System and method for automated feeding a bioreactor
The automated bioreactor feeding system addresses the inefficiencies of manual and complex feeding systems by using a positive displacement pump and controller to supply materials with high precision, improving accuracy and efficiency.
Patent Information
- Application Number
- PCT/CN2023/113381
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-08-16
- Publication Date
- 2025-02-20
AI Technical Summary
Existing bioreactor feeding systems are labor-intensive and complex, often requiring manual dosage and intermediate vessels, which can lead to inaccuracies and inefficiencies in material supply.
A system comprising a supply bottle, a pipeline, a positive displacement pump, a stop valve, and a controller that automatically controls the material supply to the bioreactor with high precision, eliminating the need for intermediate vessels and manual intervention.
The system enables precise and automated feeding of bioreactors, improving dosage accuracy and reducing material residue, thus enhancing the efficiency and reliability of bioreactor operations.
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Figure CN2023113381_20022025_PF_FP_ABST
Abstract
Description
SYSTEM AND METHOD FOR AUTOMATED FEEDING A BIOREACTORFIELD
[0001] Embodiments of the present disclosure generally relate to industrial bioreactor feeding.BACKGROUND
[0002] Bioreactors are widely used in industrial processes and are used to produce pharmaceuticals, vaccines, antibodies, and the like. The bioreactor include a vessel and the vessel is adapted to provide biologically active environment suitable for growing organisms (yeast, bacteria, animal cells and the like) under controlled conditions. The bioreactors may include a stirrer which is configured to stir contents within the bioreactor to ensure a homogeneous environment for organism growth.
[0003] During culturing process of the organisms in the bioreactor, outer mediums should be periodically supplied to the bioreactor. Dosage of the material should be accurate which is crucial for organism growth. Conventionally, the dosage of the material is manually realized which is labor intensive. Some system may realize automatic feeding of the material. However, the system is typically very complex. For example, one conventional system comprises one or more material vessels and an intermediate vessel arranged between the material vessel and the bioreactor. A pump may be arranged between the intermediate vessel and the material vessel and is configured to supply the material to the intermediate vessel from the material vessel. The material is further supplied to the bioreactor from the intermediate vessel by a metering device and a pressure controlled device. The configuration of this system requires an intermediate vessel and a pressure controlled device. This is a need to further improve material feeding for a bioreactor.SUMMARY
[0004] Example embodiments of the present disclosure provide a system and a method for automated feeding a bioreactor which can automatically supplying a material from a supply bottle to a bioreactor with high dosage precision.
[0005] In a first aspect of the present disclosure, there is provided a system for feeding a bioreactor. The system comprises: at least one supply bottle configured to contain materials to be fed to the bioreactor; a pipeline connecting the supply bottle to the bioreactor; a positive displacement pump configured to supply the material in the supply bottle to the bioreactor; a stop valve configured to cut off the material supply from the supply bottle to the bioreactor; and a controller communicatively coupled to the positive displacement pump and the stop valve and configured to control the positive displacement pump and the stop valve in accordance with a material amount required to be supplied from the supply bottle to the bioreactor. With this arrangement, the bioreactor can be automatically fed with high precision.
[0006] In some embodiments, the stop valve may be arranged downstream the positive displacement pump. With this arrangement, the material supply from the supply bottle to the bioreactor can be cut off with a good time-response.
[0007] In some embodiments, the system may further comprise a flowmeter arranged downstream the positive displacement pump and configured to acquire a flow rate flowing through the pipeline, the flow meter being communicatively coupled to the controller. With the flowmeter, the flow supplied from the supply bottle to the bioreactor can be more accurately measured.
[0008] In some embodiments, the controller may be further configured to control the positive displacement pump and the stop valve based on the measured flow rate of the flowmeter.
[0009] In some embodiments, the flowmeter may be an ultrasonic flowmeter.
[0010] In some embodiments, the system may further comprise a second stop valve arranged in the pipeline downstream the flowmeter and communicatively coupled to the controller. With this arrangement, the material residue in the pipeline can be further reduced, with improved dosage precision.
