Fluid coupling network for sample collection from bioreactors

Abstract

The present invention provides a computer-implemented method for controlling a fluid connection network (170), the fluid connection network (170) configured to be fluidly connectable to a bioreactor (110), a gas supply (120), a buffer supply (140), a waste port (150), a processing system (160), and a conduit reservoir (208), the fluid connection network (170) comprising a barrier unit (220) configured to sterilely separate flow paths within the fluid connection network (170), the fluid connection network (170) being controllable to sample from the bioreactor (110), the method comprising a step (510) of obtaining a fluid sample from the bioreactor (110) by drawing a conduit from the bioreactor (110) to fill the conduit reservoir (208) with fluid from the bioreactor (110). and a step (540) of returning a residual fluid sample to the bioreactor (110), the residual fluid sample being contained by a portion of the fluid connection network (170) separated by a barrier unit (220), the step (540) comprising controlling the flow of gas from the gas source (120) to the bioreactor (110) through the portion of the fluid connection network (170).

Description

Technical Field

[0004] , , , ,

[0003]

[0001] The present invention relates to a fluid connection network that is controllable for sampling from a bioreactor. The present invention further relates to a method, a barrier unit, a control unit, a computer program, and a computer program product.

Background Art

[0002] A bioreactor is typically a vessel in which a chemical process involving an organism or a biochemically active substance derived from such an organism is carried out. In the biotechnology industry, bioreactors that operate for long periods of time are sometimes used. Specifically, bioreactors are used in the biotechnology industry for growing organisms such as cells, bacteria, or fungi. Organisms can produce substances such as biopolymers (e.g., proteins) or various types of viruses / parts of viruses. In such bioreactors suitable for producing organisms or biochemically active substances, there is a need for periodic sampling of the fluid in the bioreactor. Therefore, it is important to avoid contamination and / or loss of sterility during such sampling. Put another way, it is necessary to avoid contamination of the container or the contained environment itself during sampling. Sampling is required, for example, to monitor and control the status and levels of nutrients required for cell growth.

[0003] Conventionally, sampling of a bioreactor could typically be performed manually by using a hypodermic needle that pierces through a membrane. Manual sampling can be a time-consuming and costly process, increasing the risk of contamination of the fluid in the bioreactor.

[0004] Some conventional systems include automated sampling of bioreactors, such as the sampling system described in Patent Document 1. However, this conventional method has the disadvantage of discarding a relatively large volume of fluid each time a fluid sample is obtained.

[0005] Therefore, there is a need for improved methods and fluid networks for bioreactor sampling. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] U.S. Patent Application Publication No. 2014 / 087413 [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The object of embodiments of the present invention is to provide solutions that mitigate or resolve the drawbacks and problems described above. [Means for solving the problem]

[0008] The above objectives are achieved by the subject matter described herein. Further advantageous embodiments of the invention are further defined herein.

[0009] According to a first aspect of the present invention, the above and other objectives are computer-implemented methods for controlling a fluid coupling network, wherein the fluid coupling network is configured to be fluidly coupled to a bioreactor, a gas source, a buffer source, a waste port, a processing system, and a conduit reservoir, the fluid coupling network comprises barrier units configured to aseptically separate flow paths within the fluid coupling network, the fluid coupling network is controllable for sampling from the bioreactor, the method comprising the steps of obtaining a fluid sample from the bioreactor, and filling a conduit reservoir with fluid from the bioreactor. This is achieved by a method comprising the steps of: controlling the flow of fluid from a bioreactor to a waste port via a conduit reservoir and a fluid coupling network; providing a fluid sample, which includes providing the fluid sample from the conduit reservoir to a processing system via a fluid coupling network; and returning a residual fluid sample to a bioreactor, wherein the residual fluid sample is contained by a portion of the fluid coupling network separated by a barrier unit, and the step of returning the residual fluid sample includes controlling the flow of gas from a gas source to the bioreactor via a portion of the fluid coupling network.

[0010] An advantage of the embodiment according to the first aspect is that the risk of contamination is reduced or minimized. A further advantage is that the required volume of fluid drawn from the bioreactor is reduced.

[0011] According to a second aspect of the present invention, the above and other objectives are to be achieved by a fluid coupling network configured to be fluidly coupling to a bioreactor, a gas supply source, a buffer supply source, a waste port, a processing system, and a conduit reservoir, wherein the fluid coupling network comprises a barrier unit configured to aseptically separate the flow path within the fluid coupling network, the fluid coupling network is controllable for sampling from the bioreactor, and the fluid coupling network is configured to obtain a fluid sample, wherein the fluid sample provides a flow path from the bioreactor to the waste port via the conduit reservoir in order to fill the conduit reservoir with fluid from the bioreactor. The system is configured to provide a fluid sample by enabling the flow of fluid from the bioreactor, the fluid sample being provided to the processing system by providing a channel from the conduit reservoir to the processing system, and to return the residual fluid sample to the bioreactor, the residual fluid sample being contained by a portion of a fluid coupling network separated by a barrier unit, the residual fluid sample being returned by providing a channel from the gas source to the bioreactor, the barrier unit is configured to separate a portion of the fluid coupling network in a sterile manner, the portion being achieved by a fluid coupling network having a channel that fluidly connects the bioreactor and the gas source.

[0012] According to a third aspect of the present invention, the above and other objectives are achieved by a barrier unit configured to sterilely separate flow paths in a fluid linkage network, the barrier unit sterilely separates a portion of the flow paths of the fluid linkage network from the rest of the flow paths of the fluid linkage network, the barrier unit operating in a first operating state allows fluid to flow from the portion of the fluid linkage network to the rest of the fluid linkage network, and the barrier unit operating in a second operating state prevents fluid from flowing from the portion of the fluid linkage network to the rest of the fluid linkage network.

[0013] According to a fourth aspect of the present invention, the above and other objectives are achieved by a control unit for a fluid coupling network that can control a bioreactor to sample, comprising a processing circuit configuration and a memory device that is executable by the processing circuit configuration and includes instructions causing the processing circuit configuration to carry out the method according to the first aspect.

[0014] According to a fifth aspect of the present invention, the above and other objectives are achieved by a computer program that includes computer-executable instructions causing a control unit to perform any of the steps of the method according to the first aspect, when performed in a processing circuit configuration included in the control unit.

