Filtration system and control method thereof

Abstract

The present application relates to a filtration system and a control method thereof, comprising: a filter assembly; a container connected to the filter assembly via a retentate line; a pump connected to the filter assembly for moving material between the filter assembly and the container; a flow sensor connected to the retentate line for sensing material flow in the retentate line; an air flow line connected to a diaphragm portion of the pump; a regulator connected to the air flow line for controlling the air flow through the air flow line; a pressure sensor connected to the air flow line for sensing pressure in the air flow line; a controller connected to the flow sensor, the pressure sensor and the regulator, the controller comprising a processor, the processor executing instructions for controlling the regulator in response to flow information received from the flow sensor and pressure information received from the pressure sensor to control the flow through the air flow line, control the air flow through the air flow line to control the pump, and thereby control the material flow between the filter assembly and the container.

Description

[0001] This application is a divisional application of the invention patent application entitled “Actuation method of alternating tangential flow diaphragm pump”, with an international application date of August 2, 2018, an international application number of PCT / US2018 / 045033, and a national application number of 202010126693.4.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 541,023, filed on August 3, 2017, and U.S. Patent Application No. 15 / 892,214, filed on February 8, 2018, the entire contents of which are incorporated herein by reference. Technical Field

[0004] The present application relates generally to actuation of diaphragm pumps, and more particularly to methods, apparatus, and systems for diaphragm pumps. Background Art

[0005] Diaphragm operated pumps use positive and negative air flows to provide liquid delivery. However, conventional systems cannot precisely control the change between positive and negative air flows or the amount of positive and negative air flows. Moreover, such systems typically have complex structures that are difficult to manufacture and maintain and include airflow restrictions. Summary of the invention

[0006] The present application discloses a control unit, which includes: a first connector, which is configured to connect a proportional pressure regulator to a positive pressure supply; a second connector, which is configured to connect the proportional pressure regulator to a negative pressure supply; at least one sensor, which is configured to detect a positive or negative air flow rate (volume per unit time) in an air flow line connected to an output part of the proportional pressure regulator; a third connector, which is configured to connect the air flow line to the air side of a diaphragm; and a controller, which is programmed to at least control the opening and closing functions of the proportional pressure regulator to obtain a desired positive or negative air flow rate (volume per unit time) in the air flow line.

[0007] The present application also discloses a method for actuating a diaphragm pump, the method comprising: selecting a capacity or size of the diaphragm pump; selecting a volume of fluid to be displaced by the diaphragm pump within a given time period; selecting a duration of the pumping operation, the duration together with the expected volume of fluid to be displaced within the duration generating a performance profile suitable for a specific application; actuating the pumping operation by alternately supplying positive and negative air flows in an air flow line connected to the air side of the diaphragm pump at one end and to the output of an air flow regulator at the opposite end; monitoring the air flow rate in the air flow line to maintain or change the volume of air flowing per unit time in the air flow line; optionally, monitoring the position of the diaphragm of the diaphragm pump at one end or both ends of its displacement; and optionally, changing the volume of air flowing per unit time in the air flow line to: affect the position of the diaphragm at one end or both ends of its displacement; or affect the duration of a partial or full cycle of displacement; or affect both.

[0008] The present application further discloses a method for controlling a diaphragm pump, the method comprising: actuating a pumping operation of pumping fluid from a first container by alternately supplying positive and negative air flows to the air side of the diaphragm pump via an air flow line connected to an output portion of an air flow regulator; drawing fluid from the first container by applying a supply of negative air flow to the air side of the diaphragm pump; adjusting the duration of a partial or complete cycle of displacement of the diaphragm pump; filtering the fluid drawn from the first container; and extracting the filtered fluid so as to direct a portion of the filtered fluid back to the first container and a portion of the filtered fluid to a second container.

[0009] The present application also discloses a method for controlling a diaphragm pump using a controller, the method comprising: alternating between supplying a positive air flow to the air side of the diaphragm pump and supplying a negative air flow to the air side of the diaphragm pump to actuate pumping of a fluid associated with a bioreactor; drawing fluid from the bioreactor by applying a supply of negative air flow to the air side of the diaphragm pump; filtering the fluid drawn from the bioreactor; extracting the filtered fluid to direct it to a container; and adjusting the duration of a partial or complete cycle of the displacement of the diaphragm pump, wherein the controller controls the delivery of the filtered fluid to the container according to processing requirements.

[0010] The disclosed embodiments may be modified and employed in various ways. For example, various configurations are apparent, including a multi-channel pumping system that can control multiple pumps in a network environment. Alternative exemplary embodiments are directed to other features and combinations of features recited in the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present disclosure will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, wherein like reference numerals, symbols or terms generally identify like components unless context dictates otherwise, and:

[0012] Figure 1 A control system is depicted according to an exemplary embodiment.

[0013] Figure 2 Depicted Figure 1 A control system is shown in FIG. 1 , wherein a side panel of the housing is removed to reveal one configuration of components within the housing.

[0014] Figure 3 An alternating tangential flow control system is depicted according to an exemplary embodiment.