[0011] In some embodiments, the controller may be further configured to control the positive displacement pump and the stop valve based at least in part on material residue within a pipeline section of the pipeline between the flowmeter and the bioreactor.
[0012] In some embodiments, the system may further comprise an alarming device configured to generate, in response to a difference between the measured flow rate and a flow rate determined by the positive displacement pump being above a predetermined threshold, an alarm.
[0013] In some embodiments, the positive displacement pump may be a peristaltic pump comprising a pump part and a pump controller configured to operate the pump part based on an instruction from the controller.
[0014] In some embodiments, the stop valve may be a pinch valve comprising an actuator and a pinch valve controller configured to operate the actuator to deform the pipeline based on an instruction from the controller.
[0015] In some embodiments, the pinch valve may be a normally-closed pinch valve.
[0016] In a first aspect of the present disclosure, there is provided a method for feeding a bioreactor. The method comprises: causing a pinch valve to open a pipeline connecting at least one supply bottle to the bioreactor; causing a peristaltic pump to operate to supply the material in the supply bottle to the bioreactor; obtaining a flow rate from a flowmeter arranged in the pipeline; determining operating time for the peristaltic pump based on the measured flow rate and the material residue within a pipeline section of the pipeline from the flowmeter to the bioreactor; and causing the peristaltic pump to stop operating and the stop valve to cut off the pipeline after the operating time.
[0017] It would be appreciated that this summary is not intended to identify key features or essential features of embodiments of the present disclosure, nor is it intended to be used to limit the scope of the present disclosure. Other features of the present disclosure will become evident through the following description.BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Through the following detailed descriptions with reference to the accompanying drawings, the above and other objectives, features and advantages of the example embodiments disclosed herein will become more comprehensible. In the drawings, several example embodiments disclosed herein will be illustrated in an example and in a non-limiting manner, wherein:
[0019] Fig. 1 is a schematic configuration of a system for feeding a bioreactor according to one example embodiment of the present disclosure;
[0020] Fig. 2 is a schematic configuration of a system for feeding a bioreactor according to another example embodiment of the present disclosure;
[0021] Fig. 3 is a schematic configuration of a system for feeding a bioreactor according to yet another example embodiment of the present disclosure;
[0022] Fig. 4 is a flowchart of a method for feeding a bioreactor according to one example embodiment of the present disclosure; and
[0023] Fig. 5 is block diagram of an example device adapted to implement the embodiments of the present disclosure.
[0024] Throughout the drawings, the same or similar reference symbols are used to indicate the same or similar elements.DETAILED DESCRIPTION OF EMBODIMENTS
[0025] Principles of the present disclosure will now be described with reference to several example embodiments shown in the drawings. Though example embodiments of the present disclosure are illustrated in the drawings, it is to be understood that the embodiments are described only to facilitate those skilled in the art in better understanding and thereby achieving the present disclosure, rather than to limit the scope of the disclosure in any manner.
[0026] The term “comprises” or “includes” and its variants are to be read as open terms that mean “includes, but is not limited to. ” The term “or” is to be read as “and / or” unless the context clearly indicates otherwise. The term “based on” is to be read as “based at least in part on.” The term “being operable to” is to mean a function, an action, a motion or a state that can be achieved by an operation induced by a user or an external mechanism. The term “one embodiment” and “an embodiment” are to be read as “at least one embodiment. ” The term “another embodiment” is to be read as “at least one other embodiment. ” The terms “first, ” “second, ” and the like may refer to different or same objects. Other definitions, explicit and implicit, may be included below. A definition of a term is consistent throughout the description unless the context clearly indicates otherwise.
