A multi-mode dynamic circulation control method and system of a tangential flow filtration system, electronic equipment and computer readable medium

Abstract

The application discloses a kind of multi-mode dynamic circulation control method and system of tangential flow filtration system, electronic equipment, computer readable medium, wherein, tangential flow filtration system includes hollow fiber column, main pump and auxiliary pump, main pump is set to the lower end of hollow fiber column, auxiliary pump is set to the upper end of hollow fiber column, method is as follows step: acquisition circulation flow signal and transmembrane pressure signal;According to circulation flow signal and transmembrane pressure signal, it is judged to adopt single pump operating mode or double-pump collaborative operating mode under current working condition;When system satisfies mode switching condition, it is smoothly switched between single pump operating mode and double-pump collaborative operating mode.The application improves control stability, reduces product damage, prolongs membrane column service life by multi-pump collaborative control architecture, intelligent flow tracking adaptive adjustment algorithm and the dynamic switching strategy of multiple operating modes.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical process control technology, and in particular to a multi-mode dynamic circulation control method and system for a tangential flow filtration system, as well as electronic equipment and computer-readable media. Background Technology

[0002] Tangential flow filtration (TFF) is a membrane separation technology that uses pressure as the driving force and the selective permeation of membranes to separate mixtures. In the biopharmaceutical field, TFF systems are widely used in key process steps such as clarifying and filtering cell culture media, concentrating and dialysis changing target products, and separating and purifying viral particles. In a TFF system, the speed control of the circulating pump directly affects the membrane surface velocity, shear force distribution, and transmembrane pressure (TMP), thus determining the filtration flux, membrane fouling rate, and product quality. The accuracy and strategy of pump speed control have a decisive impact on the performance of the entire filtration process. However, traditional TFF pump speed control has the following technical drawbacks: Constant speed control: The pump runs continuously at a fixed speed, and the circulating flow rate within the system remains constant. This method is simple to implement, but the fixed flow velocity distribution on the membrane surface easily leads to the formation of a stable concentration polarization layer and filter cake layer, resulting in rapid decline in membrane flux. Frequent membrane column replacements significantly increase production costs and the risk of process interruption.

[0003] Low level of automation: Operators adjust the pump speed at set time points based on experience, resulting in stepped flow rate changes. This method relies on operator experience, has poor adjustment accuracy, struggles to respond to TMP changes in real time, and cannot guarantee consistency between different batches.

[0004] Short membrane column lifespan: Only a single PID closed-loop control is used to maintain a constant flow rate. Although the flow rate stability is good, there is a lack of an active flow disturbance mechanism, which cannot actively disrupt the stable deposition of the fouling layer on the membrane surface, resulting in limited membrane fouling inhibition effect.

[0005] Product damage: Existing backwashing technologies typically use a simple start-stop method to switch between pumps. The large flow fluctuations during switching cause sudden changes in system pressure, which can impact membrane modules and products. Summary of the Invention

[0006] According to a first aspect of the present invention, a multi-mode dynamic circulation control method for a tangential flow filtration system is provided. The tangential flow filtration system includes a hollow fiber column, a main pump, and an auxiliary pump. The main pump is disposed at the lower end of the hollow fiber column, and the auxiliary pump is disposed at the upper end of the hollow fiber column. The control method includes the following steps: Acquire circulating flow rate and transmembrane pressure signals; Based on the circulating flow rate signal and the transmembrane pressure signal, determine whether to adopt a single pump operation mode or a dual pump cooperative operation mode under the current operating conditions; In single-pump operation mode, only the main pump is controlled to operate, and the main pump speed is adjusted in real time using a closed-loop feedback control method to maintain the circulating flow at the set value; when the reversing backflush condition is met, the auxiliary pump is switched to run independently and circulate in reverse based on the cross-gradient dual-pump speed matching strategy. In the dual-pump cooperative operation mode, the operation of the main pump and the auxiliary pump is controlled simultaneously. The main pump drives the overall circulation flow direction, while the auxiliary pump provides reverse pressure. Based on the real-time deviation of the circulation flow and transmembrane pressure, the main pump and the auxiliary pump are adaptively coordinated and adjusted by a master-slave coordination strategy. When the reversing backflush condition is met, the driving roles of the main pump and the auxiliary pump are interchanged and reversed based on the cross-gradient dual-pump speed allocation strategy. When the system meets the mode switching conditions, it smoothly switches between single-pump operation mode and dual-pump collaborative operation mode.

