Tanks for biopharmaceutical processes

Abstract

The present invention relates to a reservoir element (200) for a tank 1 of a biopharmaceutical process line. The reservoir element (200) comprises a body element (210) and at least one shell element (220, 222). The body element (210) has a first end (212) and a second end (214) opposite the first end, each of the first end and the second end comprising an orifice, where the body element tapers from the first end to the second end, where an internal volume is defined between the first end and the second end. The body element and / or the at least one shell element comprises at least one groove (216, 217), where the at least one shell element (220, 222) is fixedly attached to the body element (210), and the body element and the at least one shell element form at least one channel across the groove. The at least one channel is adapted to conduct at least one biochemical medium and / or a working medium.

Description

Technical Field

[0001] The present invention relates to a tank system including a reservoir element for a tank, a tank assembly, a tank, a clean room bag, and a method of assembling the tank. The tank and / or the tank system can be used in a biopharmaceutical process. Further, for example, it can be adapted for the manufacture and / or development of biopharmaceuticals, and / or the development and / or testing of their commercial manufacturing processes.

[0002] Background Art For example, biopharmaceuticals as drugs for cancer treatment, gene therapy, and / or cell therapy are currently manufactured in so-called biopharmaceutical process lines.

[0003] Known biopharmaceutical process lines are, for example, stainless steel tanks interconnected by pipes and the like. These known biopharmaceutical process lines are difficult to maintain and clean. Therefore, so-called disposable biopharmaceutical process lines that are replaced after use have been developed. Here, disposable containers such as bags function as reservoirs for extracts and / or products of biopharmaceutical process lines. The bags are usually supported within a rigid container such as a stainless steel container and are interconnected by hoses. These known rigid containers are bulky and require a lot of storage space when not in use, leading to an increase in storage and transportation costs.

[0004] Setting up a conventional disposable biopharmaceutical process line requires complex manual assembly, leading to an increase in costs. For example, it is necessary to connect a plurality of bags, filters, sensors, valves, etc. via various hoses. Complex assembly involves a significant risk of malfunction of the biopharmaceutical process line due to improper or inaccurate assembly.

[0005] Furthermore, disposable biopharmaceutical process lines are susceptible to damage because the (hose-based) connections and / or bags of disposable containers tend to leak during operation. If a leak or malfunction occurs, the extracts and / or products throughout the entire biopharmaceutical process line may be damaged, or even destroyed. Therefore, there is a significant economic risk for the operator of the biopharmaceutical process line.

[0006] Furthermore, known disposable biopharmaceutical process lines typically contain different materials that come into contact with extracts and / or products, increasing the risk of contamination. This contamination can be caused by extracts, particularly leachates, that are present in the various materials of the biopharmaceutical process line from the outset. Additionally, cell proliferation and / or other biochemical process steps may be distorted. In particular, if fluids containing extracts and / or products are transported through the biopharmaceutical process line using pumps, there is a risk of particle generation due to abrasion.

[0007] Because disposable biopharmaceutical process lines are complexly constructed, automating their assembly and operation is extremely difficult and costly. Therefore, biopharmaceutical process lines, especially small ones, are often operated manually.

[0008] Furthermore, all components of a single-use biopharmaceutical process line are often not cleanable or recyclable, and are therefore typically discarded after use.

[0009] In consideration of the above, the object of the present invention is to provide reservoir elements for tanks, tanks and tank systems that can be used in biopharmaceutical process lines, as well as tank assemblies and methods for assembling tanks that overcome the above-mentioned drawbacks. Furthermore, the costs and time required for the development and manufacture of biopharmaceuticals will be reduced, thereby shortening the time to market. In particular, the tanks and / or tank systems need to be adapted to be operated automatically. Furthermore, the tanks and / or tank systems need to be adapted to be assembled automatically.

[0010] Summary of the Invention This objective is achieved by the reservoir elements, tanks, tank assemblies, tank systems, cleanroom bags, and methods for assembling tanks as described in the independent claims. Further embodiments are described in the dependent claims and the following description. The portion of the description not included in the claims is provided for a better understanding of the invention described in the claims.

[0011] In particular, this objective is achieved by a reservoir element for a tank in a biopharmaceutical process line, the reservoir element comprising a body element and at least one shell element. The body element has a first end and a second end opposite the first end, with each of the first and second ends containing an orifice, where the body element tapers from the first end to the second end. Furthermore, the internal volume is defined between the first and second ends.

[0012] The main body element and / or at least one shell element includes at least one groove, where at least one shell element is fixedly attached to the main body element, and the main body element and at least one shell form at least one channel across the groove. The at least one channel is adapted to guide at least one biochemical medium and / or working medium.

[0013] The main body elements can be manufactured by injection molding, injection blow molding, extrusion blow molding, or thermoforming. Therefore, the side walls of the internal volume are integrally formed, thereby increasing the airtightness of the reservoir element, and especially the tank containing the reservoir element. Furthermore, injection-molded or thermoformed elements can be manufactured efficiently, cost-effectively, and with high quality. Consequently, the cost of tanks and / or tank systems for biopharmaceutical process lines can be reduced compared to conventional biopharmaceutical process lines.

[0014] At least one shell element can be fixedly attached to one or more side walls of the main body element. For example, the shell element may be formed to cover all side walls of the main body element when attached. In another embodiment, the shell element may be formed to cover only one or some (at least two) side walls of the main body element when attached. The shell element can be attached to the inside or outside of the main body element.

[0015] In particular, at least one shell element can be welded to the body element, preferably by ultrasonic welding or other suitable welding techniques (laser welding, clear-to-clear welding, friction welding). In further embodiments, at least one shell element is bonded to the body element. For example, reactive or non-reactive adhesives such as hot-melt adhesives can be used. In addition, or instead, the shell element can be attached to the body element using mechanical fasteners such as screws, bolts, or rivets. A sealing member may be provided to seal the body element and the shell element. The sealing member may be a sealing gasket or a liquid seal.

[0016] The main body element and the shell element should be formed from a plastic material, preferably the same plastic material. For example, the main body element and the shell element may be formed from COC (cyclic olefin copolymer), COP (cyclic olefin polymer), PP (polypropylene), PC (polycarbonate), PET (polyethylene terephthalate), etc.

[0017] Grooves in at least one body element and / or at least one shell element may have any suitable cross-section (e.g., semicircular, triangular, quadrilateral, etc.). In particular, a first groove may be formed in the body element and a corresponding second groove may be formed in the shell element. Thus, when the shell element is attached to the body element, a channel is formed by the first and second grooves. For example, a channel having a circular cross-section can be formed by a semicircular first groove and a corresponding semicircular second groove.

[0018] Using grooves to form channels allows for the creation of complex channel shapes that cannot be formed by injection molding of a single component. For example, a heating channel or a cooling channel may include several curves within the sidewall of a reservoir element.

[0019] At least one channel can be selected from a group of different channel types, including channel types such as inlet channels, outlet channels, bypass channels, heating or cooling channels, and sampling channels.

[0020] The inlet channel serves to guide the biochemical medium and / or working medium into the internal volume (i.e., the reservoir of the assembled tank). The inlet channel may include a sparger or may be coupled to a sparger. The outlet channel serves to remove the biochemical medium and / or working medium from the internal volume (i.e., the reservoir of the assembled tank). If connected to a further (second) tank, the outlet channel of the first tank may be connected to the inlet channel of the second tank to transfer the medium from the reservoir of the first tank to the reservoir of the second tank.

[0021] Furthermore, channels may be provided, for example, for transferring and returning the retaining fluid from the filter or membrane to the internal volume of each tank. These channels may be separate retaining fluid channels, or they may be formed integrally with the outlet channels. To transfer and return the retaining fluid, the working fluid can be flowed through the filter or membrane in the opposite direction to the working direction. The working direction is the direction in which the medium flows during filtration. During filtration, the permeate passes through the membrane / filter, and the retaining fluid is held by the membrane / filter.

[0022] Further channels may be provided for transferring and returning the permeate and / or filtrate to the reservoir volume of each tank and / or another tank. Positive pressure may be applied to the permeate side or filtrate side of the filter, respectively, to transfer the permeate and / or filtrate. This can be achieved by introducing a working medium, such as pressurized (sterile) air, to the permeate side or filtrate side, respectively. The working medium can push the permeate toward the permeate channel and return the permeate / filtrate to the reservoir of the assembled tank and / or another tank. The direction of flow can be controlled by opening and closing the respective valves associated with each channel.

[0023] Further channels that may be provided to function for recirculating the medium within the assembled tank (recirculation channels). Wetting or flushing components of the assembled tank, especially with at least one filter (wetting channels, flushing fluid channels). For removing the product (product channels). For supplying the medium (supply channels). For removing / recirculating the permeate / filtrate (permeate or filtrate channels). For removing waste (waste channels). For cell harvesting (cell bleed channels). For supplying, removing, and / or transferring cells (cell channels). For pressurizing at least a portion of the assembled tank (pressure channels), and / or for loading different solutions into the assembled tank, especially cartridges for chromatography, i.e., washing, cleaning, and eluting (washing channels, cleaning channels, elution channels).

[0024] Bypass channels serve to guide biochemical and / or working media. In this configuration, the bypass channel is not connected to the internal volume of a reservoir element (to the reservoir of each assembled tank). Therefore, the medium can bypass the assembled tank without communicating with its reservoir. For example, if three tanks are connected such that the first and third tanks sandwich the second tank, the fluid may be guided from the reservoir of the first tank to the reservoir of the third tank, bypassing the reservoir of the second tank. In this case, the bypass channel may be located within the reservoir element of the second tank. Optionally, the bypass channel can be adapted to be fluidically separated or connected to the internal volume of the assembled tank or its respective reservoir. This can be achieved, for example, by a valve. Depending on the valve's position (open / closed), the bypass channel may or may not communicate with the tank's internal volume / reservoir. Thus, in a process line, the flow of the medium can be controlled by whether or not it bypasses the tank's reservoir.

[0025] For example, a bypass channel can be used to supply biochemical media, such as buffers, to be used in various tanks in a biopharmaceutical process line within a large storage tank. The biochemical media can then be transferred from the storage tank to all tanks that require the media (e.g., buffer). If a tank does not require the media, the media can bypass the tank's reservoir. Furthermore, by providing a valve in the bypass channel, the supply of the media (e.g., quantity or time) can be controlled. Additionally, the bypass channel can function to transfer biochemical media, such as cell culture media, from a first tank (e.g., a seed tank) to at least two subsequent tanks that can function as further bioreactors. Thus, biochemical media can be routed from a single tank to multiple subsequent tanks.

[0026] The heating or cooling channels function to conduct a temperature-controlled heating or cooling medium to thermally condition the assembled tank. Depending on the degree of heating / cooling, the medium received within the tank may evaporate or condense. Further, the reservoir element can comprise at least one longitudinal rib. The at least one longitudinal rib can project into the internal volume. The heating or cooling channel can be at least partially received within the at least one longitudinal rib. Thus, the heating or cooling efficiency can be enhanced.

[0027] The sampling channel functions to take samples of biochemical and / or operating media from the reservoir of the assembled tank. Thus, extracts, products, intermediates, or process lines can be removed for analysis.

[0028] In particular, the reservoir element can comprise a plurality of channels formed by respective grooves formed in the body element and / or at least one shell element. These channels can be adapted to conduct different biochemical and / or operating media when the reservoir element is assembled within the tank and the tank is in use. By providing respective reservoir elements, the function of the assembled tank can be adapted to the specific needs of respective process lines.

[0029] In particular, the assembled tank can be a multi-functional tank comprising a plurality of channels of different channel types and / or the same channel type. At least one channel can be opened and closed, for example, using valves, closures, etc. Thus, depending on the required function, one or more channels can be closed. These closed channels are not used. At least one other channel or a plurality of other channels can be opened and used, thereby defining the function of the multi-functional tank.

[0030] At least one of the plurality of channels may communicate with the internal volume (i.e., a part of the reservoir of the assembled tank) and / or may bypass the internal volume. Further, the reservoir element may include additional channels formed within a tube, such as a rigid tube, that can be inserted into the internal volume through an opening of the body element and / or the plate element. The tube may be received in a sealed manner within each of the respective openings. The additional channels may be configured to guide at least one biochemical medium and / or operating medium from outside the assembled tank into the reservoir of the tank.

[0031] The channels may have an equivalent diameter in the range of 0.1 to 3 inches (0.25 to 7.6 cm), preferably in the range of 0.2 to 2 inches (0.5 to 5.1 cm), more preferably in the range of 0.3 to 1.5 inches (0.75 to 3.8 cm), even more preferably in the range of 0.5 to 1 inch (1.2 to 2.5 cm), and most preferably about 0.75 inches (1.9 cm). Further, different channels may have different diameters and / or the diameter of the channels may vary. Thus, for example, nozzles may be provided. The equivalent diameter of a channel having a non-circular cross-section is equal to the diameter of a channel having a circular cross-section. In that case, both channels (non-circular and circular) have the same cross-sectional area. Thus, in the case of a channel with a circular cross-section, the diameter and the equivalent diameter are the same.

[0032] Furthermore, the body element may have a polygonal cross-section in a plane parallel to the first end. There, at least one shell element may be plate-like. The polygonal cross-section can provide a substantially flat side wall. The substantially flat side wall facilitates attaching the shell element to each side wall of the body element. Alternatively, the shell element may have a polygonal cross-section. In yet another alternative, the shell element may be formed to cover only a part of the body element, for example, at least two side walls, when attached.