[0015] Figure 4 A control method according to an exemplary embodiment is described.

[0016] Figure 5 Depicted is a schematic diagram according to an exemplary embodiment. DETAILED DESCRIPTION

[0017] A preferred embodiment relates to a control unit, comprising: a first connector, which is configured to connect a proportional pressure regulator to a positive pressure supply; a second connector, which is configured to connect the proportional pressure regulator to a negative pressure supply; at least one sensor, which is configured to detect a positive or negative air flow (volume per unit time) in an air flow line connected to an output of the proportional pressure regulator; a third connector, which is configured to connect the air flow line to the air side of the diaphragm; and a controller, which is programmed to at least control the opening and closing functions of the proportional pressure regulator to obtain a desired positive or negative air flow (volume per unit time) in the air flow line.

[0018] Another preferred embodiment relates to a method for actuating a diaphragm pump, the method comprising: selecting a capacity or size of the pump; selecting a volume of fluid to be displaced by the diaphragm pump within a given time period; selecting a duration of the pumping operation, the duration together with the expected volume of fluid to be displaced within the duration generating an execution profile suitable for a specific application; actuating the pumping operation by alternatingly supplying positive and negative air flows in an air flow line connected to the air side of the diaphragm pump via a connector 4 at one end and to the output of an air flow regulator at an opposite end; monitoring the air flow rate in the air flow line to maintain or change the volume of air flowing in the air flow line per unit time; optionally, monitoring the position of the diaphragm at both ends of its displacement; and optionally, changing the volume of air flowing in the air flow line per unit time to: affect the position of the diaphragm at one or both ends of its displacement; or affect the duration of a partial or complete cycle of the displacement; or affect both.

[0019] Yet another preferred embodiment relates to a method for controlling a diaphragm pump, the method comprising: actuating a pumping operation of pumping fluid from a first container by alternately supplying positive and negative air flows to the air side of the diaphragm pump via an air flow line connected to an output portion of an air flow regulator; drawing fluid from the first container by supplying a negative air flow to the air side of the diaphragm pump; regulating the duration of a partial or complete cycle of displacement of the diaphragm pump; filtering the fluid drawn from the first container; and extracting the filtered fluid so as to direct a portion of the fluid back to the first container and a portion of the fluid to a second container.

[0020] Yet another preferred embodiment relates to a method of controlling a diaphragm pump using a controller, the method comprising alternating between applying positive and negative air flows to the air side of the diaphragm pump to actuate pumping of a fluid associated with a bioreactor; drawing fluid from the bioreactor by applying a negative air flow to the air side of the diaphragm pump; filtering the fluid drawn from the bioreactor; extracting the filtered fluid to direct the fluid to a container; and adjusting the duration of a partial or complete cycle of displacement of the diaphragm pump, wherein the controller controls delivery of the filtered fluid to the container based on processing requirements.

[0021] Detailed Description

[0022] Before turning to the drawings showing exemplary embodiments in detail, it should be understood that the present application is not limited to the details or methods set forth in the specification or shown in the drawings. It should also be understood that the terms are for descriptive purposes only and should not be considered restrictive. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be restrictive. Other embodiments may be utilized and other changes may be made without departing from the spirit or scope of the subject matter presented herein. It is readily understood that the various aspects of the present disclosure as outlined herein and shown in the drawings may be arranged, replaced, combined, and designed in a variety of different configurations, and all arrangements, replacements, combinations, and designs are expressly contemplated and constitute a part of the present disclosure.

[0023] Among other embodiments, filtration of biological fluids can be performed to separate blood into blood cells and plasma. It is important for biomedical applications to be able to effectively clean systems for such filtration in order to achieve sterile or substantially sterile conditions in accordance with Good Manufacturing Practice (GMP) guidelines and to prevent contamination. For example, the alternating tangential flow system includes stainless steel components that are sterilized by steam or gamma irradiation. In particular, the "single use" components of the alternating tangential flow system can be sterilized by gamma irradiation.

[0024] The alternating tangential flow of fluid can be used to perform filtration. More particularly, continuous filtration can be achieved by alternating the tangential flow of fluid through the filter element. For example, an alternating tangential flow system is described in U.S. Pat. No. 6,544,424 to Shevitz, the entire contents of which are incorporated herein as background, equipment and technical content.

[0025] Filtration can be performed for purification, selective removal of unwanted components and / or for maintaining cultures in a perfused state at high cell concentrations. Various types of filters can be used, including hollow fiber filters comprising a plurality of hollow fibers bundled together. For example, filtration using the above-described alternating tangential flow can be performed by a diaphragm pump in which positive and negative air flows are delivered in an alternating manner to activate liquid transfer. Current systems are unable to precisely regulate the duration of the transition between the positive and negative air flows or the air flow rate. In addition, current systems typically involve many difficult-to-maintain components in complex assemblies. On the other hand, embodiments of the present disclosure allow for precise control of the duration and amount of the transition and, among other benefits, allow for self-cleaning, as described in more detail below.