[0015] According to a sixth aspect of the present invention, the above-mentioned and other objectives are achieved by a computer program product comprising a computer-readable storage medium on which a computer program according to the fifth aspect is embodied.

[0016] The advantages of the embodiments according to the second to sixth aspects are at least the same as those of the first aspect.

[0017] Further uses and advantages of embodiments of the present invention will become apparent from the following detailed description. [Brief explanation of the drawing]

[0018] [Figure 1] This is a diagram of a bioprocess system comprising a fluid coupling network according to one or more embodiments of the present disclosure. [Figure 2] This figure shows details of a fluid coupling network according to one or more embodiments of the present disclosure. [Figure 3] This figure shows the operating state of a controllable valve according to one or more embodiments of the present disclosure. [Figure 4] This is a diagram of a control unit according to one or more embodiments of the present disclosure. [Figure 5] This is a flowchart of a method according to one or more embodiments of the present disclosure. [Figure 6] FIG. of an embodiment of a barrier unit according to one or more embodiments of the present disclosure. [Figure 7] FIG. of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure. [Figure 8] FIG. of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure. [Figure 9] FIG. of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION

[0019] A more complete understanding of embodiments of the present invention and an understanding of additional advantages of the present invention are provided to those skilled in the art by considering the following detailed description of one or more embodiments. It should be understood that like reference numerals are used to identify like elements shown in one or more of the figures.

[0020] In this description and the corresponding claims, "or" is understood as the mathematical OR (logical sum) that encompasses both "and" and "or", and is not understood as XOR (exclusive logical sum). The indefinite article "a" in this description and the claims is not limited to one, and can also be understood as "one or more", that is, as plural.

[0021] In the present disclosure, "bioreactor" means a container / insert configured to perform a chemical process in a container, and the chemical process involves organisms or biochemically active substances derived from such organisms. Examples of bioreactors include disposable reactors (e.g., Cytiva WAVE / Xcellerex), stainless steel reactors. Examples of process modes used in bioreactors include perfusion culture, fed-batch culture, and batch culture.

[0022] In this disclosure, the term “fluid coupling network” typically refers to an arrangement for providing flow paths to and from a bioreactor, such as from a bioreactor to a bioprocess system or biological analysis system, such as a chromatograph.

[0023] In this disclosure, the term “flow path” means an assembly of components configured to transport fluid, such as a conduit fluidly connected to one or more fluid valves. A flow path typically comprises a fluid inlet and one or more conduits connecting a fluid outlet and any intermediate devices such as filters, ventilators, sensors, and valves.

[0024] In this disclosure, the term “gas source” means a configuration for supplying gas, such as a cylindrical canister of compressed air.

[0025] In this disclosure, the term “buffer source” means a configuration for providing a buffer fluid, such as a container and / or pump arranged to provide the buffer fluid. The buffer fluid may include, for example, phosphoric acid, acetate, tris, citrate, hepes, acetonitrile, methanol, formic acid, trifluoroacetic acid (TFA), salts, and / or additives (cleaning agents).

[0026] In this disclosure, the term “stationary clean supply source” or “CIP supply source” means a configuration for providing CIP fluid, such as a container and / or pump arranged to provide the CIP fluid. Examples of CIP fluids include oxidizing agents (NaClO, peracetic acid, H2O2), organic solvents (IPA, EtOH), acids (HNO3, HAc), bases (NAOH), and vapors.

[0027] In this disclosure, the terms “discard port” or simply “discard” mean a configuration for receiving fluid, such as a drain, inlet, or other receiving section. A discard port may include, for example, a valve or check valve that can be controlled / switched to an open / closed operating state.

[0028] In this disclosure, the term “processing system” means equipment for processing samples from a bioreactor, such as a group of instruments, a chromatography system, or a filtration unit.

[0029] In this disclosure, the term “conduit reservoir” means a configuration for holding a sample from a bioreactor, such as a looped conduit, container, tube, syringe, air trap, or superloop. A key feature of a “conduit reservoir” is that it is configured to allow cleaning by enabling fluid flow throughout the reservoir. By using reservoirs with substantially the same cross-sectional area, the entire reservoir is effectively cleaned. This is the case, for example, with Cytiva’s variable sample volume reservoir Superloop®. In other words, preferably, the “conduit” is a “looped conduit reservoir” through which a cleaning fluid can flow and clean the reservoir.

[0030] In this disclosure, the term “controllable valve” means a configuration or device configured to allow or prevent fluid from being received from the inlet to the outlet of the controllable valve. A controllable valve typically comprises a valve unit, an actuator unit, and control logic, the control logic which can accept a control signal and control the actuator unit to move the valve to an open operating state in which fluid is fully allowed to flow from the inlet to the outlet, a closed operating state in which fluid is prevented from flowing from the inlet to the outlet, or optionally, an intermediate operating state in which a reduced flow is allowed to flow from the inlet to the outlet. In all embodiments described herein, the change in the operating state of the controllable valve is made in response to an accepted control signal. In one example, the control unit sends a control signal to the controllable valve indicating a desired operating state.

[0031] As mentioned in the background technology section, conventional bioreactor sampling is time-consuming and can contaminate the processes within the bioreactor. Sampling typically allows for the measurement of fluid properties within the bioreactor, such as cell counts, oxygen levels, and pH levels.

[0032] This disclosure improves the sampling process by providing a controllable fluid coupling network and a method for controlling the fluid coupling network. A sample is obtained, held in a conduit reservoir, and then provided to a processing system, typically to determine the properties of the bioreactor fluid. Therefore, this disclosure reduces the impact of the sample by returning the residual fluid to the bioreactor, thereby reducing the volume of fluid removed from the bioreactor. Therefore, this disclosure prepares the controllable fluid coupling network for the next sampling by cleaning the controllable fluid coupling network.

[0033] Figure 1 shows a bioprocess system 100 comprising a fluid coupling network 170 according to one or more embodiments of the present disclosure. The fluid coupling network 170 is configured to be fluidly coupled to a bioreactor 110, a gas supply source 120, a buffer supply source 140, a waste port 150, a processing system or fluid sample handling system 160, and a conduit reservoir 208. The fluid coupling network 170 further comprises a barrier unit 220 configured to aseptically separate the flow paths within the fluid coupling network 170. The fluid coupling network 170 is controllable to collect samples from the bioreactor 110 or to provide fluid samples from the bioreactor 110.