[0007] Furthermore, closed-loop feedback control methods include: A fuzzy adaptive PID control algorithm is adopted to tune the PID control parameters in real time. Based on the calibrated PID parameters and the deviation between the circulating flow signal and the set value, the centrifugal pump speed is adjusted in real time, so that the system dynamically maintains the set value of circulating flow in response to changes in the membrane column state.

[0008] Furthermore, the switching logic between single-pump operation mode and dual-pump collaborative operation mode is as follows: When single-pump operation is sufficient to meet the system's set requirements for transmembrane pressure and circulation flow, maintain single-pump operation mode; When a single pump cannot simultaneously meet the requirements for both the circulation flow rate setting and the transmembrane pressure setting, the control unit automatically starts another pump, entering a dual-pump cooperative operation mode.

[0009] Furthermore, the cross-gradient dual-pump speed tuning strategy includes: Record the current speed of the main pump and the auxiliary pump, and adjust them by increasing or decreasing the speed of the other pump as the target speed. During the speed regulation process, when the speeds of the two pumps are equal, the circulation flow rate returns to zero. After that, the two pumps continue to increase or decrease the speed in the second half of the process, and finally complete the exchange of speeds and the switching of circulation direction between the two pumps, so that the original main pump becomes the auxiliary pump and the original auxiliary pump becomes the main pump. After the transition is completed, the system enters a steady-state closed-loop feedback control of circulating flow and transmembrane pressure.

[0010] Furthermore, it also includes system startup control steps: At the start of batch operation, the main pump speed is gradually increased according to a gradual increase strategy until the system circulation flow rate is met, thus avoiding hydraulic shock at the moment of startup.

[0011] According to a second aspect of the present invention, a multi-mode dynamic circulation control system for a tangential flow filtration system is provided, comprising: Hollow fiber column; The main pump is located at the lower end of the hollow fiber column; Auxiliary pump, located at the upper end of the hollow fiber column; Flow sensors are used to collect circulating flow signals; Pressure sensors are used to acquire transmembrane pressure signals; The control unit is communicatively connected to the main pump, auxiliary pump, flow sensor, and pressure sensor. The control unit is configured to execute a multi-mode dynamic cyclic control method for a tangential flow filtration system, as described in the first aspect.

[0012] According to a third aspect of the present invention, an electronic device is provided, comprising: a memory, a processor, and a computer program, wherein the computer program is stored in the memory, and the processor executes the computer program to perform a multi-mode dynamic cyclic control method for a tangential flow filtering system according to the first aspect.

[0013] According to a fourth aspect of the present invention, a computer-readable medium having processor-executable non-volatile program code is provided, the program code causing the processor to perform a multi-mode dynamic cyclic control method for a tangential flow filtering system according to the first aspect.

[0014] A multi-mode dynamic cyclic control method for a tangential flow filtration system according to an embodiment of the present invention has the following beneficial effects: 1. This invention abandons the single-operation mode of traditional single-pump TFF control technology and innovatively provides two operating modes: single-pump and dual-pump. Dual-pump coordinated operation can meet the steady-state requirements of high TMP, ensuring processing efficiency under high flow rate conditions; single-pump operation is suitable for traditional TFF scenarios. The two modes can be flexibly switched according to process requirements, covering full-scenario applications with different batch sizes and product types.

[0015] 2. This invention integrates fuzzy adaptive PID control, closed-loop feedback control, and other control methods to construct an adaptive hybrid control system. The system can sense process disturbances in real time, automatically adjust control parameters, and smoothly switch operating modes, achieving automated operation throughout the entire process.

[0016] 3. This invention automatically decides on the switching between multiple operating modes, such as gradual start-up, dual-pump collaboration, single-pump circulation, and soft stop protection, through the control unit, covering the entire lifecycle of the TFF process without manual intervention. This ensures a high degree of consistency in process parameters between batches, significantly improving production efficiency and product quality stability.

