate bidirectional pump.

5. Tubing system according to any one of claims 1 to 3, wherein the first channel and the second channel are configured to connect to the main conduit via a unified connection by sharing at least a section of their length, preferably adjacent to the main conduit, wherein preferably the bidirectional pump is located in the shared section of the first channel and the second channel.

6. Tubing system according to any one of the preceding claims, further comprising at least one further port (Tl, T3) configured for connection to external elements, wherein each port (Tl, T2, T3, T4) is fluidically connected to every other port via a main conduit, wherein the main conduits can, independently from one another, be entirely separate or share a section of their length, and wherein at least one second channel opens into the main conduit at a location between each pair of ports, wherein preferably, a first channel leading to a metering vessel opens into the main conduit at a location between each pair of ports.

7. Tubing system according to any one of the preceding claims, wherein the metering vessel (MV) is configured for being reversibly sealed and unsealed, wherein preferably, reversible sealing is achieved through welding.

8. Tubing system according to any one of the preceding claims, wherein the main conduit comprises at least two distinct connection points for a second channel, which can lead to the same or different air access points (F), wherein each second channel comprises a valve being operable to open or close the respective second channel so as to allow fluid to flow independently through each second channel.

9. Tubing system according to claim 8, wherein the bidirectional pump is located between the connection points of the second channels.

10. Tubing system according to claim 8 or 9, wherein in addition to two second channels, a first channel opens into the main conduit at a location between each pair of ports.

11. Tubing system according to any one of the preceding claims, wherein all main conduits share a section of their length (shared main conduit), wherein preferably the bidirectional pump is located in the shared main conduit.

12. Method for transferring a metered amount of a liquid using a tubing system according to any one of the preceding claims, the method comprising: transferring a first amount of the liquid from a first port into a metering vessel, preferably through a bidirectional pump, clearing the tubing section between the first port and the metering vessel from the liquid by transferring the remaining liquid to the first port using the air access point, pumping a metered amount of the liquid from the metering vessel to a second port, preferably through the bidirectional pump, and clearing the tubing section between the metering vessel and the second port from the liquid by transferring the remaining liquid to the second port using the air access point.

13. Method for transferring a bulk amount of a liquid using a tubing system according to any one of claims 8 to 11, the method comprising: transferring an intended bulk amount of the liquid from a first port into a second port through a bidirectional pump, clearing the tubing section between the bidirectional pump and the second port by transferring the remaining liquid to the second port, and / or clearing the tubing section between the first port and the bidirectional pump by transferring the remaining liquid to the first port.

14. Tubing cassette comprising a tubing system according to any one of claims 1 to 10, wherein the tubing cassette is configured that the tubing system contained therein can be fluidically connected to an external element in a reversible fashion.

15. Tubing cassette according to claim 14, wherein the tubing cassette is configured to mate with an interface on a bioprocessing station.

16. Bioprocessing method comprising: providing a bioprocessing station, - providing a tubing system according to any one of claims 1 to 11, fluidically connecting the tubing system to the bioprocessing station, preferably by welding, performing a method according to claim 12 or 13, and disconnecting the tubing system from the bioprocessing station, preferably by sealing and cutting.

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