[0034] The bioprocess system 100 is formed by fluidly connecting a fluid connection network 170 to a bioreactor 110, a gas supply source 120, a buffer supply source 140, a waste port 150, a processing system 160, and a conduit storage container 208. The bioprocess system 100 is further formed by communicating the fluid connection network 170 to a control unit CU.

[0035] In a typical sampling cycle of the bioreactor 110, the system 100 is configured to control the fluid coupling network 170 by a control unit CU to obtain a fluid sample from the bioreactor 110, and the step of obtaining the fluid sample includes controlling the flow of fluid from the bioreactor 110 to the conduit reservoir 208 and the waste port 150 via the fluid coupling network 170 in order to fill the conduit reservoir 208 with fluid from the bioreactor 110.

[0036] In other words, the fluid connection network 170 is configured / controlled to provide a flow path from the bioreactor 110 through the conduit reservoir 208 to a port connectable to the waste port 150. The conduit reservoir 208 can be a looped conduit, which may be selected / configured to have an inner diameter and / or length to contain a specific fluid sample volume required to measure / determine the properties of the fluid sample. The advantage of this is that the volume can be adapted by cutting the conduit, such as a tube, to a length that matches the required sample volume.

[0037] Therefore, the fluid connection network 170 is configured / controlled to provide a fluid sample. The fluid connection network 170 provides the fluid sample from the conduit reservoir 208 to the processing system 160 via the fluid connection network 170. In other words, the fluid connection network 170 is configured / controlled to provide a flow path from the conduit reservoir 208 to a port connectable to the processing system 160.

[0038] Therefore, the fluid coupling network 170 is configured / controlled to return the residual fluid sample to the bioreactor 110. The residual fluid sample is contained by a portion / first portion 1701 of the fluid coupling network 170 separated by a barrier unit 220. The step of returning the residual fluid sample includes controlling the flow of gas from the gas source 120 to the bioreactor 110 through the portion / first portion 1701 of the fluid coupling network 170. In other words, the fluid coupling network 170 is configured / controlled to provide a flow path from the gas source 120 to a port connectable to the bioreactor 110.

[0039] When supplying / transferring a fluid sample from the conduit reservoir 208, such areas of the flow path are filled with buffer fluid to ensure that the flow path does not contain / include undesirable fluids such as air.

[0040] In one embodiment, the fluid coupling network 170 is further configured / controlled to fill a certain area of ​​the fluid coupling network by controlling the flow of buffer fluid from the buffer source 140 to the processing system 160 via the fluid coupling network 170. In other words, the fluid coupling network 170 is configured / controlled to provide a flow path from the buffer source 140 to a port connectable to the processing system 160. This step prepares the fluid coupling network 170 for providing a fluid sample by ensuring that the flow paths in the area of ​​the fluid coupling network are filled with buffer fluid that is not an undesirable fluid such as air.

[0041] To ensure that the entire sample is supplied from the conduit reservoir 208, the conduit reservoir 208 can be rinsed using a buffer fluid in a further embodiment.

[0042] In one embodiment, the fluid coupling network 170 is configured / controlled to rinse the conduit reservoir 208 by controlling the flow of buffer fluid from the buffer source 140 to the conduit reservoir 208 and the processing system 160 via the fluid coupling network 170. In other words, the fluid coupling network 170 is configured / controlled to provide a flow path from the buffer source 140 to the processing system 160 via the conduit reservoir 208.

[0043] To prepare the fluid coupling network 170 for the next fluid sampling cycle, a cleaning fluid or a clean-in-place (CIP) fluid is allowed to flow through the fluid coupling network 170.

[0044] In one embodiment, the fluid coupling network 170 is further configured / controlled to be fluidically coupled to a clean-in-place (CIP) supply source 130. The fluid coupling network 170 is further configured / controlled to clean a certain area of ​​the fluid coupling network by controlling the flow of cleaning fluid from the CIP supply source 130 to the processing system 160 via the fluid coupling network 170. In other words, the fluid coupling network 170 is configured / controlled to provide a flow path from the CIP supply source 130 to the processing system 160.

[0045] In addition or alternatively, in one embodiment, the fluid coupling network 170 is further configured / controlled to clean the conduit reservoir 208 by controlling the flow of cleaning fluid from the CIP supply source 130 through the conduit reservoir 208 to the waste port 150.

[0046] In the exemplary embodiment, the disclosure in Figure 1 is carried out using controllable valves that are fluidly connected by using conduits or piping.

[0047] Figure 2 shows details of a fluid coupling network 170 according to one or more embodiments of the present disclosure. Figure 2 shows how a barrier unit 220 is configured to separate the fluid coupling network 170 into a portion / first portion 1701 and a remaining portion / second portion 1702. The (first) portion comprises a flow path that fluidly connects the bioreactor 110 and the gas supply source 120, and the remaining (second) portion comprises the remaining flow path of the fluid coupling network 170.

[0048] The fluid coupling network 170 is configured to be fluidically connectable to the bioreactor 110, gas supply source 120, buffer supply source 140, waste port 150, processing system 160, and conduit reservoir 208. The fluid coupling network 170 further comprises a barrier unit 220 configured to isolate the flow path in a sterile manner within the fluid coupling network 170. The barrier unit 220 is further described in relation to Figures 6 to 9. The fluid coupling network 170 is controllable to take a sample from the bioreactor 110. The fluid coupling network 170 is configured to obtain a fluid sample, which is obtained by enabling the flow of fluid from the bioreactor 110 by providing a flow path from the bioreactor 110 to the waste port 150 via the conduit reservoir 208 in order to fill the conduit reservoir 208 with fluid from the bioreactor 110.

[0049] The fluid connection network 170 is configured to provide a fluid sample, which is supplied to the processing system 160 by providing a flow path from the conduit reservoir 208 to the processing system 160.

[0050] The fluid coupling network 170 is configured to return the residual fluid sample to the bioreactor 110, and the residual fluid sample is contained by a portion / first portion 1701 of the fluid coupling network 170 separated by a barrier unit 220. The residual fluid sample is returned by providing a channel from the gas supply source 120 to the bioreactor 110.

[0051] The barrier unit 220 is configured to isolate a portion of the fluid connection network 170 in a sterile state, and the portion includes a flow path that fluidly connects the bioreactor 110 and the gas supply source 120.