[0027] Fig. 1 shows a schematic configuration of a system 1 for feeding a bioreactor 10 according to one example embodiment of the present disclosure. As shown in Fig. 1, the system 1 for feeding a bioreactor 10 includes a bioreactor 10 and one or more supply bottles 20. The bioreactor 10 provides a controlled environment which is proper for growing organisms, such as yeast, bacteria, animal cells and the like. Typically, the bioreactor 10 may include a stirrer for stirring contents within the bioreactor 10 to ensure a homogeneous environment for organism growth. The supply bottle 20 contains materials to be fed to the bioreactor 10 periodically according to requirements for organism growth. In the shown example, merely one supply bottle 20 is shown. It is to be understood that it is merely illustrative and the number of the supply bottle 20s may be more than one.
[0028] As shown in Fig. 1, a pipeline 30 connects the supply bottle 20 to the bioreactor 10. A positive displacement pump 50 is arranged in the pipeline 30. When the positive displacement pump 50 operates, the material in the supply bottle 20 is supplied to the bioreactor 10. A stop valve 60 is arranged in the pipeline 30. The stop valve 60 can be operated to close or open the pipeline 30. When the stop valve 60 is open, the material in the pipeline 30 is allowed to go through the pipeline 30 from the upstream supply bottle 20 to the downstream bioreactor 10. When the stop valve 60 is closed, the material in the pipeline 30 is stopped from going there through. A controller 40 is communicatively connected to the positive displacement pump 50 and the stop valve 60 and is configured to control operations of the positive displacement pump 50 and switching states of the stop valve 60. In some embodiments, the controller 40 may be a remote controller.
[0029] The remote controller 40 may include setting parameters for feeding the material, such as a desired dosage of the material to be supplied to the bioreactor 10 from the supply bottle 20, supply timing, and the like. These dosage parameters may be set or input by an operator in advance. The remote controller 40 is configured to control the positive displacement pump 50 and the stop valve 60 to cut off the material supply based on the dosage parameters. When it is the material supply timing, the remote controller 40 sends instructions to the positive displacement pump 50 to start running, and the remote controller 40 also sends instructions to the positive displacement pump 50 to open the pipeline 30. When it is determined that the material amount that is supplied to the bioreactor 10 reaches a threshold ratio of a preset dosage, e.g. 95%, 96%, or 99%of the preset dosage, the remote controller 40 sends instructions to the positive displacement pump 50 to stop running, and the remote controller 40 also sends instructions to the stop valve 60 to cut off the pipeline 30. The preset dosage may be set in advance by the user and may correspond to the actual required dosage. Thus, automatic dosage of the material from the supply bottle 20 to the bioreactor 10 can be realized. By setting the threshold ratio smaller than 1, the actual supplied material amount can be prevented from being over supplied. The threshold ratio may be set according to the length of the pipeline, the performances of the positive displacement pump. Due to the arrangement of the stop valve 60, the material supply can be shut off immediately.
[0030] According to the present disclosure, the material amount that is supplied to the bioreactor 10 may be determined by the positive displacement pump 50, for example, according to its rotation speed and its running time. Once the stop valve 60 is closed, the material supply in the pipeline is stopped. By combination of the positive displacement pump 50 and the stop valve 60, the dosage to be supplied to the bioreactor 10 can be controlled with increased accuracy.
[0031] In some embodiments, as shown in Fig. 1, the stop valve 60 is arranged downstream the positive displacement pump 50. Typically, there is a material residue in the pipeline 30 from the positive displacement pump 50 to the bioreactor 10 even if the positive displacement pump 50 stops running. By positioning the stop valve 60 arranged between the positive displacement pump 50 and the bioreactor 10, a measurement of the material amount that is supplied to the bioreactor 10 can be improved since the material supply from the bottle to the bioreactor 10 is immediately stopped once the stop valve 60 is cut off. It is possible to improve the dosage precision when the material residue in the pipeline section from the stop valve 60 to the bioreactor 10 is taken into account during control of the operation of the positive displacement pump 50. The material residue in the pipeline section from the stop valve 60 to the bioreactor 10, for example, can be known by test. During control of the positive displacement pump 50, the operation of the positive displacement pump 50 takes the material residue into account. In this way, the dosage precision can be improved.