[0017] 4. This invention employs an alternating clockwise and counterclockwise operation strategy with a single pump to periodically change the flow field direction on the membrane surface, disturbing the deposited layer and effectively mitigating the formation of irreversible membrane fouling. This alternating reversal mechanism significantly extends the effective service life of the membrane column, reducing replacement frequency and consumable costs.

[0018] 5. This invention eliminates hydraulic shock through gradual start-up and avoids abrupt flow changes through a soft switching strategy, achieving a low-shear rate process environment from multiple dimensions. Especially for shear-sensitive biopharmaceuticals, this design can significantly improve product activity retention and ensure final product quality.

[0019] It should be understood that both the foregoing general description and the following detailed description are exemplary and intended to provide further illustration of the claimed technology. Attached Figure Description

[0020] Figure 1 This is a flowchart of a multi-mode dynamic cyclic control method for a tangential flow filtration system according to an embodiment of the present invention.

[0021] Figure 2 This is a diagram showing the dual-pump reversing backwash curve of a multi-mode dynamic circulation control method for a tangential flow filtration system according to an embodiment of the present invention.

[0022] Figure 3 This is a structural diagram of a multi-mode dynamic circulation control system for a tangential flow filtration system according to an embodiment of the present invention.

[0023] Figure 4 This is a structural diagram of an electronic device according to an embodiment of the present invention. Detailed Implementation

[0024] The preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings, further illustrating the present invention.

[0025] First, combine Figures 1-2 This invention describes a multi-mode dynamic cyclic control method for a tangential flow filtration system, which is widely used for the control of tangential flow filtration systems.

[0026] like Figures 1-2 As shown in the figure, an embodiment of the present invention provides a multi-mode dynamic circulation control method for a tangential flow filtration system. The tangential flow filtration system includes a hollow fiber column, a main pump, and an auxiliary pump. The main pump is located at the lower end of the hollow fiber column, and the auxiliary pump is located at the upper end of the hollow fiber column. The control method includes the following steps: like Figure 1 As shown, in S1, the circulating flow rate signal and the transmembrane pressure signal are acquired.

[0027] like Figure 1As shown, in S2, based on the circulating flow signal and the transmembrane pressure signal, it is determined whether to adopt a single pump operation mode or a dual pump cooperative operation mode under the current operating conditions. In single-pump operation mode, only the main pump is controlled to operate, and the main pump speed is adjusted in real time using a closed-loop feedback control method to maintain the circulating flow at the set value; when the reversing backflush condition is met, the auxiliary pump is switched to run independently and circulate in reverse based on the cross-gradient dual-pump speed matching strategy. In the dual-pump cooperative operation mode, the operation of the main pump and the auxiliary pump is controlled simultaneously. The main pump drives the overall circulation direction, while the auxiliary pump provides reverse pressure. Based on the real-time deviation of the circulation flow rate and transmembrane pressure, the main pump and the auxiliary pump are adaptively coordinated and adjusted by a master-slave coordination strategy. When the reversing backflush condition is met, the driving roles of the main pump and the auxiliary pump are interchanged and reversed based on the cross-gradient dual-pump speed allocation strategy.

[0028] like Figure 1 As shown, in S3, when the system meets the mode switching conditions, it smoothly switches between single-pump operation mode and dual-pump cooperative operation mode.

[0029] Furthermore, in this embodiment, the closed-loop feedback control method includes: using a fuzzy adaptive PID control algorithm to tune the PID control parameters in real time; adjusting the centrifugal pump speed in real time based on the deviation between the tuned PID parameters and the circulating flow signal and the set value, so that the system dynamically maintains the set value of the circulating flow in response to changes in the membrane column state, ensuring that the required circulating flow setting of the system is always maintained.

[0030] Furthermore, in this embodiment, the switching logic between the single-pump operation mode and the dual-pump cooperative operation mode is as follows: when the operation of a single pump is sufficient to meet the system's requirements for the setting of transmembrane pressure and circulation flow rate, the single-pump operation mode is maintained; when the operation of a single pump cannot simultaneously meet the requirements for the setting of circulation flow rate and transmembrane pressure, the control unit automatically starts another pump and enters the dual-pump cooperative operation mode.