[0052] In one or more embodiments, the fluid coupling network 170 includes a first controllable valve 201 that is fluidically coupled to a first port IP1 connectable to the bioreactor 110 and configured to allow or prevent fluid from flowing between the bioreactor 110 and the fluid coupling network 170.

[0053] The fluid coupling network 170 includes a second controllable valve 206 that is fluidically coupled to the outlet of a first controllable valve 201 and the inlet of a conduit reservoir 208, and is configured to allow or prevent fluid received from either of the first controllable valves 201 from flowing into the conduit reservoir 208. Optionally, the fluid coupling network 170 further includes a controllable valve 203 that is fluidly coupled between the first controllable valve 201 and the second controllable valve 206.

[0054] The fluid coupling network 170 further comprises a third controllable valve 207 that is fluidically coupled to the outlet of the conduit reservoir 208 and configured to allow or prevent fluid from flowing out of the conduit reservoir 208.

[0055] The fluid coupling network 170 is fluidically coupled to the outlet of a third controllable valve 207 and a port OP1 connectable to a waste port 150, and includes a fourth controllable valve 209 configured to allow or prevent fluid from flowing from the outlet of the third controllable valve 207 to the waste port 150. The fluid coupling network 170 is controlled to obtain a fluid sample and provide a flow path by controlling the first controllable valve 201, the second controllable valve 206, the third controllable valve 207, and the fourth controllable valve 209 to an open state that allows fluid to flow. In other words, the fluid coupling network 170 is controlled to provide a flow path from a first port IP1 connectable to a bioreactor 110 to a port OP1 connectable to a waste port 150.

[0056] In addition or alternatively, the fluid coupling network 170 includes a fifth controllable valve 205 that is fluidically connected to a second port IP2 connectable to a buffer supply source 140 and configured to allow or prevent fluid from flowing from the buffer supply source 140 to the fluid coupling network 170. In this embodiment, the fluid coupling network 170 further includes a sixth controllable valve 210 that is fluidically connected to the outlet of a third controllable valve 207 and to a port OP2 connectable to a processing system 160 and configured to allow or prevent fluid from flowing to the processing system 160. In this embodiment, the fluid coupling network 170 is controlled to provide a fluid sample and a flow path by controlling the second controllable valve 206, the third controllable valve 207, the fifth controllable valve 205, and the sixth controllable valve 210 to an open state that allows fluid to flow, and by controlling the first controllable valve 201 and the fourth controllable valve 209 to a closed state that prevents fluid from flowing.

[0057] In addition or alternatively, the fluid coupling network 170 further comprises a seventh controllable valve 202, which is fluidically coupled to a third port IP3 connectable to a gas source 120 and configured to allow or prevent gas from flowing from the gas source 120 to a portion of the fluid coupling network 170. In this embodiment, the fluid coupling network 170 is controlled to return the residual fluid sample to the bioreactor 110 and to provide a flow path by controlling the first controllable valve 201 and the seventh controllable valve 202 to an open state that allows fluid to flow, and by controlling the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, the fifth controllable valve 205, and the sixth controllable valve 210 to a closed state that prevents fluid from flowing.

[0058] In addition or alternatively, the fluid coupling network 170 further comprises an eighth controllable valve 211, which is fluidically coupled to the inlet of a second controllable valve 206 and the outlet of a third controllable valve 207 and configured to allow or prevent fluid from flowing between the inlet of the second controllable valve 206 and the outlet of the third controllable valve 207. In this embodiment, the fluid coupling network 170 is configured to fill a certain area of ​​the fluid coupling network and provide a flow path by controlling the fifth controllable valve 205, the sixth controllable valve 210, and the eighth controllable valve 211 to an open operating state that allows fluid to flow, and by controlling the first controllable valve 201, the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, and the seventh controllable valve 202 to a closed operating state that prevents fluid from flowing.

[0059] In addition or alternatively, the fluid coupling network 170 is configured to rinse the conduit reservoir 208 and provide a flow path by controlling the second controllable valve 206, the third controllable valve 207, the fifth controllable valve 205, and the sixth controllable valve 210 to an open state that allows fluid to flow, and by controlling the first controllable valve 201, the fourth controllable valve 209, the seventh controllable valve 202, and the eighth controllable valve 211 to a closed state that prevents fluid from flowing.

[0060] In addition or alternatively, the fluid coupling network 170 further comprises a ninth controllable valve 204 fluidly coupled to a fourth port IP4 connectable to a clean-in-place (CIP) supply source 130. In this embodiment, the fluid coupling network 170 is configured to clean areas of the fluid coupling network and provide pathways by controlling the sixth controllable valve 210, the eighth controllable valve 211, and the ninth controllable valve 204 to an open state that allows fluid to flow, and by controlling the first controllable valve 201, the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, the fifth controllable valve 205, and the seventh controllable valve 202 to a closed state that prevents fluid from flowing.

[0061] In addition or alternatively, the fluid coupling network 170 is configured to flush the conduit reservoir 208 and provide a flow path by controlling the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, and the ninth controllable valve 204 to an open state that allows fluid to flow, and by controlling the first controllable valve 201, the fifth controllable valve 205, the sixth controllable valve 210, the seventh controllable valve 202, and the eighth controllable valve 211 to a closed state that prevents fluid from flowing.

[0062] In one embodiment, the fluid coupling network 170 may be provided with a housing, or it may be arranged as an integrated unit.

[0063] In one embodiment, the fluid coupling network 170 may be provided as an assembly of components such as a floating valve and a conduit.

[0064] Figure 3 shows the operating states of controllable valves according to one or more embodiments of the present disclosure. Controllable valves in the open operating state are indicated by blank circles, and controllable valves in the closed operating state are indicated by circles marked with an "X".

[0065] During the step of obtaining the sample, the first controllable valve 201, the second controllable valve 206, the third controllable valve 207, and the fourth controllable valve 209 are controlled to the open state. The remaining controllable valves are controlled to the closed state.

[0066] During the step of providing the sample, the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, and the fifth controllable valve 205 are controlled to the open state.

[0067] During the step of returning the residual fluid sample, the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, and the fifth controllable valve 205 are controlled to the open state, and the first controllable valve 201 and the seventh controllable valve 202 are controlled to the open state. The remaining controllable valves are controlled to the closed state.