[0033] The internal volume and the first orifice are configured to accommodate the reservoir element at least partially with respect to additional reservoir elements. As a result, multiple reservoir elements can be stacked on top of each other. Therefore, the reservoir elements require little storage space and can be easily transported and stored. Consequently, costs can be further reduced.

[0034] Furthermore, the reservoir element may include a plate element. The plate element is sealed and attached to the first or second end of the main element, covering the respective orifice. The plate element may include at least one channel, in which at least one channel communicates with a channel formed by the main element and at least one shell element.

[0035] The plate elements may be sealed and attached to the first or second end of the main body element by, for example, welding, preferably ultrasonic welding, or other suitable welding techniques (e.g., laser welding, clear-to-clear welding, friction welding). In a further embodiment, at least one shell element is bonded to the main body element. For example, reactive or non-reactive adhesives such as hot melt adhesives can be used. In addition, or instead, the plate elements may be attached to the main body element using mechanical fasteners such as screws, bolts, or rivets. Further sealing members may be provided to seal the main body element and the plate elements. The sealing members may be sealing gaskets or liquid seals. The plate elements may be integrally formed parts or may be formed from multiple layers. For example, the plate element may have a two-layer structure, where the first layer and / or second layer include at least one groove, where the first layer is fixedly attached to the second layer, and the first and second layers sandwich the groove, forming at least one channel, where at least one channel is adapted to guide at least one biochemical medium and / or working medium. Furthermore, the channel may be in fluid communication with a channel formed between the main element and at least one shell element.

[0036] The reservoir element may also include at least one insert adapted to at least partially cover any undercuts in the internal volume. The insert may be formed integrally with the body element and / or plate element, or it may be a separate part. The insert allows for covering of the undercuts in the internal volume. As a result, dead space within the internal volume can be prevented or at least reduced. Furthermore, the insert can enhance the mechanical stability of the reservoir element.

[0037] In an alternative embodiment, the reservoir element may be formed using 3D printing technology. For example, the body element and at least one shell element can be formed integrally. In this embodiment, grooves / channels may be formed integrally within the walls of the reservoir element. Furthermore, plate elements and / or inserts may be formed using 3D printing technology. Thus, the entire reservoir element can be formed integrally.

[0038] The first and / or second ends of the reservoir element may include a sealing surface for sealing and connecting the reservoir element to another reservoir element. In particular, the sealing surface may include at least one sealing member for providing a sealed connection between adjacent reservoir elements. The sealing member may be circumferentially arranged around the orifice of the first and / or second end. When the reservoir elements are assembled to form the reservoir of the tank, the sealing member may be compressed.

[0039] Furthermore, a reservoir element, particularly a plate element, can contain at least one port, where at least one port is associated with each channel. The port is selected from a group of port types, including the following: 〇 Fluid inlet port 〇Gas inlet port 〇 Fluid outlet port 〇 Heating / cooling ports 〇Gas outlet port Cell bleed port ○ Cell transfer port Media supply port 〇 Media removal port Element interconnection ports 〇 Tank interconnection ports

[0040] Inlet ports (for fluids or gases) function to supply biochemical media and / or working media to the internal volume. In the assembled state, the internal volume can form part of the reservoir of the tank in a biopharmaceutical process line. Heating / cooling ports function to supply temperature-controlled heating / cooling fluid to the heating / cooling channels. Outlet ports (for fluids or gases) function to remove biochemical media and / or working media from the internal volume of the tank or their respective reservoirs. Medium supply ports allow the medium (biochemical media and / or working media) to be supplied to the internal volume / tank. Medium removal ports allow the medium (or part thereof) to be removed from the internal volume / tank. Medium removal ports may also function, for example, to transfer and return retaining fluid from a filter or membrane to the internal volume / tank. Tank interconnection ports function to fluidically couple the channels of the reservoir element of the first tank to the corresponding channels of the reservoir element of the second tank when the first tank is connected to the second tank. This is done, for example, by using connector devices, as will be described in more detail below. The tanks may be connected side-by-side (the first and second tanks adjacent to each other), or the first tank may be placed above the second tank. Tank interconnection ports may function as medium supply ports and / or medium removal ports. Cell bleed ports function to remove cells from the tank's internal volume / reservoir. The cells may be discarded or transferred to further tanks or other devices for further processing.

[0041] At least one port may be associated with a valve that can preferably be controlled by a handling manipulator (or multiple handling manipulators). Thus, the flow of the medium from the tank and the flow of the medium to the tank can be controlled by opening and closing the valve. In particular, the valve may be a flow control valve that can adjust the flow in stages.

[0042] For example, a channel can be associated with tank interconnection ports and fluid outlet ports. Thus, the channel can function to transfer a medium, such as a fluid, from the internal volume / reservoir of one tank to another. If a valve is installed at the tank interconnection port, the flow of the medium being transferred can be controlled. Alternatively, or in addition, the flow may be controlled by controlling the pressure (positive and / or negative pressure) within the associated tank.

[0043] At least one port may include a protruding shroud that at least partially surrounds the associated channel. The shroud may be arranged concentrically around the channel end of the associated channel. Furthermore, at least one port may include a recess that at least partially surrounds the associated channel. The recess may be arranged concentrically around the channel end of the associated channel. The port may be adapted to be coupled to a hose or pipe element to fluidly connect the reservoir element and / or tank to further surrounding objects. For example, a tank with the reservoir element may be integrated into a conventional biopharmaceutical process line. To connect the channel / tank, the port may include a snap-fit ​​connector adapted to engage with a corresponding snap-fit ​​connector. This snap-fit ​​connection can provide a releaseable and secure connection.

[0044] Furthermore, ports (e.g., tank interconnection ports or element interconnection ports) can be adapted to engage with corresponding ports (e.g., corresponding tank interconnection ports or element interconnection ports) where the ports and corresponding ports are formed to provide a positive lock. For example, a reservoir element may have a port on a first side and a corresponding port on a second side, where the first and second sides may be opposing outer surfaces of the reservoir element. A tank containing such a reservoir element can be coupled to further tanks using the ports and corresponding ports, and the respective channels can be fluidly connected when the tanks are coupled. Thus, a medium can be transferred from a first tank to a second tank without using intermediate conduit elements such as pipes or hoses. This makes it easier to assemble tank systems, for example, in a biopharmaceutical process line, and reduces the likelihood of assembly errors.

[0045] Furthermore, the first reservoir element of the tank may be provided with a port, and the second reservoir element of the tank may be provided with a corresponding port. This allows the reservoir elements to be joined together to form the reservoir of the tank. This allows the channels of each reservoir element to be fluidly connected when assembling the tank. Thus, the medium can be guided through the channels formed in at least two reservoir elements of the tank. This makes the assembly of the tank easier and reduces the likelihood of assembly errors.

[0046] The port may include a sealing member (e.g., a flexible sealing member such as a rubber seal, silicone seal, or Teflon seal). The sealing member may be a radial and / or axial seal. For example, the sealing member may be provided on the shroud and / or within a recess of the port. The sealing member may be provided as a sealing gasket that enables sealing of multiple ports of the reservoir element. Furthermore, the sealing member may be port-specific and adapted to seal only a single port.

[0047] Reservoir elements may also be provided with multiple tank interconnection ports to offer an interconnection interface that allows for easy coupling of tanks to other tanks. Furthermore, each reservoir element of a tank may be provided with multiple element interconnection ports to offer an interconnection interface that allows for easy coupling of different reservoir elements of a tank to assemble a tank.

[0048] Furthermore, at least one of the aforementioned ports associated with each channel may be equipped with a sterile quick connector. This allows tanks to be aseptically connected to each other in different environments. For example, when tanks are delivered in a sterile condition and assembled, for example, at the customer's site of use, the tanks can be connected using the sterile quick connector.

[0049] Furthermore, a reservoir element, particularly a plate element, may contain at least one filter. There, at least one port may be covered by at least one filter. There, the filter may be selected from a group of filter types, including the following filter types: 〇 Pre-filter 〇 Sterile filter 〇 Bacteria filter Virus filter Mycoplasma filter Ultrafiltration filter ○ Diafiltration filter Cell filter Cell Harvest Filter Fluid filter Bioburden filter ○ Air filter, and 〇 Gas filter

[0050] The filter can be placed within the internal volume of the reservoir element. Therefore, when assembled into a tank, the filter can be placed within the tank's reservoir. Thus, each tank can function as a filtration unit for filtering the medium received in the tank's reservoir. The air filter may be a syringe filter. The filter may be a liquid filter. The liquid filter can function as a buffer solution for flushing.

[0051] Furthermore, the filter may be integrated with the reservoir elements, particularly the shell or plate elements of each reservoir element. For example, the reservoir elements (e.g., the upper plate or side wall elements of a tank) may be formed integrally with the filter housing.

[0052] Furthermore, at least one port of the reservoir element may be covered by a filter. Providing a filter-covered port allows for retaining a portion of the medium within the assembled tank and / or preventing other portions of the medium from entering the tank. If the inlet port is covered by a filter, only the filtrate can enter the internal volume of the reservoir element of each tank. If the outlet port is covered, only the filtrate can exit the internal volume of the reservoir element of each tank. For example, the gas inlet port may be covered by a sterile filter. Thus, sterile pressurized air can be introduced into the internal volume of the reservoir element of each tank. Thus, for example, the medium contained in the reservoir of a tank can be blown out of the reservoir for transfer to another tank.

[0053] Furthermore, the filter covering at least one port may be heated and / or cooled. Thus, the medium entering and leaving the reservoir element (each tank) can be controlled to a desired temperature. Additionally, heating the filter allows for high-temperature filtration, while cooling the filter allows for low-temperature filtration. Heating the filter can prevent undesirable condensation.

[0054] Furthermore, the reservoir element, particularly the plate element, may include at least one valve. At least one valve is associated with at least one channel, where the valve may be a flow control valve, a cutoff valve, a pressure relief valve, or a check valve, etc. Furthermore, the reservoir element may comprise multiple valves of the same and / or different types. In particular, valves can be provided at the junctions of at least two channels formed within the reservoir element. Thus, depending on the position of the valve, the medium can be directed to different channels and / or ports. Therefore, the fluid flow rate can be controlled.

[0055] Flow control valves allow control of the amount of fluid flowing through a channel per unit time (e.g., a flow rate of liters / second). Flow control valves may be configured to dynamically control the flow rate and thus control the biochemical processes within the tank containing the reservoir element. Cutoff valves allow channels to be opened and closed. Bypass channels may be provided with cutoff valves. Thus, bypass channels may be fluidically isolated from the tank's internal volume or their respective reservoirs (valves closed), or they may be in communication with the internal volume / tank's reservoirs (valves open). Furthermore, cutoff valves allow channels not used within the tank to be closed and channels that are used to be opened, depending on the function of the tank.

[0056] A check valve may be provided in the channel to prevent the medium being removed from the internal volume / tank from flowing back into the internal volume / tank. Thus, for example, contamination of the internal volume / tank can be prevented. Furthermore, the check valve can prevent the medium that has entered the internal volume / tank from flowing back into it. Thus, the tank can be pressurized (e.g., by pressurized air), and the medium contained in the tank's reservoir can be guided in a desired direction, for example, for filtration purposes. By using a pressurized tank, the medium can be guided without using a pump. Thus, contamination of the medium and the generation of particles (e.g., by abrasion) can be effectively reduced, and even prevented. Furthermore, the cost of tanks and / or tank systems in biopharmaceutical process lines is reduced because (expensive) pumps such as disposable pumps and pump heads are not required. Furthermore, by avoiding pumps, cleaning, maintenance, and / or sterilization of the tank are made easier.

[0057] At least one valve can have any suitable configuration. For example, at least one valve could be a ball valve, butterfly valve, diaphragm valve, gate valve, needle valve, pinch valve, etc.

[0058] At least one valve may be configured to be operated manually and / or automatically. For example, a valve may be configured to be operated mechanically, pneumatically, hydraulically, magnetically, electrically, etc. Furthermore, at least one valve may be configured to be operated from outside the tank by an actuator. In particular, the valve may be a mechanical valve configured to be operable from outside the tank by an actuator. The actuator may be an actuator rod connecting a valve closing member that contacts the medium to the outside of the tank. The actuator rod may be supported and sealed within at least one reservoir element forming the tank. Furthermore, the actuator rod may include several sections, where each section of the actuator rod is supported within its respective reservoir element. When assembling a tank from multiple reservoir elements, sections of the actuator rod can be joined so that a valve in a first reservoir element can be operated by first acting the actuator rod of another (e.g., a second) reservoir element.

[0059] To open and close a valve, the actuation mechanism can be rotated or axially displaced, depending on the type of valve involved. Furthermore, the actuation device may include a magnet (permanent magnet or electromagnet) adapted to open and close the valve. The magnet allows each magnetic valve to be actuated from outside the tank. By providing a magnetic actuation device, the valve closing member and the actuation device can be separated from each other, for example, by a continuous wall section, thus facilitating valve sealing.

[0060] In certain embodiments, the valve is initially closed and can be opened by axially displacing the valve body. This can be done, for example, using an actuation rod or magnetic force. In the closed initial state, the valve may be preloaded by a spring member or magnetic member. Therefore, when not in operation, the valve may remain closed. The valve opens only when operated (for example, manually or via a handling manipulator).

[0061] Furthermore, the valve may be equipped with a switching mechanism equivalent to that of a ballpoint pen. Thus, the valve can be opened and closed by axially displacing the valve's actuator. This allows for the performance of specific photometric measurements. Moreover, a stable switching state can be established. The axial displacement can be achieved by a handling manipulator. In particular, the valve equipped with the switching mechanism can be operated via a cleanroom bag, as described herein.

