CN113952786A

CN113952786A - Biological filtration system and control method thereof

Info

Publication number: CN113952786A
Application number: CN202111226940.9A
Authority: CN
Inventors: 刘禹; 陈睿
Original assignee: Shanghai Aizhong Biotechnology Co Ltd
Current assignee: Alite Biotechnology Shanghai Co ltd
Priority date: 2021-10-21
Filing date: 2021-10-21
Publication date: 2022-01-21

Abstract

The embodiment of the specification provides a biofiltration system and a control method thereof. The biofiltration system is used for filtering a solution in a bioreactor, and comprises: a filtration device having a top end and a bottom end, one of the top and bottom ends for fluid communication with the bioreactor to filter a solution within the bioreactor; a liquid chamber in fluid communication with the other of the top and bottom ends for buffering a solution within the filtration device; a positive pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the liquid chamber to the bioreactor; a negative pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the bioreactor to the liquid chamber.

Description

Biological filtration system and control method thereof

Technical Field

The specification relates to the field of biological filtration, in particular to a biological filtration system and a control method thereof.

Background

A biological filtration system is a system for treating or filtering a biological solution, and is generally applied to a filtration process such as replacement of a fresh culture solution, separation of a cell metabolite, and separation of cells and a culture solution. The main components of the biological filtration system comprise a filtration device and a diaphragm pump, wherein the filtration device is communicated with the bioreactor, and the diaphragm pump is arranged at the end part of the filtration device and used for providing driving force for the filtration device and driving the biological solution to circularly and reciprocally flow between the filtration device and the bioreactor so as to achieve the aim of selectively separating each component in the biological solution.

Disclosure of Invention

One aspect of the present description provides a biofiltration system. The biofiltration system comprises: a filtration device having a top end and a bottom end, one of the top and bottom ends for fluid communication with the bioreactor to filter a solution within the bioreactor; a liquid chamber in fluid communication with the other of the top and bottom ends for buffering a solution within the filtration device; a positive pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the liquid chamber to the bioreactor; a negative pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the bioreactor to the liquid chamber.

In some embodiments, the filter device includes a filter portion disposed proximate the bottom end of the filter device and a buffer portion disposed proximate the top end of the filter device, the buffer portion is configured as a hollow chamber to form the liquid chamber, and the buffer portion is in direct communication with the filter portion.

In some embodiments, the liquid chamber comprises a single cavity that directly interfaces with the top end of the filtration device.

In some embodiments, the liquid chamber comprises a single cavity connected to the top end or the bottom end of the filtration device by a conduit.

In some embodiments, the liquid chamber comprises a plurality of cavities, each of which is connected to the top end or the bottom end of the filter device by a tube.

In some embodiments, the biological filtration system includes a first conduit through which the bottom end of the filtration device is connected to the bioreactor, the positive pressure pump is configured to drive the solution within the filtration device to flow along the first conduit to the bioreactor, and the negative pressure pump is configured to drive the solution within the bioreactor to flow along the first conduit to the filtration device.

In some embodiments, the biological filter system comprises a second pipeline and a third pipeline, the bottom end of the filter device is connected with the bioreactor through the second pipeline and the third pipeline, the second pipeline is provided with a first one-way valve to enable the solution in the filter device to flow to the bioreactor in one way, and the third pipeline is provided with a second one-way valve to enable the solution in the bioreactor to flow to the filter device in one way.

In some embodiments, the biological filtration system comprises a fourth conduit, a fifth conduit, and a sixth conduit, one of the top end and the bottom end of the filtration device is connected to the cavity by the fourth conduit, the other of the top end and the bottom end of the filtration device is connected to the bioreactor by the fifth conduit, the cavity is connected to the bioreactor by the sixth conduit, the positive pressure pump is configured to drive the solution within the cavity to flow to the bioreactor via the filtration device, and the negative pressure pump is configured to drive the solution within the bioreactor to flow to the cavity; or the positive pressure pump is used for driving the solution in the cavity to flow to the bioreactor, and the negative pressure pump is used for driving the solution in the bioreactor to flow to the cavity through the filtering device.

In some embodiments, the biofiltration system further comprises a first sensor for detecting liquid level information within the liquid chamber, the first sensor being disposed at a preset interval from a top of the liquid chamber, and a second sensor disposed at a bottom of the liquid chamber.

In some embodiments, the biofiltration system further comprises a third sensor and a fourth sensor for detecting fluid level information within the filtration device, the filtration device comprising a reaction fluid port and a retentate port, the third sensor being disposed at the reaction fluid port and the fourth sensor being disposed at the retentate port.

In some embodiments, the biofiltration system further comprises a gas purifier disposed in a flow path of the liquid chamber connecting the positive pressure pump and the negative pressure pump.

In some embodiments, the biofiltration system further comprises a cooling device disposed in correspondence with the liquid chamber for cooling air entering the gas purifier.

In some embodiments, the biofiltration system further comprises a reservoir disposed in a flow path between the gas purifier and the negative pressure pump, the reservoir configured to collect condensed water.

In some embodiments, the biofiltration system further comprises a check valve disposed on a flow path between the gas purifier and the negative pressure pump for preventing condensed water from flowing back into the gas purifier.

In some embodiments, the biofiltration system further comprises a heating device disposed in correspondence with the gas purifier and/or the liquid chamber.

In some embodiments, the biofiltration system further comprises a first pressure regulating device and a second pressure regulating device, wherein the first pressure regulating device is arranged at the outlet of the positive pressure pump and used for regulating the pumping gas pressure of the positive pressure pump, and the second pressure regulating device is arranged at the outlet of the negative pressure pump and used for regulating the pumping gas pressure of the negative pressure pump.

In some embodiments, the biofiltration system further comprises a pressure relief bypass disposed in a flow path between the liquid chamber and the positive pressure pump and/or the negative pressure pump for relieving gas pressure within the biofiltration system.

In some embodiments, the filtration device is provided with a permeate port, the biofiltration system further comprising a collection vessel to which the permeate port is connected and a flow control device disposed between the collection vessel and the filtration device for controlling the flow rate of the solution in the filtration device to the collection vessel.

In some embodiments, the biofiltration system further comprises at least one pressure sensor for detecting a pressure signal of the solution and/or gas; wherein the pressure sensor is disposed in a flow path between the filter device and the liquid chamber; and/or the pressure sensor is arranged on a flow path between the liquid chamber and the positive pressure pump and/or the negative pressure pump; and/or the pressure sensor is arranged on a flow path between the filtering device and the bioreactor.

In some embodiments, the biofiltration system further comprises a processor for:

acquiring a first liquid level signal in the filtering device or the liquid chamber;

controlling a positive pressure pump to drive the solution in the filtering device to flow to a bioreactor based on the first liquid level signal;

acquiring a second liquid level signal in the filter device or the liquid chamber;

controlling a negative pressure pump to drive the solution in the bioreactor to flow to the filtering device based on the second liquid level signal.

In some embodiments, the processor is further configured to:

acquiring a first time for triggering the first liquid level signal;

acquiring a second time for triggering the second liquid level signal;

adjusting the flow rate of the solution based on the time difference between the first time and the second time.

In some embodiments, the processor adjusts the flow rate of the solution based on a time difference between the first time and the second time, comprising:

comparing the time difference with a preset time difference;

if the time difference is smaller than the preset time difference, controlling a pressure regulating device of the biological filtration system to reduce the pressure so as to reduce the flow speed of the solution;

and if the time difference is larger than the preset time difference, controlling the pressure regulating device to increase the pressure so as to increase the flow speed of the solution.

In some embodiments, the processor is further configured to:

monitoring a pressure signal within the biofiltration system;

comparing the pressure signal with a preset pressure threshold value, and judging whether the biological filtration system is blocked or not;

and if the blockage exists, sending alarm information.

Another aspect of the present description provides a method of controlling a biofiltration system. The control method is applied to the biofiltration system, and comprises the following steps:

In some embodiments, the method further comprises:

acquiring a first time for triggering the first liquid level signal;

acquiring a second time for triggering the second liquid level signal;

In some embodiments, said adjusting the flow rate of said solution based on the time difference between the first time and the second time comprises:

comparing the time difference with a preset time difference;

In some embodiments, the method further comprises:

monitoring a pressure signal within the biofiltration system;

and if the blockage exists, sending alarm information.

Drawings

The present description will be further explained by way of exemplary embodiments, which will be described in detail by way of the accompanying drawings. These embodiments are not intended to be limiting, and in these embodiments like numerals are used to indicate like structures, wherein:

FIG. 1A is a schematic illustration of an exemplary biofiltration system according to a first embodiment of the present description;

FIG. 1B is a schematic illustration of an exemplary biofiltration system, as shown, in accordance with an embodiment of the present disclosure;

FIG. 2A is a schematic view of an exemplary biofiltration system according to example two of the present description;

FIG. 2B is a schematic view of an exemplary biofiltration system according to example two of the present description;

FIG. 3A is a schematic illustration of an exemplary biofiltration system according to example III of the present disclosure;

FIG. 3B is a schematic illustration of an exemplary biofiltration system according to example III of the present disclosure;

FIG. 3C is a schematic illustration of an exemplary biofiltration system according to example III of the present description;

FIG. 3D is a schematic illustration of an exemplary biofiltration system according to a third embodiment of the present description;

FIG. 4A is a schematic illustration of an exemplary biofiltration system according to example four of the present description;

FIG. 4B is a schematic illustration of an exemplary biofiltration system according to example four of the present description;

FIG. 5 is a schematic flow diagram of a method of controlling an exemplary biofiltration system according to some embodiments of the present description;

FIG. 6 is a schematic flow diagram of a method of controlling an exemplary biofiltration system according to some embodiments of the present description;

FIG. 7 is a schematic flow diagram of a method of controlling an exemplary biofiltration system according to some embodiments of the present description;

FIG. 8 is a schematic flow diagram of a method of controlling an exemplary biofiltration system according to some embodiments of the present description;

fig. 9 is a schematic diagram of an exemplary configuration of a treatment device of a biofiltration system according to some embodiments of the present disclosure.

In the figures, 10, 20, 30, 40 is a biological filtration system, 50 is a biological reactor, 101 is a filtration device, 1011 is a top end, 1012 is a bottom end, 1013 is a reaction liquid port, 1014 is a retentate port, 1015 is a permeate port, 1016 is a filter section, 1017 is a buffer section, 102, 202, 302, 402 are liquid chambers, 103 is a positive pressure pump, 104 is a negative pressure pump, 1051 is a main line, 1052 is a positive pressure branch line, 1053 is a negative pressure branch line, 106 is a first pipe, 107 is a second pipe, 108 is a third pipe, 125 is a fourth pipe, 126 is a fifth pipe, 127 is a sixth pipe, 1054 is a first multi-way pipe, 1055 is a second multi-way pipe, 109 is a first check valve, 110 is a second check valve, 111 is a first sensor, 112 is a second sensor, 203 is a third sensor, 204 is a fourth sensor, 113 is a gas purifier, 114 is a cooling device, 115 is a heating device, 116 is a liquid storage tank, 117 as a check valve, 118 as a first pressure regulating device, 119 as a second pressure regulating device, 120 as a pressure relief bypass, 121 as a collecting container, 122 as a flow control device, 123 as an electromagnetic valve, 124 as a pressure sensor, 900 as a processing device, 910 as a storage medium, and 920 as a processor.

Detailed Description

In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings used in the description of the embodiments will be briefly described below. It is obvious that the drawings in the following description are only examples or embodiments of the present description, and that for a person skilled in the art, the present description can also be applied to other similar scenarios on the basis of these drawings without inventive effort. Unless otherwise apparent from the context, or otherwise indicated, like reference numbers in the figures refer to the same structure or operation.