[0068] During the step of filling an area of ​​the fluid coupling network, the fifth controllable valve 205, the sixth controllable valve 210, and the eighth controllable valve 211 are controlled to the open state. The remaining controllable valves are controlled to the closed state.

[0069] During the rinsing step of the reservoir 208, the second controllable valve 206, the third controllable valve 207, the fifth controllable valve 205, and the sixth controllable valve 210 are controlled to the open position. The remaining controllable valves are controlled to the closed position.

[0070] During the cleaning step of the reservoir, the second controllable valve 206, the third controllable valve 207, the fourth controllable valve 209, and the ninth controllable valve 204 are controlled to the open position. The remaining controllable valves are controlled to the closed position.

[0071] During the cleaning step of the area, the sixth controllable valve 210, the eighth controllable valve 211, and the ninth controllable valve 204 are controlled to the open position. The remaining controllable valves are controlled to the closed position.

[0072] Figure 4 shows a control unit CU according to one or more embodiments of the present disclosure. The control unit CU may take the form of a computer, such as an electronic control unit, server, built-in control unit, stationary computing device, laptop control unit, tablet control unit, portable control unit, wrist-worn control unit, smartwatch, smartphone, or smart TV. The control unit CU may include a processing circuit configuration 412 that is communicatively connected to a communication interface, such as a transceiver 404 configured for wired or wireless communication. The control unit CU may further include at least one optional antenna (not shown in the figure). The antenna can be connected to the transceiver 404 and is configured to transmit, send, and / or receive wired or wireless signals in a communication network such as Wi-Fi®, Bluetooth®, 3G, 4G, or 5G. In one example, the processing circuit configuration 412 may be a processing unit, a central processing unit, a processing unit module, and / or a selection of a plurality of processing units configured to cooperate with one another. Furthermore, the control unit CU may further comprise a storage device 415 that is communicatively connected to the processing circuit configuration 412. The storage device 415 may include, for example, hard RAM, disk drives, floppy disk drives, flash drives, other removable or fixed media drives, or any other suitable storage device known in the technical sense. The storage device 415 may include instructions that can be executed by the processing circuit configuration to carry out any step or method described herein. The processing circuit configuration 412 may be communicatively connected to either the transceiver 404 or the storage device 415. The control unit CU may be configured to transmit / receive control signals directly to / from any of the above units or to an external node, or to transmit / receive control signals via a wired and / or wireless communication network.

[0073] The wired / wireless transceiver 404 and / or wired / wireless communication interface may be configured to transmit and / or receive data values ​​or parameters to, from, the processing circuit configuration 412, or other external nodes.

[0074] In this embodiment, the transceiver 404 communicates with an external node either directly or via a wireless communication network.

[0075] In one or more embodiments, the control unit CU may further include an input device 417 configured to receive inputs or instructions from a user and to transmit user input signals indicating user inputs or instructions to a processing circuit configuration 412.

[0076] In one or more embodiments, the control unit CU may further include a display device 418 configured to receive a display signal from the processing circuit configuration 412 indicating a provided object, such as a user input object of characters or graphics, and to display the received signal as an object, such as a user input object of characters or graphics.

[0077] In one embodiment, the display device 418 is integrated with the user input device 417 and is configured to receive a display signal from the processing circuit configuration 412 indicating a provided object, such as a user input object of characters or a graphic, and to display the received signal as an object, such as a user input object of characters or a graphic; and / or to receive input or instructions from the user and to transmit a user input signal indicating the user's input or instructions to the processing circuit configuration 412.

[0078] In further embodiments, the control unit CU may further comprise and / or be further coupled to one or more additional sensors (not shown in the figure) configured to receive, obtain, and / or measure physical characteristics associated with the bioprocess system 100, and to transmit one or more sensor signals indicating the physical characteristics to the processing circuit configuration 412. An example of such additional sensors may be an ambient air pressure sensor configured to measure the ambient air pressure in which the bioprocess system 100 is positioned.

[0079] In one or more embodiments, the processing circuit configuration 412 is further connected to communicate with an input device 417, a display device 418, and / or additional sensors.

[0080] In the embodiment, the communication network includes Local Area Network (LAN), Metropolitan Area Network (MAN), Global System for Mobile Network (GSM), Enhanced Data GSM Environment (EDGE), Universal Mobile Communication System, Long Term Evolution, High Speed ​​Downlink Packet Access (HSDPA), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TDMA), Bluetooth®, Zigbee®, Wi-Fi®, Voice over Internet Protocol (VoIP), LTE Advanced, IEEE 802.16m, WirelessMAN-Advanced, Evolved High-Speed ​​Packet Access (HSPA+), 3GPP® Long Term Evolution (LTE), Mobile WiMAX (IEEE 802.16e), Ultra Mobile Broadband (UMB) (formerly Evolution-Data Optimized (EV-DO) Rev. C), and Fast Low-latency Access with Seamless Handoff. Using wired or wireless communication technologies, including, but not limited to, at least one of the following: Orthogonal Frequency Division Multiplexing (Flash-OFDM), Massive Spatial Division Multiple Access (iBurst®), and Mobile Broadband Wireless Connectivity (MBWA) (IEEE 802.20) systems, High Performance Wireless Metropolitan Area Network (HIPERMAN), Beam Division Multiple Access (BDMA), Microwave Access (Wi-MAX), and World Interoperability for Ultrasonic Communications.

[0081] Furthermore, it will be understood by those skilled in the art that the control unit CU may be equipped with the necessary communication capabilities, for example, in the form of functions, means, units, and elements, for implementing the present solution. Other examples of such means, units, elements, and functions include processing units, memory devices, buffers, control logic, encoders, decoders, rate matching circuits, derate matching circuits, mapping units, multipliers, decision units, selection units, switches, interleavers, deinterleavers, modulators, demodulators, inputs, outputs, antennas, amplifiers, receiver units, transmitter units, DSPs, MSDs, TCM encoders, TCM decoders, power supply units, power supply units, communication interfaces, communication protocols, etc., which can be appropriately arranged together to implement the present solution.