[0026] Figure 1 A system 100 is depicted according to an exemplary embodiment. Figure 1Certain components of the system 100 shown in the figure may be disposed within the housing 7. However, it should be understood that in some embodiments, the system 100 may include a pumping module component located outside the controller housing 7, and the pumping module component may communicate directly or indirectly with components within the housing 7. The system 100 includes a first connector, which is configured to connect a proportional pressure regulator 6 housed in the housing 7 to the positive pressure supply 1. The proportional pressure regulator 6 may also be referred to as a proportional pressure valve. In at least one embodiment, the proportional pressure regulator 6 is a TR pneumatic pressure control system, model number TR-010-g10-s, manufactured by Shelton, Connecticut, USA. Technologies. The system also includes a second connector configured to connect the proportional pressure regulator 6 to the negative pressure supply 2. The positive pressure supply 1 and the negative pressure supply 2 are configured to provide positive and negative air flows, respectively, as discussed in more detail below. The configuration of the positive and negative air pressure supplies 1, 2 is such that the air flow to the diaphragm is not restricted, thereby allowing operation at lower inlet positive and negative pressures, thereby enhancing system safety. Figure 2 An exemplary representation of the system 100 is depicted wherein a side panel of the housing is removed.

[0027] The system 100 includes at least one sensor 3 and a third connector, wherein the at least one sensor is configured to detect a positive or negative air flow (volume per unit time) in an airflow line 8 in a housing 7, and the third connector is configured to connect the housing to the air side of a diaphragm pump. More specifically, the airflow line 8 is disposed in the housing and arranged between a proportional pressure regulator 6 and the third connector, so that the airflow line 8 is connected to the output of the proportional pressure regulator 6. The airflow line 8 applies an air flow acting on the diaphragm pump. In addition, the system includes a controller (also referred to as a control system, a control module, or a control unit) 5, which is programmed to at least control the opening and closing functions of the proportional pressure regulator 6 to achieve a desired positive or negative air flow (volume per unit time) in the airflow line 8.

[0028] In addition, the controller 5 is programmed to adjust the fluid flow of the diaphragm pump by controlling the positive and negative air flows applied via the above-mentioned third connector. Therefore, the controller 5 adjusts the operation of the diaphragm pump. In addition, the controller 5 can adjust the fluid flow from the diaphragm pump to meet the processing requirements. For example, in response to the setting input by the user, the controller 5 can make the diaphragm pump output a specified volume of fluid (for example, 100L in a day) within a predetermined time period. The operator can provide input to the controller 5 to specify the desired output volume, and the controller 5 is programmed to control the diaphragm pump to achieve the desired amount. For example, the controller 5 is programmed to determine the number of pumping cycles (for example, the number of cycles per minute) according to the user input to achieve the specified output. In addition, the controller 5 is configured to adjust the operation of the pump and the supply of positive and negative air flows to take into account changes. For example, in a time period such as a day, the fluid viscosity may change over time, and the controller 5 is programmed to automatically control the fluid flow to take into account this change, in order to achieve the flow output specified by the user.

[0029] The controller may include: a processor or microprocessor configured to run an operating system; an application specific integrated circuit (ASIC); a field programmable gate array (FPGA), etc.; or a combination thereof. The controller may include a memory, which may include, but is not limited to, electronic, optical, magnetic, or any other storage or transmission device capable of providing program instructions to the processor, ASIC, FPGA, etc. The memory may include a memory chip, an electrically erasable programmable read-only memory (EEPROM), an erasable programmable read-only memory (EPROM), a flash memory, or any other suitable memory from which the controller can read instructions. The instructions may include code from any suitable programming language.

[0030] In addition, in some embodiments, a user interface 16 is provided, at which a user of the control system 100 can input and / or monitor various aspects of the operation of the control system 100 and the associated pump. For example, the user interface 16 can be programmed to display one or more graphical outputs of the data received and analyzed by the controller 5. The user interface 16 can also display other data stored in the memory of the controller 5, including data related to the duration and amount of the positive and negative air flows supplied by the positive pressure supply 1 and the negative pressure supply 2 at each step in a plurality of processing steps. Other information that can be displayed on the user interface 16 includes data showing the minimum and maximum air flow and volume, and the minimum and maximum air flow and volume include a tolerance range for the air flow. Further, additional parameters that can be displayed to the user at the user interface 16 include flow and cycle time for one or more processing steps. The user interface 16 can be optionally provided at a station near the control system 100. In some embodiments, the user interface 16 can communicate with a user interface 12 connected to a server SV, a switch SW, and a wireless router R. The user interface 12 can be located at a location away from the workstation. In some embodiments, user interface 12 may be used for all input and / or monitoring functions, and user interface 16 may not be present. For example, in some embodiments, user interface 12 may be a mobile computing unit such as a laptop or tablet computer, and user interface 16 may include a small interactive display positioned near control system 100.