[0031] Furthermore, in this embodiment, as Figure 2 As shown, the cross-gradient dual-pump speed adjustment strategy includes: recording the current speed of the main pump and the auxiliary pump, and adjusting them by increasing or decreasing the speed of the other pump as the target speed; during the speed adjustment process, when the speeds of the two pumps are equal, the circulating flow rate is reduced to zero, and then the two pumps continue to increase or decrease the speed in the second half of the process, finally completing the exchange of speeds and the switching of the circulation direction, so that the original main pump becomes the auxiliary pump and the original auxiliary pump becomes the main pump; after the transition is completed, the system enters the closed-loop feedback control of the circulating flow rate and transmembrane pressure under steady state.

[0032] It should be noted that, to slow down membrane fouling and extend membrane column lifespan, this invention employs a cross-gradient dual-pump speed control strategy. Under this strategy, the main pump and auxiliary pump alternately act as the primary drive source, propelling the feed solution through the membrane module in clockwise and counterclockwise directions respectively. This continuously agitates the concentration polarization layer and deposition layer on the membrane surface, reducing the formation of irreversible membrane fouling. Simultaneously, this smooth, soft switching maintains a low system shear rate, which is beneficial for protecting shear-sensitive products. Furthermore, this approach effectively avoids the water hammer effect caused by direct start-up and shutdown, significantly reducing product damage while ensuring no sudden changes in system flow rate or pressure during switching.

[0033] Furthermore, in this embodiment, the multi-mode dynamic circulation control method of the tangential flow filtration system of the present invention also includes a system start-up control step: at the start of batch operation, the main pump speed is controlled to gradually increase according to a gradual increment strategy until the system circulation flow rate setting value is met, so as to avoid hydraulic shock at the moment of start-up.

[0034] The above combined with the appendix Figures 1-2 A multi-mode dynamic cyclic control method for a tangential flow filtration system according to an embodiment of the present invention is described. Furthermore, the present invention can also be applied to a multi-mode dynamic cyclic control system for a tangential flow filtration system.

[0035] like Figure 3 As shown, according to a second aspect of the present invention, a multi-mode dynamic circulation control system for a tangential flow filtration system is provided, comprising: Hollow fiber column; The main pump is located at the lower end of the hollow fiber column; Auxiliary pump, located at the upper end of the hollow fiber column; Flow sensors are used to collect circulating flow signals; Pressure sensors are used to acquire transmembrane pressure signals; The control unit is communicatively connected to the main pump, auxiliary pump, flow sensor, and pressure sensor. The control unit is configured to execute a multi-mode dynamic cyclic control method for a tangential flow filtration system, as described in the first aspect.

[0036] The above combined with the appendix Figure 3 A multi-mode dynamic cyclic control method for a tangential flow filtration system according to an embodiment of the present invention is described. Furthermore, the present invention can also be applied to an electronic device.

[0037] like Figure 4 As shown, according to a third aspect of the present invention, an electronic device is provided, comprising: a memory, a processor, and a computer program, wherein the computer program is stored in the memory, and the processor executes the computer program to perform a multi-mode dynamic cyclic control method for a tangential flow filtering system according to the first aspect.

[0038] According to a fourth aspect of the present invention, a computer-readable medium having processor-executable non-volatile program code is provided, the program code causing the processor to perform a multi-mode dynamic cyclic control method for a tangential flow filtering system according to the first aspect.