[0082] In particular, the processing circuit configurations of the present disclosure may comprise one or more examples of processing units, a plurality of processor modules and a plurality of processing units configured to cooperate with one another, a central processing unit (CPU), a processing unit, a processing circuit, a processing unit, an application-specific integrated circuit (ASIC), a microprocessor, a field-programmable gate array (FPGA), or other processing logic capable of interpreting and executing instructions. Accordingly, the expressions “processing circuit configuration” and / or “processing means” may refer to a processing circuit configuration comprising a plurality of processing circuits, including any, some, or all of those described above. The processing means may further implement data processing functions for data input, output, and processing, including data buffering and device control functions, such as call processing control or user interface control.

[0083] Figure 5 shows a flowchart of Method 500 according to one or more embodiments of the present disclosure. The Method can be carried out by a fluid coupling network controlled by a control unit CU and includes the following steps:

[0084] Step 510 is the step of obtaining a fluid sample from the bioreactor 110. In one embodiment, the step of obtaining a fluid sample includes controlling the flow of fluid from the bioreactor 110 to the waste port 150 via the conduit reservoir 208 and the fluid coupling network 170 in order to fill the conduit reservoir 208 with fluid from the bioreactor 110.

[0085] Step 530 is a step of providing a fluid sample, which includes providing the fluid sample from the conduit reservoir 208 to the processing system 160 via the fluid connection network 170.

[0086] Step 540 is the step of returning the residual fluid sample to the bioreactor 110. In one embodiment, the residual fluid sample is contained by a portion of the fluid coupling network 170 separated by a barrier unit 220, and the step of returning the residual fluid sample includes controlling the flow of gas from the gas supply source 120 to the bioreactor 110 through the portion of the fluid coupling network 170.

[0087] To prepare for the step of providing a fluid sample, the region of the flow path included by the fluid coupling network 170 is filled with buffer fluid.

[0088] In one or more embodiments, the method further includes step 520 of filling a region of the fluid-connecting network by controlling the flow of buffer fluid from a buffer source 140 to a processing system 160 via the fluid-connecting network 170.

[0089] After the fluid sample is provided to the processing system 160, the conduit reservoir 208 is rinsed to draw out all of the fluid sample.

[0090] In one or more embodiments, the method further includes the step 550 of rinsing the conduit reservoir 208 by controlling the flow of buffer fluid from the buffer source 140 to the conduit reservoir 208 and the processing system 160 via the fluid connection network 170.

[0091] To prepare the fluid coupling network 170 for the next sample collection cycle, the area containing the fluid coupling network 170 is cleaned.

[0092] In one or more embodiments, the fluid coupling network 170 is further configured to be fluidically coupled to a clean-in-place (CIP) supply source 130, and the method further includes the step of cleaning an area of ​​the fluid coupling network by controlling the flow of cleaning fluid from the CIP supply source 130 to a processing system 160 through the fluid coupling network 170 560.

[0093] To prepare the fluid coupling network 170 for the next sampling cycle, the conduit reservoir 208 and the associated flow paths of the fluid coupling network 170 are cleaned.

[0094] In one or more embodiments, the fluid coupling network 170 is further configured to be fluidly coupled to a clean-in-place (CIP) supply source 130, and the method further includes the step of cleaning the conduit reservoir 208 by controlling the flow of cleaning fluid from the CIP supply source 130 to the conduit reservoir 208 and the waste port 150 via the fluid coupling network 170.

[0095] As previously mentioned, the barrier unit 220 is configured to separate the flow path in the fluid coupling network 170 in a sterile manner. Specifically, it separates the flow path of the fluid coupling network 170 into a portion / first portion 1701 and the remaining portion / second portion 1702. In other words, the barrier unit 220 ensures that fluids that are not likely to be contaminated are returned to the bioreactor 110 and thereby do not interfere with the chemical process. Various embodiments of the barrier unit 220 are shown in Figures 6 to 9.

[0096] Figure 6 shows an embodiment of a barrier unit 220 according to one or more embodiments of the present disclosure. In one embodiment, the barrier unit 220 comprises at least two series-connected valves 601, 602 which are operated in a continuous manner when transitioning between an open state and a closed state. The transition of the valves between the open state and the closed state is time-controlled such that the last valve 602 is always closed before valve 601 is opened, and the last valve 602 is always open after valve 601 is opened. This creates a kind of "fluid lock" that ensures unidirectional flow from the bioreactor so that any contamination of the bioreactor originating from the rest of the bioreactor is avoided.

[0097] In one or more embodiments, a barrier unit 220 is provided which is configured to sterilely separate a flow path within a fluid linkage network 170. The barrier unit 220 sterilely separates the flow path of a portion / first portion 1701 of the fluid linkage network 170 from the flow path of the remaining portion / second portion 1702 of the fluid linkage network 170. When operating in a first operating state, the barrier unit 220 allows fluid to flow from the portion / first portion 1701 of the fluid linkage network 170 to the remaining portion / second portion 1702 of the fluid linkage network 170. When operating in a second operating state, the barrier unit 220 prevents the flow of fluid from the portion / first portion 1701 of the fluid linkage network 170 to the remaining portion / second portion 1702 of the fluid linkage network 170.

[0098] In one or more embodiments, the barrier unit 220 further comprises a tenth controllable valve 601 that is fluidly connectable to a fluid connection network 170. The barrier unit 220 further comprises an eleventh controllable valve 602 that is fluidly connectable to the fluid connection network 170. The tenth controllable valve 601 and the eleventh controllable valve 602 are configured to be controlled to an open state when the barrier unit 220 is operating in a first operating state. The tenth controllable valve 601 is configured to be controlled to an open state before the eleventh controllable valve 602 is controlled to an open state. Alternatively, the tenth controllable valve 601 and the eleventh controllable valve 602 are configured to be controlled to a closed state when the barrier unit 220 is operating in a second operating state. The tenth controllable valve 601 is configured to be controlled to a closed state after the eleventh controllable valve 602 is controlled to a closed state. The flow path 604 typically fluidly connects the outlet of the 11th controllable valve 602 to the rest of the fluid coupling network 170 / second portion 1702.

[0099] In other words, the continuous control of the 10th controllable valve 601 and the 11th controllable valve 602 ensures that any fluid pressure originating from a portion of the fluid coupling network 170 / first portion 1701 is applied to the fluid in the flow path between the 10th controllable valve 601 and the 11th controllable valve 602 before any fluid pressure originating from the rest of the fluid coupling network 170 / second portion 1702. This ensures that the fluid flow is maintained in one direction, from the bioreactor to the rest of the fluid coupling network 170 / second portion 1702.