[0031] In addition, the user interface 12, 16 of certain exemplary embodiments allows the user to control the start or stop of the control process performed by the controller 5. In some embodiments, the start and stop functions can be controlled by buttons provided on, for example, a touch screen display. The user interface 12, 16 also allows the input (entry) of specified control parameters. For example, the user can input a desired amount of positive or negative pressure into the controller 5 at the user interface 12, 16. When the diaphragm is connected to the housing 7, the desired amount of positive or negative air flow is associated with the position of the diaphragm at the two ends of its displacement.

[0032] In particular, for example, the user can instruct the controller 5 at the user interface 12, 16 to apply a constant positive air flow to the first connector in the housing 7 and a constant negative air flow to the second connector. The user can initially set the size (e.g., in terms of volume) of the diaphragm pump connected to the third connector. The controller 5 automatically resets the displacement of the diaphragm based on the size of the pump. Next, the user can set the volume of fluid to be discharged by the diaphragm pump in a given time period, where the flow rate is the product of the number of complete cycles per minute and the discharge volume per cycle. The controller is also programmed to adjust the duration of a complete cycle of diaphragm displacement in a single pumping cycle or multiple pumping cycles, and control the discharge of a certain volume of fluid within a predetermined time period.

[0033] In addition, manually or according to an algorithm or mathematical scheme, the user can further input the expected duration of the pumping operation, which generates an execution profile suitable for a specific application together with the expected volume of the fluid to be expelled within the duration, such as cell harvesting. The execution profile can be based at least in part on the determination duration of the partial or complete cycle of the displacement of one or more pumps. The sensor 3 monitors the air flow of each step and allows the actual detected air flow to be compared with a predetermined threshold value (e.g., corresponding to the air flow of the allowed pressure). In addition, in at least one embodiment, the control system 100 allows the pumping of fluids with a constant or variable flow through the pump according to the execution profile. The execution profile is based on the determined duration and intensity of multiple processing steps. For example, an execution profile can be generated based on the selection of the duration of the pumping operation, and the execution profile is included in the predetermined positive and negative air flow in a given processing step. The controller 5 also allows the user to adjust the degree of opening and / or closing of the regulator 6 according to the duration of the partial or complete cycle of the displacement of the diaphragm pump, which can be performed according to the execution profile. Furthermore, the controller 5 allows the transition of the proportional pressure regulator 6 from opening to closing to be regulated according to the transition between the supply of the positive and negative air flows. Thus, the "switch" between the positive and negative air flows can be precisely controlled. In particular, the controller 5 is configured to regulate the duration of a partial or complete cycle of the displacement of the diaphragm pump to meet the process requirements. Thus, the delivery of the filtered fluid to the container can be controlled according to the process requirements.

[0034] The control system 100 may also be configured to provide information to the controller 5 from one or more sensors other than the sensor 3. For example, in at least one embodiment, the controller 5 is configured to receive an indication from at least one proximity sensor. The proximity sensor is arranged near the diaphragm and is configured to detect the position of the diaphragm at one or both ends of its displacement (i.e., the displacement obtained at the end position of the diaphragm under positive and negative pressures). For example, the controller 5 responds to the output of the proximity sensor, which is arranged near the diaphragm and is configured to detect at least the position of the diaphragm at the end of its displacement (the "bottom" displacement) when the negative air flow transitions to the positive air flow and / or the position of the diaphragm at the end of its displacement (the "top" displacement) when the positive air flow transitions to the negative air flow. Thus, the proximity sensor provides information indicating the relative position of the diaphragm to the controller 5. The controller 5 adjusts the fluid flow in response to the detection of the position by the proximity sensor. In particular, the diaphragm end position can be continuously monitored by the proximity sensor.

[0035] The diaphragm position must reach its maximum end position in order to obtain full displacement within each cycle and to obtain full flow within a given time period. When the controller 5 determines, based on information from the proximity sensor, that one or more end positions are not met, the controller is configured to automatically adjust the opening of the regulator 6 to increase the positive or negative air flow. When the controller detects a fault, for example, when the diaphragm fails to reach the correct position within a given number of cycles, the controller 5 can cause the system 100 to issue an audible warning. As another example, the controller 5 can receive information from a probe configured to detect a property of a fluid flowing in the system 100, such as a glucose probe designed to indicate the glucose content of the fluid.

[0036] In addition, the control system 100 can also be configured to provide information to the controller 5 from one or more sensors other than pressure or proximity sensors. For example, in at least one embodiment, the controller 5 is configured to receive indications from at least one liquid flow meter (flow sensor) configured to detect fluid flow and / or diaphragm pump displacement. The flow rate is directly related to the diaphragm pump displacement controlled by the positive and negative air flows. An additional flow meter (flow sensor) on the filtrate side can inform the user of the volume of the final product at any given time.