[0062] The actuator can be adapted to be coupled with an actuator mechanism, which may be part of a handling manipulator that enables automatic control of the actuator, tank, and / or tank system.

[0063] In particular, when using mechanical and / or magnetic valves, it is possible to avoid integrating the components of electric valves into the tank. Therefore, tank recycling is promoted and improved.

[0064] The valves, valve bodies, and / or actuators may be initially integrated with each reservoir element of the tank, or they may be adapted to be integrated with each reservoir element of the tank after or during the tank assembly. This facilitates the assembly of tanks and / or tank systems in biopharmaceutical process lines. This means that, as in conventional biopharmaceutical process lines, the valves are typically supplied as separate (disposable) components that need to be manually connected to other parts of the process line, such as bags.

[0065] Furthermore, the internal volume and / or the inner surface of at least one channel can be coated. In addition, at least the valve, port, and / or filter components of the reservoir element that may come into contact with the biochemical medium and / or working medium can be coated. The coating may be a silicon dioxide coating, a glass-based coating, etc. The coating reduces the number of different contact materials that come into contact with the biochemical medium and / or working medium. Thus, the risk of contamination of the biochemical and / or working medium, and / or the risk of strain on cell proliferation and / or other biochemical process steps can be reduced.

[0066] Furthermore, the coating can form a gas barrier and / or provide internal volume and / or an inert inner surface of at least one channel. The coating may be heat resistant so that the reservoir element and each tank can be heated and / or cooled. In addition, the reservoir element forming the tank can be formed from the same (partially coated) material, thus facilitating the recycling of the reservoir element. The coating can be applied, for example, during injection molding and / or thermoforming, during or after the manufacture of the reservoir element.

[0067] The reservoir element may further comprise at least one assembly connector and / or at least one corresponding assembly connector, where the assembly connector and the corresponding assembly connector are configured to engage with each other to secure an assembly of at least two adjacent reservoir elements. These assembly connectors may be configured to automatically engage with the corresponding connector, for example, using an assembly manipulator.

[0068] For example, the assembly connector may be a threaded member integrated with the reservoir element. The threaded member may have a female or male thread and may be formed integrally with the reservoir element. Optionally, or in addition, the threaded member may be an inlay, such as a metal inlay, which is securely held within the reservoir element. The inlay may be, for example, overmolded or bonded to the reservoir element. The corresponding assembly connector may have a trough opening that can align with a threaded member having a female thread. Thus, the reservoir element can be connected and engaged by screwing a screw through the opening into the threaded member. Furthermore, the corresponding assembly connector may have a trough opening that receives a threaded member having a male thread. Thus, the reservoir element can be connected and engaged by screwing a nut or the like into the threaded member, thereby engaging the reservoir element.

[0069] Furthermore, the assembly connector may be a protrusion such as a bolt. The protrusion may be formed integrally with the reservoir element or may be an inlay. The inlay may be, for example, overmolded or bonded to the reservoir element. The corresponding assembly connector may be a corresponding recess. The recess may be formed integrally with the reservoir element or may be an inlay such as a sleeve. The inlay may be, for example, overmolded or bonded to the reservoir element. During assembly, the assembly connector engages with the corresponding assembly connector to provide a positive lock. The engagement between the assembly connector and the corresponding assembly connector may be a self-retaining engagement. A self-retaining engagement can be achieved by a retaining force provided by a flexible member that may be provided between the engaged reservoir elements (e.g., an upper plate element and a side wall element, two side wall elements, and / or a lower plate element and a side wall element). During assembly, the flexible member is compressed, thereby providing the retaining force. In particular, the flexible member may be a sealing member that seals the reservoir formed by the reservoir elements.

[0070] Furthermore, the assembly connector may include a latching member such as a hook. There, the corresponding assembly connector may include a recess formed for engaging with the hook. This objective is further achieved by a tank assembly adapted to be assembled to a tank, where the tank assembly comprises at least two reservoir elements as described above. Furthermore, the tank assembly may include two reservoir elements having plate elements sealed and attached to the first or second end of a body element, and at least one, preferably at least two, further reservoir elements that do not have such plate elements.

[0071] The first end of each reservoir element in a tank assembly may be of the same size and shape, and the second end of each reservoir element in a tank assembly may also be of the same size and shape. It should be understood that if the body element of the reservoir element tapers from the first end to the second end, the first and second ends may differ in size and / or shape.

[0072] In particular, reservoir elements can have different heights (distance between the first and second ends). Therefore, by combining reservoir elements of different heights, tanks of different volumes can be assembled. Furthermore, different volumes can be achieved by assembling multiple reservoir elements.

[0073] The tank assembly is adapted to be assembled into a tank as described below, and since it includes the reservoir elements mentioned above, all the advantages described regarding the tank and reservoir elements can be achieved by the tank assembly, at least when assembled. Furthermore, the tank assembly allows the disassembled tank to be transported and stored with minimal space requirements.

[0074] This objective is further achieved by tanks for biopharmaceutical process lines. The tank comprises an upper plate element, optionally at least one side wall element, and a bottom plate element. The optional at least one side wall element is a reservoir element without a plate element, and the upper plate element and bottom plate element are reservoir elements having plate elements that are sealed and attached to the first or second end of the respective body element.

[0075] The upper plate element, an optional at least one sidewall element, and a bottom plate element are arranged to form a reservoir for receiving at least one biochemical medium. The tank further comprises at least one channel for guiding at least one biochemical medium and / or working medium, where at least one channel extends into the interior of at least one upper plate element, at least one sidewall element, and / or bottom plate element. The length of at least one channel is longer than the thickness of each of the upper plate element, sidewall element, and / or bottom plate element.

[0076] Generally, all channels and / or reservoirs in a tank can be configured to automatically empty. That is, any medium that enters a channel and / or reservoir can be drained out of that channel and / or reservoir by gravity.

[0077] The assembled tank may comprise one reservoir or multiple (at least two) reservoirs, formed by an upper plate element, at least one side wall element, and a bottom plate element. In the case of multiple reservoirs, the reservoirs may be arranged in series or in parallel. A medium flowing through series reservoirs flows through a single reservoir successively. A medium flowing through parallel reservoirs flows through a single reservoir in parallel. Combinations of series and parallel arrangements of reservoirs are also possible.

[0078] The tank (and corresponding reservoir element) is adapted for use in biopharmaceutical process lines, in the manufacture and / or development of biopharmaceuticals, and / or in the development and / or testing of commercial manufacturing processes for these products. Furthermore, the tank may be used in other manufacturing lines and may be adapted for automatic and / or manual operation.

[0079] The biochemical medium and / or working medium may be any extract or product of a process line, such as a sample-containing medium, cell-containing medium, drug-containing medium, buffer medium, acid, base, etc. The medium may include at least one of the following: small molecule APIs, antibodies, drug conjugates, RNA or its fragments, rec proteins, viral vaccines, bacterial / microbial processes, virus-like particles, viral vectors, ADCs, DNA, etc. Furthermore, the working medium may include a heating or cooling fluid, pressurized air, or gas, etc. For example, when pressurized air is used as the working medium, the working medium may function to drive the biochemical medium through a channel into (or out of) the reservoir of the tank.

[0080] Biochemical media and / or working media may be supplied in liquid and / or gaseous form, as well as in solution and / or emulsion and / or suspension form.

[0081] In particular, a working medium such as pressurized air can be used to transfer a biochemical medium to and / or from a tank. Thus, the tank is operable via the working medium. When transferring a biochemical medium from a tank, a positive pressure can be applied to the first tank by applying the working medium to the tank. Thus, for example, the biochemical medium is pushed out of the tank toward a second tank and / or filter. To transfer a biochemical medium to a tank, a negative pressure can be established, for example, by removing (operating) the medium from the tank. When pressurized air is used as the working medium, sterile pressurized air is preferably used. Sterile pressurized air can be obtained by directing pressurized air to each sterile filter before it enters the tank. The working medium, such as pressurized air, can be supplied to or removed from the tank through its respective gas inlet and / or outlet ports.

[0082] The terms top plate element, side wall element, and bottom plate element do not specify the orientation of the tank during assembly or use. Rather, an assembled tank can be used in any orientation. Typically, the bottom plate element functions as a base and can optionally be provided on a stand to adjust the tank's height during use / operation. For example, the tank can be oriented upright (i.e., top plate element on top), lying down (i.e., side wall element on top), or upside down (bottom plate element on top).

[0083] Furthermore, the upper plate element functions to support the tank and can be adapted to be supported within a support rail, as will be described in more detail below. In this case, the tank is in a suspended configuration, and the bottom plate element may not be in contact with the ground. In addition to the suspension support of the upper plate element, a support member can be provided to support the tank with the bottom plate element. The support member can be adapted to be height-adjustable by a linear drive, such as a magnetic drive, electric drive, pneumatic drive, and / or hydraulic drive. The support member may include a weighing member that allows the weight of the supported tank to be measured. The weight of each tank can be used to control the process line.

[0084] By providing reservoir elements such as a top plate element, optionally at least one side wall element, and a bottom plate element, which are assembled into a tank and arranged to form a reservoir for receiving at least one biochemical medium, cleaning and maintenance of the tank after use are facilitated. Thus, each reservoir element or at least a portion of the reservoir elements can be reused and / or recycled separately. Furthermore, the tank (each element forming the reservoir) can be easily cleaned and sterilized before use.

[0085] At least one channel extends into at least one of the top plate element, at least one sidewall element, and bottom plate element. Different reservoir elements or different channels in the same reservoir element may be provided so that each reservoir element (top plate element, optional at least one sidewall element, and / or bottom plate element) may have at least one (or more) channels.

[0086] Optionally, the transfer of the medium to and / or from the tank's reservoir can be achieved solely by at least one or more channels extending within the upper plate element, at least one sidewall element, and / or the bottom plate element. Thus, at least one channel in contact with the medium and the reservoir surface may be made of the same material. In this way, the risk of contamination of extracts and / or products (i.e., biochemical mediums and / or working media) in the biopharmaceutical process line can be reduced by undesirable combinations of different materials, and cell proliferation and / or other biochemical process steps will not be distorted.

[0087] By using channels to transfer the medium, high lot-to-lot consistency in a product line can be achieved. This is because, for example, with conventional fluid connections using hoses (e.g., as conventional disposable lines), there is variation in contact materials from lot to lot. This leads to undesirable and unexpected contamination of the transferred fluid. By using channels in tank elements to transfer the medium, the number of different contact materials can be minimized, thereby increasing lot-to-lot consistency in a product line.

[0088] At least one channel may extend within at least one sidewall element, top plate element, and bottom plate element. In another example, at least one channel may extend within the top plate element and at least one sidewall element. At least one additional channel may extend within at least one sidewall element, top plate element, and / or bottom plate element.

[0089] The biochemical medium can be removed from the bottom of the tank through at least one channel (or additional channels, each) (e.g., through the first end of a channel provided in the bottom plate element or a side wall element adjacent to the bottom plate element). It can then be guided to the top of the tank for transfer to another tank (e.g., through the second end of a channel provided in the top plate element or a side wall element adjacent to the top plate element). Accordingly, the biochemical medium can be removed from the top of the tank (e.g., through the first end of a channel provided in the top plate element or a side wall element adjacent to the top plate element). It can then be guided to the bottom of the tank for transfer to another tank (e.g., through the second end of a channel provided in the bottom plate element or a side wall element adjacent to the bottom plate element). Furthermore, a working medium, such as a heating medium or a cooling medium, may be guided into at least one side wall element and at least one top plate element and bottom plate element to provide proper cooling / heating of the assembled tank. The heating or cooling medium can be introduced into the upper plate element, at least one side wall element, and / or the bottom plate element without contact with the reservoir. Thus, the heating or cooling medium and the biochemical medium are separated from each other.

[0090] Generally, a tank functions as a reservoir for extracts or products of a process line, such as biochemical media and / or working media. Thus, the accepted media can be stored and / or transported. Furthermore, the tank may be configured to mix different media accepted within the tank's reservoir. Additionally, the tank can function as a bioreactor, supporting a biologically active environment. For example, a chemical process involving an organism or a biochemically active substance derived from such an organism can be carried out within the tank. Furthermore, the tank may be designed to grow cells or tissues in cell culture. The tank can be used as a batch bioreactor, a fed-batch bioreactor, a concentrated fed-batch bioreactor, or a continuous bioreactor, and / or a perfusion bioreactor. In addition, or optionally, the tank can function as a filtration unit for filtering the media accepted within the tank's reservoir. In this case, the filter may be located in or on the upper plate element, at least one sidewall element, and / or the bottom plate element. Furthermore, the tank can function for preparing biochemical media such as buffer media and / or for performing preparative chromatography. Furthermore, the tank may be equipped with cross-flow cassettes and / or hollow fiber modules for virus filtration, cell harvesting and / or ultrafiltration or dialysis filtration.

[0091] The tank reservoirs may have volumes of at least approximately 10 ml, at least approximately 15 ml, at least approximately 20 ml, at least approximately 50 ml, at least approximately 100 ml, at least approximately 200 ml, at least approximately 250 ml, at least approximately 500 ml, at least approximately 1 liter, at least approximately 2 liters, at least approximately 5 liters, at least approximately 10 liters, at least approximately 20 liters, at least approximately 50 liters, at least approximately 100 liters, at least approximately 200 liters, at least approximately 500 liters, at least approximately 1000 liters, at least approximately 2000 liters, at least approximately 3000 liters, at least approximately 4000 liters, or at least approximately 5000 liters. Thus, the biopharmaceutical process line can be expanded. For example, smaller capacity tanks are used during development. Larger tanks are used during subsequent manufacturing. Furthermore, tank systems in biopharmaceutical process lines can combine tanks of different volumes.