[0032] Fig. 2 is a schematic configuration of a system 1 for feeding a bioreactor according to another example embodiment of the present disclosure. The system shown in Fig. 2 is analogous to that shown in Fig. 1. The main difference is that the system shown in Fig. 2 further comprise a flowmeter 70 arranged in the pipeline 30 downstream the stop valve 60. The flowmeter 70 is configured to acquire a flow rate flowing through the flowmeter 70. The flowmeter 70 is communicatively connected to the controller 40. The controller 40 may be configured to control the positive displacement pump 50 and the stop valve 60 based on the flow rate from the flowmeter 70. In some embodiments, the flowmeter may be an ultrasonic flowmeter 70. In this case, the flow following through the pipe can be measured without contacting the material within the pipeline 30. The flowmeter may be of any other proper types.
[0033] The provision of the flowmeter 70 can further improve the dosage accuracy. Typically, according to operations of the positive displacement pump 50, for example, running time, rotation speed, and the like, it is possible to determine the flow rate in the pipeline. In some cases, the flow rate determined based on the operations of the positive displacement pump 50 may not be sufficient to meet precision requirements. When the flowmeter 70, typically of high precision, is arranged in the pipeline, the operations of the positive displacement pump 50 can be controlled based on the measured flow rate by the flowmeter 70.
[0034] Typically, there is a length from the positive displacement pump 50 to the bioreactor 10.In particular, when the positive displacement pump 50 is configured to be operated based on a predetermined dosage, the actual supplied amount is different (e.g., greater than) from the predetermined dosage. Even if the positive displacement pump 50 stops, the remaining material in the pipeline section from the positive displacement pump 50 to the bioreactor 10 may still flow toward the bioreactor 10 which may cause dosage error. By arranging the flowmeter 70 downstream the positive displacement pump 50, the actual supplied amount can be more precisely measured.
[0035] In some embodiments, the controller 40 is further configured to control the positive displacement pump 50 and the stop valve 60 taking the material residue within a pipeline 30 section of the pipeline 30 between the flowmeter 70 and the bioreactor 10 into account. In particular, a distance from the flowmeter to the bioreactor may be fixed and may be used to determine a material residue in this pipeline section which is in turn used to control operation of the positive displacement pump 50. This can further improve dosage precision.
[0036] In some embodiments, a failure of the positive displacement pump 50 can be analyzed by the flowmeter 70. In particular, the measured flow rate by the flowmeter 70 may be compared to the flow rate determined by the positive displacement pump 50. When the difference between the measured flow rate and the determined flow rate exceeds a predetermined threshold, there is high possibility that the positive displacement pump 50 and / or the flowmeter fails. In some embodiments, the system may further include an alarming device configured to send an alarm when a difference between the measured flow rate and a flow rate determined by the peristaltic pump exceeds a predetermined threshold. In this way, the operation status of the flowmeter 70 and the positive displacement pump 50 can be monitored.
[0037] Fig. 3 is a schematic configuration of a system 1 for feeding a bioreactor according to yet another example embodiment of the present disclosure. The system shown in Fig. 3 is analogous to that shown in Fig. 2. The main difference is that the system shown in Fig. 3 further comprise a second stop valve 60 arranged in the pipeline 30 downstream the flowmeter 70. The second stop valve 60 is controlled to stop once the measured flow arrives at the predetermined flow. By provision of the second stop valve 60, the distance from the second stop valve 60 to the bioreactor 10 can be further reduced. Thus, dosage errors caused by the material residual in the pipeline 30 can be further reduced.
[0038] In some embodiments, the positive displacement pump 50 may be a peristaltic pump. The peristaltic pump may include a pump part and a pump controller for controlling the pump part. The pump controller may be connected to the controller 40. The pump controller may control the operations of the pump part in response to instructions from the controller 40. Due to the high precision of the peristaltic pump, the dosage accuracy can be improved.