[0037] In addition, at least one embodiment allows the execution of a cleaning function. In particular, the controller 5 controls the pressure supply 1, 2 so as to deliver a burst of air pressure at a specified time to clean the filter of the pump. The controller 5 is programmed to cause the pump to perform a regular filter cleaning cycle to remove unwanted particles or debris from the filter. The cleaning cycle can be manually started, for example, by selecting the "cleaning cycle" option on the user interface, or it can be automatically started, for example, when the controller determines that a cleaning cycle should be performed based on data collection or the time interval since the last cleaning. In addition, the controller is programmed to cause the corresponding pressure supply 1, 2 to supply at least one of the positive or negative air flows with a first flow rate and to clean the filter by delivering at least one burst of air flow at a second flow rate greater than the first flow rate. For example, the filter can be cleaned by applying a negative air flow and then delivering at least one burst of positive air flow at a second flow rate greater than the first flow rate. For example, in at least one embodiment, a burst of air flow can be provided at a second flow rate that is at least twice the first flow rate. In addition, a pump can be used for cleaning. For example, the controller 5 can control the pump to increase the pumping flow rate briefly and then return to a lower constant flow rate, which can advantageously increase the life expectancy of the filter. In particular, the pump advances the filtrate flow to the second container, and the pump can be stopped or reversed to increase back pressure, thereby generating a backflow and producing the desired cleaning effect. In addition, an effective cleaning process can be performed by utilizing both the air burst and pump flow control as described above in conjunction with each other. Further, as part of the cleaning process, in addition to reversing or stopping the pump, the controller 5 can also control the timing of the burst fluid flow.

[0038] In addition, the controller 5 is programmed to control the timing of the air pressure delivery to achieve a predetermined amount of air flow to the air flow line in the housing 7. That is, in addition to the specified amount and flow rate, the user can also enter timing information (start, stop, duration) at the user interface. For example, the user can enter the start and stop times to define a predetermined time period, and then the controller can control the pressure supply parts 1, 2 to output a continuous air flow within the predetermined time period. In particular, the controller 5 adjusts the positive or negative air flow so that the air flow is output at a first rate in a first time period and at a second rate in a second time period, wherein the first time period is shorter than the second time period, and the first rate is higher than the second rate, and vice versa.

[0039] As described above, in at least one embodiment, the controller is configured to perform control of the alternating tangential flow pump. However, in at least one embodiment, the controller is configured to activate the tangential filtration flow in a continuous manner rather than a reciprocating action. In addition, in at least one embodiment, the controller is configured to enable the independent pump to operate according to the alternating tangential filtration flow function or the tangential filtration flow function by activating and controlling the independent pump. When the pump is operated according to the tangential filtration flow function, the controller performs a startup process to enable the pump to start the tangential filtration flow. Thereafter, the controller performs monitoring of the flow. In such an embodiment, when the tangential filtration flow function is executed, the proportional pressure regulator 6 is not actuated.

[0040] Now turn to Figure 3 , according to an exemplary embodiment, Figure 1 The system 100 shown in can be arranged in the bioreactor control system. The bioreactor control system of at least one embodiment is a multiplex system and can be included in the bioreactor with multiple pumping modules 26, or a controller 5 serves two or more bioreactors. In particular, in at least one embodiment, the housing 7 can accommodate multiple pumping modules, thereby allowing to be connected with multiple pumping modules 26. The controller 5 determines the operating speed of each pump. Other components of the bioreactor control system include bioreactor 18 and bioreactor controller 28, scale 30, hollow filter module 22 and a platform 24 for it, and the height of the platform is adjustable.

[0041] In addition, the control system allows the user to start the perfusion process. The perfusion process includes supplying culture medium and supplying glucose when there is no glucose or no required amount of glucose in the culture medium. The perfusion process further includes performing cell separation, osmotic harvesting and cell bleeding. In order to maintain a constant reactor volume, the steps of the above-mentioned perfusion process must be coordinated. For example, culture medium should be added at a rate substantially the same as the rate of the permeate outflow system. In addition, the addition rate of the culture medium can be adjusted according to the glucose content and the cell discharge rate to ensure that the reactor has a constant volume. Cell discharge and / or glucose addition are performed intermittently to maintain the required cell density. In addition, cell separation itself is completed using alternating tangential flow. Alternating tangential flow is established by the action of an oscillating diaphragm, which allows the cell culture to reciprocate through the hollow fiber membrane of the filter. The flow rate of the osmotic pump can be synchronized with the diaphragm action to achieve a desired permeate flow rate.

[0042] Figure 5 A schematic diagram of a bioreactor control system according to an exemplary embodiment is depicted. The bioreactor control system includes a plurality of pumps including a medium pump MP, a glucose pump GP, a bleed pump BP, and a perfusion pump PP. A controller (eg, controller 5) may use a plurality of flow meters.