It should be understood that "system", "device", "unit" and/or "module" as used herein is a method for distinguishing different components, elements, parts, portions or assemblies at different levels. However, other words may be substituted by other expressions, provided that they accomplish the same purpose.

As used in this specification and the appended claims, the terms "a," "an," "the," and/or "the" are not intended to be inclusive in the singular, but rather are intended to be inclusive in the plural unless the context clearly dictates otherwise. In general, the terms "comprises" and "comprising" merely indicate that steps and elements are included which are explicitly identified, that the steps and elements do not form an exclusive list, and that a method or apparatus may include other steps or elements.

Although various references are made herein to certain modules or units in a system according to embodiments of the present description, any number of different modules or units may be used and run on the client and/or server. The modules are merely illustrative and different aspects of the systems and methods may use different modules.

Flow charts are used in this description to illustrate operations performed by a system according to embodiments of the present description. It should be understood that the preceding or following operations are not necessarily performed in the exact order in which they are performed. Rather, the various steps may be processed in reverse order or simultaneously. Meanwhile, other operations may be added to the processes, or a certain step or several steps of operations may be removed from the processes.

In the related art of cell culture and the like, a biofiltration system filters a reaction solution in a bioreactor based on physical and/or chemical properties to obtain a desired culture solution. In some embodiments of the present disclosure, the biofiltration system may filter a reaction solution in the bioreactor, where the reaction solution refers to a solution to be filtered; the filtered solution comprises a retentate, which is the solution blocked by the filtering means in the biofiltration system and which can be re-introduced into the bioreactor for re-filtration, and a permeate, which is the solution that permeates the filtering means in the biofiltration system. Wherein the retentate may be the desired culture solution and the permeate may be the waste solution, or the retentate may be the waste solution and the permeate may be the desired culture solution. In some embodiments, the retentate in the biofiltration system may be re-discharged into the bioreactor to form a new reaction solution. For simplicity of description, the reaction solution, the retentate and the permeate are collectively referred to as a solution in the present specification.

In some embodiments of the present disclosure, the filtering device and the liquid chamber are integrally formed, the filtering device includes a filtering portion and a buffer portion, and the liquid chamber is integrated in the buffer portion and directly communicated with the filtering portion, so that the liquid chamber is integrated in the filtering device, which makes the design more compact, and not only simplifies the structure of the biological filtering system, but also reduces the space occupied by the filtering device and the liquid chamber. In some embodiments, the liquid chamber comprises a single cavity that interfaces directly with the top end of the filtration device, which can reduce the amount of solution circulating outside the bioreactor and filtration device. In some embodiments, the liquid chamber comprises a single cavity, and the cavity is connected with the top end or the bottom end of the filter device through a pipeline, so that the flexibility of the arrangement position of the liquid chamber can be increased. In some embodiments, the liquid chamber is disposed separately from the filtration device and includes a plurality of chambers, each chamber being in fluid communication with a positive pressure pump and a negative pressure pump, respectively, and each chamber being in communication with the filtration device, respectively, such that the positive pressure pump delivers positive pressure to a portion of the chambers while the negative pressure pump delivers negative pressure to another portion of the chambers, increasing the filtration efficiency of the solution between the filtration device and the bioreactor. In some embodiments, multiple biofiltration systems may be associated with the same bioreactor to increase the efficiency of filtration of the solution within the bioreactor.

Fig. 1A and 1B are schematic diagrams of an exemplary biofiltration system according to an embodiment of the present disclosure.

Referring to fig. 1A and 1B, an embodiment of the present disclosure provides a biofiltration system 10, the biofiltration system 10 being configured to be coupled to a bioreactor 50 and to drive a solution in the bioreactor 50 to circulate/reciprocate between the biofiltration system 10 and the bioreactor 50 to filter the solution in the bioreactor 50. In some embodiments, bioreactor 50 may be a container that holds or handles the reaction fluid that requires filtration.

In one embodiment, the bio-filtration system 10 may include components of a filtration device 101, a liquid chamber 102, a positive pressure pump 103, and a negative pressure pump 104.

In some embodiments, the filtering device 101 refers to a device capable of performing selective separation based on physical and/or chemical properties of certain components in a solution, for example, the filtering device 101 may be various types of filtering devices 101 such as a biofilm filtering device 101, a hollow fiber column filtering device 101, and the like, which is not limited in this specification. In some embodiments, the filter apparatus 101 has a top end 1011 and a bottom end 1012, wherein the top end 1011 and the bottom end 1012 are defined based on a conventionally used orientation of the filter apparatus 101, e.g., the filter apparatus 101 is generally vertically oriented, then the top end 1011 may be an upper end of the filter apparatus 101 and the bottom end 1012 may be a lower end of the filter apparatus 101, although the filter apparatus 101 may be oriented in any suitable orientation, and the top end 1011 and the bottom end 1012 may be rotationally adjusted as appropriate to its orientation.

In some embodiments, the filtration device 101 can include a reaction port 1013, a retentate port 1014, and a permeate port 1015, wherein reaction fluid enters the filtration device 101 from the reaction port 1013, and is filtered inside the filtration device 101 to form a retentate and a permeate, wherein the retentate exits the filtration device 101 from the retentate port 1014 or the retentate returns to the reaction port 1013 and exits the filtration device 101, and wherein the permeate exits the filtration device 101 from the permeate port 1015. In some embodiments, the reactant port 1013 can be located at the bottom end 1012 of the filtration device 101, the retentate port 1014 can be located at the top end 1011 of the filtration device 101, and the permeate port 1015 can be located at the side of the filtration device 101.

In the first embodiment, the bottom end 1012 of the filtering device 101 is configured to be in fluid communication with the bioreactor 50, and further, the reaction solution port 1013 of the bottom end 1012 of the filtering device 101 is in fluid communication with the bioreactor 50, so that the solution in the bioreactor 50 can flow into the filtering device 101 from the reaction solution port 1013. Where fluid communication refers to a coupling or connection that allows fluid flow between filtration device 101 and bioreactor 50, including but not limited to a tubing connection, an interface connection, or a direct communication connection. The fluid communication referred to hereinafter in this specification is analogous to that defined herein and will not be described in detail hereinafter.

In some embodiments, the liquid chamber 102 may be a container for buffering a solution, or may be a chamber that provides a buffer space for a solution flowing out of the filtering device 101. In some embodiments, the liquid chamber 102 may be integrated with the filtration device 101 into a unitary structure, such as the biofiltration system 10 provided in the first embodiment. In some embodiments, the liquid chamber 102 may be designed separately from the filtration device 101, for example, see the biological filtration system 10 provided in examples two-four.

In one embodiment, the liquid chamber 102 may be integrated with the filter device 101 into a unitary structure. In some embodiments, filter device 101 includes a filter portion 1016 and a buffer portion 1017, wherein filter portion 1016 may be near an end where reaction fluid port 1013 is located, i.e., filter portion 1016 is near a bottom end 1012 of filter device 101, and buffer portion 1017 may be near an end where retentate port 1014 is located, i.e., buffer portion 1017 is near a top end 1011 of filter device 101. In some embodiments, filter portion 1016 is provided with a filter element such as a filter membrane or a hollow fiber column. In some embodiments, the buffer portion 1017 is configured as a hollow chamber to form the liquid chamber 102, i.e., the liquid chamber 102 and the buffer portion 1017 are integrated into a unitary structure. In some embodiments, the ratio of the height of buffer portion 1017 to the height of filter portion 1016 in the height direction of filter device 101 may be 1/2, 2/3, 3/4, etc., which is not limited by this specification.

In some embodiments, the buffer portion 1017 is in direct communication with the filter portion 1016, i.e., the buffer portion 1017 is disposed adjacent to the filter portion 1016 and does not communicate through other elements, and the outlet of the filter element may be the inlet of the buffer portion 1017. In some embodiments, the caching portion 1017 and the filtering portion 1016 may be integrally formed structures separated from each other by a spacer. In some embodiments, buffer portion 1017 may buffer the solution, i.e., the solution in filter portion 1016 enters buffer portion 1017, and then returns to the bottom of buffer portion 1017 and enters filter portion 1016 after buffer portion 1017 has accumulated a certain volume, and then exits filter device 101 from the bottom of filter portion 1016. In some embodiments, the buffer portion 1017 may provide a buffer space for the solution, i.e., the solution enters the buffer portion 1017 after reaching the top of the filter element, the solution enters the top of the filter portion 1016, the buffer portion 1017 may prevent the solution from flowing into other elements (e.g., the gas purifier 113 mentioned below), and may allow the solution to completely submerge the filter portion 1016, making the filtration more sufficient.

The integrated design of the liquid chamber 102 inside the filter device 101 allows for a more compact design, which not only simplifies the construction of the bio-filtration system 10, but also reduces the volume of space occupied by the filter device 101 and the liquid chamber 102. Moreover, the liquid chamber 102 is directly communicated with the filtering part 1016, and the solution flows into the liquid chamber 102 without obstruction after passing through the filtering part 1016, so that the resistance of the fluid is reduced, and the power loss of the biological filtering system 10 is reduced.

In some embodiments, power for the biofiltration system 10 may be provided by a positive pressure pump 103 and a negative pressure pump 104. The positive pressure pump 103 is in fluid communication with the liquid chamber 102 (i.e., the buffer portion 1017), such as via a pipe. In some embodiments, positive pressure pump 103 is capable of pumping gas into liquid chamber 102, providing positive pressure to the solution within liquid chamber 102 by pumping gas, thereby driving the flow of solution from liquid chamber 102 to bioreactor 50.

In some embodiments, the negative pressure pump 104 is in fluid communication with the liquid chamber 102 (i.e., the buffer portion 1017), such as by tubing, for example. In some embodiments, the negative pressure pump 104 is capable of pumping gas out of the liquid chamber 102 to provide negative pressure to the solution in the liquid chamber 102 via the pumped gas, thereby driving the flow of the solution from the bioreactor 50 to the liquid chamber 102.

In the first embodiment, a retentate port 1014 at the top of the filter device 101 is communicated with the buffer portion 1017, and the positive pressure pump 103 and the negative pressure pump 104 can be connected with the retentate port 1014 through three-way pipes. In some embodiments, the tee includes a main line 1051, a positive pressure branch 1052, and a negative pressure branch 1053, the main line 1051 having one end connected to the retentate port 1014, the positive pressure branch 1052 having one end connected to the positive pressure pump 103, and the negative pressure branch 1053 having one end connected to the negative pressure pump 104.

In some embodiments, the positive pressure pump 103 and the negative pressure pump 104 may be controlled separately depending on the particular situation of use. For example, in some application scenarios where it is desired to drive a slow flow of solution from bioreactor 50 to filter apparatus 101 and then a fast flow of solution from filter apparatus 101 to bioreactor 50, the power of positive pressure pump 103 and negative pressure pump 104 may be set separately to provide different pressure values to liquid chamber 102 at different stages as desired. For another example, in some application scenarios, for a biological filtration system having a plurality of cavities (see embodiment four specifically), for a cavity requiring positive pressure and a cavity requiring negative pressure, the powers of the positive pressure pump 103 and the negative pressure pump 104 may be set according to needs, and different pressure values may be provided for different cavities. The positive pressure pump 103 and the negative pressure pump 104 are arranged to apply positive pressure and negative pressure to the liquid chamber 102 respectively to drive the flow of the solution between the biological filtration system 10 and the bioreactor 50, the positive pressure pump 103 and the negative pressure pump 104 are not affected each other during operation, and the operation time and power of the positive pressure pump 103 and the negative pressure pump 104 can be controlled independently, so that the control flexibility is improved. Further, the negative pressure pump 103 and the positive pressure pump 104 serve as power sources, and pressure can be quickly built up in the liquid chamber and is stable.