[0092] Tanks of different volumes can be achieved by assembling reservoir elements with different heights (distance between the first and second ends) and / or by assembling multiple reservoir elements. If all first ends of each reservoir element in the tank assembly are the same size and shape, and the second ends of each reservoir element in the tank assembly are particularly the same size and shape, then tanks of different volumes can be assembled by arbitrarily combining reservoir elements. Therefore, many different tanks can be assembled based on a small number of different reservoir elements.

[0093] In this embodiment, the upper plate element and the bottom plate element can be substantially the same as reservoir elements, and tanks with different volumes can be provided and used as reservoir elements of different heights or as side wall elements of multiple reservoir elements.

[0094] For example, the reservoir element may have a width in the range of 80 mm to 1500 mm, preferably in the range of 200 mm to 1200 mm, more preferably in the range of 300 mm to 1000 mm, and most preferably in the range of 450 mm to 600 mm. Furthermore, the reservoir element may have a height in the range of 150 mm to 2000 mm, preferably in the range of 200 mm to 1300 mm, more preferably in the range of 500 mm to 1000 mm, and most preferably in the range of 450 mm to 650 mm.

[0095] A tank may have height, depth, and width dimensions. The height:depth:width ratio may be approximately 2:1:1. If the tank is to be used as a bioreactor, this ratio should be preferred. Other dimensions may also be selected depending on the desired function of the tank.

[0096] The tank may be equipped with heating or cooling fingers that can be inserted into the tank through an upper plate element, at least one side wall element, and / or a bottom plate element. The heating or cooling fingers serve to guide a temperature-controlled heating or cooling medium to temperature the tank, where the heating or cooling medium guided by the heating or cooling fingers is separated from the contents of the reservoir. Depending on the degree of heating / cooling, the medium received into the tank may evaporate or condense.

[0097] Furthermore, the tank may be provided with at least one port, which can be located on at least one of the reservoir elements. There, at least one port can be associated with each channel. The ports can be selected from a group of port types, including the following: as mentioned above with respect to the reservoir elements, fluid inlet ports, gas inlet ports, fluid outlet ports, gas outlet ports, cell bleed ports, tank interconnection ports, element interconnection ports, medium supply ports, medium removal ports, etc.

[0098] A tank may be equipped with at least one filter. The filter may be provided in at least one of the reservoir elements. There, at least one filter can be selected from a group of filter types, including the following: pre-filter, sterile filter, bacterial filter, viral filter, mycoplasma filter, ultrafiltration filter, diafiltration filter, cell filter, cell harvest filter, liquid filter, air filter, gas filter, etc.

[0099] The tank may be equipped with at least one valve. The valve may be located in at least one of the reservoir elements. The at least one valve may be associated with at least one channel. The at least one valve may be a flow control valve, a cutoff valve, a pressure relief valve, or a check valve, etc. Furthermore, the tank may be equipped with multiple valves of the same and / or different types. In particular, valves may be located at the junctions of at least two channel sections. Thus, depending on the location of the valves, the medium can be directed to different channels and / or tanks, as described above with respect to the reservoir elements.

[0100] The tank may further include an adapter plate element, which is attached to the upper plate element. The adapter plate element may be configured to at least partially cover the filter and / or the tank's ports. In certain embodiments, the upper plate element of the tank and the associated adapter plate element may form a filter housing. Furthermore, the adapter plate element may be configured to support a valve actuator.

[0101] The adapter plate elements and upper plate elements can sandwich a barrier element, where the barrier element is part of the cleanroom. The cleanroom could be, for example, a cleanroom bag or a tent. In this case, the adapter plate elements may be located outside the cleanroom, while the upper plate elements of the assembled tank may be located inside the cleanroom.

[0102] Furthermore, the adapter plate element may provide access to at least one port of the tank, at least one filter of the tank, and / or at least one actuator of a valve of the tank. If a barrier element is sandwiched between the adapter plate element and the upper plate element, the upper plate element, as well as at least one side wall element and bottom plate element of the tank, can be kept within the cleanroom. There, access to the tank from outside the cleanroom is possible via the access provided by the adapter plate element. Thus, biochemical media and / or working media can be supplied to and / or removed from the tank from outside the cleanroom. Furthermore, at least one valve can be operated and controlled from outside the cleanroom.

[0103] The tank may further comprise at least one connector device for interconnecting one tank (the first tank) with another (the second) tank. The connector device may be included in at least one of the reservoir elements forming the tank. The connector device enables rapid setup of a tank system comprising multiple tanks, as the tanks can be interconnected by the connector device. This thus facilitates and / or accelerates the assembly of a biopharmaceutical process line. In addition, it reduces the risk of malfunction or leakage due to improper assembly. In particular, the connector device can be adapted for automated interconnection. As a result, the tank system of the biopharmaceutical process line can be automated, thereby further reducing the risk of improper assembly.

[0104] The connector device may be a screw-type connector device such as screws and their respective nuts and / or belts or straps that interconnect the first and second tanks.

[0105] The connector device may be a latch connector device. In this configuration, the tank is provided with a first latch connector device for directly interconnecting a tank with a further tank having a corresponding latch connector device. The first latch connector device may be a latch arm including a latch projection. The latch projection may be adapted to latch with a corresponding latch connector device, which may be formed as a latch recess.

[0106] Tanks, particularly each reservoir element of a tank, may optionally or additionally include a second latching connector device configured to latch with a mutual latching connector device. This mutual latching connector device is adapted to latch with a second latching connector device of a further tank. As a result, the tanks can be directly interconnected with the further tanks via the mutual latching connector devices. The second latching connector device may include protrusions, such as knobs, adapted to latch with a mutual latching connector device having corresponding recesses to provide a positive lock. The mutual latching connector device may be a flexible mutual latching connector device that, when latched with the second latching connector device of a tank, applies tension, thereby pressing the first tank against the second tank.

[0107] The connector device can provide a fluid connection between a first tank and a second tank. For example, the connector device can be designed and shaped so that, when latched, the tank interconnection ports of the first and second tanks engage with each other, and their respective channels align (seal) to allow fluid communication. Thus, the assembly of tank systems in biopharmaceutical process lines can be facilitated and accelerated.

[0108] Connector devices, particularly latching connector devices, can be provided on the upper plate element, at least one side wall element, and / or the bottom plate element. Furthermore, connector devices may be provided in recesses of the upper plate element, at least one side wall element, and / or the bottom plate element to prevent damage to the connector devices during transport and / or storage.

[0109] In particular, the connector device can be configured to operate automatically and / or without the use of tools. The connector device can provide permanent or detachable interconnections of tanks.

[0110] At least one connector device of the tank may be configured as a bottom drain pipe. The bottom drain pipe can provide a fluid connection between the first tank and the second tank and may be located in the lower half of the first tank, particularly in the bottom plate element. The bottom drain pipe may be configured to allow the first tank to empty automatically and / or by applying pressure.

[0111] Either the reservoir element or / or the tank may be sterilizable before, during, or after assembly by autoclaving, ETO gas, X-rays, and / or gamma irradiation. Sterilization is facilitated because the tank can be assembled from the reservoir element (top plate element, optional at least one side wall element, and / or bottom plate element). If sterilization is required after the tank is assembled, ports can be used to allow ETO gas or vapor to enter or leave the tank. In general, either the reservoir element or / or the tank may be sterilizable by any gas that enables sterilization.

[0112] Furthermore, the tank may be equipped with assembly reinforcement devices to strengthen the assembly of the tank's reservoir elements (e.g., the top plate element, at least one side wall element, and / or the bottom plate element). The assembly reinforcement devices may include threaded devices such as threaded rods, straps, and / or belts. For example, at least two reservoir elements may be equipped with through openings for receiving threaded rods. These reservoir elements can then be assembled by using at least one threaded component, such as a nut, which threads into the threaded rod. Furthermore, at least one strap or belt may be wrapped around the tank to reinforce the assembly of the reservoir elements. In addition, the assembly reinforcement devices can improve the airtightness of the tank. Thus, leaks can be prevented and the assembly of the tank can be facilitated.

[0113] Furthermore, the tank may be mounted on an external frame that functions as a reinforcement device. The external frame may be configured to apply force to the assembled tank. For example, at least one hydraulic plate may reinforce the tank assembly. Additionally, the external frame may be part of a guide rail system for a handling manipulator that enables automatic control of the tank and / or the tank system.

[0114] The tank may have multiple side wall elements, where the top plate element, side wall elements, and bottom plate element are arranged to form a reservoir. This allows for a smaller package size when the tank is disassembled (i.e., the tank assembly).

[0115] Generally, a tank may be configured to withstand an internal pressure of at least 2 bar, or at least 4 bar, or at least 10 bar (without leakage). The normal operating pressure of a tank / tank system may be in the range of 0.1 to 1 bar, preferably 0.2 to 0.6 bar, and more preferably 0.25 to 0.5 bar. In particular, the operating pressure may be less than 0.5 bar, preferably less than 0.3 bar.

[0116] Depending on the cross-section of the tank's reservoir element, the tank's reservoir can have a substantially rectangular, hexagonal, or octagonal cross-section when viewed from the upper plate element side. If the cross-section is rectangular, the tank can be directly interconnected with up to four adjacent tanks. If the cross-section is hexagonal, the tank can be directly interconnected with up to six adjacent tanks. If the cross-section is octagonal, the tank can be directly interconnected with up to eight adjacent tanks. A tank system can combine tanks of the same and / or different configurations, such as those with different cross-sections. Therefore, process lines, such as biopharmaceutical process lines, can be installed in very confined spaces. This can reduce costs such as cleanroom expenses.

[0117] The tank may further comprise at least one pumping device. The pumping device may be separated from the reservoir and / or at least one channel by a flexible membrane to prevent direct contact between the pumping device and at least one biochemical medium. The pumping device may be contained within the reservoir element.

[0118] The tank may further include at least one agitator, which may be driveable from outside the tank. For example, the agitator may be driven by a magnetic actuator. Using a magnetic actuator allows the agitator to be driven from outside the tank and facilitates sealing, for example, by separating the magnetic actuator from the actual agitator by a continuous wall section. The agitator may be contained within a reservoir element, particularly a bottom plate element. Furthermore, the agitator may include an actuation rod. The actuation rod may be supported and sealed within the reservoir element of the tank. The actuation rod can engage with a drive mechanism, such as an electric or magnetic drive mechanism, located outside the tank. Preferably, the actuation rod protrudes from the upper plate element. The drive mechanism may be part of a handling manipulator that enables automatic control of the tank and / or tank system.

[0119] The agitator may be supported within the tank by an operating rod. Furthermore, the agitator may be suspended within the tank, for example, by a magnetic bearing. To drive the agitator, a handling manipulator can be magnetically coupled to the suspended agitator from outside the tank, allowing the agitator to be driven from outside the tank.

[0120] Furthermore, the handling manipulator can be mechanically and / or otherwise appropriately coupled to the agitator from outside the tank, and the agitator can be driven from outside the tank.

[0121] Furthermore, at least one handling manipulator can be provided above or below the tank to drive the agitator.

[0122] The agitator may comprise at least one agitator, which comprises multiple agitator blades. These agitator blades can be provided in various forms, such as Rushton agitator blades, pitched blades, and gentlemarine blades. Furthermore, the agitator may comprise multiple agitator blades provided, for example, to tanks at different levels. Additionally, the agitator may include an integrated sparger.

[0123] The agitator may be capable of operating in pulse mode. This generates waves, allowing the filter to be cleaned from the reservoir side. Furthermore, additional agitators adapted to rotate in close proximity to the filter may be provided for cleaning the filter. Depending on the type of filter, the reservoir side may be the permeate side or the retaining liquid side of the filter.

[0124] For example, the agitator may comprise at least two agitators, each comprising multiple agitator blades. The first of the at least two agitators may be located on the bottom plate element, and the second of the at least two agitators may be located on the top plate element. Furthermore, a handling manipulator can be coupled magnetically, mechanically, and / or otherwise suitablely to at least two agitators from outside the tank, and the agitator can be driven from outside the tank. For example, the agitators may be driven collectively or individually by magnetic actuators and / or superconductors of the handling manipulator.

[0125] The tank may further comprise at least one mixing device, such as a fluid deflection plate, which may be formed integrally with one of the reservoir elements. Furthermore, the mixing device may be a separate means provided within the tank's reservoir. At least one mixing device may be associated with the inlet port of the tank / each reservoir element.

[0126] The tank may further include at least one device for preventing foaming of at least one biochemical medium and / or working medium. The at least one device for preventing foaming can reduce the velocity, drop height and / or flow characteristics of at least one biochemical medium and / or working medium. The at least one device for preventing foaming may be a fluid deflection plate and / or channel (e.g., a rigid tube), as described above. In the case of a channel, the opening of the channel may be directed toward any of the side wall elements, upper plate elements and / or bottom plate elements. As a result, the biochemical medium and / or working medium are deflected when they enter the reservoir. The at least one device for preventing foaming may be formed integrally with one of the reservoir elements. Furthermore, the at least one device for preventing foaming may be a separate device provided within the reservoir of the tank. The at least one device for preventing foaming may be associated with the inlet port of the tank.