[0043] like Figure 5 As further shown, a container containing fresh medium FM is connected to a medium pump and at least one flow controller FC. A container containing glucose G is connected to a glucose pump and another flow controller FC. The speed and timing of the glucose flow can be controlled by an operator. The fresh medium container, the glucose container and their respective pumps are fluidly connected to the bioreactor, such as Figure 5 in the form of a jacketed mixing vessel as shown in . One or more regulators can be used to control the direction of material flow to and from the bioreactor. A weight transmitter or weight sensor WT can be used to weigh the material flowing into or out of the bioreactor, and the measured weight can be transmitted to a controller or visually displayed on a scale indicator separate from the controller. In addition, the bioreactor communicates with an analyzer transmitter AT and a flow controller FC downstream of the bioreactor. The operator can provide input to the analyzer transmitter AT, such as a valuable cell density (VCD) set point (SP). The analyzer transmitter AT and the flow controller FC downstream of the bioreactor are configured to be connected to a discharge pump BP. The discharge pump BP is in turn configured to discharge the discharge waste BW into a discharge waste tank. A fluid channel connects the diaphragm regulator to the bioreactor, wherein a flowmeter FM1 (first flowmeter) is arranged in the fluid channel to measure the fluid properties of the fluid flowing out of the bioreactor.

[0044] The system also includes a positive air pressure supply (air supply A) (as shown by supply line B) and a negative air pressure supply (e.g., from a vacuum V) (as shown by supply line C) connected to a regulator (corresponding to the proportional pressure regulator 6). For illustration purposes, Figure 5 The regulator is shown on the outside of the housing. The regulator is connected to the perfusion pump PP and to at least one flow meter (flow transmitter or flow sensor), such as a second flow meter FM2. Figure 5As shown in , a flow transmitter FT1 (first flow transmitter) is arranged near the bioreactor, and a flow transmitter FT2 (second flow transmitter) is arranged near the perfusion pump PP. The perfusion pump fluid is connected to a container containing the harvest medium HM. At least one flow controller (e.g., a controller such as controller 5) is configured to receive volume and speed settings that can be input by an operator, for example, at user interfaces 12 and 16. For example, the settings may include setting a daily container volume (WD) set point. For example, pressure transmitters (pressure sensors) PT1, PT2, PT3A may be arranged to measure the pressure between the bioreactor and the filter, between the filter and the regulator, and between the filter and the perfusion pump, respectively. The pressure transmitter PT1 is the first pressure transmitter, PT2 is the second pressure transmitter, and PT3A is the third pressure transmitter. In addition, at least one flow controller is configured to receive the desired shear rate of the fluid flow in the system as input, which can be input at user interfaces 12 and 16. In addition, the flow controller is configured to receive a daily container value (VVD) as input. The daily container value is the volumetric amount filtered, which generally corresponds to the capacity of the container.The controller 5 is also configured to receive as input parameters such as the valuable cell density (VCD) and / or the set point (SP), for example.

[0045] Such an embodiment can be practiced in a network environment using a logical connection with one or more remote computers having a processor. It will be appreciated by those skilled in the art that such a network computing environment can encompass many types of computers, including personal computers, handheld devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, mainframe computers, etc. Implementation methods can also be practiced in a distributed computing environment, in which tasks are performed by local and remote processing devices linked (by a hardwired link, a wireless link, or by a combination of a hardwired link or a wireless link) through a communication network (e.g., a local area network (LAN) 14). In a distributed computing environment, program modules can be located in local and remote storage devices.

[0046] The bioreactor control system also includes at least one communication unit, which can be coupled to a switch SW and a router R to provide a communication link between the system and the network. In this way, the communication unit enables the processor to communicate with other electronic systems coupled to the network in wired or wireless communication. For example, the communication unit can be coupled to an Ethernet line that connects the system to the Internet or another network. In other embodiments, the communication unit can be coupled to an antenna (not shown) and provide the function of sending and receiving information through an optional wireless communication interface 10 (wireless user interface) about the network. The wireless user interface 10 can be used instead of the user interface 12 and / or the user interface 16.

[0047] In various embodiments, the communication unit may include one or more transceivers configured to perform data communications according to one or more communication protocols, including but not limited to WLAN protocols (e.g., IEEE 802.11a / b / g / n / ac / ad, IEEE 802.16, IEEE 802.20, etc.). Thus, the bioreactor control system allows monitoring and control of pumping operations in an entire network environment. Data collection and analysis may also be performed on multiple pumping modules. In addition, information such as sensed pressure levels from a diaphragm pressure sensor built into or attached to the diaphragm housing may also be transmitted to the controller 5. Sensed data indicating fluid flow at the housing holding the diaphragm pump may also be obtained and provided to the controller.

[0048] As a further example, the controller 5 can be connected to another controller via a network, such as an independent controller of a bioreactor container. In addition, in at least one embodiment, the controller 5 can communicate with a group of sensors that monitor the operating temperature, fluid level, and rheology of the fluid. For example, an optical turbidity monitor can be provided that sends turbidity data to the controller 5. In addition, information about the composition of the biological fluid can also be relayed to the controller 5 and transmitted to the user through the user interface 16. For example, the cell density in the biological fluid can be determined and displayed to the user. In addition, data analysis can be performed to determine an execution profile based on data from multiple pumps of the pumping system of the bioreactor control system. In addition, a statistical distribution of interest can be generated based on data from multiple pumps, and it can be used to evaluate the performance of the pump system.