In some embodiments, filtration device 101 and bioreactor 50 may be in communication via tubing. In the first embodiment, the reaction solution port 1013 of the bottom end 1012 of the filtering device 101 is in communication with the bioreactor 50 through a pipe, and the filtering device 101 may be in communication with the bioreactor 50 through one pipe or in communication with the bioreactor 50 through two pipes.

In some embodiments, referring to fig. 1A, biofiltration system 10 may include a first conduit 106, with a bottom end 1012 of filtration device 101 being connected to bioreactor 50 via first conduit 106. In some embodiments, when positive pressure pump 103 is operated, the solution in filter apparatus 101 can flow along first conduit 106 to bioreactor 50, and when negative pressure pump 104 is operated, the solution in bioreactor 50 can flow along first conduit 106 to filter apparatus 101, i.e. the solution flows back and forth along first conduit 106.

In some embodiments, referring to fig. 1B, biofiltration system 10 may include second conduit 107 and third conduit 108, with bottom end 1012 of filtration device 101 being connected to bioreactor 50 via second conduit 107 and third conduit 108. In some embodiments, when the positive pressure pump 103 is operated, the solution in the filtering device 101 can flow to the bioreactor 50 along the second pipe 107, and when the negative pressure pump 104 is operated, the solution in the bioreactor 50 can flow to the filtering device 101 along the third pipe 108, i.e. the solution circulates along the second pipe 107 and the third pipe 108.

In some embodiments, a first one-way valve 109 is disposed on second conduit 107 to provide one-way flow of the solution within filtration device 101 (through second conduit 107) to bioreactor 50, and a second one-way valve 110 is disposed on third conduit 108 to provide one-way flow of the solution within bioreactor 50 (through third conduit 108) to filtration device 101. In this way, the first check valve 109 and the second check valve 110 can control the circulation flow direction of the solution, and a controller is not required to participate in the flow direction control of the solution, thereby simplifying the control strategy.

In some embodiments, the liquid chamber 102 may be a container for buffer solution, and the bio-filtration system 10 further includes a first sensor 111 and a second sensor 112 for detecting liquid level information within the liquid chamber 102 to facilitate determining the amount of solution within the liquid chamber 102. In some embodiments, the level information may be height position information of the solution within the liquid chamber 102. In some embodiments, the first sensor 111 and the second sensor 112 include, but are not limited to, various types of sensors, such as contact level sensors and non-contact level sensors.

In some embodiments, the first sensor 111 may be arranged at a preset interval from the top of the liquid chamber 102, the position of the first sensor 111 being used to determine the allowed high liquid level within the liquid chamber 102. The preset interval refers to a height distance from the first sensor 111 to the top of the liquid chamber 102, for example, the preset interval may be 1/2, 1/3, 1/4, etc. of the entire height of the liquid chamber 102, and is not limited herein. In some embodiments, the space between the first sensor 111 and the top of the liquid chamber 102 may provide a buffer for the solution, avoiding the solution from overflowing the top of the liquid chamber 102 to the positive pressure branch 1052 and the negative pressure branch 1053.

In some embodiments, a second sensor 112 is disposed at the bottom of the liquid chamber 102, the position of the second sensor 112 being used to determine the allowable low liquid level within the liquid chamber 102. In one embodiment, the second sensor 112 can be disposed proximate to an upper surface of a filter element of the filter apparatus 101. In the third and fourth embodiments, the second sensor 112 may be disposed at the bottom inside the liquid chamber 10. By arranging the second sensor 112, the positive pressure pump 103 can be controlled to stop running in time when the solution reaches the lowest position of the liquid chamber 102, and gas or bubbles can be prevented from entering the filtering part 1016 of the filtering device 101 to affect the filtering effect of the filtering device 101.

In the first embodiment, under the action of the negative pressure pump 104, the solution in the bioreactor 50 gradually flows into the filtering device 101, and the solution level in the liquid chamber 102 gradually rises until the first sensor 111 detects a level signal, which indicates that the solution reaches the high liquid level line, and at this time, the operation of the negative pressure pump 104 is stopped. In some embodiments, the solution in the filter apparatus 101 gradually flows into the bioreactor 50 under the action of the positive pressure pump 103, and the solution level in the liquid chamber 102 gradually decreases until the second sensor 112 detects a level signal indicating that the solution reaches the low liquid level, at which time the operation of the positive pressure pump 103 is stopped. The operation strategies of the positive pressure pump 103 and the negative pressure pump 104 can be controlled more accurately through the first sensor 111 and the second sensor 112, and the efficiency of the circulation/reciprocating flow of the solution between the filtering device 101 and the bioreactor 50 is improved.

In some embodiments, the biofiltration system 10 further comprises a gas purifier 113, the gas purifier 113 being for filtering gas entering and exiting the liquid chamber 102. In some embodiments, the gas purifier 113 may be a sterile filter that primarily filters contaminants such as impurities, bacteria, etc. in the gas. In some embodiments, the gas pumped by the positive pressure pump 103 flows through the gas purifier 113 and into the liquid chamber 102, preventing contamination of the solution within the liquid chamber 102; the gas pumped out of the liquid chamber 102 by the negative pressure pump 104 passes through a gas filter to purge the gas in the negative pressure branch 1053, so that even if the gas remaining in the negative pressure branch 1053 returns to the liquid chamber 102 when the positive pressure pump 103 is operated, the solution is not contaminated.

In some embodiments, there are two gas purifiers 113, wherein one gas purifier 113 is disposed on the positive pressure branch 1052 connected to the positive pressure pump 103, and the other gas purifier 113 is disposed on the negative pressure branch 1053 connected to the negative pressure pump 104. In some embodiments, the gas purifier 113 is one, and the gas purifier 113 is disposed on the main line 1051 connecting the liquid chambers 102.

In some embodiments, the solutions within bioreactor 50 and filtration device 101 generally need to be maintained within a constant temperature range, for example, certain biological cell reaction solutions may be maintained at around 37 °. The gas in the liquid chamber 102 contains a large amount of moisture at a relatively high temperature, and the gas having a large moisture content tends to wet the filter element of the gas purifier 113 when passing through the gas purifier 113, resulting in failure of the gas purifier 113. Based on this, in some embodiments, the biofiltration system 10 further comprises a cooling device 114, and the cooling device 114 may be disposed corresponding to the liquid chamber 102 for cooling the gas entering the gas purifier 113 to partially condense the moisture in the gas into condensed water to reduce the moisture content of the gas.

In the first embodiment, the cooling device 114 may be disposed on the outer surface of the buffer portion and in the region between the first sensor 111 and the top of the liquid chamber 102. In some embodiments, the cooling device 114 may be a heat sink or a condenser, which may accelerate heat exchange between the gas and the outside, so that a part of the water in the gas is condensed into condensed water and returned to the solution in the liquid chamber 102.

In some embodiments, the biofiltration system 10 further comprises a heating device 115, the heating device 115 being disposed in correspondence with the gas purifier 113 and/or the liquid chamber 102. In some embodiments, the heating device 115 is disposed corresponding to the gas purifier 113 to prevent moisture in the gas purifier 113 from condensing and wetting the filter element. In some embodiments, the heating device 115 is disposed corresponding to the liquid chamber 102, for example, the heating device 115 may be disposed corresponding to a portion of the liquid chamber 102 between the first sensor 111 and the second sensor 112 for maintaining the temperature of the solution in the liquid chamber 102. In some embodiments, the heating device 115 is disposed in correspondence with both the gas purifier 113 and the liquid chamber 102.

In some embodiments, only the heating device 115 may be disposed outside the liquid chamber 102, and no condensing device may be disposed, in other words, the heating device 115 may be disposed corresponding to the entire liquid chamber 102. In some embodiments, the heating device 115 may be one, and the liquid chamber 102 and the gas purifier 113 are both within the heat radiation range of the same heating device 115.

In some embodiments, a cooling device 114 is provided at the liquid chamber 102, and a heating device 115 is provided at the gas purifier 113, then the cooling device 114 first cools the gas in the liquid chamber 102, increasing the humidity of the gas and even saturating it to extract condensed water, thereby reducing the moisture content in the gas. Then, after the gas enters the gas purifier 113, the heating device 115 heats the gas to reduce the humidity of the gas, thereby avoiding wetting the filter element of the gas purifier 113.

In some embodiments, the heating device 115 may be a warm air device capable of blowing hot air toward the gas purifier 113 and/or the liquid chamber 102. In some embodiments, the heating device 115 may be a heating wire that is coated on the outer surface of the gas purifier 113 and/or the liquid chamber 102 by an insulation medium (e.g., insulation wool, insulation foam, etc.) to provide heat to the gas purifier 113 and/or the liquid chamber 102.

In some embodiments, the biofiltration system 10 further comprises a reservoir 116, the reservoir 116 being disposed in the flow path between the gas purifier 113 and the negative pressure pump 104, the reservoir 116 being configured to collect the condensed water. In some embodiments, the gas flowing out of the gas purifier 113 is cooled in a pipeline to form condensed water, and the liquid storage box 116 can collect the condensed water and collect the condensed water at the bottom of the liquid storage box 116, so as to prevent the condensed water from flowing back to the gas purifier 113.

In some embodiments, the reservoir 116 includes a top port in fluid communication with the liquid chamber 102 through tubing and a bottom port in fluid communication with the negative pressure pump 104 through tubing. In some embodiments, no air cleaner is disposed on the negative pressure branch 1053, and the top port of the reservoir cartridge 116 is in direct communication with the liquid chamber 102. In some embodiments, an air purifier is also disposed between the top port of the reservoir cartridge 116 and the liquid chamber 102, the top port of the reservoir cartridge 116 being in communication with the liquid chamber 102 via the air purifier. The condensed water enters the liquid storage box 116 from the top port and is collected at the bottom of the liquid storage box 116, and the condensed water is continuously pumped to the outside to be discharged under the action of the negative pressure pump 104, so that the condensed water is prevented from filling the liquid storage box 116.

In some embodiments, the heating device 115 may also be disposed corresponding to the liquid storage box 116, the negative pressure pump 104 may be capable of pumping most of the condensed water to the outside, and when the negative pressure pump 104 stops working, the heating device 115 may heat the condensed water and the gas remaining in the liquid storage box 116, so as to keep the condensed water in a high temperature state, and prevent the condensed water from being separated out from the gas, thereby reducing the amount of the condensed water. In some embodiments, the reservoir 116, the gas purifier 113, and the liquid chamber 102 may be simultaneously within the heat radiation range of the same heating device 115. In some embodiments, the reservoir 116 and the gas purifier 113 are both in the heat radiation range of the same heating device 115, the portion of the liquid chamber 102 corresponding to the space between the first sensor 111 and the second sensor 112 is in the heat radiation range of another heating device 115, and the portion of the liquid chamber 102 from the top to the first sensor 111 is in the radiation range of the cooling device 114.

In some embodiments, biofiltration system 10 further comprises a check valve 117, check valve 117 being disposed in the flow path between gas purifier 113 and negative pressure pump 104, check valve 117 allowing one-way flow of fluid, such as gas, condensate, etc., from gas purifier 113 to negative pressure pump 104, preventing condensate from flowing back into gas purifier 113. In some embodiments, a check valve 117 may be disposed between the gas purifier 113 and the reservoir 116. In some embodiments, a check valve 117 may be disposed between the reservoir 116 and the negative pressure pump 104.

In some embodiments, the biofiltration system 10 further comprises a first pressure regulating device 118 and a second pressure regulating device 119. The rate of solution flow between the liquid chamber 102 and the bioreactor 50 can be controlled by a first pressure regulating device 118 and a second pressure regulating device 119.