[0127] The tank may further comprise at least one cell harvesting device. The cell harvesting device may include a filter and / or filter cartridge that can be coupled to or integrated with the reservoir element, particularly the bottom plate element of the tank. The cell harvesting device may include a medium removal port (also called a cell bleed port) for removing the medium or a portion of the medium (such as cells) contained in the tank's reservoir. The medium removal port may also be located on the bottom plate element and / or at least one side wall element. In particular, the medium removal port may be located anywhere on the reservoir side of the cell harvesting device's filter for removing retaining fluid such as cells, and / or on the opposite side for removing the filtrate (permeate). Furthermore, the cell harvesting device may include an (operating) medium supply port that allows rinsing of the cell harvesting device's filter.

[0128] Furthermore, the tank may be associated with at least one magnet, where at least one magnet may be used for cell selection, cell activation, transduction, and / or proliferation. At least one magnet may be placed directly on the top plate element, at least one side wall element, and / or the bottom plate element. At least one manipulator may be adapted to place and / or remove the at least one magnet.

[0129] The working medium supply port can be provided on either the permeate side or the filtrate side of the filter, respectively. Therefore, when positive pressure (gasic or fluid) is applied to the permeate / filtrate side of the filter, for example, the retained portion of the supplied or retained fluid can be returned to the tank via the (operating) medium supply port, or transferred back from the medium removal port and / or waste port. Furthermore, negative pressure can be applied to the retained fluid side of the filter to transfer the retained fluid back to the tank and / or to discharge it from the medium removal port.

[0130] Applying positive pressure to the permeate / filtrate side of the filter (preferably by providing a pressurized working medium) and / or negative pressure to the retaining liquid / upstream side of the filter can flush out the filter. Therefore, blocked filters, such as cell filters, can be blown away.

[0131] In addition, positive pressure (gasic or fluid) is applied to either the permeate or filtrate side of the filter. For example, the permeate / filtrate can be forced into the permeate channel or the respective filtrate channel via the (operating) medium supply port. Thus, the permeate / filtrate can be returned to the reservoir and / or further tanks. Preferably, positive pressure is applied by providing sterile pressurized air to either the permeate or filtrate side.

[0132] The tank may further include at least one cartridge for chromatography so that preparative chromatography can be performed. Furthermore, the tank may include at least one resin device, membrane absorber, etc. The tank may further include at least one cross-flow cassette so that cross-flow filtration or tangential flow filtration can be performed within the tank.

[0133] The tank may further include at least one hollow fiber device for cell harvesting, diafiltration, microfiltration, ultrafiltration, etc. The hollow fiber device may be housed in a cartridge that can be integrated into the tank's reservoir, or in a cartridge that can be located outside the tank's reservoir. For example, the hollow fiber device may be coupled to at least one of the tank's reservoir elements using its respective ports. Furthermore, the tank may include multiple hollow fiber devices. In particular, the tank may be used, for example, to increase the cell concentration of a cell-containing solution by filtering out a solvent. This allows for the harvesting of cultured cells.

[0134] Reservoir elements, such as at least one sidewall element or bottom plate element, can be integrally formed with the aforementioned filters, cell harvesting devices, chromatography cartridges, cross-flow cassettes, resin devices, hollow fiber devices, and / or other fluid storage or induction components.

[0135] In particular, any of the aforementioned filters, cell harvesting devices, chromatography cartridges, cross-flow cassettes, resin devices, hollow fiber devices, and / or other fluid storage or induction components may include a capsule, where the capsule houses the respective filter, device, cassette, and / or component. Furthermore, the capsule and at least one sidewall element and / or bottom plate element may be integrally formed, where at least one channel of the tank may extend into the capsule (i.e., at least one sidewall element and / or bottom plate element). Alternatively, the capsule may be connected to at least one reservoir element, which may be permanent or reversible.

[0136] The tank may further include at least one rupture disc that can be provided within the reservoir element. The rupture disc may be formed of a different material such as stainless steel, graphite, silicon, or plastic. The rupture disc may be positioned, for example, to block the tank's outlet port or media removal port. If the pressure in the reservoir exceeds a predetermined threshold (for example, due to a clogged filter), the rupture disc will rupture, and the media will be released out of the reservoir through its respective port without damaging the tank. In addition, or instead, a pressure relief valve may be provided that can release excess pressure from the tank's reservoir.

[0137] The tank may be further equipped with at least one bag, where the bag can line the inner wall of the reservoir formed by the reservoir element. Thus, for example, by replacing the bag, the tank's reservoir can be easily prepared to accept additional fluid.

[0138] The tank may be connectable to a sensor module comprising at least one sensor or more sensors, where at least one sensor and the sensors in the sensor module are selected from a group such as pH sensors, temperature sensors, dissolved oxygen sensors, biomass sensors, foam sensors, pressure sensors, flow sensors, O2 sensors, N2 sensors, and CO2 sensors. Furthermore, at least one sensor may be a spectrometer such as a RAMAN, NIR, and / or UV spectrometer. Furthermore, the sensor or sensor module may be connected to the tank, particularly to the reservoir element of the tank. Furthermore, the sensor or sensor module may be a disposable sensor / sensor module. Furthermore, the flow sensor may be an ultrasonic sensor and optionally located in at least one channel of the tank. Furthermore, the sensor or sensor module may be washable and optionally sterilizable.

[0139] To measure the pressure in the tank and / or its channel, the channel may include a flexible membrane. This membrane can be associated with a pressure sensor that matches the pressure in the tank and / or channel. Furthermore, the pressure in the tank and / or channel can be measured using a hydrophobic filter, such as a vent filter attached to the upper plate element. This filter can be isolated from the tank reservoir by a valve. When measuring the pressure, the valve can be opened.

[0140] The ability to measure the pressure in the tank and / or its channels enables leak testing of the tank and / or non-destructive integrity testing of filters installed in the tank. Before the test, the tank is pressurized, for example, by adding pressurized air. The pressure drop can then be measured and compared to predefined pressure values. Thus, leaks can be detected. If the measured pressure drop exceeds the predefined pressure value, the test fails.

[0141] To test the integrity of a filter, for example, all input and output channels of the tank must be closed using the respective valves. Closing the valves is preferably done by a handling manipulator, i.e., automatically. Furthermore, the filter must be moistened before testing. Moistening the filter can be achieved by opening the wetting channel associated with the filter under test. The wetting channel allows buffer to flow to the filter, moistening it. The tank, in particular the permeate side (filtrate side) and / or retaining side (upstream side) of the filter, can then be pressurized, and the pressure drop over time can be measured. To pressurize, positive and / or negative pressure can be applied so that a differential pressure is applied to the filter. The measured pressure drop can be compared to a predefined threshold to determine whether the integrity test is passed. This integrity test can be performed for each filter in the tank. Subsequently, integrity can be tested using, for example, a pressure retention test, a pressure drop test, and / or a forward flow test.

[0142] To test consistency, you can perform the following steps: a) The filter to be tested is moistened with a wetting solution, for example, by applying a buffer solution. The buffer solution may be applied through a cartridge or tank containing the buffer solution, preferably by using a handling manipulator, i.e., automatically. To moisten the filter, a channel is opened that fluidly connects the cartridge or tank containing the buffer solution to the tank containing the filter under test. This is done, for example, by opening the respective valves and / or by connecting the cartridge or tank containing the buffer solution to the tank containing the filter under test. The operation of the valves and the connection of the cartridge containing the buffer solution can be performed by a handling manipulator.

[0143] Furthermore, it is possible to monitor whether wetting is complete. For example, completion of the wetting step can be detected by detecting the permeate and / or filtrate that has passed through the filter under test. This can be done by providing fluid sensors, such as capacitive sensors, by weighing them. In addition, or alternatively, the wetting fluid and their respective pressures can be provided at predetermined times to ensure proper wetting of the filter. Excess wetting fluid can be removed through a waste channel, for example, and led to a waste tank. Furthermore, if necessary, back pressure can be applied via a valve to improve the wetting of the filter.

[0144] b) After wetting is complete, for example, the permeate side (filtrate side) and / or retaining liquid side (upstream side) of the filter are pressurized, preferably by applying sterile pressurized air. Before pressurizing, all valves that allow pressurized air to exit from the pressurized side of the filter must be closed, preferably by their respective handling manipulators.

[0145] When testing a membrane filter, the upstream side of the filter is typically pressurized. Channels may also be opened on the filtrate side of the filter. For example, waste channels are opened, preferably by activating their respective valves. This allows pressurized air that has passed through the filter to be removed from the filtrate side.

[0146] When testing cross-flow cassettes and / or hollow fiber modules, pressure can preferably be applied to the retaining fluid side through the retaining fluid outlet channel of the tank. The retaining fluid outlet channel may be openable and closable by the associated valve. The supply channel of the cross-flow cassette and / or hollow fiber module may be closed for integrity testing. The permeate channel of the cross-flow cassette and / or hollow fiber module may also be opened for integrity testing. Channels may be opened on the permeate side of the filter. For example, preferably by operating the respective valves, one permeate channel is connected to a waste channel. This allows pressurized air that has passed through the filter to be removed from the permeate side.

[0147] c) During or after pressurization, the pressure drop over time can be measured and compared to a predetermined threshold. Preferably, the measurement is started after a predetermined stabilization time. If the pressure drop exceeds the threshold, the test fails.

[0148] After the test, the pressurized air can be removed from the tank through the outlet port.

[0149] In conventional bag-based process lines, integrity testing is extremely difficult because the applied pressure causes the bags and / or hose connections to expand. Therefore, test results are distorted. Consequently, conventional bag-based process lines require expensive helium leak testing. Furthermore, helium leak testing is complex and typically cannot be performed on the interconnected bags of conventional bag-based process lines, or even the entire biopharmaceutical process line. In particular, bag interconnections cannot be tested. Therefore, the ability to use integrity testing on easily assembled process lines and / or easily assembled tanks significantly reduces the risk of leaks. Additionally, the cost of operating the process line is also reduced.

[0150] At least one reservoir element of the tank (top plate element, optionally at least one side wall element, and / or bottom plate element) may include a sensor module connection portion that allows a sensor or a sensor module comprising multiple sensors to be connected to the tank. The sensor and / or sensor module may include a wired or wireless data transfer unit for transferring the acquired sensor data to a control unit. Furthermore, the sensor and / or sensor module may include a rechargeable battery and / or a power interface for supplying power to the sensor and / or sensor module. The power interface may be wired or wireless, such as an inductive or capacitive power interface. Furthermore, the sensor and / or sensor module may be configured for multi-purpose use. In particular, the sensor and / or sensor module may be sterilizable.

[0151] Sensors and / or sensor modules may be connected to their respective handling manipulators. The connection may be wired or wireless. Data can then be transferred between the sensors and / or sensor modules and the handling manipulators. Furthermore, the connection may allow the sensors to be powered by the handling manipulators.

[0152] The reservoir element and tank do not necessarily need to contain electrical or electronic components, but they can be connected to them (for example, sensors or sensor modules). Therefore, the reservoir element and tank can be easily recycled.

[0153] Furthermore, this objective is achieved by a tank system comprising multiple tanks as described above. When the second tank is positioned adjacent to the first tank, the first tank of the tank system can be interconnected with the second tank by at least one connector device. Moreover, when the first tank is interconnected with the second tank, at least one channel of the first tank is fluidically connected to each channel of the second tank. Thus, process lines such as biopharmaceutical process lines can be easily set up and automated. In particular, the number of hose or pipe-based fluid connections can be significantly reduced compared to conventional process lines.

[0154] In particular, when the second tank is located directly adjacent to the first tank, the first tank of the tank system may be directly interconnected with the second tank by at least one connector device. Alternatively, or in addition, hose-based fluid connections may also be used.

[0155] To facilitate connection, the upper plate elements of the first and second tanks, particularly the plate elements, can project laterally above the side wall elements. Therefore, the tanks are connected easily, as the side wall elements do not interfere with the connection. Furthermore, the bottom plate elements can project laterally above the side wall elements. Thus, the tanks may be additionally connected via the bottom plate elements.

[0156] Furthermore, the height dimension of the first tank may be smaller than that of the second tank. To compensate for the height difference, the tank system may be equipped with support rails, which are adapted to support at least two tanks. When the tanks are supported by support rails, the support rails can engage with the top plate elements of each tank (here, for example, the first and second tanks) so that the top plate elements of tanks of different heights are placed at the same level. In addition, or instead, the support rails can engage with the side wall elements of each tank so that (additional) support for the tanks is provided. The support rails may include at least one weighing member that can weigh the supported tanks individually. The weight of each tank can then be used to control the process line formed by the tanks.

[0157] It should be understood that the support rails can also be used for tanks of the same height. In particular, the support rails may be included, at least partially, in the cleanroom bag.

[0158] Therefore, all upper plate elements of the tank system can be positioned at substantially the same height. This makes it possible to mount each adapter plate element on top of the plate elements, where the adapter plate elements are also positioned at substantially the same height. Thus, the actuators for the tank ports, tank filters, and / or tank valves can be accessed and operated at substantially the same height. This facilitates automated operation and management of the tank system. Furthermore, if the adapter plate elements and top plate elements sandwich a barrier element that is part of the cleanroom, the cleanroom can have a substantially flat top surface, eliminating the need for complex shapes.

[0159] Furthermore, at least one adapter plate is configured to be attached to multiple upper elements of different tanks, thereby enhancing the interconnection of the tanks.