[0039] The readable storage medium can be a computer storage medium or a communication medium. A communication medium includes any medium that facilitates the transfer of a computer program from one location to another. A computer storage medium can be any available medium accessible to a general-purpose or special-purpose computer. For example, a readable storage medium is coupled to a processor, enabling the processor to read information from and write information to the readable storage medium. Of course, the readable storage medium can also be a component of the processor. The processor and the readable storage medium can reside in an application-specific integrated circuit (ASIC). Alternatively, the ASIC can reside within a device. Of course, the processor and the readable storage medium can also exist as discrete components in a communication device. The readable storage medium can be a read-only memory (ROM), random access memory (RAM), CD-ROM, magnetic tape, floppy disk, and optical data storage device, etc. The present invention also provides a program product including executable instructions stored in the readable storage medium. At least one processor of the device can read the executable instructions from the readable storage medium, and the at least one processor executes the executable instructions, causing the device to implement the method for creating infinite viewpoints and rapidly switching between multiple viewpoints in a three-dimensional scene provided by the various embodiments described above. In the embodiments of the above-described device, it should be understood that the processor can be a Central Processing Unit (CPU), or other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), etc. The general-purpose processor can be a microprocessor or any conventional processor. The steps of the method disclosed in this invention can be directly manifested as being executed by a hardware processor, or executed by a combination of hardware and software modules within the processor.

[0040] To further explain this solution, the following application example is used: This embodiment describes a typical application scenario of the present invention in cell perfusion culture. The control method is deployed in the external circulation pipeline of the bioreactor and used in conjunction with a tangential flow filtration device as a cell retention unit. This retains cells within the bioreactor while continuously discharging the culture medium containing the target product, achieving high-density, long-term continuous perfusion culture.

[0041] Detailed description of the operation process: Initial Stage – Single-Pump Alternating Cyclic Operation: After system startup, the main pump adopts a gradual speed increase strategy to avoid hydraulic shock at startup. In the initial stage of system operation, the single pump meets the circulation flow requirements while also meeting the set TMP requirements. Therefore, there is no need to activate a second pump. The process requirements are met by relying on the single-pump circulation. The circulating pump is switched at fixed intervals for reversing backflushing to inhibit cell deposition and the formation of concentration polarization layer.

[0042] Mid-term stage – Dual-pump alternating cooperative operation: After continuous perfusion for a certain period, a cell deposition layer will still form on the membrane surface, and the membrane flux will show a downward trend. Single-pump operation cannot simultaneously meet the set requirements of circulation flow rate and transmembrane pressure (TMP). The control unit automatically starts the auxiliary pump, and the system enters the dual-pump cooperative operation mode. The main pump drives the feed liquid circulation, and the auxiliary pump synchronously provides reverse pressure. The circulation flow rate and TMP are maintained at steady state levels under the regulation of the dual pumps. In addition, a reverse backflushing is triggered at fixed intervals to slow down the membrane column clogging rate and ensure the long-term stable operation of the perfusion system.

[0043] Later Stage – Dual-Pump Coordinated Speed ​​Regulation: In the later stages of perfusion, the cell deposition layer on the membrane column surface gradually increases, and membrane flux continues to decrease. At this point, the system control unit, relying on the advantages of dual-pump speed regulation, adjusts the speed of the two pumps within the speed threshold without damaging the cells, increasing the pressure inside the hollow fiber membrane, maintaining the stability of the system's total measurand density (TMP), and ensuring the continued stable operation of the perfusion system.

[0044] Process effect verification: After the operation of this embodiment, cell activity and product expression levels both met the process requirements, and the continuous perfusion operation time was significantly extended compared to the traditional single-pump solution. The cumulative service life of the membrane module was greatly improved, and the cell growth curves and product quality indicators of multiple consecutive batches showed good consistency, fully verifying the technical advantages of this control method in high-density cell perfusion culture scenarios, including stable pressure control, low shear rate, extended membrane column life, and multi-mode switching.