In some embodiments, a first pressure regulating device 118 is provided at the outlet of the positive pressure pump 103 for regulating the pumping gas pressure of the positive pressure pump 103. In some embodiments, when the first pressure regulating device 118 regulates the pressure of the gas pumped by the positive pressure pump 103, the flow rate of the solution from the liquid chamber 102 to the bioreactor 50 is increased. In some embodiments, when the first pressure regulating device 118 reduces the pressure of the gas pumped by the positive pressure pump 103, the rate of solution flow from the liquid chamber 102 to the bioreactor 50 is slowed.

In some embodiments, a second pressure regulating device 119 is provided at the outlet of the negative pressure pump 104 for regulating the suction gas pressure of the negative pressure pump 104. In some embodiments, when the second pressure regulating device 119 increases the pressure of the gas pumped by the negative pressure pump 104, the flow rate of the solution from the bioreactor 50 to the liquid chamber 102 is increased. In some embodiments, when the second pressure regulating device 119 reduces the pressure of the gas pumped by the negative pressure pump 104, the flow rate of the solution from the bioreactor 50 to the liquid chamber 102 is reduced.

In some embodiments, solenoid valves 123 are further disposed on the negative pressure branch 1053 and the positive pressure branch 1052, respectively. When the positive pressure pump 103 operates, the electromagnetic valve 123 on the positive pressure branch 1052 is opened, and the electromagnetic valve 123 on the negative pressure branch 1053 is closed; when the negative pressure pump 104 is running, the solenoid valve 123 on the negative pressure branch 1053 is opened, and the solenoid valve 123 on the positive pressure branch 1052 is closed. By arranging the electromagnetic valve 123, the positive pressure branch 1052 and the negative pressure branch 1053 can be cut off and connected in time according to the pumping states of the positive pressure pump 103 and the negative pressure pump 104, and the rising or falling of the solution in the liquid chamber 102 can be controlled more accurately.

In some embodiments, biofiltration system 10 further comprises a pressure relief bypass 120, pressure relief bypass 120 being disposed in the flow path between liquid chamber 102 and positive pressure pump 103 and/or negative pressure pump 104 for relieving the pressure of gas within biofiltration system 10.

In some embodiments, when the first sensor 111 or the second sensor 112 detects the liquid level information, the positive pressure pump 103 or the negative pressure pump 104 stops operating, and the solution continues to flow in the primary flow direction because the positive pressure or the negative pressure still exists in the liquid chamber 102. In order to rapidly stop the solution in the liquid chamber 102 at the high liquid level line and the low liquid level line, after the positive pressure pump 103 or the negative pressure pump 104 stops operating, the pressure relief bypass 120 may be opened to communicate the liquid chamber 102 with the outside, so that the gas in the liquid chamber 102 is balanced with the outside air pressure, and the solution can be rapidly stopped at the high liquid level line or the low liquid level line. In some embodiments, after the pressure relief bypass 120 is opened, the positive and negative pressures inside the liquid chamber 102 can reach equilibrium with atmospheric pressure for a very short time (e.g., 1 second, 2 seconds, 5 seconds, etc.), thereby quickly stopping the liquid line of the solution.

In some embodiments, the pressure relief bypass 120 may include a bypass conduit and a pressure relief valve, one end of which is in communication with the outside and the other end of which is in communication with the liquid chamber 102 through the bypass conduit. When the pressure relief valve is opened, the positive pressure of the gas in the liquid chamber 102 may be released from the pressure relief valve, or the external gas may quickly replenish the negative pressure of the gas in the liquid chamber 102, balancing the gas with the external gas pressure. When the pressure relief valve is closed, the pressure in the liquid chamber 102 is regulated by the pressure regulating means.

In some embodiments, the filtration device 101 is provided with a permeate port 1015, and the biological filtration system 10 further comprises a collection vessel 121, the permeate port 1015 being connected to the collection vessel 121, the collection vessel 121 being adapted to collect and hold permeate.

In some embodiments, the bio-filtration system 10 further comprises a flow control device 122, the flow control device 122 being disposed between the collection vessel 121 and the filtration device 101 for controlling a flow rate of the solution in the filtration device 101 to the collection vessel 121, which may be a removal rate of the permeate within the filtration device 101, by adjusting the flow rate, i.e., adjusting the removal rate of the permeate, thereby adjusting the filtration permeation rate of the filtration device 101. By arranging the flow control device 122, the proper permeation speed can be controlled according to solutions with different components and/or different filtering requirements, and the filtering effect is improved.

In some embodiments, the flow control device 122 may be a peristaltic pump, and the power of the peristaltic pump is adjusted to adjust the flow rate of the solution in the filtration device 101 to the collection container 121.

In some embodiments, the biofiltration system 10 further comprises at least one pressure sensor 124 for detecting pressure signals of the solution and/or gas. In some embodiments, the pressure signal of the bio-filter system 10 detected by the pressure sensor 124 may be compared with a predetermined pressure threshold, and based on the comparison, it is determined whether a blockage is present in the bio-filter system 10, thereby providing a warning to the user.

In one embodiment, referring to fig. 1A and 1B, a pressure sensor 124 is disposed in the flow path between the liquid chamber 102 and the positive pressure pump 103 and/or the negative pressure pump 104 to detect the pressure in the positive pressure branch 1052 and the negative pressure branch 1053, i.e., the pressure sensor 124 may be disposed in each of the positive pressure branch 1052 and the negative pressure branch 1053. In some embodiments, the pressure sensor 124 may be disposed between the solenoid valve 123 and the first pressure regulating device 118 on the positive pressure branch 1052, and the pressure sensor 124 may be disposed between the solenoid valve 123 and the second pressure regulating device 119 on the negative pressure branch 1053. In some embodiments, when the solenoid valve 123 of the positive pressure branch 1052 or the negative pressure branch 1053 is opened, the first pressure regulating device 118 and the second pressure regulating device 119 may perform more precise pressure regulation according to the pressure value fed back by the pressure sensor 124. In some embodiments, if the pressure sensor 124 detects an excessive pressure, it may be determined that a blockage exists between the liquid chamber 102 and the positive pressure pump 103 or the negative pressure pump 104.

In some embodiments, pressure sensor 124 may be disposed between filtration device 101 and collection vessel 121, for example, pressure sensor 124 may be disposed between flow control device 122 and filtration device 101. In some embodiments, if pressure sensor 124 detects an overpressure, this indicates a blockage between flow control device 122 and filter device 101; if pressure sensor 124 detects an under-pressure condition, this indicates that there is a blockage in the filter element of filter apparatus 101.

In some embodiments, pressure sensor 124 may also be disposed between filtration device 101 and the bioreactor, for example pressure sensor 124 is disposed on first conduit 106 as in fig. 1A, or pressure sensor 124 is disposed on second conduit 107 and third conduit 108 as in fig. 1B. If the pressure sensor 124 detects an excessive pressure, it indicates that the pipe corresponding to the pressure sensor 124 is clogged.

Fig. 2A-2B are schematic diagrams of an exemplary biofiltration system according to example two of the present disclosure.

Referring to fig. 2A and 2B, a second embodiment of the present disclosure further provides a biofiltration system 20, and it should be firstly explained that most of the structures in the second embodiment may refer to the biofiltration system 10 shown in fig. 1A and 1B and the related description thereof, and hereinafter, different parts of the second embodiment with respect to the first embodiment will be mainly described, and the same structures will not be repeated.

The liquid chamber 202 in the second embodiment of the present specification is disposed outside the filter device 101. In some embodiments, the liquid chamber 202 comprises a single cavity that interfaces directly with the top end 1011 of the filter apparatus 101. Where directly interfaced means that the two components are directly connected without the aid of other structures, such as the interface of the liquid chamber 202 and the retentate port 1014 of the filtration device 101.

In some embodiments, the liquid chamber 202 includes a first port 2021 and a second port 2022, the first port 2021 is disposed at the top end 1011 of the cavity, and the second port 2022 is disposed at the bottom end 1012 of the cavity. In some embodiments, the first interface 2021 is in fluid communication with the positive pressure pump 103 and the negative pressure pump 104, such as via a tee, as can be seen in particular in fig. 1A and 1B and their associated description. In some embodiments, the second port 2022 is directly connected to the filtration device 101, i.e., the second port 2022 may be directly connected to the retentate port 1014 of the filtration device 101. The direct connection of the liquid chamber 202 to the filter device 101 allows to reduce the number of pipes and thus the fluid resistance of the solution.

In some embodiments, the liquid chamber 202 may be a container for buffer solution, and the first sensor 111 and the second sensor 112 may be disposed therein to detect the liquid level information in the liquid chamber 202, as can be seen in fig. 1A and 1B and the related description.

In some embodiments, the liquid chamber 202 may be a chamber for providing a buffer space for the solution flowing out of the filtering device 101, that is, after the solution reaches the top of the filtering device 101, the solution enters the liquid chamber 202 under the action of inertia, and the liquid chamber 202 provides a buffer space for the solution, which can prevent the solution from flowing into the gas purifier 113 and other elements. In some embodiments, the solution circulates primarily between the filtration device 101 and the bioreactor 50, and no liquid is buffered in the liquid chamber 202 for a long period of time, thus effectively reducing the amount of solution circulating outside the bioreactor 50 and the filtration device 101.

Referring to fig. 2A and 2B, in some embodiments, liquid chamber 202 serves as a buffer space for the solution that circulates primarily between filtration device 101 and bioreactor 50, negative pressure pump 104 flows the solution from bioreactor 50 into filtration device 101 until filtration device 101 is full, and positive pressure pump 103 flows the solution from filtration device 101 into bioreactor 50 until filtration device 101 is empty. The bio-filtration system 20 further comprises a third sensor 203 and a fourth sensor 204 for detecting fluid level information within the filtration device 101, the third sensor 203 being disposed at the reaction fluid port 1013 of the filtration device 101 and the fourth sensor 204 being disposed at the retentate port 1014 of the filtration device 101. In some embodiments, the third sensor 203 and the fourth sensor 204 include, but are not limited to, various types of sensors, such as contact level sensors and non-contact level sensors.

In some embodiments, the third sensor 203 can detect whether the solution smoothly enters the filtration device when the bio-filtration system is initially operating, and the fourth sensor 204 can detect whether the solution fills the filtration device when the bio-filtration system is initially operating.

In some embodiments, when positive pressure pump 103 is operating, gas applies a positive pressure to the solution within filtration device 101 via liquid chamber 202, the solution within filtration device 101 flows toward bioreactor 50, and when the liquid level within filtration device 101 drops to the position of third sensor 203, third sensor 203 is triggered to respond, at which time operation of positive pressure pump 103 is stopped.

In some embodiments, when negative pressure pump 104 is running, gas within filter apparatus 101 is pumped out to provide negative pressure, and solution within bioreactor 50 flows toward filter apparatus 101, and when the liquid level within filter apparatus 101 rises to the position of fourth sensor 204, fourth sensor 204 is triggered to respond, at which time negative pressure pump 104 stops running and liquid chamber 202 provides a buffer effect for solution reaching the position of fourth sensor 204.

In some embodiments, the biofiltration system 20 may also be provided with a gas purifier 113 for purifying gas entering and exiting the liquid chamber 202. In some embodiments, referring to fig. 2A, two gas purifiers 113 may be provided, respectively on the positive pressure branch 1052 and the negative pressure branch 1053. Can more accurately filter the gas of positive pressure branch road and negative pressure branch road through setting up two gas purification wares 113 to can require to set up the gas purification ware of different grade type according to the filter effect. In some embodiments, referring to fig. 2B, the gas purifier 113 can be a single gas purifier, which is disposed on the main line 1051 connecting the liquid chambers 202, and by providing a single gas purifier 113, the cost can be saved and the number of components in the biofiltration system can be reduced.