[0049] In addition, the bioreactor control system includes a plurality of holding devices (containers). For example, in at least one embodiment, the control system includes a first container for storing unfiltered material and a second container for storing filtered material. The material can be a biological fluid, such as a fluid containing animal, human or microbial cells. The pump is activated so that a portion of the fluid is pumped from the first container through the filter and the filtered fluid is delivered to the second container. More specifically, a negative air flow is applied to the airflow line 8 in the housing 7, and the fluid can be sucked from the first container. The fluid can be delivered to a diaphragm pump or another container from the first container according to the alternating supply of positive and negative air flow control. The discharge of fluid from the pump or container can be controlled in the same manner as the delivery fluid. Therefore, in at least one embodiment, the biological fluid is sucked from the bioreactor to the container, and a portion of the fluid can be returned to the bioreactor, and another portion can be directed to the container (e.g., the second container). In some embodiments, the second container can be refrigerated. For example, a filter (e.g., a hollow fiber filter) can be used to separate the biological fluid and direct a portion of the filtrate to the second container. Alternating tangential flow can be used to continuously filter the fluid until it reaches the second container.

[0050] In addition, the pump can be operated to pump part of the fluid from the first container back to the first container (return flow). In addition, the controller 5 can be operated to allow or limit the flow of the fluid from the second container to allow or limit the backflow of the fluid from the second container to the first container (return flow). When the backflow function is not used to clean the filter (that is, when the control system temporarily does not use the backflow function in the cleaning state), the controller 5 can limit the backflow.

[0051] Figure 4 Described is the control process 400 according to an embodiment.Process 400 relates to the actuation operation of the pump equipped with a diaphragm.The process includes selecting the volume or size of the pump (step 401) and selecting the flow rate (volume per minute) (step 402).The process also includes selecting the duration of the pumping operation (including the predetermined positive and negative air flow rates at the given processing step) to generate an execution profile suitable for a specific application (step 403).In addition, the process includes actuating the pumping operation (step 404) by alternately supplying positive and negative air flows via a regulator contained in the housing.In addition, the process includes monitoring the positive or negative air flow in the airflow line in the housing to maintain or change the air volume flowing per unit time in the airflow line (step 405).Alternatively, additional processing steps can be performed. For example, the control process 400 also includes optionally monitoring the position of the diaphragm at one or both ends of its displacement (step 406) and optionally changing the volume of air flowing per unit time in the air flow line to: affect the position of the diaphragm at one or both ends of its displacement; or affect the duration of a partial or complete cycle of displacement; or affect both (step 407).

[0052] Although this specification contains specific implementation details, these should not be interpreted as limitations on the scope of the claims, but should be interpreted as descriptions of features specific to a particular embodiment. Certain features described in the context of separate embodiments in this specification may also be implemented in combination in a single embodiment. On the contrary, the various features described in the context of a single embodiment may also be implemented individually in multiple embodiments or in any suitable sub-combination. Moreover, although features may be described above as working in certain combinations and even initially claimed as such, in some cases, one or more features from the claimed combination may be removed from the combination, and the claimed combination may be directed to a sub-combination or a variation of the sub-combination.

[0053] Similarly, although operations are depicted in a particular order in the drawings, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve the desired effect. In some cases, the separation of various system components in the above-described embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the components and systems described can generally be integrated into a single product or packaged into multiple products.

[0054] As used herein, the term "substantially" and similar terms are intended to have a broad meaning consistent with the common and recognized usage by those of ordinary skill in the art to which the subject matter of the present disclosure belongs. It should be understood by those skilled in the art who review this disclosure that these terms are intended to allow for the description of certain features described and claimed without limiting the scope of these features to the precise numerical ranges provided. Therefore, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the present invention as described in the appended claims.

[0055] As used herein, the terms "coupled," "connected," and the like refer to the joining of two components directly or indirectly to one another. Such joining may be fixed (e.g., permanent) or movable (e.g., removable or releasable). Such joining may be achieved by the two components or the two components and any additional intermediate components (which are integrally formed with each other or with the two components) or the two components and any additional intermediate components (which are attached to one another).

[0056] As used herein, the terms "fluid coupling", "fluid communication", and the like refer to two components or objects having a path formed between the two components or objects in which a fluid such as water, air, biological fluid, etc. can flow, with or without intermediate components or objects. Examples of fluid couplings or structures for achieving fluid communication may include pipes, channels, or any other suitable components for allowing fluid to flow from one component or object to another component or object.

[0057] It is important to note that the construction and arrangement of the systems shown in the various exemplary embodiments are merely illustrative and not restrictive in nature. It is desired to protect all changes and modifications within the spirit and / or scope of the described embodiments. It should be understood that certain features are not necessary, and implementations lacking various features can be imagined, which are also within the scope of the present application, which is defined by the appended claims. When reading the claims, when words such as "one", "one", "at least one" or "at least one portion" are used, unless there is an explicit statement to the contrary in the claims, it is not intended to limit the claim to only one item. When the language "at least a portion" and / or "a portion" is used, unless there is an explicit statement to the contrary, the item may include a portion and / or the entire item.