[0100] In one embodiment, a flow sensor (not shown) is positioned in the flow path between a tenth controllable valve 601 and an eleventh controllable valve 602. The flow sensor is configured to detect backflow / flow from the eleventh controllable valve 602 toward the tenth controllable valve 601 and to transmit a control signal to a control unit CU. The control unit CU can then activate visual or auditory instructions to the user of the system 100.

[0101] To further reduce the risk of contamination, some of the flow paths 604 may be exposed to radiation from a radiation source.

[0102] Figure 7 shows further embodiments of the barrier unit 220 according to one or more embodiments of the present disclosure.

[0103] In this embodiment, the barrier unit 220 further comprises a radiation source 603 configured to irradiate the interior of the flow path 604 of the barrier unit 220 with radiation to sterilize the flow path. An example of a radiation source is an ultraviolet UV light source, such as a UV lamp or light-emitting diode that emits UV light. The flow path 604 typically fluidly connects the outlet of an eleventh controllable valve 602 to the rest of the fluid coupling network 170 / second part 1702.

[0104] To further reduce the risk of contamination, some flow paths may receive additional negative pressure from a vacuum source 605. Examples of vacuum sources 605 include vacuum pumps, ejectors, or vacuum tanks.

[0105] Figure 8 shows further embodiments of the barrier unit 220 according to one or more embodiments of the present disclosure.

[0106] In this embodiment, the barrier unit 220 further comprises a vacuum source 605 that is fluidically connected to a flow path 604 included by the barrier unit 220 and configured to receive fluid from the flow path 604. The flow path 604 typically fluidly connects the outlet of an eleventh controllable valve 602 to the rest of the fluid connection network 170 / second portion 1702.

[0107] To further reduce the risk of contamination, a constant flow of buffer fluid is maintained in certain channels.

[0108] Figure 9 shows further embodiments of the barrier unit 220 according to one or more embodiments of the present disclosure.

[0109] In this embodiment, the barrier unit 220 according to any of the prior claims further comprises a 12th controllable valve 606 that is fluidly connectable to a buffer supply source 140 and a 13th controllable valve 607 that is fluidly connectable to a waste port 150. The 12th controllable valve 606 and the 13th controllable valve 607 are configured to be controlled to an open state when the barrier unit 220 is operating in a first operating state. Alternatively, the 12th controllable valve 606 and the 13th controllable valve 607 are configured to be controlled to a closed state when the barrier unit 220 is operating in a second operating state.

[0110] It is understood that all embodiments described in Figures 6 to 9 can be combined in any combination without departing from the present disclosure.

[0111] In all embodiments shown in Figures 6 to 9, the barrier unit 220 changes between a first operating state and a second operating state in response to the received control signal.

[0112] Finally, it should be understood that the present invention is not limited to the embodiments described above, but incorporates all embodiments within the scope of the appended independent claims. [Explanation of Symbols]

[0113] 100 Bioprocess Systems 110 Bioreactor 120 gas supply sources 130 Stationary Cleaning (CIP) Supply Source 140 Buffer Source 150 Discard Ports 160 Processing Systems, Fluid Sample Processing Systems 170 Fluid Coupling Network 1701 Part / First Part 1702 The Remaining Part / Part 2 201 First controllable valve 202 The seventh controllable valve 203 Controllable valve 205 Fifth controllable valve 206 Second controllable valve 207 Third controllable valve 208 Conduit storage 209 Fourth controllable valve 210 Sixth controllable valve 211 The eighth controllable valve 220 Barrier Units 404 Transceiver 412 Processing Circuit Configuration 415 Storage device 417 User Input Devices 418 Display device 601 Tenth controllable valve 602 Eleventh controllable valve 603 Radiation source 604 Flow channel 605 Vacuum Generator 606 The 12th controllable valve 607 13th controllable valve CU Control Unit IP1 Port 1 IP2 second port IP3 third port IP4 fourth port OP1 port OP2 port

Claims

1. A computer-implemented method for controlling a fluid coupling network (170), wherein the fluid coupling network (170) is configured to be fluidly coupled to a bioreactor (110), a gas supply source (120), a buffer supply source (140), a waste port (150), a processing system (160), and a conduit reservoir (208), the fluid coupling network (170) comprises a barrier unit (220) configured to aseptically separate the flow path within the fluid coupling network (170), the fluid coupling network (170) is controllable for sampling from the bioreactor (110), and the method is: Step (510) of obtaining a fluid sample from the bioreactor (110), which includes controlling the flow of fluid from the bioreactor (110) to the waste port (150) via the conduit reservoir (208) and the fluid connection network (170) in order to fill the conduit reservoir (208) with the fluid sample from the bioreactor (110), Step (530) of providing the fluid sample, which includes providing the fluid sample from the conduit reservoir (208) to the processing system (160) via the fluid connection network (170), Step (540) of returning the residual fluid sample to the bioreactor (110), wherein the residual fluid sample is contained by a portion of the fluid coupling network (170) separated by the barrier unit (220), and the step of returning the residual fluid sample includes controlling the flow of gas from the gas supply source (120) to the bioreactor (110) through the portion of the fluid coupling network (170), A computer-based method, including.

2. The method according to claim 1, further comprising the step (520) of controlling the flow of buffer fluid from the buffer source (140) to the processing system (160) via the fluid connection network (170) to fill a certain area of ​​the fluid connection network.

3. The method according to claim 1 or 2, further comprising the step (550) of rinsing the conduit reservoir (208) by controlling the flow of buffer fluid from the buffer source (140) to the processing system (160) via the conduit reservoir (208) and the fluid connection network (170).

4. The fluid connection network (170) is further configured to be fluidly connectable to a clean-in-place (CIP) supply source (130), and the method is The method according to any one of claims 1 to 3, further comprising the step of cleaning an area of ​​the fluid-connecting network by controlling (560) the flow of cleaning fluid from the stationary cleaning (CIP) supply source (130) to the processing system (160) via the fluid-connecting network (170).

5. The fluid connection network (170) is further configured to be fluidly connectable to a clean-in-place (CIP) supply source (130), and the method is The method according to any one of claims 1 to 4, further comprising the step of cleaning the conduit reservoir (208) by controlling (570) the flow of cleaning fluid from the stationary cleanup (CIP) supply source (130) to the conduit reservoir (208) and the waste port (150) via the fluid connection network (170).