In some embodiments, to reduce the moisture content of the gas entering the gas purifier 113, a cooling device 114 may be disposed around the liquid chamber 202, causing the moisture of the gas within the liquid chamber 202 to condense into condensed water. In some embodiments, the cooling device 114 may be disposed in the upper half of the liquid chamber 202 to avoid affecting the temperature of the solution buffered in the lower half of the liquid chamber 202. Additional description of the gas purifier 113 and the cooling device 114 can be found in particular in fig. 1A and 1B and their associated description.

In some embodiments, referring to fig. 2A, the negative pressure branch 1053 may be provided with a liquid storage box 116 and a check valve 117 for collecting condensed water and preventing the condensed water from flowing back to the gas purifier 113, and other descriptions of the liquid storage box 116 and the check valve 117 may be specifically referred to fig. 1A and 1B and the related description. In some embodiments, referring to fig. 2B, the negative pressure branch 1053 may be eliminated with the reservoir 116 and the check valve 117, so as to simplify the overall structure.

In some embodiments, in order to maintain the temperature of the solution in the filtering device 101 and prevent the solution from entering the liquid chamber 202 to cool and affect the filtering effect, the outer surface of the liquid chamber 202 may further be provided with a heating device 115, and the heating device 115 corresponds to the lower half of the liquid chamber 202 and may provide heat for the solution buffered to the lower half of the liquid chamber 202. Additional description of the heating device 115 may be found in particular in fig. 1A and 1B and their associated description.

In some embodiments, referring to fig. 2A, filtration device 101 and bioreactor 50 may be connected by a first conduit 106. In some embodiments, referring to fig. 2B, filtration device 101 and bioreactor 50 may be connected by second conduit 107 and third conduit 108. The connection between the filtration device 101 and the bioreactor 50 can be seen in fig. 1A and 1B and their associated description.

Fig. 3A-3D are schematic diagrams of an exemplary biofiltration system according to example three of the present disclosure.

Referring to fig. 3A to 3D, a biofiltration system 30 is further provided in the third embodiment of the present disclosure, and it should be firstly explained that most of the structures in the third embodiment may refer to the biofiltration system shown in fig. 1A to 2B and the related descriptions thereof, and hereinafter, different portions of the third embodiment with respect to the first embodiment and the second embodiment will be mainly described, and the same structures will not be repeated.

The liquid chamber 302 in the third embodiment of the present specification is provided separately from the filter device 101 and is in fluid communication with the filter device through a pipe, which can increase flexibility in the arrangement position of the liquid chamber 302. In some embodiments, the liquid chamber 302 comprises a single cavity that is plumbed to either the top end 1011 or the bottom end 1012 of the filter apparatus 101. In some embodiments, referring to fig. 3A, 3B, and 3D, the liquid chamber 302 is connected to a retentate port 1014 of the top end 1011 of the filtration device 101 via a tube. In some embodiments, referring to fig. 3C, the liquid chamber 302 is connected by tubing to a reaction liquid port 1013 at the bottom end 1012 of the filtration device 101.

In some embodiments, one of the top end 1011 and the bottom end 1012 of the filtration device 101 is used in fluid communication with the bioreactor 50 to filter the solution within the bioreactor 50. Referring to fig. 3A, 3B and 3D, bioreactor 50 is connected by tubing to a reaction solution port 1013 at the bottom end 1012 of filtration device 101. In some embodiments, referring to fig. 3C, bioreactor 50 is connected by tubing to retentate port 1014 of top end 1011 of filtration device 101. In some embodiments, referring to fig. 3C and 3D, fluid chamber 302 and bioreactor 50 are also connected by tubing.

In example three, referring to fig. 3A, the reaction solution port 1013 of the bottom end 1012 of the filtration apparatus 101 may be connected to the bioreactor 50 via the first conduit 106. Positive pressure pump 103 and negative pressure pump 104 are used to drive the solution to and from the filter apparatus 101 and bioreactor 50 through first conduit 106. Further features regarding the first conduit 106 can be seen in fig. 1A and its associated description.

Referring to fig. 3B, the reaction solution port 1013 of the bottom end 1012 of the filtering device 101 may be connected to the bioreactor 50 through the second pipe 107 and the third pipe 108. Positive pressure pump 103 is used to drive the flow of solution from filtration apparatus 101 to bioreactor 50 through second conduit 107, and negative pressure pump 104 is used to drive the flow of solution from bioreactor 50 to filtration apparatus 101 through third conduit 108. Further features regarding the second conduit 107 and the third conduit 108 can be seen in fig. 1B and its associated description.

In some embodiments, biofiltration system 30 includes fourth conduit 125, fifth conduit 126 and sixth conduit 127, one of top end 1011 and bottom end 1012 of filtration apparatus 101 is connected to cavity via fourth conduit 125, the other of top end 1011 and bottom end 1012 of filtration apparatus 101 is connected to bioreactor 50 via fifth conduit 126, and cavity is connected to bioreactor 50 via sixth conduit 127. The filtering device 101, the bioreactor 50 and the liquid chamber 302 are connected through the fourth pipeline 125, the fifth pipeline 126 and the sixth pipeline 127 to form a loop, the positive pressure pump 103 and the negative pressure pump 104 drive the solution to circularly flow in the loop, and the solution flows in the filtering device 101 in a single direction through the connection mode, so that continuous filtering is realized, and the filtering efficiency is improved.

In some embodiments, referring to fig. 3C, the bottom end 1012 of the filter apparatus 101 is connected to the liquid chamber 302 via the fourth conduit 125, i.e., the reactant liquid port 1013 of the filter apparatus 101 is connected to the liquid chamber 302; the top end 1011 of the filtration device 101 is connected to the bioreactor 50 via the fifth conduit 126, i.e. the retentate port 1014 of the filtration device 101 is connected to the bioreactor 50; the liquid chamber 302 is connected to the bioreactor 50 via a sixth conduit 127.

In some embodiments, positive pressure pump 103 is used to drive the solution within the cavity to flow to bioreactor 50 via filtration device 101, and negative pressure pump 104 is used to drive the solution within bioreactor 50 to flow to the cavity, such that the solution circulates along filtration device 101, bioreactor 50, and liquid chamber 302 in sequence.

In some embodiments, a one-way valve is disposed on each of the fourth, fifth and

sixth conduits

125, 126 and 127, wherein the one-way valve of the fourth conduit 125 is used for one-way flow of the solution in the liquid chamber 302 to the filtering device 101, the one-way valve of the fifth conduit 126 is used for one-way flow of the solution in the filtering device 101 to the bioreactor 50, and the one-way valve of the sixth conduit 127 is used for one-way flow of the solution in the bioreactor 50 to the liquid chamber 302. The solution can be prevented from flowing back in the flowing direction by arranging the one-way valve.

In some embodiments, referring to fig. 3D, the top end 1011 of the filtration device 101 is connected to the liquid chamber 302 via the fourth conduit 125, i.e. the retentate port 1014 of the filtration device 101 is connected to the liquid chamber 302; the bottom end 1012 of the filtering apparatus 101 is connected to the bioreactor 50 through the fifth pipe 126, i.e. the reaction solution port 1013 of the filtering apparatus 101 is connected to the bioreactor 50; the liquid chamber 302 is connected to the bioreactor 50 via a sixth conduit 127.

In some embodiments, positive pressure pump 103 is used to drive the solution in the cavity to flow to bioreactor 50, and negative pressure pump 104 is used to drive the solution in bioreactor 50 to flow to the cavity via filtration device 101 to form a circulation loop to circulate the solution between liquid chamber 302, bioreactor 50, and filtration device 101 in sequence.

sixth conduits

125, 126 and 127, wherein the one-way valve of the fourth conduit 125 is used for one-way flow of the solution in the filtering device 101 to the liquid chamber 302, and the one-way valve of the fifth conduit 126 is used for one-way flow of the solution in the bioreactor 50 to the one-way valve of the sixth conduit 127 of the filtering device 101 is used for one-way flow of the solution in the liquid chamber 302 to the bioreactor 50.

Referring to fig. 3C and 3D, the fourth pipe 125, the fifth pipe 126 and the sixth pipe 127 are connected in such a manner that the solution has opposite flow directions among the filtering device 101, the bioreactor 50 and the liquid chamber 302, and a biological filtering system having different flow directions can be selected according to the nature of the solution. For example, for the embodiment of fig. 3C, the solution flowing out of bioreactor 50 enters liquid chamber 302, and the solution may be buffered and allowed to stand in liquid chamber 302 for a period of time, which may reduce the entry of air bubbles into filter apparatus 101. For another example, with respect to the arrangement of fig. 3D, where the solution flows from bioreactor 50 directly into filter apparatus 101 for filtration, the solution flowing from filter apparatus 101 may be buffered and allowed to stand in liquid chamber 302 for a period of time before entering bioreactor 50, which may reduce the ingress of air bubbles into bioreactor 50.

In some embodiments, a first sensor 111 and a second sensor 112 are further disposed in the liquid chamber 302, the first sensor 111 is used for detecting whether the solution in the liquid chamber 302 reaches the high liquid level, and the second sensor 112 is used for detecting whether the solution in the liquid chamber 302 reaches the low liquid level.

In some embodiments, the biofiltration system 30 also includes at least one pressure sensor 124. In some embodiments, referring to fig. 3A-3D, a pressure sensor 124 may be disposed in the flow path between the filter apparatus 101 and the liquid chamber 302 to detect the presence of a blockage therebetween. In some embodiments, pressure sensor 124 is disposed in the flow path between filtration device 101 and bioreactor 50 to detect the presence of a blockage therebetween. In some embodiments, referring to fig. 3C and 3D, a pressure sensor 124 may be disposed in the flow path between bioreactor 50 and liquid chamber 302 to detect the presence of a blockage therebetween. Other features and other arrangements of pressure sensor 124 can be seen in fig. 1A and 1B and their associated description.

In some embodiments, the flow paths may all be provided with pressure sensors 124. In some embodiments, some of the flow paths are provided with pressure sensors 124, and the rest are not provided with pressure sensors 124. The embodiments of the present description are not limited in this regard.

Fig. 4A-4B are schematic diagrams of an exemplary biofiltration system according to example four of the present disclosure.

Referring to fig. 4A and 4B, a biofiltration system 40 is further provided in the fourth embodiment of the present disclosure, and it should be firstly explained that most of the structures in the fourth embodiment may refer to the biofiltration system shown in fig. 1A to 3D and the related descriptions thereof, and hereinafter, different parts of the fourth embodiment with respect to the first embodiment will be mainly described, and the description of the same structures will not be repeated.

The liquid chamber 402 in the fourth embodiment of the present specification is provided separately from the filter device 101 and includes a plurality of cavities, each of which is in fluid communication with the positive pressure pump 103 or the negative pressure pump 104, respectively, and each of which is in communication with the filter device 101, respectively. In some embodiments, positive pressure pump 103 delivers positive pressure to one portion of the chamber while negative pressure pump 104 delivers negative pressure to another portion of the chamber, increasing the efficiency of the filtration of the solution between filtration device 101 and bioreactor 50. In some embodiments, the number of the cavities may be 2 to 10, for example, 2, 3, 4, 6, and the like, which is not limited in this specification.

In some embodiments, the positive pressure pump 103 may be in fluid communication with the plurality of cavities through the first multichannel conduit 1054. In some embodiments, the first multichannel conduit 1054 includes a first main channel having one end connected to the positive pressure pump 103, and a plurality of first branches connected to the plurality of chambers in a one-to-one correspondence, respectively. In some embodiments, a solenoid valve 123 is disposed on each first branch, and the solenoid valve 123 is used for controlling the conduction and the closing of each first branch respectively.