Claims

1. A filtering system comprising: Filter components; a container coupled to the filter assembly via a pipeline; a pump coupled to the filter assembly for moving material between the filter assembly and the container; A flow sensor connected to the pipeline connecting the container and the filter assembly, for sensing the material flow in the pipeline connecting the container and the filter assembly; a gas flow line coupled to the diaphragm portion of the pump; a regulator coupled to the gas flow line for controlling gas flow through the gas flow line; a pressure sensor connected to the gas flow line for sensing the pressure in the gas flow line; and A controller coupled to the flow sensor, the pressure sensor, and the regulator, the controller comprising a processor that executes instructions to control the regulator in response to flow information received from the flow sensor and pressure information received from the pressure sensor to control air flow through the air flow line, wherein controlling the air flow through the air flow line controls the pump to control material flow between the filter assembly and the container.

2. A system according to claim 1, wherein the regulator is connected to a positive pressure supply for supplying a positive air flow to the diaphragm portion of the pump through an air flow line, and wherein the regulator is connected to a negative pressure supply for providing a negative air flow from the diaphragm portion of the pump through the air flow line.

3. The system of claim 1, wherein the processor is programmed to execute instructions for comparing the pressure information to a predetermined threshold and, in response thereto, further adjusting the flow of gas through the gas flow line to control the flow of material between the filter assembly and the container.

4. The system of claim 1, wherein the processor is programmed to execute instructions for comparing the sensed flow information to a predetermined threshold and, in response thereto, further adjusting the flow of gas through the gas flow line to control the flow of material between the filter assembly and the container.

5. The system of claim 1, wherein the processor is programmed to execute instructions for controlling the regulator to adjust the duration of a partial or full cycle of the pump.

6. The system of claim 1, wherein the regulator comprises a proportional pressure regulator.

7. The system of claim 1, wherein the filter assembly comprises a hollow fiber filter, the container is a bioreactor, and the pump is controlled by the controller to induce alternating tangential flow within the filter assembly.

8. A filtering system comprising: Filter components; a container coupled to the filter assembly via a pipeline; a pump coupled to the filter assembly for moving material between the filter assembly and the container; A flow sensor coupled to a pipeline connecting the container and the filter assembly for sensing a material flow in the pipeline; A pressure sensor coupled to a pipeline connecting the container and the filter assembly for sensing the pressure of the material in the pipeline; a gas flow line coupled to the diaphragm portion of the pump; a regulator coupled to the gas flow line for controlling gas flow through the gas flow line; a pressure sensor connected to the gas flow line for sensing the pressure in the gas flow line; an air flow sensor coupled to the air flow line for sensing air flow through the air flow line; and A controller coupled to the flow sensor, the pressure sensor, the airflow sensor, and the regulator, the controller comprising a processor that executes instructions for controlling the regulator in response to flow information received from the flow sensor, the airflow sensor, and pressure information received from the pressure sensor to control airflow through the airflow line, wherein controlling the airflow through the airflow line controls a pump to control material flow between the filter assembly and the container.

9. A system according to claim 8, wherein the regulator is connected to a positive pressure supply for supplying a positive air flow to the diaphragm portion of the pump through an air flow line, and wherein the regulator is connected to a negative pressure supply for providing a negative air flow from the diaphragm portion of the pump through the air flow line.

10. The system of claim 8, further comprising a weight sensor coupled to the filter assembly for sensing a weight of the filter assembly, the weight sensor coupled to the controller for providing weight information to the controller.

11. The system of claim 8, wherein the processor is programmed to execute instructions for controlling the regulator to adjust the duration of a partial or full cycle of the pump.

12. The system of claim 8, wherein the regulator comprises a proportional pressure regulator.

13. The system of claim 8, wherein the filter assembly comprises a hollow fiber filter, the container is a bioreactor, and the pump is controlled by the controller to induce alternating tangential flow within the filter assembly.

14. A method for controlling a filtration system, comprising: actuating a pump to cause material to flow through a line coupled between the container and the filter assembly; Sensing material flow through pipelines; sensing air pressure in an air flow line coupled between the regulator and a diaphragm portion of the pump; and Based on the sensed material flow through the line coupling the container and the filter assembly and the sensed pressure in the gas flow line, gas flow through the gas flow line is adjusted to control operation of the pump to control material flow between the container and the filter assembly.

15. The method of claim 14, wherein regulating the air flow through the air flow line comprises controlling a positive air flow or a negative air flow through the air flow line via a regulator.

16. The method of claim 14, further comprising sensing material pressure in a pipeline connecting the container and the filter assembly, and further adjusting airflow through the airflow pipeline to control operation of the pump to control material flow between the filter assembly and the container based at least in part on the sensed material pressure in the pipeline connecting the container and the filter assembly.

17. The method of claim 14, further comprising sensing a weight of the filter assembly, and further adjusting air flow through the air flow line based at least in part on the sensed weight of the filter assembly to control operation of the pump to control material flow between the filter assembly and the container.

18. The method of claim 14, further comprising automatically controlling the flow of material between the container and the filter assembly to account for changes in material viscosity over time to achieve a flow output specified by a user.

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