6. A fluid connection network (170) is configured to be fluidly connectable to a bioreactor (110), a gas supply source (120), a buffer supply source (140), a waste port (150), a processing system (160), and a conduit storage container (208), the fluid connection network (170) comprises a barrier unit (220) configured to separate the flow path in a sterile manner within the fluid connection network (170), and the fluid connection network (170) is controllable for sampling from the bioreactor (110). The fluid connection network (170) is configured to obtain a fluid sample, which is obtained by enabling the flow of fluid from the bioreactor (110) by providing a flow path from the bioreactor (110) to the waste port (150) via the conduit reservoir (208) in order to fill the conduit reservoir (208) with fluid from the bioreactor (110). The fluid connection network (170) is configured to provide the fluid sample, and the fluid sample is provided to the processing system (160) by providing a flow path from the conduit reservoir (208) to the processing system (160), and The fluid coupling network (170) is configured to return the residual fluid sample to the bioreactor (110), the residual fluid sample is included by a portion of the fluid coupling network (170) separated by the barrier unit (220), and the residual fluid sample is returned by providing a flow path from the gas supply source (120) to the bioreactor (110). The barrier unit (220) is configured to separate a portion of the fluid coupling network (170) in a sterile state, and the portion of the fluid coupling network (170) includes a flow path that fluidly connects the bioreactor (110) and the gas supply source (120).

7. A first controllable valve (201) is fluidically connected to a first port (IP1) connectable to the bioreactor (110) and configured to allow or prevent fluid from flowing between the bioreactor (110) and the fluid connection network (170), A second controllable valve (206) is fluidically connected to the outlet of the first controllable valve (201) and the inlet of the conduit reservoir (208), and is configured to allow or prevent fluid received from either of the first controllable valves (201) from flowing into the conduit reservoir (208), A third controllable valve (207) is fluidically connected to the outlet of the conduit reservoir (208) and configured to allow or prevent fluid from flowing out of the conduit reservoir (208), A fourth controllable valve (209) is fluidically connected to the outlet of the third controllable valve (207) and the waste port (150), and is configured to allow or prevent fluid from flowing from the outlet of the third controllable valve (207) to the waste port (150), Furthermore, The fluid coupling network (170) according to claim 6, wherein the fluid coupling network (170) is controlled to obtain a fluid sample and provide a flow path by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), and the fourth controllable valve (209) to an open state that allows fluid to flow.

8. A fifth controllable valve (205) is fluidly connected to a second port (IP2) connectable to the buffer supply source (140) and configured to allow or prevent fluid from flowing from the buffer supply source (140) to the fluid connection network (170), A sixth controllable valve (210) is fluidically connected to the outlet of the third controllable valve (207) and to a port (OP2) connectable to the processing system (160), and is configured to allow or prevent fluid from flowing to the processing system (160), Furthermore, The fluid coupling network (170) is controlled to provide the fluid sample and the flow path by controlling the second controllable valve (206), the third controllable valve (207), the fifth controllable valve (205), and the sixth controllable valve (210) to an open state that allows fluid to flow, and by controlling the first controllable valve (201) and the fourth controllable valve (209) to a closed state that prevents fluid from flowing. The fluid coupling network (170) according to claim 7.

9. The system further comprises a seventh controllable valve (202) which is fluidly connected to a third port (IP3) connectable to a gas supply source (120) and configured to allow or prevent gas from flowing from the gas supply source (120) to the portion of the fluid connection network (170), The fluid coupling network (170) is controlled to return the residual fluid sample to the bioreactor (110) and to provide a flow path by controlling the first controllable valve (201) and the seventh controllable valve (202) to an open state that allows fluid to flow, and by controlling the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), the fifth controllable valve (205), and the sixth controllable valve (210) to a closed state that prevents fluid from flowing, according to claim 8.

10. The system further comprises an eighth controllable valve (211) which is fluidically connected to the inlet of the second controllable valve (206) and the outlet of the third controllable valve (207), and is configured to allow or prevent fluid from flowing between the inlet of the second controllable valve (206) and the outlet of the third controllable valve (207), The fluid coupling network (170) is configured to fill a certain area of ​​the fluid coupling network (520) and provide a flow path by controlling the fifth controllable valve (205), the sixth controllable valve (210), and the eighth controllable valve (211) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), and the seventh controllable valve (202) to a closed state that prevents fluid from flowing, as described in claim 9.

11. The fluid coupling network (170) is configured to rinse the conduit reservoir (208) and provide a flow path by controlling the second controllable valve (206), the third controllable valve (207), the fifth controllable valve (205), and the sixth controllable valve (210) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the fourth controllable valve (209), the seventh controllable valve (202), and the eighth controllable valve (211) to a closed state that prevents fluid from flowing, according to claim 10.

12. The system further comprises a ninth controllable valve (204) which is fluidly connected to a fourth port (IP4) that can be connected to a CIP (Cleaning Intensive Care) supply source (130), The fluid coupling network (170) is configured to clean the area of ​​the fluid coupling network and provide a flow path by controlling the sixth controllable valve (210), the eighth controllable valve (211), and the ninth controllable valve (204) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), the fifth controllable valve (205), and the seventh controllable valve (202) to a closed state that prevents fluid from flowing, as described in claim 10.

13. The fluid coupling network (170) is configured to clean the conduit reservoir (208) and provide a flow path by controlling the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), and the ninth controllable valve (204) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the fifth controllable valve (205), the sixth controllable valve (210), the seventh controllable valve (202), and the eighth controllable valve (211) to a closed state that prevents fluid from flowing, as described in claim 10.

14. A control unit (CU) for a fluid coupling network (170) that can control a bioreactor (110) to take samples, Processing circuit configuration (412), A storage device (415) includes an instruction that can be executed by the processing circuit configuration (412), which causes the processing circuit configuration (412) to perform the method described in any one of claims 1 to 5, A control unit (CU) equipped with this.

15. A computer program comprising a computer executable instruction, which, when executed in a processing circuit configuration (412) included in a control unit (CU), causes the control unit to perform any of the steps of the method according to any one of claims 1 to 5.

16. A computer program product comprising a computer-readable storage medium on which the computer program described in claim 15 is embodied.

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