In some embodiments, the negative pressure pump 104 can be in fluid communication with the plurality of cavities through the second multichannel conduit 1055. In some embodiments, the second multi-way pipe 1055 includes a second main line having one end connected to the positive pressure pump 103, and a plurality of second branches connected to the plurality of chambers in a one-to-one correspondence, respectively. In some embodiments, a solenoid valve 123 is disposed on each second branch, and the solenoid valve 123 is used for controlling the conduction and the closing of each second branch respectively.

In some embodiments, each cavity is connected to the top end 1011 or the bottom end 1012 of the filter apparatus 101 by a tube, for example, multiple cavities can be connected to the filter apparatus 101 by multi-channel tubes. In some embodiments, biofiltration system 40 comprises fourth conduit 125, fifth conduit 126 and sixth conduit 127, fourth conduit 125 is connected between liquid chamber 402 and filtration device 101, fifth conduit 126 is connected between bioreactor 50 and filtration device 101, sixth conduit 127 is connected between bioreactor 50 and liquid chamber 402, wherein fourth conduit 125 and sixth conduit 127 may be multi-pass conduits capable of communicating with each cavity separately.

In some embodiments, referring to fig. 4A, the liquid chamber 402 is connected to the reactant fluid port 1013 of the bottom end 1012 of the filtration device 101 via the fourth conduit 125, the retentate port 1014 of the top of the filtration device 101 is connected to the bioreactor 50 via the fifth conduit 126, and the bioreactor 50 is connected to the liquid chamber 402 via the sixth conduit 127.

In some embodiments, a one-way valve is further disposed on each of the fourth, fifth and

sixth pipelines

125, 126 and 127, wherein the one-way valve of the fourth pipeline 125 is used for one-way flowing of the solution in the liquid chamber 402 to the filtering device 101, the one-way valve of the fifth pipeline 126 is used for one-way flowing of the solution in the filtering device 101 to the bioreactor 50, and the one-way valve of the sixth pipeline 127 is used for one-way flowing of the solution in the bioreactor 50 to the liquid chamber 402.

In some embodiments, the circulation of the solution between the biofiltration system 40 and the bioreactor 50 is illustrated by way of example in a liquid chamber 402 having two chambers. The liquid chamber 402 includes a first chamber and a second chamber, when the biological filtration system 40 works, the negative pressure pump 104 provides negative pressure to the first chamber to drive the solution in the bioreactor 50 to flow to the first chamber, the positive pressure pump 103 works with the negative pressure pump 104, the positive pressure pump 103 provides positive pressure to the second chamber to drive the solution in the second chamber to flow to the filtration device 101, and the solution is filtered by the filtration device 101 and then flows to the bioreactor 50. When the solution in the first cavity reaches the first sensor 111 and the solution in the second cavity reaches the second sensor 112, the negative pressure pump 104 provides negative pressure to the second cavity to drive the solution in the bioreactor 50 to flow to the second cavity, the positive pressure pump 103 provides positive pressure to the first cavity to drive the solution in the first cavity to flow to the filtering device 101, and the solution is filtered by the filtering device 101 and then flows to the bioreactor 50. The solution in the biofiltration system 40 is continuously circulated according to such a rule.

In some embodiments, referring to fig. 4B, the liquid chamber 402 is connected to the retentate port 1014 at the top end 1011 of the filtration device 101 via the fourth conduit 125, the reactant port 1013 at the bottom end 1012 of the filtration device 101 is connected to the filtration device 101 via the fifth conduit 126, and the bioreactor 50 is connected to the liquid chamber 402 via the sixth conduit 127.

sixth pipelines

125, 126 and 127, wherein the one-way valve of the fourth pipeline 125 is used for one-way flowing of the solution in the filtering device 101 to the liquid chamber 402, the one-way valve of the fifth pipeline 126 is used for one-way flowing of the solution in the bioreactor 50 to the filtering device 101, and the one-way valve of the sixth pipeline 127 is used for one-way flowing of the solution in the liquid chamber 402 to the bioreactor 50. The solution circulation process in this scheme is similar to the scheme in fig. 4A, except that the solution flow direction is different from that in the scheme in fig. 4A, and the description is omitted here.

The biofiltration system in the first embodiment to the fourth embodiment may further include a processor, and the processor is configured to be in signal connection with each component in the biofiltration system, and may acquire a signal of each component or send a control command to each component. The method specifically comprises the following steps:

in some embodiments, the processor is connected to the first to fourth sensors 111 to 204, and can acquire the liquid level signals of the first to fourth sensors 111 to 204 and process the liquid level signals.

In some embodiments, the processor is connected to the solenoid valves 123 of the positive pressure branch and the negative pressure branch, and can control the opening and closing of the solenoid valves 123 based on the liquid level signals fed back by the first sensor 111 to the fourth sensor 204.

In some embodiments, the processor is connected to the positive pressure pump 103 and the negative pressure pump 104 for controlling the start and stop of the positive pressure pump 103 and the negative pressure pump 104 based on the liquid level signals fed back by the first sensor 111 to the fourth sensor 204.

In some embodiments, the processor is in signal communication with the solenoid valve 123 of the pressure relief bypass 120 to selectively relieve positive or negative pressure in the fluid chamber 102 based on the switching state of the positive pressure pump 103 and the negative pressure pump 104.

In some embodiments, the processor is connected to the pressure sensors 124 of the positive pressure branch and the negative pressure branch for obtaining the pressure signals detected by the pressure sensors 124.

In some embodiments, the processor is in signal connection with the first pressure regulating device 118 and the second pressure regulating device 119, and is configured to control the first pressure regulating device 118 and the second pressure regulating device 119 to regulate the pressures of the positive pressure branch and the negative pressure branch based on the pressure signals fed back by the pressure sensors 124 of the positive pressure branch and the negative pressure branch.

In some embodiments, the processor is in signal communication with the flow control device 122 for controlling the flow control device 122 to adjust the flow rate of the solution into the collection vessel 121.

In some embodiments, the processor is in signal communication with a pressure sensor 124 between the liquid chamber 102 and the filtration device 101, with a pressure sensor 124 between the filtration device 101 and the bioreactor 50, and with a pressure sensor 124 between the filtration device 101 and the collection vessel 121 for obtaining a pressure signal from the pressure sensor 124 to determine whether a blockage is present in the biological filtration system.

Fig. 5 is a flow diagram illustrating a method of controlling an exemplary biofiltration system according to some embodiments of the present description.

Referring to fig. 5, in some embodiments, a method of controlling a biofiltration system may include a process 500. In some embodiments, the biological filtration system may further include a processor, and the process 500 may be performed by the processor and include the steps of:

a first level signal within the filter apparatus 101 or the liquid chamber 102 is obtained 510.

In some embodiments, the first level signal may be a signal that is triggered when the solution within the liquid chamber 102 or the filtration device 101 is at a high level. In some embodiments, the first liquid level signal may be collected by the first sensor 111 or the fourth sensor 204, and further description regarding the first sensor 111 and the fourth sensor 204 may be found in fig. 1A-4B and their associated description.

In some embodiments, the first sensor 111 is disposed within the liquid chamber 102 and is arranged at a preset interval from the top of the liquid chamber 102. In some embodiments, when the solution in the liquid chamber 102 rises to the liquid level line corresponding to the first sensor 111, the first sensor 111 may be triggered to generate a first liquid level signal, and the first sensor 111 sends the first liquid level signal to the processor.

In some embodiments, the fourth sensor 204 is disposed at a retentate port 1014 at a top end 1011 of the filtration device 101. In some embodiments, the solution in the filtration device 101 rising to the retentate port 1014 corresponding to the fourth sensor 204 may trigger the fourth sensor 204 to generate the first level signal, and the fourth sensor 204 sends the first level signal to the processor.

And step 520, controlling the positive pressure pump 103 to drive the solution in the filtering device 101 to flow to the bioreactor 50 based on the first liquid level signal.

In some embodiments, after the processor acquires the first level signal, it may determine that the level of the solution within the filtration device 101 or the liquid chamber 102 has risen to the high level line identified by the first sensor 111 or the fourth sensor 204. Based on the first level signal, the processor controls the positive pressure pump 103 to be activated, and the positive pressure pump 103 pumps gas to the liquid chamber 102 to provide positive pressure, thereby driving the solution in the filtration device 101 to flow to the bioreactor 50, so that the level of the solution in the filtration device 101 or the liquid chamber 102 is lowered.

For the biofiltration system in the first to fourth embodiments, controlling the positive pressure pump 103 to drive the solution in the filtration device 101 to flow to the bioreactor 50 includes:

step one, the electromagnetic valve 123 between the negative pressure pump 104 and the cavity generating the first liquid level signal is closed, and the negative pressure supply to the cavity generating the first liquid level signal is stopped.

In some embodiments, the liquid chamber 102 includes a single cavity, and the cavity corresponding to the first liquid level signal is the liquid chamber 102 itself, for example, the biological filtration system in the first to third embodiments. In some embodiments, the liquid chamber 102 includes a plurality of chambers, and the chamber for generating the first liquid level signal is a part of the chambers, such as the biological filtration system in the fourth embodiment.

In some embodiments, after the processor obtains the first liquid level signal, the solenoid valve 123 between the negative pressure pump 104 and the chamber generating the first liquid level signal is turned off, and the negative pressure supply to the chamber generating the first liquid level signal is stopped, so that the solution does not continue to rise after reaching the high liquid level line.

For the biofiltration systems in the first to third embodiments, after the processor obtains the first liquid level signal, the electromagnetic valve 123 on the negative pressure branch 1053 may be closed, and at the same time, the processor may also control the negative pressure pump 104 to stop operating, so as to avoid that the negative pressure in the pipeline between the electromagnetic valve 123 and the negative pressure pump 104 is too large due to the continuous operation of the negative pressure pump 104.

For the biofiltration system of the fourth embodiment, after the processor obtains the first liquid level signal, the solenoid valve 123 on the second multi-way pipe 1055 can be closed to cut off the negative pressure between the negative pressure pump 104 and the chamber generating the first liquid level signal, but at this time, the negative pressure pump 104 can continue to operate to provide negative pressure for the other chambers not generating the first liquid level signal.

Step two, the pressure relief bypass 120 is opened to release the residual negative pressure in the cavity generating the first liquid level signal, and then the pressure relief bypass 120 is closed.

In some embodiments, after the processor closes the solenoid valve 123, the processor controls the pressure relief bypass 120 to open, so that the external gas can quickly supplement the negative pressure of the gas in the liquid chamber 102, thereby balancing the solution, the gas and the external gas pressure, and preventing the solution from continuously rising or generating bubbles under the action of the residual negative pressure.

In some embodiments, the time at which the pressure relief bypass 120 is open may be determined by a timer. In some embodiments, the processor may preset the pressure relief time, which is the time required after the pressure relief bypass 120 completes the relief of the residual negative pressure in the liquid chamber 102. In some embodiments, after the pressure relief bypass 120 is opened, a timer starts to count time to obtain a timing pressure relief time, and when the timing pressure relief time is equal to a preset pressure relief time, the processor closes the pressure relief bypass 120.

In some embodiments, the time at which pressure relief bypass 120 is open may be determined by pressure sensor 124. In some embodiments, a pressure sensor 124 is disposed on the pressure relief bypass 120 or on a pipeline between the pressure relief bypass 120 and the liquid chamber, and the processor closes the pressure relief bypass 120 when a pressure value detected by the pressure sensor 124 is equal to an external atmospheric pressure.