[0160] Furthermore, the volume of the first tank may be smaller than that of the second tank, and the first tank may be configured to be installed above the second tank. The first and second tanks may be fluidically connected, where the fluid connection (channel) may be controlled by a valve. The first tank may function to supply a working medium and / or biochemical medium to the second tank. Because the first tank is installed above the second tank, gravity can be used to transfer fluid from the first tank to the second tank. Thus, the use of a pump can be avoided.

[0161] Furthermore, the medium can be transferred from the first tank to the second tank by pressurizing at least one tank. When it is necessary to transfer the medium from the first tank to the second tank, positive pressure can be applied to the first tank and / or negative pressure to the second tank. Thus, the medium is pushed from the first tank to the second tank. If a filter is provided between the first and second tanks (for example, in an interconnection channel and / or in the upper plate element of the second tank if the first tank is installed above the second tank), filtration can be controlled by controlling the pressure levels in the first and / or second tanks. Positive pressure can be established by supplying a (working) medium, such as pressurized air, to the tanks. Negative pressure can be established by removing (working) the medium from each tank. When pressurized air is used as the working medium, sterile pressurized air is preferably used. Sterile pressurized air can be obtained by directing pressurized air to each sterile filter before it enters the tanks.

[0162] Furthermore, the tank system may include a connecting plate element. The connecting plate element may include at least one channel and may be adapted to interconnect tanks that are not directly adjacent to each other. The connecting plate element facilitates the interconnection of spaced-out tanks, which can, for example, sandwich one or more further tanks. Furthermore, the connecting plate element may be configured to multiplex or reverse multiplex the flow of media. For example, the connecting plate element may include a channel joint or a channel manifold. Thus, media received from a first tank can be supplied to multiple other tanks (multiplexing). Furthermore, different media can be mixed within the connecting plate element and supplied together to a single tank (reverse multiplexing). Furthermore, the connecting plate element may be integrally formed with an upper plate element, at least one side wall element, and / or a bottom plate element.

[0163] The upper plate element, the bottom plate element, and / or connecting plate element may also be available as separate products. For example, the upper plate element and / or the bottom plate element may function as a filter unit with at least one filter as described throughout this disclosure. Further example, the upper plate element and / or the bottom plate element may function as a fluid flow control unit with at least one valve as described throughout this disclosure.

[0164] Furthermore, the tank system may include an adapter. The adapter may be adapted to interconnect the first tank and the second tank. Optionally, the adapter may be adapted to interconnect the first tank and the second tank by at least one connector device.

[0165] The adapter may include at least one channel and at least one fluid module. If the adapter interconnects a first tank and a second tank, at least one channel of the adapter may be fluidically connected to each channel of the first tank and each channel of the second tank.

[0166] At least one fluid module may function to filter, mix, separate, and / or activate a flow of a medium (biochemical medium and / or working medium). At least one fluid module may be at least one of the following: a cross-flow cassette, a cross-flow hollow fiber module, a hollow fiber filter, a resin capsule, a filter capsule, and / or a magnetic tube. It should be understood that an adapter may contain multiple fluid modules of the same and / or different types.

[0167] Furthermore, at least one fluid module may be replaceable. Therefore, maintenance can be facilitated. In particular, at least one fluid module may be replaceable with a different type of fluid module. Thus, the adapter's function can be adapted with less effort. Furthermore, at least one fluid module may be replaceable with a fluid module of the same type. Therefore, for example, a worn-out filter can be easily replaced.

[0168] Furthermore, adapters can be adapted to interconnect tanks that are not directly adjacent to each other. Adapters facilitate the interconnection of spaced-out tanks. These spaced-out tanks can, for example, sandwich one or more additional tanks. Additionally, adapters, like connecting plate elements, can be configured to multiplex or demultiplex the flow of media.

[0169] The system may further comprise at least one cleanroom bag. Furthermore, several objectives are achieved by the cleanroom bag. The cleanroom bag is configured to accept at least one tank. Also, when at least one tank is accepted into the cleanroom bag, it provides a cleanroom environment to at least one tank. To provide access to the tank from outside the cleanroom bag by defining at least one access point via an access plate element, the cleanroom bag comprises at least one foil portion adapted to be sandwiched between the tank's access plate element, for example, the tank's upper plate element and adapter plate element. Furthermore, at least one tank may be accessible from outside the cleanroom bag via the access plate element using a handling manipulator.

[0170] Cleanroom bags can be installed in virtually any environment, such as conventional factory halls. Therefore, the planning and construction of expensive and time-consuming pharmaceutical process line installations can be avoided. Consequently, biopharmaceutical process lines can be set up very quickly. Furthermore, since the cleanroom bag itself provides at least minimal cleanroom conditions, there is no need to install expensive conventional cleanrooms. Additionally, in the case of disposable cleanroom bags, expensive and time-consuming cleaning and testing can be avoided.

[0171] Cleanroom bags are preferably flexible bags that require little storage space when not in use. Cleanroom bags can be pre-sterilized and inflated / expanded for use. Therefore, they can provide a sterile or at least cleanroom environment.

[0172] Cleanroom bags provide at least cleanroom conditions. They can provide at least ISO 8 (ISO 14644-1 and ISO 14698) conditions. Depending on the required environment, cleanroom conditions down to ISO 1 are also possible. More preferably, cleanroom bags provide a sterile environment for operating the tank. Cleanroom bags may be sterilized by, for example, ETO, gamma ray sterilization, X-ray sterilization, or autoclave sterilization.

[0173] The system may further comprise at least one adapter plate element, which is associated with at least one tank. In particular, the adapter plate element may be associated with a single tank or multiple tanks. The adapter plate element can be attached to at least one tank such that one of at least one foil portion of the cleanroom bag is sandwiched between the tank's access plate element and the adapter plate element. The access plate element may be a top plate element, at least one side wall element, or a bottom plate element. Particularly preferably, the top plate element is the access plate element.

[0174] Furthermore, the adapter plate element is configured to define at least one access point via the access plate element to provide access to the tank from outside the cleanroom bag.

[0175] Therefore, the tank can be installed in a cleanroom or sterile environment, while simultaneously being accessible from outside the cleanroom bag. Consequently, handling manipulators and other control or actuators can be mounted outside the cleanroom bag. Thus, the size of the cleanroom bag can be minimized.

[0176] The adapter plate element may be configured to at least partially cover the filter and / or tank ports. Thus, the medium (biochemical medium and / or working medium) can be transferred from outside the cleanroom bag to the tank and / or removed from the tank. The foil portion of the cleanroom bag sandwiched between the tank access plate element and the adapter plate element may be provided to be removable and / or perforated in the area of ​​the tank's filter and / or ports. Thus, access to the tank can be provided from outside the cleanroom bag.

[0177] To access the tank from outside the cleanroom bag, the handling manipulator can perform the following steps:

[0178] Step 1: Attach the adapter plate element to at least one tank so that at least one foil portion of the cleanroom bag is sandwiched between the tank's access plate element and the adapter plate element. Optionally, remove any cover elements, such as caps, from the through-holes (access points) of the adapter plate element.

[0179] Step 2: Perforate at least one foil portion of the cleanroom bag using a perforating device such as a knife, needle, or laser. Perforation can be performed in a way that separates the foil portion from the cleanroom bag.

[0180] Step 3: Optionally, use a gripping device such as a vacuum gripper on a handling manipulator to grip the separated foil portion.

[0181] Step 4: Optionally, preferably using a handling manipulator, weld the remaining foil portion to the adapter plate element and / or top plate element.

[0182] Step 5: Optionally, a connector device, such as a quick connector device, is placed in the area of ​​the removed / perforated foil portion on the adapter plate. The adapter plate element may be configured to support valve actuators and / or tank operating devices (such as agitators). The foil portion may also be provided therein in a removable and / or perforated manner in the area of ​​the valve actuators and / or tank operating devices to provide access to the tank. As described above, this can be accessed using a handling manipulator. Thus, operating devices such as valves and agitators can be operated from outside the cleanroom bag.

[0183] Furthermore, the cleanroom bag may be adapted to be sealed and coupled to an assembly room that serves to assemble at least one tank. There, the cleanroom bag may be further configured to receive at least one assembled tank from the assembly room. The assembly room may also provide a cleanroom and / or sterile environment for assembling the tank. Thus, the risk of contamination of the tank during assembly is reduced.

[0184] Cleanroom bags may be sterile bags and optionally disposable bags. Cleanroom bags may be sterilized beforehand or sterilizable on-site at the biopharmaceutical manufacturer. Providing disposable bags further reduces the risk of tank contamination. In addition, cleaning of cleanroom bags after use is unnecessary.

[0185] The cleanroom bag may be held by a support structure. The support structure may be a rigid support structure such as a frame. Alternatively, the support structure may be inflatable. It is also possible to inflate the cleanroom bag itself. Thus, a movable, self-supporting cleanroom can be provided.

[0186] A cleanroom bag may have a multilayer outer shell, where the first layer of the shell is the outermost layer, and the second layer of the shell is the innermost layer. The space enclosed by the second layer of the shell may be pressurized at a pressure lower than the pressure applied between the first and second layers of the shell. A colored gas may be supplied between the first and second layers of the shell. Therefore, if the second layer of the shell leaks, the colored gas enters the space enclosed by the second layer. This can be detected and suggests the intrusion of contaminants into the sterile and / or cleanroom environment.

[0187] The cleanroom bag may include a sealable opening configured to receive an assembled tank. When the cleanroom bag is sealed and coupled to an assembly room, the sealable opening of the cleanroom bag may be configured to open together with a corresponding sealable opening in the assembly room. Furthermore, the tank can be removed from the cleanroom bag using the sealable opening. The cleanroom bag may include multiple sealable openings. This facilitates the transfer of assembled tanks from the assembly room to the cleanroom bag, or their removal from the cleanroom bag.

[0188] As mentioned above, when cleanroom bags are sealed and coupled to the assembly room, sterilization of the assembly room can function to sterilize the outside of the sealable opening of the cleanroom bag. Thus, sterile transfer to the cleanroom bag can be facilitated.

[0189] The sealable opening of the cleanroom bag may be covered by at least one cover element. The corresponding sealable opening of the assembly room may be covered by at least one corresponding cover element. The at least one cover element and the at least one corresponding cover element are configured to connect with each other and open together.

[0190] For example, the sealable opening and the corresponding sealable opening may be provided as sliding doors. At least one cover element / corresponding cover element may be the door of each sliding door. The coupling of the cover element and the corresponding cover element can be achieved, for example, by a magnetic device, a positive locking device, or other coupling or locking device. Preferably, magnets (permanent magnets) are distributed at least on the edges of the cover element / corresponding cover element. This makes it possible to couple the cover element with the corresponding cover element in a defined manner. Thus, the non-sterile outer surfaces of the cover element / corresponding cover element cover each other after coupling. Thus, the risk of contamination of the assembled tank when it is transferred from the assembly room to the cleanroom bag through the sealable opening can be further reduced.

[0191] The cover element / corresponding cover element is movable relative to the cleanroom bag and / or assembly room. The cover element / corresponding cover element and the cleanroom bag / assembly room may be sealed by, for example, at least one brush seal, lip seal, etc. More preferably, the cover element / corresponding cover element may be connected to the cleanroom bag or assembly room via a flexible portion, such as a seal foil portion. The flexible portion may be connected to the cover element on a first side and to the cleanroom bag on a second side. Similarly, the flexible portion may be connected to the corresponding cover element on a first side and to the assembly room on a second side. Thus, a sealable opening can be opened and closed without creating a gap between the cover element and the cleanroom bag, and / or between the corresponding cover element and the assembly room. Thus, the risk of contamination can be further reduced.

[0192] The cleanroom bag may further include a sealing frame, or may be associated with a sealing frame. The sealing frame may be configured to surround a sealable opening in the assembly room. Thus, when the opening is opened, an additional seal is provided to seal the opening from the environment. Thus, the risk of contamination can be further reduced. The sealing frame may be a separate frame or may be provided in the assembly room.

[0193] This system may further include a UV light source. The UV light source may be associated with a sealable opening in the assembly room. Thus, any possible contaminants on the outer surface of the sealable opening can be removed / destroyed before and / or while the sealable opening is open. At least one UV light source may be provided within the seal frame. Preferably, the UV light source is configured to illuminate the sealable opening from different directions. Thus, contaminants can be effectively removed / destroyed.

[0194] The seal frame may further include ports that allow the space between the seal frame in the assembly room and the closed, sealable opening to be vented before the sealable opening is opened. Thus, particles and / or contaminants can be effectively removed, further reducing the risk of contamination.

[0195] The cleanroom bag may be equipped with at least one rail for guiding at least one assembled tank received into the cleanroom bag. This facilitates the positioning of the assembled tank within the cleanroom bag. For example, a first tank may be placed on the rail. A second tank may also be interconnected with the first tank and placed on the rail. This allows the first tank to be further guided into the cleanroom bag. By repeating this process, the entire process line can be assembled and guided into the cleanroom bag.

[0196] The rail may be a support rail for guiding at least one assembled tank into the cleanroom bag. The support rail is adapted to support at least two tanks. When the tanks are supported by the support rail, the support rail can engage with the upper plate elements and / or side wall elements of each tank so that the upper plate elements of tanks of different heights are positioned at the same level. In this case, the tanks are in a suspended configuration, and the bottom plate elements may not be in contact with the ground. In addition to the suspension supports for the upper plate elements, support members can be provided to support the tanks with the bottom plate elements.