[0039] In some embodiments, at least one of the stop valves 60 is a pinch valve. The pinch valve may include an actuator for deforming the pipeline 30 to cut off the pipe line and a pinch valve controller. The pinch valve controller may be connected to the controller 40. The pinch valve controller may control operations of the actuator in response to instructions from the controller 40. The pipeline is a typically hose. The pinch valve has good response performances since the pipeline 30 is configured cut off by its deformation. This is advantageous in ensuring the dosage precision. In some embodiments, the pinch valve may be a normally closed pinch valve.
[0040] Fig. 4 is a flowchart of a method 100 for feeding a bioreactor according to one example embodiment of the present disclosure. At a block 102, a pinch valve is caused to open a pipeline 30 connecting at least one supply bottle 20 to the bioreactor 10. At a block 104, a peristaltic pump 50 arranged in the pipeline 30 is caused to operate to supply the material in the supply bottle 20 to the bioreactor 10. At a block 106, a flow rate from a flowmeter 70 arranged in the pipeline 30 is obtained. At a block 108, operating time for the peristaltic pump 50 is determined based on the measured flow rate and the material residue within a pipeline 30 section of the pipeline 30 from the flowmeter 70 to the bioreactor 10. At a block 110, the peristaltic pump 50 is caused to stop operating and the stop valve 60 is caused to cut off the pipeline 30 after the operating time.
[0041] Fig. 5 illustrates a block diagram of an example device 40 adapted to implement the method embodiments of the present disclosure. As shown in Fig. 5, the device 200 comprises a central processing unit (CPU) 201 that may perform various appropriate actions and processing based on computer program instructions stored in a read-only memory (ROM) 202 or computer program instructions loaded from a memory unit 208 to a random access memory (RAM) 203. In the RAM 203, various programs and data needed for operations of the device 2000 may also be stored. The CPU 201, ROM 202 and RAM 203 are connected to each other via a bus 204. An input / output (I / O) interface 205 is also connected to the bus 204.
[0042] Various components in the device 200 are connected to the I / O interface 205, including: an input unit 206 such as a keyboard, a mouse and the like; an output unit 207 such as various kinds of displays and a loudspeaker, etc.; a storage unit 208 such as a magnetic disk, an optical disk, and etc.; a communication unit 209 such as a network card, a modem, and a wireless communication transceiver, etc. The communication unit 209 allows the device 200 to exchange information / data with other devices through a computer network such as the Internet and / or various kinds of telecommunications networks.
[0043] Various processes and processing described above, e.g., method 200, may be executed by the processing unit 201. For example, in some embodiments, the methods 200-400 may be implemented as a computer software program that is tangibly embodied on a machine readable medium, e.g., the storage unit 2008. In some embodiments, part or all of the computer program may be loaded and / or mounted onto the device 200 via ROM 202 and / or communication unit 209. When the computer program is loaded to the RAM 203 and executed by the CPU 201, one or more steps of the method 200 as described above may be executed.
[0044] Embodiments of the present disclosure relate to a method, device, system and / or computer program product. The computer program product may include a computer readable storage medium on which computer readable program instructions for executing various aspects of the present disclosure are embodied.
[0045] The computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device. The computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing. A non-exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM) , a read-only memory (ROM) , an erasable programmable read-only memory (EPROM or Flash memory) , a static random access memory (SRAM) , a portable compact disc read-only memory (CD-ROM) , a digital versatile disk (DVD) , a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing. A computer readable storage medium, as used herein, is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable) , or electrical signals transmitted through a wire.
[0046] Computer readable program instructions described herein can be downloaded to respective computing / processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and / or a wireless network. The network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and / or edge servers. A network adapter card or network interface in each computing / processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing / processing device.
[0047] Computer readable program instructions for carrying out operations of the present invention may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The computer readable program instructions may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN) , or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider) . In some embodiments, electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA) , or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present invention.
[0048] Aspects of the present invention are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems) , and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer readable program instructions.
[0049] These computer readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / actions specified in the flowchart and / or block diagram block or blocks. These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and / or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function / act specified in the flowchart and / or block diagram block or blocks.
[0050] The computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions / actions specified in the flowchart and / or block diagram block or blocks.