And step three, opening the electromagnetic valve 123 between the positive pressure pump 103 and the cavity generating the first liquid level signal, and providing positive pressure to the cavity generating the first liquid level signal.

In some embodiments, after the residual negative pressure within the liquid chamber 102 has been vented, the solenoid valve 123 between the positive pressure pump 103 and the chamber generating the first level signal is opened to provide a positive pressure to the chamber generating the first level signal to lower the level of the solution. For the bio-filtration system of embodiments one through three, the processor may open the solenoid valve 123 on the positive pressure branch 1052 while the processor controls the positive pressure pump 103 to start running, pumping gas through the positive pressure pump 103 to provide positive pressure to the liquid chamber 102. For the biofiltration system of the fourth embodiment, the processor may open the solenoid valve 123 on the first multichannel conduit 1054, turn on the positive pressure pump 103 and the chamber that generated the first level signal and provide positive pressure to the chamber.

At 530, a second level signal within the filter apparatus 101 or the fluid chamber 102 is obtained.

In some embodiments, the second level signal may be a signal that is triggered when the solution within the liquid chamber 102 or the filtration device 101 is at a low level. In some embodiments, the second liquid level signal may be collected by the second sensor 112 or the third sensor 203, and further description regarding the second sensor 112 and the third sensor 203 may be found in fig. 1A-4B and their associated description.

In some embodiments, the second sensor 112 is disposed at the bottom of the liquid chamber 102. In some embodiments, when the solution in the liquid chamber 102 drops to the liquid level line corresponding to the second sensor 112, the second sensor 112 may be triggered to generate a second liquid level signal, and the second sensor 112 sends the second liquid level signal to the processor.

In some embodiments, the third sensor 203 is disposed at the reaction solution port 1013 of the bottom end 1012 of the filtration device 101. In some embodiments, when the solution in the filtering device 101 drops to the reaction solution port 1013 corresponding to the third sensor 203, the third sensor 203 may be triggered to generate a second liquid level signal, and the third sensor 203 sends the second liquid level signal to the processor.

And 540, controlling the negative pressure pump 104 to drive the solution in the bioreactor 50 to flow to the filtering device 101 based on the second liquid level signal.

In some embodiments, after the processor acquires the second level signal, it may determine that the level of the solution within the filtration device 101 or the liquid chamber 102 has fallen to the low level line identified by the second sensor 112 or the third sensor 203. Based on the second level signal, the processor controls the negative pressure pump 104 to be activated, and the negative pressure pump 104 pumps gas to the liquid chamber 102 to provide negative pressure, thereby driving the solution in the bioreactor 50 to flow to the filtration device 101, so that the level of the solution in the filtration device 101 or the liquid chamber 102 rises.

For the biofiltration system in the first to fourth embodiments, controlling the negative pressure pump 104 to drive the solution in the bioreactor 50 to flow to the filtering apparatus 101 includes:

step one, the electromagnetic valve 123 between the positive pressure pump 103 and the cavity generating the second liquid level signal is closed, and the positive pressure supply to the cavity generating the second liquid level signal is stopped.

In some embodiments, the liquid chamber 102 includes a single cavity, and the cavity corresponding to the second liquid level signal is the liquid chamber 102 itself, such as the biological filtration system of the first to third embodiments. In some embodiments, the fluid chamber 102 includes a plurality of chambers, and the chamber for generating the second fluid level signal is a portion of the chamber, such as the biological filtration system of the fourth embodiment.

In some embodiments, after the processor obtains the second level signal, the solenoid valve 123 between the positive pressure pump 103 and the chamber generating the second level signal is closed, and the positive pressure supply to the chamber generating the second level signal is stopped, so that the solution does not further descend after reaching the low level.

For the biofiltration system in the first embodiment to the third embodiment, after the processor obtains the second liquid level signal, the solenoid valve 123 on the positive pressure branch 1052 can be closed, and meanwhile, the processor can also control the positive pressure pump 103 to stop running, so that the situation that the positive pressure pump 103 continues to run to cause the excessive positive pressure in the pipeline between the solenoid valve 123 and the positive pressure pump 103 is avoided.

For the bio-filtration system of the fourth embodiment, after the processor obtains the second level signal, the solenoid valve 123 on the first multi-way pipe 1054 may be closed to cut off the positive pressure between the positive pressure pump 103 and the chamber generating the second level signal, but at this time, the positive pressure pump 103 may continue to operate to provide positive pressure to another chamber not generating the second level signal.

Step two, the pressure relief bypass 120 is opened to release the residual positive pressure in the cavity generating the second liquid level signal, and then the pressure relief bypass 120 is closed.

In some embodiments, after the processor closes the solenoid valve 123, the processor controls the pressure relief bypass 120 to open, so that the residual positive pressure in the liquid chamber 102 is released to the outside, thereby balancing the solution and the gas with the outside air pressure, and preventing the solution from continuously rising or generating bubbles under the action of the residual positive pressure.

In some embodiments, the time at which pressure relief bypass 120 is open may be determined by a timer or pressure sensor 124. For more description of the timer or pressure sensor 124, reference may be made to step 520 and its description.

And step three, opening the electromagnetic valve 123 between the negative pressure pump 104 and the cavity generating the second liquid level signal, and providing negative pressure for the cavity generating the second liquid level signal.

In some embodiments, after the residual positive pressure within the fluid chamber 102 is vented, the solenoid valve 123 between the negative pressure pump 104 and the chamber that generated the second fluid level signal is opened to provide a negative pressure to the chamber that generated the second fluid level signal, causing the fluid level of the solution to rise. For the biofiltration systems of embodiments one to three, the processor may open the solenoid valve 123 on the negative pressure branch 1053, and at the same time, the processor controls the negative pressure pump 104 to start running, and the negative pressure pump 104 pumps gas to provide negative pressure to the liquid chamber 102. For the biofiltration system of the fourth embodiment, the processor may open the solenoid valve 123 on the second multi-way conduit 1055, turn on the negative pressure pump 104 and the chamber generating the second level signal and provide negative pressure to the chamber.

In some embodiments, after step 540 is performed, the process continues by returning to step 510, and the process is cycled such that the solution is continuously cycled between the filtration device 101 and the bioreactor 50.

Fig. 6 is a flow diagram illustrating a method of controlling an exemplary biofiltration system according to some embodiments of the present description.

Referring to fig. 6, in some embodiments, a method of controlling a biofiltration system may include a process 600. In some embodiments, flow 600 may be performed by a processor and include the steps of:

step 610, a first time to trigger a first level signal is obtained.

In some embodiments, the first sensor 111 or the fourth sensor 204, upon acquiring the first level signal, the processor simultaneously records a first time to trigger the first level signal.

In step 620, a second time for triggering the second liquid level signal is obtained.

In some embodiments, the second sensor 112 or the third sensor 203 simultaneously records a second time to trigger the second level signal when the second level signal is acquired.

The flow rate of the solution is adjusted based on the time difference between the first time and the second time, step 630.

In some embodiments, the processor may pre-store parameters such as the preset time difference, the volume of the chamber, the cross-sectional area of the chamber, the preset flow rate, and the like. In some embodiments, the processor adjusts the flow rate of the solution based on a relationship between the time difference between the first time and the second time and a predetermined time difference, see process 700 for further description of the predetermined time difference. In some embodiments, the processor may calculate the flow rate of the solution in the liquid chamber 102 based on the time difference between the first time and the second time, and the parameter information such as the volume of the chamber and the cross-sectional area of the chamber, and adjust the flow rate to satisfy the predetermined flow rate, so as to optimize the efficiency and the filtering effect of the flow rate of the solution in the liquid chamber 102.

Fig. 7 is a flow diagram illustrating a method of controlling an exemplary biofiltration system according to some embodiments of the present description.

Referring to fig. 7, in some embodiments, step 630 may comprise flow 700. In some embodiments, flow 700 may be performed by a processor and include the steps of:

step 710, comparing the time difference with a preset time difference.

In some embodiments, the processor may retrieve from the storage medium a pre-stored preset time difference, which may be a one-way time required for the level of the solution to move between the high and low fluid levels while optimizing efficiency and filtration. In some embodiments, the preset time difference may be a time value. In some embodiments, the preset time difference may be a time range.

In some embodiments, the processor calculates a time difference between the first time and the second time, compares the time difference between the first time and the second time with a preset time difference, and adjusts the flow rate of the solution through the first pressure adjusting device 118 and/or the second pressure adjusting device 119 according to the comparison result. For more description of the first pressure regulating device 118 and the second pressure regulating device 119, reference may be made to fig. 1A to 4B and their related description.

And 720, if the time difference is smaller than the preset time difference, controlling a pressure regulating device of the biological filtration system to reduce the pressure so as to reduce the flow speed of the solution. Wherein the pressure reduction may be a reduction of the positive pressure pumped by the positive pressure pump 103 and/or a reduction of the negative pressure pumped by the negative pressure pump 104.

In some embodiments, if the time difference between the first time and the second time is less than the predetermined time difference, indicating that the flow rate of the solution is too fast, the positive pressure and/or the negative pressure in the liquid chamber 102 can be reduced by the first pressure regulating device 118 and/or the second pressure regulating device 119.

And step 730, if the time difference is larger than the preset time difference, controlling the pressure regulating device to increase the pressure so as to increase the flow speed of the solution.

In some embodiments, if the time difference between the first time and the second time is greater than the predetermined time difference, which indicates that the flow rate of the solution is too slow, the positive or negative pressure in the liquid chamber 102 can be increased by the first pressure regulating device 118 or the second pressure regulating device 119.

In some embodiments, if the time difference between the first time and the second time is equal to or within the preset time difference, it indicates that the flow rate of the solution satisfies the optimization of the efficiency and the filtering effect, and the flow rate of the solution does not need to be adjusted.

In some embodiments, the processor may continuously adjust the first and second pressure regulating devices based on a pid (probability Integration differentiation) control algorithm until a time difference between the first and second times is equal to or within a preset time difference.

Fig. 8 is a flow diagram illustrating a method of controlling an exemplary biofiltration system according to some embodiments of the present description.

Referring to fig. 8, in some embodiments, a method of controlling a biofiltration system may include a process 800. In some embodiments, flow 800 may be performed by a processor and include the steps of:

at step 810, a pressure signal within the biofiltration system is monitored.

In some embodiments, the pressure signal may be a pressure value of a solution or a pressure value of a gas in a conduit in the biofiltration system.

In some embodiments, the bio-filtration system further includes at least one pressure sensor 124 for detecting a pressure signal of the solution and/or gas, and for further description of the pressure sensor 124, refer to fig. 1A-4B and related description thereof. In some embodiments, the processor may acquire and process pressure signals collected by pressure sensor 124.

And step 820, comparing the pressure signal with a preset pressure threshold value, and judging whether the biological filtration system is blocked or not.

In some embodiments, the preset pressure threshold may be a pressure threshold at which the solution or gas cannot flow or flows too slowly.

In some embodiments, the processor compares the pressure signal collected by pressure sensor 124 to a preset pressure threshold value and determines whether a blockage is present within the biofiltration system based on the comparison. In some embodiments, if the pressure signal is less than the predetermined pressure threshold, it indicates that there is no blockage in the biofiltration system and that the solution or gas is free to flow. In some embodiments, if the pressure signal is greater than or equal to the predetermined pressure threshold, it indicates that there is a blockage in the bio-filtration system, and that the solution or gas is unable to flow or is flowing slowly.

And 830, if the blockage exists, sending alarm information.

In some embodiments, if the processor determines that the pressure signal is greater than or equal to the preset pressure threshold, which indicates that the bio-filtration system is blocked, the processor may send an alarm message to prompt the relevant personnel, so that the relevant personnel can check and maintain the bio-filtration system in time.