[0197] The support rail may be formed from multiple support rail sections so that the cleanroom bag is foldable. In particular, the support rail sections may be made from plastic material and may be injection molded. In certain embodiments, the foil portion and the support rail sections are fixed and bonded to each other (e.g., welded or glued), or even formed integrally. To increase the load-bearing capacity of the support rail sections, those sections may include metal inserts.

[0198] Furthermore, the support rail section may be configured to receive a corresponding support rail of a frame, which may be part of a handling manipulator. The frame may include a corresponding rigid support rail, such as a metal support rail. The support rail section can be formed to fit a corresponding support rail of the frame. In addition, the support rail section may include a latching device that engages the support rail section with the corresponding support rail of the frame, preferably by a snap fit.

[0199] Furthermore, to improve the guidance of the tank within the support rails, upper plate elements, side wall elements, and / or support rails, each support rail section may include a support wheel or support roller. The support roller / wheel may be included in a roller member connectable to each upper plate element and / or side wall element of the tank. The support roller / wheel is then guided within the support rails to support and guide the tank in a suspended configuration.

[0200] The support rail / support rail section may include at least one weighing member capable of weighing each supported tank individually. The weight of each tank can then be used to control the process line formed by the tanks.

[0201] This objective is also achieved by the method of assembling the tank, which includes the following steps: providing an upper plate element, optionally providing at least one sidewall element, providing a bottom plate element, and assembling the upper plate element and the bottom plate element, and optionally at least one sidewall element, to form a reservoir for receiving at least one biochemical medium.

[0202] Assembly can be fully automated. Furthermore, assembly is preferably carried out in a cleanroom or even a sterile environment. Additional components of the tank described above can also be assembled. [Brief explanation of the drawing]

[0203] The following describes the attached drawings which schematically illustrate embodiments of the present invention. [Figure 1A] A schematic diagram of the reservoir element is shown. [Figure 1B] A schematic diagram of the further reservoir elements is shown below. [Figure 2] The reservoir elements are shown in general terms. [Figure 3] The reservoir elements are shown in general terms. [Figure 4]A schematic diagram of reservoir elements that can be used as bottom plate elements for a tank is shown. [Figure 5] A schematic diagram of reservoir elements that can be used as the upper plate elements of a tank is shown. [Figure 6] A schematic diagram of the assembled tank is shown. [Figure 7] A through C describe the outlines of assembled tanks with different volumes. [Figure 8] The tank system is shown in a schematic manner. [Figure 9] A schematic diagram of the reservoir element is shown. [Figure 10] A schematic diagram illustrating a further expansion of the reservoir elements is shown below. [Figure 10A] This shows a cross-section of the valve attached to the upper plate element. [Figure 10B] The exploded view of the aforementioned valve is shown. [Figure 11] Further aspects of the tank system are outlined below. [Figure 12] A cleanroom bag is shown in general terms. [Figure 13] A schematic diagram of the cleanroom bag is shown. [Figure 14] A schematic flow chart of the tank assembly method is shown.

[0204] Detailed description of the drawing Figures 1A and 1B schematically show exploded views of different reservoir elements 200 and 200a of tank 1 (see Figure 6) in a biopharmaceutical process line. Reservoir element 200 includes a body element 210 and multiple shell elements 220 and 222 (see Figure 1A). Reservoir element 200a includes a body element 210a and a single shell element 220a (see Figure 1B). The body element has first ends 212 and 212a and second ends 214 and 214a opposite the first ends, with each of the first and second ends containing an orifice, where the body elements 210 and 210a taper from the first ends 212 and 212a to the second ends 214 and 214a, where the internal volume is defined between the first and second ends.

[0205] The main body elements 210 and 210a shown in Figures 1A and 1B have a polygonal (quadrilateral) cross-section in a plane parallel to the first ends 212 and 212a. Thus, the main body elements form four substantially flat side wall portions. In Figure 1A, each shell element 220 and 222 is similarly plate-like. Alternatively, the shell element 220b may also have a polygonal cross-section, as shown in Figure 1B. In yet another alternative, the shell elements may be formed so as to cover only a portion of the main body elements 210 and 210a when installed, for example, at least two side wall elements.

[0206] The main body element and / or at least one shell element includes at least one groove 216, 217, 218, where grooves 216, 217, 218 are contained within the main body element. Groove 217 extends from a first end to a second end, where groove 216 extends from a first end 212 to a port 230 of the reservoir element, which may be a fluid inlet port. Groove 218 begins and ends at the first end 212 but includes several curves. In Figure 2, the shell elements 220, 222 are fixedly attached to the main body element 210 (e.g., by welding or bonding), and the main body element 210 and the shell elements 220, 222 form channels with their respective grooves 216, 217 in between. These channels are adapted to guide at least one biochemical medium and / or working medium. For example, channels formed by groove 216 can be used to guide biochemical fluids into the internal volume of the reservoir element (through port 230). Channels formed by groove 217 are adapted to transfer fluid from the first end to the second end, and channels formed by the curved groove 218 can be used as heating / cooling channels.

[0207] Furthermore, the first end 212 of the reservoir element 200 includes a sealing surface 213 for sealing and connecting the reservoir element 200 to a further reservoir element, as shown as an example in Figure 6.

[0208] Figure 3 schematically shows two reservoir elements 200 and 200' stacked on top of each other. In particular, the internal volume and first orifice of the reservoir elements 200 and 200' are configured to allow reservoir element 200 to at least partially accept a further reservoir element 200'. As a result, multiple reservoir elements can be stacked on top of each other, thus minimizing storage space.

[0209] Figure 4 schematically shows a reservoir element 300 that can be used as a bottom plate element of a tank. The reservoir element 300 includes a tapered main body element 310 and a plurality of shell elements 320, 322 fixedly attached to the main body element.

[0210] Furthermore, the reservoir element 300 includes a plate element 330 sealed and attached to the first end 312 of the main body element 320 so as to cover each orifice. The plate element 330 may include multiple layers, and in particular may include at least one channel (not shown) in which at least one channel can communicate with a channel formed by the main body element 310 and at least one shell element 320, 322. The reservoir element 300 further includes an insert 340 that at least partially covers any undercuts in the internal volume. Thus, the formation of dead volume is prevented. Furthermore, the reservoir element includes an actuator 352 which may be used to open and close a valve (not shown). The valve may be a magnetic valve.

[0211] Figure 5 schematically shows a reservoir element 100 that can be used as the upper plate element of a tank. Furthermore, the reservoir element 100 includes a plate element 130 that is sealed and attached to the first end 112 of the main body element 120 so as to cover each orifice. The plate element 130 may include multiple layers and in particular may include at least one channel (not shown) in which at least one channel can communicate with a channel formed by the main body element 110 and at least one shell element 120, 122. The reservoir element 100 further includes an insert 140 that at least partially covers an undercut of the internal volume. Thus, the formation of dead volume is prevented. Furthermore, the reservoir element 100 includes an actuator 152 that can be used to open and close a valve (not shown). The valve may be a magnetic valve.

[0212] The reservoir elements 100, 200, 200', and 300 can form a tank assembly adapted to be assembled in tank 1 as shown in Figure 6. The first ends 112, 212, and 312 of each reservoir element are particularly the same size and shape. Similarly, the second ends 114, 214, and 314 of each reservoir element are particularly the same size and shape. It should be understood that the first and second ends differ in size and / or shape as the body elements 110, 210, and 310 of each reservoir element 100, 200, and 300 taper from the first end to the second end. By providing the first ends 112, 212, and 312 which are particularly the same size and shape, and the second ends 114, 214, and 314 which are particularly the same size and shape, it becomes possible to assemble each reservoir element in tanks of different volumes (see, for example, Figure 7).

[0213] Figure 6 shows an assembled tank 1 for a biopharmaceutical process line. The tank comprises an upper plate element 100, two side wall elements 200, 200', and a bottom plate element 300. The side wall elements are the side wall elements 200, 200' described with respect to Figures 1 to 3. The bottom plate element and the upper plate element may have substantially the same configuration. They may also be reservoir elements, as shown in Figures 4 and 5, respectively.

[0214] The upper plate element 100, the side wall elements 200, 200', and the bottom plate element 300 are arranged to form at least one reservoir 500 for receiving at least one biochemical medium. Since the reservoir element contains at least one channel, the tank also has at least one channel (not shown) for guiding at least one biochemical medium and / or working medium, where at least one channel extends into the interior of at least one upper plate element, at least one side wall element, and / or bottom plate element. At least one channel in each of the reservoir elements 100, 200, 200', and 300 can be connected to form a joint channel in the tank.

[0215] To form a tank, the second end 114 of reservoir element 100 is sealed and joined to the second end 214 of reservoir element 100. Similarly, the first ends 112 and 112' of reservoir elements 200 and 200' are sealed and joined, and the second end 214' of reservoir element 200' is sealed and joined to the second end 314 of reservoir element 300.

[0216] Each of the reservoir elements 100, 200, and 300 may include at least one assembly connector 160, 260, 260' and corresponding assembly connectors 262, 262', and 362. The assembly connector may include a latching member such as a hook. The corresponding assembly connector may include a recess formed for engaging with the hook. When engaged, a sealed connection between adjacent reservoir elements can be achieved.

[0217] In alternative embodiments (not shown), the assembly connector may be a threaded member integrated with the reservoir element. The threaded member may have a female thread (e.g., a nut) or a male thread (e.g., a threaded shaft or screw) and may be formed integrally with the reservoir element. Optionally, or in addition, the threaded member may be an inlay, such as a metal inlay, which is securely held within the reservoir element. The inlay may be, for example, overmolded or bonded to the reservoir element. The corresponding assembly connector may have a trough opening that can align with a threaded member having a female thread. Thus, the reservoir element can be connected and engaged by screwing a screw through the opening into the threaded member. Furthermore, the corresponding assembly connector may have a trough opening that receives a threaded member having a male thread. Thus, the reservoir element can be connected and engaged by screwing a nut or the like into the threaded member, thereby engaging the reservoir element.

[0218] In particular, each of the first and second ends can be associated with an assembly connector and a corresponding assembly connector. As a result, different reservoir elements can be arbitrarily coupled.

[0219] Furthermore, the actuators 152 and 352 of the upper plate element 100 and the lower plate element 300 can be interconnected by the actuators 252 and 252' of the side wall elements 200 and 200', respectively. Therefore, for example, the operation of a valve provided on the lower plate element (not shown) can be made possible by operating the actuator 152 of the upper plate element 100.

[0220] Each element (top plate element 100, side wall elements 200, 200', and bottom plate element 300) may be adapted to include sensors and / or sensor modules. A sensor module may include multiple sensors, for example, at least one pH sensor, temperature sensor, dissolved oxygen sensor, biomass sensor, bubble sensor, pressure sensor, flow sensor, O2 sensor, N2 sensor, CO2 sensor, and a spectrometer such as a RAMAN, NIR, and / or UV spectrometer. A sensor module may be connectable to each of the top plate elements 100, side wall elements 200, 200', and / or bottom plate elements 300. The sensor module may be provided with a power source, such as a rechargeable battery, which enables the sensor module to operate autonomously. Furthermore, the sensor module may include a data interface, in particular a wireless data interface for transferring measured sensor data to the respective control unit or storage unit.

[0221] Furthermore, the tank, in particular the upper plate element 100, may include at least one filter. The filter may be located within the internal volume of the reservoir element 100. Furthermore, the filter may be integrated with the plate element 130 of the reservoir element 100. Additionally, the adapter plate element may be configured to at least partially cover the filter and / or the tank's ports. In certain embodiments, the upper plate element of the tank and the associated adapter plate element may form a filter housing.

[0222] As shown in Figures 7A-7C, the reservoir elements are suitable for forming tanks of different volumes. In Figure 7A, a tank is assembled including a top plate element 100, four side wall elements 200, 200', 200'', 200''', and a bottom plate element 300. The side wall elements are the reservoir elements 200, 200', 200'', 200''' described in relation to Figures 1-3. The bottom plate element and the top plate element may have substantially the same configuration. They may also be the reservoir elements shown in Figures 4 and 5, respectively. Thus, the tank in Figure 7A can be assembled from the same elements as the tank shown in Figure 6, which has approximately twice the volume.

[0223] Figure 7B shows a further tank similar to the tank shown in Figure 7A. In this configuration, the side wall element 200 is replaced by the side wall element 200a. The side wall element 200a has a lower height dimension than the side wall element 200, but its first and second ends have the same shape and size as the first and second ends of the side wall element 200. This makes it possible to replace the side wall elements 200 and 200a.

[0224] Figure 7C shows a configuration without side wall elements. The tank is formed only from an upper plate element 100 and a bottom plate element 300. Therefore, a very small volume can be achieved.

[0225] Figure 8 schematically shows a tank system comprising two tanks 1 and 2. Both tanks are configured as described with respect to Figure 6. The first tank 1 is interconnected with the second tank 2 by at least one connector device (not shown). When the first tank 1 is interconnected with the second tank 2, at least one channel of the first tank 1 is fluidically connected to the respective channels of the second tank 2. Thus, a medium can be transferred from the first tank to the second tank, or vice versa.

[0226] The upper plate elements 100a, 100b of the first and second tanks 1 and 2, and especially the plate elements 130a, 130b, can project laterally over the side wall elements 200a, 200'a; 200b, 200'b. Therefore, the connection of tanks 1 and 2 is facilitated as the side wall elements do not interfere with the connection. Furthermore, the bottom plate elements 300a, 300b can project laterally over the side wall elements 200a, 200'a; 200b, 200'b. Therefore, the tanks may be additionally connected via the bottom plate elements.