[0045] It should be noted that, in this specification, the terms "comprising," "including," or any other variations thereof are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0046] Although the present invention has been described in detail through the preferred embodiments above, it should be understood that the above description should not be considered as a limitation of the present invention. Various modifications and substitutions to the present invention will be apparent to those skilled in the art after reading the above. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. A multi-mode dynamic circulation control method for a tangential flow filtration system, the tangential flow filtration system comprising a hollow fiber column, a main pump, and an auxiliary pump, wherein the main pump is disposed at the lower end of the hollow fiber column, and the auxiliary pump is disposed at the upper end of the hollow fiber column, characterized in that, The control method includes the following steps: Acquire circulating flow rate and transmembrane pressure signals; Based on the circulating flow signal and the transmembrane pressure signal, determine whether to adopt a single-pump operation mode or a dual-pump cooperative operation mode under the current operating conditions. In single-pump operation mode, only the main pump is controlled to operate, and the main pump speed is adjusted in real time using a closed-loop feedback control method to maintain the circulating flow at the set value; when the reversal backflush condition is met, the auxiliary pump is switched to operate alone and circulate in reverse based on the cross-gradual dual-pump speed matching strategy. In the dual-pump cooperative operation mode, the main pump and the auxiliary pump are controlled to operate simultaneously. The main pump drives the overall circulation flow direction, and the auxiliary pump provides reverse pressure. Based on the real-time deviation of the circulation flow rate and transmembrane pressure, the speed of the main pump and the auxiliary pump is adaptively coordinated and adjusted using a master-slave coordination strategy. When the reversing backflush condition is met, the driving roles of the main pump and the auxiliary pump are interchanged and reversed based on a cross-gradient dual-pump speed allocation strategy. When the system meets the mode switching conditions, it smoothly switches between the single-pump operation mode and the dual-pump collaborative operation mode.

2. The multi-mode dynamic cyclic control method for the tangential flow filtration system as described in claim 1, characterized in that, The closed-loop feedback control method includes: A fuzzy adaptive PID control algorithm is adopted to tune the PID control parameters in real time. Based on the calibrated PID parameters and the deviation between the circulating flow signal and the set value, the centrifugal pump speed is adjusted in real time, so that the system dynamically maintains the set value of circulating flow in response to changes in the membrane column state.

3. The multi-mode dynamic cyclic control method for the tangential flow filtration system as described in claim 1, characterized in that, The switching logic between the single-pump operation mode and the dual-pump collaborative operation mode is as follows: When single-pump operation is sufficient to meet the system's set requirements for transmembrane pressure and circulation flow, maintain single-pump operation mode; When a single pump cannot simultaneously meet the requirements for both the circulation flow rate setting and the transmembrane pressure setting, the control unit automatically starts another pump, entering a dual-pump cooperative operation mode.

4. The multi-mode dynamic cyclic control method for the tangential flow filtration system as described in claim 1, characterized in that, The cross-gradient dual-pump speed adjustment strategy includes: Record the current speed of the main pump and the auxiliary pump, and adjust them by increasing or decreasing the speed of the other pump as the target speed. During the speed regulation process, when the speeds of the two pumps are equal, the circulation flow rate returns to zero. After that, the two pumps continue to increase or decrease the speed in the second half of the process, and finally complete the exchange of speeds and the switching of circulation direction between the two pumps, so that the original main pump becomes the auxiliary pump and the original auxiliary pump becomes the main pump. After the transition is completed, the system enters a steady-state closed-loop feedback control of circulating flow and transmembrane pressure.

5. The multi-mode dynamic cyclic control method for the tangential flow filtration system as described in claim 1, characterized in that, It also includes system startup control steps: At the start of batch operation, the main pump speed is controlled to gradually increase according to a gradual increment strategy until the system circulation flow rate setting value is met.

6. A multi-mode dynamic circulation control system for a tangential flow filtration system, characterized in that, Include: Hollow fiber column; The main pump is located at the lower end of the hollow fiber column; An auxiliary pump is located at the upper end of the hollow fiber column; Flow sensors are used to collect circulating flow signals; Pressure sensors are used to acquire transmembrane pressure signals; The control unit is communicatively connected to the main pump, the auxiliary pump, the flow sensor, and the pressure sensor, and is configured to perform a multi-mode dynamic cyclic control method for a tangential flow filtration system according to any one of claims 1 to 5.

7. An electronic device, characterized in that, include: The system includes a memory, a processor, and a computer program, wherein the computer program is stored in the memory, and the processor executes the computer program to perform a multi-mode dynamic cyclic control method for a tangential flow filtering system according to any one of claims 1 to 5.

8. A computer-readable medium having processor-executable non-volatile program code, characterized in that, The program code causes the processor to run a multi-mode dynamic cyclic control method for a tangential flow filtering system as described in any one of claims 1-5.

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