[0051] The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, section, or portion of code, which comprises one or more executable instructions for implementing the specified logical function (s) . It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and / or flowchart illustration, and combinations of blocks in the block diagrams and / or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or actions, or combinations of special purpose hardware and computer instructions.
[0052] Through the teachings provided herein in the above description and relevant drawings, many modifications and other embodiments of the disclosure given herein will be appreciated by those skilled in the art to which the disclosure pertains. Therefore, it is understood that the embodiments of the disclosure are not limited to the specific embodiments of the disclosure, and the modifications and other embodiments are intended to fall within the scope of the disclosure. In addition, while exemplary embodiments have been described in the above description and relevant drawings in the context of some illustrative combinations of components and / or functions, it should be realized that different combinations of components and / or functions can be provided in alternative embodiments without departing from the scope of the disclosure. In this regard, for example, it is anticipated that other combinations of components and / or functions that are different from the above definitely described will also fall within the scope of the disclosure. While specific terms are used herein, they are only used in a general and descriptive sense rather than limiting.
Claims
1.A system for feeding a bioreactor (10) , comprisingat least one supply bottle (20) configured to contain materials to be fed to the bioreactor (10) ;a pipeline (30) connecting the supply bottle (20) to the bioreactor (10) ;a positive displacement pump (50) configured to supply the material in the supply bottle (20) to the bioreactor (10) ;a stop valve (60) configured to cut off the material supply from the supply bottle (20) to the bioreactor (10) ; anda controller (40) communicatively coupled to the positive displacement pump (50) and the stop valve (60) and configured to control the positive displacement pump (50) and the stop valve (60) in accordance with a material amount required to be supplied from the supply bottle (20) to the bioreactor (10) .2.The system of claim 1, wherein the stop valve (60) is arranged downstream the positive displacement pump (50) .3.The system according to claim 1, further comprising a flowmeter (70) arranged downstream the positive displacement pump (50) and configured to acquire a flow rate flowing through the pipeline (30) , the flow meter (70) being communicatively coupled to the controller (40) .4.The system according to claim 3, wherein the controller (40) is further configured to control the positive displacement pump (50) and the stop valve (60) based on the measured flow rate of the flowmeter (70) .5.The system of claim 3, wherein the flowmeter is an ultrasonic flowmeter (70) .6.The system of any of claims 3-5, further comprising a second stop valve arranged in the pipeline (30) downstream the flowmeter (70) and communicatively coupled to the controller (40) .7.The system of any of claims 3-6, wherein the controller (40) is further configured to control the positive displacement pump (50) and the stop valve (60) based at least in part on material residue within a pipeline section of the pipeline (30) between the flowmeter (70) and the bioreactor (10) .8.The system according to any of claims 3-7, further comprising an alarming device configured to generate, in response to a difference between the measured flow rate and a flow rate determined by the positive displacement pump (50) being above a predetermined threshold, an alarm.9.The system according to any of the proceeding claims, wherein the positive displacement pump (50) is a peristaltic pump comprising a pump part and a pump controller configured to operate the pump part based on an instruction from the controller (40) .10.The system according to any of the proceeding claims, wherein the stop valve (60) is a pinch valve comprising an actuator and a pinch valve controller configured to operate the actuator to deform the pipeline (30) based on an instruction from the controller (40) .11.The system of claim 10, wherein the pinch valve is a normally-closed pinch valve.12.A method for feeding a bioreactor (10) , comprisingcausing a pinch valve to open a pipeline (30) connecting at least one supply bottle (20) to the bioreactor (10) ;causing a peristaltic pump to operate to supply the material in the supply bottle (20) to the bioreactor (10) ;obtaining a flow rate from a flowmeter (70) arranged in the pipeline (30) ;determining operating time for the peristaltic pump based on the measured flow rate and the material residue within a pipeline section of the pipeline (30) from the flowmeter (70) to the bioreactor (10) ; andcausing the peristaltic pump to stop operating and the stop valve (60) to cut off the pipeline (30) after the operating time.
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