[0227] Figures 9 and 10 schematically show enlarged views of a reservoir element, which may be a bottom plate element 300. In particular, plate elements such as the plate element 330 of the reservoir element 300 are shown (see Figure 9). Figure 10 shows a different configuration of the plate element 330'. The plate element 330;330' comprises an agitator 90, which may be driveable from outside the tank. The agitator comprises an actuation rod 92, which may include a gear mechanism (not shown). The gear mechanism can provide an angle (90 degrees in this case) between the drive portion 92a and the output portion 92b of the actuation rod 92. The actuation rod 92 can be coupled to a drive mechanism 80, such as an electric drive mechanism located outside the tank. The drive mechanism may be part of a handling manipulator (not shown) that enables automatic control of the tank and / or tank system. This coupling can be achieved by a magnetic coupling 89. Thus, when the drive mechanism 80 rotates, the magnetic coupling 89 transmits its rotation to the drive portion 92a. This rotation is transmitted to the agitator 90 via the output unit 92b. The output unit 92b and the agitator 90 may be magnetically coupled (see magnetic coupling 98 in Figure 10) or mechanically coupled as shown in Figure 9.

[0228] Furthermore, the plate element 330 may include a channel 336 associated with two ports 337, 338. Port 337 may be a fluid inlet or outlet port for supplying a biochemical medium to / from the internal volume of the reservoir element. Port 338 is associated with a valve 339, which may be a solenoid valve. Preferably, the magnetic valve can be opened and closed by a drive mechanism 80 by inducing magnetic coupling. In certain embodiments, the drive mechanism 80 can move to the magnetic coupling of an operating rod 92 and the magnetic valve 39. Thus, the drive mechanism 80 can be used to actuate the valve 339 and the agitator 90. Magnetic coupling allows, for example, the tank to be placed inside a cleanroom bag. The handling manipulator and drive mechanism 80 are located outside the cleanroom bag.

[0229] In an alternative embodiment, the drive mechanism may be located beneath the bottom plate element 300. Therefore, a gear device is not required.

[0230] The magnetic valve 39 may be a needle valve. The valve may be closed in its initial state and can be opened by axially displacing the valve body. This can be achieved, for example, by applying a magnetic force. In the closed initial state, the valve may be preloaded by a spring member or a magnetic member. Therefore, when not in operation, the valve may remain closed. The valve opens only when operated (for example, manually or via a handling manipulator).

[0231] Figure 10A shows details of the upper plate element 100, where a valve 50 is mounted. The valve 50 has a switching mechanism equivalent to the switching mechanism of a ballpoint pen. Thus, the valve 50 can be opened and closed by axially displacing the actuator 51 of the valve 50. In this embodiment, the actuator 51 is the valve actuator body 51. In Figure 10A, the valve 50 is in the open position, allowing a fluid flow rate 60 through the passage 55. The illustrated upper plate element 100 comprises three plate elements with a seal between them. The valve 50 extends into the interior of all three plate elements. The valve 50 is sealed to the upper plate element by a seal 52.

[0232] Figure 10B shows an exploded view of the valve 50 of Figure 10A. The valve 50 comprises the valve actuating body 51, a valve housing 53, a switching element 54, a fluid control element 56, and a spring 57. The valve actuating body 51, the switching element 54, and the fluid control element 56 are arranged to be axially displaceable within the valve housing 53. Thereafter, the switching element 54 is configured to rotate relative to the valve housing 53 when displaced axially. In particular, the switching element 54 is configured to engage with an inclined surface 58 within the valve housing 53. The fluid control element 56 includes a seal 59 configured to seal the fluid control element 56 against the valve housing 53. Furthermore, the fluid control element 56 is adapted to control the fluid flow rate 60 by opening and closing a passage 55. The spring 57 may be located elsewhere and / or may be a polymer spring. In another particularly preferred embodiment, the spring 57 is positioned so as to avoid fluid contact with the spring 57.

[0233] Figure 11 schematically shows further aspects of the tank system. The tank system comprises multiple tanks. In the viewpoint of Figure 11, only tank 1 is shown. The first tank 1 may be interconnected with a second tank (not shown). The tanks may be as shown in Figure 6.

[0234] Tank 1 comprises an access plate element, in this case an upper plate element 100, which is part of the assembled tank 1. The access plate element 100 is configured to provide access to Tank 1. Furthermore, to improve the guidance of the tank within the support rails, upper plate element, side wall elements and / or support rails, each support rail section may include support wheels or support rollers.

[0235] Support rollers / wheels may be included in roller members that can be connected to each upper plate element and / or side wall element of the tank. The support rollers / wheels are then guided within support rails to support and guide the tank in a suspended configuration.

[0236] The system may further comprise at least one handling manipulator 13000, 13100, 13200. For example, a first handling manipulator 13000 may be positioned above the tank 1, a second handling manipulator 13100 below the tank 1, and a third handling manipulator 13200 to the side of the tank 1. The handling manipulators are positioned to be movable relative to the tank 1, for example, to access and control at least one tank via an access plate element 100. In particular, the handling manipulators may include guide rails 12000 that allow the handling manipulators to move in at least one axial direction. In certain embodiments, the handling manipulators include a gantry robot.

[0237] In particular, the handling manipulators 13000, 13100, and 13200 may be adapted to supply working fluid to tank 1 and / or remove working fluid from each tank in order to transfer biochemical fluid to and / or from the tank.

[0238] The handling manipulators 13000, 13100, and 13200 may be equipped with a drive unit (not shown) that can be coupled to a tank actuator for driving pumps, agitators, etc., and / or for opening and closing valves.

[0239] Furthermore, the handling manipulators 13000, 13100, and 13200 may be configured to supply / hold biochemical media and / or working media to the tank. In particular, the biochemical media can be transferred to and / or from the tank using a working media such as pressurized air. Thus, the tank is operable via the working media. When transferring biochemical media from the tank, a positive pressure can be applied to the first tank 1 (e.g., by the handling manipulators 13000, 13100, and 13200) by applying the working media to the tank. Thus, the biochemical media is pushed out of tank 1, for example, toward a second tank 2 and / or filter.

[0240] To transfer the biochemical medium to the tank, a negative pressure can be established, for example, by removing or operating the medium from the tank, particularly by the handling manipulators 13000, 13100, and 13200. When pressurized air is used as the working medium, sterile pressurized air is preferably used. Sterile pressurized air can be obtained by directing the pressurized air to each sterile filter before it enters the tank.

[0241] A working medium, such as pressurized air, can be supplied to or removed from tank 1 using handling manipulators 13000, 13100, and 13200, through their respective gas inlet and / or outlet ports. The application of the medium to the tank and / or removal of the medium from the tank can be performed, for example, by pressure control, volume control, and / or mass control.

[0242] Furthermore, at least one handling manipulator, such as the handling manipulator 13200, may include a weighing member that enables weighing the tanks of the tank system. The weight of each tank can then be used to control the process line formed by the tanks.

[0243] The system may further include at least one cleanroom bag 8000 (shown by a dashed line in Figure 11). The cleanroom bag 8000 comprises at least one foil portion 8500. The cleanroom bag is configured to receive at least one tank 1. Also, when at least one tank 1 is received in the cleanroom bag, it provides the at least one tank 1 with a cleanroom environment 8000. The at least one tank 1 is accessible from outside the cleanroom bag 8000 using handling manipulators 13000, 13100, and 13200.

[0244] Furthermore, the system includes at least one adapter plate element 600. The adapter plate element 600 can be associated with and attached to at least one tank 1 such that one of at least one foil portion 8500 of the cleanroom bag 8000 is sandwiched between the access plate element 100 of the tank 1 and the adapter plate element 600.

[0245] The adapter plate element 600 is configured to define at least one access point (not shown) for providing access to the tank from outside the cleanroom bag 8000 via the access plate element 100. For example, the adapter plate element 600 is configured to at least partially cover the filter and / or the port of the tank 1.

[0246] The foil portion 8500 is provided in a removable and / or perforated manner in the area of ​​the tank's filter and / or port to provide access to the tank 1. The adapter plate element 600 may be further configured to support a valve actuator 152 (not shown).

[0247] As best shown in Figure 12, the cleanroom bag 8000 includes at least one support rail 8015 for guiding at least one accepted assembled tank within the cleanroom bag 8000. The support rail 8015 is adapted to support at least two tanks. When supported by the support rail 8015, the support rail 8015 engages with the upper plate element 100 of each tank 1 such that the upper plate elements 100 of tanks of different heights are positioned at the same level.

[0248] Furthermore, as shown in Figure 13, the support rail 8015 may be formed from a plurality of support rail sections 8015a, 8015b, and 8015c. These sections may be separated by a foil portion so that the cleanroom bag 8000 is foldable. In particular, the support rail sections 8015a, 8015b, and 8015c may be made from plastic material and may be injection molded. In certain embodiments, the foil portion 8500 and the support rail sections 8015a, 8015b, and 8015c may be fixed and bonded to each other (e.g., welded or glued), or even formed integrally. To increase the load-bearing capacity of the support rail sections 8015a, 8015b, and 8015c, these sections may include metal inserts.

[0249] Furthermore, the support rail sections 8015a, 8015b, and 8015c may be configured to receive corresponding support rails of a frame 7000, which may be part of a handling manipulator. The frame 7000 may include a corresponding rigid support rail 7015, such as a metal support rail. The support rail sections 8015a, 8015b, and 8015c can be formed to fit the corresponding support rail 7015 of the frame 7000. Furthermore, the support rail sections 8015a, 8015b, and 8015c may include latching devices 8020a and 8020b, which preferably snap-fit, to engage the support rail sections 8015a, 8015b, and 8015c with the corresponding support rail 7015 of the frame 7000.

[0250] The support rail may include a weighing member that can weigh each supported tank individually. The weight of each tank can then be used to control the process line formed by the tanks.

[0251] As shown in Figure 11, the support rail 8015 further supports the tank 1 in a suspended configuration, where the bottom plate element 300 does not come into contact with the ground. In addition to the suspension support for the upper plate element 100, a support member 8300 can be provided to support the tank 1 at the bottom plate element 300. The support member may be adapted to be height-adjustable by a linear drive, such as a magnetic drive, electric drive, pneumatic drive, and / or hydraulic drive. The support member may also include a weighing member that allows the weight of the supported tank to be measured. The weight of each tank can be used to control the process line.

[0252] The cleanroom bag 8000 may further include a sealable opening (not shown) configured to receive an assembled tank. When the cleanroom bag is sealed and coupled to the assembly room 9000, the sealable opening of the cleanroom bag is configured to open together with a corresponding sealable opening in the assembly room. Furthermore, the tank can be removed from the cleanroom bag using the sealable opening. The cleanroom bag may include multiple sealable openings. This facilitates the transfer of assembled tanks from the assembly room to the cleanroom bag, or their removal from the cleanroom bag.

[0253] Figure 14 schematically shows a flow diagram of method 2000 for assembling the tank. This method includes the following steps: providing an upper plate element 2100; providing at least one side wall element 2200; providing a bottom plate element 2300, assembling the upper and lower plate elements and at least one side wall element 2400, forming a reservoir for receiving at least one biochemical medium.

Claims

1. A reservoir element (200) for a tank (1) of a biopharmaceutical process line, wherein the reservoir element (200) includes the following: Main element (210) and It has at least one shell element (220, 222), The main element (210) has a first end (212) and a second end (214) opposite the first end, and each of the first and second ends includes an orifice where the main element tapers from the first end to the second end. The internal volume is defined between the first end and the second end. There, the main body element and / or at least one shell element includes at least one groove (216, 217), There, at least one shell element (220, 222) is fixedly attached to the main body element (210), and the main body element and at least one shell form at least one channel with a groove in between. At least one channel is adapted to guide at least one biochemical medium and / or working medium. The internal volume and the first orifice are configured such that the reservoir element (200) can at least partially accept a further reservoir element (200'), and as a result, multiple reservoir elements can be stacked on top of each other.

2. In the reservoir element (200) according to claim 1, The main body element has a polygonal cross-section in a plane parallel to the first end (212), where at least one shell element (220, 222) may be plate-shaped.

3. In the reservoir element (200) according to claim 1, The first end (212) and / or second end (214) of the reservoir element (200) include a sealing surface (215) for sealing and connecting the reservoir element to another reservoir element.

4. In the reservoir element (200) according to claim 1, The reservoir element (200) includes at least one of the following: ● At least one port (230). There, at least one port is associated with each channel. There, the port is selected from a group of port types, which include the following port types: 〇 Fluid inlet port 〇Gas inlet port 〇 Fluid outlet port 〇 Heating / cooling ports 〇Gas outlet port Cell bleed port ○ Cell transfer port Media supply port 〇 Media removal port Element interconnection ports 〇 Tank interconnection ports ● At least one filter. There, at least one port (230) may be covered by at least one filter. There, the filter may be selected from a group of filter types, including the following filter types: 〇 Pre-filter 〇 Sterile filter 〇 Bacteria filter Virus filter Mycoplasma filter Ultrafiltration filter ○ Diafiltration filter Cell filter Cell Harvest Filter Fluid filter Bioburden filter ○ Air filter, and 〇 Gas filter There, the filter covering at least one port may be heated and / or cooled.

5. In the reservoir element (200) according to claim 1, It comprises at least one assembly connection device (260), and / or at least one corresponding assembly connection device (262'), where The assembly connector (260) and the corresponding assembly connector (262') are configured to engage with each other to secure an assembly of at least two adjacent reservoir elements, where the assembly connector (260) and the corresponding assembly connector (262') engage.

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