As shown in fig. 9, the biofiltration system according to the first to fourth embodiments may further include a processing unit 900. In some embodiments, the processing device 900 includes a storage medium 910, a processor 920, and a communication bus. The storage medium 910 and the processor 920 may implement a communication process through a communication bus. The processor 920 may be configured to perform a control method in the biofiltration system provided by any of the above embodiments of the present application.

In some embodiments, processor 920 may be implemented using a central processor, a server, a terminal device, or any other possible processing device. In some embodiments, the central processor, server, terminal device, or other processing device described above may be implemented on a cloud platform. In some embodiments, the central processor, server, or other processing device may be interconnected with various terminal devices, which may perform information processing tasks or portions thereof.

In some embodiments, storage medium 910 (or computer-readable storage medium) may store data and/or instructions. In some embodiments, the storage medium 910 may store computer instructions, which the processor 920 (or a computer) may read to execute the control method of the catheter pump provided in any embodiment of the present description. In some embodiments, the storage device may include mass storage, removable storage, volatile read-write memory, read-only memory (ROM), and the like, or any combination thereof. In some embodiments, the storage device may be implemented on a cloud platform.

The beneficial effects that may be brought by the embodiments of the present description include, but are not limited to: (1) in some embodiments, the filtering device and the liquid chamber are integrally formed, the filtering device comprises a filtering part and a buffer part, and the liquid chamber is integrated in the buffer part and is directly communicated with the filtering part, so that the liquid chamber is integrated in the filtering device, the design is more compact, the structure of the biological filtering system can be simplified, and the space volume occupied by the filtering device and the liquid chamber can be reduced; (2) in some embodiments, the liquid chamber comprises a single cavity that interfaces directly with the top end of the filtration device, which can reduce the amount of solution circulating outside the bioreactor and filtration device; (3) in some embodiments, the liquid chamber comprises a single cavity, and the cavity is connected with the top end or the bottom end of the filtering device through a pipeline, so that the flexibility of the arrangement position of the liquid chamber can be increased; (4) in some embodiments, the liquid chamber is disposed separately from the filtration device and includes a plurality of chambers, each chamber in fluid communication with a positive pressure pump and a negative pressure pump, respectively, and each chamber in fluid communication with the filtration device, respectively, such that the positive pressure pump delivers positive pressure to a portion of the chambers while the negative pressure pump delivers negative pressure to another portion of the chambers, increasing the filtration efficiency of the solution between the filtration device and the bioreactor. It is to be noted that different embodiments may produce different advantages, and in different embodiments, any one or combination of the above advantages may be produced, or any other advantages may be obtained.

Having thus described the basic concept, it will be apparent to those skilled in the art that the foregoing detailed disclosure is to be regarded as illustrative only and not as limiting the present specification. Various modifications, improvements and adaptations to the present description may occur to those skilled in the art, although not explicitly described herein. Such modifications, improvements and adaptations are proposed in the present specification and thus fall within the spirit and scope of the exemplary embodiments of the present specification.

Also, the description uses specific words to describe embodiments of the description. Reference to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the specification is included. Therefore, it is emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, some features, structures, or characteristics of one or more embodiments of the specification may be combined as appropriate.

Moreover, those skilled in the art will appreciate that aspects of the present description may be illustrated and described in terms of several patentable species or situations, including any new and useful combination of processes, machines, manufacture, or materials, or any new and useful improvement thereof. Accordingly, aspects of this description may be performed entirely by hardware, entirely by software (including firmware, resident software, micro-code, etc.), or by a combination of hardware and software. The above hardware or software may be referred to as "data block," module, "" engine, "" unit, "" component, "or" system. Furthermore, aspects of the present description may be represented as a computer product, including computer readable program code, embodied in one or more computer readable media.

Additionally, the order in which the elements and sequences of the process are recited in the specification, the use of alphanumeric characters, or other designations, is not intended to limit the order in which the processes and methods of the specification occur, unless otherwise specified in the claims. While various presently contemplated embodiments of the invention have been discussed in the foregoing disclosure by way of example, it is to be understood that such detail is solely for that purpose and that the appended claims are not limited to the disclosed embodiments, but, on the contrary, are intended to cover all modifications and equivalent arrangements that are within the spirit and scope of the embodiments herein. For example, although the system components described above may be implemented by hardware devices, they may also be implemented by software-only solutions, according to the installation of the described system on an existing processing device or mobile device.

Similarly, it should be noted that in the preceding description of embodiments of the present specification, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure aiding in the understanding of one or more of the embodiments. This method of disclosure, however, is not intended to imply that more features than are expressly recited in a claim. Indeed, the embodiments may be characterized as having less than all of the features of a single embodiment disclosed above.

Finally, it should be understood that the embodiments described herein are merely illustrative of the principles of the embodiments of the present disclosure. Other variations are also possible within the scope of the present description. Thus, by way of example, and not limitation, alternative configurations of the embodiments of the specification can be considered consistent with the teachings of the specification. Accordingly, the embodiments of the present description are not limited to only those embodiments explicitly described and depicted herein.

Claims

1. A biofiltration system for filtering a solution within a bioreactor, comprising:

a filtration device having a top end and a bottom end, one of the top and bottom ends for fluid communication with the bioreactor to filter a solution within the bioreactor;

a liquid chamber in fluid communication with the other of the top and bottom ends for buffering a solution within the filtration device;

a positive pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the liquid chamber to the bioreactor;

a negative pressure pump in fluid communication with the liquid chamber for driving a flow of solution from the bioreactor to the liquid chamber.

2. The biofiltration system according to claim 1, wherein the filtration device includes a filter portion and a buffer portion, the filter portion being disposed proximate the bottom end of the filtration device, the buffer portion being disposed proximate the top end of the filtration device, the buffer portion being configured as a hollow chamber to form the liquid chamber, and the buffer portion being in direct communication with the filter portion.

3. The biofiltration system as claimed in claim 1, wherein the liquid chamber comprises a single cavity that interfaces directly with the top end of the filtration device.

4. The biofiltration system as claimed in claim 1, wherein the liquid chamber comprises a single cavity connected to the top end or the bottom end of the filtration device by a conduit.

5. The biofiltration system as claimed in claim 1, wherein the liquid chamber comprises a plurality of chambers, each of which is connected to the top end or the bottom end of the filtration device by a conduit, respectively.

6. The biofiltration system as claimed in any one of claims 2 to 4, wherein the biofiltration system comprises a first conduit through which the bottom end of the filtration unit is connected to the bioreactor, the positive pressure pump being adapted to drive the solution within the filtration unit to flow along the first conduit to the bioreactor, and the negative pressure pump being adapted to drive the solution within the bioreactor to flow along the first conduit to the filtration unit.

7. The biofiltration system according to any one of claims 2 to 4, wherein the biofiltration system comprises a second pipe and a third pipe, the bottom end of the filtration device is connected with the bioreactor through the second pipe and the third pipe, the second pipe is provided with a first one-way valve to enable the solution in the filtration device to flow to the bioreactor in one direction, and the third pipe is provided with a second one-way valve to enable the solution in the bioreactor to flow to the filtration device in one direction.

8. The biofiltration system as claimed in claim 4 or 5, wherein the biofiltration system comprises a fourth pipe, a fifth pipe and a sixth pipe, one of the top and bottom ends of the filtration device is connected to the chamber through the fourth pipe, the other of the top and bottom ends of the filtration device is connected to the bioreactor through the fifth pipe, and the chamber is connected to the bioreactor through the sixth pipe,

the positive pressure pump is used for driving the solution in the cavity to flow to the bioreactor through the filtering device, and the negative pressure pump is used for driving the solution in the bioreactor to flow to the cavity; or,

the positive pressure pump is used for driving the solution in the cavity to flow to the bioreactor, and the negative pressure pump is used for driving the solution in the bioreactor to flow to the cavity through the filtering device.

9. The biofiltration system as claimed in any one of claims 1 to 5, further comprising a first sensor and a second sensor for detecting liquid level information within the liquid chamber, the first sensor being disposed at a preset interval from the top of the liquid chamber, the second sensor being disposed at the bottom of the liquid chamber.

10. The biofiltration system as claimed in any one of claims 1-5, further comprising a third sensor and a fourth sensor for detecting fluid level information within the filtration device, the filtration device including a reaction fluid port and a retentate port, the third sensor being disposed at the reaction fluid port and the fourth sensor being disposed at the retentate port.

11. The biofiltration system as claimed in any one of claims 1-5, further comprising a gas purifier disposed on a flow path of the liquid chamber connecting the positive pressure pump and the negative pressure pump.

12. The biofiltration system as claimed in claim 11, further comprising a cooling device disposed in correspondence with the liquid chamber for cooling air entering the gas purifier.

13. The biofiltration system according to claim 11, further comprising a reservoir disposed in the flow path between the gas purifier and the negative pressure pump, the reservoir configured to collect condensed water.

14. The biofiltration system according to claim 11, further comprising a check valve disposed on a flow path between the gas purifier and the negative pressure pump for preventing backflow of condensed water into the gas purifier.

15. The biofiltration system according to claim 11, further comprising a heating device disposed in correspondence with the gas purifier and/or the liquid chamber.

16. The biofiltration system according to claim 1, further comprising a first pressure regulating device and a second pressure regulating device, wherein the first pressure regulating device is disposed at an outlet of the positive pressure pump for regulating a pumping gas pressure of the positive pressure pump, and the second pressure regulating device is disposed at an outlet of the negative pressure pump for regulating a pumping gas pressure of the negative pressure pump.

17. The biofiltration system according to claim 1, further comprising a pressure relief bypass disposed in a flow path between the liquid chamber and the positive and/or negative pressure pump for relieving gas pressure within the biofiltration system.

18. The biofiltration system as claimed in claim 1, wherein the filtration device is provided with a permeate port, the biofiltration system further comprising a collection vessel to which the permeate port is connected and a flow control device disposed between the collection vessel and the filtration device for controlling the flow rate of the solution in the filtration device to the collection vessel.

19. The biofiltration system as claimed in claim 1, further comprising at least one pressure sensor for detecting a pressure signal of the solution and/or gas; wherein,

the pressure sensor is arranged on a flow path between the filtering device and the liquid chamber; and/or the presence of a gas in the gas,

the pressure sensor is arranged on a flow path between the liquid chamber and the positive pressure pump and/or the negative pressure pump; and/or the presence of a gas in the gas,

the pressure sensor is disposed in a flow path between the filtration device and the bioreactor.

20. The biofiltration system as claimed in claim 1, further comprising a processor for:

21. The biofiltration system of claim 20, wherein the processor is further configured to:

acquiring a first time for triggering the first liquid level signal;

acquiring a second time for triggering the second liquid level signal;

22. The biofiltration system of claim 21, wherein the processor adjusts the flow rate of the solution based on the time difference between the first time and the second time, comprising:

comparing the time difference with a preset time difference;

23. The biofiltration system of claim 20, wherein the processor is further configured to:

monitoring a pressure signal within the biofiltration system;

and if the blockage exists, sending alarm information.

24. A control method of a biofiltration system, applied to the biofiltration system as set forth in any one of claims 1-23, comprising:

25. The control method according to claim 24, characterized in that the method further comprises:

acquiring a first time for triggering the first liquid level signal;

acquiring a second time for triggering the second liquid level signal;

26. The control method of claim 25, wherein adjusting the flow rate of the solution based on the time difference between the first time and the second time comprises:

comparing the time difference with a preset time difference;

27. The control method according to claim 24, characterized in that the method further comprises:

monitoring a pressure signal within the biofiltration system;

and if the blockage exists, sending alarm information.